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TRAF2

Domain

The coiled coil domain mediates homo- and hetero-oligomerization.

The MATH/TRAF domain binds to receptor cytoplasmic domains.

The RING-type zinc finger domain is essential for E3 ubiquitin-protein ligase activity. It is not essential for the stabilization of BIRC2, or for the ubiquitination of RIPK1 in response to TNFR1 signaling.

Function

Regulates activation of NF-kappa-B and JNK and plays a central role in the regulation of cell survival and apoptosis (PubMed:22212761). 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.

Pathway

Protein modification; protein ubiquitination.

Post-translational modifications

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). Ubiquitinated at Lys-320 by the SCF(FBXL2) complex, leading to its degradation by the proteasome (By similarity). Ubiquitinated by E3 ubiquitin-protein ligase complex containing FBXO7; leading to repression of NF-kappa-B signaling (PubMed:22212761).

Sequence Similarities

Belongs to the TNF receptor-associated factor family. A subfamily.

Cellular localization

Alternative names

TRAP3, TRAF2, TNF receptor-associated factor 2, E3 ubiquitin-protein ligase TRAF2, RING-type E3 ubiquitin transferase TRAF2, Tumor necrosis factor type 2 receptor-associated protein 3

swissprot:Q12933 entrezGene:7186 omim:601895

Other research areas