1.A.25.2.5
Mouse Pannexin 1 of 426 aas and 4 TMSs.  Pannexins are ubiquitously expressed in human and mouse tissues. Pannexin 1 (Panx1), the most thoroughly characterized member of this family, forms plasmalemmal membrane channels permeable to relatively large molecules, such as ATP. Although human and mouse Panx1 amino acid sequences are conserved in the presently known regulatory sites involved in trafficking and modulation of the channel, differences occur in the N- and C-termini of the protein.  Cibelli et al. 2023 used a neuroblastoma cell line to study the activation properties of endogenous mPanx1 and exogenously expressed hPanx1. Dye uptake and electrophysiological recordings revealed that in contrast to mouse Panx1, the human ortholog is insensitive to stimulation with high extracellular K⁺ but responds similarly to activation of the purinergic P2X7 receptor. The two most frequent Panx1 polymorphisms found in the human population, Q5H (rs1138800) and E390D (rs74549886), exogenously expressed in Panx1-null N2a cells revealed that regarding P2X7 receptor mediated Panx1 activation, the Q5H mutant is a gain of function whereas the E390D mutant is a loss of function variant. Collectively, they demonstrated differences in the activation between human and mouse Panx1 orthologs and suggest that these differences may have translational implications for studies where Panx1 has been shown to have a significant impact (Cibelli et al. 2023).