Glycophorin C 979514 195322473 2008-03-02T14:15:15Z Boghog2 2428506 added CD cat + navbox + MeSH link {{protein | Name = | caption = | image = | width = | HGNCid = 4704 | Symbol = GYPC | AltSymbols = GPC, GYPD, Ge, CD236, CD236R | EntrezGene = 2995 | OMIM = 110750 | RefSeq = NM_002101 | UniProt = P04921 | PDB = | ECnumber = | Chromosome = 2 | Arm = q | Band = 14 | LocusSupplementaryData = -q21 }} '''Glycophorin C''' (GYPC; CD236/CD236R; glycoprotein beta; glycoconnectin; PAS-2') is an [[integral membrane protein]] of the [[erythrocyte]] and acts as the [[receptor (biology)|receptor]] for the ''[[Plasmodium falciparum]]'' protein PfEBP-2 (erythrocyte binding protein 2; baebl; EBA-140). == Genomics == Glycophorin C (GPC) is a single [[polypeptide]] chain of 128 [[amino acids]] and is encoded by a [[gene]] on the long arm of [[Chromosome]] 2 (2q14-q21). Two [[isoform]]s are known and the gene is expressed in a wide variety of [[biological tissue|tissues]] including [[kidney]], [[thymus]], [[stomach]], [[breast]], adult [[liver]] and erythrocyte. In the non erythroid cell lines, expression is lower than in the erythrocyte and the protein is differentially [[glycosylation|glycosylated]]. In the erythrocyte glycophorin C makes up ~4% of the membrane [[sialoglycoproteins]]. The GPC gene is organized in four [[exon]]s distributed over 13.5 kilobase pairs of [[DNA]] and contains two directly repeated domains 3.4 kilobase pairs long which may be derived from a recent duplication of a single ancestral domain. The [[gene]] is expressed early in the development of the erythrocyte, specifically in the [[erythroid burst-forming unit]] and [[erythroid colony-forming unit]]. The mRNA from human erythroblasts is ~1.4 kilobases long and the transcription start site in erythroid cells has been mapped to 1050 base pairs 5' of the start codon. A second [[antigen]], glycophorin D (GPD), is generated from the glycophorin C [[messenger RNA]] by leaky translation at an in frame AUG at [[codon]] 30: glycophorin D = [[glycophorin]] C residues 30 to 128. Glycophorin C shows very little homology with the major [[red blood cell|erythrocyte membrane]] [[glycophorin]]s A and B. The latter two proteins are closely related and carry the [[blood group]] MN and Ss [[antigen]]s respectively. There are ~225,000 molecules of GPC and GPD per erythrocyte. GPC appears to be synthesized in excess in the erythrocyte and that the membrane content is regulated by band 4.1 (protein 4.1). Data on the regulation of glycophorin C is [http://srs6.bionet.nsc.ru/srs6bin/cgi-bin/wgetz?-e+TRRDGENES4-AC:A00322 here]. == Molecular biology == Glycophorin C possesses a single transmembrane domain (residues 49-88) and a cytoplasmic domain and in the erythrocyte interacts with [[band 4.1]] (an 80-kDa protein) and p55 (a [[palmitoylation|palmitoylated]] peripheral membrane phosphoprotein) to form a [[ternary complex]] that is critical for the shape and stability of erythrocytes. The major attachment sites between the erythrocyte [[spectrin]]-[[actin]] [[cytoskeleton]] and the lipid bilayer are glycophorin C and [[band 3]]. The interaction with band 4.1 and p55 is mediated by the N terminal 30 kD domain of band 4.1 binding to a 12 amino acid segment within the cytoplasmic domain of glycophorin C and to a positively charged 39 amino acid motif in p55. About 90% of the glycophorin C present in the erythrocyte is bound to the cytoskeleton and the remaining 10% moves freely within the membrane. The majority of [[protein 4.1]] is bound to glycophorin C. The magnitude of the strength of the interaction between glycophorin C and band 4.1 has been estimated to be 6.9 microNewtons per meter, a figure typical of protein–protein interactions. == Molecular medicine == Glycophorin C and D encode the Gerbich (Ge) [[antigen]]s which were described in [[1960]] and are named after one of the three original patients. There are four [[allelle]]s, Ge-1 to Ge-4. Three types of Ge antigen negativity are known: Ge-1,-2,-3 (Leach phenotype), Ge-2,-3 and Ge-2,+3. A 3.4 kilobase pair deletion within the gene, which probably arose because of unequal crossing over between the two repeated domains, is responsible for the formation of the Ge-2,-3 [[genotype]]. The breakpoints of the deletion are located within [[intron]]s 2 and 3 and results in the deletion of [[exon]] 3. This mutant gene is transcribed as a [[messenger RNA]] with a continuous [[open reading frame]] extending over 300 [[nucleotide]]s and is translated into the [[sialoglycoprotein]] found on Ge-2,-3 red cells. A second 3.4 kilobase pair deletion within the glycophorin C gene eliminates only exon 2 by a similar mechanism and generates the mutant [[gene]] encoding for the abnormal glycoprotein found on Ge-2,+3 erythrocytes. The Yussef (Yus) [[phenotype]] is due to a 57 base pair deletion corresponding to exon 2. The rare Webb (Wb) antigen (~1/1000 donors), originally described in [[1963]] in [[Australia]], is the result of an alteration in [[glycosylation]] of glycophorin C: an A to G transition at nucleotide 23 results in an [[asparagine]] residue instead of the normal [[serine]] residue with the resultant loss of glycoslation. The rare Duch (Dh) antigen - discovered in [[Aarhus]], [[Denmark]] ([[1968]]) - is due to a C to T [[transition]] at [[nucleotide]] 40 resulting in the replacement of [[leucine]] by [[phenylalanine]]. Antibodies to the Gerbich antigens have been associated with transfusion reactions and mild [[hemolytic disease]] of the newborn. The relatively rare Leach phenotype is due either to a deletion in exons 3 and 4 or to a [[frameshift mutation]] causing a premature stop codon in the glycophorin C gene, and persons with this phenotype are less susceptible (~60% of the control rate) to invasion by ''[[Plasmodium falciparum]]''. Such individuals have a subtype of a condition called [[hereditary elliptocytosis]]. Other antigens associated with this gene are Lewis II (Lsa; Ge-6) and Ahonen (Ana). Lsa has insert of 84 nucleotides into the ancestral GPC gene, an insert that corresponds to the entire sequence of exon 3. Two subtypes of Lsa are known: beta Lsa which carries the Ge3 epitope and gamma Lsa which carries both the Ge2 and Ge3 epitopes. Ana, a rare blood group antigen, is expressed on GPD positive cells only. Glycophorin C mutations are rare in most of the Western world, but are more common in some places where malaria is endemic. In [[Melanesia]] a greater percentage of the population is Gerbich negative (46.5%) than in any other part of the world. Naturally occurring anti-Ge antibodies have been found and appear to be of no clinical significance. Immunological tolerance towards Ge antigen has been suggested. == External links == * [http://dwknowles.lbl.gov/membrane/membrane.html Erythrocyte membrane cartoon] * {{MeshName|GYPC+protein,+human}} {{Clusters of differentiation}} {{Glycoproteins}} [[Category:Clusters of differentiation]] [[Category:Glycoproteins]] [[Category:Transmembrane receptors]]