title: Vitamin K-dependent proteins in Ciona intestinalis, a basal chordate lacking a blood coagulation cascade.
abstract: We have isolated and sequenced several cDNAs derived from the sea squirt Ciona intestinalis that encode vitamin K-dependent proteins. Four of these encode gamma-carboxyglutamic acid (Gla) domain-containing proteins, which we have named Ci-Gla1 through Ci-Gla4. Two additional cDNAs encode the apparent orthologs of gamma-glutamyl carboxylase and vitamin K epoxide reductase. Ci-Gla1 undergoes gamma-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, gamma-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.
authors.affiliation: Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
authors.forename: John D
authors.initials: JD
authors.lastname: Kulman
authors.forename: Jeff E
authors.initials: JE
authors.lastname: Harris
authors.forename: Noriko
authors.initials: N
authors.lastname: Nakazawa
authors.forename: Michio
authors.initials: M
authors.lastname: Ogasawara
authors.forename: Masanobu
authors.initials: M
authors.lastname: Satake
authors.forename: Earl W
authors.initials: EW
authors.lastname: Davie
mesh_terms: D015055:1-Carboxyglutamic Acid / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001777:Blood Coagulation; D002938:Ciona intestinalis / Q000737:chemistry / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D017124:Conserved Sequence; D015870:Gene Expression / Q000235:genetics; D017403:In Situ Hybridization; D008969:Molecular Sequence Data; D011506:Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D014812:Vitamin K / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D011506:Proteins; D014812:Vitamin K; D015055:1-Carboxyglutamic Acid