IRF

interferon regulatory factor

• SMART accession number: SM00348
• Description: interferon regulatory factor, also known as trytophan pentad repeat
• Interpro abstract (IPR001346): The expression of type I interferon genes (interferons alpha and beta) is induced by many agents, including viral attack (PUBMED:3409321). Induction is mediated by the binding of interferon regulatory factor 1 (IRF-1) to a region known as the interferon consensus sequence (ICS), located upstream of the interferon genes (PUBMED:1460054). Other factors may also bind to the ICS, including IRF-2, which does not function as an activator, but rather suppresses the function of IRF-1 under certain circumstances (PUBMED:2475256). IRF proteins contain a conserved N-terminal region of about 120 amino acids, which folds into a structure that binds specifically to the ICS; the remaining parts of the sequences vary depending on the precise function of the protein (PUBMED:1460054).
• GO process: regulation of transcription, DNA-dependent (GO:0006355)
• GO component: nucleus (GO:0005634)
• GO function: transcription factor activity (GO:0003700)

There are 357 IRF domains in 356 proteins in SMART's nrdb database.

Literature (relevant references for this domain)

Primary literature is listed below; Automatically-derived, secondary literature is also avaliable.

• Escalante CR, Yie J, Thanos D, Aggarwal AK
• Structure of IRF-1 with bound DNA reveals determinants of interferon regulation.
• Nature. 1998; 391: 103-6

The family of interferon regulatory factor (IRF) transcription factors is important in the regulation of interferons in response to infection by virus and in the regulation of interferon-inducible genes. The IRF family is characterized by a unique 'tryptophan cluster' DNA-binding region. Here we report the crystal structure of the IRF-1 region bound to the natural positive regulatory domain I (PRD I) DNA element from the interferon-beta promoter. The structure provides the first three-dimensional view of a member of the growing IRF family, revealing a new helix-turn-helix motif that latches onto DNA through three of the five conserved tryptophans. The motif selects a short GAAA core sequence through an obliquely angled recognition helix, with an accompanying bending of the DNA axis in the direction of the protein. Together, these features suggest a basis for the occurrence of GAAA repeats within IRF response elements and provide clues to the assembly of the higher-order interferon-beta enhancesome.

• Veals SA et al.
• Subunit of an alpha-interferon-responsive transcription factor is related to interferon regulatory factor and Myb families of DNA-binding proteins.
• Mol Cell Biol. 1992; 12: 3315-24

Alpha interferon stimulates transcription by converting the positive transcriptional regulator ISGF3 from a latent to an active form. This receptor-mediated event occurs in the cytoplasm, with subsequent translocation of the activated factor to the nucleus. ISGF3 has two components, termed ISGF3 alpha and ISGF3 gamma. ISGF3 gamma serves as the DNA recognition subunit, while ISGF3 alpha, which appears to consist of three polypeptides, is a target for alpha interferon signaling and serves as a regulatory component whose activation is required to form ISGF3. ISGF3 gamma DNA-binding activity was identified as a 48-kDa polypeptide, and partial amino acid sequence has allowed isolation of cDNA clones. ISGF3 gamma translated in vitro from recombinant clones bound DNA with a specificity indistinguishable from that of ISGF3 gamma purified from HeLa cells. Sequencing of ISGF3 gamma cDNA clones revealed significant similarity to the interferon regulatory factor (IRF) family of DNA binding proteins in the amino-terminal 117 residues of ISGF3 gamma. The other IRF family proteins bind DNA with a specificity related to but distinct from that of ISGF3 gamma. We note sequence similarities between the related regions of IRF family proteins and the imperfect tryptophan repeats which constitute the DNA-binding domain of the c-myb oncoprotein. These sequence similarities suggest that ISGF3 gamma and IRF proteins and the c-myb oncoprotein use a common structural motif for DNA recognition. Recombinant ISGF3 gamma, like the natural protein, interacted with HeLa cell ISGF3 alpha to form the mature ISGF3 DNA-binding complex.(ABSTRACT TRUNCATED AT 250 WORDS)

• Taniguchi T
• Regulation of interferon-beta gene: structure and function of cis-elements and trans-acting factors.
• J Interferon Res. 1989; 9: 633-40

Commonly viral infections induce expression of type I interferon (IFN) genes. The induction is primarily due to transcriptional activation of the genes. Soon after the isolation of the genes encoding IFN-alpha and IFN-beta, the IFN system became a subject of intensive study in the context of switching on or off the otherwise silent genes by extracellular stimulation signals. Hence, the IFN system serves as a typical model in studying the genetic events occurring in many cytokine systems. The IFN genes contain within their 5'-flanking region positive elements that function efficiently in cells induced by viruses and other stimuli such as double-stranded RNA. At least three transcription factors have been identified and molecularly cloned. Of these, two factors, designated interferon regulatory factors IRF-1 and IRF-2, are unique in their function; they interact with identical DNA sequence elements of IFN and IFN-inducible genes. Results of the functional studies on these factors suggest that transcription of the IFN and IFN-inducible genes is regulated by two similar trans-acting factors that apparently compete for the same cis-acting recognition sequences, but mediate opposite effects.

Metabolism (metabolic pathways involving proteins which contain this domain)

% proteins involved	KEGG pathway ID	Description
84.00	map04620	Toll-like receptor signaling pathway
16.00	map04630	Jak-STAT signaling pathway

This information is based on mapping of SMART genomic protein database to KEGG orthologous groups. Percentage points are related to the number of proteins with IRF domain which could be assigned to a KEGG orthologous group, and not all proteins containing IRF domain. Please note that proteins can be included in multiple pathways, ie. the numbers above will not always add up to 100%.

Structure (3D structures containing this domain)

3D Structures of IRF domains in PDB

PDB code	Title
1if1	Interferon regulatory factor 1 (irf-1) complex with dna
1irf	Interferon regulatory factor-2 dna binding domain, nmr, minimized average structure
1irg	Interferon regulatory factor-2 dna binding domain, nmr, 20 structures
1t2k	Structure of the dna binding domains of irf3, atf-2 and jun bound to dna
2dll	Solution structure of the irf domain of human interferon regulator factors 4
2irf	Crystal structure of an irf-2/dna complex.
2o61	Crystal structure of nfkb, irf7, irf3 bound to the interferon-b enhancer
2o6g	Crystal structure of irf-3 bound to the interferon-b enhancer
2pi0	Crystal structure of irf-3 bound to the prdiii-i regulatory element of the human interferon-b enhancer

Links (links to other resources describing this domain)

• PFAM: IRF
• INTERPRO: IPR001346
• PROSITE: IRF