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FLASH GENE
Symbol DLX5 contributors: mct/npt/pgu - updated : 03-04-2019
HGNC name distal-less homeobox 5
HGNC id 2918
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • helix-turn-helix, DNA binding domain
  • HOMOLOGY
    interspecies homolog to Drosophila distal less Dlx5
    intraspecies paralog to DLX6
    Homologene
    FAMILY
  • distal-less homeobox family
  • CATEGORY transcription factor , protooncogene
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm
    intracellular,nucleus,chromatin/chromosome
    basic FUNCTION
  • playing a role in forebrain and craniofacial development
  • regulating development of peripheral and central components of the olfactory system
  • playing an important role in production of GABAergic neurons
  • acting as an oncogene in lymphomas and lung cancers
  • promotes cell proliferation by transcriptionally regulating MYC
  • has a restricted pattern of expression in adult tissues
  • with DLX6 are functionally equivalent in the endochondral skeleton, in that the requirement for DLX5 and DLX6 function during chondrocyte hypertrophy can be satisfied with DLX5 alone
  • with DLX6, are required for development and function of somal innervating (parvalbumin(+)) neocortical interneurons
  • is a novel target of AKT1 and activity of DLX5 could be modulated by a novel mechanism involving AKT1 during osteoblast differentiation
  • DLX5 and MSX2 play potentially a critical role in controlling cranial neural tube morphogenesis by regulating cell adhesion via the EPHA5 and EPHA7 pathway
  • DLX5 and DLX6 expression determines uterine architecture and adenogenesis and is needed for implantation
  • DLX5 and DLX6 are quantitatively indistinguishable on a variety of natural cis-regulatory sequences in a heterologous cellular context but observed quantitatively different transcriptional outputs in cells that normally express these genes, suggesting differential interactions with co-evolved co-activators
  • is part of the human-specific regulatory network of trophoblast differentiation
  • STAT5A activates distal-less homeobox 5 (DLX5) in human bone marrow-derived stromal cells (hBMSCs) and enhances osteogenesis
  • DLX5/DLX6 expression is required during vertebrate posterior axis formation
  • CELLULAR PROCESS cell life, differentiation
    nucleotide, transcription
    cell organization/biogenesis
    PHYSIOLOGICAL PROCESS development
    text
  • osteoblast differentiation
  • bone development, fracture healing
  • neurogenesis
  • PATHWAY
    metabolism
    signaling
  • DLX5-FGF10 signaling cascade controls cranial neural crest and myoblast interaction during oropharyngeal patterning and development
  • a component
    INTERACTION
    DNA
  • binding
  • binding to the promoter of MYC
  • RNA
    small molecule
    protein
  • target of MECP2
  • binds to the MYC promoter
  • directly associated with TP63
  • interacting with MSX1 (MSX1/DLX5 interaction is crucial for osteogenic induction during frontal bone development)
  • PRKACA phosphorylates DLX5 and its activation increases the protein stability, osteogenic activity and transcriptional activity of DLX5
  • DLX3 and DLX5 proteins were found to activate the GPNMB transcription, whereas, MSX2 suppressed BMP2-induced GPNMB transcription
  • enhances osteoblastogenesis through upregulation of the expression of RUNX2 and osteoblast marker genes while suppressing adipogenesis through the downregulation of PPARG
  • EDN1 regulates neural crest deployment and fate to form great vessels through DLX5/DLX6-independent mechanisms
  • GATA4 interacted with DLX5 and subsequently decreased DLX5 binding activity to RUNX2 promoter region
  • NDN modulates osteogenic cell differentiation by regulating DLX5 and MAGED1
  • cell & other
    REGULATION
    induced by bone morphogenetic proteins
    Phosphorylated by AKT1 (AKT1 interacts with and phosphorylates DLX5)
    Other downregulated by PSA1 through its ubiquitin ligase activity for the DLX/MSX interacting Dlxin-1 protein
    regulated by TP63 (TP63 binds to an enhancer element in the SHFM1 locus and this element controls expression of DLX6 and possibly DLX5, both of which are important for limb development
    regulated post-translationally by protein kinases such as MAPK14 and CaMK2A
    ASSOCIATED DISORDERS
    corresponding disease(s) SHFM1 , DEL7Q21
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional germinal mutation LOI    
    dysregulated (LOI) by mutations of MECP2 in Rett syndrome
    tumoral     --over  
    in endometriod adenocarcinomas
    constitutional     --low  
    in endometriotic lesions
    constitutional       gain of function
    in 70p100 of preeclamptic placentas
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancer  
    because of a restricted pattern of expression in adult tissues, it may serve as a potential therapeutic target for the treatment of cancers that overexpress it
    ANIMAL & CELL MODELS
  • Dlx5/Dlx6 double mutants exhibit hindlimb ectrodactyly
  • Dlx5/6-inactivation in the mouse results in a phenotype reminiscent of NTDs characterized by open thoracic and lumbar vertebral arches and failure of epaxial muscle formation at the dorsal midline