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    USP3 ubiquitin specific peptidase 3 [ Homo sapiens (human) ]

    Gene ID: 9960, updated on 10-Dec-2024

    Summary

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    Official Symbol
    USP3provided by HGNC
    Official Full Name
    ubiquitin specific peptidase 3provided by HGNC
    Primary source
    HGNC:HGNC:12626
    See related
    Ensembl:ENSG00000140455 MIM:604728; AllianceGenome:HGNC:12626
    Gene type
    protein coding
    RefSeq status
    VALIDATED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    UBP; SIH003
    Summary
    Enables deubiquitinase activity and histone binding activity. Involved in DNA repair and DNA repair-dependent chromatin remodeling. Located in several cellular components, including Flemming body; cytoplasmic ribonucleoprotein granule; and nucleoplasm. [provided by Alliance of Genome Resources, Dec 2024]
    Expression
    Ubiquitous expression in bone marrow (RPKM 9.8), spleen (RPKM 5.3) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See USP3 in Genome Data Viewer
    Location:
    15q22.31
    Exon count:
    20
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 15 NC_000015.10 (63504593..63594633)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 15 NC_060939.1 (61311846..61401872)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 15 NC_000015.9 (63796792..63886832)

    Chromosome 15 - NC_000015.10Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC124903506 Neighboring gene uncharacterized LOC124903505 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr15:63630428-63631324 Neighboring gene ReSE screen-validated silencer GRCh37_chr15:63637609-63637796 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_40513 Neighboring gene carbonic anhydrase 12 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr15:63673729-63674249 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr15:63674250-63674769 Neighboring gene long intergenic non-protein coding RNA 2568 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9529 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9530 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9531 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9532 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9533 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9534 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9535 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 6515 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9536 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9537 Neighboring gene NANOG-H3K4me1 hESC enhancer GRCh37_chr15:63795072-63795865 Neighboring gene NANOG-H3K4me1 hESC enhancer GRCh37_chr15:63795866-63796658 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 6519 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 6517 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 6518 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9539 Neighboring gene Sharpr-MPRA regulatory region 15501 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr15:63851884-63852437 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr15:63882664-63883863 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9540 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr15:63892143-63892860 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr15:63893123-63893940 Neighboring gene USP3 antisense RNA 1 Neighboring gene F-box and leucine rich repeat protein 22 Neighboring gene HECT and RLD domain containing E3 ubiquitin protein ligase family member 1 Neighboring gene ReSE screen-validated silencer GRCh37_chr15:63958187-63958357 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr15:64006451-64006952 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr15:64006953-64007452 Neighboring gene ReSE screen-validated silencer GRCh37_chr15:64014173-64014349 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr15:64057331-64058088 Neighboring gene H3K27ac hESC enhancer GRCh37_chr15:64058904-64059404 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 6522 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr15:64107893-64108654 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr15:64114122-64114622 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr15:64125303-64126168

    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. USP3: Key deubiquitylation enzyme in human diseases. Zhang H, et al. Cancer Sci, 2024 Jul. PMID 38651282, Free PMC Article
    2. UCP3 polymorphisms, hand grip performance and survival at old age: association analysis in two Danish middle aged and elderly cohorts. Dato S, et al. Mech Ageing Dev, 2012 Aug. PMID 22743239, Free PMC Article
    3. USP3 inhibition is Active Against Chemo-resistant Hepatocellular Carcinoma Anchorage-independent Growth via Suppressing Wnt/β-catenin. Xu J, et al. Curr Mol Med, 2024. PMID 37921189
    4. Ubiquitin-specific protease 3 overexpression promotes gastric carcinogenesis and is predictive of poor patient prognosis. Fang CL, et al. Cancer Sci, 2018 Nov. PMID 30168892, Free PMC Article
    5. Characterization and chromosomal localization of USP3, a novel human ubiquitin-specific protease. Sloper-Mould KE, et al. J Biol Chem, 1999 Sep 17. PMID 10480896

    See all (66) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. USP3: Key deubiquitylation enzyme in human diseases.
      Title: USP3: Key deubiquitylation enzyme in human diseases.
    2. USP3 inhibition is Active Against Chemo-resistant Hepatocellular Carcinoma Anchorage-independent Growth via Suppressing Wnt/beta-catenin.
      Title: USP3 inhibition is Active Against Chemo-resistant Hepatocellular Carcinoma Anchorage-independent Growth via Suppressing Wnt/β-catenin.
    3. USP3 promotes cisplatin resistance in non-small cell lung cancer cells by suppressing ACOT7-regulated ferroptosis.
      Title: USP3 promotes cisplatin resistance in non-small cell lung cancer cells by suppressing ACOT7-regulated ferroptosis.
    4. USP3 promotes osteosarcoma progression via deubiquitinating EPHA2 and activating the PI3K/AKT signaling pathway.
      Title: USP3 promotes osteosarcoma progression via deubiquitinating EPHA2 and activating the PI3K/AKT signaling pathway.
    5. CRISPR/Cas9-based genome-wide screening of the deubiquitinase subfamily identifies USP3 as a protein stabilizer of REST blocking neuronal differentiation and promotes neuroblastoma tumorigenesis.
      Title: CRISPR/Cas9-based genome-wide screening of the deubiquitinase subfamily identifies USP3 as a protein stabilizer of REST blocking neuronal differentiation and promotes neuroblastoma tumorigenesis.
    6. Deubiquitinase ubiquitin-specific protease 3 (USP3) inhibits HIV-1 replication via promoting APOBEC3G (A3G) expression in both enzyme activity-dependent and -independent manners.
      Title: Deubiquitinase ubiquitin-specific protease 3 (USP3) inhibits HIV-1 replication via promoting APOBEC3G (A3G) expression in both enzyme activity-dependent and -independent manners.
    7. USP3 promotes gastric cancer progression and metastasis by deubiquitination-dependent COL9A3/COL6A5 stabilisation.
      Title: USP3 promotes gastric cancer progression and metastasis by deubiquitination-dependent COL9A3/COL6A5 stabilisation.
    8. MicroRNA-146-5p Promotes Pulmonary Artery Endothelial Cell Proliferation under Hypoxic Conditions through Regulating USP3.
      Title: MicroRNA-146-5p Promotes Pulmonary Artery Endothelial Cell Proliferation under Hypoxic Conditions through Regulating USP3.
    9. Protein deubiquitylase USP3 stabilizes Aurora A to promote proliferation and metastasis of esophageal squamous cell carcinoma.
      Title: Protein deubiquitylase USP3 stabilizes Aurora A to promote proliferation and metastasis of esophageal squamous cell carcinoma.
    10. Genome-scale screening of deubiquitinase subfamily identifies USP3 as a stabilizer of Cdc25A regulating cell cycle in cancer.
      Title: Genome-scale screening of deubiquitinase subfamily identifies USP3 as a stabilizer of Cdc25A regulating cell cycle in cancer.
    Submit: New GeneRIF Correction See all GeneRIFs (27)

    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
    Association of genome-wide variation with the risk of incident heart failure in adults of European and African ancestry: a prospective meta-analysis from the cohorts for heart and aging research in genomic epidemiology (CHARGE) consortium.
    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)

    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • MGC129878, MGC129879

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables RNA polymerase II cis-regulatory region sequence-specific DNA binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables cysteine-type deubiquitinase activity IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    enables histone H2A deubiquitinase activity IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    enables histone H2B deubiquitinase activity IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    enables histone binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables promoter-specific chromatin binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables zinc ion binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    Process Evidence Code Pubs
    involved_in DNA repair IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in DNA repair-dependent chromatin remodeling IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in negative regulation of transcription by RNA polymerase II IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in protein deubiquitination IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in proteolysis IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    located_in Flemming body IDA
    Inferred from Direct Assay
    more info
    		  
    located_in chromatin IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    is_active_in cytoplasm IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in cytoplasmic ribonucleoprotein granule IDA
    Inferred from Direct Assay
    more info
    		  
    located_in nucleoplasm IDA
    Inferred from Direct Assay
    more info
    		  
    located_in nucleoplasm TAS
    Traceable Author Statement
    more info
    		  
    is_active_in nucleus IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  

    General protein information

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    Preferred Names
    ubiquitin carboxyl-terminal hydrolase 3
    Names
    deubiquitinating enzyme 3
    ubiquitin thioesterase 3
    ubiquitin thiolesterase 3
    ubiquitin-specific-processing protease 3
    NP_001243631.1
    NP_006528.2
    XP_016878252.1
    XP_016878253.1
    XP_016878254.1
    XP_047289349.1
    XP_047289350.1
    XP_047289351.1
    XP_054235272.1
    XP_054235273.1
    XP_054235274.1
    XP_054235275.1
    XP_054235276.1
    XP_054235277.1

    NCBI Reference Sequences (RefSeq)

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    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_001256702.2 → NP_001243631.1  ubiquitin carboxyl-terminal hydrolase 3 isoform 2

      Status: VALIDATED

      Description
      Transcript Variant: This variant (2) lacks an exon in the 5' coding region, but maintains the reading frame, compared to variant 1. The encoded isoform (2) is shorter than isoform 1.
      Source sequence(s)
      AC118274, AK301236, BC065300, DA557812
      Consensus CDS
      CCDS58370.1
      UniProtKB/TrEMBL
      H0YKU8
      Related
      ENSP00000445828.1, ENST00000540797.5
      Conserved Domains (3) summary
      cl02553
      Location:116 → 465
      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 ...
      pfam00443
      Location:114 → 464
      UCH; Ubiquitin carboxyl-terminal hydrolase
      cl09957
      Location:29 → 53
      zf-UBP; Zn-finger in ubiquitin-hydrolases and other protein

    2. NM_006537.4 → NP_006528.2  ubiquitin carboxyl-terminal hydrolase 3 isoform 1

      See identical proteins and their annotated locations for NP_006528.2

      Status: VALIDATED

      Description
      Transcript Variant: This variant (1) encodes the longer isoform (1).
      Source sequence(s)
      AC118274, AK314223
      Consensus CDS
      CCDS32265.1
      UniProtKB/Swiss-Prot
      B4DVU5, F5H1A6, Q8WVD0, Q9Y6I4
      UniProtKB/TrEMBL
      H0YMI4
      Related
      ENSP00000369681.3, ENST00000380324.8
      Conserved Domains (2) summary
      pfam00443
      Location:159 → 508
      UCH; Ubiquitin carboxyl-terminal hydrolase
      pfam02148
      Location:29 → 105
      zf-UBP; Zn-finger in ubiquitin-hydrolases and other protein

    RNA

    1. NR_046341.2 RNA Sequence

      Status: VALIDATED

      Description
      Transcript Variant: This variant (3) includes an alternate internal exon, compared to variant 1. This variant is represented as non-coding because the use of the 5'-most expected translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).
      Source sequence(s)
      AC118274, AY461579, DA557812

    2. NR_046342.2 RNA Sequence

      Status: VALIDATED

      Description
      Transcript Variant: This variant (4) includes an alternate internal exon, compared to variant 1. This variant is represented as non-coding because the use of the 5'-most expected translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).
      Source sequence(s)
      AC118274, BC065300, BX647760, DA557812
      Related
      ENST00000559192.5

    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_000015.10 Reference GRCh38.p14 Primary Assembly

      Range
      63504593..63594633
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047433394.1 → XP_047289350.1  ubiquitin carboxyl-terminal hydrolase 3 isoform X1

      UniProtKB/TrEMBL
      E9PE27, H0YMI4, Q6JHV3
      Related
      ENSP00000268049.7, ENST00000268049.11

    2. XM_047433393.1 → XP_047289349.1  ubiquitin carboxyl-terminal hydrolase 3 isoform X1

      UniProtKB/TrEMBL
      E9PE27, H0YMI4, Q6JHV3

    3. XM_017022765.2 → XP_016878254.1  ubiquitin carboxyl-terminal hydrolase 3 isoform X1

      UniProtKB/TrEMBL
      E9PE27, H0YMI4, Q6JHV3
      Conserved Domains (3) summary
      cl02553
      Location:138 → 487
      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 ...
      pfam00443
      Location:136 → 486
      UCH; Ubiquitin carboxyl-terminal hydrolase
      pfam02148
      Location:8 → 83
      zf-UBP; Zn-finger in ubiquitin-hydrolases and other protein

    4. XM_017022763.2 → XP_016878252.1  ubiquitin carboxyl-terminal hydrolase 3 isoform X1

      UniProtKB/TrEMBL
      E9PE27, H0YMI4, Q6JHV3
      Conserved Domains (3) summary
      cl02553
      Location:138 → 487
      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 ...
      pfam00443
      Location:136 → 486
      UCH; Ubiquitin carboxyl-terminal hydrolase
      pfam02148
      Location:8 → 83
      zf-UBP; Zn-finger in ubiquitin-hydrolases and other protein

    5. XM_017022764.2 → XP_016878253.1  ubiquitin carboxyl-terminal hydrolase 3 isoform X1

      UniProtKB/TrEMBL
      E9PE27, H0YMI4, Q6JHV3
      Conserved Domains (3) summary
      cl02553
      Location:138 → 487
      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 ...
      pfam00443
      Location:136 → 486
      UCH; Ubiquitin carboxyl-terminal hydrolase
      pfam02148
      Location:8 → 83
      zf-UBP; Zn-finger in ubiquitin-hydrolases and other protein

    6. XM_047433395.1 → XP_047289351.1  ubiquitin carboxyl-terminal hydrolase 3 isoform X2

      UniProtKB/TrEMBL
      H0YKU8
      Related
      ENSP00000452947.1, ENST00000559257.5

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060939.1 Alternate T2T-CHM13v2.0

      Range
      61311846..61401872
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054379299.1 → XP_054235274.1  ubiquitin carboxyl-terminal hydrolase 3 isoform X1

      UniProtKB/TrEMBL
      E9PE27, H0YMI4, Q6JHV3

    2. XM_054379300.1 → XP_054235275.1  ubiquitin carboxyl-terminal hydrolase 3 isoform X1

      UniProtKB/TrEMBL
      E9PE27, H0YMI4, Q6JHV3

    3. XM_054379298.1 → XP_054235273.1  ubiquitin carboxyl-terminal hydrolase 3 isoform X1

      UniProtKB/TrEMBL
      E9PE27, H0YMI4, Q6JHV3

    4. XM_054379297.1 → XP_054235272.1  ubiquitin carboxyl-terminal hydrolase 3 isoform X1

      UniProtKB/TrEMBL
      E9PE27, H0YMI4, Q6JHV3

    5. XM_054379301.1 → XP_054235276.1  ubiquitin carboxyl-terminal hydrolase 3 isoform X1

      UniProtKB/TrEMBL
      E9PE27, H0YMI4, Q6JHV3

    6. XM_054379302.1 → XP_054235277.1  ubiquitin carboxyl-terminal hydrolase 3 isoform X2

      UniProtKB/TrEMBL
      H0YKU8
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q9Y6I4.2 GenPept UniProtKB/Swiss-Prot:Q9Y6I4

    Gene LinkOut

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