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Usp4 ubiquitin specific peptidase 4 (proto-oncogene) [ Mus musculus (house mouse) ]

Gene ID: 22258, updated on 18-Apr-2024

Summary

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Official Symbol
Usp4provided by MGI
Official Full Name
ubiquitin specific peptidase 4 (proto-oncogene)provided by MGI
Primary source
MGI:MGI:98905
See related
Ensembl:ENSMUSG00000032612 AllianceGenome:MGI:98905
Gene type
protein coding
RefSeq status
VALIDATED
Organism
Mus musculus
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as
Unp; mKIAA4155; F730026I20Rik
Summary
Predicted to enable adenosine receptor binding activity; identical protein binding activity; and thiol-dependent deubiquitinase. Predicted to be involved in several processes, including negative regulation of protein ubiquitination; protein localization to cell surface; and spliceosomal tri-snRNP complex assembly. Predicted to act upstream of or within proteolysis. Predicted to be located in cytosol and plasma membrane. Predicted to be active in nucleus. Orthologous to human USP4 (ubiquitin specific peptidase 4). [provided by Alliance of Genome Resources, Apr 2022]
Expression
Ubiquitous expression in testis adult (RPKM 35.9), CNS E11.5 (RPKM 25.1) and 28 other tissues See more
Orthologs
human all
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Genomic context

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Location:
9 F2; 9 59.25 cM
Exon count:
22
Annotation release Status Assembly Chr Location
RS_2024_02 current GRCm39 (GCF_000001635.27) 9 NC_000075.7 (108223763..108269744)
108.20200622 previous assembly GRCm38.p6 (GCF_000001635.26) 9 NC_000075.6 (108346564..108392545)

Chromosome 9 - NC_000075.7Genomic Context describing neighboring genes Neighboring gene STARR-positive B cell enhancer ABC_E6805 Neighboring gene STARR-seq mESC enhancer starr_25204 Neighboring gene ras homolog family member A Neighboring gene STARR-seq mESC enhancer starr_25205 Neighboring gene STARR-positive B cell enhancer ABC_E10585 Neighboring gene glutathione peroxidase 1 Neighboring gene ribosomal protein S2, pseudogene 11 Neighboring gene RIKEN cDNA 1700102P08 gene Neighboring gene interactor of HORMAD1 1 Neighboring gene predicted gene, 25456

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: Mouse ENCODE transcriptome data
  • Description: RNA profiling data sets generated by the Mouse ENCODE project.
  • BioProject: PRJNA66167
  • Publication: PMID 25409824
  • Analysis date: n/a

Bibliography

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Related articles in PubMed

  1. USP4 is pathogenic in allergic airway inflammation by inhibiting regulatory T cell response. Hou X, et al. Life Sci, 2021 Sep 15. PMID 34144056
  2. Nuclear-cytoplasmic shuttling of the oncogenic mouse UNP/USP4 deubiquitylating enzyme. Soboleva TA, et al. J Biol Chem, 2005 Jan 7. PMID 15494318
  3. Characterization of the ubiquitin-specific protease activity of the mouse/human Unp/Unph oncoprotein. Gilchrist CA, et al. Biochim Biophys Acta, 2000 Sep 29. PMID 11018721
  4. The Deubiquitylase USP4 Interacts with the Water Channel AQP2 to Modulate Its Apical Membrane Accumulation and Cellular Abundance. Murali SK, et al. Cells, 2019 Mar 21. PMID 30901874, Free PMC Article
  5. Ubiquitin-Specific Protease 4 Is an Endogenous Negative Regulator of Metabolic Dysfunctions in Nonalcoholic Fatty Liver Disease in Mice. Zhao Y, et al. Hepatology, 2018 Sep. PMID 29573006

See all (45) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. 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.
  2. USP4 is pathogenic in allergic airway inflammation by inhibiting regulatory T cell response.
    Title: USP4 is pathogenic in allergic airway inflammation by inhibiting regulatory T cell response.
  3. a novel H19/miR-148a/USP4 axis which promoted liver fibrosis via TGF-beta pathway in both hepatic stellate cells and hepatocytes, is reported.
    Title: H19/miR-148a/USP4 axis facilitates liver fibrosis by enhancing TGF-β signaling in both hepatic stellate cells and hepatocytes.
  4. Interference with or inhibition of USP4 prevented the activity of the TGFbeta/Smad pathway signaling and inhibited the formation of pathological scars.
    Title: Inhibition of USP4 attenuates pathological scarring by downregulation of the TGF‑β/Smad signaling pathway.
  5. functions as a pivotal suppressor in nonalcoholic fatty liver disease
    Title: Ubiquitin-Specific Protease 4 Is an Endogenous Negative Regulator of Metabolic Dysfunctions in Nonalcoholic Fatty Liver Disease in Mice.
  6. USP4 is a key regulator of AQP2 deubiquitylation.
    Title: The Deubiquitylase USP4 Interacts with the Water Channel AQP2 to Modulate Its Apical Membrane Accumulation and Cellular Abundance.
  7. USP4 deficiency plays a detrimental role in hepatic I/R injury by promoting activation of the TAK1/JNK signalling pathways.
    Title: USP4 deficiency exacerbates hepatic ischaemia/reperfusion injury via TAK1 signalling.
  8. USP4 positively regulates RLR-induced NF-kappaB signalling while inhibiting EV71 replication, by targeting TRAF6 for K48-linked deubiquitination.
    Title: USP4 positively regulates RLR-induced NF-κB activation by targeting TRAF6 for K48-linked deubiquitination and inhibits enterovirus 71 replication.
  9. In this study, we identified ubiquitin-specific protease 4 (USP4), one of deubiquitinating enzymes, as a suppressor of MRFs by demonstrating that a knockdown of USP4 enhances myogenesis by controlling MyoD and the level of myogenesis marker proteins in C2C12 cells... we propose that USP4 is a key player in myogenic differentiation; it controls myogenic regulatory factors in a catalytic-independent manner
    Title: Ubiquitin-specific protease 4 (USP4) suppresses myoblast differentiation by down regulating MyoD activity in a catalytic-independent manner.
  10. The authors demonstrated that ubiquitin-specific protease (USP) 4 strongly induces activin/BMP signaling by removing the inhibitory monoubiquitination from SMAD4.
    Title: USP4 inhibits SMAD4 monoubiquitination and promotes activin and BMP signaling.
Submit: New GeneRIF Correction See all GeneRIFs (14)

Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics  (MGI)
  • Targeted (2)  1 citation
  • Gene trapped (1) 
  • Endonuclease-mediated (1) 

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

  • KIAA4155

Gene Ontology Provided by MGI

Function Evidence Code Pubs
enables adenosine receptor binding ISO
Inferred from Sequence Orthology
more info
  
enables cysteine-type deubiquitinase activity ISO
Inferred from Sequence Orthology
more info
  
enables cysteine-type peptidase activity IEA
Inferred from Electronic Annotation
more info
  
enables hydrolase activity IEA
Inferred from Electronic Annotation
more info
  
enables identical protein binding ISO
Inferred from Sequence Orthology
more info
  
enables metal ion binding IEA
Inferred from Electronic Annotation
more info
  
enables peptidase activity 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 ISO
Inferred from Sequence Orthology
more info
  
involved_in positive regulation of TORC1 signaling ISO
Inferred from Sequence Orthology
more info
  
involved_in protein deubiquitination ISO
Inferred from Sequence Orthology
more info
  
involved_in protein localization to cell surface ISO
Inferred from Sequence Orthology
more info
  
acts_upstream_of_or_within proteolysis IEA
Inferred from Electronic Annotation
more info
  
involved_in regulation of protein stability ISO
Inferred from Sequence Orthology
more info
  
involved_in spliceosomal tri-snRNP complex assembly ISO
Inferred from Sequence Orthology
more info
  
Component Evidence Code Pubs
located_in cytoplasm ISO
Inferred from Sequence Orthology
more info
  
located_in cytosol ISO
Inferred from Sequence Orthology
more info
  
is_active_in nucleus IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in nucleus ISO
Inferred from Sequence Orthology
more info
  
located_in plasma membrane ISO
Inferred from Sequence Orthology
more info
  

General protein information

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Preferred Names
ubiquitin carboxyl-terminal hydrolase 4
Names
deubiquitinating enzyme 4
ubiquitin specific protease 4 (proto-oncogene)
ubiquitin thioesterase 4
ubiquitin thiolesterase 4
ubiquitin-specific-processing protease 4
ubiquitous nuclear protein
NP_001298086.1
NP_035808.2
XP_006511759.1
XP_006511760.1
XP_006511762.1
XP_006511763.1

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.

mRNA and Protein(s)

  1. NM_001311157.1 → NP_001298086.1  ubiquitin carboxyl-terminal hydrolase 4 isoform 2

    See identical proteins and their annotated locations for NP_001298086.1

    Status: VALIDATED

    Description
    Transcript Variant: This variant (2) lacks an alternate in-frame exon in the 5' coding region compared to variant 1. It encodes isoform 2, which is shorter than isoform 1.
    Source sequence(s)
    AC161260, AK164245, AK187607, AK199674, BB770947, BE982062, BY322979, CA548182, CK624008
    Consensus CDS
    CCDS81074.1
    UniProtKB/TrEMBL
    A0A0A6YW28, Q921M8
    Related
    ENSMUSP00000141368.2, ENSMUST00000194959.6
    Conserved Domains (6) summary
    smart00695
    Location:27 → 125
    DUSP; Domain in ubiquitin-specific proteases
    COG5560
    Location:35 → 875
    UBP12; Ubiquitin C-terminal hydrolase [Posttranslational modification, protein turnover, chaperones]
    cd02674
    Location:728 → 873
    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

  2. NM_011678.2 → NP_035808.2  ubiquitin carboxyl-terminal hydrolase 4 isoform 1

    See identical proteins and their annotated locations for NP_035808.2

    Status: VALIDATED

    Description
    Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).
    Source sequence(s)
    AK149964, BY322979, CD741063
    Consensus CDS
    CCDS23523.1
    UniProtKB/Swiss-Prot
    O54704, P35123, Q8BTL9
    UniProtKB/TrEMBL
    Q3TEX8
    Related
    ENSMUSP00000035237.7, ENSMUST00000035237.12
    Conserved Domains (6) summary
    smart00695
    Location:27 → 125
    DUSP; Domain in ubiquitin-specific proteases
    COG5560
    Location:35 → 922
    UBP12; Ubiquitin C-terminal hydrolase [Posttranslational modification, protein turnover, chaperones]
    cd02674
    Location:775 → 920
    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:302 → 486
    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:504 → 567
    USP7_C2; Ubiquitin-specific protease C-terminal
    pfam14836
    Location:139 → 226
    Ubiquitin_3; Ubiquitin-like domain

RefSeqs of Annotated Genomes: GCF_000001635.27-RS_2024_02

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCm39 C57BL/6J

Genomic

  1. NC_000075.7 Reference GRCm39 C57BL/6J

    Range
    108223763..108269744
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_006511696.2 → XP_006511759.1  ubiquitin carboxyl-terminal hydrolase 4 isoform X1

    UniProtKB/TrEMBL
    Q3TEX8
    Conserved Domains (1) summary
    COG5560
    Location:35 → 927
    UBP12; Ubiquitin C-terminal hydrolase [Posttranslational modification, protein turnover, chaperones]

  2. XM_006511699.4 → XP_006511762.1  ubiquitin carboxyl-terminal hydrolase 4 isoform X3

    UniProtKB/TrEMBL
    Q3TEX8
    Conserved Domains (1) summary
    COG5560
    Location:35 → 850
    UBP12; Ubiquitin C-terminal hydrolase [Posttranslational modification, protein turnover, chaperones]

  3. XM_006511700.3 → XP_006511763.1  ubiquitin carboxyl-terminal hydrolase 4 isoform X4

    UniProtKB/TrEMBL
    Q3TEX8
    Related
    ENSMUSP00000141321.2, ENSMUST00000194224.6
    Conserved Domains (1) summary
    COG5560
    Location:35 → 845
    UBP12; Ubiquitin C-terminal hydrolase [Posttranslational modification, protein turnover, chaperones]

  4. XM_006511697.2 → XP_006511760.1  ubiquitin carboxyl-terminal hydrolase 4 isoform X2

    UniProtKB/TrEMBL
    Q921M8
    Conserved Domains (1) summary
    COG5560
    Location:35 → 880
    UBP12; Ubiquitin C-terminal hydrolase [Posttranslational modification, protein turnover, chaperones]
Nucleotide Protein Strain
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
P35123.3 GenPept UniProtKB/Swiss-Prot:P35123

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