CD46
GeneName
CD46
Summary
CD46, also known as MCP, TLX, or membrane cofactor protein, is a 44 kDa glycoprotein expressed on the surface of various cells, including leukocytes and epithelial cells. It is primarily localised to the plasma membrane and plays a multifaceted role in the immune system. CD46 functions as a cofactor for complement regulation, particularly in the classical pathway, and is involved in cell signalling as a receptor for viruses. Additionally, it participates in the regulation of T cell responses and influences gene expression, including the production of interleukin-10 and transforming growth factor beta.
Importance
CD46 is relevant to: - Immune regulation and tolerance through its role in modulating T cell activation and differentiation - Viral infections, as it serves as a receptor for several pathogens, impacting viral entry and immune evasion - Fertilisation processes, particularly in sperm-egg interactions, due to its presence in the acrosome - Complement-mediated diseases, where dysregulation of CD46 can contribute to autoimmune conditions and inflammatory responses
Top Products
For researchers investigating CD46, we highly recommend the top-selling recombinant antibody, Anti-CD46 antibody [EPR4014] (ab108307). This well-cited antibody has garnered 15 citations, reflecting its reliability and trust within the scientific community. It has been validated in knockout models and is suitable for a variety of applications, including Western blotting (WB) and immunohistochemistry (IHC). This versatility makes it an excellent choice for those seeking consistent and effective detection of CD46 in their studies. The Recombinant Human CD46 protein (His tag) ELISA Kit (ab271543) is an excellent option for researchers looking to measure CD46 in their experiments.
Abcam Product Citation Summary
The data indicates that CD46 is being studied in the context of systemic sclerosis (SSc), with applications in both western blotting and immunostaining of skin biopsies and sections from healthy controls and SSc patients. This suggests a focus on understanding the role of CD46 in this autoimmune condition.
Abcam Product Citation Table
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:11260136, PubMed:11971006, PubMed:7708671, PubMed:9379894).
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
CD46, MCP, MIC10, Membrane cofactor protein, TLX, Trophoblast leukocyte common antigen