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Review
. 2013 Apr-Jun;34(2-3):396-412.
doi: 10.1016/j.mam.2012.10.009.

The SLCO (former SLC21) superfamily of transporters

Bruno Hagenbuch  1 , Bruno Stieger
Affiliations
Review

The SLCO (former SLC21) superfamily of transporters

Bruno Hagenbuch et al. Mol Aspects Med. 2013 Apr-Jun.

Abstract

The members of the organic anion transporting polypeptide superfamily (OATPs) are classified within the SLCO solute carrier family. All functionally well characterized members are predicted to have 12 transmembrane domains and are sodium-independent transport systems that mediate the transport of a broad range of endo- as well as xenobiotics. Substrates are mainly amphipathic organic anions with a molecular weight of more than 300Da, but some of the known transported substrates are also neutral or even positively charged. Among the well characterized substrates are numerous drugs including statins, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, antibiotics, antihistaminics, antihypertensives and anticancer drugs. Based on their amino acid sequence identities, the different OATPs cluster into families (in general with more than 40% amino acid sequence identity) and subfamilies (more than 60% amino acid identity). With the sequencing of genomes from different species and the computerized prediction of encoded proteins more than 300 OATPs can be found in the databases, however only a fraction of them have been identified in humans, rodents, and some additional species important for pharmaceutical research like the rhesus monkey (Macaca mulatta), the dog (Canis lupus familiaris) and the pig (Sus scrofa). These OATPs form 6 families (OATP1-OATP6) and 13 subfamilies. In this review we try to summarize what is currently known about OATPs with respect to endogenous substrates, tissue distribution, transport mechanisms, regulation of expression, structure-function relationship and mutations and polymorphisms.

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Figures

Figure 1
Figure 1
Phylogenetic tree and classification of 70 members of the OATP/SLCO superfamily of transporters. Human (all capitalized OATP), monkey (maOATP), dog (dOATP), pig (sOATP), rat (rOATP) and mouse (mOATP) proteins are grouped into families (with more than 40% amino acid sequence identity) and subfamilies (with more than 60% amino acid sequence identity).
Figure 2
Figure 2
Distribution of OATPs in selected human epithelial tissues. The OATPs within the same subfamily are labelled with the same color. For more details see text.
Figure 3
Figure 3
Topology models for OATP1B1. A) The predicted secondary structure model for OATP1B1 is shown with 12 transmembrane domains. The extracellular conserved cysteine residues are labelled in black. B) Homology modelling was performed as described (Roth et al., 2012) based on the E. coli glycerol-3-phosphate transporter. OATP1B1 is shown from the extracellular side (left) and from within the lipid bilayer (right). Colors of the transmembrane domains match the colors used in the secondary structure model.
See this image and copyright information in PMC

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