IRF9: Proteins and Enzymes

Interferon regulator transcription factors (IRF) are a family characterized by a helix-turn-helix DNA binding domain enriched in tryptophan repeats. IRF family members show diverse cellular regulation of interferon-stimulated gene transcription, viral-mediated gene activation, apoptosis, differentiation, and cellular growth. IRF2 functions as a regulator of type I interferons influencing cellular proliferation and immune response through transcriptional regulation. IRF2 competitively inhibits IRF1 gene activation, as well as, stimulating transcription on its own. Human IRF3 is a transcription factor that binds the interferon-sensitive response element (ISRE) and is activated by Toll-like receptors, TLR3 and TLR4.

IRF9 (interferon regulatory factor 9; also ISGF3-gamma) is a 48 kDa member of the IRF family of proteins. It is widely expressed, and serves as a component of the ISGF3 complex. Following activation of IFNAR by IFN-alpha/beta, IRF9 is acetylated by CBP on Lys81. IRF9 then associates with activated STAT1 and STAT2 to form an ISGF3 complex that is translocated into the nucleus. Human IRF9 is 393 amino acids (aa) in length. It contains an N-terminal DNA-binding region (aa 11 - 112) that contains an NLS (aa 66 - 85), plus a STAT-binding domain (aa 200 - 393). There are two potential isoform variants. One shows a deletion of aa 218 - 331 and 340 - 393, while another shows a five aa substitution for aa 217 - 393. Over aa 238 - 393, human IRF9 shares 79% aa identity with mouse IRF9.