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P70396

- DLX5_MOUSE

UniProt

P70396 - DLX5_MOUSE

Protein

Homeobox protein DLX-5

Gene

Dlx5

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 121 (01 Oct 2014)
      Sequence version 1 (01 Feb 1997)
      Previous versions | rss
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    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. protein binding Source: IntAct
    4. RNA polymerase II core promoter proximal region sequence-specific DNA binding Source: BHF-UCL
    5. RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription Source: BHF-UCL
    6. 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

    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

    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 vitro2 Publications
    Modified residuei217 – 2171Phosphoserine; by MAPK14; in vitro2 Publications

    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

    ArrayExpressiP70396.
    BgeeiP70396.
    CleanExiMM_DLX5.
    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.
    GeneTreeiENSGT00720000108450.
    HOGENOMiHOG000231940.
    HOVERGENiHBG005493.
    InParanoidiP70396.
    KOiK09315.
    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

    MTGVFDRRVP SIRSGDFQAP FPTSAAMHHP SQESPTLPES SATDSDYYSP    50
    AGAAPHGYCS PTSASYGKAL NPYQYQYHGV NGSAAGYPAK AYADYGYASP 100
    YHQYGGAYNR VPSATSQPEK EVAEPEVRMV NGKPKKVRKP RTIYSSFQLA 150
    ALQRRFQKTQ YLALPERAEL AASLGLTQTQ VKIWFQNKRS KIKKIMKNGE 200
    MPPEHSPSSS DPMACNSPQS PAVWEPQGSS RSLSHHPHAH PPTSNQSPAS 250
    SYLENSASWY PSAASSINSH LPPPGSLQHP LALASGTLY 289
    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:
    EMBL
    GenBank
    DDBJ
    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:
    EMBL
    GenBank
    DDBJ
    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 ENSGT00720000108450.
    HOGENOMi HOG000231940.
    HOVERGENi HBG005493.
    InParanoidi P70396.
    KOi K09315.
    OMAi QSPAVWD.
    OrthoDBi EOG70W3F8.
    PhylomeDBi P70396.
    TreeFami TF350606.

    Miscellaneous databases

    NextBioi 283772.
    PROi P70396.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P70396.
    Bgeei P70396.
    CleanExi MM_DLX5.
    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: October 1, 2014
    This is version 121 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