TISIDB

Summary
Symbol	USP6
Name	ubiquitin specific peptidase 6
Aliases	Tre-2; TRE17; Tre2; ubiquitin carboxyl-terminal hydrolase 6; TBC1D3 and USP32 fusion; Tre-2 oncogene; HRP1; ......
Chromosomal Location	17p13
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	Cell membrane. Cytoplasm. Endosome. Note=Localizes to the plasma membrane and to filamentous structures within the cell corresponding to ARF6 regulated tubular endosomes. Activation of RAC1 and CDC42 can direct the relocalization of USP6 to the plasma membrane in a manner that depends on the integrity of the actin cytoskeleton.
Domain	PF00566 Rab-GTPase-TBC domain PF00443 Ubiquitin carboxyl-terminal hydrolase
Function	Deubiquitinase with an ATP-independent isopeptidase activity, cleaving at the C-terminus of the ubiquitin moiety. Catalyzes its own deubiquitination. In vitro, isoform 2, but not isoform 3, shows deubiquitinating activity. Promotes plasma membrane localization of ARF6 and selectively regulates ARF6-dependent endocytic protein trafficking. Is able to initiate tumorigenesis by inducing the production of matrix metalloproteinases following NF-kappa-B activation.

> Gene Ontology [ TOP ]
Biological Process	GO:0016579 protein deubiquitination GO:0060627 regulation of vesicle-mediated transport GO:0070646 protein modification by small protein removal
Molecular Function	GO:0004175 endopeptidase activity GO:0004197 cysteine-type endopeptidase activity GO:0004843 thiol-dependent ubiquitin-specific protease activity GO:0005516 calmodulin binding GO:0008234 cysteine-type peptidase activity GO:0019783 ubiquitin-like protein-specific protease activity GO:0036459 thiol-dependent ubiquitinyl hydrolase activity GO:0101005 ubiquitinyl hydrolase activity
Cellular Component	GO:0055037 recycling endosome

> KEGG and Reactome Pathway [ TOP ]
KEGG	-
Reactome	-

Summary
Symbol	USP6
Name	ubiquitin specific peptidase 6
Aliases	Tre-2; TRE17; Tre2; ubiquitin carboxyl-terminal hydrolase 6; TBC1D3 and USP32 fusion; Tre-2 oncogene; HRP1; ......
Chromosomal Location	17p13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between USP6 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	USP6
Name	ubiquitin specific peptidase 6
Aliases	Tre-2; TRE17; Tre2; ubiquitin carboxyl-terminal hydrolase 6; TBC1D3 and USP32 fusion; Tre-2 oncogene; HRP1; ......
Chromosomal Location	17p13
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 USP6 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	NA/NS	NA/NS
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	USP6
Name	ubiquitin specific peptidase 6
Aliases	Tre-2; TRE17; Tre2; ubiquitin carboxyl-terminal hydrolase 6; TBC1D3 and USP32 fusion; Tre-2 oncogene; HRP1; ......
Chromosomal Location	17p13
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 USP6 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	0.125	0.38
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	0.133	0.709
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0.122	0.65
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.094	0.849
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0.523	0.718
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	-0.453	0.788
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.026	0.927
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.225	0.791
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	-0.16	0.858
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.191	0.627
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	0.153	0.787
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.142	0.637

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of USP6 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	5.9	-5.9	1
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	0	33.3	-33.3	0.231
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	11.1	5.5	5.6	0.384
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	11.1	6.8	4.3	0.673
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	28.6	0	28.6	0.0241
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	46.2	0	46.2	0.0162
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	11.1	12.5	-1.4	1
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	20	11.1	8.9	1
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	15.8	3.7	12.1	0.224
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	27.3	7.7	19.6	0.22
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	0	0	0	1
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	USP6
Name	ubiquitin specific peptidase 6
Aliases	Tre-2; TRE17; Tre2; ubiquitin carboxyl-terminal hydrolase 6; TBC1D3 and USP32 fusion; Tre-2 oncogene; HRP1; ......
Chromosomal Location	17p13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of USP6. 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	USP6
Name	ubiquitin specific peptidase 6
Aliases	Tre-2; TRE17; Tre2; ubiquitin carboxyl-terminal hydrolase 6; TBC1D3 and USP32 fusion; Tre-2 oncogene; HRP1; ......
Chromosomal Location	17p13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of USP6. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by USP6. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	USP6
Name	ubiquitin specific peptidase 6
Aliases	Tre-2; TRE17; Tre2; ubiquitin carboxyl-terminal hydrolase 6; TBC1D3 and USP32 fusion; Tre-2 oncogene; HRP1; ......
Chromosomal Location	17p13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of USP6. 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	USP6
Name	ubiquitin specific peptidase 6
Aliases	Tre-2; TRE17; Tre2; ubiquitin carboxyl-terminal hydrolase 6; TBC1D3 and USP32 fusion; Tre-2 oncogene; HRP1; ......
Chromosomal Location	17p13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of USP6 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	USP6
Name	ubiquitin specific peptidase 6
Aliases	Tre-2; TRE17; Tre2; ubiquitin carboxyl-terminal hydrolase 6; TBC1D3 and USP32 fusion; Tre-2 oncogene; HRP1; ......
Chromosomal Location	17p13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between USP6 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	USP6
Name	ubiquitin specific peptidase 6
Aliases	Tre-2; TRE17; Tre2; ubiquitin carboxyl-terminal hydrolase 6; TBC1D3 and USP32 fusion; Tre-2 oncogene; HRP1; ......
Chromosomal Location	17p13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting USP6 collected from DrugBank database.

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

Browse USP6