9pmd

Structural highlights

Disease

S22A5_HUMAN Systemic primary carnitine deficiency. The disease is caused by variants affecting the gene represented in this entry. Expression in colon is increased in Crohn's disease and human ulcerative colitis (at protein level).^[1]

Function

S22A5_HUMAN Sodium-ion dependent, high affinity carnitine transporter. Involved in the active cellular uptake of carnitine. Transports one sodium ion with one molecule of carnitine (PubMed:10454528, PubMed:10525100, PubMed:10966938, PubMed:17509700, PubMed:20722056, PubMed:33124720). Also transports organic cations such as tetraethylammonium (TEA) without the involvement of sodium. Relative uptake activity ratio of carnitine to TEA is 11.3 (PubMed:10454528, PubMed:10525100, PubMed:10966938). In intestinal epithelia, transports the quorum-sensing pentapeptide CSF (competence and sporulation factor) from B.subtilis which induces cytoprotective heat shock proteins contributing to intestinal homeostasis (PubMed:18005709). May also contribute to regulate the transport of organic compounds in testis across the blood-testis-barrier (Probable).^{[2] [3] [4] [5] [6] [7] [8]} Retained in the ER, unable to perform carnitine uptake.^[9]

References

1. ↑ Fujiya M, Inaba Y, Musch MW, Hu S, Kohgo Y, Chang EB. Cytokine regulation of OCTN2 expression and activity in small and large intestine. Inflamm Bowel Dis. 2011 Apr;17(4):907-16. PMID:20722056 doi:10.1002/ibd.21444
2. ↑ Wu X, Huang W, Prasad PD, Seth P, Rajan DP, Leibach FH, Chen J, Conway SJ, Ganapathy V. Functional characteristics and tissue distribution pattern of organic cation transporter 2 (OCTN2), an organic cation/carnitine transporter. J Pharmacol Exp Ther. 1999 Sep;290(3):1482-92 PMID:10454528
3. ↑ Ohashi R, Tamai I, Yabuuchi H, Nezu JI, Oku A, Sai Y, Shimane M, Tsuji A. Na(+)-dependent carnitine transport by organic cation transporter (OCTN2): its pharmacological and toxicological relevance. J Pharmacol Exp Ther. 1999 Nov;291(2):778-84 PMID:10525100
4. ↑ Wagner CA, Lükewille U, Kaltenbach S, Moschen I, Bröer A, Risler T, Bröer S, Lang F. Functional and pharmacological characterization of human Na(+)-carnitine cotransporter hOCTN2. Am J Physiol Renal Physiol. 2000 Sep;279(3):F584-91. PMID:10966938 doi:10.1152/ajprenal.2000.279.3.F584
5. ↑ Maekawa S, Mori D, Nishiya T, Takikawa O, Horinouchi T, Nishimoto A, Kajita E, Miwa S. OCTN2VT, a splice variant of OCTN2, does not transport carnitine because of the retention in the endoplasmic reticulum caused by insertion of 24 amino acids in the first extracellular loop of OCTN2. Biochim Biophys Acta. 2007 Jun;1773(6):1000-6. PMID:17509700 doi:10.1016/j.bbamcr.2007.04.005
6. ↑ Fujiya M, Musch MW, Nakagawa Y, Hu S, Alverdy J, Kohgo Y, Schneewind O, Jabri B, Chang EB. The Bacillus subtilis quorum-sensing molecule CSF contributes to intestinal homeostasis via OCTN2, a host cell membrane transporter. Cell Host Microbe. 2007 Jun 14;1(4):299-308. PMID:18005709 doi:10.1016/j.chom.2007.05.004
7. ↑ Fujiya M, Inaba Y, Musch MW, Hu S, Kohgo Y, Chang EB. Cytokine regulation of OCTN2 expression and activity in small and large intestine. Inflamm Bowel Dis. 2011 Apr;17(4):907-16. PMID:20722056 doi:10.1002/ibd.21444
8. ↑ 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
9. ↑ Maekawa S, Mori D, Nishiya T, Takikawa O, Horinouchi T, Nishimoto A, Kajita E, Miwa S. OCTN2VT, a splice variant of OCTN2, does not transport carnitine because of the retention in the endoplasmic reticulum caused by insertion of 24 amino acids in the first extracellular loop of OCTN2. Biochim Biophys Acta. 2007 Jun;1773(6):1000-6. PMID:17509700 doi:10.1016/j.bbamcr.2007.04.005