Seroatlas · Human Serome Atlas

USP18

Ubl carboxyl-terminal hydrolase 18

Also known as: UBP18_HUMAN

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

Protein identityUniProt · HPA

UniProt accession
Q9UMW8
Gene
USP18
Ensembl
ENSG00000184979
Chromosome
22
Canonical length
372 aa
Protein class
Disease related genes, Enzymes, Human disease related genes, Metabolic proteins, Potential drug targets, Predicted intracellular proteins
Subcellular location
Vesicles,Cytosol

OverviewNCBI Gene

The protein encoded by this gene belongs to the ubiquitin-specific proteases (UBP) family of enzymes that cleave ubiquitin from ubiquitinated protein substrates. It is highly expressed in liver and thymus, and is localized to the nucleus. This protein efficiently cleaves only ISG15 (a ubiquitin-like protein) fusions, and deletion of this gene in mice results in a massive increase of ISG15 conjugates in tissues, indicating that this protein is a major ISG15-specific protease. Mice lacking this gene are also hypersensitive to interferon, suggesting a function of this protein in downregulating interferon responses, independent of its isopeptidase activity towards ISG15. [provided by RefSeq, Sep 2011]

Canonical amino-acid sequenceUniProt

372 residues, UniProt reviewed canonical sequence.

>Q9UMW8|USP18
     1  MSKAFGLLRQ ICQSILAESS QSPADLEEKK EEDSNMKREQ PRERPRAWDY PHGLVGLHNI
    61  GQTCCLNSLI QVFVMNVDFT RILKRITVPR GADEQRRSVP FQMLLLLEKM QDSRQKAVRP
   121  LELAYCLQKC NVPLFVQHDA AQLYLKLWNL IKDQITDVHL VERLQALYTI RVKDSLICVD
   181  CAMESSRNSS MLTLPLSLFD VDSKPLKTLE DALHCFFQPR ELSSKSKCFC ENCGKKTRGK
   241  QVLKLTHLPQ TLTIHLMRFS IRNSQTRKIC HSLYFPQSLD FSQILPMKRE SCDAEEQSGG
   301  QYELFAVIAH VGMADSGHYC VYIRNAVDGK WFCFNDSNIC LVSWEDIQCT YGNPNYHWQE
   361  TAYLLVYMKM EC

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against USP18 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)
0.33
Highest tissue expression
21 nTPM

Expression across tissuesHPA

Tissue

  • liver: 21 nTPM
  • thymus: 14 nTPM
  • salivary gland: 13 nTPM
  • adipose tissue: 11 nTPM
  • spleen: 9.8 nTPM
  • breast: 9.1 nTPM

Single-cell type

  • oocytes: 60 nCPM
  • endometrial ciliated cells: 21 nCPM
  • tuft cells: 12 nCPM
  • gonadotrophs: 7.8 nCPM
  • fibro-adipogenic progenitors: 7.3 nCPM
  • pituitary stem cells: 7.2 nCPM

Immune cell

  • NK-cell: 13 nTPM
  • T-reg: 13 nTPM
  • memory CD8 T-cell: 11 nTPM
  • intermediate monocyte: 11 nTPM
  • MAIT T-cell: 11 nTPM
  • naive CD8 T-cell: 9.5 nTPM

Brain region

  • spinal cord: 9.1 nTPM
  • medulla oblongata: 5.8 nTPM
  • pons: 4.2 nTPM
  • thalamus: 4.2 nTPM
  • hypothalamus: 3.9 nTPM
  • choroid plexus: 3.8 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about USP18.

Disease | AllUniProt

Conditions USP18 is implicated in, by any mechanism.

Disease | GeneticClinVar

4 pathogenic / likely-pathogenic of 85 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

  • Pseudo-TORCH syndrome 2

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)
0.74
gnomAD pLI
0
gnomAD missense Z
0.84
DepMap mean gene effect
-0.42
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

Molecular functions

Cellular components

Protein domainsUniProt · Pfam · InterPro

KeywordsUniProt

InteractionsUniProt · HPA

Protein binding partners of USP18 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 USP18 as an antibody target. Whether an autoantibody or antibody against USP18 could matter depends on whether native USP18 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

USP18 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 USP18 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

Canonical record: https://seroatlas.com/gene/USP18. Study-independent annotations aggregated from UniProt, Human Protein Atlas, PubMed, IEDB, Pfam, InterPro, Gene Ontology, AlphaFold, gnomAD, DepMap, ClinVar, TCGA. Catalog release seroatlas-reviewed-human-uniprot-20260313.

Seroatlas is the reference for exploring autoantibody and antibody serology at the human-protein level: the autoreactome and human serome, multiplex serology (HuProt, HuScan, VirScan, PhIP-Seq).

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