Please send any suggestions/comments to: switches@elm.eu.org
| Motif | Protein | Start | End | Switch Type | Switch Subtype | Switch description | Information | Evidence |
(Reactome - 2676022) | ||||||||
| LIG_TYR_ITAM | CD79A_MOUSE | 179 | 196 | Avidity‑sensing | Phosphorylation of Y182 and Y193 in the ITAM motif of B-cell antigen receptor complex-associated protein alpha chain (Cd79a) induces high-avidity binding to the tandem SH2 domains of Tyrosine-protein kinase SYK (Syk). Maximal Syk activation requires both Syk SH2 domains and phosphorylation of both ITAM tyrosine residues. | Curated | ||
| LIG_TYR_ITAM | CD79A_MOUSE | 179 | 196 | Avidity‑sensing | Phosphorylation of Y182 and Y193 in the ITAM motif of B-cell antigen receptor complex-associated protein alpha chain (Cd79a) induces high-avidity binding to the tandem SH2 domains of Tyrosine-protein kinase SYK (Syk). Maximal Syk activation requires both Syk SH2 domains and phosphorylation of both ITAM tyrosine residues. | Curated | ||
(Reactome - 2676436) | ||||||||
| MOD_CDK_1 | CDN1B_HUMAN | 184 | 190 | Pre‑assembly | Composite binding site formation | Binding of Cyclin-dependent kinase inhibitor 1B (CDKN1B) (p27) to the SCF-Skp2 ubiquitin ligase complex requires phosphorylation of p27 (CDKN1B) at T187, and association of the F-box protein S-phase kinase-associated protein 2 (SKP2) with the regulatory Cyclin-dependent kinases regulatory subunit 1 (CKS1B). SKP2 and CKS1B together generate a composite binding site for p27 (CDKN1B). While some residues, including the phosphorylated T187, bind to CKS1B and others to SKP2, the E185 makes contact with residues of both CKS1B and SKP2. | Curated | |
| DEG_SCF_SKP2-CKS1_1 | CDN1B_HUMAN | 183 | 190 | Pre‑assembly | Composite binding site formation | Binding of Cyclin-dependent kinase inhibitor 1B (CDKN1B) (p27) to the SCF-Skp2 ubiquitin ligase complex requires phosphorylation of p27 (CDKN1B) at T187, and association of the F-box protein S-phase kinase-associated protein 2 (SKP2) with the regulatory Cyclin-dependent kinases regulatory subunit 1 (CKS1B). SKP2 and CKS1B together generate a composite binding site for p27 (CDKN1B). While some residues, including the phosphorylated T187, bind to CKS1B and others to SKP2, the E185 makes contact with residues of both CKS1B and SKP2. | Curated | |
(Reactome - 2721265) | ||||||||
| LIG_14-3-3_1 | BAD_RAT | 134 | 139 | Binary | Physicochemical compatibility | Phosphorylation of S137 by RAC-alpha serine/threonine-protein kinase (Akt1) in the 14-3-3-binding motif of Bcl2 antagonist of cell death (Bad) induces binding to the 14-3-3 protein beta/alpha (YWHAB) protein. This interaction inhibits the pro-apoptotic activity of Bcl2 antagonist of cell death (Bad). | Curated | |
APC/C-mediated degradation of cell cycle proteins (Reactome - 174143) | ||||||||
| DEG_APCC_DBOX_3 | NEK2_HUMAN | 423 | 445 | Binary | Pre‑translational | Alternative splicing removes the extended D-box degron motif of Serine/threonine-protein kinase Nek2 (NEK2), abrogating binding to Cell division cycle protein 20 homolog (CDC20). NEK2-A is targeted by APC/C-Cdc20 in early mitosis whereas Isoform Nek2B of Serine/threonine-protein kinase Nek2 (NEK2) persists into late mitosis. Degradation of Isoform Nek2A of Serine/threonine-protein kinase Nek2 (NEK2) may be necessary to allow re-establishment of the intercentriolar linkage in late mitosis. | Curated | |
Aldosterone-regulated sodium reabsorption (KEGG - hsa04960) | ||||||||
| LIG_14-3-3_1 | NED4L_HUMAN | 465 | 470 | Specificity | Domain hiding | Phosphorylation of Isoform Nedd4-2a of E3 ubiquitin-protein ligase NEDD4-like (NEDD4L) by Serine/threonine-protein kinase Sgk1 (SGK1) induces binding to 14-3-3 protein eta (YWHAH). This inhibits (whether allosterically or sterically is not known) interactions of NEDD4L via its WW domains with the PY motif in Amiloride-sensitive sodium channel subunit gamma (SCNN1G) (ENaC). As a result, ENaC does not get degraded and ENaC-mediated Na+ currents increase. | Inferred | |
| LIG_WW_1 | SCNNG_HUMAN | 624 | 627 | Specificity | Domain hiding | Phosphorylation of Isoform Nedd4-2a of E3 ubiquitin-protein ligase NEDD4-like (NEDD4L) by Serine/threonine-protein kinase Sgk1 (SGK1) induces binding to 14-3-3 protein eta (YWHAH). This inhibits (whether allosterically or sterically is not known) interactions of NEDD4L via its WW domains with the PY motif in Amiloride-sensitive sodium channel subunit gamma (SCNN1G) (ENaC). As a result, ENaC does not get degraded and ENaC-mediated Na+ currents increase. | Inferred | |
| LIG_SH2_STAT5 | INSR_HUMAN | 1361 | 1364 | Specificity | Domain hiding | PIP3 (1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate), a product of PI3-kinase, binds to the SH2 domains of PI3K (Phosphatidylinositol 3-kinase regulatory subunit alpha (PIK3R1)) and thereby blocks its interaction with tyrosine-phosphorylated SH2 motif containing proteins. | Inferred | |
Apoptosis (KEGG - hsa04210) | ||||||||
| CLV_C14_caspase-8-10 | CASP3_HUMAN | 172 | 175 | Binary | Physicochemical compatibility | Phosphorylation of S176 adjacent to the cleavage motif of Caspase-3 (CASP3) by CK2 subfamily prevents cleavage by Caspase-8 (CASP8) and thus activation of Caspase-3 (CASP3). | Curated | |
| LIG_BIR_III_2 | CASP9_HUMAN | 315 | 319 | Binary | Physicochemical compatibility | Binding of the BIR domain-binding motif of Caspase-9 (CASP9) to the BIR domains of Baculoviral IAP repeat-containing protein 4 (XIAP) requires cleavage of Caspase-9 (CASP9) at D315, since this results in a functional neo N-terminal motif. BIR domains are found in Inhibitor of Apoptosis Proteins (IAPs) that suppress the activity of activated caspases, either by directly inhibiting caspase catalytic activity, or by targeting caspases for degradation by ubiquitin modification. | Inferred | |
| LIG_BIR_III_2 | CASP9_HUMAN | 315 | 319 | Binary | Physicochemical compatibility | Binding of the BIR domain-binding motif of Caspase-9 (CASP9) to the BIR domains of Baculoviral IAP repeat-containing protein 2 (BIRC2) requires cleavage of Caspase-9 (CASP9) at D315, since this results in a functional neo N-terminal motif. BIR domains are found in Inhibitor of Apoptosis Proteins (IAPs) that suppress the activity of activated caspases, either by directly inhibiting caspase catalytic activity, or by targeting caspases for degradation by ubiquitin modification. | Inferred | |
| LIG_BIR_III_2 | CASP7_HUMAN | 23 | 27 | Binary | Physicochemical compatibility | Binding of the BIR domain-binding motif of Caspase-7 (CASP7) to the BIR domains of Baculoviral IAP repeat-containing protein 2 (BIRC2) requires cleavage of Caspase-7 (CASP7) at D23, since this results in a functional neo N-terminal motif. BIR domains are found in Inhibitor of Apoptosis Proteins (IAPs) that suppress the activity of activated caspases, either by directly inhibiting caspase catalytic activity, or by targeting caspases for degradation by ubiquitin modification. | Curated | |
| LIG_BIR_III_2 | CASP7_HUMAN | 23 | 27 | Binary | Physicochemical compatibility | Binding of the BIR domain-binding motif of Caspase-7 (CASP7) to the BIR domains of Baculoviral IAP repeat-containing protein 2 (BIRC2) requires cleavage of Caspase-7 (CASP7) at D23, since this results in a functional neo N-terminal motif. BIR domains are found in Inhibitor of Apoptosis Proteins (IAPs) that suppress the activity of activated caspases, either by directly inhibiting caspase catalytic activity, or by targeting caspases for degradation by ubiquitin modification. | Curated | |
| LIG_BIR_III_2 | CASP7_HUMAN | 23 | 27 | Binary | Physicochemical compatibility | Binding of the BIR domain-binding motif of Caspase-7 (CASP7) to the BIR domains of Baculoviral IAP repeat-containing protein 2 (BIRC2) requires cleavage of Caspase-7 (CASP7) at D23, since this results in a functional neo N-terminal motif. BIR domains are found in Inhibitor of Apoptosis Proteins (IAPs) that suppress the activity of activated caspases, either by directly inhibiting caspase catalytic activity, or by targeting caspases for degradation by ubiquitin modification. | Curated | |
Apoptotic execution phase (Reactome - 75153) | ||||||||
| CLV_C14_caspase-8-10 | CASP3_HUMAN | 172 | 175 | Binary | Physicochemical compatibility | Phosphorylation of S176 adjacent to the cleavage motif of Caspase-3 (CASP3) by CK2 subfamily prevents cleavage by Caspase-8 (CASP8) and thus activation of Caspase-3 (CASP3). | Curated | |
| CLV_C14_Caspase3-7 | KPCD_HUMAN | 326 | 330 | Binary | Pre‑translational | Alternative splicing inserts exons within the Caspase-3 scission motif of Protein kinase C delta type (PRKCD), abrogating binding to Caspase-3 (CASP3). Cleavage of PKCdeltaI Protein kinase C delta type (PRKCD) by caspase-3 releases a catalytically active C-terminal fragment that is sufficient to induce apoptosis. This inserted exon disrupts scission motifs and therefore the PKCdeltaVIII (GENBANK:DQ516383) splice variant functions as an anti-apoptotic protein in NT2 cells. | Curated | |
| LIG_BIR_III_2 | CASP7_HUMAN | 23 | 27 | Binary | Physicochemical compatibility | Binding of the BIR domain-binding motif of Caspase-7 (CASP7) to the BIR domains of Baculoviral IAP repeat-containing protein 2 (BIRC2) requires cleavage of Caspase-7 (CASP7) at D23, since this results in a functional neo N-terminal motif. BIR domains are found in Inhibitor of Apoptosis Proteins (IAPs) that suppress the activity of activated caspases, either by directly inhibiting caspase catalytic activity, or by targeting caspases for degradation by ubiquitin modification. | Curated | |
| LIG_BIR_III_2 | CASP7_HUMAN | 23 | 27 | Binary | Physicochemical compatibility | Binding of the BIR domain-binding motif of Caspase-7 (CASP7) to the BIR domains of Baculoviral IAP repeat-containing protein 2 (BIRC2) requires cleavage of Caspase-7 (CASP7) at D23, since this results in a functional neo N-terminal motif. BIR domains are found in Inhibitor of Apoptosis Proteins (IAPs) that suppress the activity of activated caspases, either by directly inhibiting caspase catalytic activity, or by targeting caspases for degradation by ubiquitin modification. | Curated | |
| LIG_BIR_III_2 | CASP7_HUMAN | 23 | 27 | Binary | Physicochemical compatibility | Binding of the BIR domain-binding motif of Caspase-7 (CASP7) to the BIR domains of Baculoviral IAP repeat-containing protein 2 (BIRC2) requires cleavage of Caspase-7 (CASP7) at D23, since this results in a functional neo N-terminal motif. BIR domains are found in Inhibitor of Apoptosis Proteins (IAPs) that suppress the activity of activated caspases, either by directly inhibiting caspase catalytic activity, or by targeting caspases for degradation by ubiquitin modification. | Curated | |
Axon guidance (KEGG - hsa04360) | ||||||||
| MOD_GSK3_1 | NFAC1_HUMAN | 287 | 294 | Binary | Physicochemical compatibility | Phosphorylation of S294 adjacent to the NLS of Nuclear factor of activated T-cells, cytoplasmic 1 (NFATC1) by cAMP subfamily primes Nuclear factor of activated T-cells, cytoplasmic 1 (NFATC1) for subsequent phosphorylation by Glycogen synthase kinase-3 beta (GSK3B), which results in inhibition of nuclear import of Nuclear factor of activated T-cells, cytoplasmic 1 (NFATC1). | Inferred | |
| MOD_GSK3_1 | NFAC1_HUMAN | 238 | 245 | Binary | Physicochemical compatibility | Phosphorylation of S245 adjacent to the NLS of Nuclear factor of activated T-cells, cytoplasmic 1 (NFATC1) by cAMP subfamily primes Nuclear factor of activated T-cells, cytoplasmic 1 (NFATC1) for subsequent phosphorylation by Glycogen synthase kinase-3 beta (GSK3B), which results in inhibition of nuclear import of Nuclear factor of activated T-cells, cytoplasmic 1 (NFATC1). | Inferred | |
| LIG_SH3_2 | PAK1_HUMAN | 13 | 18 | Binary | Physicochemical compatibility | Phosphorylation of S21 adjacent to the SH3-binding motif of Serine/threonine-protein kinase PAK 1 (PAK1) by RAC subfamily inhibits binding to Cytoplasmic protein NCK1 (NCK1), which regulates its localization to focal contacts. | Inferred | |
| MOD_ProDKin_1 | MYC_HUMAN | 59 | 65 | Specificity | Altered binding specificity | Phosphorylation of Myc proto-oncogene protein (MYC) at S62 by Mitogen-activated protein kinase 1 (MAPK1) primes MYC for phosphorylation by Glycogen synthase kinase-3 beta (GSK3B), which targets MYC to the SCF ubiquitin ligase complex, F-box/WD repeat-containing protein 7 (FBXW7) that marks MYC for degradation. | Inferred | |
| MOD_GSK3_1 | MYC_HUMAN | 55 | 62 | Specificity | Altered binding specificity | Phosphorylation of Myc proto-oncogene protein (MYC) at S62 by Mitogen-activated protein kinase 1 (MAPK1) primes MYC for phosphorylation by Glycogen synthase kinase-3 beta (GSK3B), which targets MYC to the SCF ubiquitin ligase complex, F-box/WD repeat-containing protein 7 (FBXW7) that marks MYC for degradation. | Inferred | |
| DEG_SCF_FBW7_1 | MYC_HUMAN | 55 | 62 | Specificity | Altered binding specificity | Phosphorylation of Myc proto-oncogene protein (MYC) at S62 by Mitogen-activated protein kinase 1 (MAPK1) primes MYC for phosphorylation by Glycogen synthase kinase-3 beta (GSK3B), which targets MYC to the SCF ubiquitin ligase complex, F-box/WD repeat-containing protein 7 (FBXW7) that marks MYC for degradation. | Inferred | |
| LIG_SH2_IA | EPHA3_HUMAN | 597 | 606 | Binary | Physicochemical compatibility | Phosphorylation of Y602 in the SH2-binding motif of Ephrin type-A receptor 3 (EPHA3) induces binding to the Cytoplasmic protein NCK1 (NCK1) protein. | Inferred | |
| LIG_SH2_IA | FAK1_HUMAN | 389 | 405 | Binary | Physicochemical compatibility | Phosphorylation of Y397 in the SH2-binding motif of Focal adhesion kinase 1 (PTK2) induces binding to the Cytoplasmic protein NCK2 (NCK2) protein. | Inferred | |
B cell receptor signaling pathway (KEGG - hsa04662) | ||||||||
| MOD_GSK3_1 | NFAC1_HUMAN | 287 | 294 | Binary | Physicochemical compatibility | Phosphorylation of S294 adjacent to the NLS of Nuclear factor of activated T-cells, cytoplasmic 1 (NFATC1) by cAMP subfamily primes Nuclear factor of activated T-cells, cytoplasmic 1 (NFATC1) for subsequent phosphorylation by Glycogen synthase kinase-3 beta (GSK3B), which results in inhibition of nuclear import of Nuclear factor of activated T-cells, cytoplasmic 1 (NFATC1). | Inferred | |
| MOD_GSK3_1 | NFAC1_HUMAN | 238 | 245 | Binary | Physicochemical compatibility | Phosphorylation of S245 adjacent to the NLS of Nuclear factor of activated T-cells, cytoplasmic 1 (NFATC1) by cAMP subfamily primes Nuclear factor of activated T-cells, cytoplasmic 1 (NFATC1) for subsequent phosphorylation by Glycogen synthase kinase-3 beta (GSK3B), which results in inhibition of nuclear import of Nuclear factor of activated T-cells, cytoplasmic 1 (NFATC1). | Inferred | |
| MOD_GSK3_1 | JUN_HUMAN | 236 | 243 | Binary | Physicochemical compatibility | Phosphorylation of Transcription factor AP-1 (JUN) at S243 primes the protein for phosphorylation at T239 by Glycogen synthase kinase-3 beta (GSK3B). | Inferred | |
| LIG_TYR_ITIM | FCG2B_HUMAN | 290 | 295 | Binary | Physicochemical compatibility | Phosphorylation of Y292 in the ITIM motif of Low affinity immunoglobulin gamma Fc region receptor II-b (FCGR2B) induces binding of Phosphatidylinositol-3,4,5-trisphosphate 5-phosphatase 1 (INPP5D) via its SH2 domain. | Inferred | |
| MOD_ProDKin_1 | MYC_HUMAN | 59 | 65 | Specificity | Altered binding specificity | Phosphorylation of Myc proto-oncogene protein (MYC) at S62 by Mitogen-activated protein kinase 1 (MAPK1) primes MYC for phosphorylation by Glycogen synthase kinase-3 beta (GSK3B), which targets MYC to the SCF ubiquitin ligase complex, F-box/WD repeat-containing protein 7 (FBXW7) that marks MYC for degradation. | Inferred | |
| MOD_GSK3_1 | MYC_HUMAN | 55 | 62 | Specificity | Altered binding specificity | Phosphorylation of Myc proto-oncogene protein (MYC) at S62 by Mitogen-activated protein kinase 1 (MAPK1) primes MYC for phosphorylation by Glycogen synthase kinase-3 beta (GSK3B), which targets MYC to the SCF ubiquitin ligase complex, F-box/WD repeat-containing protein 7 (FBXW7) that marks MYC for degradation. | Inferred | |
| DEG_SCF_FBW7_1 | MYC_HUMAN | 55 | 62 | Specificity | Altered binding specificity | Phosphorylation of Myc proto-oncogene protein (MYC) at S62 by Mitogen-activated protein kinase 1 (MAPK1) primes MYC for phosphorylation by Glycogen synthase kinase-3 beta (GSK3B), which targets MYC to the SCF ubiquitin ligase complex, F-box/WD repeat-containing protein 7 (FBXW7) that marks MYC for degradation. | Inferred | |
| MOD_GSK3_1 | JUN_HUMAN | 236 | 243 | Specificity | Altered binding specificity | Transcription factor AP-1 (JUN) is primed by an unknown kinase for phosphorylation by Glycogen synthase kinase-3 beta (GSK3B), which targets JUN to the SCF ubiquitin ligase complex, F-box/WD repeat-containing protein 7 (FBXW7) that marks JUN for degradation. In v-Jun (Viral jun-transforming protein (JUN)) the residue corresponding to S243 is mutated to phenylalanine, which protects v-Jun (JUN) from degradation. | Inferred | |
| DEG_SCF_FBW7_1 | JUN_HUMAN | 236 | 243 | Specificity | Altered binding specificity | Transcription factor AP-1 (JUN) is primed by an unknown kinase for phosphorylation by Glycogen synthase kinase-3 beta (GSK3B), which targets JUN to the SCF ubiquitin ligase complex, F-box/WD repeat-containing protein 7 (FBXW7) that marks JUN for degradation. In v-Jun (Viral jun-transforming protein (JUN)) the residue corresponding to S243 is mutated to phenylalanine, which protects v-Jun (JUN) from degradation. | Inferred | |
B cell receptor signaling pathway (KEGG - mmu04662) | ||||||||
| LIG_TYR_ITAM | CD79A_MOUSE | 179 | 196 | Avidity‑sensing | Phosphorylation of Y182 and Y193 in the ITAM motif of B-cell antigen receptor complex-associated protein alpha chain (Cd79a) induces high-avidity binding to the tandem SH2 domains of Tyrosine-protein kinase SYK (Syk). Maximal Syk activation requires both Syk SH2 domains and phosphorylation of both ITAM tyrosine residues. | Curated | ||
| LIG_TYR_ITAM | CD79A_MOUSE | 179 | 196 | Avidity‑sensing | Phosphorylation of Y182 and Y193 in the ITAM motif of B-cell antigen receptor complex-associated protein alpha chain (Cd79a) induces high-avidity binding to the tandem SH2 domains of Tyrosine-protein kinase SYK (Syk). Maximal Syk activation requires both Syk SH2 domains and phosphorylation of both ITAM tyrosine residues. | Curated | ||
| LIG_SH2_IIA | SHIP1_HUMAN | 918 | 921 | Binary | Pre‑translational | Alternative splicing partially removes the SH2-binding motif of Phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 1 (Inpp5d), partially inhibiting binding to Phosphatidylinositol 3-kinase regulatory subunit alpha (Pik3r1). | Inferred | |
| LIG_SH2_IIA | SHIP1_HUMAN | 918 | 921 | Binary | Pre‑translational | Alternative splicing partially removes the SH2-binding motif of Phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 1 (Inpp5d), partially inhibiting binding to Phosphatidylinositol 3-kinase regulatory subunit alpha (Pik3r1). | Inferred | |
Base excision repair (KEGG - ko03410) | ||||||||
| LIG_PCNA_PIPBox_1 | DPOD3_HUMAN | 456 | 465 | Binary | Physicochemical compatibility | Phosphorylation of S458 in the PCNA-binding motif of DNA polymerase delta subunit 3 (POLD3) by cAMP subfamily reduces the affinity of binding to the Proliferating cell nuclear antigen (PCNA) and decreases the processivity of the polymerase complex. | Curated | |
Calcium signaling pathway (KEGG - hsa04020) | ||||||||
| LIG_PDZ_Class_1 | AT2B4_HUMAN | 1236 | 1241 | Binary | Pre‑translational | Alternative splicing removes the PDZ-binding motif of Plasma membrane calcium-transporting ATPase 4 (ATP2B4), abrogating binding to Nitric oxide synthase, brain (NOS1). PMCA4b acts as a negative regulator of Nitric oxide synthase, brain (NOS1), reducing production of nitric oxide in heart tissue. This negative regulation was not dependent on a conformational change due to binding of the PDZ ligand, but on Ca2+ depletion in close proximity of the enzyme. Nitric oxide production by NOS1 is known to be important in the regulation of excitation-contraction (EC) coupling and subsequently contractility. | Inferred | |
| LIG_IQ_2 | AT2B1_HUMAN | 1114 | 1128 | Binary | Pre‑translational | Alternative splicing partially removes the IQ motif of Isoform CI of Plasma membrane calcium-transporting ATPase 1 (ATP2B1), partially inhibiting binding to Calmodulin (CALM1). | Inferred | |
| LIG_IQ_2 | AT2B1_HUMAN | 1114 | 1128 | Binary | Pre‑translational | Alternative splicing partially removes the IQ motif of Isoform CI of Plasma membrane calcium-transporting ATPase 1 (ATP2B1), partially inhibiting binding to Calmodulin (CALM1). | Inferred | |
| LIG_SH2_SRC | EGFR_HUMAN | 1016 | 1019 | Binary | Physicochemical compatibility | Phosphorylation of Y1016 in the SH2-binding motif of Epidermal growth factor receptor (EGFR) induces binding to 1-phosphatidylinositol-4,5-bisphosphate phosphodiesterase gamma-1 (PLCG1). | Curated | |
Calcium signaling pathway (KEGG - rno04020) | ||||||||
| LIG_IQ | CAC1D_RAT | 1650 | 1669 | Binary | Pre‑translational | Alternative splicing removes the IQ motif of Voltage-dependent L-type calcium channel subunit alpha-1D (Cacna1d) abrogating binding to Calmodulin (Calm1). CaV1.3IQdelta (IQ-deleted Isoform CACN4B of Voltage-dependent L-type calcium channel subunit alpha-1D (Cacna1d)) channels exhibit a lack of calcium-dependent inactivation. CaV1.3IQdelta channel immunoreactivity was preferentially localised to cochlear outer hair cells (OHCs), whereas that of CaV1.3IQfull channels (IQ-possessing Isoform CACN4A of Voltage-dependent L-type calcium channel subunit alpha-1D (Cacna1d)) labelled inner hair cells (IHCs). | Inferred | |
Cell cycle (KEGG - hsa04110) | ||||||||
| LIG_PLK | MPIP3_HUMAN | 129 | 131 | Binary | Physicochemical compatibility | Phosphorylation of T130 in the PLK-docking motif of M-phase inducer phosphatase 3 (CDC25C) by Cyclin-dependent kinase 1 (CDK1)-Cyclin AB subfamily generates a recruitment site for Serine/threonine-protein kinase PLK1 (PLK1), which then phosphorylates M-phase inducer phosphatase 3 (CDC25C). This results in inactivation of the NES of M-phase inducer phosphatase 3 (CDC25C), thereby promoting its nuclear localization. | Curated | |
| LIG_PLK | MPIP2_HUMAN | 49 | 51 | Binary | Physicochemical compatibility | Phosphorylation of S50 in the PLK-docking motif of M-phase inducer phosphatase 2 (CDC25B) by Cyclin-dependent kinase 1 (CDK1)-Cyclin AB subfamily generates a recruitment site for Serine/threonine-protein kinase PLK1 (PLK1), which then phosphorylates and activates M-phase inducer phosphatase 2 (CDC25B). | Curated | |
| LIG_14-3-3_3 | MPIP3_HUMAN | 213 | 218 | Binary | Physicochemical compatibility | Phosphorylation of S216 in a 14-3-3-binding motif of M-phase inducer phosphatase 3 (CDC25C) by Serine/threonine-protein kinase Chk1 (CHEK1) induces binding to 14-3-3 protein beta/alpha (YWHAB), which negatively regulates M-phase inducer phosphatase 3 (CDC25C). | Curated | |
| MOD_GSK3_1 | P53_HUMAN | 30 | 37 | Binary | Physicochemical compatibility | Phosphorylation of Cellular tumor antigen p53 (TP53) at S37 primes the protein for phosphorylation at S33 by Glycogen synthase kinase-3 beta (GSK3B). | Inferred | |
| MOD_GSK3_1 | CCNE1_HUMAN | 392 | 399 | Binary | Physicochemical compatibility | Phosphorylation of G1/S-specific cyclin-E1 (CCNE1) at S399 by Cyclin-dependent kinase 2 (CDK2) primes the protein for subsequent phosphorylation at T395 by Glycogen synthase kinase-3 beta (GSK3B). | Inferred | |
| TRG_NES_CRM1_1 | MPIP3_HUMAN | 189 | 203 | Binary | Physicochemical compatibility | Phosphorylation of S198 in the NES of M-phase inducer phosphatase 3 (CDC25C) by Serine/threonine-protein kinase PLK1 (PLK1) inhibits binding to Exportin-1 (XPO1), thus promoting nuclear localization of M-phase inducer phosphatase 3 (CDC25C). | Curated | |
| LIG_14-3-3_3 | MPIP2_HUMAN | 320 | 325 | Binary | Physicochemical compatibility | Phosphorylation of S321 in the 14-3-3-binding motif of M-phase inducer phosphatase 2 (CDC25B) by Cyclin-dependent kinase 1 (CDK1) during mitosis abolishes binding of the motif, phosphorylated at S323, to 14-3-3 protein beta/alpha (YWHAB), thereby maintaining active Cdc25B. | Curated | |
| LIG_MAD2 | CDC20_HUMAN | 129 | 137 | Binary | Allostery | Binding of Mad1-bound Closed (C-) Mitotic spindle assembly checkpoint protein MAD2A (MAD2L1) to Open (O-) Mitotic spindle assembly checkpoint protein MAD2A (MAD2L1) switches conformation of the latter to the C conformation, making the binding site for Cell division cycle protein 20 homolog (CDC20) available. This sequesters Cell division cycle protein 20 homolog (CDC20) to the spindle assembly checkpoint and prevents onset of anaphase. | Curated | |
| MOD_GSK3_1 | CCNE1_HUMAN | 377 | 384 | Specificity | Altered binding specificity | Phosphorylation of Isoform E-S of G1/S-specific cyclin-E1 (CCNE1) at S384 by CDK2 primes CCNE1 for phosphorylation by Glycogen synthase kinase-3 beta (GSK3B) at T380, which creates a recognition site for F box proteins of the SCF ubiquitin ligase complex (F-box/WD repeat-containing protein 7 (FBXW7)) that target CCNE1 for degradation. | Inferred | |
| DEG_SCF_FBW7_1 | CCNE1_HUMAN | 378 | 384 | Specificity | Altered binding specificity | Phosphorylation of Isoform E-S of G1/S-specific cyclin-E1 (CCNE1) at S384 by CDK2 primes CCNE1 for phosphorylation by Glycogen synthase kinase-3 beta (GSK3B) at T380, which creates a recognition site for F box proteins of the SCF ubiquitin ligase complex (F-box/WD repeat-containing protein 7 (FBXW7)) that target CCNE1 for degradation. | Inferred | |
| DOC_WW_Pin1_4 | SMAD3_HUMAN | 176 | 181 | Specificity | Altered binding specificity | CDK8/9 phosphorylates Mothers against decapentaplegic homolog 3 (SMAD3) at T179 and S208. Phosphorylation of T179 creates a binding site for the WW domain of Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1), while phosphorylation of S208 primes SMAD3 for phosphorylation of S204 by Glycogen synthase kinase-3 beta (GSK3B). The pS204-pS208 forms a binding site for the third WW domain of E3 ubiquitin-protein ligase NEDD4-like (NEDD4L), whose second WW domain will displace the WW domain of PIN1 at the pT179-PY box site of SMAD3. This regulation couples SMAD3 activation to SMAD3 destruction in an ordered fashion. See also switch details and switch details. | Inferred | |
| MOD_GSK3_1 | SMAD3_HUMAN | 201 | 208 | Specificity | Altered binding specificity | CDK8/9 phosphorylates Mothers against decapentaplegic homolog 3 (SMAD3) at T179 and S208. Phosphorylation of T179 creates a binding site for the WW domain of Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1), while phosphorylation of S208 primes SMAD3 for phosphorylation of S204 by Glycogen synthase kinase-3 beta (GSK3B). The pS204-pS208 forms a binding site for the third WW domain of E3 ubiquitin-protein ligase NEDD4-like (NEDD4L), whose second WW domain will displace the WW domain of PIN1 at the pT179-PY box site of SMAD3. This regulation couples SMAD3 activation to SMAD3 destruction in an ordered fashion. See also switch details and switch details. | Inferred | |
| LIG_WW_Nedd4L | SMAD3_HUMAN | 203 | 210 | Specificity | Altered binding specificity | CDK8/9 phosphorylates Mothers against decapentaplegic homolog 3 (SMAD3) at T179 and S208. Phosphorylation of T179 creates a binding site for the WW domain of Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1), while phosphorylation of S208 primes SMAD3 for phosphorylation of S204 by Glycogen synthase kinase-3 beta (GSK3B). The pS204-pS208 forms a binding site for the third WW domain of E3 ubiquitin-protein ligase NEDD4-like (NEDD4L), whose second WW domain will displace the WW domain of PIN1 at the pT179-PY box site of SMAD3. This regulation couples SMAD3 activation to SMAD3 destruction in an ordered fashion. See also switch details and switch details. | Inferred | |
| LIG_WW_1 | SMAD3_HUMAN | 181 | 184 | Specificity | Altered binding specificity | CDK8/9 phosphorylates Mothers against decapentaplegic homolog 3 (SMAD3) at T179 and S208. Phosphorylation of T179 creates a binding site for the WW domain of Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1), while phosphorylation of S208 primes SMAD3 for phosphorylation of S204 by Glycogen synthase kinase-3 beta (GSK3B). The pS204-pS208 forms a binding site for the third WW domain of E3 ubiquitin-protein ligase NEDD4-like (NEDD4L), whose second WW domain will displace the WW domain of PIN1 at the pT179-PY box site of SMAD3. This regulation couples SMAD3 activation to SMAD3 destruction in an ordered fashion. See also switch details and switch details. | Inferred | |
| MOD_CDK | MK67I_HUMAN | 235 | 241 | Specificity | Altered binding specificity | Phosphorylation of T238 of MKI67 FHA domain-interacting nucleolar phosphoprotein (MKI67IP) by Cyclin-dependent kinase 1 (CDK1) primes for phosphorylation of T234 by Glycogen synthase kinase-3 beta (GSK3B), which primes for phosphorylation of S230 by GSK3B. Triple-phosphorylated hNIFK (MKI67IP) binds strongly to Antigen KI-67 (MKI67). | Inferred | |
| MOD_GSK3_1 | MK67I_HUMAN | 231 | 238 | Specificity | Altered binding specificity | Phosphorylation of T238 of MKI67 FHA domain-interacting nucleolar phosphoprotein (MKI67IP) by Cyclin-dependent kinase 1 (CDK1) primes for phosphorylation of T234 by Glycogen synthase kinase-3 beta (GSK3B), which primes for phosphorylation of S230 by GSK3B. Triple-phosphorylated hNIFK (MKI67IP) binds strongly to Antigen KI-67 (MKI67). | Inferred | |
| MOD_GSK3_1 | MK67I_HUMAN | 227 | 234 | Specificity | Altered binding specificity | Phosphorylation of T238 of MKI67 FHA domain-interacting nucleolar phosphoprotein (MKI67IP) by Cyclin-dependent kinase 1 (CDK1) primes for phosphorylation of T234 by Glycogen synthase kinase-3 beta (GSK3B), which primes for phosphorylation of S230 by GSK3B. Triple-phosphorylated hNIFK (MKI67IP) binds strongly to Antigen KI-67 (MKI67). | Inferred | |
| LIG_FHA_2 | MK67I_HUMAN | 238 | 244 | Specificity | Altered binding specificity | Phosphorylation of T238 of MKI67 FHA domain-interacting nucleolar phosphoprotein (MKI67IP) by Cyclin-dependent kinase 1 (CDK1) primes for phosphorylation of T234 by Glycogen synthase kinase-3 beta (GSK3B), which primes for phosphorylation of S230 by GSK3B. Triple-phosphorylated hNIFK (MKI67IP) binds strongly to Antigen KI-67 (MKI67). | Inferred | |
| MOD_ProDKin_1 | MYC_HUMAN | 59 | 65 | Specificity | Altered binding specificity | Phosphorylation of Myc proto-oncogene protein (MYC) at S62 by Mitogen-activated protein kinase 1 (MAPK1) primes MYC for phosphorylation by Glycogen synthase kinase-3 beta (GSK3B), which targets MYC to the SCF ubiquitin ligase complex, F-box/WD repeat-containing protein 7 (FBXW7) that marks MYC for degradation. | Inferred | |
| MOD_GSK3_1 | MYC_HUMAN | 55 | 62 | Specificity | Altered binding specificity | Phosphorylation of Myc proto-oncogene protein (MYC) at S62 by Mitogen-activated protein kinase 1 (MAPK1) primes MYC for phosphorylation by Glycogen synthase kinase-3 beta (GSK3B), which targets MYC to the SCF ubiquitin ligase complex, F-box/WD repeat-containing protein 7 (FBXW7) that marks MYC for degradation. | Inferred | |
| DEG_SCF_FBW7_1 | MYC_HUMAN | 55 | 62 | Specificity | Altered binding specificity | Phosphorylation of Myc proto-oncogene protein (MYC) at S62 by Mitogen-activated protein kinase 1 (MAPK1) primes MYC for phosphorylation by Glycogen synthase kinase-3 beta (GSK3B), which targets MYC to the SCF ubiquitin ligase complex, F-box/WD repeat-containing protein 7 (FBXW7) that marks MYC for degradation. | Inferred | |
| MOD_GSK3_1 | CCNE1_HUMAN | 392 | 399 | Specificity | Altered binding specificity | Phosphorylation of G1/S-specific cyclin-E1 (CCNE1) at S399 generates a docking site for Glycogen synthase kinase-3 beta (GSK3B). Subsequent phosphorylation of CCNE1 by Glycogen synthase kinase-3 beta (GSK3B) at T395 switches the specificity of CCNE1 to the F-box/WD repeat-containing protein 7 (FBXW7), which recruits CCNE1 to the SCF ubiquitin ligase complex to mark CCNE1 for degradation. | Inferred | |
| DEG_SCF_FBW7_1 | CCNE1_HUMAN | 393 | 399 | Specificity | Altered binding specificity | Phosphorylation of G1/S-specific cyclin-E1 (CCNE1) at S399 generates a docking site for Glycogen synthase kinase-3 beta (GSK3B). Subsequent phosphorylation of CCNE1 by Glycogen synthase kinase-3 beta (GSK3B) at T395 switches the specificity of CCNE1 to the F-box/WD repeat-containing protein 7 (FBXW7), which recruits CCNE1 to the SCF ubiquitin ligase complex to mark CCNE1 for degradation. | Inferred | |
| MOD_CDK_1 | CDN1B_HUMAN | 184 | 190 | Pre‑assembly | Composite binding site formation | Binding of Cyclin-dependent kinase inhibitor 1B (CDKN1B) (p27) to the SCF-Skp2 ubiquitin ligase complex requires phosphorylation of p27 (CDKN1B) at T187, and association of the F-box protein S-phase kinase-associated protein 2 (SKP2) with the regulatory Cyclin-dependent kinases regulatory subunit 1 (CKS1B). SKP2 and CKS1B together generate a composite binding site for p27 (CDKN1B). While some residues, including the phosphorylated T187, bind to CKS1B and others to SKP2, the E185 makes contact with residues of both CKS1B and SKP2. | Curated | |
| DEG_SCF_SKP2-CKS1_1 | CDN1B_HUMAN | 183 | 190 | Pre‑assembly | Composite binding site formation | Binding of Cyclin-dependent kinase inhibitor 1B (CDKN1B) (p27) to the SCF-Skp2 ubiquitin ligase complex requires phosphorylation of p27 (CDKN1B) at T187, and association of the F-box protein S-phase kinase-associated protein 2 (SKP2) with the regulatory Cyclin-dependent kinases regulatory subunit 1 (CKS1B). SKP2 and CKS1B together generate a composite binding site for p27 (CDKN1B). While some residues, including the phosphorylated T187, bind to CKS1B and others to SKP2, the E185 makes contact with residues of both CKS1B and SKP2. | Curated | |
| MOD_CDK_1 | CDN1C_HUMAN | 307 | 313 | Pre‑assembly | Composite binding site formation | Binding of Cyclin-dependent kinase inhibitor 1C (CDKN1C) (p57) to the SCF-Skp2 ubiquitin ligase complex requires phosphorylation of p57 (CDKN1C) at T310, and association of the F-box protein S-phase kinase-associated protein 2 (SKP2) with the regulatory Cyclin-dependent kinases regulatory subunit 1 (CKS1B). SKP2 and CKS1B together generate a composite binding site for p57 (CDKN1C). | Curated | |
| DEG_SCF_SKP2-CKS1_1 | CDN1C_HUMAN | 306 | 313 | Pre‑assembly | Composite binding site formation | Binding of Cyclin-dependent kinase inhibitor 1C (CDKN1C) (p57) to the SCF-Skp2 ubiquitin ligase complex requires phosphorylation of p57 (CDKN1C) at T310, and association of the F-box protein S-phase kinase-associated protein 2 (SKP2) with the regulatory Cyclin-dependent kinases regulatory subunit 1 (CKS1B). SKP2 and CKS1B together generate a composite binding site for p57 (CDKN1C). | Curated | |
| DOC_CYCLIN_1 | CDN1B_HUMAN | 30 | 33 | Specificity | Domain hiding | Binding of the CDK-cyclin inhibitor p27 (Cyclin-dependent kinase inhibitor 1B (CDKN1B)) blocks the substrate recruitment site on Cyclin-A2 (CCNA2). | Curated | |
| DOC_CYCLIN_1 | CDC6_HUMAN | 94 | 98 | Specificity | Domain hiding | Binding of the CDK-cyclin inhibitor p27 (Cyclin-dependent kinase inhibitor 1B (CDKN1B)) blocks the substrate recruitment site on Cyclin-A2 (CCNA2). | Curated | |
| DOC_CYCLIN_1 | CDN1A_HUMAN | 19 | 22 | Specificity | Competition | Cyclin-dependent kinase inhibitor 1 (CDKN1A) (p21) and the M-phase inducer phosphatase 1 (CDC25A) bind the same site on Cyclin proteins (e.g. G1/S-specific cyclin-E1 (CCNE1)), making their interactions mutually exclusive. | Curated | |
| DOC_CYCLIN_1 | MPIP1_HUMAN | 11 | 15 | Specificity | Competition | Cyclin-dependent kinase inhibitor 1 (CDKN1A) (p21) and the M-phase inducer phosphatase 1 (CDC25A) bind the same site on Cyclin proteins (e.g. G1/S-specific cyclin-E1 (CCNE1)), making their interactions mutually exclusive. | Curated | |
| DOC_CYCLIN_1 | RB_HUMAN | 873 | 877 | Specificity | Competition | The docking sites for PP1 (e.g. Serine/threonine-protein phosphatase PP1-alpha catalytic subunit (PPP1CA)) and Cdk-Cyclins (e.g. Cyclin-A2 (CCNA2)) on Retinoblastoma-associated protein (RB1) overlap, which makes their binding to RB1 mutually exclusive. Hypophosphorylated RB1 blocks E2F-dependent transcription, while hyperphosphorylation inactivates RB1 as a repressor, thereby promoting cell cycle progression. | Inferred | |
| DOC_PP1 | RB_HUMAN | 872 | 878 | Specificity | Competition | The docking sites for PP1 (e.g. Serine/threonine-protein phosphatase PP1-alpha catalytic subunit (PPP1CA)) and Cdk-Cyclins (e.g. Cyclin-A2 (CCNA2)) on Retinoblastoma-associated protein (RB1) overlap, which makes their binding to RB1 mutually exclusive. Hypophosphorylated RB1 blocks E2F-dependent transcription, while hyperphosphorylation inactivates RB1 as a repressor, thereby promoting cell cycle progression. | Inferred | |
| DEG_MDM2_1 | P53_HUMAN | 19 | 26 | Binary | Physicochemical compatibility | Phosphorylation of Cellular tumor antigen p53 (TP53) on T18 (in vitro by Casein kinase I subfamily, requiring prior phosphorylation of S15) inhibits its binding to E3 ubiquitin-protein ligase Mdm2 (MDM2). In vivo, T18 is phosphorylated in response to DNA damage. | Curated | |
| LIG_TAZ2 | P53_HUMAN | 19 | 25 | Cumulative | Rheostatic | Multisite phosphorylation of S15 and T18 and S20 and S33 and S37 and S46 in the TAD region of Cellular tumor antigen p53 (TP53) additively enhances its affinity for CREB-binding protein (CREBBP). | Curated | |
| DEG_APCC_KENBOX_2 | MPIP2_HUMAN | 191 | 195 | Binary | Pre‑translational | Alternative splicing removes the APC/C KEN-box degron motif of M-phase inducer phosphatase 2 (CDC25B), abrogating binding to Fizzy-related protein homolog (FZR1). The motif-lacking Isoform CDC25B2 of M-phase inducer phosphatase 2 (CDC25B) is not degraded during mitosis, unlike other isoforms. | Curated | |
| DEG_MDM2_1 | P53_HUMAN | 19 | 26 | Binary | Pre‑translational | Alternative promoter usage and alternative splicing removes the E3 ubiquitin ligase MDM2-binding motif of Cellular tumor antigen p53 (TP53), abrogating binding to E3 ubiquitin-protein ligase Mdm2 (MDM2). The splice variant without this motif is resistant to MDM2-mediated degradation, leading to a longer half-life. | Curated | |
| DEG_APCC_KENBOX_2 | BUB1B_HUMAN | 303 | 307 | Specificity | Domain hiding | Binding of the second KEN-box motif of Mitotic checkpoint serine/threonine-protein kinase BUB1 beta (BUB1B), a subunit of the Spindle Assembly Checkpoint (SAC), to the substrate recruitment site of Cell division cycle protein 20 homolog (CDC20), the substrate recognition subunit of the Anaphase Promoting Complex/Cyclosome (APC/C), blocks binding of the Cdc20 substrate G2/mitotic-specific cyclin-B1 (CCNB1). As a result, G2/mitotic-specific cyclin-B1 (CCNB1) is not targeted for proteasomal degradation until metaphase, when the SAC is inhibited. Destruction of G2/mitotic-specific cyclin-B1 (CCNB1) is required for progression to the anaphase of the cell cycle. | Curated | |
| DEG_APCC_DBOX_1 | CCNB1_HUMAN | 41 | 49 | Specificity | Domain hiding | Binding of the second KEN-box motif of Mitotic checkpoint serine/threonine-protein kinase BUB1 beta (BUB1B), a subunit of the Spindle Assembly Checkpoint (SAC), to the substrate recruitment site of Cell division cycle protein 20 homolog (CDC20), the substrate recognition subunit of the Anaphase Promoting Complex/Cyclosome (APC/C), blocks binding of the Cdc20 substrate G2/mitotic-specific cyclin-B1 (CCNB1). As a result, G2/mitotic-specific cyclin-B1 (CCNB1) is not targeted for proteasomal degradation until metaphase, when the SAC is inhibited. Destruction of G2/mitotic-specific cyclin-B1 (CCNB1) is required for progression to the anaphase of the cell cycle. | Curated | |
| DEG_APCC_KENBOX_2 | BUB1B_HUMAN | 303 | 307 | Specificity | Domain hiding | Binding of the second KEN-box motif of Mitotic checkpoint serine/threonine-protein kinase BUB1 beta (BUB1B), a subunit of the Spindle Assembly Checkpoint (SAC), to the substrate recruitment site of Cell division cycle protein 20 homolog (CDC20), the substrate recognition subunit of the Anaphase Promoting Complex/Cyclosome (APC/C), blocks binding of the Cdc20 substrate Securin (PTTG1). As a result, Securin (PTTG1) is not targeted for proteasomal degradation until metaphase, when the SAC is inhibited. Destruction of Securin (PTTG1) is required for progression to the anaphase of the cell cycle. | Curated | |
| DEG_APCC_DBOX_1 | PTTG1_HUMAN | 60 | 68 | Specificity | Domain hiding | Binding of the second KEN-box motif of Mitotic checkpoint serine/threonine-protein kinase BUB1 beta (BUB1B), a subunit of the Spindle Assembly Checkpoint (SAC), to the substrate recruitment site of Cell division cycle protein 20 homolog (CDC20), the substrate recognition subunit of the Anaphase Promoting Complex/Cyclosome (APC/C), blocks binding of the Cdc20 substrate Securin (PTTG1). As a result, Securin (PTTG1) is not targeted for proteasomal degradation until metaphase, when the SAC is inhibited. Destruction of Securin (PTTG1) is required for progression to the anaphase of the cell cycle. | Curated | |
| TRG_NLS | CDN1B_HUMAN | 152 | 166 | Specificity | Motif hiding | Phosphorylation of a 14-3-3-binding motif in the NLS of Cyclin-dependent kinase inhibitor 1B (CDKN1B) by RAC-alpha serine/threonine-protein kinase (AKT1) induces binding of 14-3-3 protein gamma (YWHAG), which hides the NLS and prevents binding to Importin subunit alpha-1 (KPNA1), thereby mediating cytoplasmic retention of Cyclin-dependent kinase inhibitor 1B (CDKN1B). Binding of 14-3-3 dimer involves an additional C-terminal 14-3-3-binding motif (see switch details). | Curated | |
| LIG_14-3-3_3 | CDN1B_HUMAN | 154 | 159 | Specificity | Motif hiding | Phosphorylation of a 14-3-3-binding motif in the NLS of Cyclin-dependent kinase inhibitor 1B (CDKN1B) by RAC-alpha serine/threonine-protein kinase (AKT1) induces binding of 14-3-3 protein gamma (YWHAG), which hides the NLS and prevents binding to Importin subunit alpha-1 (KPNA1), thereby mediating cytoplasmic retention of Cyclin-dependent kinase inhibitor 1B (CDKN1B). Binding of 14-3-3 dimer involves an additional C-terminal 14-3-3-binding motif (see switch details). | Curated | |
| LIG_14-3-3_3 | CDN1B_HUMAN | 154 | 159 | Avidity‑sensing | Phosphorylation of two 14-3-3-binding motifs in Cyclin-dependent kinase inhibitor 1B (CDKN1B) by RAC-alpha serine/threonine-protein kinase (AKT1) and ribosomal protein S6 kinases (Ribosomal protein S6 kinase alpha-1 (RPS6KA1), Ribosomal protein S6 kinase alpha-3 (RPS6KA3)) induces binding of 14-3-3 dimer. Binding of 14-3-3 results in cytoplasmic localisation of Cyclin-dependent kinase inhibitor 1B (CDKN1B) (see switch details), thereby alleviating Cyclin-dependent kinase inhibitor 1B (CDKN1B)-mediated inhibition of cyclin-dependent kinases and cell cycle progression. | Curated | ||
| LIG_14-3-3_3 | CDN1B_HUMAN | 193 | 198 | Avidity‑sensing | Phosphorylation of two 14-3-3-binding motifs in Cyclin-dependent kinase inhibitor 1B (CDKN1B) by RAC-alpha serine/threonine-protein kinase (AKT1) and ribosomal protein S6 kinases (Ribosomal protein S6 kinase alpha-1 (RPS6KA1), Ribosomal protein S6 kinase alpha-3 (RPS6KA3)) induces binding of 14-3-3 dimer. Binding of 14-3-3 results in cytoplasmic localisation of Cyclin-dependent kinase inhibitor 1B (CDKN1B) (see switch details), thereby alleviating Cyclin-dependent kinase inhibitor 1B (CDKN1B)-mediated inhibition of cyclin-dependent kinases and cell cycle progression. | Curated | ||
| LIG_PCNA_PIPBox_1 | CDN1A_HUMAN | 144 | 153 | Binary | Physicochemical compatibility | Phosphorylation of T145 in the PCNA-binding motif of Cyclin-dependent kinase inhibitor 1 (CDKN1A) by RAC-alpha serine/threonine-protein kinase (AKT1) inhibits binding to Proliferating cell nuclear antigen (PCNA). As a result, Cyclin-dependent kinase inhibitor 1 (CDKN1A) no longer inhibits Proliferating cell nuclear antigen (PCNA) and blocking of DNA replication is relieved. | Curated | |
| LIG_PCNA_PIPBox_1 | CDN1A_HUMAN | 144 | 153 | Binary | Physicochemical compatibility | Phosphorylation of S146 in the PCNA-binding motif of Cyclin-dependent kinase inhibitor 1 (CDKN1A) by PKC subfamily inhibits binding to Proliferating cell nuclear antigen (PCNA). As a result, Cyclin-dependent kinase inhibitor 1 (CDKN1A) no longer inhibits Proliferating cell nuclear antigen (PCNA) and blocking of DNA replication is relieved. | Curated | |
Cell cycle (KEGG - mmu04110) | ||||||||
| MOD_CDK_1 | CDN1C_MOUSE | 339 | 345 | Pre‑assembly | Composite binding site formation | Binding of Cyclin-dependent kinase inhibitor 1C (Cdkn1c) (p57) to the SCF-Skp2 ubiquitin ligase complex requires phosphorylation of p57 (Cdkn1c) at T342, and association of the F-box protein S-phase kinase-associated protein 2 (SKP2) with the regulatory Cyclin-dependent kinases regulatory subunit 1 (CKS1B). SKP2 and CKS1B together generate a composite binding site for p57 (Cdkn1c). | Curated | |
| DEG_SCF_SKP2-CKS1_1 | CDN1C_MOUSE | 338 | 345 | Pre‑assembly | Composite binding site formation | Binding of Cyclin-dependent kinase inhibitor 1C (Cdkn1c) (p57) to the SCF-Skp2 ubiquitin ligase complex requires phosphorylation of p57 (Cdkn1c) at T342, and association of the F-box protein S-phase kinase-associated protein 2 (SKP2) with the regulatory Cyclin-dependent kinases regulatory subunit 1 (CKS1B). SKP2 and CKS1B together generate a composite binding site for p57 (Cdkn1c). | Curated | |
Cell cycle (KEGG - sce04111) | ||||||||
| LIG_FHA_1 | RAD9_YEAST | 601 | 607 | Binary | Physicochemical compatibility | Phosphorylation of T603 in the FHA-binding motif of DNA repair protein RAD9 (RAD9) induces binding to the Serine/threonine-protein kinase RAD53 (RAD53) protein. | Curated | |
| LIG_FHA_2 | RAD9_YEAST | 153 | 159 | Binary | Physicochemical compatibility | Phosphorylation of T155 in the FHA-binding motif of DNA repair protein RAD9 (RAD9) induces binding to the Serine/threonine-protein kinase RAD53 (RAD53) protein. | Curated | |
| LIG_FHA_2 | RAD9_YEAST | 190 | 196 | Binary | Physicochemical compatibility | Phosphorylation of T192 in the FHA-binding motif of DNA repair protein RAD9 (RAD9) induces binding to the Serine/threonine-protein kinase RAD53 (RAD53) protein. | Curated | |
| DEG_APCC_KENBOX_2 | ACM1_YEAST | 97 | 101 | Specificity | Domain hiding | The KEN-box motif of APC/C-CDH1 modulator 1 (ACM1) binds to the substrate recruitment site of APC/C activator protein CDH1 (CDH1), the substrate recognition subunit of the Anaphase Promoting Complex/Cyclosome (APC/C), and thereby blocks recruitment, and subsequent targeting for proteasomal degradation, of the Cdh1 substrate G2/mitotic-specific cyclin-2 (CLB2). Degradation of G2/mitotic-specific cyclin-2 (CLB2) is required for mitotic exit and maintenance of the G1 phase of the cell cycle and is allowed by Cdc20-dependent degradation of APC/C-CDH1 modulator 1 (ACM1) in anaphase. | Curated | |
| DEG_APCC_KENBOX_2 | CG22_YEAST | 99 | 103 | Specificity | Domain hiding | The KEN-box motif of APC/C-CDH1 modulator 1 (ACM1) binds to the substrate recruitment site of APC/C activator protein CDH1 (CDH1), the substrate recognition subunit of the Anaphase Promoting Complex/Cyclosome (APC/C), and thereby blocks recruitment, and subsequent targeting for proteasomal degradation, of the Cdh1 substrate G2/mitotic-specific cyclin-2 (CLB2). Degradation of G2/mitotic-specific cyclin-2 (CLB2) is required for mitotic exit and maintenance of the G1 phase of the cell cycle and is allowed by Cdc20-dependent degradation of APC/C-CDH1 modulator 1 (ACM1) in anaphase. | Curated | |
| DEG_APCC_KENBOX_2 | ACM1_YEAST | 97 | 101 | Specificity | Domain hiding | The KEN-box motif of APC/C-CDH1 modulator 1 (ACM1) binds to the substrate recruitment site of APC/C activator protein CDH1 (CDH1), the substrate recognition subunit of the Anaphase Promoting Complex/Cyclosome (APC/C), and thereby blocks recruitment, and subsequent targeting for proteasomal degradation, of the Cdh1 substrate Kinesin-like protein CIN8 (CIN8). Degradation of Kinesin-like protein CIN8 (CIN8) is required for mitotic exit and maintenance of the G1 phase of the cell cycle and is allowed by Cdc20-dependent degradation of APC/C-CDH1 modulator 1 (ACM1) in anaphase. | Curated | |
| DEG_APCC_KENBOX_2 | CIN8_YEAST | 931 | 935 | Specificity | Domain hiding | The KEN-box motif of APC/C-CDH1 modulator 1 (ACM1) binds to the substrate recruitment site of APC/C activator protein CDH1 (CDH1), the substrate recognition subunit of the Anaphase Promoting Complex/Cyclosome (APC/C), and thereby blocks recruitment, and subsequent targeting for proteasomal degradation, of the Cdh1 substrate Kinesin-like protein CIN8 (CIN8). Degradation of Kinesin-like protein CIN8 (CIN8) is required for mitotic exit and maintenance of the G1 phase of the cell cycle and is allowed by Cdc20-dependent degradation of APC/C-CDH1 modulator 1 (ACM1) in anaphase. | Curated | |
| DEG_APCC_KENBOX_2 | ACM1_YEAST | 97 | 101 | Specificity | Domain hiding | The KEN-box motif of APC/C-CDH1 modulator 1 (ACM1) binds to the substrate recruitment site of APC/C activator protein CDH1 (CDH1), the substrate recognition subunit of the Anaphase Promoting Complex/Cyclosome (APC/C), and thereby blocks recruitment, and subsequent targeting for proteasomal degradation, of the Cdh1 substrate Probable serine/threonine-protein kinase HSL1 (HSL1). Degradation of Probable serine/threonine-protein kinase HSL1 (HSL1) is required for mitotic exit and maintenance of the G1 phase of the cell cycle and is allowed by Cdc20-dependent degradation of APC/C-CDH1 modulator 1 (ACM1) in anaphase. | Curated | |
| DEG_APCC_KENBOX_2 | HSL1_YEAST | 774 | 778 | Specificity | Domain hiding | The KEN-box motif of APC/C-CDH1 modulator 1 (ACM1) binds to the substrate recruitment site of APC/C activator protein CDH1 (CDH1), the substrate recognition subunit of the Anaphase Promoting Complex/Cyclosome (APC/C), and thereby blocks recruitment, and subsequent targeting for proteasomal degradation, of the Cdh1 substrate Probable serine/threonine-protein kinase HSL1 (HSL1). Degradation of Probable serine/threonine-protein kinase HSL1 (HSL1) is required for mitotic exit and maintenance of the G1 phase of the cell cycle and is allowed by Cdc20-dependent degradation of APC/C-CDH1 modulator 1 (ACM1) in anaphase. | Curated | |
Cell cycle (KEGG - spo04111) | ||||||||
| LIG_FHA_2 | MRC1_SCHPO | 643 | 649 | Binary | Physicochemical compatibility | Phosphorylation of T645 in the FHA-binding motif of Mediator of replication checkpoint protein 1 (mrc1) induces binding to the Serine/threonine-protein kinase cds1 (cds1) protein. | Inferred | |
Centrosome maturation (Reactome - 380287) | ||||||||
| MOD_CDK_1 | ODFP2_HUMAN | 793 | 799 | Binary | Pre‑translational | Alternative splicing removes the cyclin-dependent kinase (CDK) phosphorylation motif of Isoform Cenexin 1 of Outer dense fiber protein 2 (ODF2), abrogating binding to Cyclin-dependent kinase 1 (CDK1). This phosphorylation is required for the recruitment of Serine/threonine-protein kinase PLK1 (PLK1). The C-terminal extension of Isoform Cenexin 1 of Outer dense fiber protein 2 (ODF2) has the ability to distinctly localise to mother centriole whereas the splice variant (e.g. Isoform Cenexin 1 of Outer dense fiber protein 2 (ODF2)), which does not have this extension, permits ODF2 to associate with sperm tail. | Curated | |
Chemokine signaling pathway (KEGG - hsa04062) | ||||||||
| MOD_ProDKin_1 | MYC_HUMAN | 59 | 65 | Specificity | Altered binding specificity | Phosphorylation of Myc proto-oncogene protein (MYC) at S62 by Mitogen-activated protein kinase 1 (MAPK1) primes MYC for phosphorylation by Glycogen synthase kinase-3 beta (GSK3B), which targets MYC to the SCF ubiquitin ligase complex, F-box/WD repeat-containing protein 7 (FBXW7) that marks MYC for degradation. | Inferred | |
| MOD_GSK3_1 | MYC_HUMAN | 55 | 62 | Specificity | Altered binding specificity | Phosphorylation of Myc proto-oncogene protein (MYC) at S62 by Mitogen-activated protein kinase 1 (MAPK1) primes MYC for phosphorylation by Glycogen synthase kinase-3 beta (GSK3B), which targets MYC to the SCF ubiquitin ligase complex, F-box/WD repeat-containing protein 7 (FBXW7) that marks MYC for degradation. | Inferred | |
| DEG_SCF_FBW7_1 | MYC_HUMAN | 55 | 62 | Specificity | Altered binding specificity | Phosphorylation of Myc proto-oncogene protein (MYC) at S62 by Mitogen-activated protein kinase 1 (MAPK1) primes MYC for phosphorylation by Glycogen synthase kinase-3 beta (GSK3B), which targets MYC to the SCF ubiquitin ligase complex, F-box/WD repeat-containing protein 7 (FBXW7) that marks MYC for degradation. | Inferred | |
| LIG_SH2_IC | SHC1_HUMAN | 423 | 435 | Binary | Physicochemical compatibility | Phosphorylation of Y427 in the SH2-binding motif of SHC-transforming protein 1 (SHC1) induces binding to the Growth factor receptor-bound protein 2 (GRB2) protein. | Inferred | |
| LIG_SH2_IB | BCAR1_HUMAN | 358 | 368 | Binary | Physicochemical compatibility | Phosphorylation of Y362 in the SH2-binding motif of Breast cancer anti-estrogen resistance protein 1 (BCAR1) induces binding to the Adapter molecule crk (CRK) protein. | Inferred | |
| LIG_FAT_LD_1 | PAXI_HUMAN | 4 | 12 | Binary | Pre‑translational | Alternative splicing removes the FAK-binding LD motif of Paxillin (PXN), abrogating binding to Focal adhesion kinase 1 (PTK2). | Inferred | |
| LIG_SH2_IB | PAXI_HUMAN | 118 | 121 | Binary | Pre‑translational | Alternative splicing removes the SH2-binding motif of Paxillin (PXN), abrogating binding to Adapter molecule crk (CRK). | Inferred | |
| LIG_SH2_IB | PAXI_HUMAN | 31 | 34 | Binary | Pre‑translational | Alternative splicing removes the SH2-binding motif of Paxillin (PXN), abrogating binding to Adapter molecule crk (CRK). | Inferred | |
| LIG_PDZ_Class_1 | PLCB1_HUMAN | 1211 | 1216 | Binary | Pre‑translational | Alternative splicing removes the PDZ-binding motif of 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 (PLCB1), abrogating binding to Partitioning defective 3 homolog (PARD3). The G protein-activated PLCB1 can directly interact with cell polarity proteins Partitioning defective 3 homolog (PARD3) and Partitioning defective 6 homolog alpha (PARD6A) to form protein complexes in the cell, which potentially modulate G protein-activated PLCB1 activity in cell polarity formation and asymmetric cell division. | Inferred | |
Circadian entrainment (KEGG - rno04713) | ||||||||
| LIG_IQ | CAC1D_RAT | 1650 | 1669 | Binary | Pre‑translational | Alternative splicing removes the IQ motif of Voltage-dependent L-type calcium channel subunit alpha-1D (Cacna1d) abrogating binding to Calmodulin (Calm1). CaV1.3IQdelta (IQ-deleted Isoform CACN4B of Voltage-dependent L-type calcium channel subunit alpha-1D (Cacna1d)) channels exhibit a lack of calcium-dependent inactivation. CaV1.3IQdelta channel immunoreactivity was preferentially localised to cochlear outer hair cells (OHCs), whereas that of CaV1.3IQfull channels (IQ-possessing Isoform CACN4A of Voltage-dependent L-type calcium channel subunit alpha-1D (Cacna1d)) labelled inner hair cells (IHCs). | Inferred | |
Circadian rhythm (KEGG - hsa04710) | ||||||||
| MOD_LATS_1 | YAP1_HUMAN | 376 | 382 | Specificity | Altered binding specificity | Phosphorylation of Yorkie homolog (YAP1) at S381 by Serine/threonine-protein kinase LATS1 (LATS1) (a key regulator of the Hippo Pathway) primes the sequence for phosphorylation by Casein kinase I isoform epsilon (CSNK1E) at S384 and S387. This targets YAP1 to the SCF ubiqutin ligase complex, F-box/WD repeat-containing protein 1A (BTRC), which marks is YAP1 for subsequent degradation by the proteasomal system. N.B. Serine/threonine-protein kinase LATS2 (LATS2) can replace LATS1 and Casein kinase I isoform delta (CSNK1D) can replace CSNK1E | Inferred | |
| MOD_CK1_1 | YAP1_HUMAN | 381 | 387 | Specificity | Altered binding specificity | Phosphorylation of Yorkie homolog (YAP1) at S381 by Serine/threonine-protein kinase LATS1 (LATS1) (a key regulator of the Hippo Pathway) primes the sequence for phosphorylation by Casein kinase I isoform epsilon (CSNK1E) at S384 and S387. This targets YAP1 to the SCF ubiqutin ligase complex, F-box/WD repeat-containing protein 1A (BTRC), which marks is YAP1 for subsequent degradation by the proteasomal system. N.B. Serine/threonine-protein kinase LATS2 (LATS2) can replace LATS1 and Casein kinase I isoform delta (CSNK1D) can replace CSNK1E | Inferred | |
| MOD_CK1_1 | YAP1_HUMAN | 384 | 390 | Specificity | Altered binding specificity | Phosphorylation of Yorkie homolog (YAP1) at S381 by Serine/threonine-protein kinase LATS1 (LATS1) (a key regulator of the Hippo Pathway) primes the sequence for phosphorylation by Casein kinase I isoform epsilon (CSNK1E) at S384 and S387. This targets YAP1 to the SCF ubiqutin ligase complex, F-box/WD repeat-containing protein 1A (BTRC), which marks is YAP1 for subsequent degradation by the proteasomal system. N.B. Serine/threonine-protein kinase LATS2 (LATS2) can replace LATS1 and Casein kinase I isoform delta (CSNK1D) can replace CSNK1E | Inferred | |
| DEG_SCF_TRCP1_2 | YAP1_HUMAN | 383 | 387 | Specificity | Altered binding specificity | Phosphorylation of Yorkie homolog (YAP1) at S381 by Serine/threonine-protein kinase LATS1 (LATS1) (a key regulator of the Hippo Pathway) primes the sequence for phosphorylation by Casein kinase I isoform epsilon (CSNK1E) at S384 and S387. This targets YAP1 to the SCF ubiqutin ligase complex, F-box/WD repeat-containing protein 1A (BTRC), which marks is YAP1 for subsequent degradation by the proteasomal system. N.B. Serine/threonine-protein kinase LATS2 (LATS2) can replace LATS1 and Casein kinase I isoform delta (CSNK1D) can replace CSNK1E | Inferred | |
DAP12 interactions (Reactome - 2172127) | ||||||||
| LIG_SH2_STAT5 | LAT_HUMAN | 161 | 164 | Binary | Physicochemical compatibility | Phosphorylation of Y161 in the SH2-binding motif of Linker for activation of T-cells family member 1 (LAT) induces binding to the 1-phosphatidylinositol-4,5-bisphosphate phosphodiesterase gamma-1 (PLCG1) protein. | Curated | |
DNA replication (KEGG - ko03030) | ||||||||
| LIG_PCNA_PIPBox_1 | DPOD3_HUMAN | 456 | 465 | Binary | Physicochemical compatibility | Phosphorylation of S458 in the PCNA-binding motif of DNA polymerase delta subunit 3 (POLD3) by cAMP subfamily reduces the affinity of binding to the Proliferating cell nuclear antigen (PCNA) and decreases the processivity of the polymerase complex. | Curated | |
Dopaminergic synapse (KEGG - rno04728) | ||||||||
| LIG_IQ | CAC1D_RAT | 1650 | 1669 | Binary | Pre‑translational | Alternative splicing removes the IQ motif of Voltage-dependent L-type calcium channel subunit alpha-1D (Cacna1d) abrogating binding to Calmodulin (Calm1). CaV1.3IQdelta (IQ-deleted Isoform CACN4B of Voltage-dependent L-type calcium channel subunit alpha-1D (Cacna1d)) channels exhibit a lack of calcium-dependent inactivation. CaV1.3IQdelta channel immunoreactivity was preferentially localised to cochlear outer hair cells (OHCs), whereas that of CaV1.3IQfull channels (IQ-possessing Isoform CACN4A of Voltage-dependent L-type calcium channel subunit alpha-1D (Cacna1d)) labelled inner hair cells (IHCs). | Inferred | |
ECM-receptor interaction (KEGG - hsa04512) | ||||||||
| LIG_RGD | EDIL3_HUMAN | 96 | 98 | Pre‑assembly | Composite binding site formation | Binding of EGF-like repeat and discoidin I-like domain-containing protein 3 (EDIL3) to integrin receptors depends on pre-assembly of Integrin alpha-V (ITGAV)-Integrin beta-3 (ITGB3) heterodimers, since association of the integrin alpha and beta subunits results in the formation of a composite binding site for the RGD motif in the ligand. | Inferred | |
| LIG_RGD | DISG_TRIAB | 51 | 53 | Pre‑assembly | Composite binding site formation | Binding of Disintegrin albolabrin to integrin receptors depends on pre-assembly of Integrin alpha-IIb (ITGA2B)-Integrin beta-3 (ITGB3) heterodimers, since association of the integrin alpha and beta subunits results in the formation of a composite binding site for the RGD motif in the ligand. | Inferred | |
| LIG_RGD | FINC_HUMAN | 1524 | 1526 | Pre‑assembly | Composite binding site formation | Binding of Fibronectin (FN1) to integrin receptors depends on pre-assembly of Integrin alpha-V (ITGAV)-Integrin beta-3 (ITGB3) heterodimers, since association of the integrin alpha and beta subunits results in the formation of a composite binding site for the RGD motif in the ligand. | Inferred | |
| LIG_RGD | POLG_FMDVO | 869 | 871 | Pre‑assembly | Composite binding site formation | Binding of Genome polyprotein to integrin receptors depends on pre-assembly of Integrin alpha-V (ITGAV)-Integrin beta-3 (ITGB3) heterodimers, since association of the integrin alpha and beta subunits results in the formation of a composite binding site for the RGD motif in the ligand. | Inferred | |
| LIG_RGD | VTNC_HUMAN | 64 | 66 | Pre‑assembly | Composite binding site formation | Binding of Vitronectin (VTN) to integrin receptors depends on pre-assembly of Integrin alpha-V (ITGAV)-Integrin beta-3 (ITGB3) heterodimers, since association of the integrin alpha and beta subunits results in the formation of a composite binding site for the RGD motif in the ligand. | Inferred | |
| LIG_RGD | VWF_HUMAN | 2507 | 2509 | Pre‑assembly | Composite binding site formation | Binding of von Willebrand factor (VWF) to integrin receptors depends on pre-assembly of Integrin alpha-V (ITGAV)-Integrin beta-3 (ITGB3) heterodimers, since association of the integrin alpha and beta subunits results in the formation of a composite binding site for the RGD motif in the ligand. | Inferred | |
| LIG_RGD | OSTP_HUMAN | 159 | 161 | Pre‑assembly | Composite binding site formation | Binding of EGF-like repeat and discoidin I-like domain-containing protein 3 (EDIL3) to integrin receptors depends on pre-assembly of Integrin alpha-V (ITGAV)-Integrin beta-3 (ITGB3) heterodimers, since association of the integrin alpha and beta subunits results in the formation of a composite binding site for the RGD motif in the ligand. | Inferred | |
| LIG_RGD | VME1_TRIEL | 459 | 461 | Pre‑assembly | Composite binding site formation | Binding of Zinc metalloproteinase/disintegrin to integrin receptors depends on pre-assembly of Integrin alpha-IIb (ITGA2B)-Integrin beta-3 (ITGB3) heterodimers, since association of the integrin alpha and beta subunits results in the formation of a composite binding site for the RGD motif in the ligand. | Inferred | |
| LIG_RGD | DISB_TRIGA | 51 | 53 | Pre‑assembly | Composite binding site formation | Binding of Disintegrin trigramin-beta-2 to integrin receptors depends on pre-assembly of Integrin alpha-IIb (ITGA2B)-Integrin beta-3 (ITGB3) heterodimers, since association of the integrin alpha and beta subunits results in the formation of a composite binding site for the RGD motif in the ligand. | Inferred | |
| LIG_RGD | POLG_CXA9 | 858 | 860 | Pre‑assembly | Composite binding site formation | Binding of Genome polyprotein to integrin receptors depends on pre-assembly of Integrin alpha-V (ITGAV)-Integrin beta-6 (ITGB6) heterodimers, since association of the integrin alpha and beta subunits results in the formation of a composite binding site for the RGD motif in the ligand. | Inferred | |
| LIG_RGD | POLG_HPE1H | 764 | 766 | Pre‑assembly | Composite binding site formation | Binding of Genome polyprotein to integrin receptors depends on pre-assembly of Integrin alpha-V (ITGAV)-Integrin beta-6 (ITGB6) heterodimers, since association of the integrin alpha and beta subunits results in the formation of a composite binding site for the RGD motif in the ligand. | Inferred | |
| LIG_Integrin_isoDGR_1 | FINC_HUMAN | 263 | 265 | Pre‑assembly | Composite binding site formation | Binding of Fibronectin (FN1) to integrin receptors depends on pre-assembly of Integrin alpha-V (ITGAV)-Integrin beta-3 (ITGB3) heterodimers, since association of the integrin alpha and beta subunits results in the formation of a composite binding site for the RGD motif in the ligand. | Inferred | |
ECM-receptor interaction (KEGG - mmu04512) | ||||||||
| LIG_RGD | FINC_MOUSE | 1614 | 1616 | Pre‑assembly | Composite binding site formation | Binding of Fibronectin (Fn1) to integrin receptors depends on pre-assembly of Integrin alpha-5 (Itga5)-Integrin beta-1 (Itgb1) heterodimers, since association of the integrin alpha and beta subunits results in the formation of a composite binding site for the RGD motif in the ligand. | Inferred | |
| LIG_RGD | VTNC_MOUSE | 64 | 66 | Pre‑assembly | Composite binding site formation | Binding of Vitronectin (Vtn) to integrin receptors depends on pre-assembly of Integrin alpha-V (Itgav)-Integrin beta-3 (Itgb3) heterodimers, since association of the integrin alpha and beta subunits results in the formation of a composite binding site for the RGD motif in the ligand. | Inferred | |
Endocytosis (KEGG - hsa04144) | ||||||||
| LIG_TKB | EGFR_HUMAN | 1069 | 1074 | Binary | Physicochemical compatibility | Phosphorylation of Y1069 in Epidermal growth factor receptor (EGFR) is necessary for binding to the TKB domain of E3 ubiquitin-protein ligase CBL (CBL). | Inferred | |
| TRG_AP2beta_CARGO_1 | ARRB1_HUMAN | 385 | 395 | Binary | Allostery | Binding of Beta-arrestin-1 (ARRB1) to ligand-induced, phosphorylated GPCRs results in a conformational change that makes the AP2-beta interaction motif in Beta-arrestin-1 (ARRB1) accessible for binding to AP-2 complex subunit beta (AP2B1), which mediates internalization of the GPCR. | Inferred | |
| TRG_ENDOCYTIC_2 | EGFR_HUMAN | 998 | 1001 | Binary | Allostery | Binding of 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate to the AP-2 complex alpha, beta and mu subunits exposes a binding site on the AP-2 complex subunit mu (AP2M1) subunit for recruitment of Epidermal growth factor receptor (EGFR) via an endocytosis motif. | Inferred | |
| TRG_ENDOCYTIC_2 | TFR1_HUMAN | 20 | 23 | Binary | Allostery | Binding of 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate to the AP-2 complex alpha, beta and mu subunits exposes a binding site on the AP-2 complex subunit mu (AP2M1) subunit for recruitment of Transferrin receptor protein 1 (TFRC) via an endocytosis motif. | Inferred | |
| LIG_TKB | EGFR_HUMAN | 1069 | 1074 | Cumulative | Rheostatic | While phosphorylation of Y1069 induces binding, additional phosphorylation of S1070 and S1071 in the TKB-binding motif of Epidermal growth factor receptor (EGFR) gradually lowers its binding affinity for E3 ubiquitin-protein ligase CBL (CBL). | Inferred | |
| DOC_WW_Pin1_4 | SMAD3_HUMAN | 176 | 181 | Specificity | Altered binding specificity | CDK8/9 phosphorylates Mothers against decapentaplegic homolog 3 (SMAD3) at T179 and S208. Phosphorylation of T179 creates a binding site for the WW domain of Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1), while phosphorylation of S208 primes SMAD3 for phosphorylation of S204 by Glycogen synthase kinase-3 beta (GSK3B). The pS204-pS208 forms a binding site for the third WW domain of E3 ubiquitin-protein ligase NEDD4-like (NEDD4L), whose second WW domain will displace the WW domain of PIN1 at the pT179-PY box site of SMAD3. This regulation couples SMAD3 activation to SMAD3 destruction in an ordered fashion. See also switch details and switch details. | Inferred | |
| MOD_GSK3_1 | SMAD3_HUMAN | 201 | 208 | Specificity | Altered binding specificity | CDK8/9 phosphorylates Mothers against decapentaplegic homolog 3 (SMAD3) at T179 and S208. Phosphorylation of T179 creates a binding site for the WW domain of Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1), while phosphorylation of S208 primes SMAD3 for phosphorylation of S204 by Glycogen synthase kinase-3 beta (GSK3B). The pS204-pS208 forms a binding site for the third WW domain of E3 ubiquitin-protein ligase NEDD4-like (NEDD4L), whose second WW domain will displace the WW domain of PIN1 at the pT179-PY box site of SMAD3. This regulation couples SMAD3 activation to SMAD3 destruction in an ordered fashion. See also switch details and switch details. | Inferred | |
| LIG_WW_Nedd4L | SMAD3_HUMAN | 203 | 210 | Specificity | Altered binding specificity | CDK8/9 phosphorylates Mothers against decapentaplegic homolog 3 (SMAD3) at T179 and S208. Phosphorylation of T179 creates a binding site for the WW domain of Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1), while phosphorylation of S208 primes SMAD3 for phosphorylation of S204 by Glycogen synthase kinase-3 beta (GSK3B). The pS204-pS208 forms a binding site for the third WW domain of E3 ubiquitin-protein ligase NEDD4-like (NEDD4L), whose second WW domain will displace the WW domain of PIN1 at the pT179-PY box site of SMAD3. This regulation couples SMAD3 activation to SMAD3 destruction in an ordered fashion. See also switch details and switch details. | Inferred | |
| LIG_WW_1 | SMAD3_HUMAN | 181 | 184 | Specificity | Altered binding specificity | CDK8/9 phosphorylates Mothers against decapentaplegic homolog 3 (SMAD3) at T179 and S208. Phosphorylation of T179 creates a binding site for the WW domain of Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1), while phosphorylation of S208 primes SMAD3 for phosphorylation of S204 by Glycogen synthase kinase-3 beta (GSK3B). The pS204-pS208 forms a binding site for the third WW domain of E3 ubiquitin-protein ligase NEDD4-like (NEDD4L), whose second WW domain will displace the WW domain of PIN1 at the pT179-PY box site of SMAD3. This regulation couples SMAD3 activation to SMAD3 destruction in an ordered fashion. See also switch details and switch details. | Inferred | |
| LIG_WW_1 | ERBB4_HUMAN | 1053 | 1056 | Specificity | Altered binding specificity | Phosphorylation-dependent binding of Receptor tyrosine-protein kinase erbB-4 (ERBB4) to the SH2 domains of Phosphatidylinositol 3-kinase regulatory subunit alpha (PIK3R1) results in signaling activation, while binding to the WW domains of E3 ubiquitin-protein ligase Itchy homolog (ITCH) to unphopshorylated ERBB4 results in ubiquitylation, endocytosis and ultimately degradation of ERBB4. | Inferred | |
| LIG_SH2_STAT5 | ERBB4_HUMAN | 1056 | 1059 | Specificity | Altered binding specificity | Phosphorylation-dependent binding of Receptor tyrosine-protein kinase erbB-4 (ERBB4) to the SH2 domains of Phosphatidylinositol 3-kinase regulatory subunit alpha (PIK3R1) results in signaling activation, while binding to the WW domains of E3 ubiquitin-protein ligase Itchy homolog (ITCH) to unphopshorylated ERBB4 results in ubiquitylation, endocytosis and ultimately degradation of ERBB4. | Inferred | |
| LIG_WW_1 | ERBB4_HUMAN | 1053 | 1056 | Binary | Pre‑translational | Alternative splicing removes the WW-binding motif of Receptor tyrosine-protein kinase erbB-4 (ERBB4), abrogating binding to E3 ubiquitin-protein ligase Itchy homolog (ITCH). The presence of a WW-binding motif mediates ERBB4 mono-ubiquitination and endocytosis by the WW domain-containing HECT-type E3 ubiquitin ligase ITCH. | Inferred | |
| LIG_WW_1 | SMAD3_HUMAN | 181 | 184 | Avidity‑sensing | CDK8/9 phosphorylates Mothers against decapentaplegic homolog 3 (SMAD3) at T179 and S208. Phosphorylation of T179 creates a binding site for the WW domain of Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1), while phosphorylation of S208 primes SMAD3 for phosphorylation of S204 by Glycogen synthase kinase-3 beta (GSK3B). The pS204-pS208 forms a binding site for the third WW domain of the E3 ubiquitin-protein ligase NEDD4-like (NEDD4L), whose second WW domain will displace the WW domain of PIN1 at the pT179-PY box site of SMAD3. This regulation couples SMAD3 activation to SMAD3 destruction in an ordered fashion. Dual phosphorylation of the two NEDD4L-binding sites mediates high-avidity binding of two WW domains of NEDD4L to SMAD3. See also switch details and switch details. | Inferred | ||
| LIG_WW_Nedd4L | SMAD3_HUMAN | 203 | 210 | Avidity‑sensing | CDK8/9 phosphorylates Mothers against decapentaplegic homolog 3 (SMAD3) at T179 and S208. Phosphorylation of T179 creates a binding site for the WW domain of Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1), while phosphorylation of S208 primes SMAD3 for phosphorylation of S204 by Glycogen synthase kinase-3 beta (GSK3B). The pS204-pS208 forms a binding site for the third WW domain of the E3 ubiquitin-protein ligase NEDD4-like (NEDD4L), whose second WW domain will displace the WW domain of PIN1 at the pT179-PY box site of SMAD3. This regulation couples SMAD3 activation to SMAD3 destruction in an ordered fashion. Dual phosphorylation of the two NEDD4L-binding sites mediates high-avidity binding of two WW domains of NEDD4L to SMAD3. See also switch details and switch details. | Inferred | ||
| LIG_WW_Nedd4L | SMAD3_HUMAN | 203 | 210 | Cumulative | Rheostatic | CDK8/9 phosphorylates Mothers against decapentaplegic homolog 3 (SMAD3) at T179 and S208. Phosphorylation of T179 creates a binding site for the WW domain of Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1), while phosphorylation of S208 primes SMAD3 for phosphorylation of S204 by Glycogen synthase kinase-3 beta (GSK3B). The pS204-pS208 forms a binding site for the third WW domain of the E3 ubiquitin-protein ligase NEDD4-like (NEDD4L), whose second WW domain will displace the WW domain of PIN1 at the pT179-PY box site of SMAD3. This regulation couples SMAD3 activation to SMAD3 destruction in an ordered fashion. Phosphorylation of S208 in SMAD3 induces binding of the third WW domain of NEDD4L, while additional phosphorylation of S204 in SMAD3 further increases the affinity of this interaction. See also switch details and switch details. | Inferred | |
| LIG_AP2alpha_2 | DAB2_HUMAN | 293 | 295 | Binary | Pre‑translational | Alternative splicing removes the AP2alpha-binding motifs of Disabled homolog 2 (DAB2), abrogating binding to AP-2 complex subunit alpha-2 (AP2A2). The p67 splice variant of Dab1 (also known as Isoform 2 of Disabled homolog 2 (DAB2)) does not localise to vesicles as it fails to bind the AP-2 complex. | Inferred | |
| LIG_AP2alpha_2 | DAB2_HUMAN | 298 | 300 | Binary | Pre‑translational | Alternative splicing removes the AP2alpha-binding motifs of Disabled homolog 2 (DAB2), abrogating binding to AP-2 complex subunit alpha-2 (AP2A2). The p67 splice variant of Dab1 (also known as Isoform 2 of Disabled homolog 2 (DAB2)) does not localise to vesicles as it fails to bind the AP-2 complex. | Inferred | |
| TRG_ENDOCYTIC_2 | PI51C_HUMAN | 649 | 652 | Binary | Physicochemical compatibility | Phosphorylation of S645 near the AP2-binding motif of Phosphatidylinositol-4-phosphate 5-kinase type-1 gamma (PIP5K1C) by Cyclin-dependent kinase 5 (Cdk5) inhibits its interaction with AP-2 complex subunit mu (AP2M1). | Inferred | |
| LIG_WW_1 | ERBB4_HUMAN | 1053 | 1056 | Binary | Pre‑translational | Alternative splicing removes the WW-binding motif of Receptor tyrosine-protein kinase erbB-4 (ERBB4), abrogating binding to E3 ubiquitin-protein ligase Itchy homolog (ITCH). The presence of a WW-binding motif mediates ERBB4 mono-ubiquitination and endocytosis by the WW domain-containing HECT-type E3 ubiquitin ligase ITCH. | Inferred | |
Endocytosis (KEGG - mmu04144) | ||||||||
| TRG_ENDOCYTIC_2 | PI51C_MOUSE | 644 | 647 | Binary | Pre‑translational | Alternative splicing removes the endocytosis motif of Phosphatidylinositol 4-phosphate 5-kinase type-1 gamma (Pip5k1c), abrogating binding to AP-2 complex subunit mu (Ap2m1). The direct interaction between the AP-2 complex and Isoform PIPKIgamma661 of Phosphatidylinositol 4-phosphate 5-kinase type-1 gamma (Pip5k1c) (PIPKIgamma661) targets this isoform to sites of endocytosis at the plasma membrane. Consequently, this results in the generation of a highly concentrated pool of PI(4,5)P2 at these sites. | Inferred | |
| TRG_AP2beta_CARGO_2 | PI51C_MOUSE | 633 | 644 | Binary | Pre‑translational | Alternative splicing removes the AP-2 beta-appendage-binding motif of Phosphatidylinositol 4-phosphate 5-kinase type-1 gamma (Pip5k1c), abrogating binding to AP-2 complex subunit beta (Ap2b1). With other enzymes (members of the eukaryotic diacylglycerol kinase family, and Synaptojanin-1 (Synj1)), Isoform PIPKIgamma661 of Phosphatidylinositol 4-phosphate 5-kinase type-1 gamma (Pip5k1c) (PIPKIgamma661) optimises the regional lipid environment necessary for clathrin coat formation. There are three different C-terminal splice variants of Pip5k1c: one (PIPKIgamma687) can bind selectively to Talin-1 (Tln1) via the C-terminal extension (switch details), one (PIPKIgamma661) can bind to both Talin-1 (Tln1) and AP-2 complex subunit beta (Ap2b1), and one (PIPKIgamma635) can bind to neither protein. This flexibility could impart importantly different biological functions to each isoform. For example, in humans PIP5K1C (PIPKIgamma661 in mouse) is proposed to act upstream of Rac/Rho and the differential regulation of PIP5K-gamma and -alpha might allow them to work in tandem to modulate the actin cytoskeleton during the attachment and ingestion phases of phagocytosis (See (here)). | Inferred | |
| TRG_AP2beta_CARGO_2 | PI51C_MOUSE | 633 | 644 | Binary | Physicochemical compatibility | Phosphorylation of S645 in Phosphatidylinositol 4-phosphate 5-kinase type-1 gamma (Pip5k1c) impedes binding to AP-2 complex subunit beta (Ap2b1), while dephosphorylation by calcineurin promotes binding. These phosphorylation and dephosphorylation events are important for the regulation of clathrin coat formation associated with synaptic vesicles. | Inferred | |
ErbB signaling pathway (KEGG - hsa04012) | ||||||||
| LIG_TKB | EGFR_HUMAN | 1069 | 1074 | Binary | Physicochemical compatibility | Phosphorylation of Y1069 in Epidermal growth factor receptor (EGFR) is necessary for binding to the TKB domain of E3 ubiquitin-protein ligase CBL (CBL). | Inferred | |
| MOD_GSK3_1 | JUN_HUMAN | 236 | 243 | Binary | Physicochemical compatibility | Phosphorylation of Transcription factor AP-1 (JUN) at S243 primes the protein for phosphorylation at T239 by Glycogen synthase kinase-3 beta (GSK3B). | Inferred | |
| LIG_PTB_Phospho_1 | ERBB3_HUMAN | 1322 | 1328 | Binary | Physicochemical compatibility | Phosphorylation of Y1328 in the PTB-binding motif of Receptor tyrosine-protein kinase erbB-3 (ERBB3) induces binding to the SHC-transforming protein 1 (SHC1) protein. | Inferred | |
| LIG_SH3_2 | PAK1_HUMAN | 13 | 18 | Binary | Physicochemical compatibility | Phosphorylation of S21 adjacent to the SH3-binding motif of Serine/threonine-protein kinase PAK 1 (PAK1) by RAC subfamily inhibits binding to Cytoplasmic protein NCK1 (NCK1), which regulates its localization to focal contacts. | Inferred | |
| LIG_TKB | EGFR_HUMAN | 1069 | 1074 | Cumulative | Rheostatic | While phosphorylation of Y1069 induces binding, additional phosphorylation of S1070 and S1071 in the TKB-binding motif of Epidermal growth factor receptor (EGFR) gradually lowers its binding affinity for E3 ubiquitin-protein ligase CBL (CBL). | Inferred | |
| MOD_ProDKin_1 | MYC_HUMAN | 59 | 65 | Specificity | Altered binding specificity | Phosphorylation of Myc proto-oncogene protein (MYC) at S62 by Mitogen-activated protein kinase 1 (MAPK1) primes MYC for phosphorylation by Glycogen synthase kinase-3 beta (GSK3B), which targets MYC to the SCF ubiquitin ligase complex, F-box/WD repeat-containing protein 7 (FBXW7) that marks MYC for degradation. | Inferred | |
| MOD_GSK3_1 | MYC_HUMAN | 55 | 62 | Specificity | Altered binding specificity | Phosphorylation of Myc proto-oncogene protein (MYC) at S62 by Mitogen-activated protein kinase 1 (MAPK1) primes MYC for phosphorylation by Glycogen synthase kinase-3 beta (GSK3B), which targets MYC to the SCF ubiquitin ligase complex, F-box/WD repeat-containing protein 7 (FBXW7) that marks MYC for degradation. | Inferred | |
| DEG_SCF_FBW7_1 | MYC_HUMAN | 55 | 62 | Specificity | Altered binding specificity | Phosphorylation of Myc proto-oncogene protein (MYC) at S62 by Mitogen-activated protein kinase 1 (MAPK1) primes MYC for phosphorylation by Glycogen synthase kinase-3 beta (GSK3B), which targets MYC to the SCF ubiquitin ligase complex, F-box/WD repeat-containing protein 7 (FBXW7) that marks MYC for degradation. | Inferred | |
| MOD_GSK3_1 | JUN_HUMAN | 236 | 243 | Specificity | Altered binding specificity | Transcription factor AP-1 (JUN) is primed by an unknown kinase for phosphorylation by Glycogen synthase kinase-3 beta (GSK3B), which targets JUN to the SCF ubiquitin ligase complex, F-box/WD repeat-containing protein 7 (FBXW7) that marks JUN for degradation. In v-Jun (Viral jun-transforming protein (JUN)) the residue corresponding to S243 is mutated to phenylalanine, which protects v-Jun (JUN) from degradation. | Inferred | |
| DEG_SCF_FBW7_1 | JUN_HUMAN | 236 | 243 | Specificity | Altered binding specificity | Transcription factor AP-1 (JUN) is primed by an unknown kinase for phosphorylation by Glycogen synthase kinase-3 beta (GSK3B), which targets JUN to the SCF ubiquitin ligase complex, F-box/WD repeat-containing protein 7 (FBXW7) that marks JUN for degradation. In v-Jun (Viral jun-transforming protein (JUN)) the residue corresponding to S243 is mutated to phenylalanine, which protects v-Jun (JUN) from degradation. | Inferred | |
| LIG_WW_1 | ERBB4_HUMAN | 1053 | 1056 | Specificity | Altered binding specificity | Phosphorylation-dependent binding of Receptor tyrosine-protein kinase erbB-4 (ERBB4) to the SH2 domains of Phosphatidylinositol 3-kinase regulatory subunit alpha (PIK3R1) results in signaling activation, while binding to the WW domains of E3 ubiquitin-protein ligase Itchy homolog (ITCH) to unphopshorylated ERBB4 results in ubiquitylation, endocytosis and ultimately degradation of ERBB4. | Inferred | |
| LIG_SH2_STAT5 | ERBB4_HUMAN | 1056 | 1059 | Specificity | Altered binding specificity | Phosphorylation-dependent binding of Receptor tyrosine-protein kinase erbB-4 (ERBB4) to the SH2 domains of Phosphatidylinositol 3-kinase regulatory subunit alpha (PIK3R1) results in signaling activation, while binding to the WW domains of E3 ubiquitin-protein ligase Itchy homolog (ITCH) to unphopshorylated ERBB4 results in ubiquitylation, endocytosis and ultimately degradation of ERBB4. | Inferred | |
| LIG_SH2_IC | EGFR_HUMAN | 1092 | 1100 | Binary | Physicochemical compatibility | Phosphorylation of Y1092 in the SH2-binding motif of Epidermal growth factor receptor (EGFR) induces binding to the Growth factor receptor-bound protein 2 (GRB2) protein. | Curated | |
| LIG_SH2_IB | CBL_HUMAN | 770 | 780 | Binary | Physicochemical compatibility | Phosphorylation of Y774 in the SH2-binding motif of E3 ubiquitin-protein ligase CBL (CBL) induces binding to the Adapter molecule crk (CRK) protein. | Inferred | |
| LIG_SH2_IC | SHC1_HUMAN | 423 | 435 | Binary | Physicochemical compatibility | Phosphorylation of Y427 in the SH2-binding motif of SHC-transforming protein 1 (SHC1) induces binding to the Growth factor receptor-bound protein 2 (GRB2) protein. | Inferred | |
| LIG_SH2_IA | FAK1_HUMAN | 389 | 405 | Binary | Physicochemical compatibility | Phosphorylation of Y397 in the SH2-binding motif of Focal adhesion kinase 1 (PTK2) induces binding to the Cytoplasmic protein NCK2 (NCK2) protein. | Inferred | |
| LIG_SH2_III | STA5A_HUMAN | 686 | 702 | Binary | Physicochemical compatibility | Phosphorylation of Y694 in the SH2-binding motif of Signal transducer and activator of transcription 5A (STAT5A) induces binding to the Signal transducer and activator of transcription 5B (STAT5B) protein. | Curated | |
| LIG_SH2_IIA | ERBB4_HUMAN | 1056 | 1059 | Binary | Pre‑translational | Alternative splicing removes the SH2-binding motif of Receptor tyrosine-protein kinase erbB-4 (ERBB4), abrogating binding to Phosphatidylinositol 3-kinase regulatory subunit alpha (PIK3R1). The SH2-binding motif overlaps with a WW-binding motif. Binding of these motifs is regulated in a phosphorylation-dependent manner, ensuring ERBB4 is either endocytosed or stabilised. | Inferred | |
| LIG_SH2_IIA | ERBB4_HUMAN | 1056 | 1059 | Binary | Pre‑translational | Alternative splicing removes the SH2-binding motif of Receptor tyrosine-protein kinase erbB-4 (ERBB4), abrogating binding to Phosphatidylinositol 3-kinase regulatory subunit alpha (PIK3R1). The SH2-binding motif overlaps with a WW-binding motif. Binding of these motifs is regulated in a phosphorylation-dependent manner, ensuring ERBB4 is either endocytosed or stabilised. | Inferred | |
| LIG_SH2_SRC | EGFR_HUMAN | 1016 | 1019 | Binary | Physicochemical compatibility | Phosphorylation of Y1016 in the SH2-binding motif of Epidermal growth factor receptor (EGFR) induces binding to 1-phosphatidylinositol-4,5-bisphosphate phosphodiesterase gamma-1 (PLCG1). | Curated | |
| LIG_SH2_SRC | EGFR_HUMAN | 1125 | 1128 | Binary | Physicochemical compatibility | Phosphorylation of Y1125 in the SH2-binding motif of Epidermal growth factor receptor (EGFR) induces binding to Adapter molecule crk (CRK). | Curated | |
| LIG_SH2_SRC | EGFR_HUMAN | 1016 | 1019 | Binary | Physicochemical compatibility | Phosphorylation of Y1016 in the SH2-binding motif of Epidermal growth factor receptor (EGFR) induces binding to Cytoplasmic protein NCK1 (NCK1). | Curated | |
| LIG_SH2_GRB2 | ERBB3_HUMAN | 1262 | 1265 | Binary | Physicochemical compatibility | Phosphorylation of Y1262 in the SH2-binding motif of Receptor tyrosine-protein kinase erbB-3 (ERBB3) induces binding to Growth factor receptor-bound protein 2 (GRB2). | Curated | |
| LIG_SH2_SRC | FAK1_HUMAN | 397 | 400 | Binary | Physicochemical compatibility | Phosphorylation of Y397 in the SH2-binding motif of Focal adhesion kinase 1 (PTK2) induces binding to Neuronal proto-oncogene tyrosine-protein kinase Src (Src). | Curated | |
| LIG_SH2_STAT5 | GAB1_HUMAN | 472 | 475 | Binary | Physicochemical compatibility | Phosphorylation of Y472 in the SH2-binding motif of GRB2-associated-binding protein 1 (GAB1) induces binding to Phosphatidylinositol 3-kinase regulatory subunit alpha (PIK3R1). | Curated | |
| LIG_SH2_STAT5 | GAB1_HUMAN | 447 | 450 | Binary | Physicochemical compatibility | Phosphorylation of Y447 in the SH2-binding motif of GRB2-associated-binding protein 1 (GAB1) induces binding to Phosphatidylinositol 3-kinase regulatory subunit alpha (PIK3R1). | Curated | |
Fanconi anemia pathway (KEGG - hsa03460) | ||||||||
| LIG_BRCT_BRCA1_1 | ATRIP_HUMAN | 238 | 242 | Binary | Physicochemical compatibility | Phosphorylation of S239 in the BRCT-binding motif of ATR-interacting protein (ATRIP) induces binding to the Breast cancer type 1 susceptibility protein (BRCA1) protein. | Inferred | |
| LIG_BRCT_BRCA1_1 | FANCJ_HUMAN | 989 | 993 | Binary | Physicochemical compatibility | Phosphorylation of S990 in the BRCT-binding motif of Fanconi anemia group J protein (BRIP1) induces binding to the Breast cancer type 1 susceptibility protein (BRCA1) protein. | Inferred | |
| LIG_BRCT_BRCA1_2 | FANCJ_HUMAN | 989 | 995 | Binary | Physicochemical compatibility | Phosphorylation of S990 in the BRCT-binding motif of Fanconi anemia group J protein (BRIP1) induces binding to the Breast cancer type 1 susceptibility protein (BRCA1) protein. | Inferred | |
Fc epsilon RI signaling pathway (KEGG - hsa04664) | ||||||||
| LIG_TYR_ITAM | FCERG_HUMAN | 62 | 79 | Avidity‑sensing | Phosphorylation of Y65 and Y76 in the ITAM motif of High affinity immunoglobulin epsilon receptor subunit gamma (FCER1G) induces high-avidity binding to the tandem SH2 domains of Tyrosine-protein kinase SYK (SYK). | Curated | ||
| LIG_TYR_ITAM | FCERG_HUMAN | 62 | 79 | Avidity‑sensing | Phosphorylation of Y65 and Y76 in the ITAM motif of High affinity immunoglobulin epsilon receptor subunit gamma (FCER1G) induces high-avidity binding to the tandem SH2 domains of Tyrosine-protein kinase SYK (SYK). | Curated | ||
| LIG_SH2_IA | FCERG_HUMAN | 75 | 79 | Binary | Physicochemical compatibility | Phosphorylation of Y76 in the SH2-binding motif of High affinity immunoglobulin epsilon receptor subunit gamma (FCER1G) induces binding to the Tyrosine-protein kinase SYK (SYK) protein. | Curated | |
Fc epsilon RI signaling pathway (KEGG - mmu04664) | ||||||||
| LIG_SH2_GRB2 | LAT_MOUSE | 175 | 178 | Binary | Physicochemical compatibility | Phosphorylation of Y175 in the SH2-binding motif of Linker for activation of T-cells family member 1 (Lat) induces binding to the Growth factor receptor-bound protein 2 (Grb2) protein. | Inferred | |
| LIG_SH2_GRB2 | LAT_MOUSE | 195 | 198 | Binary | Physicochemical compatibility | Phosphorylation of Y195 in the SH2-binding motif of Linker for activation of T-cells family member 1 (Lat) induces binding to the Growth factor receptor-bound protein 2 (Grb2) protein. | Inferred | |
| LIG_SH2_GRB2 | LAT_MOUSE | 235 | 238 | Binary | Physicochemical compatibility | Phosphorylation of Y235 in the SH2-binding motif of Linker for activation of T-cells family member 1 (Lat) induces binding to the Growth factor receptor-bound protein 2 (Grb2) protein. | Inferred | |
| LIG_SH2_IIA | SHIP1_HUMAN | 918 | 921 | Binary | Pre‑translational | Alternative splicing partially removes the SH2-binding motif of Phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 1 (Inpp5d), partially inhibiting binding to Phosphatidylinositol 3-kinase regulatory subunit alpha (Pik3r1). | Inferred | |
| LIG_SH2_IIA | SHIP1_HUMAN | 918 | 921 | Binary | Pre‑translational | Alternative splicing partially removes the SH2-binding motif of Phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 1 (Inpp5d), partially inhibiting binding to Phosphatidylinositol 3-kinase regulatory subunit alpha (Pik3r1). | Inferred | |
Fc gamma R-mediated phagocytosis (KEGG - hsa04666) | ||||||||
| LIG_TYR_ITIM | FCG2B_HUMAN | 290 | 295 | Binary | Physicochemical compatibility | Phosphorylation of Y292 in the ITIM motif of Low affinity immunoglobulin gamma Fc region receptor II-b (FCGR2B) induces binding of Phosphatidylinositol-3,4,5-trisphosphate 5-phosphatase 1 (INPP5D) via its SH2 domain. | Inferred | |
| LIG_TYR_ITAM | FCG2A_HUMAN | 285 | 307 | Avidity‑sensing | Phosphorylation of Y288 and Y304 in the ITAM motif of Low affinity immunoglobulin gamma Fc region receptor II-a (FCGR2A) induces high-avidity binding to the tandem SH2 domains of Tyrosine-protein kinase SYK (SYK). | Curated | ||
| LIG_TYR_ITAM | FCG2A_HUMAN | 285 | 307 | Avidity‑sensing | Phosphorylation of Y288 and Y304 in the ITAM motif of Low affinity immunoglobulin gamma Fc region receptor II-a (FCGR2A) induces high-avidity binding to the tandem SH2 domains of Tyrosine-protein kinase SYK (SYK). | Curated | ||
Fc gamma R-mediated phagocytosis (KEGG - mmu04666) | ||||||||
| LIG_SH2_IIA | SHIP1_HUMAN | 918 | 921 | Binary | Pre‑translational | Alternative splicing partially removes the SH2-binding motif of Phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 1 (Inpp5d), partially inhibiting binding to Phosphatidylinositol 3-kinase regulatory subunit alpha (Pik3r1). | Inferred | |
| LIG_SH2_IIA | SHIP1_HUMAN | 918 | 921 | Binary | Pre‑translational | Alternative splicing partially removes the SH2-binding motif of Phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 1 (Inpp5d), partially inhibiting binding to Phosphatidylinositol 3-kinase regulatory subunit alpha (Pik3r1). | Inferred | |
Focal adhesion (KEGG - hsa04510) | ||||||||
| MOD_GSK3_1 | JUN_HUMAN | 236 | 243 | Binary | Physicochemical compatibility | Phosphorylation of Transcription factor AP-1 (JUN) at S243 primes the protein for phosphorylation at T239 by Glycogen synthase kinase-3 beta (GSK3B). | Inferred | |
| LIG_PTB_Phospho_1 | ITB3_HUMAN | 779 | 785 | Binary | Physicochemical compatibility | Phosphorylation of Y785 in the PTB-binding motif of Integrin beta-3 (ITGB3) induces binding to the SHC-transforming protein 1 (SHC1) protein. | Inferred | |
| LIG_PTB_Phospho_1 | ITB4_HUMAN | 1590 | 1596 | Binary | Physicochemical compatibility | Phosphorylation of Y1596 in the PTB-binding motif of Integrin beta-4 (ITGB4) induces binding to the SHC-transforming protein 1 (SHC1) protein. | Inferred | |
| LIG_PTB_Talin | PI51C_HUMAN | 650 | 653 | Binary | Physicochemical compatibility | Phosphorylation of S650 in the PTB-binding motif of Phosphatidylinositol-4-phosphate 5-kinase type-1 gamma (PIP5K1C) blocks its interaction with Talin-1 (TLN1). Phosphorylation of Y649 by Src kinase enhances the interaction, possibly indirectly by inhibiting S650 phosphorylation. | Inferred | |
| LIG_PTB_Phospho_1 | ITB3_HUMAN | 779 | 785 | Binary | Physicochemical compatibility | Phosphorylation of T779 in the PTB-binding motif of Integrin beta-3 (ITGB3) inhibits its interaction with SHC-transforming protein 1 (SHC1). | Inferred | |
| LIG_PTB_Phospho_1 | ITB3_HUMAN | 779 | 785 | Cumulative | Rheostatic | While phosphorylation of Y785 in the PTB-binding motif of Integrin beta-3 (ITGB3) induces binding to SHC-transforming protein 1 (SHC1), additional phosphorylation of Y773 further increases the strength of the interaction. | Inferred | |
| LIG_PTB_Apo_2 | ITB3_HUMAN | 767 | 774 | Specificity | Altered binding specificity | Phosphorylation of Y773 in Integrin beta-3 (ITGB3) switches the specificity of ITGB3 from Talin-1 (TLN1) to Docking protein 1 (DOK1), with a 2-fold decrease of the affinity for TLN1 and close to a 400-fold increase of the affinity for DOK1. This switch results in negative regulation of integrin activation. | Inferred | |
| LIG_PTB_Phospho_1 | ITB3_HUMAN | 767 | 773 | Specificity | Altered binding specificity | Phosphorylation of Y773 in Integrin beta-3 (ITGB3) switches the specificity of ITGB3 from Talin-1 (TLN1) to Docking protein 1 (DOK1), with a 2-fold decrease of the affinity for TLN1 and close to a 400-fold increase of the affinity for DOK1. This switch results in negative regulation of integrin activation. | Inferred | |
| MOD_ProDKin_1 | MYC_HUMAN | 59 | 65 | Specificity | Altered binding specificity | Phosphorylation of Myc proto-oncogene protein (MYC) at S62 by Mitogen-activated protein kinase 1 (MAPK1) primes MYC for phosphorylation by Glycogen synthase kinase-3 beta (GSK3B), which targets MYC to the SCF ubiquitin ligase complex, F-box/WD repeat-containing protein 7 (FBXW7) that marks MYC for degradation. | Inferred | |
| MOD_GSK3_1 | MYC_HUMAN | 55 | 62 | Specificity | Altered binding specificity | Phosphorylation of Myc proto-oncogene protein (MYC) at S62 by Mitogen-activated protein kinase 1 (MAPK1) primes MYC for phosphorylation by Glycogen synthase kinase-3 beta (GSK3B), which targets MYC to the SCF ubiquitin ligase complex, F-box/WD repeat-containing protein 7 (FBXW7) that marks MYC for degradation. | Inferred | |
| DEG_SCF_FBW7_1 | MYC_HUMAN | 55 | 62 | Specificity | Altered binding specificity | Phosphorylation of Myc proto-oncogene protein (MYC) at S62 by Mitogen-activated protein kinase 1 (MAPK1) primes MYC for phosphorylation by Glycogen synthase kinase-3 beta (GSK3B), which targets MYC to the SCF ubiquitin ligase complex, F-box/WD repeat-containing protein 7 (FBXW7) that marks MYC for degradation. | Inferred | |
| MOD_GSK3_1 | JUN_HUMAN | 236 | 243 | Specificity | Altered binding specificity | Transcription factor AP-1 (JUN) is primed by an unknown kinase for phosphorylation by Glycogen synthase kinase-3 beta (GSK3B), which targets JUN to the SCF ubiquitin ligase complex, F-box/WD repeat-containing protein 7 (FBXW7) that marks JUN for degradation. In v-Jun (Viral jun-transforming protein (JUN)) the residue corresponding to S243 is mutated to phenylalanine, which protects v-Jun (JUN) from degradation. | Inferred | |
| DEG_SCF_FBW7_1 | JUN_HUMAN | 236 | 243 | Specificity | Altered binding specificity | Transcription factor AP-1 (JUN) is primed by an unknown kinase for phosphorylation by Glycogen synthase kinase-3 beta (GSK3B), which targets JUN to the SCF ubiquitin ligase complex, F-box/WD repeat-containing protein 7 (FBXW7) that marks JUN for degradation. In v-Jun (Viral jun-transforming protein (JUN)) the residue corresponding to S243 is mutated to phenylalanine, which protects v-Jun (JUN) from degradation. | Inferred | |
| LIG_PTB_Apo_2 | ITB3_HUMAN | 779 | 786 | Specificity | Altered binding specificity | Phosphorylation of Integrin beta-3 (ITGB3) at Y785 switches the specificity of integrin from Kindlin-2 (Fermitin family homolog 2 (FERMT2)) to the adaptor protein SHC-transforming protein 1 (SHC1). | Inferred | |
| LIG_PTB_Phospho_1 | ITB3_HUMAN | 779 | 785 | Specificity | Altered binding specificity | Phosphorylation of Integrin beta-3 (ITGB3) at Y785 switches the specificity of integrin from Kindlin-2 (Fermitin family homolog 2 (FERMT2)) to the adaptor protein SHC-transforming protein 1 (SHC1). | Inferred | |
| LIG_RGD | EDIL3_HUMAN | 96 | 98 | Pre‑assembly | Composite binding site formation | Binding of EGF-like repeat and discoidin I-like domain-containing protein 3 (EDIL3) to integrin receptors depends on pre-assembly of Integrin alpha-V (ITGAV)-Integrin beta-3 (ITGB3) heterodimers, since association of the integrin alpha and beta subunits results in the formation of a composite binding site for the RGD motif in the ligand. | Inferred | |
| LIG_RGD | DISG_TRIAB | 51 | 53 | Pre‑assembly | Composite binding site formation | Binding of Disintegrin albolabrin to integrin receptors depends on pre-assembly of Integrin alpha-IIb (ITGA2B)-Integrin beta-3 (ITGB3) heterodimers, since association of the integrin alpha and beta subunits results in the formation of a composite binding site for the RGD motif in the ligand. | Inferred | |
| LIG_RGD | FINC_HUMAN | 1524 | 1526 | Pre‑assembly | Composite binding site formation | Binding of Fibronectin (FN1) to integrin receptors depends on pre-assembly of Integrin alpha-V (ITGAV)-Integrin beta-3 (ITGB3) heterodimers, since association of the integrin alpha and beta subunits results in the formation of a composite binding site for the RGD motif in the ligand. | Inferred | |
| LIG_RGD | POLG_FMDVO | 869 | 871 | Pre‑assembly | Composite binding site formation | Binding of Genome polyprotein to integrin receptors depends on pre-assembly of Integrin alpha-V (ITGAV)-Integrin beta-3 (ITGB3) heterodimers, since association of the integrin alpha and beta subunits results in the formation of a composite binding site for the RGD motif in the ligand. | Inferred | |
| LIG_RGD | VTNC_HUMAN | 64 | 66 | Pre‑assembly | Composite binding site formation | Binding of Vitronectin (VTN) to integrin receptors depends on pre-assembly of Integrin alpha-V (ITGAV)-Integrin beta-3 (ITGB3) heterodimers, since association of the integrin alpha and beta subunits results in the formation of a composite binding site for the RGD motif in the ligand. | Inferred | |
| LIG_RGD | VWF_HUMAN | 2507 | 2509 | Pre‑assembly | Composite binding site formation | Binding of von Willebrand factor (VWF) to integrin receptors depends on pre-assembly of Integrin alpha-V (ITGAV)-Integrin beta-3 (ITGB3) heterodimers, since association of the integrin alpha and beta subunits results in the formation of a composite binding site for the RGD motif in the ligand. | Inferred | |
| LIG_RGD | OSTP_HUMAN | 159 | 161 | Pre‑assembly | Composite binding site formation | Binding of EGF-like repeat and discoidin I-like domain-containing protein 3 (EDIL3) to integrin receptors depends on pre-assembly of Integrin alpha-V (ITGAV)-Integrin beta-3 (ITGB3) heterodimers, since association of the integrin alpha and beta subunits results in the formation of a composite binding site for the RGD motif in the ligand. | Inferred | |
| LIG_RGD | VME1_TRIEL | 459 | 461 | Pre‑assembly | Composite binding site formation | Binding of Zinc metalloproteinase/disintegrin to integrin receptors depends on pre-assembly of Integrin alpha-IIb (ITGA2B)-Integrin beta-3 (ITGB3) heterodimers, since association of the integrin alpha and beta subunits results in the formation of a composite binding site for the RGD motif in the ligand. | Inferred | |
| LIG_RGD | DISB_TRIGA | 51 | 53 | Pre‑assembly | Composite binding site formation | Binding of Disintegrin trigramin-beta-2 to integrin receptors depends on pre-assembly of Integrin alpha-IIb (ITGA2B)-Integrin beta-3 (ITGB3) heterodimers, since association of the integrin alpha and beta subunits results in the formation of a composite binding site for the RGD motif in the ligand. | Inferred | |
| LIG_RGD | POLG_CXA9 | 858 | 860 | Pre‑assembly | Composite binding site formation | Binding of Genome polyprotein to integrin receptors depends on pre-assembly of Integrin alpha-V (ITGAV)-Integrin beta-6 (ITGB6) heterodimers, since association of the integrin alpha and beta subunits results in the formation of a composite binding site for the RGD motif in the ligand. | Inferred | |
| LIG_RGD | POLG_HPE1H | 764 | 766 | Pre‑assembly | Composite binding site formation | Binding of Genome polyprotein to integrin receptors depends on pre-assembly of Integrin alpha-V (ITGAV)-Integrin beta-6 (ITGB6) heterodimers, since association of the integrin alpha and beta subunits results in the formation of a composite binding site for the RGD motif in the ligand. | Inferred | |
| LIG_Integrin_isoDGR_1 | FINC_HUMAN | 263 | 265 | Pre‑assembly | Composite binding site formation | Binding of Fibronectin (FN1) to integrin receptors depends on pre-assembly of Integrin alpha-V (ITGAV)-Integrin beta-3 (ITGB3) heterodimers, since association of the integrin alpha and beta subunits results in the formation of a composite binding site for the RGD motif in the ligand. | Inferred | |
| LIG_Talin | ITB7_HUMAN | 770 | 779 | Specificity | Competition | The integrin regulator Talin-1 (TLN1) and the actin-crosslinking Filamins Filamin-A (FLNA) use overlapping binding sites on the cytoplasmic tails of beta integrin subunits Integrin beta-7 (ITGB7), which makes their interaction with beta integrin mutually exclusive. | Inferred | |
| LIG_Filamin | ITB7_HUMAN | 776 | 787 | Specificity | Competition | The integrin regulator Talin-1 (TLN1) and the actin-crosslinking Filamins Filamin-A (FLNA) use overlapping binding sites on the cytoplasmic tails of beta integrin subunits Integrin beta-7 (ITGB7), which makes their interaction with beta integrin mutually exclusive. | Inferred | |
| LIG_SH2_IC | MET_HUMAN | 1351 | 1360 | Binary | Physicochemical compatibility | Phosphorylation of Y1356 in the SH2-binding motif of Hepatocyte growth factor receptor (MET) induces binding to the Growth factor receptor-bound protein 2 (GRB2) protein. | Inferred | |
| LIG_SH2_IIA | PGFRB_HUMAN | 751 | 755 | Binary | Physicochemical compatibility | Phosphorylation of Y751 in the SH2-binding motif of Platelet-derived growth factor receptor beta (PDGFRB) induces binding to the Phosphatidylinositol 3-kinase regulatory subunit alpha (PIK3R1) protein. | Inferred | |
| LIG_SH2_IC | SHC1_HUMAN | 423 | 435 | Binary | Physicochemical compatibility | Phosphorylation of Y427 in the SH2-binding motif of SHC-transforming protein 1 (SHC1) induces binding to the Growth factor receptor-bound protein 2 (GRB2) protein. | Inferred | |
| LIG_SH2_IB | BCAR1_HUMAN | 358 | 368 | Binary | Physicochemical compatibility | Phosphorylation of Y362 in the SH2-binding motif of Breast cancer anti-estrogen resistance protein 1 (BCAR1) induces binding to the Adapter molecule crk (CRK) protein. | Inferred | |
| LIG_Talin | ITB1_HUMAN | 775 | 785 | Binary | Pre‑translational | Alternative splicing alters the flanking regions of the PTB-binding motif of Isoform Beta-1D of Integrin beta-1 (ITGB1), inducing higher affinity binding to Talin-1 (TLN1). Alteration of residue 788 from G to Q and alteration of residue 786 from A to P increases the binding affinity from 491 micromolar in the canonical Isoform Beta-1A of Integrin beta-1 (ITGB1) to 95 micromolar in Isoform Beta-1D of Integrin beta-1 (ITGB1). | Inferred | |
| LIG_Talin | ITB1_HUMAN | 775 | 785 | Binary | Pre‑translational | Alternative splicing alters the flanking regions of the PTB-binding motif of Isoform Beta-1D of Integrin beta-1 (ITGB1), inducing higher affinity binding to Talin-2 (TLN2). The alteration of residue 788 from G to Q and alteration of residue 786 from A to P increases the binding affinity from 652 micromolar in the canonical Isoform Beta-1A of Integrin beta-1 (ITGB1) to 36 micromolar in Isoform Beta-1D of Integrin beta-1 (ITGB1). | Inferred | |
| LIG_Filamin_2 | ITB1_HUMAN | 783 | 791 | Binary | Pre‑translational | Alternative splicing strongly inhibits the binding of the filamin-binding motif of Integrin beta-1 (ITGB1) to Filamin-A (FLNA), primarily due to the alteration of A to P it seems. | Inferred | |
| LIG_Filamin_2 | ITB1_HUMAN | 783 | 791 | Binary | Pre‑translational | Alternative splicing strongly inhibits the binding of the filamin-binding motif of Integrin beta-1 (ITGB1) to Filamin-B (FLNB), primarily due to the alteration of A to P it seems. Splicing of FLNB also affects this interaction. | Inferred | |
| LIG_FAT_LD_1 | PAXI_HUMAN | 4 | 12 | Binary | Pre‑translational | Alternative splicing removes the FAK-binding LD motif of Paxillin (PXN), abrogating binding to Focal adhesion kinase 1 (PTK2). | Inferred | |
| LIG_SH2_IB | PAXI_HUMAN | 118 | 121 | Binary | Pre‑translational | Alternative splicing removes the SH2-binding motif of Paxillin (PXN), abrogating binding to Adapter molecule crk (CRK). | Inferred | |
| LIG_SH2_IB | PAXI_HUMAN | 31 | 34 | Binary | Pre‑translational | Alternative splicing removes the SH2-binding motif of Paxillin (PXN), abrogating binding to Adapter molecule crk (CRK). | Inferred | |
Focal adhesion (KEGG - mmu04510) | ||||||||
| LIG_RGD | FINC_MOUSE | 1614 | 1616 | Pre‑assembly | Composite binding site formation | Binding of Fibronectin (Fn1) to integrin receptors depends on pre-assembly of Integrin alpha-5 (Itga5)-Integrin beta-1 (Itgb1) heterodimers, since association of the integrin alpha and beta subunits results in the formation of a composite binding site for the RGD motif in the ligand. | Inferred | |
| LIG_RGD | VTNC_MOUSE | 64 | 66 | Pre‑assembly | Composite binding site formation | Binding of Vitronectin (Vtn) to integrin receptors depends on pre-assembly of Integrin alpha-V (Itgav)-Integrin beta-3 (Itgb3) heterodimers, since association of the integrin alpha and beta subunits results in the formation of a composite binding site for the RGD motif in the ligand. | Inferred | |
| LIG_PTB_Talin | PI51C_MOUSE | 645 | 648 | Binary | Pre‑translational | Alternative splicing removes the PTB domain-binding motif of Phosphatidylinositol 4-phosphate 5-kinase type-1 gamma (Pip5k1c), abrogating binding to Talin-1 (Tln1). Integrin receptors, Tln1 and Isoform PIPKIgamma661 of Phosphatidylinositol 4-phosphate 5-kinase type-1 gamma (Pip5k1c) (PIPKIgamma661) are recruited to focal adhesions, inducing synthesis of PI(4,5)P2. The regulated and localised generation of PI(4,5)P2 facilitates the assembly and/or disassembly of focal adhesions. | Inferred | |
| LIG_PTB_Talin | PI51C_MOUSE | 645 | 648 | Binary | Physicochemical compatibility | Phosphorylation of S645 in the PTB-binding motif of Phosphatidylinositol 4-phosphate 5-kinase type-1 gamma (Pip5k1c) by Cyclin-dependent kinase 5 (Cdk5) inhibits its interaction with Talin-1 (Tln1). | Inferred | |
| LIG_PTB_Talin | PI51C_MOUSE | 645 | 648 | Binary | Physicochemical compatibility | Phosphorylation of Y644 in Phosphatidylinositol 4-phosphate 5-kinase type-1 gamma (Pip5k1c) promotes its association with Talin-1 (Tln1). | Inferred | |
G1/S DNA Damage Checkpoints (Reactome - 69615) | ||||||||
| LIG_TAZ2 | P53_HUMAN | 19 | 25 | Cumulative | Rheostatic | Multisite phosphorylation of S15 and T18 and S20 and S33 and S37 and S46 in the TAD region of Cellular tumor antigen p53 (TP53) additively enhances its affinity for CREB-binding protein (CREBBP). | Curated | |
G2/M Transition (Reactome - 69275) | ||||||||
| TRG_NES_CRM1_1 | MPIP3_HUMAN | 189 | 203 | Binary | Physicochemical compatibility | Phosphorylation of S198 in the NES of M-phase inducer phosphatase 3 (CDC25C) by Serine/threonine-protein kinase PLK1 (PLK1) inhibits binding to Exportin-1 (XPO1), thus promoting nuclear localization of M-phase inducer phosphatase 3 (CDC25C). | Curated | |
GABAergic synapse (KEGG - hsa04727) | ||||||||
| TRG_ER_diArg_1 | GABR1_HUMAN | 923 | 926 | Specificity | Motif hiding | Interaction of the GABA receptor R2 subunit (Gamma-aminobutyric acid type B receptor subunit 2 (GABBR2)) with the R1 subunit (Gamma-aminobutyric acid type B receptor subunit 1 (GABBR1)) via coiled-coil forming domains masks the ER retention motif in the R1 subunit (Gamma-aminobutyric acid type B receptor subunit 1 (GABBR1)), thereby promoting surface expression of fully assembled GABA receptors. | Inferred | |
Glutamatergic synapse (KEGG - hsa04724) | ||||||||
| LIG_PDZ_Class_1 | NMDZ1_HUMAN | 917 | 922 | Binary | Pre‑translational | Alternative splicing removes the PDZ-binding motif of Isoform 4 of Glutamate [NMDA] receptor subunit zeta-1 (GRIN1), abrogating binding to Disks large homolog 4 (DLG4). Binding of the PDZ domain of DLG4 suppresses an ER-retention motif in GRIN1, promoting its cell surface expression in a splice variant-specific manner. | Inferred | |
| LIG_PDZ_Class_1 | NMDZ1_HUMAN | 917 | 922 | Specificity | Motif hiding | Binding of the PDZ domain of Disks large homolog 4 (DLG4) suppresses the ER-retention motif of Isoform 4 of Glutamate receptor subunit zeta-1 (GRIN1) in a splice variant-specific manner, thereby promoting cell surface expression of this particular isoform. This supports the hypothesis that local regulation of receptor exit from neuronal ER plays a role in modifying discrete synaptic receptor number. | Inferred | |
| TRG_ER_diArg_1 | NMDZ1_HUMAN | 893 | 895 | Specificity | Motif hiding | Binding of the PDZ domain of Disks large homolog 4 (DLG4) suppresses the ER-retention motif of Isoform 4 of Glutamate receptor subunit zeta-1 (GRIN1) in a splice variant-specific manner, thereby promoting cell surface expression of this particular isoform. This supports the hypothesis that local regulation of receptor exit from neuronal ER plays a role in modifying discrete synaptic receptor number. | Inferred | |
| LIG_SH3_3 | PLCB1_HUMAN | 1162 | 1168 | Binary | Pre‑translational | Alternative splicing removes the SH3-binding motif of Isoform B of 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 (PLCB1), abrogating binding to SH3 and multiple ankyrin repeat domains protein 3 (SHANK3). PLCB1 associates with a SHANK3 complex in cardiomyocytes via its splice variant-specific C-terminal tail. Studies show that Isoform B of 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 (PLCB1) selectively mediates downstream responses initiated by Gq-coupled receptors, in particular hypertrophy and apoptosis. | Inferred | |
| LIG_PDZ_Class_1 | NMDZ1_HUMAN | 917 | 922 | Binary | Pre‑translational | Alternative splicing removes the PDZ-binding motif of Isoform 4 of Glutamate [NMDA] receptor subunit zeta-1 (GRIN1), abrogating binding to Disks large homolog 4 (DLG4). Binding of the PDZ domain of DLG4 suppresses an ER-retention motif in GRIN1, promoting its cell surface expression in a splice variant-specific manner. | Inferred | |
| LIG_PDZ_Class_1 | NMDZ1_HUMAN | 917 | 922 | Specificity | Motif hiding | Binding of the PDZ domain of Disks large homolog 4 (DLG4) suppresses the ER-retention motif of Isoform 4 of Glutamate receptor subunit zeta-1 (GRIN1) in a splice variant-specific manner, thereby promoting cell surface expression of this particular isoform. This supports the hypothesis that local regulation of receptor exit from neuronal ER plays a role in modifying discrete synaptic receptor number. | Inferred | |
| TRG_ER_diArg_1 | NMDZ1_HUMAN | 893 | 895 | Specificity | Motif hiding | Binding of the PDZ domain of Disks large homolog 4 (DLG4) suppresses the ER-retention motif of Isoform 4 of Glutamate receptor subunit zeta-1 (GRIN1) in a splice variant-specific manner, thereby promoting cell surface expression of this particular isoform. This supports the hypothesis that local regulation of receptor exit from neuronal ER plays a role in modifying discrete synaptic receptor number. | Inferred | |
| LIG_PDZ_Class_1 | NMDZ1_HUMAN | 917 | 922 | Binary | Pre‑translational | Alternative splicing removes the PDZ-binding motif of Isoform 4 of Glutamate [NMDA] receptor subunit zeta-1 (GRIN1), abrogating binding to Disks large homolog 4 (DLG4). Binding of the PDZ domain of DLG4 suppresses an ER-retention motif in GRIN1, promoting its cell surface expression in a splice variant-specific manner. | Inferred | |
| LIG_PDZ_Class_1 | NMDZ1_HUMAN | 917 | 922 | Specificity | Motif hiding | Binding of the PDZ domain of Disks large homolog 4 (DLG4) suppresses the ER-retention motif of Isoform 4 of Glutamate receptor subunit zeta-1 (GRIN1) in a splice variant-specific manner, thereby promoting cell surface expression of this particular isoform. This supports the hypothesis that local regulation of receptor exit from neuronal ER plays a role in modifying discrete synaptic receptor number. | Inferred | |
| TRG_ER_diArg_1 | NMDZ1_HUMAN | 893 | 895 | Specificity | Motif hiding | Binding of the PDZ domain of Disks large homolog 4 (DLG4) suppresses the ER-retention motif of Isoform 4 of Glutamate receptor subunit zeta-1 (GRIN1) in a splice variant-specific manner, thereby promoting cell surface expression of this particular isoform. This supports the hypothesis that local regulation of receptor exit from neuronal ER plays a role in modifying discrete synaptic receptor number. | Inferred | |
Glutamatergic synapse (KEGG - rno04724) | ||||||||
| LIG_EVH1_2 | GRM1_RAT | 1152 | 1156 | Binary | Pre‑translational | Alternative splicing removes the EVH1-binding motif of Metabotropic glutamate receptor 1 (Grm1), abrogating binding to Homer protein homolog 1 (Homer1), which is important for spatial targeting of Grm1. | Inferred | |
GnRH signaling pathway (KEGG - rno04912) | ||||||||
| LIG_IQ | CAC1D_RAT | 1650 | 1669 | Binary | Pre‑translational | Alternative splicing removes the IQ motif of Voltage-dependent L-type calcium channel subunit alpha-1D (Cacna1d) abrogating binding to Calmodulin (Calm1). CaV1.3IQdelta (IQ-deleted Isoform CACN4B of Voltage-dependent L-type calcium channel subunit alpha-1D (Cacna1d)) channels exhibit a lack of calcium-dependent inactivation. CaV1.3IQdelta channel immunoreactivity was preferentially localised to cochlear outer hair cells (OHCs), whereas that of CaV1.3IQfull channels (IQ-possessing Isoform CACN4A of Voltage-dependent L-type calcium channel subunit alpha-1D (Cacna1d)) labelled inner hair cells (IHCs). | Inferred | |
Growth hormone receptor signaling (Reactome - 982772) | ||||||||
| LIG_SH2_III | STA5A_HUMAN | 686 | 702 | Binary | Physicochemical compatibility | Phosphorylation of Y694 in the SH2-binding motif of Signal transducer and activator of transcription 5A (STAT5A) induces binding to the Signal transducer and activator of transcription 5B (STAT5B) protein. | Curated | |
HIF-1 signaling pathway (KEGG - hsa04066) | ||||||||
| DEG_ODPH_VHL_1 | HIF1A_HUMAN | 400 | 413 | Binary | Physicochemical compatibility | Hydroxylation of P402 in the VHL-binding motif of Hypoxia-inducible factor 1-alpha (HIF1A) induces binding to the Von Hippel-Lindau disease tumor suppressor (VHL) protein. | Curated | |
| DEG_ODPH_VHL_1 | HIF1A_HUMAN | 562 | 574 | Binary | Physicochemical compatibility | Hydroxylation of P564 in the VHL-binding motif of Hypoxia-inducible factor 1-alpha (HIF1A) induces binding to the Von Hippel-Lindau disease tumor suppressor (VHL) protein. | Curated | |
| LIG_TAZ1 | HIF1A_HUMAN | 792 | 795 | Binary | Physicochemical compatibility | Under normoxic conditions interaction of Hypoxia-inducible factor 1-alpha (HIF1A) with transcriptional coactivators such as CREB-binding protein (Crebbp) is inhibited by hydroxylation of N803. | Curated | |
| LIG_SH2_STAT5 | INSR_HUMAN | 1361 | 1364 | Specificity | Domain hiding | PIP3 (1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate), a product of PI3-kinase, binds to the SH2 domains of PI3K (Phosphatidylinositol 3-kinase regulatory subunit alpha (PIK3R1)) and thereby blocks its interaction with tyrosine-phosphorylated SH2 motif containing proteins. | Inferred | |
Hedgehog signaling pathway (KEGG - hsa04340) | ||||||||
| MOD_GSK3_1 | FGD1_HUMAN | 280 | 287 | Specificity | Altered binding specificity | Phosphorylation of FYVE, RhoGEF and PH domain-containing protein 1 (FGD1), a GEF for CDC42 small effector protein 2 (CDC42SE2), by Glycogen synthase kinase-3 beta (GSK3B) targets FGD1 to the SCF ubiquitin ligase complex, F-box/WD repeat-containing protein 1A (BTRC), which marks FGD1 for degradation. | Inferred | |
| DEG_SCF_TRCP1_1 | FGD1_HUMAN | 282 | 287 | Specificity | Altered binding specificity | Phosphorylation of FYVE, RhoGEF and PH domain-containing protein 1 (FGD1), a GEF for CDC42 small effector protein 2 (CDC42SE2), by Glycogen synthase kinase-3 beta (GSK3B) targets FGD1 to the SCF ubiquitin ligase complex, F-box/WD repeat-containing protein 1A (BTRC), which marks FGD1 for degradation. | Inferred | |
| MOD_GSK3_1 | FGD3_HUMAN | 77 | 84 | Specificity | Altered binding specificity | Phosphorylation of FYVE, RhoGEF and PH domain-containing protein 3 (FGD3), a GEF for CDC42 small effector protein 2 (CDC42SE2), by Glycogen synthase kinase-3 beta (GSK3B) targets FGD3 to the SCF ubiquitin ligase complex, F-box/WD repeat-containing protein 1A (BTRC), which marks FGD3 for degradation. | Inferred | |
| MOD_GSK3_1 | FGD3_HUMAN | 73 | 80 | Specificity | Altered binding specificity | Phosphorylation of FYVE, RhoGEF and PH domain-containing protein 3 (FGD3), a GEF for CDC42 small effector protein 2 (CDC42SE2), by Glycogen synthase kinase-3 beta (GSK3B) targets FGD3 to the SCF ubiquitin ligase complex, F-box/WD repeat-containing protein 1A (BTRC), which marks FGD3 for degradation. | Inferred | |
| DEG_SCF_TRCP1_1 | FGD3_HUMAN | 75 | 80 | Specificity | Altered binding specificity | Phosphorylation of FYVE, RhoGEF and PH domain-containing protein 3 (FGD3), a GEF for CDC42 small effector protein 2 (CDC42SE2), by Glycogen synthase kinase-3 beta (GSK3B) targets FGD3 to the SCF ubiquitin ligase complex, F-box/WD repeat-containing protein 1A (BTRC), which marks FGD3 for degradation. | Inferred | |
| MOD_GSK3_1 | SNAI1_HUMAN | 93 | 100 | Specificity | Altered binding specificity | Phosphorylation of Zinc finger protein SNAI1 (SNAI1) at S100 generates a docking site for Glycogen synthase kinase-3 beta (GSK3B). Subsequent phosphorylation of S96 by GSK3B targets Zinc finger protein SNAI1 (SNAI1) to the SCF ubiquitin ligase complexes F-box/WD repeat-containing protein 1A (BTRC), which marks it for degradation. | Inferred | |
| DEG_SCF_TRCP1_1 | SNAI1_HUMAN | 95 | 100 | Specificity | Altered binding specificity | Phosphorylation of Zinc finger protein SNAI1 (SNAI1) at S100 generates a docking site for Glycogen synthase kinase-3 beta (GSK3B). Subsequent phosphorylation of S96 by GSK3B targets Zinc finger protein SNAI1 (SNAI1) to the SCF ubiquitin ligase complexes F-box/WD repeat-containing protein 1A (BTRC), which marks it for degradation. | Inferred | |
| MOD_LATS_1 | YAP1_HUMAN | 376 | 382 | Specificity | Altered binding specificity | Phosphorylation of Yorkie homolog (YAP1) at S381 by Serine/threonine-protein kinase LATS1 (LATS1) (a key regulator of the Hippo Pathway) primes the sequence for phosphorylation by Casein kinase I isoform epsilon (CSNK1E) at S384 and S387. This targets YAP1 to the SCF ubiqutin ligase complex, F-box/WD repeat-containing protein 1A (BTRC), which marks is YAP1 for subsequent degradation by the proteasomal system. N.B. Serine/threonine-protein kinase LATS2 (LATS2) can replace LATS1 and Casein kinase I isoform delta (CSNK1D) can replace CSNK1E | Inferred | |
| MOD_CK1_1 | YAP1_HUMAN | 381 | 387 | Specificity | Altered binding specificity | Phosphorylation of Yorkie homolog (YAP1) at S381 by Serine/threonine-protein kinase LATS1 (LATS1) (a key regulator of the Hippo Pathway) primes the sequence for phosphorylation by Casein kinase I isoform epsilon (CSNK1E) at S384 and S387. This targets YAP1 to the SCF ubiqutin ligase complex, F-box/WD repeat-containing protein 1A (BTRC), which marks is YAP1 for subsequent degradation by the proteasomal system. N.B. Serine/threonine-protein kinase LATS2 (LATS2) can replace LATS1 and Casein kinase I isoform delta (CSNK1D) can replace CSNK1E | Inferred | |
| MOD_CK1_1 | YAP1_HUMAN | 384 | 390 | Specificity | Altered binding specificity | Phosphorylation of Yorkie homolog (YAP1) at S381 by Serine/threonine-protein kinase LATS1 (LATS1) (a key regulator of the Hippo Pathway) primes the sequence for phosphorylation by Casein kinase I isoform epsilon (CSNK1E) at S384 and S387. This targets YAP1 to the SCF ubiqutin ligase complex, F-box/WD repeat-containing protein 1A (BTRC), which marks is YAP1 for subsequent degradation by the proteasomal system. N.B. Serine/threonine-protein kinase LATS2 (LATS2) can replace LATS1 and Casein kinase I isoform delta (CSNK1D) can replace CSNK1E | Inferred | |
| DEG_SCF_TRCP1_2 | YAP1_HUMAN | 383 | 387 | Specificity | Altered binding specificity | Phosphorylation of Yorkie homolog (YAP1) at S381 by Serine/threonine-protein kinase LATS1 (LATS1) (a key regulator of the Hippo Pathway) primes the sequence for phosphorylation by Casein kinase I isoform epsilon (CSNK1E) at S384 and S387. This targets YAP1 to the SCF ubiqutin ligase complex, F-box/WD repeat-containing protein 1A (BTRC), which marks is YAP1 for subsequent degradation by the proteasomal system. N.B. Serine/threonine-protein kinase LATS2 (LATS2) can replace LATS1 and Casein kinase I isoform delta (CSNK1D) can replace CSNK1E | Inferred | |
Hematopoietic cell lineage (KEGG - hsa04640) | ||||||||
| LIG_RGD | DISG_TRIAB | 51 | 53 | Pre‑assembly | Composite binding site formation | Binding of Disintegrin albolabrin to integrin receptors depends on pre-assembly of Integrin alpha-IIb (ITGA2B)-Integrin beta-3 (ITGB3) heterodimers, since association of the integrin alpha and beta subunits results in the formation of a composite binding site for the RGD motif in the ligand. | Inferred | |
| LIG_RGD | VME1_TRIEL | 459 | 461 | Pre‑assembly | Composite binding site formation | Binding of Zinc metalloproteinase/disintegrin to integrin receptors depends on pre-assembly of Integrin alpha-IIb (ITGA2B)-Integrin beta-3 (ITGB3) heterodimers, since association of the integrin alpha and beta subunits results in the formation of a composite binding site for the RGD motif in the ligand. | Inferred | |
| LIG_RGD | DISB_TRIGA | 51 | 53 | Pre‑assembly | Composite binding site formation | Binding of Disintegrin trigramin-beta-2 to integrin receptors depends on pre-assembly of Integrin alpha-IIb (ITGA2B)-Integrin beta-3 (ITGB3) heterodimers, since association of the integrin alpha and beta subunits results in the formation of a composite binding site for the RGD motif in the ligand. | Inferred | |
Insulin signaling pathway (KEGG - hsa04910) | ||||||||
| LIG_PTB_Phospho_1 | INSR_HUMAN | 993 | 999 | Binary | Physicochemical compatibility | Phosphorylation of Y999 in the PTB-binding motif of Insulin receptor (INSR) induces binding to the SHC-transforming protein 1 (SHC1) protein. | Inferred | |
| MOD_ProDKin_1 | MYC_HUMAN | 59 | 65 | Specificity | Altered binding specificity | Phosphorylation of Myc proto-oncogene protein (MYC) at S62 by Mitogen-activated protein kinase 1 (MAPK1) primes MYC for phosphorylation by Glycogen synthase kinase-3 beta (GSK3B), which targets MYC to the SCF ubiquitin ligase complex, F-box/WD repeat-containing protein 7 (FBXW7) that marks MYC for degradation. | Inferred | |
| MOD_GSK3_1 | MYC_HUMAN | 55 | 62 | Specificity | Altered binding specificity | Phosphorylation of Myc proto-oncogene protein (MYC) at S62 by Mitogen-activated protein kinase 1 (MAPK1) primes MYC for phosphorylation by Glycogen synthase kinase-3 beta (GSK3B), which targets MYC to the SCF ubiquitin ligase complex, F-box/WD repeat-containing protein 7 (FBXW7) that marks MYC for degradation. | Inferred | |
| DEG_SCF_FBW7_1 | MYC_HUMAN | 55 | 62 | Specificity | Altered binding specificity | Phosphorylation of Myc proto-oncogene protein (MYC) at S62 by Mitogen-activated protein kinase 1 (MAPK1) primes MYC for phosphorylation by Glycogen synthase kinase-3 beta (GSK3B), which targets MYC to the SCF ubiquitin ligase complex, F-box/WD repeat-containing protein 7 (FBXW7) that marks MYC for degradation. | Inferred | |
| MOD_GSK3_1 | SRBP1_HUMAN | 422 | 430 | Specificity | Altered binding specificity | Phosphorylation of SREBP-1 (Sterol regulatory element-binding protein 1 (SREBF1)) at S430 generates a docking site for Glycogen synthase kinase-3 beta (GSK3B). Subsequent phosphorylation of SREBP-1 (SREBF1) by GSK3B at T426 switches the specificity of SREBP-1 (SREBF1) to the F-box/WD repeat-containing protein 7 (FBXW7), which recruits SREBP-1 (SREBF1) to the SCF ubiquitin ligase complex to mark SREBP-1 (SREBF1) for degradation. | Inferred | |
| DEG_SCF_FBW7_1 | SRBP1_HUMAN | 425 | 430 | Specificity | Altered binding specificity | Phosphorylation of SREBP-1 (Sterol regulatory element-binding protein 1 (SREBF1)) at S430 generates a docking site for Glycogen synthase kinase-3 beta (GSK3B). Subsequent phosphorylation of SREBP-1 (SREBF1) by GSK3B at T426 switches the specificity of SREBP-1 (SREBF1) to the F-box/WD repeat-containing protein 7 (FBXW7), which recruits SREBP-1 (SREBF1) to the SCF ubiquitin ligase complex to mark SREBP-1 (SREBF1) for degradation. | Inferred | |
| LIG_SH2_STAT5 | INSR_HUMAN | 1361 | 1364 | Specificity | Domain hiding | PIP3 (1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate), a product of PI3-kinase, binds to the SH2 domains of PI3K (Phosphatidylinositol 3-kinase regulatory subunit alpha (PIK3R1)) and thereby blocks its interaction with tyrosine-phosphorylated SH2 motif containing proteins. | Inferred | |
| LIG_SH2_IB | CBL_HUMAN | 770 | 780 | Binary | Physicochemical compatibility | Phosphorylation of Y774 in the SH2-binding motif of E3 ubiquitin-protein ligase CBL (CBL) induces binding to the Adapter molecule crk (CRK) protein. | Inferred | |
| LIG_SH2_IC | SHC1_HUMAN | 423 | 435 | Binary | Physicochemical compatibility | Phosphorylation of Y427 in the SH2-binding motif of SHC-transforming protein 1 (SHC1) induces binding to the Growth factor receptor-bound protein 2 (GRB2) protein. | Inferred | |
| LIG_eIF4E_1 | 4EBP1_HUMAN | 54 | 60 | Binary | Physicochemical compatibility | Phosphorylation of S65 flanking the eIF4E-binding motif of Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1) by Serine/threonine-protein kinase mTOR (MTOR) inhibits binding to Eukaryotic translation initiation factor 4E (EIF4E) in response to growth factors and nutrients. This results in release of Eukaryotic translation initiation factor 4E (EIF4E), which associates with other initiation factors to form the eIF-4F complex that mediates initiation of translation. However, disruption of the interaction between Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1) and Eukaryotic translation initiation factor 4E (EIF4E) has been shown to be dependent on hyperphosphorylation of Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1) by FRAP/mTOR, PI3K and ERK pathways. According to the current model, Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1) is phosphorylated on multiple residues in a well-defined order. Basal phosphorylation of T37 and T46 serves as a priming event for subsequent serum-induced phosphorylation of T70, which primes for subsequent phosphorylation of S65. | Curated | |
Insulin signaling pathway (KEGG - rno04910) | ||||||||
| LIG_SH2_GRB2 | IRS1_RAT | 895 | 898 | Binary | Physicochemical compatibility | Phosphorylation of Y895 in the SH2-binding motif of Insulin receptor substrate 1 (Irs1) induces binding to the Growth factor receptor-bound protein 2 (Grb2) protein. | Inferred | |
Jak-STAT signaling pathway (KEGG - hsa04630) | ||||||||
| LIG_TKB | SPY2_HUMAN | 55 | 60 | Binary | Physicochemical compatibility | Phosphorylation of Y55 in Protein sprouty homolog 2 (SPRY2) is necessary for binding to the TKB domain of E3 ubiquitin-protein ligase CBL (CBL). | Inferred | |
| LIG_TKB | SPY2_HUMAN | 55 | 60 | Cumulative | Rheostatic | While phosphorylation of Y55 induces binding, additional phosphorylation of T56 in the TKB-binding motif of Protein sprouty homolog 2 (SPRY2) lowers its binding affinity for E3 ubiquitin-protein ligase CBL (CBL). | Inferred | |
| LIG_SH2_IIA | GHR_HUMAN | 591 | 600 | Binary | Physicochemical compatibility | Phosphorylation of Y595 in the SH2-binding motif of Growth hormone receptor (GHR) induces binding to the Tyrosine-protein phosphatase non-receptor type 11 (PTPN11) protein. | Inferred | |
| LIG_SH2_III | GHR_HUMAN | 428 | 444 | Binary | Physicochemical compatibility | Phosphorylation of Y436 in the SH2-binding motif of Growth hormone receptor (GHR) induces binding to the Signal transducer and activator of transcription 5B (STAT5B) protein. | Inferred | |
| LIG_SH2_III | IL2RB_HUMAN | 531 | 540 | Binary | Physicochemical compatibility | Phosphorylation of Y536 in the SH2-binding motif of Interleukin-2 receptor subunit beta (IL2RB) induces binding to the Signal transducer and activator of transcription 5A (STAT5A) protein. | Inferred | |
| LIG_SH2_III | IL2RB_HUMAN | 528 | 544 | Binary | Physicochemical compatibility | Phosphorylation of Y536 in the SH2-binding motif of Interleukin-2 receptor subunit beta (IL2RB) induces binding to the Signal transducer and activator of transcription 5B (STAT5B) protein. | Inferred | |
| LIG_SH2_III | INGR1_HUMAN | 457 | 461 | Binary | Physicochemical compatibility | Phosphorylation of Y457 in the SH2-binding motif of Interferon gamma receptor 1 (IFNGR1) induces binding to the Signal transducer and activator of transcription 1-alpha/beta (STAT1) protein. | Inferred | |
| LIG_SH2_IE | INAR1_HUMAN | 458 | 474 | Binary | Physicochemical compatibility | Phosphorylation of Y466 in the SH2-binding motif of Interferon alpha/beta receptor 1 (IFNAR1) induces binding to the Non-receptor tyrosine-protein kinase TYK2 (TYK2) protein. | Inferred | |
| LIG_SH2_IE | INAR1_HUMAN | 473 | 489 | Binary | Physicochemical compatibility | Phosphorylation of Y481 in the SH2-binding motif of Interferon alpha/beta receptor 1 (IFNAR1) induces binding to the Non-receptor tyrosine-protein kinase TYK2 (TYK2) protein. | Inferred | |
| LIG_SH2_III | EPOR_HUMAN | 360 | 376 | Binary | Physicochemical compatibility | Phosphorylation of Y368 in the SH2-binding motif of Erythropoietin receptor (EPOR) induces binding to the Signal transducer and activator of transcription 5B (STAT5B) protein. | Inferred | |
| LIG_SH2_III | EPOR_HUMAN | 418 | 434 | Binary | Physicochemical compatibility | Phosphorylation of Y426 in the SH2-binding motif of Erythropoietin receptor (EPOR) induces binding to the Signal transducer and activator of transcription 5B (STAT5B) protein. | Inferred | |
| LIG_SH2_III | EPOR_HUMAN | 496 | 508 | Binary | Physicochemical compatibility | Phosphorylation of Y504 in the SH2-binding motif of Erythropoietin receptor (EPOR) induces binding to the Signal transducer and activator of transcription 5B (STAT5B) protein. | Inferred | |
| LIG_SH2_III | IL4RA_HUMAN | 566 | 585 | Binary | Physicochemical compatibility | Phosphorylation of Y575 in the SH2-binding motif of Interleukin-4 receptor subunit alpha (IL4R) induces binding to the Signal transducer and activator of transcription 6 (STAT6) protein. | Inferred | |
| LIG_SH2_III | IL4RA_HUMAN | 594 | 613 | Binary | Physicochemical compatibility | Phosphorylation of Y603 in the SH2-binding motif of Interleukin-4 receptor subunit alpha (IL4R) induces binding to the Signal transducer and activator of transcription 6 (STAT6) protein. | Inferred | |
| LIG_SH2_III | IL4RA_HUMAN | 622 | 641 | Binary | Physicochemical compatibility | Phosphorylation of Y631 in the SH2-binding motif of Interleukin-4 receptor subunit alpha (IL4R) induces binding to the Signal transducer and activator of transcription 6 (STAT6) protein. | Inferred | |
| LIG_SH2_IIA | IL4RA_HUMAN | 706 | 721 | Binary | Physicochemical compatibility | Phosphorylation of Y713 in the SH2-binding motif of Interleukin-4 receptor subunit alpha (IL4R) induces binding to the Tyrosine-protein phosphatase non-receptor type 11 (PTPN11) protein. | Inferred | |
| LIG_SH2_IIA | CSF3R_HUMAN | 747 | 758 | Binary | Physicochemical compatibility | Phosphorylation of Y752 in the SH2-binding motif of Granulocyte colony-stimulating factor receptor (CSF3R) induces binding to the Suppressor of cytokine signaling 3 (SOCS3) protein. | Inferred | |
| LIG_SH2_III | STA5A_HUMAN | 686 | 702 | Binary | Physicochemical compatibility | Phosphorylation of Y694 in the SH2-binding motif of Signal transducer and activator of transcription 5A (STAT5A) induces binding to the Signal transducer and activator of transcription 5B (STAT5B) protein. | Curated | |
| LIG_SH2_IIA | IL4RA_HUMAN | 706 | 721 | Binary | Physicochemical compatibility | Phosphorylation of Y713 in the SH2-binding motif of Interleukin-4 receptor subunit alpha (IL4R) induces binding to the Tyrosine-protein phosphatase non-receptor type 6 (PTPN6) protein. | Inferred | |
| LIG_SH2_STAT5 | PRLR_HUMAN | 342 | 345 | Binary | Pre‑translational | Alternative Splicing removes the degron motif of Prolactin receptor (PRLR), abrogating binding to Signal transducer and activator of transcription 5A (STAT5A). The PRLR S1a (Isoform Short form 1a of Prolactin receptor (PRLR)) and S1b and (Isoform Short form 1b of Prolactin receptor (PRLR)) isoforms were unable to mediate the transcriptional activation of the beta-casein promoter via the JAK-STAT5 pathway. Therefore these two splice variants act as dominant negatives on the full-length version LF (Isoform 1 of Prolactin receptor (PRLR)). Another study showed that different splice variants of heterodimers (e.g. LF/S1a, LF/S1b) that were able to induce JAK2 phosphorylation but not further signalling events due to lack of STAT recruitment (Qazi et al. (2006) (here)). | Inferred | |
Kinetochore capture of astral microtubules (Reactome - 375302) | ||||||||
| LIG_SxIP_EBH_1 | KIF2C_HUMAN | 93 | 104 | Binary | Physicochemical compatibility | Phosphorylation of S95 and S109 and S111 adjacent to the EB1-binding motif of Kinesin-like protein KIF2C (KIF2C) by Aurora kinase B (AURKB) and Aurora kinase B (AURKB) and Aurora kinase B (AURKB) inhibits its interaction with Microtubule-associated protein RP/EB family member 1 (MAPRE1), thereby inhibiting microtubule tip tracking. | Curated | |
| LIG_SxIP_EBH_1 | CLAP2_HUMAN | 515 | 525 | Binary | Physicochemical compatibility | Phosphorylation of several serine residues surrounding the EB1-binding motifs of CLIP-associating protein 2 (CLASP2) by Glycogen synthase kinase-3 beta (GSK3B) and Glycogen synthase kinase-3 beta (GSK3B) and Glycogen synthase kinase-3 beta (GSK3B) and Glycogen synthase kinase-3 beta (GSK3B) and Glycogen synthase kinase-3 beta (GSK3B) inhibits its interaction with Microtubule-associated protein RP/EB family member 1 (MAPRE1). | Curated | |
Leukocyte transendothelial migration (KEGG - hsa04670) | ||||||||
| LIG_FAT_LD_1 | PAXI_HUMAN | 4 | 12 | Binary | Pre‑translational | Alternative splicing removes the FAK-binding LD motif of Paxillin (PXN), abrogating binding to Focal adhesion kinase 1 (PTK2). | Inferred | |
MAPK signaling pathway (KEGG - hsa04010) | ||||||||
| MOD_ProDKin_1 | MYC_HUMAN | 59 | 65 | Specificity | Altered binding specificity | Phosphorylation of Myc proto-oncogene protein (MYC) at S62 by Mitogen-activated protein kinase 1 (MAPK1) primes MYC for phosphorylation by Glycogen synthase kinase-3 beta (GSK3B), which targets MYC to the SCF ubiquitin ligase complex, F-box/WD repeat-containing protein 7 (FBXW7) that marks MYC for degradation. | Inferred | |
| MOD_GSK3_1 | MYC_HUMAN | 55 | 62 | Specificity | Altered binding specificity | Phosphorylation of Myc proto-oncogene protein (MYC) at S62 by Mitogen-activated protein kinase 1 (MAPK1) primes MYC for phosphorylation by Glycogen synthase kinase-3 beta (GSK3B), which targets MYC to the SCF ubiquitin ligase complex, F-box/WD repeat-containing protein 7 (FBXW7) that marks MYC for degradation. | Inferred | |
| DEG_SCF_FBW7_1 | MYC_HUMAN | 55 | 62 | Specificity | Altered binding specificity | Phosphorylation of Myc proto-oncogene protein (MYC) at S62 by Mitogen-activated protein kinase 1 (MAPK1) primes MYC for phosphorylation by Glycogen synthase kinase-3 beta (GSK3B), which targets MYC to the SCF ubiquitin ligase complex, F-box/WD repeat-containing protein 7 (FBXW7) that marks MYC for degradation. | Inferred | |
| LIG_SH2_IC | EGFR_HUMAN | 1092 | 1100 | Binary | Physicochemical compatibility | Phosphorylation of Y1092 in the SH2-binding motif of Epidermal growth factor receptor (EGFR) induces binding to the Growth factor receptor-bound protein 2 (GRB2) protein. | Curated | |
MAPK signaling pathway (KEGG - mmu04010) | ||||||||
| LIG_14-3-3_3 | KSR1_MOUSE | 294 | 299 | Avidity‑sensing | Phosphorylation of two 14-3-3-binding motifs in Kinase suppressor of Ras 1 (Ksr1) by Q03141 induces high-avidity binding to dimeric 14-3-3 protein beta/alpha (Ywhab). This interaction prevents Kinase suppressor of Ras 1 (Ksr1) to localise to the membrane where it is involved in activation of MAP kinases by Q99N57 in response to growth factors. | Curated | ||
| LIG_14-3-3_3 | KSR1_MOUSE | 389 | 394 | Avidity‑sensing | Phosphorylation of two 14-3-3-binding motifs in Kinase suppressor of Ras 1 (Ksr1) by Q03141 induces high-avidity binding to dimeric 14-3-3 protein beta/alpha (Ywhab). This interaction prevents Kinase suppressor of Ras 1 (Ksr1) to localise to the membrane where it is involved in activation of MAP kinases by Q99N57 in response to growth factors. | Curated | ||
Meiosis (KEGG - sce04113) | ||||||||
| LIG_FHA_1 | RAD9_YEAST | 601 | 607 | Binary | Physicochemical compatibility | Phosphorylation of T603 in the FHA-binding motif of DNA repair protein RAD9 (RAD9) induces binding to the Serine/threonine-protein kinase RAD53 (RAD53) protein. | Curated | |
| LIG_FHA_2 | RAD9_YEAST | 153 | 159 | Binary | Physicochemical compatibility | Phosphorylation of T155 in the FHA-binding motif of DNA repair protein RAD9 (RAD9) induces binding to the Serine/threonine-protein kinase RAD53 (RAD53) protein. | Curated | |
| LIG_FHA_2 | RAD9_YEAST | 190 | 196 | Binary | Physicochemical compatibility | Phosphorylation of T192 in the FHA-binding motif of DNA repair protein RAD9 (RAD9) induces binding to the Serine/threonine-protein kinase RAD53 (RAD53) protein. | Curated | |
Melanogenesis (KEGG - hsa04916) | ||||||||
| MOD_ProDKin_1 | MYC_HUMAN | 59 | 65 | Specificity | Altered binding specificity | Phosphorylation of Myc proto-oncogene protein (MYC) at S62 by Mitogen-activated protein kinase 1 (MAPK1) primes MYC for phosphorylation by Glycogen synthase kinase-3 beta (GSK3B), which targets MYC to the SCF ubiquitin ligase complex, F-box/WD repeat-containing protein 7 (FBXW7) that marks MYC for degradation. | Inferred | |
| MOD_GSK3_1 | MYC_HUMAN | 55 | 62 | Specificity | Altered binding specificity | Phosphorylation of Myc proto-oncogene protein (MYC) at S62 by Mitogen-activated protein kinase 1 (MAPK1) primes MYC for phosphorylation by Glycogen synthase kinase-3 beta (GSK3B), which targets MYC to the SCF ubiquitin ligase complex, F-box/WD repeat-containing protein 7 (FBXW7) that marks MYC for degradation. | Inferred | |
| DEG_SCF_FBW7_1 | MYC_HUMAN | 55 | 62 | Specificity | Altered binding specificity | Phosphorylation of Myc proto-oncogene protein (MYC) at S62 by Mitogen-activated protein kinase 1 (MAPK1) primes MYC for phosphorylation by Glycogen synthase kinase-3 beta (GSK3B), which targets MYC to the SCF ubiquitin ligase complex, F-box/WD repeat-containing protein 7 (FBXW7) that marks MYC for degradation. | Inferred | |
Mismatch repair (KEGG - ko03430) | ||||||||
| LIG_PCNA_PIPBox_1 | DPOD3_HUMAN | 456 | 465 | Binary | Physicochemical compatibility | Phosphorylation of S458 in the PCNA-binding motif of DNA polymerase delta subunit 3 (POLD3) by cAMP subfamily reduces the affinity of binding to the Proliferating cell nuclear antigen (PCNA) and decreases the processivity of the polymerase complex. | Curated | |
Mitotic G1-G1/S phases (Reactome - 453279) | ||||||||
| DOC_CYCLIN_1 | CDN1A_HUMAN | 19 | 22 | Specificity | Competition | Cyclin-dependent kinase inhibitor 1 (CDKN1A) (p21) and the M-phase inducer phosphatase 1 (CDC25A) bind the same site on Cyclin proteins (e.g. G1/S-specific cyclin-E1 (CCNE1)), making their interactions mutually exclusive. | Curated | |
| DOC_CYCLIN_1 | MPIP1_HUMAN | 11 | 15 | Specificity | Competition | Cyclin-dependent kinase inhibitor 1 (CDKN1A) (p21) and the M-phase inducer phosphatase 1 (CDC25A) bind the same site on Cyclin proteins (e.g. G1/S-specific cyclin-E1 (CCNE1)), making their interactions mutually exclusive. | Curated | |
Mitotic Spindle Checkpoint (Reactome - 69618) | ||||||||
| LIG_MAD2 | CDC20_HUMAN | 129 | 137 | Binary | Allostery | Binding of Mad1-bound Closed (C-) Mitotic spindle assembly checkpoint protein MAD2A (MAD2L1) to Open (O-) Mitotic spindle assembly checkpoint protein MAD2A (MAD2L1) switches conformation of the latter to the C conformation, making the binding site for Cell division cycle protein 20 homolog (CDC20) available. This sequesters Cell division cycle protein 20 homolog (CDC20) to the spindle assembly checkpoint and prevents onset of anaphase. | Curated | |
NF-kappa B signaling pathway (KEGG - hsa04064) | ||||||||
| LIG_SH2_STAT5 | LAT_HUMAN | 161 | 164 | Binary | Physicochemical compatibility | Phosphorylation of Y161 in the SH2-binding motif of Linker for activation of T-cells family member 1 (LAT) induces binding to the 1-phosphatidylinositol-4,5-bisphosphate phosphodiesterase gamma-1 (PLCG1) protein. | Curated | |
Natural killer cell mediated cytotoxicity (KEGG - hsa04650) | ||||||||
| LIG_SH2_STAT5 | LAT_HUMAN | 161 | 164 | Binary | Physicochemical compatibility | Phosphorylation of Y161 in the SH2-binding motif of Linker for activation of T-cells family member 1 (LAT) induces binding to the 1-phosphatidylinositol-4,5-bisphosphate phosphodiesterase gamma-1 (PLCG1) protein. | Curated | |
| LIG_TYR_ITIM | KI3L2_HUMAN | 396 | 401 | Binary | Physicochemical compatibility | Phosphorylation of Y398 in the ITIM motif of Killer cell immunoglobulin-like receptor 3DL2 (KIR3DL2) induces binding of Tyrosine-protein phosphatase non-receptor type 6 (PTPN6) via one of its SH2 domains. | Inferred | |
| LIG_TYR_ITAM | FCERG_HUMAN | 62 | 79 | Avidity‑sensing | Phosphorylation of Y65 and Y76 in the ITAM motif of High affinity immunoglobulin epsilon receptor subunit gamma (FCER1G) induces high-avidity binding to the tandem SH2 domains of Tyrosine-protein kinase SYK (SYK). | Curated | ||
| LIG_TYR_ITAM | FCERG_HUMAN | 62 | 79 | Avidity‑sensing | Phosphorylation of Y65 and Y76 in the ITAM motif of High affinity immunoglobulin epsilon receptor subunit gamma (FCER1G) induces high-avidity binding to the tandem SH2 domains of Tyrosine-protein kinase SYK (SYK). | Curated | ||
| LIG_SH2_IC | SHC1_HUMAN | 423 | 435 | Binary | Physicochemical compatibility | Phosphorylation of Y427 in the SH2-binding motif of SHC-transforming protein 1 (SHC1) induces binding to the Growth factor receptor-bound protein 2 (GRB2) protein. | Inferred | |
| LIG_SH2_IA | FCERG_HUMAN | 75 | 79 | Binary | Physicochemical compatibility | Phosphorylation of Y76 in the SH2-binding motif of High affinity immunoglobulin epsilon receptor subunit gamma (FCER1G) induces binding to the Tyrosine-protein kinase SYK (SYK) protein. | Curated | |
Natural killer cell mediated cytotoxicity (KEGG - mmu04650) | ||||||||
| LIG_SH2_GRB2 | LAT_MOUSE | 175 | 178 | Binary | Physicochemical compatibility | Phosphorylation of Y175 in the SH2-binding motif of Linker for activation of T-cells family member 1 (Lat) induces binding to the Growth factor receptor-bound protein 2 (Grb2) protein. | Inferred | |
| LIG_SH2_GRB2 | LAT_MOUSE | 195 | 198 | Binary | Physicochemical compatibility | Phosphorylation of Y195 in the SH2-binding motif of Linker for activation of T-cells family member 1 (Lat) induces binding to the Growth factor receptor-bound protein 2 (Grb2) protein. | Inferred | |
| LIG_SH2_GRB2 | LAT_MOUSE | 235 | 238 | Binary | Physicochemical compatibility | Phosphorylation of Y235 in the SH2-binding motif of Linker for activation of T-cells family member 1 (Lat) induces binding to the Growth factor receptor-bound protein 2 (Grb2) protein. | Inferred | |
Neuroactive ligand-receptor interaction (KEGG - hsa04080) | ||||||||
| TRG_ER_diArg_1 | GABR1_HUMAN | 923 | 926 | Specificity | Motif hiding | Interaction of the GABA receptor R2 subunit (Gamma-aminobutyric acid type B receptor subunit 2 (GABBR2)) with the R1 subunit (Gamma-aminobutyric acid type B receptor subunit 1 (GABBR1)) via coiled-coil forming domains masks the ER retention motif in the R1 subunit (Gamma-aminobutyric acid type B receptor subunit 1 (GABBR1)), thereby promoting surface expression of fully assembled GABA receptors. | Inferred | |
Neurotrophin signaling pathway (KEGG - hsa04722) | ||||||||
| MOD_GSK3_1 | P53_HUMAN | 30 | 37 | Binary | Physicochemical compatibility | Phosphorylation of Cellular tumor antigen p53 (TP53) at S37 primes the protein for phosphorylation at S33 by Glycogen synthase kinase-3 beta (GSK3B). | Inferred | |
| MOD_GSK3_1 | JUN_HUMAN | 236 | 243 | Binary | Physicochemical compatibility | Phosphorylation of Transcription factor AP-1 (JUN) at S243 primes the protein for phosphorylation at T239 by Glycogen synthase kinase-3 beta (GSK3B). | Inferred | |
| LIG_PTB_Phospho_1 | NTRK1_HUMAN | 490 | 496 | Binary | Physicochemical compatibility | Phosphorylation of Y496 in the PTB-binding motif of High affinity nerve growth factor receptor (NTRK1) induces binding to the SHC-transforming protein 1 (SHC1) protein. | Inferred | |
| MOD_ProDKin_1 | MYC_HUMAN | 59 | 65 | Specificity | Altered binding specificity | Phosphorylation of Myc proto-oncogene protein (MYC) at S62 by Mitogen-activated protein kinase 1 (MAPK1) primes MYC for phosphorylation by Glycogen synthase kinase-3 beta (GSK3B), which targets MYC to the SCF ubiquitin ligase complex, F-box/WD repeat-containing protein 7 (FBXW7) that marks MYC for degradation. | Inferred | |
| MOD_GSK3_1 | MYC_HUMAN | 55 | 62 | Specificity | Altered binding specificity | Phosphorylation of Myc proto-oncogene protein (MYC) at S62 by Mitogen-activated protein kinase 1 (MAPK1) primes MYC for phosphorylation by Glycogen synthase kinase-3 beta (GSK3B), which targets MYC to the SCF ubiquitin ligase complex, F-box/WD repeat-containing protein 7 (FBXW7) that marks MYC for degradation. | Inferred | |
| DEG_SCF_FBW7_1 | MYC_HUMAN | 55 | 62 | Specificity | Altered binding specificity | Phosphorylation of Myc proto-oncogene protein (MYC) at S62 by Mitogen-activated protein kinase 1 (MAPK1) primes MYC for phosphorylation by Glycogen synthase kinase-3 beta (GSK3B), which targets MYC to the SCF ubiquitin ligase complex, F-box/WD repeat-containing protein 7 (FBXW7) that marks MYC for degradation. | Inferred | |
| MOD_GSK3_1 | JUN_HUMAN | 236 | 243 | Specificity | Altered binding specificity | Transcription factor AP-1 (JUN) is primed by an unknown kinase for phosphorylation by Glycogen synthase kinase-3 beta (GSK3B), which targets JUN to the SCF ubiquitin ligase complex, F-box/WD repeat-containing protein 7 (FBXW7) that marks JUN for degradation. In v-Jun (Viral jun-transforming protein (JUN)) the residue corresponding to S243 is mutated to phenylalanine, which protects v-Jun (JUN) from degradation. | Inferred | |
| DEG_SCF_FBW7_1 | JUN_HUMAN | 236 | 243 | Specificity | Altered binding specificity | Transcription factor AP-1 (JUN) is primed by an unknown kinase for phosphorylation by Glycogen synthase kinase-3 beta (GSK3B), which targets JUN to the SCF ubiquitin ligase complex, F-box/WD repeat-containing protein 7 (FBXW7) that marks JUN for degradation. In v-Jun (Viral jun-transforming protein (JUN)) the residue corresponding to S243 is mutated to phenylalanine, which protects v-Jun (JUN) from degradation. | Inferred | |
| LIG_14-3-3_3 | IRS1_HUMAN | 371 | 376 | Avidity‑sensing | Phosphorylation of two 14-3-3-binding motifs in Insulin receptor substrate 1 (IRS1) induces high-avidity binding to dimeric 14-3-3 protein epsilon (YWHAE). | Inferred | ||
| LIG_14-3-3_3 | IRS1_HUMAN | 638 | 643 | Avidity‑sensing | Phosphorylation of two 14-3-3-binding motifs in Insulin receptor substrate 1 (IRS1) induces high-avidity binding to dimeric 14-3-3 protein epsilon (YWHAE). | Inferred | ||
| LIG_SH2_IIB | NTRK1_HUMAN | 782 | 796 | Binary | Physicochemical compatibility | Phosphorylation of Y791 in the SH2-binding motif of High affinity nerve growth factor receptor (NTRK1) induces binding to the SHC-transforming protein 1 (SHC1) protein. | Inferred | |
| LIG_SH2_IB | NTRK1_HUMAN | 783 | 796 | Binary | Physicochemical compatibility | Phosphorylation of Y791 in the SH2-binding motif of High affinity nerve growth factor receptor (NTRK1) induces binding to the Megakaryocyte-associated tyrosine-protein kinase (MATK) protein. | Inferred | |
| LIG_SH2_IC | SHC1_HUMAN | 423 | 435 | Binary | Physicochemical compatibility | Phosphorylation of Y427 in the SH2-binding motif of SHC-transforming protein 1 (SHC1) induces binding to the Growth factor receptor-bound protein 2 (GRB2) protein. | Inferred | |
| LIG_SH2_IC | FRS2_HUMAN | 191 | 200 | Binary | Physicochemical compatibility | Phosphorylation of Y196 in the SH2-binding motif of Fibroblast growth factor receptor substrate 2 (FRS2) induces binding to the Growth factor receptor-bound protein 2 (GRB2) protein. | Inferred | |
| LIG_SH2_IC | FRS2_HUMAN | 301 | 310 | Binary | Physicochemical compatibility | Phosphorylation of Y306 in the SH2-binding motif of Fibroblast growth factor receptor substrate 2 (FRS2) induces binding to the Growth factor receptor-bound protein 2 (GRB2) protein. | Inferred | |
| LIG_SH2_IC | FRS2_HUMAN | 345 | 355 | Binary | Physicochemical compatibility | Phosphorylation of Y349 in the SH2-binding motif of Fibroblast growth factor receptor substrate 2 (FRS2) induces binding to the Growth factor receptor-bound protein 2 (GRB2) protein. | Inferred | |
| LIG_SH2_IC | FRS2_HUMAN | 385 | 395 | Binary | Physicochemical compatibility | Phosphorylation of Y392 in the SH2-binding motif of Fibroblast growth factor receptor substrate 2 (FRS2) induces binding to the Growth factor receptor-bound protein 2 (GRB2) protein. | Inferred | |
| LIG_SH2_IIA | FRS2_HUMAN | 431 | 440 | Binary | Physicochemical compatibility | Phosphorylation of Y436 in the SH2-binding motif of Fibroblast growth factor receptor substrate 2 (FRS2) induces binding to the Tyrosine-protein phosphatase non-receptor type 11 (PTPN11) protein. | Inferred | |
| LIG_SH2_IIA | FRS2_HUMAN | 465 | 475 | Binary | Physicochemical compatibility | Phosphorylation of Y471 in the SH2-binding motif of Fibroblast growth factor receptor substrate 2 (FRS2) induces binding to the Tyrosine-protein phosphatase non-receptor type 11 (PTPN11) protein. | Inferred | |
Neurotrophin signaling pathway (KEGG - rno04722) | ||||||||
| LIG_SH2_GRB2 | IRS1_RAT | 895 | 898 | Binary | Physicochemical compatibility | Phosphorylation of Y895 in the SH2-binding motif of Insulin receptor substrate 1 (Irs1) induces binding to the Growth factor receptor-bound protein 2 (Grb2) protein. | Inferred | |
Nucleotide excision repair (KEGG - ko03420) | ||||||||
| LIG_PCNA_PIPBox_1 | DPOD3_HUMAN | 456 | 465 | Binary | Physicochemical compatibility | Phosphorylation of S458 in the PCNA-binding motif of DNA polymerase delta subunit 3 (POLD3) by cAMP subfamily reduces the affinity of binding to the Proliferating cell nuclear antigen (PCNA) and decreases the processivity of the polymerase complex. | Curated | |
Oocyte meiosis (KEGG - hsa04114) | ||||||||
| DEG_SCF_TRCP1_1 | FBX5_HUMAN | 144 | 149 | Binary | Physicochemical compatibility | Dual phosphorylation of S145 and S149 in the TrCP1-binding motif of F-box only protein 5 (FBXO5) targets the protein to the SCF ubiquitin ligase complex, which marks it for degradation. | Curated | |
Osteoclast differentiation (KEGG - hsa04380) | ||||||||
| LIG_TYR_ITAM | FCG2A_HUMAN | 285 | 307 | Avidity‑sensing | Phosphorylation of Y288 and Y304 in the ITAM motif of Low affinity immunoglobulin gamma Fc region receptor II-a (FCGR2A) induces high-avidity binding to the tandem SH2 domains of Tyrosine-protein kinase SYK (SYK). | Curated | ||
| LIG_TYR_ITAM | FCG2A_HUMAN | 285 | 307 | Avidity‑sensing | Phosphorylation of Y288 and Y304 in the ITAM motif of Low affinity immunoglobulin gamma Fc region receptor II-a (FCGR2A) induces high-avidity binding to the tandem SH2 domains of Tyrosine-protein kinase SYK (SYK). | Curated | ||
| LIG_SH2_III | INGR1_HUMAN | 457 | 461 | Binary | Physicochemical compatibility | Phosphorylation of Y457 in the SH2-binding motif of Interferon gamma receptor 1 (IFNGR1) induces binding to the Signal transducer and activator of transcription 1-alpha/beta (STAT1) protein. | Inferred | |
| LIG_SH2_IE | INAR1_HUMAN | 458 | 474 | Binary | Physicochemical compatibility | Phosphorylation of Y466 in the SH2-binding motif of Interferon alpha/beta receptor 1 (IFNAR1) induces binding to the Non-receptor tyrosine-protein kinase TYK2 (TYK2) protein. | Inferred | |
| LIG_SH2_IE | INAR1_HUMAN | 473 | 489 | Binary | Physicochemical compatibility | Phosphorylation of Y481 in the SH2-binding motif of Interferon alpha/beta receptor 1 (IFNAR1) induces binding to the Non-receptor tyrosine-protein kinase TYK2 (TYK2) protein. | Inferred | |
Osteoclast differentiation (KEGG - mmu04380) | ||||||||
| LIG_TRAF2_3 | CYLD_MOUSE | 449 | 453 | Binary | Pre‑translational | Alternative splicing removes the TRAF2-binding motif of Ubiquitin carboxyl-terminal hydrolase CYLD (Cyld), abrogating binding to TNF receptor-associated factor 2 (Traf2). Mice expressing solely the alternatively spliced Isoform 3 of Ubiquitin carboxyl-terminal hydrolase CYLD (Cyld) (sCYLD) show an altered B-cell expansion profile and have more stable NF-kB proteins. | Inferred | |
PI3K-Akt signaling pathway (KEGG - hsa04151) | ||||||||
| MOD_GSK3_1 | MYC_HUMAN | 55 | 62 | Binary | Physicochemical compatibility | Phosphorylation of Myc proto-oncogene protein (MYC) at S62 primes the protein for phosphorylation at T58 by Glycogen synthase kinase-3 beta (GSK3B). | Curated | |
| MOD_GSK3_1 | P53_HUMAN | 30 | 37 | Binary | Physicochemical compatibility | Phosphorylation of Cellular tumor antigen p53 (TP53) at S37 primes the protein for phosphorylation at S33 by Glycogen synthase kinase-3 beta (GSK3B). | Inferred | |
| MOD_GSK3_1 | CCNE1_HUMAN | 392 | 399 | Binary | Physicochemical compatibility | Phosphorylation of G1/S-specific cyclin-E1 (CCNE1) at S399 by Cyclin-dependent kinase 2 (CDK2) primes the protein for subsequent phosphorylation at T395 by Glycogen synthase kinase-3 beta (GSK3B). | Inferred | |
| LIG_14-3-3_2 | TF65_HUMAN | 41 | 47 | Binary | Physicochemical compatibility | Phosphorylation of S45 by in the 14-3-3-binding motif of Transcription factor p65 (RELA) induces binding to the 14-3-3 protein eta (YWHAH) protein. | Inferred | |
| LIG_PTB_Phospho_1 | IL4RA_HUMAN | 491 | 497 | Binary | Physicochemical compatibility | Phosphorylation of Y497 in the PTB-binding motif of Interleukin-4 receptor subunit alpha (IL4R) induces binding to the Insulin receptor substrate 1 (IRS1) protein. | Inferred | |
| LIG_14-3-3_1 | RAF1_HUMAN | 256 | 261 | Binary | Physicochemical compatibility | Phosphorylation of S257 in the 14-3-3-binding motif of RAF proto-oncogene serine/threonine-protein kinase (RAF1) abolishes binding of the motif, phosphorylated at S259, to 14-3-3 protein zeta/delta (YWHAZ). | Inferred | |
| MOD_GSK3_1 | CCNE1_HUMAN | 377 | 384 | Specificity | Altered binding specificity | Phosphorylation of Isoform E-S of G1/S-specific cyclin-E1 (CCNE1) at S384 by CDK2 primes CCNE1 for phosphorylation by Glycogen synthase kinase-3 beta (GSK3B) at T380, which creates a recognition site for F box proteins of the SCF ubiquitin ligase complex (F-box/WD repeat-containing protein 7 (FBXW7)) that target CCNE1 for degradation. | Inferred | |
| DEG_SCF_FBW7_1 | CCNE1_HUMAN | 378 | 384 | Specificity | Altered binding specificity | Phosphorylation of Isoform E-S of G1/S-specific cyclin-E1 (CCNE1) at S384 by CDK2 primes CCNE1 for phosphorylation by Glycogen synthase kinase-3 beta (GSK3B) at T380, which creates a recognition site for F box proteins of the SCF ubiquitin ligase complex (F-box/WD repeat-containing protein 7 (FBXW7)) that target CCNE1 for degradation. | Inferred | |
| MOD_ProDKin_1 | MYC_HUMAN | 59 | 65 | Specificity | Altered binding specificity | Phosphorylation of Myc proto-oncogene protein (MYC) at S62 by Mitogen-activated protein kinase 1 (MAPK1) primes MYC for phosphorylation by Glycogen synthase kinase-3 beta (GSK3B), which targets MYC to the SCF ubiquitin ligase complex, F-box/WD repeat-containing protein 7 (FBXW7) that marks MYC for degradation. | Inferred | |
| MOD_GSK3_1 | MYC_HUMAN | 55 | 62 | Specificity | Altered binding specificity | Phosphorylation of Myc proto-oncogene protein (MYC) at S62 by Mitogen-activated protein kinase 1 (MAPK1) primes MYC for phosphorylation by Glycogen synthase kinase-3 beta (GSK3B), which targets MYC to the SCF ubiquitin ligase complex, F-box/WD repeat-containing protein 7 (FBXW7) that marks MYC for degradation. | Inferred | |
| DEG_SCF_FBW7_1 | MYC_HUMAN | 55 | 62 | Specificity | Altered binding specificity | Phosphorylation of Myc proto-oncogene protein (MYC) at S62 by Mitogen-activated protein kinase 1 (MAPK1) primes MYC for phosphorylation by Glycogen synthase kinase-3 beta (GSK3B), which targets MYC to the SCF ubiquitin ligase complex, F-box/WD repeat-containing protein 7 (FBXW7) that marks MYC for degradation. | Inferred | |
| MOD_GSK3_1 | CCNE1_HUMAN | 392 | 399 | Specificity | Altered binding specificity | Phosphorylation of G1/S-specific cyclin-E1 (CCNE1) at S399 generates a docking site for Glycogen synthase kinase-3 beta (GSK3B). Subsequent phosphorylation of CCNE1 by Glycogen synthase kinase-3 beta (GSK3B) at T395 switches the specificity of CCNE1 to the F-box/WD repeat-containing protein 7 (FBXW7), which recruits CCNE1 to the SCF ubiquitin ligase complex to mark CCNE1 for degradation. | Inferred | |
| DEG_SCF_FBW7_1 | CCNE1_HUMAN | 393 | 399 | Specificity | Altered binding specificity | Phosphorylation of G1/S-specific cyclin-E1 (CCNE1) at S399 generates a docking site for Glycogen synthase kinase-3 beta (GSK3B). Subsequent phosphorylation of CCNE1 by Glycogen synthase kinase-3 beta (GSK3B) at T395 switches the specificity of CCNE1 to the F-box/WD repeat-containing protein 7 (FBXW7), which recruits CCNE1 to the SCF ubiquitin ligase complex to mark CCNE1 for degradation. | Inferred | |
| LIG_RGD | EDIL3_HUMAN | 96 | 98 | Pre‑assembly | Composite binding site formation | Binding of EGF-like repeat and discoidin I-like domain-containing protein 3 (EDIL3) to integrin receptors depends on pre-assembly of Integrin alpha-V (ITGAV)-Integrin beta-3 (ITGB3) heterodimers, since association of the integrin alpha and beta subunits results in the formation of a composite binding site for the RGD motif in the ligand. | Inferred | |
| LIG_RGD | DISG_TRIAB | 51 | 53 | Pre‑assembly | Composite binding site formation | Binding of Disintegrin albolabrin to integrin receptors depends on pre-assembly of Integrin alpha-IIb (ITGA2B)-Integrin beta-3 (ITGB3) heterodimers, since association of the integrin alpha and beta subunits results in the formation of a composite binding site for the RGD motif in the ligand. | Inferred | |
| LIG_RGD | FINC_HUMAN | 1524 | 1526 | Pre‑assembly | Composite binding site formation | Binding of Fibronectin (FN1) to integrin receptors depends on pre-assembly of Integrin alpha-V (ITGAV)-Integrin beta-3 (ITGB3) heterodimers, since association of the integrin alpha and beta subunits results in the formation of a composite binding site for the RGD motif in the ligand. | Inferred | |
| LIG_RGD | POLG_FMDVO | 869 | 871 | Pre‑assembly | Composite binding site formation | Binding of Genome polyprotein to integrin receptors depends on pre-assembly of Integrin alpha-V (ITGAV)-Integrin beta-3 (ITGB3) heterodimers, since association of the integrin alpha and beta subunits results in the formation of a composite binding site for the RGD motif in the ligand. | Inferred | |
| LIG_RGD | VTNC_HUMAN | 64 | 66 | Pre‑assembly | Composite binding site formation | Binding of Vitronectin (VTN) to integrin receptors depends on pre-assembly of Integrin alpha-V (ITGAV)-Integrin beta-3 (ITGB3) heterodimers, since association of the integrin alpha and beta subunits results in the formation of a composite binding site for the RGD motif in the ligand. | Inferred | |
| LIG_RGD | VWF_HUMAN | 2507 | 2509 | Pre‑assembly | Composite binding site formation | Binding of von Willebrand factor (VWF) to integrin receptors depends on pre-assembly of Integrin alpha-V (ITGAV)-Integrin beta-3 (ITGB3) heterodimers, since association of the integrin alpha and beta subunits results in the formation of a composite binding site for the RGD motif in the ligand. | Inferred | |
| LIG_RGD | OSTP_HUMAN | 159 | 161 | Pre‑assembly | Composite binding site formation | Binding of EGF-like repeat and discoidin I-like domain-containing protein 3 (EDIL3) to integrin receptors depends on pre-assembly of Integrin alpha-V (ITGAV)-Integrin beta-3 (ITGB3) heterodimers, since association of the integrin alpha and beta subunits results in the formation of a composite binding site for the RGD motif in the ligand. | Inferred | |
| LIG_RGD | VME1_TRIEL | 459 | 461 | Pre‑assembly | Composite binding site formation | Binding of Zinc metalloproteinase/disintegrin to integrin receptors depends on pre-assembly of Integrin alpha-IIb (ITGA2B)-Integrin beta-3 (ITGB3) heterodimers, since association of the integrin alpha and beta subunits results in the formation of a composite binding site for the RGD motif in the ligand. | Inferred | |
| LIG_RGD | DISB_TRIGA | 51 | 53 | Pre‑assembly | Composite binding site formation | Binding of Disintegrin trigramin-beta-2 to integrin receptors depends on pre-assembly of Integrin alpha-IIb (ITGA2B)-Integrin beta-3 (ITGB3) heterodimers, since association of the integrin alpha and beta subunits results in the formation of a composite binding site for the RGD motif in the ligand. | Inferred | |
| LIG_RGD | POLG_CXA9 | 858 | 860 | Pre‑assembly | Composite binding site formation | Binding of Genome polyprotein to integrin receptors depends on pre-assembly of Integrin alpha-V (ITGAV)-Integrin beta-6 (ITGB6) heterodimers, since association of the integrin alpha and beta subunits results in the formation of a composite binding site for the RGD motif in the ligand. | Inferred | |
| LIG_RGD | POLG_HPE1H | 764 | 766 | Pre‑assembly | Composite binding site formation | Binding of Genome polyprotein to integrin receptors depends on pre-assembly of Integrin alpha-V (ITGAV)-Integrin beta-6 (ITGB6) heterodimers, since association of the integrin alpha and beta subunits results in the formation of a composite binding site for the RGD motif in the ligand. | Inferred | |
| LIG_Integrin_isoDGR_1 | FINC_HUMAN | 263 | 265 | Pre‑assembly | Composite binding site formation | Binding of Fibronectin (FN1) to integrin receptors depends on pre-assembly of Integrin alpha-V (ITGAV)-Integrin beta-3 (ITGB3) heterodimers, since association of the integrin alpha and beta subunits results in the formation of a composite binding site for the RGD motif in the ligand. | Inferred | |
| LIG_SH2_STAT5 | INSR_HUMAN | 1361 | 1364 | Specificity | Domain hiding | PIP3 (1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate), a product of PI3-kinase, binds to the SH2 domains of PI3K (Phosphatidylinositol 3-kinase regulatory subunit alpha (PIK3R1)) and thereby blocks its interaction with tyrosine-phosphorylated SH2 motif containing proteins. | Inferred | |
| LIG_14-3-3_1 | RAF1_HUMAN | 256 | 261 | Avidity‑sensing | Phosphorylation of two 14-3-3-binding motifs in RAF proto-oncogene serine/threonine-protein kinase (RAF1) in response to growth factors induces high-avidity binding to dimeric 14-3-3 protein zeta/delta (YWHAZ), with pS621 being the high-affinity interaction site. This interaction locks RAF proto-oncogene serine/threonine-protein kinase (RAF1) in an inhibited conformation. | Curated | ||
| LIG_14-3-3_1 | RAF1_HUMAN | 618 | 623 | Avidity‑sensing | Phosphorylation of two 14-3-3-binding motifs in RAF proto-oncogene serine/threonine-protein kinase (RAF1) in response to growth factors induces high-avidity binding to dimeric 14-3-3 protein zeta/delta (YWHAZ), with pS621 being the high-affinity interaction site. This interaction locks RAF proto-oncogene serine/threonine-protein kinase (RAF1) in an inhibited conformation. | Curated | ||
| LIG_14-3-3_3 | FOXO3_HUMAN | 250 | 255 | Avidity‑sensing | Phosphorylation of two 14-3-3-binding motifs in Forkhead box protein O3 (FOXO3) by RAC-alpha serine/threonine-protein kinase (AKT1) induces high-avidity binding to dimeric 14-3-3 protein beta/alpha (YWHAB). This interaction results in cytoplasmic retention and inactivation of Forkhead box protein O3 (FOXO3). | Curated | ||
| LIG_14-3-3_3 | FOXO3_HUMAN | 29 | 34 | Avidity‑sensing | Phosphorylation of two 14-3-3-binding motifs in Forkhead box protein O3 (FOXO3) by RAC-alpha serine/threonine-protein kinase (AKT1) induces high-avidity binding to dimeric 14-3-3 protein beta/alpha (YWHAB). This interaction results in cytoplasmic retention and inactivation of Forkhead box protein O3 (FOXO3). | Curated | ||
| LIG_14-3-3_3 | IRS1_HUMAN | 371 | 376 | Avidity‑sensing | Phosphorylation of two 14-3-3-binding motifs in Insulin receptor substrate 1 (IRS1) induces high-avidity binding to dimeric 14-3-3 protein epsilon (YWHAE). | Inferred | ||
| LIG_14-3-3_3 | IRS1_HUMAN | 638 | 643 | Avidity‑sensing | Phosphorylation of two 14-3-3-binding motifs in Insulin receptor substrate 1 (IRS1) induces high-avidity binding to dimeric 14-3-3 protein epsilon (YWHAE). | Inferred | ||
| LIG_SH2_IC | EGFR_HUMAN | 1092 | 1100 | Binary | Physicochemical compatibility | Phosphorylation of Y1092 in the SH2-binding motif of Epidermal growth factor receptor (EGFR) induces binding to the Growth factor receptor-bound protein 2 (GRB2) protein. | Curated | |
| LIG_SH2_IE | EGFR_HUMAN | 1008 | 1024 | Binary | Physicochemical compatibility | Phosphorylation of Y1016 in the SH2-binding motif of Epidermal growth factor receptor (EGFR) induces binding to the Tyrosine-protein kinase JAK1 (JAK1) protein. | Inferred | |
| LIG_SH2_IE | EGFR_HUMAN | 1008 | 1024 | Binary | Physicochemical compatibility | Phosphorylation of Y1016 in the SH2-binding motif of Epidermal growth factor receptor (EGFR) induces binding to the Tyrosine-protein kinase JAK2 (JAK2) protein. | Inferred | |
| LIG_SH2_IC | MET_HUMAN | 1351 | 1360 | Binary | Physicochemical compatibility | Phosphorylation of Y1356 in the SH2-binding motif of Hepatocyte growth factor receptor (MET) induces binding to the Growth factor receptor-bound protein 2 (GRB2) protein. | Inferred | |
| LIG_SH2_IIA | PGFRB_HUMAN | 751 | 755 | Binary | Physicochemical compatibility | Phosphorylation of Y751 in the SH2-binding motif of Platelet-derived growth factor receptor beta (PDGFRB) induces binding to the Phosphatidylinositol 3-kinase regulatory subunit alpha (PIK3R1) protein. | Inferred | |
| TRG_NLS | CDN1B_HUMAN | 152 | 166 | Specificity | Motif hiding | Phosphorylation of a 14-3-3-binding motif in the NLS of Cyclin-dependent kinase inhibitor 1B (CDKN1B) by RAC-alpha serine/threonine-protein kinase (AKT1) induces binding of 14-3-3 protein gamma (YWHAG), which hides the NLS and prevents binding to Importin subunit alpha-1 (KPNA1), thereby mediating cytoplasmic retention of Cyclin-dependent kinase inhibitor 1B (CDKN1B). Binding of 14-3-3 dimer involves an additional C-terminal 14-3-3-binding motif (see switch details). | Curated | |
| LIG_14-3-3_3 | CDN1B_HUMAN | 154 | 159 | Specificity | Motif hiding | Phosphorylation of a 14-3-3-binding motif in the NLS of Cyclin-dependent kinase inhibitor 1B (CDKN1B) by RAC-alpha serine/threonine-protein kinase (AKT1) induces binding of 14-3-3 protein gamma (YWHAG), which hides the NLS and prevents binding to Importin subunit alpha-1 (KPNA1), thereby mediating cytoplasmic retention of Cyclin-dependent kinase inhibitor 1B (CDKN1B). Binding of 14-3-3 dimer involves an additional C-terminal 14-3-3-binding motif (see switch details). | Curated | |
| LIG_14-3-3_3 | CDN1B_HUMAN | 154 | 159 | Avidity‑sensing | Phosphorylation of two 14-3-3-binding motifs in Cyclin-dependent kinase inhibitor 1B (CDKN1B) by RAC-alpha serine/threonine-protein kinase (AKT1) and ribosomal protein S6 kinases (Ribosomal protein S6 kinase alpha-1 (RPS6KA1), Ribosomal protein S6 kinase alpha-3 (RPS6KA3)) induces binding of 14-3-3 dimer. Binding of 14-3-3 results in cytoplasmic localisation of Cyclin-dependent kinase inhibitor 1B (CDKN1B) (see switch details), thereby alleviating Cyclin-dependent kinase inhibitor 1B (CDKN1B)-mediated inhibition of cyclin-dependent kinases and cell cycle progression. | Curated | ||
| LIG_14-3-3_3 | CDN1B_HUMAN | 193 | 198 | Avidity‑sensing | Phosphorylation of two 14-3-3-binding motifs in Cyclin-dependent kinase inhibitor 1B (CDKN1B) by RAC-alpha serine/threonine-protein kinase (AKT1) and ribosomal protein S6 kinases (Ribosomal protein S6 kinase alpha-1 (RPS6KA1), Ribosomal protein S6 kinase alpha-3 (RPS6KA3)) induces binding of 14-3-3 dimer. Binding of 14-3-3 results in cytoplasmic localisation of Cyclin-dependent kinase inhibitor 1B (CDKN1B) (see switch details), thereby alleviating Cyclin-dependent kinase inhibitor 1B (CDKN1B)-mediated inhibition of cyclin-dependent kinases and cell cycle progression. | Curated | ||
| LIG_eIF4E_1 | 4EBP1_HUMAN | 54 | 60 | Binary | Physicochemical compatibility | Phosphorylation of S65 flanking the eIF4E-binding motif of Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1) by Serine/threonine-protein kinase mTOR (MTOR) inhibits binding to Eukaryotic translation initiation factor 4E (EIF4E) in response to growth factors and nutrients. This results in release of Eukaryotic translation initiation factor 4E (EIF4E), which associates with other initiation factors to form the eIF-4F complex that mediates initiation of translation. However, disruption of the interaction between Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1) and Eukaryotic translation initiation factor 4E (EIF4E) has been shown to be dependent on hyperphosphorylation of Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1) by FRAP/mTOR, PI3K and ERK pathways. According to the current model, Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1) is phosphorylated on multiple residues in a well-defined order. Basal phosphorylation of T37 and T46 serves as a priming event for subsequent serum-induced phosphorylation of T70, which primes for subsequent phosphorylation of S65. | Curated | |
PI3K-Akt signaling pathway (KEGG - mmu04151) | ||||||||
| LIG_RGD | FINC_MOUSE | 1614 | 1616 | Pre‑assembly | Composite binding site formation | Binding of Fibronectin (Fn1) to integrin receptors depends on pre-assembly of Integrin alpha-5 (Itga5)-Integrin beta-1 (Itgb1) heterodimers, since association of the integrin alpha and beta subunits results in the formation of a composite binding site for the RGD motif in the ligand. | Inferred | |
| LIG_RGD | VTNC_MOUSE | 64 | 66 | Pre‑assembly | Composite binding site formation | Binding of Vitronectin (Vtn) to integrin receptors depends on pre-assembly of Integrin alpha-V (Itgav)-Integrin beta-3 (Itgb3) heterodimers, since association of the integrin alpha and beta subunits results in the formation of a composite binding site for the RGD motif in the ligand. | Inferred | |
| LIG_14-3-3_3 | KSR1_MOUSE | 294 | 299 | Avidity‑sensing | Phosphorylation of two 14-3-3-binding motifs in Kinase suppressor of Ras 1 (Ksr1) by Q03141 induces high-avidity binding to dimeric 14-3-3 protein beta/alpha (Ywhab). This interaction prevents Kinase suppressor of Ras 1 (Ksr1) to localise to the membrane where it is involved in activation of MAP kinases by Q99N57 in response to growth factors. | Curated | ||
| LIG_14-3-3_3 | KSR1_MOUSE | 389 | 394 | Avidity‑sensing | Phosphorylation of two 14-3-3-binding motifs in Kinase suppressor of Ras 1 (Ksr1) by Q03141 induces high-avidity binding to dimeric 14-3-3 protein beta/alpha (Ywhab). This interaction prevents Kinase suppressor of Ras 1 (Ksr1) to localise to the membrane where it is involved in activation of MAP kinases by Q99N57 in response to growth factors. | Curated | ||
| LIG_14-3-3_1 | BAD_MOUSE | 133 | 138 | Binary | Physicochemical compatibility | Phosphorylation of S136 in Bcl2 antagonist of cell death (Bad) by RAC-alpha serine/threonine-protein kinase (Akt1) in response to survival and growth signals such as Interleukin-3 (Il3) induces binding to 14-3-3 protein theta (Ywhaq). Binding of 14-3-3 protein theta (Ywhaq) results in dissociation of Bcl2 antagonist of cell death (Bad) from Bcl-2-like protein 1 (Bcl2l1), and thereby inhibits the pro-apoptotic activity of Bcl2 antagonist of cell death (Bad) by allowing liberated Bcl-2-like protein 1 (Bcl2l1) to exert its anti-apoptotic effect on pro-apoptotic proteins like Apoptosis regulator BAX (Bax). | Inferred | |
PI3K-Akt signaling pathway (KEGG - rno04151) | ||||||||
| LIG_14-3-3_1 | BAD_RAT | 134 | 139 | Binary | Physicochemical compatibility | Phosphorylation of S137 by RAC-alpha serine/threonine-protein kinase (Akt1) in the 14-3-3-binding motif of Bcl2 antagonist of cell death (Bad) induces binding to the 14-3-3 protein beta/alpha (YWHAB) protein. This interaction inhibits the pro-apoptotic activity of Bcl2 antagonist of cell death (Bad). | Curated | |
| LIG_SH2_GRB2 | IRS1_RAT | 895 | 898 | Binary | Physicochemical compatibility | Phosphorylation of Y895 in the SH2-binding motif of Insulin receptor substrate 1 (Irs1) induces binding to the Growth factor receptor-bound protein 2 (Grb2) protein. | Inferred | |
Peroxisome (KEGG - hsa04146) | ||||||||
| TRG_PTS1 | AMACR_HUMAN | 379 | 382 | Binary | Pre‑translational | Alternative splicing removes the type 1 peroxisomal targeting signal (PTS1) of Alpha-methylacyl-CoA racemase (AMACR), abrogating binding to Peroxisomal targeting signal 1 receptor (PEX5) and import into the peroxisome. Only the major AMACR IA (also known as Isoform 1 of Alpha-methylacyl-CoA racemase (AMACR)) form localises to the peroxisome. | Inferred | |
Phagosome (KEGG - hsa04145) | ||||||||
| LIG_RGD | EDIL3_HUMAN | 96 | 98 | Pre‑assembly | Composite binding site formation | Binding of EGF-like repeat and discoidin I-like domain-containing protein 3 (EDIL3) to integrin receptors depends on pre-assembly of Integrin alpha-V (ITGAV)-Integrin beta-3 (ITGB3) heterodimers, since association of the integrin alpha and beta subunits results in the formation of a composite binding site for the RGD motif in the ligand. | Inferred | |
| LIG_RGD | FINC_HUMAN | 1524 | 1526 | Pre‑assembly | Composite binding site formation | Binding of Fibronectin (FN1) to integrin receptors depends on pre-assembly of Integrin alpha-V (ITGAV)-Integrin beta-3 (ITGB3) heterodimers, since association of the integrin alpha and beta subunits results in the formation of a composite binding site for the RGD motif in the ligand. | Inferred | |
| LIG_RGD | POLG_FMDVO | 869 | 871 | Pre‑assembly | Composite binding site formation | Binding of Genome polyprotein to integrin receptors depends on pre-assembly of Integrin alpha-V (ITGAV)-Integrin beta-3 (ITGB3) heterodimers, since association of the integrin alpha and beta subunits results in the formation of a composite binding site for the RGD motif in the ligand. | Inferred | |
| LIG_RGD | VTNC_HUMAN | 64 | 66 | Pre‑assembly | Composite binding site formation | Binding of Vitronectin (VTN) to integrin receptors depends on pre-assembly of Integrin alpha-V (ITGAV)-Integrin beta-3 (ITGB3) heterodimers, since association of the integrin alpha and beta subunits results in the formation of a composite binding site for the RGD motif in the ligand. | Inferred | |
| LIG_RGD | VWF_HUMAN | 2507 | 2509 | Pre‑assembly | Composite binding site formation | Binding of von Willebrand factor (VWF) to integrin receptors depends on pre-assembly of Integrin alpha-V (ITGAV)-Integrin beta-3 (ITGB3) heterodimers, since association of the integrin alpha and beta subunits results in the formation of a composite binding site for the RGD motif in the ligand. | Inferred | |
| LIG_RGD | OSTP_HUMAN | 159 | 161 | Pre‑assembly | Composite binding site formation | Binding of EGF-like repeat and discoidin I-like domain-containing protein 3 (EDIL3) to integrin receptors depends on pre-assembly of Integrin alpha-V (ITGAV)-Integrin beta-3 (ITGB3) heterodimers, since association of the integrin alpha and beta subunits results in the formation of a composite binding site for the RGD motif in the ligand. | Inferred | |
| LIG_Integrin_isoDGR_1 | FINC_HUMAN | 263 | 265 | Pre‑assembly | Composite binding site formation | Binding of Fibronectin (FN1) to integrin receptors depends on pre-assembly of Integrin alpha-V (ITGAV)-Integrin beta-3 (ITGB3) heterodimers, since association of the integrin alpha and beta subunits results in the formation of a composite binding site for the RGD motif in the ligand. | Inferred | |
Phagosome (KEGG - mmu04145) | ||||||||
| LIG_RGD | FINC_MOUSE | 1614 | 1616 | Pre‑assembly | Composite binding site formation | Binding of Fibronectin (Fn1) to integrin receptors depends on pre-assembly of Integrin alpha-5 (Itga5)-Integrin beta-1 (Itgb1) heterodimers, since association of the integrin alpha and beta subunits results in the formation of a composite binding site for the RGD motif in the ligand. | Inferred | |
| LIG_RGD | VTNC_MOUSE | 64 | 66 | Pre‑assembly | Composite binding site formation | Binding of Vitronectin (Vtn) to integrin receptors depends on pre-assembly of Integrin alpha-V (Itgav)-Integrin beta-3 (Itgb3) heterodimers, since association of the integrin alpha and beta subunits results in the formation of a composite binding site for the RGD motif in the ligand. | Inferred | |
Phosphatidylinositol signaling system (KEGG - mmu04070) | ||||||||
| LIG_SH2_IIA | SHIP1_HUMAN | 918 | 921 | Binary | Pre‑translational | Alternative splicing partially removes the SH2-binding motif of Phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 1 (Inpp5d), partially inhibiting binding to Phosphatidylinositol 3-kinase regulatory subunit alpha (Pik3r1). | Inferred | |
| LIG_SH2_IIA | SHIP1_HUMAN | 918 | 921 | Binary | Pre‑translational | Alternative splicing partially removes the SH2-binding motif of Phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 1 (Inpp5d), partially inhibiting binding to Phosphatidylinositol 3-kinase regulatory subunit alpha (Pik3r1). | Inferred | |
RIG-I-like receptor signaling pathway (KEGG - hsa04622) | ||||||||
| DOC_WW_Pin1_4 | TF65_HUMAN | 251 | 256 | Binary | Physicochemical compatibility | Phosphorylation of T254 in the Pin1-binding motif of Transcription factor p65 (RELA) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein. | Inferred | |
| DOC_WW_Pin1_4 | IRF3_HUMAN | 336 | 341 | Binary | Physicochemical compatibility | Phosphorylation of S339 in the Pin1-binding motif of Interferon regulatory factor 3 (IRF3) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein. | Inferred | |
RIG-I-like receptor signaling pathway (KEGG - mmu04622) | ||||||||
| LIG_TRAF2_3 | CYLD_MOUSE | 449 | 453 | Binary | Pre‑translational | Alternative splicing removes the TRAF2-binding motif of Ubiquitin carboxyl-terminal hydrolase CYLD (Cyld), abrogating binding to TNF receptor-associated factor 2 (Traf2). Mice expressing solely the alternatively spliced Isoform 3 of Ubiquitin carboxyl-terminal hydrolase CYLD (Cyld) (sCYLD) show an altered B-cell expansion profile and have more stable NF-kB proteins. | Inferred | |
RNA transport (KEGG - hsa03013) | ||||||||
| MOD_SUMO | PML_HUMAN | 159 | 162 | Uncategorised | Uncategorised | Sumoylation of K160 induces binding to the Protein PML (PML) protein. SUMO-modified forms of PML are essential for the recruitment of Protein PML (PML) to PML nuclear bodies. | Inferred | |
| LIG_SUMO_SBM_1 | DAXX_HUMAN | 733 | 740 | Uncategorised | Uncategorised | Sumoylation of K160 induces binding to the Protein PML (PML) protein. SUMO-modified forms of PML are essential for the recruitment of Death domain-associated protein 6 (DAXX) to PML nuclear bodies. | Inferred | |
| MOD_SUMO | PML_HUMAN | 159 | 162 | Uncategorised | Uncategorised | Sumoylation of K160 induces binding to the Protein PML (PML) protein. SUMO-modified forms of PML are essential for the recruitment of Death domain-associated protein 6 (DAXX) to PML nuclear bodies. | Inferred | |
| LIG_SUMO_SBM_1 | DAXX_HUMAN | 733 | 740 | Uncategorised | Uncategorised | Sumoylation of K160 induces binding to the Protein PML (PML) protein. SUMO-modified forms of PML are essential for the recruitment of Death domain-associated protein 6 (DAXX) to PML nuclear bodies. | Inferred | |
Regulation of Hypoxia-inducible Factor (HIF) by Oxygen (Reactome - 1234174) | ||||||||
| DEG_ODPH_VHL_1 | HIF1A_HUMAN | 400 | 413 | Binary | Physicochemical compatibility | Hydroxylation of P402 in the VHL-binding motif of Hypoxia-inducible factor 1-alpha (HIF1A) induces binding to the Von Hippel-Lindau disease tumor suppressor (VHL) protein. | Curated | |
| DEG_ODPH_VHL_1 | HIF1A_HUMAN | 562 | 574 | Binary | Physicochemical compatibility | Hydroxylation of P564 in the VHL-binding motif of Hypoxia-inducible factor 1-alpha (HIF1A) induces binding to the Von Hippel-Lindau disease tumor suppressor (VHL) protein. | Curated | |
| DEG_ODPH_VHL_1 | EPAS1_HUMAN | 403 | 416 | Binary | Physicochemical compatibility | Hydroxylation of P405 in the VHL-binding motif of Endothelial PAS domain-containing protein 1 (EPAS1) induces binding to the Von Hippel-Lindau disease tumor suppressor (VHL) protein. | Curated | |
| DEG_ODPH_VHL_1 | EPAS1_HUMAN | 529 | 542 | Binary | Physicochemical compatibility | Hydroxylation of P531 in the VHL-binding motif of Endothelial PAS domain-containing protein 1 (EPAS1) induces binding to the Von Hippel-Lindau disease tumor suppressor (VHL) protein. | Curated | |
| DEG_ODPH_VHL_1 | HIF3A_HUMAN | 490 | 502 | Binary | Physicochemical compatibility | Hydroxylation of P492 in the VHL-binding motif of Hypoxia-inducible factor 3-alpha (HIF3A) induces binding to the Von Hippel-Lindau disease tumor suppressor (VHL) protein. | Curated | |
| LIG_TAZ1 | HIF1A_HUMAN | 792 | 795 | Binary | Physicochemical compatibility | Under normoxic conditions interaction of Hypoxia-inducible factor 1-alpha (HIF1A) with transcriptional coactivators such as CREB-binding protein (Crebbp) is inhibited by hydroxylation of N803. | Curated | |
Regulation of actin cytoskeleton (KEGG - hsa04810) | ||||||||
| LIG_RGD | EDIL3_HUMAN | 96 | 98 | Pre‑assembly | Composite binding site formation | Binding of EGF-like repeat and discoidin I-like domain-containing protein 3 (EDIL3) to integrin receptors depends on pre-assembly of Integrin alpha-V (ITGAV)-Integrin beta-3 (ITGB3) heterodimers, since association of the integrin alpha and beta subunits results in the formation of a composite binding site for the RGD motif in the ligand. | Inferred | |
| LIG_RGD | DISG_TRIAB | 51 | 53 | Pre‑assembly | Composite binding site formation | Binding of Disintegrin albolabrin to integrin receptors depends on pre-assembly of Integrin alpha-IIb (ITGA2B)-Integrin beta-3 (ITGB3) heterodimers, since association of the integrin alpha and beta subunits results in the formation of a composite binding site for the RGD motif in the ligand. | Inferred | |
| LIG_RGD | FINC_HUMAN | 1524 | 1526 | Pre‑assembly | Composite binding site formation | Binding of Fibronectin (FN1) to integrin receptors depends on pre-assembly of Integrin alpha-V (ITGAV)-Integrin beta-3 (ITGB3) heterodimers, since association of the integrin alpha and beta subunits results in the formation of a composite binding site for the RGD motif in the ligand. | Inferred | |
| LIG_RGD | POLG_FMDVO | 869 | 871 | Pre‑assembly | Composite binding site formation | Binding of Genome polyprotein to integrin receptors depends on pre-assembly of Integrin alpha-V (ITGAV)-Integrin beta-3 (ITGB3) heterodimers, since association of the integrin alpha and beta subunits results in the formation of a composite binding site for the RGD motif in the ligand. | Inferred | |
| LIG_RGD | VTNC_HUMAN | 64 | 66 | Pre‑assembly | Composite binding site formation | Binding of Vitronectin (VTN) to integrin receptors depends on pre-assembly of Integrin alpha-V (ITGAV)-Integrin beta-3 (ITGB3) heterodimers, since association of the integrin alpha and beta subunits results in the formation of a composite binding site for the RGD motif in the ligand. | Inferred | |
| LIG_RGD | VWF_HUMAN | 2507 | 2509 | Pre‑assembly | Composite binding site formation | Binding of von Willebrand factor (VWF) to integrin receptors depends on pre-assembly of Integrin alpha-V (ITGAV)-Integrin beta-3 (ITGB3) heterodimers, since association of the integrin alpha and beta subunits results in the formation of a composite binding site for the RGD motif in the ligand. | Inferred | |
| LIG_RGD | OSTP_HUMAN | 159 | 161 | Pre‑assembly | Composite binding site formation | Binding of EGF-like repeat and discoidin I-like domain-containing protein 3 (EDIL3) to integrin receptors depends on pre-assembly of Integrin alpha-V (ITGAV)-Integrin beta-3 (ITGB3) heterodimers, since association of the integrin alpha and beta subunits results in the formation of a composite binding site for the RGD motif in the ligand. | Inferred | |
| LIG_RGD | VME1_TRIEL | 459 | 461 | Pre‑assembly | Composite binding site formation | Binding of Zinc metalloproteinase/disintegrin to integrin receptors depends on pre-assembly of Integrin alpha-IIb (ITGA2B)-Integrin beta-3 (ITGB3) heterodimers, since association of the integrin alpha and beta subunits results in the formation of a composite binding site for the RGD motif in the ligand. | Inferred | |
| LIG_RGD | DISB_TRIGA | 51 | 53 | Pre‑assembly | Composite binding site formation | Binding of Disintegrin trigramin-beta-2 to integrin receptors depends on pre-assembly of Integrin alpha-IIb (ITGA2B)-Integrin beta-3 (ITGB3) heterodimers, since association of the integrin alpha and beta subunits results in the formation of a composite binding site for the RGD motif in the ligand. | Inferred | |
| LIG_RGD | POLG_CXA9 | 858 | 860 | Pre‑assembly | Composite binding site formation | Binding of Genome polyprotein to integrin receptors depends on pre-assembly of Integrin alpha-V (ITGAV)-Integrin beta-6 (ITGB6) heterodimers, since association of the integrin alpha and beta subunits results in the formation of a composite binding site for the RGD motif in the ligand. | Inferred | |
| LIG_RGD | POLG_HPE1H | 764 | 766 | Pre‑assembly | Composite binding site formation | Binding of Genome polyprotein to integrin receptors depends on pre-assembly of Integrin alpha-V (ITGAV)-Integrin beta-6 (ITGB6) heterodimers, since association of the integrin alpha and beta subunits results in the formation of a composite binding site for the RGD motif in the ligand. | Inferred | |
| LIG_Integrin_isoDGR_1 | FINC_HUMAN | 263 | 265 | Pre‑assembly | Composite binding site formation | Binding of Fibronectin (FN1) to integrin receptors depends on pre-assembly of Integrin alpha-V (ITGAV)-Integrin beta-3 (ITGB3) heterodimers, since association of the integrin alpha and beta subunits results in the formation of a composite binding site for the RGD motif in the ligand. | Inferred | |
| LIG_SH2_IIA | PGFRB_HUMAN | 751 | 755 | Binary | Physicochemical compatibility | Phosphorylation of Y751 in the SH2-binding motif of Platelet-derived growth factor receptor beta (PDGFRB) induces binding to the Phosphatidylinositol 3-kinase regulatory subunit alpha (PIK3R1) protein. | Inferred | |
| LIG_SH2_IB | BCAR1_HUMAN | 358 | 368 | Binary | Physicochemical compatibility | Phosphorylation of Y362 in the SH2-binding motif of Breast cancer anti-estrogen resistance protein 1 (BCAR1) induces binding to the Adapter molecule crk (CRK) protein. | Inferred | |
| LIG_FAT_LD_1 | PAXI_HUMAN | 4 | 12 | Binary | Pre‑translational | Alternative splicing removes the FAK-binding LD motif of Paxillin (PXN), abrogating binding to Focal adhesion kinase 1 (PTK2). | Inferred | |
| LIG_SH2_IB | PAXI_HUMAN | 118 | 121 | Binary | Pre‑translational | Alternative splicing removes the SH2-binding motif of Paxillin (PXN), abrogating binding to Adapter molecule crk (CRK). | Inferred | |
| LIG_SH2_IB | PAXI_HUMAN | 31 | 34 | Binary | Pre‑translational | Alternative splicing removes the SH2-binding motif of Paxillin (PXN), abrogating binding to Adapter molecule crk (CRK). | Inferred | |
Regulation of actin cytoskeleton (KEGG - mmu04810) | ||||||||
| LIG_RGD | FINC_MOUSE | 1614 | 1616 | Pre‑assembly | Composite binding site formation | Binding of Fibronectin (Fn1) to integrin receptors depends on pre-assembly of Integrin alpha-5 (Itga5)-Integrin beta-1 (Itgb1) heterodimers, since association of the integrin alpha and beta subunits results in the formation of a composite binding site for the RGD motif in the ligand. | Inferred | |
| LIG_RGD | VTNC_MOUSE | 64 | 66 | Pre‑assembly | Composite binding site formation | Binding of Vitronectin (Vtn) to integrin receptors depends on pre-assembly of Integrin alpha-V (Itgav)-Integrin beta-3 (Itgb3) heterodimers, since association of the integrin alpha and beta subunits results in the formation of a composite binding site for the RGD motif in the ligand. | Inferred | |
S Phase (Reactome - 69242) | ||||||||
| DOC_CYCLIN_1 | CDN1B_HUMAN | 30 | 33 | Specificity | Domain hiding | Binding of the CDK-cyclin inhibitor p27 (Cyclin-dependent kinase inhibitor 1B (CDKN1B)) blocks the substrate recruitment site on Cyclin-A2 (CCNA2). | Curated | |
| DOC_CYCLIN_1 | CDC6_HUMAN | 94 | 98 | Specificity | Domain hiding | Binding of the CDK-cyclin inhibitor p27 (Cyclin-dependent kinase inhibitor 1B (CDKN1B)) blocks the substrate recruitment site on Cyclin-A2 (CCNA2). | Curated | |
SCF-beta-TrCP mediated degradation of Emi1 (Reactome - 174113) | ||||||||
| DEG_SCF_TRCP1_1 | FBX5_HUMAN | 144 | 149 | Binary | Physicochemical compatibility | Dual phosphorylation of S145 and S149 in the TrCP1-binding motif of F-box only protein 5 (FBXO5) targets the protein to the SCF ubiquitin ligase complex, which marks it for degradation. | Curated | |
Salivary secretion (KEGG - hsa04970) | ||||||||
| LIG_PDZ_Class_1 | AT2B4_HUMAN | 1236 | 1241 | Binary | Pre‑translational | Alternative splicing removes the PDZ-binding motif of Plasma membrane calcium-transporting ATPase 4 (ATP2B4), abrogating binding to Nitric oxide synthase, brain (NOS1). PMCA4b acts as a negative regulator of Nitric oxide synthase, brain (NOS1), reducing production of nitric oxide in heart tissue. This negative regulation was not dependent on a conformational change due to binding of the PDZ ligand, but on Ca2+ depletion in close proximity of the enzyme. Nitric oxide production by NOS1 is known to be important in the regulation of excitation-contraction (EC) coupling and subsequently contractility. | Inferred | |
| LIG_IQ_2 | AT2B1_HUMAN | 1114 | 1128 | Binary | Pre‑translational | Alternative splicing partially removes the IQ motif of Isoform CI of Plasma membrane calcium-transporting ATPase 1 (ATP2B1), partially inhibiting binding to Calmodulin (CALM1). | Inferred | |
| LIG_IQ_2 | AT2B1_HUMAN | 1114 | 1128 | Binary | Pre‑translational | Alternative splicing partially removes the IQ motif of Isoform CI of Plasma membrane calcium-transporting ATPase 1 (ATP2B1), partially inhibiting binding to Calmodulin (CALM1). | Inferred | |
Synthesis of DNA (Reactome - 69239) | ||||||||
| LIG_PCNA_PIPBox_1 | DPOD3_HUMAN | 456 | 465 | Binary | Physicochemical compatibility | Phosphorylation of S458 in the PCNA-binding motif of DNA polymerase delta subunit 3 (POLD3) by cAMP subfamily reduces the affinity of binding to the Proliferating cell nuclear antigen (PCNA) and decreases the processivity of the polymerase complex. | Curated | |
T cell receptor signaling pathway (KEGG - hsa04660) | ||||||||
| LIG_SH2_STAT5 | LAT_HUMAN | 161 | 164 | Binary | Physicochemical compatibility | Phosphorylation of Y161 in the SH2-binding motif of Linker for activation of T-cells family member 1 (LAT) induces binding to the 1-phosphatidylinositol-4,5-bisphosphate phosphodiesterase gamma-1 (PLCG1) protein. | Curated | |
| MOD_GSK3_1 | NFAC1_HUMAN | 287 | 294 | Binary | Physicochemical compatibility | Phosphorylation of S294 adjacent to the NLS of Nuclear factor of activated T-cells, cytoplasmic 1 (NFATC1) by cAMP subfamily primes Nuclear factor of activated T-cells, cytoplasmic 1 (NFATC1) for subsequent phosphorylation by Glycogen synthase kinase-3 beta (GSK3B), which results in inhibition of nuclear import of Nuclear factor of activated T-cells, cytoplasmic 1 (NFATC1). | Inferred | |
| MOD_GSK3_1 | NFAC1_HUMAN | 238 | 245 | Binary | Physicochemical compatibility | Phosphorylation of S245 adjacent to the NLS of Nuclear factor of activated T-cells, cytoplasmic 1 (NFATC1) by cAMP subfamily primes Nuclear factor of activated T-cells, cytoplasmic 1 (NFATC1) for subsequent phosphorylation by Glycogen synthase kinase-3 beta (GSK3B), which results in inhibition of nuclear import of Nuclear factor of activated T-cells, cytoplasmic 1 (NFATC1). | Inferred | |
| MOD_GSK3_1 | JUN_HUMAN | 236 | 243 | Binary | Physicochemical compatibility | Phosphorylation of Transcription factor AP-1 (JUN) at S243 primes the protein for phosphorylation at T239 by Glycogen synthase kinase-3 beta (GSK3B). | Inferred | |
| LIG_SH3_2 | PAK1_HUMAN | 13 | 18 | Binary | Physicochemical compatibility | Phosphorylation of S21 adjacent to the SH3-binding motif of Serine/threonine-protein kinase PAK 1 (PAK1) by RAC subfamily inhibits binding to Cytoplasmic protein NCK1 (NCK1), which regulates its localization to focal contacts. | Inferred | |
| LIG_SH3_5 | CD3E_HUMAN | 184 | 188 | Binary | Allostery | Ligand binding to the T cell receptor complex TCR-CD3 results in a conformational change that exposes an SH3-binding motif in T-cell surface glycoprotein CD3 epsilon chain (CD3E), resulting in recruitment of Cytoplasmic protein NCK2 (NCK2), involved in T cell activation. | Inferred | |
| MOD_ProDKin_1 | MYC_HUMAN | 59 | 65 | Specificity | Altered binding specificity | Phosphorylation of Myc proto-oncogene protein (MYC) at S62 by Mitogen-activated protein kinase 1 (MAPK1) primes MYC for phosphorylation by Glycogen synthase kinase-3 beta (GSK3B), which targets MYC to the SCF ubiquitin ligase complex, F-box/WD repeat-containing protein 7 (FBXW7) that marks MYC for degradation. | Inferred | |
| MOD_GSK3_1 | MYC_HUMAN | 55 | 62 | Specificity | Altered binding specificity | Phosphorylation of Myc proto-oncogene protein (MYC) at S62 by Mitogen-activated protein kinase 1 (MAPK1) primes MYC for phosphorylation by Glycogen synthase kinase-3 beta (GSK3B), which targets MYC to the SCF ubiquitin ligase complex, F-box/WD repeat-containing protein 7 (FBXW7) that marks MYC for degradation. | Inferred | |
| DEG_SCF_FBW7_1 | MYC_HUMAN | 55 | 62 | Specificity | Altered binding specificity | Phosphorylation of Myc proto-oncogene protein (MYC) at S62 by Mitogen-activated protein kinase 1 (MAPK1) primes MYC for phosphorylation by Glycogen synthase kinase-3 beta (GSK3B), which targets MYC to the SCF ubiquitin ligase complex, F-box/WD repeat-containing protein 7 (FBXW7) that marks MYC for degradation. | Inferred | |
| MOD_GSK3_1 | JUN_HUMAN | 236 | 243 | Specificity | Altered binding specificity | Transcription factor AP-1 (JUN) is primed by an unknown kinase for phosphorylation by Glycogen synthase kinase-3 beta (GSK3B), which targets JUN to the SCF ubiquitin ligase complex, F-box/WD repeat-containing protein 7 (FBXW7) that marks JUN for degradation. In v-Jun (Viral jun-transforming protein (JUN)) the residue corresponding to S243 is mutated to phenylalanine, which protects v-Jun (JUN) from degradation. | Inferred | |
| DEG_SCF_FBW7_1 | JUN_HUMAN | 236 | 243 | Specificity | Altered binding specificity | Transcription factor AP-1 (JUN) is primed by an unknown kinase for phosphorylation by Glycogen synthase kinase-3 beta (GSK3B), which targets JUN to the SCF ubiquitin ligase complex, F-box/WD repeat-containing protein 7 (FBXW7) that marks JUN for degradation. In v-Jun (Viral jun-transforming protein (JUN)) the residue corresponding to S243 is mutated to phenylalanine, which protects v-Jun (JUN) from degradation. | Inferred | |
| LIG_SH3_5 | CD3E_HUMAN | 184 | 188 | Specificity | Altered binding specificity | Phosphorylation of T-cell surface glycoprotein CD3 epsilon chain (CD3E) by Lck (Tyrosine-protein kinase Lck (LCK)) during T cell activation switches the specificity of CD3E from SH3 domain containing proteins like Epidermal growth factor receptor kinase substrate 8-like protein 1 (EPS8L1) to SH2 domain containing proteins like Tyrosine-protein kinase ZAP-70 (ZAP70). | Inferred | |
| LIG_TYR_ITAM | CD3E_HUMAN | 185 | 202 | Specificity | Altered binding specificity | Phosphorylation of T-cell surface glycoprotein CD3 epsilon chain (CD3E) by Lck (Tyrosine-protein kinase Lck (LCK)) during T cell activation switches the specificity of CD3E from SH3 domain containing proteins like Epidermal growth factor receptor kinase substrate 8-like protein 1 (EPS8L1) to SH2 domain containing proteins like Tyrosine-protein kinase ZAP-70 (ZAP70). | Inferred | |
| LIG_TYR_ITAM | CD3Z_HUMAN | 69 | 86 | Avidity‑sensing | Phosphorylation of Y72 and Y83 in the ITAM motif of T-cell surface glycoprotein CD3 zeta chain (CD247) induces high-avidity binding to the tandem SH2 domains of Tyrosine-protein kinase ZAP-70 (ZAP70). | Curated | ||
| LIG_TYR_ITAM | CD3Z_HUMAN | 69 | 86 | Avidity‑sensing | Phosphorylation of Y72 and Y83 in the ITAM motif of T-cell surface glycoprotein CD3 zeta chain (CD247) induces high-avidity binding to the tandem SH2 domains of Tyrosine-protein kinase ZAP-70 (ZAP70). | Curated | ||
| LIG_TYR_ITAM | CD3Z_HUMAN | 108 | 126 | Avidity‑sensing | Phosphorylation of Y111 and Y123 in the ITAM motif of T-cell surface glycoprotein CD3 zeta chain (CD247) induces high-avidity binding to the tandem SH2 domains of Tyrosine-protein kinase ZAP-70 (ZAP70). | Curated | ||
| LIG_TYR_ITAM | CD3Z_HUMAN | 108 | 126 | Avidity‑sensing | Phosphorylation of Y111 and Y123 in the ITAM motif of T-cell surface glycoprotein CD3 zeta chain (CD247) induces high-avidity binding to the tandem SH2 domains of Tyrosine-protein kinase ZAP-70 (ZAP70). | Curated | ||
| LIG_TYR_ITAM | CD3Z_HUMAN | 139 | 156 | Avidity‑sensing | Phosphorylation of Y142 and Y153 in the ITAM motif of T-cell surface glycoprotein CD3 zeta chain (CD247) induces high-avidity binding to the tandem SH2 domains of Tyrosine-protein kinase ZAP-70 (ZAP70). | Curated | ||
| LIG_TYR_ITAM | CD3Z_HUMAN | 139 | 156 | Avidity‑sensing | Phosphorylation of Y142 and Y153 in the ITAM motif of T-cell surface glycoprotein CD3 zeta chain (CD247) induces high-avidity binding to the tandem SH2 domains of Tyrosine-protein kinase ZAP-70 (ZAP70). | Curated | ||
| LIG_TYR_ITAM | CD3G_HUMAN | 157 | 174 | Avidity‑sensing | Phosphorylation of Y160 and Y171 in the ITAM motif of T-cell surface glycoprotein CD3 gamma chain (CD3G) induces high-avidity binding to the tandem SH2 domains of Tyrosine-protein kinase ZAP-70 (ZAP70). | Curated | ||
| LIG_TYR_ITAM | CD3G_HUMAN | 157 | 174 | Avidity‑sensing | Phosphorylation of Y160 and Y171 in the ITAM motif of T-cell surface glycoprotein CD3 gamma chain (CD3G) induces high-avidity binding to the tandem SH2 domains of Tyrosine-protein kinase ZAP-70 (ZAP70). | Curated | ||
| LIG_SH2_IIC | ZAP70_HUMAN | 284 | 300 | Binary | Physicochemical compatibility | Phosphorylation of Y292 in the SH2-binding motif of Tyrosine-protein kinase ZAP-70 (ZAP70) induces binding to the E3 ubiquitin-protein ligase CBL-B (CBLB) protein. | Inferred | |
T cell receptor signaling pathway (KEGG - mmu04660) | ||||||||
| LIG_SH2_GRB2 | LAT_MOUSE | 175 | 178 | Binary | Physicochemical compatibility | Phosphorylation of Y175 in the SH2-binding motif of Linker for activation of T-cells family member 1 (Lat) induces binding to the Growth factor receptor-bound protein 2 (Grb2) protein. | Inferred | |
| LIG_SH2_GRB2 | LAT_MOUSE | 195 | 198 | Binary | Physicochemical compatibility | Phosphorylation of Y195 in the SH2-binding motif of Linker for activation of T-cells family member 1 (Lat) induces binding to the Growth factor receptor-bound protein 2 (Grb2) protein. | Inferred | |
| LIG_SH2_GRB2 | LAT_MOUSE | 235 | 238 | Binary | Physicochemical compatibility | Phosphorylation of Y235 in the SH2-binding motif of Linker for activation of T-cells family member 1 (Lat) induces binding to the Growth factor receptor-bound protein 2 (Grb2) protein. | Inferred | |
| LIG_SH2_IA | LCP2_MOUSE | 143 | 148 | Binary | Physicochemical compatibility | Phosphorylation of Y145 in the SH2-binding motif of Lymphocyte cytosolic protein 2 (Lcp2) induces binding to the Tyrosine-protein kinase ITK/TSK (Itk) protein. | Inferred | |
TCR signaling (Reactome - 202403) | ||||||||
| LIG_SH2_STAT5 | LAT_HUMAN | 161 | 164 | Binary | Physicochemical compatibility | Phosphorylation of Y161 in the SH2-binding motif of Linker for activation of T-cells family member 1 (LAT) induces binding to the 1-phosphatidylinositol-4,5-bisphosphate phosphodiesterase gamma-1 (PLCG1) protein. | Curated | |
| LIG_TYR_ITAM | CD3Z_HUMAN | 69 | 86 | Avidity‑sensing | Phosphorylation of Y72 and Y83 in the ITAM motif of T-cell surface glycoprotein CD3 zeta chain (CD247) induces high-avidity binding to the tandem SH2 domains of Tyrosine-protein kinase ZAP-70 (ZAP70). | Curated | ||
| LIG_TYR_ITAM | CD3Z_HUMAN | 69 | 86 | Avidity‑sensing | Phosphorylation of Y72 and Y83 in the ITAM motif of T-cell surface glycoprotein CD3 zeta chain (CD247) induces high-avidity binding to the tandem SH2 domains of Tyrosine-protein kinase ZAP-70 (ZAP70). | Curated | ||
| LIG_TYR_ITAM | CD3Z_HUMAN | 108 | 126 | Avidity‑sensing | Phosphorylation of Y111 and Y123 in the ITAM motif of T-cell surface glycoprotein CD3 zeta chain (CD247) induces high-avidity binding to the tandem SH2 domains of Tyrosine-protein kinase ZAP-70 (ZAP70). | Curated | ||
| LIG_TYR_ITAM | CD3Z_HUMAN | 108 | 126 | Avidity‑sensing | Phosphorylation of Y111 and Y123 in the ITAM motif of T-cell surface glycoprotein CD3 zeta chain (CD247) induces high-avidity binding to the tandem SH2 domains of Tyrosine-protein kinase ZAP-70 (ZAP70). | Curated | ||
| LIG_TYR_ITAM | CD3Z_HUMAN | 139 | 156 | Avidity‑sensing | Phosphorylation of Y142 and Y153 in the ITAM motif of T-cell surface glycoprotein CD3 zeta chain (CD247) induces high-avidity binding to the tandem SH2 domains of Tyrosine-protein kinase ZAP-70 (ZAP70). | Curated | ||
| LIG_TYR_ITAM | CD3Z_HUMAN | 139 | 156 | Avidity‑sensing | Phosphorylation of Y142 and Y153 in the ITAM motif of T-cell surface glycoprotein CD3 zeta chain (CD247) induces high-avidity binding to the tandem SH2 domains of Tyrosine-protein kinase ZAP-70 (ZAP70). | Curated | ||
| LIG_TYR_ITAM | CD3G_HUMAN | 157 | 174 | Avidity‑sensing | Phosphorylation of Y160 and Y171 in the ITAM motif of T-cell surface glycoprotein CD3 gamma chain (CD3G) induces high-avidity binding to the tandem SH2 domains of Tyrosine-protein kinase ZAP-70 (ZAP70). | Curated | ||
| LIG_TYR_ITAM | CD3G_HUMAN | 157 | 174 | Avidity‑sensing | Phosphorylation of Y160 and Y171 in the ITAM motif of T-cell surface glycoprotein CD3 gamma chain (CD3G) induces high-avidity binding to the tandem SH2 domains of Tyrosine-protein kinase ZAP-70 (ZAP70). | Curated | ||
TGF-beta signaling pathway (KEGG - hsa04350) | ||||||||
| MOD_ProDKin_1 | MYC_HUMAN | 59 | 65 | Specificity | Altered binding specificity | Phosphorylation of Myc proto-oncogene protein (MYC) at S62 by Mitogen-activated protein kinase 1 (MAPK1) primes MYC for phosphorylation by Glycogen synthase kinase-3 beta (GSK3B), which targets MYC to the SCF ubiquitin ligase complex, F-box/WD repeat-containing protein 7 (FBXW7) that marks MYC for degradation. | Inferred | |
| MOD_GSK3_1 | MYC_HUMAN | 55 | 62 | Specificity | Altered binding specificity | Phosphorylation of Myc proto-oncogene protein (MYC) at S62 by Mitogen-activated protein kinase 1 (MAPK1) primes MYC for phosphorylation by Glycogen synthase kinase-3 beta (GSK3B), which targets MYC to the SCF ubiquitin ligase complex, F-box/WD repeat-containing protein 7 (FBXW7) that marks MYC for degradation. | Inferred | |
| DEG_SCF_FBW7_1 | MYC_HUMAN | 55 | 62 | Specificity | Altered binding specificity | Phosphorylation of Myc proto-oncogene protein (MYC) at S62 by Mitogen-activated protein kinase 1 (MAPK1) primes MYC for phosphorylation by Glycogen synthase kinase-3 beta (GSK3B), which targets MYC to the SCF ubiquitin ligase complex, F-box/WD repeat-containing protein 7 (FBXW7) that marks MYC for degradation. | Inferred | |
Ubiquitin mediated proteolysis (KEGG - hsa04120) | ||||||||
| MOD_SUMO | PML_HUMAN | 489 | 492 | Binary | Pre‑translational | Alternative splicing removes the SUMO motif of Protein PML (PML), abrogating binding to SUMO-conjugating enzyme UBC9 (UBE2I). The study identified a major sumoylation site within the nuclear localisation signal (NLS) of PML. Although they did not determine whether the lysine residue regulates the NLS, they found that sumoylation was not necessary for nuclear localisation and that SUMO-modification only occurs in the nucleus. | Inferred | |
| MOD_SUMO | PML_HUMAN | 159 | 162 | Uncategorised | Uncategorised | Sumoylation of K160 induces binding to the Protein PML (PML) protein. SUMO-modified forms of PML are essential for the recruitment of Protein PML (PML) to PML nuclear bodies. | Inferred | |
| LIG_SUMO_SBM_1 | DAXX_HUMAN | 733 | 740 | Uncategorised | Uncategorised | Sumoylation of K160 induces binding to the Protein PML (PML) protein. SUMO-modified forms of PML are essential for the recruitment of Death domain-associated protein 6 (DAXX) to PML nuclear bodies. | Inferred | |
| MOD_SUMO | PML_HUMAN | 159 | 162 | Uncategorised | Uncategorised | Sumoylation of K160 induces binding to the Protein PML (PML) protein. SUMO-modified forms of PML are essential for the recruitment of Death domain-associated protein 6 (DAXX) to PML nuclear bodies. | Inferred | |
| LIG_SUMO_SBM_1 | DAXX_HUMAN | 733 | 740 | Uncategorised | Uncategorised | Sumoylation of K160 induces binding to the Protein PML (PML) protein. SUMO-modified forms of PML are essential for the recruitment of Death domain-associated protein 6 (DAXX) to PML nuclear bodies. | Inferred | |
VEGF signaling pathway (KEGG - hsa04370) | ||||||||
| LIG_FAT_LD_1 | PAXI_HUMAN | 4 | 12 | Binary | Pre‑translational | Alternative splicing removes the FAK-binding LD motif of Paxillin (PXN), abrogating binding to Focal adhesion kinase 1 (PTK2). | Inferred | |
Vascular smooth muscle contraction (KEGG - rno04270) | ||||||||
| LIG_IQ | CAC1D_RAT | 1650 | 1669 | Binary | Pre‑translational | Alternative splicing removes the IQ motif of Voltage-dependent L-type calcium channel subunit alpha-1D (Cacna1d) abrogating binding to Calmodulin (Calm1). CaV1.3IQdelta (IQ-deleted Isoform CACN4B of Voltage-dependent L-type calcium channel subunit alpha-1D (Cacna1d)) channels exhibit a lack of calcium-dependent inactivation. CaV1.3IQdelta channel immunoreactivity was preferentially localised to cochlear outer hair cells (OHCs), whereas that of CaV1.3IQfull channels (IQ-possessing Isoform CACN4A of Voltage-dependent L-type calcium channel subunit alpha-1D (Cacna1d)) labelled inner hair cells (IHCs). | Inferred | |
Wnt signaling pathway (KEGG - hsa04310) | ||||||||
| MOD_GSK3_1 | NFAC1_HUMAN | 287 | 294 | Binary | Physicochemical compatibility | Phosphorylation of S294 adjacent to the NLS of Nuclear factor of activated T-cells, cytoplasmic 1 (NFATC1) by cAMP subfamily primes Nuclear factor of activated T-cells, cytoplasmic 1 (NFATC1) for subsequent phosphorylation by Glycogen synthase kinase-3 beta (GSK3B), which results in inhibition of nuclear import of Nuclear factor of activated T-cells, cytoplasmic 1 (NFATC1). | Inferred | |
| MOD_GSK3_1 | NFAC1_HUMAN | 238 | 245 | Binary | Physicochemical compatibility | Phosphorylation of S245 adjacent to the NLS of Nuclear factor of activated T-cells, cytoplasmic 1 (NFATC1) by cAMP subfamily primes Nuclear factor of activated T-cells, cytoplasmic 1 (NFATC1) for subsequent phosphorylation by Glycogen synthase kinase-3 beta (GSK3B), which results in inhibition of nuclear import of Nuclear factor of activated T-cells, cytoplasmic 1 (NFATC1). | Inferred | |
| MOD_GSK3_1 | P53_HUMAN | 30 | 37 | Binary | Physicochemical compatibility | Phosphorylation of Cellular tumor antigen p53 (TP53) at S37 primes the protein for phosphorylation at S33 by Glycogen synthase kinase-3 beta (GSK3B). | Inferred | |
| MOD_GSK3_1 | JUN_HUMAN | 236 | 243 | Binary | Physicochemical compatibility | Phosphorylation of Transcription factor AP-1 (JUN) at S243 primes the protein for phosphorylation at T239 by Glycogen synthase kinase-3 beta (GSK3B). | Inferred | |
| DOC_WW_Pin1_4 | SMAD3_HUMAN | 176 | 181 | Specificity | Altered binding specificity | CDK8/9 phosphorylates Mothers against decapentaplegic homolog 3 (SMAD3) at T179 and S208. Phosphorylation of T179 creates a binding site for the WW domain of Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1), while phosphorylation of S208 primes SMAD3 for phosphorylation of S204 by Glycogen synthase kinase-3 beta (GSK3B). The pS204-pS208 forms a binding site for the third WW domain of E3 ubiquitin-protein ligase NEDD4-like (NEDD4L), whose second WW domain will displace the WW domain of PIN1 at the pT179-PY box site of SMAD3. This regulation couples SMAD3 activation to SMAD3 destruction in an ordered fashion. See also switch details and switch details. | Inferred | |
| MOD_GSK3_1 | SMAD3_HUMAN | 201 | 208 | Specificity | Altered binding specificity | CDK8/9 phosphorylates Mothers against decapentaplegic homolog 3 (SMAD3) at T179 and S208. Phosphorylation of T179 creates a binding site for the WW domain of Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1), while phosphorylation of S208 primes SMAD3 for phosphorylation of S204 by Glycogen synthase kinase-3 beta (GSK3B). The pS204-pS208 forms a binding site for the third WW domain of E3 ubiquitin-protein ligase NEDD4-like (NEDD4L), whose second WW domain will displace the WW domain of PIN1 at the pT179-PY box site of SMAD3. This regulation couples SMAD3 activation to SMAD3 destruction in an ordered fashion. See also switch details and switch details. | Inferred | |
| LIG_WW_Nedd4L | SMAD3_HUMAN | 203 | 210 | Specificity | Altered binding specificity | CDK8/9 phosphorylates Mothers against decapentaplegic homolog 3 (SMAD3) at T179 and S208. Phosphorylation of T179 creates a binding site for the WW domain of Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1), while phosphorylation of S208 primes SMAD3 for phosphorylation of S204 by Glycogen synthase kinase-3 beta (GSK3B). The pS204-pS208 forms a binding site for the third WW domain of E3 ubiquitin-protein ligase NEDD4-like (NEDD4L), whose second WW domain will displace the WW domain of PIN1 at the pT179-PY box site of SMAD3. This regulation couples SMAD3 activation to SMAD3 destruction in an ordered fashion. See also switch details and switch details. | Inferred | |
| LIG_WW_1 | SMAD3_HUMAN | 181 | 184 | Specificity | Altered binding specificity | CDK8/9 phosphorylates Mothers against decapentaplegic homolog 3 (SMAD3) at T179 and S208. Phosphorylation of T179 creates a binding site for the WW domain of Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1), while phosphorylation of S208 primes SMAD3 for phosphorylation of S204 by Glycogen synthase kinase-3 beta (GSK3B). The pS204-pS208 forms a binding site for the third WW domain of E3 ubiquitin-protein ligase NEDD4-like (NEDD4L), whose second WW domain will displace the WW domain of PIN1 at the pT179-PY box site of SMAD3. This regulation couples SMAD3 activation to SMAD3 destruction in an ordered fashion. See also switch details and switch details. | Inferred | |
| MOD_GSK3_1 | FGD1_HUMAN | 280 | 287 | Specificity | Altered binding specificity | Phosphorylation of FYVE, RhoGEF and PH domain-containing protein 1 (FGD1), a GEF for CDC42 small effector protein 2 (CDC42SE2), by Glycogen synthase kinase-3 beta (GSK3B) targets FGD1 to the SCF ubiquitin ligase complex, F-box/WD repeat-containing protein 1A (BTRC), which marks FGD1 for degradation. | Inferred | |
| DEG_SCF_TRCP1_1 | FGD1_HUMAN | 282 | 287 | Specificity | Altered binding specificity | Phosphorylation of FYVE, RhoGEF and PH domain-containing protein 1 (FGD1), a GEF for CDC42 small effector protein 2 (CDC42SE2), by Glycogen synthase kinase-3 beta (GSK3B) targets FGD1 to the SCF ubiquitin ligase complex, F-box/WD repeat-containing protein 1A (BTRC), which marks FGD1 for degradation. | Inferred | |
| MOD_GSK3_1 | FGD3_HUMAN | 77 | 84 | Specificity | Altered binding specificity | Phosphorylation of FYVE, RhoGEF and PH domain-containing protein 3 (FGD3), a GEF for CDC42 small effector protein 2 (CDC42SE2), by Glycogen synthase kinase-3 beta (GSK3B) targets FGD3 to the SCF ubiquitin ligase complex, F-box/WD repeat-containing protein 1A (BTRC), which marks FGD3 for degradation. | Inferred | |
| MOD_GSK3_1 | FGD3_HUMAN | 73 | 80 | Specificity | Altered binding specificity | Phosphorylation of FYVE, RhoGEF and PH domain-containing protein 3 (FGD3), a GEF for CDC42 small effector protein 2 (CDC42SE2), by Glycogen synthase kinase-3 beta (GSK3B) targets FGD3 to the SCF ubiquitin ligase complex, F-box/WD repeat-containing protein 1A (BTRC), which marks FGD3 for degradation. | Inferred | |
| DEG_SCF_TRCP1_1 | FGD3_HUMAN | 75 | 80 | Specificity | Altered binding specificity | Phosphorylation of FYVE, RhoGEF and PH domain-containing protein 3 (FGD3), a GEF for CDC42 small effector protein 2 (CDC42SE2), by Glycogen synthase kinase-3 beta (GSK3B) targets FGD3 to the SCF ubiquitin ligase complex, F-box/WD repeat-containing protein 1A (BTRC), which marks FGD3 for degradation. | Inferred | |
| MOD_ProDKin_1 | MYC_HUMAN | 59 | 65 | Specificity | Altered binding specificity | Phosphorylation of Myc proto-oncogene protein (MYC) at S62 by Mitogen-activated protein kinase 1 (MAPK1) primes MYC for phosphorylation by Glycogen synthase kinase-3 beta (GSK3B), which targets MYC to the SCF ubiquitin ligase complex, F-box/WD repeat-containing protein 7 (FBXW7) that marks MYC for degradation. | Inferred | |
| MOD_GSK3_1 | MYC_HUMAN | 55 | 62 | Specificity | Altered binding specificity | Phosphorylation of Myc proto-oncogene protein (MYC) at S62 by Mitogen-activated protein kinase 1 (MAPK1) primes MYC for phosphorylation by Glycogen synthase kinase-3 beta (GSK3B), which targets MYC to the SCF ubiquitin ligase complex, F-box/WD repeat-containing protein 7 (FBXW7) that marks MYC for degradation. | Inferred | |
| DEG_SCF_FBW7_1 | MYC_HUMAN | 55 | 62 | Specificity | Altered binding specificity | Phosphorylation of Myc proto-oncogene protein (MYC) at S62 by Mitogen-activated protein kinase 1 (MAPK1) primes MYC for phosphorylation by Glycogen synthase kinase-3 beta (GSK3B), which targets MYC to the SCF ubiquitin ligase complex, F-box/WD repeat-containing protein 7 (FBXW7) that marks MYC for degradation. | Inferred | |
| MOD_GSK3_1 | JUN_HUMAN | 236 | 243 | Specificity | Altered binding specificity | Transcription factor AP-1 (JUN) is primed by an unknown kinase for phosphorylation by Glycogen synthase kinase-3 beta (GSK3B), which targets JUN to the SCF ubiquitin ligase complex, F-box/WD repeat-containing protein 7 (FBXW7) that marks JUN for degradation. In v-Jun (Viral jun-transforming protein (JUN)) the residue corresponding to S243 is mutated to phenylalanine, which protects v-Jun (JUN) from degradation. | Inferred | |
| DEG_SCF_FBW7_1 | JUN_HUMAN | 236 | 243 | Specificity | Altered binding specificity | Transcription factor AP-1 (JUN) is primed by an unknown kinase for phosphorylation by Glycogen synthase kinase-3 beta (GSK3B), which targets JUN to the SCF ubiquitin ligase complex, F-box/WD repeat-containing protein 7 (FBXW7) that marks JUN for degradation. In v-Jun (Viral jun-transforming protein (JUN)) the residue corresponding to S243 is mutated to phenylalanine, which protects v-Jun (JUN) from degradation. | Inferred | |
| MOD_GSK3_1 | CTNB1_HUMAN | 34 | 41 | Specificity | Altered binding specificity | Phosphorylation of Catenin beta-1 (CTNNB1) at T41 generates a docking site for Glycogen synthase kinase-3 beta (GSK3B), which then phosphorylates S37, thereby generating a new docking site for GSK3B. Subsequent phosphorylation of S33 by GSK3B switches the specificity of CTNNB1 to the F-box/WD repeat-containing protein 1A (BTRC), which recruits CTNNB1 to the SCF ubiquitin ligase complex. | Curated | |
| MOD_GSK3_1 | CTNB1_HUMAN | 30 | 37 | Specificity | Altered binding specificity | Phosphorylation of Catenin beta-1 (CTNNB1) at T41 generates a docking site for Glycogen synthase kinase-3 beta (GSK3B), which then phosphorylates S37, thereby generating a new docking site for GSK3B. Subsequent phosphorylation of S33 by GSK3B switches the specificity of CTNNB1 to the F-box/WD repeat-containing protein 1A (BTRC), which recruits CTNNB1 to the SCF ubiquitin ligase complex. | Curated | |
| DEG_SCF_TRCP1_1 | CTNB1_HUMAN | 32 | 37 | Specificity | Altered binding specificity | Phosphorylation of Catenin beta-1 (CTNNB1) at T41 generates a docking site for Glycogen synthase kinase-3 beta (GSK3B), which then phosphorylates S37, thereby generating a new docking site for GSK3B. Subsequent phosphorylation of S33 by GSK3B switches the specificity of CTNNB1 to the F-box/WD repeat-containing protein 1A (BTRC), which recruits CTNNB1 to the SCF ubiquitin ligase complex. | Curated | |
| MOD_GSK3_1 | SNAI1_HUMAN | 93 | 100 | Specificity | Altered binding specificity | Phosphorylation of Zinc finger protein SNAI1 (SNAI1) at S100 generates a docking site for Glycogen synthase kinase-3 beta (GSK3B). Subsequent phosphorylation of S96 by GSK3B targets Zinc finger protein SNAI1 (SNAI1) to the SCF ubiquitin ligase complexes F-box/WD repeat-containing protein 1A (BTRC), which marks it for degradation. | Inferred | |
| DEG_SCF_TRCP1_1 | SNAI1_HUMAN | 95 | 100 | Specificity | Altered binding specificity | Phosphorylation of Zinc finger protein SNAI1 (SNAI1) at S100 generates a docking site for Glycogen synthase kinase-3 beta (GSK3B). Subsequent phosphorylation of S96 by GSK3B targets Zinc finger protein SNAI1 (SNAI1) to the SCF ubiquitin ligase complexes F-box/WD repeat-containing protein 1A (BTRC), which marks it for degradation. | Inferred | |
| MOD_LATS_1 | YAP1_HUMAN | 376 | 382 | Specificity | Altered binding specificity | Phosphorylation of Yorkie homolog (YAP1) at S381 by Serine/threonine-protein kinase LATS1 (LATS1) (a key regulator of the Hippo Pathway) primes the sequence for phosphorylation by Casein kinase I isoform epsilon (CSNK1E) at S384 and S387. This targets YAP1 to the SCF ubiqutin ligase complex, F-box/WD repeat-containing protein 1A (BTRC), which marks is YAP1 for subsequent degradation by the proteasomal system. N.B. Serine/threonine-protein kinase LATS2 (LATS2) can replace LATS1 and Casein kinase I isoform delta (CSNK1D) can replace CSNK1E | Inferred | |
| MOD_CK1_1 | YAP1_HUMAN | 381 | 387 | Specificity | Altered binding specificity | Phosphorylation of Yorkie homolog (YAP1) at S381 by Serine/threonine-protein kinase LATS1 (LATS1) (a key regulator of the Hippo Pathway) primes the sequence for phosphorylation by Casein kinase I isoform epsilon (CSNK1E) at S384 and S387. This targets YAP1 to the SCF ubiqutin ligase complex, F-box/WD repeat-containing protein 1A (BTRC), which marks is YAP1 for subsequent degradation by the proteasomal system. N.B. Serine/threonine-protein kinase LATS2 (LATS2) can replace LATS1 and Casein kinase I isoform delta (CSNK1D) can replace CSNK1E | Inferred | |
| MOD_CK1_1 | YAP1_HUMAN | 384 | 390 | Specificity | Altered binding specificity | Phosphorylation of Yorkie homolog (YAP1) at S381 by Serine/threonine-protein kinase LATS1 (LATS1) (a key regulator of the Hippo Pathway) primes the sequence for phosphorylation by Casein kinase I isoform epsilon (CSNK1E) at S384 and S387. This targets YAP1 to the SCF ubiqutin ligase complex, F-box/WD repeat-containing protein 1A (BTRC), which marks is YAP1 for subsequent degradation by the proteasomal system. N.B. Serine/threonine-protein kinase LATS2 (LATS2) can replace LATS1 and Casein kinase I isoform delta (CSNK1D) can replace CSNK1E | Inferred | |
| DEG_SCF_TRCP1_2 | YAP1_HUMAN | 383 | 387 | Specificity | Altered binding specificity | Phosphorylation of Yorkie homolog (YAP1) at S381 by Serine/threonine-protein kinase LATS1 (LATS1) (a key regulator of the Hippo Pathway) primes the sequence for phosphorylation by Casein kinase I isoform epsilon (CSNK1E) at S384 and S387. This targets YAP1 to the SCF ubiqutin ligase complex, F-box/WD repeat-containing protein 1A (BTRC), which marks is YAP1 for subsequent degradation by the proteasomal system. N.B. Serine/threonine-protein kinase LATS2 (LATS2) can replace LATS1 and Casein kinase I isoform delta (CSNK1D) can replace CSNK1E | Inferred | |
mTOR signaling pathway (KEGG - hsa04150) | ||||||||
| LIG_eIF4E_1 | 4EBP1_HUMAN | 54 | 60 | Binary | Physicochemical compatibility | Phosphorylation of S65 flanking the eIF4E-binding motif of Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1) by Serine/threonine-protein kinase mTOR (MTOR) inhibits binding to Eukaryotic translation initiation factor 4E (EIF4E) in response to growth factors and nutrients. This results in release of Eukaryotic translation initiation factor 4E (EIF4E), which associates with other initiation factors to form the eIF-4F complex that mediates initiation of translation. However, disruption of the interaction between Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1) and Eukaryotic translation initiation factor 4E (EIF4E) has been shown to be dependent on hyperphosphorylation of Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1) by FRAP/mTOR, PI3K and ERK pathways. According to the current model, Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1) is phosphorylated on multiple residues in a well-defined order. Basal phosphorylation of T37 and T46 serves as a priming event for subsequent serum-induced phosphorylation of T70, which primes for subsequent phosphorylation of S65. | Curated | |
p53 signaling pathway (KEGG - hsa04115) | ||||||||
| CLV_C14_Caspase3-7 | PTEN_HUMAN | 381 | 385 | Binary | Physicochemical compatibility | Phosphorylation of S385 adjacent to the cleavage motif of Phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN (PTEN) by CK2 subfamily prevents cleavage by Caspase-3 (CASP3). | Inferred | |
| DEG_MDM2_1 | P53_HUMAN | 19 | 26 | Binary | Physicochemical compatibility | Phosphorylation of Cellular tumor antigen p53 (TP53) on T18 (in vitro by Casein kinase I subfamily, requiring prior phosphorylation of S15) inhibits its binding to E3 ubiquitin-protein ligase Mdm2 (MDM2). In vivo, T18 is phosphorylated in response to DNA damage. | Curated | |
| DEG_MDM2_1 | P53_HUMAN | 19 | 26 | Binary | Pre‑translational | Alternative promoter usage and alternative splicing removes the E3 ubiquitin ligase MDM2-binding motif of Cellular tumor antigen p53 (TP53), abrogating binding to E3 ubiquitin-protein ligase Mdm2 (MDM2). The splice variant without this motif is resistant to MDM2-mediated degradation, leading to a longer half-life. | Curated | |
p53-Dependent G1/S DNA damage checkpoint (Reactome - 69580) | ||||||||
| DEG_MDM2_1 | P53_HUMAN | 19 | 26 | Binary | Physicochemical compatibility | Phosphorylation of Cellular tumor antigen p53 (TP53) on T18 (in vitro by Casein kinase I subfamily, requiring prior phosphorylation of S15) inhibits its binding to E3 ubiquitin-protein ligase Mdm2 (MDM2). In vivo, T18 is phosphorylated in response to DNA damage. | Curated | |
| DEG_MDM2_1 | P53_HUMAN | 19 | 26 | Binary | Pre‑translational | Alternative promoter usage and alternative splicing removes the E3 ubiquitin ligase MDM2-binding motif of Cellular tumor antigen p53 (TP53), abrogating binding to E3 ubiquitin-protein ligase Mdm2 (MDM2). The splice variant without this motif is resistant to MDM2-mediated degradation, leading to a longer half-life. | Curated | |