Matrix Gla protein and osteocalcin: from gene duplication to neofunctionalization

Arch Biochem Biophys. 2014 Nov 1;561:56-63. doi: 10.1016/ Epub 2014 Jul 25.


Osteocalcin (OC or bone Gla protein, BGP) and matrix Gla protein (MGP) are two members of the growing family of vitamin K-dependent (VKD) proteins. They were the first VKD proteins found not to be involved in coagulation and synthesized outside the liver. Both proteins were isolated from bone although it is now known that only OC is synthesized by bone cells under normal physiological conditions, but since both proteins can bind calcium and hydroxyapatite, they can also accumulate in bone. Both OC and MGP share similar structural features, both in terms of protein domains and gene organization. OC gene is likely to have appeared from MGP through a tandem gene duplication that occurred concomitantly with the appearance of the bony vertebrates. Despite their relatively close relationship and the fact that both can bind calcium and affect mineralization, their functions are not redundant and they also have other unrelated functions. Interestingly, these two proteins appear to have followed quite different evolutionary strategies in order to acquire novel functionalities, with OC following a gene duplication strategy while MGP variability was obtained mostly by the use of multiple promoters and alternative splicing, leading to proteins with additional functional characteristics and alternative gene regulatory pathways.

Keywords: Gene architecture; Gene duplication; Matrix Gla protein; Molecular evolution; Osteocalcin; Protein structure; Splicing variants.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Bone and Bones / physiology*
  • Calcium-Binding Proteins / genetics*
  • Evolution, Molecular
  • Extracellular Matrix Proteins / genetics*
  • Gene Duplication / genetics*
  • Gene Expression Regulation, Developmental / physiology
  • Humans
  • Models, Genetic
  • Osteocalcin / genetics*


  • Calcium-Binding Proteins
  • Extracellular Matrix Proteins
  • matrix Gla protein
  • Osteocalcin