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USP15 ubiquitin specific peptidase 15 [ Homo sapiens (human) ]

Gene ID: 9958, updated on 21-Dec-2019

Summary

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Official Symbol
USP15provided by HGNC
Official Full Name
ubiquitin specific peptidase 15provided by HGNC
Primary source
HGNC:HGNC:12613
See related
Ensembl:ENSG00000135655 MIM:604731
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
UNPH4; UNPH-2
Summary
This gene encodes a member of the ubiquitin specific protease (USP) family of deubiquitinating enzymes. USP enzymes play critical roles in ubiquitin-dependent processes through polyubiquitin chain disassembly and hydrolysis of ubiquitin-substrate bonds. The encoded protein associates with the COP9 signalosome, and also plays a role in transforming growth factor beta signalling through deubiquitination of receptor-activated SMAD transcription factors. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene, and a pseudogene of this gene is located on the long arm of chromosome 2. [provided by RefSeq, Nov 2011]
Expression
Ubiquitous expression in bone marrow (RPKM 16.1), appendix (RPKM 8.0) and 24 other tissues See more
Orthologs
mouse all

Genomic context

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See USP15 in Genome Data Viewer
Location:
12q14.1
Exon count:
27
Annotation release Status Assembly Chr Location
109.20191205 current GRCh38.p13 (GCF_000001405.39) 12 NC_000012.12 (62260340..62416389)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 12 NC_000012.11 (62654121..62803501)

Chromosome 12 - NC_000012.12Genomic Context describing neighboring genes Neighboring gene TAFA chemokine like family member 2 Neighboring gene ribosomal protein S3 pseudogene 6 Neighboring gene Kruppel like factor 17 pseudogene 1 Neighboring gene microRNA 6125 Neighboring gene RNA, U6 small nuclear 595, pseudogene Neighboring gene MON2 homolog, regulator of endosome-to-Golgi trafficking Neighboring gene RNA, U6 small nuclear 399, pseudogene Neighboring gene long intergenic non-protein coding RNA 1465

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. USP15 Participates in Hepatitis C Virus Propagation through Regulation of Viral RNA Translation and Lipid Droplet Formation. Kusakabe S, et al. J Virol, 2019 Mar 15. PMID 30626683, Free PMC Article
  2. Deubiquitylation of hepatitis B virus X protein (HBx) by ubiquitin-specific peptidase 15 (USP15) increases HBx stability and its transactivation activity. Su ZJ, et al. Sci Rep, 2017 Jan 11. PMID 28074857, Free PMC Article
  3. The deubiquitylase USP15 stabilizes newly synthesized REST and rescues its expression at mitotic exit. Faronato M, et al. Cell Cycle, 2013 Jun 15. PMID 23708518, Free PMC Article
  4. Structure of the USP15 N-terminal domains: a β-hairpin mediates close association between the DUSP and UBL domains. Harper S, et al. Biochemistry, 2011 Sep 20. PMID 21848306
  5. USP15 plays an essential role for caspase-3 activation during Paclitaxel-induced apoptosis. Xu M, et al. Biochem Biophys Res Commun, 2009 Oct 16. PMID 19665996

See all (119) citations in PubMed

See citations in PubMed for homologs of this gene provided by HomoloGene

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. USP15 participates in HCV propagation in hepatic cells.
    Title: USP15 Participates in Hepatitis C Virus Propagation through Regulation of Viral RNA Translation and Lipid Droplet Formation.
  2. Study reports that USP15 affects cancer cell response to PARP inhibitors by regulating homologous recombination repair. USP15 is recruited to DNA double-strand breaks (DSBs) by MDC1. USP15 deubiquitinates BARD1 BRCT domain, and promotes BARD1-HP1gamma interaction, resulting in BRCA1/BARD1 retention at DSBs. Cancer-associated USP15 mutations, with decreased USP15-BARD1 interaction, increases PARP inhibitor sensitivity.
    Title: The deubiquitylating enzyme USP15 regulates homologous recombination repair and cancer cell response to PARP inhibitors.
  3. First example of isoform-specific deubiquitylase phospho-regulation and a novel role for USP15 in guarding genome integrity. USP15 is required for TOP2A accumulation, and USP15 depletion leads to the formation of anaphase chromosome bridges.
    Title: The deubiquitylase USP15 regulates topoisomerase II alpha to maintain genome integrity.
  4. a USP15-dependent lysosomal pathway controls p53-R175H turnover in ovarian cancer cells
    Title: USP15-dependent lysosomal pathway controls p53-R175H turnover in ovarian cancer cells.
  5. USP15 could increase the level of HPV16 E6 by inhibiting E6 degradation.
    Title: USP15 inhibits HPV16 E6 degradation and catalytically inactive USP15 has reduced inhibitory activity.
  6. Data indicate that mysterin/RNF213 is a substrate of ubiquitin specific protease 15 (USP15), and that the conserved skipping of exon 7 significantly decreases its specific affinity for mysterin.
    Title: Alternative exon skipping biases substrate preference of the deubiquitylase USP15 for mysterin/RNF213, the moyamoya disease susceptibility factor.
  7. Deubiquitylation of hepatitis B virus X protein (HBx) by ubiquitin-specific peptidase 15 (USP15) increases HBx stability and its transactivation activity. These results suggest that USP15 plays an essential role in stabilizing HBx and subsequently affects the biological function of HBx.
    Title: Deubiquitylation of hepatitis B virus X protein (HBx) by ubiquitin-specific peptidase 15 (USP15) increases HBx stability and its transactivation activity.
  8. HPV E6 oncoprotein antagonizes the activation of the cytoplasmic innate immune sensor RIG-I by targeting its upstream regulatory enzymes TRIM25 and USP15. We further show that the RIG-I signaling cascade is important for an antiviral innate immune response to HPV16 infection
    Title: The Human Papillomavirus E6 Oncoprotein Targets USP15 and TRIM25 To Suppress RIG-I-Mediated Innate Immune Signaling.
  9. these data indicate that Nef and USP15 are vital in regulating degradation of viral and cellular proteins and thus HIV-1 replication, and specific degradation of viral, not cellular proteins.
    Title: Function of ubiquitin (Ub) specific protease 15 (USP15) in HIV-1 replication and viral protein degradation.
  10. We show that PRP31, a component of U4 snRNP, is modified with K63-linked ubiquitin chains by the PRP19 complex and deubiquitinated by USP15 and its substrate targeting factor SART3. USP15SART3 makes a complex with USP4 and this ternary complex serves as a platform to deubiquitinate PRP31 and PRP3
    Title: USP15 regulates dynamic protein-protein interactions of the spliceosome through deubiquitination of PRP31.
Submit: New GeneRIF Correction See all GeneRIFs (36)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

NHGRI GWAS Catalog

Description
Genome-wide association study of lung function decline in adults with and without asthma.
NHGRI GWA Catalog

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Clone Names

  • FLJ55073, KIAA0529, MGC74854, MGC131982, MGC149838

Gene Ontology Provided by GOA

Function Evidence Code Pubs
SMAD binding IPI
Inferred from Physical Interaction
more info
 PubMed 
cysteine-type endopeptidase activity IMP
Inferred from Mutant Phenotype
more info
 PubMed 
identical protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
thiol-dependent ubiquitin-specific protease activity IDA
Inferred from Direct Assay
more info
 PubMed 
thiol-dependent ubiquitinyl hydrolase activity IDA
Inferred from Direct Assay
more info
 PubMed 
thiol-dependent ubiquitinyl hydrolase activity TAS
Traceable Author Statement
more info
  
transforming growth factor beta receptor binding IPI
Inferred from Physical Interaction
more info
 PubMed 
ubiquitin modification-dependent histone binding IDA
Inferred from Direct Assay
more info
 PubMed 
Process Evidence Code Pubs
BMP signaling pathway IDA
Inferred from Direct Assay
more info
 PubMed 
histone H2B conserved C-terminal lysine deubiquitination IDA
Inferred from Direct Assay
more info
 PubMed 
monoubiquitinated protein deubiquitination IDA
Inferred from Direct Assay
more info
 PubMed 
pathway-restricted SMAD protein phosphorylation IMP
Inferred from Mutant Phenotype
more info
 PubMed 
protein deubiquitination IDA
Inferred from Direct Assay
more info
 PubMed 
protein deubiquitination TAS
Traceable Author Statement
more info
  
transforming growth factor beta receptor signaling pathway IDA
Inferred from Direct Assay
more info
 PubMed 
transforming growth factor beta receptor signaling pathway IMP
Inferred from Mutant Phenotype
more info
 PubMed 
ubiquitin-dependent protein catabolic process IEA
Inferred from Electronic Annotation
more info
  
Component Evidence Code Pubs
cytoplasm IDA
Inferred from Direct Assay
more info
 PubMed 
cytosol IDA
Inferred from Direct Assay
more info
  
cytosol TAS
Traceable Author Statement
more info
  
mitochondrion IEA
Inferred from Electronic Annotation
more info
  
nucleus IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
nucleus IDA
Inferred from Direct Assay
more info
 PubMed 

General protein information

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Preferred Names
ubiquitin carboxyl-terminal hydrolase 15
Names
deubiquitinating enzyme 15
ubiquitin thioesterase 15
ubiquitin thiolesterase 15
ubiquitin-specific-processing protease 15
NP_001239007.1
NP_001239008.1
NP_001338088.1
NP_001338089.1
NP_001338090.1
NP_001338091.1
NP_001338092.1
NP_001338093.1
NP_001338094.1
NP_001338095.1
NP_006304.1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

  1. NM_001252078.2 → NP_001239007.1  ubiquitin carboxyl-terminal hydrolase 15 isoform 1

    See identical proteins and their annotated locations for NP_001239007.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) encodes the longest isoform (1).
    Source sequence(s)
    AC079035, AF153604
    Consensus CDS
    CCDS58251.1
    UniProtKB/Swiss-Prot
    Q9Y4E8
    Related
    ENSP00000280377.5, ENST00000280377.10
    Conserved Domains (1) summary
    cl02553
    Location:12 → 932
    Peptidase_C19; Peptidase C19 contains ubiquitinyl hydrolases. They are intracellular peptidases that remove ubiquitin molecules from polyubiquinated peptides by cleavage of isopeptide bonds. They hydrolyse bonds involving the carboxyl group of the C-terminal Gly ...

  2. NM_001252079.1 → NP_001239008.1  ubiquitin carboxyl-terminal hydrolase 15 isoform 3

    See identical proteins and their annotated locations for NP_001239008.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) differs in the 3' UTR and lacks a large portion of the 3' coding region, compared to variant 1. The encoded isoform (3) is shorter and has a distinct C-terminus, compared to isoform 1.
    Source sequence(s)
    AI027693, BC063454, DB451322
    Consensus CDS
    CCDS58250.1
    UniProtKB/Swiss-Prot
    Q9Y4E8
    Related
    ENSP00000309240.6, ENST00000312635.10
    Conserved Domains (2) summary
    smart00695
    Location:24 → 121
    DUSP; Domain in ubiquitin-specific proteases
    pfam14836
    Location:135 → 222
    Ubiquitin_3; Ubiquitin-like domain

  3. NM_001351159.2 → NP_001338088.1  ubiquitin carboxyl-terminal hydrolase 15 isoform 4

    Status: REVIEWED

    Source sequence(s)
    AC048342, AC079035, AC117370
    Conserved Domains (2) summary
    pfam14836
    Location:14 → 101
    Ubiquitin_3; Ubiquitin-like domain
    cl02553
    Location:162 → 811
    Peptidase_C19; Peptidase C19 contains ubiquitinyl hydrolases. They are intracellular peptidases that remove ubiquitin molecules from polyubiquinated peptides by cleavage of isopeptide bonds. They hydrolyse bonds involving the carboxyl group of the C-terminal Gly ...

  4. NM_001351160.2 → NP_001338089.1  ubiquitin carboxyl-terminal hydrolase 15 isoform 5

    Status: REVIEWED

    Source sequence(s)
    AC048342, AC079035, AC117370
    Conserved Domains (1) summary
    COG5560
    Location:34 → 683
    UBP12; Ubiquitin C-terminal hydrolase [Posttranslational modification, protein turnover, chaperones]

  5. NM_001351161.2 → NP_001338090.1  ubiquitin carboxyl-terminal hydrolase 15 isoform 6

    Status: REVIEWED

    Source sequence(s)
    AC048342, AC079035, AC117370
    Conserved Domains (1) summary
    smart00695
    Location:24 → 116
    DUSP; Domain in ubiquitin-specific proteases

  6. NM_001351162.1 → NP_001338091.1  ubiquitin carboxyl-terminal hydrolase 15 isoform 7

    Status: REVIEWED

    Source sequence(s)
    AC048342, AC117370
    Conserved Domains (1) summary
    pfam06337
    Location:27 → 75
    DUSP; DUSP domain

  7. NM_001351163.2 → NP_001338092.1  ubiquitin carboxyl-terminal hydrolase 15 isoform 8

    Status: REVIEWED

    Description
    Transcript Variant: This variant (8), as well as variants 9-11, encodes isoform 8.
    Source sequence(s)
    AC048342, AC079035, AC117370
    Conserved Domains (1) summary
    COG5560
    Location:1 → 599
    UBP12; Ubiquitin C-terminal hydrolase [Posttranslational modification, protein turnover, chaperones]

  8. NM_001351164.2 → NP_001338093.1  ubiquitin carboxyl-terminal hydrolase 15 isoform 8

    Status: REVIEWED

    Description
    Transcript Variant: This variant (9), as well as variants 8, 10, and 11, encodes isoform 8.
    Source sequence(s)
    AC048342, AC079035, AC117370
    Conserved Domains (1) summary
    COG5560
    Location:1 → 599
    UBP12; Ubiquitin C-terminal hydrolase [Posttranslational modification, protein turnover, chaperones]

  9. NM_001351165.2 → NP_001338094.1  ubiquitin carboxyl-terminal hydrolase 15 isoform 8

    Status: REVIEWED

    Description
    Transcript Variant: This variant (10), as well as variants 8, 9, and 11, encodes isoform 8.
    Source sequence(s)
    AC048342, AC079035, AC117370
    Conserved Domains (1) summary
    COG5560
    Location:1 → 599
    UBP12; Ubiquitin C-terminal hydrolase [Posttranslational modification, protein turnover, chaperones]

  10. NM_001351166.2 → NP_001338095.1  ubiquitin carboxyl-terminal hydrolase 15 isoform 8

    Status: REVIEWED

    Description
    Transcript Variant: This variant (11), as well as variants 8-10, encodes isoform 8.
    Source sequence(s)
    AC048342, AC079035, AC117370
    Conserved Domains (1) summary
    COG5560
    Location:1 → 599
    UBP12; Ubiquitin C-terminal hydrolase [Posttranslational modification, protein turnover, chaperones]

  11. NM_006313.3 → NP_006304.1  ubiquitin carboxyl-terminal hydrolase 15 isoform 2

    See identical proteins and their annotated locations for NP_006304.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) lacks an exon in the coding region, but maintains the reading frame, compared to variant 1. The encoded isoform (2) is shorter than isoform 1.
    Source sequence(s)
    AC079035, AF106069, BC125123, DB451322
    Consensus CDS
    CCDS8963.1
    UniProtKB/Swiss-Prot
    Q9Y4E8
    Related
    ENSP00000258123.4, ENST00000353364.7
    Conserved Domains (1) summary
    cl02553
    Location:12 → 903
    Peptidase_C19; Peptidase C19 contains ubiquitinyl hydrolases. They are intracellular peptidases that remove ubiquitin molecules from polyubiquinated peptides by cleavage of isopeptide bonds. They hydrolyse bonds involving the carboxyl group of the C-terminal Gly ...

RNA

  1. NR_147078.2 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AC048342, AC079035, AC117370

  2. NR_147079.2 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AC048342, AC079035, AC117370

  3. NR_147080.2 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AC048342, AC079035, AC117370

  4. NR_147081.2 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AC048342, AC079035, AC117370

  5. NR_147082.2 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AC048342, AC079035, AC117370

RefSeqs of Annotated Genomes: Homo sapiens Updated Annotation Release 109.20191205

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p13 Primary Assembly

Genomic

  1. NC_000012.12 Reference GRCh38.p13 Primary Assembly

    Range
    62260340..62416389
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q9Y4E8.3 GenPept UniProtKB/Swiss-Prot:Q9Y4E8

Gene LinkOut

The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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