| 2.A.45 The Arsenite-Antimonite (ArsB) Efflux Family
Arsenite resistance (Ars) efflux pumps of bacteria consist either of two proteins (ArsB, the integral membrane constituent with twelve transmembrane spanners), and ArsA (the ATP-hydrolyzing, transport energizing subunit, as for the chromosomally-encoded E. coli system), or of one protein (the ArsB integral membrane protein of the plasmid-encoded Staphylococcus system) (Rensing et al., 1999; Rosen, 1996; Xu et al., 1998). ArsA proteins have two ATP binding domains and probably arose by a tandem gene duplication event. ArsB proteins all possess twelve transmembrane spanners and may also have arisen by a tandem gene duplication event. Structurally, the Ars pumps resemble ABC-type efflux pumps, but there is no significant sequence similarity between the Ars and ABC pumps. When only ArsB is present, the system operates by a pmf-dependent mechanism, and consequently belongs in TC subclass 2.A. When ArsA is also present, ATP hydrolysis drives efflux, and consequently the system belongs in TC subclass 3.A. ArsB therefore appears twice in the TC system but ArsA appears only once. These pumps actively expel both arsenite and antimonite.
Homologues of ArsB are found in Gram-negative and Gram-positive bacteria as well as cyanobacteria, and several paralogues are sometimes found in a single organism. Homologues are also found in archaea and eukarya. Among the distant homologues found in eukaryotes are members of the DASS family (TC #2.A.47) including the rat renal Na+:sulfate cotransporter (spQ07782) and the human renal Na+:dicarboxylate cotransporter (gbU26209). ArsB proteins are therefore members of a superfamily (called the IT (ion transporter) superfamily) (Prakash et al., 2003; Rabus et al., 1999). However, ArsB has uniquely gained the ability to function in conjunction with ArsA in order to couple ATP hydrolysis to anion efflux.
A unique member of the ArsB family is the rice silicon (silicate) efflux pump, Lsi2 (2.A.45.2.4). The silicon uptake systems, Lsi1 (1.A.8.12.2), and Lsi2 are expressed in roots, on the plasma membranes of cells in both the exodermis and the endodermis. In contrast to Lsi1, which is localized on the distal side, Lsi2 is localized on the proximal side of the same cells. Thus these cells have an influx transporter on one side and an efflux transporter on the other side of the cell to permit the effective transcellular transport of the nutrient.
ArsA homologues are found in bacteria, archaea and eukarya (both animals and plants), but there are far fewer of them in the databases than ArsB proteins, suggesting that many ArsB homologues function by a pmf-dependent mechanism, probably an arsenite:H+ antiport mechanism (Meng et al., 2004). ArsA proteins are homologous to nitrogenase iron (NifH) proteins 2 of bacteria and to protochlorophyllide reductase iron sulfur ATP-binding proteins of cyanobacteria, algae and plants.
The overall reaction catalyzed by ArsB (presumably by uniport) is:
Arsenite or Antimonite (in)  Arsenite or Antimonite (out).
The overall reaction catalyzed by Lsi2 is:
silicate (in) → silicate (out)
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This family belongs to the IT Superfamily.
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| References: |
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Bellono, N.W., I.E. Escobar, A.J. Lefkovith, M.S. Marks, and E. Oancea. (2014). An intracellular anion channel critical for pigmentation. Elife 3: e04543.
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Bruhn, D.F., J. Li, S. Silver, F. Roberto and B.P. Rosen (1996). The arsenical resistance operon of IncN plasmid R46. FEMS Microbiol. Lett. 139: 149-153.
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Cho, E., K.E. Hyung, Y.H. Choi, H. Chun, D. Kim, S.H. Jun, and N.G. Kang. (2024). Modulating Expression as a Promising Approach to Enhance Skin Brightness and Reduce Dark Spots. Biomolecules 14:.
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Kuroda, M., S. Dey, O.I. Sanders and B.P. Rosen (1997). Alternate energy coupling of ArsB, the membrane subunit of the Ars anion-translocating ATPase. J. Biol. Chem. 272: 326-331.
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Lee, S.-T., R.D. Nicholls, M.T.C. Jong, K. Fukai and R.A. Spritz (1995). Organization and sequence of the human P gene and identification of a new family of transport proteins. Genomics 26: 354-363.
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Ma J.F., N. Yamaji, N. Mitani, K. Tamai, S. Konishi, T. Fujiwara, M. Katsuhara, M. Yano. (2007a). An efflux transporter of silicon in rice. Nature. 448: 209-212.
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Ma, J.F., N. Yamaji, K. Tamai, and N. Mitani. (2007b). Genotypic difference in silicon uptake and expression of silicon transporter genes in rice. Plant Physiol. 145: 919-924.
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Meng, Y.-L., Z. Liu, and B.P. Rosen. (2004). As(III) and Sb(III) uptake by GlpF and efflux by ArsB in Escherichia coli. J. Biol. Chem. 279: 18334-18341.
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Murat, D., A. Quinlan, H. Vali, and A. Komeili. (2010). Comprehensive genetic dissection of the magnetosome gene island reveals the step-wise assembly of a prokaryotic organelle. Proc. Natl. Acad. Sci. USA 107: 5593-5598.
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Panchal, P., C. Bhatia, Y. Chen, M. Sharma, J. Bhadouria, L. Verma, K. Maurya, A.J. Miller, and J. Giri. (2023). A citrate efflux transporter important for manganese distribution and phosphorus uptake in rice. Plant J. [Epub: Ahead of Print]
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Prakash, S., G. Cooper, S. Singhi, and M.H. Saier, Jr. (2003). The ion transporter superfamily. Biochim. Biophys. Acta 1618: 79-92.
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Rabus, R., D.L. Jack, D.J. Kelly and M.H. Saier, Jr. (1999). TRAP transporters: an ancient family of extracytoplasmic solute-receptor-dependent secondary active transporters. Microbiology 145: 3431-3445.
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Rensing, C., M. Ghosh and B.P. Rosen (1999). Families of soft-metal-ion transporting ATPase. J. Bacteriol. 181: 5891-5897.
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Rosen, B.R. (1996). Bacterial resistance to heavy metals and metalloids. JBIC 1: 273-277.
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Silver, S., G. Ji, S. Bröer, S. Dey, D. Dou and B.P. Rosen (1993). Orphan enzyme or patriarch of a new tribe: The arsenic resistance ATPase of bacterial plasmids. Mol. Microbiol. 8: 637-642.
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Uebe, R. and D. Schüler. (2016). Magnetosome biogenesis in magnetotactic bacteria. Nat. Rev. Microbiol. 14: 621-637.
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Walmsley, A.R., T. Zhou, M.I. Borges-Walmsley and B.P. Rosen (2001). A kinetic model for the action of a resistance efflux pump. J. Biol. Chem. 276: 6378-6391.
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Wiriyasermkul, P., S. Moriyama, and S. Nagamori. (2020). Membrane transport proteins in melanosomes: Regulation of ions for pigmentation. Biochim. Biophys. Acta. Biomembr 1862: 183318.
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Xu, C., T. Zhou, M. Kuroda and B.P. Rosen (1998). Metalloid resistance mechanisms in prokaryotes. J. Biochem. 123: 16-23.
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| Examples: |
| TC# | Name | Organismal Type | Example |
| 2.A.45.1.1 | Arsenical resistance efflux pump (exports As(III) and Sb(III) probably as polymers of the hydroxides using an H+ antiport mechanism) (Meng et al., 2004) | Bacteria; eukaryotes; archaea | ArsB of Staphylococcus aureus |
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| 2.A.45.1.2 | Arsenic transporter, ArsB, of 422 aas and 11 TMSs. | | ArsB of Campylobacter coli |
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| Examples: |
| TC# | Name | Organismal Type | Example |
| 2.A.45.2.1 | P-protein; possible tyrosine transporter (also called "melanocyte-specific transporter", "oculocutaneous albinism-related protein (Oca2)" and "pink-eyed dilution gene product"). It has been reported to exhibit chloride-selective anion channel activity and to be required for melanin production, possibly by controling melanosome pH (Bellono et al. 2014). Its function has been reviewed (Wiriyasermkul et al. 2020). The oculocutaneous albinism II (OCA2) gene encodes a melanosomal
transmembrane protein involved in melanogenesis. Genome-wide
association studies have identified several single nucleotide
polymorphisms within OCA2 genes that are involved in skin pigmentation (Cho et al. 2024). | Animals | P-protein of Homo sapiens |
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| 2.A.45.2.2 | Uncharacterized transporter Mb2703 | Actinobacteria | Mb2703 of Mycobacterium bovis |
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| 2.A.45.2.3 |
Putative ion transporter in magnetosome membranes of magentotactic bacteria, MamN of 437 aas and 10 TMSs (Murat et al. 2010). Uebe and Schüler 2016 considered that MamN might be a proton exporter that releases H+ from the magentosome matrix to the cytosol. | Bacteria | MamN of Magnetospirillum gryphiswaldense
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| 2.A.45.2.4 | The plasma membrane silicon (silicate) efflux pump, Low Silicon 2, Lsi2 (localized to the proximal side of the cell, whereas the silicon uptake system, Lsi1 (TC# 1.A.8.12.2) is localized to the distal side of the same cells) (Ma et al., 2007a, b). It has 472 aas and 10 TMSs in a 5 + 5 TMS arrangement. | Plants | Lsi2 of Oryza sativa
(Q10SY9) |
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| 2.A.45.2.5 | Inner membrane protein YbiR | Bacteria | YBIR of Escherichia coli K-12 |
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| 2.A.45.2.6 | Putative plasma membrane low silicon efflux pump, Lsi2, of 393 aas and 12 TMSs. | | Lsi2 of Bifidobacterium asteroides |
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| 2.A.45.2.7 | Citrate transporter, OsCT1 of 567 aas and 12 TMSs in a 3 + 1 + 1 + 1 + 3 + 1 + 1 + 1 TMS arrangement. It differs from previously known plant citrate
transporters and is structurally close to rice silicon transporters (Panchal et al. 2023). OsCT1 carries a bacterial citrate-metal transporter domain, CitMHS.
and showed citrate efflux activity when expressed in Xenopus laevis oocytes, being localized to the cell plasma membrane. It is highly
expressed in the shoots and reproductive tissues of rice, and its
promoter activity was visible in cells surrounding the vasculature. The
OsCT1 knockout (KO) lines showed a reduced citrate content in the shoots
and the root exudates, whereas the overexpression (OE) line showed higher
citrate exudation from their roots. Further, the KO and OE lines showed
variations in the manganese (Mn) distribution as expected if citrate and Mn2+ were co-transported. | | OsCT1 of Oryza sativa Japonica Group (Japanese rice) |
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| Examples: |
| TC# | Name | Organismal Type | Example |
| 2.A.45.3.1 | Putative transporter of 461 aas and 14 TMSs in a 3 + 3 + 1 + 3 + 3 + 1 TMS arrangement. | Bacteria | Putative transporter of Bacillus cereus (gi 30021968) |
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| 2.A.45.3.2 | Uncharaterized protein of 570 aas and 14 TMSs in a 7 + 7 arrangement. | | UP of Nocardioides sp. |
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