8.A.154.  The Retinoschisin (RS1) Family 

RS1 binds negatively charged membrane lipids, such as phosphatidylserine and phosphoinositides. It may play a role in cell-cell adhesion processes in the retina, via homomeric interaction between octamers present on the surface of two neighboring cells (Tolun et al. 2016). t is required for normal structure and function of the retina (Lesch et al. 2008). Mutations in the RS1 gene, which encodes retinoschisin, cause X-linked juvenile retinoschisis, a retinal dystrophy in males. Retinoschisin specifically interacts with the retinal sodium-potassium adenosine triphosphatase (Na/K-ATPase), a transmembrane ion pump. Na/K-ATPases (see TC# 3.A.3.1) also bind cardiac glycosides that control the activity of the pump and have been linked to disturbances in retinal homeostasis (Schmid et al. 2020). Cardiac glycosides displace retinoschisin from the retinal Na/K-ATPase. However, retinoschisin does not affect cardiac glycoside binding.  Cardiac glycosides reduce the capacity of retinoschisin to regulate Na/K-ATPase localization and to protect against photoreceptor degeneration. Thus, opposing effects of retinoschisin and cardiac glycosides are observed for retinal Na/K-ATPase binding and on retinal integrity, suggesting that a fine-tuned interplay between these two components is required to maintain retinal homeostasis (Schmid et al. 2020). Several members of this family are large (700 - 900 aas; ~ twice as large as the monodomain proteins), and they contain at least two domains, an N-terminal domain belonging to TC family 8.A.47, and a fused domain belonging to TC family 8.A.154.  In view of this fact, it can be surmised that the members of these two families may function together, wither fused or not.

References: