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FLASH GENE
Symbol MSX2 contributors: mct/npt/pgu - updated : 18-09-2014
HGNC name msh homeobox 2
HGNC id 7392
Corresponding disease
CRS2 craniosynostosis, syndromatic 2
DUP5QD chromosome 5q distal duplication
PFM2 parietal foramina permagna 2
Location 5q35.2      Physical location : 174.151.574 - 174.157.901
Synonym name msh homeo box homolog 2 (Drosophila)
Synonym symbol(s) HOX8, HOX-8, Msx-2, PFM1, FPP, MSH, PFM
DNA
TYPE functioning gene
STRUCTURE 6.33 kb     2 Exon(s)
10 Kb 5' upstream gene genomic sequence study
regulatory sequence Promoter
text structure
  • FOXC1 occupies a conserved element in the MSX2 promoter, and can stimulate the activity of the both human and mouse MSX2 promoters
  • MAPPING cloned Y linked N status confirmed
    Map see D5S2360
    Physical map
    KIAA1181 5q35.2 KIAA1181 protein LOC389344 5 LOC389344 RPL26L1 5q35.2 ribosomal protein L26-like 1 LOC285591 5q35.2 inorganic pyrophosphatase pseudogene ATP6V0E 5q35.3 ATPase, H+ transporting, lysosomal 9kDa, V0 subunit e LOC153222 5q35.2 adult retina protein BNIP1 5q33-q34 BCL2/adenovirus E1B 19kDa interacting protein 1 LOC391850 5 similar to 60S ribosomal protein L7a (Surfeit locus protein 3) (PLA-X polypeptide) NKX2-5 5q34-q35.3 NK2 transcription factor related, locus 5 (Drosophila) STC2 5p14.2-q15 stanniocalcin 2 LOC389345 5 LOC389345 LOC91272 5q35.2 hypothetical protein BC007436 CPEB4 5q21 cytoplasmic polyadenylation element binding protein 4 HMP19 5q35.2 HMP19 protein GAPDL16 5q33.1-q35.3 glyceraldehyde-3-phosphate dehydrogenase-like 16 MSX2 5q35.1 msh homeo box homolog 2 (Drosophila) DRD1 5q35.1 dopamine receptor D1 SFXN1 5q35.3 sideroflexin 1 HRH2 5q35.3 histamine receptor H2 CPLX2 5q35.1-q35.3 complexin 2 LOC389346 5 similar to hypothetical protein THOC3 5q35.2-q35.3 THO complex 3 LOC391851 5 similar to olfactory receptor MOR126-1 LOC389347 5 similar to NY-REN-7 antigen LOC391852 5 similar to MGC68922 protein LOC391853 5 similar to selenophosphate synthetase 1 FLJ44216 5q35.3 FLJ44216 protein KIAA1191 5q35.3 KIAA1191 protein MGC2198 5q35.3 hypothetical protein MGC2198 FLJ39249 5q35.3 ADP-ribosylation factor-like membrane-associated protein HSPC111 5q35.3 hypothetical protein HSPC111 CLTB 4q2-q3 clathrin, light polypeptide (Lcb) ETEA 5q35.3 expressed in T-cells and eosinophils in atopic dermatitis RNF44 5q35.3 ring finger protein 44
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    2 - 2224 - 267 - 2008 18349132
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectivebone   
    Connectivedenseligamentperidontal ligament 
    Connectivedensetendon  
    Epithelialbarrier liningepidermis highly
    cell lineage
    cell lines high in several cell lines
    fluid/secretion
    at STAGE
    physiological period embryo, fetal, pregnancy
    Text
  • developing teeth progenitor cells of orofacial skeletal structure (mandible, Meckel's cartilage), extra-embryonic tissues such as placenta
  • in the epidermis, hair follicles, and fibroblasts of the developing fetal skin
  • PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • helix-turn-helix, DNA binding domain
  • HOMOLOGY
    interspecies homolog to Drosophila,muscle segment (msh) 2
    Homologene
    FAMILY
  • MSH homeobox protein family (non HOX)
  • CATEGORY transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm
    intracellular,nucleus,chromatin/chromosome
    text detected as a diffuse cytoplasmic signal in fetal epidermis and portions of the hair follicle and dermis, but was localized to the nucleus in adult epidermis
    basic FUNCTION
  • involved in the enhancing of parietal bone growth and skull patterning
  • involved in epithelial-mesenchymal signaling in many organs
  • RNA polymerase 2 transcription factor, activating OSX and regulating osteogenic versus adipogenic differentiation of aortic myofibroblasts and of multipotent mesenchymal progenitor
  • involved in maintaining the suture space by stimulating suture mesenchymal cell proliferation
  • plays a pivotal role in craniofacial and limb development and tissue organogenesis
  • major regulator of the proliferation of MSX2-expressing osteoprogenitor cells and subsequent osteoblast differentiation
  • plays a crucial role in pancreatic cancer development by inducing changes consistent with epithelial to mesenchymal transition through enhanced expression of TWIST1
  • could induce apoptosis of optic vesicle
  • possesses dual regulatory functions in controlling cell cycle progression of retinal progenitor cells (RPCs) and timing of retinal ganglion cells differentiation
  • MSX1, MSX2 have a dual role in calvarial development
  • with RUNX2 function together to induce ENPP1 expression in osteoblastic cells
  • functioning as a transcriptional enhancer downstream of FGF2 in calvarial pre-osteoblasts
  • important functions for MSX2 and FOXN1 in regulating differentiation of the keratogenous zone, proliferation of distal nail matrix cells, and organization of the nail bed
  • homeodomain transcription factor that play a crucial role in limb development
  • mesenchymal expression of MSX1 and MSX2 is required for proper SHH and BMP4 signaling to specify digit number and identity
  • MSX1 and MSX2 promote meiosis initiation
  • DLX5 and MSX2 play potentially a critical role in controlling cranial neural tube morphogenesis by regulating cell adhesion via the EPHA5 and EPHA7 pathway
  • CELLULAR PROCESS nucleotide, transcription
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
  • a FOXC1/MSX2 regulatory network functions in the initial stages of osteoblast differentiation
  • a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interacting with MSX1 in mouse limb bud patterning through BMP4 regulation
  • regulating with TWIST1 the expression of EFNA4
  • inhibits the function of key osteogenic regulators, such as RUNX2, DLX3, and DLX5
  • promotes transcription of ENPP1 downstream of FGF2
  • direct downstream transcriptional target of CTNNB1/TCF and has a key contributing role in the cancer phenotype of ovarian endometrioid adenocarcinomas carrying WNT/CTNNB1 pathway defects
  • DLX3 and DLX5 proteins were found to activate the GPNMB transcription, whereas, MSX2 suppressed BMP2-induced GPNMB transcription
  • TNF enhances the WNT/CTNNB1 signaling pathway by inducing MSX2 expression, which in turn suppresses adipocytic differentiation
  • expression of MSX2 was down-regulated by HR, which in turn down-regulated expression of FOXN1 and LEF1, MSX2 target genes
  • MSX2 controls mesendoderm lineage commitment by simultaneous suppression of SOX2 and induction of NODAL expression through direct binding and activation of the NODAL promoter
  • complex feedback regulatory network may exist between BCL11B and MSX2
  • cell & other
    REGULATION
    induced by bone morphogenetic proteins
    Other affinity for DNA enhanced by PSIAX (MIZ1)
    ASSOCIATED DISORDERS
    corresponding disease(s) CRS2 , PFM2 , DUP5QD
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --other  
    various tumors of mesenchymal origin
    tumoral     --over  
    significantly correlated with higher tumor grade, vascular invasion, and TWIST1 expression
    tumoral     --other  
    aberrantly methylated promoter associated CpG islands in acute lymphocytic leukemia
    constitutional     --over  
    regulated retinal cells by affecting cell cycle and proliferation and caused delay in retinal ganglion cell commitment and differentiation
    constitutional       loss of function
    inactivation of its repressive activity may be one cause of Wormian bones, ectopic bones that are a feature of a variety of pathological conditions in which calvarial bone development is compromised
    tumoral     --over  
    markedly increased in primary human and murine OEAs with dysregulated CTNNB1compared with ovarian endometrioid adenocarcinoma with intact CTNNB1regulation
    Susceptibility to ankylosing spondylitis
    Variant & Polymorphism SNP increasing the risk of ankylosing spondylitis
    Candidate gene in cranial vault morphogenesis, sensitive to gene dosage; in cleft lip/palate
    Marker
  • it is possible to differentiate pancreatic ductal adenocarcinoma from chronic pancreatitis by evaluating MSX2 expression level
  • Therapy target
    ANIMAL & CELL MODELS
  • defects in bone growth and ectodermal organ formation in Msx2 deficient mice, premature cranial suture closure
  • expression of the Msx2 homeobox gene, an essential regulator of calvarial bone development is absent in the skull mesenchymal progenitors of Foxc1 mutant mice
  • Msx1;Msx2 double mutants are characterized by the loss of derivatives of the anterior limb mesoderm which is not observed in either of the simple mutants