Vitamin K-dependent proteins in Ciona intestinalis, a basal chordate lacking a blood coagulation cascade

John D. Kulman, Jeff E. Harris, Noriko Nakazawa, Michio Ogasawara, Masanobu Satake, Earl W. Davie

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29 Citations (Scopus)


We have isolated and sequenced several cDNAs derived from the sea squirt Ciona intestinalis that encode vitamin K-dependent proteins. Four of these encode γ-carboxyglutamic acid (Gla) domain-containing proteins, which we have named Ci-Gla1 through Ci-Gla4. Two additional cDNAs encode the apparent orthologs of γ-glutamyl carboxylase and vitamin K epoxide reductase. Ci-Gla1 undergoes γ-glutamyl carboxylation when expressed in CHO cells and is homologous to Gla-RTK, a putative receptor tyrosine kinase previously identified in a related ascidian. The remaining three Gla domain proteins are similar to proteins that participate in fundamental developmental processes, complement regulation, and blood coagulation. These proteins are generally expressed at low levels throughout development and exhibit either relatively constant expression (Ci-Gla1, γ-glutamyl carboxylase, and vitamin K epoxide reductase) or spatiotemporal regulation (Ci-Gla2, -3, and -4). These results demonstrate the evolutionary emergence of the vitamin K-dependent Gla domain before the divergence of vertebrates and urochordates and suggest novel functions for Gla domain proteins distinct from their roles in vertebrate hemostasis. In addition, these findings highlight the usefulness of C. intestinalis as a model organism for investigating vitamin K-dependent physiological phenomena, which may be conserved among the chordate subphyla.

Original languageEnglish
Pages (from-to)15794-15799
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number43
Publication statusPublished - 2006 Oct 24
Externally publishedYes


  • Ascidian
  • Urochordate
  • Warfarin
  • γ-carboxyglutamic acid

ASJC Scopus subject areas

  • General


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