Mus musculus Protein: Traf6
InnateDB Protein IDBP-193224.6
Last Modified 2014-10-13 [Report errors or provide feedback]
Gene Symbol Traf6
Protein Name TNF receptor-associated factor 6
Synonyms 2310003F17Rik; AI851288; C630032O20Rik;
Species Mus musculus
Ensembl Protein ENSMUSP00000004949
InnateDB Gene IDBG-193222 (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 (By similarity). 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:0000250, ECO:0000269PubMed:10215628, ECO:0000269PubMed:10421844, ECO:0000269PubMed:12881420, ECO:0000269PubMed:14499111, ECO:0000269PubMed:15322147, ECO:0000269PubMed:17092936, ECO:0000269PubMed:17633018}.
Subcellular Localization Cytoplasm {ECO:0000250}. Cytoplasm, cell cortex {ECO:0000250}. Nucleus {ECO:0000250}. Lipid droplet {ECO:0000269PubMed:21435586}. Note=RSAD2/viperin recruits it to the lipid droplet.
Disease Associations
Tissue Specificity Highly expressed in brain, lung, liver, skeletal muscle, and kidney; lower expression in heart, spleen, and testis.
Number of Interactions This gene and/or its encoded proteins are associated with 161 experimentally validated interaction(s) in this database.
They are also associated with 476 interaction(s) predicted by orthology.
Experimentally validated
Total 161 [view]
Protein-Protein 160 [view]
Protein-DNA 0
Protein-RNA 0
DNA-DNA 1 [view]
Predicted by orthology
Total 476 [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:0000209 protein polyubiquitination
GO:0001503 ossification
GO:0001843 neural tube closure
GO:0002726 positive regulation of T cell cytokine production
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:0031666 positive regulation of lipopolysaccharide-mediated signaling pathway
GO:0032147 activation of protein kinase activity
GO:0032743 positive regulation of interleukin-2 production
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: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:0048468 cell development
GO:0048661 positive regulation of smooth muscle cell proliferation
GO:0050852 T cell receptor signaling pathway
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:0051865 protein autoubiquitination
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: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:0031965 nuclear membrane
GO:0035631 CD40 receptor complex
GO:0043234 protein complex
GO:0048471 perinuclear region of cytoplasm
Protein Structure and Domains
PDB ID MGI:108072
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 P70196
PhosphoSite PhosphoSite-P70196
UniProt Splice Variant
Entrez Gene 22034
UniGene Mm.413318
RefSeq NP_033450
MGI Symbol Traf6
EMBL AK041172 AK155434 AL929571 BC060705 CH466519 D84655
GenPept AAH60705 BAA12705 BAC30850 BAE33263 CAM20505 EDL27656 EDL27657