Multiple isoforms of guinea pig decay-accelerating factor (DAF) generated by alternative splicing.
Human decay-accelerating factor (DAF, CD55), which is one of the regulators of complement activation (RCA), prevents complement activation on homologous cell membranes, resulting in a functional discrimination between self cells and invading microorganisms. DAF is a glycosylphosphatidylinositol (GPI)-anchored glycoprotein and has been identified at the molecular level only in primates. We have isolated guinea pig DAF cDNA clones from a spleen library and identified six different classes. All encode the same four short consensus repeat domains with 58% amino acid sequence identity to human DAF, but show variability in the C-terminal region. Alternative splicing of two optional exons generates transmembrane, GPI-anchored, and secreted forms of guinea pig DAF, and differential usage of splice sites in the single exon composed of internally quintuplicated sequences generates variable Ser/Thr-rich regions. Multiple isoforms were expressed ubiquitously in all tissues and cells tested. Similar variability in the Ser/Thr-rich region has been reported in human membrane cofactor protein (MCP), another membrane inhibitor of the RCA family. There seems to be a common ancestral sequence in DAF and MCP consisting of a Ser/Thr-rich region, but obviously multiplication occurred independently, indicating the importance of variability of the Ser/Thr-rich region for the effective regulation of complement activation.
Nonaka
M
M
Department of Molecular Biology, Nagoya City University School of Medicine, Japan.
Miwa
T
T
Okada
N
N
Nonaka
M
M
Okada
H
H
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD / Q000235:genetics*; D001483:Base Sequence; D018958:CD55 Antigens; D018076:DNA, Complementary / Q000235:genetics* / Q000302:isolation & purification; D006168:Guinea Pigs; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics*; D008969:Molecular Sequence Data; D012313:RNA / Q000032:analysis; D012091:Repetitive Sequences, Nucleic Acid; D016415:Sequence Alignment; D013154:Spleen / Q000737:chemistry*
D015703:Antigens, CD; D018958:CD55 Antigens; D018076:DNA, Complementary; D008562:Membrane Glycoproteins; D012313:RNA