Phospho-IRF-7 (Ser437/Ser438) Antibody - #AF3886

Key transcriptional regulator of type I interferon (IFN)-dependent immune responses and plays a critical role in the innate immune response against DNA and RNA viruses. Regulates the transcription of type I IFN genes (IFN-alpha and IFN-beta) and IFN-stimulated genes (ISG) by binding to an interferon-stimulated response element (ISRE) in their promoters. Can efficiently activate both the IFN-beta (IFNB) and the IFN-alpha (IFNA) genes and mediate their induction via both the virus-activated, MyD88-independent pathway and the TLR-activated, MyD88-dependent pathway. Induces transcription of ubiquitin hydrolase USP25 mRNA in response to lipopolysaccharide (LPS) or viral infection in a type I IFN-dependent manner. Required during both the early and late phases of the IFN gene induction but is more critical for the late than for the early phase. Exists in an inactive form in the cytoplasm of uninfected cells and following viral infection, double-stranded RNA (dsRNA), or toll-like receptor (TLR) signaling, becomes phosphorylated by IKBKE and TBK1 kinases. This induces a conformational change, leading to its dimerization and nuclear localization where along with other coactivators it can activate transcription of the type I IFN and ISG genes. Can also play a role in regulating adaptive immune responses by inducing PSMB9/LMP2 expression, either directly or through induction of IRF1. Binds to the Q promoter (Qp) of EBV nuclear antigen 1 a (EBNA1) and may play a role in the regulation of EBV latency. Can activate distinct gene expression programs in macrophages and regulate the anti-tumor properties of primary macrophages.

Acetylation inhibits its DNA-binding ability and activity.

In response to a viral infection, phosphorylated by TBK1 and IKBKE1. Phosphorylation, and subsequent activation is inhibited by vaccinia virus protein E3. In TLR7- and TLR9-mediated signaling pathway, phosphorylated by IRAK1 (By similarity).

TRAF6-mediated ubiquitination is required for IRF7 activation. TRIM35 mediates IRF7 'Lys-48'-linked polyubiquitination and subsequent proteasomal degradation (By similarity). 'Lys-48'-linked polyubiquitination and subsequent proteasomal degradation is NMI-dependent in response to Sendai virus infection. Ubiquitinated by UBE3C, leading to its degradation (By similarity).

Sumoylated by TRIM28, which inhibits its transactivation activity.

Nucleus. Cytoplasm.
Note: The phosphorylated and active form accumulates selectively in the nucleus.

Monomer. Homodimer; phosphorylation-induced. Heterodimer with IRF3. Interacts with TICAM1 and TICAM2. Interacts with MYD88 AND TRAF6. Interacts with NMI; the interaction is direct and leads to the inhibition of IRF7-mediated type I IFN production.

Belongs to the IRF family.