PROSITE documentation PDOC00522IRF 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.
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| 1 | Authors | Taniguchi T. |
| Title | Regulation of interferon-beta gene: structure and function of cis-elements and trans-acting factors. | |
| Source | J. Interferon Res. 9:633-640(1989). | |
| PubMed ID | 2691585 |
| 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). | |
| PubMed ID | 2111015 |
| 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). | |
| PubMed ID | 1630447 |
| 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). | |
| PubMed ID | 10933732 |
| 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. | |
| Source | Nature 391:103-106(1998). | |
| PubMed ID | 9422515 | |
| DOI | 10.1038/34224 |
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