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P46937 Proteins WW domain Repeats
Uniprot ID:P46937
Protein name: Transcriptional coactivator YAP1
Gene : YAP1 YAP65
Protein Family:YAP1 family
Squence Length : 504
Sequnce
>P46937 505 MDPGQQPPPQPAPQGQGQPPSQPPQGQGPPSGPGQPAPAATQAAPQAPPAGHQIVHVRGDSETDLEALFNAVMNPKTANVPQTVPMRLRKLPDSFFKPPEPKSHSRQASTDAGTAGALTPQHVRAHSSPASLQLGAVSPGTLTPTGVVSGPAATPTAQHLRQSSFEIPDDVPLPAGWEMAKTSSGQRYFLNHIDQTTTWQDPRKAMLSQMNVTAPTSPPVQQNMMNSASGPLPDGWEQAMTQDGEIYYINHKNKTTSWLDPRLDPRFAMNQRISQSAPVKQPPPLAPQSPQGGVMGGSNSNQQQQMRLQQLQMEKERLRLKQQELLRQAMRNINPSTANSPKCQELALRSQLPTLEQDGGTQNPVSSPGMSQELRTMTTNSSDPFLNSGTYHSRDESTDSGLSMSSYSVPRTPDDFLNSVDEMDTGDTINQSTLPSQQNRFPDYLEAIPGTNVDLGTLEGDGMNIEGEELMPSLQEALSSDILNDMESVLAATKLDKESFLTWL
Domains
DOMAIN 171 204 WW 1 DOMAIN 230 263 WW 2
WW sequence regions
171 - 204 LPAGWEMAKTSSGQRYFLNHIDQTTTWQDPRKAM 230 - 263 LPDGWEQAMTQDGEIYYINHKNKTTSWLDPRLDP
Function
"Transcriptional regulator which can act both as a coactivator and a corepressor and is the critical downstream regulatory target in the Hippo signaling pathway that plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis (PubMed:17974916, PubMed:18280240, PubMed:18579750, PubMed:21364637). The core of this pathway is composed of a kinase cascade wherein STK3/MST2 and STK4/MST1, in complex with its regulatory protein SAV1, phosphorylates and activates LATS1/2 in complex with its regulatory protein MOB1, which in turn phosphorylates and inactivates YAP1 oncoprotein and WWTR1/TAZ (PubMed:18158288). Plays a key role in tissue tension and 3D tissue shape by regulating cortical actomyosin network formation. Acts via ARHGAP18, a Rho GTPase activating protein that suppresses F-actin polymerization (PubMed:25778702). Plays a key role to control cell proliferation in response to cell contact. Phosphorylation of YAP1 by LATS1/2 inhibits its translocation into the nucleus to regulate cellular genes important for cell proliferation, cell death, and cell migration (PubMed:18158288). The presence of TEAD transcription factors are required for it to stimulate gene expression, cell growth, anchorage-independent growth, and epithelial mesenchymal transition (EMT) induction (PubMed:18579750).; Isoform 2: Isoform 2 and isoform 3 can activate the C-terminal fragment (CTF) of ERBB4 (isoform 3)"
Mutation
"61 61 S->A: In YAP-4SA prevents phosphorylation by LATS1 and LATS2, promoting retention in the nucleus when associated with A-109 A-127 and A-164 80 80 V->A: No change in interaction with TEAD4 when associated with A-84 and A-85 84 84 V->A: Reduced interaction with TEAD4 and transforming ability when associated with A-80 and A-85 85 85 P->A: Reduced interaction with TEAD4 and transforming ability when associated with A-80 and A-84 86 86 M->A: Complete loss of interaction with TEAD1 89 89 R->A: Complete loss of interaction with TEAD1 91 91 L->A: Complete loss of interaction with TEAD1 94 94 S->A: Loss of interaction with TEAD1, TEAD2, TEAD3 and TEAD4 95 95 F->A: Complete loss of interaction with TEAD1 96 96 F->A: Loss of interaction with TEAD1 109 109 S->A: In YAP-4SA prevents phosphorylation by LATS1 and LATS2, promoting retention in the nucleus when associated with A-61 A-127 and A-164 122 122 H->A,R,N,K: Loss of phosphorylation by LATS1 122 122 H->L,Y: Significantly decreased phosphorylation at S-127 and decreased interaction with YWHAB 124 124 R->A: Loss of phosphorylation by LATS1 127 127 S->A: Reduced phosphorylation by LATS2, loss of phosphorylation by LATS1, loss of interaction with YWHAB, decreased interaction with ERBB4 and increased nuclear localization and transcriptional coactivation activity toward ERBB4 prevents phosphorylation by LATS1 and LATS2, promoting retention in the nucleus when associated with A-61 A-109 A-127 and A-164 129 129 P->D: No effect on phosphorylation but loss of interaction with YWHAB 164 164 S->A: In YAP-4SA prevents phosphorylation by LATS1 and LATS2, promoting retention in the nucleus when associated with A-61 A-109 and A-127 199 199 W->A: Loss of interaction with ERBB4 and loss of transcriptional coactivation function toward CTF when associated with A-202 202 202 P->A: Loss of interaction with ERBB4 and loss of transcriptional coactivation function toward CTF when associated with A-199 397 397 S->A: Loss of phosphorylation by LATS1 407 407 Y->E: Enhanced interaction with TP73 407 407 Y->F: No phosphorylation by ABL1 and partial loss of binding to TP73"
Disease
"DISEASE: Coloboma, ocular, with or without hearing impairment, cleft lip/palate, and/or mental retardation (COB1) [MIM:120433]: An autosomal dominant disease characterized by uveal colobomata, microphthalmia, cataract and cleft lip/palate Considerable variability is observed among patients, uveal colobomata being the most constant feature Some patients manifest mental retardation of varying degree and/or sensorineural, mid-frequency hearing loss Note=The disease is caused by mutations affecting the gene represented in this entry"