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P70396

- DLX5_MOUSE

UniProt

P70396 - DLX5_MOUSE

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Protein

Homeobox protein DLX-5

Gene

Dlx5

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

Functioni

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.3 Publications

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
DNA bindingi137 – 19660HomeoboxPROSITE-ProRule annotationAdd
BLAST

GO - Molecular functioni

  1. DNA binding Source: MGI
  2. HMG box domain binding Source: UniProtKB
  3. RNA polymerase II core promoter proximal region sequence-specific DNA binding Source: BHF-UCL
  4. RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription Source: BHF-UCL
  5. transcription regulatory region DNA binding Source: UniProtKB

GO - Biological processi

  1. anatomical structure formation involved in morphogenesis Source: MGI
  2. axon guidance Source: MGI
  3. axonogenesis Source: MGI
  4. BMP signaling pathway Source: BHF-UCL
  5. bone morphogenesis Source: MGI
  6. cell proliferation Source: UniProtKB
  7. cellular response to BMP stimulus Source: BHF-UCL
  8. ear development Source: MGI
  9. embryonic limb morphogenesis Source: MGI
  10. endochondral ossification Source: UniProtKB
  11. epithelial cell differentiation Source: MGI
  12. face morphogenesis Source: MGI
  13. head development Source: MGI
  14. inner ear morphogenesis Source: MGI
  15. olfactory pit development Source: MGI
  16. osteoblast differentiation Source: UniProtKB
  17. palate development Source: MGI
  18. positive regulation of canonical Wnt signaling pathway Source: MGI
  19. positive regulation of epithelial cell proliferation Source: MGI
  20. positive regulation of osteoblast differentiation Source: Ensembl
  21. positive regulation of transcription, DNA-templated Source: UniProtKB
  22. positive regulation of transcription from RNA polymerase II promoter Source: MGI
  23. positive regulation of transcription from RNA polymerase II promoter involved in cellular response to chemical stimulus Source: BHF-UCL
  24. regulation of transcription, DNA-templated Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Activator, Developmental protein

Keywords - Biological processi

Osteogenesis, Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Homeobox protein DLX-5
Gene namesi
Name:Dlx5
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 6

Organism-specific databases

MGIiMGI:101926. Dlx5.

Subcellular locationi

Nucleus 1 PublicationPROSITE-ProRule annotation

GO - Cellular componenti

  1. cytoplasm Source: MGI
  2. nuclear chromatin Source: BHF-UCL
  3. nucleus Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi34 – 341S → A: Inhibits its transcriptional activity; when associated with A-217. 1 Publication
Mutagenesisi217 – 2171S → A: Inhibits its transcriptional activity; when associated with A-34. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 289289Homeobox protein DLX-5PRO_0000049032Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei34 – 341Phosphoserine; by MAPK14; in vitro1 Publication
Modified residuei217 – 2171Phosphoserine; by MAPK14; in vitro1 Publication

Post-translational modificationi

Phosphorylated. Phosphorylation of Ser-34 and Ser-217 by MAPK14 enhances its transcriptional activity. Phosphorylation by CaMK2 increases its protein stability.2 Publications

Keywords - PTMi

Phosphoprotein

Proteomic databases

PRIDEiP70396.

PTM databases

PhosphoSiteiP70396.

Expressioni

Tissue specificityi

Expressed in osteoblasts and chondrocytes.1 Publication

Developmental stagei

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.1 Publication

Inductioni

Up-regulated by BMP2.2 Publications

Gene expression databases

BgeeiP70396.
CleanExiMM_DLX5.
ExpressionAtlasiP70396. baseline and differential.
GenevestigatoriP70396.

Interactioni

Subunit structurei

Interacts with XRCC6 (Ku70).By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
Maged1Q9QYH62EBI-1801294,EBI-1801274

Protein-protein interaction databases

BioGridi199238. 11 interactions.
IntActiP70396. 1 interaction.

Structurei

3D structure databases

ProteinModelPortaliP70396.
SMRiP70396. Positions 138-194.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the distal-less homeobox family.Curated
Contains 1 homeobox DNA-binding domain.PROSITE-ProRule annotation

Keywords - Domaini

Homeobox

Phylogenomic databases

eggNOGiNOG263092.
GeneTreeiENSGT00770000120486.
HOGENOMiHOG000231940.
HOVERGENiHBG005493.
InParanoidiP70396.
KOiK18489.
OMAiQSPAVWD.
OrthoDBiEOG70W3F8.
PhylomeDBiP70396.
TreeFamiTF350606.

Family and domain databases

Gene3Di1.10.10.60. 1 hit.
InterProiIPR022135. Distal-less_N.
IPR017970. Homeobox_CS.
IPR001356. Homeobox_dom.
IPR020479. Homeobox_metazoa.
IPR009057. Homeodomain-like.
IPR000047. HTH_motif.
[Graphical view]
PfamiPF12413. DLL_N. 1 hit.
PF00046. Homeobox. 1 hit.
[Graphical view]
PRINTSiPR00024. HOMEOBOX.
PR00031. HTHREPRESSR.
SMARTiSM00389. HOX. 1 hit.
[Graphical view]
SUPFAMiSSF46689. SSF46689. 1 hit.
PROSITEiPS00027. HOMEOBOX_1. 1 hit.
PS50071. HOMEOBOX_2. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. Align

Isoform 1 (identifier: P70396-1) [UniParc]FASTAAdd to Basket

Also known as: Alpha

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MTGVFDRRVP SIRSGDFQAP FPTSAAMHHP SQESPTLPES SATDSDYYSP
60 70 80 90 100
AGAAPHGYCS PTSASYGKAL NPYQYQYHGV NGSAAGYPAK AYADYGYASP
110 120 130 140 150
YHQYGGAYNR VPSATSQPEK EVAEPEVRMV NGKPKKVRKP RTIYSSFQLA
160 170 180 190 200
ALQRRFQKTQ YLALPERAEL AASLGLTQTQ VKIWFQNKRS KIKKIMKNGE
210 220 230 240 250
MPPEHSPSSS DPMACNSPQS PAVWEPQGSS RSLSHHPHAH PPTSNQSPAS
260 270 280
SYLENSASWY PSAASSINSH LPPPGSLQHP LALASGTLY
Length:289
Mass (Da):31,396
Last modified:February 1, 1997 - v1
Checksum:iC53555610E9F8777
GO
Isoform 2 (identifier: P70396-2) [UniParc]FASTAAdd to Basket

Also known as: Beta

The sequence of this isoform differs from the canonical sequence as follows:
     147-251: Missing.

Show »
Length:184
Mass (Da):19,772
Checksum:iC96A32599A6AD931
GO
Isoform 3 (identifier: P70396-3) [UniParc]FASTAAdd to Basket

Also known as: Gamma

The sequence of this isoform differs from the canonical sequence as follows:
     119-146: EKEVAEPEVRMVNGKPKKVRKPRTIYSS → AFSWPLYREGFRRLSTSPCQNARSWPPL
     147-289: Missing.

Show »
Length:146
Mass (Da):15,858
Checksum:i55BAEA4F6C3251B6
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti98 – 992AS → H in AAB94580. (PubMed:9415433)Curated
Sequence conflicti98 – 992AS → H in AAB94581. (PubMed:9415433)Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei119 – 14628EKEVA…TIYSS → AFSWPLYREGFRRLSTSPCQ NARSWPPL in isoform 3. 2 PublicationsVSP_002237Add
BLAST
Alternative sequencei147 – 289143Missing in isoform 3. 2 PublicationsVSP_002238Add
BLAST
Alternative sequencei147 – 251105Missing in isoform 2. 1 PublicationVSP_002239Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U67840 mRNA. Translation: AAC52843.1.
AF033011 mRNA. Translation: AAB86899.1.
AF022075 mRNA. Translation: AAB94580.1.
AF022076 mRNA. Translation: AAB94581.1.
AF022077 mRNA. Translation: AAB94582.1.
AF072452 mRNA. Translation: AAF86636.1.
AF072453 mRNA. Translation: AAF86637.1.
CCDSiCCDS19905.1. [P70396-1]
CCDS59691.1. [P70396-3]
RefSeqiNP_034186.2. NM_010056.3. [P70396-1]
NP_942151.1. NM_198854.2. [P70396-3]
UniGeneiMm.4873.

Genome annotation databases

EnsembliENSMUST00000052609; ENSMUSP00000052559; ENSMUSG00000029755. [P70396-1]
ENSMUST00000142635; ENSMUSP00000138264; ENSMUSG00000029755. [P70396-3]
GeneIDi13395.
KEGGimmu:13395.
UCSCiuc009awy.1. mouse. [P70396-3]
uc009awz.1. mouse. [P70396-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U67840 mRNA. Translation: AAC52843.1 .
AF033011 mRNA. Translation: AAB86899.1 .
AF022075 mRNA. Translation: AAB94580.1 .
AF022076 mRNA. Translation: AAB94581.1 .
AF022077 mRNA. Translation: AAB94582.1 .
AF072452 mRNA. Translation: AAF86636.1 .
AF072453 mRNA. Translation: AAF86637.1 .
CCDSi CCDS19905.1. [P70396-1 ]
CCDS59691.1. [P70396-3 ]
RefSeqi NP_034186.2. NM_010056.3. [P70396-1 ]
NP_942151.1. NM_198854.2. [P70396-3 ]
UniGenei Mm.4873.

3D structure databases

ProteinModelPortali P70396.
SMRi P70396. Positions 138-194.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 199238. 11 interactions.
IntActi P70396. 1 interaction.

PTM databases

PhosphoSitei P70396.

Proteomic databases

PRIDEi P70396.

Protocols and materials databases

DNASUi 13395.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000052609 ; ENSMUSP00000052559 ; ENSMUSG00000029755 . [P70396-1 ]
ENSMUST00000142635 ; ENSMUSP00000138264 ; ENSMUSG00000029755 . [P70396-3 ]
GeneIDi 13395.
KEGGi mmu:13395.
UCSCi uc009awy.1. mouse. [P70396-3 ]
uc009awz.1. mouse. [P70396-1 ]

Organism-specific databases

CTDi 1749.
MGIi MGI:101926. Dlx5.

Phylogenomic databases

eggNOGi NOG263092.
GeneTreei ENSGT00770000120486.
HOGENOMi HOG000231940.
HOVERGENi HBG005493.
InParanoidi P70396.
KOi K18489.
OMAi QSPAVWD.
OrthoDBi EOG70W3F8.
PhylomeDBi P70396.
TreeFami TF350606.

Miscellaneous databases

NextBioi 283772.
PROi P70396.
SOURCEi Search...

Gene expression databases

Bgeei P70396.
CleanExi MM_DLX5.
ExpressionAtlasi P70396. baseline and differential.
Genevestigatori P70396.

Family and domain databases

Gene3Di 1.10.10.60. 1 hit.
InterProi IPR022135. Distal-less_N.
IPR017970. Homeobox_CS.
IPR001356. Homeobox_dom.
IPR020479. Homeobox_metazoa.
IPR009057. Homeodomain-like.
IPR000047. HTH_motif.
[Graphical view ]
Pfami PF12413. DLL_N. 1 hit.
PF00046. Homeobox. 1 hit.
[Graphical view ]
PRINTSi PR00024. HOMEOBOX.
PR00031. HTHREPRESSR.
SMARTi SM00389. HOX. 1 hit.
[Graphical view ]
SUPFAMi SSF46689. SSF46689. 1 hit.
PROSITEi PS00027. HOMEOBOX_1. 1 hit.
PS50071. HOMEOBOX_2. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

  1. Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    Strain: Swiss Webster.
  2. "A BMP-inducible gene, dlx5, regulates osteoblast differentiation and mesoderm induction."
    Miyama K., Yamada G., Yamamoto T.S., Takagi C., Miyado K., Sakai M., Ueno N., Shibuya H.
    Dev. Biol. 208:123-133(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
  3. "Dlx genes encode DNA-binding proteins that are expressed in an overlapping and sequential pattern during basal ganglia differentiation."
    Liu J.K., Ghattas I., Liu S., Chen S., Rubenstein J.L.R.
    Dev. Dyn. 210:498-512(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 3).
  4. "An early phase of embryonic Dlx5 expression defines the rostral boundary of the neural plate."
    Yang L., Zhang H., Hu G., Wang H., Abate-Shen C., Shen M.M.
    J. Neurosci. 18:8322-8330(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 3).
    Tissue: Embryonic head.
  5. "Bone morphogenetic protein-2-induced alkaline phosphatase expression is stimulated by Dlx5 and repressed by Msx2."
    Kim Y.J., Lee M.H., Wozney J.M., Cho J.Y., Ryoo H.M.
    J. Biol. Chem. 279:50773-50780(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, DNA-BINDING, INDUCTION.
  6. "BMP-2 induces Osterix expression through up-regulation of Dlx5 and its phosphorylation by p38."
    Ulsamer A., Ortuno M.J., Ruiz S., Susperregui A.R., Osses N., Rosa J.L., Ventura F.
    J. Biol. Chem. 283:3816-3826(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, PHOSPHORYLATION AT SER-34 AND SER-217, MUTAGENESIS OF SER-34 AND SER-217, SUBCELLULAR LOCATION, INDUCTION.
  7. "Calmodulin-dependent kinase II regulates Dlx5 during osteoblast differentiation."
    Seo J.H., Jin Y.H., Jeong H.M., Kim Y.J., Jeong H.G., Yeo C.Y., Lee K.Y.
    Biochem. Biophys. Res. Commun. 384:100-104(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION.
  8. "Dlx5 Is a cell autonomous regulator of chondrocyte hypertrophy in mice and functionally substitutes for Dlx6 during endochondral ossification."
    Zhu H., Bendall A.J.
    PLoS ONE 4:E8097-E8097(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE.

Entry informationi

Entry nameiDLX5_MOUSE
AccessioniPrimary (citable) accession number: P70396
Secondary accession number(s): O54876
, O54877, O54878, Q9JJ45
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: February 1, 1997
Last modified: November 26, 2014
This is version 123 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3