| Structural highlights
Disease
S22A4_HUMAN Disease susceptibility is associated with variants affecting the gene represented in this entry.
Function
S22A4_HUMAN Transporter that mediates the transport of endogenous and microbial zwitterions and organic cations (PubMed:10215651, PubMed:15107849, PubMed:15795384, PubMed:16729965, PubMed:20601551, PubMed:22206629, PubMed:22569296, PubMed:29530864). Functions as a Na(+)-dependent and pH-dependent high affinity microbial symporter of potent food-derived antioxidant ergothioeine (PubMed:15795384, PubMed:29530864, PubMed:33124720). Transports one sodium ion with one ergothioeine molecule (By similarity). Involved in the absorption of ergothioneine from the luminal/apical side of the small intestine and renal tubular cells, and into non-parenchymal liver cells, thereby contributing to maintain steady-state ergothioneine level in the body (PubMed:20601551). Also mediates the bidirectional transport of acetycholine, although the exact transport mechanism has not been fully identified yet (PubMed:22206629). Most likely exports anti-inflammatory acetylcholine in non-neuronal tissues, thereby contributing to the non-neuronal cholinergic system (PubMed:22206629, PubMed:22569296). Displays a general physiological role linked to better survival by controlling inflammation and oxidative stress, which may be related to ergothioneine and acetycholine transports (PubMed:15795384, PubMed:22206629). May also function as a low-affinity Na(+)-dependent transporter of L-carnitine through the mitochondrial membrane, thereby maintaining intracellular carnitine homeostasis (PubMed:10215651, PubMed:15107849, PubMed:16729965). May contribute to regulate the transport of cationic compounds in testis across the blood-testis-barrier (PubMed:35307651).[UniProtKB:Q9R141][1] [2] [3] [4] [5] [6] [7] [8] [9]
References
- ↑ PMID: https://pubmed.ncbi.nlm.nih.gov/10215651/
- ↑ Peltekova VD, Wintle RF, Rubin LA, Amos CI, Huang Q, Gu X, Newman B, Van Oene M, Cescon D, Greenberg G, Griffiths AM, St George-Hyslop PH, Siminovitch KA. Functional variants of OCTN cation transporter genes are associated with Crohn disease. Nat Genet. 2004 May;36(5):471-5. doi: 10.1038/ng1339. Epub 2004 Apr 11. PMID:15107849 doi:https://dx.doi.org/10.1038/ng1339
- ↑ Grundemann D, Harlfinger S, Golz S, Geerts A, Lazar A, Berkels R, Jung N, Rubbert A, Schomig E. Discovery of the ergothioneine transporter. Proc Natl Acad Sci U S A. 2005 Apr 5;102(14):5256-61. doi: , 10.1073/pnas.0408624102. Epub 2005 Mar 28. PMID:15795384 doi:https://dx.doi.org/10.1073/pnas.0408624102
- ↑ Lamhonwah AM, Tein I. Novel localization of OCTN1, an organic cation/carnitine transporter, to mammalian mitochondria. Biochem Biophys Res Commun. 2006 Jul 14;345(4):1315-25. doi: , 10.1016/j.bbrc.2006.05.026. Epub 2006 May 12. PMID:16729965 doi:https://dx.doi.org/10.1016/j.bbrc.2006.05.026
- ↑ Sugiura T, Kato S, Shimizu T, Wakayama T, Nakamichi N, Kubo Y, Iwata D, Suzuki K, Soga T, Asano M, Iseki S, Tamai I, Tsuji A, Kato Y. Functional expression of carnitine/organic cation transporter OCTN1/SLC22A4 in mouse small intestine and liver. Drug Metab Dispos. 2010 Oct;38(10):1665-72. doi: 10.1124/dmd.110.032763. Epub , 2010 Jul 2. PMID:20601551 doi:https://dx.doi.org/10.1124/dmd.110.032763
- ↑ Pochini L, Scalise M, Galluccio M, Pani G, Siminovitch KA, Indiveri C. The human OCTN1 (SLC22A4) reconstituted in liposomes catalyzes acetylcholine transport which is defective in the mutant L503F associated to the Crohn's disease. Biochim Biophys Acta. 2012 Mar;1818(3):559-65. doi: 10.1016/j.bbamem.2011.12.014. , Epub 2011 Dec 21. PMID:22206629 doi:https://dx.doi.org/10.1016/j.bbamem.2011.12.014
- ↑ Pochini L, Scalise M, Galluccio M, Indiveri C. Regulation by physiological cations of acetylcholine transport mediated by human OCTN1 (SLC22A4). Implications in the non-neuronal cholinergic system. Life Sci. 2012 Nov 27;91(21-22):1013-6. doi: 10.1016/j.lfs.2012.04.027. Epub 2012 , Apr 30. PMID:22569296 doi:https://dx.doi.org/10.1016/j.lfs.2012.04.027
- ↑ Tschirka J, Kreisor M, Betz J, Grundemann D. Substrate Selectivity Check of the Ergothioneine Transporter. Drug Metab Dispos. 2018 Jun;46(6):779-785. doi: 10.1124/dmd.118.080440. Epub 2018 , Mar 12. PMID:29530864 doi:https://dx.doi.org/10.1124/dmd.118.080440
- ↑ Hau RK, Klein RR, Wright SH, Cherrington NJ. Localization of Xenobiotic Transporters Expressed at the Human Blood-Testis Barrier. Drug Metab Dispos. 2022 Jun;50(6):770-780. PMID:35307651 doi:10.1124/dmd.121.000748
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