Homo sapiens Protein: TRAF6
InnateDB Protein IDBP-586776.3
Last Modified 2014-10-13 [Report errors or provide feedback]
Gene Symbol TRAF6
Protein Name TNF receptor-associated factor 6
Synonyms MGC:3310; RNF85;
Species Homo sapiens
Ensembl Protein ENSP00000433623
InnateDB Gene IDBG-40102 (TRAF6)
Protein Structure
UniProt Annotation
Function E3 ubiquitin ligase that, together with UBE2N and UBE2V1, mediates the synthesis of 'Lys-63'-linked-polyubiquitin chains conjugated to proteins, such as IKBKG, IRAK1, AKT1 and AKT2. Also mediates ubiquitination of free/unanchored polyubiquitin chain that leads to MAP3K7 activation. Leads to the activation of NF-kappa-B and JUN. May be essential for the formation of functional osteoclasts. Seems to also play a role in dendritic cells (DCs) maturation and/or activation. Represses c- Myb-mediated transactivation, in B-lymphocytes. Adapter protein that seems to play a role in signal transduction initiated via TNF receptor, IL-1 receptor and IL-17 receptor. Regulates osteoclast differentiation by mediating the activation of adapter protein complex 1 (AP-1) and NF-kappa-B, in response to RANK-L stimulation. Together with MAP3K8, mediates CD40 signals that activate ERK in B-cells and macrophages, and thus may play a role in the regulation of immunoglobulin production. {ECO:0000269PubMed:11057907, ECO:0000269PubMed:12140561, ECO:0000269PubMed:16378096, ECO:0000269PubMed:17135271, ECO:0000269PubMed:18093978, ECO:0000269PubMed:18347055, ECO:0000269PubMed:18758450, ECO:0000269PubMed:19465916, ECO:0000269PubMed:19675569, ECO:0000269PubMed:19713527, ECO:0000269PubMed:8837778}.
Subcellular Localization Cytoplasm {ECO:0000269PubMed:18093978}. Cytoplasm, cell cortex {ECO:0000269PubMed:18093978}. Nucleus {ECO:0000269PubMed:18093978}. Lipid droplet {ECO:0000250}. Note=Found in the nuclei of some aggressive B-cell lymphoma cell lines as well as in the nuclei of both resting and activated T- and B-lymphocytes. Found in punctate nuclear body protein complexes. Ubiquitination may occur in the cytoplasm and sumoylation in the nucleus. RSAD2/viperin recruits it to the lipid droplet (By similarity). {ECO:0000250}.
Disease Associations
Tissue Specificity Expressed in heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas.
Number of Interactions This gene and/or its encoded proteins are associated with 398 experimentally validated interaction(s) in this database.
They are also associated with 95 interaction(s) predicted by orthology.
Experimentally validated
Total 398 [view]
Protein-Protein 387 [view]
Protein-DNA 3 [view]
Protein-RNA 0
DNA-DNA 6 [view]
RNA-RNA 2 [view]
Predicted by orthology
Total 95 [view]
Gene Ontology

Molecular Function
Accession GO Term
GO:0004842 ubiquitin-protein transferase activity
GO:0004871 signal transducer activity
GO:0005164 tumor necrosis factor receptor binding
GO:0005515 protein binding
GO:0008270 zinc ion binding
GO:0016874 ligase activity
GO:0019901 protein kinase binding
GO:0031435 mitogen-activated protein kinase kinase kinase binding
GO:0031624 ubiquitin conjugating enzyme binding
GO:0031625 ubiquitin protein ligase binding
GO:0031996 thioesterase binding
GO:0042826 histone deacetylase binding
GO:0043422 protein kinase B binding
GO:0046872 metal ion binding
GO:0047485 protein N-terminus binding
Biological Process
GO:0000122 negative regulation of transcription from RNA polymerase II promoter
GO:0000187 activation of MAPK activity
GO:0000209 protein polyubiquitination
GO:0001503 ossification
GO:0001843 neural tube closure
GO:0002224 toll-like receptor signaling pathway
GO:0002726 positive regulation of T cell cytokine production
GO:0002755 MyD88-dependent toll-like receptor signaling pathway
GO:0002756 MyD88-independent toll-like receptor signaling pathway
GO:0006461 protein complex assembly
GO:0006955 immune response
GO:0007165 signal transduction
GO:0007249 I-kappaB kinase/NF-kappaB signaling
GO:0007250 activation of NF-kappaB-inducing kinase activity
GO:0007254 JNK cascade
GO:0009887 organ morphogenesis
GO:0016567 protein ubiquitination
GO:0019221 cytokine-mediated signaling pathway
GO:0019886 antigen processing and presentation of exogenous peptide antigen via MHC class II
GO:0030316 osteoclast differentiation
GO:0031293 membrane protein intracellular domain proteolysis
GO:0031398 positive regulation of protein ubiquitination
GO:0031666 positive regulation of lipopolysaccharide-mediated signaling pathway
GO:0032147 activation of protein kinase activity
GO:0032743 positive regulation of interleukin-2 production
GO:0034134 toll-like receptor 2 signaling pathway
GO:0034138 toll-like receptor 3 signaling pathway
GO:0034142 toll-like receptor 4 signaling pathway
GO:0034146 toll-like receptor 5 signaling pathway
GO:0034162 toll-like receptor 9 signaling pathway
GO:0034166 toll-like receptor 10 signaling pathway
GO:0035666 TRIF-dependent toll-like receptor signaling pathway
GO:0035872 nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway
GO:0038095 Fc-epsilon receptor signaling pathway
GO:0038123 toll-like receptor TLR1:TLR2 signaling pathway
GO:0038124 toll-like receptor TLR6:TLR2 signaling pathway
GO:0042088 T-helper 1 type immune response
GO:0042102 positive regulation of T cell proliferation
GO:0042475 odontogenesis of dentin-containing tooth
GO:0042981 regulation of apoptotic process
GO:0043011 myeloid dendritic cell differentiation
GO:0043065 positive regulation of apoptotic process
GO:0043066 negative regulation of apoptotic process
GO:0043123 positive regulation of I-kappaB kinase/NF-kappaB signaling
GO:0043507 positive regulation of JUN kinase activity
GO:0045084 positive regulation of interleukin-12 biosynthetic process
GO:0045087 innate immune response (InnateDB)
GO:0045410 positive regulation of interleukin-6 biosynthetic process
GO:0045453 bone resorption
GO:0045672 positive regulation of osteoclast differentiation
GO:0045892 negative regulation of transcription, DNA-templated
GO:0045944 positive regulation of transcription from RNA polymerase II promoter
GO:0046849 bone remodeling
GO:0048011 neurotrophin TRK receptor signaling pathway
GO:0048468 cell development
GO:0048661 positive regulation of smooth muscle cell proliferation
GO:0050852 T cell receptor signaling pathway
GO:0050870 positive regulation of T cell activation
GO:0051023 regulation of immunoglobulin secretion
GO:0051091 positive regulation of sequence-specific DNA binding transcription factor activity
GO:0051092 positive regulation of NF-kappaB transcription factor activity
GO:0051403 stress-activated MAPK cascade
GO:0051865 protein autoubiquitination
GO:0070423 nucleotide-binding oligomerization domain containing signaling pathway
GO:0070498 interleukin-1-mediated signaling pathway
GO:0070534 protein K63-linked ubiquitination
GO:0070555 response to interleukin-1
GO:0071222 cellular response to lipopolysaccharide
GO:0097190 apoptotic signaling pathway
GO:2000679 positive regulation of transcription regulatory region DNA binding
Cellular Component
GO:0005634 nucleus
GO:0005730 nucleolus
GO:0005737 cytoplasm
GO:0005739 mitochondrion
GO:0005811 lipid particle
GO:0005829 cytosol
GO:0005886 plasma membrane
GO:0005938 cell cortex
GO:0009898 cytoplasmic side of plasma membrane
GO:0010008 endosome membrane
GO:0035631 CD40 receptor complex
GO:0043234 protein complex
GO:0048471 perinuclear region of cytoplasm
Protein Structure and Domains
InterPro IPR001293 Zinc finger, TRAF-type
IPR001841 Zinc finger, RING-type
IPR002083 MATH
IPR008974 TRAF-like
IPR012227 TNF receptor-associated factor TRAF
IPR018957 Zinc finger, C3HC4 RING-type
PFAM PF13639
Post-translational Modifications
SwissProt Q9Y4K3
PhosphoSite PhosphoSite-Q9Y4K3
UniProt Splice Variant
Entrez Gene 7189
UniGene Hs.444172
RefSeq NP_004611
OMIM 602355
HPRD 03833
EMBL AC009656 AC061999 AK292978 AY228337 BC031052 CH471064 U78798
GenPept AAB38751 AAH31052 AAO38054 BAF85667 EAW68119 EAW68120 EAW68122