Glycophorin A (GYPA) (GYPA)

Glycophorin A (GYPA), also designated as CD235a, is the major sialoglycoprotein of the human erythrocyte membrane, comprising approximately 2% of the total membrane protein mass (UniProt P02724). It is characterized by a heavily glycosylated extracellular domain rich in sialic acid, which provides the red blood cell with a strong negative surface charge, essential for preventing cell-cell aggregation and adhesion to the endothelium (Wikipedia). GYPA carries the M and N blood group antigens and acts as a critical receptor for the invasion of Plasmodium falciparum merozoites by binding to the parasite's erythrocyte-binding antigen 175 (EBA-175) (PubMed: 35835865). Additionally, it serves as a receptor for other pathogens, including the Hepatitis A virus and influenza virus, and functions as a molecular chaperone for the anion exchanger Band 3 (SLC4A1) (PubMed: 11313283). In clinical oncology, GYPA is utilized as a specific biomarker for identifying erythroid differentiation in acute leukemias, and it is currently being explored as a target for malaria vaccines and as an anchor for erythrocyte-based drug delivery systems (Biocare; NIH).

Other names

CD235aMN sialoglycoproteinPAS-2Sialoglycoprotein alphaGPA

Blocking the interaction between the extracellular domain of Glycophorin A and pathogen ligands, such as Plasmodium falciparum EBA-175, prevents cellular invasion. Enzymatic removal of sialic acid residues by neuraminidase also inhibits pathogen binding by disrupting the glycan-dependent recognition sites.