Laboratory for Molecular Diagnostics
Center for Nephrology and Metabolic Disorders

C4b-binding protein alpha chain

C4b-binding protein is composed of alpha and beta chains. Three isoforms can be distinguished that constitute 7 alpha and one or none beta or 6 alpha and one beta chains, which are covalently bound by disulfid bridges. Function includes inactivation of activated complement factor 4 in the classical complement activation pathway and binding of coagulation factor protein S. 60% of plasma protein S is non covalently bound to C4b-binding protein. Hence variations of the genes have been associated with various conditions such as thrombophilia, atypical HUS, various infections, immunological type 1 diabetes, and even schizophrenia.

Genetests:

Clinic Method Carrier testing
Turnaround 5 days
Specimen type genomic DNA
Clinic Method Massive parallel sequencing
Turnaround 25 days
Specimen type genomic DNA
Research Method Genomic sequencing of the entire coding region
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

References:

1.

Brodeur SR et al. (2003) C4b-binding protein (C4BP) activates B cells through the CD40 receptor.

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2.

Hing S et al. (1988) Assignment of complement components C4 binding protein (C4BP) and factor H (FH) to human chromosome 1q, using cDNA probes.

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3.

Rodriguez de Cordoba S et al. (1985) Human genes for three complement components that regulate the activation of C3 are tightly linked.

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4.

Gigli I et al. (1979) Modulation of the classical pathway C3 convertase by plasma proteins C4 binding protein and C3b inactivator.

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5.

Aso T et al. (1991) Genomic organization of the alpha chain of the human C4b-binding protein gene.

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6.

Andersson A et al. (1990) Genes for C4b-binding protein alpha- and beta-chains (C4BPA and C4BPB) are located on chromosome 1, band 1q32, in humans and on chromosome 13 in rats.

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7.

Rey-Campos J et al. (1988) A physical map of the human regulator of complement activation gene cluster linking the complement genes CR1, CR2, DAF, and C4BP.

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8.

Barnum SR et al. (1989) Molecular analysis of the murine C4b-binding protein gene. Chromosome assignment and partial gene organization.

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9.

Matsuguchi T et al. (1989) Molecular cloning of the cDNA coding for proline-rich protein (PRP): identity of PRP as C4b-binding protein.

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10.

Hatch JA et al. (1984) Evaluation of linkage of the human C3b/C4b receptor to HLA.

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11.

Rodriguez de Cordoba S et al. (1984) Evidence for linkage between the loci coding for the binding protein for the fourth component of human complement (C4BP) and for the C3b/C4b receptor.

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12.

de Cordoba SR et al. (1983) Genetic polymorphism of human C4-binding protein.

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13.

Kaidoh T et al. (1981) Murine binding protein of the fourth component of complement: structural polymorphism and its linkage to the major histocompatibility complex.

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14.

Nagasawa S et al. (1980) Purification and characterization of a macromolecular weight cofactor for C3b-inactivator, C4bC3bINA-cofactor, of human plasma.

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15.

Sánchez-Corral P et al. (1993) C4BPAL1, a member of the human regulator of complement activation (RCA) gene cluster that resulted from the duplication of the gene coding for the alpha-chain of C4b-binding protein.

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16.

Ngampasutadol J et al. (2005) Human C4b-binding protein selectively interacts with Neisseria gonorrhoeae and results in species-specific infection.

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17.

Blom AM et al. (2008) A novel non-synonymous polymorphism (p.Arg240His) in C4b-binding protein is associated with atypical hemolytic uremic syndrome and leads to impaired alternative pathway cofactor activity.

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18.

Buil A et al. (2010) C4BPB/C4BPA is a new susceptibility locus for venous thrombosis with unknown protein S-independent mechanism: results from genome-wide association and gene expression analyses followed by case-control studies.

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19.

Nonaka MI et al. (2003) Complement C4b-binding protein as a novel murine epididymal secretory protein.

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20.

Törn C et al. (2016) Complement gene variants in relation to autoantibodies to beta cell specific antigens and type 1 diabetes in the TEDDY Study.

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21.

Dahlbäck B et al. (1981) High molecular weight complex in human plasma between vitamin K-dependent protein S and complement component C4b-binding protein.

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22.

Scharfstein J et al. (1978) Human C4-binding protein. I. Isolation and characterization.

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23.

NCBI article

NCBI 722 [^]
24.

OMIM.ORG article

Omim 120830 [^]
Update: April 29, 2019