TISIDB

Summary
Symbol	USP2
Name	ubiquitin specific peptidase 2
Aliases	UBP41; ubiquitin specific protease 2; USP9; 41 kDa ubiquitin-specific protease; deubiquitinating enzyme 2; u ......
Chromosomal Location	11q23.3
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	Cytoplasm Cytoplasm, perinuclear region Note=Localizes in the spermatid head in late-elongating spermatids in the thin area between the outer acrosomal membrane and the plasma membrane. ; SUBCELLULAR LOCATION: Isoform 4: Nucleus Membrane Peripheral membrane protein Cytoplasm Note=Predominantly expressed at membranes.
Domain	PF00443 Ubiquitin carboxyl-terminal hydrolase
Function	Hydrolase that deubiquitinates polyubiquitinated target proteins such as MDM2, MDM4 and CCND1 (PubMed:17290220, PubMed:19917254, PubMed:19838211). Isoform 1 and isoform 4 possess both ubiquitin-specific peptidase and isopeptidase activities (By similarity). Deubiquitinates MDM2 without reversing MDM2-mediated p53/TP53 ubiquitination and thus indirectly promotes p53/TP53 degradation and limits p53 activity (PubMed:17290220, PubMed:19838211). Has no deubiquitinase activity against p53/TP53 (PubMed:17290220). Prevents MDM2-mediated degradation of MDM4 (PubMed:17290220). Plays a role in the G1/S cell-cycle progression in normal and cancer cells (PubMed:19917254). Regulates the circadian clock by modulating its intrinsic circadian rhythm and its capacity to respond to external cues (By similarity). Associates with clock proteins and deubiquitinates core clock component PER1 but does not affect its overall stability (By similarity). Regulates the nucleocytoplasmic shuttling and nuclear retention of PER1 and its repressive role on the clock transcription factors CLOCK and ARNTL/BMAL1 (By similarity). Plays a role in the regulation of myogenic differentiation of embryonic muscle cells (By similarity). ; FUNCTION: Isoform 4: Circadian clock output effector that regulates Ca(2+) absorption in the small intestine. Probably functions by regulating protein levels of the membrane scaffold protein NHERF4 in a rhythmic manner, and is therefore likely to control Ca(2+) membrane permeability mediated by the Ca(2+) channel TRPV6 in the intestine.

> Gene Ontology [ TOP ]
Biological Process	GO:0007346 regulation of mitotic cell cycle GO:0007517 muscle organ development GO:0007519 skeletal muscle tissue development GO:0007622 rhythmic behavior GO:0007623 circadian rhythm GO:0007626 locomotory behavior GO:0009314 response to radiation GO:0009416 response to light stimulus GO:0009648 photoperiodism GO:0009649 entrainment of circadian clock GO:0014706 striated muscle tissue development GO:0016202 regulation of striated muscle tissue development GO:0016579 protein deubiquitination GO:0031647 regulation of protein stability GO:0032922 circadian regulation of gene expression GO:0042752 regulation of circadian rhythm GO:0043153 entrainment of circadian clock by photoperiod GO:0045475 locomotor rhythm GO:0045787 positive regulation of cell cycle GO:0045843 negative regulation of striated muscle tissue development GO:0045844 positive regulation of striated muscle tissue development GO:0045931 positive regulation of mitotic cell cycle GO:0048511 rhythmic process GO:0048512 circadian behavior GO:0048634 regulation of muscle organ development GO:0048635 negative regulation of muscle organ development GO:0048636 positive regulation of muscle organ development GO:0048641 regulation of skeletal muscle tissue development GO:0048642 negative regulation of skeletal muscle tissue development GO:0048643 positive regulation of skeletal muscle tissue development GO:0050821 protein stabilization GO:0060537 muscle tissue development GO:0060538 skeletal muscle organ development GO:0070646 protein modification by small protein removal GO:1901861 regulation of muscle tissue development GO:1901862 negative regulation of muscle tissue development GO:1901863 positive regulation of muscle tissue development
Molecular Function	GO:0004175 endopeptidase activity GO:0004197 cysteine-type endopeptidase activity GO:0004843 thiol-dependent ubiquitin-specific protease activity GO:0008234 cysteine-type peptidase activity GO:0019783 ubiquitin-like protein-specific protease activity GO:0030332 cyclin binding GO:0031625 ubiquitin protein ligase binding GO:0036459 thiol-dependent ubiquitinyl hydrolase activity GO:0044389 ubiquitin-like protein ligase binding GO:0101005 ubiquitinyl hydrolase activity
Cellular Component	GO:0005813 centrosome GO:0005938 cell cortex GO:0099568 cytoplasmic region

> KEGG and Reactome Pathway [ TOP ]
KEGG	-
Reactome	R-HSA-73887: Death Receptor Signalling R-HSA-5688426: Deubiquitination R-HSA-74160: Gene Expression R-HSA-212436: Generic Transcription Pathway R-HSA-392499: Metabolism of proteins R-HSA-597592: Post-translational protein modification R-HSA-5357905: Regulation of TNFR1 signaling R-HSA-5633007: Regulation of TP53 Activity R-HSA-6804757: Regulation of TP53 Degradation R-HSA-6806003: Regulation of TP53 Expression and Degradation R-HSA-162582: Signal Transduction R-HSA-75893: TNF signaling R-HSA-5357956: TNFR1-induced NFkappaB signaling pathway R-HSA-5357786: TNFR1-induced proapoptotic signaling R-HSA-3700989: Transcriptional Regulation by TP53 R-HSA-5689880: Ub-specific processing proteases

> KEGG and Reactome Pathway

[ TOP ]

KEGG

Reactome

R-HSA-73887: Death Receptor Signalling
R-HSA-5688426: Deubiquitination
R-HSA-74160: Gene Expression
R-HSA-212436: Generic Transcription Pathway
R-HSA-392499: Metabolism of proteins
R-HSA-597592: Post-translational protein modification
R-HSA-5357905: Regulation of TNFR1 signaling
R-HSA-5633007: Regulation of TP53 Activity
R-HSA-6804757: Regulation of TP53 Degradation
R-HSA-6806003: Regulation of TP53 Expression and Degradation
R-HSA-162582: Signal Transduction
R-HSA-75893: TNF signaling
R-HSA-5357956: TNFR1-induced NFkappaB signaling pathway
R-HSA-5357786: TNFR1-induced proapoptotic signaling
R-HSA-3700989: Transcriptional Regulation by TP53
R-HSA-5689880: Ub-specific processing proteases

Summary
Symbol	USP2
Name	ubiquitin specific peptidase 2
Aliases	UBP41; ubiquitin specific protease 2; USP9; 41 kDa ubiquitin-specific protease; deubiquitinating enzyme 2; u ......
Chromosomal Location	11q23.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between USP2 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	USP2
Name	ubiquitin specific peptidase 2
Aliases	UBP41; ubiquitin specific protease 2; USP9; 41 kDa ubiquitin-specific protease; deubiquitinating enzyme 2; u ......
Chromosomal Location	11q23.3
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 USP2 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	USP2
Name	ubiquitin specific peptidase 2
Aliases	UBP41; ubiquitin specific protease 2; USP9; 41 kDa ubiquitin-specific protease; deubiquitinating enzyme 2; u ......
Chromosomal Location	11q23.3
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

[ TOP ]

Points in the above scatter plot represent the expression difference of USP2 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	1.12	0.00392
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	0.364	0.648
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	1.678	0.00311
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	-0.131	0.816
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.442	0.781
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.26	0.891
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	-0.45	0.349
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.13	0.869
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	-1.034	0.196
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.355	0.683
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	1.398	0.197
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.271	0.138

> Mutation difference between responders and non-responders

[ TOP ]

Points in the above scatter plot represent the mutation difference of USP2 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	0	1.4	-1.4	1
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	0	1.7	-1.7	1
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	6.2	-6.2	1
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	11.1	-11.1	1
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0	0	0	1
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	2.6	0	2.6	1
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	4.5	0	4.5	1
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	USP2
Name	ubiquitin specific peptidase 2
Aliases	UBP41; ubiquitin specific protease 2; USP9; 41 kDa ubiquitin-specific protease; deubiquitinating enzyme 2; u ......
Chromosomal Location	11q23.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of USP2. 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	USP2
Name	ubiquitin specific peptidase 2
Aliases	UBP41; ubiquitin specific protease 2; USP9; 41 kDa ubiquitin-specific protease; deubiquitinating enzyme 2; u ......
Chromosomal Location	11q23.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of USP2. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by USP2. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	USP2
Name	ubiquitin specific peptidase 2
Aliases	UBP41; ubiquitin specific protease 2; USP9; 41 kDa ubiquitin-specific protease; deubiquitinating enzyme 2; u ......
Chromosomal Location	11q23.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of USP2. 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	USP2
Name	ubiquitin specific peptidase 2
Aliases	UBP41; ubiquitin specific protease 2; USP9; 41 kDa ubiquitin-specific protease; deubiquitinating enzyme 2; u ......
Chromosomal Location	11q23.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of USP2 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	USP2
Name	ubiquitin specific peptidase 2
Aliases	UBP41; ubiquitin specific protease 2; USP9; 41 kDa ubiquitin-specific protease; deubiquitinating enzyme 2; u ......
Chromosomal Location	11q23.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between USP2 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	USP2
Name	ubiquitin specific peptidase 2
Aliases	UBP41; ubiquitin specific protease 2; USP9; 41 kDa ubiquitin-specific protease; deubiquitinating enzyme 2; u ......
Chromosomal Location	11q23.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting USP2 collected from DrugBank database.

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

Browse USP2