8.A.108. The Curvature-stabilizing Protein YOP1 (YOP1) Family The endoplasmic reticulum is a dynamic network of interconnected membrane tubules. Powers et al. 2017 reconstituted a dynamic tubular membrane network with purified endoplasmic reticulum proteins. Proteoliposomes containing the membrane-fusing GTPase Sey1p (TC# 1.N.5.1.6) and the curvature-stabilizing protein Yop1p from Saccharomyces cerevisiae (TC# 8.A.108.1.1) formed a tubular network upon addition of GTP. The tubules rapidly fragment when GTP hydrolysis by Sey1p is inhibited, indicating that network maintenance requires continuous membrane fusion and that Yop1p favours the generation of highly curved membrane structures. Sey1p also forms networks with other curvature-stabilizing proteins, including reticulon and receptor expression-enhancing proteins (REEPs) from different species. Atlastin, the vertebrate orthologue of Sey1p, forms a GTP-hydrolysis-dependent network on its own, serving as both a fusion and curvature-stabilizing protein. Thus, organelle shape can be generated by a surprisingly small set of proteins and represents an energy-dependent steady state between formation and disassembly (Powers et al. 2017). Yop1 may function together with LNP1 (Sey1) (TC#s 8.A.109.1.1) to promote ER membrane fusion.
References:
Falk, J., M. Rohde, M.M. Bekhite, S. Neugebauer, P. Hemmerich, M. Kiehntopf, T. Deufel, C.A. Hübner, and C. Beetz. (2014). Functional mutation analysis provides evidence for a role of REEP1 in lipid droplet biology. Hum Mutat 35: 497-504.
Park, S.H., P.P. Zhu, R.L. Parker, and C. Blackstone. (2010). Hereditary spastic paraplegia proteins REEP1, spastin, and atlastin-1 coordinate microtubule interactions with the tubular ER network. J Clin Invest 120: 1097-1110.
Powers, R.E., S. Wang, T.Y. Liu, and T.A. Rapoport. (2017). Reconstitution of the tubular endoplasmic reticulum network with purified components. Nature 543: 257-260.
Tseng, C.C., C.C. Hung, C.W. Shu, C.H. Lee, C.F. Chen, M.S. Kuo, Y.Y. Kao, C.L. Chen, L.P. Ger, and P.F. Liu. (2023). The Clinical and Biological Effects of Receptor Expression-Enhancing Protein 6 in Tongue Squamous Cell Carcinoma. Biomedicines 11:.
Examples:
TC#	Name	Organismal Type	Example
8.A.108.1.1	*The ER curvature-stabilizing protein, YOP1, of 180 aas and 4 probable TMSs in a 2 + 2 arrangement (Powers et al.* 2017). See family description for details.**		*YOP1 of Saccharomyces cerevisiae* (Baker's yeast)**

8.A.108.1.2	Uncharacterized receptor expression-enhancing protein 3-like isoform X2 of 229 aas and 3 putative TMSs.		UP of Neolamprologus brichardi

8.A.108.1.3	Uncharacterized protein of 221aas and 3 TMSs		UP of Sarcophaga bullata

8.A.108.1.4	Uncharacterized protein of 197 aas and 3 TMSs		UP of Aphanomyces invadans

8.A.108.1.5	Uncharacterized protein of 161 aas and 2 - 4 TMSs. If 4 TMSs as for other family members, they occur in a 2 + 2 TMS arrangement.		UP of Caenorhabditis elegans

8.A.108.1.6	Uncharacterized protein of 270 aas and (3 or) 4 TMSs with a possible 1 + 2 + 1 TMS arrangement.		UP of Malassezia vespertilionis

8.A.108.1.7	S-phase cyclin A-associated protein in the endoplasmic reticulum, isoform X1 of 415 aas and 3 N-terminal TMSs in a 1 + 2 TMS arrangement.		Cyclin A of Sesamum indicum

8.A.108.1.8	Atlastine, REEP1 or SPG31 of 201 aas and 3 N-terminal TMSs in a 1 + 2 TMS arrangement. The protein is required for endoplasmic reticulum (ER) network formation, shaping and remodeling; it links ER tubules to the cytoskeleton and may also enhance the cell surface expression of odorant receptors (Park et al. 2010). It may also play a role in long-term axonal maintenance (Falk et al. 2014)		*REEP1 of Homo sapiens* (Human)**

8.A.108.1.9	Receptor Expression-Enhancing Protein 6, REEP6, of 211 aas and probably 4 TMSs in a 2 + 2 TMS arrangement. The clinical and biological effects of REEP6 on tongue squamous cell carcinoma (TSCC) have been studied (Tseng et al. 2023). REEP6 controls the expression or transport of a subset of proteins/receptors. Thus, REEP6 is involved in the malignancy of TSCC and might serve as a potential diagnostic/prognostic biomarker and therapeutic target for TSCC patients (Tseng et al. 2023).		REEP6 of Homo sapiens