M. Yagi et al., HUMAN PLATELET GLYCOPROTEIN-V AND GLYCOPROTEIN-IX - MAPPING OF 2 LEUCINE-RICH GLYCOPROTEIN GENES TO CHROMOSOME-3 AND ANALYSIS OF STRUCTURES, Biochemistry, 34(49), 1995, pp. 16132-16137
Human platelet glycoproteins Ib alpha, Ib beta, V, and IX comprise an
interrelated set of molecules (the Ib-V-IX system) that together form
a surface adhesion receptor for the ligand, von Willebrand factor. To
complete the primary structural characterization of the genes involved
in this system, we have analyzed cosmid clones for both the glycoprot
ein V and IX genes and used these clones to localize the two genes by
fluorescence in situ hybridization. Both genes were found on the long
arm of chromosome 3, but at distinct sites, the GPV gene on 3 band q29
and the GP IX gene on 3 band q21. The transcriptional start site of t
he GPV gene was defined by ''anchored'' PCR and primer extension. The
GPV gene contains two exons, the first consisting of approximately 37
bases and the second of approximately 3500 bases, interrupted by a sin
gle 958 base intron. The GPV transcript has multiple start sites sprea
d over a twenty base region. The 5' flanking region of the GPV gene ha
s a series of potential consensus regulatory elements including GATA,
ets, and Sp-1 sites, similar to those found in other described megakar
yocyte/platelet genes, including those of the Ib-V-IX system. In asses
sing the four Ib-V-IX genes as a group, all four have a simple, ''intr
on-depleted'' structure with the entire open reading frame of the matu
re polypeptide located within a single exon. The Ib-V-IX genes may hav
e evolved from a single site on the long arm of chromosome 3, related
to the GP IX gene; and the system of genes may have developed through
a sequential acquisition of structural domains to produce the activati
on-independent, shear-dependent, multisubunit receptor for von Willebr
and factor.