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    USP2 ubiquitin specific peptidase 2 [ Homo sapiens (human) ]

    Gene ID: 9099, updated on 2-Nov-2024

    Summary

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    Official Symbol
    USP2provided by HGNC
    Official Full Name
    ubiquitin specific peptidase 2provided by HGNC
    Primary source
    HGNC:HGNC:12618
    See related
    Ensembl:ENSG00000036672 MIM:604725; AllianceGenome:HGNC:12618
    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
    USP9; UBP41
    Summary
    This gene encodes a member of the family of de-ubiquitinating enzymes, which belongs to the peptidase C19 superfamily. The encoded protein is a ubiquitin-specific protease which is required for TNF-alpha (tumor necrosis factor alpha) -induced NF-kB (nuclear factor kB) signaling. This protein deubiquitinates polyubiquitinated target proteins such as fatty acid synthase, murine double minute 2 (MDM2), MDM4/MDMX and cyclin D1. MDM2 and MDM4 are negative regulators of the p53 tumor suppressor and cyclin D1 is required for cell cycle G1/S transition. Multiple alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Aug 2011]
    Expression
    Biased expression in testis (RPKM 31.4), kidney (RPKM 15.4) and 10 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See USP2 in Genome Data Viewer
    Location:
    11q23.3
    Exon count:
    16
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 11 NC_000011.10 (119355215..119381690, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 11 NC_060935.1 (119376744..119403221, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 11 NC_000011.9 (119225925..119252400, complement)

    Chromosome 11 - NC_000011.10Genomic Context describing neighboring genes Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:119204879-119205770 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3979 Neighboring gene C1q and TNF related 5 Neighboring gene ring finger protein 26 Neighboring gene membrane frizzled-related protein Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr11:119228534-119229733 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 5630 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3980 Neighboring gene HNF4 motif-containing MPRA enhancer 223 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:119243670-119244170 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:119247037-119247615 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:119247932-119248520 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:119251478-119252467 Neighboring gene USP2 antisense RNA 1 Neighboring gene major facilitator superfamily domain containing 14B pseudogene Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:119290361-119290928 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:119292628-119293194 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:119293195-119293760 Neighboring gene Thy-1 cell surface antigen

    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. USP2a negatively regulates IL-1β- and virus-induced NF-κB activation by deubiquitinating TRAF6. He X, et al. J Mol Cell Biol, 2013 Feb. PMID 22611252
    2. Decreased USP2a Expression Inhibits Trophoblast Invasion and Associates With Recurrent Miscarriage. Wang J, et al. Front Immunol, 2021. PMID 34489969, Free PMC Article
    3. USP2 promotes cell migration and invasion in triple negative breast cancer cell lines. Qu Q, et al. Tumour Biol, 2015 Jul. PMID 25687182
    4. Ubiquitin-specific peptidase 2 inhibits epithelial-mesenchymal transition in clear cell renal cell carcinoma metastasis by downregulating the NF-κB pathway. Duan J, et al. Bioengineered, 2022 Feb. PMID 35152855, Free PMC Article
    5. An RNAi screen identifies USP2 as a factor required for TNF-α-induced NF-κB signaling. Metzig M, et al. Int J Cancer, 2011 Aug 1. PMID 21480224

    See all (146) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Age-related genes USP2 and ARG2 are involved in the reduction of immune cell infiltration in elderly patients with rheumatoid arthritis.
      Title: Age-related genes USP2 and ARG2 are involved in the reduction of immune cell infiltration in elderly patients with rheumatoid arthritis.
    2. USP2 Inhibits Lung Cancer Pathogenesis by Reducing ARID2 Protein Degradation via Ubiquitination.
      Title: USP2 Inhibits Lung Cancer Pathogenesis by Reducing ARID2 Protein Degradation via Ubiquitination.
    3. Ubiquitin-Specific Protease 2 in the Ventromedial Hypothalamus Modifies Blood Glucose Levels by Controlling Sympathetic Nervous Activation.
      Title: Ubiquitin-Specific Protease 2 in the Ventromedial Hypothalamus Modifies Blood Glucose Levels by Controlling Sympathetic Nervous Activation.
    4. Loss of deubiquitylase USP2 triggers development of glioblastoma via TGF-beta signaling.
      Title: Loss of deubiquitylase USP2 triggers development of glioblastoma via TGF-β signaling.
    5. High Ubiquitin-Specific Protease 2a Expression Level Predicts Poor Prognosis in Upper Tract Urothelial Carcinoma.
      Title: High Ubiquitin-Specific Protease 2a Expression Level Predicts Poor Prognosis in Upper Tract Urothelial Carcinoma.
    6. Ubiquitin-specific peptidase 2 inhibits epithelial-mesenchymal transition in clear cell renal cell carcinoma metastasis by downregulating the NF-kappaB pathway.
      Title: Ubiquitin-specific peptidase 2 inhibits epithelial-mesenchymal transition in clear cell renal cell carcinoma metastasis by downregulating the NF-κB pathway.
    7. Decreased USP2a Expression Inhibits Trophoblast Invasion and Associates With Recurrent Miscarriage.
      Title: Decreased USP2a Expression Inhibits Trophoblast Invasion and Associates With Recurrent Miscarriage.
    8. USP2 is an SKP2 deubiquitylase that stabilizes both SKP2 and its substrates.
      Title: USP2 is an SKP2 deubiquitylase that stabilizes both SKP2 and its substrates.
    9. Ubiquitin-specific protease 2a promotes hepatocellular carcinoma progression via deubiquitination and stabilization of RAB1A.
      Title: Ubiquitin-specific protease 2a promotes hepatocellular carcinoma progression via deubiquitination and stabilization of RAB1A.
    10. The deubiquitylase USP2 maintains ErbB2 abundance via counteracting endocytic degradation and represents a therapeutic target in ErbB2-positive breast cancer.
      Title: The deubiquitylase USP2 maintains ErbB2 abundance via counteracting endocytic degradation and represents a therapeutic target in ErbB2-positive breast cancer.
    Submit: New GeneRIF Correction See all GeneRIFs (48)

    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 analyses identify 18 new loci associated with serum urate concentrations.
    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

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables cyclin 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 IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    enables cysteine-type deubiquitinase activity TAS
    Traceable Author Statement
    more info
    		  
    enables cysteine-type endopeptidase activity TAS
    Traceable Author Statement
    more info
    		 PubMed 
    enables identical protein binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables metal ion binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables ubiquitin protein ligase binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in circadian behavior ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in circadian regulation of gene expression ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in entrainment of circadian clock by photoperiod ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in locomotor rhythm ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in muscle organ development IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in negative regulation of transcription by RNA polymerase II IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in positive regulation of mitotic cell cycle IMP
    Inferred from Mutant Phenotype
    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 protein stabilization IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in protein stabilization IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in proteolysis IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in regulation of signal transduction by p53 class mediator TAS
    Traceable Author Statement
    more info
    		  
    Component Evidence Code Pubs
    located_in centrosome IEA
    Inferred from Electronic Annotation
    more info
    		  
    is_active_in cytoplasm IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in membrane IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in nucleoplasm TAS
    Traceable Author Statement
    more info
    		  
    located_in perinuclear region of cytoplasm IEA
    Inferred from Electronic Annotation
    more info
    		  

    General protein information

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    Preferred Names
    ubiquitin carboxyl-terminal hydrolase 2
    Names
    41 kDa ubiquitin-specific protease
    deubiquitinating enzyme 2
    ubiquitin specific protease 12
    ubiquitin specific protease 9
    ubiquitin thioesterase 2
    ubiquitin-specific-processing protease 2
    NP_001230688.1
    NP_004196.4
    NP_741994.1
    XP_005271778.1
    XP_005271779.1
    XP_016874028.1
    XP_054226438.1
    XP_054226439.1
    XP_054226440.1

    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.

    Genomic

    1. NG_029825.2 RefSeqGene

      Range
      5037..31512
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001243759.2 → NP_001230688.1  ubiquitin carboxyl-terminal hydrolase 2 isoform c

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) lacks an internal exon in the 5' region, compared to variant 1. The resulting isoform (c) has a shorter and different N-terminus compared to isoform a.
      Source sequence(s)
      AP003396, BC041366, DB065104
      Consensus CDS
      CCDS58189.1
      UniProtKB/TrEMBL
      B7Z7C2
      Related
      ENSP00000407842.2, ENST00000455332.6
      Conserved Domains (2) summary
      cd02674
      Location:25 → 354
      Peptidase_C19R; A subfamily of peptidase C19. Peptidase C19 contains ubiquitinyl hydrolases. They are intracellular peptidases that remove ubiquitin molecules from polyubiquinated peptides by cleavage of isopeptide bonds. They hydrolyze bonds involving the carboxyl ...
      pfam00443
      Location:23 → 353
      UCH; Ubiquitin carboxyl-terminal hydrolase

    2. NM_004205.5 → NP_004196.4  ubiquitin carboxyl-terminal hydrolase 2 isoform a

      See identical proteins and their annotated locations for NP_004196.4

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) encodes the longest isoform (a).
      Source sequence(s)
      AI806430, AK057225, BC002955, BC041366, DB065104, DB098786
      Consensus CDS
      CCDS8422.1
      UniProtKB/Swiss-Prot
      B0YJB8, E9PPM2, O75604, Q8IUM2, Q8IW04, Q96MB9, Q9BQ21
      Related
      ENSP00000260187.2, ENST00000260187.7
      Conserved Domains (1) summary
      pfam00443
      Location:267 → 596
      UCH; Ubiquitin carboxyl-terminal hydrolase

    3. NM_171997.3 → NP_741994.1  ubiquitin carboxyl-terminal hydrolase 2 isoform b

      See identical proteins and their annotated locations for NP_741994.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) is missing 2 exons from the 5' end, and contains an alternate 5' terminal exon compared to transcript variant 1. This results in a shorter isoform (b) with a different N-terminus compared to isoform a.
      Source sequence(s)
      AF440755, AI806430, AK057225, AP003396, BC041366
      Consensus CDS
      CCDS8423.1
      UniProtKB/TrEMBL
      B7Z7C2
      Related
      ENSP00000436952.1, ENST00000525735.1
      Conserved Domains (1) summary
      pfam00443
      Location:58 → 387
      UCH; Ubiquitin carboxyl-terminal hydrolase

    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_000011.10 Reference GRCh38.p14 Primary Assembly

      Range
      119355215..119381690 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_005271721.6 → XP_005271778.1  ubiquitin carboxyl-terminal hydrolase 2 isoform X1

      See identical proteins and their annotated locations for XP_005271778.1

      UniProtKB/Swiss-Prot
      B0YJB8, E9PPM2, O75604, Q8IUM2, Q8IW04, Q96MB9, Q9BQ21
      Conserved Domains (1) summary
      pfam00443
      Location:267 → 596
      UCH; Ubiquitin carboxyl-terminal hydrolase

    2. XM_005271722.3 → XP_005271779.1  ubiquitin carboxyl-terminal hydrolase 2 isoform X1

      See identical proteins and their annotated locations for XP_005271779.1

      UniProtKB/Swiss-Prot
      B0YJB8, E9PPM2, O75604, Q8IUM2, Q8IW04, Q96MB9, Q9BQ21
      Conserved Domains (1) summary
      pfam00443
      Location:267 → 596
      UCH; Ubiquitin carboxyl-terminal hydrolase

    3. XM_017018539.1 → XP_016874028.1  ubiquitin carboxyl-terminal hydrolase 2 isoform X2

      UniProtKB/TrEMBL
      B7Z7C2

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060935.1 Alternate T2T-CHM13v2.0

      Range
      119376744..119403221 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054370463.1 → XP_054226438.1  ubiquitin carboxyl-terminal hydrolase 2 isoform X1

      UniProtKB/Swiss-Prot
      B0YJB8, E9PPM2, O75604, Q8IUM2, Q8IW04, Q96MB9, Q9BQ21

    2. XM_054370464.1 → XP_054226439.1  ubiquitin carboxyl-terminal hydrolase 2 isoform X1

      UniProtKB/Swiss-Prot
      B0YJB8, E9PPM2, O75604, Q8IUM2, Q8IW04, Q96MB9, Q9BQ21

    3. XM_054370465.1 → XP_054226440.1  ubiquitin carboxyl-terminal hydrolase 2 isoform X2

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    O75604.2 GenPept UniProtKB/Swiss-Prot:O75604

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