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9.B.27 The Death Effector Domain A (DedA) Family

The ubiquitous DedA family (family UPF0043) includes bacterial, archaeal and eukaryotic proteins. The bacterial proteins are of about 200-250 residues with 5 or 6 putative TMSs. They are related to the DedA protein of E. coli (TC# 9.B.27.2.3) and several functionally unchararcterized proteins in eukaryotes (yeasts, plants and animals).YdjX and YdjZ may be involved as dimers in selenite transport (Ledgham et al., 2005). Potential functions of these proteins such as in membrane homeostasis have been summarized by Doerrler et al., (2013). Mutations in DedA proteins exhibit phenotypes such as cell division defects, temperature sensitivity, altered lipid compositions, elevated envelope-related stress responses and loss of the proton motive force. DedA proteins are essential is some bacterial species (Doerrler et al., 2013; Sikdar et al., 2013).

An oxalate-fermenting brown rot fungus, Fomitopsis palustris, secretes large amounts of oxalic acid during wood decay. Secretion of oxalic acid is indispensable for the degradation of wood cell walls. Watanabe et al., (2010) characterized an oxalate transporter, FpOAR, using membrane vesicles of F. palustris. FpOAR (Fomitopsis palustris oxalic acid resistance), from F. palustris by functional screening of yeast transformants with cDNAs grown on oxalic acid-containing plates. FpOAR is predicted to be a membrane protein that possesses six TMSs. A yeast transformant possessing FpOAR (FpOAR-transformant) acquired resistance to oxalic acid and contained less oxalate than the control transformant. FpOAR probably plays a role in wood decay by acting as a secondary transporter responsible for secretion of oxalate by F. palustris.

The DedA/Tvp38 family is a highly conserved and ancient family of membrane proteins with representatives in most sequenced genomes (Doerrler et al., 2013). Recent genetic approaches have revealed important roles for certain bacterial DedA family members in membrane homeostasis. Bacterial DedA family mutants display phenotypes such as cell division defects, temperature sensitivity, altered membrane lipid composition, elevated envelope-related stress responses, and loss of the proton motive force. The DedA family is essential in at least two species of bacteria:Borrelia burgdorferi and Escherichia coli under some conditions. Doerrler et al., (2013) described the phylogenetic distribution of the family and summarized progress toward understanding the functions of DedA proteins.

E. coli can normally grow between pH 5.5 and 9.5 while maintaining a cytoplasmic pH of about 7.6. Under alkaline conditions, bacteria rely upon proton-dependent transporters to maintain a constant cytoplasmic pH. The DedA/Tvp38 protein, YqjA, is critical for E. coli to survive between pH 8.5 and 9.5. YqjA requires sodium and potassium for this function. At low cation concentrations, osmolytes, including sucrose, can facilitate rescue of growth by YqjA at high pH suggesting that YqjA functions as an osmosensing cation-dependent proton transporter (Kumar and Doerrler 2015).

References associated with 9.B.27 family:

Boughner, L.A. and W.T. Doerrler. (2012). Multiple deletions reveal the essentiality of the DedA membrane protein family in Escherichia coli. Microbiology 158: 1162-1171. 22301910
Daley, D.O., M. Rapp, E. Granseth, K. Melén, D. Drew, and G. von Heijne. (2005). Global topology analysis of the Escherichia coli inner membrane proteome. Science 308: 1321-1323. 15919996
Doerrler, W.T., R. Sikdar, S. Kumar, and L.A. Boughner. (2013). New functions for the ancient DedA membrane protein family. J. Bacteriol. 195: 3-11. 23086209
Kim, H., T. Kim, B.C. Jeong, I.T. Cho, D. Han, N. Takegahara, T. Negishi-Koga, H. Takayanagi, J.H. Lee, J.Y. Sul, V. Prasad, S.H. Lee, and Y. Choi. (2013). Tmem64 modulates calcium signaling during RANKL-mediated osteoclast differentiation. Cell Metab 17: 249-260. 23395171
Kumar, S. and W.T. Doerrler. (2015). Escherichia coli YqjA, a Member of the Conserved DedA/Tvp38 Membrane Protein Family, Is a Putative Osmosensing Transporter Required for Growth at Alkaline pH. J. Bacteriol. 197: 2292-2300. 25917916
Ledgham, F., B. Quest, T. Vallaeys, M. Mergeay, and J. Covès. (2005). A probable link between the DedA protein and resistance to selenite. Res. Microbiol. 156: 367-374. 15808941
Lin, B., Y. Xue, C. Qi, X. Chen, and W. Mao. (2018). Expression of transmembrane protein 41A is associated with metastasis via the modulation of E‑cadherin in radically resected gastric cancer. Mol Med Rep 18: 2963-2972. 30015937
Morita, K., Y. Hama, T. Izume, N. Tamura, T. Ueno, Y. Yamashita, Y. Sakamaki, K. Mimura, H. Morishita, W. Shihoya, O. Nureki, H. Mano, and N. Mizushima. (2018). Genome-wide CRISPR screen identifies as a gene required for autophagosome formation. J. Cell Biol. 217: 3817-3828. 30093494
Panta, P.R., S. Kumar, C.F. Stafford, C.E. Billiot, M.V. Douglass, C.M. Herrera, M.S. Trent, and W.T. Doerrler. (2019). A DedA Family Membrane Protein Is Required for Colistin Resistance. Front Microbiol 10: 2532. 31827463
Shoemaker, C.J., T.Q. Huang, N.R. Weir, N.J. Polyakov, S.W. Schultz, and V. Denic. (2019). CRISPR screening using an expanded toolkit of autophagy reporters identifies TMEM41B as a novel autophagy factor. PLoS Biol 17: e2007044. 30933966
Sikdar, R., A.R. Simmons, and W.T. Doerrler. (2013). Multiple envelope stress response pathways are activated in an Escherichia coli strain with mutations in two members of the DedA membrane protein family. J. Bacteriol. 195: 12-24. 23042993
Thompkins, K., B. Chattopadhyay, Y. Xiao, M.C. Henk, and W.T. Doerrler. (2008). Temperature sensitivity and cell division defects in an Escherichia coli strain with mutations in yghB and yqjA, encoding related and conserved inner membrane proteins. J. Bacteriol. 190: 4489-4500. 18456815
Van Alstyne, M., F. Lotti, A. Dal Mas, E. Area-Gomez, and L. Pellizzoni. (2018). Stasimon/Tmem41b localizes to mitochondria-associated ER membranes and is essential for mouse embryonic development. Biochem. Biophys. Res. Commun. 506: 463-470. 30352685
Watanabe, T., N. Shitan, S. Suzuki, T. Umezawa, M. Shimada, K. Yazaki, and T. Hattori. (2010). Oxalate efflux transporter from the brown rot fungus Fomitopsis palustris. Appl. Environ. Microbiol. 76: 7683-7690. 20889782