DLX4_HUMAN
ID DLX4_HUMAN Reviewed; 240 AA.
AC Q92988; D3DTX2; D3DTX3; O60480; Q13265; Q6PJK0; Q9HBE0;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 24-JAN-2006, sequence version 4.
DT 03-AUG-2022, entry version 185.
DE RecName: Full=Homeobox protein DLX-4;
DE AltName: Full=Beta protein 1;
DE AltName: Full=Homeobox protein DLX-7;
DE AltName: Full=Homeobox protein DLX-8;
GN Name=DLX4; Synonyms=BP1, DLX7, DLX8, DLX9;
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 [MRNA] (ISOFORM 2).
RC TISSUE=Leukemia;
RX PubMed=8975708; DOI=10.1006/geno.1996.0634;
RA Nakamura S., Stock D.W., Wydner K.L., Bollekens J.A., Takeshita K.,
RA Nagai B.M., Chiba S., Kitamura T., Freeland T.M., Zhao Z., Minowada J.,
RA Lawrence J.B., Weiss K.M., Ruddle F.H.;
RT "Genomic analysis of a new mammalian distal-less gene: Dlx7.";
RL Genomics 38:314-324(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
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 [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY.
RX PubMed=11069021; DOI=10.1038/sj.leu.2401912;
RA Haga S.B., Fu S., Karp J.E., Ross D.D., Williams D.M., Hankins W.D.,
RA Behm F., Ruscetti F.W., Chang M., Smith B.D., Becton D., Raimondi S.C.,
RA Berg P.E.;
RT "BP1, a new homeobox gene, is frequently expressed in acute leukemias.";
RL Leukemia 14:1867-1875(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, AND FUNCTION.
RX PubMed=11909945; DOI=10.1128/mcb.22.8.2505-2514.2002;
RA Chase M.B., Fu S., Haga S.B., Davenport G., Stevenson H., Do K., Morgan D.,
RA Mah A.L., Berg P.E.;
RT "BP1, a homeodomain-containing isoform of DLX4, represses the beta-globin
RT gene.";
RL Mol. Cell. Biol. 22:2505-2514(2002).
RN [5]
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [7]
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 [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
RC TISSUE=Placenta, and Uterus;
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 [9]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-177.
RC TISSUE=Placenta;
RX PubMed=9073066; DOI=10.1016/s0378-1119(96)00706-8;
RA Quinn L.M., Johnson B.V., Nicholl J., Sutherland G.R., Kalionis B.;
RT "Isolation and identification of homeobox genes from the human placenta
RT including a novel member of the Distal-less family, DLX4.";
RL Gene 187:55-61(1997).
RN [10]
RP INVOLVEMENT IN OFC15, FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=25954033; DOI=10.1093/hmg/ddv167;
RA Wu D., Mandal S., Choi A., Anderson A., Prochazkova M., Perry H.,
RA Gil-Da-Silva-Lopes V.L., Lao R., Wan E., Tang P.L., Kwok P.Y., Klein O.,
RA Zhuan B., Slavotinek A.M.;
RT "DLX4 is associated with orofacial clefting and abnormal jaw development.";
RL Hum. Mol. Genet. 24:4340-4352(2015).
CC -!- FUNCTION: May play a role in determining the production of hemoglobin
CC S. May act as a repressor. During embryonic development, plays a role
CC in palatogenesis. {ECO:0000269|PubMed:11909945,
CC ECO:0000269|PubMed:25954033}.
CC -!- INTERACTION:
CC Q92988; P16333: NCK1; NbExp=3; IntAct=EBI-1752755, EBI-389883;
CC Q92988; Q13485: SMAD4; NbExp=5; IntAct=EBI-1752755, EBI-347263;
CC Q92988; P08047: SP1; NbExp=4; IntAct=EBI-1752755, EBI-298336;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:25954033}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Comment=Additional isoforms seem to exist. PubMed:9073066 (AAC51171)
CC sequence may be an additional isoform.;
CC Name=1;
CC IsoId=Q92988-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q92988-2; Sequence=VSP_002236;
CC Name=3;
CC IsoId=Q92988-3; Sequence=VSP_002236, VSP_017043;
CC -!- TISSUE SPECIFICITY: Expressed in leukemia cells and placenta. Also
CC expressed in kidney and fetal liver. {ECO:0000269|PubMed:11069021,
CC ECO:0000269|PubMed:11909945}.
CC -!- DISEASE: Non-syndromic orofacial cleft 15 (OFC15) [MIM:616788]: A birth
CC defect consisting of cleft lips with or without cleft palate. Cleft
CC lips are associated with cleft palate in two-third of cases. A cleft
CC lip can occur on one or both sides and range in severity from a simple
CC notch in the upper lip to a complete opening in the lip extending into
CC the floor of the nostril and involving the upper gum. OFC15 inheritance
CC is autosomal dominant. {ECO:0000269|PubMed:25954033}. Note=The disease
CC is caused by variants affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the distal-less homeobox family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/DLX4ID49827ch17q21.html";
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DR EMBL; U73328; AAC50942.1; -; mRNA.
DR EMBL; AF028235; AAC14398.1; -; Genomic_DNA.
DR EMBL; AF254115; AAG31975.1; -; mRNA.
DR EMBL; AF452638; AAL99503.1; -; Genomic_DNA.
DR EMBL; BT006978; AAP35624.1; -; mRNA.
DR EMBL; CH471109; EAW94651.1; -; Genomic_DNA.
DR EMBL; CH471109; EAW94653.1; -; Genomic_DNA.
DR EMBL; CH471109; EAW94654.1; -; Genomic_DNA.
DR EMBL; CH471109; EAW94655.1; -; Genomic_DNA.
DR EMBL; BC005812; AAH05812.1; -; mRNA.
DR EMBL; BC014419; AAH14419.1; -; mRNA.
DR EMBL; BC016145; AAH16145.1; -; mRNA.
DR EMBL; U31762; AAC51171.1; -; mRNA.
DR CCDS; CCDS11555.1; -. [Q92988-1]
DR CCDS; CCDS45728.1; -. [Q92988-2]
DR PIR; G01958; G01958.
DR RefSeq; NP_001925.2; NM_001934.3. [Q92988-2]
DR RefSeq; NP_612138.1; NM_138281.2. [Q92988-1]
DR RefSeq; XP_016879780.1; XM_017024291.1. [Q92988-2]
DR AlphaFoldDB; Q92988; -.
DR SMR; Q92988; -.
DR BioGRID; 108092; 9.
DR IntAct; Q92988; 15.
DR MINT; Q92988; -.
DR STRING; 9606.ENSP00000240306; -.
DR iPTMnet; Q92988; -.
DR PhosphoSitePlus; Q92988; -.
DR BioMuta; DLX4; -.
DR DMDM; 85700416; -.
DR MassIVE; Q92988; -.
DR PaxDb; Q92988; -.
DR PeptideAtlas; Q92988; -.
DR PRIDE; Q92988; -.
DR Antibodypedia; 17993; 435 antibodies from 32 providers.
DR DNASU; 1748; -.
DR Ensembl; ENST00000240306.5; ENSP00000240306.3; ENSG00000108813.11. [Q92988-1]
DR Ensembl; ENST00000411890.3; ENSP00000410622.2; ENSG00000108813.11. [Q92988-2]
DR Ensembl; ENST00000611342.1; ENSP00000480366.1; ENSG00000108813.11. [Q92988-3]
DR GeneID; 1748; -.
DR KEGG; hsa:1748; -.
DR MANE-Select; ENST00000240306.5; ENSP00000240306.3; NM_138281.3; NP_612138.1.
DR UCSC; uc002ipv.4; human. [Q92988-1]
DR CTD; 1748; -.
DR DisGeNET; 1748; -.
DR GeneCards; DLX4; -.
DR HGNC; HGNC:2917; DLX4.
DR HPA; ENSG00000108813; Tissue enhanced (placenta, skin).
DR MalaCards; DLX4; -.
DR MIM; 601911; gene.
DR MIM; 616788; phenotype.
DR neXtProt; NX_Q92988; -.
DR OpenTargets; ENSG00000108813; -.
DR Orphanet; 199306; Cleft lip/palate.
DR PharmGKB; PA27372; -.
DR VEuPathDB; HostDB:ENSG00000108813; -.
DR eggNOG; KOG0850; Eukaryota.
DR GeneTree; ENSGT00940000162259; -.
DR HOGENOM; CLU_074733_2_1_1; -.
DR InParanoid; Q92988; -.
DR OMA; GNNFGAW; -.
DR OrthoDB; 1416398at2759; -.
DR PhylomeDB; Q92988; -.
DR TreeFam; TF315720; -.
DR PathwayCommons; Q92988; -.
DR SignaLink; Q92988; -.
DR BioGRID-ORCS; 1748; 15 hits in 1093 CRISPR screens.
DR GeneWiki; DLX4; -.
DR GenomeRNAi; 1748; -.
DR Pharos; Q92988; Tbio.
DR PRO; PR:Q92988; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; Q92988; protein.
DR Bgee; ENSG00000108813; Expressed in buccal mucosa cell and 129 other tissues.
DR Genevisible; Q92988; HS.
DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; NAS:UniProtKB.
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:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; IDA:NTNU_SB.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:NTNU_SB.
DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:MGI.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; IDA:ARUK-UCL.
DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:NTNU_SB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; NAS:UniProtKB.
DR CDD; cd00086; homeodomain; 1.
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; 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 Alternative splicing; Developmental protein; DNA-binding; Homeobox;
KW Nucleus; Reference proteome.
FT CHAIN 1..240
FT /note="Homeobox protein DLX-4"
FT /id="PRO_0000049028"
FT DNA_BIND 117..176
FT /note="Homeobox"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00108"
FT REGION 80..120
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 90..113
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 1..94
FT /note="MTSLPCPLPGRDASKAVFPDLAPVPSVAAAYPLGLSPTTAASPNLSYSRPYG
FT HLLSYPYTEPANPGDSYLSCQQPAALSQPLCGPAEHPQELEA -> MKLSVLPPRSLLA
FT PYTVLCCPP (in isoform 2 and isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:8975708"
FT /id="VSP_002236"
FT VAR_SEQ 162..240
FT /note="KIWFQNKRSKYKKLLKQNSGGQEGDFPGRTFSVSPCSPPLPSLWDLPKAGTL
FT PTSGYGNSFGAWYQHHSSDVLASPQMM -> GPVSSFPISHLPWFSGNSSPSPSCE
FT (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_017043"
FT CONFLICT 1..94
FT /note="MTSLPCPLPGRDASKAVFPDLAPVPSVAAAYPLGLSPTTAASPNLSYSRPYG
FT HLLSYPYTEPANPGDSYLSCQQPAALSQPLCGPAEHPQELEA -> GGSLSLPPEPLCA
FT RCPTKEGAAPRRPGFWGSLETQAATVWRGRHGHFSCRVRLSRGAARYSRRGQGKPGVTI
FT SAARLVFKVLSAGPLTHPAGRSRRLPRGHRLKPLSIALSLCLQCPSSVISRPRLSPGPS
FT LSAPPYPKLAPPPVAELRPPTAGAAVPWLWPSARFLPRVTGPIRVGAPLGAELRLVSPG
FT AVNVGVETLHAE (in Ref. 9)"
FT /evidence="ECO:0000305"
FT CONFLICT 113
FT /note="P -> A (in Ref. 1; AAC50942)"
FT /evidence="ECO:0000305"
FT CONFLICT 203
FT /note="S -> Y (in Ref. 1; AAC50942)"
FT /evidence="ECO:0000305"
FT CONFLICT 224
FT /note="A -> P (in Ref. 1; AAC50942)"
FT /evidence="ECO:0000305"
FT CONFLICT 235
FT /note="Missing (in Ref. 1; AAC50942)"
FT /evidence="ECO:0000305"
FT CONFLICT Q92988-2:8
FT /note="P -> H (in Ref. 1; AAC50942)"
FT /evidence="ECO:0000305"
FT CONFLICT Q92988-2:15
FT /note="Y -> N (in Ref. 1; AAC50942)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 240 AA; 26263 MW; 18EE52CF20C126EB CRC64;
MTSLPCPLPG RDASKAVFPD LAPVPSVAAA YPLGLSPTTA ASPNLSYSRP YGHLLSYPYT
EPANPGDSYL SCQQPAALSQ PLCGPAEHPQ ELEADSEKPR LSPEPSERRP QAPAKKLRKP
RTIYSSLQLQ HLNQRFQHTQ YLALPERAQL AAQLGLTQTQ VKIWFQNKRS KYKKLLKQNS
GGQEGDFPGR TFSVSPCSPP LPSLWDLPKA GTLPTSGYGN SFGAWYQHHS SDVLASPQMM
