Molecular Target Synopsis
Overview
Domains and Structures
Drugs and Clinical Candidates
Druggability
Chemistry
Ligand Efficiency Plot
Pathways
Family Cladogram
Interaction Network
Gene Expression
Gene Copy Number Variation
RNAi
Mutations
Germline Genetics

YAP1 (P46937) - Overview - Molecular Target Synopsis

Protein


YAP1, Transcriptional coactivator YAP1
UniProt P46937

Also Known as YAP1_HUMAN, YAP1, YAP65

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). Binds to the SH3 domain of the YES kinase. Binds to WBP1 and WBP2 (PubMed:9202023). Binds, in vitro, through the WW1 domain, to neural isoforms of ENAH that contain the PPSY motif (By similarity). The phosphorylated form interacts with YWHAB (PubMed:17974916). Interacts (via WW domains) with LATS1 (via PPxY motif 2) (PubMed:18158288). Interacts with LATS2 (PubMed:18158288). Isoform 2 and isoform 3 interact (via WW domain 1) with isoform 3 of ERBB4 (via PPxY motif 2) (PubMed:12807903). Interacts with TEAD1, TEAD2, TEAD3 and TEAD4 (PubMed:18579750, PubMed:20123905, PubMed:20123908). Interacts with TP73 (PubMed:18280240). Interacts with RUNX1 (PubMed:18280240). Interacts with HCK (PubMed:17535448). Interacts (via WW domains) with PTPN14 (via PPxY motif 2); this interaction leads to the cytoplasmic sequestration of YAP1 and inhibits its transcriptional coactivator activity (PubMed:22525271).

6G6X
7 RESIDUE FRAGMENT OF
TRANSCRIPTIONAL COACTIVATOR YAP1
IN THE STRUCTURE OF
14-3-3SIGMA IN COMPLEX WITH A P129BETA3P MUTATED YAP PS127 PHOSPHOPEPTIDE
RCSB/PDB
Inspect Structure
See all 3D Structures for YAP1

Isoforms / Transcripts (Protein Coding)


Sub-cellular localization


UniProt: YAP1 is active in the following subcellular-locations: cytoplasm, nucleus.
GO terms: YAP1 is active in the following subcellular-locations: cytoplasm, cytosol, membrane, nucleoplasm, nucleus, TEAD-1-YAP complex, TEAD-2-YAP complex.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project YAP1 has gain in 15 cell-lines, loss in 7 cell-lines and no signal in 983 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: SF_268, EKVX, OVCAR_4

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: SF268, Detroit 562, Ca Ski

In Array Express (RNA-seq of long poly adenylated RNA and long non poly adenylated RNA from ENCODE cell lines), the highest expressing cell lines are: NHLF, HSMM, HMEC

(see details)

3D Structures


For YAP1 there are:
29 structures (38 chains) solved
1 are solved in complex with at least one small molecule ligand



(see details)
Molecular Target 3D Synopsis