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

Gene ID: 9958, updated on 5-Jul-2025
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; AllianceGenome:HGNC:12613
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
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See USP15 in Genome Data Viewer
Location:
12q14.1
Exon count:
27
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 12 NC_000012.12 (62260404..62416389)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 12 NC_060936.1 (62239218..62395185)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 12 NC_000012.11 (62654185..62810169)

Chromosome 12 - NC_000012.12Genomic Context describing neighboring genes Neighboring gene TAFA chemokine like family member 2 Neighboring gene uncharacterized LOC124902950 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:62585946-62586479 Neighboring gene Sharpr-MPRA regulatory region 3206 Neighboring gene ReSE screen-validated silencer GRCh37_chr12:62626842-62627014 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6576 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4604 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4605 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6577 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6578 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:62655915-62656415 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:62655414-62655914 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6579 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6580 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4606 Neighboring gene Kruppel like factor 17 pseudogene 1 Neighboring gene microRNA 6125 Neighboring gene MPRA-validated peak1750 silencer Neighboring gene RNA, U6 small nuclear 595, pseudogene Neighboring gene Sharpr-MPRA regulatory region 15489 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:62828889-62829698 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4607 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6581 Neighboring gene H3K27ac hESC enhancer GRCh37_chr12:62860763-62861262 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:62862931-62863431 Neighboring gene MON2 antisense RNA 1 Neighboring gene MON2 regulator of endosome-to-Golgi trafficking Neighboring gene RNA, U6 small nuclear 399, pseudogene

Go to nucleotide: Graphics FASTA GenBank

  • Project title: Tissue-specific circular RNA induction during human fetal development
  • Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
  • BioProject: PRJNA270632
  • Publication: PMID 26076956
  • Analysis date: Mon Apr 2 22:54:59 2018

Related articles in PubMed

  1. Ubiquitin-specific peptidase 15 regulates the TFAP4/PCGF1 axis facilitating liver metastasis of colorectal cancer and cell stemness. Yin H, et al. Biochem Pharmacol, 2024 Aug. PMID 38801926
  2. USP15 facilitates the progression of bladder cancer by amplifying the activation of the NF-κB signaling pathway. Li Y, et al. Aging (Albany NY), 2024 Mar 28. PMID 38656882, Free PMC Article
  3. The deubiquitinase USP15 modulates cellular redox and is a therapeutic target in acute myeloid leukemia. Niederkorn M, et al. Leukemia, 2022 Feb. PMID 34465865, Free PMC Article
  4. Ubiquitin-specific protease 15 contributes to gastric cancer progression by regulating the Wnt/β-catenin signaling pathway. Zhong M, et al. World J Gastroenterol, 2021 Jul 14. PMID 34326621, Free PMC Article
  5. 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

See all (222) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Ubiquitin-specific peptidase 15 regulates the TFAP4/PCGF1 axis facilitating liver metastasis of colorectal cancer and cell stemness.
    Title: Ubiquitin-specific peptidase 15 regulates the TFAP4/PCGF1 axis facilitating liver metastasis of colorectal cancer and cell stemness.
  2. In vivo CRISPR screens reveal SCAF1 and USP15 as drivers of pancreatic cancer.
    Title: In vivo CRISPR screens reveal SCAF1 and USP15 as drivers of pancreatic cancer.
  3. USP15 facilitates the progression of bladder cancer by amplifying the activation of the NF-kappaB signaling pathway.
    Title: USP15 facilitates the progression of bladder cancer by amplifying the activation of the NF-κB signaling pathway.
  4. ACVRL1 drives resistance to multitarget tyrosine kinase inhibitors in colorectal cancer by promoting USP15-mediated GPX2 stabilization.
    Title: ACVRL1 drives resistance to multitarget tyrosine kinase inhibitors in colorectal cancer by promoting USP15-mediated GPX2 stabilization.
  5. USP15-USP7 Axis and UBE2T Differential Expression May Predict Pathogenesis and Poor Prognosis in De Novo Myelodysplastic Neoplasm.
    Title: USP15-USP7 Axis and UBE2T Differential Expression May Predict Pathogenesis and Poor Prognosis in De Novo Myelodysplastic Neoplasm.
  6. Loss of the receptors ER, PR and HER2 promotes USP15-dependent stabilization of PARP1 in triple-negative breast cancer.
    Title: Loss of the receptors ER, PR and HER2 promotes USP15-dependent stabilization of PARP1 in triple-negative breast cancer.
  7. Over-expression of USP15/MMP3 predict poor prognosis and promote growth, migration in non-small cell lung cancer cells.
    Title: Over-expression of USP15/MMP3 predict poor prognosis and promote growth, migration in non-small cell lung cancer cells.
  8. USP15 negatively regulates lung cancer progression through the TRAF6-BECN1 signaling axis for autophagy induction.
    Title: USP15 negatively regulates lung cancer progression through the TRAF6-BECN1 signaling axis for autophagy induction.
  9. The deubiquitinase USP15 modulates cellular redox and is a therapeutic target in acute myeloid leukemia.
    Title: The deubiquitinase USP15 modulates cellular redox and is a therapeutic target in acute myeloid leukemia.
  10. USP15 Enhances the Proliferation, Migration, and Collagen Deposition of Hypertrophic Scar-Derived Fibroblasts by Deubiquitinating TGF-betaR1 In Vitro.
    Title: USP15 Enhances the Proliferation, Migration, and Collagen Deposition of Hypertrophic Scar-Derived Fibroblasts by Deubiquitinating TGF-βR1 In Vitro.
Submit: New GeneRIF Correction See all GeneRIFs (59)

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

Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

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

See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Products Interactant Other Gene Complex Source Pubs Description

Markers

Homology

Clone Names

  • FLJ55073, KIAA0529, MGC74854, MGC131982, MGC149838

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables K48-linked deubiquitinase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables SMAD binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables catalytic activity IEA
Inferred from Electronic Annotation
more info
  
enables cysteine-type deubiquitinase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables cysteine-type deubiquitinase activity IEA
Inferred from Electronic Annotation
more info
  
enables cysteine-type deubiquitinase activity TAS
Traceable Author Statement
more info
 PubMed 
enables cysteine-type endopeptidase activity IMP
Inferred from Mutant Phenotype
more info
 PubMed 
enables cysteine-type endopeptidase activity TAS
Traceable Author Statement
more info
 PubMed 
enables cysteine-type peptidase activity IEA
Inferred from Electronic Annotation
more info
  
enables deubiquitinase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables deubiquitinase activity IEA
Inferred from Electronic Annotation
more info
  
enables hydrolase activity IEA
Inferred from Electronic Annotation
more info
  
enables identical protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables peptidase activity IEA
Inferred from Electronic Annotation
more info
  
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables transforming growth factor beta receptor binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables ubiquitin-modified histone reader activity IDA
Inferred from Direct Assay
more info
 PubMed 
Process Evidence Code Pubs
involved_in BMP signaling pathway IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in monoubiquitinated protein deubiquitination IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in negative regulation of antifungal innate immune response IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in negative regulation of transforming growth factor beta receptor signaling pathway IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in positive regulation of RIG-I signaling pathway IDA
Inferred from Direct Assay
more info
 PubMed 
acts_upstream_of_or_within positive regulation of canonical NF-kappaB signal transduction IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in protein K27-linked deubiquitination IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in protein deubiquitination IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in protein deubiquitination IEA
Inferred from Electronic Annotation
more info
  
involved_in protein deubiquitination TAS
Traceable Author Statement
more info
  
involved_in proteolysis IEA
Inferred from Electronic Annotation
more info
  
acts_upstream_of_or_within regulation of RNA metabolic process IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in regulation of RNA metabolic process IDA
Inferred from Direct Assay
more info
 PubMed 
acts_upstream_of_or_within regulation of intrinsic apoptotic signaling pathway in response to osmotic stress by p53 class mediator IEA
Inferred from Electronic Annotation
more info
  
involved_in transcription elongation-coupled chromatin remodeling IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in transcription elongation-coupled chromatin remodeling IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in transforming growth factor beta receptor signaling pathway IDA
Inferred from Direct Assay
more info
 PubMed 
Component Evidence Code Pubs
located_in cytoplasm IDA
Inferred from Direct Assay
more info
 PubMed 
located_in cytoplasm IEA
Inferred from Electronic Annotation
more info
  
located_in cytosol IDA
Inferred from Direct Assay
more info
  
located_in cytosol TAS
Traceable Author Statement
more info
  
located_in mitochondrion IEA
Inferred from Electronic Annotation
more info
  
located_in nuclear body IDA
Inferred from Direct Assay
more info
  
located_in nucleoplasm IDA
Inferred from Direct Assay
more info
  
is_active_in nucleus IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in nucleus IDA
Inferred from Direct Assay
more info
 PubMed 
located_in nucleus IEA
Inferred from Electronic Annotation
more info
  
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

NEW Try the new Transcript table

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
    Q08AL5, Q9H8G9, Q9HCA6, Q9UNP0, Q9Y4E8, Q9Y5B5
    Related
    ENSP00000280377.5, ENST00000280377.10
    Conserved Domains (1) summary
    COG5560
    Location:12 → 932
    UBP12; Ubiquitin C-terminal hydrolase [Posttranslational modification, protein turnover, chaperones]

  2. NM_001252079.2 → 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
    Consensus CDS
    CCDS58250.1
    UniProtKB/TrEMBL
    Q2NL66
    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
    COG5560
    Location:162 → 811
    UBP12; Ubiquitin C-terminal hydrolase [Posttranslational modification, protein turnover, chaperones]
    pfam14836
    Location:14 → 101
    Ubiquitin_3; Ubiquitin-like domain

  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
    UniProtKB/TrEMBL
    B4DN46
    Conserved Domains (1) summary
    smart00695
    Location:24 → 116
    DUSP; Domain in ubiquitin-specific proteases

  6. NM_001351162.2 → 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
    COG5560
    Location:12 → 903
    UBP12; Ubiquitin C-terminal hydrolase [Posttranslational modification, protein turnover, chaperones]

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: GCF_000001405.40-RS_2024_08

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

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000012.12 Reference GRCh38.p14 Primary Assembly

    Range
    62260404..62416389
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060936.1 Alternate T2T-CHM13v2.0

    Range
    62239218..62395185
    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

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