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FLASH GENE

Symbol

BMPER

contributors: mct/ - updated : 18-09-2013

HGNC name	BMP binding endothelial regulator
HGNC id	24154

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	DIASD diaphanospondylodysostosis
Location	7p14.3      Physical location : 33.945.111 - 34.194.111
Synonym name	crossveinless 2
	likely ortholog of mouse BMP-binding endothelial regulator precursor protein
	bone morphogenetic protein-binding endothelial cell precursor-derived regulator
Synonym symbol(s)	CRIM3, CV-2, CV2, KIAA1965

DNA

TYPE	functioning gene
SPECIAL FEATURE	arranged in tandem
STRUCTURE	250.96 kb     15 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

N

status

provisional

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_133468 15 - 3399 NP_597725 - 685 - 2008 18787191

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 Cardiovascular heart         Homo sapiens Digestive mouth tongue     highly Homo sapiens   stomach       moderately Mus musculus Lymphoid/Immune spleen       highly Mus musculus Nervous brain       highly Mus musculus Respiratory lung         Homo sapiens   lung       highly Mus musculus Skin/Tegument skin         Homo sapiens

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Connective adipose     moderately Mus musculus Muscular smooth vessel   highly Homo sapiens Muscular striatum skeletal     Homo sapiens

cells

System Cell Pubmed Species Stage Rna symbol Cardiovascular endothelial cell Homo sapiens not specific chondrocyte Homo sapiens

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

embryo, pregnancy

Text	placenta, in embryonic endothelial precursor cells

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	five N-terminal well conserved cysteine repeat regions (CR1–5), which are involved in BMP binding
	five tandem von Willebrand C-like domains at the N-terminal side, which are considered to form a BMP-binding site, one of five VWCs from chordin, can bind BMPs
	five Chordin-like cysteine-rich domains
	C-terminal containing a furin-like, a von Willebrand type D, and a trypsin inhibitor domain

HOMOLOGY

interspecies

ortholog to Drosophila melanogaster Crossveinless-2

Homologene

FAMILY

crossveinless 2 family

CATEGORY

regulatory

SUBCELLULAR LOCALIZATION	extracellular
	intracellular
	intracellular,cytoplasm,organelle,membrane
	intracellular,cytoplasm,organelle,endoplasmic reticulum

basic FUNCTION	involved in cell adhesion and, binding of sperm to zona pellucida
	antagonizing bone morphogenetic protein signaling and endothelial cell differentiation
	regulating BMP responsiveness of osteoblasts and chondrocytes and inhibitor of BMP function
	with chordin, and CHRDL2, regulate BMP2 signaling by different recognition mechanisms
	permissive and necessary role for SMAD1/5 phosphorylation and induces Erk1/2 activation (necessary for BMP4 to exert its activating role in endothelial function and to induce SMAD1/5 activation)
	dose-dependent endothelial cell activator that plays a unique and pivotal role in fine-tuning BMP activity in angiogenesis
	plays an important role in endothelial cell function and blood vessel formation (Helbing 2009)
	key regulator of BMP4 activity and a prerequisite for BMP pathway activation by BMP4 in endothelial cells
	requirement for BMPER-mediated signaling in vertebral development
	is a new protective regulator of vascular inflammation that modulates leukocyte adhesion and migration
	BMP modulator BMPER is highly expressed in malignant tumors and tumor growth is dependent on the presence of BMPER
	was more potent at inhibiting BMP effects compared with TWSG1, and there was no evidence of a significant additive anti-BMP effect of BMPER and TWSG1 together
	may play a role in suppressing hepcidin in other forms of severe chronic anemia with iron loading or in diseases where there is a significant amount of angiogenesis
	mutual regulation by GDF2 and BMPER is essential in regulating the development of the vascular endothelium
	critical regulator of BMP-mediated vascular inflammation and that the fine-tuning of BMP and BMPER levels is essential in the maintenance of normal vascular homeostasis
	is a novel regulator of osteoblast-like differentiation of VSMCs
	is a novel regulator of the osteoblast-like differentiation of human coronary artery SMCs
	appears to play a role in regulating both vessel density and cardiac development
	BMPER and TWSG1 maintain a fine-tuned equilibrium that controls BMP pathway activity and is necessary for vascular cell homeostasis

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

INTERACTION

DNA

RNA

small molecule

protein	with BMP2, BMP4, and BMP6
	downstream target of FOXO3a and consistently exerts activating effects on endothelial cell sprouting and migration
	inhibited the effects of both BMP2 and BMP6 on hepcidin production, although the effect on BMP6 was less pronounced than that for BMP2
	disrupts complex formation involving ALK2, ALK1, BMP4, and GDF2 required for the induction of both BMP antagonists
	TWSG1 and BMPER interfere with each other to enhance proangiogenic events

cell & other

REGULATION

activated by

Krüppel-like factor (KLF)15 (KLF15 is a transducer of endothelin-1 activity on BMPER expression)

inhibited by

endothelin-1 in a dose-dependent fashion and in parallel to KLF15

ASSOCIATED DISORDERS

corresponding disease(s)

DIASD

Susceptibility

Variant & Polymorphism

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed miscelleaneous vascular   may be a potential target for prevention of vascular calcification

ANIMAL & CELL MODELS