DLX5

DLX5
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2DJN, 4RDU
Identifiers
Aliases	DLX5, SHFM1D, AI385752, distal-less homeobox 5, SHFM1
External IDs	OMIM: 600028; MGI: 101926; HomoloGene: 3825; GeneCards: DLX5; OMA:DLX5 - orthologs
Gene location (Human) Chr. Chromosome 7 (human) Band 7q21.3 Start 97,020,396 bp End 97,024,950 bp
Gene location (Mouse) Chr. Chromosome 6 (mouse) Band 6 A1|6 2.83 cM Start 6,877,805 bp End 6,882,085 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in tibia gonad skin of leg endometrium skin of abdomen testicle Achilles tendon placenta periodontal fiber ganglionic eminence Top expressed in neural plate neural groove neural fold molar medial ganglionic eminence genital tubercle Apical ectodermal ridge subthalamus surface ectoderm mandibular prominence More reference expression data BioGPS More reference expression data
Gene ontology Molecular function DNA binding sequence-specific DNA binding HMG box domain binding DNA-binding transcription activator activity, RNA polymerase II-specific RNA polymerase II cis-regulatory region sequence-specific DNA binding DNA-binding transcription factor activity, RNA polymerase II-specific DNA-binding transcription factor activity Cellular component cytoplasm nucleus Biological process skeletal system development roof of mouth development regulation of transcription, DNA-templated epithelial cell differentiation axonogenesis ossification positive regulation of epithelial cell proliferation positive regulation of canonical Wnt signaling pathway anatomical structure formation involved in morphogenesis bone morphogenesis head development cellular response to BMP stimulus ear development endochondral ossification transcription by RNA polymerase II BMP signaling pathway olfactory pit development transcription, DNA-templated nervous system development axon guidance positive regulation of transcription, DNA-templated multicellular organism development embryonic limb morphogenesis inner ear morphogenesis osteoblast differentiation cell population proliferation face morphogenesis positive regulation of transcription by RNA polymerase II positive regulation of transcription from RNA polymerase II promoter involved in cellular response to chemical stimulus positive regulation of gene expression olfactory bulb interneuron differentiation interneuron axon guidance regulation of transcription by RNA polymerase II cell differentiation Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 1749 13395 Ensembl ENSG00000105880 ENSMUSG00000029755 UniProt P56178 P70396 RefSeq (mRNA) NM_005221 NM_010056 NM_198854 RefSeq (protein) NP_005212 NP_034186 NP_942151 Location (UCSC) Chr 7: 97.02 – 97.02 Mb Chr 6: 6.88 – 6.88 Mb PubMed search
Wikidata
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Homeobox protein DLX-5 is a protein that in humans is encoded by the distal-less homeobox 5 gene, or DLX5 gene. DLX5 is a member of the DLX gene family.

Function

This gene encodes a member of a homeobox transcription factor gene family similar to the Drosophila distal-less (Dll) gene. The encoded protein may play a role in bone development and fracture healing. Current research holds that the homeobox gene family is important in appendage development. DLX5 and DLX6 can be seen to work in conjunction and are both necessary for proper craniofacial, axial, and appendicular skeleton development. Mutations in this gene, which is located in a tail-to-tail configuration with DLX6 on the long arm of chromosome 7, may be associated with split-hand/split-foot malformation.

DLX5 also acts as the early BMP-responsive transcriptional activator needed for osteoblast differentiation by stimulating the up-regulation of a variety of promoters (ALPL promoter, SP7 promoter, MYC promoter).

Clinical significance

Mutations in the DLX5 gene have been shown to be involved in the split hand and foot malformation syndrome (SHFM). SHFM is a heterogenous limb defect in which the development of the central digital rays is hindered, leading to missing central digits and claw-like distal extremities. Other defects associated with DLX5 include sensorineural hearing loss, mental retardation, ectodermal and craniofacial findings, and orofacial clefting.

In mice, the targeted disruption of DLX1, DLX2, DLX1/2, or DLX5 orthologs yields craniofacial, bone, and vestibular defects. If DLX5 is disrupted in conjunction with DLX6, bone, inner ear, and severe craniofacial defects are prevalent. Research utilizing Dlx5/6-nulls suggests that these genes have both unique and redundant functions.

Role in development

DLX5 begins to express DLX5 protein in the facial and branchial arch mesenchyme, otic vesicles, and frontonasal ectoderm at around day 8.5-9. By day 12.5, DLX5 protein begins to be expressed in the brain, bones, and all remaining skeletal structures. Expression in the brain and skeleton begins to decrease by day 17.

Interactions

DLX5 has been shown to interact with DLX1, DLX2, DLX6, MSX1 and MSX2.

Further reading

• Bapat S, Galande S (Jul 2005). "Association by guilt: identification of DLX5 as a target for MeCP2 provides a molecular link between genomic imprinting and Rett syndrome". BioEssays. 27 (7): 676–80. doi:10.1002/bies.20266. PMID 15954098.
• Scherer SW, Poorkaj P, Massa H, Soder S, Allen T, Nunes M, Geshuri D, Wong E, Belloni E, Little S (Aug 1994). "Physical mapping of the split hand/split foot locus on chromosome 7 and implication in syndromic ectrodactyly". Human Molecular Genetics. 3 (8): 1345–54. doi:10.1093/hmg/3.8.1345. PMID 7987313.
• Zhang H, Hu G, Wang H, Sciavolino P, Iler N, Shen MM, Abate-Shen C (May 1997). "Heterodimerization of Msx and Dlx homeoproteins results in functional antagonism". Molecular and Cellular Biology. 17 (5): 2920–32. doi:10.1128/mcb.17.5.2920. PMC 232144. PMID 9111364.
• Newberry EP, Latifi T, Towler DA (Aug 1999). "The RRM domain of MINT, a novel Msx2 binding protein, recognizes and regulates the rat osteocalcin promoter". Biochemistry. 38 (33): 10678–90. doi:10.1021/bi990967j. PMID 10451362.
• Eisenstat DD, Liu JK, Mione M, Zhong W, Yu G, Anderson SA, Ghattas I, Puelles L, Rubenstein JL (Nov 1999). "DLX-1, DLX-2, and DLX-5 expression define distinct stages of basal forebrain differentiation". The Journal of Comparative Neurology. 414 (2): 217–37. doi:10.1002/(SICI)1096-9861(19991115)414:2<217::AID-CNE6>3.0.CO;2-I. PMID 10516593. S2CID 20182781.
• Masuda Y, Sasaki A, Shibuya H, Ueno N, Ikeda K, Watanabe K (Feb 2001). "Dlxin-1, a novel protein that binds Dlx5 and regulates its transcriptional function". The Journal of Biological Chemistry. 276 (7): 5331–8. doi:10.1074/jbc.M008590200. PMID 11084035.
• Yu G, Zerucha T, Ekker M, Rubenstein JL (Oct 2001). "Evidence that GRIP, a PDZ-domain protein which is expressed in the embryonic forebrain, co-activates transcription with DLX homeodomain proteins". Brain Research. Developmental Brain Research. 130 (2): 217–30. doi:10.1016/S0165-3806(01)00239-5. PMID 11675124.
• Sasaki A, Masuda Y, Iwai K, Ikeda K, Watanabe K (Jun 2002). "A RING finger protein Praja1 regulates Dlx5-dependent transcription through its ubiquitin ligase activity for the Dlx/Msx-interacting MAGE/Necdin family protein, Dlxin-1". The Journal of Biological Chemistry. 277 (25): 22541–6. doi:10.1074/jbc.M109728200. PMID 11959851.
• Willis DM, Loewy AP, Charlton-Kachigian N, Shao JS, Ornitz DM, Towler DA (Oct 2002). "Regulation of osteocalcin gene expression by a novel Ku antigen transcription factor complex". The Journal of Biological Chemistry. 277 (40): 37280–91. doi:10.1074/jbc.M206482200. PMID 12145306.
• Okita C, Meguro M, Hoshiya H, Haruta M, Sakamoto YK, Oshimura M (Jun 2003). "A new imprinted cluster on the human chromosome 7q21-q31, identified by human-mouse monochromosomal hybrids". Genomics. 81 (6): 556–9. doi:10.1016/S0888-7543(03)00052-1. PMID 12782124.

External links

• DLX5 protein, human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)

This article incorporates text from the United States National Library of Medicine, which is in the public domain.