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| Domain hiding | Altered binding specificity | Motif hiding | Composite binding site formation |
| Uncategorised | Rheostatic | Allostery | Avidity-sensing |
| Physicochemical compatibility | Pre-translational | Competition |
| Protein | Start | End | Switch Type | Switch Subtype | Switch Description | Information |
CLV_C14_Caspase3-7 - Caspase3 and Caspase7 cleavage site | |||||||
| PTEN_HUMAN | 381 | 385 | Binary | Physicochemical compatibility | Phosphorylation of S385 adjacent to the cleavage motif of Phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN (PTEN) by CK2 subfamily prevents cleavage by Caspase-3 (CASP3). | ||
| KPCD_HUMAN | 326 | 330 | Binary | Pre‑translational | Alternative splicing inserts exons within the Caspase-3 scission motif of Protein kinase C delta type (PRKCD), abrogating binding to Caspase-3 (CASP3). Cleavage of PKCdeltaI Protein kinase C delta type (PRKCD) by caspase-3 releases a catalytically active C-terminal fragment that is sufficient to induce apoptosis. This inserted exon disrupts scission motifs and therefore the PKCdeltaVIII (GENBANK:DQ516383) splice variant functions as an anti-apoptotic protein in NT2 cells. | ||
CLV_C14_caspase-8-10 - | |||||||
| CASP3_HUMAN | 172 | 175 | Binary | Physicochemical compatibility | Phosphorylation of S176 adjacent to the cleavage motif of Caspase-3 (CASP3) by CK2 subfamily prevents cleavage by Caspase-8 (CASP8) and thus activation of Caspase-3 (CASP3). | ||
CLV_CASPASE3_1 - | |||||||
| CEAM1_MOUSE | 457 | 460 | Binary | Pre‑translational | Alternative splicing removes the caspase-3 scission site of Carcinoembryonic antigen-related cell adhesion molecule 1 (Ceacam1), preventing cleavage by Caspase-3 (Casp3). The presence of cleavage sites allows production of a stronger adhession molecule. | ||
DEG_APCC_DBOX_1 - An RxxL-based motif that binds to the Cdh1 and Cdc20 components of APC/C thereby targeting the protein for destruction in a cell cycle dependent manner | |||||||
| CCNB1_HUMAN | 41 | 49 | Specificity | Domain hiding | Binding of the second KEN-box motif of Mitotic checkpoint serine/threonine-protein kinase BUB1 beta (BUB1B), a subunit of the Spindle Assembly Checkpoint (SAC), to the substrate recruitment site of Cell division cycle protein 20 homolog (CDC20), the substrate recognition subunit of the Anaphase Promoting Complex/Cyclosome (APC/C), blocks binding of the Cdc20 substrate G2/mitotic-specific cyclin-B1 (CCNB1). As a result, G2/mitotic-specific cyclin-B1 (CCNB1) is not targeted for proteasomal degradation until metaphase, when the SAC is inhibited. Destruction of G2/mitotic-specific cyclin-B1 (CCNB1) is required for progression to the anaphase of the cell cycle. | ||
| PTTG1_HUMAN | 60 | 68 | Specificity | Domain hiding | Binding of the second KEN-box motif of Mitotic checkpoint serine/threonine-protein kinase BUB1 beta (BUB1B), a subunit of the Spindle Assembly Checkpoint (SAC), to the substrate recruitment site of Cell division cycle protein 20 homolog (CDC20), the substrate recognition subunit of the Anaphase Promoting Complex/Cyclosome (APC/C), blocks binding of the Cdc20 substrate Securin (PTTG1). As a result, Securin (PTTG1) is not targeted for proteasomal degradation until metaphase, when the SAC is inhibited. Destruction of Securin (PTTG1) is required for progression to the anaphase of the cell cycle. | ||
DEG_APCC_DBOX_3 - | |||||||
| NEK2_HUMAN | 423 | 445 | Binary | Pre‑translational | Alternative splicing removes the extended D-box degron motif of Serine/threonine-protein kinase Nek2 (NEK2), abrogating binding to Cell division cycle protein 20 homolog (CDC20). NEK2-A is targeted by APC/C-Cdc20 in early mitosis whereas Isoform Nek2B of Serine/threonine-protein kinase Nek2 (NEK2) persists into late mitosis. Degradation of Isoform Nek2A of Serine/threonine-protein kinase Nek2 (NEK2) may be necessary to allow re-establishment of the intercentriolar linkage in late mitosis. | ||
DEG_APCC_KENBOX_2 - Motif conserving the exact sequence KEN that binds to the APC/C subunit Cdh1 causing the protein to be targeted for 26S proteasome mediated degradation. | |||||||
| MPIP2_HUMAN | 191 | 195 | Binary | Pre‑translational | Alternative splicing removes the APC/C KEN-box degron motif of M-phase inducer phosphatase 2 (CDC25B), abrogating binding to Fizzy-related protein homolog (FZR1). The motif-lacking Isoform CDC25B2 of M-phase inducer phosphatase 2 (CDC25B) is not degraded during mitosis, unlike other isoforms. | ||
| BUB1B_HUMAN | 303 | 307 | Specificity | Domain hiding | Binding of the second KEN-box motif of Mitotic checkpoint serine/threonine-protein kinase BUB1 beta (BUB1B), a subunit of the Spindle Assembly Checkpoint (SAC), to the substrate recruitment site of Cell division cycle protein 20 homolog (CDC20), the substrate recognition subunit of the Anaphase Promoting Complex/Cyclosome (APC/C), blocks binding of the Cdc20 substrate G2/mitotic-specific cyclin-B1 (CCNB1). As a result, G2/mitotic-specific cyclin-B1 (CCNB1) is not targeted for proteasomal degradation until metaphase, when the SAC is inhibited. Destruction of G2/mitotic-specific cyclin-B1 (CCNB1) is required for progression to the anaphase of the cell cycle. | ||
| BUB1B_HUMAN | 303 | 307 | Specificity | Domain hiding | Binding of the second KEN-box motif of Mitotic checkpoint serine/threonine-protein kinase BUB1 beta (BUB1B), a subunit of the Spindle Assembly Checkpoint (SAC), to the substrate recruitment site of Cell division cycle protein 20 homolog (CDC20), the substrate recognition subunit of the Anaphase Promoting Complex/Cyclosome (APC/C), blocks binding of the Cdc20 substrate Securin (PTTG1). As a result, Securin (PTTG1) is not targeted for proteasomal degradation until metaphase, when the SAC is inhibited. Destruction of Securin (PTTG1) is required for progression to the anaphase of the cell cycle. | ||
| ACM1_YEAST | 97 | 101 | Specificity | Domain hiding | The KEN-box motif of APC/C-CDH1 modulator 1 (ACM1) binds to the substrate recruitment site of APC/C activator protein CDH1 (CDH1), the substrate recognition subunit of the Anaphase Promoting Complex/Cyclosome (APC/C), and thereby blocks recruitment, and subsequent targeting for proteasomal degradation, of the Cdh1 substrate G2/mitotic-specific cyclin-2 (CLB2). Degradation of G2/mitotic-specific cyclin-2 (CLB2) is required for mitotic exit and maintenance of the G1 phase of the cell cycle and is allowed by Cdc20-dependent degradation of APC/C-CDH1 modulator 1 (ACM1) in anaphase. | ||
| CG22_YEAST | 99 | 103 | Specificity | Domain hiding | The KEN-box motif of APC/C-CDH1 modulator 1 (ACM1) binds to the substrate recruitment site of APC/C activator protein CDH1 (CDH1), the substrate recognition subunit of the Anaphase Promoting Complex/Cyclosome (APC/C), and thereby blocks recruitment, and subsequent targeting for proteasomal degradation, of the Cdh1 substrate G2/mitotic-specific cyclin-2 (CLB2). Degradation of G2/mitotic-specific cyclin-2 (CLB2) is required for mitotic exit and maintenance of the G1 phase of the cell cycle and is allowed by Cdc20-dependent degradation of APC/C-CDH1 modulator 1 (ACM1) in anaphase. | ||
| ACM1_YEAST | 97 | 101 | Specificity | Domain hiding | The KEN-box motif of APC/C-CDH1 modulator 1 (ACM1) binds to the substrate recruitment site of APC/C activator protein CDH1 (CDH1), the substrate recognition subunit of the Anaphase Promoting Complex/Cyclosome (APC/C), and thereby blocks recruitment, and subsequent targeting for proteasomal degradation, of the Cdh1 substrate Kinesin-like protein CIN8 (CIN8). Degradation of Kinesin-like protein CIN8 (CIN8) is required for mitotic exit and maintenance of the G1 phase of the cell cycle and is allowed by Cdc20-dependent degradation of APC/C-CDH1 modulator 1 (ACM1) in anaphase. | ||
| CIN8_YEAST | 931 | 935 | Specificity | Domain hiding | The KEN-box motif of APC/C-CDH1 modulator 1 (ACM1) binds to the substrate recruitment site of APC/C activator protein CDH1 (CDH1), the substrate recognition subunit of the Anaphase Promoting Complex/Cyclosome (APC/C), and thereby blocks recruitment, and subsequent targeting for proteasomal degradation, of the Cdh1 substrate Kinesin-like protein CIN8 (CIN8). Degradation of Kinesin-like protein CIN8 (CIN8) is required for mitotic exit and maintenance of the G1 phase of the cell cycle and is allowed by Cdc20-dependent degradation of APC/C-CDH1 modulator 1 (ACM1) in anaphase. | ||
| ACM1_YEAST | 97 | 101 | Specificity | Domain hiding | The KEN-box motif of APC/C-CDH1 modulator 1 (ACM1) binds to the substrate recruitment site of APC/C activator protein CDH1 (CDH1), the substrate recognition subunit of the Anaphase Promoting Complex/Cyclosome (APC/C), and thereby blocks recruitment, and subsequent targeting for proteasomal degradation, of the Cdh1 substrate Probable serine/threonine-protein kinase HSL1 (HSL1). Degradation of Probable serine/threonine-protein kinase HSL1 (HSL1) is required for mitotic exit and maintenance of the G1 phase of the cell cycle and is allowed by Cdc20-dependent degradation of APC/C-CDH1 modulator 1 (ACM1) in anaphase. | ||
| HSL1_YEAST | 774 | 778 | Specificity | Domain hiding | The KEN-box motif of APC/C-CDH1 modulator 1 (ACM1) binds to the substrate recruitment site of APC/C activator protein CDH1 (CDH1), the substrate recognition subunit of the Anaphase Promoting Complex/Cyclosome (APC/C), and thereby blocks recruitment, and subsequent targeting for proteasomal degradation, of the Cdh1 substrate Probable serine/threonine-protein kinase HSL1 (HSL1). Degradation of Probable serine/threonine-protein kinase HSL1 (HSL1) is required for mitotic exit and maintenance of the G1 phase of the cell cycle and is allowed by Cdc20-dependent degradation of APC/C-CDH1 modulator 1 (ACM1) in anaphase. | ||
DEG_MDM2_1 - Motif found in p53 family members which confers binding to the N-terminal domain of MDM2. | |||||||
| P53_HUMAN | 19 | 26 | Binary | Physicochemical compatibility | Phosphorylation of Cellular tumor antigen p53 (TP53) on T18 (in vitro by Casein kinase I subfamily, requiring prior phosphorylation of S15) inhibits its binding to E3 ubiquitin-protein ligase Mdm2 (MDM2). In vivo, T18 is phosphorylated in response to DNA damage. | ||
| P53_HUMAN | 19 | 26 | Binary | Pre‑translational | Alternative promoter usage and alternative splicing removes the E3 ubiquitin ligase MDM2-binding motif of Cellular tumor antigen p53 (TP53), abrogating binding to E3 ubiquitin-protein ligase Mdm2 (MDM2). The splice variant without this motif is resistant to MDM2-mediated degradation, leading to a longer half-life. | ||
DEG_ODPH_VHL_1 - Oxygen dependent prolyl hydroxylation motif in the unstructured region of hypoxia-inducible factor protein and bound by the VHL ligand. | |||||||
| HIF1A_HUMAN | 400 | 413 | Binary | Physicochemical compatibility | Hydroxylation of P402 in the VHL-binding motif of Hypoxia-inducible factor 1-alpha (HIF1A) induces binding to the Von Hippel-Lindau disease tumor suppressor (VHL) protein. | ||
| HIF1A_HUMAN | 562 | 574 | Binary | Physicochemical compatibility | Hydroxylation of P564 in the VHL-binding motif of Hypoxia-inducible factor 1-alpha (HIF1A) induces binding to the Von Hippel-Lindau disease tumor suppressor (VHL) protein. | ||
| EPAS1_HUMAN | 403 | 416 | Binary | Physicochemical compatibility | Hydroxylation of P405 in the VHL-binding motif of Endothelial PAS domain-containing protein 1 (EPAS1) induces binding to the Von Hippel-Lindau disease tumor suppressor (VHL) protein. | ||
| EPAS1_HUMAN | 529 | 542 | Binary | Physicochemical compatibility | Hydroxylation of P531 in the VHL-binding motif of Endothelial PAS domain-containing protein 1 (EPAS1) induces binding to the Von Hippel-Lindau disease tumor suppressor (VHL) protein. | ||
| HIF3A_HUMAN | 490 | 502 | Binary | Physicochemical compatibility | Hydroxylation of P492 in the VHL-binding motif of Hypoxia-inducible factor 3-alpha (HIF3A) induces binding to the Von Hippel-Lindau disease tumor suppressor (VHL) protein. | ||
| HIF3A_HUMAN | 490 | 502 | Binary | Pre‑translational | Alternative splicing removes the VHL-hydroxyproline-modified binding motif of Hypoxia-inducible factor 3-alpha (HIF3A), abrogating binding to Von Hippel-Lindau disease tumor suppressor (VHL). Other studies have shown that the HIF-3 alpha-4 splice variant (Isoform HIF-3alpha4 of Hypoxia-inducible factor 3-alpha (HIF3A)) can act as a dominant negative form with tumour-suppressive activity (see Maynard et al. (2007) (here)). | ||
DEG_SCF_COI1_1 - This degron motif is present in JAZ transcriptional repressor proteins and binds to the COI1 F-box protein of the SCF E3 ubiquitin ligase in a jasmonate-dependent manner. | |||||||
| TIF6B_ARATH | 303 | 320 | Pre‑assembly | Composite binding site formation | Binding of Protein TIFY 6B (TIFY6B) to Coronatine-insensitive protein 1 (COI1), an F-box substrate recognition subunit of the SCF E3 ubiquitin ligase, depends on binding of the plant hormone jasmonate to COI1, as this pre-assembled complex provides a composite binding site for the degron motif in TIFY6B. Subsequent ubiquitylation of TIFY6B by the SCF targets this transcriptional repressor for proteasomal degradation, a pre-requisite for the transcriptional response to jasmonate. | ||
| TI10A_ARATH | 203 | 220 | Pre‑assembly | Composite binding site formation | Binding of Protein TIFY 10A (TIFY10A) to Coronatine-insensitive protein 1 (COI1), an F-box substrate recognition subunit of the SCF E3 ubiquitin ligase, depends on binding of the plant hormone jasmonate to COI1, as this pre-assembled complex provides a composite binding site for the degron motif in TIFY10A. Subsequent ubiquitylation of TIFY10A by the SCF targets this transcriptional repressor for proteasomal degradation, a pre-requisite for the transcriptional response to jasmonate. | ||
| TIF7_ARATH | 221 | 238 | Pre‑assembly | Composite binding site formation | Binding of Protein TIFY 7 (TIFY7) to Coronatine-insensitive protein 1 (COI1), an F-box substrate recognition subunit of the SCF E3 ubiquitin ligase, depends on binding of the plant hormone jasmonate to COI1, as this pre-assembled complex provides a composite binding site for the degron motif in TIFY7. Subsequent ubiquitylation of TIFY7 by the SCF targets this transcriptional repressor for proteasomal degradation, a pre-requisite for the transcriptional response to jasmonate. | ||
| TI10B_ARATH | 205 | 222 | Pre‑assembly | Composite binding site formation | Binding of Protein TIFY 10B (TIFY10B) to Coronatine-insensitive protein 1 (COI1), an F-box substrate recognition subunit of the SCF E3 ubiquitin ligase, depends on binding of the plant hormone jasmonate to COI1, as this pre-assembled complex provides a composite binding site for the degron motif in TIFY10B. Subsequent ubiquitylation of TIFY10B by the SCF targets this transcriptional repressor for proteasomal degradation, a pre-requisite for the transcriptional response to jasmonate. | ||
| A7XXZ0_SOLLC | 199 | 216 | Pre‑assembly | Composite binding site formation | Binding of LOC100134911 to Coi1, an F-box substrate recognition subunit of the SCF E3 ubiquitin ligase, depends on binding of the plant hormone jasmonate to COI1, as this pre-assembled complex provides a composite binding site for the degron motif in the JAZ protein. Subsequent ubiquitylation of the JAZ protein by the SCF targets this transcriptional repressor for proteasomal degradation, a pre-requisite for the transcriptional response to jasmonate. | ||
| B2XVS2_SOLLC | 251 | 268 | Pre‑assembly | Composite binding site formation | Binding of to Coi1, an F-box substrate recognition subunit of the SCF E3 ubiquitin ligase, depends on binding of the plant hormone jasmonate to COI1, as this pre-assembled complex provides a composite binding site for the degron motif in the JAZ protein. Subsequent ubiquitylation of the JAZ protein by the SCF targets this transcriptional repressor for proteasomal degradation, a pre-requisite for the transcriptional response to jasmonate. | ||
DEG_SCF_FBW7_1 - The TPxxS phospho-dependent degron binds the FBW7 F box proteins of the SCF (Skp1_Cullin-Fbox) complex. | |||||||
| CCNE1_HUMAN | 378 | 384 | Specificity | Altered binding specificity | Phosphorylation of Isoform E-S of G1/S-specific cyclin-E1 (CCNE1) at S384 by CDK2 primes CCNE1 for phosphorylation by Glycogen synthase kinase-3 beta (GSK3B) at T380, which creates a recognition site for F box proteins of the SCF ubiquitin ligase complex (F-box/WD repeat-containing protein 7 (FBXW7)) that target CCNE1 for degradation. | ||
| MYC_HUMAN | 55 | 62 | Specificity | Altered binding specificity | Phosphorylation of Myc proto-oncogene protein (MYC) at S62 by Mitogen-activated protein kinase 1 (MAPK1) primes MYC for phosphorylation by Glycogen synthase kinase-3 beta (GSK3B), which targets MYC to the SCF ubiquitin ligase complex, F-box/WD repeat-containing protein 7 (FBXW7) that marks MYC for degradation. | ||
| JUN_HUMAN | 236 | 243 | Specificity | Altered binding specificity | Transcription factor AP-1 (JUN) is primed by an unknown kinase for phosphorylation by Glycogen synthase kinase-3 beta (GSK3B), which targets JUN to the SCF ubiquitin ligase complex, F-box/WD repeat-containing protein 7 (FBXW7) that marks JUN for degradation. In v-Jun (Viral jun-transforming protein (JUN)) the residue corresponding to S243 is mutated to phenylalanine, which protects v-Jun (JUN) from degradation. | ||
| CCNE1_HUMAN | 393 | 399 | Specificity | Altered binding specificity | Phosphorylation of G1/S-specific cyclin-E1 (CCNE1) at S399 generates a docking site for Glycogen synthase kinase-3 beta (GSK3B). Subsequent phosphorylation of CCNE1 by Glycogen synthase kinase-3 beta (GSK3B) at T395 switches the specificity of CCNE1 to the F-box/WD repeat-containing protein 7 (FBXW7), which recruits CCNE1 to the SCF ubiquitin ligase complex to mark CCNE1 for degradation. | ||
| SRBP1_HUMAN | 425 | 430 | Specificity | Altered binding specificity | Phosphorylation of SREBP-1 (Sterol regulatory element-binding protein 1 (SREBF1)) at S430 generates a docking site for Glycogen synthase kinase-3 beta (GSK3B). Subsequent phosphorylation of SREBP-1 (SREBF1) by GSK3B at T426 switches the specificity of SREBP-1 (SREBF1) to the F-box/WD repeat-containing protein 7 (FBXW7), which recruits SREBP-1 (SREBF1) to the SCF ubiquitin ligase complex to mark SREBP-1 (SREBF1) for degradation. | ||
DEG_SCF_FBW7_2 - The TPxxE phospho-dependent degron binds the FBW7 F box proteins of the SCF (Skp1_Cullin-Fbox) complex. | |||||||
| LT_SV40 | 699 | 705 | Binary | Physicochemical compatibility | Phosphorylation of T701 in the degron of Large T antigen induces binding to the F-box/WD repeat-containing protein 7 (FBXW7) protein, which recruits it to the SCF ubiquitin ligase complex where it is marked for degradation. | ||
| NOTC1_HUMAN | 2508 | 2515 | Binary | Physicochemical compatibility | Phosphorylation of T2511 in the degron of Neurogenic locus notch homolog protein 1 (NOTCH1) induces binding to the F-box/WD repeat-containing protein 7 (FBXW7) protein, which recruits it to the SCF ubiquitin ligase complex where it is marked for degradation. | ||
DEG_SCF_SKP2-CKS1_1 - Degradation motif recognised by a pre-assembled complex consisting of Skp2 (an F box protein of the SCF E3 ubiquitin ligase) and Cks1, which leads to ubiquitylation and subsequent proteosomal degradation. | |||||||
| CDN1B_HUMAN | 183 | 190 | Pre‑assembly | Composite binding site formation | Binding of Cyclin-dependent kinase inhibitor 1B (CDKN1B) (p27) to the SCF-Skp2 ubiquitin ligase complex requires phosphorylation of p27 (CDKN1B) at T187, and association of the F-box protein S-phase kinase-associated protein 2 (SKP2) with the regulatory Cyclin-dependent kinases regulatory subunit 1 (CKS1B). SKP2 and CKS1B together generate a composite binding site for p27 (CDKN1B). While some residues, including the phosphorylated T187, bind to CKS1B and others to SKP2, the E185 makes contact with residues of both CKS1B and SKP2. | ||
| CDN1C_HUMAN | 306 | 313 | Pre‑assembly | Composite binding site formation | Binding of Cyclin-dependent kinase inhibitor 1C (CDKN1C) (p57) to the SCF-Skp2 ubiquitin ligase complex requires phosphorylation of p57 (CDKN1C) at T310, and association of the F-box protein S-phase kinase-associated protein 2 (SKP2) with the regulatory Cyclin-dependent kinases regulatory subunit 1 (CKS1B). SKP2 and CKS1B together generate a composite binding site for p57 (CDKN1C). | ||
| CDN1C_MOUSE | 338 | 345 | Pre‑assembly | Composite binding site formation | Binding of Cyclin-dependent kinase inhibitor 1C (Cdkn1c) (p57) to the SCF-Skp2 ubiquitin ligase complex requires phosphorylation of p57 (Cdkn1c) at T342, and association of the F-box protein S-phase kinase-associated protein 2 (SKP2) with the regulatory Cyclin-dependent kinases regulatory subunit 1 (CKS1B). SKP2 and CKS1B together generate a composite binding site for p57 (Cdkn1c). | ||
DEG_SCF_TIR1_1 - This degron motif is present in Aux/IAA transcriptional repressor proteins and binds to TIR1/AFB F-box proteins of the SCF E3 ubiquitin ligase in an auxin-dependent manner. | |||||||
| IAA7_ARATH | 82 | 93 | Pre‑assembly | Composite binding site formation | Binding of Auxin-responsive protein IAA7 (IAA7) to Protein TRANSPORT INHIBITOR RESPONSE 1 (TIR1), an F-box substrate recognition subunit of the SCF E3 ubiquitin ligase, depends on binding of the plant hormone auxin to TIR1, as this pre-assembled complex provides a composite binding site for the degron motif in IAA7. Subsequent ubiquitylation of IAA7 by the SCF targets this transcriptional repressor for proteasomal degradation, a pre-requisite for the transcriptional response to auxin. | ||
| IAA17_ARATH | 82 | 93 | Pre‑assembly | Composite binding site formation | Binding of Auxin-responsive protein IAA17 (IAA17) to Protein TRANSPORT INHIBITOR RESPONSE 1 (TIR1), an F-box substrate recognition subunit of the SCF E3 ubiquitin ligase, depends on binding of the plant hormone auxin to TIR1, as this pre-assembled complex provides a composite binding site for the degron motif in IAA17. Subsequent ubiquitylation of IAA17 by the SCF targets this transcriptional repressor for proteasomal degradation, a pre-requisite for the transcriptional response to auxin. | ||
| IAA1_ARATH | 55 | 66 | Pre‑assembly | Composite binding site formation | Binding of Auxin-responsive protein IAA1 (IAA1) to Protein TRANSPORT INHIBITOR RESPONSE 1 (TIR1), an F-box substrate recognition subunit of the SCF E3 ubiquitin ligase, depends on binding of the plant hormone auxin to TIR1, as this pre-assembled complex provides a composite binding site for the degron motif in IAA1. Subsequent ubiquitylation of IAA1 by the SCF targets this transcriptional repressor for proteasomal degradation, a pre-requisite for the transcriptional response to auxin. | ||
| IAA28_ARATH | 48 | 59 | Pre‑assembly | Composite binding site formation | Binding of Auxin-responsive protein IAA28 (IAA28) to Protein TRANSPORT INHIBITOR RESPONSE 1 (TIR1), an F-box substrate recognition subunit of the SCF E3 ubiquitin ligase, depends on binding of the plant hormone auxin to TIR1, as this pre-assembled complex provides a composite binding site for the degron motif in IAA28. Subsequent ubiquitylation of IAA28 by the SCF targets this transcriptional repressor for proteasomal degradation, a pre-requisite for the transcriptional response to auxin. | ||
| IAA12_ARATH | 69 | 80 | Pre‑assembly | Composite binding site formation | Binding of Auxin-responsive protein IAA12 (IAA12) to Protein TRANSPORT INHIBITOR RESPONSE 1 (TIR1), an F-box substrate recognition subunit of the SCF E3 ubiquitin ligase, depends on binding of the plant hormone auxin to TIR1, as this pre-assembled complex provides a composite binding site for the degron motif in IAA12. Subsequent ubiquitylation of IAA12 by the SCF targets this transcriptional repressor for proteasomal degradation, a pre-requisite for the transcriptional response to auxin. | ||
| IAA3_ARATH | 64 | 75 | Pre‑assembly | Composite binding site formation | Binding of Auxin-responsive protein IAA3 (IAA3) to Protein TRANSPORT INHIBITOR RESPONSE 1 (TIR1), an F-box substrate recognition subunit of the SCF E3 ubiquitin ligase, depends on binding of the plant hormone auxin to TIR1, as this pre-assembled complex provides a composite binding site for the degron motif in IAA3. Subsequent ubiquitylation of IAA3 by the SCF targets this transcriptional repressor for proteasomal degradation, a pre-requisite for the transcriptional response to auxin. | ||
DEG_SCF_TRCP1_1 - The DSGxxS phospho-dependent degron binds the F box protein of the SCF-betaTrCP1 complex. The degron is found in various proteins that function in regulation of cell state. | |||||||
| IKBE_HUMAN | 156 | 161 | Binary | Physicochemical compatibility | Dual phosphorylation of S157 and S161 in the TrCP1-binding motif of NF-kappa-B inhibitor epsilon (NFKBIE) targets the protein to the SCF ubiquitin ligase complex, which marks it for degradation. | ||
| LMP1_EBVB9 | 210 | 215 | Binary | Physicochemical compatibility | Dual phosphorylation of S211 and S215 in the TrCP1-binding motif of Latent membrane protein 1 (LMP1) targets the protein to the SCF ubiquitin ligase complex, which marks it for degradation. | ||
| VPU_HV1BR | 51 | 56 | Binary | Physicochemical compatibility | Dual phosphorylation of S52 and S56 in the TrCP1-binding motif of Protein Vpu (vpu) targets the protein to the SCF ubiquitin ligase complex, which marks it for degradation. | ||
| PRLR_HUMAN | 348 | 353 | Binary | Physicochemical compatibility | Dual phosphorylation of S349 and S353 in the TrCP1-binding motif of Prolactin receptor (PRLR) targets the protein to the SCF ubiquitin ligase complex, which marks it for degradation. | ||
| ATF4_HUMAN | 218 | 224 | Binary | Physicochemical compatibility | Dual phosphorylation of S219 and S224 in the TrCP1-binding motif of Cyclic AMP-dependent transcription factor ATF-4 (ATF4) targets the protein to the SCF ubiquitin ligase complex, which marks it for degradation. | ||
| NFKB1_HUMAN | 926 | 932 | Binary | Physicochemical compatibility | Dual phosphorylation of S927 and S932 in the TrCP1-binding motif of Nuclear factor NF-kappa-B p105 subunit (NFKB1) targets the protein to the SCF ubiquitin ligase complex, which marks it for degradation. | ||
| IKBA_HUMAN | 31 | 36 | Binary | Physicochemical compatibility | Dual phosphorylation of S32 and S36 in the TrCP1-binding motif of NF-kappa-B inhibitor alpha (NFKBIA) targets the protein to the SCF ubiquitin ligase complex, which marks it for degradation. | ||
| DLG1_HUMAN | 597 | 602 | Binary | Physicochemical compatibility | Dual phosphorylation of S598 and S602 in the TrCP1-binding motif of Disks large homolog 1 (DLG1) targets the protein to the SCF ubiquitin ligase complex, which marks it for degradation. | ||
| IKBB_HUMAN | 18 | 23 | Binary | Physicochemical compatibility | Dual phosphorylation of S19 and S23 in the TrCP1-binding motif of NF-kappa-B inhibitor beta (NFKBIB) targets the protein to the SCF ubiquitin ligase complex, which marks it for degradation. | ||
| PDCD4_HUMAN | 70 | 76 | Binary | Physicochemical compatibility | Dual phosphorylation of S71 and S76 in the TrCP1-binding motif of Programmed cell death protein 4 (PDCD4) targets the protein to the SCF ubiquitin ligase complex, which marks it for degradation. | ||
| BORA_HUMAN | 496 | 501 | Binary | Physicochemical compatibility | Dual phosphorylation of S497 and T501 in the TrCP1-binding motif of Protein aurora borealis (BORA) targets the protein to the SCF ubiquitin ligase complex, which marks it for degradation. | ||
| CLSPN_HUMAN | 29 | 34 | Binary | Physicochemical compatibility | Dual phosphorylation of S30 and S34 in the TrCP1-binding motif of Claspin (CLSPN) targets the protein to the SCF ubiquitin ligase complex, which marks it for degradation. | ||
| FBX5_HUMAN | 144 | 149 | Binary | Physicochemical compatibility | Dual phosphorylation of S145 and S149 in the TrCP1-binding motif of F-box only protein 5 (FBXO5) targets the protein to the SCF ubiquitin ligase complex, which marks it for degradation. | ||
| FGD1_HUMAN | 282 | 287 | Specificity | Altered binding specificity | Phosphorylation of FYVE, RhoGEF and PH domain-containing protein 1 (FGD1), a GEF for CDC42 small effector protein 2 (CDC42SE2), by Glycogen synthase kinase-3 beta (GSK3B) targets FGD1 to the SCF ubiquitin ligase complex, F-box/WD repeat-containing protein 1A (BTRC), which marks FGD1 for degradation. | ||
| FGD3_HUMAN | 75 | 80 | Specificity | Altered binding specificity | Phosphorylation of FYVE, RhoGEF and PH domain-containing protein 3 (FGD3), a GEF for CDC42 small effector protein 2 (CDC42SE2), by Glycogen synthase kinase-3 beta (GSK3B) targets FGD3 to the SCF ubiquitin ligase complex, F-box/WD repeat-containing protein 1A (BTRC), which marks FGD3 for degradation. | ||
| CTNB1_HUMAN | 32 | 37 | Specificity | Altered binding specificity | Phosphorylation of Catenin beta-1 (CTNNB1) at T41 generates a docking site for Glycogen synthase kinase-3 beta (GSK3B), which then phosphorylates S37, thereby generating a new docking site for GSK3B. Subsequent phosphorylation of S33 by GSK3B switches the specificity of CTNNB1 to the F-box/WD repeat-containing protein 1A (BTRC), which recruits CTNNB1 to the SCF ubiquitin ligase complex. | ||
| SNAI1_HUMAN | 95 | 100 | Specificity | Altered binding specificity | Phosphorylation of Zinc finger protein SNAI1 (SNAI1) at S100 generates a docking site for Glycogen synthase kinase-3 beta (GSK3B). Subsequent phosphorylation of S96 by GSK3B targets Zinc finger protein SNAI1 (SNAI1) to the SCF ubiquitin ligase complexes F-box/WD repeat-containing protein 1A (BTRC), which marks it for degradation. | ||
| PRLR_HUMAN | 348 | 353 | Binary | Pre‑translational | Alternative Splicing removes the degron motif of Prolactin receptor (PRLR) abrogating binding to F-box/WD repeat-containing protein 11 (FBXW11). SCF-beta-TrCP2 negatively regulates the long isoform of PRLR (Isoform 1 of Prolactin receptor (PRLR)). Should be noted that TrCP2 has a predominately cytoplasmic localisation compared to TrCP1 that is located in the nucleus. The mechanism for the down-regulation of the intermediate (Isoform Intermediate of Prolactin receptor (PRLR)) and short (Isoform Short form 1a of Prolactin receptor (PRLR) and Isoform Short form 1b of Prolactin receptor (PRLR)) that lack the TrCP degron is still not known. However it should be noted that the short and intermediate are either partially deficient or entirely deficient in mediating the signal transduction pathways induced by PRL (see Kine et al. (1999) (here) and Ross et al. (1997) (here)). This though is likely due to the missing STAT5-SH2-binding motif. | ||
DEG_SCF_TRCP1_2 - | |||||||
| B2L11_HUMAN | 93 | 98 | Binary | Pre‑translational | Alternative splicing removes the extended SCF-TrCP degron motif of Bcl-2-like protein 11 (BCL2L11), abrogating binding to F-box/WD repeat-containing protein 1A (BTRC). Upon mitogen survival signals, RPS6KA1 and RPS6KA2 kinases are up-regulated and rapidly phosphorylate the three serines of Isoform Bim(EL) of Bcl-2-like protein 11 (BCL2L11). This facilitates the binding of betaTrCP and subsequent ubiquitination and degradation of Isoform Bim(EL) of Bcl-2-like protein 11 (BCL2L11). | ||
| REST_HUMAN | 1008 | 1013 | Binary | Pre‑translational | Alternative splicing removes the beta-TrCP-binding degron of RE1-silencing transcription factor (REST), abrogating binding to F-box/WD repeat-containing protein 1A (BTRC), and therefore altering the half-life of the variant. Up-regulation of the protein isoform without the degron has been linked to cancer. | ||
| YAP1_HUMAN | 383 | 387 | Specificity | Altered binding specificity | Phosphorylation of Yorkie homolog (YAP1) at S381 by Serine/threonine-protein kinase LATS1 (LATS1) (a key regulator of the Hippo Pathway) primes the sequence for phosphorylation by Casein kinase I isoform epsilon (CSNK1E) at S384 and S387. This targets YAP1 to the SCF ubiqutin ligase complex, F-box/WD repeat-containing protein 1A (BTRC), which marks is YAP1 for subsequent degradation by the proteasomal system. N.B. Serine/threonine-protein kinase LATS2 (LATS2) can replace LATS1 and Casein kinase I isoform delta (CSNK1D) can replace CSNK1E | ||
DOC_AGCK_PIF_1 - The DOC_AGCK_PIF_1 motif contains a phosphorylatable serine/threonine residue that allows fine-tuning of the affinity of the motif for the PIF pocket, with the phosphorylated motif showing a higher affinity. | |||||||
| AKT1_HUMAN | 469 | 474 | Binary | Physicochemical compatibility | Phosphorylation of S473 in the PIF motif of RAC-alpha serine/threonine-protein kinase (AKT1) by Serine/threonine-protein kinase mTOR (MTOR) (as part of mTORC2 complex) induces intramolecular interaction with the PIF-binding pocket, resulting in cis-activation of RAC-alpha serine/threonine-protein kinase (AKT1). Dephosphorylation of the PIF motif by PHLPP1/2 (PHLPP1 for Akt2/3 and PHLPP2 for Akt1/3) results in reduced Akt activity, probably by disrupting the interaction with the Akt PIF pocket and thus cis-activation. | ||
| KPCB_HUMAN | 656 | 661 | Binary | Physicochemical compatibility | Dephosphorylation of the PIF motif by PHLPP1/2 results in reduced stability and increased degradation of PKC. This is countered by autophosphorylation of the PIF motif, but mTORC2 might also contribute. | ||
| SGK1_HUMAN | 418 | 423 | Binary | Physicochemical compatibility | Phosphorylation of S422 by Serine/threonine-protein kinase mTOR (MTOR) (as part of mTORC2 complex) in the PIF pocket-binding motif of Serine/threonine-protein kinase Sgk1 (SGK1) induces intramolecular binding and kinase cis-activation. | ||
| SCH9_YEAST | 733 | 738 | Binary | Physicochemical compatibility | Phosphorylation of T737 by Serine/threonine-protein kinase TOR1 (TOR1) in the PIF pocket-binding motif of Serine/threonine-protein kinase SCH9 (SCH9) induces intramolecular binding and kinase cis-activation. | ||
| KS6A3_MOUSE | 382 | 387 | Binary | Physicochemical compatibility | Auto-phosphorylation of S386 in the PIF pocket-binding motif of Ribosomal protein S6 kinase alpha-3 (Rps6ka3) induces intramolecular binding and kinase cis-activation. | ||
| AKT2_HUMAN | 470 | 475 | Binary | Physicochemical compatibility | Phosphorylation of S474 in the PIF pocket-binding motif of RAC-beta serine/threonine-protein kinase (AKT2) induces intramolecular binding and kinase cis-activation. | ||
| KS6B1_RAT | 408 | 413 | Binary | Physicochemical compatibility | Phosphorylation of T412 in the PIF pocket-binding motif of Ribosomal protein S6 kinase beta-1 (Rps6kb1) induces intramolecular binding and kinase cis-activation. | ||
| ROCK1_HUMAN | 394 | 399 | Binary | Physicochemical compatibility | Phosphorylation of T398 in the PIF pocket-binding motif of Rho-associated protein kinase 1 (ROCK1) induces intramolecular binding and kinase cis-activation. | ||
| SGK3_HUMAN | 482 | 487 | Binary | Physicochemical compatibility | Phosphorylation of S486 in the PIF pocket-binding motif of Serine/threonine-protein kinase Sgk3 (SGK3) induces intramolecular binding and kinase cis-activation. | ||
| SGK3_MOUSE | 482 | 487 | Binary | Physicochemical compatibility | Phosphorylation of S486 in the PIF pocket-binding motif of Serine/threonine-protein kinase Sgk3 (Sgk3) induces intramolecular binding and kinase cis-activation. | ||
DOC_CYCLIN_1 - Substrate recognition site that interacts with cyclin and thereby increases phosphorylation by cyclin/cdk complexes. Predicted proteins should have a CDK phosphorylation site. Also used by cyclin/cdk inhibitors. | |||||||
| CDN1B_HUMAN | 30 | 33 | Specificity | Domain hiding | Binding of the CDK-cyclin inhibitor p27 (Cyclin-dependent kinase inhibitor 1B (CDKN1B)) blocks the substrate recruitment site on Cyclin-A2 (CCNA2). | ||
| CDC6_HUMAN | 94 | 98 | Specificity | Domain hiding | Binding of the CDK-cyclin inhibitor p27 (Cyclin-dependent kinase inhibitor 1B (CDKN1B)) blocks the substrate recruitment site on Cyclin-A2 (CCNA2). | ||
| CDN1A_HUMAN | 19 | 22 | Specificity | Competition | Cyclin-dependent kinase inhibitor 1 (CDKN1A) (p21) and the M-phase inducer phosphatase 1 (CDC25A) bind the same site on Cyclin proteins (e.g. G1/S-specific cyclin-E1 (CCNE1)), making their interactions mutually exclusive. | ||
| MPIP1_HUMAN | 11 | 15 | Specificity | Competition | Cyclin-dependent kinase inhibitor 1 (CDKN1A) (p21) and the M-phase inducer phosphatase 1 (CDC25A) bind the same site on Cyclin proteins (e.g. G1/S-specific cyclin-E1 (CCNE1)), making their interactions mutually exclusive. | ||
| RB_HUMAN | 873 | 877 | Specificity | Competition | The docking sites for PP1 (e.g. Serine/threonine-protein phosphatase PP1-alpha catalytic subunit (PPP1CA)) and Cdk-Cyclins (e.g. Cyclin-A2 (CCNA2)) on Retinoblastoma-associated protein (RB1) overlap, which makes their binding to RB1 mutually exclusive. Hypophosphorylated RB1 blocks E2F-dependent transcription, while hyperphosphorylation inactivates RB1 as a repressor, thereby promoting cell cycle progression. | ||
| AKA12_MOUSE | 501 | 504 | Binary | Physicochemical compatibility | Phosphorylation of S507 adjacent to the cyclin-binding motif of A-kinase anchor protein 12 (Akap12) by PKC subfamily blocks binding to the G1/S-specific cyclin-D1 (Ccnd1). As a result, the function of A-kinase anchor protein 12 (Akap12) as a scaffold is inhibited and G1/S-specific cyclin-D1 (Ccnd1) is translocated to the nucleus where it regulates progression of the cell cycle from G1 to S phase. | ||
DOC_PP1 - Protein phosphatase 1 catalytic subunit (PP1c) interacting motif binds targeting proteins that dock to the substrate for dephosphorylation. The motif defined is [RK]{0,1}[VI][^P][FW]. | |||||||
| RB_HUMAN | 872 | 878 | Specificity | Competition | The docking sites for PP1 (e.g. Serine/threonine-protein phosphatase PP1-alpha catalytic subunit (PPP1CA)) and Cdk-Cyclins (e.g. Cyclin-A2 (CCNA2)) on Retinoblastoma-associated protein (RB1) overlap, which makes their binding to RB1 mutually exclusive. Hypophosphorylated RB1 blocks E2F-dependent transcription, while hyperphosphorylation inactivates RB1 as a repressor, thereby promoting cell cycle progression. | ||
| NEK2_HUMAN | 380 | 387 | Binary | Pre‑translational | Alternative splicing removes the PP1-docking motif of Serine/threonine-protein kinase Nek2 (NEK2), abrogating binding to Serine/threonine-protein phosphatase PP1-gamma catalytic subunit (PPP1CC). Isoform Nek2A of Serine/threonine-protein kinase Nek2 (NEK2) is localised at centrosomes and causes centrosome splitting. Isoform Nek2B of Serine/threonine-protein kinase Nek2 (NEK2) is expressed at a different point in the cell cycle and is required for assembly/maintenance of centrosomes. | ||
| NEK2_HUMAN | 380 | 387 | Binary | Pre‑translational | Alternative splicing removes the PP1-docking motif of Serine/threonine-protein kinase Nek2 (NEK2), abrogating binding to Serine/threonine-protein phosphatase PP1-alpha catalytic subunit (PPP1CA). Isoform Nek2A of Serine/threonine-protein kinase Nek2 (NEK2) is localised at centrosomes and causes centrosome splitting. Isoform Nek2B of Serine/threonine-protein kinase Nek2 (NEK2) is expressed at a different point in the cell cycle and required for assembly/maintenance of centrosomes. | ||
| AKAP1_HUMAN | 151 | 158 | Binary | Pre‑translational | Alternative splicing removes the PP1-binding motif of A-kinase anchor protein 1, mitochondrial (AKAP1), abrogating binding to PP-1 subfamily. Isoform AKAP149 of A-kinase anchor protein 1, mitochondrial (AKAP1) may conceivably position PKA and PP1 in close proximity where they can reversibly modulate the phosphorylation of nuclear substrates such as NPP1, DNA-binding cAMP response elements, B-type lamins and inner nuclear membrane proteins LBR and lamina-associated polypeptides, which all harbor PKA phosphorylation sites. | ||
| NEB1_RAT | 455 | 461 | Binary | Physicochemical compatibility | Phosphorylation of S461 in the PP1-binding motif of Neurabin-1 (Ppp1r9a) by cAMP subfamily inhibits binding to the Serine/threonine-protein phosphatase PP1-alpha catalytic subunit (Ppp1ca). Binding of Neurabin-1 (Ppp1r9a) inhibits activity of the phosphatase. | ||
DOC_PP2B_1 - Calcineurin substrate docking site, leads to the effective dephosphorylation of serine/threonine phosphorylation sites. | |||||||
| DYN1_HUMAN | 844 | 849 | Binary | Pre‑translational | Alternative splicing removes the PP2B-binding motif of Isoform 3 of Dynamin-1 (DNM1), abrogating binding to Serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform (PPP3CA). This splice-specific motif in Isoform 3 of Dynamin-1 (DNM1) allows the docking of calcineurin phosphatase. The dephosphorylation of DNM1 by calcineurin, upon NGF stimulation, promotes the internalisation of the High affinity nerve growth factor receptor (NTRK1) (TrkA). | ||
DOC_USP7_1 - The USP7 NTD domain binding motif variant based on the MDM2 and P53 interactions. | |||||||
| P53_HUMAN | 359 | 363 | Binary | Pre‑translational | Alternative splicing removes the deubiquitinating enzyme USP7-binding motif of Cellular tumor antigen p53 (TP53), abrogating binding to Ubiquitin carboxyl-terminal hydrolase 7 (USP7). | ||
| P53_HUMAN | 364 | 368 | Binary | Pre‑translational | Alternative splicing removes the deubiquitinating enzyme USP7-binding motif of Cellular tumor antigen p53 (TP53), abrogating binding to Ubiquitin carboxyl-terminal hydrolase 7 (USP7). | ||
| MDM4_HUMAN | 398 | 402 | Binary | Physicochemical compatibility | Phosphorylation of S403 adjacent to the USP7-binding motif of Protein Mdm4 (MDM4) by Serine-protein kinase ATM (ATM) inhibits binding to the Ubiquitin carboxyl-terminal hydrolase 7 (USP7), thereby reducing deubiquitylation of Protein Mdm4 (MDM4). As a result, ubiquitylation by E3 ubiquitin-protein ligase Mdm2 (MDM2) is not countered and Protein Mdm4 (MDM4) is targeted for proteasomal degradation. | ||
DOC_WW_Pin1_4 - The Class IV WW domain interaction motif is recognised primarily by the Pin1 phosphorylation-dependent prolyl isomerase. | |||||||
| TFCP2_HUMAN | 326 | 331 | Binary | Physicochemical compatibility | Phosphorylation of T329 in the Pin1-binding motif of Alpha-globin transcription factor CP2 (TFCP2) induces binding to Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1), which isomerises the peptide bonds at the nearby-phosphorylated SP motifs (S291 and S309) to the trans configuration, thereby facilitating their dephosphorylation, which is required for the transcriptional activity of Alpha-globin transcription factor CP2 (TFCP2). | ||
| P73_HUMAN | 409 | 414 | Binary | Physicochemical compatibility | Phosphorylation of S412 in the Pin1-binding motif of Tumor protein p73 (TP73) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein. | ||
| P73_HUMAN | 439 | 444 | Binary | Physicochemical compatibility | Phosphorylation of T442 in the Pin1-binding motif of Tumor protein p73 (TP73) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein. | ||
| P73_HUMAN | 479 | 484 | Binary | Physicochemical compatibility | Phosphorylation of T482 in the Pin1-binding motif of Tumor protein p73 (TP73) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein. | ||
| B2L11_MOUSE | 62 | 67 | Binary | Physicochemical compatibility | Phosphorylation of S65 in the Pin1-binding motif of Bcl-2-like protein 11 (Bcl2l11) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) protein. | ||
| FOS_MOUSE | 229 | 234 | Binary | Physicochemical compatibility | Phosphorylation of T232 in the Pin1-binding motif of Proto-oncogene c-Fos (Fos) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) protein. | ||
| FOS_MOUSE | 322 | 327 | Binary | Physicochemical compatibility | Phosphorylation of T325 in the Pin1-binding motif of Proto-oncogene c-Fos (Fos) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) protein. | ||
| FOS_MOUSE | 328 | 333 | Binary | Physicochemical compatibility | Phosphorylation of T331 in the Pin1-binding motif of Proto-oncogene c-Fos (Fos) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) protein. | ||
| FOS_MOUSE | 371 | 376 | Binary | Physicochemical compatibility | Phosphorylation of S374 in the Pin1-binding motif of Proto-oncogene c-Fos (Fos) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) protein. | ||
| MYC_HUMAN | 55 | 60 | Binary | Physicochemical compatibility | Phosphorylation of T58 in the Pin1-binding motif of Myc proto-oncogene protein (MYC) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein. | ||
| TAX_HTL1A | 157 | 162 | Binary | Physicochemical compatibility | Phosphorylation of S160 in the Pin1-binding motif of Protein Tax-1 (tax) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein. | ||
| P53_HUMAN | 30 | 35 | Binary | Physicochemical compatibility | Phosphorylation of S33 in the Pin1-binding motif of Cellular tumor antigen p53 (TP53) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein. | ||
| P53_HUMAN | 312 | 317 | Binary | Physicochemical compatibility | Phosphorylation of S315 in the Pin1-binding motif of Cellular tumor antigen p53 (TP53) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein. | ||
| P53_HUMAN | 78 | 83 | Binary | Physicochemical compatibility | Phosphorylation of T81 in the Pin1-binding motif of Cellular tumor antigen p53 (TP53) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein. | ||
| JUN_HUMAN | 60 | 65 | Binary | Physicochemical compatibility | Phosphorylation of S63 in the Pin1-binding motif of Transcription factor AP-1 (JUN) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein. | ||
| JUN_HUMAN | 70 | 75 | Binary | Physicochemical compatibility | Phosphorylation of S73 in the Pin1-binding motif of Transcription factor AP-1 (JUN) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein. | ||
| MYB_MOUSE | 525 | 530 | Binary | Physicochemical compatibility | Phosphorylation of S528 in the Pin1-binding motif of Transcriptional activator Myb (Myb) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) protein. | ||
| RARA_HUMAN | 74 | 79 | Binary | Physicochemical compatibility | Phosphorylation of S77 in the Pin1-binding motif of Retinoic acid receptor alpha (RARA) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein. | ||
| NCF1_HUMAN | 342 | 347 | Binary | Physicochemical compatibility | Phosphorylation of S345 in the Pin1-binding motif of Neutrophil cytosol factor 1 (NCF1) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein. | ||
| NR4A1_HUMAN | 137 | 142 | Binary | Physicochemical compatibility | Phosphorylation of S140 in the Pin1-binding motif of Nuclear receptor subfamily 4 group A member 1 (NR4A1) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein. | ||
| NR4A1_HUMAN | 428 | 433 | Binary | Physicochemical compatibility | Phosphorylation of S431 in the Pin1-binding motif of Nuclear receptor subfamily 4 group A member 1 (NR4A1) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein. | ||
| NR4A1_HUMAN | 92 | 97 | Binary | Physicochemical compatibility | Phosphorylation of S95 in the Pin1-binding motif of Nuclear receptor subfamily 4 group A member 1 (NR4A1) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein. | ||
| CCND1_MOUSE | 283 | 288 | Binary | Physicochemical compatibility | Phosphorylation of T286 in the Pin1-binding motif of G1/S-specific cyclin-D1 (Ccnd1) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) protein. | ||
| PML_HUMAN | 400 | 405 | Binary | Physicochemical compatibility | Phosphorylation of S403 in the Pin1-binding motif of Protein PML (PML) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein. | ||
| PML_HUMAN | 502 | 507 | Binary | Physicochemical compatibility | Phosphorylation of S505 in the Pin1-binding motif of Protein PML (PML) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein. | ||
| PML_HUMAN | 515 | 520 | Binary | Physicochemical compatibility | Phosphorylation of S518 in the Pin1-binding motif of Protein PML (PML) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein. | ||
| PML_HUMAN | 524 | 529 | Binary | Physicochemical compatibility | Phosphorylation of S527 in the Pin1-binding motif of Protein PML (PML) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein. | ||
| AKT1_HUMAN | 447 | 452 | Binary | Physicochemical compatibility | Phosphorylation of T450 in the Pin1-binding motif of RAC-alpha serine/threonine-protein kinase (AKT1) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein. | ||
| AKT1_HUMAN | 89 | 94 | Binary | Physicochemical compatibility | Phosphorylation of T92 in the Pin1-binding motif of RAC-alpha serine/threonine-protein kinase (AKT1) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein. | ||
| STF1_MOUSE | 200 | 205 | Binary | Physicochemical compatibility | Phosphorylation of S203 in the Pin1-binding motif of Steroidogenic factor 1 (Nr5a1) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) protein. | ||
| CTNB1_HUMAN | 243 | 248 | Binary | Physicochemical compatibility | Phosphorylation of S246 in the Pin1-binding motif of Catenin beta-1 (CTNNB1) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein. | ||
| IRS1_HUMAN | 431 | 436 | Binary | Physicochemical compatibility | Phosphorylation of S434 in the Pin1-binding motif of Insulin receptor substrate 1 (IRS1) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein. | ||
| BTK_MOUSE | 112 | 117 | Binary | Physicochemical compatibility | Phosphorylation of S115 in the Pin1-binding motif of Tyrosine-protein kinase BTK (Btk) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) protein. | ||
| BTK_MOUSE | 18 | 23 | Binary | Physicochemical compatibility | Phosphorylation of S21 in the Pin1-binding motif of Tyrosine-protein kinase BTK (Btk) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) protein. | ||
| STAT3_HUMAN | 724 | 729 | Binary | Physicochemical compatibility | Phosphorylation of S727 in the Pin1-binding motif of Signal transducer and activator of transcription 3 (STAT3) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein. | ||
| CDN1B_HUMAN | 184 | 189 | Binary | Physicochemical compatibility | Phosphorylation of T187 in the Pin1-binding motif of Cyclin-dependent kinase inhibitor 1B (CDKN1B) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein. | ||
| NOTC1_HUMAN | 2118 | 2123 | Binary | Physicochemical compatibility | Phosphorylation of S2121 in the Pin1-binding motif of Neurogenic locus notch homolog protein 1 (NOTCH1) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein. | ||
| NOTC1_HUMAN | 2129 | 2134 | Binary | Physicochemical compatibility | Phosphorylation of T2132 in the Pin1-binding motif of Neurogenic locus notch homolog protein 1 (NOTCH1) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein. | ||
| NOTC1_HUMAN | 2133 | 2138 | Binary | Physicochemical compatibility | Phosphorylation of S2136 in the Pin1-binding motif of Neurogenic locus notch homolog protein 1 (NOTCH1) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein. | ||
| TERF1_HUMAN | 146 | 151 | Binary | Physicochemical compatibility | Phosphorylation of T149 in the Pin1-binding motif of Telomeric repeat-binding factor 1 (TERF1) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein. | ||
| X_HBVA3 | 38 | 43 | Binary | Physicochemical compatibility | Phosphorylation of S41 in the Pin1-binding motif of Protein X (X) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein. | ||
| BTG2_HUMAN | 144 | 149 | Binary | Physicochemical compatibility | Phosphorylation of S147 in the Pin1-binding motif of Protein BTG2 (BTG2) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein. | ||
| SMAD3_HUMAN | 176 | 181 | Binary | Physicochemical compatibility | Phosphorylation of T179 in the Pin1-binding motif of Mothers against decapentaplegic homolog 3 (SMAD3) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein. | ||
| SMAD3_HUMAN | 201 | 206 | Binary | Physicochemical compatibility | Phosphorylation of S204 in the Pin1-binding motif of Mothers against decapentaplegic homolog 3 (SMAD3) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein. | ||
| SMAD3_HUMAN | 205 | 210 | Binary | Physicochemical compatibility | Phosphorylation of S208 in the Pin1-binding motif of Mothers against decapentaplegic homolog 3 (SMAD3) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein. | ||
| SMAD3_HUMAN | 210 | 215 | Binary | Physicochemical compatibility | Phosphorylation of S213 in the Pin1-binding motif of Mothers against decapentaplegic homolog 3 (SMAD3) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein. | ||
| PO5F1_HUMAN | 9 | 14 | Binary | Physicochemical compatibility | Phosphorylation of S12 in the Pin1-binding motif of POU domain, class 5, transcription factor 1 (POU5F1) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein. | ||
| TF65_HUMAN | 251 | 256 | Binary | Physicochemical compatibility | Phosphorylation of T254 in the Pin1-binding motif of Transcription factor p65 (RELA) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein. | ||
| FAK1_HUMAN | 907 | 912 | Binary | Physicochemical compatibility | Phosphorylation of S910 in the Pin1-binding motif of Focal adhesion kinase 1 (PTK2) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein. | ||
| IRF3_HUMAN | 336 | 341 | Binary | Physicochemical compatibility | Phosphorylation of S339 in the Pin1-binding motif of Interferon regulatory factor 3 (IRF3) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein. | ||
| CRTC2_MOUSE | 133 | 138 | Binary | Physicochemical compatibility | Phosphorylation of S136 in the Pin1-binding motif of CREB-regulated transcription coactivator 2 (Crtc2) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) protein. | ||
| CCNE1_MOUSE | 382 | 387 | Binary | Physicochemical compatibility | Phosphorylation of S385 in the Pin1-binding motif of G1/S-specific cyclin-E1 (Ccne1) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) protein. | ||
| NANOG_MOUSE | 49 | 54 | Binary | Physicochemical compatibility | Phosphorylation of S52 in the Pin1-binding motif of Homeobox protein NANOG (Nanog) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) protein. | ||
| NANOG_MOUSE | 62 | 67 | Binary | Physicochemical compatibility | Phosphorylation of S65 in the Pin1-binding motif of Homeobox protein NANOG (Nanog) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) protein. | ||
| CEP55_MOUSE | 420 | 425 | Binary | Physicochemical compatibility | Phosphorylation of S423 in the Pin1-binding motif of Centrosomal protein of 55 kDa (Cep55) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) protein. | ||
| CEP55_MOUSE | 423 | 428 | Binary | Physicochemical compatibility | Phosphorylation of S426 in the Pin1-binding motif of Centrosomal protein of 55 kDa (Cep55) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) protein. | ||
| GEPH_MOUSE | 185 | 190 | Binary | Physicochemical compatibility | Phosphorylation of S188 in the Pin1-binding motif of Gephyrin (Gphn) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) protein. | ||
| GEPH_MOUSE | 191 | 196 | Binary | Physicochemical compatibility | Phosphorylation of S194 in the Pin1-binding motif of Gephyrin (Gphn) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) protein. | ||
| GEPH_MOUSE | 197 | 202 | Binary | Physicochemical compatibility | Phosphorylation of S200 in the Pin1-binding motif of Gephyrin (Gphn) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) protein. | ||
| MEF2C_MOUSE | 107 | 112 | Binary | Physicochemical compatibility | Phosphorylation of S110 in the Pin1-binding motif of Myocyte-specific enhancer factor 2C (Mef2c) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) protein. | ||
| MEF2C_MOUSE | 95 | 100 | Binary | Physicochemical compatibility | Phosphorylation of S98 in the Pin1-binding motif of Myocyte-specific enhancer factor 2C (Mef2c) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) protein. | ||
| FUBP2_HUMAN | 178 | 183 | Binary | Physicochemical compatibility | Phosphorylation of S181 in the Pin1-binding motif of Far upstream element-binding protein 2 (KHSRP) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein. | ||
| NONO_MOUSE | 409 | 414 | Binary | Physicochemical compatibility | Phosphorylation of T412 in the Pin1-binding motif of Non-POU domain-containing octamer-binding protein (Nono) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) protein. | ||
| NONO_MOUSE | 427 | 432 | Binary | Physicochemical compatibility | Phosphorylation of T430 in the Pin1-binding motif of Non-POU domain-containing octamer-binding protein (Nono) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) protein. | ||
| NONO_MOUSE | 449 | 454 | Binary | Physicochemical compatibility | Phosphorylation of T452 in the Pin1-binding motif of Non-POU domain-containing octamer-binding protein (Nono) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) protein. | ||
| ARBK1_MOUSE | 667 | 672 | Binary | Physicochemical compatibility | Phosphorylation of S670 in the Pin1-binding motif of Beta-adrenergic receptor kinase 1 (Adrbk1) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) protein. | ||
| ST4A1_HUMAN | 5 | 10 | Binary | Physicochemical compatibility | Phosphorylation of T8 in the Pin1-binding motif of Sulfotransferase 4A1 (SULT4A1) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein. | ||
| ST4A1_HUMAN | 8 | 13 | Binary | Physicochemical compatibility | Phosphorylation of T11 in the Pin1-binding motif of Sulfotransferase 4A1 (SULT4A1) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein. | ||
| TFCP2_MOUSE | 288 | 293 | Binary | Physicochemical compatibility | Phosphorylation of S291 in the Pin1-binding motif of Alpha-globin transcription factor CP2 (Tcfcp2) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) protein. | ||
| TFCP2_MOUSE | 306 | 311 | Binary | Physicochemical compatibility | Phosphorylation of S309 in the Pin1-binding motif of Alpha-globin transcription factor CP2 (Tcfcp2) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) protein. | ||
| TFCP2_MOUSE | 326 | 331 | Binary | Physicochemical compatibility | Phosphorylation of T329 in the Pin1-binding motif of Alpha-globin transcription factor CP2 (Tcfcp2) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) protein. | ||
| NEK6_HUMAN | 212 | 217 | Binary | Physicochemical compatibility | Phosphorylation of S215 in the Pin1-binding motif of Serine/threonine-protein kinase Nek6 (NEK6) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein. | ||
| NEK6_HUMAN | 242 | 247 | Binary | Physicochemical compatibility | Phosphorylation of S245 in the Pin1-binding motif of Serine/threonine-protein kinase Nek6 (NEK6) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein. | ||
| AATF_HUMAN | 143 | 148 | Binary | Physicochemical compatibility | Phosphorylation of T146 in the Pin1-binding motif of Protein AATF (AATF) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein. | ||
| DAXX_HUMAN | 175 | 180 | Binary | Physicochemical compatibility | Phosphorylation of S178 in the Pin1-binding motif of Death domain-associated protein 6 (DAXX) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein. | ||
| NCOR2_HUMAN | 1238 | 1243 | Binary | Physicochemical compatibility | Phosphorylation of T1241 in the Pin1-binding motif of Nuclear receptor corepressor 2 (NCOR2) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein. | ||
| NCOR2_HUMAN | 1441 | 1446 | Binary | Physicochemical compatibility | Phosphorylation of T1444 in the Pin1-binding motif of Nuclear receptor corepressor 2 (NCOR2) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein. | ||
| SNCAP_HUMAN | 208 | 213 | Binary | Physicochemical compatibility | Phosphorylation of S211 in the Pin1-binding motif of Synphilin-1 (SNCAIP) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein. | ||
| SNCAP_HUMAN | 212 | 217 | Binary | Physicochemical compatibility | Phosphorylation of S215 in the Pin1-binding motif of Synphilin-1 (SNCAIP) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein. | ||
| WEE1B_XENLA | 183 | 188 | Binary | Physicochemical compatibility | Phosphorylation of T186 in the Pin1-binding motif of Wee1-like protein kinase 1-B (wee1-b) induces binding to the pin1 protein. | ||
| FBX5A_XENLA | 7 | 12 | Binary | Physicochemical compatibility | Phosphorylation of S10 in the Pin1-binding motif of F-box only protein 5-A (fbxo5-a) induces binding to the pin1 protein. | ||
| SPT23_YEAST | 651 | 656 | Binary | Physicochemical compatibility | Phosphorylation of S654 in the Pin1-binding motif of Protein SPT23 (SPT23) induces binding to the Peptidyl-prolyl cis-trans isomerase ESS1 (ESS1) protein. | ||
| SOC1_ARATH | 192 | 197 | Binary | Physicochemical compatibility | Phosphorylation of S195 in the Pin1-binding motif of MADS-box protein SOC1 (SOC1) induces binding to the Peptidyl-prolyl cis-trans isomerase Pin1 (PIN1) protein. | ||
| SOC1_ARATH | 46 | 51 | Binary | Physicochemical compatibility | Phosphorylation of S49 in the Pin1-binding motif of MADS-box protein SOC1 (SOC1) induces binding to the Peptidyl-prolyl cis-trans isomerase Pin1 (PIN1) protein. | ||
| AGL24_ARATH | 199 | 204 | Binary | Physicochemical compatibility | Phosphorylation of T202 in the Pin1-binding motif of MADS-box protein AGL24 (AGL24) induces binding to the Peptidyl-prolyl cis-trans isomerase Pin1 (PIN1) protein. | ||
| FAK1_MOUSE | 907 | 912 | Binary | Physicochemical compatibility | Phosphorylation of S910 in the Pin1-binding motif of Isoform 3 of Focal adhesion kinase 1 (Ptk2) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) protein. | ||
| SMAD3_HUMAN | 176 | 181 | Specificity | Altered binding specificity | CDK8/9 phosphorylates Mothers against decapentaplegic homolog 3 (SMAD3) at T179 and S208. Phosphorylation of T179 creates a binding site for the WW domain of Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1), while phosphorylation of S208 primes SMAD3 for phosphorylation of S204 by Glycogen synthase kinase-3 beta (GSK3B). The pS204-pS208 forms a binding site for the third WW domain of E3 ubiquitin-protein ligase NEDD4-like (NEDD4L), whose second WW domain will displace the WW domain of PIN1 at the pT179-PY box site of SMAD3. This regulation couples SMAD3 activation to SMAD3 destruction in an ordered fashion. See also switch details and switch details. | ||
| P73_HUMAN | 479 | 484 | Binary | Pre‑translational | Alternative splicing removes the WW-binding motif of Tumor protein p73 (TP73), abrogating binding to Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1). Isoforms lacking WW-binding motifs have decreased transcriptional activity. | ||
| P73_HUMAN | 439 | 444 | Binary | Pre‑translational | Alternative splicing removes the WW-binding motif of Tumor protein p73 (TP73), abrogating binding to Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1). Isoforms lacking WW-binding motifs have decreased transcriptional activity. | ||
| P73_HUMAN | 409 | 414 | Binary | Pre‑translational | Alternative splicing removes the WW-binding motif of Tumor protein p73 (TP73), abrogating binding to Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1). Isoforms lacking WW-binding motifs have decreased transcriptional activity. | ||
| FBXW7_HUMAN | 202 | 207 | Binary | Physicochemical compatibility | Phosphorylation of T205 in the Pin1-binding motif of F-box/WD repeat-containing protein 7 (FBXW7) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein. Pin1 interacts with Fbw7 in a phoshorylation-dependent manner and promotes Fbw7 self-ubiquitination and protein degradation by disrupting Fbw7 dimerization. Paper also shows the over-expression of Pin1 suppresses the ability of Fbw7 to inhibit cell transformation and proliferation, suggesting a link between Pin1 overexpression and cancer. | ||
LIG_14-3-3_1 - Mode 1 interacting phospho-motif for 14-3-3 proteins with key conservation RxxSxP. | |||||||
| BAD_RAT | 134 | 139 | Binary | Physicochemical compatibility | Phosphorylation of S137 by RAC-alpha serine/threonine-protein kinase (Akt1) in the 14-3-3-binding motif of Bcl2 antagonist of cell death (Bad) induces binding to the 14-3-3 protein beta/alpha (YWHAB) protein. This interaction inhibits the pro-apoptotic activity of Bcl2 antagonist of cell death (Bad). | ||
| MT_POVM3 | 254 | 259 | Binary | Physicochemical compatibility | Phosphorylation of S257 in the 14-3-3-binding motif of Middle T antigen induces binding to the 14-3-3 protein zeta/delta (YWHAZ) protein. | ||
| ATX1_HUMAN | 772 | 777 | Binary | Physicochemical compatibility | Phosphorylation of S775 by RAC-alpha serine/threonine-protein kinase (AKT1) in the 14-3-3-binding motif of Ataxin-1 (ATXN1) induces binding to the 14-3-3 protein zeta/delta (YWHAZ) protein. | ||
| M3K5_HUMAN | 963 | 968 | Binary | Physicochemical compatibility | Phosphorylation of S966 in the 14-3-3-binding motif of Mitogen-activated protein kinase kinase kinase 5 (MAP3K5) induces binding to the 14-3-3 protein zeta/delta (YWHAZ) protein. This interaction inhibits the pro-apoptotic activity of Mitogen-activated protein kinase kinase kinase 5 (MAP3K5). | ||
| RAF1_HUMAN | 256 | 261 | Binary | Physicochemical compatibility | Phosphorylation of S257 in the 14-3-3-binding motif of RAF proto-oncogene serine/threonine-protein kinase (RAF1) abolishes binding of the motif, phosphorylated at S259, to 14-3-3 protein zeta/delta (YWHAZ). | ||
| YAP1_MOUSE | 109 | 114 | Binary | Physicochemical compatibility | Phosphorylation of S112 in the 14-3-3 binding motif of Yorkie homolog (Yap1) induces binding to the 14-3-3 protein epsilon (Ywhae) protein. 14-3-3 retains phosphorylated YAP in the cytosol, negatively regulating its function. | ||
| ATX1_HUMAN | 772 | 777 | Specificity | Altered binding specificity | Phosphorylation of S775 switches binding specificity of Ataxin-1 (ATXN1) from the splicing factor Splicing factor U2AF 65 kDa subunit (U2AF2) to 14-3-3 proteins (e.g. 14-3-3 protein zeta/delta (YWHAZ)). While association with the spliceosome protects ATXN1 from self-association, its phosphorylation-dependent recruitment to 14-3-3 proteins (e.g. YWHAZ) might result in aggregation. | ||
| NED4L_HUMAN | 465 | 470 | Specificity | Domain hiding | Phosphorylation of Isoform Nedd4-2a of E3 ubiquitin-protein ligase NEDD4-like (NEDD4L) by Serine/threonine-protein kinase Sgk1 (SGK1) induces binding to 14-3-3 protein eta (YWHAH). This inhibits (whether allosterically or sterically is not known) interactions of NEDD4L via its WW domains with the PY motif in Amiloride-sensitive sodium channel subunit gamma (SCNN1G) (ENaC). As a result, ENaC does not get degraded and ENaC-mediated Na+ currents increase. | ||
| MEI2_SCHPO | 435 523 | 440 529 | Specificity | Domain hiding | Binding of meiRNA meiotic non-coding RNA (meiRNA) to the RRM domains of Meiosis protein mei2 (mei2) is essential for promotion of premeiotic DNA synthesis and meiosis I and is blocked by Pat1-mediated phosphorylation-induced binding of the 14-3-3 protein DNA damage checkpoint protein rad24 (rad24) to 2 14-3-3 binding motifs in mei2 | ||
| RAF1_HUMAN | 256 | 261 | Avidity‑sensing | Phosphorylation of two 14-3-3-binding motifs in RAF proto-oncogene serine/threonine-protein kinase (RAF1) in response to growth factors induces high-avidity binding to dimeric 14-3-3 protein zeta/delta (YWHAZ), with pS621 being the high-affinity interaction site. This interaction locks RAF proto-oncogene serine/threonine-protein kinase (RAF1) in an inhibited conformation. | |||
| RAF1_HUMAN | 618 | 623 | Avidity‑sensing | Phosphorylation of two 14-3-3-binding motifs in RAF proto-oncogene serine/threonine-protein kinase (RAF1) in response to growth factors induces high-avidity binding to dimeric 14-3-3 protein zeta/delta (YWHAZ), with pS621 being the high-affinity interaction site. This interaction locks RAF proto-oncogene serine/threonine-protein kinase (RAF1) in an inhibited conformation. | |||
| MEI2_SCHPO | 435 | 440 | Avidity‑sensing | Phosphorylation of two 14-3-3-binding motifs in Meiosis protein mei2 (mei2) by Negative regulator of sexual conjugation and meiosis (ran1) induces high-avidity binding to dimeric DNA damage checkpoint protein rad24 (rad24), with pT527 being the high-affinity interaction site. | |||
| WWTR1_HUMAN | 86 | 91 | Binary | Physicochemical compatibility | Phosphorylation of S89 in the 14-3-3-binding motif of WW domain-containing transcription regulator protein 1 (WWTR1) induces binding to 14-3-3 protein epsilon (YWHAE), retaining phosphorylated WWTR1 in the cytosol, negatively regulating its function. | ||
| MDM4_HUMAN | 364 | 369 | Avidity‑sensing | Optimal binding of 14-3-3 dimer to Hdmx in response to DNA damage requires phosphorylation of two 14-3-3-binding motifs by Chk2 kinase. Binding of 14-3-3 dimer is involved in inactivation of Hdmx, a negative regulator of p53, in response to DNA damage. | |||
| FOXO4_HUMAN | 29 | 34 | Avidity‑sensing | Phosphorylation of two 14-3-3-binding motifs in Foxo4 by PKB induces binding of 14-3-3 dimer. In the nucleus, this blocks binding to DNA, while in the cytoplasm it blocks reimport of Foxo4 into the nucleus by blocking its Nuclear Localisation Signal (NLS). Since binding of 14-3-3 to a single motif occurs with an affinity similar to the affinity of Foxo4 for DNA, multivalent binding of 14-3-3 dimer is required for efficient inhibition of DNA binding. | |||
| BAD_MOUSE | 133 | 138 | Binary | Physicochemical compatibility | Phosphorylation of S136 in Bcl2 antagonist of cell death (Bad) by RAC-alpha serine/threonine-protein kinase (Akt1) in response to survival and growth signals such as Interleukin-3 (Il3) induces binding to 14-3-3 protein theta (Ywhaq). Binding of 14-3-3 protein theta (Ywhaq) results in dissociation of Bcl2 antagonist of cell death (Bad) from Bcl-2-like protein 1 (Bcl2l1), and thereby inhibits the pro-apoptotic activity of Bcl2 antagonist of cell death (Bad) by allowing liberated Bcl-2-like protein 1 (Bcl2l1) to exert its anti-apoptotic effect on pro-apoptotic proteins like Apoptosis regulator BAX (Bax). | ||
LIG_14-3-3_2 - Longer mode 2 interacting phospho-motif for 14-3-3 proteins with key conservation RxxxS#p. | |||||||
| PTPN3_MOUSE | 355 | 361 | Binary | Physicochemical compatibility | Phosphorylation of S359 in the 14-3-3-binding motif of Tyrosine-protein phosphatase non-receptor type 3 (Ptpn3) induces binding to the 14-3-3 protein beta/alpha (Ywhab) protein. | ||
| NAC1_HUMAN | 388 | 394 | Binary | Physicochemical compatibility | Phosphorylation of S392 in the 14-3-3-binding motif of Sodium/calcium exchanger 1 (SLC8A1) induces binding to the 14-3-3 protein epsilon (YWHAE) protein. This interaction inhibits the activity of Sodium/calcium exchanger 1 (SLC8A1). | ||
| FOXO4_HUMAN | 193 | 199 | Binary | Physicochemical compatibility | Phosphorylation of S197 by in the 14-3-3-binding motif of Forkhead box protein O4 (FOXO4) induces binding to the 14-3-3 protein zeta/delta (YWHAZ) protein. | ||
| TF65_HUMAN | 41 | 47 | Binary | Physicochemical compatibility | Phosphorylation of S45 by in the 14-3-3-binding motif of Transcription factor p65 (RELA) induces binding to the 14-3-3 protein eta (YWHAH) protein. | ||
| PDE3A_HUMAN | 424 | 430 | Binary | Physicochemical compatibility | Phosphorylation of S428 by in the 14-3-3-binding motif of cGMP-inhibited 3',5'-cyclic phosphodiesterase A (PDE3A) induces binding to the 14-3-3 protein zeta/delta (YWHAZ) protein. | ||
| TESK1_RAT | 435 | 441 | Binary | Physicochemical compatibility | Phosphorylation of S439 in the 14-3-3-binding motif of Dual specificity testis-specific protein kinase 1 (Tesk1) induces binding to the 14-3-3 protein beta/alpha (Ywhab) protein. This interaction inhibits the kinase activity of Dual specificity testis-specific protein kinase 1 (Tesk1). | ||
| MEI2_SCHPO | 435 523 | 440 529 | Specificity | Domain hiding | Binding of meiRNA meiotic non-coding RNA (meiRNA) to the RRM domains of Meiosis protein mei2 (mei2) is essential for promotion of premeiotic DNA synthesis and meiosis I and is blocked by Pat1-mediated phosphorylation-induced binding of the 14-3-3 protein DNA damage checkpoint protein rad24 (rad24) to 2 14-3-3 binding motifs in mei2 | ||
| MEI2_SCHPO | 523 | 529 | Avidity‑sensing | Phosphorylation of two 14-3-3-binding motifs in Meiosis protein mei2 (mei2) by Negative regulator of sexual conjugation and meiosis (ran1) induces high-avidity binding to dimeric DNA damage checkpoint protein rad24 (rad24), with pT527 being the high-affinity interaction site. | |||
| FOXO4_HUMAN | 193 | 199 | Avidity‑sensing | Phosphorylation of two 14-3-3-binding motifs in Foxo4 by PKB induces binding of 14-3-3 dimer. In the nucleus, this blocks binding to DNA, while in the cytoplasm it blocks reimport of Foxo4 into the nucleus by blocking its Nuclear Localisation Signal (NLS). Since binding of 14-3-3 to a single motif occurs with an affinity similar to the affinity of Foxo4 for DNA, multivalent binding of 14-3-3 dimer is required for efficient inhibition of DNA binding. | |||
LIG_14-3-3_3 - Consensus derived from reported natural interactors which do not match the Mode 1 and Mode 2 ligands. | |||||||
| MPIP3_HUMAN | 213 | 218 | Binary | Physicochemical compatibility | Phosphorylation of S216 in a 14-3-3-binding motif of M-phase inducer phosphatase 3 (CDC25C) by Serine/threonine-protein kinase Chk1 (CHEK1) induces binding to 14-3-3 protein beta/alpha (YWHAB), which negatively regulates M-phase inducer phosphatase 3 (CDC25C). | ||
| RIM15_YEAST | 1072 | 1077 | Binary | Physicochemical compatibility | Phosphorylation of T1075 in the 14-3-3-binding motif of Serine/threonine-protein kinase RIM15 (RIM15) induces binding to the Protein BMH2 (BMH2) protein. This interaction sequesters Serine/threonine-protein kinase RIM15 (RIM15) in the cytoplasm, thereby inhibiting its function. | ||
| HDAC4_HUMAN | 629 | 634 | Binary | Physicochemical compatibility | Phosphorylation of S632 in the 14-3-3-binding motif of Histone deacetylase 4 (HDAC4) induces binding to the 14-3-3 protein beta/alpha (YWHAB) protein. This interaction sequesters Histone deacetylase 4 (HDAC4) in the cytoplasm, thereby inhibiting their transcription repression activity. | ||
| MPIP2_HUMAN | 320 | 325 | Binary | Physicochemical compatibility | Phosphorylation of S321 in the 14-3-3-binding motif of M-phase inducer phosphatase 2 (CDC25B) by Cyclin-dependent kinase 1 (CDK1) during mitosis abolishes binding of the motif, phosphorylated at S323, to 14-3-3 protein beta/alpha (YWHAB), thereby maintaining active Cdc25B. | ||
| ITB2_HUMAN | 755 | 760 | Specificity | Altered binding specificity | Phosphorylation of T758 in Integrin beta-2 (ITGB2) switches the specificity of ITGB2 from Filamin-A (FLNA) to 14-3-3 proteins (e.g. 14-3-3 protein zeta/delta (YWHAZ)). | ||
| ADA22_HUMAN | 831 854 | 836 859 | Specificity | Motif hiding | Phosphorylation-induced binding of dimeric 14-3-3 protein beta/alpha (YWHAB) to Disintegrin and metalloproteinase domain-containing protein 22 (ADAM22) blocks ER retention motifs in Disintegrin and metalloproteinase domain-containing protein 22 (ADAM22) and regulates transport of this protein to the membrane. | ||
| HG2A_HUMAN | 5 | 10 | Specificity | Motif hiding | The basic ER retention motif of HLA class II histocompatibility antigen gamma chain (CD74) is blocked from binding to Coatomer subunit beta (COPB1) by phosphorylation-induced binding of 14-3-3 protein beta/alpha (YWHAB), regulating its release from the ER and trafficking to the plasma membrane. | ||
| KPCE_HUMAN | 343 | 348 | Avidity‑sensing | Phosphorylation of two 14-3-3-binding motifs in Protein kinase C epsilon type (PRKCE) induces high-avidity binding to dimeric 14-3-3 protein zeta/delta (YWHAZ). | |||
| KPCE_HUMAN | 365 | 370 | Avidity‑sensing | Phosphorylation of two 14-3-3-binding motifs in Protein kinase C epsilon type (PRKCE) induces high-avidity binding to dimeric 14-3-3 protein zeta/delta (YWHAZ). | |||
| FOXO3_HUMAN | 250 | 255 | Avidity‑sensing | Phosphorylation of two 14-3-3-binding motifs in Forkhead box protein O3 (FOXO3) by RAC-alpha serine/threonine-protein kinase (AKT1) induces high-avidity binding to dimeric 14-3-3 protein beta/alpha (YWHAB). This interaction results in cytoplasmic retention and inactivation of Forkhead box protein O3 (FOXO3). | |||
| FOXO3_HUMAN | 29 | 34 | Avidity‑sensing | Phosphorylation of two 14-3-3-binding motifs in Forkhead box protein O3 (FOXO3) by RAC-alpha serine/threonine-protein kinase (AKT1) induces high-avidity binding to dimeric 14-3-3 protein beta/alpha (YWHAB). This interaction results in cytoplasmic retention and inactivation of Forkhead box protein O3 (FOXO3). | |||
| PTN3_HUMAN | 356 | 361 | Avidity‑sensing | Phosphorylation of two 14-3-3-binding motifs in Tyrosine-protein phosphatase non-receptor type 3 (PTPN3) induces high-avidity binding to dimeric 14-3-3 protein beta/alpha (YWHAB). | |||
| PTN3_HUMAN | 832 | 837 | Avidity‑sensing | Phosphorylation of two 14-3-3-binding motifs in Tyrosine-protein phosphatase non-receptor type 3 (PTPN3) induces high-avidity binding to dimeric 14-3-3 protein beta/alpha (YWHAB). | |||
| KSR1_MOUSE | 294 | 299 | Avidity‑sensing | Phosphorylation of two 14-3-3-binding motifs in Kinase suppressor of Ras 1 (Ksr1) by Q03141 induces high-avidity binding to dimeric 14-3-3 protein beta/alpha (Ywhab). This interaction prevents Kinase suppressor of Ras 1 (Ksr1) to localise to the membrane where it is involved in activation of MAP kinases by Q99N57 in response to growth factors. | |||
| KSR1_MOUSE | 389 | 394 | Avidity‑sensing | Phosphorylation of two 14-3-3-binding motifs in Kinase suppressor of Ras 1 (Ksr1) by Q03141 induces high-avidity binding to dimeric 14-3-3 protein beta/alpha (Ywhab). This interaction prevents Kinase suppressor of Ras 1 (Ksr1) to localise to the membrane where it is involved in activation of MAP kinases by Q99N57 in response to growth factors. | |||
| SLOB_DROME | 51 | 56 | Avidity‑sensing | Phosphorylation of two 14-3-3-binding motifs in Slowpoke-binding protein (Slob) by Calcium/calmodulin-dependent protein kinase type II alpha chain (CaMKII) induces high-avidity binding to dimeric 14-3-3 protein zeta (14-3-3zeta). This interaction recruits 14-3-3 protein zeta (14-3-3zeta) to Calcium-activated potassium channel slowpoke (slo) in the presynapse of neuromuscular junctions. | |||
| SLOB_DROME | 76 | 81 | Avidity‑sensing | Phosphorylation of two 14-3-3-binding motifs in Slowpoke-binding protein (Slob) by Calcium/calmodulin-dependent protein kinase type II alpha chain (CaMKII) induces high-avidity binding to dimeric 14-3-3 protein zeta (14-3-3zeta). This interaction recruits 14-3-3 protein zeta (14-3-3zeta) to Calcium-activated potassium channel slowpoke (slo) in the presynapse of neuromuscular junctions. | |||
| IRS1_HUMAN | 371 | 376 | Avidity‑sensing | Phosphorylation of two 14-3-3-binding motifs in Insulin receptor substrate 1 (IRS1) induces high-avidity binding to dimeric 14-3-3 protein epsilon (YWHAE). | |||
| IRS1_HUMAN | 638 | 643 | Avidity‑sensing | Phosphorylation of two 14-3-3-binding motifs in Insulin receptor substrate 1 (IRS1) induces high-avidity binding to dimeric 14-3-3 protein epsilon (YWHAE). | |||
| SLOB_DROME | 76 | 81 | Binary | Pre‑translational | Alternative splicing removes the 14-3-3-binding motif of Slowpoke-binding protein (Slob), abrogating binding to 14-3-3 family. Another 14-3-3 motif exists in this protein (50-RSNS-54) that is not altered by Alternative splicing. The removal of this motif therefore decreases the avidity of the interaction with 14-3-3 proteins. | ||
| MDM4_HUMAN | 339 | 344 | Avidity‑sensing | Optimal binding of 14-3-3 dimer to Hdmx in response to DNA damage requires phosphorylation of two 14-3-3-binding motifs by Chk2 kinase. Binding of 14-3-3 dimer is involved in inactivation of Hdmx, a negative regulator of p53, in response to DNA damage. | |||
| CDN1B_HUMAN | 154 | 159 | Specificity | Motif hiding | Phosphorylation of a 14-3-3-binding motif in the NLS of Cyclin-dependent kinase inhibitor 1B (CDKN1B) by RAC-alpha serine/threonine-protein kinase (AKT1) induces binding of 14-3-3 protein gamma (YWHAG), which hides the NLS and prevents binding to Importin subunit alpha-1 (KPNA1), thereby mediating cytoplasmic retention of Cyclin-dependent kinase inhibitor 1B (CDKN1B). Binding of 14-3-3 dimer involves an additional C-terminal 14-3-3-binding motif (see switch details). | ||
| CDN1B_HUMAN | 154 | 159 | Avidity‑sensing | Phosphorylation of two 14-3-3-binding motifs in Cyclin-dependent kinase inhibitor 1B (CDKN1B) by RAC-alpha serine/threonine-protein kinase (AKT1) and ribosomal protein S6 kinases (Ribosomal protein S6 kinase alpha-1 (RPS6KA1), Ribosomal protein S6 kinase alpha-3 (RPS6KA3)) induces binding of 14-3-3 dimer. Binding of 14-3-3 results in cytoplasmic localisation of Cyclin-dependent kinase inhibitor 1B (CDKN1B) (see switch details), thereby alleviating Cyclin-dependent kinase inhibitor 1B (CDKN1B)-mediated inhibition of cyclin-dependent kinases and cell cycle progression. | |||
| CDN1B_HUMAN | 193 | 198 | Avidity‑sensing | Phosphorylation of two 14-3-3-binding motifs in Cyclin-dependent kinase inhibitor 1B (CDKN1B) by RAC-alpha serine/threonine-protein kinase (AKT1) and ribosomal protein S6 kinases (Ribosomal protein S6 kinase alpha-1 (RPS6KA1), Ribosomal protein S6 kinase alpha-3 (RPS6KA3)) induces binding of 14-3-3 dimer. Binding of 14-3-3 results in cytoplasmic localisation of Cyclin-dependent kinase inhibitor 1B (CDKN1B) (see switch details), thereby alleviating Cyclin-dependent kinase inhibitor 1B (CDKN1B)-mediated inhibition of cyclin-dependent kinases and cell cycle progression. | |||
LIG_14-3-3_4 - | |||||||
| GPR15_HUMAN | 356 | 360 | Specificity | Motif hiding | Phosphorylation-induced binding of 14-3-3 protein beta/alpha (YWHAB) promotes cell surface expression of G-protein coupled receptor 15 (GPR15) by releasing the receptor from the ER retrieval/retention pathway that is mediated by the interaction of its ER retention motif with Coatomer subunit beta (COPB1). | ||
| HAP1_RAT | 594 | 598 | Binary | Pre‑translational | Alternative splicing removes the 14-3-3-binding motif of Isoform Short of Huntingtin-associated protein 1 (Hap1), abrogating binding to 14-3-3 protein zeta/delta (Ywhaz). The association of HAP1A (Isoform Short of Huntingtin-associated protein 1 (Hap1)) with 14-3-3 protein zeta/delta (Ywhaz) inhibits binding of the splice variant to members of the kinesin light chain family and diminishes trafficking of Hap1 to neural processes and neurite tips. The result is a decrease in neurite outgrowth. | ||
LIG_ALG2 - | |||||||
| PDC6I_HUMAN | 801 | 810 | Binary | Allostery | Binding of calcium(2+) to Programmed cell death protein 6 (PDCD6) opens a hydrophobic pocket on Programmed cell death protein 6 (PDCD6) that is required for binding of Programmed cell death 6-interacting protein (PDCD6IP). | ||
LIG_AP2alpha_2 - DPF/W motif binds alpha and beta subunits of AP2 adaptor complex. | |||||||
| SYNJ1_HUMAN | 1323 | 1325 | Binary | Pre‑translational | Alternative splicing removes the AP2alpha-binding motif of Synaptojanin-1 (SYNJ1), abrogating binding to AP-2 complex subunit alpha-2 (AP2A2). Isoform Synaptojanin-170 of Synaptojanin-1 (SYNJ1) is associated with clathrin-mediated endocytosis as a negative regulator of coat-membrane interaction. This isoform is virtually absent from mature neuronal synapses, where clathrin-mediated endocytosis plays a critical role and where Isoform Synaptojanin-145 of Synaptojanin-1 (SYNJ1) is by far the major synaptojanin isoform. Isoform Synaptojanin-145 of Synaptojanin-1 (SYNJ1) may be recruited early to clathrin-coated pits of synapses, either indirectly by adaptors that bind clathrin and AP-2, such as Amphiphysin (AMPH), or by interactions of endophilin family dimers with synaptic vesicle cargo, such as the vesicular glutamate transport. | ||
| SYNJ1_HUMAN | 1555 | 1557 | Binary | Pre‑translational | Alternative splicing removes the AP2alpha-binding motif of Synaptojanin-1 (SYNJ1), abrogating binding to AP-2 complex subunit alpha-2 (AP2A2). Isoform Synaptojanin-170 of Synaptojanin-1 (SYNJ1) is associated with clathrin-mediated endocytosis as a negative regulator of coat-membrane interaction. This isoform is virtually absent from mature neuronal synapses, where clathrin-mediated endocytosis plays a critical role and where Isoform Synaptojanin-145 of Synaptojanin-1 (SYNJ1) is by far the major synaptojanin isoform. Isoform Synaptojanin-145 of Synaptojanin-1 (SYNJ1) may be recruited early to clathrin-coated pits of synapses, either indirectly by adaptors that bind clathrin and AP-2, such as Amphiphysin (AMPH), or by interactions of endophilin family dimers with synaptic vesicle cargo, such as the vesicular glutamate transport. | ||
| DAB2_HUMAN | 293 | 295 | Binary | Pre‑translational | Alternative splicing removes the AP2alpha-binding motifs of Disabled homolog 2 (DAB2), abrogating binding to AP-2 complex subunit alpha-2 (AP2A2). The p67 splice variant of Dab1 (also known as Isoform 2 of Disabled homolog 2 (DAB2)) does not localise to vesicles as it fails to bind the AP-2 complex. | ||
| DAB2_HUMAN | 298 | 300 | Binary | Pre‑translational | Alternative splicing removes the AP2alpha-binding motifs of Disabled homolog 2 (DAB2), abrogating binding to AP-2 complex subunit alpha-2 (AP2A2). The p67 splice variant of Dab1 (also known as Isoform 2 of Disabled homolog 2 (DAB2)) does not localise to vesicles as it fails to bind the AP-2 complex. | ||
LIG_Actin_DMD - | |||||||
| DMD_HUMAN | 5 | 10 | Binary | Pre‑translational | Alternative splicing removes the actin-binding motif of Isoform Dp71 of Dystrophin (DMD), abrogating binding to Actin, alpha skeletal muscle (ACTA1). The presence of the actin-binding motif in Isoform Dp71 of Dystrophin (DMD) may allow it to participate in the clustering of sodium channels by anchoring the syntrophin/channel complex to the actin cytoskeleton. | ||
LIG_Actin_RPEL_3 - RPEL motif, present in proteins in several repeats, mediates binding to the hydrophobic cleft created by subdomains 1 and 3 of G-actin. | |||||||
| MKL1_MOUSE | 17 61 105 | 36 80 124 | Specificity | Motif hiding | Hiding of the NLS of MKL/myocardin-like protein 1 (Mkl1) by binding of G-actin to the RPEL motifs of MKL/myocardin-like protein 1 (Mkl1) prevents translocation of this transcription factor to the nucleus. | ||
| MYCD_MOUSE | 20 | 39 | Binary | Pre‑translational | Alternative promoter usage removes the RPEL-binding motif of Myocardin (Myocd), abrogating binding to Actin, alpha skeletal muscle (Acta1). 3 RPEL motifs are found in Myocd. The shortened form lacks 2 RPEL motifs but no definitive comparison of binding to actin has been undertaken between isoforms. | ||
| MYCD_MOUSE | 64 | 83 | Binary | Pre‑translational | Alternative promoter usage removes the RPEL-binding motif of Myocardin (Myocd), abrogating binding to Actin, alpha skeletal muscle (Acta1). 3 RPEL motifs are found in Myocd. The shortened form lacks 2 RPEL motifs but no definitive comparison of binding to actin has been undertaken between isoforms. | ||
LIG_BIR_III_2 - These IBMs are found at the N-terminal regions of caspase subunits where they mediate the inhibition of activated caspases by binding to conserved surface grooves on type III BIR domains of Inhibitor of Apoptosis Proteins (IAPs). | |||||||
| CASP9_HUMAN | 315 | 319 | Binary | Physicochemical compatibility | Binding of the BIR domain-binding motif of Caspase-9 (CASP9) to the BIR domains of Baculoviral IAP repeat-containing protein 4 (XIAP) requires cleavage of Caspase-9 (CASP9) at D315, since this results in a functional neo N-terminal motif. BIR domains are found in Inhibitor of Apoptosis Proteins (IAPs) that suppress the activity of activated caspases, either by directly inhibiting caspase catalytic activity, or by targeting caspases for degradation by ubiquitin modification. | ||
| CASP9_HUMAN | 315 | 319 | Binary | Physicochemical compatibility | Binding of the BIR domain-binding motif of Caspase-9 (CASP9) to the BIR domains of Baculoviral IAP repeat-containing protein 2 (BIRC2) requires cleavage of Caspase-9 (CASP9) at D315, since this results in a functional neo N-terminal motif. BIR domains are found in Inhibitor of Apoptosis Proteins (IAPs) that suppress the activity of activated caspases, either by directly inhibiting caspase catalytic activity, or by targeting caspases for degradation by ubiquitin modification. | ||
| CASP7_HUMAN | 23 | 27 | Binary | Physicochemical compatibility | Binding of the BIR domain-binding motif of Caspase-7 (CASP7) to the BIR domains of Baculoviral IAP repeat-containing protein 2 (BIRC2) requires cleavage of Caspase-7 (CASP7) at D23, since this results in a functional neo N-terminal motif. BIR domains are found in Inhibitor of Apoptosis Proteins (IAPs) that suppress the activity of activated caspases, either by directly inhibiting caspase catalytic activity, or by targeting caspases for degradation by ubiquitin modification. | ||
| CASP7_HUMAN | 23 | 27 | Binary | Physicochemical compatibility | Binding of the BIR domain-binding motif of Caspase-7 (CASP7) to the BIR domains of Baculoviral IAP repeat-containing protein 2 (BIRC2) requires cleavage of Caspase-7 (CASP7) at D23, since this results in a functional neo N-terminal motif. BIR domains are found in Inhibitor of Apoptosis Proteins (IAPs) that suppress the activity of activated caspases, either by directly inhibiting caspase catalytic activity, or by targeting caspases for degradation by ubiquitin modification. | ||
| CASP7_HUMAN | 23 | 27 | Binary | Physicochemical compatibility | Binding of the BIR domain-binding motif of Caspase-7 (CASP7) to the BIR domains of Baculoviral IAP repeat-containing protein 2 (BIRC2) requires cleavage of Caspase-7 (CASP7) at D23, since this results in a functional neo N-terminal motif. BIR domains are found in Inhibitor of Apoptosis Proteins (IAPs) that suppress the activity of activated caspases, either by directly inhibiting caspase catalytic activity, or by targeting caspases for degradation by ubiquitin modification. | ||
LIG_BIR_III_4 - These IBMs are found in the N-terminal regions of arthropodal caspase subunits where they mediate the inhibition of activated caspases by binding to conserved surface grooves on type III BIR domains of Inhibitor of Apoptosis Proteins (IAPs). | |||||||
| CASP1_DROME | 33 | 37 | Binary | Physicochemical compatibility | Binding of the BIR domain-binding motif of Caspase-1 (Dcp-1) to the BIR domains of Apoptosis 1 inhibitor (th) requires cleavage of Caspase-1 (Dcp-1) at D33, since this results in a functional neo N-terminal motif. BIR domains are found in Inhibitor of Apoptosis Proteins (IAPs) that suppress the activity of activated caspases, either by directly inhibiting caspase catalytic activity, or by targeting caspases for degradation by ubiquitin modification. | ||
| ICE_DROME | 28 | 32 | Binary | Physicochemical compatibility | Binding of the BIR domain-binding motif of Caspase (Ice) to the BIR domains of Apoptosis 1 inhibitor (th) requires cleavage of Caspase (Ice) at D28, since this results in a functional neo N-terminal motif. BIR domains are found in Inhibitor of Apoptosis Proteins (IAPs) that suppress the activity of activated caspases, either by directly inhibiting caspase catalytic activity, or by targeting caspases for degradation by ubiquitin modification. | ||
LIG_BIR_internal - | |||||||
| DBLOH_HUMAN | 56 | 59 | Binary | Pre‑translational | Alternative splicing removes the BIR-binding motif of Diablo homolog, mitochondrial (DIABLO), abrogating binding to Baculoviral IAP repeat-containing protein 4 (XIAP). Isoform SMAC3 of Diablo homolog, mitochondrial (DIABLO) is localised to mitochondria via its mitochondrial localisation signal (MLS). Upon entry in mitochondria the MLS is cleaved and Isoform SMAC3 of Diablo homolog, mitochondrial (DIABLO) is found localised with cytochrome-c. During apoptosis, Isoform SMAC3 of Diablo homolog, mitochondrial (DIABLO) binds to the second/third BIR domain of Baculoviral IAP repeat-containing protein 4 (XIAP). This interaction disrupts binding of XIAP to processed Caspase-9 (CASP9) and promotes Caspase-3 (CASP3) activation. Isoform SMAC3 of Diablo homolog, mitochondrial (DIABLO) also promotes ubiquitination of XIAP and subsequent degradation. Isoform 1 of Diablo homolog, mitochondrial (DIABLO) on the other hand did not cause degradation of XIAP. | ||
| DBLOH_HUMAN | 56 | 59 | Binary | Pre‑translational | Alternative splicing removes the BIR-binding motif of Diablo homolog, mitochondrial (DIABLO), abrogating binding to Baculoviral IAP repeat-containing protein 4 (XIAP). Isoform SMAC3 of Diablo homolog, mitochondrial (DIABLO) is localised to mitochondria via its mitochondrial localisation signal (MLS). Upon entry in mitochondria the MLS is cleaved and Isoform SMAC3 of Diablo homolog, mitochondrial (DIABLO) is found localised with cytochrome-c. During apoptosis, Isoform SMAC3 of Diablo homolog, mitochondrial (DIABLO) binds to the second/third BIR domain of Baculoviral IAP repeat-containing protein 4 (XIAP). This interaction disrupts binding of XIAP to processed Caspase-9 (CASP9) and promotes Caspase-3 (CASP3) activation. Isoform SMAC3 of Diablo homolog, mitochondrial (DIABLO) also promotes ubiquitination of XIAP and subsequent degradation. Isoform 1 of Diablo homolog, mitochondrial (DIABLO) on the other hand did not cause degradation of XIAP. | ||
LIG_BRCT_BRCA1_1 - Phosphopeptide motif which directly interacts with the BRCT (carboxy-terminal) domain of the Breast Cancer Gene BRCA1 with low affinity | |||||||
| ACACA_HUMAN | 1262 | 1266 | Binary | Physicochemical compatibility | Phosphorylation of S1263 in the BRCT-binding motif of Acetyl-CoA carboxylase 1 (ACACA) induces binding to the Breast cancer type 1 susceptibility protein (BRCA1) protein. | ||
| F175A_HUMAN | 405 | 409 | Binary | Physicochemical compatibility | Phosphorylation of S406 in the BRCT-binding motif of BRCA1-A complex subunit Abraxas (FAM175A) induces binding to the Breast cancer type 1 susceptibility protein (BRCA1) protein. | ||
| ATRIP_HUMAN | 238 | 242 | Binary | Physicochemical compatibility | Phosphorylation of S239 in the BRCT-binding motif of ATR-interacting protein (ATRIP) induces binding to the Breast cancer type 1 susceptibility protein (BRCA1) protein. | ||
| COM1_HUMAN | 326 | 330 | Binary | Physicochemical compatibility | Phosphorylation of S327 in the BRCT-binding motif of DNA endonuclease RBBP8 (RBBP8) induces binding to the Breast cancer type 1 susceptibility protein (BRCA1) protein. | ||
| FANCJ_HUMAN | 989 | 993 | Binary | Physicochemical compatibility | Phosphorylation of S990 in the BRCT-binding motif of Fanconi anemia group J protein (BRIP1) induces binding to the Breast cancer type 1 susceptibility protein (BRCA1) protein. | ||
LIG_BRCT_BRCA1_2 - Phosphopeptide motif which directly interacts with the BRCT (carboxy-terminal) domain of the Breast Cancer Gene BRCA1 with high affinity. | |||||||
| FANCJ_HUMAN | 989 | 995 | Binary | Physicochemical compatibility | Phosphorylation of S990 in the BRCT-binding motif of Fanconi anemia group J protein (BRIP1) induces binding to the Breast cancer type 1 susceptibility protein (BRCA1) protein. | ||
LIG_BRCT_MDC1_1 - Phosphopeptide motif which is specifically recognized by the BRCT (Carboxy-terminal) repeats of MDC1 | |||||||
| H2AX_HUMAN | 139 | 143 | Binary | Physicochemical compatibility | Phosphorylation of S140 in the BRCT-binding motif of Histone H2A.x (H2AFX) induces binding to the Mediator of DNA damage checkpoint protein 1 (MDC1) protein. | ||
LIG_BROMO - | |||||||
| SUMO2_HUMAN | 33 | 33 | Specificity | Altered binding specificity | Acetylation of K33 in the SUMO2 inhibits binding to the Death domain-associated protein 6 (DAXX) protein see switch details. SUMO-modified forms of Protein PML (PML) are essential for the recruitment of Small ubiquitin-related modifier 2 (SUMO2) to PML nuclear bodies. The acetylated versions of SUMO1/2 failed to trigger recruitment of Small ubiquitin-related modifier 2 (SUMO2) into the nuclear bodies. An additional interaction is also possible upon acetylation with the Bromodomain of Histone acetyltransferase p300 (EP300) shown to bind the acetylated version of SUMO2. This does not occur with acetylated SUMO1. Acetylation is countered by Histone deacetylase family, HD type 1 subfamily. | ||
LIG_CORNRBOX - The corepressor nuclear receptor box motif confers binding to nuclear receptors. | |||||||
| NCOR1_HUMAN | 2051 | 2059 | Binary | Allostery | Binding of the all-trans-retinoic acid ligand to the nuclear Retinoic acid receptor alpha (RARA) makes the binding site for the CORNRBOX motif of Nuclear receptor corepressor 1 (NCOR1) inaccessible. | ||
| NCOR1_HUMAN | 2263 | 2271 | Binary | Allostery | Binding of the all-trans-retinoic acid ligand to the nuclear Retinoic acid receptor alpha (RARA) makes the binding site for the CORNRBOX motif of Nuclear receptor corepressor 1 (NCOR1) inaccessible. | ||
| NCOR2_HUMAN | 2143 | 2151 | Binary | Allostery | Binding of the leukotriene D4 ligand to the nuclear Peroxisome proliferator-activated receptor alpha (PPARA) makes the binding site for the CORNRBOX motif of Nuclear receptor corepressor 2 (NCOR2) inaccessible. | ||
| NCOR2_HUMAN | 2350 | 2358 | Binary | Allostery | Binding of the leukotriene D4 ligand to the nuclear Peroxisome proliferator-activated receptor alpha (PPARA) makes the binding site for the CORNRBOX motif of Nuclear receptor corepressor 2 (NCOR2) inaccessible. | ||
LIG_Clathr_ClatBox_1 - Clathrin box motif found on cargo adaptor proteins, it interacts with the beta propeller structure located at the N-terminus of Clathrin heavy chain. | |||||||
| BIN1_HUMAN | 390 | 394 | Binary | Pre‑translational | Alternative splicing removes the Clathrin I-binding motif of Myc box-dependent-interacting protein 1 (BIN1), abrogating binding to Clathrin heavy chain 1 (CLTC). | ||
| AMPH_HUMAN | 351 | 355 | Binary | Physicochemical compatibility | Phosphorylation of T350 adjacent to the clathrin-binding motif of Amphiphysin (AMPH) by CK2 subfamily inhibits binding to the Clathrin heavy chain 1 (CLTC). A second clathrin-binding motif in Amphiphysin (AMPH) is regulated in a similar manner (see switch details). Both these motifs cooperate in avidity-based binding to Clathrin heavy chain 1 (CLTC) (see switch details). | ||
| AMPH_HUMAN | 351 | 355 | Avidity‑sensing | Amphiphysin 1 contains two distinct motifs that bind to distinct sites on N-terminal beta-propeller domain of clathrin, resulting in increased binding strength to free domain. This, in combination with binding of its BAR domain to curved membranes, results in localisation of amphipysin to the periphery of the assembling clathrin lattice. The two clathrin-binding motifs are regulated by phosphorylation of adjacent modification sites (see switch details and switch details). | |||
LIG_Clathr_ClatBox_2 - Clathrin box motif found on cargo adaptor proteins, it mediates binding to the N-terminal beta propeller of clathrin heavy chain. Also called W box, it is found in the central region of Amphiphysins where it coexists with a classical clathrin box. | |||||||
| BIN1_HUMAN | 415 | 420 | Binary | Pre‑translational | Alternative splicing removes the Clathrin II-binding motif of Myc box-dependent-interacting protein 1 (BIN1), abrogating binding to Clathrin heavy chain 1 (CLTC). | ||
| AMPH_HUMAN | 380 | 385 | Binary | Physicochemical compatibility | Phosphorylation of T387 adjacent to the clathrin-binding motif of Amphiphysin (AMPH) by CK2 subfamily inhibits binding to the Clathrin heavy chain 1 (CLTC). A second clathrin-binding motif in Amphiphysin (AMPH) is regulated in a similar manner (see switch details). Both these motifs cooperate in avidity-based binding to Clathrin heavy chain 1 (CLTC) (see switch details). | ||
| AMPH_HUMAN | 380 | 385 | Avidity‑sensing | Amphiphysin 1 contains two distinct motifs that bind to distinct sites on N-terminal beta-propeller domain of clathrin, resulting in increased binding strength to free domain. This, in combination with binding of its BAR domain to curved membranes, results in localisation of amphipysin to the periphery of the assembling clathrin lattice. The two clathrin-binding motifs are regulated by phosphorylation of adjacent modification sites (see switch details and switch details). | |||
LIG_Dynein_DLC8_1 - The [KR]xTQT motif interacts with the common target-accepting grooves of 8kDa Dynein Light Chain dimer. | |||||||
| B2L11_HUMAN | 50 | 56 | Binary | Physicochemical compatibility | Phosphorylation of T56 by Mitogen-activated protein kinase 8 (MAPK8) in the Dynein-binding motif of Isoform Bim(L) of Bcl-2-like protein 11 (BCL2L11) inhibits binding to Dynein light chain 1, cytoplasmic (DYNLL1). Most Bim in healthy cells is sequestered away bound to light chain dynein molecules. Cells exposed to environmental stress up-regulate c-Jun NH(2)-terminal kinase (JNK) that phosphorylates both Bim and Bmf, releasing them from motor complexes and promoting apoptosis. | ||
| B2L11_HUMAN | 110 | 116 | Binary | Pre‑translational | Alternative splicing removes the Dynein-binding motif of Bcl-2-like protein 11 (BCL2L11), abrogating binding to Dynein light chain 1, cytoplasmic (DYNLL1). Most BCL2L11 in healthy cells is sequestered away bound to DYNLL1 (the exception is Bim-S Isoform BCL2-like 11 transcript variant 9 of Bcl-2-like protein 11 (BCL2L11)). Cells exposed to environmental stress up-regulate c-Jun NH(2)-terminal kinases (JNK) that phosphorylate both BCL2L11 and BMF, releasing them from motor complexes and promoting apoptosis. | ||
LIG_Dynein_DLC8_2 - | |||||||
| MYO5A_HUMAN | 1286 | 1290 | Binary | Pre‑translational | Alternative splicing removes the dynein-binding motif of Unconventional myosin-Va (MYO5A), abrogating binding to Dynein light chain 2, cytoplasmic (DYNLL2). DYNLL2 (also known as DLC2) globally protects the tail domains of MYO5A against limited proteolysis. | ||
LIG_EABR_CEP55_1 - This proline-rich motif binds to the EABR domain of Cep55 and is involved in both cytokinesis of somatic cells and intercellular bridge formation in differentiating germ cells. | |||||||
| TEX14_MOUSE | 791 | 797 | Specificity | Domain hiding | The switch from cytokinesis to intracellular bridge formation in differentiating male germ cells is mediated by Testis-expressed protein 14 (Tex14). Binding of Tex14 to Centrosomal protein of 55 kDa (Cep55) prevents binding of ALIX (Programmed cell death 6-interacting protein (Pdcd6ip)) and Tumor susceptibility gene 101 protein (Tsg101) to Cep55, which is required for abscission at the end of cytokinesis. Tex14 uses the same site on Cep55 as ALIX (Pdcd6ip) and Tsg101. The strong interaction between Tex14 and Cep55 together with the avidity effect that results from interaction of MKLP1 with both Tex14 and Cep55 prevent recruitment of ALIX (Pdcd6ip) and Tsg101 for abscission. | ||
| TS101_MOUSE | 158 | 164 | Specificity | Domain hiding | The switch from cytokinesis to intracellular bridge formation in differentiating male germ cells is mediated by Testis-expressed protein 14 (Tex14). Binding of Tex14 to Centrosomal protein of 55 kDa (Cep55) prevents binding of ALIX (Programmed cell death 6-interacting protein (Pdcd6ip)) and Tumor susceptibility gene 101 protein (Tsg101) to Cep55, which is required for abscission at the end of cytokinesis. Tex14 uses the same site on Cep55 as ALIX (Pdcd6ip) and Tsg101. The strong interaction between Tex14 and Cep55 together with the avidity effect that results from interaction of MKLP1 with both Tex14 and Cep55 prevent recruitment of ALIX (Pdcd6ip) and Tsg101 for abscission. | ||
| TEX14_MOUSE | 791 | 797 | Specificity | Domain hiding | The switch from cytokinesis to intracellular bridge formation in differentiating male germ cells is mediated by Testis-expressed protein 14 (Tex14). Binding of Tex14 to Centrosomal protein of 55 kDa (Cep55) prevents binding of ALIX (Programmed cell death 6-interacting protein (Pdcd6ip)) and Tumor susceptibility gene 101 protein (Tsg101) to Cep55, which is required for abscission at the end of cytokinesis. Tex14 uses the same site on Cep55 as ALIX (Pdcd6ip) and Tsg101. The strong interaction between Tex14 and Cep55 together with the avidity effect that results from interaction of MKLP1 with both Tex14 and Cep55 prevent recruitment of ALIX (Pdcd6ip) and Tsg101 for abscission. | ||
| PDC6I_MOUSE | 801 | 807 | Specificity | Domain hiding | The switch from cytokinesis to intracellular bridge formation in differentiating male germ cells is mediated by Testis-expressed protein 14 (Tex14). Binding of Tex14 to Centrosomal protein of 55 kDa (Cep55) prevents binding of ALIX (Programmed cell death 6-interacting protein (Pdcd6ip)) and Tumor susceptibility gene 101 protein (Tsg101) to Cep55, which is required for abscission at the end of cytokinesis. Tex14 uses the same site on Cep55 as ALIX (Pdcd6ip) and Tsg101. The strong interaction between Tex14 and Cep55 together with the avidity effect that results from interaction of MKLP1 with both Tex14 and Cep55 prevent recruitment of ALIX (Pdcd6ip) and Tsg101 for abscission. | ||
LIG_EH1_1 - The engrailed homology domain 1 motif is found in homeodomain containing active repressors and other transcription families, and allows for the recruitment of Groucho/TLE corepressors. | |||||||
| GSC_HUMAN | 5 | 13 | Specificity | Competition | The Transducin-like enhancer protein 1 (TLE1) can recruit a wide range of transcriptional repressors via its WD domain, to which the WRPW motif of Transcription factor HES-1 (HES1) and the EH1 motif of Homeobox protein goosecoid (GSC) can bind using overlapping sites. | ||
LIG_EH_1 - NPF motif interacting with EH domains, usually during regulation of endocytotic processes | |||||||
| SYNJ1_HUMAN | 1393 | 1397 | Binary | Pre‑translational | Alternative splicing removes the EH-binding motif of Synaptojanin-1 (SYNJ1), abrogating binding to Epidermal growth factor receptor substrate 15 (EPS15). Isoform Synaptojanin-170 of Synaptojanin-1 (SYNJ1) is associated with clathrin-mediated endocytosis as a negative regulator of coat-membrane interaction. This isoform is virtually absent from mature neuronal synapses, where clathrin-mediated endocytosis plays a critical role and where Isoform Synaptojanin-145 of Synaptojanin-1 (SYNJ1) is by far the major synaptojanin isoform. Isoform Synaptojanin-145 of Synaptojanin-1 (SYNJ1) may be recruited early to clathrin-coated pits of synapses, either indirectly by adaptors that bind clathrin and AP-2, such as Amphiphysin (AMPH), or by interactions of endophilin family dimers with synaptic vesicle cargo, such as the vesicular glutamate transport. | ||
| SYNJ1_HUMAN | 1403 | 1407 | Binary | Pre‑translational | Alternative splicing removes the EH-binding motif of Synaptojanin-1 (SYNJ1), abrogating binding to Epidermal growth factor receptor substrate 15 (EPS15). Isoform Synaptojanin-170 of Synaptojanin-1 (SYNJ1) is associated with clathrin-mediated endocytosis as a negative regulator of coat-membrane interaction. This isoform is virtually absent from mature neuronal synapses, where clathrin-mediated endocytosis plays a critical role and where Isoform Synaptojanin-145 of Synaptojanin-1 (SYNJ1) is by far the major synaptojanin isoform. Isoform Synaptojanin-145 of Synaptojanin-1 (SYNJ1) may be recruited early to clathrin-coated pits of synapses, either indirectly by adaptors that bind clathrin and AP-2, such as Amphiphysin (AMPH), or by interactions of endophilin family dimers with synaptic vesicle cargo, such as the vesicular glutamate receptor transport. | ||
| SYNJ1_HUMAN | 1414 | 1418 | Binary | Pre‑translational | Alternative splicing removes the EH-binding motif of Synaptojanin-1 (SYNJ1), abrogating binding to Epidermal growth factor receptor substrate 15 (EPS15). Isoform Synaptojanin-170 of Synaptojanin-1 (SYNJ1) is associated with clathrin-mediated endocytosis as a negative regulator of coat-membrane interaction. This isoform is virtually absent from mature neuronal synapses, where clathrin-mediated endocytosis plays a critical role and where Isoform Synaptojanin-145 of Synaptojanin-1 (SYNJ1) is by far the major synaptojanin isoform. Isoform Synaptojanin-145 of Synaptojanin-1 (SYNJ1) may be recruited early to clathrin-coated pits of synapses, either indirectly by adaptors that bind clathrin and AP-2, such as Amphiphysin (AMPH), or by interactions of endophilin family dimers with synaptic vesicle cargo, such as the vesicular glutamate receptor transport. | ||
| SYNJ1_HUMAN | 1393 | 1397 | Binary | Pre‑translational | Alternative splicing removes the EH-binding motif of Synaptojanin-1 (SYNJ1), abrogating binding to Epidermal growth factor receptor substrate 15 (EPS15). Isoform Synaptojanin-170 of Synaptojanin-1 (SYNJ1) is associated with clathrin-mediated endocytosis as a negative regulator of coat-membrane interaction. This isoform is virtually absent from mature neuronal synapses, where clathrin-mediated endocytosis plays a critical role and where Isoform Synaptojanin-145 of Synaptojanin-1 (SYNJ1) is by far the major synaptojanin isoform. Isoform Synaptojanin-145 of Synaptojanin-1 (SYNJ1) may be recruited early to clathrin-coated pits of synapses, either indirectly by adaptors that bind clathrin and AP-2, such as Amphiphysin (AMPH), or by interactions of endophilin family dimers with synaptic vesicle cargo, such as the vesicular glutamate transport. | ||
| SYNJ1_HUMAN | 1403 | 1407 | Binary | Pre‑translational | Alternative splicing removes the EH-binding motif of Synaptojanin-1 (SYNJ1), abrogating binding to Epidermal growth factor receptor substrate 15 (EPS15). Isoform Synaptojanin-170 of Synaptojanin-1 (SYNJ1) is associated with clathrin-mediated endocytosis as a negative regulator of coat-membrane interaction. This isoform is virtually absent from mature neuronal synapses, where clathrin-mediated endocytosis plays a critical role and where Isoform Synaptojanin-145 of Synaptojanin-1 (SYNJ1) is by far the major synaptojanin isoform. Isoform Synaptojanin-145 of Synaptojanin-1 (SYNJ1) may be recruited early to clathrin-coated pits of synapses, either indirectly by adaptors that bind clathrin and AP-2, such as Amphiphysin (AMPH), or by interactions of endophilin family dimers with synaptic vesicle cargo, such as the vesicular glutamate receptor transport. | ||
| SYNJ1_HUMAN | 1414 | 1418 | Binary | Pre‑translational | Alternative splicing removes the EH-binding motif of Synaptojanin-1 (SYNJ1), abrogating binding to Epidermal growth factor receptor substrate 15 (EPS15). Isoform Synaptojanin-170 of Synaptojanin-1 (SYNJ1) is associated with clathrin-mediated endocytosis as a negative regulator of coat-membrane interaction. This isoform is virtually absent from mature neuronal synapses, where clathrin-mediated endocytosis plays a critical role and where Isoform Synaptojanin-145 of Synaptojanin-1 (SYNJ1) is by far the major synaptojanin isoform. Isoform Synaptojanin-145 of Synaptojanin-1 (SYNJ1) may be recruited early to clathrin-coated pits of synapses, either indirectly by adaptors that bind clathrin and AP-2, such as Amphiphysin (AMPH), or by interactions of endophilin family dimers with synaptic vesicle cargo, such as the vesicular glutamate receptor transport. | ||
| SYNJ1_HUMAN | 1393 | 1397 | Binary | Pre‑translational | Alternative splicing removes the EH-binding motif of Synaptojanin-1 (SYNJ1), abrogating binding to Epidermal growth factor receptor substrate 15 (EPS15). Isoform Synaptojanin-170 of Synaptojanin-1 (SYNJ1) is associated with clathrin-mediated endocytosis as a negative regulator of coat-membrane interaction. This isoform is virtually absent from mature neuronal synapses, where clathrin-mediated endocytosis plays a critical role and where Isoform Synaptojanin-145 of Synaptojanin-1 (SYNJ1) is by far the major synaptojanin isoform. Isoform Synaptojanin-145 of Synaptojanin-1 (SYNJ1) may be recruited early to clathrin-coated pits of synapses, either indirectly by adaptors that bind clathrin and AP-2, such as Amphiphysin (AMPH), or by interactions of endophilin family dimers with synaptic vesicle cargo, such as the vesicular glutamate transport. | ||
| SYNJ1_HUMAN | 1403 | 1407 | Binary | Pre‑translational | Alternative splicing removes the EH-binding motif of Synaptojanin-1 (SYNJ1), abrogating binding to Epidermal growth factor receptor substrate 15 (EPS15). Isoform Synaptojanin-170 of Synaptojanin-1 (SYNJ1) is associated with clathrin-mediated endocytosis as a negative regulator of coat-membrane interaction. This isoform is virtually absent from mature neuronal synapses, where clathrin-mediated endocytosis plays a critical role and where Isoform Synaptojanin-145 of Synaptojanin-1 (SYNJ1) is by far the major synaptojanin isoform. Isoform Synaptojanin-145 of Synaptojanin-1 (SYNJ1) may be recruited early to clathrin-coated pits of synapses, either indirectly by adaptors that bind clathrin and AP-2, such as Amphiphysin (AMPH), or by interactions of endophilin family dimers with synaptic vesicle cargo, such as the vesicular glutamate receptor transport. | ||
| SYNJ1_HUMAN | 1414 | 1418 | Binary | Pre‑translational | Alternative splicing removes the EH-binding motif of Synaptojanin-1 (SYNJ1), abrogating binding to Epidermal growth factor receptor substrate 15 (EPS15). Isoform Synaptojanin-170 of Synaptojanin-1 (SYNJ1) is associated with clathrin-mediated endocytosis as a negative regulator of coat-membrane interaction. This isoform is virtually absent from mature neuronal synapses, where clathrin-mediated endocytosis plays a critical role and where Isoform Synaptojanin-145 of Synaptojanin-1 (SYNJ1) is by far the major synaptojanin isoform. Isoform Synaptojanin-145 of Synaptojanin-1 (SYNJ1) may be recruited early to clathrin-coated pits of synapses, either indirectly by adaptors that bind clathrin and AP-2, such as Amphiphysin (AMPH), or by interactions of endophilin family dimers with synaptic vesicle cargo, such as the vesicular glutamate receptor transport. | ||
LIG_EVH1_1 - Proline-rich motif binding to signal transduction class I EVH1 domains. | |||||||
| XIRP1_HUMAN | 22 | 26 | Binary | Pre‑translational | Alternative splicing removes the EVH1-binding motif of Xin actin-binding repeat-containing protein 1 (XIRP1), abrogating binding to Protein enabled homolog (ENAH). | ||
| XIRP1_HUMAN | 22 | 26 | Binary | Pre‑translational | Alternative splicing removes the EVH1-binding motif of Xin actin-binding repeat-containing protein 1 (XIRP1), abrogating binding to Vasodilator-stimulated phosphoprotein (VASP). | ||
LIG_EVH1_2 - Proline-rich motif binding to signal transduction class II EVH1 domains. | |||||||
| GRM1_RAT | 1152 | 1156 | Binary | Pre‑translational | Alternative splicing removes the EVH1-binding motif of Metabotropic glutamate receptor 1 (Grm1), abrogating binding to Homer protein homolog 1 (Homer1), which is important for spatial targeting of Grm1. | ||
LIG_FAT_LD_1 - The paxillin LD motif is recognized by FAK and other focal adhesion proteins mainly involved in cytoskeletal regulation | |||||||
| PAXI_HUMAN | 4 | 12 | Binary | Pre‑translational | Alternative splicing removes the FAK-binding LD motif of Paxillin (PXN), abrogating binding to Focal adhesion kinase 1 (PTK2). | ||
LIG_FHA_1 - Phosphothreonine motif binding a subset of FHA domains that show a preference for a large aliphatic amino acid at the pT+3 position. | |||||||
| Y1827_MYCTU | 19 | 25 | Binary | Physicochemical compatibility | Phosphorylation of T21 in the FHA-binding motif of Uncharacterized protein Rv1827/MT1875 (Rv1827) by Probable serine/threonine-protein kinase pknG (pknG) results in auto-inhibition due to an intramolecular interaction with the FHA domain. As a result, phosphorylation-independent interactions of the FHA domain with metabolic enzymes, which regulate the catalytic activity of these enzymes, are blocked (See also switch details). | ||
| CHK2_HUMAN | 66 | 72 | Binary | Physicochemical compatibility | Phosphorylation of T68 in the FHA-binding motif of Serine/threonine-protein kinase Chk2 (CHEK2) induces binding to the Serine/threonine-protein kinase Chk2 (CHEK2) protein. | ||
| RAD9_YEAST | 601 | 607 | Binary | Physicochemical compatibility | Phosphorylation of T603 in the FHA-binding motif of DNA repair protein RAD9 (RAD9) induces binding to the Serine/threonine-protein kinase RAD53 (RAD53) protein. | ||
| PIN4_YEAST | 303 | 309 | Binary | Physicochemical compatibility | Phosphorylation of T305 in the FHA-binding motif of RNA-binding protein PIN4 (PIN4) induces binding to the Serine/threonine-protein kinase RAD53 (RAD53) protein. | ||
| CLV1_ARATH | 866 | 872 | Binary | Physicochemical compatibility | Phosphorylation of T868 in the FHA-binding motif of Receptor protein kinase CLAVATA1 (CLV1) induces binding to the Protein phosphatase 2C 70 (KAPP) protein. | ||
| Y1827_MYCTU | 20 | 26 | Binary | Physicochemical compatibility | Phosphorylation of T22 in the FHA-binding motif of Uncharacterized protein Rv1827/MT1875 (Rv1827) by Serine/threonine-protein kinase pknB (pknB) results in auto-inhibition due to an intramolecular interaction with the FHA domain. As a result, phosphorylation-independent interactions of the FHA domain with metabolic enzymes, which regulate the catalytic activity of these enzymes, are blocked (See also switch details). | ||
LIG_FHA_2 - Phosphothreonine motif binding a subset of FHA domains that have a preference for an acidic amino acid at the pT+3 position. | |||||||
| RAD9_YEAST | 153 | 159 | Binary | Physicochemical compatibility | Phosphorylation of T155 in the FHA-binding motif of DNA repair protein RAD9 (RAD9) induces binding to the Serine/threonine-protein kinase RAD53 (RAD53) protein. | ||
| RAD9_YEAST | 190 | 196 | Binary | Physicochemical compatibility | Phosphorylation of T192 in the FHA-binding motif of DNA repair protein RAD9 (RAD9) induces binding to the Serine/threonine-protein kinase RAD53 (RAD53) protein. | ||
| XRCC1_HUMAN | 521 | 527 | Binary | Physicochemical compatibility | Phosphorylation of T523 in the FHA-binding motif of DNA repair protein XRCC1 (XRCC1) by Casein kinase II subunit alpha (CSNK2A1) induces binding to the Aprataxin (APTX) protein. | ||
| XRCC4_HUMAN | 231 | 237 | Binary | Physicochemical compatibility | Phosphorylation of T233 in the FHA-binding motif of DNA repair protein XRCC4 (XRCC4) by Casein kinase II subunit alpha (CSNK2A1) induces binding to the Bifunctional polynucleotide phosphatase/kinase (PNKP) protein. | ||
| XRCC4_MOUSE | 229 | 235 | Binary | Physicochemical compatibility | Phosphorylation of T231 in the FHA-binding motif of DNA repair protein XRCC4 (Xrcc4) induces binding to the Bifunctional polynucleotide phosphatase/kinase (Pnkp) protein. | ||
| MRC1_SCHPO | 643 | 649 | Binary | Physicochemical compatibility | Phosphorylation of T645 in the FHA-binding motif of Mediator of replication checkpoint protein 1 (mrc1) induces binding to the Serine/threonine-protein kinase cds1 (cds1) protein. | ||
| XRCC1_HUMAN | 517 521 | 523 527 | Cumulative | Rheostatic | Two Bifunctional polynucleotide phosphatase/kinase (PNKP) molecules interact with two FHA-binding motifs in DNA repair protein XRCC1 (XRCC1) upon phosphorylation of T519 and T523 in the motifs. Additional phosphorylation of S518 and S525 further increases the affinity of the interaction. S518 and T523 are consensus CK2 phosphorylation sites, T519 and S525 atypical. | ||
| MK67I_HUMAN | 238 | 244 | Specificity | Altered binding specificity | Phosphorylation of T238 of MKI67 FHA domain-interacting nucleolar phosphoprotein (MKI67IP) by Cyclin-dependent kinase 1 (CDK1) primes for phosphorylation of T234 by Glycogen synthase kinase-3 beta (GSK3B), which primes for phosphorylation of S230 by GSK3B. Triple-phosphorylated hNIFK (MKI67IP) binds strongly to Antigen KI-67 (MKI67). | ||
| XRCC1_HUMAN | 517 | 523 | Avidity‑sensing | Hierarchical cooperative binding of two Bifunctional polynucleotide phosphatase/kinase (PNKP) molecules to one DNA repair protein XRCC1 (XRCC1) molecule upon phosphorylation of a primary and secondary FHA-binding motif in DNA repair protein XRCC1 (XRCC1) by Casein kinase II subunit alpha (CSNK2A1). | |||
| XRCC1_HUMAN | 521 | 527 | Avidity‑sensing | Hierarchical cooperative binding of two Bifunctional polynucleotide phosphatase/kinase (PNKP) molecules to one DNA repair protein XRCC1 (XRCC1) molecule upon phosphorylation of a primary and secondary FHA-binding motif in DNA repair protein XRCC1 (XRCC1) by Casein kinase II subunit alpha (CSNK2A1). | |||
| MK67I_HUMAN | 238 | 244 | Cumulative | Rheostatic | Phosphorylation of T238 in MKI67 FHA domain-interacting nucleolar phosphoprotein (MKI67IP) by Cyclin-dependent kinase 1 (CDK1) primes for phosphorylation of T234 by Glycogen synthase kinase-3 beta (GSK3B), which primes for phosphorylation of S230 by Glycogen synthase kinase-3 beta (GSK3B). Triple-phosphorylated hNIFK (MKI67 FHA domain-interacting nucleolar phosphoprotein (MKI67IP)) binds strongly to Antigen KI-67 (MKI67). See also switch details | ||
LIG_Filamin - | |||||||
| ITB2_HUMAN | 753 | 763 | Specificity | Altered binding specificity | Phosphorylation of T758 in Integrin beta-2 (ITGB2) switches the specificity of ITGB2 from Filamin-A (FLNA) to 14-3-3 proteins (e.g. 14-3-3 protein zeta/delta (YWHAZ)). | ||
| ITB7_HUMAN | 776 | 787 | Specificity | Competition | The integrin regulator Talin-1 (TLN1) and the actin-crosslinking Filamins Filamin-A (FLNA) use overlapping binding sites on the cytoplasmic tails of beta integrin subunits Integrin beta-7 (ITGB7), which makes their interaction with beta integrin mutually exclusive. | ||
LIG_Filamin_2 - | |||||||
| ITB1_HUMAN | 783 | 791 | Binary | Pre‑translational | Alternative splicing strongly inhibits the binding of the filamin-binding motif of Integrin beta-1 (ITGB1) to Filamin-A (FLNA), primarily due to the alteration of A to P it seems. | ||
| ITB1_HUMAN | 783 | 791 | Binary | Pre‑translational | Alternative splicing strongly inhibits the binding of the filamin-binding motif of Integrin beta-1 (ITGB1) to Filamin-B (FLNB), primarily due to the alteration of A to P it seems. Splicing of FLNB also affects this interaction. | ||
LIG_GBD_WASP_1 - | |||||||
| WASP_HUMAN | 466 | 476 | Uncategorised | Uncategorised | Phosphorylation of Wiskott-Aldrich syndrome protein (WAS) at Y291 by Src kinases, e.g. , destabilises the auto-inhibitory intramolecular interaction of Wiskott-Aldrich syndrome protein (WAS). | ||
| WASL_HUMAN | 467 | 477 | Uncategorised | Uncategorised | Phosphorylation of Neural Wiskott-Aldrich syndrome protein (WASL) at Y256 destabilises the auto-inhibitory intramolecular interaction of Neural Wiskott-Aldrich syndrome protein (WASL). | ||
| WASP_HUMAN | 466 | 476 | Binary | Allostery | Binding of Cell division control protein 42 homolog (CDC42) to Wiskott-Aldrich syndrome protein (WAS) allosterically relieves an auto-inhibitory intramolecular interaction in Wiskott-Aldrich syndrome protein (WAS), which becomes active. | ||
| WASP_HUMAN | 466 | 476 | Binary | Allostery | Binding of 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate to Wiskott-Aldrich syndrome protein (WAS) allosterically relieves an auto-inhibitory intramolecular interaction in Wiskott-Aldrich syndrome protein (WAS), which becomes active. | ||
| WASL_HUMAN | 467 | 477 | Binary | Allostery | Binding of Cell division control protein 42 homolog (CDC42) to Neural Wiskott-Aldrich syndrome protein (WASL) allosterically relieves an auto-inhibitory intramolecular interaction in Neural Wiskott-Aldrich syndrome protein (WASL), which becomes active. | ||
| WASL_HUMAN | 467 | 477 | Binary | Allostery | Binding of 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate to Neural Wiskott-Aldrich syndrome protein (WASL) allosterically relieves an auto-inhibitory intramolecular interaction in Neural Wiskott-Aldrich syndrome protein (WASL), which becomes active. | ||
LIG_GYF - LIG_GYF is a proline-rich sequence specifically recognized by GYF domains | |||||||
| CD2_HUMAN | 295 | 303 | Specificity | Competition | T-cell surface antigen CD2 (CD2) uses overlapping motifs to bind to CD2 antigen cytoplasmic tail-binding protein 2 (CD2BP2) and Fyn, which makes their interactions mutually exclusive. Since CD2BP2 and Tyrosine-protein kinase Fyn (FYN) reside in different subcellular locations, the specificity of CD2 for the two competitors is switched by changing its cellular localization, from non-raft membranes to lipid raft membranes. | ||
LIG_Glycolytic_Aldolase - | |||||||
| SNX9_HUMAN | 165 | 169 | Binary | Physicochemical compatibility | Phosphorylation of the LC4 region of Sorting nexin-9 (SNX9) abolishes its interaction with Fructose-bisphosphate aldolase A (ALDOA). However, the exact position of the residues that are phosphorylated and regulate binding is not known. | ||
| SNX9_HUMAN | 165 | 169 | Specificity | Competition | Sorting nexin-9 (SNX9) and fructose-1,6-bisphosphate (D-fructose 1,6-bisphosphate) bind mutually exclusive and with similar affinities to Fructose-bisphosphate aldolase A (ALDOA). | ||
LIG_HP1_1 - Ligand to interface formed by dimerisation of two chromoshadow domains in HP1 proteins. | |||||||
| TIF1B_MOUSE | 486 | 490 | Binary | Physicochemical compatibility | Phosphorylation of S473 close to the Chromo shadow domain-binding motif of Transcription intermediary factor 1-beta (Trim28) by Protein kinase C delta type (Prkcd) negatively regulates its interaction with Chromobox protein homolog 1 (Cbx1), which is crucial for heterochromatin formation and maintenance. This results in relief of transcription repression and promotion of cell cycle progression. | ||
LIG_IQ - Calmodulin binding helical peptide motif | |||||||
| S61A1_CANFA | 13 | 31 | Binary | Allostery | Binding of calcium(2+) to Calmodulin (Calm1) exposes a binding site on Calmodulin (Calm1) for the Calmodulin-binding IQ motif of Protein transport protein Sec61 subunit alpha isoform 1 (SEC61A1), an interaction that results in closure of the protein-conducting channel located in the ER. | ||
| CAC1D_RAT | 1650 | 1669 | Binary | Pre‑translational | Alternative splicing removes the IQ motif of Voltage-dependent L-type calcium channel subunit alpha-1D (Cacna1d) abrogating binding to Calmodulin (Calm1). CaV1.3IQdelta (IQ-deleted Isoform CACN4B of Voltage-dependent L-type calcium channel subunit alpha-1D (Cacna1d)) channels exhibit a lack of calcium-dependent inactivation. CaV1.3IQdelta channel immunoreactivity was preferentially localised to cochlear outer hair cells (OHCs), whereas that of CaV1.3IQfull channels (IQ-possessing Isoform CACN4A of Voltage-dependent L-type calcium channel subunit alpha-1D (Cacna1d)) labelled inner hair cells (IHCs). | ||
| S61A1_CANFA | 13 | 31 | Binary | Allostery | Binding of calcium(2+) to Calmodulin (Calm1) exposes a binding site on Calmodulin (Calm1) for the Calmodulin-binding IQ motif of Protein transport protein Sec61 subunit alpha isoform 1 (SEC61A1), an interaction that results in closure of the protein-conducting channel located in the ER. | ||
LIG_IQ_2 - | |||||||
| AT2B1_HUMAN | 1114 | 1128 | Binary | Pre‑translational | Alternative splicing partially removes the IQ motif of Isoform CI of Plasma membrane calcium-transporting ATPase 1 (ATP2B1), partially inhibiting binding to Calmodulin (CALM1). | ||
| AT2B1_HUMAN | 1114 | 1128 | Binary | Pre‑translational | Alternative splicing partially removes the IQ motif of Isoform CI of Plasma membrane calcium-transporting ATPase 1 (ATP2B1), partially inhibiting binding to Calmodulin (CALM1). | ||
LIG_Integrin_isoDGR_1 - NGR motif is present in proteins of extracellular matrix which upon deamidation forms a biologically active isoDGR motif that binds to various members of integrin family. | |||||||
| FINC_HUMAN | 263 | 265 | Pre‑assembly | Composite binding site formation | Binding of Fibronectin (FN1) to integrin receptors depends on pre-assembly of Integrin alpha-V (ITGAV)-Integrin beta-3 (ITGB3) heterodimers, since association of the integrin alpha and beta subunits results in the formation of a composite binding site for the RGD motif in the ligand. | ||
LIG_MAD2 - Mad2 binding motif | |||||||
| CDC20_HUMAN | 129 | 137 | Binary | Allostery | Binding of Mad1-bound Closed (C-) Mitotic spindle assembly checkpoint protein MAD2A (MAD2L1) to Open (O-) Mitotic spindle assembly checkpoint protein MAD2A (MAD2L1) switches conformation of the latter to the C conformation, making the binding site for Cell division cycle protein 20 homolog (CDC20) available. This sequesters Cell division cycle protein 20 homolog (CDC20) to the spindle assembly checkpoint and prevents onset of anaphase. | ||
LIG_NRBOX - The nuclear receptor box motif (LXXLL) confers binding to nuclear receptors. | |||||||
| NRIP1_HUMAN | 132 | 138 | Binary | Allostery | Binding of the estrogen ligand to the nuclear Estrogen receptor (ESR1) makes the binding site for the NRBOX motif of Nuclear receptor-interacting protein 1 (NRIP1) accessible. | ||
| NRIP1_HUMAN | 184 | 190 | Binary | Allostery | Binding of the estrogen ligand to the nuclear Estrogen receptor (ESR1) makes the binding site for the NRBOX motif of Nuclear receptor-interacting protein 1 (NRIP1) accessible. | ||
| NRIP1_HUMAN | 20 | 26 | Binary | Allostery | Binding of the estrogen ligand to the nuclear Estrogen receptor (ESR1) makes the binding site for the NRBOX motif of Nuclear receptor-interacting protein 1 (NRIP1) accessible. | ||
| NRIP1_HUMAN | 265 | 271 | Binary | Allostery | Binding of the estrogen ligand to the nuclear Estrogen receptor (ESR1) makes the binding site for the NRBOX motif of Nuclear receptor-interacting protein 1 (NRIP1) accessible. | ||
| NRIP1_HUMAN | 379 | 385 | Binary | Allostery | Binding of the estrogen ligand to the nuclear Estrogen receptor (ESR1) makes the binding site for the NRBOX motif of Nuclear receptor-interacting protein 1 (NRIP1) accessible. | ||
| NRIP1_HUMAN | 499 | 505 | Binary | Allostery | Binding of the estrogen ligand to the nuclear Estrogen receptor (ESR1) makes the binding site for the NRBOX motif of Nuclear receptor-interacting protein 1 (NRIP1) accessible. | ||
| NRIP1_HUMAN | 500 | 506 | Binary | Allostery | Binding of the estrogen ligand to the nuclear Estrogen receptor (ESR1) makes the binding site for the NRBOX motif of Nuclear receptor-interacting protein 1 (NRIP1) accessible. | ||
| NRIP1_HUMAN | 712 | 718 | Binary | Allostery | Binding of the estrogen ligand to the nuclear Estrogen receptor (ESR1) makes the binding site for the NRBOX motif of Nuclear receptor-interacting protein 1 (NRIP1) accessible. | ||
| NRIP1_HUMAN | 818 | 824 | Binary | Allostery | Binding of the estrogen ligand to the nuclear Estrogen receptor (ESR1) makes the binding site for the NRBOX motif of Nuclear receptor-interacting protein 1 (NRIP1) accessible. | ||
| NRIP1_HUMAN | 935 | 941 | Binary | Allostery | Binding of the estrogen ligand to the nuclear Estrogen receptor (ESR1) makes the binding site for the NRBOX motif of Nuclear receptor-interacting protein 1 (NRIP1) accessible. | ||
| NCOA2_HUMAN | 640 | 646 | Binary | Allostery | Binding of the glucocorticoid ligand to the nuclear Glucocorticoid receptor (NR3C1) makes the binding site for the NRBOX motif of Nuclear receptor coactivator 2 (NCOA2) accessible. | ||
| NCOA2_HUMAN | 689 | 695 | Binary | Allostery | Binding of the glucocorticoid ligand to the nuclear Glucocorticoid receptor (NR3C1) makes the binding site for the NRBOX motif of Nuclear receptor coactivator 2 (NCOA2) accessible. | ||
| NCOA2_HUMAN | 744 | 750 | Binary | Allostery | Binding of the glucocorticoid ligand to the nuclear Glucocorticoid receptor (NR3C1) makes the binding site for the NRBOX motif of Nuclear receptor coactivator 2 (NCOA2) accessible. | ||
| MED1_HUMAN | 603 | 609 | Binary | Allostery | Binding of the 3,3',5-triiodo-L-thyronine ligand to the nuclear Thyroid hormone receptor alpha (THRA) makes the binding site for the NRBOX motif of Mediator of RNA polymerase II transcription subunit 1 (MED1) accessible. | ||
| MED1_HUMAN | 644 | 650 | Binary | Allostery | Binding of the 3,3',5-triiodo-L-thyronine ligand to the nuclear Thyroid hormone receptor alpha (THRA) makes the binding site for the NRBOX motif of Mediator of RNA polymerase II transcription subunit 1 (MED1) accessible. | ||
| NCOA6_MOUSE | 1494 | 1500 | Binary | Allostery | Binding of the 15-deoxy-Delta(12,14)-prostaglandin J2 ligand to the nuclear Peroxisome proliferator-activated receptor gamma (Pparg) makes the binding site for the NRBOX motif of Nuclear receptor coactivator 6 (Ncoa6) accessible. | ||
| TRXR1_HUMAN | 46 | 52 | Binary | Pre‑translational | Alternative splicing removes the NRBOX motif of Isoform TXNRD1_v2 of Thioredoxin reductase 1, cytoplasmic (TXNRD1), abrogating binding to Estrogen receptor (ESR1). Unlike splice variants without the NRBOX motif, TrxR1b (also known as Isoform TXNRD1_v2 of Thioredoxin reductase 1, cytoplasmic (TXNRD1)) is identified within the nucleus. TrxR1b enhanced the transcriptional activity of the estrogen receptors ESR1 and ESR2, possibly by providing a reduced environment in the immediate vicinity of the ERs. | ||
| TRXR1_HUMAN | 46 | 52 | Binary | Pre‑translational | Alternative splicing removes the NRBOX motif of Isoform TXNRD1_v2 of Thioredoxin reductase 1, cytoplasmic (TXNRD1), abrogating binding to Estrogen receptor beta (ESR2). Unlike splice variants without the NRBOX motif, TrxR1b (also known as Isoform TXNRD1_v2 of Thioredoxin reductase 1, cytoplasmic (TXNRD1)) is identified within the nucleus. TrxR1b enhanced the transcriptional activity of the estrogen receptors ESR1 and ESR2, possibly by providing a reduced environment in the immediate vicinity of the ERs. | ||
LIG_PCNA_2 - | |||||||
| ING1_HUMAN | 9 | 15 | Binary | Pre‑translational | Alternative splicing removes the PCNA-binding motif of Isoform Variant A of Inhibitor of growth protein 1 (ING1), abrogating binding to Proliferating cell nuclear antigen (PCNA). P33-ING1b (also known as Isoform Variant A of Inhibitor of growth protein 1 (ING1)) binds specially to PCNA, resulting in a major change in subcellular localisation and the import of this isoform into the nucleus. This is theorised to act by limiting access to the PCNA-binding domain but eventually it promotes apoptosis (though this may not be its physiological effect). | ||
LIG_PCNA_PIPBox_1 - The PCNA binding PIP box motif is found in proteins involved in DNA replication, repair and cell cycle control. | |||||||
| DPOD3_HUMAN | 456 | 465 | Binary | Physicochemical compatibility | Phosphorylation of S458 in the PCNA-binding motif of DNA polymerase delta subunit 3 (POLD3) by cAMP subfamily reduces the affinity of binding to the Proliferating cell nuclear antigen (PCNA) and decreases the processivity of the polymerase complex. | ||
| CDN1A_HUMAN | 144 | 153 | Binary | Physicochemical compatibility | Phosphorylation of T145 in the PCNA-binding motif of Cyclin-dependent kinase inhibitor 1 (CDKN1A) by RAC-alpha serine/threonine-protein kinase (AKT1) inhibits binding to Proliferating cell nuclear antigen (PCNA). As a result, Cyclin-dependent kinase inhibitor 1 (CDKN1A) no longer inhibits Proliferating cell nuclear antigen (PCNA) and blocking of DNA replication is relieved. | ||
| CDN1A_HUMAN | 144 | 153 | Binary | Physicochemical compatibility | Phosphorylation of S146 in the PCNA-binding motif of Cyclin-dependent kinase inhibitor 1 (CDKN1A) by PKC subfamily inhibits binding to Proliferating cell nuclear antigen (PCNA). As a result, Cyclin-dependent kinase inhibitor 1 (CDKN1A) no longer inhibits Proliferating cell nuclear antigen (PCNA) and blocking of DNA replication is relieved. | ||
LIG_PDZ_Class_1 - The C-terminal class 1 PDZ-binding motif is classically represented by a pattern like (ST)X(VIL)* | |||||||
| CCG2_MOUSE | 318 | 323 | Binary | Physicochemical compatibility | Phosphorylation of T321 in the PDZ-binding motif of Voltage-dependent calcium channel gamma-2 subunit (Cacng2) by cAMP subfamily prevents binding to the PDZ domain of Disks large homolog 4 (Dlg4), an interaction involved in regulating synaptic targeting of AMPA-selective glutamate receptors. | ||
| IRK4_HUMAN | 440 | 445 | Binary | Physicochemical compatibility | Phosphorylation of S443 in the PDZ-binding motif of Inward rectifier potassium channel 4 (KCNJ4) by inhibits its interaction with the Disks large homolog 4 (DLG4) protein. | ||
| ADRB2_HUMAN | 408 | 413 | Binary | Physicochemical compatibility | Phosphorylation of S411 in the PDZ-binding motif of Beta-2 adrenergic receptor (ADRB2) by inhibits its interaction with the Na(+)/H(+) exchange regulatory cofactor NHE-RF1 (SLC9A3R1) protein. | ||
| BCR_HUMAN | 1266 | 1271 | Binary | Physicochemical compatibility | Phosphorylation of T1269 in the PDZ-binding motif of Breakpoint cluster region protein (BCR) inhibits its interaction with the Afadin (MLLT4) protein. | ||
| CTNB1_HUMAN | 776 | 781 | Binary | Allostery | Binding of Ezrin (EZR) via its FERM domain to the EB domain of Na(+)/H(+) exchange regulatory cofactor NHE-RF1 (SLC9A3R1) results in allosteric coupling to the second PDZ domain of Na(+)/H(+) exchange regulatory cofactor NHE-RF1 (SLC9A3R1), which results in relief of the intramolecular interaction with the PDZ binding ligand, thereby increasing the affinity of the PDZ domain for other ligands, including Catenin beta-1 (CTNNB1). | ||
| GRASP_RAT | 389 | 394 | Specificity | Motif hiding | Binding of the PDZ-binding motif of General receptor for phosphoinositides 1-associated scaffold protein (Grasp) (Tamalin) to the Tamalin Grasp PDZ domain locks this protein in an auto-inhibited conformation. Binding of the PDZ-binding motif of Metabotropic glutamate receptor 5 (Grm5) to the Tamalin GraspPDZ domain results in disruption of the weaker intramolecular Tamalin (Grasp) interactions. The PDZ-binding motif of Tamalin (General receptor for phosphoinositides 1-associated scaffold protein (Grasp)) becomes available to interact with the PDZ domain of Membrane-associated guanylate kinase, WW and PDZ domain-containing protein 2 (Magi2) (S-SCAM), which functions as a receptor for kinesin motor proteins. See also switch details. | ||
| GRASP_RAT | 389 | 394 | Specificity | Motif hiding | Binding of the PDZ-binding motif of General receptor for phosphoinositides 1-associated scaffold protein (Grasp) (Tamalin) to the Tamalin Grasp PDZ domain locks this protein in an auto-inhibited conformation. Binding of the PDZ-binding motif of Metabotropic glutamate receptor 5 (Grm5) to the Tamalin GraspPDZ domain results in disruption of the weaker intramolecular Tamalin (Grasp) interactions. The PDZ-binding motif of Tamalin (General receptor for phosphoinositides 1-associated scaffold protein (Grasp)) becomes available to interact with the PDZ domain of Membrane-associated guanylate kinase, WW and PDZ domain-containing protein 2 (Magi2) (S-SCAM), which functions as a receptor for kinesin motor proteins. See also switch details. | ||
| NHRF1_HUMAN | 353 | 358 | Specificity | Domain hiding | Binding of Ezrin via its FERM domain to the EB domain of Na(+)/H(+) exchange regulatory cofactor NHE-RF1 (SLC9A3R1) results in allosteric coupling to the second PDZ domain of SLC9A3R1. This relieves the intramolecular interaction with the SLC9A3R1 PDZ-binding ligand and increases the affinity of the PDZ domain for other ligands including Catenin beta-1 (CTNNB1). | ||
| CTNB1_HUMAN | 776 | 781 | Specificity | Domain hiding | Binding of Ezrin via its FERM domain to the EB domain of Na(+)/H(+) exchange regulatory cofactor NHE-RF1 (SLC9A3R1) results in allosteric coupling to the second PDZ domain of SLC9A3R1. This relieves the intramolecular interaction with the SLC9A3R1 PDZ-binding ligand and increases the affinity of the PDZ domain for other ligands including Catenin beta-1 (CTNNB1). | ||
| GRM5_RAT | 1198 | 1203 | Specificity | Domain hiding | Binding of the PDZ-binding motif of General receptor for phosphoinositides 1-associated scaffold protein (Grasp) (Tamalin) to the Tamalin (Grasp) PDZ domain locks this protein in an auto-inhibited conformation. Binding of the PDZ-binding motif of Metabotropic glutamate receptor 5 (Grm5) to the Tamalin (Grasp) PDZ domain results in disruption of the weaker intramolecular Tamalin (Grasp) interactions. The PDZ-binding motif of Tamalin (Grasp) becomes available to interact with the PDZ domain of Membrane-associated guanylate kinase, WW and PDZ domain-containing protein 2 (Magi2) (S-SCAM), which functions as a receptor for kinesin motor proteins. See also switch details. | ||
| GRASP_RAT | 389 | 394 | Specificity | Domain hiding | Binding of the PDZ-binding motif of General receptor for phosphoinositides 1-associated scaffold protein (Grasp) (Tamalin) to the Tamalin (Grasp) PDZ domain locks this protein in an auto-inhibited conformation. Binding of the PDZ-binding motif of Metabotropic glutamate receptor 5 (Grm5) to the Tamalin (Grasp) PDZ domain results in disruption of the weaker intramolecular Tamalin (Grasp) interactions. The PDZ-binding motif of Tamalin (Grasp) becomes available to interact with the PDZ domain of Membrane-associated guanylate kinase, WW and PDZ domain-containing protein 2 (Magi2) (S-SCAM), which functions as a receptor for kinesin motor proteins. See also switch details. | ||
| CFTR_HUMAN | 1475 | 1480 | Specificity | Competition | The PDZ domains of Na(+)/H(+) exchange regulatory cofactor NHE-RF1 (SLC9A3R1) and SH3 and multiple ankyrin repeat domains protein 2 (SHANK2) compete for the PDZ-binding motif of Cystic fibrosis transmembrane conductance regulator (CFTR). SLC9A3R1 positively regulates CFTR activity by recruiting a PKA-containing complex, while SH3 and multiple ankyrin repeat domains protein 2 (SHANK2) negatively affects CFTR activity by recruiting PDE4D. | ||
| CFTR_HUMAN | 1475 | 1480 | Specificity | Competition | The PDZ domains of Na(+)/H(+) exchange regulatory cofactor NHE-RF1 (SLC9A3R1) and SH3 and multiple ankyrin repeat domains protein 2 (SHANK2) compete for the PDZ-binding motif of Cystic fibrosis transmembrane conductance regulator (CFTR). SLC9A3R1 positively regulates CFTR activity by recruiting a PKA-containing complex, while SH3 and multiple ankyrin repeat domains protein 2 (SHANK2) negatively affects CFTR activity by recruiting PDE4D. | ||
| ADA22_HUMAN | 901 | 906 | Binary | Pre‑translational | Alternative splicing removes the PDZ-binding motif of Disintegrin and metalloproteinase domain-containing protein 22 (ADAM22), abrogating binding to Disks large homolog 4 (DLG4). The motif-containing Isoform Epsilon of Disintegrin and metalloproteinase domain-containing protein 22 (ADAM22) forms part of a complex containing Leucine-rich glioma-inactivated protein 1 (LGI1), AMPA-R (e.g. Glutamate receptor 1 (GRIA1)) and AMPA-R regulatory proteins (e.g. Voltage-dependent calcium channel gamma-2 subunit (CACNG2)), and is closely associated with epilepsy. | ||
| AT2B2_HUMAN | 1238 | 1243 | Binary | Pre‑translational | Alternative splicing removes the PDZ-binding motif of Plasma membrane calcium-transporting ATPase 2 (ATP2B2), abrogating binding to Na(+)/H(+) exchange regulatory cofactor NHE-RF2 (SLC9A3R2), altering the location of this Ca2+ pump. Despite the similarity in C-terminal between the 'b' splice variants of Plasma membrane calcium-transporting ATPase 4 (ATP2B4) (-ETSV) and Plasma membrane calcium-transporting ATPase 2 (ATP2B2) (-ETSL), 'b' splice variants of ATP2B4 did not interact with either of the NHERFs whereas PMCA2b selectively preferred Na(+)/H(+) exchange regulatory cofactor NHE-RF2 (SLC9A3R2) over Na(+)/H(+) exchange regulatory cofactor NHE-RF1 (SLC9A3R1). NHERFs have been previously implicated in the targeting, retention and regulation of membrane proteins including the β2-adrenergic receptor, cystic fibrosis transmembrane conductance regulator, and Trp4 Ca2+channel. This study suggests Plasma membrane calcium-transporting ATPase 2 (ATP2B2) may be under similar regulation. | ||
| AT2B4_HUMAN | 1236 | 1241 | Binary | Pre‑translational | Alternative splicing removes the PDZ-binding motif of Plasma membrane calcium-transporting ATPase 4 (ATP2B4), abrogating binding to Nitric oxide synthase, brain (NOS1). PMCA4b acts as a negative regulator of Nitric oxide synthase, brain (NOS1), reducing production of nitric oxide in heart tissue. This negative regulation was not dependent on a conformational change due to binding of the PDZ ligand, but on Ca2+ depletion in close proximity of the enzyme. Nitric oxide production by NOS1 is known to be important in the regulation of excitation-contraction (EC) coupling and subsequently contractility. | ||
| AT2B4_HUMAN | 1236 | 1241 | Binary | Pre‑translational | Alternative splicing removes the PDZ-binding motif of Plasma membrane calcium-transporting ATPase 4 (ATP2B4), abrogating binding to Disks large homolog 3 (DLG3). Disks large homolog 3 (DLG3) did not bind to 'b' isoform of PMCA2. There is therefore an interaction selectivity between 'b' isoforms of ATP2B4 and DLG3 as opposed to the promiscuity of 'b' isoforms of ATP2B2 and ATP2B4 in interacting with other SAPs. Same study DLG4, DLG2 and DLG1 shown to bind to PDZ-binding motifs in 'b' isoforms of ATP2B4 and ATP2B2. | ||
| AT2B4_HUMAN | 1236 | 1241 | Binary | Pre‑translational | Alternative splicing removes the PDZ-binding motif of Plasma membrane calcium-transporting ATPase 4 (ATP2B4), abrogating binding to Disks large homolog 1 (DLG1). A much lower affinity was recorded for the third PDZ domain of DLG1 (in in the micromolar range (KD = 1.2 microM) compared to nanomolar affinity (KD = 1.6 nM)). PMCA4b and DLG1 are co-expressed in kidney and intestinal epithelial cells as well as in several areas of the brain. Should be noted that the 'b' isoforms of Plasma membrane calcium-transporting ATPase 2 (ATP2B2) bind much more weakly to all PDZ domains of DLG1 | ||
| AT2B4_HUMAN | 1236 | 1241 | Binary | Pre‑translational | Alternative splicing removes the PDZ-binding motif of Plasma membrane calcium-transporting ATPase 4 (ATP2B4), abrogating binding to Peripheral plasma membrane protein CASK (CASK). The PDZ domain-containing protein CASK and PMCA4b co-precipitate in kidney and brain. Similar to NOS1, binding to PMCA4b allows Ca2+ dependent regulation. Depletion of local Ca2+ by PMCA4b in close proximity to CASK may inhibit Ca2+/calmodulin binding. This can subsequently inhibit binding to T-box brain protein 1 (TBR1) and/or translocation of CASK or the CASK/TBR1 complex to the nucleus. | ||
| 5HT4R_MOUSE | 382 | 387 | Binary | Pre‑translational | Alternative splicing removes the PDZ-binding motif of Isoform 5-HT4(A) of 5-hydroxytryptamine receptor 4 (Htr4), abrogating binding to Sorting nexin-27 (Snx27). Snx27 is responsible for targeting of the Isoform 5-HT4(A) of 5-hydroxytryptamine receptor 4 (Htr4) to early endosomes. | ||
| 5HT4R_MOUSE | 382 | 387 | Binary | Pre‑translational | Alternative splicing removes the PDZ-binding motif of Isoform 5-HT4(A) of 5-hydroxytryptamine receptor 4 (Htr4), abrogating binding to Na(+)/H(+) exchange regulatory cofactor NHE-RF1 (Slc9a3r1). Isoform 5-HT4(A) of 5-hydroxytryptamine receptor 4 (Htr4) interacts specifically with a protein complex including Slc9a3r1 and Ezrin (Ezr) that might participate in its targeting to specialised subcellular regions, such as microvilli. | ||
| IRK6_MOUSE | 420 | 425 | Binary | Pre‑translational | Alternative splicing removes the PDZ-binding motif of G protein-activated inward rectifier potassium channel 2 (Kcnj6), abrogating binding to Sorting nexin-27 (Snx27). | ||
| KIF1B_MOUSE | 1145 | 1150 | Binary | Pre‑translational | Alternative splicing removes the PDZ-binding motif of Isoform 3 of Kinesin-like protein KIF1B (Kif1b), abrogating binding to PDZ domain-containing protein GIPC1 (Gipc1). | ||
| GRIK1_RAT | 900 | 905 | Binary | Pre‑translational | Alternative splicing removes the PDZ-binding motif of Isoform Glur5-2 of Glutamate receptor ionotropic, kainate 1 (Grik1), abrogating binding to PRKCA-binding protein (Pick1). The ER-retention motif of Grik1 splice variants can be inhibited by PKC phosphorylation and association with a PDZ protein. It has also been shown that the PDZ domain-containing proteins Disks large homolog 4 (Dlg4) and Syntenin-1 (Sdcbp) are able to bind. | ||
| GRIK1_RAT | 900 | 905 | Binary | Pre‑translational | Alternative splicing removes the PDZ-binding motif of Glutamate receptor, ionotropic kainate 1 (Grik1), abrogating binding to Glutamate receptor-interacting protein 1 (Grip1). The ER retention of Grik1 splice variants can be inhibited by PKC phosphorylation and association with a PDZ domain-containing protein. Also shown that the PDZ-binding containing proteins PSD95 and syntenin are able to bind. | ||
| GUAD_HUMAN | 449 | 454 | Binary | Pre‑translational | Alternative splicing removes the PDZ-binding motif of Guanine deaminase (GDA) (Nedasin), abrogating binding to Disks large homolog 3 (DLG3). Isoform 1 of Guanine deaminase (GDA) (Nedasin S) is predominately expressed in neuronal tissues and binds PDZ domains. Isoform 3 of Guanine deaminase (GDA) (Nedasin V1), which is predominately expressed in non-neuronal tissues, does not bind PDZ domains. The presence of Nedasin S inhibits binding of NMDA receptors and K+ channels to PDZ domain-containing proteins such as members of the MAGUK family. This suggests that GDA might modulate the receptor clustering function of the PDZ domains of MAGUK family members, and this modulation is regulated by alternative splicing of GDA transcripts. | ||
| NMDZ1_HUMAN | 917 | 922 | Binary | Pre‑translational | Alternative splicing removes the PDZ-binding motif of Isoform 4 of Glutamate [NMDA] receptor subunit zeta-1 (GRIN1), abrogating binding to Disks large homolog 4 (DLG4). Binding of the PDZ domain of DLG4 suppresses an ER-retention motif in GRIN1, promoting its cell surface expression in a splice variant-specific manner. | ||
| NMDZ1_HUMAN | 917 | 922 | Specificity | Motif hiding | Binding of the PDZ domain of Disks large homolog 4 (DLG4) suppresses the ER-retention motif of Isoform 4 of Glutamate receptor subunit zeta-1 (GRIN1) in a splice variant-specific manner, thereby promoting cell surface expression of this particular isoform. This supports the hypothesis that local regulation of receptor exit from neuronal ER plays a role in modifying discrete synaptic receptor number. | ||
| SYNJ2_RAT | 1288 | 1293 | Binary | Pre‑translational | Alternative splicing removes the PDZ-binding motif of Isoform 7.5kb of Synaptojanin-2 (Synj2), abrogating binding to Synaptojanin-2-binding protein (Synj2bp). Isoform 7.5kb of Synaptojanin-2 (Synj2) (Synaptojanin 2A) is recruited to mitochondria through the interaction with the PDZ domain of the mitochondrial outer membrane protein Synj2bp. | ||
| CLCN3_HUMAN | 861 | 866 | Binary | Pre‑translational | Alternative splicing removes the PDZ-binding motif of Isoform ClC-3B of H(+)/Cl(-) exchange transporter 3 (CLCN3), abrogating binding to Na(+)/H(+) exchange regulatory cofactor NHE-RF1 (SLC9A3R1). Isoform ClC-3B of H(+)/Cl(-) exchange transporter 3 (CLCN3) is expressed at the leading edge of membrane ruffles. The interaction of CLCN3 with SLC9A3R1 is important for localising outwardly rectifying chloride channels at the leading edge. | ||
| PKHG5_MOUSE | 1068 | 1073 | Binary | Pre‑translational | Alternative splicing removes the PDZ-binding motif of Pleckstrin homology domain-containing family G member 5 (Plekhg5), abrogating binding to PDZ domain-containing protein GIPC1 (Gipc1). The PDZ adaptor protein Gipc1 (Synectin) bound the longer splice variant, Isoform SYX1 of Pleckstrin homology domain-containing family G member 5 (Plekhg5) (Syx1), which was targeted to the plasma membrane in a Synectin-dependent manner. The shorter variant, Isoform SYX2 of Pleckstrin homology domain-containing family G member 5 (Plekhg5) (Syx2), was diffusely distributed in the cytoplasm. Expression of Syx1 augmented endothelial cell migration and tube formation, whereas Syx2 expression did not. Significant expression of Syx2 was only seen in brain tumour cells, which also exhibited high basal Transforming protein RhoA (Rhoa) activity. | ||
| KALRN_RAT | 1649 | 1654 | Binary | Pre‑translational | Alternative splicing removes the PDZ-binding motif of Isoform Kalirin-7 of Kalirin (Kalrn), abrogating binding to Disks large homolog 4 (Dlg4). Isoform Kalirin-7 of Kalirin (Kalrn) is the most prevalent isoform in the adult rat hippocampus where it locates to the postsynaptic density via an interaction with Dlg4 and regulates dendritic morphogenesis. | ||
| PLCB1_HUMAN | 1211 | 1216 | Binary | Pre‑translational | Alternative splicing removes the PDZ-binding motif of 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 (PLCB1), abrogating binding to Partitioning defective 3 homolog (PARD3). The G protein-activated PLCB1 can directly interact with cell polarity proteins Partitioning defective 3 homolog (PARD3) and Partitioning defective 6 homolog alpha (PARD6A) to form protein complexes in the cell, which potentially modulate G protein-activated PLCB1 activity in cell polarity formation and asymmetric cell division. | ||
| PLCB1_MOUSE | 1211 | 1216 | Binary | Pre‑translational | Alternative splicing removes the PDZ-binding motif of 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 (Plcb1), abrogating binding to Na(+)/H(+) exchange regulatory cofactor NHE-RF1 (Slc9a3r1). Plcb1 does not bind to Slc9a3r2. | ||
| BAIP2_HUMAN | 516 | 521 | Binary | Pre‑translational | Alternative splicing removes the PDZ-binding motif of Isoform BAIAP2-alpha of Brain-specific angiogenesis inhibitor 1-associated protein 2 (BAIAP2), abrogating binding to Disks large homolog 3 (DLG3). The SH3 domain of Isoform BAIAP2-alpha of Brain-specific angiogenesis inhibitor 1-associated protein 2 (BAIAP2) also binds to SH3 and multiple ankyrin repeat domains protein 1 (SHANK1), meaning it can link two prominent proteins of the postsynaptic NMDA-receptor complex, namely SHANK1 and DLG3. | ||
| AT2B4_HUMAN | 1236 | 1241 | Binary | Pre‑translational | Alternative splicing removes the PDZ-binding motif of Plasma membrane calcium-transporting ATPase 4 (ATP2B4), abrogating binding to Disks large homolog 1 (DLG1). A much lower affinity was recorded for the third PDZ domain of DLG1 (in in the micromolar range (KD = 1.2 microM) compared to nanomolar affinity (KD = 1.6 nM)). PMCA4b and DLG1 are co-expressed in kidney and intestinal epithelial cells as well as in several areas of the brain. | ||
| AT2B4_HUMAN | 1236 | 1241 | Binary | Pre‑translational | Alternative splicing removes the PDZ-binding motif of Plasma membrane calcium-transporting ATPase 4 (ATP2B4), abrogating binding to Disks large homolog 3 (DLG3). Disks large homolog 3 (DLG3) did not bind to 'b' isoform of PMCA2. There is therefore an interaction selectivity between 'b' isoforms of ATP2B4 and DLG3 as opposed to the promiscuity of 'b' isoforms of ATP2B2 and ATP2B4 in interacting with other SAPs. Same study DLG4, DLG2 and DLG1 shown to bind to PDZ-binding motifs in 'b' isoforms of ATP2B4 and ATP2B2. | ||
| KALRN_RAT | 1649 | 1654 | Binary | Pre‑translational | Alternative splicing removes the PDZ-binding motif of Isoform Kalirin-7 of Kalirin (Kalrn), abrogating binding to Disks large homolog 4 (Dlg4). Isoform Kalirin-7 of Kalirin (Kalrn) is the most prevalent isoform in the adult rat hippocampus where it locates to the postsynaptic density via an interaction with Dlg4 and regulates dendritic morphogenesis. | ||
| KALRN_RAT | 1649 | 1654 | Binary | Pre‑translational | Alternative splicing removes the PDZ-binding motif of Isoform Kalirin-7 of Kalirin (Kalrn), abrogating binding to Disks large homolog 4 (Dlg4). Isoform Kalirin-7 of Kalirin (Kalrn) is the most prevalent isoform in the adult rat hippocampus where it locates to the postsynaptic density via an interaction with Dlg4 and regulates dendritic morphogenesis. | ||
| NMDZ1_HUMAN | 917 | 922 | Binary | Pre‑translational | Alternative splicing removes the PDZ-binding motif of Isoform 4 of Glutamate [NMDA] receptor subunit zeta-1 (GRIN1), abrogating binding to Disks large homolog 4 (DLG4). Binding of the PDZ domain of DLG4 suppresses an ER-retention motif in GRIN1, promoting its cell surface expression in a splice variant-specific manner. | ||
| NMDZ1_HUMAN | 917 | 922 | Specificity | Motif hiding | Binding of the PDZ domain of Disks large homolog 4 (DLG4) suppresses the ER-retention motif of Isoform 4 of Glutamate receptor subunit zeta-1 (GRIN1) in a splice variant-specific manner, thereby promoting cell surface expression of this particular isoform. This supports the hypothesis that local regulation of receptor exit from neuronal ER plays a role in modifying discrete synaptic receptor number. | ||
| NMDZ1_HUMAN | 917 | 922 | Binary | Pre‑translational | Alternative splicing removes the PDZ-binding motif of Isoform 4 of Glutamate [NMDA] receptor subunit zeta-1 (GRIN1), abrogating binding to Disks large homolog 4 (DLG4). Binding of the PDZ domain of DLG4 suppresses an ER-retention motif in GRIN1, promoting its cell surface expression in a splice variant-specific manner. | ||
| NMDZ1_HUMAN | 917 | 922 | Specificity | Motif hiding | Binding of the PDZ domain of Disks large homolog 4 (DLG4) suppresses the ER-retention motif of Isoform 4 of Glutamate receptor subunit zeta-1 (GRIN1) in a splice variant-specific manner, thereby promoting cell surface expression of this particular isoform. This supports the hypothesis that local regulation of receptor exit from neuronal ER plays a role in modifying discrete synaptic receptor number. | ||
| GUAD_HUMAN | 449 | 454 | Binary | Pre‑translational | Alternative splicing removes the PDZ-binding motif of Guanine deaminase (GDA) (Nedasin), abrogating binding to Disks large homolog 3 (DLG3). Isoform 1 of Guanine deaminase (GDA) (Nedasin S) is predominately expressed in neuronal tissues and binds PDZ domains. Isoform 3 of Guanine deaminase (GDA) (Nedasin V1), which is predominately expressed in non-neuronal tissues, does not bind PDZ domains. The presence of Nedasin S inhibits binding of NMDA receptors and K+ channels to PDZ domain-containing proteins such as members of the MAGUK family. This suggests that GDA might modulate the receptor clustering function of the PDZ domains of MAGUK family members, and this modulation is regulated by alternative splicing of GDA transcripts. | ||
| 5HT4R_MOUSE | 382 | 387 | Binary | Pre‑translational | Alternative splicing removes the PDZ-binding motif of Isoform 5-HT4(A) of 5-hydroxytryptamine receptor 4 (Htr4), abrogating binding to Na(+)/H(+) exchange regulatory cofactor NHE-RF1 (Slc9a3r1). Isoform 5-HT4(A) of 5-hydroxytryptamine receptor 4 (Htr4) interacts specifically with a protein complex including Slc9a3r1 and Ezrin (Ezr) that might participate in its targeting to specialised subcellular regions, such as microvilli. | ||
| PGFRB_HUMAN | 1101 | 1106 | Binary | Physicochemical compatibility | Phosphorylation of S1104 in the PDZ-binding motif of Platelet-derived growth factor receptor beta (PDGFRB) by Beta-adrenergic receptor kinase 1 (ADRBK1) inhibits binding to Na(+)/H(+) exchange regulatory cofactor NHE-RF1 (SLC9A3R1). Binding of Platelet-derived growth factor receptor beta (PDGFRB) to Na(+)/H(+) exchange regulatory cofactor NHE-RF1 (SLC9A3R1) potentiates dimerisation and signalling of the receptor, while phosphorylation at S1104 desensitises the receptor. | ||
LIG_PDZ_Class_2 - The C-terminal class 2 PDZ-binding motif is classically represented by a pattern such as (VYF)X(VIL)* | |||||||
| SDC1_HUMAN | 305 | 310 | Binary | Physicochemical compatibility | Phosphorylation of Y309 in the PDZ-binding motif of Syndecan-1 (SDC1) prevents binding to the PDZ domain of Syntenin-1 (SDCBP), an interaction involved in the formation of cellular protrusions. | ||
| APBA1_HUMAN | 832 | 837 | Specificity | Domain hiding | An intramolecular interaction of the C-terminal PDZ binding motif of Amyloid beta A4 precursor protein-binding family A member 1 (APBA1) (also known as X11alpha/Mint1) with the PDZ domain tandem of APBA1 results in an auto-inhibited conformation of APBA1, where binding of ligands containing a PDZ binding motif such as Presenilin-1 (PSEN1) is blocked. Binding of these ligands might be regulated by phosphorylation of Y836 in the APBA1 PDZ-binding motif, as its mutation to glutamate releases autoinhibition and enhances the interaction of the APBA1 PDZ tandem with presenilin. | ||
| PSN1_HUMAN | 462 | 467 | Specificity | Domain hiding | An intramolecular interaction of the C-terminal PDZ binding motif of Amyloid beta A4 precursor protein-binding family A member 1 (APBA1) (also known as X11alpha/Mint1) with the PDZ domain tandem of APBA1 results in an auto-inhibited conformation of APBA1, where binding of ligands containing a PDZ binding motif such as Presenilin-1 (PSEN1) is blocked. Binding of these ligands might be regulated by phosphorylation of Y836 in the APBA1 PDZ-binding motif, as its mutation to glutamate releases autoinhibition and enhances the interaction of the APBA1 PDZ tandem with presenilin. | ||
| 5HT4R_MOUSE | 368 | 371 | Binary | Pre‑translational | Alternative splicing removes the PDZ-binding motif of Isoform 5-HT4(E) of 5-hydroxytryptamine receptor 4 (Htr4), abrogating binding to InaD-like protein (Inadl). | ||
| GRIA2_RAT | 878 | 883 | Binary | Pre‑translational | Alternative splicing removes the PDZ-binding motif of Glutamate receptor 2 (Gria2), abrogating binding to PRKCA-binding protein (Pick1). The presence of PDZ-binding motifs is also seen in the short isoforms of Gria3 (Isoform Flop of Glutamate receptor 3 (Gria3)) and Gria4 (Isoform 4C flop of Glutamate receptor 4 (Gria4)). PRKCA-binding protein (Pick1) recruits both Protein kinase C alpha type (Prkca) and Gria2 simultaneously, possibly allowing Pick1 to play a role in the selective targeting to and possible anchoring of GluRshort-containing AMPA receptors to intracellular membrane-associated Prkca. | ||
LIG_PH_Tfb1 - | |||||||
| P53_HUMAN | 50 | 56 | Cumulative | Rheostatic | Multisite phosphorylation of S46 and T55 in the PH-like binding motif of Cellular tumor antigen p53 (TP53) gradually enhances its affinity for General transcription factor IIH subunit 1 (GTF2H1), an interaction involved in activation of transcription initiation and elongation by Cellular tumor antigen p53 (TP53). | ||
LIG_PI(4,5)P2 - | |||||||
| BIN1_HUMAN | 258 | 266 | Binary | Pre‑translational | Alternative splicing removes the PI(4,5)P2-binding motif of Isoform BIN1 of Myc box-dependent-interacting protein 1 (BIN1), abrogating binding to 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate. Splice-specific motifs in Isoform BIN1 of Myc box-dependent-interacting protein 1 (BIN1) engage in an intra-molecular interaction with its own SH3 domain. Auto-inhibition is relieved at the plasma membrane when an overlapping lipid-binding motif outcompetes the SH3-binding motif. This means that the SH3 domain is only available for inter-molecular interactions at the plasma membrane. | ||
LIG_PLK - | |||||||
| MPIP3_HUMAN | 129 | 131 | Binary | Physicochemical compatibility | Phosphorylation of T130 in the PLK-docking motif of M-phase inducer phosphatase 3 (CDC25C) by Cyclin-dependent kinase 1 (CDK1)-Cyclin AB subfamily generates a recruitment site for Serine/threonine-protein kinase PLK1 (PLK1), which then phosphorylates M-phase inducer phosphatase 3 (CDC25C). This results in inactivation of the NES of M-phase inducer phosphatase 3 (CDC25C), thereby promoting its nuclear localization. | ||
| MPIP2_HUMAN | 49 | 51 | Binary | Physicochemical compatibility | Phosphorylation of S50 in the PLK-docking motif of M-phase inducer phosphatase 2 (CDC25B) by Cyclin-dependent kinase 1 (CDK1)-Cyclin AB subfamily generates a recruitment site for Serine/threonine-protein kinase PLK1 (PLK1), which then phosphorylates and activates M-phase inducer phosphatase 2 (CDC25B). | ||
LIG_PTB_Apo_2 - These phosphorylation-independent motifs bind to Dab-like PTB domains. Binding is not driven by contacts at the 0 or FY position, but instead is dependent upon the large number of hydrophobic and hydrogen bond contacts between motif and domain. | |||||||
| A4_HUMAN | 756 | 763 | Binary | Physicochemical compatibility | Phosphorylation of T743 adjacent to the PTB-binding motif of Amyloid beta A4 protein (APP) reduces the affinity for Amyloid beta A4 precursor protein-binding family B member 1 (APBB1). | ||
| ITB3_HUMAN | 767 | 774 | Specificity | Altered binding specificity | Phosphorylation of Y773 in Integrin beta-3 (ITGB3) switches the specificity of ITGB3 from Talin-1 (TLN1) to Docking protein 1 (DOK1), with a 2-fold decrease of the affinity for TLN1 and close to a 400-fold increase of the affinity for DOK1. This switch results in negative regulation of integrin activation. | ||
| A4_HUMAN | 756 | 763 | Specificity | Altered binding specificity | Phosphorylation of Y757 in APP (Amyloid beta A4 protein (APP)) switches its specificity from PTB domain containing proteins, like Amyloid beta A4 precursor protein-binding family B member 1 (APBB1), which is involved in trafficking and processing of APP, to SH2 domain containing proteins, such as Growth factor receptor-bound protein 2 (GRB2). | ||
| ITB3_HUMAN | 779 | 786 | Specificity | Altered binding specificity | Phosphorylation of Integrin beta-3 (ITGB3) at Y785 switches the specificity of integrin from Kindlin-2 (Fermitin family homolog 2 (FERMT2)) to the adaptor protein SHC-transforming protein 1 (SHC1). | ||
LIG_PTB_Phospho_1 - This phosphorylation-dependent motif binds to Shc-like and IRS-like PTB domains. The pTyr is positioned within a highly basic-charged anchoring pocket. A hydrophobic residue -5 (compared to pY) increases the affinity of the interaction. | |||||||
| EGFR_HUMAN | 1104 | 1110 | Binary | Physicochemical compatibility | Phosphorylation of Y1110 in the PTB-binding motif of Epidermal growth factor receptor (EGFR) induces binding to the Docking protein 1 (DOK1) protein. | ||
| ERBB3_HUMAN | 1322 | 1328 | Binary | Physicochemical compatibility | Phosphorylation of Y1328 in the PTB-binding motif of Receptor tyrosine-protein kinase erbB-3 (ERBB3) induces binding to the SHC-transforming protein 1 (SHC1) protein. | ||
| IL2RB_HUMAN | 358 | 364 | Binary | Physicochemical compatibility | Phosphorylation of Y364 in the PTB-binding motif of Interleukin-2 receptor subunit beta (IL2RB) induces binding to the SHC-transforming protein 1 (SHC1) protein. | ||
| IL4RA_HUMAN | 491 | 497 | Binary | Physicochemical compatibility | Phosphorylation of Y497 in the PTB-binding motif of Interleukin-4 receptor subunit alpha (IL4R) induces binding to the Insulin receptor substrate 1 (IRS1) protein. | ||
| INSR_HUMAN | 993 | 999 | Binary | Physicochemical compatibility | Phosphorylation of Y999 in the PTB-binding motif of Insulin receptor (INSR) induces binding to the SHC-transforming protein 1 (SHC1) protein. | ||
| ITB3_HUMAN | 767 | 773 | Binary | Physicochemical compatibility | Phosphorylation of Y773 in the PTB-binding motif of Integrin beta-3 (ITGB3) induces binding to the Docking protein 1 (DOK1) protein. | ||
| ITB3_HUMAN | 779 | 785 | Binary | Physicochemical compatibility | Phosphorylation of Y785 in the PTB-binding motif of Integrin beta-3 (ITGB3) induces binding to the SHC-transforming protein 1 (SHC1) protein. | ||
| ITB4_HUMAN | 1590 | 1596 | Binary | Physicochemical compatibility | Phosphorylation of Y1596 in the PTB-binding motif of Integrin beta-4 (ITGB4) induces binding to the SHC-transforming protein 1 (SHC1) protein. | ||
| LRP1_HUMAN | 4501 | 4507 | Binary | Physicochemical compatibility | Phosphorylation of Y4507 in the PTB-binding motif of Prolow-density lipoprotein receptor-related protein 1 (LRP1) induces binding to the SHC-transforming protein 1 (SHC1) protein. | ||
| MT_POVMA | 244 | 250 | Binary | Physicochemical compatibility | Phosphorylation of Y250 in the PTB-binding motif of Middle T antigen induces binding to the SHC-transforming protein 1 (Shc1) protein. | ||
| MUSK_MOUSE | 547 | 553 | Binary | Physicochemical compatibility | Phosphorylation of Y553 in the PTB-binding motif of Muscle, skeletal receptor tyrosine-protein kinase (Musk) induces binding to the Protein Dok-7 (Dok7) protein. | ||
| NTRK1_HUMAN | 490 | 496 | Binary | Physicochemical compatibility | Phosphorylation of Y496 in the PTB-binding motif of High affinity nerve growth factor receptor (NTRK1) induces binding to the SHC-transforming protein 1 (SHC1) protein. | ||
| RET_MOUSE | 1057 | 1063 | Binary | Physicochemical compatibility | Phosphorylation of Y1063 in the PTB-binding motif of Proto-oncogene tyrosine-protein kinase receptor Ret (Ret) induces binding to the Docking protein 1 (Dok1) protein. | ||
| SHIP1_HUMAN | 1016 | 1022 | Binary | Physicochemical compatibility | Phosphorylation of Y1022 in the PTB-binding motif of Phosphatidylinositol-3,4,5-trisphosphate 5-phosphatase 1 (INPP5D) induces binding to the SHC-transforming protein 1 (SHC1) protein. | ||
| SHIP1_HUMAN | 909 | 915 | Binary | Physicochemical compatibility | Phosphorylation of Y915 in the PTB-binding motif of Phosphatidylinositol-3,4,5-trisphosphate 5-phosphatase 1 (INPP5D) induces binding to the SHC-transforming protein 1 (SHC1) protein. | ||
| ITB3_HUMAN | 779 | 785 | Binary | Physicochemical compatibility | Phosphorylation of T779 in the PTB-binding motif of Integrin beta-3 (ITGB3) inhibits its interaction with SHC-transforming protein 1 (SHC1). | ||
| ITB3_HUMAN | 779 | 785 | Cumulative | Rheostatic | While phosphorylation of Y785 in the PTB-binding motif of Integrin beta-3 (ITGB3) induces binding to SHC-transforming protein 1 (SHC1), additional phosphorylation of Y773 further increases the strength of the interaction. | ||
| ITB3_HUMAN | 767 | 773 | Specificity | Altered binding specificity | Phosphorylation of Y773 in Integrin beta-3 (ITGB3) switches the specificity of ITGB3 from Talin-1 (TLN1) to Docking protein 1 (DOK1), with a 2-fold decrease of the affinity for TLN1 and close to a 400-fold increase of the affinity for DOK1. This switch results in negative regulation of integrin activation. | ||
| ITB3_HUMAN | 779 | 785 | Specificity | Altered binding specificity | Phosphorylation of Integrin beta-3 (ITGB3) at Y785 switches the specificity of integrin from Kindlin-2 (Fermitin family homolog 2 (FERMT2)) to the adaptor protein SHC-transforming protein 1 (SHC1). | ||
LIG_PTB_Talin - | |||||||
| PI51C_HUMAN | 650 | 653 | Binary | Physicochemical compatibility | Phosphorylation of S650 in the PTB-binding motif of Phosphatidylinositol-4-phosphate 5-kinase type-1 gamma (PIP5K1C) blocks its interaction with Talin-1 (TLN1). Phosphorylation of Y649 by Src kinase enhances the interaction, possibly indirectly by inhibiting S650 phosphorylation. | ||
| PI51C_MOUSE | 645 | 648 | Binary | Pre‑translational | Alternative splicing removes the PTB domain-binding motif of Phosphatidylinositol 4-phosphate 5-kinase type-1 gamma (Pip5k1c), abrogating binding to Talin-1 (Tln1). Integrin receptors, Tln1 and Isoform PIPKIgamma661 of Phosphatidylinositol 4-phosphate 5-kinase type-1 gamma (Pip5k1c) (PIPKIgamma661) are recruited to focal adhesions, inducing synthesis of PI(4,5)P2. The regulated and localised generation of PI(4,5)P2 facilitates the assembly and/or disassembly of focal adhesions. | ||
| PI51C_MOUSE | 645 | 648 | Binary | Physicochemical compatibility | Phosphorylation of S645 in the PTB-binding motif of Phosphatidylinositol 4-phosphate 5-kinase type-1 gamma (Pip5k1c) by Cyclin-dependent kinase 5 (Cdk5) inhibits its interaction with Talin-1 (Tln1). | ||
| PI51C_MOUSE | 645 | 648 | Binary | Physicochemical compatibility | Phosphorylation of Y644 in Phosphatidylinositol 4-phosphate 5-kinase type-1 gamma (Pip5k1c) promotes its association with Talin-1 (Tln1). | ||
LIG_RGD - The RGD motif can be found in many proteins of the extracellular matrix and it is recognized by different members of the integrin family. The structure of the tenth type III module of fibronectin has shown that the RGD motif lies on an exposed flexible lo | |||||||
| EDIL3_HUMAN | 96 | 98 | Pre‑assembly | Composite binding site formation | Binding of EGF-like repeat and discoidin I-like domain-containing protein 3 (EDIL3) to integrin receptors depends on pre-assembly of Integrin alpha-V (ITGAV)-Integrin beta-3 (ITGB3) heterodimers, since association of the integrin alpha and beta subunits results in the formation of a composite binding site for the RGD motif in the ligand. | ||
| DISG_TRIAB | 51 | 53 | Pre‑assembly | Composite binding site formation | Binding of Disintegrin albolabrin to integrin receptors depends on pre-assembly of Integrin alpha-IIb (ITGA2B)-Integrin beta-3 (ITGB3) heterodimers, since association of the integrin alpha and beta subunits results in the formation of a composite binding site for the RGD motif in the ligand. | ||
| FINC_HUMAN | 1524 | 1526 | Pre‑assembly | Composite binding site formation | Binding of Fibronectin (FN1) to integrin receptors depends on pre-assembly of Integrin alpha-V (ITGAV)-Integrin beta-3 (ITGB3) heterodimers, since association of the integrin alpha and beta subunits results in the formation of a composite binding site for the RGD motif in the ligand. | ||
| POLG_FMDVO | 869 | 871 | Pre‑assembly | Composite binding site formation | Binding of Genome polyprotein to integrin receptors depends on pre-assembly of Integrin alpha-V (ITGAV)-Integrin beta-3 (ITGB3) heterodimers, since association of the integrin alpha and beta subunits results in the formation of a composite binding site for the RGD motif in the ligand. | ||
| VTNC_HUMAN | 64 | 66 | Pre‑assembly | Composite binding site formation | Binding of Vitronectin (VTN) to integrin receptors depends on pre-assembly of Integrin alpha-V (ITGAV)-Integrin beta-3 (ITGB3) heterodimers, since association of the integrin alpha and beta subunits results in the formation of a composite binding site for the RGD motif in the ligand. | ||
| VWF_HUMAN | 2507 | 2509 | Pre‑assembly | Composite binding site formation | Binding of von Willebrand factor (VWF) to integrin receptors depends on pre-assembly of Integrin alpha-V (ITGAV)-Integrin beta-3 (ITGB3) heterodimers, since association of the integrin alpha and beta subunits results in the formation of a composite binding site for the RGD motif in the ligand. | ||
| OSTP_HUMAN | 159 | 161 | Pre‑assembly | Composite binding site formation | Binding of EGF-like repeat and discoidin I-like domain-containing protein 3 (EDIL3) to integrin receptors depends on pre-assembly of Integrin alpha-V (ITGAV)-Integrin beta-3 (ITGB3) heterodimers, since association of the integrin alpha and beta subunits results in the formation of a composite binding site for the RGD motif in the ligand. | ||
| FINC_MOUSE | 1614 | 1616 | Pre‑assembly | Composite binding site formation | Binding of Fibronectin (Fn1) to integrin receptors depends on pre-assembly of Integrin alpha-5 (Itga5)-Integrin beta-1 (Itgb1) heterodimers, since association of the integrin alpha and beta subunits results in the formation of a composite binding site for the RGD motif in the ligand. | ||
| VME1_TRIEL | 459 | 461 | Pre‑assembly | Composite binding site formation | Binding of Zinc metalloproteinase/disintegrin to integrin receptors depends on pre-assembly of Integrin alpha-IIb (ITGA2B)-Integrin beta-3 (ITGB3) heterodimers, since association of the integrin alpha and beta subunits results in the formation of a composite binding site for the RGD motif in the ligand. | ||
| DISB_TRIGA | 51 | 53 | Pre‑assembly | Composite binding site formation | Binding of Disintegrin trigramin-beta-2 to integrin receptors depends on pre-assembly of Integrin alpha-IIb (ITGA2B)-Integrin beta-3 (ITGB3) heterodimers, since association of the integrin alpha and beta subunits results in the formation of a composite binding site for the RGD motif in the ligand. | ||
| POLG_CXA9 | 858 | 860 | Pre‑assembly | Composite binding site formation | Binding of Genome polyprotein to integrin receptors depends on pre-assembly of Integrin alpha-V (ITGAV)-Integrin beta-6 (ITGB6) heterodimers, since association of the integrin alpha and beta subunits results in the formation of a composite binding site for the RGD motif in the ligand. | ||
| VTNC_MOUSE | 64 | 66 | Pre‑assembly | Composite binding site formation | Binding of Vitronectin (Vtn) to integrin receptors depends on pre-assembly of Integrin alpha-V (Itgav)-Integrin beta-3 (Itgb3) heterodimers, since association of the integrin alpha and beta subunits results in the formation of a composite binding site for the RGD motif in the ligand. | ||
| POLG_HPE1H | 764 | 766 | Pre‑assembly | Composite binding site formation | Binding of Genome polyprotein to integrin receptors depends on pre-assembly of Integrin alpha-V (ITGAV)-Integrin beta-6 (ITGB6) heterodimers, since association of the integrin alpha and beta subunits results in the formation of a composite binding site for the RGD motif in the ligand. | ||
LIG_RhoGAP_OCRL_1 - | |||||||
| DP13A_HUMAN | 403 | 415 | Binary | Physicochemical compatibility | Phosphorylation of S403 in the RhoGAP-binding motif of DCC-interacting protein 13-alpha (APPL1), possibly by PKA, inhibits its interaction with Inositol polyphosphate 5-phosphatase OCRL-1 (OCRL). | ||
| DP13A_HUMAN | 403 | 415 | Binary | Physicochemical compatibility | Phosphorylation of S410 in the RhoGAP-binding motif of DCC-interacting protein 13-alpha (APPL1) inhibits its interaction with Inositol polyphosphate 5-phosphatase OCRL-1 (OCRL). | ||
LIG_SH2_GRB2 - GRB2-like Src Homology 2 (SH2) domains binding motif. | |||||||
| IRS1_RAT | 895 | 898 | Binary | Physicochemical compatibility | Phosphorylation of Y895 in the SH2-binding motif of Insulin receptor substrate 1 (Irs1) induces binding to the Growth factor receptor-bound protein 2 (Grb2) protein. | ||
| A4_HUMAN | 757 | 760 | Cumulative | Rheostatic | While phosphorylation of Y757 in the SH2-binding motif of Amyloid beta A4 protein (APP) induces binding to Growth factor receptor-bound protein 2 (GRB2), additional phosphorylation of T743 further increases the strength of the interaction. | ||
| A4_HUMAN | 757 | 760 | Specificity | Altered binding specificity | Phosphorylation of Y757 in APP (Amyloid beta A4 protein (APP)) switches its specificity from PTB domain containing proteins, like Amyloid beta A4 precursor protein-binding family B member 1 (APBB1), which is involved in trafficking and processing of APP, to SH2 domain containing proteins, such as Growth factor receptor-bound protein 2 (GRB2). | ||
| LAT_MOUSE | 175 | 178 | Binary | Physicochemical compatibility | Phosphorylation of Y175 in the SH2-binding motif of Linker for activation of T-cells family member 1 (Lat) induces binding to the Growth factor receptor-bound protein 2 (Grb2) protein. | ||
| LAT_MOUSE | 195 | 198 | Binary | Physicochemical compatibility | Phosphorylation of Y195 in the SH2-binding motif of Linker for activation of T-cells family member 1 (Lat) induces binding to the Growth factor receptor-bound protein 2 (Grb2) protein. | ||
| LAT_MOUSE | 235 | 238 | Binary | Physicochemical compatibility | Phosphorylation of Y235 in the SH2-binding motif of Linker for activation of T-cells family member 1 (Lat) induces binding to the Growth factor receptor-bound protein 2 (Grb2) protein. | ||
| ERBB3_HUMAN | 1262 | 1265 | Binary | Physicochemical compatibility | Phosphorylation of Y1262 in the SH2-binding motif of Receptor tyrosine-protein kinase erbB-3 (ERBB3) induces binding to Growth factor receptor-bound protein 2 (GRB2). | ||
LIG_SH2_IA - | |||||||
| IL2RB_HUMAN | 409 | 428 | Binary | Physicochemical compatibility | Phosphorylation of Y418 in the SH2-binding motif of Interleukin-2 receptor subunit beta (IL2RB) induces binding to the Tyrosine-protein kinase Lck (LCK) protein. | ||
| EPHA3_HUMAN | 597 | 606 | Binary | Physicochemical compatibility | Phosphorylation of Y602 in the SH2-binding motif of Ephrin type-A receptor 3 (EPHA3) induces binding to the Cytoplasmic protein NCK1 (NCK1) protein. | ||
| FCERG_HUMAN | 75 | 79 | Binary | Physicochemical compatibility | Phosphorylation of Y76 in the SH2-binding motif of High affinity immunoglobulin epsilon receptor subunit gamma (FCER1G) induces binding to the Tyrosine-protein kinase SYK (SYK) protein. | ||
| FAK1_HUMAN | 389 | 405 | Binary | Physicochemical compatibility | Phosphorylation of Y397 in the SH2-binding motif of Focal adhesion kinase 1 (PTK2) induces binding to the Cytoplasmic protein NCK2 (NCK2) protein. | ||
| NTRK2_HUMAN | 714 | 730 | Binary | Physicochemical compatibility | Phosphorylation of Y727 in the SH2-binding motif of BDNF/NT-3 growth factors receptor (NTRK2) induces binding to the Cytoplasmic protein NCK2 (NCK2) protein. | ||
| LCP2_MOUSE | 143 | 148 | Binary | Physicochemical compatibility | Phosphorylation of Y145 in the SH2-binding motif of Lymphocyte cytosolic protein 2 (Lcp2) induces binding to the Tyrosine-protein kinase ITK/TSK (Itk) protein. | ||
| GBLP_RAT | 241 | 250 | Binary | Physicochemical compatibility | Phosphorylation of Y246 in the SH2-binding motif of Guanine nucleotide-binding protein subunit beta-2-like 1 (Gnb2l1) induces binding to the Proto-oncogene tyrosine-protein kinase Src (SRC) protein. | ||
| DCD_HUMAN | 15 | 25 | Binary | Physicochemical compatibility | Phosphorylation of Y20 in the SH2-binding motif of Dermcidin (DCD) induces binding to the Cytoplasmic protein NCK1 (NCK1) protein. | ||
| DAB1_MOUSE | 212 | 228 | Binary | Physicochemical compatibility | Phosphorylation of Y220 in the SH2-binding motif of Disabled homolog 1 (Dab1) induces binding to the Cytoplasmic protein NCK2 (NCK2) protein. | ||
| DAB1_MOUSE | 220 | 223 | Binary | Pre‑translational | Alternative splicing removes the SH2-binding motif of Disabled homolog 1 (Dab1), abrogating binding to Cytoplasmic protein NCK2 (NCK2). NCK2-beta has a clear preference for splice variant 2 (with the YQYI motif) over splice variant 3 (with the YQTI motif). The authors theorise that since Adapter molecule crk (Crk) is directly linked to the C3G-Rap1 pathway, and NCK2-beta is linked to the Breast cancer anti-estrogen resistance protein 1 (Bcar1) (p130Cas) pathway, it is likely that isoforms 2 and 3 connect to different downstream cascades. It was suggested that the ability of different Dab1 isoforms to recruit distinct sets of SH2 domains implies a fine-tuning role of Dab1 splicing in the intricate series of events that underlie neuronal migration (Gao et al. (2012) (here)) (See also Katyal and Godbout (2004) (here) and Gao et al. (2010) (here)). | ||
| DAB1_MOUSE | 232 | 235 | Binary | Pre‑translational | Alternative splicing removes the SH2-binding motif of Disabled homolog 1 (Dab1), abrogating binding to Cytoplasmic protein NCK2 (NCK2). The NCK2-beta has a clear preference for splice variant 2 (with YQYI motif) over splice variant 3 (with YQTI motif). The authors theorise that since Adapter molecule crk (Crk) is directly linked to the C3G-Rap1 pathway, and NCK2-beta is linked to the Breast cancer anti-estrogen resistance protein 1 (Bcar1) (p130Cas) pathway, it is likely that isoforms 2 and 3 connect to different downstream cascades. It was suggested that the ability of different Dab1 isoforms to recruit distinct sets of SH2 domains implies a fine-tuning role of Dab1 splicing in the intricate series of events that underlie neuronal migration (Gao et al. (2012) (here)) (See also Katyal and Godbout (2004) (here) and Gao et al. (2010) (here)). | ||
| DAB1_MOUSE | 220 | 223 | Binary | Pre‑translational | Alternative splicing removes the SH2-binding motif of Disabled homolog 1 (Dab1), abrogating binding to Adapter molecule crk (Crk). Both Adapter molecule crk (Crk) and Crk-like protein (Crkl) bind equally well to variants 2 and 3. The authors theorise that since Adapter molecule crk (Crk) is directly linked to the C3G-Rap1 pathway, and NCK2-beta is linked to the Breast cancer anti-estrogen resistance protein 1 (Bcar1) (p130Cas) pathway, it is likely that isoforms 2 and 3 connect to different downstream cascades. It was suggested that the ability of different Dab1 isoforms to recruit distinct sets of SH2 domains implies a fine-tuning role of Dab1 splicing in the intricate series of events that underlie neuronal migration (Gao et al. (2012) (here)) (See also Katyal and Godbout (2004) (here) and Gao et al. (2010) (here)). | ||
| DAB1_MOUSE | 232 | 235 | Binary | Pre‑translational | Alternative splicing removes the SH2-binding motif of Disabled homolog 1 (Dab1), abrogating binding to Adapter molecule crk (Crk). Both Adapter molecule crk (Crk) and Crk-like protein (Crkl) bind equally well to variants 2 and 3. The authors theorise that since Adapter molecule crk (Crk) is directly linked to the C3G-Rap1 pathway, and NCK2-beta is linked to the Breast cancer anti-estrogen resistance protein 1 (Bcar1) (p130Cas) pathway, it is likely that isoforms 2 and 3 connect to different downstream cascades. It was suggested that the ability of different Dab1 isoforms to recruit distinct sets of SH2 domains implies a fine-tuning role of Dab1 splicing in the intricate series of events that underlie neuronal migration (Gao et al. (2012) (here)) (See also Katyal and Godbout (2004) (here) and Gao et al. (2010) (here)). | ||
| DAB1_MOUSE | 185 | 188 | Binary | Pre‑translational | Alternative splicing removes the SH2-binding motif of Disabled homolog 1 (Dab1), abrogating binding to Neuronal proto-oncogene tyrosine-protein kinase Src (Src). Splice variants 2 and 3 (only containing one of the YQxI motifs, i.e. Y185 and Y198) exhibit decreased tyrosine phosphorylation, suggesting both motifs are required for full activation of Dab1. Dab1 is likely to recruit Neuronal proto-oncogene tyrosine-protein kinase Src (Src) via these two YQxI motifs, which subsequently phosphorylates adjacent YxVP motifs (here). This was also suggested for Phosphatidylinositol 3-kinase regulatory subunit alpha (Pik3r1) and Suppressor of cytokine signaling 2 (Socs2). Gao et al. (2012) (here) suggests that the ability of different Dab1 isoforms to recruit distinct sets of SH2 domains allows a fine-tuning role for Dab1 splicing in the intricate series of events that underlie neuronal migration (See also Katyal & Godbout (2004) (here) and Gao et al. (2010) (here)). | ||
| DAB1_MOUSE | 232 | 235 | Binary | Physicochemical compatibility | Phosphorylation of Y232 in the SH2-binding motif of Disabled homolog 1 (Dab1) induces binding to Cytoplasmic protein NCK2 (NCK2). | ||
| DAB1_MOUSE | 232 | 235 | Binary | Physicochemical compatibility | Phosphorylation of Y232 in the SH2-binding motif of Disabled homolog 1 (Dab1) induces binding to Adapter molecule crk (Crk). | ||
| DAB1_MOUSE | 185 | 188 | Binary | Physicochemical compatibility | Phosphorylation of Y185 in the SH2-binding motif of Disabled homolog 1 (Dab1) induces binding to Neuronal proto-oncogene tyrosine-protein kinase Src (Src). | ||
LIG_SH2_IB - | |||||||
| DAB1_HUMAN | 211 | 230 | Binary | Physicochemical compatibility | Phosphorylation of Y220 in the SH2-binding motif of Disabled homolog 1 (DAB1) induces binding to the Adapter molecule crk (CRK) protein. | ||
| NTRK1_HUMAN | 783 | 796 | Binary | Physicochemical compatibility | Phosphorylation of Y791 in the SH2-binding motif of High affinity nerve growth factor receptor (NTRK1) induces binding to the Megakaryocyte-associated tyrosine-protein kinase (MATK) protein. | ||
| CBL_HUMAN | 770 | 780 | Binary | Physicochemical compatibility | Phosphorylation of Y774 in the SH2-binding motif of E3 ubiquitin-protein ligase CBL (CBL) induces binding to the Adapter molecule crk (CRK) protein. | ||
| DOK1_HUMAN | 447 | 454 | Binary | Physicochemical compatibility | Phosphorylation of Y449 in the SH2-binding motif of Docking protein 1 (DOK1) induces binding to the SH2 domain-containing protein 1A (SH2D1A) protein. | ||
| SLAF1_HUMAN | 276 | 286 | Binary | Physicochemical compatibility | Phosphorylation of Y281 in the SH2-binding motif of Signaling lymphocytic activation molecule (SLAMF1) induces binding to the SH2 domain-containing protein 1A (SH2D1A) protein. | ||
| SLAF1_HUMAN | 273 | 286 | Binary | Physicochemical compatibility | Phosphorylation of Y281 in the SH2-binding motif of Signaling lymphocytic activation molecule (SLAMF1) induces binding to the SH2 domain-containing protein 1B (Sh2d1b) protein. | ||
| FAK2_HUMAN | 394 | 410 | Binary | Physicochemical compatibility | Phosphorylation of Y402 in the SH2-binding motif of Protein-tyrosine kinase 2-beta (PTK2B) induces binding to the Megakaryocyte-associated tyrosine-protein kinase (MATK) protein. | ||
| BCAR1_HUMAN | 358 | 368 | Binary | Physicochemical compatibility | Phosphorylation of Y362 in the SH2-binding motif of Breast cancer anti-estrogen resistance protein 1 (BCAR1) induces binding to the Adapter molecule crk (CRK) protein. | ||
| EPHB2_MOUSE | 601 | 610 | Binary | Physicochemical compatibility | Phosphorylation of Y604 in the SH2-binding motif of Ephrin type-B receptor 2 (Ephb2) induces binding to the Adapter molecule crk (CRK) protein. | ||
| EPHB2_MOUSE | 606 | 620 | Binary | Physicochemical compatibility | Phosphorylation of Y610 in the SH2-binding motif of Ephrin type-B receptor 2 (Ephb2) induces binding to the Adapter molecule crk (CRK) protein. | ||
| PAXI_HUMAN | 118 | 121 | Binary | Pre‑translational | Alternative splicing removes the SH2-binding motif of Paxillin (PXN), abrogating binding to Ras GTPase-activating protein 1 (RASA1). | ||
| PAXI_HUMAN | 118 | 121 | Binary | Pre‑translational | Alternative splicing removes the SH2-binding motif of Paxillin (PXN), abrogating binding to Adapter molecule crk (CRK). | ||
| PAXI_HUMAN | 31 | 34 | Binary | Pre‑translational | Alternative splicing removes the SH2-binding motif of Paxillin (PXN), abrogating binding to Adapter molecule crk (CRK). | ||
| PAXI_HUMAN | 118 | 121 | Binary | Pre‑translational | Alternative splicing removes the SH2-binding motif of Paxillin (PXN), abrogating binding to Ras GTPase-activating protein 1 (RASA1). | ||
LIG_SH2_IC - | |||||||
| A9UF02_HUMAN | 174 | 180 | Binary | Physicochemical compatibility | Phosphorylation of Y177 in the SH2-binding motif of BCR/ABL fusion induces binding to the Growth factor receptor-bound protein 2 (GRB2) protein. | ||
| PDPK1_HUMAN | 376 | 379 | Binary | Physicochemical compatibility | Phosphorylation of Y376 in the SH2-binding motif of 3-phosphoinositide-dependent protein kinase 1 (PDPK1) induces binding to the Tensin-1 (TNS1) protein. | ||
| LAT_HUMAN | 198 | 203 | Binary | Physicochemical compatibility | Phosphorylation of Y200 in the SH2-binding motif of Linker for activation of T-cells family member 1 (LAT) induces binding to the GRB2-related adaptor protein 2 (Grap2) protein. | ||
| LAT_HUMAN | 218 | 223 | Binary | Physicochemical compatibility | Phosphorylation of Y220 in the SH2-binding motif of Linker for activation of T-cells family member 1 (LAT) induces binding to the GRB2-related adaptor protein 2 (Grap2) protein. | ||
| DOK2_HUMAN | 402 | 405 | Binary | Physicochemical compatibility | Phosphorylation of Y402 in the SH2-binding motif of Docking protein 2 (DOK2) induces binding to the Tensin-1 (TNS1) protein. | ||
| EGFR_HUMAN | 1092 | 1100 | Binary | Physicochemical compatibility | Phosphorylation of Y1092 in the SH2-binding motif of Epidermal growth factor receptor (EGFR) induces binding to the Growth factor receptor-bound protein 2 (GRB2) protein. | ||
| ERBB2_HUMAN | 1135 | 1144 | Binary | Physicochemical compatibility | Phosphorylation of Y1139 in the SH2-binding motif of Receptor tyrosine-protein kinase erbB-2 (ERBB2) induces binding to the Growth factor receptor-bound protein 7 (GRB7) protein. | ||
| MET_HUMAN | 1351 | 1360 | Binary | Physicochemical compatibility | Phosphorylation of Y1356 in the SH2-binding motif of Hepatocyte growth factor receptor (MET) induces binding to the Growth factor receptor-bound protein 2 (GRB2) protein. | ||
| SHC1_HUMAN | 423 | 435 | Binary | Physicochemical compatibility | Phosphorylation of Y427 in the SH2-binding motif of SHC-transforming protein 1 (SHC1) induces binding to the Growth factor receptor-bound protein 2 (GRB2) protein. | ||
| FRS2_HUMAN | 191 | 200 | Binary | Physicochemical compatibility | Phosphorylation of Y196 in the SH2-binding motif of Fibroblast growth factor receptor substrate 2 (FRS2) induces binding to the Growth factor receptor-bound protein 2 (GRB2) protein. | ||
| FRS2_HUMAN | 301 | 310 | Binary | Physicochemical compatibility | Phosphorylation of Y306 in the SH2-binding motif of Fibroblast growth factor receptor substrate 2 (FRS2) induces binding to the Growth factor receptor-bound protein 2 (GRB2) protein. | ||
| FRS2_HUMAN | 345 | 355 | Binary | Physicochemical compatibility | Phosphorylation of Y349 in the SH2-binding motif of Fibroblast growth factor receptor substrate 2 (FRS2) induces binding to the Growth factor receptor-bound protein 2 (GRB2) protein. | ||
| FRS2_HUMAN | 385 | 395 | Binary | Physicochemical compatibility | Phosphorylation of Y392 in the SH2-binding motif of Fibroblast growth factor receptor substrate 2 (FRS2) induces binding to the Growth factor receptor-bound protein 2 (GRB2) protein. | ||
LIG_SH2_ID - | |||||||
| EGFR_HUMAN | 1008 | 1024 | Binary | Physicochemical compatibility | Phosphorylation of Y1016 in the SH2-binding motif of Epidermal growth factor receptor (EGFR) induces binding to the SH2 domain-containing protein 3C (SH2D3C) protein. | ||
| EGFR_HUMAN | 1008 | 1024 | Binary | Physicochemical compatibility | Phosphorylation of Y1016 in the SH2-binding motif of Epidermal growth factor receptor (EGFR) induces binding to the SH2 domain-containing protein 3A (SH2D3A) protein. | ||
| ERBB2_HUMAN | 1131 | 1147 | Binary | Physicochemical compatibility | Phosphorylation of Y1139 in the SH2-binding motif of Receptor tyrosine-protein kinase erbB-2 (ERBB2) induces binding to the Breast cancer anti-estrogen resistance protein 3 (BCAR3) protein. | ||
| ERBB2_HUMAN | 1015 | 1031 | Binary | Physicochemical compatibility | Phosphorylation of Y1023 in the SH2-binding motif of Receptor tyrosine-protein kinase erbB-2 (ERBB2) induces binding to the SH2 domain-containing protein 3A (SH2D3A) protein. | ||
| ERBB3_HUMAN | 860 | 876 | Binary | Physicochemical compatibility | Phosphorylation of Y868 in the SH2-binding motif of Receptor tyrosine-protein kinase erbB-3 (ERBB3) induces binding to the Breast cancer anti-estrogen resistance protein 3 (BCAR3) protein. | ||
| ERBB3_HUMAN | 1268 | 1284 | Binary | Physicochemical compatibility | Phosphorylation of Y1276 in the SH2-binding motif of Receptor tyrosine-protein kinase erbB-3 (ERBB3) induces binding to the Breast cancer anti-estrogen resistance protein 3 (BCAR3) protein. | ||
| ERBB3_HUMAN | 1281 | 1297 | Binary | Physicochemical compatibility | Phosphorylation of Y1289 in the SH2-binding motif of Receptor tyrosine-protein kinase erbB-3 (ERBB3) induces binding to the Breast cancer anti-estrogen resistance protein 3 (BCAR3) protein. | ||
| ERBB3_HUMAN | 1320 | 1336 | Binary | Physicochemical compatibility | Phosphorylation of Y1328 in the SH2-binding motif of Receptor tyrosine-protein kinase erbB-3 (ERBB3) induces binding to the Breast cancer anti-estrogen resistance protein 3 (BCAR3) protein. | ||
| ERBB3_HUMAN | 1320 | 1336 | Binary | Physicochemical compatibility | Phosphorylation of Y1328 in the SH2-binding motif of Receptor tyrosine-protein kinase erbB-3 (ERBB3) induces binding to the SH2 domain-containing protein 3A (SH2D3A) protein. | ||
LIG_SH2_IE - | |||||||
| EGFR_HUMAN | 1011 | 1020 | Binary | Physicochemical compatibility | Phosphorylation of Y1016 in the SH2-binding motif of Epidermal growth factor receptor (EGFR) induces binding to the Ras and Rab interactor 1 (RIN1) protein. | ||
| EGFR_HUMAN | 1191 | 1200 | Binary | Physicochemical compatibility | Phosphorylation of Y1197 in the SH2-binding motif of Epidermal growth factor receptor (EGFR) induces binding to the Ras and Rab interactor 1 (RIN1) protein. | ||
| EGFR_HUMAN | 1008 | 1024 | Binary | Physicochemical compatibility | Phosphorylation of Y1016 in the SH2-binding motif of Epidermal growth factor receptor (EGFR) induces binding to the Tyrosine-protein kinase JAK1 (JAK1) protein. | ||
| EGFR_HUMAN | 1008 | 1024 | Binary | Physicochemical compatibility | Phosphorylation of Y1016 in the SH2-binding motif of Epidermal growth factor receptor (EGFR) induces binding to the Tyrosine-protein kinase JAK2 (JAK2) protein. | ||
| ERBB2_HUMAN | 1015 | 1031 | Binary | Physicochemical compatibility | Phosphorylation of Y1023 in the SH2-binding motif of Receptor tyrosine-protein kinase erbB-2 (ERBB2) induces binding to the Tyrosine-protein kinase JAK1 (JAK1) protein. | ||
| ERBB2_HUMAN | 1015 | 1031 | Binary | Physicochemical compatibility | Phosphorylation of Y1023 in the SH2-binding motif of Receptor tyrosine-protein kinase erbB-2 (ERBB2) induces binding to the Tyrosine-protein kinase JAK2 (JAK2) protein. | ||
| INAR1_HUMAN | 458 | 474 | Binary | Physicochemical compatibility | Phosphorylation of Y466 in the SH2-binding motif of Interferon alpha/beta receptor 1 (IFNAR1) induces binding to the Non-receptor tyrosine-protein kinase TYK2 (TYK2) protein. | ||
| INAR1_HUMAN | 473 | 489 | Binary | Physicochemical compatibility | Phosphorylation of Y481 in the SH2-binding motif of Interferon alpha/beta receptor 1 (IFNAR1) induces binding to the Non-receptor tyrosine-protein kinase TYK2 (TYK2) protein. | ||
| ERBB3_HUMAN | 1320 | 1336 | Binary | Physicochemical compatibility | Phosphorylation of Y1328 in the SH2-binding motif of Receptor tyrosine-protein kinase erbB-3 (ERBB3) induces binding to the Tyrosine-protein kinase JAK1 (JAK1) protein. | ||
| ERBB3_HUMAN | 1320 | 1336 | Binary | Physicochemical compatibility | Phosphorylation of Y1328 in the SH2-binding motif of Receptor tyrosine-protein kinase erbB-3 (ERBB3) induces binding to the Tyrosine-protein kinase JAK2 (JAK2) protein. | ||
| ERBB3_HUMAN | 1268 | 1284 | Binary | Physicochemical compatibility | Phosphorylation of Y1276 in the SH2-binding motif of Receptor tyrosine-protein kinase erbB-3 (ERBB3) induces binding to the Tyrosine-protein kinase JAK2 (JAK2) protein. | ||
| ERBB3_HUMAN | 1268 | 1284 | Binary | Physicochemical compatibility | Phosphorylation of Y1276 in the SH2-binding motif of Receptor tyrosine-protein kinase erbB-3 (ERBB3) induces binding to the Tyrosine-protein kinase JAK3 (JAK3) protein. | ||
LIG_SH2_IIA - | |||||||
| PGFRB_HUMAN | 751 | 755 | Binary | Physicochemical compatibility | Phosphorylation of Y751 in the SH2-binding motif of Platelet-derived growth factor receptor beta (PDGFRB) induces binding to the Phosphatidylinositol 3-kinase regulatory subunit alpha (PIK3R1) protein. | ||
| PGFRB_HUMAN | 1018 | 1029 | Binary | Physicochemical compatibility | Phosphorylation of Y1021 in the SH2-binding motif of Platelet-derived growth factor receptor beta (PDGFRB) induces binding to the 1-phosphatidylinositol-4,5-bisphosphate phosphodiesterase gamma-1 (PLCG1) protein. | ||
| GHR_HUMAN | 591 | 600 | Binary | Physicochemical compatibility | Phosphorylation of Y595 in the SH2-binding motif of Growth hormone receptor (GHR) induces binding to the Tyrosine-protein phosphatase non-receptor type 11 (PTPN11) protein. | ||
| IL4RA_HUMAN | 706 | 721 | Binary | Physicochemical compatibility | Phosphorylation of Y713 in the SH2-binding motif of Interleukin-4 receptor subunit alpha (IL4R) induces binding to the Tyrosine-protein phosphatase non-receptor type 11 (PTPN11) protein. | ||
| FRS2_HUMAN | 431 | 440 | Binary | Physicochemical compatibility | Phosphorylation of Y436 in the SH2-binding motif of Fibroblast growth factor receptor substrate 2 (FRS2) induces binding to the Tyrosine-protein phosphatase non-receptor type 11 (PTPN11) protein. | ||
| FRS2_HUMAN | 465 | 475 | Binary | Physicochemical compatibility | Phosphorylation of Y471 in the SH2-binding motif of Fibroblast growth factor receptor substrate 2 (FRS2) induces binding to the Tyrosine-protein phosphatase non-receptor type 11 (PTPN11) protein. | ||
| CSF3R_HUMAN | 747 | 758 | Binary | Physicochemical compatibility | Phosphorylation of Y752 in the SH2-binding motif of Granulocyte colony-stimulating factor receptor (CSF3R) induces binding to the Suppressor of cytokine signaling 3 (SOCS3) protein. | ||
| IL6RB_MOUSE | 750 | 764 | Binary | Physicochemical compatibility | Phosphorylation of Y757 in the SH2-binding motif of Interleukin-6 receptor subunit beta (Il6st) induces binding to the Suppressor of cytokine signaling 3 (Socs3) protein. | ||
| IL4RA_HUMAN | 706 | 721 | Binary | Physicochemical compatibility | Phosphorylation of Y713 in the SH2-binding motif of Interleukin-4 receptor subunit alpha (IL4R) induces binding to the Tyrosine-protein phosphatase non-receptor type 6 (PTPN6) protein. | ||
| ERBB4_HUMAN | 1056 | 1059 | Binary | Pre‑translational | Alternative splicing removes the SH2-binding motif of Receptor tyrosine-protein kinase erbB-4 (ERBB4), abrogating binding to Phosphatidylinositol 3-kinase regulatory subunit alpha (PIK3R1). The SH2-binding motif overlaps with a WW-binding motif. Binding of these motifs is regulated in a phosphorylation-dependent manner, ensuring ERBB4 is either endocytosed or stabilised. | ||
| SHIP1_HUMAN | 918 | 921 | Binary | Pre‑translational | Alternative splicing partially removes the SH2-binding motif of Phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 1 (Inpp5d), partially inhibiting binding to Phosphatidylinositol 3-kinase regulatory subunit alpha (Pik3r1). | ||
| SHIP1_HUMAN | 918 | 921 | Binary | Pre‑translational | Alternative splicing partially removes the SH2-binding motif of Phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 1 (Inpp5d), partially inhibiting binding to Phosphatidylinositol 3-kinase regulatory subunit alpha (Pik3r1). | ||
| ERBB4_HUMAN | 1056 | 1059 | Binary | Pre‑translational | Alternative splicing removes the SH2-binding motif of Receptor tyrosine-protein kinase erbB-4 (ERBB4), abrogating binding to Phosphatidylinositol 3-kinase regulatory subunit alpha (PIK3R1). The SH2-binding motif overlaps with a WW-binding motif. Binding of these motifs is regulated in a phosphorylation-dependent manner, ensuring ERBB4 is either endocytosed or stabilised. | ||
LIG_SH2_IIB - | |||||||
| JAK2_HUMAN | 804 | 823 | Binary | Physicochemical compatibility | Phosphorylation of Y813 in the SH2-binding motif of Tyrosine-protein kinase JAK2 (JAK2) induces binding to the SH2B adapter protein 1 (SH2B1) protein. | ||
| NTRK1_HUMAN | 782 | 796 | Binary | Physicochemical compatibility | Phosphorylation of Y791 in the SH2-binding motif of High affinity nerve growth factor receptor (NTRK1) induces binding to the SHC-transforming protein 1 (SHC1) protein. | ||
| RET_HUMAN | 976 | 985 | Binary | Physicochemical compatibility | Phosphorylation of Y981 in the SH2-binding motif of Proto-oncogene tyrosine-protein kinase receptor Ret (RET) induces binding to the SH2B adapter protein 1 (SH2B1) protein. | ||
| IL2RB_HUMAN | 361 | 370 | Binary | Physicochemical compatibility | Phosphorylation of Y364 in the SH2-binding motif of Interleukin-2 receptor subunit beta (IL2RB) induces binding to the SHC-transforming protein 1 (SHC1) protein. | ||
| VAV_HUMAN | 165 | 180 | Binary | Physicochemical compatibility | Phosphorylation of Y174 in the SH2-binding motif of Proto-oncogene vav (VAV1) induces binding to the SH2 domain-containing adapter protein B (SHB) protein. | ||
| PGFRA_HUMAN | 705 | 729 | Binary | Physicochemical compatibility | Phosphorylation of Y720 in the SH2-binding motif of Platelet-derived growth factor receptor alpha (PDGFRA) induces binding to the SH2 domain-containing adapter protein F (SHF) protein. | ||
| IL4RA_HUMAN | 706 | 721 | Binary | Physicochemical compatibility | Phosphorylation of Y713 in the SH2-binding motif of Interleukin-4 receptor subunit alpha (IL4R) induces binding to the SHC-transforming protein 1 (SHC1) protein. | ||
| IL4RA_HUMAN | 706 | 721 | Binary | Physicochemical compatibility | Phosphorylation of Y713 in the SH2-binding motif of Interleukin-4 receptor subunit alpha (IL4R) induces binding to the Phosphatidylinositol-3,4,5-trisphosphate 5-phosphatase 1 (INPP5D) protein. | ||
| M4K1_HUMAN | 372 | 391 | Binary | Physicochemical compatibility | Phosphorylation of Y381 in the SH2-binding motif of Mitogen-activated protein kinase kinase kinase kinase 1 (MAP4K1) induces binding to the B-cell linker protein (BLNK) protein. | ||
| DOK1_HUMAN | 203 | 206 | Binary | Physicochemical compatibility | Phosphorylation of Y203 in the SH2-binding motif of Docking protein 1 (DOK1) induces binding to the Phosphatidylinositol-3,4,5-trisphosphate 5-phosphatase 1 (INPP5D) protein. | ||
| LCP2_HUMAN | 105 | 118 | Binary | Physicochemical compatibility | Phosphorylation of Y113 in the SH2-binding motif of Lymphocyte cytosolic protein 2 (LCP2) induces binding to the SH2 domain-containing adapter protein B (SHB) protein. | ||
| LCP2_HUMAN | 120 | 133 | Binary | Physicochemical compatibility | Phosphorylation of Y128 in the SH2-binding motif of Lymphocyte cytosolic protein 2 (LCP2) induces binding to the SH2 domain-containing adapter protein B (SHB) protein. | ||
| LCP2_HUMAN | 137 | 150 | Binary | Physicochemical compatibility | Phosphorylation of Y145 in the SH2-binding motif of Lymphocyte cytosolic protein 2 (LCP2) induces binding to the SH2 domain-containing adapter protein B (SHB) protein. | ||
LIG_SH2_IIC - | |||||||
| ZAP70_HUMAN | 284 | 300 | Binary | Physicochemical compatibility | Phosphorylation of Y292 in the SH2-binding motif of Tyrosine-protein kinase ZAP-70 (ZAP70) induces binding to the E3 ubiquitin-protein ligase CBL-B (CBLB) protein. | ||
| KSYK_HUMAN | 315 | 331 | Binary | Physicochemical compatibility | Phosphorylation of Y323 in the SH2-binding motif of Tyrosine-protein kinase SYK (SYK) induces binding to the E3 ubiquitin-protein ligase CBL-B (CBLB) protein. | ||
LIG_SH2_III - | |||||||
| EGFR_HUMAN | 1008 | 1024 | Binary | Physicochemical compatibility | Phosphorylation of Y1016 in the SH2-binding motif of Epidermal growth factor receptor (EGFR) induces binding to the Signal transducer and activator of transcription 6 (STAT6) protein. | ||
| ERBB2_HUMAN | 1131 | 1147 | Binary | Physicochemical compatibility | Phosphorylation of Y1139 in the SH2-binding motif of Receptor tyrosine-protein kinase erbB-2 (ERBB2) induces binding to the Signal transducer and activator of transcription 6 (STAT6) protein. | ||
| GHR_HUMAN | 428 | 444 | Binary | Physicochemical compatibility | Phosphorylation of Y436 in the SH2-binding motif of Growth hormone receptor (GHR) induces binding to the Signal transducer and activator of transcription 5B (STAT5B) protein. | ||
| IL2RB_HUMAN | 531 | 540 | Binary | Physicochemical compatibility | Phosphorylation of Y536 in the SH2-binding motif of Interleukin-2 receptor subunit beta (IL2RB) induces binding to the Signal transducer and activator of transcription 5A (STAT5A) protein. | ||
| IL2RB_HUMAN | 528 | 544 | Binary | Physicochemical compatibility | Phosphorylation of Y536 in the SH2-binding motif of Interleukin-2 receptor subunit beta (IL2RB) induces binding to the Signal transducer and activator of transcription 5B (STAT5B) protein. | ||
| INGR1_HUMAN | 457 | 461 | Binary | Physicochemical compatibility | Phosphorylation of Y457 in the SH2-binding motif of Interferon gamma receptor 1 (IFNGR1) induces binding to the Signal transducer and activator of transcription 1-alpha/beta (STAT1) protein. | ||
| EPOR_HUMAN | 360 | 376 | Binary | Physicochemical compatibility | Phosphorylation of Y368 in the SH2-binding motif of Erythropoietin receptor (EPOR) induces binding to the Signal transducer and activator of transcription 5B (STAT5B) protein. | ||
| EPOR_HUMAN | 418 | 434 | Binary | Physicochemical compatibility | Phosphorylation of Y426 in the SH2-binding motif of Erythropoietin receptor (EPOR) induces binding to the Signal transducer and activator of transcription 5B (STAT5B) protein. | ||
| EPOR_HUMAN | 496 | 508 | Binary | Physicochemical compatibility | Phosphorylation of Y504 in the SH2-binding motif of Erythropoietin receptor (EPOR) induces binding to the Signal transducer and activator of transcription 5B (STAT5B) protein. | ||
| ERBB3_HUMAN | 1320 | 1336 | Binary | Physicochemical compatibility | Phosphorylation of Y1328 in the SH2-binding motif of Receptor tyrosine-protein kinase erbB-3 (ERBB3) induces binding to the Signal transducer and activator of transcription 6 (STAT6) protein. | ||
| IL4RA_HUMAN | 566 | 585 | Binary | Physicochemical compatibility | Phosphorylation of Y575 in the SH2-binding motif of Interleukin-4 receptor subunit alpha (IL4R) induces binding to the Signal transducer and activator of transcription 6 (STAT6) protein. | ||
| IL4RA_HUMAN | 594 | 613 | Binary | Physicochemical compatibility | Phosphorylation of Y603 in the SH2-binding motif of Interleukin-4 receptor subunit alpha (IL4R) induces binding to the Signal transducer and activator of transcription 6 (STAT6) protein. | ||
| IL4RA_HUMAN | 622 | 641 | Binary | Physicochemical compatibility | Phosphorylation of Y631 in the SH2-binding motif of Interleukin-4 receptor subunit alpha (IL4R) induces binding to the Signal transducer and activator of transcription 6 (STAT6) protein. | ||
| JAK2_MOUSE | 804 | 820 | Binary | Physicochemical compatibility | Phosphorylation of Y813 in the SH2-binding motif of Tyrosine-protein kinase JAK2 (Jak2) induces binding to the Signal transducer and activator of transcription 5B (Stat5b) protein. | ||
| STA5A_HUMAN | 686 | 702 | Binary | Physicochemical compatibility | Phosphorylation of Y694 in the SH2-binding motif of Signal transducer and activator of transcription 5A (STAT5A) induces binding to the Signal transducer and activator of transcription 5B (STAT5B) protein. | ||
| LEPR_MOUSE | 1129 | 1148 | Binary | Physicochemical compatibility | Phosphorylation of Y1138 in the SH2-binding motif of Leptin receptor (Lepr) induces binding to the Signal transducer and activator of transcription 3 (STAT3) protein. | ||
LIG_SH2_SRC - Src-family Src Homology 2 (SH2) domains binding motif. | |||||||
| SRC_HUMAN | 530 | 533 | Binary | Physicochemical compatibility | Phosphorylation of Y530 in the SH2-binding motif of Proto-oncogene tyrosine-protein kinase Src (SRC) induces an intramolecular interaction with the SH2 domain of Proto-oncogene tyrosine-protein kinase Src (SRC) resulting in inhibition of its activity and preventing intermolecular interactions of its SH2 domain. | ||
| DAG1_HUMAN | 892 | 895 | Specificity | Altered binding specificity | Adhesion-dependent phosphorylation of Y892 in Dystroglycan (DAG1) by Src kinase (Proto-oncogene tyrosine-protein kinase Src (SRC)) switches the specificity of DAG1 from the WW domain containing cytoskeletal linker Dystrophin (DMD) to the SH2 domain containing Tyrosine-protein kinase Fyn (FYN). | ||
| DAG1_HUMAN | 892 | 895 | Specificity | Altered binding specificity | Adhesion-dependent phosphorylation of Y892 in Dystroglycan (DAG1) by c-Src (SRC) switches the specificity of DAG1 from WW domain containing proteins like Utrophin (UTRN) to SH2 domain containing proteins like Tyrosine-protein kinase CSK (CSK). | ||
| DAB1_MOUSE | 198 | 201 | Binary | Pre‑translational | Alternative splicing removes the SH2-binding motif of Disabled homolog 1 (Dab1), abrogating binding to Neuronal proto-oncogene tyrosine-protein kinase Src (Src). Splice variants 2 and 3 (only containing one of the YQxI motifs, i.e. Y185 and Y198) exhibit decreased tyrosine phosphorylation, suggesting both motifs are required for full activation of Dab1. Dab1 is likely to recruit Neuronal proto-oncogene tyrosine-protein kinase Src (Src) via these two YQxI motifs, which subsequently phosphorylates adjacent YxVP motifs (here). This was also suggested for Phosphatidylinositol 3-kinase regulatory subunit alpha (Pik3r1) and Suppressor of cytokine signaling 2 (Socs2). Gao et al. (2012) (here) suggests that the ability of different Dab1 isoforms to recruit distinct sets of SH2 domains allows a fine-tuning role for Dab1 splicing in the intricate series of events that underlie neuronal migration (See also Katyal & Godbout (2004) (here) and Gao et al. (2010) (here)). | ||
| DAB1_MOUSE | 198 | 201 | Binary | Physicochemical compatibility | Phosphorylation of Y198 in the SH2-binding motif of Disabled homolog 1 (Dab1) induces binding to Neuronal proto-oncogene tyrosine-protein kinase Src (Src). | ||
| EGFR_HUMAN | 1016 | 1019 | Binary | Physicochemical compatibility | Phosphorylation of Y1016 in the SH2-binding motif of Epidermal growth factor receptor (EGFR) induces binding to 1-phosphatidylinositol-4,5-bisphosphate phosphodiesterase gamma-1 (PLCG1). | ||
| EGFR_HUMAN | 1125 | 1128 | Binary | Physicochemical compatibility | Phosphorylation of Y1125 in the SH2-binding motif of Epidermal growth factor receptor (EGFR) induces binding to Adapter molecule crk (CRK). | ||
| EGFR_HUMAN | 1016 | 1019 | Binary | Physicochemical compatibility | Phosphorylation of Y1016 in the SH2-binding motif of Epidermal growth factor receptor (EGFR) induces binding to Cytoplasmic protein NCK1 (NCK1). | ||
| FAK1_HUMAN | 397 | 400 | Binary | Physicochemical compatibility | Phosphorylation of Y397 in the SH2-binding motif of Focal adhesion kinase 1 (PTK2) induces binding to Neuronal proto-oncogene tyrosine-protein kinase Src (Src). | ||
LIG_SH2_STAT5 - STAT5 Src Homology 2 (SH2) domain binding motif. | |||||||
| LAT_HUMAN | 161 | 164 | Binary | Physicochemical compatibility | Phosphorylation of Y161 in the SH2-binding motif of Linker for activation of T-cells family member 1 (LAT) induces binding to the 1-phosphatidylinositol-4,5-bisphosphate phosphodiesterase gamma-1 (PLCG1) protein. | ||
| CTLA4_MOUSE | 201 | 204 | Specificity | Altered binding specificity | Dephosphorylation of Y201 of Cytotoxic T-lymphocyte protein 4 (Ctla4) switches the specificity of Ctla4 from SH2 domain-containing proteins like Tyrosine-protein phosphatase non-receptor type 11 (Ptpn11) to the AP-2 complex mu subunit (AP-2 complex subunit mu (Ap2m1)), thereby switching from inhibitory signal transmission and negative regulation of T cell responses to internalization and inactivation of Ctla4. | ||
| ERBB4_HUMAN | 1056 | 1059 | Specificity | Altered binding specificity | Phosphorylation-dependent binding of Receptor tyrosine-protein kinase erbB-4 (ERBB4) to the SH2 domains of Phosphatidylinositol 3-kinase regulatory subunit alpha (PIK3R1) results in signaling activation, while binding to the WW domains of E3 ubiquitin-protein ligase Itchy homolog (ITCH) to unphopshorylated ERBB4 results in ubiquitylation, endocytosis and ultimately degradation of ERBB4. | ||
| INSR_HUMAN | 1361 | 1364 | Specificity | Domain hiding | PIP3 (1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate), a product of PI3-kinase, binds to the SH2 domains of PI3K (Phosphatidylinositol 3-kinase regulatory subunit alpha (PIK3R1)) and thereby blocks its interaction with tyrosine-phosphorylated SH2 motif containing proteins. | ||
| STA5A_HUMAN | 694 | 697 | Binary | Pre‑translational | Alternative splicing removes the regulatory Y694 residue of Signal transducer and activator of transcription 5A (STAT5A). The phosphorylation of Y694 by Proto-oncogene tyrosine-protein kinase Src (SRC) has been shown to be essential for DNA binding. This event acts as an important regulatory mechanism (See Clark et al. (2005) (here) and Okutani et al. (2001) (here)). The exact function of Y694 remains uncertain as is binding to STAT5 in dimer. The STAT5A-DeltaE18 does not enter nucleus upon PRLR stimulation. | ||
| PRLR_HUMAN | 342 | 345 | Binary | Pre‑translational | Alternative Splicing removes the degron motif of Prolactin receptor (PRLR), abrogating binding to Signal transducer and activator of transcription 5A (STAT5A). The PRLR S1a (Isoform Short form 1a of Prolactin receptor (PRLR)) and S1b and (Isoform Short form 1b of Prolactin receptor (PRLR)) isoforms were unable to mediate the transcriptional activation of the beta-casein promoter via the JAK-STAT5 pathway. Therefore these two splice variants act as dominant negatives on the full-length version LF (Isoform 1 of Prolactin receptor (PRLR)). Another study showed that different splice variants of heterodimers (e.g. LF/S1a, LF/S1b) that were able to induce JAK2 phosphorylation but not further signalling events due to lack of STAT recruitment (Qazi et al. (2006) (here)). | ||
| GAB1_HUMAN | 472 | 475 | Binary | Physicochemical compatibility | Phosphorylation of Y472 in the SH2-binding motif of GRB2-associated-binding protein 1 (GAB1) induces binding to Phosphatidylinositol 3-kinase regulatory subunit alpha (PIK3R1). | ||
| GAB1_HUMAN | 447 | 450 | Binary | Physicochemical compatibility | Phosphorylation of Y447 in the SH2-binding motif of GRB2-associated-binding protein 1 (GAB1) induces binding to Phosphatidylinositol 3-kinase regulatory subunit alpha (PIK3R1). | ||
LIG_SH3_2 - This is the motif recognized by class II SH3 domains | |||||||
| MYC_HUMAN | 60 | 65 | Binary | Physicochemical compatibility | Phosphorylation of S62 in the SH3-binding motif of Myc proto-oncogene protein (MYC) by GSK-3 subfamily disrupts its interaction with Myc box-dependent-interacting protein 1 (BIN1). | ||
| PAK1_HUMAN | 13 | 18 | Binary | Physicochemical compatibility | Phosphorylation of S21 adjacent to the SH3-binding motif of Serine/threonine-protein kinase PAK 1 (PAK1) by RAC subfamily inhibits binding to Cytoplasmic protein NCK1 (NCK1), which regulates its localization to focal contacts. | ||
| MYC_HUMAN | 60 | 65 | Specificity | Domain hiding | An intramolecular interaction of an SH3 binding motif, encoded by exon 12A, in Isoform II2 of Myc box-dependent-interacting protein 1 (BIN1) with the SH3 domain of Bin1 prevents interaction of the Bin1 SH3 domain with the SH3 binding motif of Myc proto-oncogene protein (MYC). | ||
| DYN2_HUMAN | 829 | 834 | Specificity | Domain hiding | An intramolecular interaction of a Bin1 SH3 binding motif, encoded by exon 10, with the Dynamin-2 (DNM2) SH3 domain prevents binding of dynamin2 to the Bin1 SH3 domain. Binding of PI(4,5)P2 to the overlapping PI(4,5)P2 binding motif encoded by exon 10 relieves the intramolecular auto-inhibitory interaction and allows the Bin1 SH3 domain to interact with the dynamin2 PxxP motif | ||
| ADA15_HUMAN | 767 | 772 | Binary | Pre‑translational | Alternative splicing removes the SH3-binding motif of Disintegrin and metalloproteinase domain-containing protein 15 (ADAM15), abrogating binding to Proto-oncogene tyrosine-protein kinase Src (SRC). The overexpression of this splice variant has been linked to clinical aggressiveness of breast cancer. | ||
| SYNJ2_RAT | 1120 | 1125 | Binary | Pre‑translational | Alternative splicing removes the SH3-binding motif of Synaptojanin-2 (Synj2), abrogating binding to Endophilin-A2 (Sh3gl1). Endophilin-A1 (Sh3gl2) and Endophilin-A3 (Sh3gl3) were also shown to bind in this study. | ||
LIG_SH3_3 - This is the motif recognized by those SH3 domains with a non-canonical class I recognition specificity | |||||||
| TAU_HUMAN | 213 | 219 | Binary | Physicochemical compatibility | Phosphorylation of S210 adjacent to the SH3-binding motif of Isoform Tau-F of Microtubule-associated protein tau (MAPT) inhibits binding to Tyrosine-protein kinase Fyn (Fyn). | ||
| BIN1_HUMAN | 305 | 311 | Specificity | Domain hiding | An intramolecular interaction of an SH3 binding motif, encoded by exon 12A, in Isoform II2 of Myc box-dependent-interacting protein 1 (BIN1) with the SH3 domain of Bin1 prevents interaction of the Bin1 SH3 domain with the SH3 binding motif of Isoform II2 of Myc box-dependent-interacting protein 1 (BIN1). | ||
| CD2_HUMAN | 294 | 300 | Specificity | Competition | T-cell surface antigen CD2 (CD2) uses overlapping motifs to bind to CD2 antigen cytoplasmic tail-binding protein 2 (CD2BP2) and Fyn, which makes their interactions mutually exclusive. Since CD2BP2 and Tyrosine-protein kinase Fyn (FYN) reside in different subcellular locations, the specificity of CD2 for the two competitors is switched by changing its cellular localization, from non-raft membranes to lipid raft membranes. | ||
| DAG1_HUMAN | 888 | 894 | Specificity | Competition | The WW-binding motif for Dystrophin (DMD) and the SH3-binding motif for Growth factor receptor-bound protein 2 (GRB2) on Dystroglycan (DAG1) overlap, making their interactions mutually exclusive and competitive. | ||
| PLCB1_HUMAN | 1162 | 1168 | Binary | Pre‑translational | Alternative splicing removes the SH3-binding motif of Isoform B of 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 (PLCB1), abrogating binding to SH3 and multiple ankyrin repeat domains protein 3 (SHANK3). PLCB1 associates with a SHANK3 complex in cardiomyocytes via its splice variant-specific C-terminal tail. Studies show that Isoform B of 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 (PLCB1) selectively mediates downstream responses initiated by Gq-coupled receptors, in particular hypertrophy and apoptosis. | ||
| DAG1_HUMAN | 888 | 894 | Specificity | Competition | The WW-binding motif for Dystrophin (DMD) and the SH3-binding motif for Growth factor receptor-bound protein 2 (GRB2) on Dystroglycan (DAG1) overlap, making their interactions mutually exclusive and competitive. | ||
LIG_SH3_5 - PXXDY motif recognized by some SH3 domains | |||||||
| CD3E_HUMAN | 184 | 188 | Binary | Allostery | Ligand binding to the T cell receptor complex TCR-CD3 results in a conformational change that exposes an SH3-binding motif in T-cell surface glycoprotein CD3 epsilon chain (CD3E), resulting in recruitment of Cytoplasmic protein NCK2 (NCK2), involved in T cell activation. | ||
| CD3E_HUMAN | 184 | 188 | Specificity | Altered binding specificity | Phosphorylation of T-cell surface glycoprotein CD3 epsilon chain (CD3E) by Lck (Tyrosine-protein kinase Lck (LCK)) during T cell activation switches the specificity of CD3E from SH3 domain containing proteins like Epidermal growth factor receptor kinase substrate 8-like protein 1 (EPS8L1) to SH2 domain containing proteins like Tyrosine-protein kinase ZAP-70 (ZAP70). | ||
LIG_SH3_8 - | |||||||
| BIN1_HUMAN | 265 | 268 | Specificity | Domain hiding | An intramolecular interaction of a Bin1 SH3 binding motif, encoded by exon 10, with the Isoform BIN1 of Myc box-dependent-interacting protein 1 (BIN1) SH3 domain prevents binding of dynamin2 to the Bin1 SH3 domain. Binding of PI(4,5)P2 to the overlapping PI(4,5)P2-binding motif encoded by exon 10 relieves the intramolecular auto-inhibitory interaction and allows the Bin1 SH3 domain to interact with the dynamin2 PxxP motif. | ||
| BIN1_HUMAN | 265 | 268 | Binary | Pre‑translational | Alternative splicing removes the SH3-binding motif of Isoform BIN1 of Myc box-dependent-interacting protein 1 (BIN1), abrogating binding to the SH3 domain of Isoform BIN1 of Myc box-dependent-interacting protein 1 (BIN1). Splice-specific motifs in Isoform BIN1 of Myc box-dependent-interacting protein 1 (BIN1) engage in an intra-molecular interaction with its own SH3 domain. Auto-inhibition is relieved at the plasma membrane when an overlapping lipid-binding motif outcompetes the SH3-binding motif. This means that the SH3 domain is only available for inter-molecular interactions at the plasma membrane. | ||
LIG_SUMO_SBM_1 - Motif that mediates binding to SUMO proteins non-covalently. | |||||||
| DAXX_HUMAN | 734 | 740 | Cumulative | Rheostatic | Multisite phosphorylation of S737 and S739 in the SUMO-binding motif of Death domain-associated protein 6 (DAXX) by CK2 subfamily and CK2 subfamily increases the strength of the interaction with Small ubiquitin-related modifier 1 (SUMO1). | ||
| PIAS1_HUMAN | 457 | 461 | Binary | Physicochemical compatibility | Phosphorylation of S466 and S467 and S468 in the SUMO-binding motif of E3 SUMO-protein ligase PIAS1 (PIAS1) by CK2 subfamily and CK2 subfamily and CK2 subfamily increases the strength of its interaction with Small ubiquitin-related modifier 1 (SUMO1). | ||
| PIAS1_HUMAN | 457 | 461 | Binary | Physicochemical compatibility | Acetylation of K33 in Small ubiquitin-related modifier 2 (SUMO2) inhibits binding to E3 SUMO-protein ligase PIAS1 (PIAS1). The acetylation counters SUMO-SIM-dependent transcriptional repression processes. An additional interaction is also possible upon acetylation with the Bromodomain of p300 shown to bind the acetylated version of SUMO2. This does not occur with acetylated SUMO1. Acetylation is countered by Histone deacetylase family, HD type 1 subfamily. | ||
| PIAS1_HUMAN | 457 | 461 | Binary | Physicochemical compatibility | Acetylation of K37 in Small ubiquitin-related modifier 1 (SUMO1) inhibits binding to E3 SUMO-protein ligase PIAS1 (PIAS1). The acetylation counters SUMO-SIM-dependent transcriptional repression processes. Acetylation is countered by Histone deacetylase family, HD type 1 subfamily. | ||
| PIAS2_HUMAN | 467 | 471 | Binary | Physicochemical compatibility | Acetylation of K33 in Small ubiquitin-related modifier 2 (SUMO2) inhibits binding to E3 SUMO-protein ligase PIAS2 (PIAS2). The acetylation counters SUMO-SIM-dependent transcriptional repression processes. An additional interaction is also possible upon acetylation with the Bromodomain of p300 shown to bind the acetylated version of SUMO2. This does not occur with acetylated SUMO1. Acetylation is countered by Histone deacetylase family, HD type 1 subfamily. | ||
| PIAS2_HUMAN | 467 | 471 | Binary | Physicochemical compatibility | Acetylation of K37 in Small ubiquitin-related modifier 1 (SUMO1) inhibits binding to E3 SUMO-protein ligase PIAS2 (PIAS2). The acetylation counters SUMO-SIM-dependent transcriptional repression processes. Acetylation is countered by Histone deacetylase family, HD type 1 subfamily. | ||
| DAXX_HUMAN | 733 | 740 | Uncategorised | Uncategorised | Sumoylation of K160 induces binding to the Protein PML (PML) protein. SUMO-modified forms of PML are essential for the recruitment of Death domain-associated protein 6 (DAXX) to PML nuclear bodies. | ||
| DAXX_HUMAN | 733 | 740 | Specificity | Altered binding specificity | Acetylation of K33 in the SUMO2 inhibits binding to the Death domain-associated protein 6 (DAXX) protein see switch details. SUMO-modified forms of Protein PML (PML) are essential for the recruitment of Small ubiquitin-related modifier 2 (SUMO2) to PML nuclear bodies. The acetylated versions of SUMO1/2 failed to trigger recruitment of Small ubiquitin-related modifier 2 (SUMO2) into the nuclear bodies. An additional interaction is also possible upon acetylation with the Bromodomain of Histone acetyltransferase p300 (EP300) shown to bind the acetylated version of SUMO2. This does not occur with acetylated SUMO1. Acetylation is countered by Histone deacetylase family, HD type 1 subfamily. | ||
| DAXX_HUMAN | 733 | 740 | Uncategorised | Uncategorised | Sumoylation of K160 induces binding to the Protein PML (PML) protein. SUMO-modified forms of PML are essential for the recruitment of Death domain-associated protein 6 (DAXX) to PML nuclear bodies. | ||
| DAXX_HUMAN | 733 | 740 | Binary | Physicochemical compatibility | Acetylation of K37 in the SUMO1 inhibits binding to the Small ubiquitin-related modifier 1 (SUMO1) protein see switch details. SUMO-modified forms of Protein PML (PML) are essential for the recruitment of DAXX to PML nuclear bodies. The acetylated versions of SUMO1/2 failed to trigger recruitment of DAXX into the nuclear bodies. Acetylation is countered by Histone deacetylase family, HD type 1 subfamily. | ||
| PML_HUMAN | 556 | 566 | Binary | Pre‑translational | Alternative splicing removes the Sumoylation interacting motif (SIM) of Protein PML (PML), abrogating binding to Small ubiquitin-related modifier 1 (SUMO1) in Isoform TRIM19epsilon of Protein PML (PML). Isoforms lacking the SIM were resistant to As2O3-induced PML degradation. | ||
LIG_SxIP_EBH_1 - SxIP motifs bind to EBH domains. | |||||||
| KIF2C_HUMAN | 93 | 104 | Binary | Physicochemical compatibility | Phosphorylation of S95 and S109 and S111 adjacent to the EB1-binding motif of Kinesin-like protein KIF2C (KIF2C) by Aurora kinase B (AURKB) and Aurora kinase B (AURKB) and Aurora kinase B (AURKB) inhibits its interaction with Microtubule-associated protein RP/EB family member 1 (MAPRE1), thereby inhibiting microtubule tip tracking. | ||
| CLAP2_HUMAN | 515 | 525 | Binary | Physicochemical compatibility | Phosphorylation of several serine residues surrounding the EB1-binding motifs of CLIP-associating protein 2 (CLASP2) by Glycogen synthase kinase-3 beta (GSK3B) and Glycogen synthase kinase-3 beta (GSK3B) and Glycogen synthase kinase-3 beta (GSK3B) and Glycogen synthase kinase-3 beta (GSK3B) and Glycogen synthase kinase-3 beta (GSK3B) inhibits its interaction with Microtubule-associated protein RP/EB family member 1 (MAPRE1). | ||
| APC_HUMAN | 2801 | 2811 | Cumulative | Rheostatic | Phosphorylation of S2789 and S2793 adjacent to the EBH-binding motif of Adenomatous polyposis coli protein (APC), by , respectively, gradually reduces the affinity of its interaction with Microtubule-associated protein RP/EB family member 1 (MAPRE1). | ||
LIG_TAZ1 - | |||||||
| HIF1A_HUMAN | 792 | 795 | Binary | Physicochemical compatibility | Under normoxic conditions interaction of Hypoxia-inducible factor 1-alpha (HIF1A) with transcriptional coactivators such as CREB-binding protein (Crebbp) is inhibited by hydroxylation of N803. | ||
LIG_TAZ2 - | |||||||
| P53_HUMAN | 19 | 25 | Cumulative | Rheostatic | Multisite phosphorylation of S15 and T18 and S20 and S33 and S37 and S46 in the TAD region of Cellular tumor antigen p53 (TP53) additively enhances its affinity for CREB-binding protein (CREBBP). | ||
LIG_TKB - | |||||||
| EGFR_HUMAN | 1069 | 1074 | Binary | Physicochemical compatibility | Phosphorylation of Y1069 in Epidermal growth factor receptor (EGFR) is necessary for binding to the TKB domain of E3 ubiquitin-protein ligase CBL (CBL). | ||
| SPY2_HUMAN | 55 | 60 | Binary | Physicochemical compatibility | Phosphorylation of Y55 in Protein sprouty homolog 2 (SPRY2) is necessary for binding to the TKB domain of E3 ubiquitin-protein ligase CBL (CBL). | ||
| EGFR_HUMAN | 1069 | 1074 | Cumulative | Rheostatic | While phosphorylation of Y1069 induces binding, additional phosphorylation of S1070 and S1071 in the TKB-binding motif of Epidermal growth factor receptor (EGFR) gradually lowers its binding affinity for E3 ubiquitin-protein ligase CBL (CBL). | ||
| SPY2_HUMAN | 55 | 60 | Cumulative | Rheostatic | While phosphorylation of Y55 induces binding, additional phosphorylation of T56 in the TKB-binding motif of Protein sprouty homolog 2 (SPRY2) lowers its binding affinity for E3 ubiquitin-protein ligase CBL (CBL). | ||
LIG_TPR_Kinesin_1 - | |||||||
| PKHM2_HUMAN | 236 | 240 | Binary | Pre‑translational | Alternative splicing removes the Kinesin Light Chain-binding motif of Pleckstrin homology domain-containing family M member 2 (PLEKHM2), abrogating binding to Kinesin light chain 2 (KLC2). Pleckstrin homology domain-containing family M member 2 (PLEKHM2) contains kinesin light chain (KLC) binding WD motifs (second motif at 205-210), and these are required for kinesin-1 recruitment and the peripheral movement of lysosomes. ADP-ribosylation factor-like protein 8B (ARL8B) and PLEKHM2 act together to recruit kinesin-1 to lysosomes and hence direct their movement toward microtubule plus ends. A splice variant of PLEKHM2 that lacks a light chain binding motif does not stimulate movement, suggesting fine-tuning by alternative splicing. | ||
LIG_TRAF2_3 - | |||||||
| CYLD_MOUSE | 449 | 453 | Binary | Pre‑translational | Alternative splicing removes the TRAF2-binding motif of Ubiquitin carboxyl-terminal hydrolase CYLD (Cyld), abrogating binding to TNF receptor-associated factor 2 (Traf2). Mice expressing solely the alternatively spliced Isoform 3 of Ubiquitin carboxyl-terminal hydrolase CYLD (Cyld) (sCYLD) show an altered B-cell expansion profile and have more stable NF-kB proteins. | ||
LIG_TYR_ITAM - ITAM (immunoreceptor tyrosine-based activatory motif). ITAM consists of partially conserved short sequence of amino acid found in the cytoplasmatic tail of antigen and Fc receptors. | |||||||
| CD3E_HUMAN | 185 | 202 | Specificity | Altered binding specificity | Phosphorylation of T-cell surface glycoprotein CD3 epsilon chain (CD3E) by Lck (Tyrosine-protein kinase Lck (LCK)) during T cell activation switches the specificity of CD3E from SH3 domain containing proteins like Epidermal growth factor receptor kinase substrate 8-like protein 1 (EPS8L1) to SH2 domain containing proteins like Tyrosine-protein kinase ZAP-70 (ZAP70). | ||
| CD3Z_HUMAN | 69 | 86 | Avidity‑sensing | Phosphorylation of Y72 and Y83 in the ITAM motif of T-cell surface glycoprotein CD3 zeta chain (CD247) induces high-avidity binding to the tandem SH2 domains of Tyrosine-protein kinase ZAP-70 (ZAP70). | |||
| CD3Z_HUMAN | 69 | 86 | Avidity‑sensing | Phosphorylation of Y72 and Y83 in the ITAM motif of T-cell surface glycoprotein CD3 zeta chain (CD247) induces high-avidity binding to the tandem SH2 domains of Tyrosine-protein kinase ZAP-70 (ZAP70). | |||
| CD79A_MOUSE | 179 | 196 | Avidity‑sensing | Phosphorylation of Y182 and Y193 in the ITAM motif of B-cell antigen receptor complex-associated protein alpha chain (Cd79a) induces high-avidity binding to the tandem SH2 domains of Tyrosine-protein kinase SYK (Syk). Maximal Syk activation requires both Syk SH2 domains and phosphorylation of both ITAM tyrosine residues. | |||
| CD79A_MOUSE | 179 | 196 | Avidity‑sensing | Phosphorylation of Y182 and Y193 in the ITAM motif of B-cell antigen receptor complex-associated protein alpha chain (Cd79a) induces high-avidity binding to the tandem SH2 domains of Tyrosine-protein kinase SYK (Syk). Maximal Syk activation requires both Syk SH2 domains and phosphorylation of both ITAM tyrosine residues. | |||
| CD3E_HUMAN | 185 | 202 | Avidity‑sensing | Phosphorylation of Y188 and Y199 in the ITAM motif of T-cell surface glycoprotein CD3 epsilon chain (CD3E) induces high-avidity binding to the tandem SH2 domains of Tyrosine-protein kinase SYK (SYK). | |||
| CD3E_HUMAN | 185 | 202 | Avidity‑sensing | Phosphorylation of Y188 and Y199 in the ITAM motif of T-cell surface glycoprotein CD3 epsilon chain (CD3E) induces high-avidity binding to the tandem SH2 domains of Tyrosine-protein kinase SYK (SYK). | |||
| CD3Z_HUMAN | 108 | 126 | Avidity‑sensing | Phosphorylation of Y111 and Y123 in the ITAM motif of T-cell surface glycoprotein CD3 zeta chain (CD247) induces high-avidity binding to the tandem SH2 domains of Tyrosine-protein kinase ZAP-70 (ZAP70). | |||
| CD3Z_HUMAN | 108 | 126 | Avidity‑sensing | Phosphorylation of Y111 and Y123 in the ITAM motif of T-cell surface glycoprotein CD3 zeta chain (CD247) induces high-avidity binding to the tandem SH2 domains of Tyrosine-protein kinase ZAP-70 (ZAP70). | |||
| CD3Z_HUMAN | 139 | 156 | Avidity‑sensing | Phosphorylation of Y142 and Y153 in the ITAM motif of T-cell surface glycoprotein CD3 zeta chain (CD247) induces high-avidity binding to the tandem SH2 domains of Tyrosine-protein kinase ZAP-70 (ZAP70). | |||
| CD3Z_HUMAN | 139 | 156 | Avidity‑sensing | Phosphorylation of Y142 and Y153 in the ITAM motif of T-cell surface glycoprotein CD3 zeta chain (CD247) induces high-avidity binding to the tandem SH2 domains of Tyrosine-protein kinase ZAP-70 (ZAP70). | |||
| CD3G_HUMAN | 157 | 174 | Avidity‑sensing | Phosphorylation of Y160 and Y171 in the ITAM motif of T-cell surface glycoprotein CD3 gamma chain (CD3G) induces high-avidity binding to the tandem SH2 domains of Tyrosine-protein kinase ZAP-70 (ZAP70). | |||
| CD3G_HUMAN | 157 | 174 | Avidity‑sensing | Phosphorylation of Y160 and Y171 in the ITAM motif of T-cell surface glycoprotein CD3 gamma chain (CD3G) induces high-avidity binding to the tandem SH2 domains of Tyrosine-protein kinase ZAP-70 (ZAP70). | |||
| FCG2A_HUMAN | 285 | 307 | Avidity‑sensing | Phosphorylation of Y288 and Y304 in the ITAM motif of Low affinity immunoglobulin gamma Fc region receptor II-a (FCGR2A) induces high-avidity binding to the tandem SH2 domains of Tyrosine-protein kinase SYK (SYK). | |||
| FCG2A_HUMAN | 285 | 307 | Avidity‑sensing | Phosphorylation of Y288 and Y304 in the ITAM motif of Low affinity immunoglobulin gamma Fc region receptor II-a (FCGR2A) induces high-avidity binding to the tandem SH2 domains of Tyrosine-protein kinase SYK (SYK). | |||
| FCERG_HUMAN | 62 | 79 | Avidity‑sensing | Phosphorylation of Y65 and Y76 in the ITAM motif of High affinity immunoglobulin epsilon receptor subunit gamma (FCER1G) induces high-avidity binding to the tandem SH2 domains of Tyrosine-protein kinase SYK (SYK). | |||
| FCERG_HUMAN | 62 | 79 | Avidity‑sensing | Phosphorylation of Y65 and Y76 in the ITAM motif of High affinity immunoglobulin epsilon receptor subunit gamma (FCER1G) induces high-avidity binding to the tandem SH2 domains of Tyrosine-protein kinase SYK (SYK). | |||
LIG_TYR_ITIM - ITIM (immunoreceptor tyrosine-based inhibitory motif). Phosphorylation of the ITIM motif, found in the cytoplasmic tail of some inhibitory receptors (KIRs) that bind MHC Class I, leads to the recruitment and activation of a protein tyrosine phosphatase. | |||||||
| FCG2B_HUMAN | 290 | 295 | Binary | Physicochemical compatibility | Phosphorylation of Y292 in the ITIM motif of Low affinity immunoglobulin gamma Fc region receptor II-b (FCGR2B) induces binding of Phosphatidylinositol-3,4,5-trisphosphate 5-phosphatase 1 (INPP5D) via its SH2 domain. | ||
| KI3L2_HUMAN | 396 | 401 | Binary | Physicochemical compatibility | Phosphorylation of Y398 in the ITIM motif of Killer cell immunoglobulin-like receptor 3DL2 (KIR3DL2) induces binding of Tyrosine-protein phosphatase non-receptor type 6 (PTPN6) via one of its SH2 domains. | ||
| OX1R_HUMAN | 356 | 361 | Avidity‑sensing | Orexin-A induced phosphorylation of the ITSM and ITIM motifs in Orexin receptor type 1 (HCRTR1) allows binding of Tyrosine-protein phosphatase non-receptor type 11 (PTPN11) via its two SH2 domains. Mutation of either tyrosine in the motifs abolishes binding of Tyrosine-protein phosphatase non-receptor type 11 (PTPN11). | |||
| SIG12_MOUSE | 430 | 435 | Binary | Pre‑translational | Alternative splicing removes the ITIM (immunoreceptor tyrosine-based inhibitory motif) of Sialic acid-binding Ig-like lectin 12 (Siglec12), abrogating binding to Tyrosine-protein phosphatase non-receptor type 6 (Ptpn6). | ||
| SIG12_MOUSE | 430 | 435 | Binary | Pre‑translational | Alternative splicing removes the ITIM (immunoreceptor tyrosine-based inhibitory motif) of Sialic acid-binding Ig-like lectin 12 (Siglec12), abrogating binding to Tyrosine-protein phosphatase non-receptor type 11 (Ptpn11). | ||
| TRML1_HUMAN | 279 | 284 | Binary | Pre‑translational | Alternative splicing removes the ITIM (immunoreceptor tyrosine-based inhibitory motif) of Trem-like transcript 1 protein (TREML1), abrogating binding to Tyrosine-protein phosphatase non-receptor type 11 (PTPN11). | ||
| SIG12_MOUSE | 430 | 435 | Binary | Pre‑translational | Alternative splicing removes the ITIM (immunoreceptor tyrosine-based inhibitory motif) of Sialic acid-binding Ig-like lectin 12 (Siglec12), abrogating binding to Tyrosine-protein phosphatase non-receptor type 6 (Ptpn6). | ||
| SIG12_MOUSE | 430 | 435 | Binary | Pre‑translational | Alternative splicing removes the ITIM (immunoreceptor tyrosine-based inhibitory motif) of Sialic acid-binding Ig-like lectin 12 (Siglec12), abrogating binding to Tyrosine-protein phosphatase non-receptor type 11 (Ptpn11). | ||
| TRML1_HUMAN | 279 | 284 | Binary | Pre‑translational | Alternative splicing removes the ITIM (immunoreceptor tyrosine-based inhibitory motif) of Trem-like transcript 1 protein (TREML1), abrogating binding to Tyrosine-protein phosphatase non-receptor type 11 (PTPN11). | ||
| OX1R_HUMAN | 356 | 361 | Avidity‑sensing | Orexin-A induced phosphorylation of the ITSM and ITIM motifs in Orexin receptor type 1 (HCRTR1) allows binding of Tyrosine-protein phosphatase non-receptor type 11 (PTPN11) via its two SH2 domains. Mutation of either tyrosine in the motifs abolishes binding of Tyrosine-protein phosphatase non-receptor type 11 (PTPN11). | |||
LIG_TYR_ITSM - ITSM (immunoreceptor tyrosine-based switch motif). This motif is present in the cytoplasmic region of the CD150 subfamily within the CD2 family and it enables these receptors to bind to and to be regulated by SH2 adaptor molecules, as SH2DIA. | |||||||
| SLAF1_HUMAN | 277 | 284 | Binary | Physicochemical compatibility | Phosphorylation of Y281 in the ITSM motif of Signaling lymphocytic activation molecule (SLAMF1) induces binding of Tyrosine-protein phosphatase non-receptor type 11 (PTPN11) via one of its SH2 domains. | ||
| SLAF1_HUMAN | 323 | 330 | Binary | Physicochemical compatibility | Phosphorylation of Y327 in the ITSM motif of Signaling lymphocytic activation molecule (SLAMF1) induces binding of Tyrosine-protein phosphatase non-receptor type 11 (PTPN11) via one of its SH2 domains. | ||
| OX1R_HUMAN | 79 | 86 | Avidity‑sensing | Orexin-A induced phosphorylation of the ITSM and ITIM motifs in Orexin receptor type 1 (HCRTR1) allows binding of Tyrosine-protein phosphatase non-receptor type 11 (PTPN11) via its two SH2 domains. Mutation of either tyrosine in the motifs abolishes binding of Tyrosine-protein phosphatase non-receptor type 11 (PTPN11). | |||
| SLAF7_HUMAN | 280 | 287 | Binary | Pre‑translational | Alternative splicing removes the ITSM (immunoreceptor tyrosine-based switch motif) motif of SLAM family member 7 (SLAMF7), abrogating binding to SH2 domain-containing protein 1A (SH2D1A). The full-length isoform (Isoform CS1-L of SLAM family member 7 (SLAMF7)) has 2 ITSM motifs and only one is missing in the shorter splice variant (Isoform 19A24 of SLAM family member 7 (SLAMF7)). However, experiments showed only Isoform CS1-L of SLAM family member 7 (SLAMF7) binds to SH2D1A. | ||
| OX1R_HUMAN | 79 | 86 | Avidity‑sensing | Orexin-A induced phosphorylation of the ITSM and ITIM motifs in Orexin receptor type 1 (HCRTR1) allows binding of Tyrosine-protein phosphatase non-receptor type 11 (PTPN11) via its two SH2 domains. Mutation of either tyrosine in the motifs abolishes binding of Tyrosine-protein phosphatase non-receptor type 11 (PTPN11). | |||
LIG_Talin - | |||||||
| ITB7_HUMAN | 770 | 779 | Specificity | Competition | The integrin regulator Talin-1 (TLN1) and the actin-crosslinking Filamins Filamin-A (FLNA) use overlapping binding sites on the cytoplasmic tails of beta integrin subunits Integrin beta-7 (ITGB7), which makes their interaction with beta integrin mutually exclusive. | ||
| ITB1_HUMAN | 775 | 785 | Binary | Pre‑translational | Alternative splicing alters the flanking regions of the PTB-binding motif of Isoform Beta-1D of Integrin beta-1 (ITGB1), inducing higher affinity binding to Talin-1 (TLN1). Alteration of residue 788 from G to Q and alteration of residue 786 from A to P increases the binding affinity from 491 micromolar in the canonical Isoform Beta-1A of Integrin beta-1 (ITGB1) to 95 micromolar in Isoform Beta-1D of Integrin beta-1 (ITGB1). | ||
| ITB1_HUMAN | 775 | 785 | Binary | Pre‑translational | Alternative splicing alters the flanking regions of the PTB-binding motif of Isoform Beta-1D of Integrin beta-1 (ITGB1), inducing higher affinity binding to Talin-2 (TLN2). The alteration of residue 788 from G to Q and alteration of residue 786 from A to P increases the binding affinity from 652 micromolar in the canonical Isoform Beta-1A of Integrin beta-1 (ITGB1) to 36 micromolar in Isoform Beta-1D of Integrin beta-1 (ITGB1). | ||
LIG_ULM_U2AF65_1 - Pattern encompassing the ULMs in SF1 and SAP155 which bind to the UHM of U2AF65 | |||||||
| ATX1_HUMAN | 770 | 775 | Specificity | Altered binding specificity | Phosphorylation of S775 switches binding specificity of Ataxin-1 (ATXN1) from the splicing factor Splicing factor U2AF 65 kDa subunit (U2AF2) to 14-3-3 proteins (e.g. 14-3-3 protein zeta/delta (YWHAZ)). While association with the spliceosome protects ATXN1 from self-association, its phosphorylation-dependent recruitment to 14-3-3 proteins (e.g. YWHAZ) might result in aggregation. | ||
LIG_WRPW_1 - The WRPW motif mediates recruitment of transcriptional co-repressors of the Groucho/transducin-like enhancer-of-split (TLE) family. LIG_WRPW_1 is based on the C-terminus located motifs found in the Hairy and Runt family proteins. | |||||||
| HES1_HUMAN | 275 | 280 | Specificity | Competition | The Transducin-like enhancer protein 1 (TLE1) can recruit a wide range of transcriptional repressors via its WD domain, to which the WRPW motif of Transcription factor HES-1 (HES1) and the EH1 motif of Homeobox protein goosecoid (GSC) can bind using overlapping sites. | ||
LIG_WW_1 - PPXY is the motif recognized by WW domains of Group I | |||||||
| SMAD3_HUMAN | 181 | 184 | Specificity | Altered binding specificity | CDK8/9 phosphorylates Mothers against decapentaplegic homolog 3 (SMAD3) at T179 and S208. Phosphorylation of T179 creates a binding site for the WW domain of Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1), while phosphorylation of S208 primes SMAD3 for phosphorylation of S204 by Glycogen synthase kinase-3 beta (GSK3B). The pS204-pS208 forms a binding site for the third WW domain of E3 ubiquitin-protein ligase NEDD4-like (NEDD4L), whose second WW domain will displace the WW domain of PIN1 at the pT179-PY box site of SMAD3. This regulation couples SMAD3 activation to SMAD3 destruction in an ordered fashion. See also switch details and switch details. | ||
| DAG1_HUMAN | 889 | 892 | Specificity | Altered binding specificity | Adhesion-dependent phosphorylation of Y892 in Dystroglycan (DAG1) by Src kinase (Proto-oncogene tyrosine-protein kinase Src (SRC)) switches the specificity of DAG1 from the WW domain containing cytoskeletal linker Dystrophin (DMD) to the SH2 domain containing Tyrosine-protein kinase Fyn (FYN). | ||
| DAG1_HUMAN | 889 | 892 | Specificity | Altered binding specificity | Adhesion-dependent phosphorylation of Y892 in Dystroglycan (DAG1) by c-Src (SRC) switches the specificity of DAG1 from WW domain containing proteins like Utrophin (UTRN) to SH2 domain containing proteins like Tyrosine-protein kinase CSK (CSK). | ||
| ERBB4_HUMAN | 1053 | 1056 | Specificity | Altered binding specificity | Phosphorylation-dependent binding of Receptor tyrosine-protein kinase erbB-4 (ERBB4) to the SH2 domains of Phosphatidylinositol 3-kinase regulatory subunit alpha (PIK3R1) results in signaling activation, while binding to the WW domains of E3 ubiquitin-protein ligase Itchy homolog (ITCH) to unphopshorylated ERBB4 results in ubiquitylation, endocytosis and ultimately degradation of ERBB4. | ||
| SCNNG_HUMAN | 624 | 627 | Specificity | Domain hiding | Phosphorylation of Isoform Nedd4-2a of E3 ubiquitin-protein ligase NEDD4-like (NEDD4L) by Serine/threonine-protein kinase Sgk1 (SGK1) induces binding to 14-3-3 protein eta (YWHAH). This inhibits (whether allosterically or sterically is not known) interactions of NEDD4L via its WW domains with the PY motif in Amiloride-sensitive sodium channel subunit gamma (SCNN1G) (ENaC). As a result, ENaC does not get degraded and ENaC-mediated Na+ currents increase. | ||
| DAG1_HUMAN | 889 | 892 | Specificity | Competition | The WW-binding motif for Dystrophin (DMD) and the SH3-binding motif for Growth factor receptor-bound protein 2 (GRB2) on Dystroglycan (DAG1) overlap, making their interactions mutually exclusive and competitive. | ||
| AMOT_HUMAN | 239 | 242 | Binary | Pre‑translational | Alternative splicing removes the WW-binding motif of Angiomotin (AMOT), abrogating binding to Yorkie homolog (YAP1). The splice specific Isoform p130 of Angiomotin (AMOT) of AMOT works within the Hippo pathway to sequester the transcription coactivator YAP1 away at tight junction. In contrast Isoform p80 of Angiomotin (AMOT) of AMOT lacks WW-binding motif. | ||
| AMOT_HUMAN | 239 | 242 | Binary | Pre‑translational | Alternative splicing removes the WW-binding motif of Angiomotin (AMOT), abrogating binding to WW domain-containing transcription regulator protein 1 (WWTR1). The splice specific Isoform p130 of Angiomotin (AMOT) of AMOT works within the Hippo pathway to sequester the transcription coactivator YAP1 away at tight junction. In contrast Isoform p80 of Angiomotin (AMOT) of AMOT lacks WW-binding motif. | ||
| ERBB4_HUMAN | 1053 | 1056 | Binary | Pre‑translational | Alternative splicing removes the WW-binding motif of Receptor tyrosine-protein kinase erbB-4 (ERBB4), abrogating binding to E3 ubiquitin-protein ligase Itchy homolog (ITCH). The presence of a WW-binding motif mediates ERBB4 mono-ubiquitination and endocytosis by the WW domain-containing HECT-type E3 ubiquitin ligase ITCH. | ||
| SMAD3_HUMAN | 181 | 184 | Avidity‑sensing | CDK8/9 phosphorylates Mothers against decapentaplegic homolog 3 (SMAD3) at T179 and S208. Phosphorylation of T179 creates a binding site for the WW domain of Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1), while phosphorylation of S208 primes SMAD3 for phosphorylation of S204 by Glycogen synthase kinase-3 beta (GSK3B). The pS204-pS208 forms a binding site for the third WW domain of the E3 ubiquitin-protein ligase NEDD4-like (NEDD4L), whose second WW domain will displace the WW domain of PIN1 at the pT179-PY box site of SMAD3. This regulation couples SMAD3 activation to SMAD3 destruction in an ordered fashion. Dual phosphorylation of the two NEDD4L-binding sites mediates high-avidity binding of two WW domains of NEDD4L to SMAD3. See also switch details and switch details. | |||
| LMP2_EBVB9 | 57 | 60 | Binary | Pre‑translational | Alternative splicing removes the WW-binding motif of Latent membrane protein 2 (LMP2), abrogating binding to E3 ubiquitin-protein ligase Itchy (Itch). | ||
| LMP2_EBVB9 | 98 | 101 | Binary | Pre‑translational | Alternative splicing removes the WW-binding motif of Latent membrane protein 2 (LMP2), abrogating binding to E3 ubiquitin-protein ligase Itchy (Itch). | ||
| LMP2_EBVB9 | 57 | 60 | Binary | Pre‑translational | Alternative splicing removes the WW-binding motif of Latent membrane protein 2 (LMP2), abrogating binding to E3 ubiquitin-protein ligase Itchy (Itch). | ||
| ERBB4_HUMAN | 1053 | 1056 | Binary | Pre‑translational | Alternative splicing removes the WW-binding motif of Receptor tyrosine-protein kinase erbB-4 (ERBB4), abrogating binding to E3 ubiquitin-protein ligase Itchy homolog (ITCH). The presence of a WW-binding motif mediates ERBB4 mono-ubiquitination and endocytosis by the WW domain-containing HECT-type E3 ubiquitin ligase ITCH. | ||
| AMOT_HUMAN | 239 | 242 | Binary | Pre‑translational | Alternative splicing removes the WW-binding motif of Angiomotin (AMOT), abrogating binding to Yorkie homolog (YAP1). The splice specific Isoform p130 of Angiomotin (AMOT) of AMOT works within the Hippo pathway to sequester the transcription coactivator YAP1 away at tight junction. In contrast Isoform p80 of Angiomotin (AMOT) of AMOT lacks WW-binding motif. | ||
| DAG1_HUMAN | 889 | 892 | Specificity | Competition | The WW-binding motif for Dystrophin (DMD) and the SH3-binding motif for Growth factor receptor-bound protein 2 (GRB2) on Dystroglycan (DAG1) overlap, making their interactions mutually exclusive and competitive. | ||
| P73_HUMAN | 484 | 487 | Specificity | Competition | The transcriptional coactivator YAP1 and the ubiquitin ligase Itch competitively bind to the same WW-binding motif of p73. Binding of YAP1 prevents Itch-mediated ubiquitylation of p73, resulting in stabilisation, and increases trancriptional activity of p73. | ||
| P73_HUMAN | 484 | 487 | Specificity | Competition | The transcriptional coactivator YAP1 and the ubiquitin ligase Itch competitively bind to the same WW-binding motif of p73. Binding of YAP1 prevents Itch-mediated ubiquitylation of p73, resulting in stabilisation, and increases trancriptional activity of p73. | ||
| JUN_MOUSE | 167 | 170 | Binary | Physicochemical compatibility | Phosphorylation of Y170 in the WW-binding motif of Transcription factor AP-1 (Jun) by Tyrosine-protein kinase ABL1 (Abl1) blocks binding to the E3 ubiquitin-protein ligase Itchy (Itch). As a result, Transcription factor AP-1 (Jun) is not ubiquitylated by E3 ubiquitin-protein ligase Itchy (Itch), and thus not targeted for proteasomal degradation. Regulation of transcriptional activity of Transcription factor AP-1 (Jun) by Tyrosine-protein kinase ABL1 (Abl1) required translocation of the kinase to the nucleus, which was triggered by T cell activation. | ||
LIG_WW_Nedd4L - | |||||||
| SMAD3_HUMAN | 203 | 210 | Specificity | Altered binding specificity | CDK8/9 phosphorylates Mothers against decapentaplegic homolog 3 (SMAD3) at T179 and S208. Phosphorylation of T179 creates a binding site for the WW domain of Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1), while phosphorylation of S208 primes SMAD3 for phosphorylation of S204 by Glycogen synthase kinase-3 beta (GSK3B). The pS204-pS208 forms a binding site for the third WW domain of E3 ubiquitin-protein ligase NEDD4-like (NEDD4L), whose second WW domain will displace the WW domain of PIN1 at the pT179-PY box site of SMAD3. This regulation couples SMAD3 activation to SMAD3 destruction in an ordered fashion. See also switch details and switch details. | ||
| SMAD3_HUMAN | 203 | 210 | Avidity‑sensing | CDK8/9 phosphorylates Mothers against decapentaplegic homolog 3 (SMAD3) at T179 and S208. Phosphorylation of T179 creates a binding site for the WW domain of Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1), while phosphorylation of S208 primes SMAD3 for phosphorylation of S204 by Glycogen synthase kinase-3 beta (GSK3B). The pS204-pS208 forms a binding site for the third WW domain of the E3 ubiquitin-protein ligase NEDD4-like (NEDD4L), whose second WW domain will displace the WW domain of PIN1 at the pT179-PY box site of SMAD3. This regulation couples SMAD3 activation to SMAD3 destruction in an ordered fashion. Dual phosphorylation of the two NEDD4L-binding sites mediates high-avidity binding of two WW domains of NEDD4L to SMAD3. See also switch details and switch details. | |||
| SMAD3_HUMAN | 203 | 210 | Cumulative | Rheostatic | CDK8/9 phosphorylates Mothers against decapentaplegic homolog 3 (SMAD3) at T179 and S208. Phosphorylation of T179 creates a binding site for the WW domain of Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1), while phosphorylation of S208 primes SMAD3 for phosphorylation of S204 by Glycogen synthase kinase-3 beta (GSK3B). The pS204-pS208 forms a binding site for the third WW domain of the E3 ubiquitin-protein ligase NEDD4-like (NEDD4L), whose second WW domain will displace the WW domain of PIN1 at the pT179-PY box site of SMAD3. This regulation couples SMAD3 activation to SMAD3 destruction in an ordered fashion. Phosphorylation of S208 in SMAD3 induces binding of the third WW domain of NEDD4L, while additional phosphorylation of S204 in SMAD3 further increases the affinity of this interaction. See also switch details and switch details. | ||
LIG_eIF4E_1 - Motif binding to the dorsal surface of eIF4E. | |||||||
| 4EBP1_HUMAN | 54 | 60 | Binary | Physicochemical compatibility | Phosphorylation of S65 flanking the eIF4E-binding motif of Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1) by Serine/threonine-protein kinase mTOR (MTOR) inhibits binding to Eukaryotic translation initiation factor 4E (EIF4E) in response to growth factors and nutrients. This results in release of Eukaryotic translation initiation factor 4E (EIF4E), which associates with other initiation factors to form the eIF-4F complex that mediates initiation of translation. However, disruption of the interaction between Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1) and Eukaryotic translation initiation factor 4E (EIF4E) has been shown to be dependent on hyperphosphorylation of Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1) by FRAP/mTOR, PI3K and ERK pathways. According to the current model, Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1) is phosphorylated on multiple residues in a well-defined order. Basal phosphorylation of T37 and T46 serves as a priming event for subsequent serum-induced phosphorylation of T70, which primes for subsequent phosphorylation of S65. | ||
MOD_CAAXbox - Generic CAAX box prenylation motif | |||||||
| CDC42_HUMAN | 188 | 191 | Binary | Pre‑translational | Alternative splicing removes the prenylation motif of Cell division control protein 42 homolog (CDC42), abrogating binding to Protein farnesyltransferase/geranylgeranyltransferase type-1 subunit alpha (FNTA). The canonical, prenylated Cdc42 isoform (Cdc42-pren or Isoform Placental of Cell division control protein 42 homolog (CDC42)) is expressed in all tissues, the variant, palmitoylated form (Cdc42-palm or Isoform Brain of Cell division control protein 42 homolog (CDC42)) is expressed only in brain. | ||
MOD_CDK - | |||||||
| MK67I_HUMAN | 235 | 241 | Specificity | Altered binding specificity | Phosphorylation of T238 of MKI67 FHA domain-interacting nucleolar phosphoprotein (MKI67IP) by Cyclin-dependent kinase 1 (CDK1) primes for phosphorylation of T234 by Glycogen synthase kinase-3 beta (GSK3B), which primes for phosphorylation of S230 by GSK3B. Triple-phosphorylated hNIFK (MKI67IP) binds strongly to Antigen KI-67 (MKI67). | ||
MOD_CDK_1 - Substrate motif for phosphorylation by CDK | |||||||
| CDN1B_HUMAN | 184 | 190 | Pre‑assembly | Composite binding site formation | Binding of Cyclin-dependent kinase inhibitor 1B (CDKN1B) (p27) to the SCF-Skp2 ubiquitin ligase complex requires phosphorylation of p27 (CDKN1B) at T187, and association of the F-box protein S-phase kinase-associated protein 2 (SKP2) with the regulatory Cyclin-dependent kinases regulatory subunit 1 (CKS1B). SKP2 and CKS1B together generate a composite binding site for p27 (CDKN1B). While some residues, including the phosphorylated T187, bind to CKS1B and others to SKP2, the E185 makes contact with residues of both CKS1B and SKP2. | ||
| CDN1C_HUMAN | 307 | 313 | Pre‑assembly | Composite binding site formation | Binding of Cyclin-dependent kinase inhibitor 1C (CDKN1C) (p57) to the SCF-Skp2 ubiquitin ligase complex requires phosphorylation of p57 (CDKN1C) at T310, and association of the F-box protein S-phase kinase-associated protein 2 (SKP2) with the regulatory Cyclin-dependent kinases regulatory subunit 1 (CKS1B). SKP2 and CKS1B together generate a composite binding site for p57 (CDKN1C). | ||
| CDN1C_MOUSE | 339 | 345 | Pre‑assembly | Composite binding site formation | Binding of Cyclin-dependent kinase inhibitor 1C (Cdkn1c) (p57) to the SCF-Skp2 ubiquitin ligase complex requires phosphorylation of p57 (Cdkn1c) at T342, and association of the F-box protein S-phase kinase-associated protein 2 (SKP2) with the regulatory Cyclin-dependent kinases regulatory subunit 1 (CKS1B). SKP2 and CKS1B together generate a composite binding site for p57 (Cdkn1c). | ||
| ODFP2_HUMAN | 793 | 799 | Binary | Pre‑translational | Alternative splicing removes the cyclin-dependent kinase (CDK) phosphorylation motif of Isoform Cenexin 1 of Outer dense fiber protein 2 (ODF2), abrogating binding to Cyclin-dependent kinase 1 (CDK1). This phosphorylation is required for the recruitment of Serine/threonine-protein kinase PLK1 (PLK1). The C-terminal extension of Isoform Cenexin 1 of Outer dense fiber protein 2 (ODF2) has the ability to distinctly localise to mother centriole whereas the splice variant (e.g. Isoform Cenexin 1 of Outer dense fiber protein 2 (ODF2)), which does not have this extension, permits ODF2 to associate with sperm tail. | ||
MOD_CK1_1 - CK1 phosphorylation site | |||||||
| YAP1_HUMAN | 381 | 387 | Specificity | Altered binding specificity | Phosphorylation of Yorkie homolog (YAP1) at S381 by Serine/threonine-protein kinase LATS1 (LATS1) (a key regulator of the Hippo Pathway) primes the sequence for phosphorylation by Casein kinase I isoform epsilon (CSNK1E) at S384 and S387. This targets YAP1 to the SCF ubiqutin ligase complex, F-box/WD repeat-containing protein 1A (BTRC), which marks is YAP1 for subsequent degradation by the proteasomal system. N.B. Serine/threonine-protein kinase LATS2 (LATS2) can replace LATS1 and Casein kinase I isoform delta (CSNK1D) can replace CSNK1E | ||
| YAP1_HUMAN | 384 | 390 | Specificity | Altered binding specificity | Phosphorylation of Yorkie homolog (YAP1) at S381 by Serine/threonine-protein kinase LATS1 (LATS1) (a key regulator of the Hippo Pathway) primes the sequence for phosphorylation by Casein kinase I isoform epsilon (CSNK1E) at S384 and S387. This targets YAP1 to the SCF ubiqutin ligase complex, F-box/WD repeat-containing protein 1A (BTRC), which marks is YAP1 for subsequent degradation by the proteasomal system. N.B. Serine/threonine-protein kinase LATS2 (LATS2) can replace LATS1 and Casein kinase I isoform delta (CSNK1D) can replace CSNK1E | ||
MOD_GSK3_1 - GSK3 phosphorylation recognition site | |||||||
| NFAC1_HUMAN | 287 | 294 | Binary | Physicochemical compatibility | Phosphorylation of S294 adjacent to the NLS of Nuclear factor of activated T-cells, cytoplasmic 1 (NFATC1) by cAMP subfamily primes Nuclear factor of activated T-cells, cytoplasmic 1 (NFATC1) for subsequent phosphorylation by Glycogen synthase kinase-3 beta (GSK3B), which results in inhibition of nuclear import of Nuclear factor of activated T-cells, cytoplasmic 1 (NFATC1). | ||
| NFAC1_HUMAN | 238 | 245 | Binary | Physicochemical compatibility | Phosphorylation of S245 adjacent to the NLS of Nuclear factor of activated T-cells, cytoplasmic 1 (NFATC1) by cAMP subfamily primes Nuclear factor of activated T-cells, cytoplasmic 1 (NFATC1) for subsequent phosphorylation by Glycogen synthase kinase-3 beta (GSK3B), which results in inhibition of nuclear import of Nuclear factor of activated T-cells, cytoplasmic 1 (NFATC1). | ||
| MYC_HUMAN | 55 | 62 | Binary | Physicochemical compatibility | Phosphorylation of Myc proto-oncogene protein (MYC) at S62 primes the protein for phosphorylation at T58 by Glycogen synthase kinase-3 beta (GSK3B). | ||
| P53_HUMAN | 30 | 37 | Binary | Physicochemical compatibility | Phosphorylation of Cellular tumor antigen p53 (TP53) at S37 primes the protein for phosphorylation at S33 by Glycogen synthase kinase-3 beta (GSK3B). | ||
| JUN_HUMAN | 236 | 243 | Binary | Physicochemical compatibility | Phosphorylation of Transcription factor AP-1 (JUN) at S243 primes the protein for phosphorylation at T239 by Glycogen synthase kinase-3 beta (GSK3B). | ||
| CCNE1_HUMAN | 392 | 399 | Binary | Physicochemical compatibility | Phosphorylation of G1/S-specific cyclin-E1 (CCNE1) at S399 by Cyclin-dependent kinase 2 (CDK2) primes the protein for subsequent phosphorylation at T395 by Glycogen synthase kinase-3 beta (GSK3B). | ||
| ATX3_HUMAN | 253 | 260 | Binary | Physicochemical compatibility | Phosphorylation of Ataxin-3 (ATXN3) at S260 primes the protein for subsequent phosphorylation at S256 by Glycogen synthase kinase-3 beta (GSK3B). | ||
| CCNE1_HUMAN | 377 | 384 | Specificity | Altered binding specificity | Phosphorylation of Isoform E-S of G1/S-specific cyclin-E1 (CCNE1) at S384 by CDK2 primes CCNE1 for phosphorylation by Glycogen synthase kinase-3 beta (GSK3B) at T380, which creates a recognition site for F box proteins of the SCF ubiquitin ligase complex (F-box/WD repeat-containing protein 7 (FBXW7)) that target CCNE1 for degradation. | ||
| SMAD3_HUMAN | 201 | 208 | Specificity | Altered binding specificity | CDK8/9 phosphorylates Mothers against decapentaplegic homolog 3 (SMAD3) at T179 and S208. Phosphorylation of T179 creates a binding site for the WW domain of Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1), while phosphorylation of S208 primes SMAD3 for phosphorylation of S204 by Glycogen synthase kinase-3 beta (GSK3B). The pS204-pS208 forms a binding site for the third WW domain of E3 ubiquitin-protein ligase NEDD4-like (NEDD4L), whose second WW domain will displace the WW domain of PIN1 at the pT179-PY box site of SMAD3. This regulation couples SMAD3 activation to SMAD3 destruction in an ordered fashion. See also switch details and switch details. | ||
| FGD1_HUMAN | 280 | 287 | Specificity | Altered binding specificity | Phosphorylation of FYVE, RhoGEF and PH domain-containing protein 1 (FGD1), a GEF for CDC42 small effector protein 2 (CDC42SE2), by Glycogen synthase kinase-3 beta (GSK3B) targets FGD1 to the SCF ubiquitin ligase complex, F-box/WD repeat-containing protein 1A (BTRC), which marks FGD1 for degradation. | ||
| FGD3_HUMAN | 77 | 84 | Specificity | Altered binding specificity | Phosphorylation of FYVE, RhoGEF and PH domain-containing protein 3 (FGD3), a GEF for CDC42 small effector protein 2 (CDC42SE2), by Glycogen synthase kinase-3 beta (GSK3B) targets FGD3 to the SCF ubiquitin ligase complex, F-box/WD repeat-containing protein 1A (BTRC), which marks FGD3 for degradation. | ||
| FGD3_HUMAN | 73 | 80 | Specificity | Altered binding specificity | Phosphorylation of FYVE, RhoGEF and PH domain-containing protein 3 (FGD3), a GEF for CDC42 small effector protein 2 (CDC42SE2), by Glycogen synthase kinase-3 beta (GSK3B) targets FGD3 to the SCF ubiquitin ligase complex, F-box/WD repeat-containing protein 1A (BTRC), which marks FGD3 for degradation. | ||
| MK67I_HUMAN | 231 | 238 | Specificity | Altered binding specificity | Phosphorylation of T238 of MKI67 FHA domain-interacting nucleolar phosphoprotein (MKI67IP) by Cyclin-dependent kinase 1 (CDK1) primes for phosphorylation of T234 by Glycogen synthase kinase-3 beta (GSK3B), which primes for phosphorylation of S230 by GSK3B. Triple-phosphorylated hNIFK (MKI67IP) binds strongly to Antigen KI-67 (MKI67). | ||
| MK67I_HUMAN | 227 | 234 | Specificity | Altered binding specificity | Phosphorylation of T238 of MKI67 FHA domain-interacting nucleolar phosphoprotein (MKI67IP) by Cyclin-dependent kinase 1 (CDK1) primes for phosphorylation of T234 by Glycogen synthase kinase-3 beta (GSK3B), which primes for phosphorylation of S230 by GSK3B. Triple-phosphorylated hNIFK (MKI67IP) binds strongly to Antigen KI-67 (MKI67). | ||
| MYC_HUMAN | 55 | 62 | Specificity | Altered binding specificity | Phosphorylation of Myc proto-oncogene protein (MYC) at S62 by Mitogen-activated protein kinase 1 (MAPK1) primes MYC for phosphorylation by Glycogen synthase kinase-3 beta (GSK3B), which targets MYC to the SCF ubiquitin ligase complex, F-box/WD repeat-containing protein 7 (FBXW7) that marks MYC for degradation. | ||
| JUN_HUMAN | 236 | 243 | Specificity | Altered binding specificity | Transcription factor AP-1 (JUN) is primed by an unknown kinase for phosphorylation by Glycogen synthase kinase-3 beta (GSK3B), which targets JUN to the SCF ubiquitin ligase complex, F-box/WD repeat-containing protein 7 (FBXW7) that marks JUN for degradation. In v-Jun (Viral jun-transforming protein (JUN)) the residue corresponding to S243 is mutated to phenylalanine, which protects v-Jun (JUN) from degradation. | ||
| CCNE1_HUMAN | 392 | 399 | Specificity | Altered binding specificity | Phosphorylation of G1/S-specific cyclin-E1 (CCNE1) at S399 generates a docking site for Glycogen synthase kinase-3 beta (GSK3B). Subsequent phosphorylation of CCNE1 by Glycogen synthase kinase-3 beta (GSK3B) at T395 switches the specificity of CCNE1 to the F-box/WD repeat-containing protein 7 (FBXW7), which recruits CCNE1 to the SCF ubiquitin ligase complex to mark CCNE1 for degradation. | ||
| SRBP1_HUMAN | 422 | 430 | Specificity | Altered binding specificity | Phosphorylation of SREBP-1 (Sterol regulatory element-binding protein 1 (SREBF1)) at S430 generates a docking site for Glycogen synthase kinase-3 beta (GSK3B). Subsequent phosphorylation of SREBP-1 (SREBF1) by GSK3B at T426 switches the specificity of SREBP-1 (SREBF1) to the F-box/WD repeat-containing protein 7 (FBXW7), which recruits SREBP-1 (SREBF1) to the SCF ubiquitin ligase complex to mark SREBP-1 (SREBF1) for degradation. | ||
| CTNB1_HUMAN | 34 | 41 | Specificity | Altered binding specificity | Phosphorylation of Catenin beta-1 (CTNNB1) at T41 generates a docking site for Glycogen synthase kinase-3 beta (GSK3B), which then phosphorylates S37, thereby generating a new docking site for GSK3B. Subsequent phosphorylation of S33 by GSK3B switches the specificity of CTNNB1 to the F-box/WD repeat-containing protein 1A (BTRC), which recruits CTNNB1 to the SCF ubiquitin ligase complex. | ||
| CTNB1_HUMAN | 30 | 37 | Specificity | Altered binding specificity | Phosphorylation of Catenin beta-1 (CTNNB1) at T41 generates a docking site for Glycogen synthase kinase-3 beta (GSK3B), which then phosphorylates S37, thereby generating a new docking site for GSK3B. Subsequent phosphorylation of S33 by GSK3B switches the specificity of CTNNB1 to the F-box/WD repeat-containing protein 1A (BTRC), which recruits CTNNB1 to the SCF ubiquitin ligase complex. | ||
| SNAI1_HUMAN | 93 | 100 | Specificity | Altered binding specificity | Phosphorylation of Zinc finger protein SNAI1 (SNAI1) at S100 generates a docking site for Glycogen synthase kinase-3 beta (GSK3B). Subsequent phosphorylation of S96 by GSK3B targets Zinc finger protein SNAI1 (SNAI1) to the SCF ubiquitin ligase complexes F-box/WD repeat-containing protein 1A (BTRC), which marks it for degradation. | ||
| ESR2_HUMAN | 5 | 12 | Binary | Physicochemical compatibility | The GSK3-beta binding site at S12 in Estrogen receptor beta (ESR2) is primed by (most likely) RAC-alpha serine/threonine-protein kinase (AKT1). This enhances the binding of SUMO-conjugating enzyme UBC9 (UBE2I) at the adjacent Sumoylation site. This site is also primed at S6 (most likely) by AKT1. The addition of SUMO at K4 stabilises ESR2 as it prevents the ubiquitination at K4 (see switch details | ||
MOD_LATS_1 - The LATS phosphorylation motif is recognised by the LATS kinases for Ser/Thr phosphorylation. Substrates are often found toward the end of the Hippo signalling pathway. | |||||||
| YAP1_HUMAN | 376 | 382 | Specificity | Altered binding specificity | Phosphorylation of Yorkie homolog (YAP1) at S381 by Serine/threonine-protein kinase LATS1 (LATS1) (a key regulator of the Hippo Pathway) primes the sequence for phosphorylation by Casein kinase I isoform epsilon (CSNK1E) at S384 and S387. This targets YAP1 to the SCF ubiqutin ligase complex, F-box/WD repeat-containing protein 1A (BTRC), which marks is YAP1 for subsequent degradation by the proteasomal system. N.B. Serine/threonine-protein kinase LATS2 (LATS2) can replace LATS1 and Casein kinase I isoform delta (CSNK1D) can replace CSNK1E | ||
MOD_NMyristoyl - Generic motif for N-Myristoylation site. | |||||||
| RECO_BOVIN | 1 | 7 | Binary | Allostery | Binding of calcium(2+) to Recoverin (RCVRN) results in a conformational change in Recoverin that makes the myristoyl moiety available for binding to the membrane. | ||
| KAPCA_HUMAN | 1 | 7 | Binary | Allostery | Phosphorylation of cAMP-dependent protein kinase catalytic subunit alpha (PRKACA) at S11 shifts the conformational equilibrium to the myristoyl-out conformation, making the myristoyl moiety available for interaction with the membrane. | ||
| PDE2A_HUMAN | 1 | 7 | Binary | Pre‑translational | Alternative splicing removes the myristoylation motif of cGMP-dependent 3',5'-cyclic phosphodiesterase (PDE2A). The soluble Isoform PDE2A1 of cGMP-dependent 3',5'-cyclic phosphodiesterase (PDE2A) is expressed in a variety of peripheral tissues, whereas the membrane-associated Isoform PDE2A3 of cGMP-dependent 3',5'-cyclic phosphodiesterase (PDE2A) is found exclusively in the brain. Isoform PDE2A3 of cGMP-dependent 3',5'-cyclic phosphodiesterase (PDE2A) requires N-myristoylation together with palmitoylation to be targeted to synapses, allowing control and crosstalk of cyclic nucleotides. | ||
MOD_PKA_1 - Main preference for PKA-type AGC kinase phosphorylation. | |||||||
| SYN_DROME | 3 | 9 | Binary | Pre‑translational | RNA editing removes the degron motif of Synapsin (Syn), abrogating binding to cAMP-dependent protein kinase catalytic subunit (Pka-C1). A genomic version of the protein sequence contains a canonical PKA-recognition motif that is highly conserved, however in Drosophilia, in all except the embryo sequences this sequence was RNA-edited to RGFS (from RRFS). | ||
MOD_PKA_2 - Secondary preference for PKA-type AGC kinase phosphorylation. | |||||||
| SPTB2_HUMAN | 2157 | 2162 | Binary | Pre‑translational | Alternative splicing removes the PKA-binding motif of Isoform Short of Spectrin beta chain, brain 1 (SPTBN1), abrogating binding to cAMP-dependent protein kinase catalytic subunit alpha (PRKACA). The phosphorylation of the short C-terminal betaII-spectrin (also known as Isoform Short of Spectrin beta chain, brain 1 (SPTBN1)) by PKA is important in allowing neuritogenesis. | ||
MOD_ProDKin_1 - Proline-Directed Kinase (e.g. MAPK) phosphorylation site in higher eukaryotes. | |||||||
| MYC_HUMAN | 59 | 65 | Specificity | Altered binding specificity | Phosphorylation of Myc proto-oncogene protein (MYC) at S62 by Mitogen-activated protein kinase 1 (MAPK1) primes MYC for phosphorylation by Glycogen synthase kinase-3 beta (GSK3B), which targets MYC to the SCF ubiquitin ligase complex, F-box/WD repeat-containing protein 7 (FBXW7) that marks MYC for degradation. | ||
MOD_SUMO - Motif recognised for modification by SUMO-1 | |||||||
| HSF4_HUMAN | 292 | 295 | Binary | Pre‑translational | Alternative splicing removes the sumoylation motif of Heat shock factor protein 4 (HSF4), abrogating binding to SUMO-conjugating enzyme UBC9 (UBE2I). The phosphorylation-dependent sumoylation of the PDSM (phosphorylation-dependent sumoylation motif) strongly represses Isoform HSF4B of Heat shock factor protein 4 (HSF4) activity. | ||
| HSF4_HUMAN | 292 | 295 | Binary | Physicochemical compatibility | The phosphorylation-dependent sumoylation of the PDSM (phosphorylation-dependent sumoylation motif) strongly represses Isoform HSF4B of Heat shock factor protein 4 (HSF4) activity. | ||
| PML_HUMAN | 489 | 492 | Binary | Pre‑translational | Alternative splicing removes the SUMO motif of Protein PML (PML), abrogating binding to SUMO-conjugating enzyme UBC9 (UBE2I). The study identified a major sumoylation site within the nuclear localisation signal (NLS) of PML. Although they did not determine whether the lysine residue regulates the NLS, they found that sumoylation was not necessary for nuclear localisation and that SUMO-modification only occurs in the nucleus. | ||
| PML_HUMAN | 159 | 162 | Uncategorised | Uncategorised | Sumoylation of K160 induces binding to the Protein PML (PML) protein. SUMO-modified forms of PML are essential for the recruitment of Protein PML (PML) to PML nuclear bodies. | ||
| PML_HUMAN | 159 | 162 | Uncategorised | Uncategorised | Sumoylation of K160 induces binding to the Protein PML (PML) protein. SUMO-modified forms of PML are essential for the recruitment of Death domain-associated protein 6 (DAXX) to PML nuclear bodies. | ||
| NFAC1_HUMAN | 701 | 704 | Binary | Pre‑translational | Alternative splicing removes the Sumoylation motif (SIM) of Nuclear factor of activated T-cells, cytoplasmic 1 (NFATC1), preventing the sumolyation of Isoform A-alpha of Nuclear factor of activated T-cells, cytoplasmic 1 (NFATC1). Both the Isoform C-alpha of Nuclear factor of activated T-cells, cytoplasmic 1 (NFATC1) and Isoform A-alpha of Nuclear factor of activated T-cells, cytoplasmic 1 (NFATC1) exert a differential effect upon IL-2 expression. However, the longer isoform, Isoform C-alpha of Nuclear factor of activated T-cells, cytoplasmic 1 (NFATC1), has a sumoylation motif and is therefore negatively regulated in a sumolyation-dependent manner. | ||
| NFAC1_HUMAN | 913 | 916 | Binary | Pre‑translational | Alternative splicing removes the Sumoylation motif (SIM) of Nuclear factor of activated T-cells, cytoplasmic 1 (NFATC1), preventing the sumolyation of Isoform A-alpha of Nuclear factor of activated T-cells, cytoplasmic 1 (NFATC1). Both the Isoform C-alpha of Nuclear factor of activated T-cells, cytoplasmic 1 (NFATC1) and Isoform A-alpha of Nuclear factor of activated T-cells, cytoplasmic 1 (NFATC1) exert a differential effect upon IL-2 expression. However, the longer isoform, Isoform C-alpha of Nuclear factor of activated T-cells, cytoplasmic 1 (NFATC1), has a sumoylation motif and is therefore negatively regulated in a sumolyation-dependent manner. | ||
MOD_SUMO_PHOS - | |||||||
| ESR2_HUMAN | 4 | 7 | Binary | Physicochemical compatibility | The GSK3-beta binding site at S12 in Estrogen receptor beta (ESR2) is primed by (most likely) RAC-alpha serine/threonine-protein kinase (AKT1). This enhances the binding of SUMO-conjugating enzyme UBC9 (UBE2I) at the adjacent Sumoylation site. This site is also primed at S6 (most likely) by AKT1. The addition of SUMO at K4 stabilises ESR2 as it prevents the ubiquitination at K4 (see switch details) | ||
| ESR2_HUMAN | 4 | 7 | Binary | Physicochemical compatibility | Sumoylation of K4 in Estrogen receptor beta (ESR2) is inhibited by ubiquitination K4. This destabilises ESR2 increasing its turnover (see also switch details) | ||
MOD_Spalmitoyl - | |||||||
| CDC42_HUMAN | 188 | 191 | Binary | Pre‑translational | Alternative splicing removes the palmitoylation motif of Isoform Brain of Cell division control protein 42 homolog (CDC42), abrogating binding to Palmitoyltransferase ZDHHC9 (ZDHHC9). The splice variant with the palmitoylation motif (Isoform Brain of Cell division control protein 42 homolog (CDC42)) is expressed in brain and is often found within raf-like domain of dendrites. Increased levels of glutamate results in rapid depalmitoylation and dislocation from dendrites. | ||
TRG_AP2beta_CARGO_1 - AP-2 beta appendage platform subdomain (top surface) binding motif used in targeting cargo for internalisation. | |||||||
| ARRB1_HUMAN | 385 | 395 | Binary | Allostery | Binding of Beta-arrestin-1 (ARRB1) to ligand-induced, phosphorylated GPCRs results in a conformational change that makes the AP2-beta interaction motif in Beta-arrestin-1 (ARRB1) accessible for binding to AP-2 complex subunit beta (AP2B1), which mediates internalization of the GPCR. | ||
TRG_AP2beta_CARGO_2 - | |||||||
| PI51C_MOUSE | 633 | 644 | Binary | Pre‑translational | Alternative splicing removes the AP-2 beta-appendage-binding motif of Phosphatidylinositol 4-phosphate 5-kinase type-1 gamma (Pip5k1c), abrogating binding to AP-2 complex subunit beta (Ap2b1). With other enzymes (members of the eukaryotic diacylglycerol kinase family, and Synaptojanin-1 (Synj1)), Isoform PIPKIgamma661 of Phosphatidylinositol 4-phosphate 5-kinase type-1 gamma (Pip5k1c) (PIPKIgamma661) optimises the regional lipid environment necessary for clathrin coat formation. There are three different C-terminal splice variants of Pip5k1c: one (PIPKIgamma687) can bind selectively to Talin-1 (Tln1) via the C-terminal extension (switch details), one (PIPKIgamma661) can bind to both Talin-1 (Tln1) and AP-2 complex subunit beta (Ap2b1), and one (PIPKIgamma635) can bind to neither protein. This flexibility could impart importantly different biological functions to each isoform. For example, in humans PIP5K1C (PIPKIgamma661 in mouse) is proposed to act upstream of Rac/Rho and the differential regulation of PIP5K-gamma and -alpha might allow them to work in tandem to modulate the actin cytoskeleton during the attachment and ingestion phases of phagocytosis (See (here)). | ||
| PI51C_MOUSE | 633 | 644 | Binary | Physicochemical compatibility | Phosphorylation of S645 in Phosphatidylinositol 4-phosphate 5-kinase type-1 gamma (Pip5k1c) impedes binding to AP-2 complex subunit beta (Ap2b1), while dephosphorylation by calcineurin promotes binding. These phosphorylation and dephosphorylation events are important for the regulation of clathrin coat formation associated with synaptic vesicles. | ||
TRG_ENDOCYTIC_2 - Tyrosine-based sorting signal responsible for the interaction with mu subunit of AP (Adaptor Protein) complex | |||||||
| PPAL_HUMAN | 413 | 416 | Uncategorised | Uncategorised | Phosphorylation of T156 in AP-2 complex subunit mu (AP2M1) by AP2-associated protein kinase 1 (AAK1) upon clathrin recruitment strengthens the interaction between AP-2 complex subunit mu (AP2M1) and cargo proteins. | ||
| TGON3_RAT | 350 | 353 | Binary | Allostery | Binding of 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate to the AP-2 complex alpha, beta and mu subunits exposes a binding site on the AP-2 complex subunit mu (Ap2m1) subunit for recruitment of Trans-Golgi network integral membrane protein TGN38 (Ttgn1) via an endocytosis motif. | ||
| EGFR_HUMAN | 998 | 1001 | Binary | Allostery | Binding of 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate to the AP-2 complex alpha, beta and mu subunits exposes a binding site on the AP-2 complex subunit mu (AP2M1) subunit for recruitment of Epidermal growth factor receptor (EGFR) via an endocytosis motif. | ||
| TFR1_HUMAN | 20 | 23 | Binary | Allostery | Binding of 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate to the AP-2 complex alpha, beta and mu subunits exposes a binding site on the AP-2 complex subunit mu (AP2M1) subunit for recruitment of Transferrin receptor protein 1 (TFRC) via an endocytosis motif. | ||
| ENV_HTLV2 | 477 | 480 | Binary | Allostery | Binding of 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate to the AP-2 complex alpha, beta and mu subunits exposes a binding site on the AP-2 complex subunit mu (AP2M1) subunit for recruitment of Envelope glycoprotein gp63 (env) via an endocytosis motif. | ||
| VGLG_VSIVA | 501 | 504 | Binary | Allostery | Binding of 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate to the AP-2 complex alpha, beta and mu subunits exposes a binding site on the AP-2 complex subunit mu (AP2M1) subunit for recruitment of Glycoprotein G (G) via an endocytosis motif. | ||
| ENV_HV1H2 | 712 | 715 | Binary | Allostery | Binding of 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate to the AP-2 complex alpha, beta and mu subunits exposes a binding site on the AP-2 complex subunit mu (AP2M1) subunit for recruitment of Envelope glycoprotein gp160 (env) via an endocytosis motif. | ||
| ENV_SIVMK | 723 | 726 | Binary | Allostery | Binding of 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate to the AP-2 complex alpha, beta and mu subunits exposes a binding site on the AP-2 complex subunit mu (AP2M1) subunit for recruitment of Envelope glycoprotein gp160 (env) via an endocytosis motif. | ||
| ASGR1_HUMAN | 5 | 8 | Binary | Allostery | Binding of 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate to the AP-2 complex alpha, beta and mu subunits exposes a binding site on the AP-2 complex subunit mu (AP2M1) subunit for recruitment of Asialoglycoprotein receptor 1 (ASGR1) via an endocytosis motif. | ||
| LAMP1_HUMAN | 414 | 417 | Binary | Allostery | Binding of 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate to the AP-2 complex alpha, beta and mu subunits exposes a binding site on the AP-2 complex subunit mu (AP2M1) subunit for recruitment of Lysosome-associated membrane glycoprotein 1 (LAMP1) via an endocytosis motif. | ||
| CTLA4_HUMAN | 201 | 204 | Binary | Allostery | Binding of 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate to the AP-2 complex alpha, beta and mu subunits exposes a binding site on the AP-2 complex subunit mu (AP2M1) subunit for recruitment of Cytotoxic T-lymphocyte protein 4 (CTLA4) via an endocytosis motif. | ||
| L1CAM_HUMAN | 1176 | 1179 | Binary | Allostery | Binding of 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate to the AP-2 complex alpha, beta and mu subunits exposes a binding site on the AP-2 complex subunit mu (AP2M1) subunit for recruitment of Neural cell adhesion molecule L1 (L1CAM) via an endocytosis motif. | ||
| ENV_BLV | 487 | 490 | Binary | Allostery | Binding of 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate to the AP-2 complex alpha, beta and mu subunits exposes a binding site on the AP-2 complex subunit mu (AP2M1) subunit for recruitment of Envelope glycoprotein (env) via an endocytosis motif. | ||
| GE_VZVO | 582 | 585 | Binary | Allostery | Binding of 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate to the AP-2 complex alpha, beta and mu subunits exposes a binding site on the AP-2 complex subunit mu (AP2M1) subunit for recruitment of Envelope glycoprotein E (gE) via an endocytosis motif. | ||
| CTLA4_MOUSE | 201 | 204 | Specificity | Altered binding specificity | Dephosphorylation of Y201 of Cytotoxic T-lymphocyte protein 4 (Ctla4) switches the specificity of Ctla4 from SH2 domain-containing proteins like Tyrosine-protein phosphatase non-receptor type 11 (Ptpn11) to the AP-2 complex mu subunit (AP-2 complex subunit mu (Ap2m1)), thereby switching from inhibitory signal transmission and negative regulation of T cell responses to internalization and inactivation of Ctla4. | ||
| L1CAM_HUMAN | 1176 | 1179 | Binary | Physicochemical compatibility | Phosphorylation of Y1176 by Proto-oncogene tyrosine-protein kinase Src (SRC) in the endocytosis motif of Neural cell adhesion molecule L1 (L1CAM) inhibits binding to AP-2 complex subunit mu (AP2M1). | ||
| L1CAM_HUMAN | 1176 | 1179 | Binary | Pre‑translational | Alternative splicing removes the endocytosis motif of Neural cell adhesion molecule L1 (L1CAM), abrogating binding to AP-2 complex subunit mu (AP2M1). This motif is required for sorting of L1CAM to the axonal growth cone of neurons and its clathrin-mediated internalisation. Non-neuronal cells, such as Schwann cells, do not require these motifs, probably because these cells are not highly polarised. | ||
| PEX5R_MOUSE | 38 | 41 | Binary | Pre‑translational | Alternative splicing removes the endocytosis motif of Isoform 3 of PEX5-related protein (Pex5l), abrogating binding to AP-2 complex subunit mu (Ap2m1). The motif is present in exon 2, and its absence causes a significant increase in channel density of members from the potassium channel HCN family. | ||
| SORC1_HUMAN | 1132 | 1135 | Binary | Pre‑translational | Alternative splicing removes the endocytosis motif of Isoform 2 of VPS10 domain-containing receptor SorCS1 (SORCS1), abrogating binding to AP-2 complex subunit mu (AP2M1). The sequence is conserved in both human and mouse. Different splice variants have different endocytosis motifs. | ||
| PI51C_MOUSE | 644 | 647 | Binary | Pre‑translational | Alternative splicing removes the endocytosis motif of Phosphatidylinositol 4-phosphate 5-kinase type-1 gamma (Pip5k1c), abrogating binding to AP-2 complex subunit mu (Ap2m1). The direct interaction between the AP-2 complex and Isoform PIPKIgamma661 of Phosphatidylinositol 4-phosphate 5-kinase type-1 gamma (Pip5k1c) (PIPKIgamma661) targets this isoform to sites of endocytosis at the plasma membrane. Consequently, this results in the generation of a highly concentrated pool of PI(4,5)P2 at these sites. | ||
| PI51C_HUMAN | 649 | 652 | Binary | Physicochemical compatibility | Phosphorylation of S645 near the AP2-binding motif of Phosphatidylinositol-4-phosphate 5-kinase type-1 gamma (PIP5K1C) by Cyclin-dependent kinase 5 (Cdk5) inhibits its interaction with AP-2 complex subunit mu (AP2M1). | ||
| L1CAM_HUMAN | 1176 | 1179 | Binary | Physicochemical compatibility | Phosphorylation of Y1176 in the endocytotic motif of Neural cell adhesion molecule L1 (L1CAM) by Proto-oncogene tyrosine-protein kinase Src (SRC) abolishes binding to the AP-2 complex subunit mu (AP2M1) and thereby inhibits internalisation of Neural cell adhesion molecule L1 (L1CAM). | ||
TRG_ER_KDEL_1 - Golgi-to-ER retrieving signal found at the C-terminus of many ER soluble proteins. It interacts with the KDEL receptor which in turns interacts with components of the coatomer (COP I). | |||||||
| PIMT_BOVIN | 225 | 228 | Binary | Pre‑translational | Alternative splicing removes the KDEL ER-retention motif of Isoform 2 of Protein-L-isoaspartate(D-aspartate) O-methyltransferase (PCMT1). | ||
| P3H1_HUMAN | 733 | 736 | Binary | Pre‑translational | Alternative splicing removes the KDEL ER-retention motif of Prolyl 3-hydroxylase 1 (LEPRE1). | ||
TRG_ER_diArg_1 - The di-Arg ER retention motif is defined by two consecutive arginine residues (RR) or with a single residue insertion (RXR). The motif is completed by an adjacent hydrophobic/arginine residue which may be on either side of the Arg pair. | |||||||
| NMDZ1_HUMAN | 893 | 895 | Binary | Physicochemical compatibility | Phosphorylation of S896 adjacent to the ER retention motif of Glutamate [NMDA] receptor subunit zeta-1 (GRIN1) by PKC subfamily (and possibly S897 by PKA) inactivates the motif and promotes delivery of the receptor to the plasma membrane. Optimal trafficking upon dual phosphorylation of S896 and S897 allows regulation of receptor trafficking by coordinated PKA and PKC signaling. | ||
| ADA22_HUMAN | 829 851 | 831 854 | Specificity | Motif hiding | Phosphorylation-induced binding of dimeric 14-3-3 protein beta/alpha (YWHAB) to Disintegrin and metalloproteinase domain-containing protein 22 (ADAM22) blocks ER retention motifs in Disintegrin and metalloproteinase domain-containing protein 22 (ADAM22) and regulates transport of this protein to the membrane. | ||
| GPR15_HUMAN | 352 | 354 | Specificity | Motif hiding | Phosphorylation-induced binding of 14-3-3 protein beta/alpha (YWHAB) promotes cell surface expression of G-protein coupled receptor 15 (GPR15) by releasing the receptor from the ER retrieval/retention pathway that is mediated by the interaction of its ER retention motif with Coatomer subunit beta (COPB1). | ||
| HG2A_HUMAN | 3 | 5 | Specificity | Motif hiding | The basic ER retention motif of HLA class II histocompatibility antigen gamma chain (CD74) is blocked from binding to Coatomer subunit beta (COPB1) by phosphorylation-induced binding of 14-3-3 protein beta/alpha (YWHAB), regulating its release from the ER and trafficking to the plasma membrane. | ||
| GABR1_HUMAN | 923 | 926 | Specificity | Motif hiding | Interaction of the GABA receptor R2 subunit (Gamma-aminobutyric acid type B receptor subunit 2 (GABBR2)) with the R1 subunit (Gamma-aminobutyric acid type B receptor subunit 1 (GABBR1)) via coiled-coil forming domains masks the ER retention motif in the R1 subunit (Gamma-aminobutyric acid type B receptor subunit 1 (GABBR1)), thereby promoting surface expression of fully assembled GABA receptors. | ||
| NMDZ1_HUMAN | 893 | 895 | Specificity | Motif hiding | Binding of the PDZ domain of Disks large homolog 4 (DLG4) suppresses the ER-retention motif of Isoform 4 of Glutamate receptor subunit zeta-1 (GRIN1) in a splice variant-specific manner, thereby promoting cell surface expression of this particular isoform. This supports the hypothesis that local regulation of receptor exit from neuronal ER plays a role in modifying discrete synaptic receptor number. | ||
| NMDZ1_HUMAN | 893 | 895 | Specificity | Motif hiding | Binding of the PDZ domain of Disks large homolog 4 (DLG4) suppresses the ER-retention motif of Isoform 4 of Glutamate receptor subunit zeta-1 (GRIN1) in a splice variant-specific manner, thereby promoting cell surface expression of this particular isoform. This supports the hypothesis that local regulation of receptor exit from neuronal ER plays a role in modifying discrete synaptic receptor number. | ||
| NMDZ1_HUMAN | 893 | 895 | Specificity | Motif hiding | Binding of the PDZ domain of Disks large homolog 4 (DLG4) suppresses the ER-retention motif of Isoform 4 of Glutamate receptor subunit zeta-1 (GRIN1) in a splice variant-specific manner, thereby promoting cell surface expression of this particular isoform. This supports the hypothesis that local regulation of receptor exit from neuronal ER plays a role in modifying discrete synaptic receptor number. | ||
TRG_ER_diArg_2 - | |||||||
| GRIK1_RAT | 937 | 941 | Binary | Pre‑translational | Alternative splicing removes the di-arginine ER-retention motif of Glutamate receptor, ionotropic kainate 1 (Grik1), abrogating binding to Coatomer subunit beta (COPB1). | ||
TRG_ER_diLys_1 - ER retention and retrieving signal found at the C-terminus of type I ER membrane proteins (cytoplasmic in this topology). Di-Lysine signal is responsible for COPI-mediated retrieval from post-ER compartments. | |||||||
| S35A2_HUMAN | 392 | 396 | Binary | Pre‑translational | Alternative splicing removes the di-lysine ER-retention motif of UDP-galactose translocator (SLC35A2), abrogating binding to Coatomer subunit alpha (COPA). This motif localises Isoform UGT1 of UDP-galactose translocator (SLC35A2) exclusively in the Golgi whereas Isoform UGT2 of UDP-galactose translocator (SLC35A2) shows dual expression in both the Golgi and the ER. This motif is considered a weak retention signal. | ||
TRG_LysEnd_APsAcLL_1 - Sorting and internalisation signal found in the cytoplasmic juxta-membrane region of type I transmembrane proteins. Targets them from the Trans Golgi Network to the lysosomal-endosomal-melanosomal compartments. Interacts with adaptor protein (AP) complexes | |||||||
| CD4_HUMAN | 434 | 439 | Binary | Allostery | Binding of 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate to the AP-2 complex alpha, beta and mu subunits exposes a binding site on the AP-2 complex subunit sigma (AP2S1) subunit for recruitment of T-cell surface glycoprotein CD4 (CD4) via an endocytosis motif. | ||
| NPC1_HUMAN | 1271 | 1276 | Binary | Allostery | Binding of 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate to the AP-2 complex alpha, beta and mu subunits exposes a binding site on the AP-2 complex subunit sigma (AP2S1) subunit for recruitment of Niemann-Pick C1 protein (NPC1) via an endocytosis motif. | ||
| HG2A_HUMAN | 19 | 24 | Binary | Allostery | Binding of 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate to the AP-2 complex alpha, beta and mu subunits exposes a binding site on the AP-2 complex subunit sigma (AP2S1) subunit for recruitment of HLA class II histocompatibility antigen gamma chain (CD74) via an endocytosis motif. | ||
| CD3D_MOUSE | 138 | 143 | Binary | Allostery | Binding of 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate to the AP-2 complex alpha, beta and mu subunits exposes a binding site on the AP-2 complex subunit sigma (Ap2s1) subunit for recruitment of T-cell surface glycoprotein CD3 delta chain (Cd3d) via an endocytosis motif. | ||
| NEF_HV1H2 | 160 | 165 | Binary | Allostery | Binding of 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate to the AP-2 complex alpha, beta and mu subunits exposes a binding site on the AP-2 complex subunit sigma (AP2S1) subunit for recruitment of Nef protein (nef) via an endocytosis motif. | ||
| NEF_HV1B8 | 159 | 164 | Binary | Allostery | Binding of 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate to the AP-2 complex alpha, beta and mu subunits exposes a binding site on the AP-2 complex subunit sigma (AP2S1) subunit for recruitment of Protein Nef (nef) via an endocytosis motif. | ||
| CD3G_MOUSE | 149 | 154 | Binary | Allostery | Binding of 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate to the AP-2 complex alpha, beta and mu subunits exposes a binding site on the AP-2 complex subunit sigma (Ap2s1) subunit for recruitment of T-cell surface glycoprotein CD3 gamma chain (Cd3g) via an endocytosis motif. | ||
| CD44_HUMAN | 708 | 713 | Binary | Allostery | Binding of 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate to the AP-2 complex alpha, beta and mu subunits exposes a binding site on the AP-2 complex subunit sigma (AP2S1) subunit for recruitment of CD44 antigen (CD44) via an endocytosis motif. | ||
| OPRD_HUMAN | 241 | 246 | Binary | Allostery | Binding of 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate to the AP-2 complex alpha, beta and mu subunits exposes a binding site on the AP-2 complex subunit sigma (AP2S1) subunit for recruitment of Delta-type opioid receptor (OPRD1) via an endocytosis motif. | ||
| BCAM_HUMAN | 604 | 609 | Binary | Allostery | Binding of 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate to the AP-2 complex alpha, beta and mu subunits exposes a binding site on the AP-2 complex subunit sigma (AP2S1) subunit for recruitment of Basal cell adhesion molecule (BCAM) via an endocytosis motif. | ||
| ENV_BLV | 463 | 468 | Binary | Allostery | Binding of 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate to the AP-2 complex alpha, beta and mu subunits exposes a binding site on the AP-2 complex subunit sigma (AP2S1) subunit for recruitment of Envelope glycoprotein (env) via an endocytosis motif. | ||
| BACE1_HUMAN | 495 | 500 | Binary | Allostery | Binding of 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate to the AP-2 complex alpha, beta and mu subunits exposes a binding site on the AP-2 complex subunit sigma (AP2S1) subunit for recruitment of Beta-secretase 1 (BACE1) via an endocytosis motif. | ||
| ATP7A_HUMAN | 1483 | 1488 | Binary | Allostery | Binding of 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate to the AP-2 complex alpha, beta and mu subunits exposes a binding site on the AP-2 complex subunit sigma (AP2S1) subunit for recruitment of Copper-transporting ATPase 1 (ATP7A) via an endocytosis motif. | ||
| PEX5R_MOUSE | 14 | 19 | Binary | Pre‑translational | Alternative splicing removes the di-leucine endocytosis motif of PEX5-related protein (Pex5l), abrogating binding to AP-2 complex subunit sigma (Ap2s1). The motif is present in exon 5. | ||
| PRLR_RAT | 301 | 306 | Binary | Pre‑translational | Alternative splicing removes the di-leucine endocytosis motif of Prolactin receptor (Prlr), partially inhibiting binding to AP-2 complex subunit sigma (AP2S1) and the rate of endocytosis. Isoform Long of Prolactin receptor (Prlr) (also known as PRLR-long) has a longer C-terminal tail than the Isoform Short of Prolactin receptor (Prlr) (also known as PRLR-short) splice variant. PRLR-long internalises faster than PRLR-short due to two additional di-leucine motifs in the C-terminus (where the adjacent phenylalanine also plays a role). PRLR-short has two di-leucine motifs whereas PRLR-long has four. | ||
TRG_LysEnd_APsAcLL_2 - | |||||||
| SORC1_HUMAN | 1136 | 1140 | Binary | Pre‑translational | Alternative splicing removes the di-leucine motif of Isoform 4 of VPS10 domain-containing receptor SorCS1 (SORCS1), abrogating binding to AP-2 complex subunit sigma (AP2S1). Human and mouse have completely different C-termini for SorCS1a (also known as Isoform 4 of VPS10 domain-containing receptor SorCS1 (SORCS1)), with only the human splice variant containing the motif. | ||
TRG_MLS - | |||||||
| CACP_HUMAN | 1 | 21 | Binary | Pre‑translational | Alternative splicing removes the mitochondrial localisation signal (MLS) motif of Carnitine O-acetyltransferase (CRAT), abrogating binding to Mitochondrial import receptor subunit TOM70 (TOMM70A). As a result, Isoform SM-1200 of Carnitine O-acetyltransferase (CRAT), which lacks the MLS, is located in peroxisomes due to a PTS1 motif in its C-terminus. | ||
| DBLOH_HUMAN | 1 | 55 | Binary | Pre‑translational | Alternative splicing removes the BIR-binding motif of Diablo homolog, mitochondrial (DIABLO), abrogating binding to Mitochondrial import receptor subunit TOM70 (TOMM70A). Isoform SMAC3 of Diablo homolog, mitochondrial (DIABLO) is localised to mitochondria via its mitochondrial localisation signal (MLS). Upon entry in mitochondria the MLS is cleaved and Isoform SMAC3 of Diablo homolog, mitochondrial (DIABLO) is found localised with cytochrome-c. During apoptosis, Isoform SMAC3 of Diablo homolog, mitochondrial (DIABLO) binds to the second/third BIR domain of Baculoviral IAP repeat-containing protein 4 (XIAP). This interaction disrupts binding of XIAP to processed Caspase-9 (CASP9) and promotes Caspase-3 (CASP3) activation. Isoform SMAC3 of Diablo homolog, mitochondrial (DIABLO) also promotes ubiquitination of XIAP and subsequent degradation. Isoform 1 of Diablo homolog, mitochondrial (DIABLO) on the other hand did not cause degradation of XIAP. | ||
| UNG_HUMAN | 1 | 44 | Binary | Pre‑translational | Alternative promoter usage removes the mitochondrial localisation signal (MLS) of Isoform UNG1 of Uracil-DNA glycosylase (UNG), abrogating binding to Mitochondrial import receptor subunit TOM70 (TOMM70A) and import into mitochondria. In Isoform UNG2 of Uracil-DNA glycosylase (UNG) the MLS present in Isoform UNG1 of Uracil-DNA glycosylase (UNG) is replaced with a nuclear localisation signal (NLS), promoting different localisations of the different protein isoforms. | ||
| TRM1_YEAST | 1 | 16 | Binary | Pre‑translational | Alternative initiation removes the mitochondrial localisation signal (MLS) motif of tRNA (guanine(26)-N(2))-dimethyltransferase, mitochondrial (TRM1), abrogating binding to Mitochondrial import receptor subunit TOM70 (TOMM70A). Both variants contain a weak nuclear localisation signal (NLS) (KKSKKKRC). However, this motif is over-powered by the MLS and therefore the full-length variant is localised to mitochondria. Alternative initiation removes the N-terminus and the MLS motif, resulting in a nuclear localisation for the truncated isoform. | ||
| MOD5_MOUSE | 1 | 47 | Binary | Pre‑translational | Alternative splicing removes the mitochondrial localisation signal (MLS) motif of tRNA dimethylallyltransferase, mitochondrial (Trit1), abrogating binding to Mitochondrial import receptor subunit TOM70 (TOMM70A). The IPPT-I isoform (also known as Isoform 1 of tRNA dimethylallyltransferase, mitochondrial (Trit1)) was found to localise to both the mitochondria and the cytosol whereas the IPPT-II isoform (also known as Isoform 2 of tRNA dimethylallyltransferase, mitochondrial (Trit1)) is only localised to the cytosol and the nucleus. No nuclear localisation signal (NLS) was identified in either splice variant. | ||
| SYK_HUMAN | 1 | 49 | Binary | Pre‑translational | Alternative splicing removes the mitochondrial localisation signal (MLS) motif of Isoform Mitochondrial of Lysine--tRNA ligase (KARS), abrogating binding to Mitochondrial import receptor subunit TOM70 (TOMM70A) and import into mitochondria. Unusually, the first two exons of Lysine--tRNA ligase (KARS) are non-constitutive. The first exon does not contain a localisation signal (resulting in cytosol localisation) whereas the second exon contains an MLS. | ||
| GLRX2_HUMAN | 1 | 21 | Binary | Pre‑translational | Alternative splicing removes the mitochondrial localisation signal (MLS) motif of Glutaredoxin-2, mitochondrial (GLRX2), abrogating binding to Mitochondrial import receptor subunit TOM70 (TOMM70A) and import into mitochondria. The Grx2a isoform Isoform Grx2a of Glutaredoxin-2, mitochondrial (GLRX2) is localised to the mitochondria whereas the Isoform Grx2b of Glutaredoxin-2, mitochondrial (GLRX2) is localised to the perinuclear region. | ||
| DUT_HUMAN | 1 | 69 | Binary | Pre‑translational | Alternative splicing removes the mitochondrial localisation signal (MLS) motif of Deoxyuridine 5'-triphosphate nucleotidohydrolase, mitochondrial (DUT), abrogating binding to Mitochondrial import receptor subunit TOM70 (TOMM70A) and import into the mitochondria. | ||
TRG_NES - | |||||||
| ACE2_YEAST | 122 | 150 | Binary | Physicochemical compatibility | Phosphorylation of S137 in the NES of Metallothionein expression activator (ACE2) inhibits binding to Exportin-1 (CRM1). Phosphorylation of S137, and to a lesser extent S122, by Cbk1 directly antagonizes the interaction of Ace2 with nuclear export machinery. | ||
| ACE2_YEAST | 122 | 150 | Binary | Physicochemical compatibility | Phosphorylation of S122 in the NES of Metallothionein expression activator (ACE2) inhibits binding to Exportin-1 (CRM1). Phosphorylation of S137, and to a lesser extent S122, by Cbk1 directly antagonizes the interaction of Ace2 with nuclear export machinery. | ||
TRG_NES_CRM1_1 - Some proteins re-exported from the nucleus contain a Leucine-rich nuclear export signal (NES) binding to the CRM1 exportin protein. | |||||||
| MPIP3_HUMAN | 189 | 203 | Binary | Physicochemical compatibility | Phosphorylation of S198 in the NES of M-phase inducer phosphatase 3 (CDC25C) by Serine/threonine-protein kinase PLK1 (PLK1) inhibits binding to Exportin-1 (XPO1), thus promoting nuclear localization of M-phase inducer phosphatase 3 (CDC25C). | ||
| P53_HUMAN | 339 | 352 | Binary | Pre‑translational | Alternative splicing removes the nuclear export signal (NES) of Cellular tumor antigen p53 (TP53), abrogating binding to Exportin-1 (XPO1) and export from the nucleus. | ||
| PML_HUMAN | 702 | 716 | Binary | Pre‑translational | Alternative splicing removes the nuclear export signal (NES) of Protein PML (PML), abrogating binding to Exportin-1 (XPO1) and export from the nucleus. | ||
| CTND1_HUMAN | 942 | 956 | Binary | Pre‑translational | Alternative splicing removes the nuclear export signal (NES) of Catenin delta-1 (CTNND1), abrogating binding to Exportin-1 (XPO1). Despite demonstration of the importance of the NES for removing Catenin delta-1 (CTNND1) from the nucleus, those isoforms without NES are rarely found in the nucleus. | ||
TRG_NES_CRM1_2 - | |||||||
| FBXW7_HUMAN | 19 | 26 | Binary | Pre‑translational | Alternative splicing removes the nuclear export signal (NES) of Isoform Archipelago beta of F-box/WD repeat-containing protein 7 (FBXW7), abrogating binding to Exportin-1 (XPO1) and export from nucleus. The presence of the NES produces an isoform with a cytoplasmic localisation. The two other isoforms of FBXW7 localise to the nucleus and the nucleolus, respectively. | ||
| SMAD4_HUMAN | 142 | 149 | Binary | Pre‑translational | Alternative splicing removes the nuclear export signal (NES) motif of Mothers against decapentaplegic homolog 4 (SMAD4), thereby inhibiting binding to Exportin-1 (XPO1) and export from the nucleus. A splice variant lacking the NES does not shuttle back and forth between nucleus and cytosol. At present, this particular splice variant is not annotated in UniProtKB. | ||
| MDM2_HUMAN | 190 | 202 | Binary | Pre‑translational | Alternative splicing removes the nuclear export signal (NES) of E3 ubiquitin-protein ligase Mdm2 (MDM2), abrogating binding to Exportin-1 (XPO1). | ||
| NF2L1_HUMAN | 251 | 259 | Binary | Pre‑translational | Alternative splicing removes the nuclear export signal (NES) of Nuclear factor erythroid 2-related factor 1 (NFE2L1), abrogating binding to Exportin-1 (XPO1). Only the full-length variant of NFE2L1 (Isoform 1 of Nuclear factor erythroid 2-related factor 1 (NFE2L1)) contains an NES and shows cytoplasmic localisation. The two other naturally occuring isoforms (of which at present only 1 is annotated in UniProtKB) lack the NES and show exclusive nuclear staining. | ||
TRG_NLS - | |||||||
| PML_HUMAN | 476 | 490 | Binary | Pre‑translational | Alternative splicing removes the nuclear localisation signal (NLS) of Protein PML (PML), abrogating binding to Importin subunit alpha-1 (KPNA1) and import into the nucleus. | ||
| CDN1B_HUMAN | 152 | 166 | Specificity | Motif hiding | Phosphorylation of a 14-3-3-binding motif in the NLS of Cyclin-dependent kinase inhibitor 1B (CDKN1B) by RAC-alpha serine/threonine-protein kinase (AKT1) induces binding of 14-3-3 protein gamma (YWHAG), which hides the NLS and prevents binding to Importin subunit alpha-1 (KPNA1), thereby mediating cytoplasmic retention of Cyclin-dependent kinase inhibitor 1B (CDKN1B). Binding of 14-3-3 dimer involves an additional C-terminal 14-3-3-binding motif (see switch details). | ||
TRG_NLS_Bipartite_1 - Bipartite variant of the classical basically charged NLS. | |||||||
| PTHR_HUMAN | 124 | 144 | Binary | Physicochemical compatibility | Phosphorylation of T121 adjacent to the NLS of Parathyroid hormone-related protein (PTHLH) by Cyclin-dependent kinase 2 (CDK2) disrupts the interaction with Importin subunit beta-1 (KPNB1) and down-regulates nuclear import. | ||
| IMA1_YEAST | 44 | 58 | Specificity | Domain hiding | An intramolecular interaction between the importin beta-binding (IBB) domain and the NLS-binding pocket of Importin subunit alpha (SRP1) prevents binding of NLS cargo (e.g. Large T antigen) in the absence of Importin subunit beta-1 (KAP95) by hiding of the NLS-binding pocket. Binding of the IBB of Importin subunit alpha (SRP1) to Importin subunit beta-1 (KAP95) relieves this auto-inhibitory interaction and increases the affinity of Importin subunit alpha (SRP1) for NLS cargo. | ||
TRG_NLS_MonoCore_2 - Monopartite variant of the classical basically charged NLS. Strong core version. | |||||||
| KCC2D_RAT | 327 | 332 | Binary | Pre‑translational | Alternative splicing removes the nuclear localisation signal (NLS) of Isoform Delta 3 of Calcium/calmodulin-dependent protein kinase type II subunit delta (Camk2d), abrogating binding to Importin subunit alpha-1 (KPNA1) and nuclear import. This is due to an 11 amino acid insert encoded by exon 14. | ||
| FBXW7_HUMAN | 10 | 15 | Binary | Pre‑translational | Alternative splicing removes the nuclear localisation signal (NLS) of F-box/WD repeat-containing protein 7 (FBXW7), abrogating binding to Importin subunit alpha-1 (KPNA1). There are two other NLS motifs in the protein, meaning the isoform can still enter the nucleus. | ||
TRG_NLS_MonoExtC_3 - Monopartite variant of the classical basically charged NLS. C-extended version. | |||||||
| PHO4_YEAST | 156 | 161 | Binary | Physicochemical compatibility | Phosphorylation of S152 adjacent to the NLS of Phosphate system positive regulatory protein PHO4 (PHO4) by the Pho80-Pho85 CDK-Cyclin complex inhibits nuclear import this protein by blocking its interaction with Importin subunit beta-3 (PSE1). Upon phosphate starvation, Pho81 inhibits the Pho80-Pho85 complex, leading to translocation of Phosphate system positive regulatory protein PHO4 (PHO4) to the nucleus, where it regulates expression of phosphate-responsive genes. | ||
| MDM2_HUMAN | 181 | 187 | Binary | Pre‑translational | Alternative splicing removes the nuclear localisation signal (NLS) of E3 ubiquitin-protein ligase Mdm2 (MDM2), abrogating binding to Importin subunit alpha-1 (KPNA1). The exclusion from the nucleus is not complete however, as another NLS (466-473) is speculated to target splice variants to the nucleus, however, to the annotator it seems more likely that splice variants can dimerise with full-length MDM2 and be simultaneously transported into nucleus. | ||
TRG_NLS_MonoExtN_4 - Monopartite variant of the classical basically charged NLS. N-extended version. | |||||||
| SWI6_YEAST | 161 | 167 | Binary | Physicochemical compatibility | Phosphorylation of S160 adjacent to the NLS of Regulatory protein SWI6 (SWI6) decreases nuclear import of this protein by decreasing the affinity for Importin subunit alpha (SRP1). | ||
| NFAC1_HUMAN | 262 | 269 | Binary | Physicochemical compatibility | Phosphorylation of S241 and S290 adjacent to the NLS of Nuclear factor of activated T-cells, cytoplasmic 1 (NFATC1) by Glycogen synthase kinase-3 beta (GSK3B) and Glycogen synthase kinase-3 beta (GSK3B) inhibits nuclear import of Nuclear factor of activated T-cells, cytoplasmic 1 (NFATC1) by disrupting its interaction with Importin subunit alpha-2 (KPNA2). Calcium-dependent dephosphorylation by calcineurin promotes nuclear import. | ||
| LT_SV40 | 126 | 132 | Specificity | Motif hiding | Inhibition of nuclear import of Large T antigen by phosphorylation-dependent (T124) binding of BRCA1-associated protein (BRAP). | ||
| LT_SV40 | 126 | 132 | Specificity | Motif hiding | Inhibition of nuclear import of Large T antigen by phosphorylation-dependent (T124) binding of BRCA1-associated protein (BRAP). | ||
| VPAP_HCMVA | 425 | 432 | Specificity | Motif hiding | Inhibition of nuclear import of DNA polymerase processivity factor (UL44) by phosphorylation-dependent (T427) binding of BRCA1-associated protein (BRAP). | ||
| VPAP_HCMVA | 425 | 432 | Specificity | Motif hiding | Inhibition of nuclear import of DNA polymerase processivity factor (UL44) by phosphorylation-dependent (T427) binding of BRCA1-associated protein (BRAP). | ||
| MKL1_MOUSE | 62 95 | 67 101 | Specificity | Motif hiding | Hiding of the NLS of MKL/myocardin-like protein 1 (Mkl1) by binding of G-actin to the RPEL motifs of MKL/myocardin-like protein 1 (Mkl1) prevents translocation of this transcription factor to the nucleus. | ||
| LT_SV40 | 126 | 132 | Specificity | Domain hiding | An intramolecular interaction between the importin beta-binding (IBB) domain and the NLS-binding pocket of Importin subunit alpha (SRP1) prevents binding of NLS cargo (e.g. Large T antigen) in the absence of Importin subunit beta-1 (KAP95) by hiding of the NLS-binding pocket. Binding of the IBB of Importin subunit alpha (SRP1) to Importin subunit beta-1 (KAP95) relieves this auto-inhibitory interaction and increases the affinity of Importin subunit alpha (SRP1) for NLS cargo. | ||
| UNG_HUMAN | 15 | 21 | Binary | Pre‑translational | Alternative splicing removes the nuclear localisation signal (NLS) of Uracil-DNA glycosylase (UNG), abrogating binding to Importin subunit alpha-1 (KPNA1) and import into the nucleus. In Isoform UNG1 of Uracil-DNA glycosylase (UNG) the NLS present in Isoform UNG2 of Uracil-DNA glycosylase (UNG) is replaced with a mitochondrial localisation signal (MLS), promoting different localisations of the different protein isoforms. | ||
| OGG1_HUMAN | 332 | 339 | Binary | Pre‑translational | Alternative splicing removes the nuclear localisation signal (NLS) motif of N-glycosylase/DNA lyase (OGG1), abrogating binding to Importin subunit alpha-1 (KPNA1) and import into the nucleus. OGG1-1a (also known as Isoform Alpha of N-glycosylase/DNA lyase (OGG1)) has a C-terminal NLS motif that is absent in OGG1-2a (also known as Isoform Beta of N-glycosylase/DNA lyase (OGG1)) . Both have a weak mitochondrial localisation signal (MLS) in the N-terminal. | ||
| BRCA1_HUMAN | 501 | 508 | Binary | Pre‑translational | Alternative splicing removes the nuclear localisation signal (NLS) of Breast cancer type 1 susceptibility protein (BRCA1), abrogating binding to Importin subunit alpha-1 (KPNA1) and import into the nucleus. The study compared the full-length Brca1 splice variant (Isoform 1 of Breast cancer type 1 susceptibility protein (BRCA1)) to the Delta11b isoform (Isoform Delta11b of Breast cancer type 1 susceptibility protein (BRCA1)). The shorter isoform is missing exon 11b and differs in a number of ways. Firstly, it lacks an NLS and therefore has a cytoplasmic localisation. Also, when over-expressed, the Delta11b isoform was not toxic, suggesting nuclear localisation is important for Brca1's toxic behaviour. | ||
| SKP2_HUMAN | 65 | 72 | Binary | Physicochemical compatibility | Acetylation of S-phase kinase-associated protein 2 (SKP2) in its NLS inhibits binding to the Importin subunit alpha-6 (KPNA5). p300 acetylates SKP2 at K68 and K71 within SKP2's nuclear localisation signal, this stabilises SKP2 from Fizzy-related protein homolog (FZR1)-mediated degradation and facilitates its translocation into the cytoplasm. This process can be reversed by NAD-dependent protein deacetylase sirtuin-3, mitochondrial (SIRT3) that specifically deacetylates SKP2 facilitating its translocation back into the nucleus. In the cytosol, SKP2 acts to promote Cadherin-1 (CDH1) degradation in a Casein Kinase I dependent manner to promote cell migration. Casein kinase I recognises the MOD_CK1_1 motif in CDH1 phosphorylating at residues Ser840 and Ser842. | ||
| SKP2_HUMAN | 65 | 72 | Binary | Physicochemical compatibility | Acetylation of S-phase kinase-associated protein 2 (SKP2) in its NLS inhibits binding to the Importin subunit alpha-7 (KPNA6). p300 acetylates SKP2 at K68 and K71 within SKP2's nuclear localisation signal, this stabilises SKP2 from Fizzy-related protein homolog (FZR1)-mediated degradation and facilitates its translocation into the cytoplasm. This process can be reversed by NAD-dependent protein deacetylase sirtuin-3, mitochondrial (SIRT3) that specifically deacetylates SKP2 facilitating its translocation back into the nucleus. In the cytosol, SKP2 acts to promote Cadherin-1 (CDH1) degradation in a Casein Kinase I dependent manner to promote cell migration. Casein kinase I recognises the MOD_CK1_1 motif in CDH1 phosphorylating at residues Ser840 and Ser842. | ||
TRG_PTS1 - Generic PTS1 ELM for all eukaryotes | |||||||
| AMACR_HUMAN | 379 | 382 | Binary | Pre‑translational | Alternative splicing removes the type 1 peroxisomal targeting signal (PTS1) of Alpha-methylacyl-CoA racemase (AMACR), abrogating binding to Peroxisomal targeting signal 1 receptor (PEX5) and import into the peroxisome. Only the major AMACR IA (also known as Isoform 1 of Alpha-methylacyl-CoA racemase (AMACR)) form localises to the peroxisome. | ||