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

Summary

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

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_000075.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

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.
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.
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.
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.
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.
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.
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.
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.
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.
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)

Gene trapped (1)
Targeted (2) 1 citation
Endonuclease-mediated (1)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

AW555420 (e-PCR)
- UniSTS:208450

Usp4 (e-PCR), detects polymorphism
- UniSTS:144732

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

EC 3.4.19.12

NP_035808.2

EC 3.4.19.12

XP_006511759.1

EC 3.4.19.12

XP_006511760.1

EC 3.4.19.12

XP_006511762.1

EC 3.4.19.12

XP_006511763.1

EC 3.4.19.12

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)

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
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

NC_000075.7 Reference GRCm39 C57BL/6J

Range

108223763..108269744

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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]
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]
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]
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]