Fig. 1. Sequence comparison of zebrafish megalin/LRP2 and cubilin with human orthologs. (A) Aligned protein structures of human megalin/LRP2 and known parts of the zebrafish ortholog that include the transmembrane domain (TM, black vertical line) and the intracellular tail (horizontally striped pattern). In contrast to the extracellular domain, which is similar in sequence in all members of the LDL receptor gene family, the cytoplasmic domain of megalin/LRP2 is unique and highly conserved across species, as shown here for comparative analysis of the respective amino acid sequence in human and zebrafish. Sequence comparison of both orthologs of the TM and intracellular tail domains shows 49.6% sequence identity and 65.7% sequence similarity. (B) Sequence alignment between two regions of the intracellular tail, including one of the NPxY motif sites (black box) of human and zebrafish megalin/LRP2. (C) Aligned protein structures of cubilin from human and zebrafish. Cubilin domains are shown as gray boxes, EGF domains are black lines, and calcium-binding EGF-like domains are dark gray lines. Both orthologs display 49.6% sequence identity and 65.7% sequence similarity over the known portion of zebrafish cubilin. (D) Sequence comparison of a single cubilin domain from human and zebrafish orthologs.