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. 1981 Jan;78(1):631–635. doi: 10.1073/pnas.78.1.631

Mg and Mc: mutations within the amino-terminal region of glycophorin A.

H Furthmayr, M N Metaxas, M Metaxas-Bühler
PMCID: PMC319108  PMID: 6166001

Abstract

M and N are the two common ("normal") alleles at the MN locus of the MNSs blood group system. The antigens M and N that they determine are located within the amino-terminal region of glycophorin A. In the serologically active and glycosylated (*) fragment of glycophorin AN the sequence is Leu-Ser*-Thr*-Thr*-Glu-, and in that of glycophorin AM it is Ser-Ser*-Thr*-Thr*-Gly-. Mg and Mc are very rare ("variant") alleles of M and N; as to the corresponding antigens, Mg is serologically quite distinct from M and N, while Mc is a compound of both. Erythrocytes of genotypes MgN, MgM, MgMg, and McM, which were the object of the present study, contain normal amounts of glycophorin A in their membrane. In glycophorin AMg the amino-terminal sequence is related to that of glycophorin AN by substitution of asparagine for threonine in position 4, and it is nonglycosylated: Leu-Ser-Thr-Asn-Glu-. The corresponding structure of glycophorin AMc is Ser-Ser*-Thr*-Thr*-Glu-; it is thus closely related to that of glycophorin AN and AM, by substitution of the amino acids in positions 1 or 5, respectively. All of these substitutions can be explained by single base changes. The distinctions in chemical structure not only confirm the location of M and N in this region of glycophorin A, because they are the only differences observed, but also indicate, because they are correlated with the distinctions in antigenic specificity, that M and N are structural genes coding for amino acid sequences. The finding that Mc contains structural features of both M and N suggests that these two forms of glycophorin A have evolved from a common ancestral gene by single base substitutions at sites in the genome coding for amino acids in positions 1 and 5 of the sequence. Carbohydrate structures, however, are also necessary for full expression of antigens M and N. Glycosylation during biosynthesis of residues within the polypeptide appears to depend on a particular protein structure.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. ALLEN F. H., Jr, CORCORAN P. A., KENTON H. B., BREARE N. Mg, a new blood group antigen in the MNS system. Vox Sang. 1958 Mar;3(2):81–91. doi: 10.1111/j.1423-0410.1958.tb03597.x. [DOI] [PubMed] [Google Scholar]
  2. Blumenfeld O. O., Adamany A. M. Structural polymorphism within the amino-terminal region of MM, NN, and MN glycoproteins (glycophorins) of the human erythrocyte membrane. Proc Natl Acad Sci U S A. 1978 Jun;75(6):2727–2731. doi: 10.1073/pnas.75.6.2727. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Blumenfeld O. O., Puglia K. V. Preparation of cyanogen bromide fragments of MM, NN, and MN glycoproteins (glycophorins) from human erythrocyte membranes of single donors. Biochim Biophys Acta. 1979 Jul 25;579(1):95–106. doi: 10.1016/0005-2795(79)90090-4. [DOI] [PubMed] [Google Scholar]
  4. Dahr W., Uhlenbruck G. Structural properties of the human MN blood group antigen receptor sites. Hoppe Seylers Z Physiol Chem. 1978 Jul;359(7):835–843. doi: 10.1515/bchm2.1978.359.2.835. [DOI] [PubMed] [Google Scholar]
  5. Furthmayr H., Galardy R. E., Tomita M., Marchesi V. T. The intramembranous segment of human erythrocyte glycophorin A. Arch Biochem Biophys. 1978 Jan 15;185(1):21–29. doi: 10.1016/0003-9861(78)90139-x. [DOI] [PubMed] [Google Scholar]
  6. Furthmayr H. Glycophorins A, B, and C: a family of sialoglycoproteins. Isolation and preliminary characterization of trypsin derived peptides. J Supramol Struct. 1978;9(1):79–95. doi: 10.1002/jss.400090109. [DOI] [PubMed] [Google Scholar]
  7. Furthmayr H. Structural comparison of glycophorins and immunochemical analysis of genetic variants. Nature. 1978 Feb 9;271(5645):519–524. doi: 10.1038/271519a0. [DOI] [PubMed] [Google Scholar]
  8. Furthmayr H., Tomita M., Marchesi V. T. Fractionation of the major sialoglycopeptides of the human red blood cell membrane. Biochem Biophys Res Commun. 1975 Jul 8;65(1):113–121. doi: 10.1016/s0006-291x(75)80068-4. [DOI] [PubMed] [Google Scholar]
  9. IKIN E. W., MOURANT A. E. A human blood-group gene intermediate between M and N. Nature. 1953 Oct 10;172(4380):688–689. doi: 10.1038/172688b0. [DOI] [PubMed] [Google Scholar]
  10. Judd W. J., Issitt P. D., Pavone B. G., Anderson J., Aminoff D. Antibodies that define NANA-independent MN-system antigens. Transfusion. 1979 Jan-Feb;19(1):12–18. doi: 10.1046/j.1537-2995.1979.19179160260.x. [DOI] [PubMed] [Google Scholar]
  11. Klapper D. G., Wilde C. E., 3rd, Capra J. D. Automated amino acid sequence of small peptides utilizing Polybrene. Anal Biochem. 1978 Mar;85(1):126–131. doi: 10.1016/0003-2697(78)90282-8. [DOI] [PubMed] [Google Scholar]
  12. Lisowska E., Waśniowska K. Immunochemical characterization of cyanogen bromide degradation products of M and N blood-group glycopeptides. Eur J Biochem. 1978 Jul 17;88(1):247–252. doi: 10.1111/j.1432-1033.1978.tb12444.x. [DOI] [PubMed] [Google Scholar]
  13. Marchesi V. T., Andrews E. P. Glycoproteins: isolation from cellmembranes with lithium diiodosalicylate. Science. 1971 Dec 17;174(4015):1247–1248. doi: 10.1126/science.174.4015.1247. [DOI] [PubMed] [Google Scholar]
  14. Springer G. F., Desai P. R., Murthy M. S., Tegtmeyer H., Scanlon E. F. Human carcinoma-associated precursor antigens of the blood group MN system and the host's immune responses to them. Prog Allergy. 1979;26:42–96. [PubMed] [Google Scholar]
  15. Springer G. F., Nagai Y., Tegtmeyer H. Isolation and properties of human blood-group NN and meconium-Vg antigens. Biochemistry. 1966 Oct;5(10):3254–3272. doi: 10.1021/bi00874a028. [DOI] [PubMed] [Google Scholar]
  16. Springer G. F. Role of human cell surface structures in interactions between man and microbes. Naturwissenschaften. 1970 Apr;57(4):162–171. doi: 10.1007/BF00592967. [DOI] [PubMed] [Google Scholar]
  17. Tomita M., Furthmayr H., Marchesi V. T. Primary structure of human erythrocyte glycophorin A. Isolation and characterization of peptides and complete amino acid sequence. Biochemistry. 1978 Oct 31;17(22):4756–4770. doi: 10.1021/bi00615a025. [DOI] [PubMed] [Google Scholar]
  18. Waśniowska K., Drzeniek Z., Lisowska E. The amino acids of M and N blood group glycopeptides are different. Biochem Biophys Res Commun. 1976 May 23;76(2):385–390. doi: 10.1016/0006-291x(77)90736-7. [DOI] [PubMed] [Google Scholar]

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