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
Gene location (Human)
Chr.	Chromosome 7 (human)[1]
End	97,024,950 bp[1]
Gene location (Mouse)
Chr.	Chromosome 6 (mouse)[2]
End	6,882,085 bp[2]
RNA expression pattern
	More reference expression data
Gene ontology
Molecular function	• DNA binding; • sequence-specific DNA binding; • HMG box domain binding; • GO:0001077, GO:0001212, GO:0001213, GO:0001211, GO:0001205 DNA-binding transcription activator activity, RNA polymerase II-specific; • GO:0000980 RNA polymerase II cis-regulatory region sequence-specific DNA binding; • GO:0001200, GO:0001133, GO:0001201 DNA-binding transcription factor activity, RNA polymerase II-specific; • GO:0001131, GO:0001151, GO:0001130, GO:0001204 DNA-binding transcription factor activity;
Cellular component	• cytoplasm; • nuclear chromatin; • cell nucleus;
Biological process	• skeletal system development; • palate 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 from RNA polymerase II promoter; • 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; • cellular proliferation; • face morphogenesis; • positive regulation of transcription from RNA polymerase II promoter; • 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 from RNA polymerase II promoter; • cell differentiation;
	Sources:Amigo / QuickGO
Orthologs
	1749
	13395
	ENSG00000105880
	ENSMUSG00000029755
	P56178
	P70396
	NM_005221
	NM_010056; NM_198854
	NP_005212
	NP_034186; NP_942151
	Wikidata
View/Edit Human	View/Edit Mouse

Homeobox protein DLX-5 is a protein that in humans is encoded by the distal-less homeobox 5 gene, or DLX5 gene.[5][6] DLX5 is a member of 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. 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.[6]

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).[7]

Clinical significance

Mutations in the DLX5 gene have been shown to be involved in the hand and foot malformation syndrome.[8] 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.[9]

Developmental Stage

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.[7]

Interactions

DLX5 has been shown to interact with DLX1,[9] DLX2,[10] DLX6,[9] MSX1[10] and MSX2.[10]

References

GRCh38: Ensembl release 89: ENSG00000105880 - Ensembl, May 2017
GRCm38: Ensembl release 89: ENSMUSG00000029755 - Ensembl, May 2017
"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
Simeone A, Acampora D, Pannese M, D'Esposito M, Stornaiuolo A, Gulisano M, Mallamaci A, Kastury K, Druck T, Huebner K (Mar 1994). "Cloning and characterization of two members of the vertebrate Dlx gene family". Proceedings of the National Academy of Sciences of the United States of America. 91 (6): 2250–4. Bibcode:1994PNAS...91.2250S. doi:10.1073/pnas.91.6.2250. PMC 43348. PMID 7907794.
"Entrez Gene: DLX5 distal-less homeobox 5".
"Homeobox protein DLX-5".
Shamseldin HE, Faden MA, Alashram W, Alkuraya FS (Jan 2012). "Identification of a novel DLX5 mutation in a family with autosomal recessive split hand and foot malformation". Journal of Medical Genetics. 49 (1): 16–20. doi:10.1136/jmedgenet-2011-100556. PMID 22121204. S2CID 25692622.
Robledo RF, Rajan L, Li X, Lufkin T (May 2002). "The Dlx5 and Dlx6 homeobox genes are essential for craniofacial, axial, and appendicular skeletal development". Genes & Development. 16 (9): 1089–101. doi:10.1101/gad.988402. PMC 186247. PMID 12000792.
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.

External links

DLX5+protein,+human at the US 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.

This article is issued from Wikipedia. The text is licensed under Creative Commons - Attribution - Sharealike. Additional terms may apply for the media files.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000105880 - Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000029755 - Ensembl, May 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[pmid7907794-5] Simeone A, Acampora D, Pannese M, D'Esposito M, Stornaiuolo A, Gulisano M, Mallamaci A, Kastury K, Druck T, Huebner K (Mar 1994). "Cloning and characterization of two members of the vertebrate Dlx gene family". Proceedings of the National Academy of Sciences of the United States of America. 91 (6): 2250–4. Bibcode:1994PNAS...91.2250S. doi:10.1073/pnas.91.6.2250. PMC 43348. PMID 7907794.

[entrez-6] "Entrez Gene: DLX5 distal-less homeobox 5".

[uniprot-7] "Homeobox protein DLX-5".

[pmid22121204-8] Shamseldin HE, Faden MA, Alashram W, Alkuraya FS (Jan 2012). "Identification of a novel DLX5 mutation in a family with autosomal recessive split hand and foot malformation". Journal of Medical Genetics. 49 (1): 16–20. doi:10.1136/jmedgenet-2011-100556. PMID 22121204. S2CID 25692622.

[pmid12000792-9] Robledo RF, Rajan L, Li X, Lufkin T (May 2002). "The Dlx5 and Dlx6 homeobox genes are essential for craniofacial, axial, and appendicular skeletal development". Genes & Development. 16 (9): 1089–101. doi:10.1101/gad.988402. PMC 186247. PMID 12000792.

[pmid9111364-10] 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.