1.A.6.1.8
Amiloride and acid-sensitive cation channels, ASIC2a and ASIC2b are splice variants of the same gene (ACCN1, ACCN, BNAC1, MDEG) product.  Regions involved in acid (proton) sensing and confering tachyphylasis have been identified (Schuhmacher et al. 2015).  ASIC2 isoforms have different subcellular distributions: ASIC2a targets the cell surface while ASIC2b resides in the ER. TMS1 and the proximal post-TMS1 domain (17 amino acids) of ASIC2a are critical for membrane targeting, and replacement of corresponding residues in ASIC2b by those of ASIC2a conferred proton-sensitivity as well as surface expression to ASIC2b (Kweon et al. 2016). This protein is 99% identical to the human ortholog with acc# Q16515.  Rapid resensitization of ASIC2a is conferred by three amino acid residues near the N terminus (Lee et al. 2019). The human ortholog of ASIC1 (UniProt acc # P783480 is 98% identical to the mouse ortholog. ASIC1 plays a role in the occurrence and development of several types of tumors (Wang et al. 2022).