9.B.385.  The TMEM39A or SUSR2 (TMEM39A) Family 

Transmembrane Protein 39A (TMEM39A) is a mediator of autoimmune disease. It seems to be involved in systemic lupus erythematosus and multiple sclerosis in humans. Tran et al. 2017 reviewed the current knowledge about TMEM39A and its possible roles in cell biology, physiology and pathology. It may play a role in brain tumors (Park et al. 2017). TMEM39A gene polymorphisms are related to various autoimmune diseases including autoimmune thyroid disease (Yao et al. 2019). It is an ER-localized transmembrane protein that acts as an adaptor protein for efficient export of proteins such as SAC1 from the ER (Miao et al. 2020). TMEM39a promotes the replication of encephalomyocarditis virus via an autophagy pathway (Li et al. 2019). A myristoylated TMEM39AS41, a cell-permeable peptide, causes lung cancer cell death (Park et al. 2020) (see TC# 1.D.124). The conserved autoimmune-disease risk gene TMEM39A regulates lysosomal dynamics (Luo et al. 2021). It also coordinates with COPII to promote collagen secretion and regulate the ER stress response (Zhang et al. 2021).


 

References:

Li, X., R. Ma, Q. Li, S. Li, H. Zhang, J. Xie, J. Bai, A. Idris, and R. Feng. (2019). Transmembrane Protein 39A Promotes the Replication of Encephalomyocarditis Virus Autophagy Pathway. Front Microbiol 10: 2680.
Luo, S., X. Wang, M. Bai, W. Jiang, Z. Zhang, Y. Chen, and D.K. Ma. (2021). The conserved autoimmune-disease risk gene regulates lysosome dynamics. Proc. Natl. Acad. Sci. USA 118:.
Miao, G., Y. Zhang, D. Chen, and H. Zhang. (2020). The ER-Localized Transmembrane Protein TMEM39A/SUSR2 Regulates Autophagy by Controlling the Trafficking of the PtdIns(4)P Phosphatase SAC1. Mol. Cell 77: 618-632.e5.
Park, J., H. Lee, Q. Tran, K. Mun, D. Kim, Y. Hong, S.H. Kwon, D. Brazil, J. Park, and S.H. Kim. (2017). Recognition of Transmembrane Protein 39A as a Tumor-Specific Marker in Brain Tumor. Toxicol Res 33: 63-69.
Park, S., M. Kim, Y. Hong, H. Lee, Q. Tran, C. Kim, S.H. Kwon, J. Park, J. Park, and S.H. Kim. (2020). Myristoylated TMEM39AS41, a cell-permeable peptide, causes lung cancer cell death. Toxicol Res 36: 123-130.
Tran, Q., J. Park, H. Lee, Y. Hong, S. Hong, S. Park, J. Park, and S.H. Kim. (2017). TMEM39A and Human Diseases: A Brief Review. Toxicol Res 33: 205-209.
Yao, Q., B. Wang, Q. Qin, X. Jia, L. Li, and J.A. Zhang. (2019). Genetic Variants in Gene Are Associated with Autoimmune Thyroid Diseases. DNA Cell Biol 38: 1249-1256.
Zhang, Z., S. Luo, G.O. Barbosa, M. Bai, T.B. Kornberg, and D.K. Ma. (2021). The conserved transmembrane protein TMEM-39 coordinates with COPII to promote collagen secretion and regulate ER stress response. PLoS Genet 17: e1009317.
Examples:

TC#NameOrganismal TypeExample
9.B.385.1.1

The TMEM39A or SUSR2 protein of 488 aas and 8 TMSs in a 4 + 2 + 2 TMS arrangement.  It plays a role in cell physiology and pathology (see the family description).  A cell penetrating peptide has been derived from it (see TC# 1.D.124). The ER-localized TMEM39A/SUSR2 regulates autophagy by controlling trafficking of the PtdIns(4)P phosphatase SAC1 (Miao et al. 2020).

TMEM39a of Homo sapiens

 
9.B.385.1.2

Uncharacterized protein of 442 aas and 8 TMSs in a 4 + 2 + 2 TMS arrangement.

UP of Salpingoeca rosetta

 
9.B.385.1.3

Uncharacterized protein of 417 aas and 8 TMSs in a 4 + 2 + 2 TMS arrangement.

UP of Acanthamoeba castellanii

 
9.B.385.1.4

Membrane protein of 8 TMSs in a 4 + 2 + 2 TMS arrangement.

Membrane protein of Tetrahymena thermophila

 
9.B.385.1.5

Uncharacterized protein (fragment?) of 356 aas and 6 - 8 TMSs.

UP of Aphanomyces euteiches