Tchem YAP1 Transcriptional coactivator YAP1

Protein Summary

Description

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). This gene encodes a downstream nuclear effector of the Hippo signaling pathway which is involved in development, growth, repair, and homeostasis. This gene is known to play a role in the development and progression of multiple cancers as a transcriptional regulator of this signaling pathway and may function as a potential target for cancer treatment. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Aug 2013]

Uniprot Accession IDs

• P46937
• B4DTY1
• B7ZA01
• E3WEB5
• E3WEB6
• E9PRV2
• F5H202
• K0KQ18
• K0KYZ8
• K0L195
• K0L1G3
• Q7Z574
• Q8IUY9
• Yes-associated protein 1

Gene Name

• YAP1

Ensembl ID

• ENST00000282441
• ENSP00000282441
• ENSG00000137693
• ENST00000345877
• ENSP00000331023
• ENST00000524575
• ENSP00000435602
• ENST00000526343
• ENSP00000434134
• ENST00000531439
• ENSP00000431574
• ENST00000537274
• ENSP00000445635
• ENST00000615667
• ENSP00000478927
• ENST00000629586
• ENSP00000487519

Symbol

• YAP65
• YAP
• YKI
• COB1
• YAP2
• YAP65

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
biological process	0.98
biological term	0.96
ligand (protein) perturbation	0.96
kinase	0.9
hub protein	0.88

Protein Classes

PANTHER Classes

Protein / Transcription Factor / Transcription Cofactor / Transcriptional Coactivator Yap1

Protein / Enzyme Modulator / Kinase Modulator / Transcriptional Coactivator Yap1

DTO Classes

Protein / Enzyme Modulator / Kinase Modulator / Transcriptional Coactivator Yap1

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 1308.92   (req: < 5)

Gene RIFs: 1232   (req: <= 3)

Antibodies: 815   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 1308.92   (req: >= 5)

Gene RIFs: 1232   (req: > 3)

Antibodies: 815   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 46

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 12

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0