InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: CD46

Summary

InnateDB Protein

IDBP-106380.7

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

CD46

Protein Name

CD46 molecule, complement regulatory protein

Synonyms

AHUS2; MCP; MIC10; TLX; TRA2.10;

Species

Homo sapiens

Ensembl Protein

ENSP00000313875

InnateDB Gene

IDBG-106372 (CD46)

Protein Structure

UniProt Annotation

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. {ECO:0000269PubMed:10843656, ECO:0000269PubMed:12540904}.

Subcellular Localization

Cytoplasmic vesicle, secretory vesicle, acrosome inner membrane {ECO:0000269PubMed:12112588, ECO:0000269PubMed:14597734, ECO:0000269PubMed:15307194}; Single- pass type I membrane protein {ECO:0000269PubMed:12112588, ECO:0000269PubMed:14597734, ECO:0000269PubMed:15307194}. 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.

Disease Associations

Hemolytic uremic syndrome atypical 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. {ECO:0000269PubMed:16386793, ECO:0000269PubMed:16621965, ECO:0000269PubMed:20513133}. Note=Disease susceptibility is associated with variations 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.

Tissue Specificity

Expressed by all cells except erythrocytes.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 25 experimentally validated interaction(s) in this database.

Experimentally validated
Total	25 [view]
Protein-Protein	23 [view]
Protein-DNA	2 [view]
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Gene Ontology

Molecular Function

Accession	GO Term
GO:0004872	receptor activity
GO:0005515	protein binding
GO:0045296	cadherin binding

Biological Process

GO:0002250	adaptive immune response
GO:0002456	T cell mediated immunity
GO:0006958	complement activation, classical pathway
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 (InnateDB)
GO:0045591	positive regulation of regulatory T cell differentiation
GO:0071636	positive regulation of transforming growth factor beta production

Cellular Component

GO:0002079	inner acrosomal membrane
GO:0005886	plasma membrane
GO:0005887	integral component of plasma membrane
GO:0009986	cell surface
GO:0070062	extracellular vesicular exosome