1.A.5.2.1
Polycystin 2 (PKD2, PC2 or TRPP2) of 968 aas and 8 or 9 TMSs (Anyatonwu and Ehrlich, 2005). It is regulated by α-actinin (AAC17470) by direct binding, influencing its channel activity (Li et al., 2007), and is also regulated also by diaphanous-related formin 1 (mDia1) (Bai et al., 2008). It has 8 TMSs with 6 TMSs in the channel domain with N- and C- termini inside (Hoffmeister et al., 2010).  PC2 interacts with the inositol 1,4,5-trisphosphate receptor (IP(3)R) to modulate Ca²⁺ signaling (Li et al. 2009). The PKD2 voltage-sensor domain retains two of four gating charges commonly found in voltage-gated ion channels. The PKD2 ion permeation pathway is constricted at the selectivity filter near the cytoplasmic end of S6, suggesting that two gates regulate ion conduction (Shen et al. 2016). 15% of cases of polycystic kidney disease result from mutations in the gene encoding this protein, while 85% are in PKD1 (Ghata and Cowley 2017). Topological changes between the closed and open sub-conductance states of the functional channel are observed with an inverse correlation between conductance and height of the channel. Intrinsic PC2 mechanosensitivity in response to external forces was also observed (Lal et al. 2018). PC2 is present in ciliary membranes of the kidney and shares a transmembrane fold with other TRP channels as well as an extracellular domain found in TRPP and TRPML channels. Wang et al. 2019 characterized the phosphatidylinositol biphosphate (PIP2) and cholesterol interactions with PC2. PC2 has  a PIP binding site close to the equivalent vanilloid/lipid binding site in the TRPV1 channel and a binding site for cholesterol. The two classes of lipid binding sites were compared with sites observed in other TRPs and in Kv channels, suggesting that PC2, in common with other ion channels, may be modulated by both PIPs and cholesterol (Wang et al. 2019). Genetic removal of c-Jun N-terminal kinases, Jnk1 and Jnk2, suppresses the nuclear accumulation of phospho c-Jun, reduces proliferation and reduces the severity of cystic disease. While Jnk1 and Jnk2 are thought to have largely overlapping functions, Jnk1 loss is nearly as effective as the double loss of Jnk1 and Jnk2 (Smith et al. 2021). Polycystin-2 (TRPP2): ion channel properties and regulation have been described (Del Rocío Cantero and Cantiello 2022). Regulation of the PKD2 channel by TACAN (TC# 1.A.119.1.2) has been described (Liu et al. 2022). The mouse ortholog is 90% identical to the human protein. The cytoplasmic tail of mechanosensitive channel Pkd2 regulates its internalization and clustering in eisosome (Malla et al. 2023).  Vascular polycystin proteins (PKD1 and PKD2) have been reviewed togehter with their involvedments in health and disease (Mbiakop and Jaggar 2023).