Selected-GenAtlas references	SOURCE	GeneCards	NCBI Gene	Swiss-Prot	Ensembl
	HGNC	UniGene	Nucleotide	OMIM	UCSC

Home Page

FLASH GENE

Symbol

DLX5

contributors: mct/npt/pgu - updated : 03-04-2019

HGNC name	distal-less homeobox 5
HGNC id	2918

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	DEL7Q21 chromosome 7q21 interstitial deletion SHFM1 split hand and foot malformation 1
Location	7q21.3      Physical location : 96.649.703 - 96.654.143

DNA

TYPE	functioning gene
SPECIAL FEATURE	tail to tail
text	closely linked to DLX6 tail to tail
STRUCTURE	4.44 kb     3 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

N

status

confirmed

Map	see SHFM1 SHFM1

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_005221 3 - 1424 NP_005212 - 289 - 1994 7907794

EXPRESSION

Type

widely

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Hearing/Equilibrium ear inner       Homo sapiens Nervous brain diencephalon         nerve spinal nerve sciatic   highly Reproductive female system placenta     highly   female system uterus       Homo sapiens Respiratory lung         Urinary kidney

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Connective bone     highly Epithelial barrier lining endometrium     Homo sapiens Nervous central       Nervous peripherous

cells

System Cell Pubmed Species Stage Rna symbol Reproductive epithelial cell Homo sapiens

cell lineage	progenitor cells of orofacial skeletal structure (mandible, Meckel's cartilage)
cell lines
fluid/secretion

at STAGE

physiological period

fetal

Text	all skeletal structures at midgestation
	normally expressed in the dorsal otic vesicle and later during differentiation of the vestibular tissues

IMPRINTING	maternally, paternally
text	paternally imprinted and having an important role for the development of gamma-aminobutyric acid (GABA)-ergic neurons
	maternally imprinted in osteoblasts

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)

Type Gene Modification Chromosome rearrangement Protein expression Protein 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
	System Type Disorder Pubmed 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