glycophorin

Glycophorin refers to a family of heavily glycosylated, sialoglycoproteins located in the plasma membrane of human red blood cells. The best known members are glycophorin A (GYPA, CD235a) and glycophorin B (GYPB, CD235b), with additional family members including glycophorin C, D, and E encoded by related genes in a gene cluster on chromosome 4. These proteins are single-pass type I membrane proteins, characterized by a long extracellular N-terminal domain rich in glycans and sialic acid, a single transmembrane segment, and a relatively short cytoplasmic tail.

The extracellular domains bear numerous O- and N-linked glycans and the abundant sialic acids impart a substantial negative surface charge to red blood cells. This glycosylation pattern contributes to the physical properties of the membrane, including reduced cell–cell adhesion and maintenance of the biconcave shape. The cytoplasmic tails link to the spectrin–ankyrin cytoskeleton, helping stabilize the membrane and coordinate membrane–cytoskeleton interactions.

Glycophorins carry major human blood group antigens. The M and N antigens are typically carried on glycophorin A, while the S, s, and U antigens are associated with glycophorin B, among other polymorphisms. As such, glycophorins are central to transfusion medicine and blood typing.

Functional and clinical relevance extends to host–pathogen interactions. Several Plasmodium falciparum merozoite invasion pathways involve glycophorin receptors, with glycophorin A identified as a receptor for parasite ligands such as EBA-175. Variation in glycophorin genes can influence susceptibility to malaria and other hematologic phenotypes, making these proteins a subject of both basic and translational research.