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Blood, 15 April 2005, Vol. 105, No. 8, pp. 3149-3154. Prepublished online as a Blood First Edition Paper on December 30, 2004; DOI 10.1182/blood-2004-06-2250. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-06-2250v1 105/8/3149    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Souri, M. Articles by Ichinose, A. Search for Related Content PubMed PubMed Citation Articles by Souri, M. Articles by Ichinose, A. Related Collections Hemostasis, Thrombosis, and Vascular Biology Clinical Trials and Observations Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY A naturally occurring E30Q mutation in the Gla domain of protein Z causes its impaired secretion and subsequent deficiency Masayoshi Souri, Shiori Koseki-Kuno, Hiroki Iwata, Bettina Kemkes-Matthes, and Akitada Ichinose From the Department of Molecular Patho-Biochemistry and Patho-Biology, Yamagata University School of Medicine, Yamagata, Japan; and the Zentrum Innere Medizin, Giessen University, Giessen, Germany. Protein Z is a vitamin K–dependent glycoprotein that plays a role in the regulation of coagulation. A nucleotide substitution of G by C in exon II of the protein Z gene, resulting in the replacement of Glu-30 with Gln (E30Q), and a G to A transition at the 79th nucleotide in intron F (IntF79G/A) were heterozygously identified in a patient with a severe thrombotic tendency, whose plasma protein Z level was about 15% of normal. Other vitamin K–dependent coagulation factors were within normal ranges. Glu-30 is one of 13 -carboxylation sites in protein Z and is well conserved among vitamin K–dependent proteins. Expression studies revealed that the E30Q mutant was not released from synthesizing cells, although wild-type protein Z was readily secreted in a vitamin K–dependent fashion. The E30Q mutant was N-glycosylated, -carboxylated, and translocated from the endoplasmic reticulum (ER) to the Golgi in the presence of vitamin K, as was the wild type. Coexpression of E30Q with wild-type protein Z interfered with the secretion of the wild type, while only a minor or no effect was observed on the secretion of factor X and plasminogen. The IntF79A allele has been reported to be also associated with lowered protein Z levels. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. Souri, H. Iwata, W. G. Zhang, and A. Ichinose Unique secretion mode of human protein Z: its Gla domain is responsible for inefficient, vitamin K-dependent and warfarin-sensitive secretion Blood, April 16, 2009; 113(16): 3857 - 3864. [Abstract] [Full Text] [PDF]

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