Glycophorin-C (GYPC)

The protein contains 128 amino acids for an estimated molecular weight of 13811 Da.

 

This protein is a minor sialoglycoprotein in human erythrocyte membranes. The blood group Gerbich antigens and receptors for Plasmodium falciparum merozoites are most likely located within the extracellular domain. Glycophorin-C plays an important role in regulating the stability of red cells. (updated: April 1, 2015)

Protein identification was indicated in the following studies:

  1. Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
  2. Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
  3. Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
  4. Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
  5. Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
  6. D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
  7. Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.

Methods

The following articles were analysed to gather the proteome content of erythrocytes.

The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.

PublicationIdentification 1Uniprot mapping 2Not mapped /
Obsolete
TrEMBLSwiss-Prot
Goodman (2013)2289 (gene list)227853205992269
Lange (2014)123412347281224
Hegedus (2015)2638262202352387
Wilson (2016)165815281702911068
d'Alessandro (2017)18261817201815
Bryk (2017)20902060101081942
Chu (2018)18531804553621387

1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry

The compilation of older studies can be retrieved from the Red Blood Cell Collection database.

The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.

No sequence conservation computed yet.

This protein is annotated as membranous in Gene Ontology, is annotated as membranous in UniProt, is predicted to be membranous by TOPCONS.


Interpro domains
Total structural coverage: 38%
Model score: 40

(right-click above to access to more options from the contextual menu)

VariantDescription
Webb (WB) antigen
Duch (DH(a)) antigen
Ahonen (AN(a)) antigen
dbSNP:rs28370000

No binding partner found

The reference OMIM entry for this protein is 110750

Glycophorin c; gypc
Gpc
Sialoglycoprotein, beta glycophorin d, included; gypd, included; gpd, included
Sialoglycoprotein, gamma, included

DESCRIPTION

The GYPC gene encodes glycophorin C (GPC) and glycophorin D (GPD) through the use of alternative translational start sites. GPC and GPD interact with protein 4.1R (EPB41; 130500) and contribute stability to the red blood cell membrane (review by Walker and Reid, 2010).

CLONING

Colin et al. (1986) isolated cDNA clones for red cell glycophorin C and deduced its complete amino acid sequence. It is a single polypeptide chain of 128 amino acids sharing little homology with the major red cell membrane glycophorins A and B, which carry the blood group MN (111300) and Ss (111740) antigens, respectively, and are closely related proteins. Le Van Kim et al. (1987) presented evidence that GPC and GPD are encoded by the same gene. El-Maliki et al. (1989) concluded from sequence data that glycophorin D is an abridged version of glycophorin C. Glycophorin C is a single polypeptide chain of 128 amino acid residues. GYPD is smaller than GYPC (24 kD vs 32 kD). Amino acid sequence showed identity of GYPD with residues of 30 to 126 of GYPC. The mechanism generating GYPC and GYPD from the same gene may involve translation of the same mRNA to in-phase AUGs by leaky translation (Cartron et al., 1990). Available sequencing information on GYPD was consistent with this model. From studies of the molecular basis of the rare blood group An(a) antigen, Daniels et al. (1993) obtained further evidence that glycophorin D is a product of the GYPC gene.

GENE STRUCTURE

In their review, Walker and Reid (2010) stated that the GYPC gene contains 4 exons and spans 13.5 kb. Exons 2 and 3 are homologous, with less than 5% nucleotide divergence.

MAPPING

Mattei et al. (1986) used a cDNA clone for GYPC in studies by in situ hybridization to assign the GYPC gene to chromosome 2q14-q21. Gross (2014) mapped the GYPC gene to chromosome 2q14.3 based on an alignment of the GYPC sequence (GenBank GENBANK AY838876) with the genomic sequence (GRCh38).

MOLECULAR GENETICS

Glycophorin C carries determinants of the Gerbich blood group (616089); Ge antigens are also present on glycophorin D. Using a cDNA prepared from the mRNA of glycophorin C, Le Van Kim et al. (1987) found that the Ge-negative condition in donors with nonelliptocytic red cells was associated with a 3-kb deletion in the glycophorin C gene. Their findings also suggested that the same gene codes for glycophorin D. Winardi et al. (1993) characterized the deficiency of glycophorins C and D in erythrocytes of the Leach phenotype of the Gerbich blood group system. They found that the deficiency was the consequence of deletion or marked alteration of exons 3 and 4 of the GYPC gene. The mutant gene encoded an mRNA stable enough to be detected in circulating reticulocytes. The protein encoded by this mRNA would not be expected to be expressed in the cell membrane because it would lack the transmembrane and cytoplasmic domains. Data on gene frequencies of allelic variants were tabulated by Roychoudhury and Nei (1988). ... More on the omim web site

The reference OMIM entry for this protein is 616089

Blood group, gerbich system; ge
Gerbich blood group system

A number sign (#) is used with this entry because the Gerbich (Ge) blood group system is based on variation in the GYPC gene (110750) on chromosome 2q14.3.

DESCRIPTION

The Gerbich blood group system contains 6 high-prevalence and 5 low-prevalence antigens that are expressed on glycophorin C (GPC), glycophorin D (GPD), or both GPC and GPD. GPC and GPD, which contribute stability to the red blood cell membrane, are encoded by the same gene, GYPC, through the use of alternative translational start sites. Deficiency of GPC and GPD is associated with hereditary elliptocytosis, and Gerbich antigens act as receptors for the malarial parasite Plasmodium falciparum (see 611162). The Gerbich antibodies anti-Ge2 and anti-Ge3 have caused hemolytic transfusion reactions, and anti-Ge3 has produced hemolytic disease of the fetus and newborn (review by Walker and Reid, 2010).

CLINICAL FEATURES

Antibody demonstrating the Ge antigen was found in cases of fetomaternal incompatibility (Barnes and Lewis, 1961). Independence of the Ge system from other systems has been demonstrated (Race and Sanger, 1975). Anstee et al. (1984) studied the red cells of 2 unrelated persons who lacked Ge blood group substance and 3 minor sialoglycoproteins that are associated with the cytoskeleton of normal red cells. About 10% of red cells in each subject were 'frankly elliptocytic.' In Melanesia there are more Gerbich-negative persons than in any other part of the world (Booth and McLoughlin, 1972). Since Gerbich-negative red cells lack beta- and gamma-sialoglycoproteins, it is reasonable to presume that Gerbich antigens are located on these proteins, also called glycophorins C and D. Glycophorin C is a minor red cell membrane component, representing about 4% of the membrane sialoglycoproteins. It is a putative receptor for the merozoites of Plasmodium falciparum (Pasvol et al., 1984). The occurrence of elliptocytosis and Gerbich-negative red cells in Melanesia may be related to the function of glycophorin C in relation to Plasmodium falciparum. However, the primary defect in the Malaysian-Melanesian type of elliptocytosis resides in the band 3 protein of the red cell membrane (109270.0002). Glycophorin C has a role in the maintenance of red cell shape (Bennett, 1985). Some rare individuals with the Gerbich-negative phenotype lack certain minor erythrocyte sialoglycoproteins. Anderson et al. (1986) reported such an individual whose erythrocytes lacked beta- and gamma-sialoglycoproteins in SDS-PAGE but had 2 additional abnormal sialoglycoproteins. Analysis using SDS-PAGE of erythrocyte membranes from his 2 children failed to reveal any similar abnormal sialoglycoproteins. This led to the suggestion by Anderson et al. (1986) that, in this instance, the Gerbich-negative phenotype may have resulted from other mechanisms, possibly defective glycosylation, rather than from a crossover involving the gene coding for the primary protein structure of the sialoglycoproteins.

INHERITANCE

By immunoblot analysis, Reid et al. (1987) demonstrated that the products of Ge alleles are inherited in an autosomal codominant manner.

MOLECULAR GENETICS

Glycophorin C carries Gerbich determinants; Ge antigens are also present on glycophorin D. Using a cDNA prepared from the mRNA of glycophorin C, Le Van Kim et al. (1987) found that the Ge-negative condition in donors with nonelliptocytic red cells was associated with a 3-kb deletion in the glycophorin C gene ... More on the omim web site

The reference OMIM entry for this protein is 611162

Malaria, susceptibility to malaria, resistance to, included
Malaria, severe, susceptibility to, included
Malaria, severe, resistance to, included
Malaria, cerebral, susceptibility to, included
Malaria, cerebral, resistance to, included

A number sign (#) is used with this entry because variation in several different genes influences susceptibility and resistance to malaria, as well as disease progression and severity. These genes include HBB (141900), ICAM1 (147840), CD36 (173510), CR1 (120620), GYPA (111300), GYPB (111740), GYPC (110750), TNF (191160), NOS2A (163730), TIRAP (606252), FCGR2B (604590), and CISH (602441). In addition, a locus associated with Plasmodium falciparum blood infection level has been mapped to chromosome 5q31-q33 (PFBI; 248310), a locus for susceptibility to mild malaria has been mapped to chromosome 6p21.3 (MALS; 609148), a locus associated with malaria fever episodes has been mapped to chromosome 10p15 (PFFE1; 611384), and a locus for susceptibility to placental malarial infection has been mapped to chromosome 6 (FUT9; 606865). Complete protection from Plasmodium vivax infection is associated with the Duffy blood group-negative phenotype (see 110700). Alpha(+)-thalassemia (141800), the X-linked disorder G6PD deficiency (300908), and Southeast Asian ovalocytosis (109270) are associated with resistance to malaria.

DESCRIPTION

Malaria, a major cause of child mortality worldwide, is caused by mosquito-borne hematoprotozoan parasites of the genus Plasmodium. Of the 4 species that infect humans, P. falciparum causes the most severe forms of malaria and is the major cause of death and disease. Although less fatal, P. malariae, P. ovale, and, in particular, P. vivax infections are major causes of morbidity. The parasite cycle involves a first stage in liver cells and a subsequent stage at erythrocytes, when malaria symptoms occur. A wide spectrum of phenotypes are observed, from asymptomatic infection to mild disease, including fever and mild anemia, to severe disease, including cerebral malaria, profound anemia, and respiratory distress. Genetic factors influence the response to infection, as well as disease progression and severity. Malaria is the strongest known selective pressure in the recent history of the human genome, and it is the evolutionary driving force behind sickle-cell disease (603903), thalassemia (see 141800), glucose-6-phosphatase deficiency (300908), and other erythrocyte defects that together constitute the most common mendelian diseases of humans (Kwiatkowski, 2005; Campino et al., 2006).

PATHOGENESIS

Compared with other microorganisms, P. falciparum malaria parasites reach very high densities in blood. P. falciparum-infected erythrocytes (PfIRBCs) induce ICAM1 (147840) expression on human brain microvascular endothelial cells (HBMECs), but not on human umbilical vein endothelial cells. PfIRBCs compromise the electrical function of brain endothelium independently of PfIRBC binding phenotype, suggesting a role for soluble parasite factors. By performing genomewide transcriptional profiling of HBMECs after exposure to isogenic PfIRBCs, followed by ELISA for protein identification, Tripathi et al. (2009) identified upregulated molecules involved in immune response, apoptosis and antiapoptosis, inflammatory response, cell-cell signaling, and signal transduction and activation of the NF-kappa-B (see 164011) cascade. Proinflammatory molecules, including CCL20 (601960), CXCL1 (155730), CXCL2 (139110), IL6 (147620), and IL8 (146930), were upregulated more than 100-fold. Tripathi et al. (2009) concluded that PfIRBC exposure to HBMECs results in a predominantly proinflammatory response mediated by NF-kappa-B activati ... More on the omim web site

Subscribe to this protein entry history

July 2, 2021: Protein entry updated
Automatic update: OMIM entry 110750 was added.

July 2, 2021: Protein entry updated
Automatic update: OMIM entry 611162 was added.

July 2, 2021: Protein entry updated
Automatic update: OMIM entry 616089 was added.

April 11, 2021: Protein entry updated
Automatic update: OMIM entry 110750 was added.

April 11, 2021: Protein entry updated
Automatic update: OMIM entry 611162 was added.

April 11, 2021: Protein entry updated
Automatic update: OMIM entry 616089 was added.

Feb. 17, 2021: Protein entry updated
Automatic update: OMIM entry 110750 was added.

Feb. 17, 2021: Protein entry updated
Automatic update: OMIM entry 611162 was added.

Feb. 17, 2021: Protein entry updated
Automatic update: OMIM entry 616089 was added.

Oct. 21, 2020: Protein entry updated
Automatic update: OMIM entry 110750 was added.

Oct. 21, 2020: Protein entry updated
Automatic update: OMIM entry 611162 was added.

Oct. 21, 2020: Protein entry updated
Automatic update: OMIM entry 616089 was added.

Aug. 25, 2020: Protein entry updated
Automatic update: OMIM entry 110750 was added.

Aug. 25, 2020: Protein entry updated
Automatic update: OMIM entry 611162 was added.

Aug. 25, 2020: Protein entry updated
Automatic update: OMIM entry 616089 was added.

June 30, 2020: Protein entry updated
Automatic update: OMIM entry 611162 was added.

June 30, 2020: Protein entry updated
Automatic update: OMIM entry 616089 was added.

June 30, 2020: Protein entry updated
Automatic update: OMIM entry 110750 was added.

April 26, 2020: Protein entry updated
Automatic update: OMIM entry 616089 was added.

April 26, 2020: Protein entry updated
Automatic update: OMIM entry 110750 was added.

April 26, 2020: Protein entry updated
Automatic update: OMIM entry 611162 was added.

March 4, 2020: Protein entry updated
Automatic update: OMIM entry 616089 was added.

March 4, 2020: Protein entry updated
Automatic update: OMIM entry 110750 was added.

March 4, 2020: Protein entry updated
Automatic update: OMIM entry 611162 was added.

Jan. 23, 2020: Protein entry updated
Automatic update: OMIM entry 110750 was added.

Jan. 23, 2020: Protein entry updated
Automatic update: OMIM entry 611162 was added.

Jan. 23, 2020: Protein entry updated
Automatic update: OMIM entry 616089 was added.

Dec. 3, 2019: Protein entry updated
Automatic update: OMIM entry 110750 was added.

Dec. 3, 2019: Protein entry updated
Automatic update: OMIM entry 611162 was added.

Dec. 3, 2019: Protein entry updated
Automatic update: OMIM entry 616089 was added.

Oct. 28, 2019: Protein entry updated
Automatic update: OMIM entry 616089 was added.

Oct. 28, 2019: Protein entry updated
Automatic update: OMIM entry 110750 was added.

Oct. 28, 2019: Protein entry updated
Automatic update: OMIM entry 611162 was added.

Sept. 23, 2019: Protein entry updated
Automatic update: OMIM entry 110750 was added.

Sept. 23, 2019: Protein entry updated
Automatic update: OMIM entry 611162 was added.

Sept. 23, 2019: Protein entry updated
Automatic update: OMIM entry 616089 was added.

Aug. 20, 2019: Protein entry updated
Automatic update: OMIM entry 110750 was added.

Aug. 20, 2019: Protein entry updated
Automatic update: OMIM entry 611162 was added.

Aug. 20, 2019: Protein entry updated
Automatic update: OMIM entry 616089 was added.

July 5, 2019: Protein entry updated
Automatic update: OMIM entry 110750 was added.

July 5, 2019: Protein entry updated
Automatic update: OMIM entry 611162 was added.

July 5, 2019: Protein entry updated
Automatic update: OMIM entry 616089 was added.

June 7, 2019: Protein entry updated
Automatic update: OMIM entry 110750 was added.

June 7, 2019: Protein entry updated
Automatic update: OMIM entry 611162 was added.

June 7, 2019: Protein entry updated
Automatic update: OMIM entry 616089 was added.

May 12, 2019: Protein entry updated
Automatic update: OMIM entry 110750 was added.

May 12, 2019: Protein entry updated
Automatic update: OMIM entry 611162 was added.

May 12, 2019: Protein entry updated
Automatic update: OMIM entry 616089 was added.

Jan. 21, 2019: Protein entry updated
Automatic update: OMIM entry 110750 was added.

Jan. 21, 2019: Protein entry updated
Automatic update: OMIM entry 611162 was added.

Jan. 21, 2019: Protein entry updated
Automatic update: OMIM entry 616089 was added.

Nov. 17, 2018: Protein entry updated
Automatic update: OMIM entry 110750 was added.

Nov. 17, 2018: Protein entry updated
Automatic update: OMIM entry 611162 was added.

Nov. 17, 2018: Protein entry updated
Automatic update: OMIM entry 616089 was added.

Oct. 20, 2018: Protein entry updated
Automatic update: OMIM entry 611162 was added.

Oct. 20, 2018: Protein entry updated
Automatic update: OMIM entry 616089 was added.

Oct. 19, 2018: Protein entry updated
Automatic update: OMIM entry 110750 was added.

Oct. 2, 2018: Protein entry updated
Automatic update: OMIM entry 110750 was added.

Oct. 2, 2018: Protein entry updated
Automatic update: OMIM entry 611162 was added.

Oct. 2, 2018: Protein entry updated
Automatic update: OMIM entry 616089 was added.

July 7, 2018: Protein entry updated
Automatic update: OMIM entry 110750 was added.

July 7, 2018: Protein entry updated
Automatic update: OMIM entry 611162 was added.

July 7, 2018: Protein entry updated
Automatic update: OMIM entry 616089 was added.

July 5, 2018: Protein entry updated
Automatic update: OMIM entry 110750 was added.

July 5, 2018: Protein entry updated
Automatic update: OMIM entry 611162 was added.

July 5, 2018: Protein entry updated
Automatic update: OMIM entry 616089 was added.

July 5, 2018: Protein entry updated
Automatic update: OMIM entry 110750 was added.

July 5, 2018: Protein entry updated
Automatic update: OMIM entry 611162 was added.

July 5, 2018: Protein entry updated
Automatic update: OMIM entry 616089 was added.

July 4, 2018: Protein entry updated
Automatic update: OMIM entry 110750 was added.

July 4, 2018: Protein entry updated
Automatic update: OMIM entry 611162 was added.

July 4, 2018: Protein entry updated
Automatic update: OMIM entry 616089 was added.

July 3, 2018: Protein entry updated
Automatic update: OMIM entry 110750 was added.

July 3, 2018: Protein entry updated
Automatic update: OMIM entry 611162 was added.

July 3, 2018: Protein entry updated
Automatic update: OMIM entry 616089 was added.

May 27, 2018: Protein entry updated
Automatic update: OMIM entry 110750 was added.

May 27, 2018: Protein entry updated
Automatic update: OMIM entry 611162 was added.

May 27, 2018: Protein entry updated
Automatic update: OMIM entry 616089 was added.

April 27, 2018: Protein entry updated
Automatic update: OMIM entry 110750 was added.

April 27, 2018: Protein entry updated
Automatic update: OMIM entry 611162 was added.

April 27, 2018: Protein entry updated
Automatic update: OMIM entry 616089 was added.

Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated

Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated

Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated

March 25, 2017: Additional information
No protein expression data in P. Mayeux work for GYPC

March 16, 2016: Protein entry updated
Automatic update: OMIM entry 110750 was added.

Jan. 24, 2016: Protein entry updated
Automatic update: model status changed