Primary structure and tissue distribution of two novel proline-rich gamma-carboxyglutamic acid proteins.
Two human cDNAs that encode novel vitamin K-dependent proteins have been cloned and sequenced. The predicted amino acid sequences suggest that both are single-pass transmembrane proteins with amino-terminal gamma-carboxyglutamic acid-containing domains preceded by the typical propeptide sequences required for posttranslational gamma-carboxylation of glutamic acid residues. The polypeptides, with deduced molecular masses of 23 and 17 kDa, are proline-rich within their putative cytoplasmic domains and contain several copies of the sequences PPXY and PXXP, motifs found in a variety of signaling and cytoskeletal proteins. Accordingly, these two proteins have been called proline-rich Gla proteins (PRGP1 and PRGP2). Unlike the gamma-carboxyglutamic acid domain-containing proteins of the blood coagulation cascade, the two PRGPs are expressed in a variety of extrahepatic tissues, with PRGP1 and PRGP2 most abundantly expressed in the spinal cord and thyroid, respectively, among those tissues tested. Thus, these observations suggest a novel physiological role for these two new members of the vitamin K-dependent family of proteins.
Kulman
J D
JD
Department of Biochemistry, University of Washington, Seattle, WA 98195, USA. jkulman@u.washington.edu
Harris
J E
JE
Haldeman
B A
BA
Davie
E W
EW
D015055:1-Carboxyglutamic Acid; D000595:Amino Acid Sequence; D001483:Base Sequence; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D010455:Peptides / Q000235:genetics* / Q000378:metabolism; D011392:Proline; D055232:Proline-Rich Protein Domains; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D016415:Sequence Alignment; D017421:Sequence Analysis; D014812:Vitamin K / Q000378:metabolism*
D018076:DNA, Complementary; D010455:Peptides; D011506:Proteins; D014812:Vitamin K; D015055:1-Carboxyglutamic Acid; D011392:Proline