Physiol. Genomics Journal of Neurophysiology
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Physiol. Genomics (March 30, 2004). doi:10.1152/physiolgenomics.00014.2004
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Submitted on January 20, 2004
Accepted on March 26, 2004

Novel slc22 transporter homologs in fly, worm, and human clarify the phylogeny of organic anion and cation transporters

Satish A Eraly1, Julio C Monte1, and Sanjay K Nigam2*

1 Department of Medicine, University of California, San Diego, La Jolla, CA, USA
2 Department of Medicine, University of California, San Diego, La Jolla, CA, USA; Department of Pediatrics, University of California, San Diego, La Jolla, CA, USA; Department of Cellular & Molecular Medicine, University of California, San Diego, La Jolla, CA, USA

* To whom correspondence should be addressed. E-mail: snigam{at}ucsd.edu.

Slc22 family organic anion and cation transporters (OATs, OCTs, and OCTNs) are transmembrane proteins expressed predominantly in kidney and liver. These proteins mediate the uptake or excretion of numerous physiologically (and pharmacologically) important compounds, and accordingly have been the focus of intensive study. Here we investigate the molecular phylogeny of the slc22 transporters, identifying homologs in Drosophila and C. elegans, several of which are developmentally regulated, as well as reporting the cloning of a novel human family member, UST6, expressed exclusively in liver in both embryo and adult. The latter helps define a sub-family within the OATs that we term USTs, that appears to have human- and rodent-specific members, raising potential issues with respect to the use of rodents as models for the transport of organic anions (which include many pharmaceuticals) in humans. Though this phylogenetic inference could not be made on the basis of sequence alignment, analysis of intron phasing suggests that the OAT, OCT, and OCTN lineages of the slc22 family formed after the divergence of vertebrates and invertebrates. Subsequently, these lineages expanded through independent tandem duplications to produce multiple gene pairs. After analyzing over 200 other transporter genes, we find such pairing to be relatively specific to vertebrate organic anion and cation transporters, suggesting selection for gene pairing operating within this family in particular. This might reflect a requirement for redundancy or broader substrate specificity in vertebrates (compared to invertebrates), due to their greater physiological complexity and thus potentially broader exposure to organic ions.




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