Membrane Cofactor Protein (CD46) Human Recombinant Protein

The protein encoded by this gene is a type I membrane protein and is a regulatory part of the complement system. The encoded protein has cofactor activity for inactivation of complement components C3b and C4b by serum factor I, which protects the host cell from damage by complement. In addition, the encoded protein can act as a receptor for the Edmonston strain of measles virus, human herpesvirus-6, and type IV pili of pathogenic Neisseria. Finally, the protein encoded by this gene may be involved in the fusion of the spermatozoa with the oocyte during fertilization. Mutations at this locus have been associated with susceptibility to hemolytic uremic syndrome. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jun 2010]

CD46: 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. Defects in CD46 are a cause of susceptibility to hemolytic uremic syndrome atypical type 2 (AHUS2). 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. 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. 16 isoforms of the human protein are produced by alternative splicing.

Protein type: Cell surface; Membrane protein, integral; Receptor, misc.

Chromosomal Location of Human Ortholog: 1q32.2

Cellular Component: cell surface; focal adhesion; integral to plasma membrane; plasma membrane

Molecular Function: cadherin binding; protein binding; receptor activity

Biological Process: adaptive immune response; interleukin-10 production; positive regulation of interleukin-10 production; positive regulation of memory T cell differentiation; positive regulation of regulatory T cell differentiation; positive regulation of T cell proliferation; regulation of complement activation; regulation of Notch signaling pathway; T cell mediated immunity

Disease: Hemolytic Uremic Syndrome, Atypical, Susceptibility To, 2