Human membrane cofactor protein (MCP, CD46): multiple isoforms and functions.
Human membrane cofactor protein (MCP, CD46) is a 45-70 kDa protein with genetic and tissue-specific heterogeneity, and is expressed on all nucleated cells. MCP consists from N-terminus of 4 short consensus repeats (SCRs), 1-3 serine/threonine-rich (ST) domains, a transmembrane domain (TM) and a cytoplasmic tail (CYT). More than 8 isoforms are generated secondary to alternative splicing due to combinations of various exons encoding the ST, TM and CYT domains. It serves as a cofactor of serine protease factor I for inactivation of complement C3b and C4b. Its primary role is to protect host cells from homologous complement attack by inactivating C3b/C4b deposited on the membrane. It also acts as receptors for measles virus (MV), some kinds of bacteria and for a putative ligand on oocytes. MV infection causes temporal host immune suppression, which may appear secondary to signaling events through MCP on macrophages and dendritic cells. These functional properties of human MCP may facilitate xenotransplantation and may be useful in the generation of animal models of measles by creating human MCP-expressing animals.
Seya
T
T
Department of Immunology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Japan. tseya@takaipro.jst.go.jp
Hirano
A
A
Matsumoto
M
M
Nomura
M
M
Ueda
S
S
D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*; D003169:Complement Inactivator Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D005091:Exons; D005260:Female; D005306:Fertilization / Q000502:physiology; D006801:Humans; D008297:Male; D008457:Measles / Q000276:immunology; D008459:Measles virus / Q000472:pathogenicity; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*; D008954:Models, Biological; D008969:Molecular Sequence Data; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D011991:Receptors, Virus / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D014183:Transplantation, Heterologous
D015703:Antigens, CD; C497857:CD46 protein, human; D003169:Complement Inactivator Proteins; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins; D020033:Protein Isoforms; D011991:Receptors, Virus