Human Gene USP4 (uc003cwq.2) Description and Page Index
  Description: Homo sapiens ubiquitin specific peptidase 4 (proto-oncogene) (USP4), transcript variant 1, mRNA.
RefSeq Summary (NM_003363): 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].
Transcript (Including UTRs)
   Position: hg19 chr3:49,314,577-49,377,536 Size: 62,960 Total Exon Count: 22 Strand: -
Coding Region
   Position: hg19 chr3:49,315,726-49,377,457 Size: 61,732 Coding Exon Count: 22 

Page IndexSequence and LinksUniProtKB CommentsGenetic AssociationsCTDGene Alleles
RNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther SpeciesGO Annotations
mRNA DescriptionsPathwaysOther NamesModel InformationMethods
Data last updated: 2013-06-14

-  Sequence and Links to Tools and Databases
Genomic Sequence (chr3:49,314,577-49,377,536)mRNA (may differ from genome)Protein (963 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
BioGPSCGAPEnsemblEntrez GeneExonPrimerGeneCards
neXtProtOMIMPubMedReactomeStanford SOURCETreefam

-  Comments and Description Text from UniProtKB
DESCRIPTION: RecName: Full=Ubiquitin carboxyl-terminal hydrolase 4; EC=; AltName: Full=Deubiquitinating enzyme 4; AltName: Full=Ubiquitin thioesterase 4; AltName: Full=Ubiquitin-specific-processing protease 4; AltName: Full=Ubiquitous nuclear protein homolog;
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. Plays a role in the regulation of quality control in the ER.
CATALYTIC ACTIVITY: 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).
SUBUNIT: Interacts with RB1 (both dephosphorylated and hypophosphorylated forms). Interacts with ADORA2A (via cytoplasmic C-terminus); the interaction is direct. Interacts with RB1, RBL1 and RBL2.
INTERACTION: P29274:ADORA2A; NbExp=4; IntAct=EBI-723290, EBI-2902702; P19474:TRIM21; NbExp=3; IntAct=EBI-723305, EBI-81290;
SUBCELLULAR LOCATION: Cytoplasm (By similarity). Nucleus (By similarity). 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 (By similarity).
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.
DOMAIN: The Ubiquitin-like domain 2 inserts into the catalytic domain and competes with the ubiquitin substrate, partially inhibiting DUB activity.
PTM: Monoubiquitinated by TRIM21. Ubiquitination does not lead to its proteasomal degradation. Autodeubiquitinated.
SIMILARITY: Belongs to the peptidase C19 family. USP4 subfamily.
SIMILARITY: Contains 1 DUSP domain.
SIMILARITY: Contains 2 ubiquitin-like domains.

-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): USP4
CDC HuGE Published Literature: USP4

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 18.91 RPKM in Cells - EBV-transformed lymphocytes
Total median expression: 530.53 RPKM

View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -40.6079-0.514 Picture PostScript Text
3' UTR -389.861149-0.339 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR006615 - Pept_C19_DUSP
IPR018200 - Pept_C19ubi-hydrolase_C_CS
IPR001394 - Peptidase_C19

Pfam Domains:
PF00443 - Ubiquitin carboxyl-terminal hydrolase
PF01473 - Putative cell wall binding repeat
PF06337 - DUSP domain
PF13423 - Ubiquitin carboxyl-terminal hydrolase
PF14836 - Ubiquitin-like domain

SCOP Domains:
54001 - Cysteine proteinases

Protein Data Bank (PDB) 3-D Structure
MuPIT help

- X-ray MuPIT

ModBase Predicted Comparative 3D Structure on Q13107
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologNo orthologNo orthologNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0004843 thiol-dependent ubiquitin-specific protease activity
GO:0005515 protein binding
GO:0008233 peptidase activity
GO:0008234 cysteine-type peptidase activity
GO:0016787 hydrolase activity
GO:0031685 adenosine receptor binding
GO:0036459 thiol-dependent ubiquitinyl hydrolase activity
GO:0042802 identical protein binding
GO:0046872 metal ion binding

Biological Process:
GO:0000244 spliceosomal tri-snRNP complex assembly
GO:0006508 proteolysis
GO:0006511 ubiquitin-dependent protein catabolic process
GO:0016579 protein deubiquitination
GO:0031397 negative regulation of protein ubiquitination
GO:0031647 regulation of protein stability
GO:0034394 protein localization to cell surface

Cellular Component:
GO:0005634 nucleus
GO:0005737 cytoplasm
GO:0005764 lysosome
GO:0005829 cytosol
GO:0005886 plasma membrane

-  Descriptions from all associated GenBank mRNAs
  BC023586 - Homo sapiens chromosome 3 open reading frame 62, mRNA (cDNA clone MGC:23381 IMAGE:4650297), complete cds.
LQ564494 - Sequence 2 from Patent WO2016135513.
AK222725 - Homo sapiens mRNA for ubiquitin specific protease, proto-oncogene isoform b variant, clone: COL07356.
BC125131 - Homo sapiens ubiquitin specific peptidase 4 (proto-oncogene), mRNA (cDNA clone MGC:149849 IMAGE:40119091), complete cds.
BC125130 - Homo sapiens ubiquitin specific peptidase 4 (proto-oncogene), mRNA (cDNA clone MGC:149848 IMAGE:40119090), complete cds.
U20657 - Human ubiquitin protease (Unph) proto-oncogene mRNA, complete cds.
AK223292 - Homo sapiens mRNA for ubiquitin specific protease, proto-oncogene isoform a variant, clone: SYN05029.
AF017305 - Homo sapiens deubiquitinating enzyme UnpEL (UNP) mRNA, complete cds.
AK127055 - Homo sapiens cDNA FLJ45112 fis, clone BRAWH3034668, highly similar to Ubiquitin carboxyl-terminal hydrolase 4 (EC
AK291795 - Homo sapiens cDNA FLJ78681 complete cds, highly similar to Homo sapiens ubiquitin specific peptidase 4 (proto-oncogene) (USP4), transcript variant 1, mRNA.
JD263797 - Sequence 244821 from Patent EP1572962.
AF017306 - Homo sapiens deubiquitinating enzyme UnpES (UNP) mRNA, complete cds.
KJ905948 - Synthetic construct Homo sapiens clone ccsbBroadEn_15618 USP4 gene, encodes complete protein.
KJ897726 - Synthetic construct Homo sapiens clone ccsbBroadEn_07120 USP4 gene, encodes complete protein.
BC068017 - Homo sapiens ubiquitin specific peptidase 4 (proto-oncogene), mRNA (cDNA clone IMAGE:5215992), with apparent retained intron.
JD449833 - Sequence 430857 from Patent EP1572962.
JD333104 - Sequence 314128 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  Reactome (by CSHL, EBI, and GO)

Protein Q13107 (Reactome details) participates in the following event(s):

R-HSA-8869456 USP4 deubiquitinate TRAF2,TRAF6
R-HSA-5689880 Ub-specific processing proteases
R-HSA-5688426 Deubiquitination
R-HSA-5357905 Regulation of TNFR1 signaling
R-HSA-597592 Post-translational protein modification
R-HSA-75893 TNF signaling
R-HSA-392499 Metabolism of proteins
R-HSA-73887 Death Receptor Signalling
R-HSA-162582 Signal Transduction

-  Other Names for This Gene
  Alternate Gene Symbols: A8K6Y0, NM_003363, NP_003354, O43452, O43453, Q08AK8, Q13107, UBP4_HUMAN, UNP, UNPH
UCSC ID: uc003cwq.2
RefSeq Accession: NM_003363
Protein: Q13107 (aka UBP4_HUMAN)
CCDS: CCDS2793.1, CCDS2794.1

-  Gene Model Information
category: coding nonsense-mediated-decay: no RNA accession: NM_003363.3
exon count: 22CDS single in 3' UTR: no RNA size: 4120
ORF size: 2892CDS single in intron: no Alignment % ID: 100.00
txCdsPredict score: 5839.50frame shift in genome: no % Coverage: 100.00
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: no # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.