TRAF6
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].
| Name | OMIM ID | Ensembl ID | HGNC ID | PHARMGKB ID | Map Location |
|---|---|---|---|---|---|
| TNF receptor associated factor 6 | MIM:602355 | Ensembl:ENSG00000175104 | HGNC:HGNC:12036 | PA36713 | 11p12 |
GO terms in TRAF6
| Term Type | Evidence Type | GO Term ID | GO Des. |
|---|---|---|---|
| CC | IDA | GO:0005634 | nucleus |
| CC | IDA | GO:0005737 | cytoplasm |
| CC | ISS | GO:0005811 | lipid droplet |
| CC | TAS | GO:0005829 | cytosol |
| CC | IDA | GO:0005886 | plasma membrane |
| CC | TAS | GO:0005886 | plasma membrane |
| CC | IEA | GO:0005938 | cell cortex |
| CC | ISS | GO:0009898 | cytoplasmic side of plasma membrane |
| CC | TAS | GO:0010008 | endosome membrane |
| CC | IDA | GO:0032991 | protein-containing complex |
| CC | ISS | GO:0035631 | CD40 receptor complex |
| CC | IDA | GO:0048471 | perinuclear region of cytoplasm |
| BP | IMP | GO:0000122 | negative regulation of transcription by RNA polymerase II |
| BP | TAS | GO:0000187 | activation of MAPK activity |
| BP | IDA | GO:0000209 | protein polyubiquitination |
| BP | IEA | GO:0001503 | ossification |
| BP | IEA | GO:0001843 | neural tube closure |
| BP | TAS | GO:0002223 | stimulatory C-type lectin receptor signaling pathway |
| BP | TAS | GO:0002224 | toll-like receptor signaling pathway |
| BP | IMP | GO:0002726 | positive regulation of T cell cytokine production |
| BP | TAS | GO:0002755 | MyD88-dependent toll-like receptor signaling pathway |
| BP | IEA | GO:0006974 | cellular response to DNA damage stimulus |
| BP | TAS | GO:0007249 | I-kappaB kinase/NF-kappaB signaling |
| BP | IMP | GO:0007250 | activation of NF-kappaB-inducing kinase activity |
| BP | TAS | GO:0007254 | JNK cascade |
| BP | TAS | GO:0016579 | protein deubiquitination |
| BP | IEA | GO:0019886 | antigen processing and presentation of exogenous peptide antigen via MHC class II |
| BP | IEA | GO:0030316 | osteoclast differentiation |
| BP | TAS | GO:0031293 | membrane protein intracellular domain proteolysis |
| BP | NAS | GO:0031398 | positive regulation of protein ubiquitination |
| BP | IEA | GO:0031666 | positive regulation of lipopolysaccharide-mediated signaling pathway |
| BP | IDA | GO:0032147 | activation of protein kinase activity |
| BP | IMP | GO:0032743 | positive regulation of interleukin-2 production |
| BP | TAS | GO:0034162 | toll-like receptor 9 signaling pathway |
| BP | TAS | GO:0038095 | Fc-epsilon receptor signaling pathway |
| BP | IEA | GO:0042088 | T-helper 1 type immune response |
| BP | IEA | GO:0042102 | positive regulation of T cell proliferation |
| BP | IEA | GO:0042475 | odontogenesis of dentin-containing tooth |
| BP | IEA | GO:0043011 | myeloid dendritic cell differentiation |
| BP | TAS | GO:0043065 | positive regulation of apoptotic process |
| BP | TAS | GO:0043066 | negative regulation of apoptotic process |
| BP | IDA | GO:0043123 | positive regulation of I-kappaB kinase/NF-kappaB signaling |
| BP | TAS | GO:0043123 | positive regulation of I-kappaB kinase/NF-kappaB signaling |
| BP | IDA | GO:0043507 | positive regulation of JUN kinase activity |
| BP | NAS | GO:0043507 | positive regulation of JUN kinase activity |
| BP | IEA | GO:0045084 | positive regulation of interleukin-12 biosynthetic process |
| BP | IEA | GO:0045410 | positive regulation of interleukin-6 biosynthetic process |
| BP | IEA | GO:0045453 | bone resorption |
| BP | IDA | GO:0045672 | positive regulation of osteoclast differentiation |
| BP | IMP | GO:0045892 | negative regulation of transcription, DNA-templated |
| BP | IDA | GO:0045944 | positive regulation of transcription by RNA polymerase II |
| BP | NAS | GO:0045944 | positive regulation of transcription by RNA polymerase II |
| BP | IEA | GO:0048468 | cell development |
| BP | IEA | GO:0048661 | positive regulation of smooth muscle cell proliferation |
| BP | IMP | GO:0050852 | T cell receptor signaling pathway |
| BP | TAS | GO:0050852 | T cell receptor signaling pathway |
| BP | IEA | GO:0051023 | regulation of immunoglobulin secretion |
| BP | IMP | GO:0051091 | positive regulation of DNA-binding transcription factor activity |
| BP | IDA | GO:0051092 | positive regulation of NF-kappaB transcription factor activity |
| BP | IMP | GO:0051092 | positive regulation of NF-kappaB transcription factor activity |
| BP | TAS | GO:0051092 | positive regulation of NF-kappaB transcription factor activity |
| BP | IDA | GO:0051865 | protein autoubiquitination |
| BP | TAS | GO:0051865 | protein autoubiquitination |
| BP | TAS | GO:0070423 | nucleotide-binding oligomerization domain containing signaling pathway |
| BP | TAS | GO:0070498 | interleukin-1-mediated signaling pathway |
| BP | IDA | GO:0070534 | protein K63-linked ubiquitination |
| BP | IGI | GO:0070534 | protein K63-linked ubiquitination |
| BP | IDA | GO:0070555 | response to interleukin-1 |
| BP | IDA | GO:0071222 | cellular response to lipopolysaccharide |
| BP | IDA | GO:2000679 | positive regulation of transcription regulatory region DNA binding |
| MF | EXP | GO:0004842 | ubiquitin-protein transferase activity |
| MF | IDA | GO:0004842 | ubiquitin-protein transferase activity |
| MF | TAS | GO:0004842 | ubiquitin-protein transferase activity |
| MF | IPI | GO:0005164 | tumor necrosis factor receptor binding |
| MF | IPI | GO:0005515 | protein binding |
| MF | IEA | GO:0008270 | zinc ion binding |
| MF | IPI | GO:0019901 | protein kinase binding |
| MF | IPI | GO:0031435 | mitogen-activated protein kinase kinase kinase binding |
| MF | IDA | GO:0031624 | ubiquitin conjugating enzyme binding |
| MF | IPI | GO:0031625 | ubiquitin protein ligase binding |
| MF | IPI | GO:0031996 | thioesterase binding |
| MF | IPI | GO:0042802 | identical protein binding |
| MF | IPI | GO:0042826 | histone deacetylase binding |
| MF | IPI | GO:0043422 | protein kinase B binding |
| MF | IPI | GO:0047485 | protein N-terminus binding |
| MF | IEA | GO:0061630 | ubiquitin protein ligase activity |
Gene expression in normal tissue: TRAF6
Gene-model tissue-cancer distribution: Bubble Plot
Gene-drug pathway distribution
Pathways in TRAF6
| Database | Pathway ID | Pathway Des. |
|---|---|---|
| biocarta | cd40pathway | cd40l signaling pathway |
| biocarta | il1rpathway | signal transduction through il1r |
| biocarta | nfkbpathway | nf-kb signaling pathway |
| biocarta | ranklpathway | bone remodeling |
| biocarta | tall1pathway | yaci and bcma stimulation of b cell immune responses |
| biocarta | tollpathway | toll-like receptor pathway |
| reactome | R-HSA-1257604 | PIP3 activates AKT signaling |
| reactome | R-HSA-1280215 | Cytokine Signaling in Immune system |
| reactome | R-HSA-1280218 | Adaptive Immune System |
| reactome | R-HSA-162582 | Signal Transduction |
| reactome | R-HSA-162582 | Signal Transduction |
| reactome | R-HSA-166016 | Toll Like Receptor 4 (TLR4) Cascade |
| reactome | R-HSA-166058 | MyD88:Mal cascade initiated on plasma membrane |
| reactome | R-HSA-166166 | MyD88-independent TLR4 cascade |
| reactome | R-HSA-168138 | Toll Like Receptor 9 (TLR9) Cascade |
| reactome | R-HSA-168142 | Toll Like Receptor 10 (TLR10) Cascade |
| reactome | R-HSA-168164 | Toll Like Receptor 3 (TLR3) Cascade |
| reactome | R-HSA-168176 | Toll Like Receptor 5 (TLR5) Cascade |
| reactome | R-HSA-168179 | Toll Like Receptor TLR1:TLR2 Cascade |
| reactome | R-HSA-168181 | Toll Like Receptor 7/8 (TLR7/8) Cascade |
| reactome | R-HSA-168188 | Toll Like Receptor TLR6:TLR2 Cascade |
| reactome | R-HSA-168249 | Innate Immune System |
| reactome | R-HSA-168249 | Innate Immune System |
| reactome | R-HSA-168256 | Immune System |
| reactome | R-HSA-168256 | Immune System |
| reactome | R-HSA-168638 | NOD1/2 Signaling Pathway |
| reactome | R-HSA-168643 | Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways |
| reactome | R-HSA-168898 | Toll-Like Receptors Cascades |
| reactome | R-HSA-168927 | TICAM1, RIP1-mediated IKK complex recruitment |
| reactome | R-HSA-168928 | DDX58/IFIH1-mediated induction of interferon-alpha/beta |
| reactome | R-HSA-168928 | DDX58/IFIH1-mediated induction of interferon-alpha/beta |
| reactome | R-HSA-181438 | Toll Like Receptor 2 (TLR2) Cascade |
| reactome | R-HSA-193639 | p75NTR signals via NF-kB |
| reactome | R-HSA-193692 | Regulated proteolysis of p75NTR |
| reactome | R-HSA-193704 | p75 NTR receptor-mediated signalling |
| reactome | R-HSA-193704 | p75 NTR receptor-mediated signalling |
| reactome | R-HSA-199418 | Negative regulation of the PI3K/AKT network |
| reactome | R-HSA-202403 | TCR signaling |
| reactome | R-HSA-202424 | Downstream TCR signaling |
| reactome | R-HSA-204998 | Cell death signalling via NRAGE, NRIF and NADE |
| reactome | R-HSA-204998 | Cell death signalling via NRAGE, NRIF and NADE |
| reactome | R-HSA-205043 | NRIF signals cell death from the nucleus |
| reactome | R-HSA-205043 | NRIF signals cell death from the nucleus |
| reactome | R-HSA-209543 | p75NTR recruits signalling complexes |
| reactome | R-HSA-209560 | NF-kB is activated and signals survival |
| reactome | R-HSA-2454202 | Fc epsilon receptor (FCERI) signaling |
| reactome | R-HSA-2871837 | FCERI mediated NF-kB activation |
| reactome | R-HSA-392499 | Metabolism of proteins |
| reactome | R-HSA-445989 | TAK1 activates NFkB by phosphorylation and activation of IKKs complex |
| reactome | R-HSA-446652 | Interleukin-1 family signaling |
| reactome | R-HSA-448424 | Interleukin-17 signaling |
| reactome | R-HSA-449147 | Signaling by Interleukins |
| reactome | R-HSA-450294 | MAP kinase activation |
| reactome | R-HSA-450302 | activated TAK1 mediates p38 MAPK activation |
| reactome | R-HSA-450321 | JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1 |
| reactome | R-HSA-5607764 | CLEC7A (Dectin-1) signaling |
| reactome | R-HSA-5621481 | C-type lectin receptors (CLRs) |
| reactome | R-HSA-5688426 | Deubiquitination |
| reactome | R-HSA-5689880 | Ub-specific processing proteases |
| reactome | R-HSA-5689896 | Ovarian tumor domain proteases |
| reactome | R-HSA-597592 | Post-translational protein modification |
| reactome | R-HSA-6811558 | PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling |
| reactome | R-HSA-73887 | Death Receptor Signalling |
| reactome | R-HSA-73887 | Death Receptor Signalling |
| reactome | R-HSA-9006925 | Intracellular signaling by second messengers |
| reactome | R-HSA-9014325 | TICAM1,TRAF6-dependent induction of TAK1 complex |
| reactome | R-HSA-9020702 | Interleukin-1 signaling |
| reactome | R-HSA-933541 | TRAF6 mediated IRF7 activation |
| reactome | R-HSA-933542 | TRAF6 mediated NF-kB activation |
| reactome | R-HSA-933542 | TRAF6 mediated NF-kB activation |
| reactome | R-HSA-937039 | IRAK1 recruits IKK complex |
| reactome | R-HSA-937041 | IKK complex recruitment mediated by RIP1 |
| reactome | R-HSA-937042 | IRAK2 mediated activation of TAK1 complex |
| reactome | R-HSA-937061 | TRIF(TICAM1)-mediated TLR4 signaling |
| reactome | R-HSA-937072 | TRAF6-mediated induction of TAK1 complex within TLR4 complex |
| reactome | R-HSA-975110 | TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling |
| reactome | R-HSA-975138 | TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation |
| reactome | R-HSA-975144 | IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation |
| reactome | R-HSA-975155 | MyD88 dependent cascade initiated on endosome |
| reactome | R-HSA-975163 | IRAK2 mediated activation of TAK1 complex upon TLR7/8 or 9 stimulation |
| reactome | R-HSA-975871 | MyD88 cascade initiated on plasma membrane |
| wikipathways | WP1449 | Regulation of toll-like receptor signaling pathway |
| wikipathways | WP1772 | Apoptosis Modulation and Signaling |
| wikipathways | WP195 | IL-1 signaling pathway |
| wikipathways | WP2018 | RANKL-RANK (Receptor activator of NFKB (ligand)) Signaling Pathway |
| wikipathways | WP2112 | IL17 signaling pathway |
| wikipathways | WP2380 | Brain-Derived Neurotrophic Factor (BDNF) signaling pathway |
| wikipathways | WP262 | EBV LMP1 signaling |
| wikipathways | WP2637 | Structural Pathway of Interleukin 1 (IL-1) |
| wikipathways | WP3298 | Melatonin metabolism and effects |
| wikipathways | WP3611 | Photodynamic therapy-induced AP-1 survival signaling. |
| wikipathways | WP3617 | Photodynamic therapy-induced NF-kB survival signaling |
| wikipathways | WP3656 | Interleukin-1 Induced Activation of NF-kappa-B |
| wikipathways | WP366 | TGF-beta Signaling Pathway |
| wikipathways | WP382 | MAPK Signaling Pathway |
| wikipathways | WP3849 | MAPK and NFkB Signalling Pathways Inhibited by Yersinia YopJ |
| wikipathways | WP3851 | TLR4 Signaling and Tolerance |
| wikipathways | WP3858 | Toll-like Receptor Signaling |
| wikipathways | WP3865 | RIG-I-like Receptor Signaling |
| wikipathways | WP3877 | Simplified Depiction of MYD88 Distinct Input-Output Pathway |
| wikipathways | WP3941 | Oxidative Damage |
| wikipathways | WP4136 | Fibrin Complement Receptor 3 Signaling Pathway |
| wikipathways | WP4239 | EMT transition in Colorectal Cancer |
| wikipathways | WP69 | T-Cell antigen Receptor (TCR) Signaling Pathway |
| wikipathways | WP75 | Toll-like Receptor Signaling Pathway |
| pid | bcr_5pathway | BCR signaling pathway |
| pid | cd40_pathway | CD40/CD40L signaling |
| pid | cd8tcrpathway | TCR signaling in naïve CD8+ T cells |
| pid | il1pathway | IL1-mediated signaling events |
| pid | nfkappabcanonicalpathway | Canonical NF-kappaB pathway |
| pid | p38_mkk3_6pathway | p38 MAPK signaling pathway |
| pid | p38alphabetapathway | Regulation of p38-alpha and p38-beta |
| pid | p75ntrpathway | p75(NTR)-mediated signaling |
| pid | tcr_pathway | TCR signaling in naïve CD4+ T cells |
| kegg | hsa04010 | MAPK signaling pathway - Homo sapiens (human) |
| kegg | hsa04064 | NF-kappa B signaling pathway - Homo sapiens (human) |
| kegg | hsa04120 | Ubiquitin mediated proteolysis - Homo sapiens (human) |
| kegg | hsa04140 | Autophagy - animal - Homo sapiens (human) |
| kegg | hsa04144 | Endocytosis - Homo sapiens (human) |
| kegg | hsa04380 | Osteoclast differentiation - Homo sapiens (human) |
| kegg | hsa04620 | Toll-like receptor signaling pathway - Homo sapiens (human) |
| kegg | hsa04621 | NOD-like receptor signaling pathway - Homo sapiens (human) |
| kegg | hsa04622 | RIG-I-like receptor signaling pathway - Homo sapiens (human) |
| kegg | hsa04657 | IL-17 signaling pathway - Homo sapiens (human) |
| kegg | hsa04722 | Neurotrophin signaling pathway - Homo sapiens (human) |
| kegg | hsa05133 | Pertussis - Homo sapiens (human) |
| kegg | hsa05140 | Leishmaniasis - Homo sapiens (human) |
| kegg | hsa05142 | Chagas disease (American trypanosomiasis) - Homo sapiens (human) |
| kegg | hsa05145 | Toxoplasmosis - Homo sapiens (human) |
| kegg | hsa05152 | Tuberculosis - Homo sapiens (human) |
| kegg | hsa05160 | Hepatitis C - Homo sapiens (human) |
| kegg | hsa05162 | Measles - Homo sapiens (human) |
| kegg | hsa05168 | Herpes simplex infection - Homo sapiens (human) |
| kegg | hsa05169 | Epstein-Barr virus infection - Homo sapiens (human) |
| kegg | hsa05200 | Pathways in cancer - Homo sapiens (human) |
| kegg | hsa05222 | Small cell lung cancer - Homo sapiens (human) |
| netpath | Pathway_BDNF | BDNF |
| netpath | Pathway_IL1 | IL1 |
| netpath | Pathway_RANKL | RANKL |
| netpath | Pathway_TNFalpha | TNFalpha |
Gene-Drug: Aster Plot
| Drug ID | Drug Name | Model Num. |
|---|---|---|
| iGMDRD158 | NSC141540 | 3 |
| iGMDRD474 | Avrainvillamide | 9 |
| iGMDRD255 | SB225002 | 2 |
| iGMDRD434 | BMS-536924 | 2 |
| iGMDRD267 | Oligomycin A | 1 |
| iGMDRD872 | BRD7137 | 3 |
| iGMDRD188 | Piperlongumine | 1 |
| iGMDRD60 | Quinoclamine | 6 |
| iGMDRD300 | Tozasertib | 7 |
| iGMDRD23 | Gossypol | 7 |
| iGMDRD889 | Compound 7d-cis | 1 |
| iGMDRD144 | NSC95397 | 1 |
| iGMDRD546 | BMS-754807 | 3 |
| iGMDRD781 | Sirolimus | 9 |
| iGMDRD405 | PIK-75 | 3 |
| iGMDRD341 | Triacsin c | 4 |
| iGMDRD61 | Kinetin riboside | 5 |
| iGMDRD394 | BX-795 | 3 |
| iGMDRD280 | CYTOCHALASIN B | 4 |
| iGMDRD679 | Bistramide A | 3 |
Gene in drug-gene network: Network Plot
Gene-drug targets distribution
Gene Structure: PDB
Models in TRAF6
CLASSFICATION
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