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   24-JAN-2024, entry version 191.
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: Transcriptional activator (By similarity). Activates
CC       transcription of GNRHR, via binding to the downstream activin
CC       regulatory element (DARE) in the gene promoter (By similarity).
CC       {ECO:0000250|UniProtKB:Q64205}.
CC   -!- SUBUNIT: Heterodimer with MEIS1 (PubMed:26550823). Interacts with IPO7;
CC       the interaction facilitates nuclear translocation of DLX3 in dental
CC       papilla cells (By similarity). {ECO:0000250|UniProtKB:Q64205,
CC       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       Cytoplasm {ECO:0000250|UniProtKB:Q64205}.
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; 5.
DR   IntAct; O60479; 17.
DR   MINT; O60479; -.
DR   STRING; 9606.ENSP00000389870; -.
DR   iPTMnet; O60479; -.
DR   PhosphoSitePlus; O60479; -.
DR   BioMuta; DLX3; -.
DR   MassIVE; O60479; -.
DR   MaxQB; O60479; -.
DR   PaxDb; 9606-ENSP00000389870; -.
DR   PeptideAtlas; O60479; -.
DR   ProteomicsDB; 49421; -.
DR   Antibodypedia; 17996; 294 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   AGR; HGNC:2916; -.
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; 2969529at2759; -.
DR   PhylomeDB; O60479; -.
DR   TreeFam; TF350606; -.
DR   PathwayCommons; O60479; -.
DR   SignaLink; O60479; -.
DR   SIGNOR; O60479; -.
DR   BioGRID-ORCS; 1747; 46 hits in 1169 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 96 other cell types or tissues.
DR   ExpressionAtlas; O60479; baseline and differential.
DR   GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR   GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR   GO; GO:0005634; C:nucleus; ISS:UniProtKB.
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:0000976; F:transcription cis-regulatory region binding; ISS:UniProtKB.
DR   GO; GO:0001568; P:blood vessel development; IEA:Ensembl.
DR   GO; GO:0030509; P:BMP signaling pathway; IEA:Ensembl.
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:0045944; P:positive regulation of transcription by RNA polymerase II; ISS:UniProtKB.
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   Gene3D; 1.10.10.60; Homeodomain-like; 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   PANTHER; PTHR24327; HOMEOBOX PROTEIN; 1.
DR   PANTHER; PTHR24327:SF28; HOMEOBOX PROTEIN DLX-3; 1.
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; Homeodomain-like; 1.
DR   PROSITE; PS00027; HOMEOBOX_1; 1.
DR   PROSITE; PS50071; HOMEOBOX_2; 1.
DR   Genevisible; O60479; HS.
PE   1: Evidence at protein level;
KW   3D-structure; Activator; Amelogenesis imperfecta; Cytoplasm;
KW   Developmental protein; DNA-binding; Homeobox; Nucleus; Reference proteome;
KW   Transcription; Transcription regulation.
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
//