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Symbol BMP2 contributors: mct - updated : 18-01-2016
HGNC name bone morphogenetic protein 2
HGNC id 1069
Corresponding disease
DEL20P12 chromosome 20p12 interstitial deletions
SSSCH short stature, skeletal anomalies, and congenital heart disease
WPW2 Wolff-Parkinson-White syndrome
Location 20p12.3      Physical location : 6.748.744 - 6.760.910
Synonym name bone morphogenetic protein 2A
Synonym symbol(s) BMP2A
TYPE functioning gene
STRUCTURE 12.17 kb     3 Exon(s)
10 Kb 5' upstream gene genomic sequence study
regulatory sequence Promoter
Binding site   silencer   transcription factor
text structure
  • binding sites for CBFA1
  • a consensus Sp1 site (GGGCGG) in the reverse orientation relative to the promoter is located in a highly GC-rich region that may include other sites that Sp1 proteins could bind (Sp1 and Sp3 complexes on the BMP2 promoter influencing BMP2 expression)
  • GC-rich sequences within the promoter region that strongly repress gene expression (Jiang 2010)
  • an autonomous BMP2 regulatory element in mesenchymal cells
  • MAPPING cloned Y linked N status confirmed
    Map pter - ADRA1D - PRNP - D20S732 - D20S192 - D20S59 - BMP2 - D20S483 - D20S755 - D20S900 - D20S115 - D20S621 - D20S1128 - D20S907 - D20S177 - cen
    Physical map
    C20orf30 20p13 chromosome 20 open reading frame 30 PCNA 20p12.3 proliferating cell nuclear antigen CDS2 20p13 CDP-diacylglycerol synthase (phosphatidate cytidylyltransferase) 2 LOC388784 20 similar to dJ680N4.2 (ubiquitin-conjugating enzyme E2D 3 (homologous to yeast UBC4/5)) GPR73L1 20p13 G protein-coupled receptor 73-like 1 LOC388785 20 hypothetical gene supported by AK090863 MGC35023 20p13 hypothetical protein MGC35023 LOC388786 20 LOC388786 LOC388787 20 LOC388787 RPS18P1 20p13 ribosomal protein S18 pseudogene 1 KIAA1434 20p13 hypothetical protein KIAA1434 EIF4EL2 20p13 eukaryotic translation initiation factor 4E-like 2 FLJ25067 20p13 hypothetical protein FLJ25067 CHGB 20p12.3 chromogranin B (secretogranin 1) LOC391230 20 similar to ankyrin repeat domain protein 15; kidney ankyrin repeat-containing protein CGI-09 20p13 CGI-09 protein MCM8 20p12.3 MCM8 minichromosome maintenance deficient 8 (S. cerevisiae) C20orf155 20p13-p12.3 chromosome 20 open reading frame 155 C20orf75 20p13 chromosome 20 open reading frame 75 C20orf42 20p12.3 chromosome 20 open reading frame 42 LOC219414 20p12.3 similar to TAR DNA binding protein LOC149844 20p12.3 NS1-associated protein 1 pseudogene BMP2 20p12 bone morphogenetic protein 2 pFUSIP1 20p12.3 FUSIP1 pseudogene HAO1 20p12.3 hydroxyacid oxidase (glycolate oxidase) 1 DJ971N18.2 20p12 hypothetical protein DJ971N18.2 PHKBP1 20p12.3-20p12.2 phosphorylase kinase, beta pseudogene 1 PLCB1 20p12 phospholipase C, beta 1 (phosphoinositide-specific)
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    3 - 3150 42.5 396 - 2011 21984813
  • preproprotein
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   lowly
    Digestiveintestinesmall intestine  lowly
     intestinelarge intestinecolon highly
     liver   lowly
    Endocrinepancreas   lowly
    Lymphoid/Immunespleen   highly
    Nervousbrain   lowly Homo sapiens
    Reproductivefemale systemplacenta  lowly
     female systemovary  lowly
     male systemprostate  lowly
    Respiratorylung   highly
    Urinarykidney   lowly
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Muscularstriatumskeletal lowly
    SystemCellPubmedSpeciesStageRna symbol
    Nervousastrocyte Homo sapiens
    Skeletonosteoclast Homo sapiens
    cell lineage
    cell lines
    at STAGE
    physiological period embryo, fetal, neonatal, pregnancy
    Text mesoderm under SHM control through the mediation of SOX9, placenta, tooth and skeletal developing structures, trabecular meshwork, cardiac myocyte
  • astacin-like domain cleaved at a consensus Arg-X-X-Arg
  • to yield C-term mature dimer
    conjugated GlycoP
    mono polymer homomer , dimer
    isoforms Precursor .proBMP-2 contains two proprotein convertase (PC) recognition sites (S1 and S2) and is postulated to be cleaved by PCs at those site
    interspecies homolog to rattus Bmp2 (92.1pc)
    homolog to murine Bmp2 (92.4pc)
  • transforming growth factor-beta (TGFB) superfamily
  • CATEGORY signaling growth factor
    text secreted
    basic FUNCTION
  • putative protease, regulating myogenesis through dosage-dependent PAX3 expression in pre-myogenic cells
  • involved in bone formation (in osteogenic differentiation, not chondrogenic)
  • promoting chondrogenic differentition of multipotential mesenchymal cells
  • inducing placental growth factor in mesenchymal stem cells
  • important regulator of osteoblast differentiation, (regulation of Notch signaling genes during differentiation of osteoblast precursor cells)
  • necessary component of the signaling cascade that governs fracture repair
  • key mediator of bone development and repair
  • promoting tumor growth
  • plays a vital role in odontoblast function via diverse signal transduction systems
  • mediates DSPP gene expression and odontoblast differentiation via NF-Y signaling during tooth development
  • control CDKN1C expression and cell growth arrest/terminal differentiation in normal primary epidermal keratinocytes
  • significantly induced latexin expression in RUNX2-deficient mesenchymal cells, during chondrocyte and osteoblast differentiation
  • induces Runx2-deficient cells to express markers related to osteoblast and chondroblast differentiation using a Runx2-independent pathway, but it failed to induce these cells to differentiate into bone-forming osteoblasts and mature chondrocytes
  • mediates embryonic cardiac contractility upstream of myocyte-specific enhancer factor 2A (MEF2A)
  • involved in the pathobiology of cartilaginous and osteogenic metaplasia observed in synovial chondromatosis
  • required for cardiac contractility and MEF2A expression can be activated by BMP2 signaling in neonatal cardiomyocytes
  • involved in the assembly of the cardiac contractile apparatus
  • BMP2 divergently regulates mRNA expression of various K(V) channel alpha-, beta-, and gamma-subunits and significantly increases whole cell K(V) currents
  • activating SOX9 (activation associated with chromatin remodeling and histone modification)
  • promotes motility and invasion of gastric cancer cells by activating PI-3 kinase/Akt pathway
  • both BMP2 and BMP4 can suppress the expression of DPYSL2 in primary cortical cells at the transcriptional level
  • morphogen that controls mesenchymal cell differentiation and behavior
  • regulates the osteogenic function of DLX5, at least in part, through PRKACA
  • regulate the function of DLX5 by post-translational modification through PRKACA, MAPK14 and possibly other kinases in addition to its regulation on DLX5 transcription
  • regulates the osteogenic function of Osterix (SP7), at least in part, through AKT1
  • induces RUNX2 expression at both the transcriptional and post-transcriptional level
  • increases ER stress, which, in turn, leads to increased expression of RUNX2
  • in coronary artery smooth muscle cell, increases oxidant stress and ER stress to increase RUNX2 expression and promote vascular smooth muscle cell calcification
  • BMP2-induced osteoblast differentiation mediates mild ER stress-activated ATF6 and directly regulates BGLAP expression
  • regulates osteoblast differentiation via RUNX2-dependent ATF6 expression and activation of ATF6 via ER stress-induced intramembrane proteolysis process
  • BMP2 mediates mild endoplasmic reticulum stress-activated ATF6 and directly regulates XBP1 splicing in the course of chondrogenesis
  • endogenous BMP2 expression in chondrocytes may play an essential role in cartilage callus maturation at an early stage of fracture healing
  • BMP2 and BMP7 both promoted odontogenic and osteogenic differentiation of tooth germ stem cells (hTGSCs)
  • important role of BMP2 in human craniofacial, skeletal, and cardiac development
    text regulator of cell cycle progression (antiproliferative agent in breast and other cancer cell lines, in multiple myeloma cells)
    signaling signal transduction
  • signaling cooperatively with LIF through a complex formed by STAT3 and MADH1, bridged by EP300, and the subsequent induction of astrocytes differentiation
  • BMP2-RUNX2-ATF6 signal pathway positively regulates osteoblast differentiation and extracellular matrix mineralization
  • BMP2 and MEF2A are key components of a pathway that controls the cardiac ventricular contractility
  • a component
  • disulfide-linked homodimer
  • heterodimer BMP2/BMP6 (BMP2/6) compared to the homodimers BMP2 or BMP6 is more potent for inducing differentiation of embryonic stem (hES) cells
    small molecule
  • STAT3, with DLX2 for the signaling to the Col2A1 in chondroblasts
  • interaction with PIK3 and AKT1 for osteoblast differentiation
  • interacting with BMPR1B, to mediates apoptosis independently of differentiation in osteoblastic cells
  • cooperatively interact with RUNX2 to stimulate osteoblast gene expression
  • regulates DSPP gene transcription and thus odontoblast differentiation
  • interacting with SOSTDC1, GREM2, RGMA, RGMB, HFE2, ASPN
  • negatively regulates BMP2-induced osteoblast differentiation through inhibition of Wnt signaling
  • WFIKKN1 and WFIKKN2 proteins are antagonists of MSTN and GDF11, but in the case of TGFB1, BMP2 and BMP4 they function as growth factor binding proteins
  • BMP2 and BMP4 bind to neogenin (NEO1) (BMP2 binding to neogenin activated RHOA)
  • enhances RUNX2 protein levels through inhibition of CDK4 and subsequent prevention of RUNX2 ubiquitylation and proteasomal degradation
  • induces osteoblast differentiation through RUNX2-dependent ATF6 expression, which directly regulates BGLAP transcription
  • differential regulation of GREM1 and GREM2 gene expressions by BMP2 may explain the critical function of these genes during osteoblast differentiation
  • S1PR1-mediated signaling enhances BMP2 induced osteoblast differentiation
  • apoptotic effect of BMP2 is dependent on cell maturation state, inducing apoptosis in committed osteoblasts through SMAD and TAB/TAK1 signaling, and is regulated by NOG
  • GATA6 promotes cell survival by regulating endoderm expression of BMP2 and basement membrane (BM)during embryonic epithelial morphogenesis
  • BMP2 is known to activate unfolded protein response signaling molecules, including XBP1 and ATF6
  • WNT/CTNNB1 signaling pathway is an upstream activator of BMP2 expression in osteoblasts
  • PARM1 may regulate EIF2AK3, ATF6, and DDIT3 expression through BMP2 expression
  • decreases periosteal cell proliferation and induces apoptosis via the activation of Wnt inhibitors DKK1 and SOST
  • BMP2 signaling regulates NPY1R expression, and raises the possibility that NPY acts in osteoblasts via an autocrine mechanism
  • transcriptional repression of BMP2 by CDKN1A links quiescence to neural stem cell maintenance
  • FBLN1 is required for bone formation and BMP2-mediated induction of SP7
  • GREM1 preferentially binds to BMP2 and this may be the dominant complex in a disease situation where levels of GREM1 and BMPs are elevated
  • CALU inhibits gamma-carboxylation of MGP preventing BMP2-dependent calcification
  • ID3 is the BMP2-induced transcriptional regulator, promoting adult neural stem/precursor cells (NSPCs) differentiation into astrocytes upon CNS injury
  • HFE2 can simultaneously bind to both BMP2 and the ubiquitously expressed cell surface receptor NEO1
  • GATA4 and LMO3 balance angiocrine signaling and autocrine inflammatory activation by BMP2 in liver sinusoidal endothelial cells
  • cell & other
  • SMADs (MADH1)
    activated by cleaved by subtilin-like convertase
    repressed by Noggin at the extracellular level
  • enhancement of BMP2 gene transcription and subsequent bone formation is due to inhibition of microtubule assembly that results in inhibition of proteasomal processing of GLI2 and intracellular accumulation
    corresponding disease(s) WPW2 , DEL20P12 , SSSCH
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    in prostate and breast cancers and in the microadenomas of familial adenomatous polyposis
    tumoral     --other  
    aberrant expression in approximately 98p100 of lung carcinomas
    constitutional     --over  
    in synovial chondromatosis
    constitutional   amplification    
    duplications involving a conserved regulatory element downstream of BMP2 are associated with brachydactyly type A2
    Susceptibility to nonsyndromic sagittal craniosynostosis
    Variant & Polymorphism SNP
  • modulating hemochromatosis penetrance
  • a 120-kb region downstream of BMP2 flanked by rs1884302, susceptibility loci for nonsyndromic sagittal craniosynostosis
  • Candidate gene to cleft palate and additional anomalies in del20p12.3
    Therapy target
    BMP antagonists such as noggin might be useful therapeutic tools for preventing chondrogenic metaplasia occurred in synovial chondromatosis
    BMP2-MEF2A pathway can offer new opportunities for the treatment of heart failure
  • short stature and skeletal anomalies in a heterozygous Bmp2-knockout mouse model
  • Bmp2-null mice show embryonic lethality with failure of amnion and chorion formation and abnormal cardiac development