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Homeobox protein DLX-4 (Beta protein 1) (Homeobox protein DLX-7) (Homeobox protein DLX-8)

 DLX4_HUMAN              Reviewed;         240 AA.
Q92988; D3DTX2; D3DTX3; O60480; Q13265; Q6PJK0; Q9HBE0;
01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
24-JAN-2006, sequence version 4.
12-SEP-2018, entry version 162.
RecName: Full=Homeobox protein DLX-4;
AltName: Full=Beta protein 1;
AltName: Full=Homeobox protein DLX-7;
AltName: Full=Homeobox protein DLX-8;
Name=DLX4; Synonyms=BP1, DLX7, DLX8, DLX9;
Homo sapiens (Human).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
Catarrhini; Hominidae; Homo.
NCBI_TaxID=9606;
[1]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
TISSUE=Leukemia;
PubMed=8975708; DOI=10.1006/geno.1996.0634;
Nakamura S., Stock D.W., Wydner K.L., Bollekens J.A., Takeshita K.,
Nagai B.M., Chiba S., Kitamura T., Freeland T.M., Zhao Z.,
Minowada J., Lawrence J.B., Weiss K.M., Ruddle F.H.;
"Genomic analysis of a new mammalian distal-less gene: Dlx7.";
Genomics 38:314-324(1996).
[2]
NUCLEOTIDE SEQUENCE [GENOMIC DNA].
PubMed=9467018; DOI=10.1093/hmg/7.3.563;
Price J.A., Bowden D.W., Wright J.T., Pettenati M.J., Hart T.C.;
"Identification of a mutation in DLX3 associated with tricho-dento-
osseous (TDO) syndrome.";
Hum. Mol. Genet. 7:563-569(1998).
[3]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY.
PubMed=11069021; DOI=10.1038/sj.leu.2401912;
Haga S.B., Fu S., Karp J.E., Ross D.D., Williams D.M., Hankins W.D.,
Behm F., Ruscetti F.W., Chang M., Smith B.D., Becton D.,
Raimondi S.C., Berg P.E.;
"BP1, a new homeobox gene, is frequently expressed in acute
leukemias.";
Leukemia 14:1867-1875(2000).
[4]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, AND
FUNCTION.
PubMed=11909945; DOI=10.1128/MCB.22.8.2505-2514.2002;
Chase M.B., Fu S., Haga S.B., Davenport G., Stevenson H., Do K.,
Morgan D., Mah A.L., Berg P.E.;
"BP1, a homeodomain-containing isoform of DLX4, represses the beta-
globin gene.";
Mol. Cell. Biol. 22:2505-2514(2002).
[5]
NUCLEOTIDE SEQUENCE [GENOMIC DNA].
TISSUE=Foreskin;
PubMed=11792834; DOI=10.1073/pnas.012584999;
Sumiyama K., Irvine S.Q., Stock D.W., Weiss K.M., Kawasaki K.,
Shimizu N., Shashikant C.S., Miller W., Ruddle F.H.;
"Genomic structure and functional control of the Dlx3-7 bigene
cluster.";
Proc. Natl. Acad. Sci. U.S.A. 99:780-785(2002).
[6]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
Phelan M., Farmer A.;
"Cloning of human full-length CDSs in BD Creator(TM) system donor
vector.";
Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
[7]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
Venter J.C.;
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
[8]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
TISSUE=Placenta, and Uterus;
PubMed=15489334; DOI=10.1101/gr.2596504;
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA
project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[9]
NUCLEOTIDE SEQUENCE [MRNA] OF 1-177.
TISSUE=Placenta;
PubMed=9073066; DOI=10.1016/S0378-1119(96)00706-8;
Quinn L.M., Johnson B.V., Nicholl J., Sutherland G.R., Kalionis B.;
"Isolation and identification of homeobox genes from the human
placenta including a novel member of the Distal-less family, DLX4.";
Gene 187:55-61(1997).
[10]
INVOLVEMENT IN OFC15, FUNCTION, AND SUBCELLULAR LOCATION.
PubMed=25954033; DOI=10.1093/hmg/ddv167;
Wu D., Mandal S., Choi A., Anderson A., Prochazkova M., Perry H.,
Gil-Da-Silva-Lopes V.L., Lao R., Wan E., Tang P.L., Kwok P.Y.,
Klein O., Zhuan B., Slavotinek A.M.;
"DLX4 is associated with orofacial clefting and abnormal jaw
development.";
Hum. Mol. Genet. 24:4340-4352(2015).
-!- FUNCTION: May play a role in determining the production of
hemoglobin S. May act as a repressor. During embryonic
development, plays a role in palatogenesis.
{ECO:0000269|PubMed:11909945, ECO:0000269|PubMed:25954033}.
-!- INTERACTION:
P16333:NCK1; NbExp=3; IntAct=EBI-1752755, EBI-389883;
Q13485:SMAD4; NbExp=5; IntAct=EBI-1752755, EBI-347263;
P08047:SP1; NbExp=4; IntAct=EBI-1752755, EBI-298336;
-!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:25954033}.
-!- ALTERNATIVE PRODUCTS:
Event=Alternative splicing; Named isoforms=3;
Comment=Additional isoforms seem to exist. PubMed:9073066
(AAC51171) sequence may be an additional isoform.;
Name=1;
IsoId=Q92988-1; Sequence=Displayed;
Name=2;
IsoId=Q92988-2; Sequence=VSP_002236;
Note=Ref.1 (AAC50942) sequence is in conflict in position:
8:P->H. Ref.1 (AAC50942) sequence is in conflict in position:
15:Y->N. {ECO:0000305};
Name=3;
IsoId=Q92988-3; Sequence=VSP_002236, VSP_017043;
-!- TISSUE SPECIFICITY: Expressed in leukemia cells and placenta. Also
expressed in kidney and fetal liver. {ECO:0000269|PubMed:11069021,
ECO:0000269|PubMed:11909945}.
-!- DISEASE: Non-syndromic orofacial cleft 15 (OFC15) [MIM:616788]: A
birth defect consisting of cleft lips with or without cleft
palate. Cleft lips are associated with cleft palate in two-third
of cases. A cleft lip can occur on one or both sides and range in
severity from a simple notch in the upper lip to a complete
opening in the lip extending into the floor of the nostril and
involving the upper gum. OFC15 inheritance is autosomal dominant.
{ECO:0000269|PubMed:25954033}. Note=The disease is caused by
mutations affecting the gene represented in this entry.
-!- SIMILARITY: Belongs to the distal-less homeobox family.
{ECO:0000305}.
-!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
and Haematology;
URL="http://atlasgeneticsoncology.org/Genes/DLX4ID49827ch17q21.html";
-----------------------------------------------------------------------
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Distributed under the Creative Commons Attribution (CC BY 4.0) License
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EMBL; U73328; AAC50942.1; -; mRNA.
EMBL; AF028235; AAC14398.1; -; Genomic_DNA.
EMBL; AF254115; AAG31975.1; -; mRNA.
EMBL; AF452638; AAL99503.1; -; Genomic_DNA.
EMBL; BT006978; AAP35624.1; -; mRNA.
EMBL; CH471109; EAW94651.1; -; Genomic_DNA.
EMBL; CH471109; EAW94653.1; -; Genomic_DNA.
EMBL; CH471109; EAW94654.1; -; Genomic_DNA.
EMBL; CH471109; EAW94655.1; -; Genomic_DNA.
EMBL; BC005812; AAH05812.1; -; mRNA.
EMBL; BC014419; AAH14419.1; -; mRNA.
EMBL; BC016145; AAH16145.1; -; mRNA.
EMBL; U31762; AAC51171.1; -; mRNA.
CCDS; CCDS11555.1; -. [Q92988-1]
CCDS; CCDS45728.1; -. [Q92988-2]
PIR; G01958; G01958.
RefSeq; NP_001925.2; NM_001934.3. [Q92988-2]
RefSeq; NP_612138.1; NM_138281.2. [Q92988-1]
RefSeq; XP_016879780.1; XM_017024291.1. [Q92988-2]
UniGene; Hs.591167; -.
ProteinModelPortal; Q92988; -.
SMR; Q92988; -.
BioGrid; 108092; 4.
IntAct; Q92988; 14.
MINT; Q92988; -.
STRING; 9606.ENSP00000240306; -.
iPTMnet; Q92988; -.
PhosphoSitePlus; Q92988; -.
BioMuta; DLX4; -.
DMDM; 85700416; -.
PaxDb; Q92988; -.
PeptideAtlas; Q92988; -.
PRIDE; Q92988; -.
ProteomicsDB; 75647; -.
ProteomicsDB; 75648; -. [Q92988-2]
ProteomicsDB; 75649; -. [Q92988-3]
DNASU; 1748; -.
Ensembl; ENST00000240306; ENSP00000240306; ENSG00000108813. [Q92988-1]
Ensembl; ENST00000411890; ENSP00000410622; ENSG00000108813. [Q92988-2]
Ensembl; ENST00000611342; ENSP00000480366; ENSG00000108813. [Q92988-3]
GeneID; 1748; -.
KEGG; hsa:1748; -.
UCSC; uc002ipv.4; human. [Q92988-1]
CTD; 1748; -.
DisGeNET; 1748; -.
EuPathDB; HostDB:ENSG00000108813.10; -.
GeneCards; DLX4; -.
HGNC; HGNC:2917; DLX4.
HPA; HPA059933; -.
MalaCards; DLX4; -.
MIM; 601911; gene.
MIM; 616788; phenotype.
neXtProt; NX_Q92988; -.
OpenTargets; ENSG00000108813; -.
PharmGKB; PA27372; -.
eggNOG; KOG0850; Eukaryota.
eggNOG; ENOG410ZHZR; LUCA.
GeneTree; ENSGT00920000148979; -.
HOVERGEN; HBG005493; -.
InParanoid; Q92988; -.
KO; K09314; -.
OMA; YSGPYGH; -.
OrthoDB; EOG091G0L8C; -.
PhylomeDB; Q92988; -.
TreeFam; TF315720; -.
GeneWiki; DLX4; -.
GenomeRNAi; 1748; -.
PRO; PR:Q92988; -.
Proteomes; UP000005640; Chromosome 17.
Bgee; ENSG00000108813; Expressed in 100 organ(s), highest expression level in tendon.
CleanEx; HS_DLX4; -.
Genevisible; Q92988; HS.
GO; GO:0005634; C:nucleus; NAS:UniProtKB.
GO; GO:0003700; F:DNA-binding transcription factor activity; TAS:ProtInc.
GO; GO:0000978; F:RNA polymerase II proximal promoter sequence-specific DNA binding; IDA:NTNU_SB.
GO; GO:0000981; F:RNA polymerase II transcription factor activity, sequence-specific DNA binding; ISA:NTNU_SB.
GO; GO:0043565; F:sequence-specific DNA binding; IDA:MGI.
GO; GO:0001078; F:transcriptional repressor activity, RNA polymerase II proximal promoter sequence-specific DNA binding; IDA:NTNU_SB.
GO; GO:0007275; P:multicellular organism development; IEA:UniProtKB-KW.
GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:NTNU_SB.
GO; GO:0006355; P:regulation of transcription, DNA-templated; NAS:UniProtKB.
CDD; cd00086; homeodomain; 1.
InterPro; IPR009057; Homeobox-like_sf.
InterPro; IPR017970; Homeobox_CS.
InterPro; IPR001356; Homeobox_dom.
InterPro; IPR020479; Homeobox_metazoa.
InterPro; IPR000047; HTH_motif.
Pfam; PF00046; Homeobox; 1.
PRINTS; PR00024; HOMEOBOX.
PRINTS; PR00031; HTHREPRESSR.
SMART; SM00389; HOX; 1.
SUPFAM; SSF46689; SSF46689; 1.
PROSITE; PS00027; HOMEOBOX_1; 1.
PROSITE; PS50071; HOMEOBOX_2; 1.
1: Evidence at protein level;
Alternative splicing; Complete proteome; Developmental protein;
DNA-binding; Homeobox; Nucleus; Reference proteome.
CHAIN 1 240 Homeobox protein DLX-4.
/FTId=PRO_0000049028.
DNA_BIND 117 176 Homeobox. {ECO:0000255|PROSITE-
ProRule:PRU00108}.
VAR_SEQ 1 94 MTSLPCPLPGRDASKAVFPDLAPVPSVAAAYPLGLSPTTAA
SPNLSYSRPYGHLLSYPYTEPANPGDSYLSCQQPAALSQPL
CGPAEHPQELEA -> MKLSVLPPRSLLAPYTVLCCPP
(in isoform 2 and isoform 3).
{ECO:0000303|PubMed:15489334,
ECO:0000303|PubMed:8975708}.
/FTId=VSP_002236.
VAR_SEQ 162 240 KIWFQNKRSKYKKLLKQNSGGQEGDFPGRTFSVSPCSPPLP
SLWDLPKAGTLPTSGYGNSFGAWYQHHSSDVLASPQMM ->
GPVSSFPISHLPWFSGNSSPSPSCE (in isoform 3).
{ECO:0000303|PubMed:15489334}.
/FTId=VSP_017043.
CONFLICT 1 94 MTSLPCPLPGRDASKAVFPDLAPVPSVAAAYPLGLSPTTAA
SPNLSYSRPYGHLLSYPYTEPANPGDSYLSCQQPAALSQPL
CGPAEHPQELEA -> GGSLSLPPEPLCARCPTKEGAAPRR
PGFWGSLETQAATVWRGRHGHFSCRVRLSRGAARYSRRGQG
KPGVTISAARLVFKVLSAGPLTHPAGRSRRLPRGHRLKPLS
IALSLCLQCPSSVISRPRLSPGPSLSAPPYPKLAPPPVAEL
RPPTAGAAVPWLWPSARFLPRVTGPIRVGAPLGAELRLVSP
GAVNVGVETLHAE (in Ref. 9). {ECO:0000305}.
CONFLICT 113 113 P -> A (in Ref. 1; AAC50942).
{ECO:0000305}.
CONFLICT 203 203 S -> Y (in Ref. 1; AAC50942).
{ECO:0000305}.
CONFLICT 224 224 A -> P (in Ref. 1; AAC50942).
{ECO:0000305}.
CONFLICT 235 235 Missing (in Ref. 1; AAC50942).
{ECO:0000305}.
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


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