Seroatlas · Human Serome Atlas

USP6

Ubiquitin carboxyl-terminal hydrolase 6

Also known as: HRP1, Tre-2, TRE17, Tre2, TRESMCR, UBP6_HUMAN

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

Protein identityUniProt · HPA

UniProt accession
P35125
Gene
USP6
Ensembl
ENSG00000129204
Chromosome
17
Canonical length
1406 aa
Protein class
Cancer-related genes, Disease related genes, Enzymes, Metabolic proteins, Potential drug targets, Predicted intracellular proteins
Subcellular location
Vesicles

OverviewNCBI Gene

Enables cysteine-type deubiquitinase activity. Involved in protein deubiquitination and regulation of postsynaptic neurotransmitter receptor internalization. Located in plasma membrane and recycling endosome. Is active in glutamatergic synapse and postsynaptic density, intracellular component. [provided by Alliance of Genome Resources, Jul 2025]

Canonical amino-acid sequenceUniProt

1406 residues, UniProt reviewed canonical sequence.

>P35125|USP6
     1  MDMVENADSL QAQERKDILM KYDKGHRAGL PEDKGPEPVG INSSIDRFGI LHETELPPVT
    61  AREAKKIRRE MTRTSKWMEM LGEWETYKHS SKLIDRVYKG IPMNIRGPVW SVLLNIQEIK
   121  LKNPGRYQIM KERGKRSSEH IHHIDLDVRT TLRNHVFFRD RYGAKQRELF YILLAYSEYN
   181  PEVGYCRDLS HITALFLLYL PEEDAFWALV QLLASERHSL PGFHSPNGGT VQGLQDQQEH
   241  VVPKSQPKTM WHQDKEGLCG QCASLGCLLR NLIDGISLGL TLRLWDVYLV EGEQVLMPIT
   301  SIALKVQQKR LMKTSRCGLW ARLRNQFFDT WAMNDDTVLK HLRASTKKLT RKQGDLPPPA
   361  KREQGSLAPR PVPASRGGKT LCKGYRQAPP GPPAQFQRPI CSASPPWASR FSTPCPGGAV
   421  REDTYPVGTQ GVPSLALAQG GPQGSWRFLE WKSMPRLPTD LDIGGPWFPH YDFEWSCWVR
   481  AISQEDQLAT CWQAEHCGEV HNKDMSWPEE MSFTANSSKI DRQKVPTEKG ATGLSNLGNT
   541  CFMNSSIQCV SNTQPLTQYF ISGRHLYELN RTNPIGMKGH MAKCYGDLVQ ELWSGTQKSV
   601  APLKLRRTIA KYAPKFDGFQ QQDSQELLAF LLDGLHEDLN RVHEKPYVEL KDSDGRPDWE
   661  VAAEAWDNHL RRNRSIIVDL FHGQLRSQVK CKTCGHISVR FDPFNFLSLP LPMDSYMDLE
   721  ITVIKLDGTT PVRYGLRLNM DEKYTGLKKQ LRDLCGLNSE QILLAEVHDS NIKNFPQDNQ
   781  KVQLSVSGFL CAFEIPVPSS PISASSPTQI DFSSSPSTNG MFTLTTNGDL PKPIFIPNGM
   841  PNTVVPCGTE KNFTNGMVNG HMPSLPDSPF TGYIIAVHRK MMRTELYFLS PQENRPSLFG
   901  MPLIVPCTVH TRKKDLYDAV WIQVSWLARP LPPQEASIHA QDRDNCMGYQ YPFTLRVVQK
   961  DGNSCAWCPQ YRFCRGCKID CGEDRAFIGN AYIAVDWHPT ALHLRYQTSQ ERVVDKHESV
  1021  EQSRRAQAEP INLDSCLRAF TSEEELGESE MYYCSKCKTH CLATKKLDLW RLPPFLIIHL
  1081  KRFQFVNDQW IKSQKIVRFL RESFDPSAFL VPRDPALCQH KPLTPQGDEL SKPRILAREV
  1141  KKVDAQSSAG KEDMLLSKSP SSLSANISSS PKGSPSSSRK SGTSCPSSKN SSPNSSPRTL
  1201  GRSKGRLRLP QIGSKNKPSS SKKNLDASKE NGAGQICELA DALSRGHMRG GSQPELVTPQ
  1261  DHEVALANGF LYEHEACGNG CGDGYSNGQL GNHSEEDSTD DQREDTHIKP IYNLYAISCH
  1321  SGILSGGHYI TYAKNPNCKW YCYNDSSCEE LHPDEIDTDS AYILFYEQQG IDYAQFLPKI
  1381  DGKKMADTSS TDEDSESDYE KYSMLQ

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against USP6 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)
0.37
Highest tissue expression
19 nTPM

Expression across tissuesHPA

Tissue

  • skeletal muscle: 19 nTPM
  • testis: 12 nTPM
  • retina: 2.7 nTPM
  • ovary: 2 nTPM
  • choroid plexus: 1.3 nTPM
  • cervix: 1 nTPM

Single-cell type

  • myonuclei: 90 nCPM
  • early primary spermatocytes: 65 nCPM
  • early spermatids: 41 nCPM
  • late spermatids: 29 nCPM
  • undifferentiated spermatogonia: 23 nCPM
  • differentiating spermatogonia: 19 nCPM

Immune cell

  • plasmacytoid DC: 0.1 nTPM
  • basophil: 0 nTPM
  • classical monocyte: 0 nTPM
  • eosinophil: 0 nTPM
  • gdT-cell: 0 nTPM
  • intermediate monocyte: 0 nTPM

Brain region

  • choroid plexus: 4.8 nTPM
  • white matter: 3.8 nTPM
  • medulla oblongata: 3.1 nTPM
  • basal ganglia: 2.7 nTPM
  • cerebral cortex: 2.7 nTPM
  • cerebellum: 2.6 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)
0.97
gnomAD pLI
0
gnomAD missense Z
-0.14
DepMap mean gene effect
-0.17
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 USP6 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 USP6 as an antibody target. Whether an autoantibody or antibody against USP6 could matter depends on whether native USP6 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

USP6 is annotated at the cell surface, where native USP6 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 USP6 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

Canonical record: https://seroatlas.com/gene/USP6. 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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