Protein domain architecture and chromosome location of human R-spondins. Schematic representations are shown for all four human R-spondin proteins. The total lengths of R-spondin1, 2, 3 and 4 are 263, 243, 292 and 234 amino acids, respectively. Three types of domains are detected: two cysteine-rich furin-like repeats, a single thrombospondin domain, and a basic amino-acid-rich domain. The relative protein sequence conservation, as a percentage of identical amino acids, within these domains is indicated. The two furin repeats jointly contain 15 conserved cysteines, conforming to the consensus sequence for this domain in each repeat. Twelve out of 60 amino acid residues are highly conserved in thrombospondin protein 1 (TSP1) domains, six of which are cysteines. Secretion is mediated by an amino-terminal endoplasmic reticulum signal peptide. Putative N-linked glycosylation sites are indicated (N).