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| | ==The solution structure of the homeobox domain of human Homeobox protein DLX-5== | | ==The solution structure of the homeobox domain of human Homeobox protein DLX-5== |
| - | <StructureSection load='2djn' size='340' side='right' caption='[[2djn]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='2djn' size='340' side='right'caption='[[2djn]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2djn]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2DJN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2DJN FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2djn]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2DJN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2DJN FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">DLX5 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">DLX5 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2djn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2djn OCA], [http://pdbe.org/2djn PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2djn RCSB], [http://www.ebi.ac.uk/pdbsum/2djn PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2djn ProSAT], [http://www.topsan.org/Proteins/RSGI/2djn TOPSAN]</span></td></tr> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2djn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2djn OCA], [https://pdbe.org/2djn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2djn RCSB], [https://www.ebi.ac.uk/pdbsum/2djn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2djn ProSAT], [https://www.topsan.org/Proteins/RSGI/2djn TOPSAN]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/DLX5_HUMAN DLX5_HUMAN]] Defects in DLX5 are the cause of split-hand/foot malformation type 1, with sensorineural hearing loss (SHFM1D) [MIM:[http://omim.org/entry/220600 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.<ref>PMID:22121204</ref> | + | [[https://www.uniprot.org/uniprot/DLX5_HUMAN DLX5_HUMAN]] Defects in DLX5 are the cause of split-hand/foot malformation type 1, with sensorineural hearing loss (SHFM1D) [MIM:[https://omim.org/entry/220600 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.<ref>PMID:22121204</ref> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/DLX5_HUMAN DLX5_HUMAN]] 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>PMID:19497851</ref> | + | [[https://www.uniprot.org/uniprot/DLX5_HUMAN DLX5_HUMAN]] 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>PMID:19497851</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Human]] | | [[Category: Human]] |
| | + | [[Category: Large Structures]] |
| | [[Category: Inoue, M]] | | [[Category: Inoue, M]] |
| | [[Category: Kigawa, T]] | | [[Category: Kigawa, T]] |
| Structural highlights
Disease
[DLX5_HUMAN] 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.[1]
Function
[DLX5_HUMAN] 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.[2]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
References
- ↑ Shamseldin HE, Faden MA, Alashram W, Alkuraya FS. Identification of a novel DLX5 mutation in a family with autosomal recessive split hand and foot malformation. J Med Genet. 2012 Jan;49(1):16-20. doi: 10.1136/jmedgenet-2011-100556. Epub 2011 , Nov 25. PMID:22121204 doi:10.1136/jmedgenet-2011-100556
- ↑ Xu J, Testa JR. DLX5 (distal-less homeobox 5) promotes tumor cell proliferation by transcriptionally regulating MYC. J Biol Chem. 2009 Jul 31;284(31):20593-601. doi: 10.1074/jbc.M109.021477. Epub, 2009 Jun 4. PMID:19497851 doi:10.1074/jbc.M109.021477
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