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Blood, Vol. 94 No. 2 (July 15), 1999:
pp. 632-641
Structural and Functional Implications of the Intron/Exon Organization
of the Human Endothelial Cell Protein C/Activated Protein C Receptor
(EPCR) Gene: Comparison With the Structure of CD1/Major
Histocompatibility Complex  1 and 2 Domains
Rachel E. Simmonds and
David A. Lane
From the Department of Haematology, Imperial College School of
Medicine, London, UK.
The endothelial cell protein C/activated protein C receptor (EPCR)
is located primarily on the surface of the large vessels of the
vasculature. In vitro studies suggest that it is involved in the
protein C anticoagulant pathway. We report the organization and
nucleotide sequence of the human EPCR gene. It spans approximately 6 kbp of genomic DNA, with a transcription initiation point 79 bp
upstream of the translation initiation (Met) codon in close proximity
to a TATA box and other promoter element consensus sequences. The human
EPCR gene has been localized to 20q11.2 and consists of four exons
interrupted by three introns, all of which obey the GT-AG rule. Exon I
encodes the 5' untranslated region and the signal peptide, and
exon IV encodes the transmembrane domain, the cytoplasmic tail, and the
3' untranslated region. Exons II and III encode most of the
extracellular region of the EPCR. These exons have been found to
correspond to those encoding the  1 and 2 domains of the CD1/major
histocompatibility complex (MHC) class I superfamily. Flanking and
intervening introns are of the same phase (phase I) and the position of
the intervening intron is identically located. Secondary structure
prediction for the amino acid sequence of exons II and III corresponds
well with the actual secondary structure elements determined for the
1 and 2 domains of HLA-A2 and murine CD1.1 from crystal
structures. These findings suggest that the EPCR folds with a  -sheet
platform supporting two -helical regions collectively forming a
potential binding pocket for protein C/activated protein C.
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