TISIDB

Summary
Symbol	WAC
Name	WW domain containing adaptor with coiled-coil
Aliases	FLJ31290; PRO1741; BM-016; MGC10753; WW domain-containing adaptor with coiled coil; WW domain-containing ada ......
Chromosomal Location	10p12.1
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 speckle Nucleus Note=In distinct nuclear speckles. Colocalizes with pre-mRNA processing complexes.
Domain	PF00397 WW domain
Function	Acts as a linker between gene transcription and histone H2B monoubiquitination at 'Lys-120' (H2BK120ub1) (PubMed:21329877). Interacts with the RNA polymerase II transcriptional machinery via its WW domain and with RNF20-RNF40 via its coiled coil region, thereby linking and regulating H2BK120ub1 and gene transcription (PubMed:21329877). Regulates the cell-cycle checkpoint activation in response to DNA damage (PubMed:21329877). Positive regulator of amino acid starvation-induced autophagy (PubMed:22354037). Also acts as a negative regulator of basal autophagy (PubMed:26812014). Positively regulates MTOR activity by promoting, in an energy-dependent manner, the assembly of the TTT complex composed of TELO2, TTI1 and TTI2 and the RUVBL complex composed of RUVBL1 and RUVBL2 into the TTT-RUVBL complex. This leads to the dimerization of the mTORC1 complex and its subsequent activation (PubMed:26812014). May negatively regulate the ubiquitin proteasome pathway (PubMed:21329877).

> Gene Ontology [ TOP ]
Biological Process	GO:0000075 cell cycle checkpoint GO:0000077 DNA damage checkpoint GO:0006513 protein monoubiquitination GO:0006914 autophagy GO:0009894 regulation of catabolic process GO:0009895 negative regulation of catabolic process GO:0010390 histone monoubiquitination GO:0010498 proteasomal protein catabolic process GO:0010506 regulation of autophagy GO:0010508 positive regulation of autophagy GO:0016236 macroautophagy GO:0016239 positive regulation of macroautophagy GO:0016241 regulation of macroautophagy GO:0016570 histone modification GO:0016574 histone ubiquitination GO:0031329 regulation of cellular catabolic process GO:0031330 negative regulation of cellular catabolic process GO:0031570 DNA integrity checkpoint GO:0032434 regulation of proteasomal ubiquitin-dependent protein catabolic process GO:0032435 negative regulation of proteasomal ubiquitin-dependent protein catabolic process GO:0033523 histone H2B ubiquitination GO:0042176 regulation of protein catabolic process GO:0042177 negative regulation of protein catabolic process GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process GO:0044783 G1 DNA damage checkpoint GO:0045861 negative regulation of proteolysis GO:0061136 regulation of proteasomal protein catabolic process GO:0071894 histone H2B conserved C-terminal lysine ubiquitination GO:1901799 negative regulation of proteasomal protein catabolic process GO:1903050 regulation of proteolysis involved in cellular protein catabolic process GO:1903051 negative regulation of proteolysis involved in cellular protein catabolic process GO:1903362 regulation of cellular protein catabolic process GO:1903363 negative regulation of cellular protein catabolic process
Molecular Function	GO:0000993 RNA polymerase II core binding GO:0001098 basal transcription machinery binding GO:0001099 basal RNA polymerase II transcription machinery binding GO:0003682 chromatin binding GO:0043175 RNA polymerase core enzyme binding GO:0070063 RNA polymerase binding
Cellular Component	GO:0005681 spliceosomal complex GO:0016604 nuclear body GO:0016607 nuclear speck

> KEGG and Reactome Pathway [ TOP ]
KEGG	-
Reactome	R-HSA-8866654: E3 ubiquitin ligases ubiquitinate target proteins R-HSA-392499: Metabolism of proteins R-HSA-597592: Post-translational protein modification R-HSA-8852135: Protein ubiquitination

Summary
Symbol	WAC
Name	WW domain containing adaptor with coiled-coil
Aliases	FLJ31290; PRO1741; BM-016; MGC10753; WW domain-containing adaptor with coiled coil; WW domain-containing ada ......
Chromosomal Location	10p12.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between WAC 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	WAC
Name	WW domain containing adaptor with coiled-coil
Aliases	FLJ31290; PRO1741; BM-016; MGC10753; WW domain-containing adaptor with coiled coil; WW domain-containing ada ......
Chromosomal Location	10p12.1
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

[ TOP ]

Statistical results of WAC 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: 0.65	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	WAC
Name	WW domain containing adaptor with coiled-coil
Aliases	FLJ31290; PRO1741; BM-016; MGC10753; WW domain-containing adaptor with coiled coil; WW domain-containing ada ......
Chromosomal Location	10p12.1
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 WAC 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	0.09	0.698
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	0.342	0.874
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.091	0.953
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.037	0.926
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.32	0.893
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.49	0.875
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.162	0.71
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.388	0.847
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	-0.107	0.962
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.06	0.97
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	0.643	0.785
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	0.062	0.325

> Mutation difference between responders and non-responders

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

No	PMID	Cancer type	Group	Drug	# Res	# NRes	% Mut/Res	% Mut/NRes	% Diff (R vs NR)	Pval
1	25765070	Non-small cell lung cancer (NSCLC)	all	Anti-PD-1 (pembrolizumab)	14	17	0	0	0	1
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	0	0	0	1
3	25765070	Non-small cell lung cancer (NSCLC)	non-smoking	Anti-PD-1 (pembrolizumab)	4	14	0	0	0	1
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	3.7	0	3.7	0.27
5	26359337	Melanoma	BRAFi	Anti-CTLA-4 (ipilimumab)	0	14	0	0	0	1
6	26359337	Melanoma	non-BRAFi	Anti-CTLA-4 (ipilimumab)	27	59	3.7	0	3.7	0.314
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	0	0	0	1
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	0	0	0	1
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	0	0	0	1
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0	25	-25	0.26
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	33.3	-33.3	0.258
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0	14.3	-14.3	1
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	0	3.7	-3.7	0.415
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	0	0	0	1
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	0	7.1	-7.1	0.467
16	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	11	13	0	0	0	1
17	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	6	1	0	0	0	1
18	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	5	12	0	0	0	1

Summary
Symbol	WAC
Name	WW domain containing adaptor with coiled-coil
Aliases	FLJ31290; PRO1741; BM-016; MGC10753; WW domain-containing adaptor with coiled coil; WW domain-containing ada ......
Chromosomal Location	10p12.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of WAC. 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	WAC
Name	WW domain containing adaptor with coiled-coil
Aliases	FLJ31290; PRO1741; BM-016; MGC10753; WW domain-containing adaptor with coiled coil; WW domain-containing ada ......
Chromosomal Location	10p12.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of WAC. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by WAC. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	WAC
Name	WW domain containing adaptor with coiled-coil
Aliases	FLJ31290; PRO1741; BM-016; MGC10753; WW domain-containing adaptor with coiled coil; WW domain-containing ada ......
Chromosomal Location	10p12.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of WAC. 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	WAC
Name	WW domain containing adaptor with coiled-coil
Aliases	FLJ31290; PRO1741; BM-016; MGC10753; WW domain-containing adaptor with coiled coil; WW domain-containing ada ......
Chromosomal Location	10p12.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of WAC expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	WAC
Name	WW domain containing adaptor with coiled-coil
Aliases	FLJ31290; PRO1741; BM-016; MGC10753; WW domain-containing adaptor with coiled coil; WW domain-containing ada ......
Chromosomal Location	10p12.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between WAC and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	WAC
Name	WW domain containing adaptor with coiled-coil
Aliases	FLJ31290; PRO1741; BM-016; MGC10753; WW domain-containing adaptor with coiled coil; WW domain-containing ada ......
Chromosomal Location	10p12.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting WAC collected from DrugBank database.

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

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