9.B.366. The TMEM117 (TMEM117) Family Mitochondrial membrane potential (ΔΨ_m) maintenance is critical as its loss causes apoptotic signalling and cell death. Accumulating DNA mutations and unfolded proteins in stressed cells activate signalling pathways for cell death induction. Cancer cells often fail to die even in the presence of some death signalling proteins. Tamaki et al. 2017 reported a short hairpin RNA (shRNA) with an artificial sequence, denoted Psi1 shRNA, which leads to ΔΨ_m loss in HCT116 cells. The Psi1 shRNA target gene encodes transmembrane protein 117 (TMEM117). TMEM117 knockdown led to ΔΨ_m loss, increased reactive oxygen species levels, up-regulation of an endoplasmic reticulum (ER) stress sensor C/EBP homologous protein and active caspase-3 expression, followed by cell growth impairment, altering homeostasis towards cell death. TMEM117 levels were down-regulated in response to the ER stressor thapsigargin and decreased when cells showed ΔΨ_m loss. These results suggested that TMEM117 RNAi allowed apoptotic cell death. Therefore, TMEM117 probably mediates the signalling of ΔΨ_m loss in ER stress-mediated mitochondria-mediated cell death (Tamaki et al. 2017). It plays a role in sheep development (Tao et al. 2020).
References:
Tamaki, T., K. Kamatsuka, T. Sato, S. Morooka, K. Otsuka, M. Hattori, and T. Sugiyama. (2017). A novel transmembrane protein defines the endoplasmic reticulum stress-induced cell death pathway. Biochem. Biophys. Res. Commun. 486: 149-155.
Tao, L., X.Y. He, L.X. Pan, J.W. Wang, S.Q. Gan, and M.X. Chu. (2020). Genome-wide association study of body weight and conformation traits in neonatal sheep. Anim Genet. [Epub: Ahead of Print]
Examples:
TC#	Name	Organismal Type	Example
9.B.366.1.1	*TMEM117 of 514 aas AND 8 TMSs. It is involved in the endoplasmic reticulum (ER) stress-induced cell death pathway (Tamaki et al.* 2017).**		TMEM117 of Homo sapiens

9.B.366.1.2	Uncharacterized protein of 932 aas and about 15 apparent TMSs with an N-terminal domain of 7 or 8 TMSs corrresponding to TMEM117, a C-terminal domain of 6 TMSs corresponding to a small conductance calcium-activated potassium channel protein, SK3 or KCNN3 (see TC#1.A.1.16.7), and 1 (or possibly 2 or 3 TMSs) between these two domains.		UP of Aphanomyces stellatus

9.B.366.1.3	Uncharacterized voltage-gated ion channel (VIC) superfamily protein showing 53% identity with 9.B.366.1.2 throughout its length, with a TMEM117 domain in the N-terminus, and VIC superfamily domain in the C-terminus, and a middle domain with at least 1 TMS.		Two domain protein of Thraustotheca clavata

9.B.366.1.4	Uncharacterized TMEM117 protein of 848 aas and 8 TMSs.		UP of Aureococcus anophagefferens

9.B.366.1.5	Uncharacterized protein of 1138 aas and 9 TMSs; TMSs 4 - 9 are homologous to TC# 9.B.366.1.1		UP of Trypanosoma theileri

9.B.366.1.6	Uncharacterized protein of 1267 aas and 9 - 11 TMSs. There are 3 - 5 TMSs in the major portion of the protein followed by a 6 TMS TMEM117 domain at the C-terminus of the protein.		UP of Symbiodinium microadriaticum