Recombinant Human TNF receptor-associated factor 3 (TRAF3)

Function

Cytoplasmic E3 ubiquitin ligase that regulates various signaling pathways, such as the NF-kappa-B, mitogen-activated protein kinase (MAPK) and interferon regulatory factor (IRF) pathways, and thus controls a lot of biological processes in both immune and non-immune cell types (PubMed:33148796, PubMed:33608556). In TLR and RLR signaling pathways, acts as an E3 ubiquitin ligase promoting the synthesis of 'Lys-63'-linked polyubiquitin chains on several substrates such as ASC that lead to the activation of the type I interferon response or the inflammasome (PubMed:25847972, PubMed:27980081). Following the activation of certain TLRs such as TLR4, acts as a negative NF-kappa-B regulator, possibly to avoid unregulated inflammatory response, and its degradation via 'Lys-48'-linked polyubiquitination is required for MAPK activation and production of inflammatory cytokines. Alternatively, when TLR4 orchestrates bacterial expulsion, TRAF3 undergoes 'Lys-33'-linked polyubiquitination and subsequently binds to RALGDS, mobilizing the exocyst complex to rapidly expel intracellular bacteria back for clearance (PubMed:27438768). Also acts as a constitutive negative regulator of the alternative NF-kappa-B pathway, which controls B-cell survival and lymphoid organ development. Required for normal antibody isotype switching from IgM to IgG. Plays a role T-cell dependent immune responses. Down-regulates proteolytic processing of NFKB2, and thereby inhibits non-canonical activation of NF-kappa-B. Promotes ubiquitination and proteasomal degradation of MAP3K14

Subcellular Location

Cytoplasm; Endosome; Mitochondrion

Disease Association

Immunodeficiency 132A (IMD132A) : An autosomal dominant immunologic disorder characterized by increased susceptibility to infection with certain pathogens, including Herpes simplex virus and Mycobacterium abscessus. Immunologic work-up shows impaired production of cytokines, including INFB and IL6. [The disease is caused by variants affecting the gene represented in this entry] | Immunodeficiency 132B (IMD132B) : An autosomal dominant immune disorder characterized by childhood onset of recurrent upper and lower respiratory infections, B-cell lymphoid hyperplasia, and dysregulation of T-cell subsets and function. Additional variable features include autoimmunity, autoinflammation, and hyper- or hypogammaglobulinemia. [The disease is caused by variants affecting the gene represented in this entry]

Subunit

(Microbial infection) Interacts with Epstein-Barr virus protein LMP1

• Hu H.M. et al. A novel RING finger protein interacts with the cytoplasmic domain of CD40. — J. Biol. Chem. (1994)
• Mosialos G. et al. The Epstein-Barr virus transforming protein LMP1 engages signaling proteins for the tumor necrosis factor receptor family. — Cell (1995)
• Sato T. et al. A novel member of the TRAF family of putative signal transducing proteins binds to the cytosolic domain of CD40. — FEBS Lett. (1995)
• Cheng G. et al. Involvement of CRAF1, a relative of TRAF, in CD40 signaling. — Science (1995)
• Li W.B. et al. Full-length cDNA libraries and normalization. (FEB-)
• Ota T. et al. Complete sequencing and characterization of 21,243 full-length human cDNAs. — Nat. Genet. (2004)
• Heilig R. et al. The DNA sequence and analysis of human chromosome 14. — Nature (2003)
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). — Genome Res. (2004)