TISIDB

Summary
Symbol	USP18
Name	ubiquitin specific peptidase 18
Aliases	ubiquitin specific protease 18; ISG43; UBP43; 43 kDa ISG15-specific protease; ISG15-specific-processing prot ......
Chromosomal Location	22q11.2
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	Isoform 1: Cytoplasm ; SUBCELLULAR LOCATION: Isoform 2: Nucleus Cytoplasm
Domain	PF00443 Ubiquitin carboxyl-terminal hydrolase
Function	Involved in the regulation of inflammatory response to interferon type 1 (PubMed:27325888). Can efficiently cleave only ISG15 fusions including native ISG15 conjugates linked via isopeptide bonds. Necessary to maintain a critical cellular balance of ISG15-conjugated proteins in both healthy and stressed organisms. ; FUNCTION: Isoform 2: Has enzymatic activity similar to isoform 1 and interferes with type I interferon signaling. Major deISGylation enzyme for nuclear proteins (PubMed:22170061).

> Gene Ontology [ TOP ]
Biological Process	GO:0001959 regulation of cytokine-mediated signaling pathway GO:0016579 protein deubiquitination GO:0034340 response to type I interferon GO:0045088 regulation of innate immune response GO:0060337 type I interferon signaling pathway GO:0060338 regulation of type I interferon-mediated signaling pathway GO:0060759 regulation of response to cytokine stimulus GO:0070646 protein modification by small protein removal GO:0071357 cellular response to type I interferon
Molecular Function	GO:0004843 thiol-dependent ubiquitin-specific protease activity GO:0008234 cysteine-type peptidase activity GO:0019783 ubiquitin-like protein-specific protease activity GO:0019785 ISG15-specific protease activity GO:0036459 thiol-dependent ubiquitinyl hydrolase activity GO:0101005 ubiquitinyl hydrolase activity
Cellular Component	-

> KEGG and Reactome Pathway [ TOP ]
KEGG	-
Reactome	R-HSA-1169410: Antiviral mechanism by IFN-stimulated genes R-HSA-1280215: Cytokine Signaling in Immune system R-HSA-5688426: Deubiquitination R-HSA-1169408: ISG15 antiviral mechanism R-HSA-168256: Immune System R-HSA-913531: Interferon Signaling R-HSA-909733: Interferon alpha/beta signaling R-HSA-392499: Metabolism of proteins R-HSA-597592: Post-translational protein modification R-HSA-912694: Regulation of IFNA signaling R-HSA-5689880: Ub-specific processing proteases

> KEGG and Reactome Pathway

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KEGG

Reactome

R-HSA-1169410: Antiviral mechanism by IFN-stimulated genes
R-HSA-1280215: Cytokine Signaling in Immune system
R-HSA-5688426: Deubiquitination
R-HSA-1169408: ISG15 antiviral mechanism
R-HSA-168256: Immune System
R-HSA-913531: Interferon Signaling
R-HSA-909733: Interferon alpha/beta signaling
R-HSA-392499: Metabolism of proteins
R-HSA-597592: Post-translational protein modification
R-HSA-912694: Regulation of IFNA signaling
R-HSA-5689880: Ub-specific processing proteases

Summary
Symbol	USP18
Name	ubiquitin specific peptidase 18
Aliases	ubiquitin specific protease 18; ISG43; UBP43; 43 kDa ISG15-specific protease; ISG15-specific-processing prot ......
Chromosomal Location	22q11.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between USP18 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

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Literatures describing the relation between USP18 and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
17374743	Myeloid Leukemia	Promote immunity	Ubp43 is an ISG15-specific isopeptidase, the expression of which is activated by IFN. Ubp43 deficiency increases the resistance to oncogenic transformation by BCR-ABL. This resistance to leukemic development is dependent on type 1 IFN (IFN-alpha/beta) signaling in Ubp43-deficient cells. These results suggest that inhibition of Ubp43-negative effect on IFN signaling can potentiate the response to increased endogenous IFN levels in innate immune responses against cancer development, indicating that pharmacological inhibition of Ubp43 may be of benefit in cancers and others diseases in which interferon is currently prescribed.
24884733	melanoma	Promote immunity (T cell function); increase the efficacy of immunotherapy	USP18 expression in B16 melanoma tumor cells regulated IFN-γ-mediated immunoediting, including upregulating MHC class-I expression, reducing tumor cell-mediated inhibition of T cell proliferation and activation, and suppressing PD-1 expression in CD4+ and CD8+ T cells in tumor-bearing mice.

Summary
Symbol	USP18
Name	ubiquitin specific peptidase 18
Aliases	ubiquitin specific protease 18; ISG43; UBP43; 43 kDa ISG15-specific protease; ISG15-specific-processing prot ......
Chromosomal Location	22q11.2
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 USP18 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	logFC: -3.28; FDR: 0.00433	Resistant to T cell-mediated killing
29301958	CRISPR-Cas9	melanoma	B16F10	OT-1 T cell	logFC: -2.95; FDR: 0.01650	Resistant to T cell-mediated killing
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	USP18
Name	ubiquitin specific peptidase 18
Aliases	ubiquitin specific protease 18; ISG43; UBP43; 43 kDa ISG15-specific protease; ISG15-specific-processing prot ......
Chromosomal Location	22q11.2
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 USP18 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	-0.521	0.189
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.157	0.917
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.792	0.51
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.572	0.207
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0.679	0.623
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.443	0.814
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.229	0.596
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.663	0.582
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	-0.277	0.839
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.49	0.63
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	0.201	0.896
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	0.168	0.222

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of USP18 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	7.4	0	7.4	0.0709
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	7.4	0	7.4	0.096
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	0	0	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	0	0	0	1
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	0	0	1
16	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	11	13	0	7.7	-7.7	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	8.3	-8.3	1

Summary
Symbol	USP18
Name	ubiquitin specific peptidase 18
Aliases	ubiquitin specific protease 18; ISG43; UBP43; 43 kDa ISG15-specific protease; ISG15-specific-processing prot ......
Chromosomal Location	22q11.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of USP18. 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	USP18
Name	ubiquitin specific peptidase 18
Aliases	ubiquitin specific protease 18; ISG43; UBP43; 43 kDa ISG15-specific protease; ISG15-specific-processing prot ......
Chromosomal Location	22q11.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of USP18. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by USP18. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	USP18
Name	ubiquitin specific peptidase 18
Aliases	ubiquitin specific protease 18; ISG43; UBP43; 43 kDa ISG15-specific protease; ISG15-specific-processing prot ......
Chromosomal Location	22q11.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of USP18. 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	USP18
Name	ubiquitin specific peptidase 18
Aliases	ubiquitin specific protease 18; ISG43; UBP43; 43 kDa ISG15-specific protease; ISG15-specific-processing prot ......
Chromosomal Location	22q11.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of USP18 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	USP18
Name	ubiquitin specific peptidase 18
Aliases	ubiquitin specific protease 18; ISG43; UBP43; 43 kDa ISG15-specific protease; ISG15-specific-processing prot ......
Chromosomal Location	22q11.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between USP18 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	USP18
Name	ubiquitin specific peptidase 18
Aliases	ubiquitin specific protease 18; ISG43; UBP43; 43 kDa ISG15-specific protease; ISG15-specific-processing prot ......
Chromosomal Location	22q11.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting USP18 collected from DrugBank database.

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

Browse USP18