JOURNAL ARTICLE
RESEARCH SUPPORT, NON-U.S. GOV'T
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The gene for human protein Z is localized to chromosome 13 at band q34 and is coded by eight regular exons and one alternative exon.

Biochemistry 1998 May 13
Human protein Z is a vitamin K-dependent plasma glycoprotein, deficiency of which leads to a mild bleeding tendency. Protein Z appears to assist hemostasis by binding thrombin and promoting its association with phospholipid vesicles. In this study, to characterize the gene for protein Z, its organization and structure were determined by a combination of PCR amplification of leukocyte DNA and isolation of phage clones from a human genomic library. The gene spanned about 14 kb and consisted of 9 exons including one alternative exon. It was of note that the gene organization was essentially identical to that of other vitamin K-dependent proteins, such as factors VII, IX, and X and protein C. The nucleotides in introns at exon/intron boundaries for eight regular exons were the consensus GT-AG sequences. In contrast, the sequence at an optional exon/intron junction was found to be GC rather than GT. The extra exon inserts a unique peptide consisting of 22 amino acids in the prepro-leader sequence. A similar situation was previously observed in factor VII, but not in other vitamin K-dependent plasma proteins. We also assigned the gene for protein Z to chromosome 13 by PCR amplification of genomic DNAs from human/hamster cell hybrids. Fluorescence in situ hybridization, employing a genomic clone coding for human protein Z, further localized the gene to band q34, where the genes of three other vitamin K-dependent proteins are clustered. These genes may have evolved via duplication of an ancestral gene at this locus.

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