Q50 homeodomain (DLX/MSX/LHX-type, TAATTA)
About half of the roughly 200 human homeodomain proteins carry glutamine at position 50 of the domain and read the palindromic hexamer TAATTA. This family gathers 275 published motifs for 89 gene symbols: DLX1-6, MSX1-3, the LIM-homeodomain proteins LHX1-9 and ISL1/2, ALX1/3/4, ARX, PRRX1/2, EMX, EN, GBX, BARHL, LMX, SHOX, VAX and TLX, plus the paired-like factors VSX1/2, RAX/RAX2, PHOX2A/2B, NOBOX, MIXL1, VENTX, PROP1, DRGX, BSX, OTP and SEBOX and, from another family again, PDX1. Grouping follows the specificity a protein actually has rather than its gene family. Many of these proteins also bind cooperatively as dimers on TAATNNNATTA palindromes, which is where most real discrimination lies; a single TAATTA match carries almost no information.
The factors
The homeodomain is a 60-residue module: three alpha-helices around a hydrophobic core, with helix 3 in the major groove and a flexible N-terminal arm in the adjacent minor groove. The human genome carries about 235 functional homeobox genes 17963489, and roughly half of the encoded homeodomains have glutamine at position 50, the last residue of the recognition helix - the residue this family is named for.
Eighty-nine gene symbols and 275 motifs are grouped here. The core set is expected: DLX1-6; MSX1-3; the LIM-homeodomain proteins LHX1-6, LHX8/9 and ISL1/2, which contact DNA through the homeodomain but assemble via LIM domains and LDB1; the aristaless-related ALX1/3/4, ARX and PRRX1/2; and EMX, EN, GBX, BARHL, BARX, DBX, GSX, EVX, HMX, LBX, LMX, MEOX, SHOX, TLX, VAX, UNCX, MNX1, HLX, ESX1, HESX1, ISX and NOTO.
The family also holds proteins whose gene families would suggest otherwise: the paired-like factors VSX1/2, RAX/RAX2, PHOX2A/2B, NOBOX, MIXL1, VENTX, PROP1, DRGX, BSX, OTP and SEBOX, plus PDX1. In standard classifications these sit beside OTX, CRX, PITX and GSC 17963489,26464018, but they carry glutamine at position 50, not lysine, and their measured motifs are TAATTA-type; the atlas groups by the specificity a protein actually has, so they belong here rather than in HD_K50.
The motif
Position 50 is a specificity switch: substituting it in Drosophila Paired transfers the preference of Fushi tarazu or Bicoid onto that protein 2572327, and the reciprocal change in Bicoid converts it into an Antennapedia-class binder 2500253. Site selection with six different residues at position 50 each gave a distinct specificity, all sharing the TAAT core and differing only in the bases immediately 3' of it 8692913.
Structurally, the invariant Asn51 hydrogen-bonds the second adenine of 5'-TAAT-3' while Arg3 and Arg5 of the N-terminal arm read the minor groove there 1977522; the position-50 side chain points at the next two. Glutamine accommodates T:A, giving TAATTA and TAATTG; lysine instead contacts C:G, giving TAATCC 8692913. Information is confined to those six base pairs, so most models here are 6-8 columns wide.
Longer models are dimeric 23332764. Paired-like homeodomains bind palindromes with two TAAT half-sites three base pairs apart (the P3 site, TAATNNNATTA) cooperatively, with up to 300-fold enhancement; residue 50 sets the spacing and the central bases 7901121, and the rules for which homeodomains can do this have recently been derived 42675056. Thirty-five of the 112 HOCOMOCO models here are 11 bp or longer: ALX4, PHOX2B, PROP1 and MIXL1 TAATTAGATTA, ARX TAATCTAATTAG, LMX1B TTAATTAATT, DRGX and PHOX2A TAATTTAATTA.
Paralogues are not separable. Cohesion is 0.84 across 275 models, the medoid is GBX1 (JASPAR MA0889.2), and the data consensus reads CTAATTA - the same site with one flanking base. Real outliers exist: BARHL1/2 prefer TAAACG, HMX1-3 and ISL1/2 give NKX-like TAAGTG models, MEOX1/2 TAATGA, VSX1/2 a distinctive TAATTAGC, and methyl-HT-SELEX models for LHX1/6/8/9, LBX2 and PRRX2 a CpG-containing TAACGA variant 28473536. Surveys quantify the point: 168 mouse homeodomains resolve into at least 65 binding activities 18585359 and 84 Drosophila homeodomains into 11 specificity groups 18585360 - real variation, but finer than a PWM resolves.
Where it acts
TAATTA sites sit in AT-rich distal enhancers rather than CpG-island promoters, and occupancy is strongly cell-type restricted. The motif is extremely common: at human base composition this self-complementary 6-mer is expected some two million times in 3.1 Gb, so even restricting to the ~4.5 million mapped DNase I footprints 32728250 leaves far more matches than any factor occupies. Members share enhancers and compete on the same sites: DLX and MSX are the classic antagonistic pair in craniofacial and limb enhancers, while VSX1/2 and RAX act in retinal progenitors, PHOX2A/2B in autonomic neurons and NOBOX in oocytes. Characterized enhancers usually contain double TAAT cores or several cores within a few hundred base pairs; one archetype here is named EMX/PAX.
Biology and disease
Human mutations are typically heterozygous and dosage-sensitive, and produce sharply localized defects. An MSX2 homeodomain substitution causes autosomal dominant craniosynostosis and MSX2 haploinsufficiency enlarged parietal foramina; MSX1 causes selective tooth agenesis, DLX3 tricho-dento-osseous syndrome, recessive ALX3 frontorhiny, SHOX deletion the short stature of Leri-Weill dyschondrosteosis and Turner syndrome, LMX1B nail-patella syndrome, LHX3 combined pituitary hormone deficiency, HESX1 septo-optic dysplasia and ARX X-linked lissencephaly. The paired-like members add PHOX2B in congenital central hypoventilation syndrome and neuroblastoma predisposition, VSX2 in microphthalmia, RAX in anophthalmia and NOBOX in premature ovarian failure. Many pathogenic substitutions lie inside the homeodomain and alter DNA binding or cooperativity directly 42675056.
Reading a hit
A TAATTA match says a Q50-class homeodomain could bind, and little else. No published matrix separates DLX5 from LHX2 or EN1 from MSX1; report the hit as a Q50 homeodomain site, not a gene. The site is too common to be informative on its own, so a bare hit means little without expression data, accessibility and ideally a second TAAT core three to five base pairs away. Evidence that these proteins bind TAATTA is strong: 107 of 112 HOCOMOCO models have in vitro HT-SELEX or methyl-HT-SELEX support and only five are ChIP-only. That is not the same as saying their ChIP peaks sit on TAATTA; peak sets routinely carry other factors' motifs 25070602. Two members are flagged as resembling other families, but not for that reason: an HT-SELEX-only VENTX model (VENTX.H14CORE.1.S.C, grade C) reads AATTTGCATA, close to the POU octamer, which co-bound partners in ChIP cannot explain, and a low-information CIS-BP VSX2 model (TATATT) matches WT1. Six CIS-BP entries (DBX1, DBX2, LHX3, HLX, OTP, SEBOX) are transferred from mouse orthologues, SEBOX at only 79% domain identity; archetype names such as DLX/LHX are majority labels, not claims of separability.
How this was worked out
- 1989highYeast transcription-activation assay; in vitro DNA binding of mutant homeodomains2500253 2572327
Two groups show that homeodomain residue 50 (residue 9 of the recognition helix) switches DNA specificity. One substitution lets Bicoid (K50) recognize Ultrabithorax and Fushi tarazu sites, and changing residue 50 of Paired confers Fushi tarazu or Bicoid specificity. This is the origin of the Q50/K50 distinction.
Still open then: Which bases residue 50 reads, and how, was unknown.
The crystal structure of the engrailed homeodomain, a Q50 protein, on DNA: the N-terminal arm lies in the minor groove with Arg3 and Arg5 near the 5' end of TAAT, and the recognition helix lies in the major groove with Ile47 and Asn51 contacting its 3' end.
Still open then: How the residue-50 side chain discriminates the bases 3' of TAAT was not resolved.
Paired-class homeodomains bind cooperatively as dimers to palindromic TAAT sites, with up to 300-fold enhancement. Residue 50 sets the preferred half-site spacing, the central bases and the strength of cooperativity.
Still open then: Which other residues allow or prevent cooperative dimerization.
In vitro selection with six different residues at position 50 gives six distinct specificities, all on a TAAT core and differing in the bases immediately 3' of it. This is the position-50 rule in its general form.
The full human catalogue (235 functional homeobox genes in 11 classes) places VSX, RAX, PHOX2, PROP1 and other Q50 paired-like genes in the same PRD class as the K50 OTX, PITX and GSC genes. Gene family and residue 50 therefore give different groupings.
Still open then: Which grouping better predicts binding was left to the binding surveys that followed.
Genome-scale surveys, protein-binding microarrays for 168 mouse homeodomains (at least 65 distinct activities) and bacterial one-hybrid selection for all 84 Drosophila homeodomains (11 specificity groups), yield a catalogue of specificity-determining residues in which position 50 is one of several. They also show variation within the TAATTA group that is finer than a single PWM captures.
HT-SELEX of human TFs (830 profiles, 239 distinct specificities) shows that homodimer spacing and orientation matter widely. Data of this kind underlie the TAATTA monomer and P3-dimer (TAATNNNATTA) models of the Q50 paired-like proteins in this family, settling that they read Q50 sites despite their gene family.
- 2026mediumStructural, biochemical and bioinformatic analysis; quantitative DNA-binding assays42675056
Analysis of the 36 human paired-like homeodomains derives 11 rules for cooperative binding to the P3 site. It identifies residues that keep Antennapedia-class homeodomains from binding cooperatively, and 11 of 12 tested disease variants change cooperativity but not affinity.
Still open then: Whether P3 cooperativity selects genomic targets in vivo for the Q50 paired-like factors.
Still unresolved
- Gene classification and measured specificity disagree for the Q50 paired-like factors. Nomenclature places VSX, RAX, PHOX2, PROP1 and their relatives in the PRD class with the K50 OTX, PITX and GSC genes, while their in vitro models are TAATTA-type almost without exception. It is not established whether their shared capacity for P3 dimer binding, rather than the monomer site, is what sets them apart in vivo from other Q50 proteins.
- How about 89 proteins with indistinguishable monomer models reach distinct targets is unresolved. Dimer spacing, LIM-domain partners such as LDB1, and specificity differences finer than a PWM (at least 65 activities among mouse homeodomains) have each been proposed, but none has been shown to account for paralogue-specific occupancy genome-wide.
- Whether the CpG-containing TAACGA variant in methyl-HT-SELEX models for LHX1, LHX6, LHX8 and LHX9 is bound at methylated genomic sites is untested. Unmethylated HT-SELEX models for the same four proteins read TAATTA, and methyl-SELEX shows only that many homeodomain proteins prefer methylated CpG in vitro.
Trust the family, not the member. A TAATTA match identifies a Q50-class homeodomain site; the 89 gene symbols here are not distinguishable by matrix, and the expected genome-wide frequency of the hexamer (order 10^6) means an isolated hit is close to uninformative. Require expression, accessibility and preferably a dimeric TAATNNNATTA arrangement. In vitro support for the motif is strong (107 of 112 HOCOMOCO models have SELEX evidence), but ChIP-derived peaks often carry other proteins' motifs. Separately, one grade-C HT-SELEX VENTX model reads an octamer-like AATTTGCATA; it is not a ChIP artifact, and whether VENTX genuinely prefers that sequence is untested. Membership follows measured specificity, not gene family: VSX1/2, RAX/RAX2, PHOX2A/2B, NOBOX, MIXL1, VENTX, PROP1, DRGX, BSX, OTP, SEBOX and PDX1 are paired-like or CDX/PDX genes that carry Q50 and read TAATTA.
References
- Treisman J, Gönczy P, Vashishtha M, et al. A single amino acid can determine the DNA binding specificity of homeodomain proteins. Cell 1989;59:553-62. PMID 2572327
- Hanes SD, Brent R. DNA specificity of the bicoid activator protein is determined by homeodomain recognition helix residue 9. Cell 1989;57:1275-83. PMID 2500253
- Wilson DS, Sheng G, Jun S, et al. Conservation and diversification in homeodomain-DNA interactions: a comparative genetic analysis. Proc Natl Acad Sci U S A 1996;93:6886-91. PMID 8692913
- Kissinger CR, Liu BS, Martin-Blanco E, et al. Crystal structure of an engrailed homeodomain-DNA complex at 2.8 A resolution: a framework for understanding homeodomain-DNA interactions. Cell 1990;63:579-90. PMID 1977522
- Wilson D, Sheng G, Lecuit T, et al. Cooperative dimerization of paired class homeo domains on DNA. Genes Dev 1993;7:2120-34. PMID 7901121
- Cain B, Wasmund C, Rowan FC, et al. Decoding the mechanisms of cooperative DNA binding by the Paired-like homeodomain family. Nat Commun 2026;17. PMID 42675056
- Noyes MB, Christensen RG, Wakabayashi A, et al. Analysis of homeodomain specificities allows the family-wide prediction of preferred recognition sites. Cell 2008;133:1277-89. PMID 18585360
- Berger MF, Badis G, Gehrke AR, et al. Variation in homeodomain DNA binding revealed by high-resolution analysis of sequence preferences. Cell 2008;133:1266-76. PMID 18585359
- Jolma A, Yan J, Whitington T, et al. DNA-binding specificities of human transcription factors. Cell 2013;152:327-39. PMID 23332764
- Holland PW, Booth HA, Bruford EA. Classification and nomenclature of all human homeobox genes. BMC Biol 2007;5:47. PMID 17963489
- Bürglin TR, Affolter M. Homeodomain proteins: an update. Chromosoma 2016;125:497-521. PMID 26464018
- Worsley Hunt R, Wasserman WW. Non-targeted transcription factors motifs are a systemic component of ChIP-seq datasets. Genome Biol 2014;15:412. PMID 25070602
- Vierstra J, Lazar J, Sandstrom R, et al. Global reference mapping of human transcription factor footprints. Nature 2020;583:729-736. PMID 32728250
- Yin Y, Morgunova E, Jolma A, et al. Impact of cytosine methylation on DNA binding specificities of human transcription factors. Science 2017;356. PMID 28473536
275 motifs in this family — JASPAR 72 · HOCOMOCO 112 · CIS-BP 76 · Vierstra 15
| motif | database | consensus | bits |
|---|---|---|---|
| AC0035:VENTX:Homeodomain | Vierstra | TAATcGGAAAaCGATTA | 25.6 |
| MIXL1.H14CORE.0.SM.BSMB | HOCOMOCO | TAATTAGATTA | 19.4 |
| PHX2B.H14CORE.0.PSM.APSMA | HOCOMOCO | TAATTAgATTA | 18.9 |
| AC0441:HMX:Homeodomain | Vierstra | CAAGTGCGTG | 18.2 |
| AC0065:MEOX:Homeodomain | Vierstra | TAATGATGATtA | 17.8 |
| ARX.H14CORE.0.S.BSB | HOCOMOCO | TAATcTAATTAg | 17.7 |
| ALX4.H14CORE.0.S.BSB | HOCOMOCO | TAATTAgATTA | 17.3 |
| LMX1B.H14CORE.2.S.BSB | HOCOMOCO | tTAATTAATtaaTtaa | 17.2 |
| VSX2.H14CORE.1.S.BSB | HOCOMOCO | CTAATTAGCcaatt | 16.9 |
| VSX1.H14CORE.1.SM.BSMB | HOCOMOCO | CTAATTAGCtAaT | 16.7 |
| ISX.H14CORE.1.S.BSB | HOCOMOCO | gcTAATTAGaTTA | 16.5 |
| AC0032:LHX:Homeodomain | Vierstra | TaATTGCAATcA | 16.5 |
| GBX1.H14CORE.1.S.BSB | HOCOMOCO | CTAATTAgcghwtaAt | 16.3 |
| Lhx3 (MA0135.2) | JASPAR | aAATTAATTAat | 16.1 |
| DRGX.H14CORE.0.S.BSB | HOCOMOCO | TAATTtAATTA | 16.1 |
| PROP1.H14CORE.0.PSM.APSMA | HOCOMOCO | TAATTAgATTA | 16.1 |
| LMX1B.H14CORE.1.SM.BSMB | HOCOMOCO | TTAATTAATT | 15.9 |
| PRRX1.H14CORE.1.S.BSB | HOCOMOCO | cTAATTAGhTaAtt | 15.9 |
| HESX1.H14CORE.1.S.BSB | HOCOMOCO | aATTaatTAATTA | 15.8 |
| ALX1.H14CORE.0.SM.BSMB | HOCOMOCO | TAATTAgATTA | 15.7 |
| EVX2.H14CORE.1.S.BSB | HOCOMOCO | TaatnaCTAATTAG | 15.7 |
| VENTX.H14CORE.1.S.CSClooks like HD_POU | HOCOMOCO | AATTTGCATA | 15.7 |
| M03144_2.00 | CIS-BP | TAATcGnTaTTTAATbg | 15.7 |
| SHOX2.H14CORE.0.S.BSB | HOCOMOCO | taattdgcTAATTAG | 15.6 |
| GBX2.H14CORE.1.S.BSB | HOCOMOCO | CTAATTAGtnhwaatt | 15.5 |
| ISX.H14CORE.2.SM.BSMB | HOCOMOCO | TAATTAATTAG | 15.5 |
| LHX2.H14CORE.1.S.CSC | HOCOMOCO | aATTangcTAATTAg | 15.5 |
| VSX2.H14CORE.0.PSM.APSMA | HOCOMOCO | TAATTAGC | 15.4 |
| ESX1.H14CORE.1.S.BSB | HOCOMOCO | tattnacTAATTAG | 15.2 |
| PROP1 (MA0715.1) | JASPAR | TAATttAATTA | 15.1 |
| PRRX2.H14CORE.1.S.BSB | HOCOMOCO | TAATTAaaTtA | 15 |
| AC0020:TLX:Homeodomain | Vierstra | AATTGbnnnnhnnnnCAATT | 15 |
| ALX3.H14CORE.1.S.BSB | HOCOMOCO | TAATTAaaTTA | 14.9 |
| BARX2.H14CORE.0.SM.BSMB | HOCOMOCO | aaAATCATTA | 14.9 |
| DLX4.H14CORE.1.S.CSC | HOCOMOCO | aatttavgTAATTA | 14.6 |
| PHOX2B (MA0681.3) | JASPAR | TAATCAAATTA | 14.4 |
| LBX2.H14CORE.1.S.BSB | HOCOMOCO | CTAATTAAttA | 14.4 |
| MSX2.H14CORE.1.SM.BSMB | HOCOMOCO | AtTannnvcTAATTAg | 14.3 |
| DLX3.H14CORE.1.S.BSB | HOCOMOCO | aattnvvcTAATTAC | 14.2 |
| MSX1.H14CORE.1.S.CSC | HOCOMOCO | cAATTArnnnnhAATta | 14.2 |
| BARH2.H14CORE.1.S.BSB | HOCOMOCO | taaakgacCAaTTAG | 14.1 |
| Hmx2 (MA0897.2) | JASPAR | AgCAATTAAwgaaT | 14 |
| DLX3.H14CORE.0.SM.BSMB | HOCOMOCO | gvTAATTAC | 14 |
| LBX2.H14CORE.0.S.BSB | HOCOMOCO | CTAATTAat | 13.9 |
| VSX1.H14CORE.0.SM.BSMB | HOCOMOCO | TAATTAGC | 13.9 |
| DLX1.H14CORE.0.S.BSB | HOCOMOCO | TAATTAcbbnaatt | 13.8 |
| DLX2.H14CORE.1.S.BSB | HOCOMOCO | TAATTAvbnhaattt | 13.7 |
| PHX2A.H14CORE.0.PS.APSA | HOCOMOCO | TAATttAATTA | 13.7 |
| LMX1B (MA0703.3) | JASPAR | TTAATTAa | 13.5 |
| HMX3.H14CORE.0.S.BSB | HOCOMOCO | TTAATTG | 13.5 |
| SHOX.H14CORE.0.SM.BSMB | HOCOMOCO | TAATTAgntna | 13.4 |
| Alx4 (MA0853.2) | JASPAR | cgcaTTAATTAA | 13.1 |
| EMX2.H14CORE.0.S.BSB | HOCOMOCO | TAATTAG | 13 |
| SHOX2.H14CORE.1.S.CSC | HOCOMOCO | CtAATTAg | 13 |
| UNC4.H14CORE.0.S.BSB | HOCOMOCO | taATTtAATTA | 13 |
| BARH2.H14CORE.2.S.CSC | HOCOMOCO | AcCGTTTAGc | 12.9 |
| RAX2.H14CORE.0.S.BSB | HOCOMOCO | AdtTAATTAG | 12.9 |
| Arx (MA0874.2) | JASPAR | aTTAATTAA | 12.8 |
| LHX8.H14CORE.0.S.BSB | HOCOMOCO | acTAATTAc | 12.8 |
| RX.H14CORE.0.SM.BSMB | HOCOMOCO | AntTAATTA | 12.8 |
| LHX6.H14CORE.1.S.BSB | HOCOMOCO | gTAATTAGc | 12.7 |
| M00451_2.00Mus musculus 0.96 | CIS-BP | ATTAATTA | 12.6 |
| Hmx1 (MA0896.2) | JASPAR | AGCAATTAA | 12.5 |
| LHX6.H14CORE.2.M.CMC | HOCOMOCO | cTAACGAG | 12.5 |
| M02097_2.00Mus musculus 0.79 | CIS-BP | TTAATTA | 12.5 |
| LHX9.H14CORE.0.PS.APSA | HOCOMOCO | cTAATTAG | 12.4 |
| M05215_2.00 | CIS-BP | TTAATTA | 12.4 |
| LMX1A (MA0702.3) | JASPAR | TTAATTA | 12.3 |
| M05233_2.00 | CIS-BP | AATTGbnnnnnnnnnnngCAATT | 12.3 |
| mix-a (MA0621.2) | JASPAR | TTAATTA | 12.2 |
| ISX.H14CORE.0.SM.BSMB | HOCOMOCO | TAATTGG | 12.2 |
| LHX8.H14CORE.1.M.CMC | HOCOMOCO | CTCGTTAac | 12.2 |
| PHOX2A (MA0713.1) | JASPAR | TAATttAATTA | 12.1 |
| HMX1.H14CORE.0.SM.BSMB | HOCOMOCO | TTAATTG | 12.1 |
| SHOX.H14CORE.1.S.BSB | HOCOMOCO | cTAATTa | 12.1 |
| AC0022:BARHL/BARX:Homeodomain | Vierstra | TAAttGntntTAAAt | 12.1 |
| Hmx3 (MA0898.2) | JASPAR | AgCAATTAA | 12 |
| DRGX.H14CORE.1.SM.BSMB | HOCOMOCO | TaAnyTAATTA | 12 |
| LBX2.H14CORE.2.M.CMC | HOCOMOCO | CTaATTAAt | 12 |
| VAX2.H14CORE.0.SM.BSMB | HOCOMOCO | TAATTAG | 12 |
| Alx1 (MA0854.2) | JASPAR | tTAATTAa | 11.9 |
| BARH1.H14CORE.1.S.BSB | HOCOMOCO | cTAAtcGnynhtaA | 11.9 |
| GBX2.H14CORE.0.SM.BSMB | HOCOMOCO | cTAATTg | 11.9 |
| HME1.H14CORE.0.PSM.APSMA | HOCOMOCO | TAATTAg | 11.9 |
| LHX5.H14CORE.0.PSM.APSMA | HOCOMOCO | tTAATTA | 11.9 |
| MNX1.H14CORE.0.SM.BSMB | HOCOMOCO | cTAATTA | 11.9 |
| AC0010:PROP/ALX:Homeodomain | Vierstra | TAATtnaATTA | 11.9 |
| DLX4.H14CORE.0.SM.BSMB | HOCOMOCO | TAATTac | 11.8 |
| MIXL1.H14CORE.1.S.BSB | HOCOMOCO | TAATTAg | 11.8 |
| ALX3.H14CORE.0.SM.BSMB | HOCOMOCO | cTAATTA | 11.7 |
| BARX1.H14CORE.1.S.BSB | HOCOMOCO | GtTAATtG | 11.7 |
| DLX5.H14CORE.0.PSM.APSMA | HOCOMOCO | TAATTac | 11.7 |
| DLX6.H14CORE.0.SM.BSMB | HOCOMOCO | TAATTa | 11.6 |
| EVX2.H14CORE.0.SM.BSMB | HOCOMOCO | CTAATTA | 11.6 |
| M05359_2.00 | CIS-BP | TAATtnaATTA | 11.6 |
| EMX1.H14CORE.0.SM.BSMB | HOCOMOCO | TAATTAG | 11.5 |
| LHX4.H14CORE.0.SM.BSMB | HOCOMOCO | TAATTAa | 11.5 |
| LMX1A.H14CORE.0.SM.BSMB | HOCOMOCO | TTAATTA | 11.5 |
| MSX1.H14CORE.0.SM.BSMB | HOCOMOCO | cAATTA | 11.5 |
| LHX9.H14CORE.1.M.BMB | HOCOMOCO | gTTAAcgAG | 11.4 |
| PRRX1.H14CORE.0.S.BSB | HOCOMOCO | TAATTA | 11.4 |
| M05237_2.00 | CIS-BP | TAATTA | 11.4 |
| ALX4.H14CORE.1.SM.BSMB | HOCOMOCO | cTAATTA | 11.3 |
| M00260_2.00 | CIS-BP | TAATTA | 11.3 |
| M02091_2.00 | CIS-BP | TTAATTAg | 11.3 |
| Dlx5 (MA1476.3) | JASPAR | GCAATTAG | 11.2 |
| DLX1.H14CORE.1.PSM.APSMA | HOCOMOCO | TAATTa | 11.2 |
| DLX2.H14CORE.0.PSM.APSMA | HOCOMOCO | TAATTa | 11.1 |
| GBX1.H14CORE.0.S.BSB | HOCOMOCO | TAATTg | 11.1 |
| GSX2.H14CORE.0.SM.BSMB | HOCOMOCO | cTAATTa | 11.1 |
| MEOX1.H14CORE.0.SM.BSMB | HOCOMOCO | TAATTA | 11.1 |
| UNC4.H14CORE.1.S.BSB | HOCOMOCO | tAATTAg | 11.1 |
| PRRX2 (MA0075.4) | JASPAR | CTAATTA | 11 |
| VENTX (MA0724.1) | JASPAR | AnCgATTAg | 11 |
| Dlx2 (MA0885.3) | JASPAR | GCAATTAG | 11 |
| LHX5 (MA1519.2) | JASPAR | TAATTA | 11 |
| PHX2A.H14CORE.1.SM.BSMB | HOCOMOCO | tAATTAg | 11 |
| M04936_2.00 | CIS-BP | TAATTA | 11 |
| LHX9 (MA0701.3) | JASPAR | CTAATTA | 10.9 |
| TLX2.H14CORE.0.SM.BSMB | HOCOMOCO | tAATTAG | 10.9 |
| M03193_2.00 | CIS-BP | TAATTag | 10.8 |
| M05195_2.00 | CIS-BP | TAATTag | 10.8 |
| Lhx1 (MA1518.3) | JASPAR | GcTAATTAgC | 10.7 |
| ARX.H14CORE.1.SM.BSMB | HOCOMOCO | tAATTAG | 10.7 |
| LHX3.H14CORE.0.P.BPB | HOCOMOCO | AttTAATTAg | 10.7 |
| PHX2B.H14CORE.1.SM.BSMB | HOCOMOCO | tTAATTa | 10.7 |
| M05153_2.00 | CIS-BP | tTAATTA | 10.7 |
| LHX6 (MA0658.2) | JASPAR | TAATTAg | 10.6 |
| BARX1.H14CORE.0.P.CPC | HOCOMOCO | TAATgGTTT | 10.6 |
| EVX1.H14CORE.0.SM.BSMB | HOCOMOCO | cTAATtA | 10.6 |
| M05221_2.00 | CIS-BP | TAATTG | 10.6 |
| HESX1.H14CORE.0.SM.BSMB | HOCOMOCO | AATTA | 10.5 |
| M05142_2.00 | CIS-BP | cTAATTA | 10.5 |
| GBX1 (MA0889.2) | JASPAR | ctAATTA | 10.4 |
| M04915_2.00 | CIS-BP | TAATggTTT | 10.4 |
| ISX (MA0654.2) | JASPAR | tAATTA | 10.3 |
| TLX2 (MA1577.2) | JASPAR | tAATTA | 10.3 |
| M03210_2.00 | CIS-BP | TAATTA | 10.3 |
| M03226_2.00 | CIS-BP | TAATTaaaTTA | 10.3 |
| EMX1 (MA0612.3) | JASPAR | TAATTA | 10.2 |
| HESX1 (MA0894.2) | JASPAR | TAATTg | 10.2 |
| LHX6.H14CORE.0.P.BPB | HOCOMOCO | TAATCAg | 10.2 |
| M05002_2.00 | CIS-BP | TAATTG | 10.2 |
| AC0002:EMX/PAX:Homeodomain | Vierstra | AATTAgctAATT | 10.2 |
| LHX2 (MA0700.3) | JASPAR | CAATTA | 10.1 |
| LHX1.H14CORE.1.M.CMC | HOCOMOCO | cbTAACGA | 10.1 |
| MEOX2.H14CORE.0.SM.BSMB | HOCOMOCO | TAATtA | 10.1 |
| MSX2.H14CORE.0.SM.BSMB | HOCOMOCO | CAATTA | 10.1 |
| VAX1.H14CORE.0.SM.BSMB | HOCOMOCO | TcATTAg | 10.1 |
| M02090_2.00 | CIS-BP | TAATTAG | 10.1 |
| LBX1 (MA0618.2) | JASPAR | TAATTAG | 10 |
| ESX1 (MA0644.3) | JASPAR | ctAATTA | 10 |
| MSX1 (MA0666.3) | JASPAR | CAATTA | 10 |
| BARX2 (MA1471.2) | JASPAR | AAAccATTA | 10 |
| Isl1 (MA1608.2) | JASPAR | CCATTAG | 10 |
| BSH.H14CORE.0.SM.BSMB | HOCOMOCO | caATTAac | 10 |
| M03201_2.00 | CIS-BP | TAATTg | 10 |
| M05126_2.00 | CIS-BP | TAATTA | 10 |
| M05210_2.00 | CIS-BP | cTAATTA | 10 |
| M05321_2.00 | CIS-BP | TTAAcGAG | 10 |
| EMX2 (MA0886.2) | JASPAR | TAATTA | 9.9 |
| HMX2.H14CORE.0.SM.BSMB | HOCOMOCO | TTAAgTG | 9.9 |
| LMX1B.H14CORE.0.P.CPC | HOCOMOCO | TAATgAAA | 9.9 |
| TLX3.H14CORE.0.SM.BSMB | HOCOMOCO | gTTAATtg | 9.9 |
| ESX1.H14CORE.0.SM.BSMB | HOCOMOCO | tAATTA | 9.8 |
| NOTO.H14CORE.0.SM.BSMB | HOCOMOCO | cTcATTA | 9.8 |
| PRRX2.H14CORE.0.SM.BSMB | HOCOMOCO | TAATTa | 9.8 |
| MSX2 (MA0708.3) | JASPAR | CAATTA | 9.7 |
| Msx3 (MA0709.2) | JASPAR | CAATTA | 9.7 |
| BARHL1 (MA0877.4) | JASPAR | CGTTTA | 9.7 |
| GBX2 (MA0890.2) | JASPAR | cAATTA | 9.7 |
| BARH2.H14CORE.0.SM.BSMB | HOCOMOCO | CaaTTAg | 9.7 |
| ISL1.H14CORE.0.PSM.APSMA | HOCOMOCO | cTAATtG | 9.7 |
| M00318_2.00 | CIS-BP | TTAATTAG | 9.6 |
| M03241_2.00 | CIS-BP | TAATTAG | 9.6 |
| ISL2.H14CORE.0.SM.BSMB | HOCOMOCO | TAAtTG | 9.5 |
| M04908_2.00 | CIS-BP | TAAGTG | 9.5 |
| MEOX1 (MA0661.2) | JASPAR | cTAATTA | 9.4 |
| NOTO (MA0710.2) | JASPAR | CTAATTA | 9.4 |
| LHX1.H14CORE.0.S.CSC | HOCOMOCO | TAATTa | 9.4 |
| M05253_2.00 | CIS-BP | TAATTa | 9.3 |
| VSX2 (MA0726.2) | JASPAR | CTAATTA | 9.2 |
| GSX1.H14CORE.0.SM.BSMB | HOCOMOCO | tTAATt | 9.2 |
| PROP1.H14CORE.1.P.CPC | HOCOMOCO | TAATTna | 9.2 |
| M03243_2.00 | CIS-BP | TTAATTGnT | 9.2 |
| AC0315:HESX/VENTX:Homeodomain | Vierstra | ATATATA | 9.2 |
| EN1 (MA0027.3) | JASPAR | tAATTA | 9.1 |
| EN2 (MA0642.3) | JASPAR | CAATTA | 9.1 |
| RAX (MA0718.2) | JASPAR | cAATTA | 9.1 |
| Nobox (MA0125.2) | JASPAR | TAATTg | 9 |
| MNX1 (MA0707.3) | JASPAR | taATTA | 9 |
| Shox2 (MA0720.2) | JASPAR | tAATTA | 9 |
| DRGX (MA1481.2) | JASPAR | tAATTA | 9 |
| M03204_2.00 | CIS-BP | TAATTg | 8.9 |
| BARX1 (MA0875.2) | JASPAR | CaATTA | 8.8 |
| M05063_2.00 | CIS-BP | TAATTA | 8.7 |
| M05329_2.00 | CIS-BP | TAATtac | 8.7 |
| BARH1.H14CORE.0.SM.BSMB | HOCOMOCO | TAAttG | 8.6 |
| GSX2 (MA0893.3) | JASPAR | gtaATTA | 8.5 |
| VENTX.H14CORE.0.SM.BSMB | HOCOMOCO | ATTAg | 8.5 |
| AC0001:DLX/LHX:Homeodomain | Vierstra | TAATTA | 8.5 |
| Lhx8 (MA0705.2) | JASPAR | TAATTA | 8.4 |
| M03191_2.00 | CIS-BP | TAATTaaATtA | 8.4 |
| BSX (MA0876.2) | JASPAR | caATTA | 8.3 |
| HME2.H14CORE.0.SM.BSMB | HOCOMOCO | cAATTA | 8.3 |
| M03078_2.00 | CIS-BP | TAATTg | 8.3 |
| M03180_2.00 | CIS-BP | TAATTg | 8.3 |
| M05204_2.00 | CIS-BP | TAAGTG | 8.3 |
| DLX6 (MA0882.2) | JASPAR | cAATTA | 8.2 |
| M03120_2.00 | CIS-BP | TAATTa | 8.2 |
| M05244_2.00 | CIS-BP | TAATT | 8.2 |
| AC0034:BARHL:Homeodomain | Vierstra | TAAACG | 8.2 |
| PRRX1 (MA0716.2) | JASPAR | tAATTA | 8.1 |
| VSX1 (MA0725.2) | JASPAR | cTAATTA | 8.1 |
| DLX1 (MA0879.3) | JASPAR | CAATTA | 8.1 |
| LHX2.H14CORE.0.PS.APSA | HOCOMOCO | TAATtaG | 8.1 |
| M04917_2.00 | CIS-BP | TAATTa | 8.1 |
| BARHL2 (MA0635.2) | JASPAR | TAAACG | 8 |
| Lhx4 (MA0704.2) | JASPAR | TAATTA | 8 |
| M03215_2.00 | CIS-BP | TAATtA | 7.8 |
| M02088_2.00 | CIS-BP | TAATtA | 7.7 |
| M03102_2.00 | CIS-BP | TAATtA | 7.7 |
| M03157_2.00 | CIS-BP | TAAAcG | 7.7 |
| M03234_2.00 | CIS-BP | TTAAtTG | 7.7 |
| M05091_2.00 | CIS-BP | TAAACG | 7.7 |
| Dlx4 (MA0881.2) | JASPAR | cAATTA | 7.5 |
| EVX2 (MA0888.2) | JASPAR | TaATTA | 7.5 |
| M02095_2.00 | CIS-BP | TAATTg | 7.5 |
| AC0026:HMX/ISL:Homeodomain | Vierstra | TAAgTG | 7.5 |
| SHOX (MA0630.2) | JASPAR | TAATTg | 7.3 |
| EVX1 (MA0887.2) | JASPAR | TaATTA | 7.3 |
| MEOX2 (MA0706.2) | JASPAR | TAATTA | 7.2 |
| M03095_2.00 | CIS-BP | TAATTa | 7.2 |
| M03166_2.00 | CIS-BP | TAATTa | 7.2 |
| M00285_2.00looks like WT1 | CIS-BP | TATATT | 7.1 |
| M03214_2.00 | CIS-BP | TAATTg | 7.1 |
| ALX3 (MA0634.2) | JASPAR | tAATTA | 7 |
| MIXL1 (MA0662.2) | JASPAR | tAATTA | 7 |
| LBX2 (MA0699.2) | JASPAR | cAATTA | 7 |
| Dlx3 (MA0880.2) | JASPAR | cAATTA | 7 |
| ISL2 (MA0914.2) | JASPAR | CACTTA | 7 |
| M01503_2.00 | CIS-BP | TAATta | 7 |
| M03233_2.00 | CIS-BP | TAAtTG | 7 |
| RAX2 (MA0717.2) | JASPAR | cAATTA | 6.9 |
| VAX2 (MA0723.3) | JASPAR | taATTA | 6.9 |
| M03168_2.00 | CIS-BP | cTAATTA | 6.9 |
| UNCX (MA0721.2) | JASPAR | tAATTA | 6.8 |
| VAX1 (MA0722.2) | JASPAR | cTAATTA | 6.8 |
| M05377_2.00 | CIS-BP | TAACG | 6.6 |
| M04901_2.00 | CIS-BP | TaATGab | 6.4 |
| M03205_2.00 | CIS-BP | TAATta | 6.3 |
| M05410_2.00 | CIS-BP | TAATtg | 6.3 |
| M04988_2.00 | CIS-BP | TaATGa | 6.2 |
| GSX1 (MA0892.2) | JASPAR | taATTA | 6 |
| M00435_2.00Mus musculus 1 | CIS-BP | TAATta | 5.9 |
| M03118_2.00 | CIS-BP | TAATTg | 5.8 |
| AC0019:TLX/PAX:Homeodomain | Vierstra | AATTG | 5.4 |
| M05258_2.00 | CIS-BP | TaAcG | 5.3 |
| M01505_2.00 | CIS-BP | TAAtdA | 4.9 |
| AC0016:MSX:Homeodomain | Vierstra | CngTAanTG | 4.9 |
| AC0440:EN:Homeodomain | Vierstra | GTAaT | 4.9 |
| M00288_2.00 | CIS-BP | TAAT | 4.8 |
| M02086_2.00 | CIS-BP | TGATT | 4.7 |
| M00291_2.00 | CIS-BP | TAAT | 4.4 |
| M00417_2.00Mus musculus 1 | CIS-BP | TAAT | 3.9 |
| M00283_2.00 | CIS-BP | TAAT | 3.3 |
| M00306_2.00 | CIS-BP | TAAT | 3.3 |
| M02084_2.00 | CIS-BP | taAT | 3.2 |
| M00266_2.00 | CIS-BP | TAAt | 3.1 |
| M02085_2.00 | CIS-BP | tAAt | 2.8 |
| M00315_2.00 | CIS-BP | AT | 2.7 |
| M02087_2.00 | CIS-BP | TAa | 2.2 |
| M00485_2.00Mus musculus 1 | CIS-BP | At | 2 |
| M00278_2.00 | CIS-BP | AT | 1.7 |
| M00499_2.00Mus musculus 0.93 | CIS-BP | T | 1.4 |
HOCOMOCO tags read as assay + quality grade: P ChIP-seq, S HT-SELEX, M methyl-HT-SELEX, G GHT-SELEX, I SMiLE-seq, B PBM; grade A means two or more assay types agreed. A P-only matrix is a record of where the protein was crosslinked, which need not be a sequence it binds itself.
The factors, elsewhere
These entries are written from the primary literature and every citation is checked against PubMed, but this one can still be out of date, too confident, or simply wrong — especially where a motif’s published site and its database matrices disagree. Corrections and additions are welcome, and they are the fastest way to make this page better for everyone.