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Homeobox protein DLX-5

 DLX5_MOUSE              Reviewed;         289 AA.
P70396; O54876; O54877; O54878; Q9JJ45;
01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
01-FEB-1997, sequence version 1.
20-DEC-2017, entry version 150.
RecName: Full=Homeobox protein DLX-5;
Name=Dlx5;
Mus musculus (Mouse).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha;
Muroidea; Muridae; Murinae; Mus; Mus.
NCBI_TaxID=10090;
[1]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
STRAIN=Swiss Webster;
PubMed=8855272; DOI=10.1073/pnas.93.20.10858;
Stock D.W., Ellies D.L., Zhao Z., Ekker M., Ruddle F.H., Weiss K.M.;
"The evolution of the vertebrate Dlx gene family.";
Proc. Natl. Acad. Sci. U.S.A. 93:10858-10863(1996).
[2]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
PubMed=10075846; DOI=10.1006/dbio.1998.9197;
Miyama K., Yamada G., Yamamoto T.S., Takagi C., Miyado K., Sakai M.,
Ueno N., Shibuya H.;
"A BMP-inducible gene, dlx5, regulates osteoblast differentiation and
mesoderm induction.";
Dev. Biol. 208:123-133(1999).
[3]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 3).
PubMed=9415433;
DOI=10.1002/(SICI)1097-0177(199712)210:4<498::AID-AJA12>3.0.CO;2-3;
Liu J.K., Ghattas I., Liu S., Chen S., Rubenstein J.L.R.;
"Dlx genes encode DNA-binding proteins that are expressed in an
overlapping and sequential pattern during basal ganglia
differentiation.";
Dev. Dyn. 210:498-512(1997).
[4]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 3).
TISSUE=Embryonic head;
PubMed=9763476;
Yang L., Zhang H., Hu G., Wang H., Abate-Shen C., Shen M.M.;
"An early phase of embryonic Dlx5 expression defines the rostral
boundary of the neural plate.";
J. Neurosci. 18:8322-8330(1998).
[5]
FUNCTION, DNA-BINDING, AND INDUCTION.
PubMed=15383550; DOI=10.1074/jbc.M404145200;
Kim Y.J., Lee M.H., Wozney J.M., Cho J.Y., Ryoo H.M.;
"Bone morphogenetic protein-2-induced alkaline phosphatase expression
is stimulated by Dlx5 and repressed by Msx2.";
J. Biol. Chem. 279:50773-50780(2004).
[6]
FUNCTION, PHOSPHORYLATION AT SER-34 AND SER-217, MUTAGENESIS OF SER-34
AND SER-217, SUBCELLULAR LOCATION, AND INDUCTION.
PubMed=18056716; DOI=10.1074/jbc.M704724200;
Ulsamer A., Ortuno M.J., Ruiz S., Susperregui A.R., Osses N.,
Rosa J.L., Ventura F.;
"BMP-2 induces Osterix expression through up-regulation of Dlx5 and
its phosphorylation by p38.";
J. Biol. Chem. 283:3816-3826(2008).
[7]
PHOSPHORYLATION.
PubMed=19393622; DOI=10.1016/j.bbrc.2009.04.082;
Seo J.H., Jin Y.H., Jeong H.M., Kim Y.J., Jeong H.G., Yeo C.Y.,
Lee K.Y.;
"Calmodulin-dependent kinase II regulates Dlx5 during osteoblast
differentiation.";
Biochem. Biophys. Res. Commun. 384:100-104(2009).
[8]
FUNCTION, TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
PubMed=19956613; DOI=10.1371/journal.pone.0008097;
Zhu H., Bendall A.J.;
"Dlx5 Is a cell autonomous regulator of chondrocyte hypertrophy in
mice and functionally substitutes for Dlx6 during endochondral
ossification.";
PLoS ONE 4:E8097-E8097(2009).
-!- FUNCTION: Transcriptional factor involved in bone development.
Acts as an immediate early BMP-responsive transcriptional
activator essential for osteoblast differentiation. Stimulates
ALPL promoter activity in a RUNX2-independent manner during
osteoblast differentiation. Stimulates SP7 promoter activity
during osteoblast differentiation. Promotes cell proliferation by
up-regulating MYC promoter activity. Involved as a positive
regulator of both chondrogenesis and chondrocyte hypertrophy in
the endochondral skeleton. Binds to the homeodomain-response
element of the ALPL and SP7 promoter. Binds to the MYC promoter.
Requires the 5'-TAATTA-3' consensus sequence for DNA-binding.
{ECO:0000269|PubMed:15383550, ECO:0000269|PubMed:18056716,
ECO:0000269|PubMed:19956613}.
-!- SUBUNIT: Interacts with XRCC6 (Ku70). {ECO:0000250}.
-!- INTERACTION:
Q9QYH6:Maged1; NbExp=2; IntAct=EBI-1801294, EBI-1801274;
-!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-
ProRule:PRU00108, ECO:0000269|PubMed:18056716}.
-!- ALTERNATIVE PRODUCTS:
Event=Alternative splicing; Named isoforms=3;
Name=1; Synonyms=Alpha;
IsoId=P70396-1; Sequence=Displayed;
Name=2; Synonyms=Beta;
IsoId=P70396-2; Sequence=VSP_002239;
Name=3; Synonyms=Gamma;
IsoId=P70396-3; Sequence=VSP_002237, VSP_002238;
-!- TISSUE SPECIFICITY: Expressed in osteoblasts and chondrocytes.
{ECO:0000269|PubMed:19956613}.
-!- DEVELOPMENTAL STAGE: Expressed in the otic vesicle, mandibular
arch, branchial arches 2 and 3, in proximal anterior mesodermal
domain in the limb, immature and proliferating chondroblasts at
14.5 dpc. {ECO:0000269|PubMed:19956613}.
-!- INDUCTION: Up-regulated by BMP2. {ECO:0000269|PubMed:15383550,
ECO:0000269|PubMed:18056716}.
-!- PTM: Phosphorylated. Phosphorylation of Ser-34 and Ser-217 by
MAPK14 enhances its transcriptional activity. Phosphorylation by
CaMK2 increases its protein stability.
{ECO:0000269|PubMed:18056716, ECO:0000269|PubMed:19393622}.
-!- SIMILARITY: Belongs to the distal-less homeobox family.
{ECO:0000305}.
-----------------------------------------------------------------------
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EMBL; U67840; AAC52843.1; -; mRNA.
EMBL; AF033011; AAB86899.1; -; mRNA.
EMBL; AF022075; AAB94580.1; -; mRNA.
EMBL; AF022076; AAB94581.1; -; mRNA.
EMBL; AF022077; AAB94582.1; -; mRNA.
EMBL; AF072452; AAF86636.1; -; mRNA.
EMBL; AF072453; AAF86637.1; -; mRNA.
CCDS; CCDS19905.1; -. [P70396-1]
CCDS; CCDS59691.1; -. [P70396-3]
RefSeq; NP_034186.2; NM_010056.3. [P70396-1]
RefSeq; NP_942151.1; NM_198854.2. [P70396-3]
UniGene; Mm.4873; -.
ProteinModelPortal; P70396; -.
SMR; P70396; -.
BioGrid; 199238; 10.
IntAct; P70396; 1.
STRING; 10090.ENSMUSP00000052559; -.
iPTMnet; P70396; -.
PhosphoSitePlus; P70396; -.
PaxDb; P70396; -.
PRIDE; P70396; -.
DNASU; 13395; -.
Ensembl; ENSMUST00000052609; ENSMUSP00000052559; ENSMUSG00000029755. [P70396-1]
Ensembl; ENSMUST00000142635; ENSMUSP00000138264; ENSMUSG00000029755. [P70396-3]
GeneID; 13395; -.
KEGG; mmu:13395; -.
UCSC; uc009awy.2; mouse. [P70396-3]
UCSC; uc009awz.2; mouse. [P70396-1]
CTD; 1749; -.
MGI; MGI:101926; Dlx5.
eggNOG; KOG0850; Eukaryota.
eggNOG; ENOG410ZHZR; LUCA.
GeneTree; ENSGT00900000140771; -.
HOGENOM; HOG000231940; -.
HOVERGEN; HBG005493; -.
InParanoid; P70396; -.
KO; K18489; -.
OMA; NSASWYP; -.
OrthoDB; EOG091G0P17; -.
PhylomeDB; P70396; -.
TreeFam; TF350606; -.
PRO; PR:P70396; -.
Proteomes; UP000000589; Chromosome 6.
Bgee; ENSMUSG00000029755; -.
CleanEx; MM_DLX5; -.
ExpressionAtlas; P70396; baseline and differential.
Genevisible; P70396; MM.
GO; GO:0005737; C:cytoplasm; IDA:MGI.
GO; GO:0000790; C:nuclear chromatin; IDA:BHF-UCL.
GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
GO; GO:0005634; C:nucleus; IDA:MGI.
GO; GO:0003677; F:DNA binding; IDA:MGI.
GO; GO:0071837; F:HMG box domain binding; IPI:UniProtKB.
GO; GO:0000978; F:RNA polymerase II core promoter proximal region sequence-specific DNA binding; IDA:BHF-UCL.
GO; GO:0044212; F:transcription regulatory region DNA binding; IDA:UniProtKB.
GO; GO:0001077; F:transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding; IDA:BHF-UCL.
GO; GO:0048646; P:anatomical structure formation involved in morphogenesis; IGI:MGI.
GO; GO:0007411; P:axon guidance; IMP:MGI.
GO; GO:0007409; P:axonogenesis; IMP:MGI.
GO; GO:0030509; P:BMP signaling pathway; IMP:BHF-UCL.
GO; GO:0060349; P:bone morphogenesis; IMP:MGI.
GO; GO:0008283; P:cell proliferation; ISS:UniProtKB.
GO; GO:0071773; P:cellular response to BMP stimulus; IMP:BHF-UCL.
GO; GO:0043583; P:ear development; IMP:MGI.
GO; GO:0030326; P:embryonic limb morphogenesis; IGI:MGI.
GO; GO:0001958; P:endochondral ossification; IMP:UniProtKB.
GO; GO:0030855; P:epithelial cell differentiation; IGI:MGI.
GO; GO:0060325; P:face morphogenesis; IMP:MGI.
GO; GO:0060322; P:head development; IGI:MGI.
GO; GO:0042472; P:inner ear morphogenesis; IMP:MGI.
GO; GO:0097376; P:interneuron axon guidance; IMP:MGI.
GO; GO:0021889; P:olfactory bulb interneuron differentiation; IMP:MGI.
GO; GO:0060166; P:olfactory pit development; IMP:MGI.
GO; GO:0001649; P:osteoblast differentiation; IDA:UniProtKB.
GO; GO:0060021; P:palate development; IMP:MGI.
GO; GO:0090263; P:positive regulation of canonical Wnt signaling pathway; IMP:MGI.
GO; GO:0050679; P:positive regulation of epithelial cell proliferation; IGI:MGI.
GO; GO:0010628; P:positive regulation of gene expression; IMP:MGI.
GO; GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IGI:MGI.
GO; GO:1901522; P:positive regulation of transcription from RNA polymerase II promoter involved in cellular response to chemical stimulus; IMP:BHF-UCL.
GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:UniProtKB.
GO; GO:0006355; P:regulation of transcription, DNA-templated; IMP:MGI.
CDD; cd00086; homeodomain; 1.
InterPro; IPR022135; Distal-less_N.
InterPro; IPR009057; Homeobox-like_sf.
InterPro; IPR017970; Homeobox_CS.
InterPro; IPR001356; Homeobox_dom.
InterPro; IPR020479; Homeobox_metazoa.
InterPro; IPR000047; HTH_motif.
Pfam; PF12413; DLL_N; 1.
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;
Activator; Alternative splicing; Complete proteome;
Developmental protein; DNA-binding; Homeobox; Nucleus; Osteogenesis;
Phosphoprotein; Reference proteome; Transcription;
Transcription regulation.
CHAIN 1 289 Homeobox protein DLX-5.
/FTId=PRO_0000049032.
DNA_BIND 137 196 Homeobox. {ECO:0000255|PROSITE-
ProRule:PRU00108}.
MOD_RES 34 34 Phosphoserine; by MAPK14; in vitro.
{ECO:0000269|PubMed:18056716}.
MOD_RES 217 217 Phosphoserine; by MAPK14; in vitro.
{ECO:0000269|PubMed:18056716}.
VAR_SEQ 119 146 EKEVAEPEVRMVNGKPKKVRKPRTIYSS -> AFSWPLYRE
GFRRLSTSPCQNARSWPPL (in isoform 3).
{ECO:0000303|PubMed:9415433,
ECO:0000303|PubMed:9763476}.
/FTId=VSP_002237.
VAR_SEQ 147 289 Missing (in isoform 3).
{ECO:0000303|PubMed:9415433,
ECO:0000303|PubMed:9763476}.
/FTId=VSP_002238.
VAR_SEQ 147 251 Missing (in isoform 2).
{ECO:0000303|PubMed:9415433}.
/FTId=VSP_002239.
MUTAGEN 34 34 S->A: Inhibits its transcriptional
activity; when associated with A-217.
{ECO:0000269|PubMed:18056716}.
MUTAGEN 217 217 S->A: Inhibits its transcriptional
activity; when associated with A-34.
{ECO:0000269|PubMed:18056716}.
CONFLICT 98 99 AS -> H (in Ref. 3; AAB94580/AAB94581).
{ECO:0000305}.
SEQUENCE 289 AA; 31396 MW; C53555610E9F8777 CRC64;
MTGVFDRRVP SIRSGDFQAP FPTSAAMHHP SQESPTLPES SATDSDYYSP AGAAPHGYCS
PTSASYGKAL NPYQYQYHGV NGSAAGYPAK AYADYGYASP YHQYGGAYNR VPSATSQPEK
EVAEPEVRMV NGKPKKVRKP RTIYSSFQLA ALQRRFQKTQ YLALPERAEL AASLGLTQTQ
VKIWFQNKRS KIKKIMKNGE MPPEHSPSSS DPMACNSPQS PAVWEPQGSS RSLSHHPHAH
PPTSNQSPAS SYLENSASWY PSAASSINSH LPPPGSLQHP LALASGTLY


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