DLX3_HUMAN
ID DLX3_HUMAN Reviewed; 287 AA.
AC O60479; B3KQL6;
DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1998, sequence version 1.
DT 03-AUG-2022, entry version 183.
DE RecName: Full=Homeobox protein DLX-3;
GN Name=DLX3;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND INVOLVEMENT IN TDO.
RX PubMed=9467018; DOI=10.1093/hmg/7.3.563;
RA Price J.A., Bowden D.W., Wright J.T., Pettenati M.J., Hart T.C.;
RT "Identification of a mutation in DLX3 associated with tricho-dento-osseous
RT (TDO) syndrome.";
RL Hum. Mol. Genet. 7:563-569(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC TISSUE=Foreskin;
RX PubMed=11792834; DOI=10.1073/pnas.012584999;
RA Sumiyama K., Irvine S.Q., Stock D.W., Weiss K.M., Kawasaki K., Shimizu N.,
RA Shashikant C.S., Miller W., Ruddle F.H.;
RT "Genomic structure and functional control of the Dlx3-7 bigene cluster.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:780-785(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Placenta;
RX PubMed=16303743; DOI=10.1093/dnares/12.2.117;
RA Otsuki T., Ota T., Nishikawa T., Hayashi K., Suzuki Y., Yamamoto J.,
RA Wakamatsu A., Kimura K., Sakamoto K., Hatano N., Kawai Y., Ishii S.,
RA Saito K., Kojima S., Sugiyama T., Ono T., Okano K., Yoshikawa Y.,
RA Aotsuka S., Sasaki N., Hattori A., Okumura K., Nagai K., Sugano S.,
RA Isogai T.;
RT "Signal sequence and keyword trap in silico for selection of full-length
RT human cDNAs encoding secretion or membrane proteins from oligo-capped cDNA
RT libraries.";
RL DNA Res. 12:117-126(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Eye, and Placenta;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP INVOLVEMENT IN AI4.
RX PubMed=15666299; DOI=10.1002/ajmg.a.30521;
RA Dong J., Amor D., Aldred M.J., Gu T., Escamilla M., MacDougall M.;
RT "DLX3 mutation associated with autosomal dominant amelogenesis imperfecta
RT with taurodontism.";
RL Am. J. Med. Genet. A 133:138-141(2005).
RN [7] {ECO:0007744|PDB:4XRS}
RP X-RAY CRYSTALLOGRAPHY (3.50 ANGSTROMS) OF 131-186 IN COMPLEX WITH MEIS1 AND
RP DNA, SUBUNIT, AND DNA-BINDING.
RX PubMed=26550823; DOI=10.1038/nature15518;
RA Jolma A., Yin Y., Nitta K.R., Dave K., Popov A., Taipale M., Enge M.,
RA Kivioja T., Morgunova E., Taipale J.;
RT "DNA-dependent formation of transcription factor pairs alters their binding
RT specificity.";
RL Nature 527:384-388(2015).
CC -!- FUNCTION: Likely to play a regulatory role in the development of the
CC ventral forebrain. May play a role in craniofacial patterning and
CC morphogenesis.
CC -!- SUBUNIT: Heterodimer with MEIS1. {ECO:0000269|PubMed:26550823}.
CC -!- INTERACTION:
CC O60479; Q92870-2: APBB2; NbExp=3; IntAct=EBI-3908248, EBI-21535880;
CC O60479; P54253: ATXN1; NbExp=3; IntAct=EBI-3908248, EBI-930964;
CC O60479; B4DE54: BANP; NbExp=3; IntAct=EBI-3908248, EBI-16429313;
CC O60479; Q8N9N5-2: BANP; NbExp=3; IntAct=EBI-3908248, EBI-11524452;
CC O60479; Q8N9N5-7: BANP; NbExp=3; IntAct=EBI-3908248, EBI-16429296;
CC O60479; P55212: CASP6; NbExp=3; IntAct=EBI-3908248, EBI-718729;
CC O60479; Q14203-5: DCTN1; NbExp=3; IntAct=EBI-3908248, EBI-25840379;
CC O60479; P22607: FGFR3; NbExp=3; IntAct=EBI-3908248, EBI-348399;
CC O60479; Q9NP62: GCM1; NbExp=2; IntAct=EBI-3908248, EBI-21194843;
CC O60479; P42858: HTT; NbExp=3; IntAct=EBI-3908248, EBI-466029;
CC O60479; P13473-2: LAMP2; NbExp=3; IntAct=EBI-3908248, EBI-21591415;
CC O60479; Q12837: POU4F2; NbExp=3; IntAct=EBI-3908248, EBI-17236143;
CC O60479; O75400-2: PRPF40A; NbExp=3; IntAct=EBI-3908248, EBI-5280197;
CC O60479; P37840: SNCA; NbExp=3; IntAct=EBI-3908248, EBI-985879;
CC O60479; Q9UMX0: UBQLN1; NbExp=3; IntAct=EBI-3908248, EBI-741480;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00108}.
CC -!- DISEASE: Trichodentoosseous syndrome (TDO) [MIM:190320]: An autosomal
CC dominant disease characterized by curly kinky hair at birth, enamel
CC hypoplasia, taurodontism, thickening of cortical bones and variable
CC expression of craniofacial morphology. {ECO:0000269|PubMed:9467018}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
CC -!- DISEASE: Amelogenesis imperfecta 4 (AI4) [MIM:104510]: An autosomal
CC dominant defect of enamel formation associated with enlarged pulp
CC chambers. Enamel is thin, teeth are small and widely spaced.
CC {ECO:0000269|PubMed:15666299}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the distal-less homeobox family. {ECO:0000305}.
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DR EMBL; AF028233; AAC14397.1; -; Genomic_DNA.
DR EMBL; AF452638; AAL99504.1; -; Genomic_DNA.
DR EMBL; AK075167; BAG52078.1; -; mRNA.
DR EMBL; CH471109; EAW94650.1; -; Genomic_DNA.
DR EMBL; BC012361; AAH12361.1; -; mRNA.
DR EMBL; BC028970; AAH28970.1; -; mRNA.
DR CCDS; CCDS11556.1; -.
DR RefSeq; NP_005211.1; NM_005220.2.
DR PDB; 4XRS; X-ray; 3.50 A; G/I=131-186.
DR PDBsum; 4XRS; -.
DR AlphaFoldDB; O60479; -.
DR SMR; O60479; -.
DR BioGRID; 108091; 4.
DR IntAct; O60479; 16.
DR STRING; 9606.ENSP00000389870; -.
DR iPTMnet; O60479; -.
DR PhosphoSitePlus; O60479; -.
DR BioMuta; DLX3; -.
DR MassIVE; O60479; -.
DR MaxQB; O60479; -.
DR PaxDb; O60479; -.
DR PeptideAtlas; O60479; -.
DR PRIDE; O60479; -.
DR ProteomicsDB; 49421; -.
DR Antibodypedia; 17996; 259 antibodies from 32 providers.
DR DNASU; 1747; -.
DR Ensembl; ENST00000434704.2; ENSP00000389870.2; ENSG00000064195.7.
DR GeneID; 1747; -.
DR KEGG; hsa:1747; -.
DR MANE-Select; ENST00000434704.2; ENSP00000389870.2; NM_005220.3; NP_005211.1.
DR UCSC; uc002ipy.3; human.
DR CTD; 1747; -.
DR DisGeNET; 1747; -.
DR GeneCards; DLX3; -.
DR HGNC; HGNC:2916; DLX3.
DR HPA; ENSG00000064195; Tissue enriched (skin).
DR MalaCards; DLX3; -.
DR MIM; 104510; phenotype.
DR MIM; 190320; phenotype.
DR MIM; 600525; gene.
DR neXtProt; NX_O60479; -.
DR OpenTargets; ENSG00000064195; -.
DR Orphanet; 100034; Hypomaturation-hypoplastic amelogenesis imperfecta with taurodontism.
DR Orphanet; 3352; Tricho-dento-osseous syndrome.
DR PharmGKB; PA27371; -.
DR VEuPathDB; HostDB:ENSG00000064195; -.
DR eggNOG; KOG0850; Eukaryota.
DR GeneTree; ENSGT00940000158951; -.
DR HOGENOM; CLU_074733_1_0_1; -.
DR InParanoid; O60479; -.
DR OMA; SWYHTQN; -.
DR OrthoDB; 1416398at2759; -.
DR PhylomeDB; O60479; -.
DR TreeFam; TF350606; -.
DR PathwayCommons; O60479; -.
DR SignaLink; O60479; -.
DR SIGNOR; O60479; -.
DR BioGRID-ORCS; 1747; 42 hits in 1089 CRISPR screens.
DR GeneWiki; DLX3; -.
DR GeneWiki; DLX3_(gene); -.
DR GenomeRNAi; 1747; -.
DR Pharos; O60479; Tbio.
DR PRO; PR:O60479; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; O60479; protein.
DR Bgee; ENSG00000064195; Expressed in skin of leg and 95 other tissues.
DR ExpressionAtlas; O60479; baseline and differential.
DR Genevisible; O60479; HS.
DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0003682; F:chromatin binding; IEA:Ensembl.
DR GO; GO:0003677; F:DNA binding; IDA:UniProtKB.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IEA:Ensembl.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; TAS:ProtInc.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISA:NTNU_SB.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; IDA:ARUK-UCL.
DR GO; GO:0001568; P:blood vessel development; IEA:Ensembl.
DR GO; GO:0030509; P:BMP signaling pathway; IEA:Ensembl.
DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR GO; GO:0030855; P:epithelial cell differentiation; IBA:GO_Central.
DR GO; GO:0010467; P:gene expression; IEA:Ensembl.
DR GO; GO:0035315; P:hair cell differentiation; IEA:Ensembl.
DR GO; GO:0071335; P:hair follicle cell proliferation; IEA:Ensembl.
DR GO; GO:0031069; P:hair follicle morphogenesis; IEA:Ensembl.
DR GO; GO:0071895; P:odontoblast differentiation; IEA:Ensembl.
DR GO; GO:0042475; P:odontogenesis of dentin-containing tooth; IEA:Ensembl.
DR GO; GO:0001890; P:placenta development; IEA:Ensembl.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0016055; P:Wnt signaling pathway; IEA:Ensembl.
DR CDD; cd00086; homeodomain; 1.
DR InterPro; IPR022135; Distal-less_N.
DR InterPro; IPR009057; Homeobox-like_sf.
DR InterPro; IPR017970; Homeobox_CS.
DR InterPro; IPR001356; Homeobox_dom.
DR InterPro; IPR020479; Homeobox_metazoa.
DR InterPro; IPR000047; HTH_motif.
DR Pfam; PF12413; DLL_N; 1.
DR Pfam; PF00046; Homeodomain; 1.
DR PRINTS; PR00024; HOMEOBOX.
DR PRINTS; PR00031; HTHREPRESSR.
DR SMART; SM00389; HOX; 1.
DR SUPFAM; SSF46689; SSF46689; 1.
DR PROSITE; PS00027; HOMEOBOX_1; 1.
DR PROSITE; PS50071; HOMEOBOX_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Amelogenesis imperfecta; Developmental protein; DNA-binding;
KW Homeobox; Nucleus; Reference proteome.
FT CHAIN 1..287
FT /note="Homeobox protein DLX-3"
FT /id="PRO_0000049026"
FT DNA_BIND 129..188
FT /note="Homeobox"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00108"
FT REGION 20..39
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 131..181
FT /note="Interaction with DNA"
FT /evidence="ECO:0000305|PubMed:26550823"
FT REGION 195..287
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 195..226
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 242..271
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 272..287
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT STRAND 138..141
FT /evidence="ECO:0007829|PDB:4XRS"
FT TURN 142..144
FT /evidence="ECO:0007829|PDB:4XRS"
FT HELIX 145..150
FT /evidence="ECO:0007829|PDB:4XRS"
FT HELIX 159..163
FT /evidence="ECO:0007829|PDB:4XRS"
FT TURN 164..166
FT /evidence="ECO:0007829|PDB:4XRS"
FT HELIX 171..178
FT /evidence="ECO:0007829|PDB:4XRS"
SQ SEQUENCE 287 AA; 31738 MW; DCA9716E51D78DD1 CRC64;
MSGSFDRKLS SILTDISSSL SCHAGSKDSP TLPESSVTDL GYYSAPQHDY YSGQPYGQTV
NPYTYHHQFN LNGLAGTGAY SPKSEYTYGA SYRQYGAYRE QPLPAQDPVS VKEEPEAEVR
MVNGKPKKVR KPRTIYSSYQ LAALQRRFQK AQYLALPERA ELAAQLGLTQ TQVKIWFQNR
RSKFKKLYKN GEVPLEHSPN NSDSMACNSP PSPALWDTSS HSTPAPARSQ LPPPLPYSAS
PSYLDDPTNS WYHAQNLSGP HLQQQPPQPA TLHHASPGPP PNPGAVY
