interferon regulatory factor 3 (IRF3)

Function: - mediates interferon-stimulated response element (ISRE) promoter activation - functions as a molecular switch for antiviral activity - dsRNA generated during the course of an viral infection leads to IRF3 phosphorylation on the C-terminal Ser/Thr cluster - induces a conformational change, leading to its dimerization, nuclear localization & association with CREB binding protein (CREBBP) to form dsRNA-activated factor 1 (DRAF1), a complex which activates the transcription of genes under the control of ISRE - complex binds to IE region on IFN-alpha & PRDIII region on IFN-beta promoters - IRF-3 does not have any transcription activation domains - constitutively phosphorylated on many Ser - C- terminal Ser/Thr cluster is phosphorylated in response of induction by IKBKE & TBK1 - Ser-385 & Ser-386 may be specifically phosphorylated in response to induction - an alternate model proposes that the five Ser/Thr between 396 & 405 are phosphorylated in response to a viral infection - phosphorylation, & subsequent activation of IRF3 is inhibited by vaccinia virus protein E3 Structure: - homodimer; phosphorylation-induced - interacts with CREBBP - may interact with MAVS - interacts with IKBKE & TBK1 - interacts with TICAM1 & TICAM2 - belongs to the IRF family - contains 1 tryptophan pentad repeat DNA-binding domain Compartment: - cytoplasm, nucleus - shuttles between cytoplasmic & nuclear compartments, with export being the prevailing effect - when activated, IRF3 interaction with CREBBP prevents its export to the cytoplasm Expression: - expressed constitutively in a variety of tissues

Properties

SIZE: entity length = 427 aa MW = 47 kD COMPARTMENT: cytoplasm cell nucleus MOTIF: DNA-binding motif SITE: 7-107 nuclear export signal {139-149} proline-rich region SITE: 151-191 MOTIF: proline residue (SEVERAL) cysteine residue {C267} MODIFICATION: cysteine residue {C289} cysteine residue {C289} MODIFICATION: cysteine residue {C267}

Database Correlations

OMIM 603734 UniProt Q14653 Pfam PF00605 Entrez Gene 3661 Kegg hsa:3661