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

Gene ID: 9099, updated on 3-Apr-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
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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_2023_10 current GRCh38.p14 (GCF_000001405.40) 11 NC_000011.10 (119355215..119381690, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 11 NC_060935.1 (119376744..119403221, complement)
105.20220307 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. High Ubiquitin-Specific Protease 2a Expression Level Predicts Poor Prognosis in Upper Tract Urothelial Carcinoma. Ke HL, et al. Appl Immunohistochem Mol Morphol, 2022 Apr 1. PMID 35384881
  2. 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
  3. Decreased USP2a Expression Inhibits Trophoblast Invasion and Associates With Recurrent Miscarriage. Wang J, et al. Front Immunol, 2021. PMID 34489969, Free PMC Article
  4. Inhibition of USP2 eliminates cancer stem cells and enhances TNBC responsiveness to chemotherapy. He J, et al. Cell Death Dis, 2019 Mar 28. PMID 30918246, Free PMC Article
  5. The Molecular Mechanisms of Regulation on USP2's Alternative Splicing and the Significance of Its Products. Zhu HQ, et al. Int J Biol Sci, 2017. PMID 29230097, Free PMC Article

See all (134) 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)

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

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 cell cycle IEA
Inferred from Electronic Annotation
more info
  
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 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_2023_10

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

Gene LinkOut

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