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{
    "metadata": {
        "accession": "PS51507",
        "entry_id": null,
        "type": "domain",
        "go_terms": null,
        "source_database": "profile",
        "member_databases": null,
        "integrated": "IPR001346",
        "hierarchy": null,
        "name": {
            "name": "IRF tryptophan pentad repeat DNA-binding domain profile",
            "short": "IRF_2"
        },
        "description": [
            {
                "text": "<p>Viral infections induce the expression of type I interferons (IFN-alpha and\nIFN-beta) genes. The induction is due to the transcriptional activation of the\nIFN genes. Interferon regulatory factor I (IRF-1) is one of the transcription\nfactors responsible for that activation. IRF-1 binds to an upstream regulatory\ncis element, known as the interferon consensus sequence (ICS), which is found\nin the promoters of type I IFN and IFN-inducible MHC class I genes. Interferon\nregulatory factor 2 (IRF-2) is a protein that also interacts with the ICS, but\nthat does not function as an activator; rather, it suppresses the function of\nIRF-1 under certain circumstances [[cite:PUB00003185]].\n\nThese proteins share a highly conserved N-terminal domain of about 100 amino\nacid residues which is involved in DNA-binding and which contain five\nconserved tryptophan. This domain is known as a 'tryptophan pentad repeat' or\na 'tryptophan cluster' and is also present in:\n\n - Interferon consensus sequence binding protein (ICSBP) [[cite:PUB00004709]],  a transcription\n   factor expressed predominantly in lymphoid tissues and induced by IFN-gamma\n   that also binds to the ICS.\n - Transcriptional regulator ISGF3 gamma subunit [[cite:PUB00003680]]. ISGF3 is responsible for\n   the initial stimulation of interferon-alpha-responsive genes. It recognizes\n   and binds to  the interferon-stimulated  response element (ISRE) within the\n   regulatory sequences of target genes.\n - Interferon regulatory factor 3 (IRF-3).\n - Interferon  regulatory  factor  4  (IRF-4)  which  binds to the interferon-\n   stimulated response element (ISRE) of the MHC class I promoter.\n - Interferon regulatory factor 5 (IRF-5).\n - Interferon regulatory factor 6 (IRF-6).\n - Interferon regulatory factor 7 (IRF-7).\n - Gamma  Herpesviruses  vIRF-1,  -2  and  -3,  proteins  with homology to the\n   cellular transcription  factors  of  the IRF family [[cite:PUB00055524]]. Neither vIRF-1 nor\n   vIRF-2 bind  to  DNA with the same specificity as cellular IRFs, indicating\n   that if  vIRFs  are  DNA-binding  proteins,  their  binding  has  a pattern\n   distinct from  that  of the cellular IRFs. Whether vIRF-3 can bind DNA with\n   the same specificity as cellular IRFs is not known.\n\nThe IRF tryptophan pentad repeat DNA-binding domain has an alpha/beta\narchitecture comprising a cluster of three alpha-helices (alpha1-alpha3)\nflanked on one side by a mixed four-stranded beta-sheet (beta1-beta4). It forms a helix-turn-helix motif that binds to ISRE consensus\nsequences found in target promoters. Three of the tryptophan residues contact\nDNA by recognizing a GAAA sequence [[cite:PUB00004269]].\n\nAs a signature for this domain, we selected the region that spans from the\nsecond to the fourth of the five conserved tryptophans. We also developed a\nprofile which covers the entire IRF tryptophan pentad repeat DNA-binding\ndomain.</p>",
                "llm": false,
                "checked": false,
                "updated": false
            }
        ],
        "wikipedia": null,
        "literature": {
            "PUB00003680": {
                "PMID": 1630447,
                "ISBN": null,
                "volume": "12",
                "issue": "8",
                "year": 1992,
                "title": "Subunit of an alpha-interferon-responsive transcription factor is related to interferon regulatory factor and Myb families of DNA-binding proteins.",
                "URL": null,
                "raw_pages": "3315-24",
                "medline_journal": "Mol Cell Biol",
                "ISO_journal": "Mol. Cell. Biol.",
                "authors": [
                    "Veals SA",
                    "Schindler C",
                    "Leonard D",
                    "Fu XY",
                    "Aebersold R",
                    "Darnell JE Jr",
                    "Levy DE."
                ],
                "DOI_URL": "http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=EBI&pubmedid=1630447"
            },
            "PUB00004269": {
                "PMID": 9422515,
                "ISBN": null,
                "volume": "391",
                "issue": "6662",
                "year": 1998,
                "title": "Structure of IRF-1 with bound DNA reveals determinants of interferon regulation.",
                "URL": null,
                "raw_pages": "103-6",
                "medline_journal": "Nature",
                "ISO_journal": "Nature",
                "authors": [
                    "Escalante CR",
                    "Yie J",
                    "Thanos D",
                    "Aggarwal AK."
                ],
                "DOI_URL": "http://dx.doi.org/10.1038/34224"
            },
            "PUB00004709": {
                "PMID": 2111015,
                "ISBN": null,
                "volume": "87",
                "issue": "10",
                "year": 1990,
                "title": "An interferon gamma-regulated protein that binds the interferon-inducible enhancer element of major histocompatibility complex class I genes.",
                "URL": null,
                "raw_pages": "3743-7",
                "medline_journal": "Proc Natl Acad Sci U S A",
                "ISO_journal": "Proc. Natl. Acad. Sci. U.S.A.",
                "authors": [
                    "Driggers PH",
                    "Ennist DL",
                    "Gleason SL",
                    "Mak WH",
                    "Marks MS",
                    "Levi BZ",
                    "Flanagan JR",
                    "Appella E",
                    "Ozato K."
                ],
                "DOI_URL": "http://ukpmc.ac.uk/picrender.cgi?tool=EBI&pubmedid=2111015&action=stream&blobtype=pdf"
            },
            "PUB00003185": {
                "PMID": 2691585,
                "ISBN": null,
                "volume": "9",
                "issue": "6",
                "year": 1989,
                "title": "Regulation of interferon-beta gene: structure and function of cis-elements and trans-acting factors.",
                "URL": null,
                "raw_pages": "633-40",
                "medline_journal": "J Interferon Res",
                "ISO_journal": "J. Interferon Res.",
                "authors": [
                    "Taniguchi T."
                ],
                "DOI_URL": null
            },
            "PUB00055524": {
                "PMID": 10933732,
                "ISBN": null,
                "volume": "74",
                "issue": "17",
                "year": 2000,
                "title": "Characterization of a novel human herpesvirus 8-encoded protein, vIRF-3, that shows homology to viral and cellular interferon regulatory factors.",
                "URL": null,
                "raw_pages": "8194-201",
                "medline_journal": "J Virol",
                "ISO_journal": "J. Virol.",
                "authors": [
                    "Lubyova B",
                    "Pitha PM."
                ],
                "DOI_URL": "http://dx.doi.org/10.1128/JVI.74.17.8194-8201.2000"
            }
        },
        "set_info": null,
        "overlaps_with": null,
        "counters": {
            "subfamilies": 0,
            "domain_architectures": 0,
            "interactions": 0,
            "matches": 11248,
            "pathways": 0,
            "proteins": 11237,
            "proteomes": 903,
            "sets": 0,
            "structural_models": {
                "alphafold": 10257,
                "bfvd": 8
            },
            "structures": 28,
            "taxa": 3230
        },
        "entry_annotations": {},
        "cross_references": {},
        "is_llm": false,
        "is_reviewed_llm": false,
        "is_updated_llm": false,
        "representative_structure": {
            "accession": "8hcl",
            "name": "zebrafish IRF-10 DBD complex with DNA"
        }
    }
}