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Beschreibung

Membrane cofactor protein (UniProt: P15529, also known as TLX, Trophoblast leukocyte common antigen, CD46) is encoded by the CD46 (also known as MCP, MIC10) gene (Gene ID: 4179) in human. CD46 is a single-pass type I membrane protein that is expressed by all cells except erythrocytes. It acts as a cofactor for complement factor I, a serine protease that protects autologous cells against complement-mediated injury by cleaving C3b and C4b deposited on host tissue. It also acts as a costimulatory factor for T-cells which induces the differentiation of CD4+ into T-regulatory 1 cells. CD46 is synthesized with a signal peptide (aa 1-34), which is cleaved off in the mature form. The mature form contains an extracellular domain (aa 35-343), a transmembrane domain (aa 344-366), and a cytoplasmic domain (aa 367-392). It also contains four Sushi domains where Sushi domains 1 and 2 are required for interaction with human adenovirus B PIV/FIBER protein and with Measles Virus H protein, domains 2 and 3 are essential for Herpes virus 6 binding, and domains 3 and 4 are required for interaction with Streptococcus Pyrogens M protein and are the most important for interaction with C3b and C4b. CD46 can be glycosylated on Asn 83, 114, and 273 and N-glycosylation on Asn 114 and 273 are required for its cytoprotective function. N-glycosylation on Asn 114 is also required for Measles virus binding and N-glycosylation on Asn-273 is required for Neisseria binding. CD46 can also be extensively O-glycosylated in the Ser/Thr-rich domain, which is required for Neisseria binding, but not for Measles virus binding. Mutations in CD46 gene have been linked to hemolytic uremic syndrome atypical 2 that has been characterized by microangiopathic hemolytic anemia, thrombocytopenia, and renal failure.