Systems Biology Analysis Reveals Eight SLC22 Transporter Subgroups, Including OATs, OCTs, and OCTNs

• DOI: 10.3390/ijms21051791
• Publication Date: 2020-03-06T12:33:46Z
• Authors: Darcy C. Engelhart; Jeffry C. Granados; Da Shi; Milton H. Saier Jr.; Michael E. Baker; Ruben Abagyan; Sanjay K. Nigam
• Keywords: 0301 basic medicine; SLC22; Organic Cation Transport Proteins; endogenous metabolism; 610; gut microbiome; Organic Anion Transporters; drug transporters; transporters; Microbiology; Article; Substrate Specificity; 03 medical and health sciences; Genetics; Medicinal and biomolecular chemistry; Animals; Humans; Gene Regulatory Networks; 2. Zero hunger; 0303 health sciences; Chemical Physics; functional subgroups; Systems Biology; Biological Transport; Biological Sciences; 3. Good health; Gene Expression Regulation; Biochemistry and cell biology; Multigene Family; Mutation; Biochemistry and Cell Biology; Other Biological Sciences; Other Chemical Sciences; remote sensing and signaling; chronic kidney disease; Signal Transduction

The SLC22 family of OATs, OCTs, and OCTNs is emerging as a central hub endogenous physiology. Despite often being referred to "drug" transporters, they facilitate the movement metabolites key signaling molecules. An in-depth reanalysis supports reassignment these proteins into eight functional subgroups, with four new subgroups arising from previously defined OAT subclade: OATS1 (SLC22A6, SLC22A8, SLC22A20), OATS2 (SLC22A7), OATS3 (SLC22A11, SLC22A12, Slc22a22), OATS4 (SLC22A9, SLC22A10, SLC22A24, SLC22A25). We propose merging OCTN (SLC22A4, SLC22A5, Slc22a21) OCT-related (SLC22A15 SLC22A16) subclades OCTN/OCTN-related subgroup. Using data GWAS, in vivo models, vitro assays, we developed an transporter-metabolite network similar subgroup networks, which suggest how multiple transporters mono-, oligo-, multi-specific substrate specificity interact regulate metabolites. Subgroup associations include: molecules, uremic toxins, odorants, cyclic nucleotides, uric acid, conjugated sex hormones, particularly etiocholanolone glucuronide, OCT neurotransmitters, ergothioneine carnitine derivatives. Our that can work among itself, well other ADME genes, optimize levels numerous involved organ crosstalk inter-organismal communication, proposed by remote sensing theory.