FHR-4A: a new factor H-related protein is encoded by the human FHR-4 gene.

Department of Immunology, Eo¨tvo¨s Lora´nd University, Budapest, HungaryWe describe a new member of the human Factor H protein family, termed Factor H-related protein 4A (FHR-4A). The corresponding cDNA sequence was isolated and encodes a secreted protein of 559 amino acids,with a predicted molecular weight of 63.2kDa. Apparently, this novel cDNA is derived from the human FHR-4gene. Genetic analysis shows that the human FHR-4 gene is composed of 10 coding exons, and two distinctmRNA transcripts are derived from this gene by alternative splicing. The short FHR-4B form represents atruncated variant and encodes a secreted protein of five domains (previously termed FHR-4). The longtranscript encodes the novel FHR-4A protein that is composed of nine complement control protein (CCP)domains. A unique feature of FHR-4A is the tandem arrangement of four CCP domains forming a ‘naturaldimer’ of the short isoform. The FHR-4A protein is identified in human plasma as a 86kDa protein. Thedifference between the predicted and observed molecular masses is explained by glycosylation. Comparisonof the deduced protein sequence of FHR-4A with peptides from a 86kDa apolipoprotein described by usearlier suggests that the long form, FHR-4A, represents this apoprotein. In summary, FHR-4A is a new FactorH-related protein with a unique domain composition, that is, an internal duplication of four CCP domains. Toour knowledge, FHR-4A provides the first evidence for alternative splicing among Factor H-related genes.European Journal of Human Genetics (2005) 13, 321–329. doi:10.1038/sj.ejhg.5201324Published online 24 November 2004Keywords: Factor H-related; FHR-4; complement; apoprotein; CCP domainIntroduction