CD46

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.

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).

Involvement in disease

Hemolytic uremic syndrome atypical 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.

None

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.

Post-translational modifications

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.

Tissue specificity

Expressed by all cells except erythrocytes.

Cellular localization

• Cytoplasmic vesicle
• Secretory vesicle
• Acrosome inner membrane
• Single-pass type I membrane protein
• 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.

Alternative names

• Membrane cofactor protein
• TLX
• Trophoblast leukocyte common antigen
• MIC10
• CD46
• MCP

Database links

• entrezGene:4179
• omim:120920
• swissprot:P15529

Target type

Proteins

Primary research area

Immunology & Infectious Disease

Molecular weight

43747Da