TISIDB

Summary
Symbol	WWTR1
Name	WW domain containing transcription regulator 1
Aliases	DKFZp586I1419; transcriptional co-activator with PDZ-binding motif; transcriptional coactivator with PDZ-bin ......
Chromosomal Location	3q23-q24
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 [ TOP ]
Subcellular Location	Nucleus. Cytoplasm. Note=Concentrates along specific portions of the plasma membrane, and accumulates in punctate nuclear bodies. When phosphorylated, is retained in cytoplasm by YWHAZ. Can be retained in the nucleus by MED15.
Domain	PF00397 WW domain
Function	Transcriptional coactivator which acts as a 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. WWTR1 enhances PAX8 and NKX2-1/TTF1-dependent gene activation. Regulates the nuclear accumulation of SMADS and has a key role in coupling them to the transcriptional machinery such as the mediator complex. Regulates embryonic stem-cell self-renewal, promotes cell proliferation and epithelial-mesenchymal transition.

> Gene Ontology [ TOP ]
Biological Process	GO:0001503 ossification GO:0001649 osteoblast differentiation GO:0001655 urogenital system development GO:0001656 metanephros development GO:0001822 kidney development GO:0001837 epithelial to mesenchymal transition GO:0001933 negative regulation of protein phosphorylation GO:0006352 DNA-templated transcription, initiation GO:0006367 transcription initiation from RNA polymerase II promoter GO:0006469 negative regulation of protein kinase activity GO:0006606 protein import into nucleus GO:0006913 nucleocytoplasmic transport GO:0007178 transmembrane receptor protein serine/threonine kinase signaling pathway GO:0007184 SMAD protein import into nucleus GO:0010498 proteasomal protein catabolic process GO:0010717 regulation of epithelial to mesenchymal transition GO:0010718 positive regulation of epithelial to mesenchymal transition GO:0016055 Wnt signaling pathway GO:0017038 protein import GO:0017145 stem cell division GO:0030111 regulation of Wnt signaling pathway GO:0030178 negative regulation of Wnt signaling pathway GO:0030856 regulation of epithelial cell differentiation GO:0031146 SCF-dependent proteasomal ubiquitin-dependent protein catabolic process GO:0032386 regulation of intracellular transport GO:0032387 negative regulation of intracellular transport GO:0032835 glomerulus development GO:0033157 regulation of intracellular protein transport GO:0033673 negative regulation of kinase activity GO:0034504 protein localization to nucleus GO:0035264 multicellular organism growth GO:0035329 hippo signaling GO:0035411 catenin import into nucleus GO:0035412 regulation of catenin import into nucleus GO:0035414 negative regulation of catenin import into nucleus GO:0035850 epithelial cell differentiation involved in kidney development GO:0042306 regulation of protein import into nucleus GO:0042308 negative regulation of protein import into nucleus GO:0042326 negative regulation of phosphorylation GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process GO:0044744 protein targeting to nucleus GO:0045444 fat cell differentiation GO:0045598 regulation of fat cell differentiation GO:0045599 negative regulation of fat cell differentiation GO:0046822 regulation of nucleocytoplasmic transport GO:0046823 negative regulation of nucleocytoplasmic transport GO:0048762 mesenchymal cell differentiation GO:0051051 negative regulation of transport GO:0051169 nuclear transport GO:0051170 nuclear import GO:0051224 negative regulation of protein transport GO:0051348 negative regulation of transferase activity GO:0060070 canonical Wnt signaling pathway GO:0060271 cilium morphogenesis GO:0060390 regulation of SMAD protein import into nucleus GO:0060485 mesenchyme development GO:0060828 regulation of canonical Wnt signaling pathway GO:0060993 kidney morphogenesis GO:0061005 cell differentiation involved in kidney development GO:0061326 renal tubule development 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: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:0090090 negative regulation of canonical Wnt signaling pathway GO:0090092 regulation of transmembrane receptor protein serine/threonine kinase signaling pathway GO:0090183 regulation of kidney development GO:0090317 negative regulation of intracellular protein transport GO:0198738 cell-cell signaling by wnt GO:1900180 regulation of protein localization to nucleus GO:1900181 negative regulation of protein localization to nucleus GO:1902593 single-organism nuclear import GO:1903533 regulation of protein targeting GO:1903828 negative regulation of cellular protein localization GO:1904589 regulation of protein import GO:1904590 negative regulation of protein import GO:1904950 negative regulation of establishment of protein localization GO:2000696 regulation of epithelial cell differentiation involved in kidney development
Molecular Function	GO:0003713 transcription coactivator activity GO:0003714 transcription corepressor activity
Cellular Component	GO:0005667 transcription factor complex

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04390 Hippo signaling pathway
Reactome	R-HSA-5576891: Cardiac conduction 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-397014: Muscle contraction R-HSA-1989781: PPARA activates gene expression R-HSA-5578768: Physiological factors R-HSA-400206: Regulation of lipid metabolism by Peroxisome proliferator-activated receptor alpha (PPARalpha) R-HSA-2173796: SMAD2/SMAD3 R-HSA-162582: Signal Transduction R-HSA-2028269: Signaling by Hippo R-HSA-170834: Signaling by TGF-beta Receptor Complex R-HSA-2173793: Transcriptional activity of SMAD2/SMAD3 R-HSA-2032785: YAP1- and WWTR1 (TAZ)-stimulated gene expression

> KEGG and Reactome Pathway

[ TOP ]

KEGG

hsa04390 Hippo signaling pathway

Reactome

R-HSA-5576891: Cardiac conduction
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-397014: Muscle contraction
R-HSA-1989781: PPARA activates gene expression
R-HSA-5578768: Physiological factors
R-HSA-400206: Regulation of lipid metabolism by Peroxisome proliferator-activated receptor alpha (PPARalpha)
R-HSA-2173796: SMAD2/SMAD3
R-HSA-162582: Signal Transduction
R-HSA-2028269: Signaling by Hippo
R-HSA-170834: Signaling by TGF-beta Receptor Complex
R-HSA-2173793: Transcriptional activity of SMAD2/SMAD3
R-HSA-2032785: YAP1- and WWTR1 (TAZ)-stimulated gene expression

Summary
Symbol	WWTR1
Name	WW domain containing transcription regulator 1
Aliases	DKFZp586I1419; transcriptional co-activator with PDZ-binding motif; transcriptional coactivator with PDZ-bin ......
Chromosomal Location	3q23-q24
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between WWTR1 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 [ TOP ]
There is no record.

Summary
Symbol	WWTR1
Name	WW domain containing transcription regulator 1
Aliases	DKFZp586I1419; transcriptional co-activator with PDZ-binding motif; transcriptional coactivator with PDZ-bin ......
Chromosomal Location	3q23-q24
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

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Statistical results of WWTR1 in screening data sets for detecting immune reponses.

PMID	Screening System	Cancer Type	Cell Line	Data Set	Statistical Results	Relation to immunity
29301958	CRISPR-Cas9	melanoma	B16F10	Pmel-1 T cell	NA/NS	NA/NS
29301958	CRISPR-Cas9	melanoma	B16F10	OT-1 T cell	NA/NS	NA/NS
28783722	CRISPR-Cas9	melanoma	Mel624	2CT-CRISPR	Second most enriched score: 0.59	Sensitive to T cell-mediated killing
28723893	CRISPR-Cas9	melanoma	B16	GVAX+Anti-PD1	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX	NA/NS	NA/NS
25691366	RNAi	Breast cancer	MCF7	Luc-CTL assay	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Primary screen	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Secondary screen	NA/NS	NA/NS

Summary
Symbol	WWTR1
Name	WW domain containing transcription regulator 1
Aliases	DKFZp586I1419; transcriptional co-activator with PDZ-binding motif; transcriptional coactivator with PDZ-bin ......
Chromosomal Location	3q23-q24
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

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Points in the above scatter plot represent the expression difference of WWTR1 in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	Log2 (Fold Change)	P value
1	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	14	12	-0.325	0.491
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.258	0.906
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.379	0.823
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.129	0.752
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0.265	0.909
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	-0.042	0.989
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	-0.087	0.879
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	-0.472	0.824
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.439	0.844
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	-0.053	0.978
11	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	2	0	0	1
12	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	2	8	0.866	0.75
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.412	0.000979

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of WWTR1 in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	% Mut/NRes	% Diff (R vs NR)	Pval
1	25765070	Non-small cell lung cancer (NSCLC)	all	Anti-PD-1 (pembrolizumab)	14	17	0	0	1
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	0	0	1
3	25765070	Non-small cell lung cancer (NSCLC)	non-smoking	Anti-PD-1 (pembrolizumab)	4	14	0	0	1
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	4.1	-4.1	0.561
5	26359337	Melanoma	BRAFi	Anti-CTLA-4 (ipilimumab)	0	14	0	0	1
6	26359337	Melanoma	non-BRAFi	Anti-CTLA-4 (ipilimumab)	27	59	5.1	-5.1	0.549
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	5.9	-5.9	0.447
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	16.7	-16.7	0.429
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	0	0	1
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	6.2	-6.2	1
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	11.1	-11.1	1
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0	0	1
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	0	0	1
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	0	0	1
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	0	0	1
16	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	11	13	0	0	1
17	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	6	1	0	0	1
18	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	5	12	0	0	1

Summary
Symbol	WWTR1
Name	WW domain containing transcription regulator 1
Aliases	DKFZp586I1419; transcriptional co-activator with PDZ-binding motif; transcriptional coactivator with PDZ-bin ......
Chromosomal Location	3q23-q24
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of WWTR1. 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 [ TOP ]

Summary
Symbol	WWTR1
Name	WW domain containing transcription regulator 1
Aliases	DKFZp586I1419; transcriptional co-activator with PDZ-binding motif; transcriptional coactivator with PDZ-bin ......
Chromosomal Location	3q23-q24
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of WWTR1. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by WWTR1. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	WWTR1
Name	WW domain containing transcription regulator 1
Aliases	DKFZp586I1419; transcriptional co-activator with PDZ-binding motif; transcriptional coactivator with PDZ-bin ......
Chromosomal Location	3q23-q24
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of WWTR1. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene. > Chemokine > Receptor

> Chemokine [ TOP ]

> Receptor [ TOP ]

Summary
Symbol	WWTR1
Name	WW domain containing transcription regulator 1
Aliases	DKFZp586I1419; transcriptional co-activator with PDZ-binding motif; transcriptional coactivator with PDZ-bin ......
Chromosomal Location	3q23-q24
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of WWTR1 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	WWTR1
Name	WW domain containing transcription regulator 1
Aliases	DKFZp586I1419; transcriptional co-activator with PDZ-binding motif; transcriptional coactivator with PDZ-bin ......
Chromosomal Location	3q23-q24
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between WWTR1 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	WWTR1
Name	WW domain containing transcription regulator 1
Aliases	DKFZp586I1419; transcriptional co-activator with PDZ-binding motif; transcriptional coactivator with PDZ-bin ......
Chromosomal Location	3q23-q24
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting WWTR1 collected from DrugBank database.

> Drugs from DrugBank database [ TOP ]
There is no record.

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