CD46
CD46 (CD46 Molecule) is a Protein Coding gene. Diseases associated with CD46 include Hemolytic Uremic Syndrome, Atypical 2 and Measles. Among its related pathways are Creation of C4 and C2 activators and Complement and coagulation cascades. Gene Ontology (GO) annotations related to this gene include receptor activity and enzyme inhibitor activity. An important paralog of this gene is C4BPA.
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.
(Microbial infection) A number of viral and bacterial pathogens seem to bind MCP in order to exploit its immune regulation property and directly induce an immunosuppressive phenotype in T-cells.
(Microbial infection) Acts as a receptor for Adenovirus subgroup B2 and Ad3.
(Microbial infection) Acts as a receptor for cultured Measles virus.
(Microbial infection) Acts as a receptor for Herpesvirus 6/HHV-6.
(Microbial infection) May act as a receptor for pathogenic bacteria Neisseria and Streptococcus pyogenes (PubMed:7708671, PubMed:9379894, PubMed:11260136, PubMed:11971006).
Biological Process
Adaptive immune response Source: UniProtKB
Complement activation, classical pathway Source: UniProtKB-KW
Innate immune response Source: UniProtKB-KW
Negative regulation of gene expression Source: UniProtKB
Positive regulation of gene expression Source: UniProtKB
Positive regulation of interleukin-10 production Source: UniProtKB
Positive regulation of memory T cell differentiation Source: UniProtKB
Positive regulation of regulatory T cell differentiation Source: UniProtKB
Positive regulation of T cell proliferation Source: UniProtKB
Positive regulation of transforming growth factor beta production Source: UniProtKB
Regulation of complement activation Source: Reactome
Regulation of Notch signaling pathway Source: UniProtKB
Sequestering of extracellular ligand from receptor Source: UniProtKB
Single fertilization Source: UniProtKB-KW
T cell mediated immunity Source: UniProtKB
Cellular Location
Acrosome inner membrane. 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.
Involvement in disease
Hemolytic uremic syndrome atypical 2 (AHUS2): Disease susceptibility is associated with variants affecting the gene represented in this entry. 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. 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.
Topology
Extracellular: 35-343
Helical: 344-366
Cytoplasmic: 367-392
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.
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.
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.
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Datasheet