USP4
Ubiquitin carboxyl-terminal hydrolase 4
Also known as: UBP4_HUMAN, UNP, Unph
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- Q13107
- Gene
- USP4
- Ensembl
- ENSG00000114316
- Chromosome
- 3
- Canonical length
- 963 aa
- Protein class
- Enzymes, Metabolic proteins, Predicted intracellular proteins
- Subcellular location
- Nucleoplasm,Vesicles,Basal body,Cytosol
OverviewNCBI 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]
Canonical amino-acid sequenceUniProt
963 residues, UniProt reviewed canonical sequence.
>Q13107|USP4
1 MAEGGGCRER PDAETQKSEL GPLMRTTLQR GAQWYLIDSR WFKQWKKYVG FDSWDMYNVG
61 EHNLFPGPID NSGLFSDPES QTLKEHLIDE LDYVLVPTEA WNKLLNWYGC VEGQQPIVRK
121 VVEHGLFVKH CKVEVYLLEL KLCENSDPTN VLSCHFSKAD TIATIEKEMR KLFNIPAERE
181 TRLWNKYMSN TYEQLSKLDN TVQDAGLYQG QVLVIEPQNE DGTWPRQTLQ SKSSTAPSRN
241 FTTSPKSSAS PYSSVSASLI ANGDSTSTCG MHSSGVSRGG SGFSASYNCQ EPPSSHIQPG
301 LCGLGNLGNT CFMNSALQCL SNTAPLTDYF LKDEYEAEIN RDNPLGMKGE IAEAYAELIK
361 QMWSGRDAHV APRMFKTQVG RFAPQFSGYQ QQDSQELLAF LLDGLHEDLN RVKKKPYLEL
421 KDANGRPDAV VAKEAWENHR LRNDSVIVDT FHGLFKSTLV CPECAKVSVT FDPFCYLTLP
481 LPLKKDRVME VFLVPADPHC RPTQYRVTVP LMGAVSDLCE ALSRLSGIAA ENMVVADVYN
541 HRFHKIFQMD EGLNHIMPRD DIFVYEVCST SVDGSECVTL PVYFRERKSR PSSTSSASAL
601 YGQPLLLSVP KHKLTLESLY QAVCDRISRY VKQPLPDEFG SSPLEPGACN GSRNSCEGED
661 EEEMEHQEEG KEQLSETEGS GEDEPGNDPS ETTQKKIKGQ PCPKRLFTFS LVNSYGTADI
721 NSLAADGKLL KLNSRSTLAM DWDSETRRLY YDEQESEAYE KHVSMLQPQK KKKTTVALRD
781 CIELFTTMET LGEHDPWYCP NCKKHQQATK KFDLWSLPKI LVVHLKRFSY NRYWRDKLDT
841 VVEFPIRGLN MSEFVCNLSA RPYVYDLIAV SNHYGAMGVG HYTAYAKNKL NGKWYYFDDS
901 NVSLASEDQI VTKAAYVLFY QRRDDEFYKT PSLSSSGSSD GGTRPSSSQQ GFGDDEACSM
961 DTNLocalizationUniProt · AlphaFold · HPA
Whether an antibody against USP4 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.
- Antibody reachability
- Intracellular
- Secreted
- No
- Transmembrane segments
- 0
- Mean surface accessibility (rSASA)
- 0.36
- Highest tissue expression
- 50 nTPM
Expression across tissuesHPA
Tissue
- bone marrow: 50 nTPM
- thymus: 34 nTPM
- choroid plexus: 33 nTPM
- spleen: 32 nTPM
- tonsil: 32 nTPM
- skin: 30 nTPM
Single-cell type
- neutrophils: 498 nCPM
- neutrophil progenitors: 197 nCPM
- early spermatids: 163 nCPM
- late spermatids: 146 nCPM
- monocytes: 142 nCPM
- kupffer cells: 122 nCPM
Immune cell
- neutrophil: 180 nTPM
- eosinophil: 95 nTPM
- classical monocyte: 84 nTPM
- non-classical monocyte: 82 nTPM
- total PBMC: 78 nTPM
- myeloid DC: 75 nTPM
Brain region
- choroid plexus: 41 nTPM
- basal ganglia: 39 nTPM
- cerebral cortex: 38 nTPM
- midbrain: 36 nTPM
- thalamus: 35 nTPM
- white matter: 35 nTPM
Genetic constraint and essentialitygnomAD · DepMap
Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.
- gnomAD LOEUF (loss-of-function intolerance)
- 0.63
- gnomAD pLI
- 0
- gnomAD missense Z
- 1.1
- DepMap mean gene effect
- -0.14
- DepMap dependency class
- selective
Cancer expressionTCGA
Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).
OntologyGO
Biological processes
- negative regulation of protein ubiquitination
- positive regulation of TORC1 signaling
- protein deubiquitination
- protein localization to cell surface
- proteolysis
- regulation of protein stability
- spliceosomal tri-snRNP complex assembly
Molecular functions
- adenosine receptor binding
- cysteine-type deubiquitinase activity
- identical protein binding
- metal ion binding
Cellular components
Protein domainsUniProt · Pfam · InterPro
- Peptidase C19, ubiquitin carboxyl-terminal hydrolase
- Peptidase C19, ubiquitin-specific peptidase, DUSP domain
- Ubiquitin specific protease, conserved site
- Ubiquitin-like domain, USP-type
- Ubiquitin specific protease UPS, catalytic domain
- DUSP-like superfamily
- Papain-like cysteine peptidase superfamily
- Ubiquitin carboxyl-terminal hydrolase
- Ubiquitin carboxyl-terminal hydrolase
- DUSP domain
- Ubiquitin-like domain
KeywordsUniProt
InteractionsUniProt · HPA
Protein binding partners of USP4 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.
Antibody and autoantibody relevanceSeroatlas analysis
Seroatlas reads USP4 as an antibody target. Whether an autoantibody or antibody against USP4 could matter depends on whether native USP4 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
USP4 is annotated as predominantly intracellular. Intracellular proteins are common autoantibody markers, becoming visible to the immune system after cell injury or altered processing, but are usually markers of disease rather than direct drivers.
Annotation status
The present source text does not explicitly label USP4 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
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