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FLASH GENE
Symbol BMPR2 contributors: mct/npt/pgu - updated : 01-10-2015
HGNC name bone morphogenetic protein receptor, type II (serine/threonine kinase)
HGNC id 1078
Corresponding disease
PPH1 pulmonary hypertension, primary
Location 2q33.2      Physical location : 203.241.049 - 203.432.473
Synonym name
  • serine/threonine kinase
  • type II activin receptor-like kinase
  • BMP type II receptor
  • type II receptor for bone morphogenetic protein-4
  • Synonym symbol(s) BMPR3, BRK3, BMR2, TALK, BMPR-II, FLJ41585, FLJ76945
    EC.number 2.7.11.30
    DNA
    TYPE functioning gene
    STRUCTURE 191.42 kb     13 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status confirmed
    Physical map
    BZW1 2q33 basic leucine zipper and W2 domains 1 LOC391472 2 similar to bA476B13.3 (KIAA0699 protein) CLK1 2q33 CDC-like kinase 1 PPIL3 2q33 peptidylprolyl isomerase (cyclophilin)-like 3 NIF3L1 2q33-q34 NIF3 NGG1 interacting factor 3-like 1 (S. pombe) ORC2L 2q33 origin recognition complex, subunit 2-like (yeast) MGC39518 2q33.2 hypothetical protein MGC39518 NDUFB3 2q31.3 NADH dehydrogenase (ubiquinone) 1 beta subcomplex, 3, 12kDa CFLAR 2q33 CASP8 and FADD-like apoptosis regulator CASP10 2q33-q34 caspase 10, apoptosis-related cysteine protease CASP8 2q33-q34 caspase 8, apoptosis-related cysteine protease ALS2CR12 2q33.2 amyotrophic lateral sclerosis 2 (juvenile) chromosome region, candidate 12 ALS2CR3 2q33 amyotrophic lateral sclerosis 2 (juvenile) chromosome region, candidate 3 ALS2CR2 2q33-q34 amyotrophic lateral sclerosis 2 (juvenile) chromosome region, candidate 2 FLJ25351 2q33.2 hypothetical protein FLJ25351 ALS2CR4 2q33 amyotrophic lateral sclerosis 2 (juvenile) chromosome region, candidate 4 MPP4 2q33.2 membrane protein, palmitoylated 4 (MAGUK p55 subfamily member 4) ALS2 2q33.2 amyotrophic lateral sclerosis 2 (juvenile) LOC151256 2q33.2 hypothetical LOC151256 ALS2CR7 2q33.2 amyotrophic lateral sclerosis 2 (juvenile) chromosome region, candidate 7 FZD7 2q33 frizzled homolog 7 (Drosophila) FLJ39061 2q33.2 hypothetical protein FLJ39061 LOC339809 2q33.2 KIAA2012 protein UBL1 2q32.3-q33 ubiquitin-like 1 (sentrin) NOP5/NOP58 2q33.2 ubiquitin-like 1 (sentrin) BMPR2 2q33-q34 bone morphogenetic protein receptor, type II (serine/threonine kinase) FLJ38771 LOC130026 ALS2CR14 2q33 amyotrophic lateral sclerosis 2 (juvenile) chromosome region, candidate 14 WDR12 2q33.2 WD repeat domain 12 ALS2CR8 2q33.2 amyotrophic lateral sclerosis 2 (juvenile) chromosome region, candidate 8 LOC130029 2q33.3 similar to CG1308-PA ALS2CR17 2q33.3 amyotrophic lateral sclerosis 2 (juvenile) chromosome region, candidate 17 CYP20A1 2q33 cytochrome P450, family 20, subfamily A, polypeptide 1 ABI-2 2q33 abl-interactor 2 MRPL50P2 2q34 abl-interactor 2 RAPH1 2q33 Ras association (RalGDS/AF-6)and plekstrin homology 1 LOC344461 2q33.3 similar to ZNF207 protein CD28 2q33 CD28 antigen (Tp44) LOC344462 2q33.3 similar to Keratin, type I cytoskeletal 18 (Cytokeratin 18) (K18) (CK 18) CTLA4 2q33 cytotoxic T-lymphocyte-associated protein 4
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    13 - 12086 115.2 1038 - 1999 9885250
    - splicing 1964 59 530 - 1995 7890683
    lacking the long cytoplasmic tail
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart    
     vessel   highly
    Digestiveintestinelarge intestinecolon  
     liver    
    Nervousnerve    
    Respiratoryrespiratory tractlarynx  highly
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period embryo
    Text trabecular meshwork
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • four discrete functional domains, including an extracellular ligand-binding domain encoded by exons 1-3,
  • a transmembrane domain (TM1) generated by exon 4
  • A GS domain
  • a cytoplasmic tail
  • a serine/threonine kinase domain from exon 5-11
  • a very large intracellular C-terminal domain of unknown function from exons 12 and 1
  • mono polymer heteromer , dimer
    isoforms Precursor
    HOMOLOGY
    interspecies ortholog to murine Bmpr2
    intraspecies homolog to ACVR2
    Homologene
    FAMILY
  • protein kinase superfamily
  • TKL Ser/Thr protein kinase family
  • TGFB receptor subfamily
  • CATEGORY receptor membrane
    SUBCELLULAR LOCALIZATION     plasma membrane
    basic FUNCTION
  • activating type I receptor kinase domain (ligand binding)
  • maintenance of vascular endothelium integrity
  • may play an important role in the pathogenesis of myelofibrosis in primary myelofibrosis and are apparently induced by cytokines such as TGFbeta-1
  • being a modulator of glucocorticoid signaling
  • contributing with ACVRL1 to growth inhibition of human pulmonary artery endothelial cells
  • plays a major role in early development, carcinogenesis, and vascular disease, particularly pulmonary arterial hypertension (PAH)
  • constitutively turned over through the lysosomal pathway by endogenous E3 ligases
  • not required for endochondral ossification in the limb where loss of BMPR2 may be compensated by BMP utilization of ACVR2A and ACVR2B
  • has tumor-suppressive function in mammary epithelia and microenvironment and that disruption can accelerate mammary carcinoma metastases
  • promotes pulmonary artery endothelial cell (PAEC) survival, proliferation, and migration
  • essential for postimplantation physiology and fertility
  • regulates SMAD1 in a biphasic manner, promoting SMAD1 signaling through its kinase domain but suppressing it through its cytoplasmic tail 9)
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS development
    text skeletal development
    PATHWAY
    metabolism
    signaling signal transduction
  • BMPR2 pathway mediate survival signaling in endothelial cells (EC), and thus the reduced activity will favor endothelial apoptosis, likely increasing the susceptibility to endothelial injury in response to various environmental triggers
  • constitutive lysosomal pathway regulating cell surface expression of BMPR2 and implicating the likely involvement of the mammalian E3 ligase, ITCH, in this process
  • a component
  • complexing with type I BMP receptors, BMPR1A, BMPR1B
  • INTERACTION
    DNA
    RNA
    small molecule
  • ATP
  • protein
  • activating Smad proteins (MAPH) when ligands are bound to preformed-receptor complex
  • binding BMP2, BMP4, BMP7
  • activating alkaline phosphatase via MAP kinase BMP2 induces recruitment of receptors
  • BMP2 induced recruitment of receptors activating the p38 MAP kinases resulting in an increase of alkaline phosphatase
  • tenascin-C is induced by mutated BMP type II receptors in familial forms of pulmonary arterial hypertension
  • caveolin-1 is an important regulator of downstream signaling and membrane targeting of BMPR2 in vascular smooth muscle cells
  • interacting with K5, the viral lytic gene, E3 ubiquitin ligase (K5 targets the membrane-proximal lysine of BMPR2, Lys-180)
  • requirement for BMPR2 in tumors to prevent CCL9 secretion and the recruitment of myeloid cells
  • BMPR2 ligands, BMP2 and BMP4, stimulate NOS3 phosphorylation at a critical regulatory site
  • PLXNA2 was associated with both type 1 and 2 BMP receptors (BMPR1A, BMPR2), and BMP2 increased the interaction between PLXNA2 and type 1 receptors
  • NIPA1 interacts with the type II BMP receptor (BMPR2) and promotes its degradation through endocytosis and lysosomal degradation
  • ACVR2A and and BMPR2 physically interact, and each also interacts with endoglin
  • SMYD2 may promote BMP signaling by directly methylating BMPR2, which, in turn, stimulates BMPR2 kinase activity and activation of the BMP pathway
  • cell & other
    REGULATION
    Other its expression is constitutively regulated by the lysosome and that an endogenous mammalian E3 ligase may be involved in this process
    ASSOCIATED DISORDERS
    corresponding disease(s) PPH1
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in myelofibrosis
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • deletion of Bmpr2 in the uterine deciduae of mice triggered midgestation abnormalities in decidualization that resulted in abnormal vascular development, trophoblast defects, and a deficiency of uterine natural killer cells