CD46

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.{{cite web | title = Entrez Gene: CD46 CD46 molecule, complement regulatory protein| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=4179}}

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.{{cite journal | vauthors = Riley-Vargas RC, Gill DB, Kemper C, Liszewski MK, Atkinson JP | title = CD46: expanding beyond complement regulation | journal = Trends in Immunology | volume = 25 | issue = 9 | pages = 496–503 | date = September 2004 | pmid = 15324743 | doi = 10.1016/j.it.2004.07.004 }}

The protein encoded by this gene may be involved in the fusion of the spermatozoa with the oocyte during fertilization.{{cite journal | vauthors = Liszewski MK, Kemper C, Price JD, Atkinson JP | title = Emerging roles and new functions of CD46 | journal = Springer Seminars in Immunopathology | volume = 27 | issue = 3 | pages = 345–358 | date = November 2005 | pmid = 16200405 | doi = 10.1007/s00281-005-0002-3 | s2cid = 28240864 }}

The encoded protein can act as a receptor for the Edmonston strain of measles virus,{{cite journal | vauthors = Dörig RE, Marcil A, Richardson CD | title = CD46, a primate-specific receptor for measles virus | journal = Trends in Microbiology | volume = 2 | issue = 9 | pages = 312–318 | date = September 1994 | pmid = 7529121 | doi = 10.1016/0966-842X(94)90447-2 }} human herpesvirus-6 (HHV-6), group B adenoviruses,{{cite journal | vauthors = Gaggar A, Shayakhmetov DM, Lieber A | title = CD46 is a cellular receptor for group B adenoviruses | journal = Nature Medicine | volume = 9 | issue = 11 | pages = 1408–1412 | date = November 2003 | pmid = 14566335 | doi = 10.1038/nm952 | s2cid = 25265753 }} and type IV pili of pathogenic Neisseria.{{cite journal | vauthors = Cattaneo R | title = Four viruses, two bacteria, and one receptor: membrane cofactor protein (CD46) as pathogens' magnet | journal = Journal of Virology | volume = 78 | issue = 9 | pages = 4385–4388 | date = May 2004 | pmid = 15078919 | pmc = 387720 | doi = 10.1128/JVI.78.9.4385-4388.2004 }}

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.{{cite journal | vauthors = Arbuckle JH, Medveczky PG | title = The molecular biology of human herpesvirus-6 latency and telomere integration | journal = Microbes and Infection | volume = 13 | issue = 8-9 | pages = 731–741 | date = August 2011 | pmid = 21458587 | pmc = 3130849 | doi = 10.1016/j.micinf.2011.03.006 }} 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.{{cite journal | vauthors = Mori Y | title = Recent topics related to human herpesvirus 6 cell tropism | journal = Cellular Microbiology | volume = 11 | issue = 7 | pages = 1001–1006 | date = July 2009 | pmid = 19290911 | doi = 10.1111/j.1462-5822.2009.01312.x | s2cid = 20827342 | doi-access = free }}

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.{{cite journal | vauthors = Studebaker AW, Kreofsky CR, Pierson CR, Russell SJ, Galanis E, Raffel C | title = Treatment of medulloblastoma with a modified measles virus | journal = Neuro-Oncology | volume = 12 | issue = 10 | pages = 1034–1042 | date = October 2010 | pmid = 20494960 | pmc = 3018921 | doi = 10.1093/neuonc/noq057 }}

Recently, CD46 has emerged as a promising target for the treatment of both adenocarcinoma and neuroendocrine types of metastatic castration-resistant prostate cancer (mCRPC).{{cite journal | vauthors = Su Y, Liu Y, Behrens CR, Bidlingmaier S, Lee NK, Aggarwal R, Sherbenou DW, Burlingame AL, Hann BC, Simko JP, Premasekharan G, Paris PL, Shuman MA, Seo Y, Small EJ, Liu B | title = Targeting CD46 for both adenocarcinoma and neuroendocrine prostate cancer | journal = JCI Insight | volume = 3 | issue = 17 | date = September 2018 | pmid = 30185663 | pmc = 6171802 | doi = 10.1172/jci.insight.121497 }}{{cite journal | vauthors = Ruan W, Sassoon A, An F, Simko JP, Liu B | title = Identification of clinically significant tumor antigens by selecting phage antibody library on tumor cells in situ using laser capture microdissection | journal = Molecular & Cellular Proteomics | volume = 5 | issue = 12 | pages = 2364–2373 | date = December 2006 | pmid = 16982673 | doi = 10.1074/mcp.m600246-mcp200 | doi-access = free }} YS5, a human full-length IgG1 with high specificity for CD46, was identified to have high binding affinity for prostate cancer tissue. YS5 has been developed into an antibody-drug conjugate, FOR46, which is currently in a phase I clinical trial (NCT03575819) for the treatment of mCRPC. Since then, a companion molecular imaging agent for CD46-targeted therapy has been developed.{{cite journal | vauthors = Wang S, Li J, Hua J, Su Y, Beckford-Vera DR, Zhao W, Jayaraman M, Huynh TL, Zhao N, Wang YH, Huang Y, Qin F, Shen S, Gioeli D, Dreicer R, Sriram R, Egusa EA, Chou J, Feng FY, Aggarwal R, Evans MJ, Seo Y, Liu B, Flavell RR, He J | title = Molecular Imaging of Prostate Cancer Targeting CD46 Using ImmunoPET | journal = Clinical Cancer Research | volume = 27 | issue = 5 | pages = 1305–1315 | date = March 2021 | pmid = 33293372 | pmc = 7925362 | doi = 10.1158/1078-0432.CCR-20-3310 }}

CD46 deficiency contributes to inflammation disorders.{{cite journal | vauthors = Liszewski MK, Atkinson JP | title = Membrane cofactor protein (MCP; CD46): deficiency states and pathogen connections | journal = Current Opinion in Immunology | volume = 72 | issue = | pages = 126–134 | date = October 2021 | pmid = 34004375 | pmc = 8123722 | doi = 10.1016/j.coi.2021.04.005 }}

CD46 has been shown to interact with CD9,{{cite journal | vauthors = Lozahic S, Christiansen D, Manié S, Gerlier D, Billard M, Boucheix C, Rubinstein E | title = CD46 (membrane cofactor protein) associates with multiple beta1 integrins and tetraspans | journal = European Journal of Immunology | volume = 30 | issue = 3 | pages = 900–907 | date = March 2000 | pmid = 10741407 | doi = 10.1002/1521-4141(200003)30:3<900::AID-IMMU900>3.0.CO;2-X | doi-access = free }} CD151 and CD29.

{{reflist}}

• [https://www.ncbi.nlm.nih.gov/books/NBK1367/ GeneReviews/NCBI/NIH/UW entry on Atypical Hemolytic-Uremic Syndrome]
• [https://www.ncbi.nlm.nih.gov/omim/277400,120700,120920,134370,134371,138470,188040,217030,235400,605336,605337,612922,612923,612924,612925,612926,120700,120920,134370,134371,138470,188040,217030,235400,605336,605337,612922,612923,612924,612925,612926 OMIM entries on Atypical Hemolytic-Uremic Syndrome]
• {{MeshName|CD46+antigen}}
• {{UCSC gene info|CD46}}
• {{PDBe-KB2|P15529|Human Membrane cofactor protein (CD46)}}

{{Clusters of differentiation}}

{{Complement system}}

Category:Clusters of differentiation