DLX5_MOUSE
ID DLX5_MOUSE Reviewed; 289 AA.
AC P70396; O54876; O54877; O54878; Q9JJ45;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1997, sequence version 1.
DT 03-AUG-2022, entry version 176.
DE RecName: Full=Homeobox protein DLX-5;
GN Name=Dlx5;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC STRAIN=Swiss Webster;
RX PubMed=8855272; DOI=10.1073/pnas.93.20.10858;
RA Stock D.W., Ellies D.L., Zhao Z., Ekker M., Ruddle F.H., Weiss K.M.;
RT "The evolution of the vertebrate Dlx gene family.";
RL Proc. Natl. Acad. Sci. U.S.A. 93:10858-10863(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=10075846; DOI=10.1006/dbio.1998.9197;
RA Miyama K., Yamada G., Yamamoto T.S., Takagi C., Miyado K., Sakai M.,
RA Ueno N., Shibuya H.;
RT "A BMP-inducible gene, dlx5, regulates osteoblast differentiation and
RT mesoderm induction.";
RL Dev. Biol. 208:123-133(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 3).
RX PubMed=9415433;
RX DOI=10.1002/(sici)1097-0177(199712)210:4<498::aid-aja12>3.0.co;2-3;
RA Liu J.K., Ghattas I., Liu S., Chen S., Rubenstein J.L.R.;
RT "Dlx genes encode DNA-binding proteins that are expressed in an overlapping
RT and sequential pattern during basal ganglia differentiation.";
RL Dev. Dyn. 210:498-512(1997).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 3).
RC TISSUE=Embryonic head;
RX PubMed=9763476; DOI=10.1523/jneurosci.18-20-08322.1998;
RA Yang L., Zhang H., Hu G., Wang H., Abate-Shen C., Shen M.M.;
RT "An early phase of embryonic Dlx5 expression defines the rostral boundary
RT of the neural plate.";
RL J. Neurosci. 18:8322-8330(1998).
RN [5]
RP FUNCTION, DNA-BINDING, AND INDUCTION.
RX PubMed=15383550; DOI=10.1074/jbc.m404145200;
RA Kim Y.J., Lee M.H., Wozney J.M., Cho J.Y., Ryoo H.M.;
RT "Bone morphogenetic protein-2-induced alkaline phosphatase expression is
RT stimulated by Dlx5 and repressed by Msx2.";
RL J. Biol. Chem. 279:50773-50780(2004).
RN [6]
RP FUNCTION, PHOSPHORYLATION AT SER-34 AND SER-217, MUTAGENESIS OF SER-34 AND
RP SER-217, SUBCELLULAR LOCATION, AND INDUCTION.
RX PubMed=18056716; DOI=10.1074/jbc.m704724200;
RA Ulsamer A., Ortuno M.J., Ruiz S., Susperregui A.R., Osses N., Rosa J.L.,
RA Ventura F.;
RT "BMP-2 induces Osterix expression through up-regulation of Dlx5 and its
RT phosphorylation by p38.";
RL J. Biol. Chem. 283:3816-3826(2008).
RN [7]
RP PHOSPHORYLATION.
RX PubMed=19393622; DOI=10.1016/j.bbrc.2009.04.082;
RA Seo J.H., Jin Y.H., Jeong H.M., Kim Y.J., Jeong H.G., Yeo C.Y., Lee K.Y.;
RT "Calmodulin-dependent kinase II regulates Dlx5 during osteoblast
RT differentiation.";
RL Biochem. Biophys. Res. Commun. 384:100-104(2009).
RN [8]
RP FUNCTION, TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=19956613; DOI=10.1371/journal.pone.0008097;
RA Zhu H., Bendall A.J.;
RT "Dlx5 Is a cell autonomous regulator of chondrocyte hypertrophy in mice and
RT functionally substitutes for Dlx6 during endochondral ossification.";
RL PLoS ONE 4:E8097-E8097(2009).
CC -!- FUNCTION: Transcriptional factor involved in bone development. Acts as
CC an immediate early BMP-responsive transcriptional activator essential
CC for osteoblast differentiation. Stimulates ALPL promoter activity in a
CC RUNX2-independent manner during osteoblast differentiation. Stimulates
CC SP7 promoter activity during osteoblast differentiation. Promotes cell
CC proliferation by up-regulating MYC promoter activity. Involved as a
CC positive regulator of both chondrogenesis and chondrocyte hypertrophy
CC in the endochondral skeleton. Binds to the homeodomain-response element
CC of the ALPL and SP7 promoter. Binds to the MYC promoter. Requires the
CC 5'-TAATTA-3' consensus sequence for DNA-binding.
CC {ECO:0000269|PubMed:15383550, ECO:0000269|PubMed:18056716,
CC ECO:0000269|PubMed:19956613}.
CC -!- SUBUNIT: Interacts with XRCC6 (Ku70). {ECO:0000250}.
CC -!- INTERACTION:
CC P70396; Q9QYH6: Maged1; NbExp=2; IntAct=EBI-1801294, EBI-1801274;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00108,
CC ECO:0000269|PubMed:18056716}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1; Synonyms=Alpha;
CC IsoId=P70396-1; Sequence=Displayed;
CC Name=2; Synonyms=Beta;
CC IsoId=P70396-2; Sequence=VSP_002239;
CC Name=3; Synonyms=Gamma;
CC IsoId=P70396-3; Sequence=VSP_002237, VSP_002238;
CC -!- TISSUE SPECIFICITY: Expressed in osteoblasts and chondrocytes.
CC {ECO:0000269|PubMed:19956613}.
CC -!- DEVELOPMENTAL STAGE: Expressed in the otic vesicle, mandibular arch,
CC branchial arches 2 and 3, in proximal anterior mesodermal domain in the
CC limb, immature and proliferating chondroblasts at 14.5 dpc.
CC {ECO:0000269|PubMed:19956613}.
CC -!- INDUCTION: Up-regulated by BMP2. {ECO:0000269|PubMed:15383550,
CC ECO:0000269|PubMed:18056716}.
CC -!- PTM: Phosphorylated. Phosphorylation of Ser-34 and Ser-217 by MAPK14
CC enhances its transcriptional activity. Phosphorylation by CaMK2
CC increases its protein stability. {ECO:0000269|PubMed:18056716,
CC ECO:0000269|PubMed:19393622}.
CC -!- SIMILARITY: Belongs to the distal-less homeobox family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; U67840; AAC52843.1; -; mRNA.
DR EMBL; AF033011; AAB86899.1; -; mRNA.
DR EMBL; AF022075; AAB94580.1; -; mRNA.
DR EMBL; AF022076; AAB94581.1; -; mRNA.
DR EMBL; AF022077; AAB94582.1; -; mRNA.
DR EMBL; AF072452; AAF86636.1; -; mRNA.
DR EMBL; AF072453; AAF86637.1; -; mRNA.
DR CCDS; CCDS19905.1; -. [P70396-1]
DR CCDS; CCDS59691.1; -. [P70396-3]
DR RefSeq; NP_034186.2; NM_010056.3. [P70396-1]
DR RefSeq; NP_942151.1; NM_198854.2. [P70396-3]
DR AlphaFoldDB; P70396; -.
DR BMRB; P70396; -.
DR SMR; P70396; -.
DR BioGRID; 199238; 10.
DR IntAct; P70396; 8.
DR STRING; 10090.ENSMUSP00000052559; -.
DR iPTMnet; P70396; -.
DR PhosphoSitePlus; P70396; -.
DR PaxDb; P70396; -.
DR PRIDE; P70396; -.
DR ProteomicsDB; 279543; -. [P70396-1]
DR ProteomicsDB; 279544; -. [P70396-2]
DR ProteomicsDB; 279545; -. [P70396-3]
DR Antibodypedia; 1428; 520 antibodies from 40 providers.
DR DNASU; 13395; -.
DR Ensembl; ENSMUST00000052609; ENSMUSP00000052559; ENSMUSG00000029755. [P70396-1]
DR Ensembl; ENSMUST00000142635; ENSMUSP00000138264; ENSMUSG00000029755. [P70396-3]
DR GeneID; 13395; -.
DR KEGG; mmu:13395; -.
DR UCSC; uc009awy.2; mouse. [P70396-3]
DR UCSC; uc009awz.2; mouse. [P70396-1]
DR CTD; 1749; -.
DR MGI; MGI:101926; Dlx5.
DR VEuPathDB; HostDB:ENSMUSG00000029755; -.
DR eggNOG; KOG0850; Eukaryota.
DR GeneTree; ENSGT00940000159188; -.
DR HOGENOM; CLU_2090288_0_0_1; -.
DR InParanoid; P70396; -.
DR OMA; THGYCSP; -.
DR PhylomeDB; P70396; -.
DR TreeFam; TF350606; -.
DR BioGRID-ORCS; 13395; 2 hits in 75 CRISPR screens.
DR PRO; PR:P70396; -.
DR Proteomes; UP000000589; Chromosome 6.
DR RNAct; P70396; protein.
DR Bgee; ENSMUSG00000029755; Expressed in neural plate and 177 other tissues.
DR ExpressionAtlas; P70396; baseline and differential.
DR Genevisible; P70396; MM.
DR GO; GO:0000785; C:chromatin; IDA:BHF-UCL.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0003677; F:DNA binding; IDA:MGI.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IDA:BHF-UCL.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central.
DR GO; GO:0071837; F:HMG box domain binding; IPI:UniProtKB.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:BHF-UCL.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; ISO:MGI.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; IDA:UniProtKB.
DR GO; GO:0048646; P:anatomical structure formation involved in morphogenesis; IGI:MGI.
DR GO; GO:0007411; P:axon guidance; IMP:MGI.
DR GO; GO:0007409; P:axonogenesis; IMP:MGI.
DR GO; GO:0030509; P:BMP signaling pathway; IMP:BHF-UCL.
DR GO; GO:0060349; P:bone morphogenesis; IMP:MGI.
DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR GO; GO:0008283; P:cell population proliferation; ISS:UniProtKB.
DR GO; GO:0071773; P:cellular response to BMP stimulus; IMP:BHF-UCL.
DR GO; GO:0043583; P:ear development; IMP:MGI.
DR GO; GO:0030326; P:embryonic limb morphogenesis; IGI:MGI.
DR GO; GO:0001958; P:endochondral ossification; IMP:UniProtKB.
DR GO; GO:0030855; P:epithelial cell differentiation; IGI:MGI.
DR GO; GO:0060325; P:face morphogenesis; IMP:MGI.
DR GO; GO:0060322; P:head development; IGI:MGI.
DR GO; GO:0042472; P:inner ear morphogenesis; IMP:MGI.
DR GO; GO:0097376; P:interneuron axon guidance; IMP:MGI.
DR GO; GO:0021889; P:olfactory bulb interneuron differentiation; IMP:MGI.
DR GO; GO:0060166; P:olfactory pit development; IMP:MGI.
DR GO; GO:0001649; P:osteoblast differentiation; IDA:UniProtKB.
DR GO; GO:0090263; P:positive regulation of canonical Wnt signaling pathway; IMP:MGI.
DR GO; GO:0050679; P:positive regulation of epithelial cell proliferation; IGI:MGI.
DR GO; GO:0010628; P:positive regulation of gene expression; IMP:MGI.
DR GO; GO:0045669; P:positive regulation of osteoblast differentiation; ISO:MGI.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IGI:MGI.
DR GO; GO:1901522; P:positive regulation of transcription from RNA polymerase II promoter involved in cellular response to chemical stimulus; IMP:BHF-UCL.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:UniProtKB.
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; IMP:MGI.
DR GO; GO:0060021; P:roof of mouth development; IMP:MGI.
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 Activator; Alternative splicing; Developmental protein; DNA-binding;
KW Homeobox; Nucleus; Osteogenesis; Phosphoprotein; Reference proteome;
KW Transcription; Transcription regulation.
FT CHAIN 1..289
FT /note="Homeobox protein DLX-5"
FT /id="PRO_0000049032"
FT DNA_BIND 137..196
FT /note="Homeobox"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00108"
FT REGION 1..49
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 198..253
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 270..289
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 25..47
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 203..253
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 34
FT /note="Phosphoserine; by MAPK14; in vitro"
FT /evidence="ECO:0000269|PubMed:18056716"
FT MOD_RES 217
FT /note="Phosphoserine; by MAPK14; in vitro"
FT /evidence="ECO:0000269|PubMed:18056716"
FT VAR_SEQ 119..146
FT /note="EKEVAEPEVRMVNGKPKKVRKPRTIYSS -> AFSWPLYREGFRRLSTSPCQ
FT NARSWPPL (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:9415433,
FT ECO:0000303|PubMed:9763476"
FT /id="VSP_002237"
FT VAR_SEQ 147..289
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:9415433,
FT ECO:0000303|PubMed:9763476"
FT /id="VSP_002238"
FT VAR_SEQ 147..251
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:9415433"
FT /id="VSP_002239"
FT MUTAGEN 34
FT /note="S->A: Inhibits its transcriptional activity; when
FT associated with A-217."
FT /evidence="ECO:0000269|PubMed:18056716"
FT MUTAGEN 217
FT /note="S->A: Inhibits its transcriptional activity; when
FT associated with A-34."
FT /evidence="ECO:0000269|PubMed:18056716"
FT CONFLICT 98..99
FT /note="AS -> H (in Ref. 3; AAB94580/AAB94581)"
FT /evidence="ECO:0000305"
SQ 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
