Type II human complement C2 deficiency. Allele-specific amino acid substitutions (Ser189 --> Phe; Gly444 --> Arg) cause impaired C2 secretion.

作者: Rick A. Wetsel , Judit Kulics , Marja-Liisa Lokki , Photini Kiepiela , Hideto Akama

DOI: 10.1074/JBC.271.10.5824

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摘要: Type II complement protein C2 deficiency is characterized by a selective block in secretion. The null allele (C2Q0) linked to two major histocompatibility haplotypes (MHC) that differ from the MHC of more common I deficiency. To determine molecular basis C2Q0 genes were isolated and transfected separately into L-cells. Subsequent biology, biosynthetic, immunofluorescence studies demonstrated secretion impaired because different missense mutations at highly conserved residues each alleles. One exon 5 (nucleotide C566 →T; Ser189 →Phe) gene haplotype A11,B35,DRw1,BFS, C4A0B1. other 11 (G1930 →A; Gly444 →Arg) A2,B5, DRw4,BFS,C4A3B1. Each mutant product retained early secretory pathway. These mutants provide models for elucidating

参考文章(44)
B. R. Shiels, W. Northemann, S. Broome, G. Widera, G. D. Virca, Simplified northern blot hybridization using 5% sodium dodecyl sulfate. BioTechniques. ,vol. 8, pp. 370- 371 ,(1990)
J.E. Volanakis, Yoshitomo Ishii, Zeng-Bian Zhu, K.J. Macon, Structure of the human C2 gene. Journal of Immunology. ,vol. 151, pp. 170- 174 ,(1993)
John E. Volanakis, Vincent J. Kidd, Kevin J. Macon, Takahiko Horiuchi, cDNA cloning and expression of human complement component C2. Journal of Immunology. ,vol. 142, pp. 2105- 2111 ,(1989)
Lori Singer, William T Whitehead, Hideto Akama, Yitzhak Katz, Zvi Fishelson, Rick A Wetsel, None, Inherited human complement C3 deficiency. An amino acid substitution in the beta-chain (ASP549 to ASN) impairs C3 secretion. Journal of Biological Chemistry. ,vol. 269, pp. 28494- 28499 ,(1994) , 10.1016/S0021-9258(18)46954-2
R A Wetsel, D T Fleischer, D L Haviland, Deficiency of the murine fifth complement component (C5). A 2-base pair gene deletion in a 5'-exon. Journal of Biological Chemistry. ,vol. 265, pp. 2435- 2440 ,(1990) , 10.1016/S0021-9258(19)39817-5
Rick A. Wetsel, Harvey R. Colten, Masaru Nonaka, Naoshi Ishikawa, Murine complement C2 and factor B genomic and cDNA cloning reveals different mechanisms for multiple transcripts of C2 and B. Journal of Biological Chemistry. ,vol. 265, pp. 19040- 19046 ,(1990) , 10.1016/S0021-9258(17)30621-X
J Melnick, S Aviel, Y Argon, The endoplasmic reticulum stress protein GRP94, in addition to BiP, associates with unassembled immunoglobulin chains. Journal of Biological Chemistry. ,vol. 267, pp. 21303- 21306 ,(1992) , 10.1016/S0021-9258(19)36608-6
David Lane, Ed Harlow, Antibodies: A Laboratory Manual ,(1988)