Matrix Gla protein explained

Matrix Gla protein (MGP) is member of a family of vitamin K₂ dependent, Gla-containing proteins. MGP has a high affinity binding to calcium ions, similar to other Gla-containing proteins. The protein acts as an inhibitor of vascular mineralization and plays a role in bone organization.^{[1] [2]}

MGP is found in a number of body tissues in mammals, birds, and fish. Its mRNA is present in bone, cartilage, heart, and kidney.^[3]

It is present in bone together with the related vitamin K2-dependent protein osteocalcin. In bone, its production is increased by vitamin D.

Genetics

The MGP was linked to the short arm of chromosome 12 in 1990.^[4] Its mRNA sequence length is 585 bases long in humans.^[5]

Physiology

MGP and osteocalcin are both calcium-binding proteins that may participate in the organisation of bone tissue. Both have glutamate residues that are post-translationally carboxylated by the enzyme gamma-glutamyl carboxylase in a reaction that requires Vitamin K hydroquinone.

Role in disease

Abnormalities in the MGP gene have been linked with Keutel syndrome, a rare condition characterised by abnormal calcium deposition in cartilage, peripheral stenosis of the pulmonary artery, and midfacial hypoplasia.^[6]

Mice that lack MGP develop to term but die within two months as a result of arterial calcification which leads to blood-vessel rupture.

Notes and References

1. Yao Y, Jumabay M, Ly A, Radparvar M, Cubberly MR, Boström KI . A role for the endothelium in vascular calcification . Circ. Res. . 113 . 5 . 495–504 . 2013 . 23852538 . 3851028 . 10.1161/CIRCRESAHA.113.301792 .
2. Luo G, Ducy P, McKee MD, Pinero GJ, Loyer E, Behringer RR, Karsenty G . Spontaneous calcification of arteries and cartilage in mice lacking matrix GLA protein . Nature . 386 . 6620 . 78–81 . March 1997 . 9052783 . 10.1038/386078a0 . 1997Natur.386...78L . 4335985 .
3. Pinto JP, Conceição N, Gavaia PJ, Cancela ML . Matrix Gla protein gene expression and protein accumulation colocalize with cartilage distribution during development of the teleost fish Sparus aurata . Bone . 32 . 3 . 201–10 . 2003 . 12667547 . 10.1016/S8756-3282(02)00981-X .
4. Cancela L, Hsieh CL, Francke U, Price PA . Molecular structure, chromosome assignment, and promoter organization of the human matrix Gla protein gene . J. Biol. Chem. . 265 . 25 . 15040–8 . 1990 . 10.1016/S0021-9258(18)77221-9 . 2394711 . free .
5. Web site: Sequence: M58549.1 : Human matrix Gla protein (MGP) mRNA, complete cds. . European Nucleotide Archive . European Bioinformatics Institute .
6. Munroe PB, Olgunturk RO, Fryns JP, Van Maldergem L, Ziereisen F, Yuksel B, Gardiner RM, Chung E . Mutations in the gene encoding the human matrix Gla protein cause Keutel syndrome . Nat. Genet. . 21 . 1 . 142–4 . 1999 . 9916809 . 10.1038/5102 . 1244954 .