Homo sapiens Gene: TRAF2
Summary
InnateDB Gene IDBG-92817.6
Last Modified 2014-10-13 [Report errors or provide feedback]
Gene Symbol TRAF2
Gene Name TNF receptor-associated factor 2
Synonyms MGC:45012; TRAP; TRAP3;
Species Homo sapiens
Ensembl Gene ENSG00000127191
Encoded Proteins
TNF receptor-associated factor 2
TNF receptor-associated factor 2
TNF receptor-associated factor 2
TNF receptor-associated factor 2
Protein Structure
Useful resources Stemformatics EHFPI ImmGen
InnateDB Annotation
Summary
TRAF2 and TRAF5 are signal transducers for the TNF receptor superfamily and are involved in TNF-induced NF-kappaB activation and protection from cell death.
TRAF2 plays a critical role in TNF signalling by directing the IKK complex to the membrane, promoting TRAF2 K63-linked ubiquitination, and positioning the IKKalpha and IKKbeta chains with the TAK1/TAB kinase.
TRAF2 competes with TRAF6 for CD40 binding, thereby limiting the capacity of CD40 engagement to induce NF-kappaB activation in human lymphocytes.
TRAF2 deficiency results in the accumulation of TNF-dependent, IL10-secreting neutrophils. Combined treatment of neutralizing antibodies against both TNF and IL10 substantially ameliorated the colitis phenotype in the Traf2 null mice. (Demonstrated in mice)
GNB2L1 (RACK1) negatively regulates NFκB activation by interacting with CHUK and IKBKB. The interaction interferes with the recruitment of the IKK complex to TRAF2 .
InnateDB Annotation from Orthologs
Summary
[Mus musculus] Traf2 deficiency results in the accumulation of Tnf-dependent, Il10-secreting neutrophils. Combined treatment of neutralizing antibodies against both Tnf and Il10 substantially ameliorated the colitis phenotype in the Traf2 null mice.
[Mus musculus] The binding of MAVS to Traf2, Traf5, and Traf6 is dependent on virus infection and MAVS polymerization . The TRAF proteins promote ubiquitination that recruits IKBKG binding to the MAVS signalling complex.
[Mus musculus] Traf2 mediates proteasome-dependent degradation of Irf5 and Rel as well as regulating macrophage polarization in tumour microenvironment and controlling tumour growth.
[Mus musculus] Traf2-deficient macrophages produce reduced levels of inflammatory cytokines in response to lipopolysaccharide or flagellin stimulation and exhibit increased susceptibility to S. Typhimurium infection.
Entrez Gene
Summary The protein encoded by this gene is a member of the TNF receptor associated factor (TRAF) protein family. TRAF proteins associate with, and mediate the signal transduction from members of the TNF receptor superfamily. This protein directly interacts with TNF receptors, and forms a heterodimeric complex with TRAF1. This protein is required for TNF-alpha-mediated activation of MAPK8/JNK and NF-kappaB. The protein complex formed by this protein and TRAF1 interacts with the inhibitor-of-apoptosis proteins (IAPs), and functions as a mediator of the anti-apoptotic signals from TNF receptors. The interaction of this protein with TRADD, a TNF receptor associated apoptotic signal transducer, ensures the recruitment of IAPs for the direct inhibition of caspase activation. BIRC2/c-IAP1, an apoptosis inhibitor possessing ubiquitin ligase activity, can unbiquitinate and induce the degradation of this protein, and thus potentiate TNF-induced apoptosis. Multiple alternatively spliced transcript variants have been found for this gene, but the biological validity of only one transcript has been determined. [provided by RefSeq, Jul 2008]
Gene Information
Type Protein coding
Genomic Location Chromosome 9:136881912-136926607
Strand Forward strand
Band q34.3
Transcripts
ENST00000247668 ENSP00000247668
ENST00000419057 ENSP00000405860
ENST00000429509 ENSP00000406524
ENST00000414589 ENSP00000397653
ENST00000474950
ENST00000482854
ENST00000469701
ENST00000466107
Interactions
Number of Interactions This gene and/or its encoded proteins are associated with 392 experimentally validated interaction(s) in this database.
They are also associated with 57 interaction(s) predicted by orthology.
Experimentally validated
Total 392 [view]
Protein-Protein 389 [view]
Protein-DNA 1 [view]
Protein-RNA 0
DNA-DNA 2 [view]
RNA-RNA 0
DNA-RNA 0
Predicted by orthology
Total 57 [view]
Gene Ontology

Molecular Function
Accession GO Term
GO:0004842 ubiquitin-protein transferase activity
GO:0004871 signal transducer activity
GO:0005102 receptor binding
GO:0005164 tumor necrosis factor receptor binding
GO:0005174 CD40 receptor binding
GO:0005515 protein binding
GO:0008270 zinc ion binding
GO:0016874 ligase activity
GO:0019899 enzyme binding
GO:0019903 protein phosphatase binding
GO:0031435 mitogen-activated protein kinase kinase kinase binding
GO:0031625 ubiquitin protein ligase binding
GO:0031996 thioesterase binding
GO:0032403 protein complex binding
GO:0042802 identical protein binding
GO:0046625 sphingolipid binding
GO:0046872 metal ion binding
Biological Process
GO:0002726 positive regulation of T cell cytokine production
GO:0006461 protein complex assembly
GO:0006915 apoptotic process
GO:0006919 activation of cysteine-type endopeptidase activity involved in apoptotic process
GO:0007165 signal transduction
GO:0007250 activation of NF-kappaB-inducing kinase activity
GO:0030163 protein catabolic process
GO:0032743 positive regulation of interleukin-2 production
GO:0033209 tumor necrosis factor-mediated signaling pathway
GO:0034351 negative regulation of glial cell apoptotic process
GO:0042981 regulation of apoptotic process
GO:0043507 positive regulation of JUN kinase activity
GO:0043623 cellular protein complex assembly
GO:0045087 innate immune response (InnateDB)
GO:0046328 regulation of JNK cascade
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:0051291 protein heterooligomerization
GO:0051865 protein autoubiquitination
GO:0070207 protein homotrimerization
GO:0070534 protein K63-linked ubiquitination
GO:0071732 cellular response to nitric oxide
GO:0090073 positive regulation of protein homodimerization activity
GO:0097190 apoptotic signaling pathway
GO:0097300 programmed necrotic cell death
GO:2001238 positive regulation of extrinsic apoptotic signaling pathway
GO:2001239 regulation of extrinsic apoptotic signaling pathway in absence of ligand
Cellular Component
GO:0005737 cytoplasm
GO:0005829 cytosol
GO:0005938 cell cortex
GO:0009898 cytoplasmic side of plasma membrane
GO:0035631 CD40 receptor complex
GO:0043234 protein complex
GO:0045121 membrane raft
Orthologs
Species
Mus musculus
Bos taurus
Gene ID
Gene Order
Method
Confidence
Comments
SSD Ortholog
Ortholog supports species divergence
Not yet available
SSD Ortholog
Ortholog supports species divergence
Pathways
NETPATH
TNFalpha pathway
RANKL pathway
TWEAK pathway
REACTOME
Extrinsic Pathway for Apoptosis pathway
Innate Immune System pathway
TRAF6 mediated IRF7 activation pathway
TRAF6 mediated NF-kB activation pathway
RIG-I/MDA5 mediated induction of IFN-alpha/beta pathways pathway
Apoptosis pathway
Immune System pathway
TNF signaling pathway
Dimerization of procaspase-8 pathway
Regulation by c-FLIP pathway
Caspase-8 activation by cleavage pathway
Death Receptor Signalling pathway
KEGG
MAPK signaling pathway pathway
Protein processing in endoplasmic reticulum pathway
Apoptosis pathway
Osteoclast differentiation pathway
RIG-I-like receptor signaling pathway pathway
Adipocytokine signaling pathway pathway
Hepatitis C pathway
Pathways in cancer pathway
Small cell lung cancer pathway
INOH
TNFR1 signaling pathway pathway
PID BIOCARTA
The 41bb-dependent immune response [Biocarta view]
Tnfr2 signaling pathway [Biocarta view]
Keratinocyte differentiation [Biocarta view]
Induction of apoptosis through dr3 and dr4/5 death receptors [Biocarta view]
Tnfr1 signaling pathway [Biocarta view]
Hiv-1 nef: negative effector of fas and tnf [Biocarta view]
Tnf/stress related signaling [Biocarta view]
Sodd/tnfr1 signaling pathway [Biocarta view]
Ceramide signaling pathway [Biocarta view]
Yaci and bcma stimulation of b cell immune responses [Biocarta view]
PID NCI
CD40/CD40L signaling
Ceramide signaling pathway
Caspase Cascade in Apoptosis
TNF receptor signaling pathway
TRAIL signaling pathway
HIV-1 Nef: Negative effector of Fas and TNF-alpha
p38 MAPK signaling pathway
Cross-References
SwissProt
TrEMBL
UniProt Splice Variant
Entrez Gene
UniGene Hs.522506
RefSeq NM_021138 XM_005266099
HUGO
OMIM
CCDS CCDS7013
HPRD 03538
IMGT
EMBL
GenPept
RNA Seq Atlas