Genomic organization of the alpha chain of the human C4b-binding protein gene

Abstract

C4b-binding protein (C4bp) is a serum glycoprotein that is one of the regulators of the complement activation (RCA) family. This protein is composed of structurally related 70-kDa (alpha chain) and 45-kDa (beta chain) polypeptides. The alpha chain of C4bp (C4bp alpha) consists of eight short consensus repeats (SCR), which constitute the amino-terminal 491 residues. Human C4bp is also one of the acute-phase reactants. In order to clarify the genetic basis of the SCR and to understand the regulatory mechanisms of C4bp synthesis, we isolated 6 genomic DNA clones covering all of the human C4bp alpha gene. This gene consists of 12 exons and spans about 40 kb. Each of the SCRs is encoded by a single exon, except for the second SCR (SCR II), which is encoded by two separate exons, demonstrating that human C4bp alpha has a split SCR at the genomic level. The 5' flanking region was sequenced up to 380 bases upstream from the putative transcription initiation site. Several possible binding sites for transcription factors were identified.