We have isolated a human gene homologous to Drosophila melanogaster rotated abdomen, rt, a poorly viable recessive mutation causing a clockwise twisted abdomen in affected flies due to defects in embryonic muscle development. The human gene, like rt, encodes a protein with high homology to the yeast mannosyl-transferases (Pmts) and has been named POMT1. POMT1 is expressed as a 3.1-kb transcript in all tissues tested, with highest levels in testis and fetal brain. Alternative splicing of several exons in all tissues predicts the generation of several protein isoforms. The most common mRNA variant encodes a 725-aa protein with 40% identity and 62.5% similarity to rt, as well as 30.5% identity and 54% similarity to yeast Pmts. Computer prediction of protein sorting suggests that the POMT1 product could be an integral protein of the endoplasmic reticulum membrane. Given the strong conservation of protein motifs between POMT1 and the yeast Pmts, POMT1 may function as a mannosyl-transferase involved in O-mannosylation of proteins, being the first of such a class found in mammals. The POMT1 locus has been assigned to human chromosome 9q34.1 by somatic cell hybrids, radiation hybrids, and linkage analysis. On the basis of the rt phenotype, POMT1 could be a candidate for uncharacterized genetic disorders of the muscular system, such as some forms of congenital muscular dystrophy or congenital myopathy.
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