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FLASH GENE

Symbol

MGP

contributors: mct/npt - updated : 04-03-2019

HGNC name	matrix Gla protein
HGNC id	7060

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	KES Keutel syndrome
Location	12p12.3      Physical location : 15.034.114 - 15.038.853
Synonym name	matrix gamma-carboxylglutamate protein
	cell growth-inhibiting gene 36 protein
Synonym symbol(s)	MGLAP, NTI, GIG36

DNA

TYPE	functioning gene
STRUCTURE	5.20 kb     4 Exon(s)

10 Kb 5' upstream gene genomic sequence study

regulatory sequence	Promoter
	Binding site
text structure	binding site in the promoter for retinoic aci and vitamin D receptors
	promoter activity stimulated by BMP4 in a TGF-beta-dependent fashion

MAPPING

cloned

Y

linked

N

status

confirmed

Map	pter - D12S864 - D12S364 - D12S269 - D12S1347E - D12S847 - D12S1097 - D12S1272 - D12S1274 - (D12S308 ,D12S70 ) - GUCY2C - D12S1247E - MGP - PDE6H - ARHGDIB - D12S932 - D12S1136E - D12S62 - PTPRO - D12S1364E - D12S930 - D12S1728 - MGST1 - LMO3 - (D12S383E ,D12S1630 ,D12S373 ) - D12S363 - cen
Authors	4st Workshop chrom.12 (97)

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_001190839 5 - 1933 NP_001177768 - 128 - 2018 29529056 NM_000900 4 - 1858 NP_000891 12 103 - 2018 29529056

EXPRESSION

Type

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 vessel aorta     highly Homo sapiens Nervous brain         Reproductive male system prostate       Respiratory lung         Urinary kidney

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Connective bone       Muscular smooth       Muscular striatum skeletal

cells

System Cell Pubmed Species Stage Rna symbol   chondrocyte

cell lineage
cell lines	tumor associated endothelial cells
fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	a transmembrane signal peptide domain
	a putative gamma-carboxylation recognition site
	a Gla-containing domain

HOMOLOGY

interspecies	homolog to murine Mgp (83.5pc)
	homolog to rattus Mgp (79.6pc)

Homologene

FAMILY

osteocalcin/matrix GLA protein family

CATEGORY

structural protein

SUBCELLULAR LOCALIZATION	extracellular
text	extracellular matrix protein

basic FUNCTION	acting as an inhibitor of bone formation (associated with the organic matrix of bone and cartilage)
	regulating calcium deposition
	is involved in elastic fiber calcification in the dermis of pseudoxanthoma elasticum patients
	may inhibit calcification via binding to vascular smooth muscle cell-derived vesicles
	role of MGP in calcium and phosphate metabolism disturbances in the course of acute pancreatitis (AP)
	MGP is a multi-functional inhibitor of normal and abnormal angiogenesis that may function by coordinating with both NOTCH1 and BMP signaling pathways
	is a potent inhibitor of extracellular matrix (ECM) mineralization
	is an important inhibitor of vascular calcification, and regulates calcification of the aortic valve
	plays a role in preserving microcirculatory integrity
	role of activated MGP in maintaining myocardial integrity and diastolic left ventricular (LV) performance
	is inhibitor of ectopic calcification in vascular diseases (VD) and osteoarticular diseases (OD)

CELLULAR PROCESS	cell life, differentiation

PHYSIOLOGICAL PROCESS

development , ossification

PATHWAY

metabolism

signaling

a component

associating with the organic matrix of bone and cartilage

INTERACTION

DNA

RNA

small molecule

protein	BMP2 (negative regulatory protein of BMP2)
	binding to vitronectin
	interacting with BMP4 (inhibited BMP4 activity similarly to that of BMP2 and interacted with BMP4 on a protein level)
	HSPA4 binds MGP and enhances BMP activity, thereby functioning as a potential link between cellular stress, inflammation, and BMP signaling
	AGT may be involved in mediating load-induced activation of MGP expression
	CALU inhibits gamma-carboxylation of MGP preventing BMP2-dependent calcification
	NOTCH1 regulates MGP and calcification gene networks in human valve endothelium

cell & other

REGULATION

activated by

vitamin-K depedent gamma carboxylation and serine phosphorylation

induced by

activation of ALK1 signaling in addition to that of VEGF, allowing for negative feedback regulation of BMP by MGP

ASSOCIATED DISORDERS

corresponding disease(s)

KES

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional     --over   high expression of MGP in varicose veins may contribute to venous wall remodeling by affecting proliferation and mineralization process constitutional       loss of function impairs nasal septum growth, causing midface hypoplasia constitutional       loss of function loss of MGP causes dysregulation of early endothelial differentiation constitutional       loss of function leads to alterations of vascular extracellular matrix (ECM) that may in turn initiate arterial calcification 2) constitutional     --over   in patients with T2D and/or IHD increased levels of plasma MGP is indicative of a progressing calcification process

Susceptibility

to atherosclerosis and aortic valve stenosis

Variant & Polymorphism other	T138C variant
	MGP gene polymorphism is associated with kidney stones

Candidate gene
Marker	measurement of the serum MGP levels may also be of value to estimate mortality in intracerebral hemorrhage
Therapy target

ANIMAL & CELL MODELS

	MGP transgenic mice model with high expression od the transgene in the lung showed a disruption of the pulmonary pattern of BMP4 and resulted in significant morphological defects in the pulmonary artery tree. Abnormalities were also found in the terminal airways and in lung cell differentiation
	Mgp(-/-)) mice show progressive deposition of hydroxyapatite minerals in the arterial walls and die within 2 months of age