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).
References:
Naveed, M., K. Imran, A. Mushtaq, A.S. Mumtaz, H.A. Janjua, and N. Khalid. (2018). functional and tumor suppressor role of hypothetical protein PCNXL2 with regulation of the Notch signaling pathway. RSC Adv 8: 21414-21430.
Examples:
TC#	Name	Organismal Type	Example
9.A.80.1.1	The pecanex-like protein 2, PCNX2 or PCNXL2, of 2137 aas and posslbly 17 TMSs in a 3 (N-terminal) + 14 (residues 840 - 1330) in a 6 + 2 + 6 TMS arrangement. It is a tumor suppressor that regulates the Notch signaling pathway (Naveed et al. 2018). It may play a role in tumorigenesis of colorectal carcinomas, and is characterized by high mutational frequencies and biallelic mutations colorectal tumors.		PCNX2 of Homo sapiens

9.A.80.1.2	Protein pecanex isoform X1, PCNX1, of 2538 aas and as many as 19 TMSs in a 2 (N-terminal) + 8 + 8 (residues 1000 - 1580) + possibly 1 (at ~residue 1910) TMS arrangement.		*PCNX1 of Contarinia nasturtii* (swede midge)**

9.A.80.1.3	Pecanex-like protein, PCNX1, of 1267 aas and possibly 14 TMSs in a 3 or 4 (N-terminal; residues residues 50 - 150) + 8 (residues 200 - 460), and possibly + 2 more TMSs, distant to each other.		PCNX1 of Hypomesus transpacificus

9.A.80.1.4	Uncharacterized protein of 1986 aas and 19 TMSs in a 3 (N-terminal; residues 1 - 100) + 8 + 8 (residues 650 - 1180).		UP of Rotaria magnacalcarata

9.A.80.1.5	Pecanex-like protein 4 of 1251 aas and as many as 18 TMSs, 16 of which are included in residues 40 - 720 aas, in pairs of TMSs, plus two possible TMSs nearer the C-terminus. This protein sequence could be a fragment without its N-terminal region.		PCNX4 of Strongylocentrotus purpuratus