9.B.27 The DedA or YdjX-Z (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).



This family belongs to the .

 

References:

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.

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.

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.

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.

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.

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.

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.

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.

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.

Examples:

TC#NameOrganismal TypeExample
9.B.27.1.1

The YdjX protein. While not individually essential, the eight E. coli DedA family proteins are collectively essential (Boughner and Doerrler 2012).

Proteobacteria

YdjX of E. coli

 
9.B.27.1.2

The YdjZ protein.  While not individually essential, the eight E. coli DedA family proteins are collectively essential (Boughner and Doerrler 2012).

Proteobacteria

YdjZ of E. coli

 
9.B.27.1.3

DedA homologue

Actinobacteria

DedA of Rhodococcus ruber

 
9.B.27.1.4

Hypothetical protein of 195 aas and 5 TMSs

Planctomycetes

HP of Rhodopirellula baltica

 
9.B.27.1.5

DedA-domain protein of 179 aas and 5 TMSs.

DedA protein of Anaerolinea thermophila

 
9.B.27.1.6

TVP38/TMEM64 family protein, YdjX, of 215 aas and 5 TMSs in a 2 + 3 TMS arrangement.

TVP38 protein of Terribacillus saccharophilus

 
Examples:

TC#NameOrganismal TypeExample
9.B.27.2.1

The YghB protein. When both YghB and YqjA are mutated, a cell division defect (219aas; 4-6TMSs) is observed (Thompkins et al., 2008).  The YqjA protein is 60% identical to YghB, and these two act synergistically to maintain a normal pmf (Kumar and Doerrler 2015).

Proteobacteria

YghB of E. coli (P0AA60)

 
9.B.27.2.10

DedA homologue of 216 aas and 5 TMSs.

DedA of Candidatus Wolfebacteria bacterium

 
9.B.27.2.2

The YqjA protein is 60% identical to YghB, and these two act synergistically to maintain a normal pmf (Kumar and Doerrler 2015). Perhaps secondarily, when both YghB and YqjA are mutated, the cells exhibit a cell division defect (Thompkins et al., 2008). It has been proposed that YqjA possesses proton-dependent transport activity that is stimulated by osmolarity and that it plays a significant role in the survival of E. coli at alkaline pH, perhaps as an osmosensory cation-dependent proton transporter (a cation:proton antiporter?) (Kumar and Doerrler 2015).

Proteobacteria

YqjA of E. coli 220aas; (220 aas; 6TMSs; 3+3) P0AA63

 
9.B.27.2.3

DedA (SNARE-associated protein) (Putative selenite transport protein, Ledgham et al., 2005). Topology known (Daley et al., 2005)

Proteobacteria

DedA of E.coli (P0ABP6)

 
9.B.27.2.4

The DedA family member involved in selenite uptake (Ledgham et al., 2005)

Proteobacteria

DedA of Ralstonia (Cupriavidus) metallidurans (ABF09780)

 
9.B.27.2.5

The SNARE-associated Golgi protein (206 aas; 5 TMSs)

Archaea

SNARE-associated Golgi protein of Candidatus Parvarchaeum acidiphilum ARMAN-5 (D6GX19)

 
9.B.27.2.6

Oxalate exporter, Fp0AR (Watanabe et al. 2010).

Fungi

Fp0AR of Fomitopsis palustris (D7UNZ8)

 
9.B.27.2.7

Uncharacterized protein of 192 aas

Proteobacteria

UP of E. coli

 
9.B.27.2.8

DedA homologue of 211 aas and 5 TMSs.

Spirochaetes

DedA of Treponema pedis

 
9.B.27.2.9

DedA homologue of 200 aas and 5 TMSs.

DedA of Candidatus Wolfebacteria bacterium

 
Examples:

TC#NameOrganismal TypeExample
9.B.27.3.1

DedA; SNARE-associated superfamilly member of 142 aas and 4 TMSs.

Proteobacteria

DedA homologue of E. coli

 
9.B.27.3.2

DedA homologue of 157 aas and 4 TMSs in a 2 + 2 arrangement.

Proteobacteria

DedA homologue of Haemophilus influenzae

 
9.B.27.3.3

Putative DedA protein of 145 aas and 4 tMSs

Proteobacteria

DedA homologue of Pseudomonas putidas

 
Examples:

TC#NameOrganismal TypeExample
9.B.27.4.1

Hypothetical SNARE-associated protein of 6 putative TMSs in a 3 + 3 arrangement.

Planctomycetes

HP of Rhodopirellula baltica

 
Examples:

TC#NameOrganismal TypeExample
9.B.27.5.1

TMEM64 of 380 aas and 6 TMSs.  Functions as a regulator of the SERCA2 Ca2+ ATPase (TC# 3.A.3.2.7) by direct interaction, thereby regulating Ca2+ oscillations (Kim et al. 2013).

Animals

TMEM64 of Homo sapiens

 
9.B.27.5.2

Tvp38p SNARE-associated Golgi protein (COG398)

Fungi

Tvp38 of Saccharomyces cerevisiae

 
9.B.27.5.3

Uncharaterized protein (DedA homologue) of 312 aas and 6 TMSs.

Plants

DedA homologue of Glycine max