USP25
Ubiquitin carboxyl-terminal hydrolase 25
Also known as: UBP25_HUMAN, USP21
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- Q9UHP3
- Gene
- USP25
- Ensembl
- ENSG00000155313
- Chromosome
- 21
- Canonical length
- 1055 aa
- Protein class
- Enzymes, Metabolic proteins, Plasma proteins, Predicted intracellular proteins
- Subcellular location
- Cytosol
- Quaternary structure
- Homotetramer
OverviewNCBI Gene
Ubiquitin (MIM 191339) is a highly conserved 76-amino acid protein involved in regulation of intracellular protein breakdown, cell cycle regulation, and stress response. Ubiquitin is released from degraded proteins by disassembly of the polyubiquitin chains, which is mediated by ubiquitin-specific proteases (USPs), such as USP25 (Valero et al., 1999 [PubMed 10644437]).[supplied by OMIM, Mar 2008]
Canonical amino-acid sequenceUniProt
1055 residues, UniProt reviewed canonical sequence.
>Q9UHP3|USP25
1 MTVEQNVLQQ SAAQKHQQTF LNQLREITGI NDTQILQQAL KDSNGNLELA VAFLTAKNAK
61 TPQQEETTYY QTALPGNDRY ISVGSQADTN VIDLTGDDKD DLQRAIALSL AESNRAFRET
121 GITDEEQAIS RVLEASIAEN KACLKRTPTE VWRDSRNPYD RKRQDKAPVG LKNVGNTCWF
181 SAVIQSLFNL LEFRRLVLNY KPPSNAQDLP RNQKEHRNLP FMRELRYLFA LLVGTKRKYV
241 DPSRAVEILK DAFKSNDSQQ QDVSEFTHKL LDWLEDAFQM KAEEETDEEK PKNPMVELFY
301 GRFLAVGVLE GKKFENTEMF GQYPLQVNGF KDLHECLEAA MIEGEIESLH SENSGKSGQE
361 HWFTELPPVL TFELSRFEFN QALGRPEKIH NKLEFPQVLY LDRYMHRNRE ITRIKREEIK
421 RLKDYLTVLQ QRLERYLSYG SGPKRFPLVD VLQYALEFAS SKPVCTSPVD DIDASSPPSG
481 SIPSQTLPST TEQQGALSSE LPSTSPSSVA AISSRSVIHK PFTQSRIPPD LPMHPAPRHI
541 TEEELSVLES CLHRWRTEIE NDTRDLQESI SRIHRTIELM YSDKSMIQVP YRLHAVLVHE
601 GQANAGHYWA YIFDHRESRW MKYNDIAVTK SSWEELVRDS FGGYRNASAY CLMYINDKAQ
661 FLIQEEFNKE TGQPLVGIET LPPDLRDFVE EDNQRFEKEL EEWDAQLAQK ALQEKLLASQ
721 KLRESETSVT TAQAAGDPEY LEQPSRSDFS KHLKEETIQI ITKASHEHED KSPETVLQSA
781 IKLEYARLVK LAQEDTPPET DYRLHHVVVY FIQNQAPKKI IEKTLLEQFG DRNLSFDERC
841 HNIMKVAQAK LEMIKPEEVN LEEYEEWHQD YRKFRETTMY LIIGLENFQR ESYIDSLLFL
901 ICAYQNNKEL LSKGLYRGHD EELISHYRRE CLLKLNEQAA ELFESGEDRE VNNGLIIMNE
961 FIVPFLPLLL VDEMEEKDIL AVEDMRNRWC SYLGQEMEPH LQEKLTDFLP KLLDCSMEIK
1021 SFHEPPKLPS YSTHELCERF ARIMLSLSRT PADGRLocalizationUniProt · AlphaFold · HPA
Whether an antibody against USP25 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)
- 0.35
- Highest tissue expression
- 113 nTPM
Expression across tissuesHPA
Tissue
- skeletal muscle: 113 nTPM
- tongue: 71 nTPM
- testis: 51 nTPM
- smooth muscle: 34 nTPM
- placenta: 27 nTPM
- heart muscle: 26 nTPM
Single-cell type
- thymic myoid cells: 379 nCPM
- myonuclei: 375 nCPM
- distal convoluted tubule cells: 360 nCPM
- neutrophils: 358 nCPM
- late spermatids: 335 nCPM
- loop of henle epithelial cells: 289 nCPM
Immune cell
- memory CD8 T-cell: 3.2 nTPM
- neutrophil: 2.9 nTPM
- T-reg: 2.2 nTPM
- naive CD8 T-cell: 2.1 nTPM
- eosinophil: 2 nTPM
- MAIT T-cell: 2 nTPM
Brain region
- basal ganglia: 58 nTPM
- cerebral cortex: 51 nTPM
- amygdala: 43 nTPM
- cerebellum: 43 nTPM
- choroid plexus: 42 nTPM
- hippocampal formation: 41 nTPM
DiseaseUniProt · ClinVar · IEDB · PubMed
Four sources answering four different questions about USP25.
Disease | AllUniProt
Conditions USP25 is implicated in, by any mechanism.
- Epilepsy, idiopathic generalized 19 (EIG19) MIM:621064
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)
- 0.33
- gnomAD pLI
- 0.75
- gnomAD missense Z
- 1.24
- DepMap mean gene effect
- 0.05
- DepMap dependency class
- selective
Cancer expressionTCGA
Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).
OntologyGO
Biological processes
- negative regulation of ERAD pathway
- negative regulation of response to oxidative stress
- protein deubiquitination
- protein K48-linked deubiquitination
- protein K63-linked deubiquitination
- protein modification process
- proteolysis
- regulation of protein stability
- negative regulation of interleukin-17-mediated signaling pathway
Molecular functions
- ATPase binding
- cysteine-type deubiquitinase activity
- deubiquitinase activity
- peptidase activity
- SUMO binding
- ubiquitin binding
- ubiquitin protein ligase binding
- ubiquitin-like protein peptidase activity
Cellular components
Protein domainsUniProt · Pfam · InterPro
- Peptidase C19, ubiquitin carboxyl-terminal hydrolase
- Ubiquitin interacting motif
- UBA-like superfamily
- Ubiquitin specific protease, conserved site
- Ubiquitin specific protease UPS, catalytic domain
- Papain-like cysteine peptidase superfamily
- Ubiquitin carboxyl-terminal hydrolases
- Ubiquitin carboxyl-terminal hydrolase 25/28, UIM
- UBA-like domain
- Ubiquitin carboxyl-terminal hydrolase
- Ubiquitin-specific protease UIM domain
- UBA-like domain
KeywordsUniProt
InteractionsUniProt · HPA
Protein binding partners of USP25 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 USP25 as an antibody target. Whether an autoantibody or antibody against USP25 could matter depends on whether native USP25 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
USP25 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 USP25 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
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