GYPB-Cedar Herald Index

Glycophorin B (MNS blood group) (gene designation GYPB) also known as sialoglycoprotein delta and SS-active sialoglycoprotein is a protein which in humans is encoded by the GYPB gene. GYPB has also recently been designated CD235b (cluster of differentiation 235b).

Function

Glycophorin A (GYPA) and B (GYPB; this protein) are major sialoglycoproteins of the human erythrocyte membrane which bear the antigenic determinants for the MN and Ss blood groups respectively. 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 the Miltenberger (Mi) complex and several isoforms of Stones (Sta); also Dantu, Sat, Henshaw (He or MNS6), Mg and deletion variants Ena, S-s-U- and Mk. Most of these are the result of gene recombinations between GYPA and GYPB.

GYPB

Genomics

The gene is located on the long arm of chromosome 4 (4q28-q31) and has 5 exons. It was first sequenced in 1987 the peptide sequence of 72 amino acids having been determined earlier that year.

GYPB

The gene has 97% sequence homology with the glycophorin A gene from the 5' UTR approximately 1 kilobase upstream from the exon encoding the transmembrane regions to the portion of the coding sequence encoding the first 45 amino acids. There is a signal sequence of 19 amino acid residues. The leader peptide differs by one amino acid and the next 26 amino acids are identical. Amino acids 27-55 of glycophorin A are absent from glycophorin B. This section includes an N-glycosylation site. Only O-glycosylation sites are found on glycoprotein B and these are linked via serine or threonine. Residues 80-100 of glycophorin A and 51-71 of glycophorin B are very similar. The intervening residues in contrast differ significantly. The antigenic determinant for the blood group Ss is located at residue 29 where S has a methionine and s a threonine. This is due to a mutation at nucleotide 143 (C->T). The S antigen is also known as MNS3 and the s antigen as MNS4.

GYPB

It seems likely that this gene evolved by gene duplication and subsequent mutation of glycophorin A. The transition site from homologous to nonhomologous sequences can be localized within Alu repeat sequences.

Molecular biology

There are ~80000 copies of glycophorin B per erythrocyte. Both glycophorin A and B are expressed on the renal endothelium and epithelium.

The first 40 amino acids of the mature protein are extracellular. The next 22 form a transmembrane segment and the remainder are intra cellular.

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% Caucasian; 74% Negroid

N: 72% Caucasian; 75% Negroid

S: 55% Caucasian; 31% Negroid

s: 89% Caucasian; 93% Negroid

Molecular medicine

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)

Glycophorin B carries the blood group antigens N, Ss and U. Both glycophorin A and B bind the Vicia graminea anti-N lectin. S and s antigens are not affected by treatment with trypsin or sialidase but are destroyed or much depressed by treatment with papain, pronase or alpha-chymotrypsin.

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 Mv, Dantu, Henshaw (He), Orriss (Or), Miltenberger, Raddon (FR) and Stones (Sta). Chimpanzees also have an MN blood antigen system. In chimpanzees M reacts strong but N only weakly.