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

More general terms

• interferon regulatory factor family

Database

• UniProt: http://www.uniprot.org/uniprot/Q14653.html
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:3661
• OMIM: https://mirror.omim.org/entry/603734
• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=3661