Structural characteristics

CD46 possesses an unusual electrophoretic pattern in that it consists of two rather heterogeneous protein species of 51-58 kDa ('lower' band) and 5968 kDa ('upper' band). This variability is inherited as three phenotypic patterns consisting of upper band predominance in 65% of the population, equivalence of both bands in 29% and predominance of the lower band in 6%. This heterogeneity represents a size polymorphism and relates to CD46 being expressed as a family of at least four isoforms that arise by alternative splicing of a single gene (Figure 1). A dominating characteristic of CD46 is the presence of four of the repeating motifs called complement control protein repeats (CCPRs) (also called short consensus repeats). These are the building blocks of RCA proteins that contain the binding sites for C3b and C4b. Sites for N-linked glycosylation are found in CCPR-1, -2 and -4. Following the CCPRs is an area enriched in serines, threonines and prolines (STP) that is extensively O-glycosylated.

This domain consists of 14 or 29 amino acids depending on whether the STP exon B (15 amino acids) is spliced out. The presence of STP-B produces the higher molecular weight protein isoforms (possessing more sialic acid) while its absence generates the lower molecular weight forms. Following this is a tract of 12 amino acids of unknown significance, a transmembrane region, intracytoplasmic anchor and one of two alternatively spliced cytoplasmic tails (CYT-1 of 16 amino acids or CYT-2 of 23 amino acids). The CD46 gene consists of 14 exons and 13 introns with a minimum length of 43 kb and resides in the RCA cluster on the long arm of chromosome one (lq3.2). A partial duplicate of CD46 is also present in this cluster but no mRNA for this species has been identified.

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