2.A.13 The C4-Dicarboxylate Uptake (Dcu) Family

Several proteins of the Dcu family have been sequenced as of 1/1998, but all are from Gram-negative bacteria. Two are from E. coli, one is from Haemophilus influenzae, one is from Serratia marscesens and one (a large, N-terminally truncated fragment) is from Wolenella succinogens. The fully sequenced proteins are of fairly uniform size (434-446 residues). They possess 12 putative transmembrane α-helical spanners, but DcuA has 10 experimentally determined TMSs with both the N- and C-termini localized to the periplasm. For DcuA, the 'positive inside' rule is obeyed, and two putative TMSs are localized to a cytoplasmic loop between TMSs 5 and 6 and in the C-terminal periplasmic region.

The two E. coli proteins, DcuA and DcuB, transport aspartate, malate, fumarate and succinate and function as antiporters with any two of these substrates. They exhibit 36% identity with 63% similarity, and both transport fumarate in exchange for succinate with the same affinity (30 μM). Since DcuA is encoded in an operon with the gene for aspartase, and DcuB is encoded in an operon with the gene for fumarase, their physiological functions may be to catalyze aspartate:fumarate and fumarate:malate exchange during the anaerobic utilization of aspartate and fumarate, respectively. However, the electroneutral antiport of fumarate for succinate during anaerobic fumarate respiration has been demonstrated, and both permeases are induced under anaerobic conditions and are subject to catabolite repression. The two transporters can apparently substitute for each other under certain physiological conditions (Engel et al., 1994; Six et al., 1994; Unden and Bongaerts, 1997).

The generalized transport reaction catalyzed by the proteins of the Dcu family is:

Dicarboxylate1 (out) + Dicarboxylate2 (in) ⇌ Dicarboxylate1 (in) + Dicarboxylate2 (out)

This family belongs to the IT Superfamily.



Bauer, J., M.J. Fritsch, T. Palmer, and G. Unden. (2011). Topology and accessibility of the transmembrane helices and the sensory site in the bifunctional transporter DcuB of Escherichia coli. Biochemistry 50: 5925-5938.

Chen, J., X. Zhu, Z. Tan, H. Xu, J. Tang, D. Xiao, and X. Zhang. (2014). Activating C4-dicarboxylate transporters DcuB and DcuC for improving succinate production. Appl. Microbiol. Biotechnol. 98: 2197-2205.

Engel, P., R. Krämer, and G. Unden. (1994). Transport of C4-dicarboxylates by anaerobically grown Escherichia coli: energetics and mechanism of exchange, uptake and efflux. Eur. J. Biochem. 222: 605-614.

Golby, P., D.J. Kelly, J.R. Guest, and S.C. Andrews. (1998). Topological analysis of DcuA, an anaerobic C4-dicarboxylate transporter of Escherichia coli. J. Bacteriol. 180: 4821-4827.

Kim, O.B., S. Lux, and G. Unden. (2007). Anaerobic growth of Escherichia coli on D-tartrate depends on the fumarate carrier DcuB and fumarase, rather than the L-tartrate carrier TtdT and L-tartrate dehydratase. Arch. Microbiol. 188: 583-589.

Kleefeld, A., B. Ackermann, J. Bauer, J. Krämer, and G. Unden. (2009). The fumarate/succinate antiporter DcuB of Escherichia coli is a bifunctional protein with sites for regulation of DcuS-dependent gene expression. J. Biol. Chem. 284: 265-275.

Saier, M.H., Jr., B.H. Eng, S. Fard, J. Garg, D.A. Haggerty, W.J. Hutchinson, D.L. Jack, E.C. Lai, H.J. Liu, D.P. Nusinew, A.M. Omar, S.S. Pao, I.T. Paulsen, J.A. Quan, M. Sliwinski, T.-T. Tseng, S. Wachi, and G.B. Young. (1999). Phylogenetic characterization of novel transport protein families revealed by genome analyses. Biochim. Biophys. Acta 1422: 1-56.

Six, S., S.C. Andrews, G. Unden, and J.R. Guest. (1994). Escherichia coli possesses two homologous anaerobic C4-dicarboxylate membrane transporters (DcuA and DcuB) distinct from the aerobic dicarboxylate transport system (Dct). J. Bacteriol. 176: 6470-6478.

Stopp, M., C. Schubert, and G. Unden. (2021). Conversion of the Sensor Kinase DcuS to the Fumarate Sensitive State by Interaction of the Bifunctional Transporter DctA at the TM2/PAS-Linker Region. Microorganisms 9:.

Unden, G. and J. Bongaerts. (1997). Alternative respiratory pathways of Escherichia coli: energetics and transcriptional regulation in response to electron acceptors. Biochim. Biophys. Acta 1320: 217-234.

Unden, G., S. Wörner, and C. Monzel. (2016). Cooperation of Secondary Transporters and Sensor Kinases in Transmembrane Signalling: The DctA/DcuS and DcuB/DcuS Sensor Complexes of Escherichia coli. Adv Microb Physiol 68: 139-167.

Wörner, S., K. Surmann, A. Ebert-Jung, U. Völker, E. Hammer, and G. Unden. (2018). Cellular Concentrations of the Transporters DctA and DcuB and the Sensor DcuS of Escherichia coli and the Contributions of Free and Complexed DcuS to Transcriptional Regulation by DcuR. J. Bacteriol. 200:.

Wösten, M.M., C.H. van de Lest, L. van Dijk, and J.P. van Putten. (2017). Function and Regulation of the C4-Dicarboxylate Transporters in Campylobacter jejuni. Front Microbiol 8: 174.

Zaharik M.L., S.S. Lamb, K.E. Baker, N.J. Krogan, J. Neuhard, R.A. Kelln. (2007). Mutations in yhiT enable utilization of exogenous pyrimidine intermediates in Salmonella enterica serovar Typhimurium. Microbiology.153: 2472-2482.

Zientz, E., S. Six, and G. Unden. (1996). Identification of a third secondary carrier (DcuC) for anaerobic C4-dicarboxylate transport in Escherichia coli: roles of the three Dcu carriers in uptake and exchange. J. Bacteriol. 178: 7241-7247.


TC#NameOrganismal TypeExample

The anaerobic C4-dicarboxylate antiporter (aspartate:fumarate antiporter; 433 aas and 12 TMSs), DctA, can catalyze both uptake and exchange (Zientz et al. 1996). The DcuS-DcuR two component system (sensor kinase-response regulator) responds to C4-dicarboxylates in a process that requires formation of a complex of DcuS with C4-dicarboxylate transporter, DctA or DcuB (Wörner et al. 2018). DcuS is in the constitutive "on" state unless complexed with DctA, in which case it becomes fumarate-sensitive (Stopp et al. 2021).


DcuA of E. coli (P0ABN5)


Anaerobic C4-dicarboxylate uptake/efflux porter, DcuB. Also catalyzes substrate:substrate antiport (fumarate:malate or fumarate:succinate antiport), but it is also a cosensor for the sensor kinase, DcuS (Kleefeld et al. 2009; Bauer et al. 2011; Chen et al. 2014) It has 12 established TMSs where the loop between TMSs 11 and 12 is the sensor. A central water-filled cavity may provide the transport pathway. The sensory domain of DcuB is composed of cytoplasmic loop XI/XII and a membrane integral region with the regulatory residues Thr396/Asp398 and Lys353. Also transports D-tartrate (Bauer et al. 2011; Kim et al. 2007).  The DcuB-DcuS interaction has been reviewed (Unden et al. 2016). The DcuS-DcuR two component system (sensor kinase-response regulator) responds to C4-dicarboxylates in a process that requires formation of the complex of DcuS with C4-dicarboxylate transporters DctA or DcuB (Wörner et al. 2018).


DcuB of E. coli (P0ABN9)


C4-dicarboxylate transporter, YhiT (probably transports succinate, fumarate, aspartate, asparagine, carbamoyl phosphate and dihydroorotate; Zaharik et al., 2007)


YhiT of Salmonella enterica


Uncharacterized C4-dicarboxylic acid transporter of 445 aas and 11 TMSs.


UP of Saccharothrix espanaensis


Dicarboxylate transporter, DcuA of 445 aas and 11 TMSs.  Takes up aspartate under low (0.3%) oxygen conditions; is regulated in response to oxygen and nitrate mediated by the RacR/RacS sensor kinase/response regulatory pair (Wösten et al. 2017).

DcuA of Campylobacter jejuni


Dicarboxylate transporter, DcuB of 474 aas and 11 TMSs.  Takes up aspartate and secretes succinate.  Subject to regulation in response to oxygen and nitrate, mediated by the sensor kinase/response regulator pair, RacR/RacS (Wösten et al. 2017).

DcuB of Campylobacter jejuni


TC#NameOrganismal TypeExample

Uncharacterized protein of 386 aas and 10 TMSs.


UP of Cardinium endosymbiont cEper1 of Encarsia pergandiella