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| Domain hiding | Altered binding specificity | Motif hiding | Composite binding site formation |
| Uncategorised | Rheostatic | Allostery | Avidity-sensing |
| Physicochemical compatibility | Pre-translational | Competition |
| Protein | Motif | Start | End | Switch description | Information |
Type: Specificity Subtype: Domain hiding | |||||||
| A domain can be sterically masked by binding of an effector when there is a large difference in intrinsic affinity of the domain for different binding partners, or a large difference in the local abundance of these partners, thereby precluding further interactions of the domain. Binding of the masking molecule can be PTM-dependent or -independent. | |||||||
| INSR_HUMAN | LIG_SH2_STAT5 | 1361 | 1364 | 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. | |||
Type: Avidity‑sensing Subtype: | |||||||
| Multiple low-affinity interactions give rise to high-avidity interactions that have increased binding strength, with more than additive affinity. | |||||||
| CD3Z_HUMAN | LIG_TYR_ITAM | 69 | 86 | Phosphorylation of Y72 and Y83 in the ITAM motif of T-cell surface glycoprotein CD3 zeta chain (CD247) induces high-avidity binding to the tandem SH2 domains of Tyrosine-protein kinase ZAP-70 (ZAP70). | |||
| CD3Z_HUMAN | LIG_TYR_ITAM | 69 | 86 | Phosphorylation of Y72 and Y83 in the ITAM motif of T-cell surface glycoprotein CD3 zeta chain (CD247) induces high-avidity binding to the tandem SH2 domains of Tyrosine-protein kinase ZAP-70 (ZAP70). | |||
| CD79A_MOUSE | LIG_TYR_ITAM | 179 | 196 | Phosphorylation of Y182 and Y193 in the ITAM motif of B-cell antigen receptor complex-associated protein alpha chain (Cd79a) induces high-avidity binding to the tandem SH2 domains of Tyrosine-protein kinase SYK (Syk). Maximal Syk activation requires both Syk SH2 domains and phosphorylation of both ITAM tyrosine residues. | |||
| CD79A_MOUSE | LIG_TYR_ITAM | 179 | 196 | Phosphorylation of Y182 and Y193 in the ITAM motif of B-cell antigen receptor complex-associated protein alpha chain (Cd79a) induces high-avidity binding to the tandem SH2 domains of Tyrosine-protein kinase SYK (Syk). Maximal Syk activation requires both Syk SH2 domains and phosphorylation of both ITAM tyrosine residues. | |||
| CD3E_HUMAN | LIG_TYR_ITAM | 185 | 202 | Phosphorylation of Y188 and Y199 in the ITAM motif of T-cell surface glycoprotein CD3 epsilon chain (CD3E) induces high-avidity binding to the tandem SH2 domains of Tyrosine-protein kinase SYK (SYK). | |||
| CD3E_HUMAN | LIG_TYR_ITAM | 185 | 202 | Phosphorylation of Y188 and Y199 in the ITAM motif of T-cell surface glycoprotein CD3 epsilon chain (CD3E) induces high-avidity binding to the tandem SH2 domains of Tyrosine-protein kinase SYK (SYK). | |||
| CD3Z_HUMAN | LIG_TYR_ITAM | 108 | 126 | Phosphorylation of Y111 and Y123 in the ITAM motif of T-cell surface glycoprotein CD3 zeta chain (CD247) induces high-avidity binding to the tandem SH2 domains of Tyrosine-protein kinase ZAP-70 (ZAP70). | |||
| CD3Z_HUMAN | LIG_TYR_ITAM | 108 | 126 | Phosphorylation of Y111 and Y123 in the ITAM motif of T-cell surface glycoprotein CD3 zeta chain (CD247) induces high-avidity binding to the tandem SH2 domains of Tyrosine-protein kinase ZAP-70 (ZAP70). | |||
| CD3Z_HUMAN | LIG_TYR_ITAM | 139 | 156 | Phosphorylation of Y142 and Y153 in the ITAM motif of T-cell surface glycoprotein CD3 zeta chain (CD247) induces high-avidity binding to the tandem SH2 domains of Tyrosine-protein kinase ZAP-70 (ZAP70). | |||
| CD3Z_HUMAN | LIG_TYR_ITAM | 139 | 156 | Phosphorylation of Y142 and Y153 in the ITAM motif of T-cell surface glycoprotein CD3 zeta chain (CD247) induces high-avidity binding to the tandem SH2 domains of Tyrosine-protein kinase ZAP-70 (ZAP70). | |||
| CD3G_HUMAN | LIG_TYR_ITAM | 157 | 174 | Phosphorylation of Y160 and Y171 in the ITAM motif of T-cell surface glycoprotein CD3 gamma chain (CD3G) induces high-avidity binding to the tandem SH2 domains of Tyrosine-protein kinase ZAP-70 (ZAP70). | |||
| CD3G_HUMAN | LIG_TYR_ITAM | 157 | 174 | 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). | |||
| OX1R_HUMAN | LIG_TYR_ITSM | 79 | 86 | Orexin-A induced phosphorylation of the ITSM and ITIM motifs in Orexin receptor type 1 (HCRTR1) allows binding of Tyrosine-protein phosphatase non-receptor type 11 (PTPN11) via its two SH2 domains. Mutation of either tyrosine in the motifs abolishes binding of Tyrosine-protein phosphatase non-receptor type 11 (PTPN11). | |||
| OX1R_HUMAN | LIG_TYR_ITIM | 356 | 361 | Orexin-A induced phosphorylation of the ITSM and ITIM motifs in Orexin receptor type 1 (HCRTR1) allows binding of Tyrosine-protein phosphatase non-receptor type 11 (PTPN11) via its two SH2 domains. Mutation of either tyrosine in the motifs abolishes binding of Tyrosine-protein phosphatase non-receptor type 11 (PTPN11). | |||
| FCG2A_HUMAN | LIG_TYR_ITAM | 285 | 307 | Phosphorylation of Y288 and Y304 in the ITAM motif of Low affinity immunoglobulin gamma Fc region receptor II-a (FCGR2A) induces high-avidity binding to the tandem SH2 domains of Tyrosine-protein kinase SYK (SYK). | |||
| FCG2A_HUMAN | LIG_TYR_ITAM | 285 | 307 | Phosphorylation of Y288 and Y304 in the ITAM motif of Low affinity immunoglobulin gamma Fc region receptor II-a (FCGR2A) induces high-avidity binding to the tandem SH2 domains of Tyrosine-protein kinase SYK (SYK). | |||
| FCERG_HUMAN | LIG_TYR_ITAM | 62 | 79 | Phosphorylation of Y65 and Y76 in the ITAM motif of High affinity immunoglobulin epsilon receptor subunit gamma (FCER1G) induces high-avidity binding to the tandem SH2 domains of Tyrosine-protein kinase SYK (SYK). | |||
| FCERG_HUMAN | LIG_TYR_ITAM | 62 | 79 | 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). | |||
| OX1R_HUMAN | LIG_TYR_ITSM | 79 | 86 | Orexin-A induced phosphorylation of the ITSM and ITIM motifs in Orexin receptor type 1 (HCRTR1) allows binding of Tyrosine-protein phosphatase non-receptor type 11 (PTPN11) via its two SH2 domains. Mutation of either tyrosine in the motifs abolishes binding of Tyrosine-protein phosphatase non-receptor type 11 (PTPN11). | |||
| OX1R_HUMAN | LIG_TYR_ITIM | 356 | 361 | Orexin-A induced phosphorylation of the ITSM and ITIM motifs in Orexin receptor type 1 (HCRTR1) allows binding of Tyrosine-protein phosphatase non-receptor type 11 (PTPN11) via its two SH2 domains. Mutation of either tyrosine in the motifs abolishes binding of Tyrosine-protein phosphatase non-receptor type 11 (PTPN11). | |||
Type: Binary Subtype: Physicochemical compatibility | |||||||
| PTM of a residue in a motif or in its flanking regions alters the physicochemical and/or structural compatibility of the motif with its binding partner. This can either induce or enhance an interaction, or result in inhibition or even abrogation of an interaction. | |||||||
| LAT_HUMAN | LIG_SH2_STAT5 | 161 | 164 | 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. | |||
| SRC_HUMAN | LIG_SH2_SRC | 530 | 533 | Phosphorylation of Y530 in the SH2-binding motif of Proto-oncogene tyrosine-protein kinase Src (SRC) induces an intramolecular interaction with the SH2 domain of Proto-oncogene tyrosine-protein kinase Src (SRC) resulting in inhibition of its activity and preventing intermolecular interactions of its SH2 domain. | |||
| FCG2B_HUMAN | LIG_TYR_ITIM | 290 | 295 | Phosphorylation of Y292 in the ITIM motif of Low affinity immunoglobulin gamma Fc region receptor II-b (FCGR2B) induces binding of Phosphatidylinositol-3,4,5-trisphosphate 5-phosphatase 1 (INPP5D) via its SH2 domain. | |||
| KI3L2_HUMAN | LIG_TYR_ITIM | 396 | 401 | 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. | |||
| SLAF1_HUMAN | LIG_TYR_ITSM | 277 | 284 | Phosphorylation of Y281 in the ITSM motif of Signaling lymphocytic activation molecule (SLAMF1) induces binding of Tyrosine-protein phosphatase non-receptor type 11 (PTPN11) via one of its SH2 domains. | |||
| SLAF1_HUMAN | LIG_TYR_ITSM | 323 | 330 | Phosphorylation of Y327 in the ITSM motif of Signaling lymphocytic activation molecule (SLAMF1) induces binding of Tyrosine-protein phosphatase non-receptor type 11 (PTPN11) via one of its SH2 domains. | |||
| IRS1_RAT | LIG_SH2_GRB2 | 895 | 898 | 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. | |||
| A9UF02_HUMAN | LIG_SH2_IC | 174 | 180 | Phosphorylation of Y177 in the SH2-binding motif of BCR/ABL fusion induces binding to the Growth factor receptor-bound protein 2 (GRB2) protein. | |||
| PDPK1_HUMAN | LIG_SH2_IC | 376 | 379 | Phosphorylation of Y376 in the SH2-binding motif of 3-phosphoinositide-dependent protein kinase 1 (PDPK1) induces binding to the Tensin-1 (TNS1) protein. | |||
| LAT_HUMAN | LIG_SH2_IC | 198 | 203 | Phosphorylation of Y200 in the SH2-binding motif of Linker for activation of T-cells family member 1 (LAT) induces binding to the GRB2-related adaptor protein 2 (Grap2) protein. | |||
| LAT_HUMAN | LIG_SH2_IC | 218 | 223 | Phosphorylation of Y220 in the SH2-binding motif of Linker for activation of T-cells family member 1 (LAT) induces binding to the GRB2-related adaptor protein 2 (Grap2) protein. | |||
| LAT_MOUSE | LIG_SH2_GRB2 | 175 | 178 | Phosphorylation of Y175 in the SH2-binding motif of Linker for activation of T-cells family member 1 (Lat) induces binding to the Growth factor receptor-bound protein 2 (Grb2) protein. | |||
| LAT_MOUSE | LIG_SH2_GRB2 | 195 | 198 | Phosphorylation of Y195 in the SH2-binding motif of Linker for activation of T-cells family member 1 (Lat) induces binding to the Growth factor receptor-bound protein 2 (Grb2) protein. | |||
| LAT_MOUSE | LIG_SH2_GRB2 | 235 | 238 | 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. | |||
| DOK2_HUMAN | LIG_SH2_IC | 402 | 405 | Phosphorylation of Y402 in the SH2-binding motif of Docking protein 2 (DOK2) induces binding to the Tensin-1 (TNS1) protein. | |||
| JAK2_HUMAN | LIG_SH2_IIB | 804 | 823 | Phosphorylation of Y813 in the SH2-binding motif of Tyrosine-protein kinase JAK2 (JAK2) induces binding to the SH2B adapter protein 1 (SH2B1) protein. | |||
| DAB1_HUMAN | LIG_SH2_IB | 211 | 230 | Phosphorylation of Y220 in the SH2-binding motif of Disabled homolog 1 (DAB1) induces binding to the Adapter molecule crk (CRK) protein. | |||
| EGFR_HUMAN | LIG_SH2_IC | 1092 | 1100 | 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. | |||
| EGFR_HUMAN | LIG_SH2_IE | 1008 | 1024 | Phosphorylation of Y1016 in the SH2-binding motif of Epidermal growth factor receptor (EGFR) induces binding to the Tyrosine-protein kinase JAK2 (JAK2) protein. | |||
| EGFR_HUMAN | LIG_SH2_ID | 1008 | 1024 | Phosphorylation of Y1016 in the SH2-binding motif of Epidermal growth factor receptor (EGFR) induces binding to the SH2 domain-containing protein 3C (SH2D3C) protein. | |||
| EGFR_HUMAN | LIG_SH2_ID | 1008 | 1024 | Phosphorylation of Y1016 in the SH2-binding motif of Epidermal growth factor receptor (EGFR) induces binding to the SH2 domain-containing protein 3A (SH2D3A) protein. | |||
| EGFR_HUMAN | LIG_SH2_III | 1008 | 1024 | Phosphorylation of Y1016 in the SH2-binding motif of Epidermal growth factor receptor (EGFR) induces binding to the Signal transducer and activator of transcription 6 (STAT6) protein. | |||
| ERBB2_HUMAN | LIG_SH2_IC | 1135 | 1144 | Phosphorylation of Y1139 in the SH2-binding motif of Receptor tyrosine-protein kinase erbB-2 (ERBB2) induces binding to the Growth factor receptor-bound protein 7 (GRB7) protein. | |||
| ERBB2_HUMAN | LIG_SH2_IE | 1015 | 1031 | Phosphorylation of Y1023 in the SH2-binding motif of Receptor tyrosine-protein kinase erbB-2 (ERBB2) induces binding to the Tyrosine-protein kinase JAK2 (JAK2) protein. | |||
| ERBB2_HUMAN | LIG_SH2_ID | 1131 | 1147 | Phosphorylation of Y1139 in the SH2-binding motif of Receptor tyrosine-protein kinase erbB-2 (ERBB2) induces binding to the Breast cancer anti-estrogen resistance protein 3 (BCAR3) protein. | |||
| ERBB2_HUMAN | LIG_SH2_ID | 1015 | 1031 | Phosphorylation of Y1023 in the SH2-binding motif of Receptor tyrosine-protein kinase erbB-2 (ERBB2) induces binding to the SH2 domain-containing protein 3A (SH2D3A) protein. | |||
| ERBB2_HUMAN | LIG_SH2_III | 1131 | 1147 | Phosphorylation of Y1139 in the SH2-binding motif of Receptor tyrosine-protein kinase erbB-2 (ERBB2) induces binding to the Signal transducer and activator of transcription 6 (STAT6) protein. | |||
| NTRK1_HUMAN | LIG_SH2_IIB | 782 | 796 | 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. | |||
| NTRK1_HUMAN | LIG_SH2_IB | 783 | 796 | 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. | |||
| RET_HUMAN | LIG_SH2_IIB | 976 | 985 | Phosphorylation of Y981 in the SH2-binding motif of Proto-oncogene tyrosine-protein kinase receptor Ret (RET) induces binding to the SH2B adapter protein 1 (SH2B1) protein. | |||
| MET_HUMAN | LIG_SH2_IC | 1351 | 1360 | 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. | |||
| PGFRB_HUMAN | LIG_SH2_IIA | 751 | 755 | Phosphorylation of Y751 in the SH2-binding motif of Platelet-derived growth factor receptor beta (PDGFRB) induces binding to the Phosphatidylinositol 3-kinase regulatory subunit alpha (PIK3R1) protein. | |||
| PGFRB_HUMAN | LIG_SH2_IIA | 1018 | 1029 | Phosphorylation of Y1021 in the SH2-binding motif of Platelet-derived growth factor receptor beta (PDGFRB) induces binding to the 1-phosphatidylinositol-4,5-bisphosphate phosphodiesterase gamma-1 (PLCG1) protein. | |||
| GHR_HUMAN | LIG_SH2_IIA | 591 | 600 | 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. | |||
| GHR_HUMAN | LIG_SH2_III | 428 | 444 | Phosphorylation of Y436 in the SH2-binding motif of Growth hormone receptor (GHR) induces binding to the Signal transducer and activator of transcription 5B (STAT5B) protein. | |||
| IL2RB_HUMAN | LIG_SH2_IA | 409 | 428 | Phosphorylation of Y418 in the SH2-binding motif of Interleukin-2 receptor subunit beta (IL2RB) induces binding to the Tyrosine-protein kinase Lck (LCK) protein. | |||
| IL2RB_HUMAN | LIG_SH2_III | 531 | 540 | Phosphorylation of Y536 in the SH2-binding motif of Interleukin-2 receptor subunit beta (IL2RB) induces binding to the Signal transducer and activator of transcription 5A (STAT5A) protein. | |||
| IL2RB_HUMAN | LIG_SH2_IIB | 361 | 370 | Phosphorylation of Y364 in the SH2-binding motif of Interleukin-2 receptor subunit beta (IL2RB) induces binding to the SHC-transforming protein 1 (SHC1) protein. | |||
| IL2RB_HUMAN | LIG_SH2_III | 528 | 544 | Phosphorylation of Y536 in the SH2-binding motif of Interleukin-2 receptor subunit beta (IL2RB) induces binding to the Signal transducer and activator of transcription 5B (STAT5B) protein. | |||
| INGR1_HUMAN | LIG_SH2_III | 457 | 461 | 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. | |||
| VAV_HUMAN | LIG_SH2_IIB | 165 | 180 | Phosphorylation of Y174 in the SH2-binding motif of Proto-oncogene vav (VAV1) induces binding to the SH2 domain-containing adapter protein B (SHB) protein. | |||
| PGFRA_HUMAN | LIG_SH2_IIB | 705 | 729 | Phosphorylation of Y720 in the SH2-binding motif of Platelet-derived growth factor receptor alpha (PDGFRA) induces binding to the SH2 domain-containing adapter protein F (SHF) protein. | |||
| EPOR_HUMAN | LIG_SH2_III | 360 | 376 | Phosphorylation of Y368 in the SH2-binding motif of Erythropoietin receptor (EPOR) induces binding to the Signal transducer and activator of transcription 5B (STAT5B) protein. | |||
| EPOR_HUMAN | LIG_SH2_III | 418 | 434 | Phosphorylation of Y426 in the SH2-binding motif of Erythropoietin receptor (EPOR) induces binding to the Signal transducer and activator of transcription 5B (STAT5B) protein. | |||
| EPOR_HUMAN | LIG_SH2_III | 496 | 508 | Phosphorylation of Y504 in the SH2-binding motif of Erythropoietin receptor (EPOR) induces binding to the Signal transducer and activator of transcription 5B (STAT5B) protein. | |||
| ERBB3_HUMAN | LIG_SH2_ID | 860 | 876 | Phosphorylation of Y868 in the SH2-binding motif of Receptor tyrosine-protein kinase erbB-3 (ERBB3) induces binding to the Breast cancer anti-estrogen resistance protein 3 (BCAR3) protein. | |||
| ERBB3_HUMAN | LIG_SH2_ID | 1268 | 1284 | Phosphorylation of Y1276 in the SH2-binding motif of Receptor tyrosine-protein kinase erbB-3 (ERBB3) induces binding to the Breast cancer anti-estrogen resistance protein 3 (BCAR3) protein. | |||
| ERBB3_HUMAN | LIG_SH2_ID | 1281 | 1297 | Phosphorylation of Y1289 in the SH2-binding motif of Receptor tyrosine-protein kinase erbB-3 (ERBB3) induces binding to the Breast cancer anti-estrogen resistance protein 3 (BCAR3) protein. | |||
| ERBB3_HUMAN | LIG_SH2_ID | 1320 | 1336 | Phosphorylation of Y1328 in the SH2-binding motif of Receptor tyrosine-protein kinase erbB-3 (ERBB3) induces binding to the Breast cancer anti-estrogen resistance protein 3 (BCAR3) protein. | |||
| ERBB3_HUMAN | LIG_SH2_ID | 1320 | 1336 | Phosphorylation of Y1328 in the SH2-binding motif of Receptor tyrosine-protein kinase erbB-3 (ERBB3) induces binding to the SH2 domain-containing protein 3A (SH2D3A) protein. | |||
| ERBB3_HUMAN | LIG_SH2_III | 1320 | 1336 | Phosphorylation of Y1328 in the SH2-binding motif of Receptor tyrosine-protein kinase erbB-3 (ERBB3) induces binding to the Signal transducer and activator of transcription 6 (STAT6) protein. | |||
| CBL_HUMAN | LIG_SH2_IB | 770 | 780 | Phosphorylation of Y774 in the SH2-binding motif of E3 ubiquitin-protein ligase CBL (CBL) induces binding to the Adapter molecule crk (CRK) protein. | |||
| IL4RA_HUMAN | LIG_SH2_III | 566 | 585 | Phosphorylation of Y575 in the SH2-binding motif of Interleukin-4 receptor subunit alpha (IL4R) induces binding to the Signal transducer and activator of transcription 6 (STAT6) protein. | |||
| IL4RA_HUMAN | LIG_SH2_III | 594 | 613 | Phosphorylation of Y603 in the SH2-binding motif of Interleukin-4 receptor subunit alpha (IL4R) induces binding to the Signal transducer and activator of transcription 6 (STAT6) protein. | |||
| IL4RA_HUMAN | LIG_SH2_III | 622 | 641 | 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. | |||
| IL4RA_HUMAN | LIG_SH2_IIA | 706 | 721 | 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. | |||
| IL4RA_HUMAN | LIG_SH2_IIB | 706 | 721 | Phosphorylation of Y713 in the SH2-binding motif of Interleukin-4 receptor subunit alpha (IL4R) induces binding to the SHC-transforming protein 1 (SHC1) protein. | |||
| IL4RA_HUMAN | LIG_SH2_IIB | 706 | 721 | Phosphorylation of Y713 in the SH2-binding motif of Interleukin-4 receptor subunit alpha (IL4R) induces binding to the Phosphatidylinositol-3,4,5-trisphosphate 5-phosphatase 1 (INPP5D) protein. | |||
| EPHA3_HUMAN | LIG_SH2_IA | 597 | 606 | Phosphorylation of Y602 in the SH2-binding motif of Ephrin type-A receptor 3 (EPHA3) induces binding to the Cytoplasmic protein NCK1 (NCK1) protein. | |||
| SHC1_HUMAN | LIG_SH2_IC | 423 | 435 | 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. | |||
| FCERG_HUMAN | LIG_SH2_IA | 75 | 79 | 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. | |||
| FRS2_HUMAN | LIG_SH2_IC | 191 | 200 | Phosphorylation of Y196 in the SH2-binding motif of Fibroblast growth factor receptor substrate 2 (FRS2) induces binding to the Growth factor receptor-bound protein 2 (GRB2) protein. | |||
| FRS2_HUMAN | LIG_SH2_IC | 301 | 310 | Phosphorylation of Y306 in the SH2-binding motif of Fibroblast growth factor receptor substrate 2 (FRS2) induces binding to the Growth factor receptor-bound protein 2 (GRB2) protein. | |||
| FRS2_HUMAN | LIG_SH2_IC | 345 | 355 | Phosphorylation of Y349 in the SH2-binding motif of Fibroblast growth factor receptor substrate 2 (FRS2) induces binding to the Growth factor receptor-bound protein 2 (GRB2) protein. | |||
| FRS2_HUMAN | LIG_SH2_IC | 385 | 395 | 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. | |||
| FRS2_HUMAN | LIG_SH2_IIA | 431 | 440 | Phosphorylation of Y436 in the SH2-binding motif of Fibroblast growth factor receptor substrate 2 (FRS2) induces binding to the Tyrosine-protein phosphatase non-receptor type 11 (PTPN11) protein. | |||
| FRS2_HUMAN | LIG_SH2_IIA | 465 | 475 | 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. | |||
| M4K1_HUMAN | LIG_SH2_IIB | 372 | 391 | Phosphorylation of Y381 in the SH2-binding motif of Mitogen-activated protein kinase kinase kinase kinase 1 (MAP4K1) induces binding to the B-cell linker protein (BLNK) protein. | |||
| CSF3R_HUMAN | LIG_SH2_IIA | 747 | 758 | 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. | |||
| DOK1_HUMAN | LIG_SH2_IIB | 203 | 206 | Phosphorylation of Y203 in the SH2-binding motif of Docking protein 1 (DOK1) induces binding to the Phosphatidylinositol-3,4,5-trisphosphate 5-phosphatase 1 (INPP5D) protein. | |||
| DOK1_HUMAN | LIG_SH2_IB | 447 | 454 | Phosphorylation of Y449 in the SH2-binding motif of Docking protein 1 (DOK1) induces binding to the SH2 domain-containing protein 1A (SH2D1A) protein. | |||
| FAK1_HUMAN | LIG_SH2_IA | 389 | 405 | Phosphorylation of Y397 in the SH2-binding motif of Focal adhesion kinase 1 (PTK2) induces binding to the Cytoplasmic protein NCK2 (NCK2) protein. | |||
| LCP2_HUMAN | LIG_SH2_IIB | 105 | 118 | Phosphorylation of Y113 in the SH2-binding motif of Lymphocyte cytosolic protein 2 (LCP2) induces binding to the SH2 domain-containing adapter protein B (SHB) protein. | |||
| LCP2_HUMAN | LIG_SH2_IIB | 120 | 133 | Phosphorylation of Y128 in the SH2-binding motif of Lymphocyte cytosolic protein 2 (LCP2) induces binding to the SH2 domain-containing adapter protein B (SHB) protein. | |||
| LCP2_HUMAN | LIG_SH2_IIB | 137 | 150 | Phosphorylation of Y145 in the SH2-binding motif of Lymphocyte cytosolic protein 2 (LCP2) induces binding to the SH2 domain-containing adapter protein B (SHB) protein. | |||
| SLAF1_HUMAN | LIG_SH2_IB | 276 | 286 | Phosphorylation of Y281 in the SH2-binding motif of Signaling lymphocytic activation molecule (SLAMF1) induces binding to the SH2 domain-containing protein 1A (SH2D1A) protein. | |||
| SLAF1_HUMAN | LIG_SH2_IB | 273 | 286 | Phosphorylation of Y281 in the SH2-binding motif of Signaling lymphocytic activation molecule (SLAMF1) induces binding to the SH2 domain-containing protein 1B (Sh2d1b) protein. | |||
| FAK2_HUMAN | LIG_SH2_IB | 394 | 410 | Phosphorylation of Y402 in the SH2-binding motif of Protein-tyrosine kinase 2-beta (PTK2B) induces binding to the Megakaryocyte-associated tyrosine-protein kinase (MATK) protein. | |||
| NTRK2_HUMAN | LIG_SH2_IA | 714 | 730 | Phosphorylation of Y727 in the SH2-binding motif of BDNF/NT-3 growth factors receptor (NTRK2) induces binding to the Cytoplasmic protein NCK2 (NCK2) protein. | |||
| LCP2_MOUSE | LIG_SH2_IA | 143 | 148 | 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. | |||
| JAK2_MOUSE | LIG_SH2_III | 804 | 820 | Phosphorylation of Y813 in the SH2-binding motif of Tyrosine-protein kinase JAK2 (Jak2) induces binding to the Signal transducer and activator of transcription 5B (Stat5b) protein. | |||
| BCAR1_HUMAN | LIG_SH2_IB | 358 | 368 | 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. | |||
| GBLP_RAT | LIG_SH2_IA | 241 | 250 | Phosphorylation of Y246 in the SH2-binding motif of Guanine nucleotide-binding protein subunit beta-2-like 1 (Gnb2l1) induces binding to the Proto-oncogene tyrosine-protein kinase Src (SRC) protein. | |||
| DCD_HUMAN | LIG_SH2_IA | 15 | 25 | Phosphorylation of Y20 in the SH2-binding motif of Dermcidin (DCD) induces binding to the Cytoplasmic protein NCK1 (NCK1) protein. | |||
| DAB1_MOUSE | LIG_SH2_IA | 212 | 228 | Phosphorylation of Y220 in the SH2-binding motif of Disabled homolog 1 (Dab1) induces binding to the Cytoplasmic protein NCK2 (NCK2) protein. | |||
| IL6RB_MOUSE | LIG_SH2_IIA | 750 | 764 | Phosphorylation of Y757 in the SH2-binding motif of Interleukin-6 receptor subunit beta (Il6st) induces binding to the Suppressor of cytokine signaling 3 (Socs3) protein. | |||
| STA5A_HUMAN | LIG_SH2_III | 686 | 702 | 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. | |||
| EPHB2_MOUSE | LIG_SH2_IB | 601 | 610 | Phosphorylation of Y604 in the SH2-binding motif of Ephrin type-B receptor 2 (Ephb2) induces binding to the Adapter molecule crk (CRK) protein. | |||
| EPHB2_MOUSE | LIG_SH2_IB | 606 | 620 | Phosphorylation of Y610 in the SH2-binding motif of Ephrin type-B receptor 2 (Ephb2) induces binding to the Adapter molecule crk (CRK) protein. | |||
| LEPR_MOUSE | LIG_SH2_III | 1129 | 1148 | Phosphorylation of Y1138 in the SH2-binding motif of Leptin receptor (Lepr) induces binding to the Signal transducer and activator of transcription 3 (STAT3) protein. | |||
| ERBB3_HUMAN | LIG_SH2_IE | 1320 | 1336 | Phosphorylation of Y1328 in the SH2-binding motif of Receptor tyrosine-protein kinase erbB-3 (ERBB3) induces binding to the Tyrosine-protein kinase JAK2 (JAK2) protein. | |||
| ERBB3_HUMAN | LIG_SH2_IE | 1268 | 1284 | Phosphorylation of Y1276 in the SH2-binding motif of Receptor tyrosine-protein kinase erbB-3 (ERBB3) induces binding to the Tyrosine-protein kinase JAK2 (JAK2) protein. | |||
| IL4RA_HUMAN | LIG_SH2_IIA | 706 | 721 | 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. | |||
| DAB1_MOUSE | LIG_SH2_IA | 232 | 235 | Phosphorylation of Y232 in the SH2-binding motif of Disabled homolog 1 (Dab1) induces binding to Cytoplasmic protein NCK2 (NCK2). | |||
| DAB1_MOUSE | LIG_SH2_IA | 232 | 235 | Phosphorylation of Y232 in the SH2-binding motif of Disabled homolog 1 (Dab1) induces binding to Adapter molecule crk (Crk). | |||
| DAB1_MOUSE | LIG_SH2_IA | 185 | 188 | Phosphorylation of Y185 in the SH2-binding motif of Disabled homolog 1 (Dab1) induces binding to Neuronal proto-oncogene tyrosine-protein kinase Src (Src). | |||
| DAB1_MOUSE | LIG_SH2_SRC | 198 | 201 | Phosphorylation of Y198 in the SH2-binding motif of Disabled homolog 1 (Dab1) induces binding to Neuronal proto-oncogene tyrosine-protein kinase Src (Src). | |||
| EGFR_HUMAN | LIG_SH2_SRC | 1016 | 1019 | Phosphorylation of Y1016 in the SH2-binding motif of Epidermal growth factor receptor (EGFR) induces binding to 1-phosphatidylinositol-4,5-bisphosphate phosphodiesterase gamma-1 (PLCG1). | |||
| EGFR_HUMAN | LIG_SH2_SRC | 1125 | 1128 | Phosphorylation of Y1125 in the SH2-binding motif of Epidermal growth factor receptor (EGFR) induces binding to Adapter molecule crk (CRK). | |||
| EGFR_HUMAN | LIG_SH2_SRC | 1016 | 1019 | Phosphorylation of Y1016 in the SH2-binding motif of Epidermal growth factor receptor (EGFR) induces binding to Cytoplasmic protein NCK1 (NCK1). | |||
| ERBB3_HUMAN | LIG_SH2_GRB2 | 1262 | 1265 | 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). | |||
| FAK1_HUMAN | LIG_SH2_SRC | 397 | 400 | 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). | |||
| GAB1_HUMAN | LIG_SH2_STAT5 | 472 | 475 | Phosphorylation of Y472 in the SH2-binding motif of GRB2-associated-binding protein 1 (GAB1) induces binding to Phosphatidylinositol 3-kinase regulatory subunit alpha (PIK3R1). | |||
| GAB1_HUMAN | LIG_SH2_STAT5 | 447 | 450 | 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). | |||
Type: Binary Subtype: Pre‑translational | |||||||
| Pre-translational mechanisms such as alternative splicing, alternative promoter-usage and/or RNA editing result in inclusion or removal of exons that contain an entire or partial motif. | |||||||
| ERBB4_HUMAN | LIG_SH2_IIA | 1056 | 1059 | 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. | |||
| SLAF7_HUMAN | LIG_TYR_ITSM | 280 | 287 | Alternative splicing removes the ITSM (immunoreceptor tyrosine-based switch motif) motif of SLAM family member 7 (SLAMF7), abrogating binding to SH2 domain-containing protein 1A (SH2D1A). The full-length isoform (Isoform CS1-L of SLAM family member 7 (SLAMF7)) has 2 ITSM motifs and only one is missing in the shorter splice variant (Isoform 19A24 of SLAM family member 7 (SLAMF7)). However, experiments showed only Isoform CS1-L of SLAM family member 7 (SLAMF7) binds to SH2D1A. | |||
| SHIP1_HUMAN | LIG_SH2_IIA | 918 | 921 | 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). | |||
| SIG12_MOUSE | LIG_TYR_ITIM | 430 | 435 | Alternative splicing removes the ITIM (immunoreceptor tyrosine-based inhibitory motif) of Sialic acid-binding Ig-like lectin 12 (Siglec12), abrogating binding to Tyrosine-protein phosphatase non-receptor type 6 (Ptpn6). | |||
| SIG12_MOUSE | LIG_TYR_ITIM | 430 | 435 | Alternative splicing removes the ITIM (immunoreceptor tyrosine-based inhibitory motif) of Sialic acid-binding Ig-like lectin 12 (Siglec12), abrogating binding to Tyrosine-protein phosphatase non-receptor type 11 (Ptpn11). | |||
| TRML1_HUMAN | LIG_TYR_ITIM | 279 | 284 | Alternative splicing removes the ITIM (immunoreceptor tyrosine-based inhibitory motif) of Trem-like transcript 1 protein (TREML1), abrogating binding to Tyrosine-protein phosphatase non-receptor type 11 (PTPN11). | |||
| STA5A_HUMAN | LIG_SH2_STAT5 | 694 | 697 | Alternative splicing removes the regulatory Y694 residue of Signal transducer and activator of transcription 5A (STAT5A). The phosphorylation of Y694 by Proto-oncogene tyrosine-protein kinase Src (SRC) has been shown to be essential for DNA binding. This event acts as an important regulatory mechanism (See Clark et al. (2005) (here) and Okutani et al. (2001) (here)). The exact function of Y694 remains uncertain as is binding to STAT5 in dimer. The STAT5A-DeltaE18 does not enter nucleus upon PRLR stimulation. | |||
| DAB1_MOUSE | LIG_SH2_IA | 220 | 223 | Alternative splicing removes the SH2-binding motif of Disabled homolog 1 (Dab1), abrogating binding to Cytoplasmic protein NCK2 (NCK2). NCK2-beta has a clear preference for splice variant 2 (with the YQYI motif) over splice variant 3 (with the YQTI motif). The authors theorise that since Adapter molecule crk (Crk) is directly linked to the C3G-Rap1 pathway, and NCK2-beta is linked to the Breast cancer anti-estrogen resistance protein 1 (Bcar1) (p130Cas) pathway, it is likely that isoforms 2 and 3 connect to different downstream cascades. It was suggested that the ability of different Dab1 isoforms to recruit distinct sets of SH2 domains implies a fine-tuning role of Dab1 splicing in the intricate series of events that underlie neuronal migration (Gao et al. (2012) (here)) (See also Katyal and Godbout (2004) (here) and Gao et al. (2010) (here)). | |||
| DAB1_MOUSE | LIG_SH2_IA | 232 | 235 | Alternative splicing removes the SH2-binding motif of Disabled homolog 1 (Dab1), abrogating binding to Cytoplasmic protein NCK2 (NCK2). The NCK2-beta has a clear preference for splice variant 2 (with YQYI motif) over splice variant 3 (with YQTI motif). The authors theorise that since Adapter molecule crk (Crk) is directly linked to the C3G-Rap1 pathway, and NCK2-beta is linked to the Breast cancer anti-estrogen resistance protein 1 (Bcar1) (p130Cas) pathway, it is likely that isoforms 2 and 3 connect to different downstream cascades. It was suggested that the ability of different Dab1 isoforms to recruit distinct sets of SH2 domains implies a fine-tuning role of Dab1 splicing in the intricate series of events that underlie neuronal migration (Gao et al. (2012) (here)) (See also Katyal and Godbout (2004) (here) and Gao et al. (2010) (here)). | |||
| DAB1_MOUSE | LIG_SH2_IA | 220 | 223 | Alternative splicing removes the SH2-binding motif of Disabled homolog 1 (Dab1), abrogating binding to Adapter molecule crk (Crk). Both Adapter molecule crk (Crk) and Crk-like protein (Crkl) bind equally well to variants 2 and 3. The authors theorise that since Adapter molecule crk (Crk) is directly linked to the C3G-Rap1 pathway, and NCK2-beta is linked to the Breast cancer anti-estrogen resistance protein 1 (Bcar1) (p130Cas) pathway, it is likely that isoforms 2 and 3 connect to different downstream cascades. It was suggested that the ability of different Dab1 isoforms to recruit distinct sets of SH2 domains implies a fine-tuning role of Dab1 splicing in the intricate series of events that underlie neuronal migration (Gao et al. (2012) (here)) (See also Katyal and Godbout (2004) (here) and Gao et al. (2010) (here)). | |||
| DAB1_MOUSE | LIG_SH2_IA | 232 | 235 | Alternative splicing removes the SH2-binding motif of Disabled homolog 1 (Dab1), abrogating binding to Adapter molecule crk (Crk). Both Adapter molecule crk (Crk) and Crk-like protein (Crkl) bind equally well to variants 2 and 3. The authors theorise that since Adapter molecule crk (Crk) is directly linked to the C3G-Rap1 pathway, and NCK2-beta is linked to the Breast cancer anti-estrogen resistance protein 1 (Bcar1) (p130Cas) pathway, it is likely that isoforms 2 and 3 connect to different downstream cascades. It was suggested that the ability of different Dab1 isoforms to recruit distinct sets of SH2 domains implies a fine-tuning role of Dab1 splicing in the intricate series of events that underlie neuronal migration (Gao et al. (2012) (here)) (See also Katyal and Godbout (2004) (here) and Gao et al. (2010) (here)). | |||
| DAB1_MOUSE | LIG_SH2_IA | 185 | 188 | Alternative splicing removes the SH2-binding motif of Disabled homolog 1 (Dab1), abrogating binding to Neuronal proto-oncogene tyrosine-protein kinase Src (Src). Splice variants 2 and 3 (only containing one of the YQxI motifs, i.e. Y185 and Y198) exhibit decreased tyrosine phosphorylation, suggesting both motifs are required for full activation of Dab1. Dab1 is likely to recruit Neuronal proto-oncogene tyrosine-protein kinase Src (Src) via these two YQxI motifs, which subsequently phosphorylates adjacent YxVP motifs (here). This was also suggested for Phosphatidylinositol 3-kinase regulatory subunit alpha (Pik3r1) and Suppressor of cytokine signaling 2 (Socs2). Gao et al. (2012) (here) suggests that the ability of different Dab1 isoforms to recruit distinct sets of SH2 domains allows a fine-tuning role for Dab1 splicing in the intricate series of events that underlie neuronal migration (See also Katyal & Godbout (2004) (here) and Gao et al. (2010) (here)). | |||
| DAB1_MOUSE | LIG_SH2_SRC | 198 | 201 | Alternative splicing removes the SH2-binding motif of Disabled homolog 1 (Dab1), abrogating binding to Neuronal proto-oncogene tyrosine-protein kinase Src (Src). Splice variants 2 and 3 (only containing one of the YQxI motifs, i.e. Y185 and Y198) exhibit decreased tyrosine phosphorylation, suggesting both motifs are required for full activation of Dab1. Dab1 is likely to recruit Neuronal proto-oncogene tyrosine-protein kinase Src (Src) via these two YQxI motifs, which subsequently phosphorylates adjacent YxVP motifs (here). This was also suggested for Phosphatidylinositol 3-kinase regulatory subunit alpha (Pik3r1) and Suppressor of cytokine signaling 2 (Socs2). Gao et al. (2012) (here) suggests that the ability of different Dab1 isoforms to recruit distinct sets of SH2 domains allows a fine-tuning role for Dab1 splicing in the intricate series of events that underlie neuronal migration (See also Katyal & Godbout (2004) (here) and Gao et al. (2010) (here)). | |||
| PRLR_HUMAN | LIG_SH2_STAT5 | 342 | 345 | 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)). | |||
| SIG12_MOUSE | LIG_TYR_ITIM | 430 | 435 | Alternative splicing removes the ITIM (immunoreceptor tyrosine-based inhibitory motif) of Sialic acid-binding Ig-like lectin 12 (Siglec12), abrogating binding to Tyrosine-protein phosphatase non-receptor type 6 (Ptpn6). | |||
| SIG12_MOUSE | LIG_TYR_ITIM | 430 | 435 | Alternative splicing removes the ITIM (immunoreceptor tyrosine-based inhibitory motif) of Sialic acid-binding Ig-like lectin 12 (Siglec12), abrogating binding to Tyrosine-protein phosphatase non-receptor type 11 (Ptpn11). | |||
| TRML1_HUMAN | LIG_TYR_ITIM | 279 | 284 | Alternative splicing removes the ITIM (immunoreceptor tyrosine-based inhibitory motif) of Trem-like transcript 1 protein (TREML1), abrogating binding to Tyrosine-protein phosphatase non-receptor type 11 (PTPN11). | |||
| SHIP1_HUMAN | LIG_SH2_IIA | 918 | 921 | Alternative splicing partially removes the SH2-binding motif of Phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 1 (Inpp5d), partially inhibiting binding to Phosphatidylinositol 3-kinase regulatory subunit alpha (Pik3r1). | |||
| ERBB4_HUMAN | LIG_SH2_IIA | 1056 | 1059 | 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. | |||
Type: Cumulative Subtype: Rheostatic | |||||||
| Rheostatic switches gradually alter the affinity of a motif for a single binding partner by addition of multiple PTMs that additively contribute to this modulation. Additional modifications can either strengthen or weaken an interaction. | |||||||
| A4_HUMAN | LIG_SH2_GRB2 | 757 | 760 | While phosphorylation of Y757 in the SH2-binding motif of Amyloid beta A4 protein (APP) induces binding to Growth factor receptor-bound protein 2 (GRB2), additional phosphorylation of T743 further increases the strength of the interaction. | |||
Type: Specificity Subtype: Altered binding specificity | |||||||
| The balance of the competition for overlapping or adjacent, mutually exclusive interaction interfaces is tipped in favor of one of the interactors by PTM-dependent modulation of the intrinsic affinity of a binding region. Multiple, successive PTMs allow sequential switching of different binding partners in an ordered manner by step-wise alteration of binding specificity. | |||||||
| CTLA4_MOUSE | LIG_SH2_STAT5 | 201 | 204 | Dephosphorylation of Y201 of Cytotoxic T-lymphocyte protein 4 (Ctla4) switches the specificity of Ctla4 from SH2 domain-containing proteins like Tyrosine-protein phosphatase non-receptor type 11 (Ptpn11) to the AP-2 complex mu subunit (AP-2 complex subunit mu (Ap2m1)), thereby switching from inhibitory signal transmission and negative regulation of T cell responses to internalization and inactivation of Ctla4. | |||
| DAG1_HUMAN | LIG_SH2_SRC | 892 | 895 | Adhesion-dependent phosphorylation of Y892 in Dystroglycan (DAG1) by Src kinase (Proto-oncogene tyrosine-protein kinase Src (SRC)) switches the specificity of DAG1 from the WW domain containing cytoskeletal linker Dystrophin (DMD) to the SH2 domain containing Tyrosine-protein kinase Fyn (FYN). | |||
| CD3E_HUMAN | LIG_TYR_ITAM | 185 | 202 | 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). | |||
| DAG1_HUMAN | LIG_SH2_SRC | 892 | 895 | Adhesion-dependent phosphorylation of Y892 in Dystroglycan (DAG1) by c-Src (SRC) switches the specificity of DAG1 from WW domain containing proteins like Utrophin (UTRN) to SH2 domain containing proteins like Tyrosine-protein kinase CSK (CSK). | |||
| ERBB4_HUMAN | LIG_SH2_STAT5 | 1056 | 1059 | 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. | |||
| A4_HUMAN | LIG_SH2_GRB2 | 757 | 760 | Phosphorylation of Y757 in APP (Amyloid beta A4 protein (APP)) switches its specificity from PTB domain containing proteins, like Amyloid beta A4 precursor protein-binding family B member 1 (APBB1), which is involved in trafficking and processing of APP, to SH2 domain containing proteins, such as Growth factor receptor-bound protein 2 (GRB2). | |||