Protein: Transcriptional coactivator YAP1 (Yes-associated protein 1) (Protein yorkie homolog) (Yes-associated protein YAP65 homolog) (P46937)
Organism: Homo sapiens (Human)
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. 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. 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. Plays a key role in controlling 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. 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. Suppresses ciliogenesis via acting as a transcriptional corepressor of the TEAD4 target genes AURKA and PLK1. In conjunction with WWTR1, involved in the regulation of TGFB1-dependent SMAD2 and SMAD3 nuclear accumulation (By similarity).
Subcellular location: Cytoplasm {ECO:0000269|PubMed:18158288, ECO:0000269|PubMed:18280240, ECO:0000269|PubMed:20048001, ECO:0000269|PubMed:21205866, ECO:0000269|PubMed:22525271, ECO:0000269|PubMed:25849865, ECO:0000269|PubMed:26598551, ECO:0000269|PubMed:29400695, ECO:0000269|PubMed:29695716, ECO:0000269|PubMed:31835537, ECO:0000269|PubMed:34404733}. Nucleus {ECO:0000269|PubMed:17974916, ECO:0000269|PubMed:18158288, ECO:0000269|PubMed:18280240, ECO:0000269|PubMed:20048001, ECO:0000269|PubMed:21145499, ECO:0000269|PubMed:21205866, ECO:0000269|PubMed:22525271, ECO:0000269|PubMed:25849865, ECO:0000269|PubMed:26598551, ECO:0000269|PubMed:28169360, ECO:0000269|PubMed:29400695, ECO:0000269|PubMed:29695716, ECO:0000269|PubMed:30447097, ECO:0000269|PubMed:31835537, ECO:0000269|PubMed:34404733, ECO:0000269|PubMed:38512451}. Cell junction, tight junction {ECO:0000250|UniProtKB:A0A8C0NGY6}. Cell membrane {ECO:0000269|PubMed:31835537}. Note=Both phosphorylation and cell density can regulate its subcellular localization (PubMed:18158288, PubMed:20048001). Phosphorylation sequesters it in the cytoplasm by inhibiting its translocation into the nucleus (PubMed:18158288, PubMed:20048001, PubMed:34404733). At low density, predominantly nuclear and is translocated to the cytoplasm at high density (PubMed:18158288, PubMed:20048001, PubMed:25849865). PTPN14 induces translocation from the nucleus to the cytoplasm (PubMed:22525271). In the nucleus, phosphorylation by PRP4K induces nuclear exclusion (PubMed:29695716). Localized mainly to the nucleus in the early stages of embryo development with expression becoming evident in the cytoplasm at the blastocyst and epiblast stages (By similarity). Localizes to the cytoplasm and tight junctions following interaction with AMOT isoform 1 (PubMed:21205866). Localizes to tight junctions following interaction with AMOTL2 (By similarity). Translocates to the nucleus in the presence of SNAIL1 (By similarity). Found at the cell membrane in keratinocytes in response to mechanical strain (PubMed:31835537). {ECO:0000250|UniProtKB:A0A8C0NGY6, ECO:0000250|UniProtKB:P46938, ECO:0000269|PubMed:18158288, ECO:0000269|PubMed:20048001, ECO:0000269|PubMed:21205866, ECO:0000269|PubMed:22525271, ECO:0000269|PubMed:25849865, ECO:0000269|PubMed:29695716, ECO:0000269|PubMed:31835537, ECO:0000269|PubMed:34404733}.
Interaction partners:
- Serine/threonine-protein kinase LATS2
- Serine/threonine-protein kinase LATS1
- Transcriptional enhancer factor TEF-1
- Transcriptional enhancer factor TEF-4
- Transcriptional enhancer factor TEF-3
- Transcriptional enhancer factor TEF-5
- Angiomotin
- Mothers against decapentaplegic homolog 7
- Catenin beta-1
- Tumor protein p73
Sequence:
MDPGQQPPPQPAPQGQGQPPSQPPQGQGPPSGPGQPAPAATQAAPQAPPAGHQIVHVRGDSETDLEALFNAVMNPKTANVPQTVPMRLRKLPDSFFKPPEPKSHSRQASTDAGTAGALTPQHVRAHSSPASLQLGAVSPGTLTPTGVVSGPAATPTAQHLRQSSFEIPDDVPLPAGWEMAKTSSGQRYFLNHIDQTTTWQDPRKAMLSQMNVTAPTSPPVQQNMMNSASGPLPDGWEQAMTQDGEIYYINHKNKTTSWLDPRLDPRFAMNQRISQSAPVKQPPPLAPQSPQGGVMGGSNSNQQQQMRLQQLQMEKERLRLKQQELLRQAMRNINPSTANSPKCQELALRSQLPTLEQDGGTQNPVSSPGMSQELRTMTTNSSDPFLNSGTYHSRDESTDSGLSMSSYSVPRTPDDFLNSVDEMDTGDTINQSTLPSQQNRFPDYLEAIPGTNVDLGTLEGDGMNIEGEELMPSLQEALSSDILNDMESVLAATKLDKESFLTWL