IRF

interferon regulatory factor
IRF
SMART accession number:SM00348
Description: interferon regulatory factor, also known as trytophan pentad repeat
Interpro abstract (IPR001346):

Viral infections induce the expression of type I interferons (IFN-alpha and IFN-beta) 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 [ (PUBMED:2691585) ].

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 tryptophans. This domain is known as a 'tryptophan pentad repeat' or a 'tryptophan cluster' and is also present in:

  • Interferon consensus sequence binding protein (ICSBP) [ (PUBMED:2111015) ], a transcription factor expressed predominantly in lymphoid tissues and induced by IFN-gamma that also binds to the ICS.
  • Transcriptional regulator ISGF3 gamma subunit [ (PUBMED:1630447) ]. ISGF3 is responsible for the initial stimulation of interferon-alpha-responsive genes. It recognises and binds to the interferon-stimulated response element (ISRE) within the regulatory sequences of target genes.
  • Interferon regulatory factor 3 (IRF-3).
  • Interferon regulatory factor 4 (IRF-4) which binds to the interferon- stimulated response element (ISRE) of the MHC class I promoter.
  • Interferon regulatory factor 5 (IRF-5).
  • Interferon regulatory factor 6 (IRF-6).
  • Interferon regulatory factor 7 (IRF-7).
  • Gamma Herpesviruses vIRF-1, -2 and -3, proteins with homology to the cellular transcription factors of the IRF family [ (PUBMED:10933732) ]. Neither vIRF-1 nor vIRF-2 bind to DNA with the same specificity as cellular IRFs, indicating that if vIRFs are DNA-binding proteins, their binding has a pattern distinct from that of the cellular IRFs. Whether vIRF-3 can bind DNA with the same specificity as cellular IRFs is not known.

The IRF tryptophan pentad repeat DNA-binding domain has an alpha/beta architecture comprising a cluster of three alpha-helices (alpha1-alpha3) flanked on one side by a mixed four-stranded beta-sheet (beta1-beta4). 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 recognising a GAAA sequence [ (PUBMED:9422515) ].

This entry represents the IRF tryptophan pentad repeat DNA-binding domain.

GO function:transcription regulatory region sequence-specific DNA binding (GO:0000976)
Family alignment:
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There are 3978 IRF domains in 3974 proteins in SMART's nrdb database.

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