Journal article

Publication year: 2005

Pages: 3149-3154

Journal: Blood

Volume number: 105

Issue number: 8

ISSN: 0006-4971

Open access status: Bronze

DOI Link: https://doi.org/10.1182/blood-2004-06-2250

Publisher: American Society of Hematology (ASH Publications)

Abstract: 
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 Gin (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 gamma-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, gamma-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. (c) 2005 by The American Society of Hematology.

Harvard Citation style: Souri, M., Koseki-Kuno, S., Iwata, H., Kemkes-Matthes, B. and Ichinose, A. (2005) A naturally occurring E30Q mutation in the Gla domain of protein Z causes its impaired secretion and subsequent deficiency, Blood, 105(8), pp. 3149-3154. https://doi.org/10.1182/blood-2004-06-2250

APA Citation style: Souri, M., Koseki-Kuno, S., Iwata, H., Kemkes-Matthes, B., & Ichinose, A. (2005). A naturally occurring E30Q mutation in the Gla domain of protein Z causes its impaired secretion and subsequent deficiency. Blood. 105(8), 3149-3154. https://doi.org/10.1182/blood-2004-06-2250