Seroatlas · Human Serome Atlas

USP14

Ubiquitin carboxyl-terminal hydrolase 14

Also known as: TGT, UBP14_HUMAN, Ubp6

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

Protein identityUniProt · HPA

UniProt accession
P54578
Gene
USP14
Ensembl
ENSG00000101557
Chromosome
18
Canonical length
494 aa
Protein class
Enzymes, Metabolic proteins, Plasma proteins, Predicted intracellular proteins
Subcellular location
Endoplasmic reticulum,Plasma membrane,Cytosol
Quaternary structure
Homodimer

OverviewNCBI Gene

This gene encodes a member of the ubiquitin-specific processing (UBP) family of proteases that is a deubiquitinating enzyme (DUB) with His and Cys domains. This protein is located in the cytoplasm and cleaves the ubiquitin moiety from ubiquitin-fused precursors and ubiquitinylated proteins. Mice with a mutation that results in reduced expression of the ortholog of this protein are retarded for growth, develop severe tremors by 2 to 3 weeks of age followed by hindlimb paralysis and death by 6 to 10 weeks of age. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

494 residues, UniProt reviewed canonical sequence.

>P54578|USP14
     1  MPLYSVTVKW GKEKFEGVEL NTDEPPMVFK AQLFALTGVQ PARQKVMVKG GTLKDDDWGN
    61  IKIKNGMTLL MMGSADALPE EPSAKTVFVE DMTEEQLASA MELPCGLTNL GNTCYMNATV
   121  QCIRSVPELK DALKRYAGAL RASGEMASAQ YITAALRDLF DSMDKTSSSI PPIILLQFLH
   181  MAFPQFAEKG EQGQYLQQDA NECWIQMMRV LQQKLEAIED DSVKETDSSS ASAATPSKKK
   241  SLIDQFFGVE FETTMKCTES EEEEVTKGKE NQLQLSCFIN QEVKYLFTGL KLRLQEEITK
   301  QSPTLQRNAL YIKSSKISRL PAYLTIQMVR FFYKEKESVN AKVLKDVKFP LMLDMYELCT
   361  PELQEKMVSF RSKFKDLEDK KVNQQPNTSD KKSSPQKEVK YEPFSFADDI GSNNCGYYDL
   421  QAVLTHQGRS SSSGHYVSWV KRKQDEWIKF DDDKVSIVTP EDILRLSGGG DWHIAYVLLY
   481  GPRRVEIMEE ESEQ

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against USP14 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)
0.32
Highest tissue expression
50 nTPM

Expression across tissuesHPA

Tissue

  • skeletal muscle: 50 nTPM
  • tongue: 34 nTPM
  • tonsil: 29 nTPM
  • prostate: 28 nTPM
  • cerebral cortex: 26 nTPM
  • placenta: 25 nTPM

Single-cell type

  • erythrocyte progenitors: 231 nCPM
  • syncytiotrophoblasts: 194 nCPM
  • prostatic glandular cells: 193 nCPM
  • endometrial glandular cells: 150 nCPM
  • alveolar cells type 1: 143 nCPM
  • megakaryocyte-erythroid progenitors: 141 nCPM

Immune cell

  • NK-cell: 40 nTPM
  • MAIT T-cell: 34 nTPM
  • memory CD8 T-cell: 30 nTPM
  • T-reg: 29 nTPM
  • gdT-cell: 28 nTPM
  • memory CD4 T-cell: 28 nTPM

Brain region

  • pons: 54 nTPM
  • hypothalamus: 54 nTPM
  • medulla oblongata: 53 nTPM
  • white matter: 47 nTPM
  • midbrain: 46 nTPM
  • thalamus: 44 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about USP14.

Disease | GeneticClinVar

1 pathogenic / likely-pathogenic of 67 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

  • See cases
  • Distal arthrogryposis and CNS involvement

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)
0.35
gnomAD pLI
0.91
gnomAD missense Z
1.94
DepMap mean gene effect
-0.11
DepMap dependency class
selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 8% 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 USP14 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 USP14 as an antibody target. Whether an autoantibody or antibody against USP14 could matter depends on whether native USP14 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

USP14 is annotated at the cell surface, where native USP14 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 USP14 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

Canonical record: https://seroatlas.com/gene/USP14. 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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