Please send any suggestions/comments to: switches@elm.eu.org
| 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. | |||||||
| SCNNG_HUMAN | LIG_WW_1 | 624 | 627 | 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. | |||
Type: Specificity Subtype: Competition | |||||||
| Competitive binding of multiple binding partners to overlapping or adjacent, mutually exclusive interaction interfaces depends on local target protein abundance, which can be regulated by changing the expression level or subcellular localisation of the competitors, or by scaffolding. | |||||||
| DAG1_HUMAN | LIG_WW_1 | 889 | 892 | The WW-binding motif for Dystrophin (DMD) and the SH3-binding motif for Growth factor receptor-bound protein 2 (GRB2) on Dystroglycan (DAG1) overlap, making their interactions mutually exclusive and competitive. | |||
| DAG1_HUMAN | LIG_WW_1 | 889 | 892 | The WW-binding motif for Dystrophin (DMD) and the SH3-binding motif for Growth factor receptor-bound protein 2 (GRB2) on Dystroglycan (DAG1) overlap, making their interactions mutually exclusive and competitive. | |||
| P73_HUMAN | LIG_WW_1 | 484 | 487 | The transcriptional coactivator YAP1 and the ubiquitin ligase Itch competitively bind to the same WW-binding motif of p73. Binding of YAP1 prevents Itch-mediated ubiquitylation of p73, resulting in stabilisation, and increases trancriptional activity of p73. | |||
| P73_HUMAN | LIG_WW_1 | 484 | 487 | The transcriptional coactivator YAP1 and the ubiquitin ligase Itch competitively bind to the same WW-binding motif of p73. Binding of YAP1 prevents Itch-mediated ubiquitylation of p73, resulting in stabilisation, and increases trancriptional activity of p73. | |||
Type: Avidity‑sensing Subtype: | |||||||
| Multiple low-affinity interactions give rise to high-avidity interactions that have increased binding strength, with more than additive affinity. | |||||||
| SMAD3_HUMAN | LIG_WW_1 | 181 | 184 | CDK8/9 phosphorylates Mothers against decapentaplegic homolog 3 (SMAD3) at T179 and S208. Phosphorylation of T179 creates a binding site for the WW domain of Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1), while phosphorylation of S208 primes SMAD3 for phosphorylation of S204 by Glycogen synthase kinase-3 beta (GSK3B). The pS204-pS208 forms a binding site for the third WW domain of the E3 ubiquitin-protein ligase NEDD4-like (NEDD4L), whose second WW domain will displace the WW domain of PIN1 at the pT179-PY box site of SMAD3. This regulation couples SMAD3 activation to SMAD3 destruction in an ordered fashion. Dual phosphorylation of the two NEDD4L-binding sites mediates high-avidity binding of two WW domains of NEDD4L to SMAD3. See also switch details and switch details. | |||
| SMAD3_HUMAN | LIG_WW_Nedd4L | 203 | 210 | 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. | |||
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. | |||||||
| TFCP2_HUMAN | DOC_WW_Pin1_4 | 326 | 331 | Phosphorylation of T329 in the Pin1-binding motif of Alpha-globin transcription factor CP2 (TFCP2) induces binding to Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1), which isomerises the peptide bonds at the nearby-phosphorylated SP motifs (S291 and S309) to the trans configuration, thereby facilitating their dephosphorylation, which is required for the transcriptional activity of Alpha-globin transcription factor CP2 (TFCP2). | |||
| P73_HUMAN | DOC_WW_Pin1_4 | 409 | 414 | Phosphorylation of S412 in the Pin1-binding motif of Tumor protein p73 (TP73) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein. | |||
| P73_HUMAN | DOC_WW_Pin1_4 | 439 | 444 | Phosphorylation of T442 in the Pin1-binding motif of Tumor protein p73 (TP73) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein. | |||
| P73_HUMAN | DOC_WW_Pin1_4 | 479 | 484 | Phosphorylation of T482 in the Pin1-binding motif of Tumor protein p73 (TP73) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein. | |||
| B2L11_MOUSE | DOC_WW_Pin1_4 | 62 | 67 | Phosphorylation of S65 in the Pin1-binding motif of Bcl-2-like protein 11 (Bcl2l11) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) protein. | |||
| FOS_MOUSE | DOC_WW_Pin1_4 | 229 | 234 | Phosphorylation of T232 in the Pin1-binding motif of Proto-oncogene c-Fos (Fos) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) protein. | |||
| FOS_MOUSE | DOC_WW_Pin1_4 | 322 | 327 | Phosphorylation of T325 in the Pin1-binding motif of Proto-oncogene c-Fos (Fos) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) protein. | |||
| FOS_MOUSE | DOC_WW_Pin1_4 | 328 | 333 | Phosphorylation of T331 in the Pin1-binding motif of Proto-oncogene c-Fos (Fos) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) protein. | |||
| FOS_MOUSE | DOC_WW_Pin1_4 | 371 | 376 | Phosphorylation of S374 in the Pin1-binding motif of Proto-oncogene c-Fos (Fos) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) protein. | |||
| MYC_HUMAN | DOC_WW_Pin1_4 | 55 | 60 | Phosphorylation of T58 in the Pin1-binding motif of Myc proto-oncogene protein (MYC) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein. | |||
| TAX_HTL1A | DOC_WW_Pin1_4 | 157 | 162 | Phosphorylation of S160 in the Pin1-binding motif of Protein Tax-1 (tax) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein. | |||
| P53_HUMAN | DOC_WW_Pin1_4 | 30 | 35 | Phosphorylation of S33 in the Pin1-binding motif of Cellular tumor antigen p53 (TP53) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein. | |||
| P53_HUMAN | DOC_WW_Pin1_4 | 312 | 317 | Phosphorylation of S315 in the Pin1-binding motif of Cellular tumor antigen p53 (TP53) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein. | |||
| P53_HUMAN | DOC_WW_Pin1_4 | 78 | 83 | Phosphorylation of T81 in the Pin1-binding motif of Cellular tumor antigen p53 (TP53) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein. | |||
| JUN_HUMAN | DOC_WW_Pin1_4 | 60 | 65 | Phosphorylation of S63 in the Pin1-binding motif of Transcription factor AP-1 (JUN) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein. | |||
| JUN_HUMAN | DOC_WW_Pin1_4 | 70 | 75 | Phosphorylation of S73 in the Pin1-binding motif of Transcription factor AP-1 (JUN) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein. | |||
| MYB_MOUSE | DOC_WW_Pin1_4 | 525 | 530 | Phosphorylation of S528 in the Pin1-binding motif of Transcriptional activator Myb (Myb) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) protein. | |||
| RARA_HUMAN | DOC_WW_Pin1_4 | 74 | 79 | Phosphorylation of S77 in the Pin1-binding motif of Retinoic acid receptor alpha (RARA) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein. | |||
| NCF1_HUMAN | DOC_WW_Pin1_4 | 342 | 347 | Phosphorylation of S345 in the Pin1-binding motif of Neutrophil cytosol factor 1 (NCF1) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein. | |||
| NR4A1_HUMAN | DOC_WW_Pin1_4 | 137 | 142 | Phosphorylation of S140 in the Pin1-binding motif of Nuclear receptor subfamily 4 group A member 1 (NR4A1) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein. | |||
| NR4A1_HUMAN | DOC_WW_Pin1_4 | 428 | 433 | Phosphorylation of S431 in the Pin1-binding motif of Nuclear receptor subfamily 4 group A member 1 (NR4A1) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein. | |||
| NR4A1_HUMAN | DOC_WW_Pin1_4 | 92 | 97 | Phosphorylation of S95 in the Pin1-binding motif of Nuclear receptor subfamily 4 group A member 1 (NR4A1) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein. | |||
| CCND1_MOUSE | DOC_WW_Pin1_4 | 283 | 288 | Phosphorylation of T286 in the Pin1-binding motif of G1/S-specific cyclin-D1 (Ccnd1) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) protein. | |||
| PML_HUMAN | DOC_WW_Pin1_4 | 400 | 405 | Phosphorylation of S403 in the Pin1-binding motif of Protein PML (PML) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein. | |||
| PML_HUMAN | DOC_WW_Pin1_4 | 502 | 507 | Phosphorylation of S505 in the Pin1-binding motif of Protein PML (PML) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein. | |||
| PML_HUMAN | DOC_WW_Pin1_4 | 515 | 520 | Phosphorylation of S518 in the Pin1-binding motif of Protein PML (PML) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein. | |||
| PML_HUMAN | DOC_WW_Pin1_4 | 524 | 529 | Phosphorylation of S527 in the Pin1-binding motif of Protein PML (PML) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein. | |||
| AKT1_HUMAN | DOC_WW_Pin1_4 | 447 | 452 | Phosphorylation of T450 in the Pin1-binding motif of RAC-alpha serine/threonine-protein kinase (AKT1) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein. | |||
| AKT1_HUMAN | DOC_WW_Pin1_4 | 89 | 94 | Phosphorylation of T92 in the Pin1-binding motif of RAC-alpha serine/threonine-protein kinase (AKT1) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein. | |||
| STF1_MOUSE | DOC_WW_Pin1_4 | 200 | 205 | Phosphorylation of S203 in the Pin1-binding motif of Steroidogenic factor 1 (Nr5a1) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) protein. | |||
| CTNB1_HUMAN | DOC_WW_Pin1_4 | 243 | 248 | Phosphorylation of S246 in the Pin1-binding motif of Catenin beta-1 (CTNNB1) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein. | |||
| IRS1_HUMAN | DOC_WW_Pin1_4 | 431 | 436 | Phosphorylation of S434 in the Pin1-binding motif of Insulin receptor substrate 1 (IRS1) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein. | |||
| BTK_MOUSE | DOC_WW_Pin1_4 | 112 | 117 | Phosphorylation of S115 in the Pin1-binding motif of Tyrosine-protein kinase BTK (Btk) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) protein. | |||
| BTK_MOUSE | DOC_WW_Pin1_4 | 18 | 23 | Phosphorylation of S21 in the Pin1-binding motif of Tyrosine-protein kinase BTK (Btk) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) protein. | |||
| STAT3_HUMAN | DOC_WW_Pin1_4 | 724 | 729 | Phosphorylation of S727 in the Pin1-binding motif of Signal transducer and activator of transcription 3 (STAT3) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein. | |||
| CDN1B_HUMAN | DOC_WW_Pin1_4 | 184 | 189 | Phosphorylation of T187 in the Pin1-binding motif of Cyclin-dependent kinase inhibitor 1B (CDKN1B) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein. | |||
| NOTC1_HUMAN | DOC_WW_Pin1_4 | 2118 | 2123 | Phosphorylation of S2121 in the Pin1-binding motif of Neurogenic locus notch homolog protein 1 (NOTCH1) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein. | |||
| NOTC1_HUMAN | DOC_WW_Pin1_4 | 2129 | 2134 | Phosphorylation of T2132 in the Pin1-binding motif of Neurogenic locus notch homolog protein 1 (NOTCH1) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein. | |||
| NOTC1_HUMAN | DOC_WW_Pin1_4 | 2133 | 2138 | Phosphorylation of S2136 in the Pin1-binding motif of Neurogenic locus notch homolog protein 1 (NOTCH1) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein. | |||
| TERF1_HUMAN | DOC_WW_Pin1_4 | 146 | 151 | Phosphorylation of T149 in the Pin1-binding motif of Telomeric repeat-binding factor 1 (TERF1) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein. | |||
| X_HBVA3 | DOC_WW_Pin1_4 | 38 | 43 | Phosphorylation of S41 in the Pin1-binding motif of Protein X (X) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein. | |||
| BTG2_HUMAN | DOC_WW_Pin1_4 | 144 | 149 | Phosphorylation of S147 in the Pin1-binding motif of Protein BTG2 (BTG2) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein. | |||
| SMAD3_HUMAN | DOC_WW_Pin1_4 | 176 | 181 | Phosphorylation of T179 in the Pin1-binding motif of Mothers against decapentaplegic homolog 3 (SMAD3) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein. | |||
| SMAD3_HUMAN | DOC_WW_Pin1_4 | 201 | 206 | Phosphorylation of S204 in the Pin1-binding motif of Mothers against decapentaplegic homolog 3 (SMAD3) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein. | |||
| SMAD3_HUMAN | DOC_WW_Pin1_4 | 205 | 210 | Phosphorylation of S208 in the Pin1-binding motif of Mothers against decapentaplegic homolog 3 (SMAD3) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein. | |||
| SMAD3_HUMAN | DOC_WW_Pin1_4 | 210 | 215 | Phosphorylation of S213 in the Pin1-binding motif of Mothers against decapentaplegic homolog 3 (SMAD3) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein. | |||
| PO5F1_HUMAN | DOC_WW_Pin1_4 | 9 | 14 | Phosphorylation of S12 in the Pin1-binding motif of POU domain, class 5, transcription factor 1 (POU5F1) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein. | |||
| TF65_HUMAN | DOC_WW_Pin1_4 | 251 | 256 | Phosphorylation of T254 in the Pin1-binding motif of Transcription factor p65 (RELA) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein. | |||
| FAK1_HUMAN | DOC_WW_Pin1_4 | 907 | 912 | Phosphorylation of S910 in the Pin1-binding motif of Focal adhesion kinase 1 (PTK2) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein. | |||
| IRF3_HUMAN | DOC_WW_Pin1_4 | 336 | 341 | Phosphorylation of S339 in the Pin1-binding motif of Interferon regulatory factor 3 (IRF3) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein. | |||
| CRTC2_MOUSE | DOC_WW_Pin1_4 | 133 | 138 | Phosphorylation of S136 in the Pin1-binding motif of CREB-regulated transcription coactivator 2 (Crtc2) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) protein. | |||
| CCNE1_MOUSE | DOC_WW_Pin1_4 | 382 | 387 | Phosphorylation of S385 in the Pin1-binding motif of G1/S-specific cyclin-E1 (Ccne1) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) protein. | |||
| NANOG_MOUSE | DOC_WW_Pin1_4 | 49 | 54 | Phosphorylation of S52 in the Pin1-binding motif of Homeobox protein NANOG (Nanog) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) protein. | |||
| NANOG_MOUSE | DOC_WW_Pin1_4 | 62 | 67 | Phosphorylation of S65 in the Pin1-binding motif of Homeobox protein NANOG (Nanog) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) protein. | |||
| CEP55_MOUSE | DOC_WW_Pin1_4 | 420 | 425 | Phosphorylation of S423 in the Pin1-binding motif of Centrosomal protein of 55 kDa (Cep55) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) protein. | |||
| CEP55_MOUSE | DOC_WW_Pin1_4 | 423 | 428 | Phosphorylation of S426 in the Pin1-binding motif of Centrosomal protein of 55 kDa (Cep55) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) protein. | |||
| GEPH_MOUSE | DOC_WW_Pin1_4 | 185 | 190 | Phosphorylation of S188 in the Pin1-binding motif of Gephyrin (Gphn) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) protein. | |||
| GEPH_MOUSE | DOC_WW_Pin1_4 | 191 | 196 | Phosphorylation of S194 in the Pin1-binding motif of Gephyrin (Gphn) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) protein. | |||
| GEPH_MOUSE | DOC_WW_Pin1_4 | 197 | 202 | Phosphorylation of S200 in the Pin1-binding motif of Gephyrin (Gphn) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) protein. | |||
| MEF2C_MOUSE | DOC_WW_Pin1_4 | 107 | 112 | Phosphorylation of S110 in the Pin1-binding motif of Myocyte-specific enhancer factor 2C (Mef2c) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) protein. | |||
| MEF2C_MOUSE | DOC_WW_Pin1_4 | 95 | 100 | Phosphorylation of S98 in the Pin1-binding motif of Myocyte-specific enhancer factor 2C (Mef2c) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) protein. | |||
| FUBP2_HUMAN | DOC_WW_Pin1_4 | 178 | 183 | Phosphorylation of S181 in the Pin1-binding motif of Far upstream element-binding protein 2 (KHSRP) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein. | |||
| NONO_MOUSE | DOC_WW_Pin1_4 | 409 | 414 | Phosphorylation of T412 in the Pin1-binding motif of Non-POU domain-containing octamer-binding protein (Nono) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) protein. | |||
| NONO_MOUSE | DOC_WW_Pin1_4 | 427 | 432 | Phosphorylation of T430 in the Pin1-binding motif of Non-POU domain-containing octamer-binding protein (Nono) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) protein. | |||
| NONO_MOUSE | DOC_WW_Pin1_4 | 449 | 454 | Phosphorylation of T452 in the Pin1-binding motif of Non-POU domain-containing octamer-binding protein (Nono) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) protein. | |||
| ARBK1_MOUSE | DOC_WW_Pin1_4 | 667 | 672 | Phosphorylation of S670 in the Pin1-binding motif of Beta-adrenergic receptor kinase 1 (Adrbk1) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) protein. | |||
| ST4A1_HUMAN | DOC_WW_Pin1_4 | 5 | 10 | Phosphorylation of T8 in the Pin1-binding motif of Sulfotransferase 4A1 (SULT4A1) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein. | |||
| ST4A1_HUMAN | DOC_WW_Pin1_4 | 8 | 13 | Phosphorylation of T11 in the Pin1-binding motif of Sulfotransferase 4A1 (SULT4A1) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein. | |||
| TFCP2_MOUSE | DOC_WW_Pin1_4 | 288 | 293 | Phosphorylation of S291 in the Pin1-binding motif of Alpha-globin transcription factor CP2 (Tcfcp2) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) protein. | |||
| TFCP2_MOUSE | DOC_WW_Pin1_4 | 306 | 311 | Phosphorylation of S309 in the Pin1-binding motif of Alpha-globin transcription factor CP2 (Tcfcp2) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) protein. | |||
| TFCP2_MOUSE | DOC_WW_Pin1_4 | 326 | 331 | Phosphorylation of T329 in the Pin1-binding motif of Alpha-globin transcription factor CP2 (Tcfcp2) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) protein. | |||
| NEK6_HUMAN | DOC_WW_Pin1_4 | 212 | 217 | Phosphorylation of S215 in the Pin1-binding motif of Serine/threonine-protein kinase Nek6 (NEK6) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein. | |||
| NEK6_HUMAN | DOC_WW_Pin1_4 | 242 | 247 | Phosphorylation of S245 in the Pin1-binding motif of Serine/threonine-protein kinase Nek6 (NEK6) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein. | |||
| AATF_HUMAN | DOC_WW_Pin1_4 | 143 | 148 | Phosphorylation of T146 in the Pin1-binding motif of Protein AATF (AATF) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein. | |||
| DAXX_HUMAN | DOC_WW_Pin1_4 | 175 | 180 | Phosphorylation of S178 in the Pin1-binding motif of Death domain-associated protein 6 (DAXX) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein. | |||
| NCOR2_HUMAN | DOC_WW_Pin1_4 | 1238 | 1243 | Phosphorylation of T1241 in the Pin1-binding motif of Nuclear receptor corepressor 2 (NCOR2) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein. | |||
| NCOR2_HUMAN | DOC_WW_Pin1_4 | 1441 | 1446 | Phosphorylation of T1444 in the Pin1-binding motif of Nuclear receptor corepressor 2 (NCOR2) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein. | |||
| SNCAP_HUMAN | DOC_WW_Pin1_4 | 208 | 213 | Phosphorylation of S211 in the Pin1-binding motif of Synphilin-1 (SNCAIP) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein. | |||
| SNCAP_HUMAN | DOC_WW_Pin1_4 | 212 | 217 | Phosphorylation of S215 in the Pin1-binding motif of Synphilin-1 (SNCAIP) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein. | |||
| WEE1B_XENLA | DOC_WW_Pin1_4 | 183 | 188 | Phosphorylation of T186 in the Pin1-binding motif of Wee1-like protein kinase 1-B (wee1-b) induces binding to the pin1 protein. | |||
| FBX5A_XENLA | DOC_WW_Pin1_4 | 7 | 12 | Phosphorylation of S10 in the Pin1-binding motif of F-box only protein 5-A (fbxo5-a) induces binding to the pin1 protein. | |||
| SPT23_YEAST | DOC_WW_Pin1_4 | 651 | 656 | Phosphorylation of S654 in the Pin1-binding motif of Protein SPT23 (SPT23) induces binding to the Peptidyl-prolyl cis-trans isomerase ESS1 (ESS1) protein. | |||
| FAK1_MOUSE | DOC_WW_Pin1_4 | 907 | 912 | Phosphorylation of S910 in the Pin1-binding motif of Isoform 3 of Focal adhesion kinase 1 (Ptk2) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) protein. | |||
| FBXW7_HUMAN | DOC_WW_Pin1_4 | 202 | 207 | Phosphorylation of T205 in the Pin1-binding motif of F-box/WD repeat-containing protein 7 (FBXW7) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein. Pin1 interacts with Fbw7 in a phoshorylation-dependent manner and promotes Fbw7 self-ubiquitination and protein degradation by disrupting Fbw7 dimerization. Paper also shows the over-expression of Pin1 suppresses the ability of Fbw7 to inhibit cell transformation and proliferation, suggesting a link between Pin1 overexpression and cancer. | |||
| JUN_MOUSE | LIG_WW_1 | 167 | 170 | Phosphorylation of Y170 in the WW-binding motif of Transcription factor AP-1 (Jun) by Tyrosine-protein kinase ABL1 (Abl1) blocks binding to the E3 ubiquitin-protein ligase Itchy (Itch). As a result, Transcription factor AP-1 (Jun) is not ubiquitylated by E3 ubiquitin-protein ligase Itchy (Itch), and thus not targeted for proteasomal degradation. Regulation of transcriptional activity of Transcription factor AP-1 (Jun) by Tyrosine-protein kinase ABL1 (Abl1) required translocation of the kinase to the nucleus, which was triggered by T cell activation. | |||
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. | |||||||
| AMOT_HUMAN | LIG_WW_1 | 239 | 242 | Alternative splicing removes the WW-binding motif of Angiomotin (AMOT), abrogating binding to Yorkie homolog (YAP1). The splice specific Isoform p130 of Angiomotin (AMOT) of AMOT works within the Hippo pathway to sequester the transcription coactivator YAP1 away at tight junction. In contrast Isoform p80 of Angiomotin (AMOT) of AMOT lacks WW-binding motif. | |||
| AMOT_HUMAN | LIG_WW_1 | 239 | 242 | Alternative splicing removes the WW-binding motif of Angiomotin (AMOT), abrogating binding to WW domain-containing transcription regulator protein 1 (WWTR1). The splice specific Isoform p130 of Angiomotin (AMOT) of AMOT works within the Hippo pathway to sequester the transcription coactivator YAP1 away at tight junction. In contrast Isoform p80 of Angiomotin (AMOT) of AMOT lacks WW-binding motif. | |||
| ERBB4_HUMAN | LIG_WW_1 | 1053 | 1056 | 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. | |||
| P73_HUMAN | DOC_WW_Pin1_4 | 479 | 484 | Alternative splicing removes the WW-binding motif of Tumor protein p73 (TP73), abrogating binding to Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1). Isoforms lacking WW-binding motifs have decreased transcriptional activity. | |||
| P73_HUMAN | DOC_WW_Pin1_4 | 439 | 444 | Alternative splicing removes the WW-binding motif of Tumor protein p73 (TP73), abrogating binding to Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1). Isoforms lacking WW-binding motifs have decreased transcriptional activity. | |||
| P73_HUMAN | DOC_WW_Pin1_4 | 409 | 414 | Alternative splicing removes the WW-binding motif of Tumor protein p73 (TP73), abrogating binding to Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1). Isoforms lacking WW-binding motifs have decreased transcriptional activity. | |||
| LMP2_EBVB9 | LIG_WW_1 | 57 | 60 | Alternative splicing removes the WW-binding motif of Latent membrane protein 2 (LMP2), abrogating binding to E3 ubiquitin-protein ligase Itchy (Itch). | |||
| LMP2_EBVB9 | LIG_WW_1 | 98 | 101 | Alternative splicing removes the WW-binding motif of Latent membrane protein 2 (LMP2), abrogating binding to E3 ubiquitin-protein ligase Itchy (Itch). | |||
| LMP2_EBVB9 | LIG_WW_1 | 57 | 60 | Alternative splicing removes the WW-binding motif of Latent membrane protein 2 (LMP2), abrogating binding to E3 ubiquitin-protein ligase Itchy (Itch). | |||
| ERBB4_HUMAN | LIG_WW_1 | 1053 | 1056 | Alternative splicing removes the WW-binding motif of Receptor tyrosine-protein kinase erbB-4 (ERBB4), abrogating binding to E3 ubiquitin-protein ligase Itchy homolog (ITCH). The presence of a WW-binding motif mediates ERBB4 mono-ubiquitination and endocytosis by the WW domain-containing HECT-type E3 ubiquitin ligase ITCH. | |||
| AMOT_HUMAN | LIG_WW_1 | 239 | 242 | Alternative splicing removes the WW-binding motif of Angiomotin (AMOT), abrogating binding to Yorkie homolog (YAP1). The splice specific Isoform p130 of Angiomotin (AMOT) of AMOT works within the Hippo pathway to sequester the transcription coactivator YAP1 away at tight junction. In contrast Isoform p80 of Angiomotin (AMOT) of AMOT lacks WW-binding motif. | |||
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. | |||||||
| SMAD3_HUMAN | LIG_WW_Nedd4L | 203 | 210 | 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. | |||
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. | |||||||
| SMAD3_HUMAN | DOC_WW_Pin1_4 | 176 | 181 | CDK8/9 phosphorylates Mothers against decapentaplegic homolog 3 (SMAD3) at T179 and S208. Phosphorylation of T179 creates a binding site for the WW domain of Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1), while phosphorylation of S208 primes SMAD3 for phosphorylation of S204 by Glycogen synthase kinase-3 beta (GSK3B). The pS204-pS208 forms a binding site for the third WW domain of E3 ubiquitin-protein ligase NEDD4-like (NEDD4L), whose second WW domain will displace the WW domain of PIN1 at the pT179-PY box site of SMAD3. This regulation couples SMAD3 activation to SMAD3 destruction in an ordered fashion. See also switch details and switch details. | |||
| SMAD3_HUMAN | LIG_WW_Nedd4L | 203 | 210 | CDK8/9 phosphorylates Mothers against decapentaplegic homolog 3 (SMAD3) at T179 and S208. Phosphorylation of T179 creates a binding site for the WW domain of Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1), while phosphorylation of S208 primes SMAD3 for phosphorylation of S204 by Glycogen synthase kinase-3 beta (GSK3B). The pS204-pS208 forms a binding site for the third WW domain of E3 ubiquitin-protein ligase NEDD4-like (NEDD4L), whose second WW domain will displace the WW domain of PIN1 at the pT179-PY box site of SMAD3. This regulation couples SMAD3 activation to SMAD3 destruction in an ordered fashion. See also switch details and switch details. | |||
| SMAD3_HUMAN | LIG_WW_1 | 181 | 184 | CDK8/9 phosphorylates Mothers against decapentaplegic homolog 3 (SMAD3) at T179 and S208. Phosphorylation of T179 creates a binding site for the WW domain of Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1), while phosphorylation of S208 primes SMAD3 for phosphorylation of S204 by Glycogen synthase kinase-3 beta (GSK3B). The pS204-pS208 forms a binding site for the third WW domain of E3 ubiquitin-protein ligase NEDD4-like (NEDD4L), whose second WW domain will displace the WW domain of PIN1 at the pT179-PY box site of SMAD3. This regulation couples SMAD3 activation to SMAD3 destruction in an ordered fashion. See also switch details and switch details. | |||
| DAG1_HUMAN | LIG_WW_1 | 889 | 892 | Adhesion-dependent phosphorylation of Y892 in Dystroglycan (DAG1) by Src kinase (Proto-oncogene tyrosine-protein kinase Src (SRC)) switches the specificity of DAG1 from the WW domain containing cytoskeletal linker Dystrophin (DMD) to the SH2 domain containing Tyrosine-protein kinase Fyn (FYN). | |||
| DAG1_HUMAN | LIG_WW_1 | 889 | 892 | 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_WW_1 | 1053 | 1056 | 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. | |||