YAP1

The first coiled-coil region mediates most of the interaction with TEAD transcription factors.

Transcriptional regulator with dual roles as a coactivator and corepressor. Critical downstream regulatory target in the Hippo signaling pathway, crucial for organ size control and tumor suppression by restricting proliferation and promoting apoptosis (PubMed:17974916, PubMed:18280240, PubMed:18579750, PubMed:21364637, PubMed:30447097). The Hippo signaling pathway core involves a kinase cascade featuring STK3/MST2 and STK4/MST1, along with its regulatory partner SAV1, which phosphorylates and activates LATS1/2 in complex with their regulatory protein, MOB1. This activation leads to the phosphorylation and inactivation of the YAP1 oncoprotein and WWTR1/TAZ (PubMed:18158288). Phosphorylation of YAP1 by LATS1/2 prevents its nuclear translocation, thereby regulating the expression of its target genes (PubMed:18158288, PubMed:26598551, PubMed:34404733). The transcriptional regulation of gene expression requires TEAD transcription factors and modulates cell growth, anchorage-independent growth, and induction of epithelial-mesenchymal transition (EMT) (PubMed:18579750). Plays a key role in tissue tension and 3D tissue shape by regulating the cortical actomyosin network, acting via ARHGAP18, a Rho GTPase activating protein that suppresses F-actin polymerization (PubMed:25778702). It also suppresses ciliogenesis by acting as a transcriptional corepressor of TEAD4 target genes AURKA and PLK1 (PubMed:25849865). In conjunction with WWTR1, regulates TGFB1-dependent SMAD2 and SMAD3 nuclear accumulation (By similarity). Synergizes with WBP2 to enhance PGR activity (PubMed:16772533).

Isoform 2

Activates the C-terminal fragment (CTF) of ERBB4 (isoform 3).

Isoform 3

Activates the C-terminal fragment (CTF) of ERBB4 (isoform 3).

Coloboma, ocular, with or without hearing impairment, cleft lip/palate, and/or impaired intellectual development

COB1

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 intellectual disability of varying degree and/or sensorineural, mid-frequency hearing loss.

None

The disease is caused by variants affecting the gene represented in this entry.

Phosphorylated by LATS1 and LATS2; leading to cytoplasmic translocation and inactivation (PubMed:18158288, PubMed:20048001). Phosphorylated by ABL1; leading to YAP1 stabilization, enhanced interaction with TP73 and recruitment onto proapoptotic genes; in response to DNA damage (PubMed:18280240). Phosphorylation at Ser-400 and Ser-403 by CK1 is triggered by previous phosphorylation at Ser-397 by LATS proteins and leads to YAP1 ubiquitination by SCF(beta-TRCP) E3 ubiquitin ligase and subsequent degradation (PubMed:20048001). Phosphorylated at Thr-119, Ser-138, Thr-154, Ser-367 and Thr-412 by MAPK8/JNK1 and MAPK9/JNK2, which is required for the regulation of apoptosis by YAP1 (PubMed:21364637). Phosphorylated in the nucleus by PRP4K; phosphorylation leads to nuclear exclusion (PubMed:29695716).

Lactylation by AARS1 promotes nuclear localization and stabilization of YAP1, leading to increased Hippo signaling pathway (PubMed:38512451). Delactylated by SIRT1 (PubMed:38512451).

Ubiquitinated by SCF(beta-TRCP) E3 ubiquitin ligase.

Belongs to the YAP1 family.

Increased expression seen in some liver and prostate cancers. Isoforms lacking the transactivation domain found in striatal neurons of patients with Huntington disease (at protein level).

• Cytoplasm
• Nucleus
• Cell junction
• Tight junction
• Cell membrane
• 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).

YAP65, YAP1, Transcriptional coactivator YAP1, Yes-associated protein 1, Protein yorkie homolog, Yes-associated protein YAP65 homolog

• entrezGene:10413
• omim:606608
• swissprot:P46937

Proteins

Oncology

• Epigenetics

54462Da