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TRAF6 TNF receptor associated factor 6 [ Homo sapiens (human) ]

Gene ID: 7189, updated on 11-Oct-2020

Summary

Official Symbol
TRAF6provided by HGNC
Official Full Name
TNF receptor associated factor 6provided by HGNC
Primary source
HGNC:HGNC:12036
See related
Ensembl:ENSG00000175104 MIM:602355
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
RNF85; MGC:3310
Summary
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 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. 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. Two alternatively spliced transcript variants, encoding an identical protein, have been reported. [provided by RefSeq, Feb 2012]
Expression
Ubiquitous expression in bone marrow (RPKM 5.9), thyroid (RPKM 3.6) and 25 other tissues See more
Orthologs

Genomic context

See TRAF6 in Genome Data Viewer
Location:
11p12
Exon count:
9
Annotation release Status Assembly Chr Location
109.20200815 current GRCh38.p13 (GCF_000001405.39) 11 NC_000011.10 (36483769..36510313, complement)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 11 NC_000011.9 (36505317..36531863, complement)

Chromosome 11 - NC_000011.10Genomic Context describing neighboring genes Neighboring gene COMM domain containing 9 Neighboring gene proline rich 5 like Neighboring gene recombination activating 1 Neighboring gene intraflagellar transport associated protein Neighboring gene recombination activating 2

Genomic regions, transcripts, and products

Expression

  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Phenotypes

Associated conditions

Description Tests
Genetics of rheumatoid arthritis contributes to biology and drug discovery.
GeneReviews: Not available

HIV-1 interactions

Protein interactions

Protein Gene Interaction Pubs
Nef nef The interaction of HIV-1 Nef with TRAF2, TRAF5, and TRAF6 proteins activates NF-kappaB, leading to the degradation of IkappaB-alpha and the increased phosphorylation of IKK-alpha and IKK-beta in monocyte-derived macrophages PubMed
nef HIV-1 Nef interacts with TRAF2, TRAF5, and TRAF6 proteins via its C-terminal region (residues 55-206) in monocyte-derived macrophages PubMed
nef TRAF2 and TRAF6 proteins are required for the HIV-1 Nef-induced tyrosine phosphorylation of STAT1 and STAT2 proteins PubMed
nef The acidic cluster AQEEEE (residues 64-69) of HIV-1 Nef binds to the residues R392, M450, R466, K469, F471, and Y473 of TRAF6 PubMed
Vpr vpr The ability of HIV-1 Vpr to activate NF-kappaB or activator protein 1-dependent luciferase expression requires TAK1, TRAF6, or TAB3 in cells PubMed
vpr HIV-1 Vpr-induced phosphorylation of TAK1 requires TRAF6 and Vpr increases the polyubiquitination of TAK1 in cells PubMed

Go to the HIV-1, Human Interaction Database

Pathways from PubChem

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
histone deacetylase binding IPI
Inferred from Physical Interaction
more info
PubMed 
identical protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
mitogen-activated protein kinase kinase kinase binding IPI
Inferred from Physical Interaction
more info
PubMed 
protein N-terminus binding IPI
Inferred from Physical Interaction
more info
PubMed 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
protein kinase B binding IPI
Inferred from Physical Interaction
more info
PubMed 
protein kinase binding IPI
Inferred from Physical Interaction
more info
PubMed 
thioesterase binding IPI
Inferred from Physical Interaction
more info
PubMed 
tumor necrosis factor receptor binding IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
tumor necrosis factor receptor binding IPI
Inferred from Physical Interaction
more info
PubMed 
ubiquitin conjugating enzyme binding IDA
Inferred from Direct Assay
more info
PubMed 
ubiquitin protein ligase activity IDA
Inferred from Direct Assay
more info
PubMed 
ubiquitin protein ligase binding IPI
Inferred from Physical Interaction
more info
PubMed 
ubiquitin-protein transferase activity EXP
Inferred from Experiment
more info
PubMed 
ubiquitin-protein transferase activity IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
ubiquitin-protein transferase activity TAS
Traceable Author Statement
more info
 
zinc ion binding IEA
Inferred from Electronic Annotation
more info
 
Process Evidence Code Pubs
Fc-epsilon receptor signaling pathway TAS
Traceable Author Statement
more info
 
I-kappaB kinase/NF-kappaB signaling TAS
Traceable Author Statement
more info
 
JNK cascade TAS
Traceable Author Statement
more info
 
MyD88-dependent toll-like receptor signaling pathway TAS
Traceable Author Statement
more info
 
T cell receptor signaling pathway IMP
Inferred from Mutant Phenotype
more info
PubMed 
T cell receptor signaling pathway TAS
Traceable Author Statement
more info
 
T-helper 1 type immune response IEA
Inferred from Electronic Annotation
more info
 
activation of MAPK activity TAS
Traceable Author Statement
more info
 
activation of NF-kappaB-inducing kinase activity IMP
Inferred from Mutant Phenotype
more info
PubMed 
activation of protein kinase activity IDA
Inferred from Direct Assay
more info
PubMed 
antigen processing and presentation of exogenous peptide antigen via MHC class II IEA
Inferred from Electronic Annotation
more info
 
bone resorption IEA
Inferred from Electronic Annotation
more info
 
cell development IEA
Inferred from Electronic Annotation
more info
 
cellular response to DNA damage stimulus IEA
Inferred from Electronic Annotation
more info
 
cellular response to cytokine stimulus IMP
Inferred from Mutant Phenotype
more info
PubMed 
cellular response to lipopolysaccharide IDA
Inferred from Direct Assay
more info
PubMed 
in utero embryonic development IEA
Inferred from Electronic Annotation
more info
 
interleukin-1-mediated signaling pathway IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
interleukin-1-mediated signaling pathway TAS
Traceable Author Statement
more info
 
membrane protein intracellular domain proteolysis TAS
Traceable Author Statement
more info
 
myeloid dendritic cell differentiation IEA
Inferred from Electronic Annotation
more info
 
negative regulation of apoptotic process TAS
Traceable Author Statement
more info
 
negative regulation of transcription by RNA polymerase II IMP
Inferred from Mutant Phenotype
more info
PubMed 
negative regulation of transcription, DNA-templated IMP
Inferred from Mutant Phenotype
more info
PubMed 
neural tube closure IEA
Inferred from Electronic Annotation
more info
 
nucleotide-binding oligomerization domain containing signaling pathway TAS
Traceable Author Statement
more info
 
odontogenesis of dentin-containing tooth IEA
Inferred from Electronic Annotation
more info
 
ossification IEA
Inferred from Electronic Annotation
more info
 
osteoclast differentiation IEA
Inferred from Electronic Annotation
more info
 
positive regulation of DNA-binding transcription factor activity IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of I-kappaB kinase/NF-kappaB signaling IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of I-kappaB kinase/NF-kappaB signaling TAS
Traceable Author Statement
more info
 
positive regulation of JNK cascade IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
positive regulation of JUN kinase activity IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of JUN kinase activity NAS
Non-traceable Author Statement
more info
PubMed 
positive regulation of NF-kappaB transcription factor activity IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of NF-kappaB transcription factor activity IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of NF-kappaB transcription factor activity TAS
Traceable Author Statement
more info
 
positive regulation of NIK/NF-kappaB signaling IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of T cell cytokine production IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of T cell proliferation IEA
Inferred from Electronic Annotation
more info
 
positive regulation of apoptotic process TAS
Traceable Author Statement
more info
 
positive regulation of interleukin-2 production IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of leukocyte adhesion to vascular endothelial cell IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of lipopolysaccharide-mediated signaling pathway IEA
Inferred from Electronic Annotation
more info
 
positive regulation of osteoclast differentiation IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of protein ubiquitination NAS
Non-traceable Author Statement
more info
PubMed 
positive regulation of smooth muscle cell proliferation IEA
Inferred from Electronic Annotation
more info
 
positive regulation of transcription by RNA polymerase II IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of transcription by RNA polymerase II NAS
Non-traceable Author Statement
more info
PubMed 
positive regulation of transcription regulatory region DNA binding IDA
Inferred from Direct Assay
more info
PubMed 
protein K63-linked ubiquitination IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
protein K63-linked ubiquitination IDA
Inferred from Direct Assay
more info
PubMed 
protein K63-linked ubiquitination IGI
Inferred from Genetic Interaction
more info
PubMed 
protein autoubiquitination IDA
Inferred from Direct Assay
more info
PubMed 
protein autoubiquitination TAS
Traceable Author Statement
more info
PubMed 
protein deubiquitination TAS
Traceable Author Statement
more info
 
protein polyubiquitination IDA
Inferred from Direct Assay
more info
PubMed 
regulation of I-kappaB kinase/NF-kappaB signaling IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
regulation of immunoglobulin secretion IEA
Inferred from Electronic Annotation
more info
 
response to interleukin-1 IDA
Inferred from Direct Assay
more info
PubMed 
stimulatory C-type lectin receptor signaling pathway TAS
Traceable Author Statement
more info
 
toll-like receptor 9 signaling pathway TAS
Traceable Author Statement
more info
 
toll-like receptor signaling pathway TAS
Traceable Author Statement
more info
 
tumor necrosis factor-mediated signaling pathway IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
Component Evidence Code Pubs
CD40 receptor complex ISS
Inferred from Sequence or Structural Similarity
more info
 
cell cortex IEA
Inferred from Electronic Annotation
more info
 
cytoplasm IDA
Inferred from Direct Assay
more info
PubMed 
cytoplasmic side of plasma membrane ISS
Inferred from Sequence or Structural Similarity
more info
 
cytosol TAS
Traceable Author Statement
more info
 
endosome membrane TAS
Traceable Author Statement
more info
 
lipid droplet ISS
Inferred from Sequence or Structural Similarity
more info
 
nucleus IDA
Inferred from Direct Assay
more info
PubMed 
perinuclear region of cytoplasm IDA
Inferred from Direct Assay
more info
PubMed 
plasma membrane IDA
Inferred from Direct Assay
more info
PubMed 
plasma membrane TAS
Traceable Author Statement
more info
 
plasma membrane receptor complex IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
protein-containing complex IDA
Inferred from Direct Assay
more info
PubMed 

General protein information

Preferred Names
TNF receptor-associated factor 6
Names
E3 ubiquitin-protein ligase TRAF6
RING finger protein 85
RING-type E3 ubiquitin transferase TRAF6
TNF receptor-associated factor 6, E3 ubiquitin protein ligase
interleukin-1 signal transducer
NP_004611.1
NP_665802.1
XP_016873709.1

NCBI Reference Sequences (RefSeq)

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

  1. NM_004620.4NP_004611.1  TNF receptor-associated factor 6

    See identical proteins and their annotated locations for NP_004611.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) lacks a segment in the 5' UTR, compared to variant 1. Variants 1 and 2 encode the same protein.
    Source sequence(s)
    AC009656, AK292978, BQ187062
    Consensus CDS
    CCDS7901.1
    UniProtKB/Swiss-Prot
    Q9Y4K3
    Related
    ENSP00000433623.1, ENST00000526995.6
    Conserved Domains (3) summary
    cd00162
    Location:69107
    RING; RING-finger (Really Interesting New Gene) domain, a specialized type of Zn-finger of 40 to 60 residues that binds two atoms of zinc; defined by the 'cross-brace' motif C-X2-C-X(9-39)-C-X(1-3)- H-X(2-3)-(N/C/H)-X2-C-X(4-48)C-X2-C; probably involved in ...
    cd03776
    Location:351500
    MATH_TRAF6; Tumor Necrosis Factor Receptor (TNFR)-Associated Factor (TRAF) family, TRAF6 subfamily, TRAF domain, C-terminal MATH subdomain; composed of proteins with similarity to human TRAF6, including the Drosophila protein DTRAF2. TRAF molecules serve as adapter ...
    pfam02176
    Location:204261
    zf-TRAF; TRAF-type zinc finger
  2. NM_145803.3NP_665802.1  TNF receptor-associated factor 6

    See identical proteins and their annotated locations for NP_665802.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longer transcript. Variants 1 and 2 encode the same protein.
    Source sequence(s)
    AC009656, AC061999, BC031052, BQ187062
    Consensus CDS
    CCDS7901.1
    UniProtKB/Swiss-Prot
    Q9Y4K3
    Related
    ENSP00000337853.5, ENST00000348124.5
    Conserved Domains (3) summary
    cd00162
    Location:69107
    RING; RING-finger (Really Interesting New Gene) domain, a specialized type of Zn-finger of 40 to 60 residues that binds two atoms of zinc; defined by the 'cross-brace' motif C-X2-C-X(9-39)-C-X(1-3)- H-X(2-3)-(N/C/H)-X2-C-X(4-48)C-X2-C; probably involved in ...
    cd03776
    Location:351500
    MATH_TRAF6; Tumor Necrosis Factor Receptor (TNFR)-Associated Factor (TRAF) family, TRAF6 subfamily, TRAF domain, C-terminal MATH subdomain; composed of proteins with similarity to human TRAF6, including the Drosophila protein DTRAF2. TRAF molecules serve as adapter ...
    pfam02176
    Location:204261
    zf-TRAF; TRAF-type zinc finger

RefSeqs of Annotated Genomes: Homo sapiens Updated Annotation Release 109.20200815

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p13 Primary Assembly

Genomic

  1. NC_000011.10 Reference GRCh38.p13 Primary Assembly

    Range
    36483769..36510313 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_017018220.1XP_016873709.1  TNF receptor-associated factor 6 isoform X1

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