CD46

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.[5] CD46 is an inhibitory complement receptor.[6]

CD46
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 3O8E, 1CKL, 2O39, 3INB, 3L89, 5FO8
Identifiers
Aliases	CD46, AHUS2, MCP, MIC10, TLX, TRA2.10, CD46 molecule
External IDs	OMIM: 120920 MGI: 1203290 HomoloGene: 7832 GeneCards: CD46
Gene location (Human) Chr. Chromosome 1 (human)[1] Band 1q32.2 Start 207,752,057 bp[1] End 207,795,513 bp[1]
Gene location (Mouse) Chr. Chromosome 1 (mouse)[2] Band 1 H6|1 98.41 cM Start 195,036,826 bp[2] End 195,092,249 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • virus receptor activity • cadherin binding • GO:0001948 protein binding • receptor activity • complement binding • endopeptidase activity • GO:0048551 enzyme inhibitor activity • signaling receptor activity Cellular component • integral component of membrane • inner acrosomal membrane • membrane • focal adhesion • cell membrane • integral component of plasma membrane • cell surface • extracellular exosome • cytoplasmic vesicle • Acrosome • cytoplasm • Golgi apparatus • basolateral plasma membrane Biological process • T cell mediated immunity • adaptive immune response • positive regulation of interleukin-10 production • immune system process • sequestering of extracellular ligand from receptor • positive regulation of regulatory T cell differentiation • negative regulation of gene expression • single fertilization • positive regulation of gene expression • positive regulation of T cell proliferation • positive regulation of memory T cell differentiation • Classical complement pathway • positive regulation of transforming growth factor beta production • viral entry • GO:0022415 viral process • regulation of Notch signaling pathway • regulation of complement activation • interleukin-10 production • innate immune system • proteolysis • GO:0048553 negative regulation of catalytic activity • negative regulation of complement activation Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	4179	17221
Ensembl	ENSG00000117335	ENSMUSG00000016493
UniProt	P15529	O88174
RefSeq (mRNA)	NM_002389 NM_153826 NM_172350 NM_172351 NM_172352 NM_172353 NM_172354 NM_172355 NM_172356 NM_172357 NM_172358 NM_172359 NM_172360 NM_172361	NM_010778
RefSeq (protein)	NP_002380 NP_722548 NP_758860 NP_758861 NP_758862 NP_758863 NP_758869 NP_758871 NP_758865 NP_758866 NP_758867 NP_758868	NP_034908
Location (UCSC)	Chr 1: 207.75 – 207.8 Mb	Chr 1: 195.04 – 195.09 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

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.[7]

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 (through cleavage) of complement components C3b and C4b by serum factor I, which protects the host cell from damage by complement.[8]

The protein encoded by this gene may be involved in the fusion of the spermatozoa with the oocyte during fertilization.[9]

Clinical significance

The encoded protein can act as a receptor for the Edmonston strain of measles virus,[10] human herpesvirus-6 (HHV-6), group B adenoviruses[11], and type IV pili of pathogenic Neisseria.[12]

The extracellular region of CD46 contains four short consensus repeats (SCR) of about 60 amino acids that fold into a compact beta-barrel domain surrounded by flexible loops.[13] As has been demonstrated for CD46 with other ligands, the CD46 protein structure is believed to linearize upon binding HHV-6. While their precise interaction has not yet been determined, the second and third SCR domains have been demonstrated to be required for HHV-6 receptor binding and cellular entry. The heterotetramer gH/gL/gQ1/gQ2 complex of HHV-6 has been identified as a CD46 ligand.[14]

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.[15]

Interactions

CD46 has been shown to interact with CD9,[16] CD151[16] and CD29.[16]

References

1. GRCh38: Ensembl release 89: ENSG00000117335 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000016493 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. 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.
6. 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.
7. "Entrez Gene: CD46 CD46 molecule, complement regulatory protein".
8. 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.
9. 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.
10. 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.
11. Gaggar A, Shayakhmetov, DM, Lieber A (2003). "CD46 is a cellular receptor for group B adenoviruses". Nat. Med. 9: 1408–1412. doi:10.1038/nm952.
12. 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.
13. Arbuckle, Jesse (2011). "The molecular biology of human herpesvirus-6 latency and telomere integration". Microbes and Infection. 13 (8–9): 731–741. doi:10.1016/j.micinf.2011.03.006. PMC 3130849. PMID 21458587.
14. Mori (2009). "Recent topics related to human herpesvirus 6 cell tropism". Cell Microbiology.
15. 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.
16. 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
• CD46+antigen at the US National Library of Medicine Medical Subject Headings (MeSH)
• Human CD46 genome location and CD46 gene details page in the UCSC Genome Browser.
• Overview of all the structural information available in the PDB for UniProt: P15529 (Human Membrane cofactor protein (CD46)) at the PDBe-KB.