USP5
Ubiquitin carboxyl-terminal hydrolase 5
Also known as: IsoT, UBP5_HUMAN
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- P45974
- Gene
- USP5
- Ensembl
- ENSG00000111667
- Chromosome
- 12
- Canonical length
- 858 aa
- Protein class
- Enzymes, Metabolic proteins, Plasma proteins, Predicted intracellular proteins
- Subcellular location
- Nucleoplasm,Cytosol
- Quaternary structure
- Homodimer
OverviewNCBI Gene
Ubiquitin (see MIM 191339)-dependent proteolysis is a complex pathway of protein metabolism implicated in such diverse cellular functions as maintenance of chromatin structure, receptor function, and degradation of abnormal proteins. A late step of the process involves disassembly of the polyubiquitin chains on degraded proteins into ubiquitin monomers. USP5 disassembles branched polyubiquitin chains by a sequential exo mechanism, starting at the proximal end of the chain (Wilkinson et al., 1995 [PubMed 7578059]).[supplied by OMIM, Mar 2010]
Canonical amino-acid sequenceUniProt
858 residues, UniProt reviewed canonical sequence.
>P45974|USP5
1 MAELSEEALL SVLPTIRVPK AGDRVHKDEC AFSFDTPESE GGLYICMNTF LGFGKQYVER
61 HFNKTGQRVY LHLRRTRRPK EEDPATGTGD PPRKKPTRLA IGVEGGFDLS EEKFELDEDV
121 KIVILPDYLE IARDGLGGLP DIVRDRVTSA VEALLSADSA SRKQEVQAWD GEVRQVSKHA
181 FSLKQLDNPA RIPPCGWKCS KCDMRENLWL NLTDGSILCG RRYFDGSGGN NHAVEHYRET
241 GYPLAVKLGT ITPDGADVYS YDEDDMVLDP SLAEHLSHFG IDMLKMQKTD KTMTELEIDM
301 NQRIGEWELI QESGVPLKPL FGPGYTGIRN LGNSCYLNSV VQVLFSIPDF QRKYVDKLEK
361 IFQNAPTDPT QDFSTQVAKL GHGLLSGEYS KPVPESGDGE RVPEQKEVQD GIAPRMFKAL
421 IGKGHPEFST NRQQDAQEFF LHLINMVERN CRSSENPNEV FRFLVEEKIK CLATEKVKYT
481 QRVDYIMQLP VPMDAALNKE ELLEYEEKKR QAEEEKMALP ELVRAQVPFS SCLEAYGAPE
541 QVDDFWSTAL QAKSVAVKTT RFASFPDYLV IQIKKFTFGL DWVPKKLDVS IEMPEELDIS
601 QLRGTGLQPG EEELPDIAPP LVTPDEPKGS LGFYGNEDED SFCSPHFSSP TSPMLDESVI
661 IQLVEMGFPM DACRKAVYYT GNSGAEAAMN WVMSHMDDPD FANPLILPGS SGPGSTSAAA
721 DPPPEDCVTT IVSMGFSRDQ ALKALRATNN SLERAVDWIF SHIDDLDAEA AMDISEGRSA
781 ADSISESVPV GPKVRDGPGK YQLFAFISHM GTSTMCGHYV CHIKKEGRWV IYNDQKVCAS
841 EKPPKDLGYI YFYQRVASLocalizationUniProt · AlphaFold · HPA
Whether an antibody against USP5 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)
- 0.31
- Highest tissue expression
- 64 nTPM
Expression across tissuesHPA
Tissue
- skeletal muscle: 64 nTPM
- cerebral cortex: 49 nTPM
- skin: 46 nTPM
- tongue: 40 nTPM
- parathyroid gland: 39 nTPM
- testis: 38 nTPM
Single-cell type
- late primary spermatocytes: 100 nCPM
- syncytiotrophoblasts: 69 nCPM
- cytotrophoblasts: 56 nCPM
- esophageal suprabasal cells: 52 nCPM
- esophageal basal cells: 51 nCPM
- migrating cytotrophoblasts: 46 nCPM
Immune cell
- myeloid DC: 28 nTPM
- total PBMC: 28 nTPM
- intermediate monocyte: 25 nTPM
- non-classical monocyte: 25 nTPM
- gdT-cell: 24 nTPM
- MAIT T-cell: 23 nTPM
Brain region
- pons: 118 nTPM
- cerebral cortex: 113 nTPM
- hypothalamus: 106 nTPM
- midbrain: 102 nTPM
- medulla oblongata: 101 nTPM
- thalamus: 96 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)
- 0.32
- gnomAD pLI
- 0.96
- gnomAD missense Z
- 3.36
- DepMap mean gene effect
- -1.36
- DepMap dependency class
- pan
Cancer expressionTCGA
Across TCGA tumor cohorts, this protein is over-expressed in roughly 9% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).
OntologyGO
Biological processes
- negative regulation of proteasomal ubiquitin-dependent protein catabolic process
- negative regulation of T cell mediated immune response to tumor cell
- negative regulation of ubiquitin-dependent protein catabolic process
- positive regulation of proteasomal ubiquitin-dependent protein catabolic process
- protein deubiquitination
- protein K48-linked deubiquitination
- protein ubiquitination
- proteolysis
- regulation of protein stability
- regulation protein catabolic process at presynapse
Molecular functions
- cysteine-type deubiquitinase activity
- cysteine-type endopeptidase activity
- deubiquitinase activity
- ubiquitin binding
- zinc ion binding
Cellular components
Protein domainsUniProt · Pfam · InterPro
- Peptidase C19, ubiquitin carboxyl-terminal hydrolase
- Zinc finger, UBP-type
- UBA-like superfamily
- Zinc finger, RING/FYVE/PHD-type
- Ubiquitin-associated domain
- Ubiquitinyl hydrolase
- Ubiquitin specific protease, conserved site
- Ubiquitin specific protease UPS, catalytic domain
- Papain-like cysteine peptidase superfamily
- Ubiquitinyl hydrolase, variant UBP zinc finger
- Ubiquitin carboxyl-terminal hydrolase
- Ubiquitin carboxyl-terminal hydrolase
- UBA/TS-N domain
- Zn-finger in ubiquitin-hydrolases and other protein
- Variant UBP zinc finger
- Ubiquitin carboxyl-terminal hydrolase 5, UBA1 domain
KeywordsUniProt
InteractionsUniProt · HPA
Protein binding partners of USP5 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 USP5 as an antibody target. Whether an autoantibody or antibody against USP5 could matter depends on whether native USP5 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
USP5 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 USP5 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
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