Schematic representation of the topologies of the Rh D, D^VICe and D^VIcE polypeptides. A proposed topology of the Rh D proteins is illustrated, based on hydropathy analyses31,32 and protein chemical studies.15,30,33 The Rh D protein has 35 or 36 amino acid differences to the Rh CcEe proteins, and these are highlighted with closed circles. The gene conversions that generate the D^VI phenotype result in the replacement of RHD residues with RHCE counterparts. The residues involved are indicated on the D^VICe and D^VIcE proteins as open circles. The presence of the fourth external loop on all proteins is indicated, as well as the protein sequence difference in this domain between the D^VICe and D^VIcE proteins (Ala226Pro). The sites of palmitoylation (at Cys-Leu-Pro motifs) of the proteins are illustrated by zigzag lines. The genomic organization of the RHD and hybrid RHD genes are represented below each predicted topology. RHD-derived exons are represented by black boxes, RHCE-derived exons as white boxes.