FHR-4A: a new factor H-related protein is encoded by the human FHR-4 gene.
We 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 63.2 kDa. Apparently, this novel cDNA is derived from the human FHR-4 gene. Genetic analysis shows that the human FHR-4 gene is composed of 10 coding exons, and two distinct mRNA transcripts are derived from this gene by alternative splicing. The short FHR-4B form represents a truncated variant and encodes a secreted protein of five domains (previously termed FHR-4). The long transcript 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 'natural dimer' of the short isoform. The FHR-4A protein is identified in human plasma as a 86 kDa protein. The difference between the predicted and observed molecular masses is explained by glycosylation. Comparison of the deduced protein sequence of FHR-4A with peptides from a 86 kDa apolipoprotein described by us earlier suggests that the long form, FHR-4A, represents this apoprotein. In summary, FHR-4A is a new Factor H-related protein with a unique domain composition, that is, an internal duplication of four CCP domains. To our knowledge, FHR-4A provides the first evidence for alternative splicing among Factor H-related genes.
Józsi
Mihály
M
Department of Infection Biology, Hans Knöll Institute for Natural Products Research, Jena, Germany. mjozsi@pmail.hki-jena.de
Richter
Heiko
H
Löschmann
Ina
I
Skerka
Christine
C
Buck
Friedrich
F
Beisiegel
Ulrike
U
Erdei
Anna
A
Zipfel
Peter F
PF
D000595:Amino Acid Sequence; D001053:Apolipoproteins / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics*; D001483:Base Sequence; D015153:Blotting, Western; D017242:Complement Factor H / Q000235:genetics*; D015723:Gene Library; D006023:Glycoproteins / Q000097:blood; D006801:Humans; D008969:Molecular Sequence Data; D020033:Protein Isoforms / Q000235:genetics; D017386:Sequence Homology, Amino Acid
D001053:Apolipoproteins; C493495:CFH protein, human; C105092:CFHR4 protein, human; D006023:Glycoproteins; D020033:Protein Isoforms; D017242:Complement Factor H