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].

TNF receptor associated factor 6MIM:602355Ensembl:ENSG00000175104HGNC:HGNC:12036PA3671311p12

GO terms in TRAF6

Term TypeEvidence TypeGO Term IDGO Des.
CCISSGO:0005811lipid droplet
CCIDAGO:0005886plasma membrane
CCTASGO:0005886plasma membrane
CCIEAGO:0005938cell cortex
CCISSGO:0009898cytoplasmic side of plasma membrane
CCTASGO:0010008endosome membrane
CCIDAGO:0032991protein-containing complex
CCISSGO:0035631CD40 receptor complex
CCIDAGO:0048471perinuclear region of cytoplasm
BPIMPGO:0000122negative regulation of transcription by RNA polymerase II
BPTASGO:0000187activation of MAPK activity
BPIDAGO:0000209protein polyubiquitination
BPIEAGO:0001843neural tube closure
BPTASGO:0002223stimulatory C-type lectin receptor signaling pathway
BPTASGO:0002224toll-like receptor signaling pathway
BPIMPGO:0002726positive regulation of T cell cytokine production
BPTASGO:0002755MyD88-dependent toll-like receptor signaling pathway
BPIEAGO:0006974cellular response to DNA damage stimulus
BPTASGO:0007249I-kappaB kinase/NF-kappaB signaling
BPIMPGO:0007250activation of NF-kappaB-inducing kinase activity
BPTASGO:0007254JNK cascade
BPTASGO:0016579protein deubiquitination
BPIEAGO:0019886antigen processing and presentation of exogenous peptide antigen via MHC class II
BPIEAGO:0030316osteoclast differentiation
BPTASGO:0031293membrane protein intracellular domain proteolysis
BPNASGO:0031398positive regulation of protein ubiquitination
BPIEAGO:0031666positive regulation of lipopolysaccharide-mediated signaling pathway
BPIDAGO:0032147activation of protein kinase activity
BPIMPGO:0032743positive regulation of interleukin-2 production
BPTASGO:0034162toll-like receptor 9 signaling pathway
BPTASGO:0038095Fc-epsilon receptor signaling pathway
BPIEAGO:0042088T-helper 1 type immune response
BPIEAGO:0042102positive regulation of T cell proliferation
BPIEAGO:0042475odontogenesis of dentin-containing tooth
BPIEAGO:0043011myeloid dendritic cell differentiation
BPTASGO:0043065positive regulation of apoptotic process
BPTASGO:0043066negative regulation of apoptotic process
BPIDAGO:0043123positive regulation of I-kappaB kinase/NF-kappaB signaling
BPTASGO:0043123positive regulation of I-kappaB kinase/NF-kappaB signaling
BPIDAGO:0043507positive regulation of JUN kinase activity
BPNASGO:0043507positive regulation of JUN kinase activity
BPIEAGO:0045084positive regulation of interleukin-12 biosynthetic process
BPIEAGO:0045410positive regulation of interleukin-6 biosynthetic process
BPIEAGO:0045453bone resorption
BPIDAGO:0045672positive regulation of osteoclast differentiation
BPIMPGO:0045892negative regulation of transcription, DNA-templated
BPIDAGO:0045944positive regulation of transcription by RNA polymerase II
BPNASGO:0045944positive regulation of transcription by RNA polymerase II
BPIEAGO:0048468cell development
BPIEAGO:0048661positive regulation of smooth muscle cell proliferation
BPIMPGO:0050852T cell receptor signaling pathway
BPTASGO:0050852T cell receptor signaling pathway
BPIEAGO:0051023regulation of immunoglobulin secretion
BPIMPGO:0051091positive regulation of DNA-binding transcription factor activity
BPIDAGO:0051092positive regulation of NF-kappaB transcription factor activity
BPIMPGO:0051092positive regulation of NF-kappaB transcription factor activity
BPTASGO:0051092positive regulation of NF-kappaB transcription factor activity
BPIDAGO:0051865protein autoubiquitination
BPTASGO:0051865protein autoubiquitination
BPTASGO:0070423nucleotide-binding oligomerization domain containing signaling pathway
BPTASGO:0070498interleukin-1-mediated signaling pathway
BPIDAGO:0070534protein K63-linked ubiquitination
BPIGIGO:0070534protein K63-linked ubiquitination
BPIDAGO:0070555response to interleukin-1
BPIDAGO:0071222cellular response to lipopolysaccharide
BPIDAGO:2000679positive regulation of transcription regulatory region DNA binding
MFEXPGO:0004842ubiquitin-protein transferase activity
MFIDAGO:0004842ubiquitin-protein transferase activity
MFTASGO:0004842ubiquitin-protein transferase activity
MFIPIGO:0005164tumor necrosis factor receptor binding
MFIPIGO:0005515protein binding
MFIEAGO:0008270zinc ion binding
MFIPIGO:0019901protein kinase binding
MFIPIGO:0031435mitogen-activated protein kinase kinase kinase binding
MFIDAGO:0031624ubiquitin conjugating enzyme binding
MFIPIGO:0031625ubiquitin protein ligase binding
MFIPIGO:0031996thioesterase binding
MFIPIGO:0042802identical protein binding
MFIPIGO:0042826histone deacetylase binding
MFIPIGO:0043422protein kinase B binding
MFIPIGO:0047485protein N-terminus binding
MFIEAGO:0061630ubiquitin protein ligase activity

Gene expression in normal tissue: TRAF6

Gene-model tissue-cancer distribution: Bubble Plot

Gene-drug pathway distribution

Pathways in TRAF6

DatabasePathway IDPathway Des.
biocartacd40pathwaycd40l signaling pathway
biocartail1rpathwaysignal transduction through il1r
biocartanfkbpathwaynf-kb signaling pathway
biocartaranklpathwaybone remodeling
biocartatall1pathwayyaci and bcma stimulation of b cell immune responses
biocartatollpathwaytoll-like receptor pathway
reactomeR-HSA-1257604PIP3 activates AKT signaling
reactomeR-HSA-1280215Cytokine Signaling in Immune system
reactomeR-HSA-1280218Adaptive Immune System
reactomeR-HSA-162582Signal Transduction
reactomeR-HSA-162582Signal Transduction
reactomeR-HSA-166016Toll Like Receptor 4 (TLR4) Cascade
reactomeR-HSA-166058MyD88:Mal cascade initiated on plasma membrane
reactomeR-HSA-166166MyD88-independent TLR4 cascade
reactomeR-HSA-168138Toll Like Receptor 9 (TLR9) Cascade
reactomeR-HSA-168142Toll Like Receptor 10 (TLR10) Cascade
reactomeR-HSA-168164Toll Like Receptor 3 (TLR3) Cascade
reactomeR-HSA-168176Toll Like Receptor 5 (TLR5) Cascade
reactomeR-HSA-168179Toll Like Receptor TLR1:TLR2 Cascade
reactomeR-HSA-168181Toll Like Receptor 7/8 (TLR7/8) Cascade
reactomeR-HSA-168188Toll Like Receptor TLR6:TLR2 Cascade
reactomeR-HSA-168249Innate Immune System
reactomeR-HSA-168249Innate Immune System
reactomeR-HSA-168256Immune System
reactomeR-HSA-168256Immune System
reactomeR-HSA-168638NOD1/2 Signaling Pathway
reactomeR-HSA-168643Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways
reactomeR-HSA-168898Toll-Like Receptors Cascades
reactomeR-HSA-168927TICAM1, RIP1-mediated IKK complex recruitment
reactomeR-HSA-168928DDX58/IFIH1-mediated induction of interferon-alpha/beta
reactomeR-HSA-168928DDX58/IFIH1-mediated induction of interferon-alpha/beta
reactomeR-HSA-181438Toll Like Receptor 2 (TLR2) Cascade
reactomeR-HSA-193639p75NTR signals via NF-kB
reactomeR-HSA-193692Regulated proteolysis of p75NTR
reactomeR-HSA-193704p75 NTR receptor-mediated signalling
reactomeR-HSA-193704p75 NTR receptor-mediated signalling
reactomeR-HSA-199418Negative regulation of the PI3K/AKT network
reactomeR-HSA-202403TCR signaling
reactomeR-HSA-202424Downstream TCR signaling
reactomeR-HSA-204998Cell death signalling via NRAGE, NRIF and NADE
reactomeR-HSA-204998Cell death signalling via NRAGE, NRIF and NADE
reactomeR-HSA-205043NRIF signals cell death from the nucleus
reactomeR-HSA-205043NRIF signals cell death from the nucleus
reactomeR-HSA-209543p75NTR recruits signalling complexes
reactomeR-HSA-209560NF-kB is activated and signals survival
reactomeR-HSA-2454202Fc epsilon receptor (FCERI) signaling
reactomeR-HSA-2871837FCERI mediated NF-kB activation
reactomeR-HSA-392499Metabolism of proteins
reactomeR-HSA-445989TAK1 activates NFkB by phosphorylation and activation of IKKs complex
reactomeR-HSA-446652Interleukin-1 family signaling
reactomeR-HSA-448424Interleukin-17 signaling
reactomeR-HSA-449147Signaling by Interleukins
reactomeR-HSA-450294MAP kinase activation
reactomeR-HSA-450302activated TAK1 mediates p38 MAPK activation
reactomeR-HSA-450321JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1
reactomeR-HSA-5607764CLEC7A (Dectin-1) signaling
reactomeR-HSA-5621481C-type lectin receptors (CLRs)
reactomeR-HSA-5689880Ub-specific processing proteases
reactomeR-HSA-5689896Ovarian tumor domain proteases
reactomeR-HSA-597592Post-translational protein modification
reactomeR-HSA-6811558PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling
reactomeR-HSA-73887Death Receptor Signalling
reactomeR-HSA-73887Death Receptor Signalling
reactomeR-HSA-9006925Intracellular signaling by second messengers
reactomeR-HSA-9014325TICAM1,TRAF6-dependent induction of TAK1 complex
reactomeR-HSA-9020702Interleukin-1 signaling
reactomeR-HSA-933541TRAF6 mediated IRF7 activation
reactomeR-HSA-933542TRAF6 mediated NF-kB activation
reactomeR-HSA-933542TRAF6 mediated NF-kB activation
reactomeR-HSA-937039IRAK1 recruits IKK complex
reactomeR-HSA-937041IKK complex recruitment mediated by RIP1
reactomeR-HSA-937042IRAK2 mediated activation of TAK1 complex
reactomeR-HSA-937061TRIF(TICAM1)-mediated TLR4 signaling
reactomeR-HSA-937072TRAF6-mediated induction of TAK1 complex within TLR4 complex
reactomeR-HSA-975110TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling
reactomeR-HSA-975138TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation
reactomeR-HSA-975144IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation
reactomeR-HSA-975155MyD88 dependent cascade initiated on endosome
reactomeR-HSA-975163IRAK2 mediated activation of TAK1 complex upon TLR7/8 or 9 stimulation
reactomeR-HSA-975871MyD88 cascade initiated on plasma membrane
wikipathwaysWP1449Regulation of toll-like receptor signaling pathway
wikipathwaysWP1772Apoptosis Modulation and Signaling
wikipathwaysWP195IL-1 signaling pathway
wikipathwaysWP2018RANKL-RANK (Receptor activator of NFKB (ligand)) Signaling Pathway
wikipathwaysWP2112IL17 signaling pathway
wikipathwaysWP2380Brain-Derived Neurotrophic Factor (BDNF) signaling pathway
wikipathwaysWP262EBV LMP1 signaling
wikipathwaysWP2637Structural Pathway of Interleukin 1 (IL-1)
wikipathwaysWP3298Melatonin metabolism and effects
wikipathwaysWP3611Photodynamic therapy-induced AP-1 survival signaling.
wikipathwaysWP3617Photodynamic therapy-induced NF-kB survival signaling
wikipathwaysWP3656Interleukin-1 Induced Activation of NF-kappa-B
wikipathwaysWP366TGF-beta Signaling Pathway
wikipathwaysWP382MAPK Signaling Pathway
wikipathwaysWP3849MAPK and NFkB Signalling Pathways Inhibited by Yersinia YopJ
wikipathwaysWP3851TLR4 Signaling and Tolerance
wikipathwaysWP3858Toll-like Receptor Signaling
wikipathwaysWP3865RIG-I-like Receptor Signaling
wikipathwaysWP3877Simplified Depiction of MYD88 Distinct Input-Output Pathway
wikipathwaysWP3941Oxidative Damage
wikipathwaysWP4136Fibrin Complement Receptor 3 Signaling Pathway
wikipathwaysWP4239EMT transition in Colorectal Cancer
wikipathwaysWP69T-Cell antigen Receptor (TCR) Signaling Pathway
wikipathwaysWP75Toll-like Receptor Signaling Pathway
pidbcr_5pathwayBCR signaling pathway
pidcd40_pathwayCD40/CD40L signaling
pidcd8tcrpathwayTCR signaling in naïve CD8+ T cells
pidil1pathwayIL1-mediated signaling events
pidnfkappabcanonicalpathwayCanonical NF-kappaB pathway
pidp38_mkk3_6pathwayp38 MAPK signaling pathway
pidp38alphabetapathwayRegulation of p38-alpha and p38-beta
pidp75ntrpathwayp75(NTR)-mediated signaling
pidtcr_pathwayTCR signaling in naïve CD4+ T cells
kegghsa04010MAPK signaling pathway - Homo sapiens (human)
kegghsa04064NF-kappa B signaling pathway - Homo sapiens (human)
kegghsa04120Ubiquitin mediated proteolysis - Homo sapiens (human)
kegghsa04140Autophagy - animal - Homo sapiens (human)
kegghsa04144Endocytosis - Homo sapiens (human)
kegghsa04380Osteoclast differentiation - Homo sapiens (human)
kegghsa04620Toll-like receptor signaling pathway - Homo sapiens (human)
kegghsa04621NOD-like receptor signaling pathway - Homo sapiens (human)
kegghsa04622RIG-I-like receptor signaling pathway - Homo sapiens (human)
kegghsa04657IL-17 signaling pathway - Homo sapiens (human)
kegghsa04722Neurotrophin signaling pathway - Homo sapiens (human)
kegghsa05133Pertussis - Homo sapiens (human)
kegghsa05140Leishmaniasis - Homo sapiens (human)
kegghsa05142Chagas disease (American trypanosomiasis) - Homo sapiens (human)
kegghsa05145Toxoplasmosis - Homo sapiens (human)
kegghsa05152Tuberculosis - Homo sapiens (human)
kegghsa05160Hepatitis C - Homo sapiens (human)
kegghsa05162Measles - Homo sapiens (human)
kegghsa05168Herpes simplex infection - Homo sapiens (human)
kegghsa05169Epstein-Barr virus infection - Homo sapiens (human)
kegghsa05200Pathways in cancer - Homo sapiens (human)
kegghsa05222Small cell lung cancer - Homo sapiens (human)

Gene-Drug: Aster Plot

Drug IDDrug NameModel Num.
iGMDRD267Oligomycin A1
iGMDRD889Compound 7d-cis1
iGMDRD341Triacsin c4
iGMDRD61Kinetin riboside5
iGMDRD679Bistramide A3

Gene in drug-gene network: Network Plot

Gene-drug targets distribution

Gene Structure: PDB

Models in TRAF6