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

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; AllianceGenome:HGNC:12036
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 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]
Annotation information: Note: This gene has been reviewed for its involvement in coronavirus biology, and is involved in immune response or antiviral activity.
Expression: Ubiquitous expression in bone marrow (RPKM 5.9), thyroid (RPKM 3.6) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 11p12

Exon count:: 8

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	11	NC_000011.10 (36483769..36510272, complement)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	11	NC_060935.1 (36626229..36653443, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	11	NC_000011.9 (36505319..36531822, complement)

Chromosome 11 - NC_000011.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

SPHK1 potentiates colorectal cancer progression and metastasis via regulating autophagy mediated by TRAF6-induced ULK1 ubiquitination.
Title: SPHK1 potentiates colorectal cancer progression and metastasis via regulating autophagy mediated by TRAF6-induced ULK1 ubiquitination.
Mechanism of miR-7 mediating TLR4/TRAF6/NF-kappaB inflammatory pathway in colorectal cancer.
Title: Mechanism of miR-7 mediating TLR4/TRAF6/NF-κB inflammatory pathway in colorectal cancer.
YTHDC1-Modified m6A Methylation of Hsa_circ_0102678 Promotes Keratinocyte Inflammation Induced by Cutibacterium acnes Biofilm through Regulating miR-146a/TRAF6 and IRAK1 Axis.
Title: YTHDC1-Modified m6A Methylation of Hsa_circ_0102678 Promotes Keratinocyte Inflammation Induced by Cutibacterium acnes Biofilm through Regulating miR-146a/TRAF6 and IRAK1 Axis.
Potential involvement of circulating exosomal miRNA-146a in disease activity and TRAF6 gene expression in juvenile proliferative lupus nephritis.
Title: Potential involvement of circulating exosomal miRNA-146a in disease activity and TRAF6 gene expression in juvenile proliferative lupus nephritis.
c-Src regulates delta-secretase activation and truncated Tau production by phosphorylating the E3 ligase Traf6.
Title: c-Src regulates δ-secretase activation and truncated Tau production by phosphorylating the E3 ligase Traf6.
POU5F1 promotes the proliferation, migration, and invasion of gastric cancer cells by reducing the ubiquitination level of TRAF6.
Title: POU5F1 promotes the proliferation, migration, and invasion of gastric cancer cells by reducing the ubiquitination level of TRAF6.
TLR9 regulates the autophagy-lysosome pathway to promote dendritic cell maturation and activation by activating the TRAF6-cGAS-STING pathway.
Title: TLR9 regulates the autophagy-lysosome pathway to promote dendritic cell maturation and activation by activating the TRAF6-cGAS-STING pathway.
The OX40-TRAF6 axis promotes CTLA-4 degradation to augment antitumor CD8[+] T-cell immunity.
Title: The OX40-TRAF6 axis promotes CTLA-4 degradation to augment antitumor CD8(+) T-cell immunity.
LncRNA AOC4P recruits TRAF6 to regulate EZH2 ubiquitination and participates in trophoblast glycolysis and M2 macrophage polarization which is associated with recurrent spontaneous abortion.
Title: LncRNA AOC4P recruits TRAF6 to regulate EZH2 ubiquitination and participates in trophoblast glycolysis and M2 macrophage polarization which is associated with recurrent spontaneous abortion.
TRAF6 promotes chemoresistance to paclitaxel of triple negative breast cancer via regulating PKM2-mediated glycolysis.
Title: TRAF6 promotes chemoresistance to paclitaxel of triple negative breast cancer via regulating PKM2-mediated glycolysis.

Submit: New GeneRIF Correction See all GeneRIFs (336)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
Genetics of rheumatoid arthritis contributes to biology and drug discovery. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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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

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Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

WI-17696 (e-PCR)
- UniSTS:83274

WI-21989 (e-PCR)
- UniSTS:16466

GDB:631813 (e-PCR)
- UniSTS:158430

TRAF6_2442 (e-PCR)
- UniSTS:281067

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables histone deacetylase binding	IPI Inferred from Physical Interaction more info	PubMed
enables identical protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein kinase B binding	IPI Inferred from Physical Interaction more info	PubMed
enables tumor necrosis factor receptor binding	IEA Inferred from Electronic Annotation more info
enables ubiquitin conjugating enzyme binding	IDA Inferred from Direct Assay more info	PubMed
enables ubiquitin protein ligase activity	IBA Inferred from Biological aspect of Ancestor more info
enables ubiquitin protein ligase activity	IDA Inferred from Direct Assay more info	PubMed
enables ubiquitin-protein transferase activity	EXP Inferred from Experiment more info	PubMed
enables ubiquitin-protein transferase activity	TAS Traceable Author Statement more info
enables ubiquitin-ubiquitin ligase activity	IDA Inferred from Direct Assay more info	PubMed
enables zinc ion binding	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in DNA damage response	IEA Inferred from Electronic Annotation more info
involved_in Fc-epsilon receptor signaling pathway	TAS Traceable Author Statement more info
involved_in MyD88-dependent toll-like receptor signaling pathway	TAS Traceable Author Statement more info
involved_in T cell receptor signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in T cell receptor signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in T cell receptor signaling pathway	TAS Traceable Author Statement more info
involved_in T-helper 1 type immune response	IEA Inferred from Electronic Annotation more info
involved_in TRIF-dependent toll-like receptor signaling pathway	TAS Traceable Author Statement more info
involved_in activation of NF-kappaB-inducing kinase activity	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in activation of protein kinase activity	IDA Inferred from Direct Assay more info	PubMed
involved_in antigen processing and presentation of exogenous peptide antigen via MHC class II	IEA Inferred from Electronic Annotation more info
involved_in antiviral innate immune response	IDA Inferred from Direct Assay more info	PubMed
involved_in autophagosome assembly	IDA Inferred from Direct Assay more info	PubMed
involved_in bone resorption	IEA Inferred from Electronic Annotation more info
involved_in canonical NF-kappaB signal transduction	IDA Inferred from Direct Assay more info	PubMed
involved_in canonical NF-kappaB signal transduction	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in canonical NF-kappaB signal transduction	TAS Traceable Author Statement more info
involved_in cellular response to cytokine stimulus	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within cellular response to lipopolysaccharide	IDA Inferred from Direct Assay more info	PubMed
involved_in cytoplasmic pattern recognition receptor signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in cytoplasmic pattern recognition receptor signaling pathway	TAS Traceable Author Statement more info
involved_in in utero embryonic development	IEA Inferred from Electronic Annotation more info
involved_in innate immune response	IBA Inferred from Biological aspect of Ancestor more info
involved_in interleukin-1-mediated signaling pathway	TAS Traceable Author Statement more info
involved_in interleukin-17-mediated signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in interleukin-17A-mediated signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in interleukin-33-mediated signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in lipopolysaccharide-mediated signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in myeloid dendritic cell differentiation	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of DNA-templated transcription	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of transcription by RNA polymerase II	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in neural tube closure	IEA Inferred from Electronic Annotation more info
involved_in non-canonical NF-kappaB signal transduction	IDA Inferred from Direct Assay more info	PubMed
involved_in odontogenesis of dentin-containing tooth	IEA Inferred from Electronic Annotation more info
involved_in ossification	IEA Inferred from Electronic Annotation more info
involved_in osteoclast differentiation	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of DNA-binding transcription factor activity	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of JUN kinase activity	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of JUN kinase activity	NAS Non-traceable Author Statement more info	PubMed
involved_in positive regulation of NF-kappaB transcription factor activity	IBA Inferred from Biological aspect of Ancestor more info
involved_in positive regulation of NF-kappaB transcription factor activity	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of NF-kappaB transcription factor activity	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of T cell cytokine production	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of T cell proliferation	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of canonical NF-kappaB signal transduction	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of interleukin-12 production	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of interleukin-2 production	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of interleukin-6 production	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of leukocyte adhesion to vascular endothelial cell	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of lipopolysaccharide-mediated signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of osteoclast differentiation	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of protein ubiquitination	NAS Non-traceable Author Statement more info	PubMed
involved_in positive regulation of transcription by RNA polymerase II	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of transcription by RNA polymerase II	NAS Non-traceable Author Statement more info	PubMed
involved_in positive regulation of transcription regulatory region DNA binding	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of type I interferon production	IEA Inferred from Electronic Annotation more info
involved_in protein K63-linked ubiquitination	IBA Inferred from Biological aspect of Ancestor more info
involved_in protein K63-linked ubiquitination	IDA Inferred from Direct Assay more info	PubMed
involved_in protein K63-linked ubiquitination	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within protein autoubiquitination	IDA Inferred from Direct Assay more info	PubMed
involved_in protein autoubiquitination	IDA Inferred from Direct Assay more info	PubMed
involved_in protein autoubiquitination	TAS Traceable Author Statement more info	PubMed
involved_in protein polyubiquitination	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of apoptotic process	IEA Inferred from Electronic Annotation more info
involved_in regulation of canonical NF-kappaB signal transduction	IBA Inferred from Biological aspect of Ancestor more info
involved_in regulation of immunoglobulin production	IEA Inferred from Electronic Annotation more info
involved_in response to interleukin-1	IDA Inferred from Direct Assay more info	PubMed
involved_in stimulatory C-type lectin receptor signaling pathway	TAS Traceable Author Statement more info
involved_in toll-like receptor 3 signaling pathway	TAS Traceable Author Statement more info
involved_in toll-like receptor 4 signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in tumor necrosis factor-mediated signaling pathway	IBA Inferred from Biological aspect of Ancestor more info

Component	Evidence Code	Pubs
part_of CD40 receptor complex	ISS Inferred from Sequence or Structural Similarity more info
located_in cell cortex	IEA Inferred from Electronic Annotation more info
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
is_active_in cytoplasm	IC Inferred by Curator more info	PubMed
is_active_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in cytoplasmic side of plasma membrane	ISS Inferred from Sequence or Structural Similarity more info
located_in cytosol	TAS Traceable Author Statement more info
located_in endosome membrane	TAS Traceable Author Statement more info
is_active_in extrinsic component of cytoplasmic side of plasma membrane	IC Inferred by Curator more info	PubMed
is_active_in extrinsic component of cytoplasmic side of plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in lipid droplet	ISS Inferred from Sequence or Structural Similarity more info
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed
located_in perinuclear region of cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	TAS Traceable Author Statement more info
part_of plasma membrane signaling receptor complex	IBA Inferred from Biological aspect of Ancestor more info
part_of protein-containing complex	IDA Inferred from Direct Assay more info	PubMed

General protein information

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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

EC 2.3.2.27

NP_665802.1

EC 2.3.2.27

NCBI Reference Sequences (RefSeq)

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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)

NM_004620.4 → NP_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

A6NKI7, A8KAB3, D3DR16, Q8NEH5, Q9Y4K3

Related

ENSP00000433623.1, ENST00000526995.6

Conserved Domains (3) summary

cd00162
Location:69 → 107

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:351 → 500

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:204 → 261

zf-TRAF; TRAF-type zinc finger
NM_145803.3 → NP_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

A6NKI7, A8KAB3, D3DR16, Q8NEH5, Q9Y4K3

Related

ENSP00000337853.5, ENST00000348124.5

Conserved Domains (3) summary

cd00162
Location:69 → 107

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:351 → 500

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:204 → 261

zf-TRAF; TRAF-type zinc finger