Seroatlas · Human Serome Atlas

USP8

Ubiquitin carboxyl-terminal hydrolase 8

Also known as: HumORF8, KIAA0055, SPG59, UBP8_HUMAN, UBPY

Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene

Protein identityUniProt · HPA

UniProt accession: P40818
Gene: USP8
Ensembl: ENSG00000138592
Chromosome: 15
Canonical length: 1118 aa
Protein class: Cancer-related genes, Disease related genes, Enzymes, Human disease related genes, Metabolic proteins, Potential drug targets, Predicted intracellular proteins
Subcellular location: Golgi apparatus,Cytosol

OverviewNCBI Gene

This gene encodes a protein that belongs to the ubiquitin-specific processing protease family of proteins. The encoded protein is thought to regulate the morphology of the endosome by ubiquitination of proteins on this organelle and is involved in cargo sorting and membrane trafficking at the early endosome stage. This protein is required for the cell to enter the S phase of the cell cycle and also functions as a positive regulator in the Hedgehog signaling pathway in development. Pseudogenes of this gene are present on chromosomes 2 and 6. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Sep 2013]

Canonical amino-acid sequenceUniProt

1118 residues, UniProt reviewed canonical sequence.

>P40818|USP8
     1  MPAVASVPKE LYLSSSLKDL NKKTEVKPEK ISTKSYVHSA LKIFKTAEEC RLDRDEERAY
    61  VLYMKYVTVY NLIKKRPDFK QQQDYFHSIL GPGNIKKAVE EAERLSESLK LRYEEAEVRK
   121  KLEEKDRQEE AQRLQQKRQE TGREDGGTLA KGSLENVLDS KDKTQKSNGE KNEKCETKEK
   181  GAITAKELYT MMTDKNISLI IMDARRMQDY QDSCILHSLS VPEEAISPGV TASWIEAHLP
   241  DDSKDTWKKR GNVEYVVLLD WFSSAKDLQI GTTLRSLKDA LFKWESKTVL RNEPLVLEGG
   301  YENWLLCYPQ YTTNAKVTPP PRRQNEEVSI SLDFTYPSLE ESIPSKPAAQ TPPASIEVDE
   361  NIELISGQNE RMGPLNISTP VEPVAASKSD VSPIIQPVPS IKNVPQIDRT KKPAVKLPEE
   421  HRIKSESTNH EQQSPQSGKV IPDRSTKPVV FSPTLMLTDE EKARIHAETA LLMEKNKQEK
   481  ELRERQQEEQ KEKLRKEEQE QKAKKKQEAE ENEITEKQQK AKEEMEKKES EQAKKEDKET
   541  SAKRGKEITG VKRQSKSEHE TSDAKKSVED RGKRCPTPEI QKKSTGDVPH TSVTGDSGSG
   601  KPFKIKGQPE SGILRTGTFR EDTDDTERNK AQREPLTRAR SEEMGRIVPG LPSGWAKFLD
   661  PITGTFRYYH SPTNTVHMYP PEMAPSSAPP STPPTHKAKP QIPAERDREP SKLKRSYSSP
   721  DITQAIQEEE KRKPTVTPTV NRENKPTCYP KAEISRLSAS QIRNLNPVFG GSGPALTGLR
   781  NLGNTCYMNS ILQCLCNAPH LADYFNRNCY QDDINRSNLL GHKGEVAEEF GIIMKALWTG
   841  QYRYISPKDF KITIGKINDQ FAGYSQQDSQ ELLLFLMDGL HEDLNKADNR KRYKEENNDH
   901  LDDFKAAEHA WQKHKQLNES IIVALFQGQF KSTVQCLTCH KKSRTFEAFM YLSLPLASTS
   961  KCTLQDCLRL FSKEEKLTDN NRFYCSHCRA RRDSLKKIEI WKLPPVLLVH LKRFSYDGRW
  1021  KQKLQTSVDF PLENLDLSQY VIGPKNNLKK YNLFSVSNHY GGLDGGHYTA YCKNAARQRW
  1081  FKFDDHEVSD ISVSSVKSSA AYILFYTSLG PRVTDVAT

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against USP8 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: Cell surface
Secreted: No
Transmembrane segments: 0
Mean surface accessibility (rSASA): 0.43
Highest tissue expression: 42 nTPM

Expression across tissuesHPA

Tissue

parathyroid gland: 42 nTPM
testis: 30 nTPM
liver: 26 nTPM
bone marrow: 26 nTPM
duodenum: 25 nTPM
kidney: 25 nTPM

Single-cell type

neutrophils: 456 nCPM
late primary spermatocytes: 267 nCPM
b-cells: 216 nCPM
neutrophil progenitors: 208 nCPM
monocytes: 202 nCPM
syncytiotrophoblasts: 199 nCPM

Immune cell

basophil: 115 nTPM
eosinophil: 50 nTPM
neutrophil: 48 nTPM
memory B-cell: 38 nTPM
non-classical monocyte: 35 nTPM
naive B-cell: 35 nTPM

Brain region

choroid plexus: 53 nTPM
hypothalamus: 45 nTPM
medulla oblongata: 45 nTPM
cerebellum: 45 nTPM
midbrain: 43 nTPM
thalamus: 43 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about USP8.

Disease | AllUniProt

Conditions USP8 is implicated in, by any mechanism.

Pituitary adenoma 4, ACTH-secreting (PITA4) MIM:219090

Disease | GeneticClinVar

5 pathogenic / likely-pathogenic of 216 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

Pituitary dependent hypercortisolism

Disease | ImmuneIEDB

Conditions an epitope on USP8 was assayed in.

narcolepsy B cell
multiple sclerosis B cell
peripheral nervous system disease B cell

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): 0.11
gnomAD pLI: 1
gnomAD missense Z: 1.87
DepMap mean gene effect: -0.79
DepMap dependency class: common

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

Molecular functions

Cellular components

Protein domainsUniProt · Pfam · InterPro

KeywordsUniProt

InteractionsUniProt · HPA

Protein binding partners of USP8 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 USP8 as an antibody target. Whether an autoantibody or antibody against USP8 could matter depends on whether native USP8 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

USP8 is annotated at the cell surface, where native USP8 is exposed to circulating antibodies and is a prime autoantibody target that could block, deplete, or overstimulate it.

Annotation status

The present source text does not explicitly label USP8 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

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