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.




Lesch, B., V. Szabó, M. Kánya, G.M. Somfai, R. Vámos, B. Varsányi, Z. Pámer, K. Knézy, G. Salacz, M. Janáky, M. Ferencz, J. Hargitai, A. Papp, and A. Farkas. (2008). Clinical and genetic findings in Hungarian patients with X-linked juvenile retinoschisis. Mol Vis 14: 2321-2332.

Schmid, V., K. Plössl, C. Schmid, S. Bernklau, B.H.F. Weber, and U. Friedrich. (2020). Retinoschisin and Cardiac Glycoside Crosstalk at the Retinal Na/K-ATPase. Invest Ophthalmol Vis Sci 61: 1.

Tolun, G., C. Vijayasarathy, R. Huang, Y. Zeng, Y. Li, A.C. Steven, P.A. Sieving, and J.B. Heymann. (2016). Paired octamer rings of retinoschisin suggest a junctional model for cell-cell adhesion in the retina. Proc. Natl. Acad. Sci. USA 113: 5287-5292.


TC#NameOrganismal TypeExample

Retinoschisin (SR1 or XLRS1) of 224 aas and 1 N-terminal TMS.  See family description for details for the protein interactions and functions (Schmid et al. 2020).

SR1 of Homo sapiens


Epithelial discoidin domain-containing receptor 1-like (EDDR1L) protein of 449  aas and one C-terminal TMS.

EDDR1L of Sarcoptes scabiei


Discoidin, CUB and LCCL domain-containing protein 1-like isoform X3 of 647 aas and 1 TMS.

Discoidin of Archocentrus centrarchus


Discoidin domain-containing receptor 2-like isoform X3of 782 aas and two TMSs, N-terminal and central.

DDR2 of Vespa mandarinia


Contactin-associated protein-like 2b, CPL2b of 1321 aas and 2 TMSs, N- and C-terminal.

CPL2b of Thalassophryne amazonica