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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

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

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

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_001204 13 - 12086 NP_001195 115.2 1038 - 1999 9885250 variant 2 - splicing 1964 isoform 2 59 530 - 1995 7890683 lacking the long cytoplasmic tail

EXPRESSION

Type	ubiquitous

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 Cardiovascular heart           vessel       highly Digestive intestine large intestine colon       liver         Nervous nerve         Respiratory respiratory tract larynx     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)

Type Gene Modification Chromosome rearrangement Protein expression Protein 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