{
 "key": "IRF",
 "name": "IRF",
 "class": "IRF",
 "aka": [
  "ISRE",
  "interferon-stimulated response element",
  "IRF-E",
  "IRF element",
  "PRD I / PRD III (interferon-beta promoter)",
  "EICE (composite with PU.1/SPIB)",
  "AICE (composite with BATF-JUN)",
  "ICSBP (IRF8)",
  "Pip (IRF4)",
  "ISGF3-gamma (IRF9)",
  "tryptophan cluster factors"
 ],
 "definition": "ISRE/AICE, AANTGAAA repeats. IRF1-9; composite EICE (with SPI1) and AICE (with BATF).",
 "consensus": "AANTGAAA",
 "dataConsensus": "CGAAACCGAAACt",
 "motifCount": 40,
 "bySource": {
  "JASPAR": 9,
  "HOCOMOCO": 17,
  "CIS-BP": 9,
  "Vierstra": 5
 },
 "symbols": [
  "IRF",
  "IRF1",
  "IRF2",
  "IRF3",
  "IRF4",
  "IRF5",
  "IRF6",
  "IRF7",
  "IRF8",
  "IRF9"
 ],
 "representative": "M03335_2.00",
 "cohesion": 0.81,
 "short": "The nine human interferon regulatory factors, IRF1 through IRF9, bind DNA with an N-terminal winged helix-turn-helix domain studded with five conserved tryptophans. Each domain reads only a short AANTGAAA half-site, so functional elements are tandem repeats of it: the interferon-stimulated response element (ISRE), written RNGAAANNGAAACT or, on the other strand, AGTTTCNNTTTC. The same half-site also appears in two named composites - the EICE with PU.1 or SPIB, and the AICE with BATF-JUN - which is how IRF4 and IRF8, weak DNA binders on their own, reach their targets. IRFs drive the type I and type II interferon responses, myeloid and lymphoid development, and plasma cell differentiation; IRF6 is the non-immune outlier, acting in epithelium, where mutations cause orofacial clefting.",
 "long": "## The factors\n\nNine IRF genes exist in humans, IRF1 to IRF9 [PMID:18303999] (an IRF10 is present in birds and fish but not in\nmammals). Each encodes an N-terminal DNA-binding domain of roughly 115 residues characterized by a\ncluster of five conserved tryptophans - the \"tryptophan cluster\" that defines the family - folded as\na variant helix-turn-helix [PMID:9422515]. Most members also carry a C-terminal IRF-association domain that\nmediates homodimers, IRF-IRF heterodimers, and complexes with non-IRF partners: STAT2 for IRF9,\nBATF-JUN for IRF4 and IRF8, PU.1 and SPIB for IRF4 and IRF8 [PMID:12453417,22983707,29317535]. Functionally the family splits along\nlines that sequence does not see. IRF1 and IRF2 are broadly expressed and act as an\ninterferon-inducible activator/repressor pair on the same sites. IRF3 is constitutive and\ncytoplasmic until phosphorylated on virus sensing, whereupon it dimerizes and drives type I\ninterferon genes; IRF7 amplifies that response and is highly expressed in plasmacytoid dendritic\ncells [PMID:18303999]. IRF9 is the constitutive DNA-binding subunit of ISGF3 [PMID:29317535]. IRF4 and IRF8 are lymphoid and myeloid,\nwith low intrinsic DNA affinity; IRF5 acts in myeloid cells and B cells. IRF6 is the outlier -\nepithelial, expressed in skin and oral periderm, with no established role in interferon signaling [PMID:12219090].\n\n## The motif\n\nThe unit is a short half-site, AANTGAAA, of which only about four bases (the GAAA) are read\nstrongly [PMID:9422515,10487755]. The crystal structure of the IRF1 domain on the PRD I element of the interferon-beta\npromoter showed why: the recognition helix lies obliquely in the major groove, contacts a short GAAA\ncore through three of the five conserved tryptophans, and bends the DNA toward the protein [PMID:9422515]. Because\nso little sequence is read per domain, affinity and specificity come from repetition, and the IRF2\nstructure showed cooperative binding to a tandem GAAA repeat driven by DNA distortion [PMID:10487755]. The canonical\nelement is therefore the ISRE, written RNGAAANNGAAACT [PMID:29317535]; the data consensus for this family,\nCGAAACCGAAACT, is the same element read on the opposite strand, whose reverse complement\nAGTTTCGGTTTCG is the familiar AGTTTCNNTTTC form. Two composites reuse the same half-site with a\ndifferent partner. The EICE, GGAAGTGAAAC, is a PU.1 or SPIB site fused to an IRF half-site [PMID:7797077,12453417]; the\nAICE joins an IRF half-site to an AP-1 site, either as AICE1 (TTTCNNNNTGASTCA, four bases of spacer)\nor AICE2 (GAAATGASTCA, directly abutting) [PMID:22983707,28346410]. Paralogue resolution from sequence is close to zero: the\nin vitro models for all nine IRFs are near-identical GAAA repeats, and what separates them in vivo is\nwhich partner they cooperate with, not which bases they read.\n\n## Where it acts\n\nISREs sit predominantly in promoters of interferon-stimulated genes, usually within a few hundred\nbase pairs of the transcription start site, and in virus-inducible enhancers such as the\ninterferon-beta enhanceosome, where PRD I and PRD III are IRF elements [PMID:9422515]. In lymphoid and myeloid\ncells, IRF4 and IRF8 occupancy is overwhelmingly composite: EICEs at immunoglobulin light-chain\nenhancers [PMID:7797077], where DNA-bound and Ser148-phosphorylated PU.1 raises IRF4 affinity 20- to 40-fold, and\nAICEs with BATF-JUN in T cells and dendritic cells [PMID:22983707]. AICE affinity grades the response to signal\nstrength: high-affinity AICEs remain occupied under weak T-cell receptor stimulation while\nlow-affinity ones only under strong stimulation [PMID:28346410]. ISGF3, the STAT1-STAT2-IRF9 trimer, accounts for\nmost ISRE occupancy in a type I interferon response, with the STAT1-STAT2 pair on the 5' GGAA and\nIRF9 on the second repeat [PMID:29317535]. IRF6 works instead in epithelial enhancers of the periderm and keratinocyte programs.\n\n## Biology and disease\n\nIRFs are the transcriptional output of innate immune sensing and are also lineage regulators.\nHuman IRF8 mutations cause dendritic cell immunodeficiency, with biallelic loss abolishing monocytes\nand dendritic cells [PMID:21524210]. IRF4 is required for plasma cell\ndifferentiation, and multiple myeloma lines die when IRF4 is depleted whether or not IRF4 itself is\nmutated [PMID:18568025]. A common IRF5 haplotype that alters splicing and expression is a reproducible risk factor\nfor systemic lupus erythematosus [PMID:16642019]. IRF6 mutations cause Van der Woude syndrome (cleft lip or palate\nwith lower lip pits) and popliteal pterygium syndrome [PMID:12219090], the clearest case of an IRF acting outside\nimmunity.\n\n## Reading a hit\n\nA single AANTGAAA half-site is not evidence of anything: with roughly six specified bases it is\nexpected on the order of a million times per strand in a 3.1-Gb genome. Require the tandem repeat,\nor a composite. The most common misreading is confusion with STAT. A STAT homodimer site (GAS) is an\ninverted repeat, TTCNNNGAA, with the two half-sites facing each other; an ISRE is a direct repeat,\nGAAANNGAAAC, with both half-sites in the same orientation - and its reverse-complement spelling\nAGTTTCNNTTTC superficially resembles a GAS. The two families genuinely overlap in biology as well,\nbecause ISGF3 contains STAT1 and STAT2 [PMID:29317535], so ISRE-shaped matrices appear under both labels; one\nfootprint archetype grouped in this family is named AC0672:IRF/STAT precisely because the clustering\ncould not separate them. Evidence for this family is comparatively good - most HOCOMOCO models here\ncarry in vitro HT-SELEX or methyl-HT-SELEX support, and most JASPAR profiles here are SELEX-derived - but two\nChIP-derived entries have absorbed a partner's site. HOCOMOCO's ChIP-based IRF8 model\n(IRF8.H14CORE.0.P.B, consensus AGDGGAAGTGAAAGT) contains GGAAGTGAAA, an EICE whose 5' half is a PU.1\nsite, not an IRF site [PMID:7797077,12453417]; and one CIS-BP model here (M07978, TGHGGAAATGARTCA) is AICE2-shaped, an IRF\nhalf-site abutting an AP-1 heptamer [PMID:22983707], and its best match across the databases lies outside the IRF\nfamily. In\nmyeloid or B-lineage data, check for an adjacent GGAA or TGASTCA before concluding that an IRF acted\nalone.",
 "caveats": "A hit identifies an IRF-type element, not an IRF protein: all nine paralogues select\nnear-identical GAAA repeats in vitro, and their specificity in cells comes from partners (PU.1/SPIB\nat an EICE, BATF-JUN at an AICE, STAT2 in ISGF3), not from the bases they read. A lone AANTGAAA\nhalf-site is far too short to be meaningful; insist on a tandem repeat or a composite. Expect\ncross-talk with the STAT family in both directions, since ISGF3 contains STAT1 and STAT2 and reads\nthe ISRE - one footprint archetype here is named IRF/STAT. Most models in this family have in vitro\nsupport, but the ChIP-derived IRF8 model contains an embedded PU.1 half-site and one CIS-BP model in\nthis family is actually an AICE, half AP-1. Neither should be read as intrinsic IRF specificity.",
 "references": [
  {
   "cite": "Escalante CR, Yie J, Thanos D, et al. Structure of IRF-1 with bound DNA reveals determinants of interferon regulation. Nature 1998;391:103-6.",
   "pmid": "9422515",
   "url": "https://pubmed.ncbi.nlm.nih.gov/9422515/"
  },
  {
   "cite": "Fujii Y, Shimizu T, Kusumoto M, et al. Crystal structure of an IRF-DNA complex reveals novel DNA recognition and cooperative binding to a tandem repeat of core sequences. EMBO J 1999;18:5028-41.",
   "pmid": "10487755",
   "url": "https://pubmed.ncbi.nlm.nih.gov/10487755/"
  },
  {
   "cite": "Tamura T, Yanai H, Savitsky D, et al. The IRF family transcription factors in immunity and oncogenesis. Annu Rev Immunol 2008;26:535-84.",
   "pmid": "18303999",
   "url": "https://pubmed.ncbi.nlm.nih.gov/18303999/"
  },
  {
   "cite": "Rengachari S, Groiss S, Devos JM, et al. Structural basis of STAT2 recognition by IRF9 reveals molecular insights into ISGF3 function. Proc Natl Acad Sci U S A 2018;115:E601-E609.",
   "pmid": "29317535",
   "url": "https://pubmed.ncbi.nlm.nih.gov/29317535/"
  },
  {
   "cite": "Escalante CR, Brass AL, Pongubala JM, et al. Crystal structure of PU.1/IRF-4/DNA ternary complex. Mol Cell 2002;10:1097-105.",
   "pmid": "12453417",
   "url": "https://pubmed.ncbi.nlm.nih.gov/12453417/"
  },
  {
   "cite": "Eisenbeis CF, Singh H, Storb U. Pip, a novel IRF family member, is a lymphoid-specific, PU.1-dependent transcriptional activator. Genes Dev 1995;9:1377-87.",
   "pmid": "7797077",
   "url": "https://pubmed.ncbi.nlm.nih.gov/7797077/"
  },
  {
   "cite": "Glasmacher E, Agrawal S, Chang AB, et al. A genomic regulatory element that directs assembly and function of immune-specific AP-1-IRF complexes. Science 2012;338:975-80.",
   "pmid": "22983707",
   "url": "https://pubmed.ncbi.nlm.nih.gov/22983707/"
  },
  {
   "cite": "Iwata A, Durai V, Tussiwand R, et al. Quality of TCR signaling determined by differential affinities of enhancers for the composite BATF-IRF4 transcription factor complex. Nat Immunol 2017;18:563-572.",
   "pmid": "28346410",
   "url": "https://pubmed.ncbi.nlm.nih.gov/28346410/"
  },
  {
   "cite": "Kondo S, Schutte BC, Richardson RJ, et al. Mutations in IRF6 cause Van der Woude and popliteal pterygium syndromes. Nat Genet 2002;32:285-9.",
   "pmid": "12219090",
   "url": "https://pubmed.ncbi.nlm.nih.gov/12219090/"
  },
  {
   "cite": "Hambleton S, Salem S, Bustamante J, et al. IRF8 mutations and human dendritic-cell immunodeficiency. N Engl J Med 2011;365:127-38.",
   "pmid": "21524210",
   "url": "https://pubmed.ncbi.nlm.nih.gov/21524210/"
  },
  {
   "cite": "Shaffer AL, Emre NC, Lamy L, et al. IRF4 addiction in multiple myeloma. Nature 2008;454:226-31.",
   "pmid": "18568025",
   "url": "https://pubmed.ncbi.nlm.nih.gov/18568025/"
  },
  {
   "cite": "Graham RR, Kozyrev SV, Baechler EC, et al. A common haplotype of interferon regulatory factor 5 (IRF5) regulates splicing and expression and is associated with increased risk of systemic lupus erythematosus. Nat Genet 2006;38:550-5.",
   "pmid": "16642019",
   "url": "https://pubmed.ncbi.nlm.nih.gov/16642019/"
  },
  {
   "cite": "Miyamoto M, Fujita T, Kimura Y, et al. Regulated expression of a gene encoding a nuclear factor, IRF-1, that specifically binds to IFN-beta gene regulatory elements. Cell 1988;54:903-13.",
   "pmid": "3409321",
   "url": "https://pubmed.ncbi.nlm.nih.gov/3409321/"
  }
 ],
 "timeline": [
  {
   "year": 1988,
   "finding": "IRF-1 is cloned as the nuclear factor that binds the upstream regulatory region of the interferon-beta gene and mediates its virus-induced transcription; the IRF1 gene is itself virus-inducible.",
   "methods": "cDNA cloning, DNA-binding assays, expression analysis",
   "confidence": "medium",
   "pmids": [
    "3409321"
   ],
   "open": "Which bases IRF-1 read, and how the same factor could act on both interferon-beta and interferon-stimulated genes, was unknown."
  },
  {
   "year": 1995,
   "finding": "Pip (IRF4) is cloned as the lymphoid partner that binds the immunoglobulin light-chain enhancer composite element only together with DNA-bound, Ser148-phosphorylated PU.1, defining the ETS-IRF composite element.",
   "methods": "cDNA cloning, EMSA, co-transfection reporter assays",
   "confidence": "medium",
   "pmids": [
    "7797077"
   ],
   "open": "How IRF4 targets genes in cells that lack PU.1 or SPIB, such as most T cells, was unexplained."
  },
  {
   "year": 1998,
   "finding": "The IRF-1 DNA-binding domain on PRD I of the interferon-beta promoter is a new helix-turn-helix that grips DNA through three of the five conserved tryptophans and reads a short GAAA core through an obliquely angled recognition helix while bending the DNA toward the protein.",
   "methods": "X-ray crystallography",
   "confidence": "high",
   "pmids": [
    "9422515"
   ],
   "open": "The structure suggested, but did not show, why IRF elements are built from GAAA repeats."
  },
  {
   "year": 1999,
   "finding": "The IRF-2 DNA-binding domain structure gives the recognition sequence AANNGAAA and shows cooperative binding to a tandem GAAA repeat driven by DNA distortion, explaining binding to both single and repeated sites.",
   "methods": "X-ray crystallography",
   "confidence": "high",
   "pmids": [
    "10487755"
   ]
  },
  {
   "year": 2002,
   "finding": "The PU.1/IRF4/DNA ternary structure shows the composite element contorted into an S shape that juxtaposes the two DNA-binding domains across the central minor groove, explaining cooperativity with IRF4 and IRF8 and anti-cooperativity with IRF1 and IRF2.",
   "methods": "X-ray crystallography",
   "confidence": "high",
   "pmids": [
    "12453417"
   ]
  },
  {
   "year": 2012,
   "finding": "In T helper 17 cells IRF4 binds AP-1-IRF composite elements (AICEs) cooperatively with BATF-containing AP-1 dimers, resolving how IRF4 and IRF8 find targets without an ETS partner; the same elements operate in TH2, B and dendritic cells.",
   "methods": "ChIP-seq, cooperative DNA-binding assays",
   "confidence": "high",
   "pmids": [
    "22983707"
   ]
  },
  {
   "year": 2017,
   "finding": "Bases flanking the AICE set the affinity of the BATF-IRF4 complex, and enhancers occupied only at strong T-cell receptor signal are low-affinity AICEs, linking motif affinity to signal strength; a high-affinity AICE2 variant at CTLA4 is associated with resistance to autoimmunity.",
   "methods": "ChIP-seq across stimulation strengths, ChIP-exo, in vitro binding",
   "confidence": "medium",
   "pmids": [
    "28346410"
   ]
  },
  {
   "year": 2018,
   "finding": "Crystal structures of the IRF9 association domain alone and bound to the STAT2 coiled-coil domain explain the selective STAT2-IRF9 pairing in ISGF3, and a model of ISGF3 on an ISRE places the STAT pair on the 5' GGAA repeat and IRF9 on the second GAAA repeat.",
   "methods": "X-ray crystallography, EMSA, structural modeling, cell-based reporter assays",
   "confidence": "medium",
   "pmids": [
    "29317535"
   ],
   "open": "The full ISGF3 complex on DNA has not been solved; its placement on the ISRE is a model."
  }
 ],
 "openQuestions": [
  "Why in vitro and ChIP-derived IRF models disagree on the base before each GAAA is unresolved: most HT-SELEX and methyl-HT-SELEX models read CGAAACCGAAAC, placing a CpG in each half-site, while ChIP-derived models read TGAAACTGAAA or GAAAGTGAAA, and whether genomic CpG depletion and methylation suppress a genuine in vitro preference or the SELEX enrichment overstates it has not been tested in the sources cited here.",
  "How ISGF3 sits on the ISRE is inferred rather than observed: the STAT2-IRF9 interface has been crystallized, but the placement of the STAT pair on the 5' GGAA and IRF9 on the second repeat comes from a docked model, so which subunit makes which base contacts is not settled.",
  "The databases cannot separate ISRE-shaped STAT models from IRF models (one archetype is named IRF/STAT), and whether ISRE-shaped STAT1 and STAT2 ChIP motifs reflect contacts by IRF9 within ISGF3 or genuine STAT preference for that element cannot be decided from the matrices alone."
 ],
 "members": [
  {
   "id": "IRF9 (MA0653.1)",
   "source": "JASPAR",
   "consensus": "AaCGAAACCGAAACT",
   "bits": 24.8
  },
  {
   "id": "M05531_2.00",
   "source": "CIS-BP",
   "consensus": "CaGTTTCgncGAAACCGAAAc",
   "bits": 24.1,
   "prov": {
    "inferred": false
   }
  },
  {
   "id": "IRF3 (MA1418.2)",
   "source": "JASPAR",
   "consensus": "gaAAhGGAAACCGAAAC",
   "bits": 23.2
  },
  {
   "id": "IRF4 (MA1419.2)",
   "source": "JASPAR",
   "consensus": "CGAAACCGAAACt",
   "bits": 23
  },
  {
   "id": "AC0666:IRF:IRF",
   "source": "Vierstra",
   "consensus": "CdGTTTCChgGAAACcGAAA",
   "bits": 22.8
  },
  {
   "id": "IRF8 (MA0652.2)",
   "source": "JASPAR",
   "consensus": "CGAAACCGAAACT",
   "bits": 22.4
  },
  {
   "id": "IRF3.H14CORE.1.SM.B",
   "source": "HOCOMOCO",
   "consensus": "CaGTTTCChGGAAACtGaaa",
   "bits": 21.9,
   "prov": {
    "evidence": "SM",
    "grade": "B"
   }
  },
  {
   "id": "M05527_2.00",
   "source": "CIS-BP",
   "consensus": "aGTtTCGntnndncGAtACT",
   "bits": 20.7,
   "prov": {
    "inferred": false
   }
  },
  {
   "id": "IRF2 (MA0051.2)",
   "source": "JASPAR",
   "consensus": "gGAAAGcGAAAccaaa",
   "bits": 20.6
  },
  {
   "id": "M03335_2.00",
   "source": "CIS-BP",
   "consensus": "CGAAACCGAAACt",
   "bits": 19.3,
   "prov": {
    "inferred": false
   }
  },
  {
   "id": "IRF6.H14CORE.1.S.C",
   "source": "HOCOMOCO",
   "consensus": "CGAaACCGAAACt",
   "bits": 18.8,
   "prov": {
    "evidence": "S",
    "grade": "C"
   }
  },
  {
   "id": "IRF2.H14CORE.0.PSM.A",
   "source": "HOCOMOCO",
   "consensus": "CGAAAGCGAAAg",
   "bits": 18.4,
   "prov": {
    "evidence": "PSM",
    "grade": "A"
   }
  },
  {
   "id": "IRF8.H14CORE.1.SM.B",
   "source": "HOCOMOCO",
   "consensus": "tGAAACTGAAACt",
   "bits": 18.2,
   "prov": {
    "evidence": "SM",
    "grade": "B"
   }
  },
  {
   "id": "M08142_2.00",
   "source": "CIS-BP",
   "consensus": "AAnnGAAAgTGAAAgt",
   "bits": 18,
   "prov": {
    "inferred": false
   }
  },
  {
   "id": "M05549_2.00",
   "source": "CIS-BP",
   "consensus": "CGAAACcGAAAC",
   "bits": 17.7,
   "prov": {
    "inferred": false
   }
  },
  {
   "id": "M03337_2.00",
   "source": "CIS-BP",
   "consensus": "CGAAAgCGAAAvT",
   "bits": 17.6,
   "prov": {
    "inferred": false
   }
  },
  {
   "id": "IRF7 (MA0772.2)",
   "source": "JASPAR",
   "consensus": "CGAAAgCGAAAvT",
   "bits": 17.4
  },
  {
   "id": "IRF1.H14CORE.0.P.B",
   "source": "HOCOMOCO",
   "consensus": "aAnnGAAAgTGAAAg",
   "bits": 17.4,
   "prov": {
    "evidence": "P",
    "grade": "B"
   }
  },
  {
   "id": "AC0673:IRF:IRF",
   "source": "Vierstra",
   "consensus": "AAnCGAAAaTCGnTT",
   "bits": 17.4
  },
  {
   "id": "IRF9.H14CORE.0.PSM.A",
   "source": "HOCOMOCO",
   "consensus": "GAAACTGAAACt",
   "bits": 17.3,
   "prov": {
    "evidence": "PSM",
    "grade": "A"
   }
  },
  {
   "id": "IRF8.H14CORE.0.P.B",
   "source": "HOCOMOCO",
   "consensus": "AgdGgAAgTGAAAgt",
   "bits": 15.8,
   "prov": {
    "evidence": "P",
    "grade": "B"
   }
  },
  {
   "id": "IRF4.H14CORE.2.SM.B",
   "source": "HOCOMOCO",
   "consensus": "AcCGAAACCGaaA",
   "bits": 15.7,
   "prov": {
    "evidence": "SM",
    "grade": "B"
   }
  },
  {
   "id": "IRF5 (MA1420.1)",
   "source": "JASPAR",
   "consensus": "CCGAAACCGAAACt",
   "bits": 15.3
  },
  {
   "id": "M03332_2.00",
   "source": "CIS-BP",
   "consensus": "CCGAAACCGAAACt",
   "bits": 15.3,
   "prov": {
    "inferred": false
   }
  },
  {
   "id": "IRF5.H14CORE.0.SM.B",
   "source": "HOCOMOCO",
   "consensus": "GAAACCGAAACt",
   "bits": 15.1,
   "prov": {
    "evidence": "SM",
    "grade": "B"
   }
  },
  {
   "id": "IRF7.H14CORE.1.SM.B",
   "source": "HOCOMOCO",
   "consensus": "AAnCGAAAvcGAAA",
   "bits": 14.7,
   "prov": {
    "evidence": "SM",
    "grade": "B"
   }
  },
  {
   "id": "IRF3.H14CORE.0.PS.A",
   "source": "HOCOMOCO",
   "consensus": "GAAAvgGAAACbGAAA",
   "bits": 14.6,
   "prov": {
    "evidence": "PS",
    "grade": "A"
   }
  },
  {
   "id": "IRF6 (MA1509.1)",
   "source": "JASPAR",
   "consensus": "ACCGAAACT",
   "bits": 14.1
  },
  {
   "id": "IRF7.H14CORE.0.S.B",
   "source": "HOCOMOCO",
   "consensus": "cAAAhCGAAAaT",
   "bits": 14,
   "prov": {
    "evidence": "S",
    "grade": "B"
   }
  },
  {
   "id": "IRF8.H14CORE.2.SM.B",
   "source": "HOCOMOCO",
   "consensus": "aAAcCGAAACT",
   "bits": 13.4,
   "prov": {
    "evidence": "SM",
    "grade": "B"
   }
  },
  {
   "id": "AC0672:IRF/STAT:IRF",
   "source": "Vierstra",
   "consensus": "GAAAccGAAAC",
   "bits": 13.3
  },
  {
   "id": "Irf1 (MA0050.4)",
   "source": "JASPAR",
   "consensus": "tGAAACTGAAA",
   "bits": 13.2
  },
  {
   "id": "AC0670:IRF/ZBED:IRF",
   "source": "Vierstra",
   "consensus": "GTTTCGntnnnncGAtAC",
   "bits": 13.2
  },
  {
   "id": "IRF4.H14CORE.0.P.B",
   "source": "HOCOMOCO",
   "consensus": "GgAAcTGAAAc",
   "bits": 12.8,
   "prov": {
    "evidence": "P",
    "grade": "B"
   }
  },
  {
   "id": "IRF6.H14CORE.0.SM.B",
   "source": "HOCOMOCO",
   "consensus": "aCCGAAACt",
   "bits": 12.7,
   "prov": {
    "evidence": "SM",
    "grade": "B"
   }
  },
  {
   "id": "IRF5.H14CORE.1.S.B",
   "source": "HOCOMOCO",
   "consensus": "CGAAAC",
   "bits": 11.2,
   "prov": {
    "evidence": "S",
    "grade": "B"
   }
  },
  {
   "id": "M07978_2.00",
   "source": "CIS-BP",
   "consensus": "tghgGAAaTGArtca",
   "bits": 10.7,
   "prov": {
    "inferred": false
   }
  },
  {
   "id": "IRF4.H14CORE.1.S.B",
   "source": "HOCOMOCO",
   "consensus": "ACCGAAAC",
   "bits": 10.5,
   "prov": {
    "evidence": "S",
    "grade": "B"
   }
  },
  {
   "id": "M05545_2.00",
   "source": "CIS-BP",
   "consensus": "GAAAgcGAAA",
   "bits": 10.3,
   "prov": {
    "inferred": false
   }
  },
  {
   "id": "AC0671:IRF:IRF",
   "source": "Vierstra",
   "consensus": "CCGAAACc",
   "bits": 10
  }
 ],
 "url": "https://motif.zhoulab.io/families/irf/",
 "generated": "2026-10-21",
 "provenance": "Entry text drafted by a language model reading the primary literature; every cited PMID verified against PubMed. Computed fields derive from JASPAR 2024, HOCOMOCO v14, CIS-BP and the Vierstra archetypes. See https://motif.zhoulab.io/families/methods/"
}