P70396 (DLX5_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Homeobox protein DLX-5

Gene names

Name:

Dlx5

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Boreoeutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	289 AA.
Sequence status	Complete.
Protein existence	Evidence 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 process	Osteogenesis Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing
Domain	Homeobox
Ligand	DNA-binding
Molecular function	Activator Developmental protein
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	BMP 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 12112878PubMed 18326838. 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_component	cytoplasm 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_function	DNA 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 protein binding Inferred from physical interaction PubMed 11084035. Source: IntAct transcription regulatory region DNA binding Inferred from direct assay Ref.5. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Maged1	Q9QYH6	2	EBI-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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 289	289	Homeobox protein DLX-5		PRO_0000049032
Regions
	DNA binding	137 – 196	60	Homeobox Ref.5
Amino acid modifications
	Modified residue	34	1	Phosphoserine; by MAPK14; in vitro Ref.6
	Modified residue	217	1	Phosphoserine; by MAPK14; in vitro Ref.6
Natural variations
	Alternative sequence	119 – 146	28	EKEVA…TIYSS → AFSWPLYREGFRRLSTSPCQ NARSWPPL in isoform 3.		VSP_002237
	Alternative sequence	147 – 289	143	Missing in isoform 3.		VSP_002238
	Alternative sequence	147 – 251	105	Missing in isoform 2.		VSP_002239
Experimental info
	Mutagenesis	34	1	S → A: Inhibits its transcriptional activity; when associated with A-217. Ref.6
	Mutagenesis	217	1	S → A: Inhibits its transcriptional activity; when associated with A-34. Ref.6
	Sequence conflict	98 – 99	2	AS → H in AAB94580. Ref.3
	Sequence conflict	98 – 99	2	AS → H in AAB94581. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (Alpha) [UniParc]. Last modified February 1, 1997. Version 1. Checksum: C53555610E9F8777	FASTA	289	31,396
	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
	Isoform 2 (Beta) [UniParc]. Checksum: C96A32599A6AD931	FASTA	184	19,772
	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 RTIYSSYLEN SASWYPSAAS SINSHLPPPG SLQHPLALAS GTLY
	Isoform 3 (Gamma) [UniParc]. Checksum: 55BAEA4F6C3251B6	FASTA	146	15,858
	10 20 30 40 50 60 MTGVFDRRVP SIRSGDFQAP FPTSAAMHHP SQESPTLPES SATDSDYYSP AGAAPHGYCS 70 80 90 100 110 120 PTSASYGKAL NPYQYQYHGV NGSAAGYPAK AYADYGYASP YHQYGGAYNR VPSATSQPAF 130 140 SWPLYREGFR RLSTSPCQNA RSWPPL

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.
CCDS	CCDS19905.1. [P70396-1] CCDS59691.1. [P70396-3]
RefSeq	NP_034186.2. NM_010056.3. [P70396-1] NP_942151.1. NM_198854.2. [P70396-3]
UniGene	Mm.4873.
3D structure databases
ProteinModelPortal	P70396.
SMR	P70396. Positions 138-194.
ModBase	Search...
MobiDB	Search...
Protein-protein interaction databases
BioGrid	199238. 11 interactions.
IntAct	P70396. 1 interaction.
PTM databases
PhosphoSite	P70396.
Proteomic databases
PRIDE	P70396.
Protocols and materials databases
DNASU	13395.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000052609; ENSMUSP00000052559; ENSMUSG00000029755. [P70396-1] ENSMUST00000142635; ENSMUSP00000138264; ENSMUSG00000029755. [P70396-3]
GeneID	13395.
KEGG	mmu:13395.
UCSC	uc009awy.1. mouse. [P70396-3] uc009awz.1. mouse. [P70396-1]
Organism-specific databases
CTD	1749.
MGI	MGI:101926. Dlx5.
Phylogenomic databases
eggNOG	NOG263092.
GeneTree	ENSGT00720000108450.
HOGENOM	HOG000231940.
HOVERGEN	HBG005493.
InParanoid	P70396.
KO	K09315.
OMA	QSPAVWD.
OrthoDB	EOG70W3F8.
PhylomeDB	P70396.
TreeFam	TF350606.
Gene expression databases
ArrayExpress	P70396.
Bgee	P70396.
CleanEx	MM_DLX5.
Genevestigator	P70396.
Family and domain databases
Gene3D	1.10.10.60. 1 hit.
InterPro	IPR022135. Distal-less_N. IPR017970. Homeobox_CS. IPR001356. Homeobox_dom. IPR020479. Homeobox_metazoa. IPR009057. Homeodomain-like. IPR000047. HTH_motif. [Graphical view]
Pfam	PF12413. DLL_N. 1 hit. PF00046. Homeobox. 1 hit. [Graphical view]
PRINTS	PR00024. HOMEOBOX. PR00031. HTHREPRESSR.
SMART	SM00389. HOX. 1 hit. [Graphical view]
SUPFAM	SSF46689. SSF46689. 1 hit.
PROSITE	PS00027. HOMEOBOX_1. 1 hit. PS50071. HOMEOBOX_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	283772.
PRO	P70396.
SOURCE	Search...

Entry information

Entry name

DLX5_MOUSE

Accession

Primary (citable) accession number: P70396
Secondary accession number(s): O54876 , O54877, O54878, Q9JJ45

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	February 1, 1997
Last modified:	July 9, 2014
This is version 120 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program