Seroatlas · Human Serome Atlas

TRAF6

TNF receptor-associated factor 6

Also known as: RNF85, TRAF6_HUMAN

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

Protein identityUniProt · HPA

UniProt accession
Q9Y4K3
Gene
TRAF6
Ensembl
ENSG00000175104
Chromosome
11
Canonical length
522 aa
Protein class
Enzymes, Predicted intracellular proteins
Subcellular location
Nucleoli,Mitochondria
Quaternary structure
Homotrimer

OverviewNCBI Gene

The protein encoded by this gene is a member of the TNF receptor associated factor (TRAF) protein family. TRAF proteins are associated with, and mediate signal transduction from, members of the TNF receptor superfamily. This protein has an amino terminal RING domain which is followed by four zinc-finger motifs, a central coiled-coil region and a highly conserved carboxyl terminal domain, known as the TRAF-C domain and mediates signaling from members of the TNF receptor superfamily as well as the Toll/IL-1 family. Signals from receptors such as CD40, TNFSF11/RANCE and IL-1 have been shown to be mediated by this protein. This protein also interacts with various protein kinases including IRAK1/IRAK, SRC and PKCzeta, which provides a link between distinct signaling pathways. This protein functions as a signal transducer in the NF-kappaB pathway that activates IkappaB kinase (IKK) in response to proinflammatory cytokines. The interaction of this protein with UBE2N/UBC13, and UBE2V1/UEV1A, which are ubiquitin conjugating enzymes catalyzing the formation of polyubiquitin chains, has been found to be required for IKK activation by this protein. This protein also interacts with the transforming growth factor (TGF) beta receptor complex and is required for Smad-independent activation of the JNK and p38 kinases. The protein encoded by this gene is a key molecule in antiviral innate and antigen-specific immune responses. [provided by RefSeq, Nov 2021]

Canonical amino-acid sequenceUniProt

522 residues, UniProt reviewed canonical sequence.

>Q9Y4K3|TRAF6
     1  MSLLNCENSC GSSQSESDCC VAMASSCSAV TKDDSVGGTA STGNLSSSFM EEIQGYDVEF
    61  DPPLESKYEC PICLMALREA VQTPCGHRFC KACIIKSIRD AGHKCPVDNE ILLENQLFPD
   121  NFAKREILSL MVKCPNEGCL HKMELRHLED HQAHCEFALM DCPQCQRPFQ KFHINIHILK
   181  DCPRRQVSCD NCAASMAFED KEIHDQNCPL ANVICEYCNT ILIREQMPNH YDLDCPTAPI
   241  PCTFSTFGCH EKMQRNHLAR HLQENTQSHM RMLAQAVHSL SVIPDSGYIS EVRNFQETIH
   301  QLEGRLVRQD HQIRELTAKM ETQSMYVSEL KRTIRTLEDK VAEIEAQQCN GIYIWKIGNF
   361  GMHLKCQEEE KPVVIHSPGF YTGKPGYKLC MRLHLQLPTA QRCANYISLF VHTMQGEYDS
   421  HLPWPFQGTI RLTILDQSEA PVRQNHEEIM DAKPELLAFQ RPTIPRNPKG FGYVTFMHLE
   481  ALRQRTFIKD DTLLVRCEVS TRFDMGSLRR EGFQPRSTDA GV

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against TRAF6 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)
0.39
Highest tissue expression
22 nTPM

Expression across tissuesHPA

Tissue

  • bone marrow: 22 nTPM
  • thyroid gland: 9 nTPM
  • thymus: 8.8 nTPM
  • blood vessel: 8.3 nTPM
  • spleen: 7.9 nTPM
  • lung: 7.8 nTPM

Single-cell type

  • neutrophil progenitors: 47 nCPM
  • esophageal apical cells: 41 nCPM
  • sertoli cells: 40 nCPM
  • cardiomyocytes: 38 nCPM
  • choroid plexus epithelial cells: 37 nCPM
  • neutrophils: 37 nCPM

Immune cell

  • basophil: 60 nTPM
  • eosinophil: 35 nTPM
  • naive CD8 T-cell: 19 nTPM
  • gdT-cell: 18 nTPM
  • intermediate monocyte: 18 nTPM
  • memory CD8 T-cell: 18 nTPM

Brain region

  • white matter: 19 nTPM
  • cerebral cortex: 17 nTPM
  • basal ganglia: 17 nTPM
  • thalamus: 17 nTPM
  • choroid plexus: 16 nTPM
  • medulla oblongata: 16 nTPM

ReferencesPubMed · IEDB

Publications for TRAF6 from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Reference: AutoantibodyPubMed

1 publication

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

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)
0.22
gnomAD pLI
1
gnomAD missense Z
2.72
DepMap mean gene effect
-0.11
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 TRAF6 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 TRAF6 as an antibody target. Whether an autoantibody or antibody against TRAF6 could matter depends on whether native TRAF6 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

TRAF6 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 TRAF6 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

Canonical record: https://seroatlas.com/gene/TRAF6. 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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