Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

P70396 (DLX5_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 117. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Homeobox protein DLX-5
Gene names
Name:Dlx5
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length289 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

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. Ref.5 Ref.6 Ref.8

Subunit structure

Interacts with XRCC6 (Ku70) By similarity.

Subcellular location

Nucleus Ref.6.

Tissue specificity

Expressed in osteoblasts and chondrocytes. Ref.8

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. Ref.8

Induction

Up-regulated by BMP2. Ref.5 Ref.6

Post-translational modification

Phosphorylated. Phosphorylation of Ser-34 and Ser-217 by MAPK14 enhances its transcriptional activity. Phosphorylation by CaMK2 increases its protein stability. Ref.6 Ref.7

Sequence similarities

Belongs to the distal-less homeobox family.

Contains 1 homeobox DNA-binding domain.

Ontologies

Keywords
   Biological processOsteogenesis
Transcription
Transcription regulation
   Cellular componentNucleus
   Coding sequence diversityAlternative splicing
   DomainHomeobox
   LigandDNA-binding
   Molecular functionActivator
Developmental protein
   PTMPhosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processBMP signaling pathway

Inferred from mutant phenotype PubMed 20843790. Source: BHF-UCL

anatomical structure formation involved in morphogenesis

Inferred from genetic interaction PubMed 17878916. Source: MGI

axon guidance

Inferred from mutant phenotype PubMed 17804636. Source: MGI

axonogenesis

Inferred from mutant phenotype PubMed 12533617. Source: MGI

bone morphogenesis

Inferred from mutant phenotype PubMed 16330189. Source: MGI

cell proliferation

Inferred from sequence or structural similarity. Source: UniProtKB

cellular response to BMP stimulus

Inferred from mutant phenotype PubMed 20843790. Source: BHF-UCL

ear development

Inferred from mutant phenotype PubMed 16330189. Source: MGI

embryonic limb morphogenesis

Inferred from genetic interaction PubMed 12112878. Source: MGI

endochondral ossification

Inferred from mutant phenotype Ref.8. Source: UniProtKB

epithelial cell differentiation

Inferred from genetic interaction PubMed 17878916. Source: MGI

face morphogenesis

Inferred from mutant phenotype PubMed 16330189. Source: MGI

head development

Inferred from genetic interaction PubMed 15306564. Source: MGI

inner ear morphogenesis

Inferred from mutant phenotype PubMed 12142028. Source: MGI

olfactory pit development

Inferred from mutant phenotype PubMed 12533617. Source: MGI

osteoblast differentiation

Inferred from direct assay Ref.5. Source: UniProtKB

palate development

Inferred from mutant phenotype PubMed 16330189. Source: MGI

positive regulation of canonical Wnt signaling pathway

Inferred from mutant phenotype PubMed 17804636. Source: MGI

positive regulation of epithelial cell proliferation

Inferred from genetic interaction PubMed 16900517. Source: MGI

positive regulation of osteoblast differentiation

Inferred from electronic annotation. Source: Ensembl

positive regulation of transcription from RNA polymerase II promoter

Inferred from genetic interaction PubMed 17420000. Source: MGI

positive regulation of transcription from RNA polymerase II promoter involved in cellular response to chemical stimulus

Inferred from mutant phenotype PubMed 20843790. Source: BHF-UCL

positive regulation of transcription, DNA-templated

Inferred from direct assay Ref.5. Source: UniProtKB

regulation of transcription, DNA-templated

Inferred from mutant phenotype PubMed 12142028. Source: MGI

   Cellular_componentcytoplasm

Inferred from direct assay PubMed 10516593. Source: MGI

nuclear chromatin

Inferred from direct assay PubMed 20843790. Source: BHF-UCL

nucleus

Inferred from direct assay PubMed 10516593. Source: MGI

   Molecular_functionDNA binding

Inferred from direct assay Ref.3. Source: MGI

HMG box domain binding

Inferred from physical interaction PubMed 16582099. Source: UniProtKB

RNA polymerase II core promoter proximal region sequence-specific DNA binding

Inferred from direct assay PubMed 20843790. Source: BHF-UCL

RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription

Inferred from direct assay PubMed 20843790. Source: BHF-UCL

transcription regulatory region DNA binding

Inferred from direct assay Ref.5. Source: UniProtKB

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Maged1Q9QYH62EBI-1801294,EBI-1801274

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P70396-1)

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.
Isoform 2 (identifier: P70396-2)

Also known as: Beta;

The sequence of this isoform differs from the canonical sequence as follows:
     147-251: Missing.
Isoform 3 (identifier: P70396-3)

Also known as: Gamma;

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 289289Homeobox protein DLX-5
PRO_0000049032

Regions

DNA binding137 – 19660Homeobox Ref.5

Amino acid modifications

Modified residue341Phosphoserine; by MAPK14; in vitro Ref.6
Modified residue2171Phosphoserine; by MAPK14; in vitro Ref.6

Natural variations

Alternative sequence119 – 14628EKEVA…TIYSS → AFSWPLYREGFRRLSTSPCQ NARSWPPL in isoform 3.
VSP_002237
Alternative sequence147 – 289143Missing in isoform 3.
VSP_002238
Alternative sequence147 – 251105Missing in isoform 2.
VSP_002239

Experimental info

Mutagenesis341S → A: Inhibits its transcriptional activity; when associated with A-217. Ref.6
Mutagenesis2171S → A: Inhibits its transcriptional activity; when associated with A-34. Ref.6
Sequence conflict98 – 992AS → H in AAB94580. Ref.3
Sequence conflict98 – 992AS → H in AAB94581. Ref.3

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (Alpha) [UniParc].

Last modified February 1, 1997. Version 1.
Checksum: C53555610E9F8777

FASTA28931,396
        10         20         30         40         50         60 
MTGVFDRRVP SIRSGDFQAP FPTSAAMHHP SQESPTLPES SATDSDYYSP AGAAPHGYCS 

        70         80         90        100        110        120 
PTSASYGKAL NPYQYQYHGV NGSAAGYPAK AYADYGYASP YHQYGGAYNR VPSATSQPEK 

       130        140        150        160        170        180 
EVAEPEVRMV NGKPKKVRKP RTIYSSFQLA ALQRRFQKTQ YLALPERAEL AASLGLTQTQ 

       190        200        210        220        230        240 
VKIWFQNKRS KIKKIMKNGE MPPEHSPSSS DPMACNSPQS PAVWEPQGSS RSLSHHPHAH 

       250        260        270        280 
PPTSNQSPAS SYLENSASWY PSAASSINSH LPPPGSLQHP LALASGTLY 

« Hide

Isoform 2 (Beta) [UniParc].

Checksum: C96A32599A6AD931
Show »

FASTA18419,772
Isoform 3 (Gamma) [UniParc].

Checksum: 55BAEA4F6C3251B6
Show »

FASTA14615,858

References

[1]"The evolution of the vertebrate Dlx gene family."
Stock D.W., Ellies D.L., Zhao Z., Ekker M., Ruddle F.H., Weiss K.M.
Proc. Natl. Acad. Sci. U.S.A. 93:10858-10863(1996) [PubMed] [Europe PMC] [Abstract]
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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
RefSeqNP_034186.2. NM_010056.3.
NP_942151.1. NM_198854.2.
UniGeneMm.4873.

3D structure databases

ProteinModelPortalP70396.
SMRP70396. Positions 138-194.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid199238. 11 interactions.
IntActP70396. 1 interaction.

PTM databases

PhosphoSiteP70396.

Proteomic databases

PRIDEP70396.

Protocols and materials databases

DNASU13395.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000052609; ENSMUSP00000052559; ENSMUSG00000029755. [P70396-1]
ENSMUST00000142635; ENSMUSP00000138264; ENSMUSG00000029755. [P70396-3]
GeneID13395.
KEGGmmu:13395.
UCSCuc009awy.1. mouse. [P70396-3]
uc009awz.1. mouse. [P70396-1]

Organism-specific databases

CTD1749.
MGIMGI:101926. Dlx5.

Phylogenomic databases

eggNOGNOG263092.
GeneTreeENSGT00720000108450.
HOGENOMHOG000231940.
HOVERGENHBG005493.
InParanoidP70396.
KOK09315.
OMAQSPAVWD.
OrthoDBEOG70W3F8.
PhylomeDBP70396.
TreeFamTF350606.

Gene expression databases

ArrayExpressP70396.
BgeeP70396.
CleanExMM_DLX5.
GenevestigatorP70396.

Family and domain databases

Gene3D1.10.10.60. 1 hit.
InterProIPR022135. Distal-less_N.
IPR017970. Homeobox_CS.
IPR001356. Homeobox_dom.
IPR020479. Homeobox_metazoa.
IPR009057. Homeodomain-like.
IPR000047. HTH_motif.
[Graphical view]
PfamPF12413. DLL_N. 1 hit.
PF00046. Homeobox. 1 hit.
[Graphical view]
PRINTSPR00024. HOMEOBOX.
PR00031. HTHREPRESSR.
SMARTSM00389. HOX. 1 hit.
[Graphical view]
SUPFAMSSF46689. SSF46689. 1 hit.
PROSITEPS00027. HOMEOBOX_1. 1 hit.
PS50071. HOMEOBOX_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio283772.
PROP70396.
SOURCESearch...

Entry information

Entry nameDLX5_MOUSE
AccessionPrimary (citable) accession number: P70396
Secondary accession number(s): O54876 expand/collapse secondary AC list , O54877, O54878, Q9JJ45
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: February 1, 1997
Last modified: April 16, 2014
This is version 117 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot