TRAF2

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]

TNF receptor-associated factor 2

Regulates activation of NF-kappa-B and JNK and plays a central role in the regulation of cell survival and apoptosis. Required for normal antibody isotype switching from IgM to IgG. Has E3 ubiquitin-protein ligase activity and promotes 'Lys-63'-linked ubiquitination of target proteins, such as BIRC3, RIPK1 and TICAM1. Is an essential constituent of several E3 ubiquitin-protein ligase complexes, where it promotes the ubiquitination of target proteins by bringing them into contact with other E3 ubiquitin ligases. Regulates BIRC2 and BIRC3 protein levels by inhibiting their autoubiquitination and subsequent degradation; this does not depend on the TRAF2 RING-type zinc finger domain. Plays a role in mediating activation of NF-kappa-B by EIF2AK2/PKR. In complex with BIRC2 or BIRC3, promotes ubiquitination of IKBKE.

Activation of NF-kappaB-inducing kinase activityManual Assertion Based On ExperimentIMP:UniProtKB
Cellular response to nitric oxideIEA:Ensembl
Interleukin-17-mediated signaling pathwayIEA:Ensembl
Intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stressManual Assertion Based On ExperimentTAS:ParkinsonsUK-UCL
mRNA stabilizationIEA:Ensembl
Negative regulation of glial cell apoptotic processIEA:Ensembl
Negative regulation of neuron deathManual Assertion Based On ExperimentTAS:ParkinsonsUK-UCL
Positive regulation of DNA-binding transcription factor activityManual Assertion Based On ExperimentIMP:BHF-UCL
Positive regulation of extrinsic apoptotic signaling pathwayManual Assertion Based On ExperimentIMP:UniProtKB
Positive regulation of I-kappaB kinase/NF-kappaB signalingManual Assertion Based On ExperimentIBA:GO_Central
Positive regulation of I-kappaB phosphorylationIEA:Ensembl
Positive regulation of interleukin-2 productionManual Assertion Based On ExperimentIMP:UniProtKB
Positive regulation of JNK cascadeManual Assertion Based On ExperimentIBA:GO_Central
Positive regulation of JUN kinase activityManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of NF-kappaB transcription factor activityManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of T cell cytokine productionManual Assertion Based On ExperimentIMP:UniProtKB
Positive regulation of tumor necrosis factor-mediated signaling pathwayIEA:Ensembl
Programmed necrotic cell deathIEA:Ensembl
Protein autoubiquitinationManual Assertion Based On ExperimentIDA:UniProtKB
Protein catabolic processIEA:Ensembl
Protein K63-linked ubiquitinationManual Assertion Based On ExperimentIDA:UniProtKB
Protein-containing complex assemblyISS:BHF-UCL
Regulation of apoptotic processManual Assertion Based On ExperimentIDA:UniProtKB
Regulation of I-kappaB kinase/NF-kappaB signalingManual Assertion Based On ExperimentIBA:GO_Central
Regulation of immunoglobulin productionIEA:Ensembl
Regulation of protein-containing complex assemblyManual Assertion Based On ExperimentIMP:UniProtKB
Response to endoplasmic reticulum stress1 PublicationNAS:ParkinsonsUK-UCL
Signal transductionManual Assertion Based On ExperimentTAS:ProtInc
Signal transduction involved in regulation of gene expressionIEA:Ensembl
Tumor necrosis factor-mediated signaling pathwayManual Assertion Based On ExperimentIDA:UniProtKB

Cytoplasm

Phosphorylated at several serine residues within the first 128 amino acid residues. Phosphorylated at Thr-117 in response to signaling via TNF and TNFRSF1A. Phosphorylation at Thr-117 is required for 'Lys-63'-linked polyubiquitination, but not for 'Lys-48'-linked polyubiquitination. Phosphorylation at Thr-117 is important for interaction with IKKA and IKKB, activation of IKK and subsequent activation of NF-kappa-B.
Undergoes both 'Lys-48'-linked and 'Lys-63'-linked polyubiquitination. Polyubiquitinated via 'Lys-63'-linked ubiquitin in response to TNF signaling; this requires prior phosphorylation at Thr-117. 'Lys-63'-linked polyubiquitination promotes TRAF2-mediated activation of NF-kappa-B. Can be polyubiquitinated at several Lys residues via 'Lys-48'-linked ubiquitin chains in response to TNF signaling, leading to proteasomal degradation. Autoubiquitinated, leading to its subsequent proteasomal degradation. Polyubiquitinated by BIRC2 and SIAH2, leading to its subsequent proteasomal degradation. Deubiquitinated by CYLD, a protease that specifically cleaves 'Lys-63'-linked polyubiquitin chains. Ubiquination is inhibited by LRRC19; inhibits proteasomal degradation (PubMed:25026888).