Human Molecular Genetics, Vol 8, 543-549, Copyright © 1999 by Oxford University Press
J Hughes, CJ Ward, R Aspinwall, R Butler and PC Harris
Previous studies have shown sequence similarity between a region of the
autosomal dominant polycystic kidney disease (ADPKD) protein, polycystin-1
and a sea urchin sperm glycoprotein involved in fertilization, the receptor
for egg jelly (suREJ). We have analysed sequence databases for novel genes
encoding PKD/REJ-like proteins and found a significant region of homology
to a large open reading frame in genomic sequence from human chromosome 22.
Northern analysis showed that this is a functional gene [termed the
polycystic kidney disease and receptor for egg jelly related gene ( PKDREJ
)], but unlike polycystin-1, has a very restricted expression pattern; the
approximately 8 kb transcript was found exclusively in testis, coincident
with the timing of sperm maturation. The PKDREJ transcript was cloned by
screening a testis cDNA library and RT-PCR which revealed a 7660 bp mRNA
terminating with a 900 bp 3'UTR and a polyA tail. Comparison with genomic
sequence showed that PKDREJ is intronless; sequencing the mouse orthologue
revealed a similar structure. The predicted human PKDREJ protein has 2253
amino acids (calculated molecular mass 255 kDa) and sequence similarity
over approximately 2000 amino acids with polycystin-1, corresponding to the
predicted membrane associated region and the area of homology (
approximately 1000 amino acids) with the suREJ protein (the REJ module).
The suREJ protein binds the glycoprotein coat of the egg (egg jelly),
triggering the acrosome reaction, which transforms the sperm into a
fusogenic cell. The sequence similarity and expression pattern suggests
that PKDREJ is a mammalian equivalent of the suREJ protein and therefore
may have a central role in human fertilization.
ARTICLES
Identification of a human homologue of the sea urchin receptor for egg jelly: a polycystic kidney disease-like protein
MRC Molecular Haematology Unit, Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford OX3 9DS, UK.
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