| GYPB | |||||||||||||||||||||||||||||||||||||||||||||||||||
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| Identifiers | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Aliases | GYPB , CD235b, GPB, GPB.NY, GYPHe.NY, GpMiIII, HGpMiIII, HGpMiVI, HGpMiX, MNS, PAS-3, SS, GYP, glycophorin B (MNS blood group), GYPA | ||||||||||||||||||||||||||||||||||||||||||||||||||
| External IDs | OMIM: 617923 GeneCards: GYPB | ||||||||||||||||||||||||||||||||||||||||||||||||||
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| Wikidata | |||||||||||||||||||||||||||||||||||||||||||||||||||
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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. [3] GYPB has also recently been designated CD235b (cluster of differentiation 235b).
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. [3]
The gene is located on the long arm of chromosome 4 (4q28-q31) and has 5 exons. It was first sequenced in 1987 [4] the peptide sequence of 72 amino acids having been determined earlier that year.
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.
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.
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.
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
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. [5] In chimpanzees M reacts strong but N only weakly.
Individuals who lack GypB have the phenotype S-s-U-. This may occur at frequencies of 20% in some African pygmies.
In individuals who lack both glycophorin A and B the phenotype has been designated Mk. [6]
The Dantu antigen was described in 1984. [7] 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. [8] The Dantu phenotype occurs with a frequency of Dantu phenotype is ~0.005 in American Blacks and < 0.001 in Germans. [9]
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 Tryptophan 1-Serine-Threonine-Serine-Glycine 5 while Henshaw has Leucine 1-Serine-Threonine-Threonine-Glutamate 5. 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 [10] and 2.7% in West Africans. [11] At least 3 variants of this antigen have been identified.
The Miltenberger (Mi) subsystem originally consisting of five phenotypes (Mia, Vw, Mur, Hil and Hut) [12] now has 11 recognised phenotypes numbered I to XI (The antigen 'Mur' is named after to the patient the original serum was isolated from - a Mrs Murrel.) The name originally given to this complex refers to the reaction erythrocytes gave to the standard Miltenberger antisera used to test them. The subclasses were based on additional reactions with other standard antisera.
Mi-I (Mia), Mi-II(Vw), Mi-VII and Mi-VIII are carried on glycophorin A. Mi-I is due to a mutation at amino acid 28 (threonine to methionine: C->T at nucleotide 83) resulting in a loss of the glycosylation at the asparagine26 residue. [13] [14] Mi-II is due to a mutation at amino acid 28 (threonine to lysine:C->A at nucleotide 83). Similar to the case of Mi-I this mutation results in a loss of the glycosylation at the asparagine 26 residue. This alteration in glycosylation is detectable by the presence of a new 32kDa glycoprotein stainable with PAS. [15] Mi-VII is due to a double mutation in glycophorin A converting an arginine residue into a threonine residue and a tyrosine residue into a serine at the positions 49 and 52 respectively. [16] The threonine-49 residue is glycosylated. This appears to be the origin of one of the Mi-VII specific antigens (Anek) which is known to lie between residues 40-61 of glycophorin A and comprises sialic acid residue(s) attached to O-glycosidically linked oligosaccharide(s). This also explains the loss of a high frequency antigen ((EnaKT)) found in normal glycophorin A which is located within the residues 46–56. Mi-VIII is due to a mutation at amino acid residue 49 (arginine->threonine). [17] M-VIII shares the Anek determinant with MiVII. [18] Mi-III, Mi-VI and Mi-X are due to rearrangements of glycophorin A and B in the order GlyA (alpha)-GlyB (delta)-GlyA (alpha). [19] Mil-IX in contrast is a reverse alpha-delta-alpha hybrid gene. [20] Mi-V, MiV(J.L.) and Sta are due to unequal but homologous crossing-over between alpha and delta glycophorin genes. [21] The MiV and MiV(J.L.) genes are arranged in the same 5' alpha-delta 3' frame whereas Sta gene is in a reciprocal 5'delta-alpha 3' configuration. [22]
Although uncommon in Caucasians (0.0098%) and Japanese (0.006%), the frequency of Mi-III is exceptionally high in several Taiwanese aboriginal tribes (up to 90%). In contrast its frequency is 2-3% in Han Taiwanese (Minnan). The Mi-III phenotype occurs in 6.28% of Hong Kong Chinese. [23]
Mi-IX (MNS32) occurs with a frequency of 0.43% in Denmark. [24]
Stones (Sta) has been shown to be the product of a hybrid gene of which the 5'-half is derived from the glycophorin B whereas the 3'-half is derived from the glycophorin A. Several isoforms are known. This antigen is now considered to be part of the Miltenberger complex.
A related antigen is Sat. This gene has six exons of which exon I to exon IV are identical to the N allele of glycophorin A whereas its 3' portion, including exon V and exon VI, are derived from the glycophorin B gene. The mature protein SAT protein contains 104 amino acid residues.
Orriss (Or) appears to be a mutant of glyphorin A but its precise nature has not yet been determined. [25]
Both anti-S and anti-s have been implicated in transfusion reactions and haemolytic disease of the newborn. Anti-M although occurring naturally has rarely been implicated in transfusion reactions. Anti-N is not considered to cause transfusion reactions. Severe reactions have been reported with anti-U and anti-Miltenberger. Anti Mi-I (Vw) and Mi-III has been recognised as a cause of haemolytic disease of the newborn. [26] Raddon has been associated with severe transfusion reactions. [27]
Glycophorin B acts as a receptor for erythrocyte binding Ligand (EBl-1) of Plasmodium falciparum involved in malaria. [28] Both the Dantu and the S-s-U- cells phenotypes have been shown to be protective against P. falciparum infection while the Henshaw phenotype is not protective. [29] [30]
Influenza A and B bind to glycophorin B. [18]
An epitope, also known as antigenic determinant, is the part of an antigen that is recognized by the immune system, specifically by antibodies, B cells, or T cells. The part of an antibody that binds to the epitope is called a paratope. Although epitopes are usually non-self proteins, sequences derived from the host that can be recognized are also epitopes.
Glycophorin C plays a functionally important role in maintaining erythrocyte shape and regulating membrane material properties, possibly through its interaction with protein 4.1. Moreover, it has previously been shown that membranes deficient in protein 4.1 exhibit decreased content of glycophorin C. It is also an integral membrane protein of the erythrocyte and acts as the receptor for the Plasmodium falciparum protein PfEBP-2.
Duffy antigen/chemokine receptor (DARC), also known as Fy glycoprotein (FY) or CD234, is a protein that in humans is encoded by the ACKR1 gene.
Complement receptor type 1 (CR1) also known as C3b/C4b receptor or CD35 is a protein that in humans is encoded by the CR1 gene.
CD36, also known as platelet glycoprotein 4, fatty acid translocase (FAT), scavenger receptor class B member 3 (SCARB3), and glycoproteins 88 (GP88), IIIb (GPIIIB), or IV (GPIV) is a protein that in humans is encoded by the CD36 gene. The CD36 antigen is an integral membrane protein found on the surface of many cell types in vertebrate animals. It imports fatty acids inside cells and is a member of the class B scavenger receptor family of cell surface proteins. CD36 binds many ligands including collagen, thrombospondin, erythrocytes parasitized with Plasmodium falciparum, oxidized low density lipoprotein, native lipoproteins, oxidized phospholipids, and long-chain fatty acids.
A glycophorin is a sialoglycoprotein of the membrane of a red blood cell. It is a membrane-spanning protein and carries sugar molecules. It is heavily glycosylated (60%). Glycophorins are rich in sialic acid, which gives the red blood cells a very hydrophilic-charged coat. This enables them to circulate without adhering to other cells or vessel walls.
Leukosialin also known as sialophorin or CD43 is a transmembrane cell surface protein that in humans is encoded by the SPN (sialophorin) gene.
Krueppel-like factor 1 is a protein that in humans is encoded by the KLF1 gene. The gene for KLF1 is on the human chromosome 19 and on mouse chromosome 8. Krueppel-like factor 1 is a transcription factor that is necessary for the proper maturation of erythroid cells.
NADH-cytochrome b5 reductase 3 is an enzyme that in humans is encoded by the CYB5R3 gene.
The Diego antigen system is composed of 21 blood factors or antigens carried on the Band 3 glycoprotein, also known as Anion Exchanger 1 (AE1). The antigens are inherited through various alleles of the gene SLC4A1, located on human chromosome 17. The AE1 glycoprotein is expressed only in red blood cells and, in a shortened form, in some cells in the kidney. The Diegoa antigen is fairly common in Indigenous peoples of the Americas and East Asians, but very rare or absent in most other populations, supporting the theory that the two groups share common ancestry.
Galactoside 3(4)-L-fucosyltransferase is an enzyme that in humans is encoded by the FUT3 gene.
Blood group Rh(CE) polypeptide is a protein that in humans is encoded by the RHCE gene. RHCE has also recently been designated CD240CE.
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).
Rh-associated glycoprotein (RHAG) is an ammonia transporter protein that in humans is encoded by the RHAG gene. RHAG has also recently been designated CD241. Mutations in the RHAG gene can cause stomatocytosis.
Ecto-ADP-ribosyltransferase 4 is an enzyme that in humans is encoded by the ART4 gene. ART4 has also been designated as CD297.
Glycophorin-E is a protein that in humans is encoded by the GYPE gene.
Human genetic resistance to malaria refers to inherited changes in the DNA of humans which increase resistance to malaria and result in increased survival of individuals with those genetic changes. The existence of these genotypes is likely due to evolutionary pressure exerted by parasites of the genus Plasmodium which cause malaria. Since malaria infects red blood cells, these genetic changes are most common alterations to molecules essential for red blood cell function, such as hemoglobin or other cellular proteins or enzymes of red blood cells. These alterations generally protect red blood cells from invasion by Plasmodium parasites or replication of parasites within the red blood cell.
Rh blood group, D antigen also known as Rh polypeptide 1 (RhPI) or cluster of differentiation 240D (CD240D) is a protein that in humans is encoded by the RHD gene.
Complement component 4B (Chido blood group) is a kind of the Complement component 4 protein that in humans is encoded by the C4B gene.
Elwira Lisowska is a Polish biochemist and professor. She made significant contributions to the biochemistry of human blood groups, especially MNS and P1PK blood group systems, and to the immunochemical characterization of glycopeptide antigens.
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
