PROSITE documentation PDOC00522
IRF tryptophan pentad repeat DNA-binding domain signature and profile


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 [1].

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:

  • Interferon consensus sequence binding protein (ICSBP) [2], a transcription factor expressed predominantly in lymphoid tissues and induced by IFN-γ that also binds to the ICS.
  • Transcriptional regulator ISGF3 γ subunit [3]. ISGF3 is responsible for the initial stimulation of interferon-α-responsive genes. It recognizes 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).
  • γ Herpesviruses vIRF-1, -2 and -3, proteins with homology to the cellular transcription factors of the IRF family [4]. 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 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 [5].

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.


Technical section

PROSITE methods (with tools and information) covered by this documentation:

IRF_2, PS51507; IRF tryptophan pentad repeat DNA-binding domain profile  (MATRIX)

IRF_1, PS00601; IRF tryptophan pentad repeat DNA-binding domain signature  (PATTERN)


1AuthorsTaniguchi T.
TitleRegulation of interferon-beta gene: structure and function of cis-elements and trans-acting factors.
SourceJ. Interferon Res. 9:633-640(1989).
PubMed ID2691585

2AuthorsDriggers P.H. Ennist D.L. Gleason S.L. Mak W.-H. Marks M.S. Levi B.-Z. Flanagan J.R. Appella E. Ozato K.
TitleAn interferon gamma-regulated protein that binds the interferon-inducible enhancer element of major histocompatibility complex class I genes.
SourceProc. Natl. Acad. Sci. U.S.A. 87:3743-3747(1990).
PubMed ID2111015

3AuthorsVeals S.A. Schindler C. Leonard D. Fu X.-Y. Aebersold R. Darnell J.E. Jr. Levy D.E.
TitleSubunit of an alpha-interferon-responsive transcription factor is related to interferon regulatory factor and Myb families of DNA-binding proteins.
SourceMol. Cell. Biol. 12:3315-3324(1992).
PubMed ID1630447

4AuthorsLubyova B. Pitha P.M.
TitleCharacterization of a novel human herpesvirus 8-encoded protein, vIRF-3, that shows homology to viral and cellular interferon regulatory factors.
SourceJ. Virol. 74:8194-8201(2000).
PubMed ID10933732

5AuthorsEscalante C.R. Yie J. Thanos D. Aggarwal A.K.
TitleStructure of IRF-1 with bound DNA reveals determinants of interferon regulation.
SourceNature 391:103-106(1998).
PubMed ID9422515

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