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Aliases for USP4 Gene

Aliases for USP4 Gene

  • Ubiquitin Specific Peptidase 4 2 3 5
  • Ubiquitin Specific Peptidase 4 (Proto-Oncogene) 2 3
  • Ubiquitous Nuclear Protein Homolog 3 4
  • Deubiquitinating Enzyme 4 3 4
  • Ubiquitin Thioesterase 4 3 4
  • Unph 3 4
  • UNP 3 4
  • Ubiquitin Specific Protease 4 (Proto-Oncogene) 3
  • Ubiquitin-Specific Processing Protease 4 3
  • Ubiquitin-Specific-Processing Protease 4 4
  • Ubiquitin Carboxyl-Terminal Hydrolase 4 3
  • Ubiquitin Carboxyl-Terminal Esterase 4 3
  • Ubiquitin Thiolesterase 4 3
  • EC 3.4.19.12 4
  • EC 3.1.2.15 61

External Ids for USP4 Gene

Previous HGNC Symbols for USP4 Gene

  • UNP

Previous GeneCards Identifiers for USP4 Gene

  • GC03P048745
  • GC03P048551
  • GC03M049160
  • GC03M049274
  • GC03M049290

Summaries for USP4 Gene

Entrez Gene Summary for USP4 Gene

  • 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]

GeneCards Summary for USP4 Gene

USP4 (Ubiquitin Specific Peptidase 4) is a Protein Coding gene. Among its related pathways are TNF signaling (REACTOME) and Deubiquitination. GO annotations related to this gene include identical protein binding and thiol-dependent ubiquitin-specific protease activity. An important paralog of this gene is USP15.

UniProtKB/Swiss-Prot for USP4 Gene

  • Hydrolase that deubiquitinates target proteins such as the receptor ADORA2A, PDPK1 and TRIM21. Deubiquitination of ADORA2A increases the amount of functional receptor at the cell surface. May regulate mRNA splicing through deubiquitination of the U4 spliceosomal protein PRPF3. This may prevent its recognition by the U5 component PRPF8 thereby destabilizing interactions within the U4/U6.U5 snRNP. May also play a role in the regulation of quality control in the ER.

Gene Wiki entry for USP4 Gene

No data available for CIViC summary , Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for USP4 Gene

Genomics for USP4 Gene

Regulatory Elements for USP4 Gene

Enhancers for USP4 Gene
GeneHancer Identifier Enhancer Score Enhancer Sources Gene-Enhancer Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Gene Targets for Enhancer
GH03G049338 1.9 FANTOM5 ENCODE dbSUPER 15 -5.3 -5338 14.7 MLX CREB3L1 ZFP64 DMAP1 YY1 SLC30A9 ZNF143 ZNF263 SP3 NFYC AMT QRICH1 IMPDH2 DALRD3 RHOA WDR6 NICN1 USP4 ENSG00000230454 RHOA-IT1
GH03G049248 1.4 FANTOM5 Ensembl ENCODE 19.8 +91.8 91783 1.5 ATF1 JUN MAX CEBPG ZNF366 EGR1 CREM HLF CEBPB ATF2 AMT WDR6 USP4 C3orf62 LAMB2 KLHDC8B CCDC71 DALRD3 RHOA ARIH2
GH03G049409 1.6 Ensembl ENCODE dbSUPER 11.4 -73.1 -73095 8.9 HDGF PKNOX1 FOXA2 ARNT CREB3L1 SIN3A ARID4B DMAP1 YY1 SLC30A9 AMT CCDC71 WDR6 SEMA3F-AS1 QRICH1 FAM212A RNA5SP130 DAG1 TMEM115 USP4
GH03G049406 1.2 Ensembl dbSUPER 14.8 -66.4 -66390 2.2 HDGF ARNT ZNF121 ZNF207 FOS NCOA1 JUNB TBX21 ZNF592 MEF2D AMT USP4 C3orf62 CCDC71 KLHDC8B MST1 TCTA RHOA-IT1
GH03G049217 1.3 Ensembl ENCODE 11.4 +122.0 122031 2.1 FOXA2 MLX ZNF133 ARID4B DMAP1 ZNF48 GTF3C2 SLC30A9 FOS SP5 AMT WDR6 QRICH1 CCDC71 NME6 MRPS18AP1 ZNF589 SEMA3F-AS1 RHOA-IT1 CCDC36
- Elite enhancer and/or Elite enhancer-gene association Download GeneHancer data dump

Enhancers around USP4 on UCSC Golden Path with GeneCards custom track

Promoters for USP4 Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters
ENSR00000152206 303 1601 HDGF FOXA2 MLX CREB3L1 ARNT ZFP64 ARID4B SIN3A DMAP1 ZNF2

Genomic Location for USP4 Gene

Chromosome:
3
Start:
49,277,144 bp from pter
End:
49,340,712 bp from pter
Size:
63,569 bases
Orientation:
Minus strand

Genomic View for USP4 Gene

Genes around USP4 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
USP4 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for USP4 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for USP4 Gene

Proteins for USP4 Gene

  • Protein details for USP4 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q13107-UBP4_HUMAN
    Recommended name:
    Ubiquitin carboxyl-terminal hydrolase 4
    Protein Accession:
    Q13107
    Secondary Accessions:
    • A8K6Y0
    • C9IY91
    • O43452
    • O43453
    • Q08AK8

    Protein attributes for USP4 Gene

    Size:
    963 amino acids
    Molecular mass:
    108565 Da
    Quaternary structure:
    • Interacts with RB1 (both dephosphorylated and hypophosphorylated forms). Interacts with RBL1 and RBL2. Interacts with ADORA2A (via cytoplasmic C-terminus); the interaction is direct. Interacts with SART3; recruits USP4 to its substrate PRPF3.

    Three dimensional structures from OCA and Proteopedia for USP4 Gene

    Alternative splice isoforms for USP4 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for USP4 Gene

Selected DME Specific Peptides for USP4 Gene

Q13107:
  • DSRWFKQWKKYVGFDSWD
  • QPQKKKK
  • SARPYVYDLIAVSNHYGAMGVGHYTAYAKN
  • AAYVLFY
  • RLWNKYMSNT
  • HQQATKK
  • RNDSVIVD
  • TLPVYFRE
  • LKEHLIDELDY
  • CIELFTT
  • FLLDGLH
  • RDDIFVYEV
  • KWYYFDD
  • QPGLCGL
  • FHGLFKSTLVCPECAK
  • NEDGTWPR
  • GNTCFMN
  • RFAPQFSG
  • FVKHCKVEVYL
  • QQQDSQELL
  • NPLGMKGE
  • DGLHEDLN
  • DPWYCPNCK
  • NLGNTCF
  • YAELIKQMWSG

Post-translational modifications for USP4 Gene

  • Monoubiquitinated by TRIM21. Ubiquitination does not lead to its proteasomal degradation. Autodeubiquitinated.
  • Ubiquitination at Lys186, posLast=632632, posLast=811811, and Lys837
  • Modification sites at PhosphoSitePlus

Other Protein References for USP4 Gene

Domains & Families for USP4 Gene

Gene Families for USP4 Gene

Suggested Antigen Peptide Sequences for USP4 Gene

Graphical View of Domain Structure for InterPro Entry

Q13107

UniProtKB/Swiss-Prot:

UBP4_HUMAN :
  • The Ubiquitin-like domain 2 inserts into the catalytic domain and competes with the ubiquitin substrate, partially inhibiting DUB activity.
  • Belongs to the peptidase C19 family. USP4 subfamily.
Domain:
  • The Ubiquitin-like domain 2 inserts into the catalytic domain and competes with the ubiquitin substrate, partially inhibiting DUB activity.
Family:
  • Belongs to the peptidase C19 family. USP4 subfamily.
genes like me logo Genes that share domains with USP4: view

Function for USP4 Gene

Molecular function for USP4 Gene

GENATLAS Biochemistry:
ubiquitin-specific protease 4,homolog to murine Unp,with two tissue specific cytoplasmic isoforms,deubiquitin enzyme family
UniProtKB/Swiss-Prot CatalyticActivity:
Thiol-dependent hydrolysis of ester, thioester, amide, peptide and isopeptide bonds formed by the C-terminal Gly of ubiquitin (a 76-residue protein attached to proteins as an intracellular targeting signal).
UniProtKB/Swiss-Prot Function:
Hydrolase that deubiquitinates target proteins such as the receptor ADORA2A, PDPK1 and TRIM21. Deubiquitination of ADORA2A increases the amount of functional receptor at the cell surface. May regulate mRNA splicing through deubiquitination of the U4 spliceosomal protein PRPF3. This may prevent its recognition by the U5 component PRPF8 thereby destabilizing interactions within the U4/U6.U5 snRNP. May also play a role in the regulation of quality control in the ER.

Enzyme Numbers (IUBMB) for USP4 Gene

Gene Ontology (GO) - Molecular Function for USP4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004843 thiol-dependent ubiquitin-specific protease activity IDA,IEA 16316627
GO:0005515 protein binding IPI 16339847
GO:0008233 peptidase activity IEA --
GO:0008234 cysteine-type peptidase activity IEA --
GO:0016787 hydrolase activity IEA --
genes like me logo Genes that share ontologies with USP4: view
genes like me logo Genes that share phenotypes with USP4: view

Animal Models for USP4 Gene

MGI Knock Outs for USP4:

Animal Model Products

  • Taconic Biosciences Mouse Models for USP4

CRISPR Products

miRNA for USP4 Gene

miRTarBase miRNAs that target USP4

Inhibitory RNA Products

Clone Products

No data available for Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for USP4 Gene

Localization for USP4 Gene

Subcellular locations from UniProtKB/Swiss-Prot for USP4 Gene

Cytoplasm. Nucleus. Note=Shuttles between the nucleus and cytoplasm. Exported to the cytoplasm in a CRM1-dependent manner and recycled back to the nucleus via the importin alpha/beta heterodimeric import receptor. The relative amounts found in the nucleus and cytoplasm vary according to the cell type. {ECO:0000269 PubMed:16316627, ECO:0000269 PubMed:20595234}.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for USP4 gene
Compartment Confidence
plasma membrane 5
nucleus 5
cytosol 5
lysosome 4
extracellular 1

Gene Ontology (GO) - Cellular Components for USP4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IDA,IEA 16339847
GO:0005737 cytoplasm IDA,IEA 16316627
GO:0005764 lysosome TAS 9827704
GO:0005829 cytosol TAS --
GO:0005886 plasma membrane IDA --
genes like me logo Genes that share ontologies with USP4: view

Pathways & Interactions for USP4 Gene

genes like me logo Genes that share pathways with USP4: view

Pathways by source for USP4 Gene

1 Qiagen pathway for USP4 Gene

Gene Ontology (GO) - Biological Process for USP4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000244 spliceosomal tri-snRNP complex assembly IMP 20595234
GO:0006508 proteolysis IEA --
GO:0006511 ubiquitin-dependent protein catabolic process IEA --
GO:0016579 protein deubiquitination TAS --
GO:0031397 negative regulation of protein ubiquitination IMP 16472766
genes like me logo Genes that share ontologies with USP4: view

No data available for SIGNOR curated interactions for USP4 Gene

Drugs & Compounds for USP4 Gene

(2) Drugs for USP4 Gene - From: ApexBio and HMDB

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Water Approved Pharma 0
PR-619 Pharma Deubiquitylating enzymes (DBUs) inhibitor, Broad spectrum DUB inhibitor 0

(1) ApexBio Compounds for USP4 Gene

Compound Action Cas Number
PR-619 Deubiquitylating enzymes (DBUs) inhibitor 2645-32-1
genes like me logo Genes that share compounds with USP4: view

Drug Products

Transcripts for USP4 Gene

Unigene Clusters for USP4 Gene

Ubiquitin specific peptidase 4 (proto-oncogene):
Representative Sequences:

CRISPR Products

Inhibitory RNA Products

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for USP4 Gene

ExUns: 1 ^ 2a · 2b ^ 3 ^ 4 ^ 5a · 5b ^ 6a · 6b ^ 7 ^ 8a · 8b ^ 9a · 9b ^ 10a · 10b · 10c ^ 11 ^ 12 ^ 13a · 13b ^ 14a · 14b ^ 15a · 15b ^ 16 ^
SP1: - - - - -
SP2: - - - - - - -
SP3:
SP4:
SP5: - -
SP6:
SP7: - -
SP8:
SP9: - -
SP10:
SP11: - - -

ExUns: 17a · 17b ^ 18 ^ 19a · 19b ^ 20 ^ 21 ^ 22a · 22b · 22c ^ 23 ^ 24 ^ 25 ^ 26a · 26b
SP1: - -
SP2: - -
SP3: - -
SP4: - - - - -
SP5: - -
SP6:
SP7:
SP8:
SP9:
SP10:
SP11:

Relevant External Links for USP4 Gene

GeneLoc Exon Structure for
USP4
ECgene alternative splicing isoforms for
USP4

Expression for USP4 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for USP4 Gene

Protein differential expression in normal tissues from HIPED for USP4 Gene

This gene is overexpressed in Monocytes (9.5), Peripheral blood mononuclear cells (6.5), CD8 Tcells (6.0), and Lymph node (6.0).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, MaxQB, and MOPED for USP4 Gene



Protein tissue co-expression partners for USP4 Gene

- Elite partner

NURSA nuclear receptor signaling pathways regulating expression of USP4 Gene:

USP4

SOURCE GeneReport for Unigene cluster for USP4 Gene:

Hs.77500

mRNA Expression by UniProt/SwissProt for USP4 Gene:

Q13107-UBP4_HUMAN
Tissue specificity: Overexpressed in small cell tumors and adenocarcinomas of the lung compared to wild-type lung (at protein level). Expressed in the hippocampal neurons.

Evidence on tissue expression from TISSUES for USP4 Gene

  • Nervous system(4.8)
  • Blood(4.3)
  • Intestine(3)
genes like me logo Genes that share expression patterns with USP4: view

Primer Products

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , mRNA differential expression in normal tissues and Phenotype-based relationships between genes and organs from Gene ORGANizer for USP4 Gene

Orthologs for USP4 Gene

This gene was present in the common ancestor of eukaryotes.

Orthologs for USP4 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia USP4 34 35
  • 99.72 (n)
dog
(Canis familiaris)
Mammalia USP4 34 35
  • 91.45 (n)
cow
(Bos Taurus)
Mammalia USP4 34 35
  • 89.96 (n)
mouse
(Mus musculus)
Mammalia Usp4 34 16 35
  • 87.84 (n)
rat
(Rattus norvegicus)
Mammalia Usp4 34
  • 87.06 (n)
oppossum
(Monodelphis domestica)
Mammalia -- 35
  • 86 (a)
OneToMany
-- 35
  • 84 (a)
OneToMany
platypus
(Ornithorhynchus anatinus)
Mammalia USP4 35
  • 76 (a)
OneToOne
chicken
(Gallus gallus)
Aves USP4 34 35
  • 70.15 (n)
lizard
(Anolis carolinensis)
Reptilia USP4 35
  • 70 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia usp4 34
  • 68.55 (n)
Str.10806 34
African clawed frog
(Xenopus laevis)
Amphibia LOC398480 34
zebrafish
(Danio rerio)
Actinopterygii usp4 34 35
  • 67.34 (n)
-- 34
fruit fly
(Drosophila melanogaster)
Insecta CG30421 36
  • 36 (a)
worm
(Caenorhabditis elegans)
Secernentea H34C03.2 36 34 35
  • 50.19 (n)
F07A11.4 36
  • 30 (a)
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes UBP12 35
  • 21 (a)
OneToMany
thale cress
(Arabidopsis thaliana)
eudicotyledons UBP5 34
  • 47.21 (n)
sea squirt
(Ciona savignyi)
Ascidiacea CSA.2770 35
  • 42 (a)
OneToMany
Species where no ortholog for USP4 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for USP4 Gene

ENSEMBL:
Gene Tree for USP4 (if available)
TreeFam:
Gene Tree for USP4 (if available)

Paralogs for USP4 Gene

Paralogs for USP4 Gene

(5) SIMAP similar genes for USP4 Gene using alignment to 5 proteins:

Pseudogenes.org Pseudogenes for USP4 Gene

genes like me logo Genes that share paralogs with USP4: view

Variants for USP4 Gene

Sequence variations from dbSNP and Humsavar for USP4 Gene

SNP ID Clin Chr 03 pos Sequence Context AA Info Type
rs1000096292 -- 49,339,760(+) TTTCC(C/G)AGAGC intron-variant
rs1000274103 -- 49,316,636(+) ATTCA(A/T)TCATT intron-variant, utr-variant-3-prime
rs1000346645 -- 49,336,555(+) GTTTC(A/G)CTCTT intron-variant
rs1000375290 -- 49,328,776(+) AATTG(C/T)TTGAA intron-variant
rs1000402604 -- 49,309,488(+) CCTGG(C/T)CTCAA intron-variant

Structural Variations from Database of Genomic Variants (DGV) for USP4 Gene

Variant ID Type Subtype PubMed ID
esv3596124 CNV loss 21293372
nsv1008750 CNV gain 25217958
nsv507094 OTHER sequence alteration 20534489
nsv512800 CNV insertion 21212237

Variation tolerance for USP4 Gene

Residual Variation Intolerance Score: 19.7% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 2.90; 48.76% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for USP4 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
USP4

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for USP4 Gene

Disorders for USP4 Gene

Relevant External Links for USP4

Genetic Association Database (GAD)
USP4
Human Genome Epidemiology (HuGE) Navigator
USP4
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
USP4

No disorders were found for USP4 Gene.

No data available for MalaCards , UniProtKB/Swiss-Prot and Genatlas for USP4 Gene

Publications for USP4 Gene

  1. The human UNP locus at 3p21.31 encodes two tissue-selective, cytoplasmic isoforms with deubiquitinating activity that have reduced expression in small cell lung carcinoma cell lines. (PMID: 9464533) Frederick A. … Chiu M.I. (Oncogene 1998) 2 3 4 64
  2. Elevated expression of Unph, a proto-oncogene at 3p21.3, in human lung tumors. (PMID: 7784062) Gray D.A. … Takahashi T. (Oncogene 1995) 3 4 22 64
  3. Ubiquitin-specific protease 4 inhibits mono-ubiquitination of the master growth factor signaling kinase PDK1. (PMID: 22347420) Uras I.Z. … Nijman S.M. (PLoS ONE 2012) 3 4 64
  4. Identification of neuroglycan C and interacting partners as potential susceptibility genes for schizophrenia in a Southern Chinese population. (PMID: 19367581) So H.C. … Sham P.C. (Am. J. Med. Genet. B Neuropsychiatr. Genet. 2010) 3 46 64
  5. Association analysis of 3p21 with Crohn's disease in a New Zealand population. (PMID: 20307617) Morgan A.R. … Ferguson L.R. (Hum. Immunol. 2010) 3 46 64

Products for USP4 Gene

Sources for USP4 Gene

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