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Browse YAP1

Summary
SymbolYAP1
NameYes-associated protein 1
Aliases YAP65; Yes-associated protein 1, 65kDa; COB1; YAP2; YKI; 65 kDa Yes-associated protein; protein yorkie homol ......
Chromosomal Location11q13
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Basic function annotation.
> Subcellular Location, Domain and Function
> Gene Ontology
> KEGG and Reactome Pathway
> Subcellular Location, Domain and Function
 
Subcellular Location Cytoplasm Nucleus Note=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 (PubMed:18158288, PubMed:20048001). PTPN14 induces translocation from the nucleus to the cytoplasm (PubMed:22525271).
Domain PF00397 WW domain
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). 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). ; FUNCTION: Isoform 2: Isoform 2 and isoform 3 can activate the C-terminal fragment (CTF) of ERBB4 (isoform 3).

> Gene Ontology
 
Biological Process GO:0001101 response to acid chemical
GO:0001570 vasculogenesis
GO:0001655 urogenital system development
GO:0001656 metanephros development
GO:0001763 morphogenesis of a branching structure
GO:0001822 kidney development
GO:0003007 heart morphogenesis
GO:0003143 embryonic heart tube morphogenesis
GO:0003401 axis elongation
GO:0006352 DNA-templated transcription, initiation
GO:0006367 transcription initiation from RNA polymerase II promoter
GO:0007498 mesoderm development
GO:0007507 heart development
GO:0008544 epidermis development
GO:0009314 response to radiation
GO:0009913 epidermal cell differentiation
GO:0010212 response to ionizing radiation
GO:0010332 response to gamma radiation
GO:0010837 regulation of keratinocyte proliferation
GO:0016055 Wnt signaling pathway
GO:0019827 stem cell population maintenance
GO:0030111 regulation of Wnt signaling pathway
GO:0030177 positive regulation of Wnt signaling pathway
GO:0030216 keratinocyte differentiation
GO:0030323 respiratory tube development
GO:0030324 lung development
GO:0030856 regulation of epithelial cell differentiation
GO:0030857 negative regulation of epithelial cell differentiation
GO:0030903 notochord development
GO:0032526 response to retinoic acid
GO:0035019 somatic stem cell population maintenance
GO:0035050 embryonic heart tube development
GO:0035239 tube morphogenesis
GO:0035265 organ growth
GO:0035329 hippo signaling
GO:0035850 epithelial cell differentiation involved in kidney development
GO:0043588 skin development
GO:0043616 keratinocyte proliferation
GO:0045927 positive regulation of growth
GO:0046620 regulation of organ growth
GO:0046622 positive regulation of organ growth
GO:0048339 paraxial mesoderm development
GO:0048368 lateral mesoderm development
GO:0048514 blood vessel morphogenesis
GO:0048562 embryonic organ morphogenesis
GO:0048568 embryonic organ development
GO:0048638 regulation of developmental growth
GO:0048639 positive regulation of developmental growth
GO:0048754 branching morphogenesis of an epithelial tube
GO:0048863 stem cell differentiation
GO:0050673 epithelial cell proliferation
GO:0050678 regulation of epithelial cell proliferation
GO:0060070 canonical Wnt signaling pathway
GO:0060242 contact inhibition
GO:0060425 lung morphogenesis
GO:0060428 lung epithelium development
GO:0060441 epithelial tube branching involved in lung morphogenesis
GO:0060449 bud elongation involved in lung branching
GO:0060479 lung cell differentiation
GO:0060485 mesenchyme development
GO:0060487 lung epithelial cell differentiation
GO:0060541 respiratory system development
GO:0060560 developmental growth involved in morphogenesis
GO:0060562 epithelial tube morphogenesis
GO:0060602 branch elongation of an epithelium
GO:0060828 regulation of canonical Wnt signaling pathway
GO:0061005 cell differentiation involved in kidney development
GO:0061138 morphogenesis of a branching epithelium
GO:0061326 renal tubule development
GO:0071214 cellular response to abiotic stimulus
GO:0071229 cellular response to acid chemical
GO:0071300 cellular response to retinoic acid
GO:0071396 cellular response to lipid
GO:0071478 cellular response to radiation
GO:0071479 cellular response to ionizing radiation
GO:0071480 cellular response to gamma radiation
GO:0072001 renal system development
GO:0072006 nephron development
GO:0072009 nephron epithelium development
GO:0072073 kidney epithelium development
GO:0072080 nephron tubule development
GO:0072089 stem cell proliferation
GO:0072091 regulation of stem cell proliferation
GO:0072160 nephron tubule epithelial cell differentiation
GO:0072170 metanephric tubule development
GO:0072182 regulation of nephron tubule epithelial cell differentiation
GO:0072202 cell differentiation involved in metanephros development
GO:0072207 metanephric epithelium development
GO:0072215 regulation of metanephros development
GO:0072234 metanephric nephron tubule development
GO:0072243 metanephric nephron epithelium development
GO:0072257 metanephric nephron tubule epithelial cell differentiation
GO:0072307 regulation of metanephric nephron tubule epithelial cell differentiation
GO:0090183 regulation of kidney development
GO:0090263 positive regulation of canonical Wnt signaling pathway
GO:0097191 extrinsic apoptotic signaling pathway
GO:0098727 maintenance of cell number
GO:0198738 cell-cell signaling by wnt
GO:1902459 positive regulation of stem cell population maintenance
GO:2000036 regulation of stem cell population maintenance
GO:2000696 regulation of epithelial cell differentiation involved in kidney development
GO:2000736 regulation of stem cell differentiation
GO:2000737 negative regulation of stem cell differentiation
GO:2001233 regulation of apoptotic signaling pathway
GO:2001234 negative regulation of apoptotic signaling pathway
GO:2001236 regulation of extrinsic apoptotic signaling pathway
GO:2001237 negative regulation of extrinsic apoptotic signaling pathway
Molecular Function GO:0000979 RNA polymerase II core promoter sequence-specific DNA binding
GO:0001046 core promoter sequence-specific DNA binding
GO:0001047 core promoter binding
GO:0001076 transcription factor activity, RNA polymerase II transcription factor binding
GO:0003682 chromatin binding
GO:0003713 transcription coactivator activity
GO:0003714 transcription corepressor activity
GO:0008022 protein C-terminus binding
GO:0070064 proline-rich region binding
Cellular Component GO:0005667 transcription factor complex
> KEGG and Reactome Pathway
 
KEGG hsa04390 Hippo signaling pathway
Reactome R-HSA-535734: Fatty acid, triacylglycerol, and ketone body metabolism
R-HSA-74160: Gene Expression
R-HSA-212436: Generic Transcription Pathway
R-HSA-1430728: Metabolism
R-HSA-556833: Metabolism of lipids and lipoproteins
R-HSA-1251985: Nuclear signaling by ERBB4
R-HSA-1989781: PPARA activates gene expression
R-HSA-400206: Regulation of lipid metabolism by Peroxisome proliferator-activated receptor alpha (PPARalpha)
R-HSA-162582: Signal Transduction
R-HSA-1236394: Signaling by ERBB4
R-HSA-2028269: Signaling by Hippo
R-HSA-2032785: YAP1- and WWTR1 (TAZ)-stimulated gene expression
Summary
SymbolYAP1
NameYes-associated protein 1
Aliases YAP65; Yes-associated protein 1, 65kDa; COB1; YAP2; YKI; 65 kDa Yes-associated protein; protein yorkie homol ......
Chromosomal Location11q13
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between YAP1 and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.
> Text Mining
 
  Literatures describing the relation between YAP1 and anti-tumor immunity in human cancer.
PMID Cancer type Relation to immunity Evidence sentences
29382670MelanomaInhibit immunity (T cell function); resistant to immunotherapyActivation of YAP, a Hippo pathway effector, is an important resistance mechanism to BRAF inhibitor (BRAFi) in melanoma. Emerging evidence also suggests that YAP is involved in suppression of the antitumor immune response. Here, we show that BRAFi-resistant melanoma cells evade CD8+ T-cell immune responses in a PD-L1-dependent manner by activating YAP, which synchronously supports melanoma cell survival upon BRAF inhibition. PD-L1 expression is elevated in BRAFi-resistant melanoma cells, in which YAP is robustly activated, and YAP knockdown decreases PD-L1 expression. In addition, constitutively active YAP (YAP-5SA) increases PD-L1 expression by binding to an upstream enhancer of the PD-L1 gene and potentiating its transcription.
29339539Breast carcinoma; Lung carcinomaInhibit immunityThe Hippo Pathway Component TAZ Promotes Immune Evasion in Human Cancer through PD-L1. The Hippo pathway component WW domain-containing transcription regulator 1 (TAZ) is a transcriptional coactivator and an oncogene in breast and lung cancer. The upstream kinases of the Hippo pathway, mammalian STE20-like kinase 1 and 2 (MST1/2), and large tumor suppressor 1 and 2 (LATS1/2), suppress PD-L1 expression while TAZ and YAP enhance PD-L1 levels in breast and lung cancer cell lines.
27546622Pancreatic Ductal AdenocarcinomaInhibit immunity (T cell function)Within Kras:p53 mutant pancreatic ductal cells, Yap drives the expression and secretion of multiple cytokines/chemokines, which in turn promote the differentiation and accumulation of myeloid-derived suppressor cells (MDSCs) both in vitro and in vivo. Pancreas-specific knockout of Yap or antibody-mediated depletion of MDSCs promoted macrophage reprogramming, reactivation of T cells, apoptosis of Kras mutant neoplastic ductal cells and pancreatic regeneration after acute pancreatitis.
Summary
SymbolYAP1
NameYes-associated protein 1
Aliases YAP65; Yes-associated protein 1, 65kDa; COB1; YAP2; YKI; 65 kDa Yes-associated protein; protein yorkie homol ......
Chromosomal Location11q13
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.
> High-throughput Screening
  Statistical results of YAP1 in screening data sets for detecting immune reponses.
PMID Screening System Cancer Type Cell Line Data Set Statistical Results Relation to immunity
29301958CRISPR-Cas9 melanomaB16F10Pmel-1 T cell NA/NSNA/NS
29301958CRISPR-Cas9 melanomaB16F10OT-1 T cell NA/NSNA/NS
28783722CRISPR-Cas9 melanomaMel6242CT-CRISPR NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX+Anti-PD1 NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX NA/NSNA/NS
25691366RNAiBreast cancerMCF7Luc-CTL assay NA/NSNA/NS
24476824shRNAmelanomaB16Primary screen NA/NSNA/NS
24476824shRNAmelanomaB16Secondary screen NA/NSNA/NS
Summary
SymbolYAP1
NameYes-associated protein 1
Aliases YAP65; Yes-associated protein 1, 65kDa; COB1; YAP2; YKI; 65 kDa Yes-associated protein; protein yorkie homol ......
Chromosomal Location11q13
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets.
> Expression difference between responders and non-responders
> Mutation difference between responders and non-responders
> Expression difference between responders and non-responders
 
Points in the above scatter plot represent the expression difference of YAP1 in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)1412-0.7110.177
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)65-1.0840.651
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)87-0.4330.8
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160.0340.905
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590.0020.999
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470.0750.981
729033130MelanomaallAnti-PD-1 (nivolumab) 2623-0.3650.487
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 1511-0.1610.937
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 1112-0.5490.804
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 480.0550.972
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 280.9190.675
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 68230-0.3020.000305
> Mutation difference between responders and non-responders
 
Points in the above scatter plot represent the mutation difference of YAP1 in various data sets.
No PMID Cancer type Group Drug # Res # NRes % Mut/Res % Mut/NRes % Diff (R vs NR) Pval Anno
125765070Non-small cell lung cancer (NSCLC)allAnti-PD-1 (pembrolizumab) 14170001
225765070Non-small cell lung cancer (NSCLC)smokingAnti-PD-1 (pembrolizumab) 1030001
325765070Non-small cell lung cancer (NSCLC)non-smokingAnti-PD-1 (pembrolizumab) 4140001
426359337MelanomaallAnti-CTLA-4 (ipilimumab) 277302.7-2.71
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 01407.1-7.11
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 275901.7-1.71
726997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)21170001
826997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)860001
926997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)13110001
1028552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160001
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590001
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470001
1329033130MelanomaallAnti-PD-1 (nivolumab) 38272.63.7-1.11
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 22134.57.7-3.21
1529033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 16140001
1629301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 11130001
1729301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 610001
1829301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 5120001
Summary
SymbolYAP1
NameYes-associated protein 1
Aliases YAP65; Yes-associated protein 1, 65kDa; COB1; YAP2; YKI; 65 kDa Yes-associated protein; protein yorkie homol ......
Chromosomal Location11q13
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of YAP1. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.
> Lymphocyte
 
Summary
SymbolYAP1
NameYes-associated protein 1
Aliases YAP65; Yes-associated protein 1, 65kDa; COB1; YAP2; YKI; 65 kDa Yes-associated protein; protein yorkie homol ......
Chromosomal Location11q13
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of YAP1. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by YAP1.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolYAP1
NameYes-associated protein 1
Aliases YAP65; Yes-associated protein 1, 65kDa; COB1; YAP2; YKI; 65 kDa Yes-associated protein; protein yorkie homol ......
Chromosomal Location11q13
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of YAP1. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolYAP1
NameYes-associated protein 1
Aliases YAP65; Yes-associated protein 1, 65kDa; COB1; YAP2; YKI; 65 kDa Yes-associated protein; protein yorkie homol ......
Chromosomal Location11q13
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of YAP1 expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolYAP1
NameYes-associated protein 1
Aliases YAP65; Yes-associated protein 1, 65kDa; COB1; YAP2; YKI; 65 kDa Yes-associated protein; protein yorkie homol ......
Chromosomal Location11q13
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between YAP1 and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolYAP1
NameYes-associated protein 1
Aliases YAP65; Yes-associated protein 1, 65kDa; COB1; YAP2; YKI; 65 kDa Yes-associated protein; protein yorkie homol ......
Chromosomal Location11q13
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting YAP1 collected from DrugBank database.
> Drugs from DrugBank database
 

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