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

Summary

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

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_000003.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

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.
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.
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.
USP4 regulates TUT1 ubiquitination status in concert with SART3.
Title: USP4 regulates TUT1 ubiquitination status in concert with SART3.
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 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.
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.
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.
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.
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 EBI GWAS CatalogPubMed
Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH41918 (e-PCR)
- UniSTS:26885

RH18550 (e-PCR)
- UniSTS:60165

SHGC-31529 (e-PCR)
- UniSTS:59146

D3S3092 (e-PCR)
- UniSTS:36624

RH45172 (e-PCR)
- UniSTS:47657

D8S2279 (e-PCR)
- UniSTS:473907

WI-14204 (e-PCR)
- UniSTS:19017

STS-U20657 (e-PCR)
- UniSTS:25174

SHGC-57737 (e-PCR)
- UniSTS:8295

SHGC-107421 (e-PCR)
- UniSTS:170349

USP4_8707 (e-PCR)
- UniSTS:468164

L17791 (e-PCR)
- UniSTS:42740

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

EC 3.4.19.12

NP_003354.2

EC 3.4.19.12

NP_955475.1

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.

Genomic

NG_030370.1 RefSeqGene

Range

5051..67960

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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
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 ...
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