ID:MCP_HUMAN DESCRIPTION: RecName: Full=Membrane cofactor protein; AltName: Full=TLX; AltName: Full=Trophoblast leukocyte common antigen; AltName: CD_antigen=CD46; Flags: Precursor; FUNCTION: Acts as a cofactor for complement factor I, a serine protease which protects autologous cells against complement- mediated injury by cleaving C3b and C4b deposited on host tissue. May be involved in the fusion of the spermatozoa with the oocyte during fertilization. Also acts as a costimulatory factor for T- cells which induces the differentiation of CD4+ into T-regulatory 1 cells. T-regulatory 1 cells suppress immune responses by secreting interleukin-10, and therefore are thought to prevent autoimmunity. A number of viral and bacterial pathogens seem to exploit this property and directly induce an immunosuppressive phenotype in T-cells by binding to CD46. SUBUNIT: Interacts with C3b and C4b. Binds to Measles virus H protein, to Human herpesvirus 6 GH protein and to human adenovirus B/D PIV/fiber protein, and acts as a receptor for these viruses. Binds to Streptococcus pyogenes M protein and to type IV pili from Neisseria, and may act as a receptor for these pathogenic bacteria. SUBCELLULAR LOCATION: Cytoplasmic vesicle, secretory vesicle, acrosome inner membrane; Single-pass type I membrane protein. Note=Inner acrosomal membrane of spermatozoa. Internalized upon binding of Measles virus, Herpesvirus 6 or Neisseria gonorrhoeae, which results in an increased susceptibility of infected cells to complement-mediated injury. In cancer cells or cells infected by Neisseria, shedding leads to a soluble peptide. TISSUE SPECIFICITY: Expressed by all cells except erythrocytes. DOMAIN: Sushi domains 1 and 2 are required for interaction with human adenovirus B PIV/FIBER protein and with Measles virus H protein. Sushi domains 2 and 3 are required for Herpesvirus 6 binding. Sushi domain 3 is required for Neisseria binding. Sushi domains 3 and 4 are required for interaction with Streptococcus pyogenes M protein and are the most important for interaction with C3b and C4b. PTM: N-glycosylated on Asn-83; Asn-114 and Asn-273 in most tissues, but probably less N-glycosylated in testis. N- glycosylation on Asn-114 and Asn-273 is required for cytoprotective function. N-glycosylation on Asn-114 is required for Measles virus binding. N-glycosylation on Asn-273 is required for Neisseria binding. N-glycosylation is not required for human adenovirus binding. PTM: Extensively O-glycosylated in the Ser/Thr-rich domain. O- glycosylation is required for Neisseria binding but not for Measles virus or human adenovirus binding. PTM: In epithelial cells, isoforms B/D/F/H/J/L/3 are phosphorylated by YES1 in response to infection by Neisseria gonorrhoeae; which promotes infectivity. In T-cells, these isoforms may be phosphorylated by Lck. DISEASE: Defects in CD46 are a cause of susceptibility to hemolytic uremic syndrome atypical type 2 (AHUS2) [MIM:612922]. An atypical form of hemolytic uremic syndrome. It is a complex genetic disease characterized by microangiopathic hemolytic anemia, thrombocytopenia, renal failure and absence of episodes of enterocolitis and diarrhea. In contrast to typical hemolytic uremic syndrome, atypical forms have a poorer prognosis, with higher death rates and frequent progression to end-stage renal disease. Note=Susceptibility to the development of atypical hemolytic uremic syndrome can be conferred by mutations in various components of or regulatory factors in the complement cascade system. Other genes may play a role in modifying the phenotype. Patients with CD46 mutations seem to have an overall better prognosis compared to patients carrying CFH mutations. SIMILARITY: Contains 4 Sushi (CCP/SCR) domains. WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/CD46"; WEB RESOURCE: Name=SeattleSNPs; URL="http://pga.gs.washington.edu/data/mcp/";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P15529
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Biological Process: GO:0002250 adaptive immune response GO:0002376 immune system process GO:0002456 T cell mediated immunity GO:0006958 complement activation, classical pathway GO:0007165 signal transduction GO:0007338 single fertilization GO:0008593 regulation of Notch signaling pathway GO:0010628 positive regulation of gene expression GO:0010629 negative regulation of gene expression GO:0016032 viral process GO:0030449 regulation of complement activation GO:0032613 interleukin-10 production GO:0032733 positive regulation of interleukin-10 production GO:0035581 sequestering of extracellular ligand from receptor GO:0042102 positive regulation of T cell proliferation GO:0043382 positive regulation of memory T cell differentiation GO:0045087 innate immune response GO:0045591 positive regulation of regulatory T cell differentiation GO:0046718 viral entry into host cell GO:0071636 positive regulation of transforming growth factor beta production
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
