Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.1.1.49 (glucose-6-phosphate dehydrogenase)
 7,794 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The normal and variant forms of GPC and GPD molecules carry antigens of the Gerbich blood group system. This blood group system comprises three high-incidence antigens (Ge2, Ge3 and Ge4) and four low-incidence antigens (Wb, Lsa, Dha and Ana). Erythrocytes of the Ge and Yus phenotypes lack normal GPC and GPD molecules but express variant molecules (denoted GPC.Ge, GPC.Yus, respectively) that functionally substitute for normal GPC and GPD in the membrane. Leach phenotype cells lack GPC and GPD molecules and are elliptocytic in shape with a membrane that is less deformable than that of normal cells. The Lsa antigen is expressed on higher molecular-weight variants of GPC (GPC.Lsa) and GPD (GPD.Lsa). Wb, Dha and Ana antigens arise from point mutations in the GYPC gene and are expressed on GPC.Wb, GPC.Dha and GPD.Ana, respectively. The structure of each of the variant GPC and GPD molecules and the location of the Gerbich blood group system antigens is discussed. The GYPC gene, located on chromosome 2q14-q21, is 13.5 kb long and comprises four exons. Exons 1, 2 and most of exon 3 encode the N-terminal extracellular domain while the remainder of exon 3 and exon 4 encode transmembrane and cytoplasmic domains of GPC. Exons 2 and 3 are highly homologous, with less than 5% nucleotide divergence. The molecular basis of generation of variation GPC and GPD molecules, and the structure of the GYPC gene from different Leach phenotype individuals, is discussed.
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PMID:Molecular basis of glycophorin C variants and their associated blood group antigens. 792 Oct 50

Four main glycophorins which can be specifically detected by periodic-acid-Schiff (PAS) staining after separation of red cell membranes by SDS-polyacrylamide gel electrophoresis have been identified and are known under different nomenclatures. Here, the designation of glycophorins A, B and C and glycophorin D will be used. A new member designated glycophorin E (GPE) has been recently identified in the course of molecular genetic studies. These glycophorins represent about 2% of the total erythrocyte membrane protein mass and have been fully characterized both at the protein and at the DNA level. Accordingly, these molecules can be subdivided into two groups that are distinguished by distinct properties such as blood group antigenic properties, apparent M(r), copy number, attached glycans, detergent solubility, and gene structure. GPC and GPD are minor sialoglycoproteins contributing to 4 and 1% to the PAS-positive material and are present at about 2.0 and 0.5 x 10(5) copies/cell, respectively. Both carry blood group Gerbich (Ge) antigens. Protein and nucleic acid analysis indicated that GPD is a truncated form of GPC in its N-terminal region and that both proteins are produced by a unique gene which is present as a single copy on chromosome 2q14-q21. GPC and GPD are produced from the same gene through use of alternative translation initiation sites. These proteins and the GYPC gene share no homology with the GPA, GPB and GPE proteins and the GYPA gene cluster, respectively. Thus, the glycophorin name, which suggests that all these sialoglycopropteins have a common genetic origin, might be now considered as a misnomer. As a further difference between the two groups of membrane proteins, GPC and GPD are expressed both in erythroid and non erythroid tissues, but the level of transcription is much higher in erythroid than in non erythroid tissues and in addition the proteins are differently glycosylated in the two cell types. Increasing evidence suggests a significant role for GPC and GPD in the regulation of the red cell shape and the membrane mechanical properties by providing a membrane linkage site for cytoskeletal proteins, especially proteins 4.1 and p55. The total lack of GPC and GPD in the red cell membrane is associated with hereditary ellyptocytosis in the Leach phenotype and the molecular basis of these defects have been elucidated.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Gerbich blood groups and minor glycophorins of human erythrocytes. 854 24

The discovery of a natural Gerbich antigen (anti-Ge2) in the serum of a propositus prompted us to study his red blood cells (RBCs) by using monoclonal anti-bodies (mAbs) directed against glycophorin (GP) C and GPD. An mAb directed against the Ge4 antigen (mAb NaM10-7G11) agglutinated both untreated and trypsin-treated cells, demonstrating the expression of a trypsin-resistant GPC (namely, GPC of the Gerbich type: GPCGe). Surprisingly, an anti-Ge3 antibody (mAb NaM19-3C4) agglutinated untreated cells, showing that they also express the Ge3 antigen that may be carried by normal GPC and CPD or by the abnormal GPC of the Yussef (Yus) type (GPCYus). Immunoblotting analysis performed with an mAb directed against the C-terminal portion of GPC showed that the propositus' RBCs do not contain normal GPC and GPD but both GPCGe and GPCYus. Analysis of RBCs from the family demonstrated that, like the propositus, 2 of the 3 sisters had inherited both the GYPCGe and the GYPCYus alleles from the parents, who carried either the GYPCGe or the GYPCYus allele. The third sister had inherited the normal GYPC alleles from her parents, whereas the child of the propositus had inherited the GYPCGe allele. Interestingly, natural anti-Ge2 antibodies were identified in the serum of 2 of the 3 Ge-negative individuals.
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PMID:Inheritance of abnormal glycophorin C of the Gerbich and Yussef type in a French family. 880 69

GYPC encodes two erythrocyte surface sialoglycoproteins in humans, glycophorin C and glycophorin D (GPC and GPD), via initiation of translation at two start codons on a single transcript. The malaria-causing parasite Plasmodium falciparum uses GPC as a means of invasion into the human red blood cell. Here, we examine the molecular evolution of GYPC among the Hominoidea (Greater and Lesser Apes) and also the pattern of polymorphism at the locus in a global human sample. We find an excess of nonsynonymous divergence among species that appears to be caused solely by accelerated evolution of GYPC in the human lineage. Moreover, we find that the ability of GYPC to encode both GPC and GPD is a uniquely human trait, caused by the evolution of the GPC start codon in the human lineage. The pattern of polymorphism among humans is consistent with a hitchhiking event at the locus, suggesting that positive natural selection affected GYPC in the relatively recent past. Because GPC is exploited by P. falciparum for invasion of the red blood cell, we hypothesize that selection for evasion of P. falciparum has caused accelerated evolution of GYPC in humans (relative to other primates) and that this positive selection has continued to act in the recent evolution of our species. These data suggest that malaria has played a powerful role in shaping molecules on the surface of the human red blood cell. In addition, our examination of GYPC reveals a novel mechanism of protein evolution: co-option of untranslated region (UTR) sequence following the formation of a new start codon. In the case of human GYPC, the ancestral protein (GPD) continues to be produced through leaky translation. Because leaky translation is a widespread phenomenon among genes and organisms, we suggest that co-option of UTR sequence may be an important source of protein innovation.
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PMID:Molecular evolution of GYPC: evidence for recent structural innovation and positive selection in humans. 1967 54