title: Membrane cofactor protein.
abstract: MCP serves to down-regulate the activation of complement on host tissue. It performs this function by serving as a cofactor for the factor I-mediated cleavage of C3b and C4b. MCP is most likely an intrinsic regulator, i.e., it primarily protects its home cell. The wide tissue distribution of MCP mirrors this critical function of host cell protection. With the exception of erythrocytes, every cell and tissue examined expresses this protein. MCP is represented as two broad heterogeneous bands on SDS-PAGE with M(r)s of 51,000-58,000 and 59,000-68,000. The quantity of each form expressed is inherited in an autosomal codominant fashion. In most cells and cell lines, four isoforms of MCP predominate and arise by alternative splicing of a single MCP gene. All forms possess four repeating modules of--60 aminoacids, an area enriched in serines, threonines, and prolines [(STP), probable site of O-linked glycosylation], a short area of unknown function, a transmembrane domain, and a cytoplasmic tail. The isoforms differ, however, in the length and composition of the STP region and in the cytoplasmic tail. Alternative splicing of a single exon within the STP region determines the protein phenotype. Alternative splicing at the COOH_terminus gives rise to two distinct cytoplasmic tails. The biological significance of these structural variations in the STP and cytoplasmic tail regions is being investigated.
authors.affiliation: Howard Hughes Medical Institute Laboratories, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110.
authors.forename: M K
authors.initials: MK
authors.lastname: Liszewski
authors.forename: J P
authors.initials: JP
authors.lastname: Atkinson
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D003179:Complement C3b / Q000378:metabolism; D015935:Complement C4b / Q000378:metabolism; D005796:Genes; D006801:Humans; D008322:Mammals / Q000378:metabolism; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D009928:Organ Specificity; D013045:Species Specificity; D013329:Structure-Activity Relationship
chemical_list: D015703:Antigens, CD; C497857:CD46 protein, human; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins; D003179:Complement C3b; D015935:Complement C4b