Summary
Specificity
Mouse, Human, Rat
Basic Information
Specificity
Mouse, Human, Rat
Application Notes
The COA includes recommended starting dilutions, optimal dilutions should be determined by the end user.
Formulations & Storage [For reference only, actual COA shall prevail!]
Purity
> 95% Purity determined by SDS-PAGE.
Storage
Store at +4°C short term (1-2 weeks). Aliquot and store at -20°C long term. Avoid repeated freezethaw cycles.
Target
Full Name
Yes Associated Protein 1
Introduction
This gene encodes a protein which binds to the SH3 domain of the Yes proto-oncogene product, a tyrosine kinase. This protein contains a WW domain, consisting of four conserved aromatic amino acids including two tryptophan residues. This conserved WW domain is found in various structural, regulatory and signaling molecules in various species, and may play a role in protein-protein interaction. 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 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. Plays a key role to control cell proliferation in response to cell contact.
Alternative Names
Yap; Yap65; Yki; Yorkie
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 (PubMed:17974916, PubMed:18280240, PubMed:18579750, PubMed:21364637, PubMed:30447097).
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 in controlling 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).
Suppresses ciliogenesis via acting as a transcriptional corepressor of the TEAD4 target genes AURKA and PLK1 (PubMed:25849865).
In conjunction with WWTR1, involved in the regulation of TGFB1-dependent SMAD2 and SMAD3 nuclear accumulation (By similarity).By Similarity
Isoform 2
Activates the C-terminal fragment (CTF) of ERBB4 (isoform 3).
Isoform 3
Activates the C-terminal fragment (CTF) of ERBB4 (isoform 3).
Biological Process
Bud elongation involved in lung branchingIEA:Ensembl
Cardiac muscle tissue regenerationIEA:Ensembl
Cell morphogenesisIEA:Ensembl
Cell population proliferationManual Assertion Based On ExperimentIDA:UniProtKB
Cellular response to DNA damage stimulusManual Assertion Based On ExperimentIDA:UniProtKB
Cellular response to gamma radiationManual Assertion Based On ExperimentIDA:UniProtKB
Cellular response to retinoic acidIEA:Ensembl
Contact inhibitionManual Assertion Based On ExperimentIDA:UniProtKB
Embryonic heart tube morphogenesisIEA:Ensembl
Heart processIEA:Ensembl
Hippo signalingManual Assertion Based On ExperimentIBA:GO_Central
Interleukin-6-mediated signaling pathwayManual Assertion Based On ExperimentIDA:UniProtKB
Intestinal epithelial cell developmentManual Assertion Based On ExperimentIDA:UniProtKB
Keratinocyte differentiationIEA:Ensembl
Lateral mesoderm developmentIEA:Ensembl
Lung epithelial cell differentiationIEA:Ensembl
Negative regulation of cilium assemblyManual Assertion Based On ExperimentIMP:UniProtKB
Negative regulation of epithelial cell apoptotic processManual Assertion Based On ExperimentIMP:CACAO
Negative regulation of epithelial cell differentiationIEA:Ensembl
Negative regulation of extrinsic apoptotic signaling pathwayIEA:Ensembl
Negative regulation of fat cell differentiationManual Assertion Based On ExperimentIMP:ARUK-UCL
Negative regulation of gene expressionManual Assertion Based On ExperimentIMP:CACAO
Negative regulation of stem cell differentiationIEA:Ensembl
Negative regulation of transcription by RNA polymerase IIManual Assertion Based On ExperimentIMP:UniProtKB
Notochord developmentIEA:Ensembl
Paraxial mesoderm developmentIEA:Ensembl
Positive regulation of canonical Wnt signaling pathwayIEA:Ensembl
Positive regulation of cardiac muscle cell proliferationIEA:Ensembl
Positive regulation of cell growthManual Assertion Based On ExperimentIDA:ComplexPortal
Positive regulation of epithelial cell proliferationManual Assertion Based On ExperimentIMP:CACAO
Positive regulation of gene expressionManual Assertion Based On ExperimentIMP:CACAO
Positive regulation of intracellular estrogen receptor signaling pathwayManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of Notch signaling pathwayManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of osteoblast differentiationManual Assertion Based On ExperimentIMP:ARUK-UCL
Positive regulation of protein localization to nucleusISS:UniProtKB
Positive regulation of stem cell population maintenanceIEA:Ensembl
Positive regulation of transcription by RNA polymerase IIManual Assertion Based On ExperimentIDA:CAFA
Positive regulation of transcription, DNA-templatedManual Assertion Based On ExperimentIDA:CAFA
Progesterone receptor signaling pathwayManual Assertion Based On ExperimentIDA:UniProtKB
Protein-containing complex assemblyManual Assertion Based On ExperimentIDA:CAFA
Regulation of keratinocyte proliferationIEA:Ensembl
Regulation of metanephric nephron tubule epithelial cell differentiationIEA:Ensembl
Regulation of neurogenesisManual Assertion Based On ExperimentIDA:MGI
Regulation of stem cell proliferationManual Assertion Based On ExperimentIDA:MGI
Response to progesteroneManual Assertion Based On ExperimentIDA:UniProtKB
Somatic stem cell population maintenanceIEA:Ensembl
Tissue homeostasisIEA:Ensembl
Trophectodermal cell differentiationIEA:Ensembl
VasculogenesisIEA:Ensembl
Wound healingIEA:Ensembl
Cellular Location
Cytoplasm
Nucleus
Both phosphorylation and cell density can regulate its subcellular localization (PubMed:18158288, PubMed:20048001).
Phosphorylation sequesters it in the cytoplasm by inhibiting its translocation into the nucleus (PubMed:18158288, PubMed:20048001).
At low density, predominantly nuclear and is translocated to the cytoplasm at high density (PubMed:18158288, PubMed:20048001, PubMed:25849865).
PTPN14 induces translocation from the nucleus to the cytoplasm (PubMed:22525271).
Localized mainly to the nucleus in the early stages of embryo development with expression becoming evident in the cytoplasm at the blastocyst and epiblast stages (By similarity).
Involvement in disease
Coloboma, ocular, with or without hearing impairment, cleft lip/palate, and/or mental retardation (COB1):
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.
PTM
Phosphorylated by LATS1 and LATS2; leading to cytoplasmic translocation and inactivation (PubMed:18158288, PubMed:20048001).
Phosphorylated by ABL1; leading to YAP1 stabilization, enhanced interaction with TP73 and recruitment onto proapoptotic genes; in response to DNA damage (PubMed:18280240).
Phosphorylation at Ser-400 and Ser-403 by CK1 is triggered by previous phosphorylation at Ser-397 by LATS proteins and leads to YAP1 ubiquitination by SCF(beta-TRCP) E3 ubiquitin ligase and subsequent degradation (PubMed:20048001).
Phosphorylated at Thr-119, Ser-138, Thr-154, Ser-367 and Thr-412 by MAPK8/JNK1 and MAPK9/JNK2, which is required for the regulation of apoptosis by YAP1 (PubMed:21364637).
Ubiquitinated by SCF(beta-TRCP) E3 ubiquitin ligase.