8.A.205. The TMEM65 (TMEM65) Family Tmem65 plays a role in cardiac development and function. It may regulate cardiac conduction and the function of the gap junction protein GJA1 (TC# 1.A.24.1.1). It may also contribute to the stability and proper localization of GJA1 in the cardiac intercalated disk, thereby regulating gap junction communication. It may also regulate mitochondrial respiration and mitochondrial DNA copy number maintenance (Nazli et al. 2017). It is critical for the structure and function of the intercalated discs in mouse hearts (Teng et al. 2022).
References:
Nazli, A., A. Safdar, A. Saleem, M. Akhtar, L.I. Brady, J. Schwartzentruber, and M.A. Tarnopolsky. (2017). A mutation in the TMEM65 gene results in mitochondrial myopathy with severe neurological manifestations. Eur J Hum Genet 25: 744-751.
Teng, A.C.T., L. Gu, M. Di Paola, R. Lakin, Z.J. Williams, A. Au, W. Chen, N.I. Callaghan, F.H. Zadeh, Y.Q. Zhou, M. Fatah, D. Chatterjee, L.J. Jourdan, J. Liu, C.A. Simmons, T. Kislinger, C.M. Yip, P.H. Backx, R.G. Gourdie, R.M. Hamilton, and A.O. Gramolini. (2022). Tmem65 is critical for the structure and function of the intercalated discs in mouse hearts. Nat Commun 13: 6166.
Zhang, J.L., Y.C. Chang, P.H. Lai, H.I. Yeh, C.W. Tsai, Y.L. Huang, T.Y. Liu, I.C. Lee, N. Foulon, Y. Xu, B. Rao, H.M. Shih, Y.C. Tu, A.V. Reyes, S.L. Xu, L. Feng, and M.F. Tsai. (2025). TMEM65 functions as the mitochondrial Na/Ca exchanger. Nat. Cell Biol. 27: 1301-1310.
Examples:
TC#	Name	Organismal Type	Example
8.A.205.1.1	Transmembrane protein 65, TMEM65, of 240 aas with possibly 5 - 7 TMSs. There is one peak of low hydrophobicity peaking at residue 30, three more of substantial hydrophobicity between residues 120 - 190) and one C-terminal TMS at residie 220. See family description for the functions and characteristics of this protein, probably relevant to other members of this family (Zhang et al. 2025).		TMEM65 of Homo sapiens

8.A.205.1.2	Uncharacterized protein of 392 aas and possibly 4 TMSs in a 1 (near the N-terminus) + 3 (towards the C-terminus). However, there are additional peaks of low hydrophobicity between these more hydrophobic regions.		UP of Trypanosoma vivax

8.A.205.1.3	Uncharacterized protein of 776 aas and 3 or 4 TMSs near the C-terminus of the protein, as well as 4 or 5 potential TMSs of low hydrophobicity near the N-terminus (residues 1 - 220).		UP of Bulinus truncatus

8.A.205.1.4	Uncharacterized protein of 304 aas with 3 TMSs near its C-terminus (residues 130 - 250).		UP of Caenorhabditis bovis

8.A.205.1.5	Uncharacterized protein of 501 aas and 1 TMS near the N-terminus (residues 50 - 70) as well as ~4 TMSs of low hydrophobicity between residues 300 and 400.		UP of Perkinsus olseni

8.A.205.1.6	Tmem65 protein of 729 aas with probably about 9 or 10 TMSs, 4 or 5 TMSs (residues 30 - 210) and 4 or 5 TMSs (residues 550 - end).		Tmem65 of Symbiodinium microadriaticum

8.A.205.1.8	GAF domain-related protein of 1179 aas with 4 or 5 N-terminal TMSs in a 3 + 1 or 2 TMS arrangement, all between residues 180 and 300.		GAF domain containing protein of Plasmodium berghei