{
 "key": "ETS_CLASS1",
 "name": "ETS class I (ETS1/ERG/FLI1)",
 "class": "ETS",
 "aka": [
  "ETS site",
  "EBS",
  "ETS-binding site",
  "GGAA core",
  "ETS class I",
  "PEA3 site",
  "TCF site",
  "Tryptophan cluster factors / Ets-related factors (TFClass)"
 ],
 "definition": "GGA(A/T) core, ACCGGAAGT. ETS1/2, ERG, FLI1, FEV, ETV1/4/5, ETV6/7, ERF, ETV3, ELK1/3/4, GABPA, SPDEF.",
 "consensus": "ACCGGAAGT",
 "dataConsensus": "ACCGGAAGT",
 "motifCount": 81,
 "bySource": {
  "JASPAR": 32,
  "HOCOMOCO": 23,
  "CIS-BP": 16,
  "Vierstra": 10
 },
 "symbols": [
  "ELK",
  "ELK1",
  "ELK3",
  "ELK4",
  "ERF",
  "ERG",
  "ETS",
  "ETS1",
  "ETS2",
  "ETV",
  "ETV1",
  "ETV3",
  "ETV3L",
  "ETV4",
  "ETV5",
  "FEV",
  "FLI",
  "FLI1",
  "GABPA",
  "SPDEF"
 ],
 "representative": "ETS1.H14CORE.0.S.B",
 "cohesion": 0.82,
 "short": "ETS proteins are a family of 28 human transcription factors that each bind DNA through a single ~85-residue winged helix-turn-helix domain and read a nine-base site whose informative part is the four-base core GGA(A/T). The class I members - ETS1 and ETS2, ERG, FLI1, FEV, the PEA3 proteins ETV1/4/5, the ternary complex factors ELK1/3/4, the repressors ERF and ETV3, and GABPA - select essentially the same sequence, ACCGGAAGT, so a match names the class rather than a protein. These sites sit just upstream of a large fraction of human promoters and, in enhancers, next to RUNX, GATA, PAX and SRF sites. Class I also contains every ETS gene recurrently rearranged in cancer: ERG in prostate cancer, FLI1 and ERG in Ewing sarcoma, ETV1 and ETV4 in both.",
 "long": "## The factors\n\nThe human genome contains 28 ETS genes. All encode one copy of the ETS domain: about 85 residues\nfolded as a winged helix-turn-helix, three alpha-helices packed on a four-stranded antiparallel\nbeta-sheet, that binds DNA as a monomer [PMID:8602247,21548782]. Profiling the DNA-binding preference of every human and\nmouse ETS protein split the family into four classes, and class I is by far the largest: the ETS\nsubfamily (ETS1, ETS2), the ERG subfamily (ERG, FLI1, FEV), the PEA3 proteins (ETV1, ETV4,\nETV5), the ternary complex factors (ELK1, ELK3, ELK4), the repressors ERF and ETV3, and GABPA [PMID:20517297].\nGABPA is the structural exception: it functions only in complex with the ankyrin-repeat subunit\nGABPB, which it recruits using the ETS domain plus a carboxy-terminal extension [PMID:9461436]. Several class I\nproteins carry autoinhibitory segments flanking the ETS domain that are relieved by partner\nbinding [PMID:10075931,21548782]. Expression ranges from near-ubiquitous (GABPA, ELK1, ERF, ETV3) through\nlymphoid-enriched (ETS1), endothelial and hematopoietic (ERG, FLI1), to narrowly restricted\n(FEV). SPDEF is grouped here in this atlas, but biochemically it is the sole class IV factor and\nprefers a GGAT core [PMID:20517297,21548782].\n\n## The motif\n\nThe site is nine base pairs, ACCGGAAGT, and nearly all of its information is in the GGA(A/T)\ncore [PMID:21548782]. Two invariant arginines in recognition helix H3 hydrogen-bond the two core guanines; a\nconserved tyrosine (Tyr395 in ETS1) supports the interface; a lysine in the wing contacts DNA 5'\nof the core and a lysine in the H2-H3 turn contacts the opposite strand 3' of it [PMID:8602247,21548782]. The core is\nread base by base, the flanks indirectly, through sequence-dependent backbone geometry [PMID:21548782]. The\nflanks separate subfamilies, and separate them weakly: class I prefers A three bases 5' of the core and disfavors C there, the ELF/EHF group\nprefers C at that position (CCCGGAAGT), SPI1/SPIB/SPIC use a purine-rich 5' flank (AGAGGAAGTG),\nand SPDEF alone prefers GGAT [PMID:20517297]. Quantitatively, different ETS proteins vary only about ten-fold in\naffinity for the same consensus, whereas one protein's affinity across variant sites spans five-\nto eighty-fold [PMID:21548782]; sequence therefore grades site quality much better than it identifies a\nparalogue, and no class I member is separable from another by motif alone. The CCGG contains a\nCpG, and methylating it blocks binding [PMID:20019798,21548782]. Tandem arrangements are a distinct case: GGAA\nmicrosatellites of four or more consecutive repeats are the response elements of the EWS-FLI1\nfusion [PMID:18626011,21548782], and some models grouped here (JASPAR MA0149.1, archetype AC0561) are GGAA repeats rather\nthan single sites.\n\n## Where it acts\n\nETS occupancy follows two logics. At promoters it is largely redundant: a strong CCGGAAGT sits\n20-40 bp upstream of the transcription start site in CpG-island housekeeping promoters - roughly\na quarter of human promoters carry an ETS site near the start site [PMID:17652178,21548782] - and different ETS proteins\nbind interchangeably, with most GABPA-occupied promoters in Jurkat cells also occupied by ETS1 [PMID:17652178,20019798].\nThese sites lie in hypomethylated CpG islands, so the CpG in the core stays unmethylated [PMID:21548782]. At\ndistal, DNase-sensitive enhancers, occupancy is factor-specific, the sequence departs from\nconsensus [PMID:17652178,20019798], and specificity comes from composite elements: ETS1 with RUNX1 at AGGA(A/T)GTGG, which\nbinds more than 30-fold cooperatively and marks over a thousand ETS1-specific regions in T cells [PMID:10075931,20019798,21548782];\nETS with GATA in hemogenic endothelium, where FLI1, GATA2 and SCL cross-regulate through\nneighboring sites [PMID:17962413]; ETS1 with PAX5 at the mb-1 promoter, where Gln22 of the PAX5 paired domain\nhydrogen-bonds Tyr395 of ETS1 [PMID:11779502,21548782]; the ternary complex factors with SRF at serum response elements [PMID:11715049,21548782];\nand ERG with the androgen receptor in prostate cancer, where the two share about 44% of sites [PMID:21548782].\nThe ETS-IRF composite element (EICE) belongs to the SPI1 subfamily and is described there.\n\n## Biology and disease\n\nClass I factors run housekeeping transcription, growth-factor responses and lineage programs.\nGabpa-null mouse embryos die before implantation [PMID:15199140], consistent with GABPA's occupancy of\nhousekeeping promoters. Ets1 loss impairs T-cell and natural killer cell development. ERG and\nFLI1 are required for endothelial and hematopoietic specification. The clinical weight of the\nclass is oncogenic rearrangement: TMPRSS2-ERG and related fusions place ERG, ETV1, ETV4 or ETV5\nunder androgen control in roughly half of prostate cancers [PMID:16254181,21548782], and EWSR1-FLI1 or EWSR1-ERG defines\nEwing sarcoma, where the fusion's prion-like EWSR1 domain converts GGAA microsatellites into de\nnovo enhancers [PMID:18626011,28844694].\n\n## Reading a hit\n\nTreat a single match as weak evidence. The four-base GGAA core is expected about 12 million times\nper strand in a 3.1-Gb genome and the full nine-mer ACCGGAAGT on the order of 10,000 times per\nstrand by base-composition arithmetic; CCGG-containing words are rarer than that because the\ngenome is CpG-depleted, but the site is still common enough that isolated hits mean little\nwithout context: conservation, accessibility, a nearby partner site, or a promoter position close\nto the start site. A hit identifies an ETS site, not an ETS protein: ETS1, ERG, FLI1, ELK1\nand GABPA are not distinguishable from sequence. ChIP-derived models carry partner signal:\nHOCOMOCO's ChIP-based ETS1 model (ETS1.H14CORE.1.P.B) has consensus ACAGGAAGTGG, whose trailing\nGTGG is the RUNX1 half-site of the ETS1-RUNX1 composite [PMID:20019798], and several other ChIP-derived ETS\nmodels converge on CAGGAAG rather than the in vitro CCGGAAGT [PMID:20019798,21548782]. Half of the JASPAR entries grouped\nhere (16 of 32) are CAP-SELEX heterodimer models such as ERF::SREBF2 or ETV5::FIGLA, where much\nof the matrix is the partner's site, not an ETS site. Finally, consensus strings are stored on\neither strand: GABPA's JASPAR model reads CACTTCCTGT, the reverse complement of ACAGGAAGTG.",
 "caveats": "A hit tells you the family, not the member: all class I ETS proteins select the\nsame nine-mer in vitro and differ only in weak flanking preferences, so a \"FLI1 site\" and an\n\"ERG site\" are the same sequence. The core is short and frequent, so a match outside an\naccessible, conserved or composite context is expected by chance. Sixteen of the 32 JASPAR models\nhere are CAP-SELEX heterodimers whose matrices are partly a bHLH, FOX, HOX or SREBF site; four\nmodels here are GGAA repeats rather than single sites and will hit any GGAA microsatellite; and the\nChIP-derived HOCOMOCO models (evidence letter P) include RUNX-extended and CAGGAAG variants that\nreflect partners and indirect binding rather than intrinsic ETS specificity. SPDEF is placed in\nthis family here but reads GGAT and is biochemically its own class.",
 "references": [
  {
   "cite": "Hollenhorst PC, McIntosh LP, Graves BJ. Genomic and biochemical insights into the specificity of ETS transcription factors. Annu Rev Biochem 2011;80:437-71.",
   "pmid": "21548782",
   "url": "https://pubmed.ncbi.nlm.nih.gov/21548782/"
  },
  {
   "cite": "Wei GH, Badis G, Berger MF, et al. Genome-wide analysis of ETS-family DNA-binding in vitro and in vivo. EMBO J 2010;29:2147-60.",
   "pmid": "20517297",
   "url": "https://pubmed.ncbi.nlm.nih.gov/20517297/"
  },
  {
   "cite": "Sharrocks AD. The ETS-domain transcription factor family. Nat Rev Mol Cell Biol 2001;2:827-37.",
   "pmid": "11715049",
   "url": "https://pubmed.ncbi.nlm.nih.gov/11715049/"
  },
  {
   "cite": "Kodandapani R, Pio F, Ni CZ, et al. A new pattern for helix-turn-helix recognition revealed by the PU.1 ETS-domain-DNA complex. Nature 1996;380:456-60.",
   "pmid": "8602247",
   "url": "https://pubmed.ncbi.nlm.nih.gov/8602247/"
  },
  {
   "cite": "Batchelor AH, Piper DE, de la Brousse FC, et al. The structure of GABPalpha/beta: an ETS domain- ankyrin repeat heterodimer bound to DNA. Science 1998;279:1037-41.",
   "pmid": "9461436",
   "url": "https://pubmed.ncbi.nlm.nih.gov/9461436/"
  },
  {
   "cite": "Hollenhorst PC, Shah AA, Hopkins C, et al. Genome-wide analyses reveal properties of redundant and specific promoter occupancy within the ETS gene family. Genes Dev 2007;21:1882-94.",
   "pmid": "17652178",
   "url": "https://pubmed.ncbi.nlm.nih.gov/17652178/"
  },
  {
   "cite": "Hollenhorst PC, Chandler KJ, Poulsen RL, et al. DNA specificity determinants associate with distinct transcription factor functions. PLoS Genet 2009;5:e1000778.",
   "pmid": "20019798",
   "url": "https://pubmed.ncbi.nlm.nih.gov/20019798/"
  },
  {
   "cite": "Kim WY, Sieweke M, Ogawa E, et al. Mutual activation of Ets-1 and AML1 DNA binding by direct interaction of their autoinhibitory domains. EMBO J 1999;18:1609-20.",
   "pmid": "10075931",
   "url": "https://pubmed.ncbi.nlm.nih.gov/10075931/"
  },
  {
   "cite": "Garvie CW, Hagman J, Wolberger C. Structural studies of Ets-1/Pax5 complex formation on DNA. Mol Cell 2001;8:1267-76.",
   "pmid": "11779502",
   "url": "https://pubmed.ncbi.nlm.nih.gov/11779502/"
  },
  {
   "cite": "Pimanda JE, Ottersbach K, Knezevic K, et al. Gata2, Fli1, and Scl form a recursively wired gene-regulatory circuit during early hematopoietic development. Proc Natl Acad Sci U S A 2007;104:17692-7.",
   "pmid": "17962413",
   "url": "https://pubmed.ncbi.nlm.nih.gov/17962413/"
  },
  {
   "cite": "Tomlins SA, Rhodes DR, Perner S, et al. Recurrent fusion of TMPRSS2 and ETS transcription factor genes in prostate cancer. Science 2005;310:644-8.",
   "pmid": "16254181",
   "url": "https://pubmed.ncbi.nlm.nih.gov/16254181/"
  },
  {
   "cite": "Gangwal K, Sankar S, Hollenhorst PC, et al. Microsatellites as EWS/FLI response elements in Ewing's sarcoma. Proc Natl Acad Sci U S A 2008;105:10149-54.",
   "pmid": "18626011",
   "url": "https://pubmed.ncbi.nlm.nih.gov/18626011/"
  },
  {
   "cite": "Karim FD, Urness LD, Thummel CS, et al. The ETS-domain: a new DNA-binding motif that recognizes a purine-rich core DNA sequence. Genes Dev 1990;4:1451-3.",
   "pmid": "2253872",
   "url": "https://pubmed.ncbi.nlm.nih.gov/2253872/"
  },
  {
   "cite": "Ristevski S, O'Leary DA, Thornell AP, et al. The ETS transcription factor GABPalpha is essential for early embryogenesis. Mol Cell Biol 2004;24:5844-9.",
   "pmid": "15199140",
   "url": "https://pubmed.ncbi.nlm.nih.gov/15199140/"
  },
  {
   "cite": "Boulay G, Sandoval GJ, Riggi N, et al. Cancer-Specific Retargeting of BAF Complexes by a Prion-like Domain. Cell 2017;171:163-178.e19.",
   "pmid": "28844694",
   "url": "https://pubmed.ncbi.nlm.nih.gov/28844694/"
  }
 ],
 "timeline": [
  {
   "year": 1990,
   "finding": "The ETS domain is named as a new DNA-binding motif shared by the ETS proteins and shown to recognize a purine-rich core centred on GGA.",
   "methods": "Sequence comparison across ETS proteins, DNA-binding assays",
   "confidence": "medium",
   "pmids": [
    "2253872"
   ],
   "open": "How one short domain read so small a core, and whether family members differed in what they bound, was unknown."
  },
  {
   "year": 1996,
   "finding": "The first ETS domain-DNA crystal structure (PU.1) shows a winged helix-turn-helix contacting ten base pairs through a loop-helix-loop: two arginines of the recognition helix read the GGA core, a wing lysine binds 5' of it and a turn lysine 3' of it on the opposite strand.",
   "methods": "X-ray crystallography",
   "confidence": "high",
   "pmids": [
    "8602247"
   ],
   "open": "No base contacts outside the core were seen, so the flanking preferences that separate subfamilies were left to indirect readout."
  },
  {
   "year": 2005,
   "finding": "Outlier-expression analysis finds ERG and ETV1 overexpressed in prostate cancer through fusion to the 5' end of the androgen-regulated TMPRSS2 gene; 23 of 29 tumors examined by FISH carry an ERG or ETV1 rearrangement.",
   "methods": "Cancer outlier profile analysis, FISH, RT-PCR, androgen stimulation of cell lines",
   "confidence": "high",
   "pmids": [
    "16254181"
   ],
   "open": "Which genomic sites the overexpressed ETS proteins act through, and whether they differ from those of the endogenous ETS factors, was not addressed."
  },
  {
   "year": 2007,
   "finding": "Promoter-array ChIP for three ETS proteins in a T-cell line finds that redundant occupancy is the rule: consensus sites near the start sites of housekeeping genes are shared, while factor-specific sites diverge from consensus, lie farther away, and include an ETS1-RUNX1 cooperative site.",
   "methods": "ChIP-chip on promoter microarrays, motif analysis",
   "confidence": "medium",
   "pmids": [
    "17652178"
   ],
   "open": "Promoter arrays could not see enhancers, where specific occupancy turned out to concentrate."
  },
  {
   "year": 2008,
   "finding": "EWS-FLI1 regulates targets such as NR0B1 through GGAA microsatellites; the NR0B1 repeat binds the fusion in vitro and in vivo, is necessary and sufficient for regulation, and activity depends on the number of consecutive GGAA motifs.",
   "methods": "ChIP-chip, in vitro binding, reporter assays, genome-wide sequence analysis",
   "confidence": "high",
   "pmids": [
    "18626011"
   ],
   "open": "Whether repeat binding was a property of the FLI1 ETS domain or required the EWS portion of the fusion was not settled."
  },
  {
   "year": 2009,
   "finding": "ETS1 ChIP-seq in Jurkat T cells separates redundant occupancy with GABPA at housekeeping promoters from ETS1-specific occupancy at T-cell enhancers, which carry either a CpG-free CAGGAAGT variant or an ETS-RUNX composite; more than a thousand specific regions show AGGA(A/T)GTGG.",
   "methods": "ChIP-seq, DNase I sensitivity, in vitro binding",
   "confidence": "medium",
   "pmids": [
    "20019798",
    "21548782"
   ],
   "open": "FLI1 and ERG also co-occupy sites with RUNX1 in stem cells, so how specific the composite is for ETS1 was left open."
  },
  {
   "year": 2010,
   "finding": "DNA-binding profiles of all human and mouse ETS proteins, from two in vitro methods, fall into four classes; every cancer-linked ETS factor (ERG, ETV1, ETV4, FLI1) is in class I, and ChIP-seq for one member of each class confirms that the small in vitro differences affect site choice in cells.",
   "methods": "High-throughput microwell binding assay, protein-binding microarrays, ChIP-seq",
   "confidence": "high",
   "pmids": [
    "20517297"
   ],
   "open": "Members within class I remained indistinguishable, so paralogue specificity had to come from elsewhere."
  },
  {
   "year": 2017,
   "finding": "Wild-type FLI1 occupies canonical ETS sites but not GGAA repeats, whereas EWS-FLI1 binds repeats, recruits BAF complexes and opens de novo enhancers, and needs the tyrosines that drive phase transitions of the EWSR1 prion-like domain to bind them. This revises the earlier view that the EWS portion contributes only transcriptional activation.",
   "methods": "ChIP-seq in mesenchymal stem cells and Ewing sarcoma cells, mutagenesis, proteomics, in vitro phase-transition assays",
   "confidence": "medium",
   "pmids": [
    "28844694"
   ]
  }
 ],
 "openQuestions": [
  "How class I paralogues reach different genomic sites despite indistinguishable in vitro preferences is only partly explained: ETS-RUNX composites account for some ETS1-specific enhancers, but RUNX1 also co-occupies sites with FLI1 and ERG, and the contributions of partner choice, autoinhibition and relative expression level to the remaining specific sites have not been separated.",
  "Why ChIP-derived models converge on CAGGAAG while in vitro models give ACCGGAAGT is unresolved: one reading is an intrinsic ETS1 preference for the variant that confers specificity, the other is that the A simply removes a CpG whose methylation would block binding at enhancers outside protected CpG islands.",
  "Whether binding to GGAA microsatellites is an intrinsic property of the ETS domain or a neomorphic property of the EWSR1 fusion is contested: in vitro and reporter work found binding that scales with repeat number and reported that several wild-type ETS proteins bind repeats, while in cells wild-type FLI1 does not occupy repeats and EWS-FLI1 needs its prion-like-domain tyrosines to do so.",
  "The databases cluster SPDEF models with class I, whereas in vitro profiling makes SPDEF the sole class IV factor with a GGAT core; whether SPDEF also uses GGAA sites in cells, or the clustering reflects only the shared CCGGA flank, is not established."
 ],
 "members": [
  {
   "id": "EWSR1-FLI1 (MA0149.1)",
   "source": "JASPAR",
   "consensus": "GGAAGGAAGGAAGGAAGG",
   "bits": 32.9
  },
  {
   "id": "M08111_2.00",
   "source": "CIS-BP",
   "consensus": "GGAAGGAAGGAAGGAAGG",
   "bits": 32.9,
   "prov": {
    "inferred": false
   }
  },
  {
   "id": "M04778_2.00",
   "source": "CIS-BP",
   "consensus": "ACCGGAAGtaCTTCCGGT",
   "bits": 26.7,
   "prov": {
    "inferred": false
   }
  },
  {
   "id": "M07950_2.00",
   "source": "CIS-BP",
   "consensus": "GCcTkCTGGGAatTGTAGTtC",
   "bits": 25,
   "prov": {
    "inferred": false
   }
  },
  {
   "id": "ERF::SREBF2 (MA1939.2)",
   "source": "JASPAR",
   "consensus": "CGGAAATCACGTGAT",
   "bits": 20.8,
   "prov": {
    "dimer": true
   }
  },
  {
   "id": "ERF::NHLH1 (MA1938.2)",
   "source": "JASPAR",
   "consensus": "aGCAGCTGCCGGAAgT",
   "bits": 20.6,
   "prov": {
    "dimer": true
   }
  },
  {
   "id": "AC0561:FLI/ZNF:Ets",
   "source": "Vierstra",
   "consensus": "TTCCTTCCtTCCTTCC",
   "bits": 19.9
  },
  {
   "id": "AC0079:ERF::NHLH:['Tryptophan_cluster_factors',_'Basic_helix-loop-helix_factors_(bHLH)']",
   "source": "Vierstra",
   "consensus": "GCAGCTGCCGGAAg",
   "bits": 19.4
  },
  {
   "id": "AC0365:SPDEF:Ets",
   "source": "Vierstra",
   "consensus": "TaATCCGGGACCA",
   "bits": 19
  },
  {
   "id": "ELK1::HOXB13 (MA1932.2)",
   "source": "JASPAR",
   "consensus": "ACCGGAAGThGTAAA",
   "bits": 18.9,
   "prov": {
    "dimer": true
   }
  },
  {
   "id": "AC0643:ETS/ETV:Ets",
   "source": "Vierstra",
   "consensus": "cGGAAGTACTTCCg",
   "bits": 18.6
  },
  {
   "id": "AC0646:ERG/FLI:Ets",
   "source": "Vierstra",
   "consensus": "CCGGAtATCCGG",
   "bits": 18.4
  },
  {
   "id": "ELK1::SREBF2 (MA1933.2)",
   "source": "JASPAR",
   "consensus": "CCGGAAGTggCGTGA",
   "bits": 18.3,
   "prov": {
    "dimer": true
   }
  },
  {
   "id": "AC0105:SPDEF:Ets",
   "source": "Vierstra",
   "consensus": "CAGdAAGAAGTAaa",
   "bits": 18.1
  },
  {
   "id": "ERF::FIGLA (MA1934.2)",
   "source": "JASPAR",
   "consensus": "CCGGAAaCAcCTG",
   "bits": 18,
   "prov": {
    "dimer": true
   }
  },
  {
   "id": "ELK1::HOXA1 (MA1931.1)",
   "source": "JASPAR",
   "consensus": "ACCGGAAGTAATT",
   "bits": 17.4,
   "prov": {
    "dimer": true
   }
  },
  {
   "id": "ETV5::FIGLA (MA1945.2)",
   "source": "JASPAR",
   "consensus": "cGGAAgCAGGTG",
   "bits": 17.4,
   "prov": {
    "dimer": true
   }
  },
  {
   "id": "ETV4.H14CORE.1.SM.B",
   "source": "HOCOMOCO",
   "consensus": "ACCGGAAGT",
   "bits": 15.7,
   "prov": {
    "evidence": "SM",
    "grade": "B"
   }
  },
  {
   "id": "M04752_2.00",
   "source": "CIS-BP",
   "consensus": "ACCGGAAGT",
   "bits": 15.2,
   "prov": {
    "inferred": false
   }
  },
  {
   "id": "AC0076:ERF::FIGLA/ETV2::FIGLA:['Tryptophan_cluster_factors',_'Basic_helix-loop-helix_factors_(bHLH)']",
   "source": "Vierstra",
   "consensus": "CGGAAgCAGgTG",
   "bits": 15.2
  },
  {
   "id": "AC0541:ETS/SIX:Ets",
   "source": "Vierstra",
   "consensus": "ACTACAacTCCCAG",
   "bits": 14.8
  },
  {
   "id": "SPDEF.H14CORE.1.SM.B",
   "source": "HOCOMOCO",
   "consensus": "AaCCGGATGTdvnnhccg",
   "bits": 14.7,
   "prov": {
    "evidence": "SM",
    "grade": "B"
   }
  },
  {
   "id": "M02973_2.00",
   "source": "CIS-BP",
   "consensus": "AcCCGGATGT",
   "bits": 14.5,
   "prov": {
    "inferred": false
   }
  },
  {
   "id": "FEV (MA0156.4)",
   "source": "JASPAR",
   "consensus": "ACCGGAAGT",
   "bits": 14.4
  },
  {
   "id": "SPDEF (MA0686.2)",
   "source": "JASPAR",
   "consensus": "AcCCGGATGT",
   "bits": 14.3
  },
  {
   "id": "GABPA.H14CORE.0.PSM.A",
   "source": "HOCOMOCO",
   "consensus": "ACCGGAAGT",
   "bits": 14.3,
   "prov": {
    "evidence": "PSM",
    "grade": "A"
   }
  },
  {
   "id": "ELK1 (MA0028.3)",
   "source": "JASPAR",
   "consensus": "ACCGGAAGT",
   "bits": 14.2
  },
  {
   "id": "ELK1.H14CORE.0.PSM.A",
   "source": "HOCOMOCO",
   "consensus": "ACCGGAAGT",
   "bits": 14.2,
   "prov": {
    "evidence": "PSM",
    "grade": "A"
   }
  },
  {
   "id": "ERG.H14CORE.1.SM.B",
   "source": "HOCOMOCO",
   "consensus": "ACCGGAAGT",
   "bits": 14.2,
   "prov": {
    "evidence": "SM",
    "grade": "B"
   }
  },
  {
   "id": "ETV5 (MA0765.4)",
   "source": "JASPAR",
   "consensus": "ACCGGAAGT",
   "bits": 14.1
  },
  {
   "id": "ETV5::HOXA2 (MA1948.2)",
   "source": "JASPAR",
   "consensus": "CGGAaGTaATTA",
   "bits": 14.1,
   "prov": {
    "dimer": true
   }
  },
  {
   "id": "FLI1::DRGX (MA1949.2)",
   "source": "JASPAR",
   "consensus": "aCCGGAAGTAATTA",
   "bits": 14.1,
   "prov": {
    "dimer": true
   }
  },
  {
   "id": "ELK3.H14CORE.0.PSM.A",
   "source": "HOCOMOCO",
   "consensus": "aCCGGAAGT",
   "bits": 14.1,
   "prov": {
    "evidence": "PSM",
    "grade": "A"
   }
  },
  {
   "id": "ELK3 (MA0759.3)",
   "source": "JASPAR",
   "consensus": "ACCGGAAGT",
   "bits": 14
  },
  {
   "id": "ETV5::FOXI1 (MA1946.2)",
   "source": "JASPAR",
   "consensus": "GTAAACAGGAaG",
   "bits": 14,
   "prov": {
    "dimer": true
   }
  },
  {
   "id": "M02734_2.00",
   "source": "CIS-BP",
   "consensus": "CGGAtaTCCG",
   "bits": 14,
   "prov": {
    "inferred": false
   }
  },
  {
   "id": "AC0054:ELK/ETV:Ets",
   "source": "Vierstra",
   "consensus": "TCGTAAATGC",
   "bits": 13.9
  },
  {
   "id": "FEV.H14CORE.0.S.B",
   "source": "HOCOMOCO",
   "consensus": "aCCGGAAGT",
   "bits": 13.8,
   "prov": {
    "evidence": "S",
    "grade": "B"
   }
  },
  {
   "id": "ETS2.H14CORE.0.S.C",
   "source": "HOCOMOCO",
   "consensus": "aCCGGAAGT",
   "bits": 13.5,
   "prov": {
    "evidence": "S",
    "grade": "C"
   }
  },
  {
   "id": "ETS2 (MA1484.2)",
   "source": "JASPAR",
   "consensus": "ACCGGAAGt",
   "bits": 13.3
  },
  {
   "id": "FLI1 (MA0475.3)",
   "source": "JASPAR",
   "consensus": "ACCGGAAgT",
   "bits": 13.2
  },
  {
   "id": "ETV5::DRGX (MA1944.2)",
   "source": "JASPAR",
   "consensus": "CGGAAGtAATTA",
   "bits": 13.2,
   "prov": {
    "dimer": true
   }
  },
  {
   "id": "ETV1.H14CORE.1.PM.A",
   "source": "HOCOMOCO",
   "consensus": "gCAGGAAGTg",
   "bits": 13.2,
   "prov": {
    "evidence": "PM",
    "grade": "A"
   }
  },
  {
   "id": "ETS1.H14CORE.1.P.B",
   "source": "HOCOMOCO",
   "consensus": "aCaGGAAGTGG",
   "bits": 13.1,
   "prov": {
    "evidence": "P",
    "grade": "B"
   }
  },
  {
   "id": "FLI1::FOXI1 (MA1950.2)",
   "source": "JASPAR",
   "consensus": "tAAACAGGAAg",
   "bits": 13,
   "prov": {
    "dimer": true
   }
  },
  {
   "id": "FLI1.H14CORE.1.P.B",
   "source": "HOCOMOCO",
   "consensus": "GgcAGGAAGbgg",
   "bits": 13,
   "prov": {
    "evidence": "P",
    "grade": "B"
   }
  },
  {
   "id": "M07952_2.00",
   "source": "CIS-BP",
   "consensus": "CCGGAAGT",
   "bits": 13,
   "prov": {
    "inferred": false
   }
  },
  {
   "id": "ERF::FOXO1 (MA1936.2)",
   "source": "JASPAR",
   "consensus": "gtaAACAGGAAG",
   "bits": 12.9,
   "prov": {
    "dimer": true
   }
  },
  {
   "id": "ERG.H14CORE.0.P.B",
   "source": "HOCOMOCO",
   "consensus": "aCCGGAAGTg",
   "bits": 12.9,
   "prov": {
    "evidence": "P",
    "grade": "B"
   }
  },
  {
   "id": "M02968_2.00",
   "source": "CIS-BP",
   "consensus": "ACCGGAAGT",
   "bits": 12.9,
   "prov": {
    "inferred": false
   }
  },
  {
   "id": "ELK4 (MA0076.3)",
   "source": "JASPAR",
   "consensus": "aCTTCCGG",
   "bits": 12.7
  },
  {
   "id": "ERF (MA0760.2)",
   "source": "JASPAR",
   "consensus": "ACCGGAAGT",
   "bits": 12.7
  },
  {
   "id": "FLI1.H14CORE.0.PSM.A",
   "source": "HOCOMOCO",
   "consensus": "aCCGGAAGTg",
   "bits": 12.7,
   "prov": {
    "evidence": "PSM",
    "grade": "A"
   }
  },
  {
   "id": "M04730_2.00",
   "source": "CIS-BP",
   "consensus": "aCCGGAAGT",
   "bits": 12.6,
   "prov": {
    "inferred": false
   }
  },
  {
   "id": "ETV1.H14CORE.0.PSM.A",
   "source": "HOCOMOCO",
   "consensus": "ACCGGAAGT",
   "bits": 12.5,
   "prov": {
    "evidence": "PSM",
    "grade": "A"
   }
  },
  {
   "id": "SPDEF.H14CORE.0.PSM.A",
   "source": "HOCOMOCO",
   "consensus": "amCCGGATgt",
   "bits": 12.5,
   "prov": {
    "evidence": "PSM",
    "grade": "A"
   }
  },
  {
   "id": "M04791_2.00",
   "source": "CIS-BP",
   "consensus": "aCCGGAAGT",
   "bits": 12.5,
   "prov": {
    "inferred": false
   }
  },
  {
   "id": "ETS1.H14CORE.0.S.B",
   "source": "HOCOMOCO",
   "consensus": "ACCGGAAGT",
   "bits": 12.4,
   "prov": {
    "evidence": "S",
    "grade": "B"
   }
  },
  {
   "id": "M07957_2.00",
   "source": "CIS-BP",
   "consensus": "CCGGAAGt",
   "bits": 12.2,
   "prov": {
    "inferred": false
   }
  },
  {
   "id": "Erg (MA0474.4)",
   "source": "JASPAR",
   "consensus": "ACAGGAAGTg",
   "bits": 12.1
  },
  {
   "id": "ETV3.H14CORE.0.SM.B",
   "source": "HOCOMOCO",
   "consensus": "ACCGGAAGT",
   "bits": 12.1,
   "prov": {
    "evidence": "SM",
    "grade": "B"
   }
  },
  {
   "id": "ETS1 (MA0098.4)",
   "source": "JASPAR",
   "consensus": "ACCGGAAgT",
   "bits": 12
  },
  {
   "id": "ERF::HOXB13 (MA1937.2)",
   "source": "JASPAR",
   "consensus": "CGGAAgtngTaAA",
   "bits": 11.9,
   "prov": {
    "dimer": true
   }
  },
  {
   "id": "GABPA (MA0062.4)",
   "source": "JASPAR",
   "consensus": "CACTTCCTGT",
   "bits": 11.7
  },
  {
   "id": "ETV1 (MA0761.3)",
   "source": "JASPAR",
   "consensus": "ACAGGAAGT",
   "bits": 11.6
  },
  {
   "id": "ETV5::FOXO1 (MA1947.2)",
   "source": "JASPAR",
   "consensus": "GtAAACAGGA",
   "bits": 11.6,
   "prov": {
    "dimer": true
   }
  },
  {
   "id": "M02970_2.00",
   "source": "CIS-BP",
   "consensus": "ACCGGAAGT",
   "bits": 11.6,
   "prov": {
    "inferred": false
   }
  },
  {
   "id": "ETV3 (MA0763.2)",
   "source": "JASPAR",
   "consensus": "ACCGGAAGT",
   "bits": 11.5
  },
  {
   "id": "ETV4 (MA0764.4)",
   "source": "JASPAR",
   "consensus": "aCCGGAAGT",
   "bits": 11.5
  },
  {
   "id": "ELK4.H14CORE.0.PSM.A",
   "source": "HOCOMOCO",
   "consensus": "CCGGAAGt",
   "bits": 11.4,
   "prov": {
    "evidence": "PSM",
    "grade": "A"
   }
  },
  {
   "id": "ETV5.H14CORE.0.PS.A",
   "source": "HOCOMOCO",
   "consensus": "CCGGAAGt",
   "bits": 11.4,
   "prov": {
    "evidence": "PS",
    "grade": "A"
   }
  },
  {
   "id": "ETS2.H14CORE.1.P.B",
   "source": "HOCOMOCO",
   "consensus": "ccGGAAGtG",
   "bits": 11.2,
   "prov": {
    "evidence": "P",
    "grade": "B"
   }
  },
  {
   "id": "ETV4.H14CORE.0.P.B",
   "source": "HOCOMOCO",
   "consensus": "CaGGAAG",
   "bits": 11,
   "prov": {
    "evidence": "P",
    "grade": "B"
   }
  },
  {
   "id": "ETV5.H14CORE.1.PM.A",
   "source": "HOCOMOCO",
   "consensus": "CCGGAAGt",
   "bits": 10.9,
   "prov": {
    "evidence": "PM",
    "grade": "A"
   }
  },
  {
   "id": "M03006_2.00",
   "source": "CIS-BP",
   "consensus": "aCCGGAAGT",
   "bits": 10.6,
   "prov": {
    "inferred": false
   }
  },
  {
   "id": "ERF.H14CORE.0.PS.A",
   "source": "HOCOMOCO",
   "consensus": "AGGAAgT",
   "bits": 9.8,
   "prov": {
    "evidence": "PS",
    "grade": "A"
   }
  },
  {
   "id": "M04800_2.00",
   "source": "CIS-BP",
   "consensus": "cCGGAaG",
   "bits": 9.6,
   "prov": {
    "inferred": false
   }
  },
  {
   "id": "ERF::FOXI1 (MA1935.2)",
   "source": "JASPAR",
   "consensus": "ACaGGAAg",
   "bits": 9.5,
   "prov": {
    "dimer": true
   }
  },
  {
   "id": "M04708_2.00",
   "source": "CIS-BP",
   "consensus": "CGGAaG",
   "bits": 8.8,
   "prov": {
    "inferred": false
   }
  },
  {
   "id": "AC0641:ETV/ETS:Ets",
   "source": "Vierstra",
   "consensus": "GGaAGGAAG",
   "bits": 7.8
  },
  {
   "id": "M01477_2.00",
   "source": "CIS-BP",
   "consensus": "GGAa",
   "bits": 5.9,
   "prov": {
    "species": "Mus musculus",
    "dbdIdentity": 1,
    "inferred": false
   }
  }
 ],
 "url": "https://motif.zhoulab.io/families/ets_class1/",
 "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/"
}