| Structural highlights
Disease
SC5A6_HUMAN The disease is caused by variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry.
Function
SC5A6_HUMAN Sodium-dependent multivitamin transporter that mediates the electrogenic transport of pantothenate, biotin, lipoate and iodide (PubMed:10329687, PubMed:15561972, PubMed:19211916, PubMed:20980265, PubMed:21570947, PubMed:22015582, PubMed:25809983, PubMed:25971966, PubMed:27904971, PubMed:28052864, PubMed:31754459). Functions as a Na(+)-coupled substrate symporter where the stoichiometry of Na(+):substrate is 2:1, creating an electrochemical Na(+) gradient used as driving force for substrate uptake (PubMed:10329687, PubMed:20980265). Required for biotin and pantothenate uptake in the intestine across the brush border membrane (PubMed:19211916). Plays a role in the maintenance of intestinal mucosa integrity, by providing the gut mucosa with biotin (By similarity). Contributes to the luminal uptake of biotin and pantothenate into the brain across the blood-brain barrier (PubMed:25809983).[UniProtKB:Q5U4D8][1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11]
References
- ↑ Wang H, Huang W, Fei YJ, Xia H, Yang-Feng TL, Leibach FH, Devoe LD, Ganapathy V, Prasad PD. Human placental Na+-dependent multivitamin transporter. Cloning, functional expression, gene structure, and chromosomal localization. J Biol Chem. 1999 May 21;274(21):14875-83. PMID:10329687 doi:10.1074/jbc.274.21.14875
- ↑ Balamurugan K, Vaziri ND, Said HM. Biotin uptake by human proximal tubular epithelial cells: cellular and molecular aspects. Am J Physiol Renal Physiol. 2005 Apr;288(4):F823-31. PMID:15561972 doi:10.1152/ajprenal.00375.2004
- ↑ Subramanian VS, Marchant JS, Boulware MJ, Ma TY, Said HM. Membrane targeting and intracellular trafficking of the human sodium-dependent multivitamin transporter in polarized epithelial cells. Am J Physiol Cell Physiol. 2009 Apr;296(4):C663-71. PMID:19211916 doi:10.1152/ajpcell.00396.2008
- ↑ de Carvalho FD, Quick M. Surprising substrate versatility in SLC5A6: Na+-coupled I Na+/multivitamin transporter (hSMVT). J Biol Chem. 2011 Jan 7;286(1):131-7. PMID:20980265 doi:10.1074/jbc.M110.167197
- ↑ Ghosal A, Subramanian VS, Said HM. Role of the putative N-glycosylation and PKC-phosphorylation sites of the human sodium-dependent multivitamin transporter (hSMVT) in function and regulation. Biochim Biophys Acta. 2011 Aug;1808(8):2073-80. PMID:21570947 doi:10.1016/j.bbamem.2011.04.014
- ↑ Ghosal A, Said HM. Cys(294) is essential for the function of the human sodium-dependent multivitamin transporter. Biochim Biophys Acta. 2012 Jan;1818(1):97-102. doi: 10.1016/j.bbamem.2011.10.003. , Epub 2011 Oct 12. PMID:22015582 doi:https://dx.doi.org/10.1016/j.bbamem.2011.10.003
- ↑ Uchida Y, Ito K, Ohtsuki S, Kubo Y, Suzuki T, Terasaki T. Major involvement of Na(+) -dependent multivitamin transporter (SLC5A6/SMVT) in uptake of biotin and pantothenic acid by human brain capillary endothelial cells. J Neurochem. 2015 Jul;134(1):97-112. doi: 10.1111/jnc.13092. Epub 2015 Apr 8. PMID:25809983 doi:https://dx.doi.org/10.1111/jnc.13092
- ↑ Zehnpfennig B, Wiriyasermkul P, Carlson DA, Quick M. Interaction of alpha-Lipoic Acid with the Human Na+/Multivitamin Transporter (hSMVT). J Biol Chem. 2015 Jun 26;290(26):16372-82. doi: 10.1074/jbc.M114.622555. Epub , 2015 May 13. PMID:25971966 doi:https://dx.doi.org/10.1074/jbc.M114.622555
- ↑ Subramanian VS, Constantinescu AR, Benke PJ, Said HM. Mutations in SLC5A6 associated with brain, immune, bone, and intestinal dysfunction in a young child. Hum Genet. 2017 Feb;136(2):253-261. doi: 10.1007/s00439-016-1751-x. Epub 2016 Nov , 30. PMID:27904971 doi:https://dx.doi.org/10.1007/s00439-016-1751-x
- ↑ Lakhan R, Said HM. Lipopolysaccharide inhibits colonic biotin uptake via interference with membrane expression of its transporter: a role for a casein kinase 2-mediated pathway. Am J Physiol Cell Physiol. 2017 Apr 1;312(4):C376-C384. doi: , 10.1152/ajpcell.00300.2016. Epub 2017 Jan 4. PMID:28052864 doi:https://dx.doi.org/10.1152/ajpcell.00300.2016
- ↑ Byrne AB, Arts P, Polyak SW, Feng J, Schreiber AW, Kassahn KS, Hahn CN, Mordaunt DA, Fletcher JM, Lipsett J, Bratkovic D, Booker GW, Smith NJ, Scott HS. Identification and targeted management of a neurodegenerative disorder caused by biallelic mutations in SLC5A6. NPJ Genom Med. 2019 Nov 14;4:28. doi: 10.1038/s41525-019-0103-x. eCollection , 2019. PMID:31754459 doi:https://dx.doi.org/10.1038/s41525-019-0103-x
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