Seroatlas · Human Serome Atlas

USP46

Ubiquitin carboxyl-terminal hydrolase 46

Also known as: FLJ12552, UBP46_HUMAN

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

Protein identityUniProt · HPA

UniProt accession
P62068
Gene
USP46
Ensembl
ENSG00000109189
Chromosome
4
Canonical length
366 aa
Protein class
Enzymes, Metabolic proteins, Plasma proteins, Predicted intracellular proteins
Subcellular location
Nucleoli,Nucleoli rim

OverviewNCBI Gene

Modification of cellular proteins by ubiquitin is an essential regulatory mechanism controlled by the coordinated action of multiple ubiquitin-conjugating and deubiquitinating enzymes. USP46 belongs to a large family of cysteine proteases that function as deubiquitinating enzymes (Quesada et al., 2004 [PubMed 14715245]).[supplied by OMIM, Jun 2009]

Canonical amino-acid sequenceUniProt

366 residues, UniProt reviewed canonical sequence.

>P62068|USP46
     1  MTVRNIASIC NMGTNASALE KDIGPEQFPI NEHYFGLVNF GNTCYCNSVL QALYFCRPFR
    61  ENVLAYKAQQ KKKENLLTCL ADLFHSIATQ KKKVGVIPPK KFISRLRKEN DLFDNYMQQD
   121  AHEFLNYLLN TIADILQEEK KQEKQNGKLK NGNMNEPAEN NKPELTWVHE IFQGTLTNET
   181  RCLNCETVSS KDEDFLDLSV DVEQNTSITH CLRDFSNTET LCSEQKYYCE TCCSKQEAQK
   241  RMRVKKLPMI LALHLKRFKY MEQLHRYTKL SYRVVFPLEL RLFNTSSDAV NLDRMYDLVA
   301  VVVHCGSGPN RGHYITIVKS HGFWLLFDDD IVEKIDAQAI EEFYGLTSDI SKNSESGYIL
   361  FYQSRE

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against USP46 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)
0.29
Highest tissue expression
30 nTPM

Expression across tissuesHPA

Tissue

  • amygdala: 30 nTPM
  • heart muscle: 27 nTPM
  • cerebellum: 25 nTPM
  • cerebral cortex: 25 nTPM
  • hippocampal formation: 25 nTPM
  • midbrain: 25 nTPM

Single-cell type

  • podocytes: 306 nCPM
  • early spermatids: 288 nCPM
  • esophageal apical cells: 149 nCPM
  • retinal bipolar cells: 142 nCPM
  • late primary spermatocytes: 102 nCPM
  • retinal amacrine cells: 72 nCPM

Immune cell

  • plasmacytoid DC: 1.4 nTPM
  • memory CD4 T-cell: 1.2 nTPM
  • myeloid DC: 0.9 nTPM
  • basophil: 0.7 nTPM
  • gdT-cell: 0.7 nTPM
  • memory CD8 T-cell: 0.6 nTPM

Brain region

  • midbrain: 51 nTPM
  • hypothalamus: 50 nTPM
  • thalamus: 48 nTPM
  • cerebral cortex: 44 nTPM
  • spinal cord: 43 nTPM
  • basal ganglia: 43 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)
0.42
gnomAD pLI
0.79
gnomAD missense Z
2.87
DepMap mean gene effect
-0.05
DepMap dependency class
selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% 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 USP46 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 USP46 as an antibody target. Whether an autoantibody or antibody against USP46 could matter depends on whether native USP46 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

USP46 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 USP46 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

Canonical record: https://seroatlas.com/gene/USP46. 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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