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MGP001891

UniProt Annotations

Entry Information
Gene NameCD46 molecule, complement regulatory protein
Protein EntryMCP_HUMAN
UniProt IDP15529
SpeciesHuman
Comments
Comment typeDescription
Alternative ProductsEvent=Alternative splicing; Named isoforms=16; Comment=Additional isoforms seem to exist. The complete sequences of the isoforms are not known. Isoforms are classified as alpha (isoform C and isoform D), beta (isoform E and isoform F), gamma (isoform A and isoform B) and delta (isoform N). Isoforms gamma are preferentially expressed in EBV-B cells and leukemic cells. Isoforms alpha (66 kDa) and isoforms beta (56 kDa) are found in all tissues except sperm. Isoform delta is expressed in spermatozoa. The exon 9 is specifically deleted in some placentae isoforms. All tissues differentially splice exon 13.; Name=A; Synonyms=no del, ABC1; IsoId=P15529-1; Sequence=Displayed; Name=B; Synonyms=del 13, ABC2; IsoId=P15529-2; Sequence=VSP_001204; Note=Contains a phosphotyrosine at position 384.; Name=C; Synonyms=del 7, BC1; IsoId=P15529-11; Sequence=VSP_009174; Name=D; Synonyms=del 7-13, BC2; IsoId=P15529-3; Sequence=VSP_009174, VSP_001204; Note=Contains a phosphotyrosine at position 369.; Name=E; Synonyms=del 7-8, C1; IsoId=P15529-12; Sequence=VSP_009175; Name=F; Synonyms=del 7-8-13, C2; IsoId=P15529-4; Sequence=VSP_009175, VSP_001204; Note=Contains a phosphotyrosine at position 354.; Name=G; Synonyms=del 9; IsoId=P15529-13; Sequence=VSP_009177; Name=H; Synonyms=del 9-13; IsoId=P15529-5; Sequence=VSP_009177, VSP_001204; Note=Contains a phosphotyrosine at position 370.; Name=I; Synonyms=del 7-9; IsoId=P15529-14; Sequence=VSP_009174, VSP_009177; Name=J; Synonyms=del 7-9-13; IsoId=P15529-6; Sequence=VSP_009174, VSP_009177, VSP_001204; Note=Contains a phosphotyrosine at position 355.; Name=K; Synonyms=del 7-8-9; IsoId=P15529-15; Sequence=VSP_009176; Name=L; Synonyms=del 7-8-9-13; IsoId=P15529-7; Sequence=VSP_009176, VSP_001204; Note=Contains a phosphotyrosine at position 340.; Name=M; Synonyms=del 7-12a-13; IsoId=P15529-8; Sequence=VSP_009174, VSP_001202, VSP_001203; Name=N; Synonyms=del 7-8-12-13; IsoId=P15529-9; Sequence=VSP_009175, VSP_009178; Note=No experimental confirmation available.; Name=2; IsoId=P15529-10; Sequence=VSP_001201; Name=3; IsoId=P15529-16; Sequence=VSP_019005, VSP_019006, VSP_001204; Note=Contains a phosphotyrosine at position 321.;
DiseaseHemolytic 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:0000269|PubMed:16386793, ECO:0000269|PubMed:16621965, ECO:0000269|PubMed: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.
DomainSushi 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.
FunctionActs 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:0000269|PubMed:10843656, ECO:0000269|PubMed:12540904}.
InteractionP78504:JAG1; NbExp=5; IntAct=EBI-2623451, EBI-2847071;
PtmExtensively O-glycosylated in the Ser/Thr-rich domain. O- glycosylation is required for Neisseria binding but not for Measles virus or human adenovirus binding.
PtmIn 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.
PtmN-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.
SimilarityContains 4 Sushi (CCP/SCR) domains. {ECO:0000255|PROSITE-ProRule:PRU00302}.
Subcellular LocationCytoplasmic vesicle, secretory vesicle, acrosome inner membrane {ECO:0000269|PubMed:12112588, ECO:0000269|PubMed:14597734, ECO:0000269|PubMed:15307194}; Single- pass type I membrane protein {ECO:0000269|PubMed:12112588, ECO:0000269|PubMed:14597734, ECO:0000269|PubMed: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.
SubunitInteracts with C3b and C4b. Binds to Measles virus H protein, to Human herpesvirus 6 GH protein and to human adenovirus B/D PIV/fiber protein, and acts as a receptor for these viruses. Binds to Streptococcus pyogenes M protein and to type IV pili from Neisseria, and may act as a receptor for these pathogenic bacteria. {ECO:0000269|PubMed:10972291, ECO:0000269|PubMed:11260136, ECO:0000269|PubMed:11971006, ECO:0000269|PubMed:12663806, ECO:0000269|PubMed:12724329, ECO:0000269|PubMed:12915534, ECO:0000269|PubMed:14566335, ECO:0000269|PubMed:15047806, ECO:0000269|PubMed:15078926, ECO:0000269|PubMed:15919905, ECO:0000269|PubMed:16254377, ECO:0000269|PubMed:1717583, ECO:0000269|PubMed:3260937, ECO:0000269|PubMed:7708671, ECO:0000269|PubMed:9379894}.
Tissue SpecificityExpressed by all cells except erythrocytes.
Web ResourceName=SeattleSNPs; URL="http://pga.gs.washington.edu/data/mcp/";
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