Gene: [01p32/C8A] complement component 8, alpha polypeptide; C8 alpha deficiency; [C81 ]

COM

 Sequences of the C8A mRNA and its polypeptide product were published first by Rao et al. (Rao-1987). Later, the authors revealed several errors in the nucleotide sequence. The corresponding corrections were submitted to the GenBank/EMBL entry EMB:M16974, in Jun-20-1988. The corresponding SwissProt entry (SWI:P07357) lacks those corrections possibly because the last amino acid sequence update is dated by Apr-01-1988."

SUM

 [1] Three distinctive polypeptide subunits of the C8 molecule have been discovered in biochemical studies, but only two forms of the inherited C8 deficiency (associated with disseminated gonococcal infection) have been described in clinical studies. The latter demonstrated that serum from patients with complete or type I C8 deficiency lacks both alpha and gamma chains, whereas only the beta subunit was found lacking in partial or type II C8 deficiency. It was suggested that alpha and gam- ma polypeptides are synthesized as a single-chain precursor and, hence, only two separate structural genes (one for alpha-gamma chains and another for the beta subunit) encode the C8 molecule. However Ng-1987 reported that a separate mRNA encodes the gamma subunit and Kaufman-1989 mapped the corresponding gene to the chromosome segment 9q22.3-32 (GEM:09q343/C8G). In independent gene linkage studies of C8 al- pha and beta polymorphisms, it was also shown that these two polypep- tides are encoded by separate genes although the two are located close to each other on Chr 1 (GEM:01p32/C8B). These data were confirmed by in situ hybridization to metaphase chromosomes (Theriault-1991).
[3] In forming the mature C8 protein, the alpha and gamma subunits un- dergo covalent binding through a disulfide bond whereas each of them is noncovalently associated with the beta subunit. This fact apparent- ly explains why one of the mentioned C8 deficiencies is the combined alpha-gamma deficit whereas another clinical form is associated with the separate beta deficit. In addition, studies of structural homology of the C8 polypeptides established that the alpha and beta subunits show an evident sequence similarity to some other complement components (C6, C7, and C9 also involved in lysis of target cells by the membrane- -attack protein complex, Haefliger-1987a) while the gamma polypeptide shows certain homology to the different - alpha-1 microglobulin - pro- tein family (RFE:Haefliger-1987b; Hunt-1987), i.e., distinctive C8 subunits have different evolutionary origin.
[4] C8 deficiencies are thought to underlie a susceptibility to recurrent meningococcal infection and possibly systemic lupus erythematosus-like disease."

REL

 GEM:01p32/C8B; GEM:09q343/C8G; GEM:05p13/C6; GEM:05p13/C7; GEM:05p13/C9.

REF

 FOG,POL,LIN,POG "Alper &: J Clin Invest, 72, 1526-1531, 1983
PAT,PHE "Densen P &: J Clin Immunol, 3, 90-99, 1983
SEQ,EVO "Haefliger J-A &: Biochemistry, 26, 3551-3556, 1987a
SEQ,EVO "Haefliger J-A &: BBRC, 149, 750-754, 1987b
SEQ,EVO "Hunt LT &: BBRC, 149, 282-288, 1987
PAT,PHE "Jasin HE: J Clin Invest, 60, 709-715, 1977
LOC,CYG,MOL "Kaufman KM &: FASEB J, 3, A799, 1989a
LOC,CYG,MOL "Kaufman KM &: Genomics, 5, 475-480, 1989b
IDN,PEP,FUN "Kolb WP, Muller-Eberhard HJ: J Exp Med, 143, 1131-1139, 1976
PAT,PHE "Matthews N &: Clin Exp Immunol, 39, 53-59, 1980
FOG,POL,LIN,POG "Nakamura &: Hum Genet, 72, 344-347, 1986
MOP,STR "Ng SC &: Biochemistry, 26, 5229-5233, 1987
PAT,PHE "Pickering RJ &: Clin Immunol Immunopathol, 23, 223-224, 1982
CLO,SEQ,COD,PEP,EVO "Rao AG &: Biochemistry, 26, 3556-3564, 1987
FOG,POL,LIN,POG "Raum D &: J Clin Invest, 64, 858-865, 1977
FOG,POL,LIN,POG "Rittner C &: AJHG, 38, N4, 482-491, 1986
FOG,POL,LIN,POG "Rittner C &: Hum Genet, 67, 166-169, 1984
FOG,POL,LIN,POG "Rogde S &: Ann Hum Genet, 50, 139-144, 1986
FOG,POL,LIN,POG "Rogde S &: Hum Genet, 70, 211-216, 1985a
FOG,POL,LIN,POG "Rogde S &: CCG, 40 (HGM8), N1-4, 734-735, 1985b
FOG,POL,LIN,POG "Rogde S &: CCG, 37 (HGM7), N1-4, 571, 1984
LOC,CYG,MOL "Snider JV &: FASEB J, 3, A802, 1989
PAT,PHE "Tedesco F &: J Clin Invest, 86, 884-888, 1990
PAT,PHE "Tedesco F &: J Clin Invest, 71, 183-191, 1983
LOC,CYG,MOL "Theriault A &: CCG, 58 (HGM11), N1-4, 1864, 1991

KEY

 imm, comp

CLA

 coding, basic

LOC

 01 p32

MIM

 MIM: 120950

SYN

 C81