8.A.65 The Endoplasmic Reticulum (ER)-Plasma Membrane (PM) Junctional Competence Regulator (TMEM110) Family 

The stromal interaction molecule (STIM)-ORAI calcium release-activated calcium modulator (ORAI) pathway (TC# 1.A.52) controls store-dependent calcium entry, a major mechanism of physiological calcium signaling in mammalian cells. The core elements of the pathway are the regulatory protein STIM1, located in the endoplasmic reticulum (ER) membrane, the calcium channel ORAI1 in the plasma membrane (PM), and sites of close contact between the ER and the plasma membrane that permit the two proteins to interact. Research on calcium signaling has centered on STIM1, ORAI1, and a few proteins that directly modulate STIM-ORAI function. Proteins that organize ER-PM junctions for STIM-ORAI-dependent calcium signaling include an ER-resident membrane protein, transmembrane protein 110 (TMEM110).  It regulates the long-term maintenance of ER-plasma membrane junctions and the short-term physiological remodeling of the junctions during store-dependent calcium signaling (Quintana et al. 2015).



Jing, J., L. He, A. Sun, A. Quintana, Y. Ding, G. Ma, P. Tan, X. Liang, X. Zheng, L. Chen, X. Shi, S.L. Zhang, L. Zhong, Y. Huang, M.Q. Dong, C.L. Walker, P.G. Hogan, Y. Wang, and Y. Zhou. (2015). Proteomic mapping of ER-PM junctions identifies STIMATE as a regulator of Ca²⁺ influx. Nat. Cell Biol. 17: 1339-1347.

Quintana A., Rajanikanth V., Farber-Katz S., Gudlur A., Zhang C., Jing J., Zhou Y., Rao A. and Hogan PG. (2015). TMEM110 regulates the maintenance and remodeling of mammalian ER-plasma membrane junctions competent for STIM-ORAI signaling. Proc Natl Acad Sci U S A. 112(51):E7083-92.


TC#NameOrganismal TypeExample

The ER-PM junctional competence regulator, TMEM110 or STIMATE of 294 aas and 5-6 TMSs (Quintana et al. 2015).  STIMATE (STIM-activating enhancer, encoded by TMEM110 gene) is a positive regulator of Ca2+ influx in vertebrates. STIMATE physically interacts with STIM1 to promote STIM1 conformational switch (Jing et al. 2015).

TMEM110 or STIMATE of Homo sapiens


STIMATE (DUF3661) protein of 302 aas and 5 predicted TMSs.

STIMATE of Paramecium tetraurelia


Uncharacterized protein of 370 aas and 5 TMSs

UP of Emericella nidulans (Aspergillus nidulans)


Uncharacterized protein of 200 aas and 5 putative TMSs.

UP of Eimeria maxima (Coccidian parasite)


Uncharacterized protein of 282 aas and 5 putative TMSs.

UP of Chlorella variabilis (Green alga)


Uncharacterized protein of 390 aas and 5 putative TMSs.

UP of Theileria annulata


Uncharacterized protein of 315 aas and 5 TMSs

UP of Plasmodium yoelii