Description: Homo sapiens distal-less homeobox 5 (DLX5), mRNA. RefSeq Summary (NM_005221): This gene encodes a member of a homeobox transcription factor gene family similiar to the Drosophila distal-less gene. The encoded protein may play a role in bone development and fracture healing. Mutation in this gene, which is located in a tail-to-tail configuration with another member of the family on the long arm of chromosome 7, may be associated with split-hand/split-foot malformation. [provided by RefSeq, Jul 2008]. Transcript (Including UTRs) Position: hg19 chr7:96,649,702-96,654,143 Size: 4,442 Total Exon Count: 3 Strand: - Coding Region Position: hg19 chr7:96,650,048-96,653,935 Size: 3,888 Coding Exon Count: 3
ID:DLX5_HUMAN DESCRIPTION: RecName: Full=Homeobox protein DLX-5; 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: Nucleus (By similarity). DEVELOPMENTAL STAGE: First expressed in embryos at 8.5-9 days in facial and branchial arch mesenchyme, otic vesicles and frontonasal ectoderm around olfactory placodes, a day later expression is seen in the developing forebrain in primordia of the ganglionic eminence and ventral diencephalic regions. In day 12.5 embryos, expressed in the brain and bones, and also in all skeletal structures of midgestation embryos after the first cartilage formation. Expression remains unaltered in both brain and skeleton in day 15 embryos and slowly decreases in day 17 embryos. PTM: 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 the 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. SIMILARITY: Contains 1 homeobox DNA-binding domain.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P56178
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Gene Ontology (GO) Annotations with Structured Vocabulary
Molecular Function: GO:0000978 RNA polymerase II core promoter proximal region sequence-specific DNA binding GO:0000981 RNA polymerase II transcription factor activity, sequence-specific DNA binding GO:0001077 transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding GO:0003677 DNA binding GO:0043565 sequence-specific DNA binding GO:0044212 transcription regulatory region DNA binding GO:0071837 HMG box domain binding
Biological Process: GO:0001501 skeletal system development GO:0001503 ossification GO:0001649 osteoblast differentiation GO:0001958 endochondral ossification GO:0006351 transcription, DNA-templated GO:0006355 regulation of transcription, DNA-templated GO:0006366 transcription from RNA polymerase II promoter GO:0007275 multicellular organism development GO:0007399 nervous system development GO:0007409 axonogenesis GO:0007411 axon guidance GO:0008283 cell proliferation GO:0010628 positive regulation of gene expression GO:0021889 olfactory bulb interneuron differentiation GO:0030326 embryonic limb morphogenesis GO:0030509 BMP signaling pathway GO:0030855 epithelial cell differentiation GO:0042472 inner ear morphogenesis GO:0043583 ear development GO:0045893 positive regulation of transcription, DNA-templated GO:0045944 positive regulation of transcription from RNA polymerase II promoter GO:0048646 anatomical structure formation involved in morphogenesis GO:0050679 positive regulation of epithelial cell proliferation GO:0060021 palate development GO:0060166 olfactory pit development GO:0060322 head development GO:0060325 face morphogenesis GO:0060349 bone morphogenesis GO:0071773 cellular response to BMP stimulus GO:0090263 positive regulation of canonical Wnt signaling pathway GO:0097376 interneuron axon guidance GO:1901522 positive regulation of transcription from RNA polymerase II promoter involved in cellular response to chemical stimulus