9.B.87 The Selenoprotein P Receptor (SelP-Receptor) Family
Selenoprotein P (SelP) contains most of the selenium in blood plasma, and it is utilized by the kidney, brain and testis as a selenium source for selenoprotein synthesis. Apolipoprotein E receptor-2 (ApoER2) is required for SelP uptake by the testis, and deletion of ApoER2 reduces testis and brain, but not kidney, selenium levels. Neither the C-terminus selenocysteine-rich domain of SelP nor ApoER2 were required for SelP uptake by proximal tubules. SelP binds megalin, a lipoprotein receptor localized to the proximal tubule epithelium. Proximal tubules don't take up SelP in megalin null mice. Thus, kidney selenium homeostasis is mediated by a megalin-dependent SelP uptake pathway in the proximal tubule (Olson et al., 2008) that may use an endocytic mechanism (Thévenod, 2010).
Homologues of SelP receptors function in various capacities including regulation of ion transporters. Therefore, this family could be assigned to subclass 8.A. For example, KRP4 (TC# 9.B.87.1.24) is involved in the formation of neuromuscular junctions, and in the regluation of acetyl choline receptors (Koppel et al. 2019). However, it is retained in family 9.B.87 because several family members appear to function in other capacities, an observation consistent with the tremendous variation in protein size and domain composition of the proteins assigned to this family.