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CD46, trophoblast leukocyte common antigen, membrane cofactor protein (MCP), TLX, MIC10
Function:
- cofactor for complement factor I proteolytic cleavage of C3b & C4b
- 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 differentiation of CD4+ into T-regulatory 1 cells
- 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
- interacts with C3b & C4b
- binds to Measles virus H protein, to human herpesvirus 6 GH protein & to human adenovirus B/D PIV/fiber protein, & acts as a receptor for these viruses
- binds to Streptococcus pyogenes M protein & to type IV pili from Neisseria, & may act as a receptor for these bacteria
Structure:
- N-glycosylated on Asn-83; Asn-114 & Asn-273 in most tissues, but probably less N-glycosylated in testis
- N-glycosylation on Asn-114 & 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
- Sushi domains 1 & 2 are required for interaction with human adenovirus B PIV/FIBER protein & with Measles virus H protein
- Sushi domains 2 & 3 are required for Herpesvirus 6 binding
- Sushi domain 3 is required for Neisseria binding
- Sushi domains 3 & 4 are required for interaction with Streptococcus pyogenes M protein & are the most important for interaction with C3b & C4b
- contains 4 Sushi (CCP/SCR) domains
Compartment:
- cytoplasmic vesicle, secretory vesicle,
- acrosome inner membrane of spermatozoa
- single-pass type 1 membrane protein
Alternative splicing: named isoforms=16; Additional isoforms seem to exist; A-N
Expression: expressed by all cells except erythrocytes
Pathology:
- specific defects in the sperm forms of CD46 were found in 3 infertile patients
- defects in CD46 are a cause of atypical hemolytic-uremic syndrome
- used by human herpesvirus 6 & measles virus as a receptor
- 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
General
cluster-of-differentiation antigen; cluster designation antigen; CD antigen
glycoprotein
Properties
SIZE: entity length = 392 aa
MW = 44 kD
COMPARTMENT: cytoplasm
cellular membrane
MOTIF: signal sequence {1-34}
Sushi domain {35-96}
MOTIF: cysteine residue {C35}
MODIFICATION: cysteine residue {C80}
cysteine residue {C64}
MODIFICATION: cysteine residue {C94}
cysteine residue {C80}
MODIFICATION: cysteine residue {C35}
N-glycosylation site {N83}
cysteine residue {C94}
MODIFICATION: cysteine residue {C64}
Sushi domain {97-159}
MOTIF: cysteine residue {C99}
MODIFICATION: cysteine residue {C141}
N-glycosylation site {N114}
cysteine residue {C127}
MODIFICATION: cysteine residue {C157}
cysteine residue {C141}
MODIFICATION: cysteine residue {C99}
cysteine residue {C157}
MODIFICATION: cysteine residue {C127}
Sushi domain {160-225}
MOTIF: cysteine residue {C162}
MODIFICATION: cysteine residue {C210}
Thr glycosylation site {T163}
cysteine residue {C191}
MODIFICATION: cysteine residue {C223}
cysteine residue {C210}
MODIFICATION: cysteine residue {C162}
cysteine residue {C223}
MODIFICATION: cysteine residue {C191}
Sushi domain {226-285}
MOTIF: cysteine residue {C228}
MODIFICATION: cysteine residue {C270}
cysteine residue {C256}
MODIFICATION: cysteine residue {C283}
cysteine residue {C270}
MODIFICATION: cysteine residue {C228}
N-glycosylation site {N273}
cysteine residue {C283}
MODIFICATION: cysteine residue {C256}
Ser glycosylation site {S290}
Ser glycosylation site {S291}
Thr glycosylation site {T292}
Ser glycosylation site {S298}
Ser glycosylation site {S300}
threonine-rich region {302-326}
MOTIF: threonine residue (SEVERAL)
Ser glycosylation site {S302}
Thr glycosylation site {T303}
Ser glycosylation site {S304}
Ser glycosylation site {S305}
Thr glycosylation site {T306}
Thr glycosylation site {T307}
Ser glycosylation site {S309}
Ser glycosylation site {S312}
Ser glycosylation site {S313}
Ser glycosylation site {S315}
Thr glycosylation site {T320}
Ser glycosylation site {S326}
transmembrane domain {344-366}
Database Correlations
OMIM correlations
MORBIDMAP 120920
UniProt P15529
Pfam PF00084
Entrez Gene 4179
Kegg hsa:4179
References
- Santoro F et al
CD46 is a cellular receptor for human herpesvirus 6.
Cell 99:817-27, 1999
PMID: 10619434
- http://www.pathologyoutlines.com/cdmarkers.html
15 October 2002
- UniProt :accession P15529
- GeneReviews
https://www.genecards.org/cgi-bin/carddisp.pl?gene=CD46
- SeattleSNPs
http://pga.gs.washington.edu/data/mcp/