TRAF3IP2
Description
The TRAF3IP2 (TRAF3 interacting protein 2) is a protein-coding gene located on chromosome 6.
The TRAF3IP2 gene encodes a protein involved in regulating responses to cytokines by the Rel/NF-kappa-B transcription factor family. This family is key for innate immunity against pathogens, inflammatory signals and stress. The TRAF3IP2 protein interacts with TRAF proteins and activates either NF-kappa-B or Jun kinase. Two alternative transcripts encoding different proteins have been identified. A third transcript, which does not encode a protein and is transcribed in the opposite orientation, has been identified. Overexpression of this transcript has been shown to reduce expression of at least one of the protein encoding transcripts, suggesting it has a regulatory role in the expression of this gene.
TRAF3IP2 is the key activator of Th17-mediated inflammatory responses but also suppresses the humoral B cell response by negatively regulating CD40L and BAFF signaling. TRAF3IP2 seems to be more specific to Brucella infections than other Gram-negative bacteria. In a study, TRAF3IP2 expression was increased fourfold in human blood DCs after exposure to the Brucella virulence factor CβG (β-1,2 cyclic glucan) compared to the E. coli lipopolysaccharides (LPS). CβG is a highly abundant virulence factor of Brucella that modulates membrane rafts of the infected cell necessary for the intracellular escape.
TRAF3IP2 is an E3 ubiquitin ligase that attaches ubiquitin chains to target proteins, specifically using a 'Lys-63' linkage. This modification strengthens protein interactions and boosts signaling pathways. TRAF3IP2 receives ubiquitin from the E2 enzymes UBE2V1 and UBE2N and delivers it to its target proteins. TRAF3IP2 is essential for IL-17A signaling. When IL-17A binds to its receptors, IL17RA and IL17RC, TRAF3IP2 binds to them through its SEFIR domains and attaches ubiquitin chains to TRAF6. This ubiquitination activates TRAF6, which then activates the NF-kappa-B and MAP kinase pathways.
TRAF3IP2 is also known as ACT1, C6orf2, C6orf4, C6orf5, C6orf6, CANDF8, CIKS, PSORS13.
