Browse USP15

Summary
SymbolUSP15
Nameubiquitin specific peptidase 15
Aliases KIAA0529; UNPH4; ubiquitin specific protease 15; UNPH-2; deubiquitinating enzyme 15; ubiquitin thioesterase ......
Chromosomal Location12q14
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
 
Subcellular Location Cytoplasm Nucleus Mitochondrion
Domain PF06337 DUSP domain
PF14836 Ubiquitin-like domain
PF00443 Ubiquitin carboxyl-terminal hydrolase
PF14533 Ubiquitin-specific protease C-terminal
Function

Hydrolase that removes conjugated ubiquitin from target proteins and regulates various pathways such as the TGF-beta receptor signaling, NF-kappa-B and RNF41/NRDP1-PRKN pathways (PubMed:21947082, PubMed:22344298, PubMed:24852371, PubMed:16005295, PubMed:17318178, PubMed:19826004, PubMed:19576224). Acts as a key regulator of TGF-beta receptor signaling pathway, but the precise mechanism is still unclear: according to a report, acts by promoting deubiquitination of monoubiquitinated R-SMADs (SMAD1, SMAD2 and/or SMAD3), thereby alleviating inhibition of R-SMADs and promoting activation of TGF-beta target genes (PubMed:21947082). According to another reports, regulates the TGF-beta receptor signaling pathway by mediating deubiquitination and stabilization of TGFBR1, leading to an enhanced TGF-beta signal (PubMed:22344298). Able to mediate deubiquitination of monoubiquitinated substrates as well as 'Lys-48'-linked polyubiquitin chains, protecting them against proteasomal degradation. May also regulate gene expression and/or DNA repair through the deubiquitination of histone H2B (PubMed:24526689). Acts as an inhibitor of mitophagy by counteracting the action of parkin (PRKN): hydrolyzes cleavage of 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains attached by parkin on target proteins such as MFN2, thereby reducing parkin's ability to drive mitophagy (PubMed:24852371). Acts as an associated component of COP9 signalosome complex (CSN) and regulates different pathways via this association: regulates NF-kappa-B by mediating deubiquitination of NFKBIA and deubiquitinates substrates bound to VCP (PubMed:16005295, PubMed:17318178, PubMed:19826004, PubMed:19576224). Involved in endosome organization by mediating deubiquitination of SQSTM1: ubiquitinated SQSTM1 forms a molecular bridge that restrains cognate vesicles in the perinuclear region and its deubiquitination releases target vesicles for fast transport into the cell periphery (PubMed:27368102). ; FUNCTION: (Microbial infection) Protects APC and human papillomavirus type 16 protein E6 against degradation via the ubiquitin proteasome pathway.

> Gene Ontology
 
Biological Process GO:0007178 transmembrane receptor protein serine/threonine kinase signaling pathway
GO:0007179 transforming growth factor beta receptor signaling pathway
GO:0016570 histone modification
GO:0016578 histone deubiquitination
GO:0016579 protein deubiquitination
GO:0030509 BMP signaling pathway
GO:0035520 monoubiquitinated protein deubiquitination
GO:0035616 histone H2B conserved C-terminal lysine deubiquitination
GO:0060389 pathway-restricted SMAD protein phosphorylation
GO:0070646 protein modification by small protein removal
GO:0071559 response to transforming growth factor beta
GO:0071560 cellular response to transforming growth factor beta stimulus
GO:0071772 response to BMP
GO:0071773 cellular response to BMP stimulus
Molecular Function GO:0004175 endopeptidase activity
GO:0004197 cysteine-type endopeptidase activity
GO:0004843 thiol-dependent ubiquitin-specific protease activity
GO:0005126 cytokine receptor binding
GO:0005160 transforming growth factor beta receptor binding
GO:0008234 cysteine-type peptidase activity
GO:0019783 ubiquitin-like protein-specific protease activity
GO:0036459 thiol-dependent ubiquitinyl hydrolase activity
GO:0042393 histone binding
GO:0046332 SMAD binding
GO:0061649 ubiquitinated histone binding
GO:0101005 ubiquitinyl hydrolase activity
Cellular Component -
> KEGG and Reactome Pathway
 
KEGG -
Reactome R-HSA-5688426: Deubiquitination
R-HSA-2173788: Downregulation of TGF-beta receptor signaling
R-HSA-392499: Metabolism of proteins
R-HSA-597592: Post-translational protein modification
R-HSA-162582: Signal Transduction
R-HSA-170834: Signaling by TGF-beta Receptor Complex
R-HSA-2173789: TGF-beta receptor signaling activates SMADs
R-HSA-5689603: UCH proteinases
R-HSA-5689880: Ub-specific processing proteases
Summary
SymbolUSP15
Nameubiquitin specific peptidase 15
Aliases KIAA0529; UNPH4; ubiquitin specific protease 15; UNPH-2; deubiquitinating enzyme 15; ubiquitin thioesterase ......
Chromosomal Location12q14
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between USP15 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
 
  Literatures describing the relation between USP15 and anti-tumor immunity in human cancer.
PMID Cancer type Relation to immunity Evidence sentences
24777531Melanoma; Colon CarcinomaInhibit immunity (T cell function)Here we identified the DUB USP15 as a crucial negative regulator of T cell activation. USP15 stabilized the E3 ubiquitin ligase MDM2, which in turn negatively regulated T cell activation by targeting the degradation of the transcription factor NFATc2. USP15 deficiency promoted T cell activation in vitro and enhanced T cell responses to bacterial infection and tumor challenge in vivo. USP15 also stabilized MDM2 in cancer cells and regulated p53 function and cancer-cell survival.
Summary
SymbolUSP15
Nameubiquitin specific peptidase 15
Aliases KIAA0529; UNPH4; ubiquitin specific protease 15; UNPH-2; deubiquitinating enzyme 15; ubiquitin thioesterase ......
Chromosomal Location12q14
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
  Statistical results of USP15 in screening data sets for detecting immune reponses.
PMID Screening System Cancer Type Cell Line Data Set Statistical Results Relation to immunity
29301958CRISPR-Cas9 melanomaB16F10Pmel-1 T cell NA/NSNA/NS
29301958CRISPR-Cas9 melanomaB16F10OT-1 T cell NA/NSNA/NS
28783722CRISPR-Cas9 melanomaMel6242CT-CRISPR NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX+Anti-PD1 NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX NA/NSNA/NS
25691366RNAiBreast cancerMCF7Luc-CTL assay NA/NSNA/NS
24476824shRNAmelanomaB16Primary screen NA/NSNA/NS
24476824shRNAmelanomaB16Secondary screen NA/NSNA/NS
Summary
SymbolUSP15
Nameubiquitin specific peptidase 15
Aliases KIAA0529; UNPH4; ubiquitin specific protease 15; UNPH-2; deubiquitinating enzyme 15; ubiquitin thioesterase ......
Chromosomal Location12q14
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
 
Points in the above scatter plot represent the expression difference of USP15 in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)1412-0.0520.86
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)65-0.0080.996
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)87-0.0750.94
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 916-0.2760.401
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59-0.4030.862
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 47-0.1180.967
729033130MelanomaallAnti-PD-1 (nivolumab) 26230.0350.93
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 15110.1120.948
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 1112-0.0220.99
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 480.490.732
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 280.5810.79
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 682300.0140.801
> Mutation difference between responders and non-responders
 
Points in the above scatter plot represent the mutation difference of USP15 in various data sets.
No PMID Cancer type Group Drug # Res # NRes % Mut/Res % Mut/NRes % Diff (R vs NR) Pval Anno
125765070Non-small cell lung cancer (NSCLC)allAnti-PD-1 (pembrolizumab) 14170001
225765070Non-small cell lung cancer (NSCLC)smokingAnti-PD-1 (pembrolizumab) 1030001
325765070Non-small cell lung cancer (NSCLC)non-smokingAnti-PD-1 (pembrolizumab) 4140001
426359337MelanomaallAnti-CTLA-4 (ipilimumab) 27733.71.42.30.469
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 0140001
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 27593.71.720.532
726997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)21179.509.50.492
826997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)8612.5012.51
926997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)13117.707.71
1028552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 91606.2-6.21
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59011.1-11.11
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470001
1329033130MelanomaallAnti-PD-1 (nivolumab) 38270001
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 22130001
1529033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 16140001
1629301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 11130001
1729301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 610001
1829301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 5120001
Summary
SymbolUSP15
Nameubiquitin specific peptidase 15
Aliases KIAA0529; UNPH4; ubiquitin specific protease 15; UNPH-2; deubiquitinating enzyme 15; ubiquitin thioesterase ......
Chromosomal Location12q14
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of USP15. 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
 
Summary
SymbolUSP15
Nameubiquitin specific peptidase 15
Aliases KIAA0529; UNPH4; ubiquitin specific protease 15; UNPH-2; deubiquitinating enzyme 15; ubiquitin thioesterase ......
Chromosomal Location12q14
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of USP15. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by USP15.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolUSP15
Nameubiquitin specific peptidase 15
Aliases KIAA0529; UNPH4; ubiquitin specific protease 15; UNPH-2; deubiquitinating enzyme 15; ubiquitin thioesterase ......
Chromosomal Location12q14
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of USP15. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolUSP15
Nameubiquitin specific peptidase 15
Aliases KIAA0529; UNPH4; ubiquitin specific protease 15; UNPH-2; deubiquitinating enzyme 15; ubiquitin thioesterase ......
Chromosomal Location12q14
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of USP15 expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolUSP15
Nameubiquitin specific peptidase 15
Aliases KIAA0529; UNPH4; ubiquitin specific protease 15; UNPH-2; deubiquitinating enzyme 15; ubiquitin thioesterase ......
Chromosomal Location12q14
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between USP15 and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolUSP15
Nameubiquitin specific peptidase 15
Aliases KIAA0529; UNPH4; ubiquitin specific protease 15; UNPH-2; deubiquitinating enzyme 15; ubiquitin thioesterase ......
Chromosomal Location12q14
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting USP15 collected from DrugBank database.
> Drugs from DrugBank database
 

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