8.A.95. The Transmembrane and TPR Repeat-containing Protein 3 (TMTC3) Family The human protein is involved in the positive regulation of proteasomal protein degradation in the endoplasmic reticulum (ER) and the control of the ER stress response (Racapé et al. 2011). Additionally, it co-localizes with the GABA transporter, VGAT, in the presynaptic neuronal membrane where it plays a role in regulation of GABAergic inhibitory synapses. Mutations in humans, rats and flies give rise to efects in neuronal migration that cause brain malformations, which are associated with intellectual disability and epilepsy (Farhan et al. 2017). These mutations can also give rise to cobblestone lissencephaly (COB), a severe brain malformation in which overmigration of neurons and glial cells into the arachnoid space results in the formation of cortical dysplasia (Jerber et al. 2016).
References:
Farhan, S.M.K., K.C.J. Nixon, M. Everest, T.N. Edwards, S. Long, D. Segal, M.J. Knip, H.H. Arts, R. Chakrabarti, J. Wang, J.F. Robinson, D. Lee, S.M. Mirsattari, C.A. Rupar, V.M. Siu, , M.O. Poulter, R.A. Hegele, and J.M. Kramer. (2017). Identification of a novel synaptic protein, TMTC3, involved in periventricular nodular heterotopia with intellectual disability and epilepsy. Hum Mol Genet. [Epub: Ahead of Print]
Jerber, J., M.S. Zaki, J.Y. Al-Aama, R.O. Rosti, T. Ben-Omran, E. Dikoglu, J.L. Silhavy, C. Caglar, D. Musaev, B. Albrecht, K.P. Campbell, T. Willer, M. Almuriekhi, A.O. Çağlayan, J. Vajsar, K. Bilgüvar, G. Ogur, R. Abou Jamra, M. Günel, and J.G. Gleeson. (2016). Biallelic Mutations in TMTC3, Encoding a Transmembrane and TPR-Containing Protein, Lead to Cobblestone Lissencephaly. Am J Hum Genet 99: 1181-1189.
LUETHY, E. and W. RUTISHAUSER. (1961). [On the differential diagnosis of brief duration unconsciousness. Pressure-postpressure syncope]. Schweiz Med Wochenschr 91: 861-864.
Racapé, M., J.P. Duong Van Huyen, R. Danger, M. Giral, F. Bleicher, Y. Foucher, A. Pallier, P. Pilet, P. Tafelmeyer, J. Ashton-Chess, E. Dugast, S. Pettré, B. Charreau, J.P. Soulillou, and S. Brouard. (2011). The involvement of SMILE/TMTC3 in endoplasmic reticulum stress response. PLoS One 6: e19321.
Examples:
TC#	Name	Organismal Type	Example
8.A.95.1.1	Transmembrane and TPR repeat-containing protein, TMTC3, of 915 aas and 11 or 12 N-terminal TMSs with an extensive C-terminal hydrophilic domain including a tetratricopeptide (TPR) repeat-containing region. It is involved in the ER stress response (Racapé et al. 2011) and co-localizes with the GABA transporter in pre-synaptic membranes and functions in the regulation of GABAergic inhibitory synapses (Farhan et al. 2017).		TMTC3 of Homo sapiens

8.A.95.1.2	Transmembrane and TPR repeat-containing protein 2 of 617 aas and 11 TMSs.		TMTC2 of Esox lucius

8.A.95.1.3	Transmembrane and TPR repeat-containing protein 2, TMTC2, of 696 aas and 10 - 11 TMSs		TMTC2 of Mus musculus

8.A.95.1.4	Uncharacterized protein of 613 aas and 11 TMSs.		UP of Spirosoma linguale

8.A.95.1.5	Tfp pilus assembly protein PilF of 680 aas and 11 or 12 TMSs.		PilF of Desulfomonile tiedjei

8.A.95.1.6	Uncharacterized protein of 613 aas and 11 TMSs.		UP of Fimbriimonas ginsengisoli

8.A.95.1.7	Uncharacterized protein of 583 aas and 11 or 12 TMSs.		UP of Sulfuritalea hydrogenivorans

8.A.95.1.8	Putative arabinosyl transferase, TfpW, of 646 aas and 11 TMSs.		TfpW of Pseudomonas aeruginosa

Examples:
TC#	Name	Organismal Type	Example
8.A.95.2.1	Uncharacterized protein of 654 aas and 12 TMSs.		UP of Geobacter bemidjiensis

8.A.95.2.2	Tetratricopeptide TPR_2 repeat protein of 577 aas and 11 TMSs.		TPR_2 repeat protein of Solibacter usitatus

8.A.95.2.3	Uncharacterized protein of 654 aas and 11 TMSs.		UP of Nitrosococcus halophilus

8.A.95.2.4	Uncharacterized protein of 575 aas and 11 TMSs.		UP of Geobacter bemidjiensis

Examples:
TC#	Name	Organismal Type	Example
8.A.95.3.1	Uncharacterized protein of 597 aas and 9 - 11 TMSs.		UP of Plesiocystis pacifica