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PubMed · 7545710

Multiple isoforms of guinea pig decay-accelerating factor (DAF) generated by alternative splicing.

M Nonaka·T Miwa·N Okada·H Okada
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Abstract

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.

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Alternative SplicingAmino Acid SequenceAnimalsAntigens, CDBase SequenceCD55 AntigensDNA, ComplementaryGuinea PigsHumansMembrane GlycoproteinsMolecular Sequence DataRNARepetitive Sequences, Nucleic AcidSequence AlignmentSpleenJournal ArticleResearch Support, Non-U.S. Gov't

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M Nonaka, T Miwa, N Okada, H Okada. 1995-09-15. Multiple isoforms of guinea pig decay-accelerating factor (DAF) generated by alternative splicing.. https://pubmed.ncbi.nlm.nih.gov/7545710/

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