Limulus factor C. An endotoxin-sensitive serine protease zymogen with a mosaic structure of complement-like, epidermal growth factor-like, and lectin-like domains.
Factor C is an endotoxin-sensitive, intracellular serine protease zymogen which initiates the coagulation cascade system in the limulus hemolymph. We have determined the entire amino acid sequence of factor C using recombinant DNA technique. The zymogen consisted of 994 amino acid residues with a calculated molecular mass of 109,648 Da. Most interestingly, factor C has five repeating units ("Sushi" domain or short consensus repeat) of about 60 amino acid residues each, which have been found in many proteins participating in the mammalian complement system. In addition to a typical serine protease domain in the carboxyl-terminal portion, characteristic segments with an epidermal growth factor-like, a lectin-like, a cysteine-rich, and a proline-rich domain were also found, revealing a unique mosaic protein structure. The serine protease domain was most analogous to human thrombin. Factor C was identified to localize in large granules in the cell, indicating that it is released from the cell by lipopolysaccharide stimulation. Furthermore, we identified a transcript possibly derived by alternative splicing of factor C mRNA, which encodes a protein sharing the amino-terminal portion of factor C. We suggest that factor C, a newly discovered type of serine protease zymogen, is a "coagulation-complement factor" which may play important roles in both hemostasis and host defense mechanisms.
Muta
T
T
Department of Molecular Biology, Graduate School of Medical Science, Kyushu University, Fukuoka, Japan.
Miyata
T
T
Misumi
Y
Y
Tokunaga
F
F
Nakamura
T
T
Toh
Y
Y
Ikehara
Y
Y
Iwanaga
S
S
D000595:Amino Acid Sequence; D000818:Animals; D060829:Arthropod Proteins; D001483:Base Sequence; D015152:Blotting, Northern; D002850:Chromatography, Gel; D004247:DNA / Q000235:genetics; D004792:Enzyme Precursors / Q000235:genetics*; D004815:Epidermal Growth Factor / Q000235:genetics*; D006737:Horseshoe Crabs; D037102:Lectins / Q000235:genetics*; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000235:genetics; D015183:Restriction Mapping; D012689:Sequence Homology, Nucleic Acid; D012697:Serine Endopeptidases / Q000235:genetics*; D014158:Transcription, Genetic
D060829:Arthropod Proteins; D004792:Enzyme Precursors; D037102:Lectins; D012333:RNA, Messenger; D004815:Epidermal Growth Factor; D004247:DNA; D012697:Serine Endopeptidases; C057151:Limulus clotting factor C