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

    Gene ID: 7375, updated on 12-Nov-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_2024_08 current GRCh38.p14 (GCF_000001405.40) 3 NC_000003.12 (49277144..49340053, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 3 NC_060927.1 (49305224..49369431, complement)
    RS_2024_09 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 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. Elevated expression of Unph, a proto-oncogene at 3p21.3, in human lung tumors. Gray DA, et al. Oncogene, 1995 Jun 1. PMID 7784062
    2. Ubiquitin-specific protease 4 improves the prognosis of the patients in esophageal cancer. Yao R, et al. Cancer Biomark, 2017 Sep 7. PMID 28946564
    3. 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
    4. USP4 expression independently predicts favorable survival in lung adenocarcinoma. Zhong M, et al. IUBMB Life, 2018 Jul. PMID 29667299
    5. 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

    See all (124) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. USP4 regulates ribosome biogenesis and protein synthesis for hematopoietic stem cell regeneration and leukemia progression.
      Title: USP4 regulates ribosome biogenesis and protein synthesis for hematopoietic stem cell regeneration and leukemia progression.
    2. USP4 promotes PTC progression by stabilizing LDHA and activating the MAPK and AKT signaling pathway.
      Title: USP4 promotes PTC progression by stabilizing LDHA and activating the MAPK and AKT signaling pathway.
    3. Deubiquitinase USP4 suppresses antitumor immunity by inhibiting IRF3 activation and tumor cell-intrinsic interferon response in colorectal cancer.
      Title: Deubiquitinase USP4 suppresses antitumor immunity by inhibiting IRF3 activation and tumor cell-intrinsic interferon response in colorectal cancer.
    4. USP4 regulates TUT1 ubiquitination status in concert with SART3.
      Title: USP4 regulates TUT1 ubiquitination status in concert with SART3.
    5. 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.
    6. 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.
    7. 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.
    8. 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.
    9. 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.
    10. 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.
    Submit: New GeneRIF Correction See all GeneRIFs (50)

    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 deubiquitination TAS
    Traceable Author Statement
    more info
    		  
    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_2024_08

    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

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

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