Molecular Cloning and Characterization of MACIF, an Inhibitor of Membrane Channel Formation of Complement1

Abstract

Human erythrocytes contain a membrane protein, MACIF, which inhibits the formation of a membrane attack complex (MAC) of complement. We have cloned and sequenced the complementary DNA of MACIF messenger RNA. The amino acid sequence predicted from its nucleotide sequence consists of 128 amino acids. The amino-terminal 25 residues may correspond to a signal peptide. The carboxy-terminal sequence confirmed that MACIF is a glycosylphosphatidylinositol (GPI)-anchored protein. The amino acid sequence of MACIF was partially determined by established techniques for protein chemistry and the resultant sequence was consistent with that predicted from the nucleotide sequence. The results of sequence analyses also suggested that asparagine at the 18th position was N-glycosylated. When mRNA obtained from the MACIF cDNA clone with SP6 RNA polymerase was microinjected into Xenopus oocytes, the oocytes synthesized a product which exhibited MACIF activity and reacted with anti-MACIF antibody. Comparison of the predicted sequence revealed significant homology with mouse Ly-6 antigens.

Dr(a-) polymorphism of decay accelerating factor. Biochemical, functional, and molecular characterization and production of allele-specific transfectants.

“…The class of GPI-anchored membrane proteins (reviewed in 14, 15) includes the complement-regulatory factors DAF, membrane inhibitor ofreactive lysis (16)(17)(18), and C8-binding protein/homologous restriction factor (19,20). The complement-regulatory function of DAF and the GPI anchoring both come into play in the disease paroxysmal nocturnal hemoglobinuria (PNH; reviewed in 21), an acquired hemolytic anemia.…”

Mouse Complement Receptor-Related Gene y/p65-Neutralized Tumor Vaccine Induces Antitumor Activity In Vivo

“…To prevent inadvertent damage to self, a series of complement-regulatory membrane molecules are expressed on host cells (1). These molecules include sialoglycolipids (2), the membrane-bound proteins, complement receptor 1 (3), decay-accelerating factor (DAF) 4 (4,5), membrane cofactor protein (MCP) (6), and 20-kDa homologous restriction factor (CD59) (7)(8)(9). These complementregulatory proteins are expressed not only on normal tissue, but also on tumor cells, often at elevated levels (10 -16).…”

The good and evil of complement activation in HIV-1 infection

“…10 CD59 restricts MAC formation by preventing C9 incorporation and polymerization, blocking all three pathways of complement activation. 11 There is a delicate balance between complement activation and complement regulation. The ability of the complement system to damage 'self' cells is the result of this delicate balance in autologous cells.…”