|PROSITE documentation PDOC00522|
Viral infections induce the expression of type I interferons (IFN-α and IFN-β) genes. The induction is due to the transcriptional activation of the IFN genes. Interferon regulatory factor I (IRF-1) is one of the transcription factors responsible for that activation. IRF-1 binds to an upstream regulatory cis element, known as the interferon consensus sequence (ICS), which is found in the promoters of type I IFN and IFN-inducible MHC class I genes. Interferon regulatory factor 2 (IRF-2) is a protein that also interacts with the ICS, but that does not function as an activator; rather, it suppresses the function of IRF-1 under certain circumstances .
These proteins share a highly conserved N-terminal domain of about 100 amino acid residues which is involved in DNA-binding and which contain five conserved tryptophan. This domain is known as a 'tryptophan pentad repeat' or a 'tryptophan cluster' and is also present in:
The IRF tryptophan pentad repeat DNA-binding domain has an α/β architecture comprising a cluster of three α-helices (α1-α3) flanked on one side by a mixed four-stranded β-sheet (β1-β4) (see <PDB:1IF1>). It forms a helix-turn-helix motif that binds to ISRE consensus sequences found in target promoters. Three of the tryptophan residues contact DNA by recognizing a GAAA sequence .
As a signature for this domain, we selected the region that spans from the second to the fourth of the five conserved tryptophans. We also developed a profile which covers the entire IRF tryptophan pentad repeat DNA-binding domain.Last update:
August 2010 / Text revised; profile added.
PROSITE methods (with tools and information) covered by this documentation:
|Title||Regulation of interferon-beta gene: structure and function of cis-elements and trans-acting factors.|
|Source||J. Interferon Res. 9:633-640(1989).|
|2||Authors||Driggers P.H. Ennist D.L. Gleason S.L. Mak W.-H. Marks M.S. Levi B.-Z. Flanagan J.R. Appella E. Ozato K.|
|Title||An interferon gamma-regulated protein that binds the interferon-inducible enhancer element of major histocompatibility complex class I genes.|
|Source||Proc. Natl. Acad. Sci. U.S.A. 87:3743-3747(1990).|
|3||Authors||Veals S.A. Schindler C. Leonard D. Fu X.-Y. Aebersold R. Darnell J.E. Jr. Levy D.E.|
|Title||Subunit of an alpha-interferon-responsive transcription factor is related to interferon regulatory factor and Myb families of DNA-binding proteins.|
|Source||Mol. Cell. Biol. 12:3315-3324(1992).|
|4||Authors||Lubyova B. Pitha P.M.|
|Title||Characterization of a novel human herpesvirus 8-encoded protein, vIRF-3, that shows homology to viral and cellular interferon regulatory factors.|
|Source||J. Virol. 74:8194-8201(2000).|
|5||Authors||Escalante C.R. Yie J. Thanos D. Aggarwal A.K.|
|Title||Structure of IRF-1 with bound DNA reveals determinants of interferon regulation.|