Dlx5 (distal-less homeobox 5) gene is a member of a homeobox gene family similiar to the Drosophila distal-less gene. The encoded Dlx5 protein is localized to the nucleus where it functions as a transcriptional regulator during neural development. In the developing CNS, Dlx5 is one of the earliest known markers before the formation of an overt neural plate. During late gastrulation Dlx5 (gene) expression becomes localized to the anterior neural ridge, which defines the rostral boundary of the neural plate, and also extends caudolaterally, marking the region of the presumptive neural crest. Subsequently, Dlx5 is expressed in tissues (olfactory epithelium, ventral cephalic epithelium) that are believed to derive from the anterior neural ridge.
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.
Subunit:
Interacts with XRCC6 (Ku70).
Subcellular Location:
Nuclear.
Post-translational modifications:
Phosphorylated. Phosphorylation of Ser-34 and Ser-217 by MAPK14 enhances its transcriptional activity. Phosphorylation by CaMK2 increases its protein stability (By similarity).
DISEASE:
Defects in DLX5 are the cause of split-hand/foot malformation type 1, with sensorineural hearing loss (SHFM1D) [MIM:220600]. A disease characterized by the association of split-hand/foot malformation with deafness. Split-hand/foot malformation is a limb malformation involving the central rays of he autopod and presenting with syndactyly, median clefts of the hands and feet, and aplasia and/or hypoplasia of the phalanges, metacarpals, and metatarsals. Some patients have been found to have mental retardation, ectodermal and craniofacial findings, and orofacial clefting.
Similarity:
Belongs to the distal-less homeobox family.
Contains 1 homeobox DNA-binding domain.
SWISS:
P56178
Gene ID:
1749
Database links:
Entrez Gene: 1749 Human
Entrez
Gene: 13395 Mouse
Entrez Gene: 25431 Rat
Omim: 600028 Human
SwissProt: P56178 Human
SwissProt: P70396 Mouse
SwissProt: P50575 Rat
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