2.A.51 The Chromate Ion Transporter (CHR) Family

Homologues of the CHR family have been identified in bacteria, eukaryotes and archaea. Two Bacillus homologues are half length with six putative TMSs each (Nies et al., 1998). These two proteins together (2.A.51.1.5), but not singly, cause chromate resistance due to formation of a heterodimer and consequent chromate efflux (Díaz-Magaña et al., 2009). Half-sized homologues are found in several bacteria. The functionally characterized chromate efflux pumps of P. aeruginosa and A. eutrophus are plasmid-encoded. They are about 400 amino acyl residues long with 10 putative transmembrane α-helical spanners (TMSs). They arose by a tandem internal gene duplication event from a putative 6 TMS primordial precursor, but the first two TMSs in the A. entrophus ChrA protein have lost their hydrophobic character (Nies et al., 1998).

In a more recent study, (Diaz-Perez et al., 2007), 77 duplicated 'bidomains' (BDs) and 58 unduplicated 'monodomains' (MDs) were identified and analyzed. The MDs clustered separately from the N-terminal BDs, and both clustered separately from the C-terminal BDs. This suggests that the MDs, possibly present in inverted orientation in the membrane, may have a unique structure and mode of action (Diaz-Perez et al., 2007).

The membrane topology of the ChrA protein of P. aeruginosa was conducted using lacZ and phoA translational fusions (Jiminez-Mejia et al., 2006). A 13 TMS topology was predicted with the N-terminus in the cytoplasm and the C-terminus in the periplasm. Predicted TMSs 1-6 proved to be homologous to predicted TMSs 8-13, but with opposite orientation in the membrane.

Synechococcus sp. PCC7942 bears an endogenous 50 Kb plasmid-encoded, sulfur-regulated CHR homologue that apparently confers chromate sensitivity (rather than chromate resistance) when grown in media containing a low sulfate concentration. This protein, designated SrpC, may be a sulfate uptake permease that can also transport chromate, but this possibility has not been established. ChrA of P. aeruginosa is a secondary carrier which might function by chromate uniport, chromate:H+ antiport, or chromate:anion antiport. It catalyzes CrO4 efflux with a Km of 80 μM. SO4= and MoO4= inhibit efflux but arsenate and vanadate do not inhibit (Pimentel et al., 2002). A pmf dependency is likely since valinomycin, nigericin and protonophores such as CCCP inhibit. Ramírez-Díaz et al. (2008) have published a review concerning the mechanisms of bacterial resistance to chromium compounds. In Neurosporal crassa, a chromate uptake transporter, Chr-1, a member of the Chr family, has been described (Flores-Alvarez et al. 2012).

The generalized transport reaction catalyzed by prokaryotic CHRs may be:

CrO42- (in) [+ nH+ (out)] → CrO42- (out) [+ nH+ (in)]

The generalized transport reaction catalyzed by SrpC or Chr-1 may be:

SO42- or CrO42- (out) + nH+ (out) → SO42- or CrO42- (in) + nH+ (in)



Aguilar-Barajas, E., E. Paluscio, C. Cervantes, and C. Rensing. (2008). Expression of chromate resistance genes from Shewanella sp. strain ANA-3 in Escherichia coli. FEMS Microbiol. Lett. 285: 97-100.

Aguilera, S., M.E. Aguilar, M.P. Chávez, J.E. López-Meza, M. Pedraza-Reyes, J. Campos-García, and C. Cervantes. (2004). Essential residues in the chromate transporter ChrA of Pseudomonas aeruginosa. FEMS Microbiol. Lett. 232: 107-112.

Alvarez, A.H., R. Moreno-Sánchez, and C. Cervantes. (1999). Chromate efflux by means of the ChrA chromate resistance protein from Pseudomonas aeruginosa. J. Bacteriol. 181: 7398-7400.

Cervantes, C., H. Ohtake, L. Chu, T.K. Misra, and S. Silver. (1990). Cloning, nucleotide sequence, and expression of the chromate resistance determinant of Pseudomonas aeruginosa plasmid pUM505. J. Bacteriol. 172: 287-291.

Diaz-Magana A., Aguilar-Barajas E., Moreno-Sanchez R., Ramirez-Diaz MI., Riveros-Rosas H., Vargas E. and Cervantes C. (2009). Short-chain chromate ion transporter proteins from Bacillus subtilis confer chromate resistance in Escherichia coli. J Bacteriol. 191(17):5441-5.

Diaz-Perez, C., C. Cervantes, J. Campos-García, A. Julián-Sánchez, and H. Riveros-Rosas. (2007). Phylogenetic analysis of the chromate ion transporter (CHR) superfamily. FEBS J. 274(23):6215-6227.

Flores-Alvarez, L.J., A.R. Corrales-Escobosa, C. Cortés-Penagos, M. Martínez-Pacheco, K. Wrobel-Zasada, K. Wrobel-Kaczmarczyk, C. Cervantes, and F. Gutiérrez-Corona. (2012). The Neurospora crassa chr-1 gene is up-regulated by chromate and its encoded CHR-1 protein causes chromate sensitivity and chromium accumulation. Curr. Genet. 58: 281-290.

Hori, K., F. Maruyama, T. Fujisawa, T. Togashi, N. Yamamoto, M. Seo, S. Sato, T. Yamada, H. Mori, N. Tajima, T. Moriyama, M. Ikeuchi, M. Watanabe, H. Wada, K. Kobayashi, M. Saito, T. Masuda, Y. Sasaki-Sekimoto, K. Mashiguchi, K. Awai, M. Shimojima, S. Masuda, M. Iwai, T. Nobusawa, T. Narise, S. Kondo, H. Saito, R. Sato, M. Murakawa, Y. Ihara, Y. Oshima-Yamada, K. Ohtaka, M. Satoh, K. Sonobe, M. Ishii, R. Ohtani, M. Kanamori-Sato, R. Honoki, D. Miyazaki, H. Mochizuki, J. Umetsu, K. Higashi, D. Shibata, Y. Kamiya, N. Sato, Y. Nakamura, S. Tabata, S. Ida, K. Kurokawa, and H. Ohta. (2014). Klebsormidium flaccidum genome reveals primary factors for plant terrestrial adaptation. Nat Commun 5: 3978.

Jimenez-Mejia, R., J. Campos-Garcia, and C. Cervantes. (2006). Membrane topology of the chromate transporter ChrA of Pseudomonas aeruginosa. FEMS Microbiol. Lett. 262: 178-184.

Martínez-Valencia, R., G. Reyes-Cortés, M.I. Ramírez-Díaz, H. Riveros-Rosas, and C. Cervantes. (2012). Antiparallel membrane topology of paired short-chain chromate transport proteins in Bacillus subtilis. FEMS Microbiol. Lett. 336: 113-121.

Nicholson, M.L. and D.E. Laudenbach. (1995). Genes encoded on a cyanobacterial plasmid are transcriptionally regulated by sulfur availability and CysR. J. Bacteriol. 177: 2143-2150.

Nies, A., D.H. Nies, and S. Silver. (1990). Nucleotide sequence and expression of a plasmid-encoded chromate resistance determinant from Alcaligenes eutrophus. J. Biol. Chem. 265: 5648-5653.

Nies, D., S. Koch, S. Wachi, N. Peitzsch, and M.H. Saier, Jr. (1998). CHR, a novel family of prokaryotic proton motive force-driven transporters probably containing chromate/sulfate antiporters. J. Bacteriol. 180: 5799-5802.

Nies, D.H. and S. Silver. (1995). Ion efflux systems involved in bacterial metal resistances. J. Indus. Microbiol. 14: 186-199.

Pimentel, B.E., R. Moreno-Sanchez, and C. Cervantes. (2002). Efflux of chromate by Pseudomonas aeruginosa cells expressing the ChrA protein. FEMS Microbiol. Lett. 212: 249-254.

Ramírez-Díaz, M.I., C. Díaz-Pérez, E. Vargas, H. Riveros-Rosas, J. Campos-García, and C. Cervantes. (2008). Mechanisms of bacterial resistance to chromium compounds. Biometals 21: 321-332.


TC#NameOrganismal TypeExample
2.A.51.1.1Chromate-resistance efflux pump Bacteria and archaea ChrA of Alcaligenes eutrophus

Uncharacterized protein of 984 aas and 13 TMSs, 1 N-terminal and 12 C-terminal.

UP of Phytophthora fragariae


Uncharacterized protein of 544 aas and 11 TMSs in a 4 + 7 TMS arrangement.

UP of Cavenderia fasciculata


Chromate transporter of 513 aas and 10 - 12 TMSs (Hori et al. 2014).

Chromate transporter of Klebsormidium nitens

2.A.51.1.2Chromate-sensitivity anion uptake permease Cyanobacteria SrpC of Synechococcus sp. PCC7942

Chromate-resistance efflux pump, ChrA of 416 aas and 11 or 12 TMSs. The chrA gene of Pseudomonas aeruginosa plasmid pUM505 encodes ChrA, which confers resistance to chromate by the energy-dependent efflux of chromate ions (Aguilera et al. 2004). Chromate-sensitive mutants were mostly point mutations affected amino acids clustered in the N-terminal half of ChrA, altering either cytoplasmic regions or transmembrane segments, and replaced residues moderately to highly conserved in ChrA homologs. PhoA and LacZ translational fusions were used to confirm the membrane topology at the N-terminal half of the ChrA protein (Aguilera et al. 2004).


ChrA of Pseudomonas aeruginosa plasmid pUM505

2.A.51.1.4Chromate efflux transporter, ChrA (Aguilar-Barajas et al., 2008)BacteriaChrA of Shewanella sp. strain ANA-3 (A0L3E7)

Chromate efflux protein Chr3N/Chr3C, or YwrB/YwrA (Díaz-Magaña et al., 2009).  Each protein has 5 TMSs, but they have antiparallel orientation in the membrane: Chr3N has the C-terminus in the cytoplasm while Chr3C has the C-terminus facing the extracellular medium (Martínez-Valencia et al. 2012).


YwrB/YwrA or Chr3N/Chr3C of Bacillus subtilis
Chr3N (O05216)
Chr3C (O05215)


Putative two component chromate porter.  The two proteins each have 5 TMSs and are of 195 and 187 aas in length.


Two component transporter of Treponema denticola


Chromate resistance protein, ChrA, of 389 aas and 11 TMSs.

ChrA of E. coli


Chromate efflux transporter, ChrA, of 420 aas and 11 TMSs.

ChrA of Euryarchaeota archaeon TMED141 (marine metagenome)


Chromate sensitivity protein, a chromate uptake protein, Chr-1, of 560 aas and 9 - 11 TMSs. N. crassa CHR-1 takes up chromate in a sulfate-independent fashon (Flores-Alvarez et al. 2012).

Chr-1 of Neurospora crassa