Yorkie homolog (Protein name
), YAP1_HUMAN from NCBI database.
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Gene name:
YAP1(YAP65);
Protein name:
Yorkie homolog;
Alternative:
65 kDa Yes-associated protein(YAP65);
Organism:
Human (Homo sapiens).
General Annotation
Sub Unit:
Binds to the SH3 domain of the YES kinase. Binds to WBP1 and WBP2. 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. Interacts (via WW domains) with LATS1 (via PPxY motif 2). Interacts with LATS2. Isoform 2 and isoform 3 interact (via WW domain 1) with isoform 3 of ERBB4 (via PPxY motif 2). Interacts with TEAD1, TEAD2, TEAD3 and TEAD4. Interacts with TP73. Interacts with RUNX1.
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).
Subcellular Location:
Cytoplasm
Nucleus
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.
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Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA];TISSUE SPECIFICITY
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Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2);FUNCTION;INTERACTION WITH ERBB4;MUTAGENESIS OF SER-127; TRP-199 AND PRO-202
3.
"YAP is a candidate oncogene for esophageal squamous-cell carcinoma." Inazawa J.
,
Imoto I.
,
Muramatsu T.
Submitted (2010-06) to the EMBL/GenBank/DDBJ databases
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Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 6)
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Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4)
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Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)
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Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 206-369 (ISOFORMS 3; 7; 8 AND 9);ALTERNATIVE SPLICING
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Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]
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Cited for: IDENTIFICATION OF ISOFORMS LACKING THE TRANSCRIPTIONAL ACTIVATION DOMAIN;TISSUE SPECIFICITY
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Cited for: FUNCTION;SUBCELLULAR LOCATION;INTERACTION WITH YWHAB;PHOSPHORYLATION AT SER-61; SER-109; SER-127; SER-164 AND SER-397;MUTAGENESIS OF HIS-122; SER-127 AND PRO-129;TISSUE SPECIFICITY
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Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-371;IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]
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Cited for: FUNCTION;INTERACTION WITH TEAD1; TEAD2; TEAD3 AND TEAD4;MUTAGENESIS OF SER-94
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Cited for: FUNCTION;SUBCELLULAR LOCATION;INTERACTION WITH LATS1 AND LATS2;PHOSPHORYLATION AT SER-61; SER-109; SER-127; SER-164 AND SER-397;MUTAGENESIS OF HIS-122; ARG-124; SER-127 AND SER-397
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Cited for: FUNCTION;PHOSPHORYLATION AT TYR-407 BY ABL1;MUTAGENESIS OF TYR-407;SUBCELLULAR LOCATION;INTERACTION WITH RUNX1 AND TP73
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Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-61; SER-127; SER-131; SER-138; THR-154; SER-274; SER-289 AND SER-367;IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]
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Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]
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Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]
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Cited for: PHOSPHORYLATION AT THR-119; SER-138; THR-154; SER-367 AND THR-412 BY MAPK8/JNK1 AND MAPK9/JNK2;FUNCTION
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Cited for: PHOSPHORYLATION AT SER-400 AND SER-403 BY CSNK1D/CK1;PHOSPHORYLATION AT SER-127 AND SER-397 BY LATS PROTEINS;UBIQUITINATION BY SCF(BETA-TRCP);SUBCELLULAR LOCATION
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Cited for: INTERACTION WITH TEAD4;MUTAGENESIS OF VAL-80; VAL-84 AND PRO-85
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Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-61; THR-63; SER-109; THR-119; SER-138; SER-274; SER-289 AND SER-367;IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]
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Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]
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Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-61; SER-289 AND SER-367;IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]
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Cited for: INVOLVEMENT IN COB1;VARIANTS LEU-139; LEU-227; VAL-330 AND GLU-462
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Cited for: STRUCTURE BY NMR OF 165-210 OF WILD-TYPE AND MUTANT LYS-190 IN COMPLEX WITH PRO-RICH PEPTIDES
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Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 50-171 IN COMPLEX WITH TEAD1;COILED-COIL REGION;INTERACTION WITH TEAD1;MUTAGENESIS OF MET-86; ARG-89; LEU-91; SER-94; PHE-95 AND PHE-96
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