Disease relevance of GYPC

• We used naturally mutated red blood cells (RBCs) with primary genetic defects resulting in the absence of protein 4.1 (4.1[-] hereditary elliptocytosis) or glycophorin C (Leach elliptocytosis) [1].
• Western blot analysis of GPC and GPD in two of these patients revealed that these mRNAs were mostly translated into the GPD molecule, suggesting that these glycoproteins might be differently processed in certain cases of erythroleukemia [2].
• Interestingly, the same deletion which lead to the rare Ge-2,-3 genetic condition, occurred spontaneously and frequently in the cloned GPC gene during the propagation of the recombinant phages in Escherichia coli [3].
• The guinea pig hepatoma (line-1) treated with anti-Forssman antibody (TA) and GPC sequentially released 86Rb, 14C from 14C aminoidobutyric acid and failed to exclude trypan blue [4].
• HLA-A*0201 mice immunized with either GPC(42-50) or GPC(60-68) were protected against challenge with a recombinant vaccinia virus that expressed LASV GPC [5].

Psychiatry related information on GYPC

• Brain extract studies demonstrated that PC and GPC were the main components responsible for the observed in vivo spectral changes after 16 and 60 weeks of alcohol consumption, respectively [6].
• The homogeneous labeling requires prolonged reaction times and removal of excess marker prior to GPC analysis by a time-consuming precipitation-washing-redissolution sequence, which is not needed in the heterogeneous approach [7].
• A multicentre, randomised, controlled study compared the efficacy of l-alpha-glyceryl-phosphorylcholine (alpha GPC) and ST200 (acetyl-l-carnitine) among 126 patients with probable senile dementia of Alzheimer's type (SDAT) of mild to moderate degree [8].

High impact information on GYPC

• Their levels correlate with extracellular NaCl concentration and, in the case of GPC, also with urea [9].
• Sorbitol, inositol, GPC, and betaine are the predominant organic osmolytes in renal medullary cells [9].
• EBA140 does not bind to GYPC in Ge-negative erythrocytes, nor can P. falciparum invade such cells using this invasion pathway [10].
• Deletion of exon 3 in the glycophorin C gene (called GYPCDeltaex3 here) has been found in Melanesians; this alteration changes the serologic phenotype of the Gerbich (Ge) blood group system, resulting in Ge negativity [10].
• The glycophorin C N-linked glycan is a critical component of the ligand for the Plasmodium falciparum erythrocyte receptor BAEBL [11].

Chemical compound and disease context of GYPC

• In melanoma extracts, the phosphorylcholine (PC)/glycerophosphorylcholine (GPC): Ala, Glu: Ser, and lactate: Ala ratios were five-, three-, and two-fold higher, respectively, than normal skin and the Val: Leu/Ile ratio was two-thirds of normal skin [12].
• Previous studies showed that human airway smooth muscle (HASM) cells treated with lysophosphatidic acid (LPA), a pertussis toxin (PTX)-sensitive G protein-coupled (GPC) mitogen, simultaneously with epidermal growth factor (EGF), a receptor tyrosine kinase (RTK) mitogen, exhibit markedly synergistic stimulation of mitogenesis [13].
• The initial stages of degradation of the poly(PHB/PEG urethane)s were monitored by carrying out the degradation experiments at pH 7.4 and 37 degrees C. The weight loss of the copolymer films was traced, and the degraded copolymer films were characterized by GPC, (1)H NMR, TGA, and SEM [14].
• Corneas from failed grafts had lower alpha-GP, ethanolamine phosphate (EP), ethanolamine phosphate and choline phosphate (EP&CP), monoesters/Pi, ATP/Pi, and energy modulus, no detectable GPE and GPC, and higher Pi, phosphorylglycans (PG), PCr, ADP, diesters, PCr/Pi, and PCr/ATP than those with Fuchs' endothelial dystrophy (p less than 0.05) [15].
• A neutral polysaccharide was obtained by hot phenol-water extraction of biomass from Campylobacter jejuni 176.83 and subsequently separated from acid-liberated core oligosaccharide of lipopolysaccharide by sequential GPC on Bio-Gel P6 and TSK-40 columns [16].

Biological context of GYPC

• Interestingly, while homozygous glycophorin C-deficient cells had no detectable levels of this sialoglycoprotein, cells from obligate heterozygotes had normal levels [17].
• We have localized the binding site for p55 on glycophorin C to residues 112-128 (glycophorin D91-107) [18].
• The amino acid sequence of the N-terminal tryptic glycopeptide from a minor human erythrocyte membrane sialoglycoprotein (component D or glycophorin C) was determined by manual sequencing [19].
• 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 called GE (Gerbich), which is present as a single copy per haploid genome and is located on chromosome 2q14-q21.(ABSTRACT TRUNCATED AT 400 WORDS)[20]
• In Papua New Guinea (PNG), the Gerbich-negative phenotype is caused by an exon 3 deletion in the glycophorin C gene (GYPCDeltaex3) while heterozygosity for a 27-base pair deletion in the SLC4A1 gene (anion exchanger 1 or erythrocyte membrane protein, band 3), SLC4A1Delta27, results in Southeast Asian ovalocytosis [21].

Anatomical context of GYPC

• Protein 4.1 content of membranes of these glycophorin C-deficient cells was also normal [17].
• The protein 4.1-glycophorin-C cross-bridge is known to be critically important for the stability and mechanical properties of human RBC plasma membrane [1].
• These data suggest that glycophorin C may be synthesized in excess by erythroid cells and its membrane content regulated by protein 4 [17].
• The increased expression of DNDS-sensitive chloride transport is highly specific to GPA, and is not observed when the cRNA to the putative glycophorin E or a very high concentration of the cRNA to glycophorin C are coexpressed with band 3 in oocytes [22].
• The MR4-130 epitope was not coordinately expressed on the cell surface with the GPC molecule in the erythroid differentiation, since it was detected at the level of the more mature erythroid colony-forming unit slightly later than the GPC polypeptide [2].

Associations of GYPC with chemical compounds

• 1. Glycophorin C is retained by Triton shells prepared from normal membranes, whereas Triton shells prepared from protein 4.1-deficient membranes are totally devoid of this sialoglycoprotein [17].
• The expected 412-bp fragment was generated, and sequencing of the amplified product showed a G-->T substitution at nucleotide 67 of the coding sequence, resulting in the substitution of alanine by serine at amino acid residue 23 of GPC and, presumably, residue 2 of GPD [23].
• The fact that PIP2 depletion induced a decrease in band 4.1 binding to Leach vesicles shows that glycophorin C or D is not required for the formation of PIP2-sensitive band 4.1 binding sites, and may not be involved in PIP2-sensitive band 4.1 binding sites even when they are present [24].
• However, a glycosylation-dependent monoclonal antibody (MR4-130) detected an epitope on GPC which appears to be erythroid specific, suggesting that lineage specificity of this glycoprotein is related to some carbohydrate structures [2].
• Glycophorins C and D (GPC and GPD) are two erythrocyte glycoproteins which originate from the same gene but differ in their NH2-terminal residues [2].

Physical interactions of GYPC

• In this paper we show that the major attachment site is glycophorin (GP) C/D, and that purified protein 4.1 can bind to two distinct sites on glycophorin C/D [18].
• In addition, p55 also binds to the cytoplasmic domain of glycophorin C, a transmembrane protein of red blood cells [25].
• The sialoglycoprotein PAS 2 has also been shown to interact with cytoskeleton and has been named glycoconnectin [26].

Regulatory relationships of GYPC

• Glycophorin C content of human erythrocyte membrane is regulated by protein 4.1 [17].
• Labelling of erythroid precursors was carried out by a monoclonal antibody directed against glycophorin C. In order to selectively stain macrophages and their activated subset we applied CD68 and the GSA-I lectin [27].

Other interactions of GYPC

• This finding suggests that protein 4.1 is necessary for association of glycophorin C with the membrane skeleton [17].
• On a stoichiometric basis, the reduction in glycophorin C (about 80%) was concomitant to the lack of p55 in RBCs devoid of protein 4 [1].
• Human erythrocyte transmembrane sialoglycoprotein, glycophorin C, plays a functionally important role in maintaining erythrocyte shape and regulating membrane material properties, possibly through its interaction with protein 4 [17].
• The order of the above markers expressed in the cultured cells in the presence of EPO was GPC, Kell-related, GPA, band 3, Lu(b), and RhD, irrespective of the type of cytokine added [28].
• Cleavage of glycophorin (GP) A, GPB, and GPC occurred at sites close to the membrane but could not be accomplished using purified GPA and purified toxins, demonstrating that cleavage was not an effect of a direct proteolytic action of the Loxosceles toxins on the glycophorins [29].

Analytical, diagnostic and therapeutic context of GYPC

• Quantitation by flow cytometry showed that the glycophorin C content of cells totally deficient in protein 4.1 was 9% of normal and that of cells partially deficient in protein 4.1 was 44% of normal [17].
• By Northern blot analysis, we found that the GPC/GPD mRNA was present at a high level in all four patient samples [2].
• Analysis by restriction mapping and DNA sequencing confirmed that the deletions causing the Gerbich and Yus phenotypes are located entirely within the glycophorin C gene [30].
• A complementary cDNA clone (900 bp) representing the 3' untranslated region and almost the entire coding sequence of the human erythrocyte membrane glycophorin C has been used to determine the chromosomal location of the blood group Gerbich locus by in situ hybridization [31].
• By Southern blot and preliminary genomic clone analyzes we have compared the status of the genes for glycophorins A and B, as well as that of the gene encoding glycophorin C, another unrelated red cell membrane glycoprotein, in the En(a-) variants and in the En(a+) control donors [32].

References