About Help Definitions Submit Search Analyse Browse Home


Group by :Switch typeMotif classProteinEnzymePathway            Group Index    Colouring Info          


x  Coloured by switch type.
  Domain hiding  Altered binding specificity  Motif hiding  Composite binding site formation
  Uncategorised  Rheostatic  Allostery  Avidity-sensing
  Physicochemical compatibility  Pre-translational  Competition

x  Index
CLV_C14_Caspase3-7CLV_C14_caspase-8-10CLV_CASPASE3_1
DEG_APCC_DBOX_1DEG_APCC_DBOX_3DEG_APCC_KENBOX_2
DEG_MDM2_1DEG_ODPH_VHL_1DEG_SCF_COI1_1
DEG_SCF_FBW7_1DEG_SCF_FBW7_2DEG_SCF_SKP2-CKS1_1
DEG_SCF_TIR1_1DEG_SCF_TRCP1_1DEG_SCF_TRCP1_2
DOC_AGCK_PIF_1DOC_CYCLIN_1DOC_PP1
DOC_PP2B_1DOC_USP7_1DOC_WW_Pin1_4
LIG_14-3-3_1LIG_14-3-3_2LIG_14-3-3_3
LIG_14-3-3_4LIG_ALG2LIG_AP2alpha_2
LIG_Actin_DMDLIG_Actin_RPEL_3LIG_BIR_III_2
LIG_BIR_III_4LIG_BIR_internalLIG_BRCT_BRCA1_1
LIG_BRCT_BRCA1_2LIG_BRCT_MDC1_1LIG_BROMO
LIG_CORNRBOXLIG_Clathr_ClatBox_1LIG_Clathr_ClatBox_2
LIG_Dynein_DLC8_1LIG_Dynein_DLC8_2LIG_EABR_CEP55_1
LIG_EH1_1LIG_EH_1LIG_EVH1_1
LIG_EVH1_2LIG_FAT_LD_1LIG_FHA_1
LIG_FHA_2LIG_FilaminLIG_Filamin_2
LIG_GBD_WASP_1LIG_GYFLIG_Glycolytic_Aldolase
LIG_HP1_1LIG_IQLIG_IQ_2
LIG_Integrin_isoDGR_1LIG_MAD2LIG_NRBOX
LIG_PCNA_2LIG_PCNA_PIPBox_1LIG_PDZ_Class_1
LIG_PDZ_Class_2LIG_PH_Tfb1LIG_PI(4,5)P2
LIG_PLKLIG_PTB_Apo_2LIG_PTB_Phospho_1
LIG_PTB_TalinLIG_RGDLIG_RhoGAP_OCRL_1
LIG_SH2_GRB2LIG_SH2_IALIG_SH2_IB
LIG_SH2_ICLIG_SH2_IDLIG_SH2_IE
LIG_SH2_IIALIG_SH2_IIBLIG_SH2_IIC
LIG_SH2_IIILIG_SH2_SRCLIG_SH2_STAT5
LIG_SH3_2LIG_SH3_3LIG_SH3_5
LIG_SH3_8LIG_SUMO_SBM_1LIG_SxIP_EBH_1
LIG_TAZ1LIG_TAZ2LIG_TKB
LIG_TPR_Kinesin_1LIG_TRAF2_3LIG_TYR_ITAM
LIG_TYR_ITIMLIG_TYR_ITSMLIG_Talin
LIG_ULM_U2AF65_1LIG_WRPW_1LIG_WW_1
LIG_WW_Nedd4LLIG_eIF4E_1MOD_CAAXbox
MOD_CDKMOD_CDK_1MOD_CK1_1
MOD_GSK3_1MOD_LATS_1MOD_NMyristoyl
MOD_PKA_1MOD_PKA_2MOD_ProDKin_1
MOD_SUMOMOD_SUMO_PHOSMOD_Spalmitoyl
TRG_AP2beta_CARGO_1TRG_AP2beta_CARGO_2TRG_ENDOCYTIC_2
TRG_ER_KDEL_1TRG_ER_diArg_1TRG_ER_diArg_2
TRG_ER_diLys_1TRG_LysEnd_APsAcLL_1TRG_LysEnd_APsAcLL_2
TRG_MLSTRG_NESTRG_NES_CRM1_1
TRG_NES_CRM1_2TRG_NLSTRG_NLS_Bipartite_1
TRG_NLS_MonoCore_2TRG_NLS_MonoExtC_3TRG_NLS_MonoExtN_4
TRG_PTS1


ProteinStartEndSwitch TypeSwitch SubtypeSwitch DescriptionInformation

CLV_C14_Caspase3-7 - Caspase3 and Caspase7 cleavage site
PTEN_HUMAN381385BinaryPhysicochemical compatibilityPhosphorylation 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).
details
KPCD_HUMAN326330BinaryPre‑translationalAlternative 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.
details

CLV_C14_caspase-8-10 -
CASP3_HUMAN172175BinaryPhysicochemical compatibilityPhosphorylation 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).
details

CLV_CASPASE3_1 -
CEAM1_MOUSE457460BinaryPre‑translationalAlternative 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.
details

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_HUMAN4149SpecificityDomain hidingBinding 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.
details
PTTG1_HUMAN6068SpecificityDomain hidingBinding 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.
details

DEG_APCC_DBOX_3 -
NEK2_HUMAN423445BinaryPre‑translationalAlternative 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.
details

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_HUMAN191195BinaryPre‑translationalAlternative 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.
details
BUB1B_HUMAN303307SpecificityDomain hidingBinding 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.
details
BUB1B_HUMAN303307SpecificityDomain hidingBinding 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.
details
ACM1_YEAST97101SpecificityDomain hidingThe 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.
details
CG22_YEAST99103SpecificityDomain hidingThe 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.
details
ACM1_YEAST97101SpecificityDomain hidingThe 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.
details
CIN8_YEAST931935SpecificityDomain hidingThe 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.
details
ACM1_YEAST97101SpecificityDomain hidingThe 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.
details
HSL1_YEAST774778SpecificityDomain hidingThe 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.
details

DEG_MDM2_1 - Motif found in p53 family members which confers binding to the N-terminal domain of MDM2.
P53_HUMAN1926BinaryPhysicochemical compatibilityPhosphorylation 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.
details
P53_HUMAN1926BinaryPre‑translationalAlternative 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.
details

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_HUMAN400413BinaryPhysicochemical compatibilityHydroxylation 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.
details
HIF1A_HUMAN562574BinaryPhysicochemical compatibilityHydroxylation 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.
details
EPAS1_HUMAN403416BinaryPhysicochemical compatibilityHydroxylation 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.
details
EPAS1_HUMAN529542BinaryPhysicochemical compatibilityHydroxylation 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.
details
HIF3A_HUMAN490502BinaryPhysicochemical compatibilityHydroxylation 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.
details
HIF3A_HUMAN490502BinaryPre‑translationalAlternative 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)).
details

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_ARATH303320Pre‑assemblyComposite binding site formationBinding 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.
details
TI10A_ARATH203220Pre‑assemblyComposite binding site formationBinding 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.
details
TIF7_ARATH221238Pre‑assemblyComposite binding site formationBinding 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.
details
TI10B_ARATH205222Pre‑assemblyComposite binding site formationBinding 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.
details
A7XXZ0_SOLLC199216Pre‑assemblyComposite binding site formationBinding 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.
details
B2XVS2_SOLLC251268Pre‑assemblyComposite binding site formationBinding 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.
details

DEG_SCF_FBW7_1 - The TPxxS phospho-dependent degron binds the FBW7 F box proteins of the SCF (Skp1_Cullin-Fbox) complex.
CCNE1_HUMAN378384SpecificityAltered binding specificityPhosphorylation 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.
details
MYC_HUMAN5562SpecificityAltered binding specificityPhosphorylation 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.
details
JUN_HUMAN236243SpecificityAltered binding specificityTranscription 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.
details
CCNE1_HUMAN393399SpecificityAltered binding specificityPhosphorylation 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.
details
SRBP1_HUMAN425430SpecificityAltered binding specificityPhosphorylation 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.
details

DEG_SCF_FBW7_2 - The TPxxE phospho-dependent degron binds the FBW7 F box proteins of the SCF (Skp1_Cullin-Fbox) complex.
LT_SV40699705BinaryPhysicochemical compatibilityPhosphorylation 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.
details
NOTC1_HUMAN25082515BinaryPhysicochemical compatibilityPhosphorylation 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.
details

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_HUMAN183190Pre‑assemblyComposite binding site formationBinding 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.
details
CDN1C_HUMAN306313Pre‑assemblyComposite binding site formationBinding 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).
details
CDN1C_MOUSE338345Pre‑assemblyComposite binding site formationBinding 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).
details

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_ARATH8293Pre‑assemblyComposite binding site formationBinding 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.
details
IAA17_ARATH8293Pre‑assemblyComposite binding site formationBinding 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.
details
IAA1_ARATH5566Pre‑assemblyComposite binding site formationBinding 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.
details
IAA28_ARATH4859Pre‑assemblyComposite binding site formationBinding 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.
details
IAA12_ARATH6980Pre‑assemblyComposite binding site formationBinding 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.
details
IAA3_ARATH6475Pre‑assemblyComposite binding site formationBinding 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.
details

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_HUMAN156161BinaryPhysicochemical compatibilityDual 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.
details
LMP1_EBVB9210215BinaryPhysicochemical compatibilityDual 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.
details
VPU_HV1BR5156BinaryPhysicochemical compatibilityDual 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.
details
PRLR_HUMAN348353BinaryPhysicochemical compatibilityDual 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.
details
ATF4_HUMAN218224BinaryPhysicochemical compatibilityDual 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.
details
NFKB1_HUMAN926932BinaryPhysicochemical compatibilityDual 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.
details
IKBA_HUMAN3136BinaryPhysicochemical compatibilityDual 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.
details
DLG1_HUMAN597602BinaryPhysicochemical compatibilityDual 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.
details
IKBB_HUMAN1823BinaryPhysicochemical compatibilityDual 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.
details
PDCD4_HUMAN7076BinaryPhysicochemical compatibilityDual 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.
details
BORA_HUMAN496501BinaryPhysicochemical compatibilityDual 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.
details
CLSPN_HUMAN2934BinaryPhysicochemical compatibilityDual 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.
details
FBX5_HUMAN144149BinaryPhysicochemical compatibilityDual 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.
details
FGD1_HUMAN282287SpecificityAltered binding specificityPhosphorylation 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.
details
FGD3_HUMAN7580SpecificityAltered binding specificityPhosphorylation 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.
details
CTNB1_HUMAN3237SpecificityAltered binding specificityPhosphorylation 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.
details
SNAI1_HUMAN95100SpecificityAltered binding specificityPhosphorylation 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.
details
PRLR_HUMAN348353BinaryPre‑translationalAlternative 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.
details

DEG_SCF_TRCP1_2 -
B2L11_HUMAN9398BinaryPre‑translationalAlternative 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).
details
REST_HUMAN10081013BinaryPre‑translationalAlternative 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.
details
YAP1_HUMAN383387SpecificityAltered binding specificityPhosphorylation 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
details

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_HUMAN469474BinaryPhysicochemical compatibilityPhosphorylation 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.
details
KPCB_HUMAN656661BinaryPhysicochemical compatibilityDephosphorylation 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.
details
SGK1_HUMAN418423BinaryPhysicochemical compatibilityPhosphorylation 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.
details
SCH9_YEAST733738BinaryPhysicochemical compatibilityPhosphorylation 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.
details
KS6A3_MOUSE382387BinaryPhysicochemical compatibilityAuto-phosphorylation of S386 in the PIF pocket-binding motif of Ribosomal protein S6 kinase alpha-3 (Rps6ka3) induces intramolecular binding and kinase cis-activation.
details
AKT2_HUMAN470475BinaryPhysicochemical compatibilityPhosphorylation of S474 in the PIF pocket-binding motif of RAC-beta serine/threonine-protein kinase (AKT2) induces intramolecular binding and kinase cis-activation.
details
KS6B1_RAT408413BinaryPhysicochemical compatibilityPhosphorylation of T412 in the PIF pocket-binding motif of Ribosomal protein S6 kinase beta-1 (Rps6kb1) induces intramolecular binding and kinase cis-activation.
details
ROCK1_HUMAN394399BinaryPhysicochemical compatibilityPhosphorylation of T398 in the PIF pocket-binding motif of Rho-associated protein kinase 1 (ROCK1) induces intramolecular binding and kinase cis-activation.
details
SGK3_HUMAN482487BinaryPhysicochemical compatibilityPhosphorylation of S486 in the PIF pocket-binding motif of Serine/threonine-protein kinase Sgk3 (SGK3) induces intramolecular binding and kinase cis-activation.
details
SGK3_MOUSE482487BinaryPhysicochemical compatibilityPhosphorylation of S486 in the PIF pocket-binding motif of Serine/threonine-protein kinase Sgk3 (Sgk3) induces intramolecular binding and kinase cis-activation.
details

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_HUMAN3033SpecificityDomain hidingBinding of the CDK-cyclin inhibitor p27 (Cyclin-dependent kinase inhibitor 1B (CDKN1B)) blocks the substrate recruitment site on Cyclin-A2 (CCNA2).
details
CDC6_HUMAN9498SpecificityDomain hidingBinding of the CDK-cyclin inhibitor p27 (Cyclin-dependent kinase inhibitor 1B (CDKN1B)) blocks the substrate recruitment site on Cyclin-A2 (CCNA2).
details
CDN1A_HUMAN1922SpecificityCompetitionCyclin-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.
details
MPIP1_HUMAN1115SpecificityCompetitionCyclin-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.
details
RB_HUMAN873877SpecificityCompetitionThe 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.
details
AKA12_MOUSE501504BinaryPhysicochemical compatibilityPhosphorylation 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.
details

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_HUMAN872878SpecificityCompetitionThe 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.
details
NEK2_HUMAN380387BinaryPre‑translationalAlternative 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.
details
NEK2_HUMAN380387BinaryPre‑translationalAlternative 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.
details
AKAP1_HUMAN151158BinaryPre‑translationalAlternative 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.
details
NEB1_RAT455461BinaryPhysicochemical compatibilityPhosphorylation 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.
details

DOC_PP2B_1 - Calcineurin substrate docking site, leads to the effective dephosphorylation of serine/threonine phosphorylation sites.
DYN1_HUMAN844849BinaryPre‑translationalAlternative 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).
details

DOC_USP7_1 - The USP7 NTD domain binding motif variant based on the MDM2 and P53 interactions.
P53_HUMAN359363BinaryPre‑translationalAlternative splicing removes the deubiquitinating enzyme USP7-binding motif of Cellular tumor antigen p53 (TP53), abrogating binding to Ubiquitin carboxyl-terminal hydrolase 7 (USP7).
details
P53_HUMAN364368BinaryPre‑translationalAlternative splicing removes the deubiquitinating enzyme USP7-binding motif of Cellular tumor antigen p53 (TP53), abrogating binding to Ubiquitin carboxyl-terminal hydrolase 7 (USP7).
details
MDM4_HUMAN398402BinaryPhysicochemical compatibilityPhosphorylation 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.
details

DOC_WW_Pin1_4 - The Class IV WW domain interaction motif is recognised primarily by the Pin1 phosphorylation-dependent prolyl isomerase.
TFCP2_HUMAN326331BinaryPhysicochemical compatibilityPhosphorylation 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).
details
P73_HUMAN409414BinaryPhysicochemical compatibilityPhosphorylation 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.
details
P73_HUMAN439444BinaryPhysicochemical compatibilityPhosphorylation 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.
details
P73_HUMAN479484BinaryPhysicochemical compatibilityPhosphorylation 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.
details
B2L11_MOUSE6267BinaryPhysicochemical compatibilityPhosphorylation 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.
details
FOS_MOUSE229234BinaryPhysicochemical compatibilityPhosphorylation 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.
details
FOS_MOUSE322327BinaryPhysicochemical compatibilityPhosphorylation 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.
details
FOS_MOUSE328333BinaryPhysicochemical compatibilityPhosphorylation 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.
details
FOS_MOUSE371376BinaryPhysicochemical compatibilityPhosphorylation 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.
details
MYC_HUMAN5560BinaryPhysicochemical compatibilityPhosphorylation 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.
details
TAX_HTL1A157162BinaryPhysicochemical compatibilityPhosphorylation 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.
details
P53_HUMAN3035BinaryPhysicochemical compatibilityPhosphorylation 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.
details
P53_HUMAN312317BinaryPhysicochemical compatibilityPhosphorylation 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.
details
P53_HUMAN7883BinaryPhysicochemical compatibilityPhosphorylation 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.
details
JUN_HUMAN6065BinaryPhysicochemical compatibilityPhosphorylation 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.
details
JUN_HUMAN7075BinaryPhysicochemical compatibilityPhosphorylation 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.
details
MYB_MOUSE525530BinaryPhysicochemical compatibilityPhosphorylation 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.
details
RARA_HUMAN7479BinaryPhysicochemical compatibilityPhosphorylation 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.
details
NCF1_HUMAN342347BinaryPhysicochemical compatibilityPhosphorylation 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.
details
NR4A1_HUMAN137142BinaryPhysicochemical compatibilityPhosphorylation 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.
details
NR4A1_HUMAN428433BinaryPhysicochemical compatibilityPhosphorylation 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.
details
NR4A1_HUMAN9297BinaryPhysicochemical compatibilityPhosphorylation 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.
details
CCND1_MOUSE283288BinaryPhysicochemical compatibilityPhosphorylation 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.
details
PML_HUMAN400405BinaryPhysicochemical compatibilityPhosphorylation 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.
details
PML_HUMAN502507BinaryPhysicochemical compatibilityPhosphorylation 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.
details
PML_HUMAN515520BinaryPhysicochemical compatibilityPhosphorylation 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.
details
PML_HUMAN524529BinaryPhysicochemical compatibilityPhosphorylation 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.
details
AKT1_HUMAN447452BinaryPhysicochemical compatibilityPhosphorylation 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.
details
AKT1_HUMAN8994BinaryPhysicochemical compatibilityPhosphorylation 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.
details
STF1_MOUSE200205BinaryPhysicochemical compatibilityPhosphorylation 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.
details
CTNB1_HUMAN243248BinaryPhysicochemical compatibilityPhosphorylation 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.
details
IRS1_HUMAN431436BinaryPhysicochemical compatibilityPhosphorylation 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.
details
BTK_MOUSE112117BinaryPhysicochemical compatibilityPhosphorylation 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.
details
BTK_MOUSE1823BinaryPhysicochemical compatibilityPhosphorylation 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.
details
STAT3_HUMAN724729BinaryPhysicochemical compatibilityPhosphorylation 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.
details
CDN1B_HUMAN184189BinaryPhysicochemical compatibilityPhosphorylation 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.
details
NOTC1_HUMAN21182123BinaryPhysicochemical compatibilityPhosphorylation 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.
details
NOTC1_HUMAN21292134BinaryPhysicochemical compatibilityPhosphorylation 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.
details
NOTC1_HUMAN21332138BinaryPhysicochemical compatibilityPhosphorylation 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.
details
TERF1_HUMAN146151BinaryPhysicochemical compatibilityPhosphorylation 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.
details
X_HBVA33843BinaryPhysicochemical compatibilityPhosphorylation 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.
details
BTG2_HUMAN144149BinaryPhysicochemical compatibilityPhosphorylation 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.
details
SMAD3_HUMAN176181BinaryPhysicochemical compatibilityPhosphorylation 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.
details
SMAD3_HUMAN201206BinaryPhysicochemical compatibilityPhosphorylation 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.
details
SMAD3_HUMAN205210BinaryPhysicochemical compatibilityPhosphorylation 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.
details
SMAD3_HUMAN210215BinaryPhysicochemical compatibilityPhosphorylation 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.
details
PO5F1_HUMAN914BinaryPhysicochemical compatibilityPhosphorylation 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.
details
TF65_HUMAN251256BinaryPhysicochemical compatibilityPhosphorylation 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.
details
FAK1_HUMAN907912BinaryPhysicochemical compatibilityPhosphorylation 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.
details
IRF3_HUMAN336341BinaryPhysicochemical compatibilityPhosphorylation 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.
details
CRTC2_MOUSE133138BinaryPhysicochemical compatibilityPhosphorylation 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.
details
CCNE1_MOUSE382387BinaryPhysicochemical compatibilityPhosphorylation 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.
details
NANOG_MOUSE4954BinaryPhysicochemical compatibilityPhosphorylation 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.
details
NANOG_MOUSE6267BinaryPhysicochemical compatibilityPhosphorylation 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.
details
CEP55_MOUSE420425BinaryPhysicochemical compatibilityPhosphorylation 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.
details
CEP55_MOUSE423428BinaryPhysicochemical compatibilityPhosphorylation 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.
details
GEPH_MOUSE185190BinaryPhysicochemical compatibilityPhosphorylation of S188 in the Pin1-binding motif of Gephyrin (Gphn) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) protein.
details
GEPH_MOUSE191196BinaryPhysicochemical compatibilityPhosphorylation of S194 in the Pin1-binding motif of Gephyrin (Gphn) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) protein.
details
GEPH_MOUSE197202BinaryPhysicochemical compatibilityPhosphorylation of S200 in the Pin1-binding motif of Gephyrin (Gphn) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) protein.
details
MEF2C_MOUSE107112BinaryPhysicochemical compatibilityPhosphorylation 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.
details
MEF2C_MOUSE95100BinaryPhysicochemical compatibilityPhosphorylation 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.
details
FUBP2_HUMAN178183BinaryPhysicochemical compatibilityPhosphorylation 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.
details
NONO_MOUSE409414BinaryPhysicochemical compatibilityPhosphorylation 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.
details
NONO_MOUSE427432BinaryPhysicochemical compatibilityPhosphorylation 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.
details
NONO_MOUSE449454BinaryPhysicochemical compatibilityPhosphorylation 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.
details
ARBK1_MOUSE667672BinaryPhysicochemical compatibilityPhosphorylation 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.
details
ST4A1_HUMAN510BinaryPhysicochemical compatibilityPhosphorylation 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.
details
ST4A1_HUMAN813BinaryPhysicochemical compatibilityPhosphorylation 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.
details
TFCP2_MOUSE288293BinaryPhysicochemical compatibilityPhosphorylation 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.
details
TFCP2_MOUSE306311BinaryPhysicochemical compatibilityPhosphorylation 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.
details
TFCP2_MOUSE326331BinaryPhysicochemical compatibilityPhosphorylation 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.
details
NEK6_HUMAN212217BinaryPhysicochemical compatibilityPhosphorylation 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.
details
NEK6_HUMAN242247BinaryPhysicochemical compatibilityPhosphorylation 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.
details
AATF_HUMAN143148BinaryPhysicochemical compatibilityPhosphorylation 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.
details
DAXX_HUMAN175180BinaryPhysicochemical compatibilityPhosphorylation 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.
details
NCOR2_HUMAN12381243BinaryPhysicochemical compatibilityPhosphorylation 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.
details
NCOR2_HUMAN14411446BinaryPhysicochemical compatibilityPhosphorylation 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.
details
SNCAP_HUMAN208213BinaryPhysicochemical compatibilityPhosphorylation 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.
details
SNCAP_HUMAN212217BinaryPhysicochemical compatibilityPhosphorylation 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.
details
WEE1B_XENLA183188BinaryPhysicochemical compatibilityPhosphorylation of T186 in the Pin1-binding motif of Wee1-like protein kinase 1-B (wee1-b) induces binding to the pin1 protein.
details
FBX5A_XENLA712BinaryPhysicochemical compatibilityPhosphorylation of S10 in the Pin1-binding motif of F-box only protein 5-A (fbxo5-a) induces binding to the pin1 protein.
details
SPT23_YEAST651656BinaryPhysicochemical compatibilityPhosphorylation of S654 in the Pin1-binding motif of Protein SPT23 (SPT23) induces binding to the Peptidyl-prolyl cis-trans isomerase ESS1 (ESS1) protein.
details
SOC1_ARATH192197BinaryPhysicochemical compatibilityPhosphorylation 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.
details
SOC1_ARATH4651BinaryPhysicochemical compatibilityPhosphorylation 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.
details
AGL24_ARATH199204BinaryPhysicochemical compatibilityPhosphorylation 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.
details
FAK1_MOUSE907912BinaryPhysicochemical compatibilityPhosphorylation 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.
details
SMAD3_HUMAN176181SpecificityAltered binding specificityCDK8/9 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.
details
P73_HUMAN479484BinaryPre‑translationalAlternative 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.
details
P73_HUMAN439444BinaryPre‑translationalAlternative 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.
details
P73_HUMAN409414BinaryPre‑translationalAlternative 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.
details
FBXW7_HUMAN202207BinaryPhysicochemical compatibilityPhosphorylation 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.
details

LIG_14-3-3_1 - Mode 1 interacting phospho-motif for 14-3-3 proteins with key conservation RxxSxP.
BAD_RAT134139BinaryPhysicochemical compatibilityPhosphorylation 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).
details
MT_POVM3254259BinaryPhysicochemical compatibilityPhosphorylation 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.
details
ATX1_HUMAN772777BinaryPhysicochemical compatibilityPhosphorylation 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.
details
M3K5_HUMAN963968BinaryPhysicochemical compatibilityPhosphorylation 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).
details
RAF1_HUMAN256261BinaryPhysicochemical compatibilityPhosphorylation 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).
details
YAP1_MOUSE109114BinaryPhysicochemical compatibilityPhosphorylation 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.
details
ATX1_HUMAN772777SpecificityAltered binding specificityPhosphorylation 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.
details
NED4L_HUMAN465470SpecificityDomain hidingPhosphorylation 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.
details
MEI2_SCHPO435
523
440
529
SpecificityDomain hidingBinding 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
details
RAF1_HUMAN256261Avidity‑sensingPhosphorylation 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.
details
RAF1_HUMAN618623Avidity‑sensingPhosphorylation 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.
details
MEI2_SCHPO435440Avidity‑sensingPhosphorylation 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.
details
WWTR1_HUMAN8691BinaryPhysicochemical compatibilityPhosphorylation 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.
details
MDM4_HUMAN364369Avidity‑sensingOptimal 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.
details
FOXO4_HUMAN2934Avidity‑sensingPhosphorylation 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.
details
BAD_MOUSE133138BinaryPhysicochemical compatibilityPhosphorylation 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).
details

LIG_14-3-3_2 - Longer mode 2 interacting phospho-motif for 14-3-3 proteins with key conservation RxxxS#p.
PTPN3_MOUSE355361BinaryPhysicochemical compatibilityPhosphorylation 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.
details
NAC1_HUMAN388394BinaryPhysicochemical compatibilityPhosphorylation 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).
details
FOXO4_HUMAN193199BinaryPhysicochemical compatibilityPhosphorylation 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.
details
TF65_HUMAN4147BinaryPhysicochemical compatibilityPhosphorylation 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.
details
PDE3A_HUMAN424430BinaryPhysicochemical compatibilityPhosphorylation 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.
details
TESK1_RAT435441BinaryPhysicochemical compatibilityPhosphorylation 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).
details
MEI2_SCHPO435
523
440
529
SpecificityDomain hidingBinding 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
details
MEI2_SCHPO523529Avidity‑sensingPhosphorylation 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.
details
FOXO4_HUMAN193199Avidity‑sensingPhosphorylation 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.
details

LIG_14-3-3_3 - Consensus derived from reported natural interactors which do not match the Mode 1 and Mode 2 ligands.
MPIP3_HUMAN213218BinaryPhysicochemical compatibilityPhosphorylation 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).
details
RIM15_YEAST10721077BinaryPhysicochemical compatibilityPhosphorylation 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.
details
HDAC4_HUMAN629634BinaryPhysicochemical compatibilityPhosphorylation 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.
details
MPIP2_HUMAN320325BinaryPhysicochemical compatibilityPhosphorylation 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.
details
ITB2_HUMAN755760SpecificityAltered binding specificityPhosphorylation 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)).
details
ADA22_HUMAN831
854
836
859
SpecificityMotif hidingPhosphorylation-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.
details
HG2A_HUMAN510SpecificityMotif hidingThe 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.
details
KPCE_HUMAN343348Avidity‑sensingPhosphorylation 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).
details
KPCE_HUMAN365370Avidity‑sensingPhosphorylation 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).
details
FOXO3_HUMAN250255Avidity‑sensingPhosphorylation 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).
details
FOXO3_HUMAN2934Avidity‑sensingPhosphorylation 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).
details
PTN3_HUMAN356361Avidity‑sensingPhosphorylation 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).
details
PTN3_HUMAN832837Avidity‑sensingPhosphorylation 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).
details
KSR1_MOUSE294299Avidity‑sensingPhosphorylation 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.
details
KSR1_MOUSE389394Avidity‑sensingPhosphorylation 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.
details
SLOB_DROME5156Avidity‑sensingPhosphorylation 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.
details
SLOB_DROME7681Avidity‑sensingPhosphorylation 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.
details
IRS1_HUMAN371376Avidity‑sensingPhosphorylation 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).
details
IRS1_HUMAN638643Avidity‑sensingPhosphorylation 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).
details
SLOB_DROME7681BinaryPre‑translationalAlternative 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.
details
MDM4_HUMAN339344Avidity‑sensingOptimal 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.
details
CDN1B_HUMAN154159SpecificityMotif hidingPhosphorylation 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).
details
CDN1B_HUMAN154159Avidity‑sensingPhosphorylation 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.
details
CDN1B_HUMAN193198Avidity‑sensingPhosphorylation 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.
details

LIG_14-3-3_4 -
GPR15_HUMAN356360SpecificityMotif hidingPhosphorylation-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).
details
HAP1_RAT594598BinaryPre‑translationalAlternative 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.
details

LIG_ALG2 -
PDC6I_HUMAN801810BinaryAllosteryBinding 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).
details

LIG_AP2alpha_2 - DPF/W motif binds alpha and beta subunits of AP2 adaptor complex.
SYNJ1_HUMAN13231325BinaryPre‑translationalAlternative 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.
details
SYNJ1_HUMAN15551557BinaryPre‑translationalAlternative 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.
details
DAB2_HUMAN293295BinaryPre‑translationalAlternative 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.
details
DAB2_HUMAN298300BinaryPre‑translationalAlternative 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.
details

LIG_Actin_DMD -
DMD_HUMAN510BinaryPre‑translationalAlternative 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.
details

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_MOUSE17
61
105
36
80
124
SpecificityMotif hidingHiding 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.
details
MYCD_MOUSE2039BinaryPre‑translationalAlternative 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.
details
MYCD_MOUSE6483BinaryPre‑translationalAlternative 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.
details

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_HUMAN315319BinaryPhysicochemical compatibilityBinding 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.
details
CASP9_HUMAN315319BinaryPhysicochemical compatibilityBinding 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.
details
CASP7_HUMAN2327BinaryPhysicochemical compatibilityBinding 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.
details
CASP7_HUMAN2327BinaryPhysicochemical compatibilityBinding 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.
details
CASP7_HUMAN2327BinaryPhysicochemical compatibilityBinding 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.
details

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_DROME3337BinaryPhysicochemical compatibilityBinding 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.
details
ICE_DROME2832BinaryPhysicochemical compatibilityBinding 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.
details

LIG_BIR_internal -
DBLOH_HUMAN5659BinaryPre‑translationalAlternative 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.
details
DBLOH_HUMAN5659BinaryPre‑translationalAlternative 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.
details

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_HUMAN12621266BinaryPhysicochemical compatibilityPhosphorylation 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.
details
F175A_HUMAN405409BinaryPhysicochemical compatibilityPhosphorylation 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.
details
ATRIP_HUMAN238242BinaryPhysicochemical compatibilityPhosphorylation of S239 in the BRCT-binding motif of ATR-interacting protein (ATRIP) induces binding to the Breast cancer type 1 susceptibility protein (BRCA1) protein.
details
COM1_HUMAN326330BinaryPhysicochemical compatibilityPhosphorylation of S327 in the BRCT-binding motif of DNA endonuclease RBBP8 (RBBP8) induces binding to the Breast cancer type 1 susceptibility protein (BRCA1) protein.
details
FANCJ_HUMAN989993BinaryPhysicochemical compatibilityPhosphorylation 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.
details

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_HUMAN989995BinaryPhysicochemical compatibilityPhosphorylation 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.
details

LIG_BRCT_MDC1_1 - Phosphopeptide motif which is specifically recognized by the BRCT (Carboxy-terminal) repeats of MDC1
H2AX_HUMAN139143BinaryPhysicochemical compatibilityPhosphorylation 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.
details

LIG_BROMO -
SUMO2_HUMAN3333SpecificityAltered binding specificityAcetylation 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.
details

LIG_CORNRBOX - The corepressor nuclear receptor box motif confers binding to nuclear receptors.
NCOR1_HUMAN20512059BinaryAllosteryBinding 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.
details
NCOR1_HUMAN22632271BinaryAllosteryBinding 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.
details
NCOR2_HUMAN21432151BinaryAllosteryBinding 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.
details
NCOR2_HUMAN23502358BinaryAllosteryBinding 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.
details

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_HUMAN390394BinaryPre‑translationalAlternative splicing removes the Clathrin I-binding motif of Myc box-dependent-interacting protein 1 (BIN1), abrogating binding to Clathrin heavy chain 1 (CLTC).
details
AMPH_HUMAN351355BinaryPhysicochemical compatibilityPhosphorylation 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).
details
AMPH_HUMAN351355Avidity‑sensingAmphiphysin 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).
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_HUMAN415420BinaryPre‑translationalAlternative splicing removes the Clathrin II-binding motif of Myc box-dependent-interacting protein 1 (BIN1), abrogating binding to Clathrin heavy chain 1 (CLTC).
details
AMPH_HUMAN380385BinaryPhysicochemical compatibilityPhosphorylation 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).
details
AMPH_HUMAN380385Avidity‑sensingAmphiphysin 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).
details

LIG_Dynein_DLC8_1 - The [KR]xTQT motif interacts with the common target-accepting grooves of 8kDa Dynein Light Chain dimer.
B2L11_HUMAN5056BinaryPhysicochemical compatibilityPhosphorylation 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.
details
B2L11_HUMAN110116BinaryPre‑translationalAlternative 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.
details

LIG_Dynein_DLC8_2 -
MYO5A_HUMAN12861290BinaryPre‑translationalAlternative 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.
details

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_MOUSE791797SpecificityDomain hidingThe 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.
details
TS101_MOUSE158164SpecificityDomain hidingThe 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.
details
TEX14_MOUSE791797SpecificityDomain hidingThe 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.
details
PDC6I_MOUSE801807SpecificityDomain hidingThe 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.
details

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_HUMAN513SpecificityCompetitionThe 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.
details

LIG_EH_1 - NPF motif interacting with EH domains, usually during regulation of endocytotic processes
SYNJ1_HUMAN13931397BinaryPre‑translationalAlternative 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.
details
SYNJ1_HUMAN14031407BinaryPre‑translationalAlternative 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.
details
SYNJ1_HUMAN14141418BinaryPre‑translationalAlternative 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.
details
SYNJ1_HUMAN13931397BinaryPre‑translationalAlternative 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.
details
SYNJ1_HUMAN14031407BinaryPre‑translationalAlternative 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.
details
SYNJ1_HUMAN14141418BinaryPre‑translationalAlternative 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.
details
SYNJ1_HUMAN13931397BinaryPre‑translationalAlternative 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.
details
SYNJ1_HUMAN14031407BinaryPre‑translationalAlternative 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.
details
SYNJ1_HUMAN14141418BinaryPre‑translationalAlternative 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.
details

LIG_EVH1_1 - Proline-rich motif binding to signal transduction class I EVH1 domains.
XIRP1_HUMAN2226BinaryPre‑translationalAlternative splicing removes the EVH1-binding motif of Xin actin-binding repeat-containing protein 1 (XIRP1), abrogating binding to Protein enabled homolog (ENAH).
details
XIRP1_HUMAN2226BinaryPre‑translationalAlternative splicing removes the EVH1-binding motif of Xin actin-binding repeat-containing protein 1 (XIRP1), abrogating binding to Vasodilator-stimulated phosphoprotein (VASP).
details

LIG_EVH1_2 - Proline-rich motif binding to signal transduction class II EVH1 domains.
GRM1_RAT11521156BinaryPre‑translationalAlternative 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.
details

LIG_FAT_LD_1 - The paxillin LD motif is recognized by FAK and other focal adhesion proteins mainly involved in cytoskeletal regulation
PAXI_HUMAN412BinaryPre‑translationalAlternative splicing removes the FAK-binding LD motif of Paxillin (PXN), abrogating binding to Focal adhesion kinase 1 (PTK2).
details

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_MYCTU1925BinaryPhysicochemical compatibilityPhosphorylation 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).
details
CHK2_HUMAN6672BinaryPhysicochemical compatibilityPhosphorylation 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.
details
RAD9_YEAST601607BinaryPhysicochemical compatibilityPhosphorylation of T603 in the FHA-binding motif of DNA repair protein RAD9 (RAD9) induces binding to the Serine/threonine-protein kinase RAD53 (RAD53) protein.
details
PIN4_YEAST303309BinaryPhysicochemical compatibilityPhosphorylation of T305 in the FHA-binding motif of RNA-binding protein PIN4 (PIN4) induces binding to the Serine/threonine-protein kinase RAD53 (RAD53) protein.
details
CLV1_ARATH866872BinaryPhysicochemical compatibilityPhosphorylation of T868 in the FHA-binding motif of Receptor protein kinase CLAVATA1 (CLV1) induces binding to the Protein phosphatase 2C 70 (KAPP) protein.
details
Y1827_MYCTU2026BinaryPhysicochemical compatibilityPhosphorylation 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).
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_YEAST153159BinaryPhysicochemical compatibilityPhosphorylation of T155 in the FHA-binding motif of DNA repair protein RAD9 (RAD9) induces binding to the Serine/threonine-protein kinase RAD53 (RAD53) protein.
details
RAD9_YEAST190196BinaryPhysicochemical compatibilityPhosphorylation of T192 in the FHA-binding motif of DNA repair protein RAD9 (RAD9) induces binding to the Serine/threonine-protein kinase RAD53 (RAD53) protein.
details
XRCC1_HUMAN521527BinaryPhysicochemical compatibilityPhosphorylation 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.
details
XRCC4_HUMAN231237BinaryPhysicochemical compatibilityPhosphorylation 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.
details
XRCC4_MOUSE229235BinaryPhysicochemical compatibilityPhosphorylation of T231 in the FHA-binding motif of DNA repair protein XRCC4 (Xrcc4) induces binding to the Bifunctional polynucleotide phosphatase/kinase (Pnkp) protein.
details
MRC1_SCHPO643649BinaryPhysicochemical compatibilityPhosphorylation 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.
details
XRCC1_HUMAN517
521
523
527
CumulativeRheostaticTwo 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.
details
MK67I_HUMAN238244SpecificityAltered binding specificityPhosphorylation 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).
details
XRCC1_HUMAN517523Avidity‑sensingHierarchical 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).
details
XRCC1_HUMAN521527Avidity‑sensingHierarchical 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).
details
MK67I_HUMAN238244CumulativeRheostaticPhosphorylation 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
details

LIG_Filamin -
ITB2_HUMAN753763SpecificityAltered binding specificityPhosphorylation 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)).
details
ITB7_HUMAN776787SpecificityCompetitionThe 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.
details

LIG_Filamin_2 -
ITB1_HUMAN783791BinaryPre‑translationalAlternative 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.
details
ITB1_HUMAN783791BinaryPre‑translationalAlternative 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.
details

LIG_GBD_WASP_1 -
WASP_HUMAN466476UncategorisedUncategorisedPhosphorylation 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).
details
WASL_HUMAN467477UncategorisedUncategorisedPhosphorylation of Neural Wiskott-Aldrich syndrome protein (WASL) at Y256 destabilises the auto-inhibitory intramolecular interaction of Neural Wiskott-Aldrich syndrome protein (WASL).
details
WASP_HUMAN466476BinaryAllosteryBinding 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.
details
WASP_HUMAN466476BinaryAllosteryBinding 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.
details
WASL_HUMAN467477BinaryAllosteryBinding 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.
details
WASL_HUMAN467477BinaryAllosteryBinding 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.
details

LIG_GYF - LIG_GYF is a proline-rich sequence specifically recognized by GYF domains
CD2_HUMAN295303SpecificityCompetitionT-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.
details

LIG_Glycolytic_Aldolase -
SNX9_HUMAN165169BinaryPhysicochemical compatibilityPhosphorylation 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.
details
SNX9_HUMAN165169SpecificityCompetitionSorting 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).
details

LIG_HP1_1 - Ligand to interface formed by dimerisation of two chromoshadow domains in HP1 proteins.
TIF1B_MOUSE486490BinaryPhysicochemical compatibilityPhosphorylation 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.
details

LIG_IQ - Calmodulin binding helical peptide motif
S61A1_CANFA1331BinaryAllosteryBinding 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.
details
CAC1D_RAT16501669BinaryPre‑translationalAlternative 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).
details
S61A1_CANFA1331BinaryAllosteryBinding 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.
details

LIG_IQ_2 -
AT2B1_HUMAN11141128BinaryPre‑translationalAlternative splicing partially removes the IQ motif of Isoform CI of Plasma membrane calcium-transporting ATPase 1 (ATP2B1), partially inhibiting binding to Calmodulin (CALM1).
details
AT2B1_HUMAN11141128BinaryPre‑translationalAlternative splicing partially removes the IQ motif of Isoform CI of Plasma membrane calcium-transporting ATPase 1 (ATP2B1), partially inhibiting binding to Calmodulin (CALM1).
details

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_HUMAN263265Pre‑assemblyComposite binding site formationBinding 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.
details

LIG_MAD2 - Mad2 binding motif
CDC20_HUMAN129137BinaryAllosteryBinding 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.
details

LIG_NRBOX - The nuclear receptor box motif (LXXLL) confers binding to nuclear receptors.
NRIP1_HUMAN132138BinaryAllosteryBinding 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.
details
NRIP1_HUMAN184190BinaryAllosteryBinding 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.
details
NRIP1_HUMAN2026BinaryAllosteryBinding 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.
details
NRIP1_HUMAN265271BinaryAllosteryBinding 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.
details
NRIP1_HUMAN379385BinaryAllosteryBinding 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.
details
NRIP1_HUMAN499505BinaryAllosteryBinding 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.
details
NRIP1_HUMAN500506BinaryAllosteryBinding 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.
details
NRIP1_HUMAN712718BinaryAllosteryBinding 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.
details
NRIP1_HUMAN818824BinaryAllosteryBinding 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.
details
NRIP1_HUMAN935941BinaryAllosteryBinding 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.
details
NCOA2_HUMAN640646BinaryAllosteryBinding 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.
details
NCOA2_HUMAN689695BinaryAllosteryBinding 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.
details
NCOA2_HUMAN744750BinaryAllosteryBinding 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.
details
MED1_HUMAN603609BinaryAllosteryBinding 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.
details
MED1_HUMAN644650BinaryAllosteryBinding 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.
details
NCOA6_MOUSE14941500BinaryAllosteryBinding 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.
details
TRXR1_HUMAN4652BinaryPre‑translationalAlternative 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.
details
TRXR1_HUMAN4652BinaryPre‑translationalAlternative 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.
details

LIG_PCNA_2 -
ING1_HUMAN915BinaryPre‑translationalAlternative 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).
details

LIG_PCNA_PIPBox_1 - The PCNA binding PIP box motif is found in proteins involved in DNA replication, repair and cell cycle control.
DPOD3_HUMAN456465BinaryPhysicochemical compatibilityPhosphorylation 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.
details
CDN1A_HUMAN144153BinaryPhysicochemical compatibilityPhosphorylation 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.
details
CDN1A_HUMAN144153BinaryPhysicochemical compatibilityPhosphorylation 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.
details

LIG_PDZ_Class_1 - The C-terminal class 1 PDZ-binding motif is classically represented by a pattern like (ST)X(VIL)*
CCG2_MOUSE318323BinaryPhysicochemical compatibilityPhosphorylation 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.
details
IRK4_HUMAN440445BinaryPhysicochemical compatibilityPhosphorylation 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.
details
ADRB2_HUMAN408413BinaryPhysicochemical compatibilityPhosphorylation 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.
details
BCR_HUMAN12661271BinaryPhysicochemical compatibilityPhosphorylation of T1269 in the PDZ-binding motif of Breakpoint cluster region protein (BCR) inhibits its interaction with the Afadin (MLLT4) protein.
details
CTNB1_HUMAN776781BinaryAllosteryBinding 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).
details
GRASP_RAT389394SpecificityMotif hidingBinding 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.
details
GRASP_RAT389394SpecificityMotif hidingBinding 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.
details
NHRF1_HUMAN353358SpecificityDomain hidingBinding 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).
details
CTNB1_HUMAN776781SpecificityDomain hidingBinding 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).
details
GRM5_RAT11981203SpecificityDomain hidingBinding 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.
details
GRASP_RAT389394SpecificityDomain hidingBinding 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.
details
CFTR_HUMAN14751480SpecificityCompetitionThe 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.
details
CFTR_HUMAN14751480SpecificityCompetitionThe 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.
details
ADA22_HUMAN901906BinaryPre‑translationalAlternative 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.
details
AT2B2_HUMAN12381243BinaryPre‑translationalAlternative 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 ╬▓2-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.
details
AT2B4_HUMAN12361241BinaryPre‑translationalAlternative 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.
details
AT2B4_HUMAN12361241BinaryPre‑translationalAlternative 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.
details
AT2B4_HUMAN12361241BinaryPre‑translationalAlternative 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
details
AT2B4_HUMAN12361241BinaryPre‑translationalAlternative 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.
details
5HT4R_MOUSE382387BinaryPre‑translationalAlternative 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.
details
5HT4R_MOUSE382387BinaryPre‑translationalAlternative 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.
details
IRK6_MOUSE420425BinaryPre‑translationalAlternative splicing removes the PDZ-binding motif of G protein-activated inward rectifier potassium channel 2 (Kcnj6), abrogating binding to Sorting nexin-27 (Snx27).
details
KIF1B_MOUSE11451150BinaryPre‑translationalAlternative splicing removes the PDZ-binding motif of Isoform 3 of Kinesin-like protein KIF1B (Kif1b), abrogating binding to PDZ domain-containing protein GIPC1 (Gipc1).
details
GRIK1_RAT900905BinaryPre‑translationalAlternative 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.
details
GRIK1_RAT900905BinaryPre‑translationalAlternative 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.
details
GUAD_HUMAN449454BinaryPre‑translationalAlternative 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.
details
NMDZ1_HUMAN917922BinaryPre‑translationalAlternative 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.
details
NMDZ1_HUMAN917922SpecificityMotif hidingBinding 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.
details
SYNJ2_RAT12881293BinaryPre‑translationalAlternative 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.
details
CLCN3_HUMAN861866BinaryPre‑translationalAlternative 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.
details
PKHG5_MOUSE10681073BinaryPre‑translationalAlternative 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.
details
KALRN_RAT16491654BinaryPre‑translationalAlternative 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.
details
PLCB1_HUMAN12111216BinaryPre‑translationalAlternative 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.
details
PLCB1_MOUSE12111216BinaryPre‑translationalAlternative 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.
details
BAIP2_HUMAN516521BinaryPre‑translationalAlternative 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.
details
AT2B4_HUMAN12361241BinaryPre‑translationalAlternative 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.
details
AT2B4_HUMAN12361241BinaryPre‑translationalAlternative 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.
details
KALRN_RAT16491654BinaryPre‑translationalAlternative 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.
details
KALRN_RAT16491654BinaryPre‑translationalAlternative 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.
details
NMDZ1_HUMAN917922BinaryPre‑translationalAlternative 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.
details
NMDZ1_HUMAN917922SpecificityMotif hidingBinding 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.
details
NMDZ1_HUMAN917922BinaryPre‑translationalAlternative 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.
details
NMDZ1_HUMAN917922SpecificityMotif hidingBinding 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.
details
GUAD_HUMAN449454BinaryPre‑translationalAlternative 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.
details
5HT4R_MOUSE382387BinaryPre‑translationalAlternative 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.
details
PGFRB_HUMAN11011106BinaryPhysicochemical compatibilityPhosphorylation 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.
details

LIG_PDZ_Class_2 - The C-terminal class 2 PDZ-binding motif is classically represented by a pattern such as (VYF)X(VIL)*
SDC1_HUMAN305310BinaryPhysicochemical compatibilityPhosphorylation 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.
details
APBA1_HUMAN832837SpecificityDomain hidingAn 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.
details
PSN1_HUMAN462467SpecificityDomain hidingAn 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.
details
5HT4R_MOUSE368371BinaryPre‑translationalAlternative splicing removes the PDZ-binding motif of Isoform 5-HT4(E) of 5-hydroxytryptamine receptor 4 (Htr4), abrogating binding to InaD-like protein (Inadl).
details
GRIA2_RAT878883BinaryPre‑translationalAlternative 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.
details

LIG_PH_Tfb1 -
P53_HUMAN5056CumulativeRheostaticMultisite 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).
details

LIG_PI(4,5)P2 -
BIN1_HUMAN258266BinaryPre‑translationalAlternative 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.
details

LIG_PLK -
MPIP3_HUMAN129131BinaryPhysicochemical compatibilityPhosphorylation 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.
details
MPIP2_HUMAN4951BinaryPhysicochemical compatibilityPhosphorylation 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).
details

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_HUMAN756763BinaryPhysicochemical compatibilityPhosphorylation 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).
details
ITB3_HUMAN767774SpecificityAltered binding specificityPhosphorylation 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.
details
A4_HUMAN756763SpecificityAltered binding specificityPhosphorylation 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).
details
ITB3_HUMAN779786SpecificityAltered binding specificityPhosphorylation 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).
details

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_HUMAN11041110BinaryPhysicochemical compatibilityPhosphorylation of Y1110 in the PTB-binding motif of Epidermal growth factor receptor (EGFR) induces binding to the Docking protein 1 (DOK1) protein.
details
ERBB3_HUMAN13221328BinaryPhysicochemical compatibilityPhosphorylation 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.
details
IL2RB_HUMAN358364BinaryPhysicochemical compatibilityPhosphorylation of Y364 in the PTB-binding motif of Interleukin-2 receptor subunit beta (IL2RB) induces binding to the SHC-transforming protein 1 (SHC1) protein.
details
IL4RA_HUMAN491497BinaryPhysicochemical compatibilityPhosphorylation of Y497 in the PTB-binding motif of Interleukin-4 receptor subunit alpha (IL4R) induces binding to the Insulin receptor substrate 1 (IRS1) protein.
details
INSR_HUMAN993999BinaryPhysicochemical compatibilityPhosphorylation of Y999 in the PTB-binding motif of Insulin receptor (INSR) induces binding to the SHC-transforming protein 1 (SHC1) protein.
details
ITB3_HUMAN767773BinaryPhysicochemical compatibilityPhosphorylation of Y773 in the PTB-binding motif of Integrin beta-3 (ITGB3) induces binding to the Docking protein 1 (DOK1) protein.
details
ITB3_HUMAN779785BinaryPhysicochemical compatibilityPhosphorylation of Y785 in the PTB-binding motif of Integrin beta-3 (ITGB3) induces binding to the SHC-transforming protein 1 (SHC1) protein.
details
ITB4_HUMAN15901596BinaryPhysicochemical compatibilityPhosphorylation of Y1596 in the PTB-binding motif of Integrin beta-4 (ITGB4) induces binding to the SHC-transforming protein 1 (SHC1) protein.
details
LRP1_HUMAN45014507BinaryPhysicochemical compatibilityPhosphorylation 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.
details
MT_POVMA244250BinaryPhysicochemical compatibilityPhosphorylation of Y250 in the PTB-binding motif of Middle T antigen induces binding to the SHC-transforming protein 1 (Shc1) protein.
details
MUSK_MOUSE547553BinaryPhysicochemical compatibilityPhosphorylation of Y553 in the PTB-binding motif of Muscle, skeletal receptor tyrosine-protein kinase (Musk) induces binding to the Protein Dok-7 (Dok7) protein.
details
NTRK1_HUMAN490496BinaryPhysicochemical compatibilityPhosphorylation 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.
details
RET_MOUSE10571063BinaryPhysicochemical compatibilityPhosphorylation 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.
details
SHIP1_HUMAN10161022BinaryPhysicochemical compatibilityPhosphorylation 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.
details
SHIP1_HUMAN909915BinaryPhysicochemical compatibilityPhosphorylation 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.
details
ITB3_HUMAN779785BinaryPhysicochemical compatibilityPhosphorylation of T779 in the PTB-binding motif of Integrin beta-3 (ITGB3) inhibits its interaction with SHC-transforming protein 1 (SHC1).
details
ITB3_HUMAN779785CumulativeRheostaticWhile 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.
details
ITB3_HUMAN767773SpecificityAltered binding specificityPhosphorylation 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.
details
ITB3_HUMAN779785SpecificityAltered binding specificityPhosphorylation 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).
details

LIG_PTB_Talin -
PI51C_HUMAN650653BinaryPhysicochemical compatibilityPhosphorylation 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.
details
PI51C_MOUSE645648BinaryPre‑translationalAlternative 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.
details
PI51C_MOUSE645648BinaryPhysicochemical compatibilityPhosphorylation 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).
details
PI51C_MOUSE645648BinaryPhysicochemical compatibilityPhosphorylation of Y644 in Phosphatidylinositol 4-phosphate 5-kinase type-1 gamma (Pip5k1c) promotes its association with Talin-1 (Tln1).
details

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_HUMAN9698Pre‑assemblyComposite binding site formationBinding 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.
details
DISG_TRIAB5153Pre‑assemblyComposite binding site formationBinding 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.
details
FINC_HUMAN15241526Pre‑assemblyComposite binding site formationBinding 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.
details
POLG_FMDVO869871Pre‑assemblyComposite binding site formationBinding 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.
details
VTNC_HUMAN6466Pre‑assemblyComposite binding site formationBinding 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.
details
VWF_HUMAN25072509Pre‑assemblyComposite binding site formationBinding 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.
details
OSTP_HUMAN159161Pre‑assemblyComposite binding site formationBinding 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.
details
FINC_MOUSE16141616Pre‑assemblyComposite binding site formationBinding 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.
details
VME1_TRIEL459461Pre‑assemblyComposite binding site formationBinding 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.
details
DISB_TRIGA5153Pre‑assemblyComposite binding site formationBinding 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.
details
POLG_CXA9858860Pre‑assemblyComposite binding site formationBinding 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.
details
VTNC_MOUSE6466Pre‑assemblyComposite binding site formationBinding 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.
details
POLG_HPE1H764766Pre‑assemblyComposite binding site formationBinding 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.
details

LIG_RhoGAP_OCRL_1 -
DP13A_HUMAN403415BinaryPhysicochemical compatibilityPhosphorylation 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).
details
DP13A_HUMAN403415BinaryPhysicochemical compatibilityPhosphorylation 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).
details

LIG_SH2_GRB2 - GRB2-like Src Homology 2 (SH2) domains binding motif.
IRS1_RAT895898BinaryPhysicochemical compatibilityPhosphorylation 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.
details
A4_HUMAN757760CumulativeRheostaticWhile 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.
details
A4_HUMAN757760SpecificityAltered binding specificityPhosphorylation 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).
details
LAT_MOUSE175178BinaryPhysicochemical compatibilityPhosphorylation 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.
details
LAT_MOUSE195198BinaryPhysicochemical compatibilityPhosphorylation 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.
details
LAT_MOUSE235238BinaryPhysicochemical compatibilityPhosphorylation 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.
details
ERBB3_HUMAN12621265BinaryPhysicochemical compatibilityPhosphorylation 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).
details

LIG_SH2_IA -
IL2RB_HUMAN409428BinaryPhysicochemical compatibilityPhosphorylation of Y418 in the SH2-binding motif of Interleukin-2 receptor subunit beta (IL2RB) induces binding to the Tyrosine-protein kinase Lck (LCK) protein.
details
EPHA3_HUMAN597606BinaryPhysicochemical compatibilityPhosphorylation of Y602 in the SH2-binding motif of Ephrin type-A receptor 3 (EPHA3) induces binding to the Cytoplasmic protein NCK1 (NCK1) protein.
details
FCERG_HUMAN7579BinaryPhysicochemical compatibilityPhosphorylation 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.
details
FAK1_HUMAN389405BinaryPhysicochemical compatibilityPhosphorylation of Y397 in the SH2-binding motif of Focal adhesion kinase 1 (PTK2) induces binding to the Cytoplasmic protein NCK2 (NCK2) protein.
details
NTRK2_HUMAN714730BinaryPhysicochemical compatibilityPhosphorylation of Y727 in the SH2-binding motif of BDNF/NT-3 growth factors receptor (NTRK2) induces binding to the Cytoplasmic protein NCK2 (NCK2) protein.
details
LCP2_MOUSE143148BinaryPhysicochemical compatibilityPhosphorylation of Y145 in the SH2-binding motif of Lymphocyte cytosolic protein 2 (Lcp2) induces binding to the Tyrosine-protein kinase ITK/TSK (Itk) protein.
details
GBLP_RAT241250BinaryPhysicochemical compatibilityPhosphorylation 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.
details
DCD_HUMAN1525BinaryPhysicochemical compatibilityPhosphorylation of Y20 in the SH2-binding motif of Dermcidin (DCD) induces binding to the Cytoplasmic protein NCK1 (NCK1) protein.
details
DAB1_MOUSE212228BinaryPhysicochemical compatibilityPhosphorylation of Y220 in the SH2-binding motif of Disabled homolog 1 (Dab1) induces binding to the Cytoplasmic protein NCK2 (NCK2) protein.
details
DAB1_MOUSE220223BinaryPre‑translationalAlternative 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)).
details
DAB1_MOUSE232235BinaryPre‑translationalAlternative 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)).
details
DAB1_MOUSE220223BinaryPre‑translationalAlternative 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)).
details
DAB1_MOUSE232235BinaryPre‑translationalAlternative 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)).
details
DAB1_MOUSE185188BinaryPre‑translationalAlternative 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)).
details
DAB1_MOUSE232235BinaryPhysicochemical compatibilityPhosphorylation of Y232 in the SH2-binding motif of Disabled homolog 1 (Dab1) induces binding to Cytoplasmic protein NCK2 (NCK2).
details
DAB1_MOUSE232235BinaryPhysicochemical compatibilityPhosphorylation of Y232 in the SH2-binding motif of Disabled homolog 1 (Dab1) induces binding to Adapter molecule crk (Crk).
details
DAB1_MOUSE185188BinaryPhysicochemical compatibilityPhosphorylation of Y185 in the SH2-binding motif of Disabled homolog 1 (Dab1) induces binding to Neuronal proto-oncogene tyrosine-protein kinase Src (Src).
details

LIG_SH2_IB -
DAB1_HUMAN211230BinaryPhysicochemical compatibilityPhosphorylation of Y220 in the SH2-binding motif of Disabled homolog 1 (DAB1) induces binding to the Adapter molecule crk (CRK) protein.
details
NTRK1_HUMAN783796BinaryPhysicochemical compatibilityPhosphorylation 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.
details
CBL_HUMAN770780BinaryPhysicochemical compatibilityPhosphorylation of Y774 in the SH2-binding motif of E3 ubiquitin-protein ligase CBL (CBL) induces binding to the Adapter molecule crk (CRK) protein.
details
DOK1_HUMAN447454BinaryPhysicochemical compatibilityPhosphorylation of Y449 in the SH2-binding motif of Docking protein 1 (DOK1) induces binding to the SH2 domain-containing protein 1A (SH2D1A) protein.
details
SLAF1_HUMAN276286BinaryPhysicochemical compatibilityPhosphorylation of Y281 in the SH2-binding motif of Signaling lymphocytic activation molecule (SLAMF1) induces binding to the SH2 domain-containing protein 1A (SH2D1A) protein.
details
SLAF1_HUMAN273286BinaryPhysicochemical compatibilityPhosphorylation of Y281 in the SH2-binding motif of Signaling lymphocytic activation molecule (SLAMF1) induces binding to the SH2 domain-containing protein 1B (Sh2d1b) protein.
details
FAK2_HUMAN394410BinaryPhysicochemical compatibilityPhosphorylation 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.
details
BCAR1_HUMAN358368BinaryPhysicochemical compatibilityPhosphorylation 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.
details
EPHB2_MOUSE601610BinaryPhysicochemical compatibilityPhosphorylation of Y604 in the SH2-binding motif of Ephrin type-B receptor 2 (Ephb2) induces binding to the Adapter molecule crk (CRK) protein.
details
EPHB2_MOUSE606620BinaryPhysicochemical compatibilityPhosphorylation of Y610 in the SH2-binding motif of Ephrin type-B receptor 2 (Ephb2) induces binding to the Adapter molecule crk (CRK) protein.
details
PAXI_HUMAN118121BinaryPre‑translationalAlternative splicing removes the SH2-binding motif of Paxillin (PXN), abrogating binding to Ras GTPase-activating protein 1 (RASA1).
details
PAXI_HUMAN118121BinaryPre‑translationalAlternative splicing removes the SH2-binding motif of Paxillin (PXN), abrogating binding to Adapter molecule crk (CRK).
details
PAXI_HUMAN3134BinaryPre‑translationalAlternative splicing removes the SH2-binding motif of Paxillin (PXN), abrogating binding to Adapter molecule crk (CRK).
details
PAXI_HUMAN118121BinaryPre‑translationalAlternative splicing removes the SH2-binding motif of Paxillin (PXN), abrogating binding to Ras GTPase-activating protein 1 (RASA1).
details

LIG_SH2_IC -
A9UF02_HUMAN174180BinaryPhysicochemical compatibilityPhosphorylation of Y177 in the SH2-binding motif of BCR/ABL fusion induces binding to the Growth factor receptor-bound protein 2 (GRB2) protein.
details
PDPK1_HUMAN376379BinaryPhysicochemical compatibilityPhosphorylation of Y376 in the SH2-binding motif of 3-phosphoinositide-dependent protein kinase 1 (PDPK1) induces binding to the Tensin-1 (TNS1) protein.
details
LAT_HUMAN198203BinaryPhysicochemical compatibilityPhosphorylation 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.
details
LAT_HUMAN218223BinaryPhysicochemical compatibilityPhosphorylation 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.
details
DOK2_HUMAN402405BinaryPhysicochemical compatibilityPhosphorylation of Y402 in the SH2-binding motif of Docking protein 2 (DOK2) induces binding to the Tensin-1 (TNS1) protein.
details
EGFR_HUMAN10921100BinaryPhysicochemical compatibilityPhosphorylation 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.
details
ERBB2_HUMAN11351144BinaryPhysicochemical compatibilityPhosphorylation 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.
details
MET_HUMAN13511360BinaryPhysicochemical compatibilityPhosphorylation 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.
details
SHC1_HUMAN423435BinaryPhysicochemical compatibilityPhosphorylation 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.
details
FRS2_HUMAN191200BinaryPhysicochemical compatibilityPhosphorylation 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.
details
FRS2_HUMAN301310BinaryPhysicochemical compatibilityPhosphorylation 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.
details
FRS2_HUMAN345355BinaryPhysicochemical compatibilityPhosphorylation 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.
details
FRS2_HUMAN385395BinaryPhysicochemical compatibilityPhosphorylation 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.
details

LIG_SH2_ID -
EGFR_HUMAN10081024BinaryPhysicochemical compatibilityPhosphorylation of Y1016 in the SH2-binding motif of Epidermal growth factor receptor (EGFR) induces binding to the SH2 domain-containing protein 3C (SH2D3C) protein.
details
EGFR_HUMAN10081024BinaryPhysicochemical compatibilityPhosphorylation of Y1016 in the SH2-binding motif of Epidermal growth factor receptor (EGFR) induces binding to the SH2 domain-containing protein 3A (SH2D3A) protein.
details
ERBB2_HUMAN11311147BinaryPhysicochemical compatibilityPhosphorylation 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.
details
ERBB2_HUMAN10151031BinaryPhysicochemical compatibilityPhosphorylation 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.
details
ERBB3_HUMAN860876BinaryPhysicochemical compatibilityPhosphorylation 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.
details
ERBB3_HUMAN12681284BinaryPhysicochemical compatibilityPhosphorylation 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.
details
ERBB3_HUMAN12811297BinaryPhysicochemical compatibilityPhosphorylation 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.
details
ERBB3_HUMAN13201336BinaryPhysicochemical compatibilityPhosphorylation 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.
details
ERBB3_HUMAN13201336BinaryPhysicochemical compatibilityPhosphorylation 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.
details

LIG_SH2_IE -
EGFR_HUMAN10111020BinaryPhysicochemical compatibilityPhosphorylation of Y1016 in the SH2-binding motif of Epidermal growth factor receptor (EGFR) induces binding to the Ras and Rab interactor 1 (RIN1) protein.
details
EGFR_HUMAN11911200BinaryPhysicochemical compatibilityPhosphorylation of Y1197 in the SH2-binding motif of Epidermal growth factor receptor (EGFR) induces binding to the Ras and Rab interactor 1 (RIN1) protein.
details
EGFR_HUMAN10081024BinaryPhysicochemical compatibilityPhosphorylation of Y1016 in the SH2-binding motif of Epidermal growth factor receptor (EGFR) induces binding to the Tyrosine-protein kinase JAK1 (JAK1) protein.
details
EGFR_HUMAN10081024BinaryPhysicochemical compatibilityPhosphorylation of Y1016 in the SH2-binding motif of Epidermal growth factor receptor (EGFR) induces binding to the Tyrosine-protein kinase JAK2 (JAK2) protein.
details
ERBB2_HUMAN10151031BinaryPhysicochemical compatibilityPhosphorylation 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.
details
ERBB2_HUMAN10151031BinaryPhysicochemical compatibilityPhosphorylation 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.
details
INAR1_HUMAN458474BinaryPhysicochemical compatibilityPhosphorylation 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.
details
INAR1_HUMAN473489BinaryPhysicochemical compatibilityPhosphorylation 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.
details
ERBB3_HUMAN13201336BinaryPhysicochemical compatibilityPhosphorylation 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.
details
ERBB3_HUMAN13201336BinaryPhysicochemical compatibilityPhosphorylation 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.
details
ERBB3_HUMAN12681284BinaryPhysicochemical compatibilityPhosphorylation 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.
details
ERBB3_HUMAN12681284BinaryPhysicochemical compatibilityPhosphorylation 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.
details

LIG_SH2_IIA -
PGFRB_HUMAN751755BinaryPhysicochemical compatibilityPhosphorylation 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.
details
PGFRB_HUMAN10181029BinaryPhysicochemical compatibilityPhosphorylation 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.
details
GHR_HUMAN591600BinaryPhysicochemical compatibilityPhosphorylation 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.
details
IL4RA_HUMAN706721BinaryPhysicochemical compatibilityPhosphorylation 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.
details
FRS2_HUMAN431440BinaryPhysicochemical compatibilityPhosphorylation 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.
details
FRS2_HUMAN465475BinaryPhysicochemical compatibilityPhosphorylation 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.
details
CSF3R_HUMAN747758BinaryPhysicochemical compatibilityPhosphorylation 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.
details
IL6RB_MOUSE750764BinaryPhysicochemical compatibilityPhosphorylation 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.
details
IL4RA_HUMAN706721BinaryPhysicochemical compatibilityPhosphorylation 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.
details
ERBB4_HUMAN10561059BinaryPre‑translationalAlternative 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.
details
SHIP1_HUMAN918921BinaryPre‑translationalAlternative 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).
details
SHIP1_HUMAN918921BinaryPre‑translationalAlternative 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).
details
ERBB4_HUMAN10561059BinaryPre‑translationalAlternative 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.
details

LIG_SH2_IIB -
JAK2_HUMAN804823BinaryPhysicochemical compatibilityPhosphorylation of Y813 in the SH2-binding motif of Tyrosine-protein kinase JAK2 (JAK2) induces binding to the SH2B adapter protein 1 (SH2B1) protein.
details
NTRK1_HUMAN782796BinaryPhysicochemical compatibilityPhosphorylation 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.
details
RET_HUMAN976985BinaryPhysicochemical compatibilityPhosphorylation 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.
details
IL2RB_HUMAN361370BinaryPhysicochemical compatibilityPhosphorylation of Y364 in the SH2-binding motif of Interleukin-2 receptor subunit beta (IL2RB) induces binding to the SHC-transforming protein 1 (SHC1) protein.
details
VAV_HUMAN165180BinaryPhysicochemical compatibilityPhosphorylation of Y174 in the SH2-binding motif of Proto-oncogene vav (VAV1) induces binding to the SH2 domain-containing adapter protein B (SHB) protein.
details
PGFRA_HUMAN705729BinaryPhysicochemical compatibilityPhosphorylation 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.
details
IL4RA_HUMAN706721BinaryPhysicochemical compatibilityPhosphorylation of Y713 in the SH2-binding motif of Interleukin-4 receptor subunit alpha (IL4R) induces binding to the SHC-transforming protein 1 (SHC1) protein.
details
IL4RA_HUMAN706721BinaryPhysicochemical compatibilityPhosphorylation 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.
details
M4K1_HUMAN372391BinaryPhysicochemical compatibilityPhosphorylation 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.
details
DOK1_HUMAN203206BinaryPhysicochemical compatibilityPhosphorylation 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.
details
LCP2_HUMAN105118BinaryPhysicochemical compatibilityPhosphorylation 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.
details
LCP2_HUMAN120133BinaryPhysicochemical compatibilityPhosphorylation 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.
details
LCP2_HUMAN137150BinaryPhysicochemical compatibilityPhosphorylation 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.
details

LIG_SH2_IIC -
ZAP70_HUMAN284300BinaryPhysicochemical compatibilityPhosphorylation 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.
details
KSYK_HUMAN315331BinaryPhysicochemical compatibilityPhosphorylation 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.
details

LIG_SH2_III -
EGFR_HUMAN10081024BinaryPhysicochemical compatibilityPhosphorylation 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.
details
ERBB2_HUMAN11311147BinaryPhysicochemical compatibilityPhosphorylation 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.
details
GHR_HUMAN428444BinaryPhysicochemical compatibilityPhosphorylation 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.
details
IL2RB_HUMAN531540BinaryPhysicochemical compatibilityPhosphorylation 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.
details
IL2RB_HUMAN528544BinaryPhysicochemical compatibilityPhosphorylation 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.
details
INGR1_HUMAN457461BinaryPhysicochemical compatibilityPhosphorylation 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.
details
EPOR_HUMAN360376BinaryPhysicochemical compatibilityPhosphorylation of Y368 in the SH2-binding motif of Erythropoietin receptor (EPOR) induces binding to the Signal transducer and activator of transcription 5B (STAT5B) protein.
details
EPOR_HUMAN418434BinaryPhysicochemical compatibilityPhosphorylation of Y426 in the SH2-binding motif of Erythropoietin receptor (EPOR) induces binding to the Signal transducer and activator of transcription 5B (STAT5B) protein.
details
EPOR_HUMAN496508BinaryPhysicochemical compatibilityPhosphorylation of Y504 in the SH2-binding motif of Erythropoietin receptor (EPOR) induces binding to the Signal transducer and activator of transcription 5B (STAT5B) protein.
details
ERBB3_HUMAN13201336BinaryPhysicochemical compatibilityPhosphorylation 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.
details
IL4RA_HUMAN566585BinaryPhysicochemical compatibilityPhosphorylation 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.
details
IL4RA_HUMAN594613BinaryPhysicochemical compatibilityPhosphorylation 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.
details
IL4RA_HUMAN622641BinaryPhysicochemical compatibilityPhosphorylation 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.
details
JAK2_MOUSE804820BinaryPhysicochemical compatibilityPhosphorylation 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.
details
STA5A_HUMAN686702BinaryPhysicochemical compatibilityPhosphorylation 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.
details
LEPR_MOUSE11291148BinaryPhysicochemical compatibilityPhosphorylation of Y1138 in the SH2-binding motif of Leptin receptor (Lepr) induces binding to the Signal transducer and activator of transcription 3 (STAT3) protein.
details

LIG_SH2_SRC - Src-family Src Homology 2 (SH2) domains binding motif.
SRC_HUMAN530533BinaryPhysicochemical compatibilityPhosphorylation 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.
details
DAG1_HUMAN892895SpecificityAltered binding specificityAdhesion-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).
details
DAG1_HUMAN892895SpecificityAltered binding specificityAdhesion-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).
details
DAB1_MOUSE198201BinaryPre‑translationalAlternative 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)).
details
DAB1_MOUSE198201BinaryPhysicochemical compatibilityPhosphorylation of Y198 in the SH2-binding motif of Disabled homolog 1 (Dab1) induces binding to Neuronal proto-oncogene tyrosine-protein kinase Src (Src).
details
EGFR_HUMAN10161019BinaryPhysicochemical compatibilityPhosphorylation 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).
details
EGFR_HUMAN11251128BinaryPhysicochemical compatibilityPhosphorylation of Y1125 in the SH2-binding motif of Epidermal growth factor receptor (EGFR) induces binding to Adapter molecule crk (CRK).
details
EGFR_HUMAN10161019BinaryPhysicochemical compatibilityPhosphorylation of Y1016 in the SH2-binding motif of Epidermal growth factor receptor (EGFR) induces binding to Cytoplasmic protein NCK1 (NCK1).
details
FAK1_HUMAN397400BinaryPhysicochemical compatibilityPhosphorylation of Y397 in the SH2-binding motif of Focal adhesion kinase 1 (PTK2) induces binding to Neuronal proto-oncogene tyrosine-protein kinase Src (Src).
details

LIG_SH2_STAT5 - STAT5 Src Homology 2 (SH2) domain binding motif.
LAT_HUMAN161164BinaryPhysicochemical compatibilityPhosphorylation 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.
details
CTLA4_MOUSE201204SpecificityAltered binding specificityDephosphorylation 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.
details
ERBB4_HUMAN10561059SpecificityAltered binding specificityPhosphorylation-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.
details
INSR_HUMAN13611364SpecificityDomain hidingPIP3 (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.
details
STA5A_HUMAN694697BinaryPre‑translationalAlternative 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.
details
PRLR_HUMAN342345BinaryPre‑translationalAlternative 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)).
details
GAB1_HUMAN472475BinaryPhysicochemical compatibilityPhosphorylation of Y472 in the SH2-binding motif of GRB2-associated-binding protein 1 (GAB1) induces binding to Phosphatidylinositol 3-kinase regulatory subunit alpha (PIK3R1).
details
GAB1_HUMAN447450BinaryPhysicochemical compatibilityPhosphorylation of Y447 in the SH2-binding motif of GRB2-associated-binding protein 1 (GAB1) induces binding to Phosphatidylinositol 3-kinase regulatory subunit alpha (PIK3R1).
details

LIG_SH3_2 - This is the motif recognized by class II SH3 domains
MYC_HUMAN6065BinaryPhysicochemical compatibilityPhosphorylation 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).
details
PAK1_HUMAN1318BinaryPhysicochemical compatibilityPhosphorylation 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.
details
MYC_HUMAN6065SpecificityDomain hidingAn 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).
details
DYN2_HUMAN829834SpecificityDomain hidingAn 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
details
ADA15_HUMAN767772BinaryPre‑translationalAlternative 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.
details
SYNJ2_RAT11201125BinaryPre‑translationalAlternative 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.
details

LIG_SH3_3 - This is the motif recognized by those SH3 domains with a non-canonical class I recognition specificity
TAU_HUMAN213219BinaryPhysicochemical compatibilityPhosphorylation 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).
details
BIN1_HUMAN305311SpecificityDomain hidingAn 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).
details
CD2_HUMAN294300SpecificityCompetitionT-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.
details
DAG1_HUMAN888894SpecificityCompetitionThe 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.
details
PLCB1_HUMAN11621168BinaryPre‑translationalAlternative 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.
details
DAG1_HUMAN888894SpecificityCompetitionThe 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.
details

LIG_SH3_5 - PXXDY motif recognized by some SH3 domains
CD3E_HUMAN184188BinaryAllosteryLigand 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.
details
CD3E_HUMAN184188SpecificityAltered binding specificityPhosphorylation 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).
details

LIG_SH3_8 -
BIN1_HUMAN265268SpecificityDomain hidingAn 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.
details
BIN1_HUMAN265268BinaryPre‑translationalAlternative 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.
details

LIG_SUMO_SBM_1 - Motif that mediates binding to SUMO proteins non-covalently.
DAXX_HUMAN734740CumulativeRheostaticMultisite 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).
details
PIAS1_HUMAN457461BinaryPhysicochemical compatibilityPhosphorylation 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).
details
PIAS1_HUMAN457461BinaryPhysicochemical compatibilityAcetylation 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.
details
PIAS1_HUMAN457461BinaryPhysicochemical compatibilityAcetylation 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.
details
PIAS2_HUMAN467471BinaryPhysicochemical compatibilityAcetylation 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.
details
PIAS2_HUMAN467471BinaryPhysicochemical compatibilityAcetylation 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.
details
DAXX_HUMAN733740UncategorisedUncategorisedSumoylation 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.
details
DAXX_HUMAN733740SpecificityAltered binding specificityAcetylation 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.
details
DAXX_HUMAN733740UncategorisedUncategorisedSumoylation 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.
details
DAXX_HUMAN733740BinaryPhysicochemical compatibilityAcetylation 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.
details
PML_HUMAN556566BinaryPre‑translationalAlternative 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.
details

LIG_SxIP_EBH_1 - SxIP motifs bind to EBH domains.
KIF2C_HUMAN93104BinaryPhysicochemical compatibilityPhosphorylation 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.
details
CLAP2_HUMAN515525BinaryPhysicochemical compatibilityPhosphorylation 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).
details
APC_HUMAN28012811CumulativeRheostaticPhosphorylation 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).
details

LIG_TAZ1 -
HIF1A_HUMAN792795BinaryPhysicochemical compatibilityUnder 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.
details

LIG_TAZ2 -
P53_HUMAN1925CumulativeRheostaticMultisite 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).
details

LIG_TKB -
EGFR_HUMAN10691074BinaryPhysicochemical compatibilityPhosphorylation of Y1069 in Epidermal growth factor receptor (EGFR) is necessary for binding to the TKB domain of E3 ubiquitin-protein ligase CBL (CBL).
details
SPY2_HUMAN5560BinaryPhysicochemical compatibilityPhosphorylation of Y55 in Protein sprouty homolog 2 (SPRY2) is necessary for binding to the TKB domain of E3 ubiquitin-protein ligase CBL (CBL).
details
EGFR_HUMAN10691074CumulativeRheostaticWhile 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).
details
SPY2_HUMAN5560CumulativeRheostaticWhile 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).
details

LIG_TPR_Kinesin_1 -
PKHM2_HUMAN236240BinaryPre‑translationalAlternative 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┬ástimulate movement, suggesting fine-tuning by alternative splicing.
details

LIG_TRAF2_3 -
CYLD_MOUSE449453BinaryPre‑translationalAlternative 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.
details

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_HUMAN185202SpecificityAltered binding specificityPhosphorylation 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).
details
CD3Z_HUMAN6986Avidity‑sensingPhosphorylation 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).
details
CD3Z_HUMAN6986Avidity‑sensingPhosphorylation 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).
details
CD79A_MOUSE179196Avidity‑sensingPhosphorylation 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.
details
CD79A_MOUSE179196Avidity‑sensingPhosphorylation 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.
details
CD3E_HUMAN185202Avidity‑sensingPhosphorylation 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).
details
CD3E_HUMAN185202Avidity‑sensingPhosphorylation 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).
details
CD3Z_HUMAN108126Avidity‑sensingPhosphorylation 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).
details
CD3Z_HUMAN108126Avidity‑sensingPhosphorylation 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).
details
CD3Z_HUMAN139156Avidity‑sensingPhosphorylation 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).
details
CD3Z_HUMAN139156Avidity‑sensingPhosphorylation 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).
details
CD3G_HUMAN157174Avidity‑sensingPhosphorylation 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).
details
CD3G_HUMAN157174Avidity‑sensingPhosphorylation 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).
details
FCG2A_HUMAN285307Avidity‑sensingPhosphorylation 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).
details
FCG2A_HUMAN285307Avidity‑sensingPhosphorylation 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).
details
FCERG_HUMAN6279Avidity‑sensingPhosphorylation 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).
details
FCERG_HUMAN6279Avidity‑sensingPhosphorylation 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).
details

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_HUMAN290295BinaryPhysicochemical compatibilityPhosphorylation 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.
details
KI3L2_HUMAN396401BinaryPhysicochemical compatibilityPhosphorylation 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.
details
OX1R_HUMAN356361Avidity‑sensingOrexin-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).
details
SIG12_MOUSE430435BinaryPre‑translationalAlternative 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).
details
SIG12_MOUSE430435BinaryPre‑translationalAlternative 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).
details
TRML1_HUMAN279284BinaryPre‑translationalAlternative 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).
details
SIG12_MOUSE430435BinaryPre‑translationalAlternative 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).
details
SIG12_MOUSE430435BinaryPre‑translationalAlternative 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).
details
TRML1_HUMAN279284BinaryPre‑translationalAlternative 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).
details
OX1R_HUMAN356361Avidity‑sensingOrexin-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).
details

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_HUMAN277284BinaryPhysicochemical compatibilityPhosphorylation 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.
details
SLAF1_HUMAN323330BinaryPhysicochemical compatibilityPhosphorylation 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.
details
OX1R_HUMAN7986Avidity‑sensingOrexin-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).
details
SLAF7_HUMAN280287BinaryPre‑translationalAlternative 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.
details
OX1R_HUMAN7986Avidity‑sensingOrexin-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).
details

LIG_Talin -
ITB7_HUMAN770779SpecificityCompetitionThe 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.
details
ITB1_HUMAN775785BinaryPre‑translationalAlternative 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).
details
ITB1_HUMAN775785BinaryPre‑translationalAlternative 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).
details

LIG_ULM_U2AF65_1 - Pattern encompassing the ULMs in SF1 and SAP155 which bind to the UHM of U2AF65
ATX1_HUMAN770775SpecificityAltered binding specificityPhosphorylation 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.
details

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_HUMAN275280SpecificityCompetitionThe 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.
details

LIG_WW_1 - PPXY is the motif recognized by WW domains of Group I
SMAD3_HUMAN181184SpecificityAltered binding specificityCDK8/9 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.
details
DAG1_HUMAN889892SpecificityAltered binding specificityAdhesion-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).
details
DAG1_HUMAN889892SpecificityAltered binding specificityAdhesion-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).
details
ERBB4_HUMAN10531056SpecificityAltered binding specificityPhosphorylation-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.
details
SCNNG_HUMAN624627SpecificityDomain hidingPhosphorylation 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.
details
DAG1_HUMAN889892SpecificityCompetitionThe 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.
details
AMOT_HUMAN239242BinaryPre‑translationalAlternative 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.
details
AMOT_HUMAN239242BinaryPre‑translationalAlternative 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.
details
ERBB4_HUMAN10531056BinaryPre‑translationalAlternative 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.
details
SMAD3_HUMAN181184Avidity‑sensingCDK8/9 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.
details
LMP2_EBVB95760BinaryPre‑translationalAlternative splicing removes the WW-binding motif of Latent membrane protein 2 (LMP2), abrogating binding to E3 ubiquitin-protein ligase Itchy (Itch).
details
LMP2_EBVB998101BinaryPre‑translationalAlternative splicing removes the WW-binding motif of Latent membrane protein 2 (LMP2), abrogating binding to E3 ubiquitin-protein ligase Itchy (Itch).
details
LMP2_EBVB95760BinaryPre‑translationalAlternative splicing removes the WW-binding motif of Latent membrane protein 2 (LMP2), abrogating binding to E3 ubiquitin-protein ligase Itchy (Itch).
details
ERBB4_HUMAN10531056BinaryPre‑translationalAlternative 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.
details
AMOT_HUMAN239242BinaryPre‑translationalAlternative 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.
details
DAG1_HUMAN889892SpecificityCompetitionThe 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.
details
P73_HUMAN484487SpecificityCompetitionThe 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.
details
P73_HUMAN484487SpecificityCompetitionThe 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.
details
JUN_MOUSE167170BinaryPhysicochemical compatibilityPhosphorylation 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.
details

LIG_WW_Nedd4L -
SMAD3_HUMAN203210SpecificityAltered binding specificityCDK8/9 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.
details
SMAD3_HUMAN203210Avidity‑sensingCDK8/9 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.
details
SMAD3_HUMAN203210CumulativeRheostaticCDK8/9 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.
details

LIG_eIF4E_1 - Motif binding to the dorsal surface of eIF4E.
4EBP1_HUMAN5460BinaryPhysicochemical compatibilityPhosphorylation 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.
details

MOD_CAAXbox - Generic CAAX box prenylation motif
CDC42_HUMAN188191BinaryPre‑translationalAlternative 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.
details

MOD_CDK -
MK67I_HUMAN235241SpecificityAltered binding specificityPhosphorylation 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).
details

MOD_CDK_1 - Substrate motif for phosphorylation by CDK
CDN1B_HUMAN184190Pre‑assemblyComposite binding site formationBinding 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.
details
CDN1C_HUMAN307313Pre‑assemblyComposite binding site formationBinding 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).
details
CDN1C_MOUSE339345Pre‑assemblyComposite binding site formationBinding 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).
details
ODFP2_HUMAN793799BinaryPre‑translationalAlternative 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.
details

MOD_CK1_1 - CK1 phosphorylation site
YAP1_HUMAN381387SpecificityAltered binding specificityPhosphorylation 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
details
YAP1_HUMAN384390SpecificityAltered binding specificityPhosphorylation 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
details

MOD_GSK3_1 - GSK3 phosphorylation recognition site
NFAC1_HUMAN287294BinaryPhysicochemical compatibilityPhosphorylation 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).
details
NFAC1_HUMAN238245BinaryPhysicochemical compatibilityPhosphorylation 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).
details
MYC_HUMAN5562BinaryPhysicochemical compatibilityPhosphorylation of Myc proto-oncogene protein (MYC) at S62 primes the protein for phosphorylation at T58 by Glycogen synthase kinase-3 beta (GSK3B).
details
P53_HUMAN3037BinaryPhysicochemical compatibilityPhosphorylation of Cellular tumor antigen p53 (TP53) at S37 primes the protein for phosphorylation at S33 by Glycogen synthase kinase-3 beta (GSK3B).
details
JUN_HUMAN236243BinaryPhysicochemical compatibilityPhosphorylation of Transcription factor AP-1 (JUN) at S243 primes the protein for phosphorylation at T239 by Glycogen synthase kinase-3 beta (GSK3B).
details
CCNE1_HUMAN392399BinaryPhysicochemical compatibilityPhosphorylation 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).
details
ATX3_HUMAN253260BinaryPhysicochemical compatibilityPhosphorylation of Ataxin-3 (ATXN3) at S260 primes the protein for subsequent phosphorylation at S256 by Glycogen synthase kinase-3 beta (GSK3B).
details
CCNE1_HUMAN377384SpecificityAltered binding specificityPhosphorylation 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.
details
SMAD3_HUMAN201208SpecificityAltered binding specificityCDK8/9 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.
details
FGD1_HUMAN280287SpecificityAltered binding specificityPhosphorylation 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.
details
FGD3_HUMAN7784SpecificityAltered binding specificityPhosphorylation 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.
details
FGD3_HUMAN7380SpecificityAltered binding specificityPhosphorylation 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.
details
MK67I_HUMAN231238SpecificityAltered binding specificityPhosphorylation 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).
details
MK67I_HUMAN227234SpecificityAltered binding specificityPhosphorylation 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).
details
MYC_HUMAN5562SpecificityAltered binding specificityPhosphorylation 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.
details
JUN_HUMAN236243SpecificityAltered binding specificityTranscription 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.
details
CCNE1_HUMAN392399SpecificityAltered binding specificityPhosphorylation 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.
details
SRBP1_HUMAN422430SpecificityAltered binding specificityPhosphorylation 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.
details
CTNB1_HUMAN3441SpecificityAltered binding specificityPhosphorylation 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.
details
CTNB1_HUMAN3037SpecificityAltered binding specificityPhosphorylation 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.
details
SNAI1_HUMAN93100SpecificityAltered binding specificityPhosphorylation 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.
details
ESR2_HUMAN512BinaryPhysicochemical compatibilityThe 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
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_HUMAN376382SpecificityAltered binding specificityPhosphorylation 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
details

MOD_NMyristoyl - Generic motif for N-Myristoylation site.
RECO_BOVIN17BinaryAllosteryBinding of calcium(2+) to Recoverin (RCVRN) results in a conformational change in Recoverin that makes the myristoyl moiety available for binding to the membrane.
details
KAPCA_HUMAN17BinaryAllosteryPhosphorylation 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.
details
PDE2A_HUMAN17BinaryPre‑translationalAlternative 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.
details

MOD_PKA_1 - Main preference for PKA-type AGC kinase phosphorylation.
SYN_DROME39BinaryPre‑translationalRNA 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).
details

MOD_PKA_2 - Secondary preference for PKA-type AGC kinase phosphorylation.
SPTB2_HUMAN21572162BinaryPre‑translationalAlternative 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.
details

MOD_ProDKin_1 - Proline-Directed Kinase (e.g. MAPK) phosphorylation site in higher eukaryotes.
MYC_HUMAN5965SpecificityAltered binding specificityPhosphorylation 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.
details

MOD_SUMO - Motif recognised for modification by SUMO-1
HSF4_HUMAN292295BinaryPre‑translationalAlternative 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.
details
HSF4_HUMAN292295BinaryPhysicochemical compatibilityThe phosphorylation-dependent sumoylation of the PDSM (phosphorylation-dependent sumoylation motif) strongly represses Isoform HSF4B of Heat shock factor protein 4 (HSF4) activity.
details
PML_HUMAN489492BinaryPre‑translationalAlternative 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.
details
PML_HUMAN159162UncategorisedUncategorisedSumoylation 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.
details
PML_HUMAN159162UncategorisedUncategorisedSumoylation 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.
details
NFAC1_HUMAN701704BinaryPre‑translationalAlternative 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.
details
NFAC1_HUMAN913916BinaryPre‑translationalAlternative 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.
details

MOD_SUMO_PHOS -
ESR2_HUMAN47BinaryPhysicochemical compatibilityThe 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)
details
ESR2_HUMAN47BinaryPhysicochemical compatibilitySumoylation of K4 in Estrogen receptor beta (ESR2) is inhibited by ubiquitination K4. This destabilises ESR2 increasing its turnover (see also switch details)
details

MOD_Spalmitoyl -
CDC42_HUMAN188191BinaryPre‑translationalAlternative 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.
details

TRG_AP2beta_CARGO_1 - AP-2 beta appendage platform subdomain (top surface) binding motif used in targeting cargo for internalisation.
ARRB1_HUMAN385395BinaryAllosteryBinding 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.
details

TRG_AP2beta_CARGO_2 -
PI51C_MOUSE633644BinaryPre‑translationalAlternative 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)).
details
PI51C_MOUSE633644BinaryPhysicochemical compatibilityPhosphorylation 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.
details

TRG_ENDOCYTIC_2 - Tyrosine-based sorting signal responsible for the interaction with mu subunit of AP (Adaptor Protein) complex
PPAL_HUMAN413416UncategorisedUncategorisedPhosphorylation 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.
details
TGON3_RAT350353BinaryAllosteryBinding 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.
details
EGFR_HUMAN9981001BinaryAllosteryBinding 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.
details
TFR1_HUMAN2023BinaryAllosteryBinding 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.
details
ENV_HTLV2477480BinaryAllosteryBinding 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.
details
VGLG_VSIVA501504BinaryAllosteryBinding 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.
details
ENV_HV1H2712715BinaryAllosteryBinding 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.
details
ENV_SIVMK723726BinaryAllosteryBinding 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.
details
ASGR1_HUMAN58BinaryAllosteryBinding 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.
details
LAMP1_HUMAN414417BinaryAllosteryBinding 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.
details
CTLA4_HUMAN201204BinaryAllosteryBinding 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.
details
L1CAM_HUMAN11761179BinaryAllosteryBinding 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.
details
ENV_BLV487490BinaryAllosteryBinding 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.
details
GE_VZVO582585BinaryAllosteryBinding 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.
details
CTLA4_MOUSE201204SpecificityAltered binding specificityDephosphorylation 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.
details
L1CAM_HUMAN11761179BinaryPhysicochemical compatibilityPhosphorylation 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).
details
L1CAM_HUMAN11761179BinaryPre‑translationalAlternative 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.
details
PEX5R_MOUSE3841BinaryPre‑translationalAlternative 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.
details
SORC1_HUMAN11321135BinaryPre‑translationalAlternative 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.
details
PI51C_MOUSE644647BinaryPre‑translationalAlternative 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.
details
PI51C_HUMAN649652BinaryPhysicochemical compatibilityPhosphorylation 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).
details
L1CAM_HUMAN11761179BinaryPhysicochemical compatibilityPhosphorylation 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).
details

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_BOVIN225228BinaryPre‑translationalAlternative splicing removes the KDEL ER-retention motif of Isoform 2 of Protein-L-isoaspartate(D-aspartate) O-methyltransferase (PCMT1).
details
P3H1_HUMAN733736BinaryPre‑translationalAlternative splicing removes the KDEL ER-retention motif of Prolyl 3-hydroxylase 1 (LEPRE1).
details

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_HUMAN893895BinaryPhysicochemical compatibilityPhosphorylation 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.
details
ADA22_HUMAN829
851
831
854
SpecificityMotif hidingPhosphorylation-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.
details
GPR15_HUMAN352354SpecificityMotif hidingPhosphorylation-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).
details
HG2A_HUMAN35SpecificityMotif hidingThe 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.
details
GABR1_HUMAN923926SpecificityMotif hidingInteraction 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.
details
NMDZ1_HUMAN893895SpecificityMotif hidingBinding 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.
details
NMDZ1_HUMAN893895SpecificityMotif hidingBinding 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.
details
NMDZ1_HUMAN893895SpecificityMotif hidingBinding 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.
details

TRG_ER_diArg_2 -
GRIK1_RAT937941BinaryPre‑translationalAlternative splicing removes the di-arginine ER-retention motif of Glutamate receptor, ionotropic kainate 1 (Grik1), abrogating binding to Coatomer subunit beta (COPB1).
details

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_HUMAN392396BinaryPre‑translationalAlternative 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.
details

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_HUMAN434439BinaryAllosteryBinding 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.
details
NPC1_HUMAN12711276BinaryAllosteryBinding 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.
details
HG2A_HUMAN1924BinaryAllosteryBinding 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.
details
CD3D_MOUSE138143BinaryAllosteryBinding 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.
details
NEF_HV1H2160165BinaryAllosteryBinding 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.
details
NEF_HV1B8159164BinaryAllosteryBinding 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.
details
CD3G_MOUSE149154BinaryAllosteryBinding 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.
details
CD44_HUMAN708713BinaryAllosteryBinding 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.
details
OPRD_HUMAN241246BinaryAllosteryBinding 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.
details
BCAM_HUMAN604609BinaryAllosteryBinding 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.
details
ENV_BLV463468BinaryAllosteryBinding 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.
details
BACE1_HUMAN495500BinaryAllosteryBinding 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.
details
ATP7A_HUMAN14831488BinaryAllosteryBinding 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.
details
PEX5R_MOUSE1419BinaryPre‑translationalAlternative 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.
details
PRLR_RAT301306BinaryPre‑translationalAlternative 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.
details

TRG_LysEnd_APsAcLL_2 -
SORC1_HUMAN11361140BinaryPre‑translationalAlternative 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.
details

TRG_MLS -
CACP_HUMAN121BinaryPre‑translationalAlternative 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.
details
DBLOH_HUMAN155BinaryPre‑translationalAlternative 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.
details
UNG_HUMAN144BinaryPre‑translationalAlternative 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.
details
TRM1_YEAST116BinaryPre‑translationalAlternative 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.
details
MOD5_MOUSE147BinaryPre‑translationalAlternative 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.
details
SYK_HUMAN149BinaryPre‑translationalAlternative 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.
details
GLRX2_HUMAN121BinaryPre‑translationalAlternative 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.
details
DUT_HUMAN169BinaryPre‑translationalAlternative 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.
details

TRG_NES -
ACE2_YEAST122150BinaryPhysicochemical compatibilityPhosphorylation 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.
details
ACE2_YEAST122150BinaryPhysicochemical compatibilityPhosphorylation 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.
details

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_HUMAN189203BinaryPhysicochemical compatibilityPhosphorylation 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).
details
P53_HUMAN339352BinaryPre‑translationalAlternative splicing removes the nuclear export signal (NES) of Cellular tumor antigen p53 (TP53), abrogating binding to Exportin-1 (XPO1) and export from the nucleus.
details
PML_HUMAN702716BinaryPre‑translationalAlternative splicing removes the nuclear export signal (NES) of Protein PML (PML), abrogating binding to Exportin-1 (XPO1) and export from the nucleus.
details
CTND1_HUMAN942956BinaryPre‑translationalAlternative 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.
details

TRG_NES_CRM1_2 -
FBXW7_HUMAN1926BinaryPre‑translationalAlternative 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.
details
SMAD4_HUMAN142149BinaryPre‑translationalAlternative 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.
details
MDM2_HUMAN190202BinaryPre‑translationalAlternative splicing removes the nuclear export signal (NES) of E3 ubiquitin-protein ligase Mdm2 (MDM2), abrogating binding to Exportin-1 (XPO1).
details
NF2L1_HUMAN251259BinaryPre‑translationalAlternative 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.
details

TRG_NLS -
PML_HUMAN476490BinaryPre‑translationalAlternative splicing removes the nuclear localisation signal (NLS) of Protein PML (PML), abrogating binding to Importin subunit alpha-1 (KPNA1) and import into the nucleus.
details
CDN1B_HUMAN152166SpecificityMotif hidingPhosphorylation 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).
details

TRG_NLS_Bipartite_1 - Bipartite variant of the classical basically charged NLS.
PTHR_HUMAN124144BinaryPhysicochemical compatibilityPhosphorylation 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.
details
IMA1_YEAST4458SpecificityDomain hidingAn 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.
details

TRG_NLS_MonoCore_2 - Monopartite variant of the classical basically charged NLS. Strong core version.
KCC2D_RAT327332BinaryPre‑translationalAlternative 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.
details
FBXW7_HUMAN1015BinaryPre‑translationalAlternative 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.
details

TRG_NLS_MonoExtC_3 - Monopartite variant of the classical basically charged NLS. C-extended version.
PHO4_YEAST156161BinaryPhysicochemical compatibilityPhosphorylation 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.
details
MDM2_HUMAN181187BinaryPre‑translationalAlternative 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.
details

TRG_NLS_MonoExtN_4 - Monopartite variant of the classical basically charged NLS. N-extended version.
SWI6_YEAST161167BinaryPhysicochemical compatibilityPhosphorylation 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).
details
NFAC1_HUMAN262269BinaryPhysicochemical compatibilityPhosphorylation 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.
details
LT_SV40126132SpecificityMotif hidingInhibition of nuclear import of Large T antigen by phosphorylation-dependent (T124) binding of BRCA1-associated protein (BRAP).
details
LT_SV40126132SpecificityMotif hidingInhibition of nuclear import of Large T antigen by phosphorylation-dependent (T124) binding of BRCA1-associated protein (BRAP).
details
VPAP_HCMVA425432SpecificityMotif hidingInhibition of nuclear import of DNA polymerase processivity factor (UL44) by phosphorylation-dependent (T427) binding of BRCA1-associated protein (BRAP).
details
VPAP_HCMVA425432SpecificityMotif hidingInhibition of nuclear import of DNA polymerase processivity factor (UL44) by phosphorylation-dependent (T427) binding of BRCA1-associated protein (BRAP).
details
MKL1_MOUSE62
95
67
101
SpecificityMotif hidingHiding 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.
details
LT_SV40126132SpecificityDomain hidingAn 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.
details
UNG_HUMAN1521BinaryPre‑translationalAlternative 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.
details
OGG1_HUMAN332339BinaryPre‑translationalAlternative 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.
details
BRCA1_HUMAN501508BinaryPre‑translationalAlternative 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.
details
SKP2_HUMAN6572BinaryPhysicochemical compatibilityAcetylation 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.
details
SKP2_HUMAN6572BinaryPhysicochemical compatibilityAcetylation 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.
details

TRG_PTS1 - Generic PTS1 ELM for all eukaryotes
AMACR_HUMAN379382BinaryPre‑translationalAlternative 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.
details
           
Please send any suggestions/comments to: switches@elm.eu.org