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USP4 ubiquitin specific peptidase 4 [ Homo sapiens (human) ]

Gene ID: 7375, updated on 5-Mar-2024

Summary

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Official Symbol
USP4provided by HGNC
Official Full Name
ubiquitin specific peptidase 4provided by HGNC
Primary source
HGNC:HGNC:12627
See related
Ensembl:ENSG00000114316 MIM:603486; AllianceGenome:HGNC:12627
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
UNP; Unph
Summary
The protein encoded by this gene is a protease that deubiquitinates target proteins such as ADORA2A and TRIM21. The encoded protein shuttles between the nucleus and cytoplasm and is involved in maintaining operational fidelity in the endoplasmic reticulum. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]
Expression
Ubiquitous expression in testis (RPKM 15.1), bone marrow (RPKM 14.6) and 25 other tissues See more
Orthologs
mouse all
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Genomic context

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See USP4 in Genome Data Viewer
Location:
3p21.31
Exon count:
23
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 3 NC_000003.12 (49277144..49340053, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 3 NC_060927.1 (49305224..49369431, complement)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 3 NC_000003.11 (49314577..49377486, complement)

Chromosome 3 - NC_000003.12Genomic Context describing neighboring genes Neighboring gene interactor of HORMAD1 1 Neighboring gene GCSH pseudogene 6 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19859 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14359 Neighboring gene chromosome 3 open reading frame 62 Neighboring gene microRNA 4271 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14360 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19860 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:49353925-49354426 Neighboring gene Sjoegren syndrome nuclear autoantigen 1 homolog Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:49354427-49354926 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14361 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr3:49377657-49378156 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19863 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19864 Neighboring gene Sharpr-MPRA regulatory region 2568 Neighboring gene GATA motif-containing MPRA enhancer 295 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19865 Neighboring gene H3K27ac hESC enhancers GRCh37_chr3:49395462-49396070 and GRCh37_chr3:49396071-49396679 Neighboring gene glutathione peroxidase 1 Neighboring gene ras homolog family member A Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr3:49423846-49424400 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr3:49424401-49424954 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr3:49426165-49426934 Neighboring gene Sharpr-MPRA regulatory region 7935

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. Transcriptome Analysis and Single-Cell Sequencing Analysis Constructed the Ubiquitination-Related Signature in Glioma and Identified USP4 as a Novel Biomarker. Tang Q, et al. Front Immunol, 2022. PMID 35774799, Free PMC Article
  2. Ubiquitin-specific protease 4 predicts an unfavorable prognosis and promotes malignant behaviors in vitro in pancreatic cancer. Wang Y, et al. Exp Cell Res, 2020 Nov 15. PMID 33038351
  3. USP4 expression independently predicts favorable survival in lung adenocarcinoma. Zhong M, et al. IUBMB Life, 2018 Jul. PMID 29667299
  4. Up-regulated deubiquitinase USP4 plays an oncogenic role in melanoma. Guo W, et al. J Cell Mol Med, 2018 May. PMID 29542252, Free PMC Article
  5. Ubiquitin-specific protease 4 improves the prognosis of the patients in esophageal cancer. Yao R, et al. Cancer Biomark, 2017 Sep 7. PMID 28946564

See all (113) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. USP4 regulates TUT1 ubiquitination status in concert with SART3.
    Title: USP4 regulates TUT1 ubiquitination status in concert with SART3.
  2. FBXO3 stabilizes USP4 and Twist1 to promote PI3K-mediated breast cancer metastasis.
    Title: FBXO3 stabilizes USP4 and Twist1 to promote PI3K-mediated breast cancer metastasis.
  3. USP4 promotes the proliferation, migration, and invasion of esophageal squamous cell carcinoma by targeting TAK1.
    Title: USP4 promotes the proliferation, migration, and invasion of esophageal squamous cell carcinoma by targeting TAK1.
  4. High USP4 mRNA is associated with an HPV-positive status in head and neck squamous cell carcinoma patients.
    Title: High USP4 mRNA is associated with an HPV-positive status in head and neck squamous cell carcinoma patients.
  5. Binding of USP4 to cortactin enhances cell migration in HCT116 human colon cancer cells.
    Title: Binding of USP4 to cortactin enhances cell migration in HCT116 human colon cancer cells.
  6. The Deubiquitinating Enzyme USP4 Functions as an Oncoprotein in Gastric Cancer and Mediates NF-kappaB Signaling by Regulating PRL-3 Expression.
    Title: The Deubiquitinating Enzyme USP4 Functions as an Oncoprotein in Gastric Cancer and Mediates NF-κB Signaling by Regulating PRL-3 Expression.
  7. Transcriptome Analysis and Single-Cell Sequencing Analysis Constructed the Ubiquitination-Related Signature in Glioma and Identified USP4 as a Novel Biomarker.
    Title: Transcriptome Analysis and Single-Cell Sequencing Analysis Constructed the Ubiquitination-Related Signature in Glioma and Identified USP4 as a Novel Biomarker.
  8. Deubiquitinating enzymes USP4 and USP17 finetune the trafficking of PDGFRbeta and affect PDGF-BB-induced STAT3 signalling.
    Title: Deubiquitinating enzymes USP4 and USP17 finetune the trafficking of PDGFRβ and affect PDGF-BB-induced STAT3 signalling.
  9. Ubiquitin-specific protease 4 predicts an unfavorable prognosis and promotes malignant behaviors in vitro in pancreatic cancer.
    Title: Ubiquitin-specific protease 4 predicts an unfavorable prognosis and promotes malignant behaviors in vitro in pancreatic cancer.
  10. The Effects of the Transforming Growth Factor-beta1 (TGF-beta1) Signaling Pathway on Cell Proliferation and Cell Migration are Mediated by Ubiquitin Specific Protease 4 (USP4) in Hypertrophic Scar Tissue and Primary Fibroblast Cultures.
    Title: The Effects of the Transforming Growth Factor-β1 (TGF-β1) Signaling Pathway on Cell Proliferation and Cell Migration are Mediated by Ubiquitin Specific Protease 4 (USP4) in Hypertrophic Scar Tissue and Primary Fibroblast Cultures.
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
A genome-wide association study identifies a novel locus at 6q22.1 associated with ulcerative colitis.
EBI GWAS Catalog
Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease.
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

Clone Names

  • MGC149848, MGC149849

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables adenosine receptor 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 identical protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables metal ion binding IEA
Inferred from Electronic Annotation
more info
  
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
Process Evidence Code Pubs
involved_in negative regulation of protein ubiquitination IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in positive regulation of TORC1 signaling IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in protein deubiquitination IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in protein deubiquitination IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in protein localization to cell surface IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in proteolysis IEA
Inferred from Electronic Annotation
more info
  
involved_in regulation of protein stability IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in spliceosomal tri-snRNP complex assembly IMP
Inferred from Mutant Phenotype
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 lysosome TAS
Traceable Author Statement
more info
 PubMed 
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 plasma membrane IDA
Inferred from Direct Assay
more info
  

General protein information

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Preferred Names
ubiquitin carboxyl-terminal hydrolase 4
Names
deubiquitinating enzyme 4
ubiquitin carboxyl-terminal esterase 4
ubiquitin specific peptidase 4 (proto-oncogene)
ubiquitin specific protease 4 (proto-oncogene)
ubiquitin thioesterase 4
ubiquitin thiolesterase 4
ubiquitin-specific processing protease 4
ubiquitous nuclear protein homolog
NP_001238806.1
NP_003354.2
NP_955475.1

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_030370.1 RefSeqGene

    Range
    5051..67960
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001251877.2 → NP_001238806.1  ubiquitin carboxyl-terminal hydrolase 4 isoform c

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) lacks several exons and its transcription extends past a splice site that is used in variant 1, resulting in a novel 3' coding region and 3' UTR compared to variant 1. It encodes isoform c, which is shorter and has a distinct C-terminus, compared to isoform a.
    Source sequence(s)
    AC121247, BC068017
    Consensus CDS
    CCDS58832.1
    UniProtKB/Swiss-Prot
    Q13107
    Related
    ENSP00000400623.1, ENST00000416417.5
    Conserved Domains (2) summary
    smart00695
    Location:27 → 125
    DUSP; Domain in ubiquitin-specific proteases
    pfam14836
    Location:139 → 226
    Ubiquitin_3; Ubiquitin-like domain

  2. NM_003363.4 → NP_003354.2  ubiquitin carboxyl-terminal hydrolase 4 isoform a

    See identical proteins and their annotated locations for NP_003354.2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (a).
    Source sequence(s)
    AI887410, BC125130, BC125131, DA267618, DB534804
    Consensus CDS
    CCDS2793.1
    UniProtKB/Swiss-Prot
    A8K6Y0, C9IY91, O43452, O43453, Q08AK8, Q13107
    UniProtKB/TrEMBL
    Q08AK7, Q53FJ3
    Related
    ENSP00000265560.4, ENST00000265560.9
    Conserved Domains (1) summary
    cl02553
    Location:35 → 923
    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 ...

  3. NM_199443.3 → NP_955475.1  ubiquitin carboxyl-terminal hydrolase 4 isoform b

    See identical proteins and their annotated locations for NP_955475.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) lacks an alternate in-frame exon compared to variant 1. The resulting isoform (b) has the same N- and C-termini but is shorter compared to isoform a.
    Source sequence(s)
    AF017306, AI887410, BC125130, BG717217, DA267618, DB534804
    Consensus CDS
    CCDS2794.1
    UniProtKB/TrEMBL
    Q53H56
    Related
    ENSP00000341028.4, ENST00000351842.8
    Conserved Domains (6) summary
    smart00695
    Location:27 → 125
    DUSP; Domain in ubiquitin-specific proteases
    COG5560
    Location:35 → 876
    UBP12; Ubiquitin C-terminal hydrolase [Posttranslational modification, protein turnover, chaperones]
    cd02674
    Location:729 → 874
    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 ...
    cl02553
    Location:255 → 439
    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 ...
    pfam14533
    Location:457 → 520
    USP7_C2; Ubiquitin-specific protease C-terminal
    pfam14836
    Location:139 → 226
    Ubiquitin_3; Ubiquitin-like domain

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_000003.12 Reference GRCh38.p14 Primary Assembly

    Range
    49277144..49340053 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060927.1 Alternate T2T-CHM13v2.0

    Range
    49305224..49369431 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q13107.3 GenPept UniProtKB/Swiss-Prot:Q13107

Gene LinkOut

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