CD46

CD46 molecule, complement regulatory protein
PDB rendering based on 1ckl.
Available structures PDB 1CKL, 1HR4, 2O39, 3INB, 3L89, 3O8E
Identifiers
Symbols	CD46; AHUS2; MCP; MGC26544; MIC10; TLX; TRA2.10
External IDs	OMIM: 120920 MGI: 1203290 HomoloGene: 7832 GeneCards: CD46 Gene
Gene Ontology Molecular function • receptor activity • protein binding Cellular component • inner acrosomal membrane • plasma membrane • integral to plasma membrane • cytoplasmic vesicle Biological process • complement activation, classical pathway • single fertilization • interspecies interaction between organisms • innate immune response Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	4179	17221
Ensembl	ENSG00000117335	ENSMUSG00000016493
UniProt	P15529	O88174
RefSeq (mRNA)	NM_002389.4	NM_010778.3
RefSeq (protein)	NP_002380.3	NP_034908.1
Location (UCSC)	Chr 1: 207.93 – 207.97 Mb	Chr 1: 196.87 – 196.92 Mb
PubMed search	[1]	[2]

CD46 complement regulatory protein also known as CD46 (cluster of differentiation 46) and Membrane Cofactor Protein is a protein which in humans is encoded by the CD46 gene.^[1] CD46 is an inhibitory complement receptor.^[2]

Gene

This gene is found in a cluster on chromosome 1q32 with other genes encoding structural components of the complement system. At least fourteen different transcript variants encoding fourteen different isoforms have been found for this gene.^[3]

Function

The protein encoded by this gene is a type I membrane protein and is a regulatory part of the complement system.

The encoded protein has cofactor activity for inactivation of complement components C3b and C4b by serum factor I, which protects the host cell from damage by complement.^[4]

The protein encoded by this gene may be involved in the fusion of the spermatozoa with the oocyte during fertilization.^[5]

Clinical Significance

The encoded protein can act as a receptor for the Edmonston strain of measles virus,^[6] human herpesvirus-6, and type IV pili of pathogenic Neisseria.^[7]

Established medulloblastoma (a malignant brain tumor common in childhood) specimens express CD46, and that medulloblastoma specimens removed from patients had a high level of CD46 expression. Therefore a vaccine made of the Edmonston strain of measles virus could treat the medulloblastoma. Such a vaccine has already been tested in a number of trials involving other tumor types which have a high expression of CD46, including one type of adult brain tumor.^[8]

Interactions

CD46 has been shown to interact with CD9,^[9] CD151^[9] and CD29.^[9]

References

1. ^ Taylor CT, Biljan MM, Kingsland CR, Johnson PM (May 1994). "Inhibition of human spermatozoon-oocyte interaction in vitro by monoclonal antibodies to CD46 (membrane cofactor protein)". Hum. Reprod. 9 (5): 907–11. PMID 7929741. http://humrep.oxfordjournals.org/cgi/content/abstract/9/5/907. 
2. ^ Liszewski MK, Post TW, Atkinson JP (1991). "Membrane cofactor protein (MCP or CD46): newest member of the regulators of complement activation gene cluster". Annu. Rev. Immunol. 9 (1): 431–55. doi:10.1146/annurev.iy.09.040191.002243. PMID 1910685. 
3. ^ "Entrez Gene: CD46 CD46 molecule, complement regulatory protein". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=4179. 
4. ^ Riley-Vargas RC, Gill DB, Kemper C, Liszewski MK, Atkinson JP (September 2004). "CD46: expanding beyond complement regulation". Trends Immunol. 25 (9): 496–503. doi:10.1016/j.it.2004.07.004. PMID 15324743. 
5. ^ Liszewski MK, Kemper C, Price JD, Atkinson JP (November 2005). "Emerging roles and new functions of CD46". Springer Semin. Immunopathol. 27 (3): 345–58. doi:10.1007/s00281-005-0002-3. PMID 16200405. 
6. ^ Dörig RE, Marcil A, Richardson CD (September 1994). "CD46, a primate-specific receptor for measles virus". Trends Microbiol. 2 (9): 312–8. doi:10.1016/0966-842X(94)90447-2. PMID 7529121. 
7. ^ Cattaneo R (May 2004). "Four viruses, two bacteria, and one receptor: membrane cofactor protein (CD46) as pathogens' magnet". J. Virol. 78 (9): 4385–8. doi:10.1128/JVI.78.9.4385-4388.2004. PMC 387720. PMID 15078919. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=387720. 
8. ^ Studebaker AW, Kreofsky CR, Pierson CR, Russell SJ, Galanis E, Raffel C (May 2010). "Treatment of medulloblastoma with a modified measles virus". Neuro Oncol 12 (10): 1034–1042. doi:10.1093/neuonc/noq057. PMC 3018921. PMID 20494960. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3018921. 
9. ^ ^{a b c} Lozahic S, Christiansen D, Manié S, Gerlier D, Billard M, Boucheix C, Rubinstein E (March 2000). "CD46 (membrane cofactor protein) associates with multiple beta1 integrins and tetraspans". Eur. J. Immunol. 30 (3): 900–7. doi:10.1002/1521-4141(200003)30:3<900::AID-IMMU900>3.0.CO;2-X. PMID 10741407. 

External links

• GeneReviews/NCBI/NIH/UW entry on Atypical Hemolytic-Uremic Syndrome
• OMIM entries on Atypical Hemolytic-Uremic Syndrome
• MeSH CD46+antigen