Laboratory for Molecular Diagnostics
Center for Nephrology and Metabolic Disorders

Membrane cofactor protein

The membrane protein encoded by the MCP gene is involved in complement activation amd measles infection. Mutations lead to atypical hemolytic uremic syndrome (aHUS) and theoretically may influence susceptibility to measles.

Protein Structure

The receptor protein passes the membrane only once. The short N-terminal portion is intracellular. The extracellular portion is of beginning from the C-terminal endcomposed 4 SCR (short consensus repeat) domains and 2 serin-, threonin-, and prolin-rich domains. The SCR are incolved in complement control and therefore sometimes also called complement control proteins (CCP) though they are not proteins but domains.

Expression

The complement binding receptor (CD46) is expressed on all human cells except erythrocytes.

Interpretation

Heterozygous mutations may result in either reduced receptor expression on the cell surface (75%) or impaired receptor function (25%). 93% of pathogenetic mutations are located in the 4 SCR (short consensus repeat) domains.

The penetrance appears to be 54%.[Error: Macro 'ref' doesn't exist]

Genetests:

Clinic Method Carrier testing
Turnaround 5 days
Specimen type genomic DNA
Clinic Method Multiplex Ligation-Dependent Probe Amplification
Turnaround 20 days
Specimen type genomic DNA
Clinic Method Genomic sequencing of the entire coding region
Turnaround 20 days
Specimen type genomic DNA
Clinic Method Massive parallel sequencing
Turnaround 25 days
Specimen type genomic DNA

Related Diseases:

Hemolytic-Uremic Syndrome
ADAMTS13
C3
C4BPA
C4BPB
CD46
CFB
CFH
CFHR1
CFHR2
CFHR3
CFHR4
CFHR5
CFI
CLU
DGKE
Methylmalonic aciduria
Methylmalonic aciduria and homocystinuria cblC
MMACHC
Methylmalonic aciduria and homocystinuria cblD
MMADHC
Methylmalonic aciduria type mut
MUT
PIGA
PLG
THBD
Measles infection susceptibility
CD46
Meningococcal infection susceptibility
C3
C5
C7
C8A
C8B
C8G
C9
CD46
CFB
CFD
CFH
CFP

References:

1.

Xiang L et al. (1999) Quantitative alleles of CR1: coding sequence analysis and comparison of haplotypes in two ethnic groups.

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2.

Nürnberger J et al. (2009) Eculizumab for atypical hemolytic-uremic syndrome.

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3.

Santoro F et al. (1999) CD46 is a cellular receptor for human herpesvirus 6.

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4.

Tatsuo H et al. (2000) SLAM (CDw150) is a cellular receptor for measles virus.

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5.

Källström H et al. (2001) Attachment of Neisseria gonorrhoeae to the cellular pilus receptor CD46: identification of domains important for bacterial adherence.

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6.

Marie JC et al. (2002) Linking innate and acquired immunity: divergent role of CD46 cytoplasmic domains in T cell induced inflammation.

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7.

Kemper C et al. (2003) Activation of human CD4+ cells with CD3 and CD46 induces a T-regulatory cell 1 phenotype.

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8.

Schneider-Schaulies J et al. (2003) Measles infection of the central nervous system.

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9.

Johansson L et al. (2003) CD46 in meningococcal disease.

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10.

Richards A et al. (2003) Mutations in human complement regulator, membrane cofactor protein (CD46), predispose to development of familial hemolytic uremic syndrome.

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11.

Gaggar A et al. (2003) CD46 is a cellular receptor for group B adenoviruses.

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12.

Noris M et al. (2003) Familial haemolytic uraemic syndrome and an MCP mutation.

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13.

Goodship TH et al. (2004) Mutations in CD46, a complement regulatory protein, predispose to atypical HUS.

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14.

Esparza-Gordillo J et al. (2005) Predisposition to atypical hemolytic uremic syndrome involves the concurrence of different susceptibility alleles in the regulators of complement activation gene cluster in 1q32.

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15.

Fremeaux-Bacchi V et al. (2005) The development of atypical haemolytic-uraemic syndrome is influenced by susceptibility factors in factor H and membrane cofactor protein: evidence from two independent cohorts.

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16.

Gaggar A et al. (2005) Localization of regions in CD46 that interact with adenovirus.

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17.

Cassiani-Ingoni R et al. (2005) CD46 on glial cells can function as a receptor for viral glycoprotein-mediated cell-cell fusion.

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18.

Yanagi Y et al. (2006) Measles virus receptors and tropism.

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19.

Tishon A et al. (2006) CD4 T cell control primary measles virus infection of the CNS: regulation is dependent on combined activity with either CD8 T cells or with B cells: CD4, CD8 or B cells alone are ineffective.

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20.

Sood R et al. (2006) Gene expression patterns in human placenta.

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21.

Caprioli J et al. (2006) Genetics of HUS: the impact of MCP, CFH, and IF mutations on clinical presentation, response to treatment, and outcome.

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22.

Richards A et al. (2007) Implications of the initial mutations in membrane cofactor protein (MCP; CD46) leading to atypical hemolytic uremic syndrome.

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23.

Yanagi Y et al. (2006) Measles virus: cellular receptors, tropism and pathogenesis.

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24.

Post TW et al. (1991) Membrane cofactor protein of the complement system: alternative splicing of serine/threonine/proline-rich exons and cytoplasmic tails produces multiple isoforms that correlate with protein phenotype.

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25.

Oliaro J et al. (2006) Ligation of the cell surface receptor, CD46, alters T cell polarity and response to antigen presentation.

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26.

Zheng XL et al. (2008) Pathogenesis of thrombotic microangiopathies.

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27.

Karosi T et al. (2008) Disease-associated novel CD46 splicing variants and pathologic bone remodeling in otosclerosis.

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28.

Yanagi Y et al. (2009) Measles virus receptors.

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29.

Kemper C et al. (2009) Measles virus and CD46.

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30.

Purcell DF et al. (1991) Identification of four different CD46 (MCP) molecules with anti-peptide antibodies.

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31.

Santiago C et al. (2010) Structure of the measles virus hemagglutinin bound to the CD46 receptor.

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32.

Haralambieva IH et al. (2011) Genetic polymorphisms in host antiviral genes: associations with humoral and cellular immunity to measles vaccine.

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33.

Ovsyannikova IG et al. (2011) The association of CD46, SLAM and CD209 cellular receptor gene SNPs with variations in measles vaccine-induced immune responses: a replication study and examination of novel polymorphisms.

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34.

Andrews PW et al. (1985) A human cell-surface antigen defined by a monoclonal antibody and controlled by a gene on human chromosome 1.

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35.

Bora NS et al. (1989) Structural gene for human membrane cofactor protein (MCP) of complement maps to within 100 kb of the 3' end of the C3b/C4b receptor gene.

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36.

Lublin DM et al. (1988) Molecular cloning and chromosomal localization of human membrane cofactor protein (MCP). Evidence for inclusion in the multigene family of complement-regulatory proteins.

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37.

Pirson Y et al. (1987) Hemolytic uremic syndrome in three adult siblings: a familial study and evolution.

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38.

McIntyre JA et al. (1983) Human trophoblast-lymphocyte cross-reactive (TLX) antigens define a new alloantigen system.

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39.

Cui W et al. (1993) Characterization of the promoter region of the membrane cofactor protein (CD46) gene of the human complement system and comparison to a membrane cofactor protein-like genetic element.

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40.

Dörig RE et al. (1993) The human CD46 molecule is a receptor for measles virus (Edmonston strain).

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41.

Källström H et al. (1997) Membrane cofactor protein (MCP or CD46) is a cellular pilus receptor for pathogenic Neisseria.

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42.

Warwicker P et al. (1998) Genetic studies into inherited and sporadic hemolytic uremic syndrome.

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Update: Sept. 26, 2018