YAP1 phospho S127
Domain
The first coiled-coil region mediates most of the interaction with TEAD transcription factors.
Function
The protein expressed by the YAP1 gene functions as a transcriptional regulator, acting both as a coactivator and corepressor. It is a critical downstream regulatory target in the Hippo signaling pathway, which is crucial for organ size control and tumor suppression, as it restricts proliferation and promotes apoptosis. The pathway involves a kinase cascade where STK3/MST2 and STK4/MST1 activate LATS1/2, which then inactivates the YAP1 oncoprotein. YAP1 plays a key role in tissue tension and 3D tissue shape by regulating cortical actomyosin network formation through ARHGAP18. It controls cell proliferation in response to cell contact, with its phosphorylation by LATS1/2 preventing nuclear translocation necessary for regulating cellular genes linked to proliferation, death, and migration. TEAD transcription factors are needed for YAP1 to stimulate gene expression, cell growth, anchorage-independent growth, and EMT induction. Additionally, YAP1 suppresses ciliogenesis by repressing TEAD4 target genes AURKA and PLK1. Isoforms 2 and 3 of YAP1 activate the C-terminal fragment of ERBB4 (isoform 3). This supplementary information is collated from multiple sources and compiled automatically.
Involvement in disease
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.
Post-translational modifications
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.
Sequence Similarities
Belongs to the YAP1 family.
Tissue Specificity
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).
Cellular localization
- 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).
Alternative names
YAP65, YAP1, Transcriptional coactivator YAP1, Yes-associated protein 1, Protein yorkie homolog, Yes-associated protein YAP65 homolog
Database links
Other research areas
- Epigenetics