The solute carrier (SLC) complement of the human genome: Phylogenetic classification reveals four major families

Abstract

Solute carriers (SLCs) is the largest group of transporters, embracing transporters for inorganic ions, amino acids, neurotransmitters, sugars, purines and fatty acids among other substrates. We mined the finished assembly of the human genome using Hidden Markov Models (HMMs) obtaining a total of 384 unique SLC sequences. Detailed clustering and phylogenetic analysis of the entire SLC family showed that 15 of the families place into four large phylogenetic clusters with the largest containing eight SLC families, suggesting that many of the distinct families of SLCs have a common evolutionary origin. This study represents the first overall genomic roadmap of the SLCs providing large sequence sets and clarifies the phylogenetic relationships among the families of the second largest group of membrane proteins.

Heptahelical protein PQLC2 is a lysosomal cationic amino acid exporter underlying the action of cysteamine in cystinosis therapy

“…T he transport of solute across membranes is crucial to eukaryotic cell physiology, as illustrated in the human species by the existence of diverse diseases associated with defective transport (1-3) and the presence of ∼400 solute transporter genes grouped into 51 families in the human genome (www.bioparadigms.org/slc/ menu.asp) (4,5). However, this inventory is far from being complete, because the function of many putative transporters remains unknown and, for technical reasons, the repertoire of elucidated activities is biased in favor of cellular uptake at the expense of less tractable activities, such as cellular export or intracellular solute compartmentalization.…”

Vesicular and conductive mechanisms of nucleotide release

“…Solute carrier (SLC) 17A9, a member of the SLC17 family of ion transporters [34][35][36], was recently de-orphaned and characterized as a vesicular nucleotide transporter (thereafter named VNUT) that contributes to the release of ATP from a variety of tissues. SLC17A9 is predicted to encode a 430 residue-long protein -dependent ATP transport activity that was inhibited by 4,4′-diisothiocyanostilbene-2,2′-disulfonate (DIDS) [37].…”

Characterization of 22 Antituberculosis Drugs for Inhibitory Interaction Potential on Organic Anionic Transporter Polypeptide (OATP)-Mediated Uptake

“…Hepatic uptake of drugs is facilitated by solute carrier (SLC) family transporters. To date, approximately 400 human SLC transporter genes have been reported within the SLC superfamily and classified into 46 subfamilies (7). Among the members of the superfamily, the OATP subfamily plays a major role in drug disposition in hepatocytes (8).…”