InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: YAP1

Summary

InnateDB Protein

IDBP-68999.5

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

YAP1

Protein Name

Yes-associated protein 1

Synonyms

COB1; YAP; YAP2; YAP65; YKI;

Species

Homo sapiens

Ensembl Protein

ENSP00000331023

InnateDB Gene

IDBG-68995 (YAP1)

Protein Structure

UniProt Annotation

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 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. 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. Isoform 2 and isoform 3 can activate the C-terminal fragment (CTF) of ERBB4 (isoform 3). {ECO:0000269PubMed:12807903, ECO:0000269PubMed:17974916, ECO:0000269PubMed:18158288, ECO:0000269PubMed:18280240, ECO:0000269PubMed:18579750, ECO:0000269PubMed:21364637}.

Subcellular Localization

Cytoplasm. Nucleus. Note=Both phosphorylation and cell density can regulate its subcellular localization. Phosphorylation sequesters it in the cytoplasm by inhibiting its translocation into the nucleus. At low density, predominantly nuclear and is translocated to the cytoplasm at high density. PTPN14 induces translocation from the nucleus to the cytoplasm.

Disease Associations

Coloboma, ocular, with or without hearing impairment, cleft lip/palate, and/or mental retardation (COCLEMR) [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. {ECO:0000269PubMed:24462371}. Note=The disease is caused by mutations affecting the gene represented in this entry.

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). {ECO:0000269PubMed:16461361, ECO:0000269PubMed:17974916, ECO:0000269PubMed:7782338}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 161 experimentally validated interaction(s) in this database.
They are also associated with 12 interaction(s) predicted by orthology.

Experimentally validated
Total	161 [view]
Protein-Protein	158 [view]
Protein-DNA	1 [view]
Protein-RNA	0
DNA-DNA	2 [view]
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	12 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0003713	transcription coactivator activity
GO:0003714	transcription corepressor activity
GO:0005515	protein binding
GO:0044212	transcription regulatory region DNA binding

Biological Process

GO:0006367	transcription initiation from RNA polymerase II promoter
GO:0006974	cellular response to DNA damage stimulus
GO:0008283	cell proliferation
GO:0010467	gene expression
GO:0035329	hippo signaling
GO:0060242	contact inhibition
GO:0071480	cellular response to gamma radiation