Human Gene DLX5 (uc003uon.3)
  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 

Page IndexSequence and LinksUniProtKB CommentsPrimersGenetic AssociationsMalaCards
CTDGene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein Structure
Other SpeciesGO AnnotationsmRNA DescriptionsPathwaysOther NamesModel Information
Methods
Data last updated at UCSC: 2013-06-14

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr7:96,649,702-96,654,143)mRNA (may differ from genome)Protein (289 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
AlphaFoldBioGPSEnsemblEntrez GeneExonPrimerGeneCards
GeneNetworkH-INVHGNCHPRDHuman Cortex Gene ExpressionLynx
MalacardsMGIneXtProtOMIMPubMedReactome
TreefamUniProtKBWikipediaBioGrid CRISPR DB

-  Comments and Description Text from UniProtKB
  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.

-  Primer design for this transcript
 

Primer3Plus can design qPCR Primers that straddle exon-exon-junctions, which amplify only cDNA, not genomic DNA.
Click here to load the transcript sequence and exon structure into Primer3Plus

Exonprimer can design one pair of Sanger sequencing primers around every exon, located in non-genic sequence.
Click here to open Exonprimer with this transcript

To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3


-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): DLX5
CDC HuGE Published Literature: DLX5

-  MalaCards Disease Associations
  MalaCards Gene Search: DLX5
Diseases sorted by gene-association score: split-hand/foot malformation 1 with sensorineural hearing loss* (1737), split hand-foot malformation 1* (436), split hand-split foot malformation* (380), split hand (61), split hand-foot malformation (42), rett syndrome (20), split foot (14), rapp-hodgkin syndrome (13), sensorineural hearing loss (11), paranoid personality disorder (9), split-hand/foot malformation 6 (8), split-hand/foot malformation 4 (7), split-hand/foot malformation 5 (6), hand-foot-uterus syndrome (6), split hand-foot malformation 2 (5), split-hand/foot malformation 3 (5)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 13.99 RPKM in Skin - Sun Exposed (Lower leg)
Total median expression: 66.46 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -55.50208-0.267 Picture PostScript Text
3' UTR -67.61346-0.195 Picture PostScript Text

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.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR022135 - Distal-less_N
IPR017970 - Homeobox_CS
IPR020479 - Homeobox_metazoa
IPR001356 - Homeodomain
IPR009057 - Homeodomain-like
IPR000047 - HTH_motif

Pfam Domains:
PF00046 - Homeobox domain
PF12413 - Homeobox protein distal-less-like N terminal

SCOP Domains:
46689 - Homeodomain-like

Protein Data Bank (PDB) 3-D Structure
MuPIT help
2DJN - NMR MuPIT


ModBase Predicted Comparative 3D Structure on P56178
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The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  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.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologGenome BrowserGenome BrowserNo orthologGenome BrowserNo ortholog
 Gene Details  Gene Details 
 Gene Sorter  Gene Sorter 
 RGDEnsembl WormBase 
 Protein SequenceProtein Sequence Protein Sequence 
 AlignmentAlignment Alignment 

-  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

Cellular Component:
GO:0000790 nuclear chromatin
GO:0005634 nucleus
GO:0005737 cytoplasm


-  Descriptions from all associated GenBank mRNAs
  LF205110 - JP 2014500723-A/12613: Polycomb-Associated Non-Coding RNAs.
BC006226 - Homo sapiens distal-less homeobox 5, mRNA (cDNA clone MGC:10672 IMAGE:3941691), complete cds.
AK023493 - Homo sapiens cDNA FLJ13431 fis, clone PLACE1002532, highly similar to HOMEOBOX PROTEIN DLX-5.
BT006903 - Homo sapiens distal-less homeo box 5 mRNA, complete cds.
KJ891056 - Synthetic construct Homo sapiens clone ccsbBroadEn_00450 DLX5 gene, encodes complete protein.
AB463570 - Synthetic construct DNA, clone: pF1KB7588, Homo sapiens DLX5 gene for distal-less homeobox 5, without stop codon, in Flexi system.
AK297614 - Homo sapiens cDNA FLJ55417 complete cds, highly similar to Homeobox protein DLX-5.
LF212005 - JP 2014500723-A/19508: Polycomb-Associated Non-Coding RNAs.
MA440687 - JP 2018138019-A/12613: Polycomb-Associated Non-Coding RNAs.
MA447582 - JP 2018138019-A/19508: Polycomb-Associated Non-Coding RNAs.

-  Biochemical and Signaling Pathways
  Reactome (by CSHL, EBI, and GO)

Protein P56178 (Reactome details) participates in the following event(s):

R-HSA-9007707 DLX5,(DLX6) binds RUNX2 gene promoter
R-HSA-8939902 Regulation of RUNX2 expression and activity
R-HSA-8878166 Transcriptional regulation by RUNX2
R-HSA-212436 Generic Transcription Pathway
R-HSA-73857 RNA Polymerase II Transcription
R-HSA-74160 Gene expression (Transcription)

-  Other Names for This Gene
  Alternate Gene Symbols: DLX5_HUMAN, NM_005221, NP_005212, P56178, Q9UPL1
UCSC ID: uc003uon.3
RefSeq Accession: NM_005221
Protein: P56178 (aka DLX5_HUMAN)
CCDS: CCDS5647.1

-  Gene Model Information
 
category: coding nonsense-mediated-decay: no RNA accession: NM_005221.5
exon count: 3CDS single in 3' UTR: no RNA size: 1424
ORF size: 870CDS single in intron: no Alignment % ID: 100.00
txCdsPredict score: 1928.00frame shift in genome: no % Coverage: 100.00
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: no # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.