9.A.80. The Pecanex-like Protein 2 (PCNX2) Family
PCNXL2 in Homo sapiens is mutated in colorectal carcinoma. The sequence of PCNXL2 was functionally and structurally characterized. PCNXL2 encodes multi-pass transmembrane proteins, the precursor having 2137 aas with 3 N-terminal TMSs and 14 TMSs between residues 840 and 1330 in a 6 + 2 + 6 TMS arrangement. Its tumor suppressor function may involve regulating Notch signaling by transporting protons across the membrane to provide a suitable membrane potential for gamma secretase function, which may liberate the Notch intracellular domain NICD from the receptor inside the cell. Domain A of PCNXL2 may exhibit nuclear transport activity of NICD from the cytoplasm to the nucleus through interaction with a nuclear localization signal that may act as an activator for Notch signaling in the nucleus (Naveed et al. 2018).