InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: TRAF6

Summary

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.

Comments

Interactions

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]
DNA-RNA	0

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

PDB ID

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
PF14634
PF00917
PF00097

PRINTS

PIRSF

PIRSF015614

SMART

SM00184
SM00061

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt