Search
Yorkie homolog; 65 kD Yes-associated protein; YAP65 (YAP1, YAP65)
Function:
- transcriptional regulator which can act both as a coactivator & a corepressor
- critical downstream regulatory target in the Hippo signaling pathway that plays a pivotal role in organ size control & tumor suppression by restricting proliferation & promoting apoptosis
- the core of this pathway is composed of a kinase cascade wherein MST1/MST2, in complex with its regulatory protein SAV1, phosphorylates & activates LATS1/2 in complex with its regulatory protein MOB1, which in turn phosphorylates & inactivates YAP1 oncoprotein
- YAP1 plays a key role to control cell proliferation in response to cell contact
- phosphorylation by LATS1/2 inhibits its translocation into the nucleus to regulate cellular genes important for cell proliferation, cell death, & cell migration
- isoform 2 & isoform 3 can activate the C-terminal fragment (CTF) of ERBB4 (isoform 3)
- phosphorylated by LATS1 & LATS2
- phosphorylation inhibits its nuclear localization & activity & enhances interaction with YWHAB
- phosphorylated by protein kinase B
- binds to the SH3 domain of the YES kinase
- binds to WBP1 & WBP2
- binds, in vitro, through the WW1 domain, to neural isoforms of ENAH that contain the PPSY motif (putative)
- the phosphorylated form interacts with YWHAB
- interacts (via WW domains) with LATS1 (via PPxY motif 2)
- interacts with LATS2 isoform 2 & isoform 3 interact (via WW domain 1) with isoform 3 of ERBB4 (via PPxY motif 2)
Structure:
- belongs to the YORKIE family
- contains 2 WW domains
Compartment:
- cytoplasm, nucleus
- both phosphorylation & 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
- translocated to the cytoplasm at high density
Alternative splicing:
- named isoforms=3
- additional isoforms lacking the transactivation domain exist
Expression:
- increased expression seen in some liver & prostate cancers
- isoforms lacking the transactivation domain found in striatal neurons of patients with Huntington disease (at protein level)
General
phosphoprotein
transcriptional adaptor protein; transcriptional coactivator
Properties
SIZE: entity length = 504 aa
MW = 54 kD
COMPARTMENT: cytoplasm
cell nucleus
MOTIF: proline-rich region
SITE: 3-49
MOTIF: proline residue (SEVERAL)
Ser phosphorylation site {S61}
Ser phosphorylation site {S109}
Thr phosphorylation site {T110}
Ser phosphorylation site {S127}
Ser phosphorylation site {S128}
Ser phosphorylation site {S131}
Ser phosphorylation site {S138}
Thr phosphorylation site {T143}
Ser phosphorylation site {S149}
Thr phosphorylation site {T154}
Ser phosphorylation site {S164}
WW domain (W/rsp5/WWP domain) {171-204}
WW domain (W/rsp5/WWP domain) {230-263}
Ser phosphorylation site {S274}
Ser phosphorylation site {S276}
Ser phosphorylation site {S289}
transcriptional activation domain
SITE: 291-504
MOTIF: Ser phosphorylation site {S340}
Ser phosphorylation site {S367}
Ser phosphorylation site {S371}
Ser phosphorylation site {S397}
Database Correlations
OMIM 606608
UniProt P46937
Pfam PF00397
Entrez Gene 10413
References
- UniProt :accession P46937
- Basu S et al.
Akt phosphorylates the Yes-associated protein, YAP, to induce
interaction with 14-3-3 and attenuation of p73-mediated
apoptosis.
Molecular Cell 11:11-23, 2003
PMID: 12535517