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

    Gene ID: 9958, updated on 10-Dec-2024

    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; 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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    Genomic context

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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 homolog, regulator of endosome-to-Golgi trafficking Neighboring gene RNA, U6 small nuclear 399, pseudogene

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Bibliography

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    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 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. Structural and Functional Characterization of Ubiquitin Variant Inhibitors of USP15. Teyra J, et al. Structure, 2019 Apr 2. PMID 30713027

    See all (216) 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)

    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

    EBI GWAS Catalog

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

    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
    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 cysteine-type deubiquitinase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables cysteine-type deubiquitinase activity TAS
    Traceable Author Statement
    more info
    		  
    enables cysteine-type endopeptidase activity IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    enables deubiquitinase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables identical protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    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 
    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 TAS
    Traceable Author Statement
    more info
    		  
    involved_in proteolysis IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in 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 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 

    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
      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

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

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