A novel human plasma protein has been identified as a universal component o
f complement deposits, when complement is detected immunohistochemically in
vivo. The protein is homologous to complement factor H and related protein
s and has been designated factor H-related protein 5 (FHR-5). FHR-5 was ide
ntified by a monoclonal antibody raised using pathologic human glomerular p
reparations as the immunogen. FHR-5 was purified by affinity chromatography
from complement-lysed erythrocytes, and the peptide sequence was obtained.
The cDNA was cloned from a human liver library, and FHR-5 was deduced to b
e a protein containing 551 amino acids organized into nine short consensus
repeat motifs. The short consensus repeats of FHR-5 show homology to Factor
H and to other Factor H-related proteins, with some unique features demons
trated. Recombinant FHR-5, expressed in insect cells, was shown to bind C3b
in vitro. The strong association of FHR-5 with tissue complement deposits
in vivo suggests that this additional member of the Factor H family of prot
eins has a function in complement regulation.