Proposed seven transmembrane spanning topology of DARC. (A) Molecular modeling predicts that DARC has topologic features similar to other members of the chemokine receptor family. (Modified and reprinted with permission.113 ) The amino terminal extracellular domain contains the binding site for anti-Fy6 MoAbs and the polymorphism resulting in the Fy^a and Fy^b blood groups. This domain has also been found to contain sequences necessary for multi-specific chemokine binding. Sequences required for binding a MoAb with anti-Fy3 specificity have been tentatively localized to the third predicted extracellular loop. (B) The deduced amino acid sequence of DARC; the first seven N-terminal amino acids shown are those predicted from the exon identified by Iwamoto111 and are thought to be present in the major DARC transcript; the N-terminal amino acids shown in parentheses and the rest of the amino acid sequence are derived from the single DARC exon as originally cloned by Chaudhuri et al.105 (Modified and reprinted with permission from Horuk R: Molecular properties of the chemokine receptor family. Trends in Pharmacological Sciences, vol 15, p 159, 1994.88 ).