Multidrug and toxin extrusion protein 2 explained

Multidrug and toxin extrusion protein 2 is a protein which in humans is encoded by the SLC47A2 gene.^[1]

Function

This gene encodes a protein belonging to a family of transporters involved in the excretion of toxic electrolytes, both endogenous and exogenous, through urine and bile. This transporter family shares homology with the bacterial MATE (multi antimicrobial extrusion protein or multidrug and toxic compound extrusion) protein family responsible for drug resistance.^[2] This gene is one of two members of the MATE transporter family located near each other on chromosome 17. Alternatively, spliced transcript variants encoding different isoforms have been identified for this gene.^[1]

Discovery

The multidrug efflux transporter NorM from V. parahaemolyticus, which mediates resistance to multiple antimicrobial agents (norfloxacin, kanamycin, ethidium bromide etc.), and its homologue from E. coli were identified in 1998.^[2] NorM seems to function as a drug/sodium antiporter, which is the first example of Na⁺-coupled multidrug efflux transporter discovered.^[3] NorM is a prototype of a new transporter family, and Brown et al. named it the multidrug and toxic compound extrusion family.^[4] The X-ray structure of the NorM was determined to be 3.65 Å, revealing an outward-facing conformation with two portals open to the outer leaflet of the membrane and a unique topology of the predicted 12 transmembrane helices distinct from any other known multidrug resistance transporter.^[5]

Further reading

• Tanihara Y, Masuda S, Sato T, Katsura T, Ogawa O, Inui K . Substrate specificity of MATE1 and MATE2-K, human multidrug and toxin extrusions/H(+)-organic cation antiporters . Biochemical Pharmacology . 74 . 2 . 359–71 . July 2007 . 17509534 . 10.1016/j.bcp.2007.04.010 . 2433/124277 . free .
• Omote H, Hiasa M, Matsumoto T, Otsuka M, Moriyama Y . The MATE proteins as fundamental transporters of metabolic and xenobiotic organic cations . Trends in Pharmacological Sciences . 27 . 11 . 587–93 . November 2006 . 16996621 . 10.1016/j.tips.2006.09.001 .
• Masuda S, Terada T, Yonezawa A, Tanihara Y, Kishimoto K, Katsura T, Ogawa O, Inui K . Identification and functional characterization of a new human kidney-specific H+/organic cation antiporter, kidney-specific multidrug and toxin extrusion 2 . Journal of the American Society of Nephrology . 17 . 8 . 2127–35 . August 2006 . 16807400 . 10.1681/ASN.2006030205 . free .
• Otsuka M, Matsumoto T, Morimoto R, Arioka S, Omote H, Moriyama Y . A human transporter protein that mediates the final excretion step for toxic organic cations . Proceedings of the National Academy of Sciences of the United States of America . 102 . 50 . 17923–8 . December 2005 . 16330770 . 1312386 . 10.1073/pnas.0506483102 . free .
• Bonaldo MF, Lennon G, Soares MB . Normalization and subtraction: two approaches to facilitate gene discovery . Genome Research . 6 . 9 . 791–806 . September 1996 . 8889548 . 10.1101/gr.6.9.791 . free .

Notes and References

1. Web site: Entrez Gene: MATE2 H+/organic cation antiporter.
2. Morita Y, Kodama K, Shiota S, Mine T, Kataoka A, Mizushima T, Tsuchiya T . NorM, a putative multidrug efflux protein, of Vibrio parahaemolyticus and its homolog in Escherichia coli . Antimicrobial Agents and Chemotherapy . 42 . 7 . 1778–82 . July 1998 . 9661020 . 105682 . 10.1128/AAC.42.7.1778.
3. Morita Y, Kataoka A, Shiota S, Mizushima T, Tsuchiya T . NorM of vibrio parahaemolyticus is an Na(+)-driven multidrug efflux pump . Journal of Bacteriology . 182 . 23 . 6694–7 . December 2000 . 11073914 . 111412 . 10.1128/JB.182.23.6694-6697.2000 .
4. Brown MH, Paulsen IT, Skurray RA . The multidrug efflux protein NorM is a prototype of a new family of transporters . Molecular Microbiology . 31 . 1 . 394–5 . January 1999 . 9987140 . 10.1046/j.1365-2958.1999.01162.x . 39261040 . free .
5. He X, Szewczyk P, Karyakin A, Evin M, Hong WX, Zhang Q, Chang G . Structure of a cation-bound multidrug and toxic compound extrusion transporter . Nature . 467 . 7318 . 991–4 . October 2010 . 20861838 . 3152480 . 10.1038/nature09408 . 2010Natur.467..991H .