9.B.147.  The Transmembrane 127 (TMEM127) Family

TMEM127 is encoded by a tumor suppressor gene associated with pheochromocytomas, paragangliomas, and renal carcinomas (Bausch et al. 2017; Flores et al. 2020). To better understand the structure of TMEM127, Flores et al. 2020 undertook cellular and molecular evaluation of patient-derived germline variants. They identified 3 subgroups of mutations and determined that 71% of the variants studied are likely pathogenic through loss of their membrane-binding ability, stability, and/or internalization capability. TMEM127 is a 4-TMS protein. A C-terminal variant with predominant plasma membrane localization revealed an atypical, extended acidic, dileucine-based motif required for TMEM127 internalization through clathrin-mediated endocytosis. Thus, several germline TMEM127 variants revealed potential structure-function features of TMEM127 (Flores et al. 2020).


 

References:

Bausch, B., F. Schiavi, Y. Ni, J. Welander, A. Patocs, J. Ngeow, U. Wellner, A. Malinoc, E. Taschin, G. Barbon, V. Lanza, P. Söderkvist, A. Stenman, C. Larsson, F. Svahn, J.L. Chen, J. Marquard, M. Fraenkel, M.A. Walter, M. Peczkowska, A. Prejbisz, B. Jarzab, K. Hasse-Lazar, S. Petersenn, L.C. Moeller, A. Meyer, N. Reisch, A. Trupka, C. Brase, M. Galiano, S.F. Preuss, P. Kwok, N. Lendvai, G. Berisha, &.#.2.1.4.;. Makay, C.C. Boedeker, G. Weryha, K. Racz, A. Januszewicz, M.K. Walz, O. Gimm, G. Opocher, C. Eng, H.P.H. Neumann, and. (2017). Clinical Characterization of the Pheochromocytoma and Paraganglioma Susceptibility Genes SDHA, TMEM127, MAX, and SDHAF2 for Gene-Informed Prevention. JAMA Oncol 3: 1204-1212.
Flores, S.K., Y. Deng, Z. Cheng, X. Zhang, S. Tao, A. Saliba, I. Chu, N. Burnichon, A.P. Gimenez-Roqueplo, E. Wang, R.C.T. Aguiar, and P.L.M. Dahia. (2020). Functional Characterization of TMEM127 Variants Reveals Novel Insights into Its Membrane Topology and Trafficking. J Clin Endocrinol Metab 105:.
Examples:

TC#NameOrganismal TypeExample
9.B.419.1.1

TMEM127 of 238 aas and 4 TMSs in a 1 + 3 TMS arrangement.  Its topology and trafficking have been studied (Flores et al. 2020).

TMEM127 of Homo sapiens

 
9.B.419.1.2

Uncharacterized protein of 232 aas and 4 TMSs in a 1 + 3 TMS arrangement.

UP of Daphnia pulex (Water flea)

 
9.B.419.1.3

TMEM127 homolog of 233 aas and 4 TMSs in a 1 + 3 TMS arrangement.

TMEM127 of Xenopus tropicalis (tropical clawed frog)

 
9.B.419.1.4

Uncharacterized protein of 237 aas and 6 TMSs.

UP of Dendroctonus ponderosae (Mountain pine beetle)

 
9.B.419.1.5

Uncharacterized protein of 249 aas and 4 or 5 TMSs in a 1 + 3 or 4 TMS arrangement.

UP of Enterobius vermicularis (human pinworm)