Figure 2

Sequence and membranous localization of podocin. (a) Skipping of the exon 5 (framed in blue) of the NPHS2 gene leads to the translation of a polypeptide lacking the amino acids 179–246 of the isoform 1 (highlighted in blue). Thus, in this isoform 2, the central part of the prohibitin homology domain is missing. Underlined in red is the transmembrane domain (TM). (b) An illustration of the membranous localization of podocin. For the membranous cholesterol binding of podocin, the prohibitin homology domain (amino acids 127–246) (indicated by the arrow) is essential. The loss of the exon 5-coded central core of this domain leads to the inability to bind cholesterol of the inner membrane.