Glycophorin A (MNS blood group), also known as GYPA, is a protein which in humans is encoded by the GYPA gene. GYPA has also recently been designated CD235a (cluster of differentiation 235a).
Function Glycophorins A (GYPA; this protein) and B (GYPB) are major sialoglycoproteins of the human erythrocyte membrane which bear the antigenic determinants for the MN and Ss blood groups. In addition to the M or N and S or s antigens, that commonly occur in all populations, about 40 related variant phenotypes have been identified. These variants include all the variants of the Miltenberger complex and several isoforms of Sta; also, Dantu, Sat, He, Mg, and deletion variants Ena, S-s-U- and Mk. Most of the variants are the result of gene recombinations between GYPA and GYPB.
Genomics GypA, GypB and GypE are members of the same family and are located on the long arm of chromosome 4 (chromosome 4q31). The family evolved via two separate gene duplication events. The initial duplication gave rise to two genes one of subsequently evolved into GypA and the other which give rise via a second duplication event to GypB and GypE. These events appear to have occurred within a relatively short time span. The second duplication appears to have occurred via an unequal crossing over event. The GypA gene itself consists of 7 exons and has 97% sequence homology with GypB and GypE from the 5' untranslated transcription region (UTR) to the coding sequence encoding the first 45 amino acids. The exon at this point encodes the transmembrane domain. Within the intron downstream of this pint is an Alu repeat. The cross over event which created the genes ancestral to GypA and GypB/E occurred within this region. GypA can be found in all primates. GypB can be found only in gorillas and some of the higher primates suggesting that the duplication events occurred only recently.
Molecular biology There are about one million copies of this protein per erythrocyte.
Blood groups The MNS blood group was the second set of antigens discovered. M and N were identified in 1927 by Landsteiner and Levine. S and s in were described later in 1947. The frequencies of these antigens are
M: 78% Caucasoid; 74% African descent N: 72% Caucasoid; 75% African descent S: 55% Caucasoid; 31% African descent s: 89% Caucasoid; 93% African descent
Molecular medicine Glycophorins carry the M and N antigens for several human blood groups. Glycophorin can be split into two groups. The first group includes glycophorin A, B, and E which carry MN and Ss blood group antigens. These three proteins are structurally homologous and essentially erythroid specific . The second group includes glycophorin C and D which carry blood group Gerbich antigens. Through protein and nucleic acid analysis, it was determined that Glycophorin D is a truncation of Glycophorin C . There is an abundance in the sequence of threonine and serine that serve as binding sites for covalent carbohydrates. Glycophorin A and B carry MNS antigens and can serve as receptors for cytokines and pathogens. They can also serve as a receptor for the malaria parasite Plasmodium falciparum.
Transfusion medicine The M and N antigens differ at two amino acid residues: the M allele has serine at position 1 (C at nucleotide 2) and glycine at position 5 (G at nucleotide 14) while the N allele has leucine at position 1 (T at nucleotide 2) and glutamate at position 5 (A at nucleotide 14). Both glycophorin A and B bind the Vicia graminea anti-N lectin. There are about 40 known variants in the MNS blood group system. These have arisen largely as a result of mutations within the 4 kb region coding for the extracellular domain. These include the antigens Mg, Dantu, Henshaw (He), Miltenberger, Nya, Osa, Orriss (Or), Raddon (FR) and Stones (Sta). Chimpanzees also have an MN blood antigen system. In chimpanzees M reacts strong but N only weakly.
Null mutants In individuals who lack both glycophorin A and B the phenotype has been designated Mk.
Dantu antigen The Dantu antigen was described in 1984. The Dantu antigen has an apparent molecular weight of 29 kilodaltons (kDa) and 99 amino acids. The first 39 amino acids of the Dantu antigen are derived from glycophorin B and residues 40-99 are derived from glycophorin A. Dantu is associated with very weak s antigen, a protease-resistant N antigen and either very weak or no U antigen. There are at least three variants: MD, NE and Ph. The Dantu phenotype occurs with a frequency of Dantu phenotype is ~0.005 in American Blacks and < 0.001 in Germans.
Henshaw antigen The Henshaw (He) antigen is due to a mutation of the N terminal region. There are three differences in the first three amino acid residues: the usual form has Tryptophan1-Serine-Threonine-Serine-Glycine5 while Henshaw has Leucine1-Serine-Threonine-Threonine-Glutamate5. This antigen is rare in Caucasians but occurs at a frequency of 2.1% in US and UK of African origin. It occurs at the rate of 7.0% in blacks in Natal and 2.7% in West Africans. At least 3 variants of this antigen have been identified.
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