ID SC5A6_HUMAN Reviewed; 635 AA. AC Q9Y289; B2RB85; D6W549; Q969Y5; DT 24-JAN-2001, integrated into UniProtKB/Swiss-Prot. DT 05-MAY-2009, sequence version 2. DT 22-FEB-2023, entry version 166. DE RecName: Full=Sodium-dependent multivitamin transporter; DE Short=Na(+)-dependent multivitamin transporter; DE AltName: Full=Solute carrier family 5 member 6; GN Name=SLC5A6; Synonyms=SMVT; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], FUNCTION, TISSUE SPECIFICITY, AND RP VARIANT PHE-481. RC TISSUE=Intestine; RX PubMed=10329687; DOI=10.1074/jbc.274.21.14875; RA Wang H., Huang W., Fei Y.-J., Xia H., Yang-Feng T.L., Leibach F.H., RA Devoe L.D., Ganapathy V., Prasad P.D.; RT "Human placental Na+-dependent multivitamin transporter. Cloning, RT functional expression, gene structure, and chromosomal localization."; RL J. Biol. Chem. 274:14875-14883(1999). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT PHE-481. RC TISSUE=Intestine; RX PubMed=10334869; DOI=10.1006/abbi.1999.1213; RA Prasad P.D., Wang H., Huang W., Fei Y.-J., Leibach F.H., Devoe L.D., RA Ganapathy V.; RT "Molecular and functional characterization of the intestinal Na+-dependent RT multivitamin transporter."; RL Arch. Biochem. Biophys. 366:95-106(1999). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT PHE-481. RC TISSUE=Placenta; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15815621; DOI=10.1038/nature03466; RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., RA Wilson R.K.; RT "Generation and annotation of the DNA sequences of human chromosomes 2 and RT 4."; RL Nature 434:724-731(2005). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT PHE-481. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Brain; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [7] RP FUNCTION, AND BIOPHYSICOCHEMICAL PROPERTIES. RX PubMed=15561972; DOI=10.1152/ajprenal.00375.2004; RA Balamurugan K., Vaziri N.D., Said H.M.; RT "Biotin uptake by human proximal tubular epithelial cells: cellular and RT molecular aspects."; RL Am. J. Physiol. 288:F823-F831(2005). RN [8] RP INTERACTION WITH PDZD11. RX PubMed=21183659; DOI=10.1152/ajpgi.00530.2010; RA Nabokina S.M., Subramanian V.S., Said H.M.; RT "Association of PDZ-containing protein PDZD11 with the human sodium- RT dependent multivitamin transporter."; RL Am. J. Physiol. 300:G561-G567(2011). RN [9] RP FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, GLYCOSYLATION, AND MUTAGENESIS OF RP ASN-138; SER-283; THR-286; ASN-489; ASN-498 AND ASN-534. RX PubMed=21570947; DOI=10.1016/j.bbamem.2011.04.014; RA Ghosal A., Subramanian V.S., Said H.M.; RT "Role of the putative N-glycosylation and PKC-phosphorylation sites of the RT human sodium-dependent multivitamin transporter (hSMVT) in function and RT regulation."; RL Biochim. Biophys. Acta 1808:2073-2080(2011). RN [10] RP FUNCTION. RX PubMed=20980265; DOI=10.1074/jbc.m110.167197; RA de Carvalho F.D., Quick M.; RT "Surprising substrate versatility in SLC5A6: Na+-coupled I- transport by RT the human Na+/multivitamin transporter (hSMVT)."; RL J. Biol. Chem. 286:131-137(2011). RN [11] RP FUNCTION, AND BIOPHYSICOCHEMICAL PROPERTIES. RX PubMed=22927035; DOI=10.1208/s12248-012-9399-5; RA Vadlapudi A.D., Vadlapatla R.K., Pal D., Mitra A.K.; RT "Functional and molecular aspects of biotin uptake via SMVT in human RT corneal epithelial (HCEC) and retinal pigment epithelial (D407) cells."; RL AAPS J. 14:832-842(2012). RN [12] RP FUNCTION, AND MUTAGENESIS OF CYS-68; CYS-104; CYS-144; CYS-187; CYS-294; RP CYS-309; CYS-358; CYS-410; CYS-443; CYS-450; CYS-577; CYS-583 AND CYS-628. RX PubMed=22015582; DOI=10.1016/j.bbamem.2011.10.003; RA Ghosal A., Said H.M.; RT "Cys(294) is essential for the function of the human sodium-dependent RT multivitamin transporter."; RL Biochim. Biophys. Acta 1818:97-102(2012). RN [13] RP FUNCTION. RX PubMed=25971966; DOI=10.1074/jbc.m114.622555; RA Zehnpfennig B., Wiriyasermkul P., Carlson D.A., Quick M.; RT "Interaction of alpha-Lipoic Acid with the Human Na+/Multivitamin RT Transporter (hSMVT)."; RL J. Biol. Chem. 290:16372-16382(2015). RN [14] RP FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RX PubMed=25809983; DOI=10.1111/jnc.13092; RA Uchida Y., Ito K., Ohtsuki S., Kubo Y., Suzuki T., Terasaki T.; RT "Major involvement of Na(+) -dependent multivitamin transporter RT (SLC5A6/SMVT) in uptake of biotin and pantothenic acid by human brain RT capillary endothelial cells."; RL J. Neurochem. 134:97-112(2015). RN [15] RP FUNCTION, SUBCELLULAR LOCATION (MICROBIAL INFECTION), AND MUTAGENESIS OF RP THR-78; SER-128; SER-242; THR-366 AND THR-627. RX PubMed=28052864; DOI=10.1152/ajpcell.00300.2016; RA Lakhan R., Said H.M.; RT "Lipopolysaccharide inhibits colonic biotin uptake via interference with RT membrane expression of its transporter: a role for a casein kinase 2- RT mediated pathway."; RL Am. J. Physiol. 312:C376-C384(2017). RN [16] RP INVOLVEMENT IN SMVTD, VARIANTS SMVTD ARG-94--635-LEU DEL AND LEU-123, RP CHARACTERIZATION OF VARIANTS SMVTD ARG-94--635-LEU DEL AND LEU-123, RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=27904971; DOI=10.1007/s00439-016-1751-x; RA Subramanian V.S., Constantinescu A.R., Benke P.J., Said H.M.; RT "Mutations in SLC5A6 associated with brain, immune, bone, and intestinal RT dysfunction in a young child."; RL Hum. Genet. 136:253-261(2017). RN [17] RP VARIANT SMVTD THR-400, AND FUNCTION. RX PubMed=31754459; DOI=10.1038/s41525-019-0103-x; RA Byrne A.B., Arts P., Polyak S.W., Feng J., Schreiber A.W., Kassahn K.S., RA Hahn C.N., Mordaunt D.A., Fletcher J.M., Lipsett J., Bratkovic D., RA Booker G.W., Smith N.J., Scott H.S.; RT "Identification and targeted management of a neurodegenerative disorder RT caused by biallelic mutations in SLC5A6."; RL NPJ Genom. Med. 4:28-28(2019). RN [18] RP VARIANTS COMNB 94-ARG--LEU-635 DEL; CYS-162 AND GLY-429, CHARACTERIZATION RP OF VARIANTS COMNB CYS-162 AND GLY-429, INVOLVEMENT IN COMNB, AND RP SUBCELLULAR LOCATION. RX PubMed=35013551; DOI=10.1038/s41431-021-01033-2; RA Holling T., Nampoothiri S., Tarhan B., Schneeberger P.E., Vinayan K.P., RA Yesodharan D., Roy A.G., Radhakrishnan P., Alawi M., Rhodes L., RA Girisha K.M., Kang P.B., Kutsche K.; RT "Novel biallelic variants expand the SLC5A6-related phenotypic spectrum."; RL Eur. J. Hum. Genet. 30:439-449(2022). CC -!- FUNCTION: Sodium-dependent multivitamin transporter that transports CC pantothenate, biotin and lipoate (PubMed:10329687, PubMed:15561972, CC PubMed:21570947, PubMed:20980265, PubMed:22927035, PubMed:22015582, CC PubMed:25971966, PubMed:25809983, PubMed:28052864, PubMed:27904971, CC PubMed:31754459). Required for biotin and pantothenate uptake in the CC instestine (By similarity). Plays a role in the maintenance of CC intestinal mucosa integrity, by providing the gut mucosa with biotin CC (By similarity). May play a role in the transport of biotin and CC pantothenate into the brain across the blood-brain barrier CC (PubMed:25809983). May also be involved in the sodium-dependent CC transport of iodide ions (PubMed:20980265). CC {ECO:0000250|UniProtKB:Q5U4D8, ECO:0000269|PubMed:10329687, CC ECO:0000269|PubMed:15561972, ECO:0000269|PubMed:20980265, CC ECO:0000269|PubMed:21570947, ECO:0000269|PubMed:22015582, CC ECO:0000269|PubMed:22927035, ECO:0000269|PubMed:25809983, CC ECO:0000269|PubMed:25971966, ECO:0000269|PubMed:27904971, CC ECO:0000269|PubMed:28052864, ECO:0000269|PubMed:31754459}. CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=12.16 uM for biotin (in proximal tubular epithelial cells at 37 CC degrees Celsius and pH 7.4) {ECO:0000269|PubMed:15561972}; CC KM=18.91 uM for biotin (in retinal pigment epithelial cells at 37 CC degrees Celsius) {ECO:0000269|PubMed:21570947}; CC KM=296.2 uM for biotin (in corneal epithelial cells at 37 degrees CC Celsius and pH 7.4) {ECO:0000269|PubMed:22927035}; CC KM=863.8 uM for biotin (in retinal pigment epithelial cells at 37 CC degrees Celsius and pH 7.4) {ECO:0000269|PubMed:22927035}; CC Vmax=2.5 pmol/min/mg enzyme toward biotin (in proximal tubular CC epithelial cells at 37 degrees Celsius and pH 7.4) CC {ECO:0000269|PubMed:15561972}; CC Vmax=0.0967 pmol/min/mg enzyme toward biotin (in retinal pigment CC epithelial cells at 37 degrees Celsius) CC {ECO:0000269|PubMed:21570947}; CC Vmax=77.2 pmol/min/mg enzyme toward biotin (in corneal epithelial CC cells at 37 degrees Celsius and pH 7.4) CC {ECO:0000269|PubMed:22927035}; CC Vmax=308.3 pmol/min/mg enzyme toward biotin (in retinal pigment CC epithelial cells at 37 degrees Celsius and pH 7.4) CC {ECO:0000269|PubMed:22927035}; CC -!- SUBUNIT: Interacts with PDZD11. {ECO:0000269|PubMed:21183659}. CC -!- INTERACTION: CC Q9Y289; Q5EBL8: PDZD11; NbExp=6; IntAct=EBI-3915941, EBI-1644207; CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:25809983, CC ECO:0000269|PubMed:27904971, ECO:0000269|PubMed:35013551}; Multi-pass CC membrane protein {ECO:0000255}. CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:28052864}; CC Multi-pass membrane protein {ECO:0000255}. Note=(Microbial infection) CC Exposure to E.coli lipopolysaccharides leeds to reduced cell membrane CC localization. {ECO:0000269|PubMed:28052864}. CC -!- TISSUE SPECIFICITY: Expressed in microvessels of the brain (at protein CC level) (PubMed:25809983). Expressed in heart, brain, placenta, lung, CC liver, skeletal muscle, kidney, and pancreas (PubMed:10329687). CC {ECO:0000269|PubMed:10329687, ECO:0000269|PubMed:25809983}. CC -!- PTM: May be glycosylated. {ECO:0000269|PubMed:21570947}. CC -!- DISEASE: Sodium-dependent multivitamin transporter deficiency (SMVTD) CC [MIM:618973]: An autosomal recessive multisystemic metabolic disorder CC characterized by early infantile onset, progressive neurodegeneration, CC global developmental delay, and developmental regression with loss of CC early motor and cognitive milestones. Additional variable features CC include seizures, ataxia, spasticity, peripheral neuropathy, immune CC defects, and osteopenia. Treatment with biotin, pantothenic acid, and CC lipoate may result in clinical improvement. CC {ECO:0000269|PubMed:27904971, ECO:0000269|PubMed:31754459}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- DISEASE: Peripheral motor neuropathy, childhood-onset, biotin- CC responsive (COMNB) [MIM:619903]: An autosomal recessive disorder CC characterized by distal muscle weakness and atrophy appearing late in CC the first decade of life. The disorder predominantly affects the upper CC limbs and hands, resulting in difficulties with fine motor skills. Some CC patients may have lower limb involvement, resulting in gait CC difficulties. Additional features may include spasticity, ataxia, and CC cerebellar signs. Sensation is intact, and patients have normal CC cognitive development. Treatment with biotin, pantothenic acid, and CC lipoic acid may result in clinical improvement. CC {ECO:0000269|PubMed:35013551}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the sodium:solute symporter (SSF) (TC 2.A.21) CC family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF116241; AAD37502.1; -; Genomic_DNA. DR EMBL; AF069307; AAD31727.1; -; mRNA. DR EMBL; AF081571; AAD37481.1; -; mRNA. DR EMBL; AK314545; BAG37132.1; -; mRNA. DR EMBL; AC013403; AAX93172.1; -; Genomic_DNA. DR EMBL; CH471053; EAX00620.1; -; Genomic_DNA. DR EMBL; CH471053; EAX00621.1; -; Genomic_DNA. DR EMBL; CH471053; EAX00622.1; -; Genomic_DNA. DR EMBL; BC012806; AAH12806.1; -; mRNA. DR EMBL; BC015631; AAH15631.1; -; mRNA. DR CCDS; CCDS1740.1; -. DR RefSeq; NP_066918.2; NM_021095.2. DR RefSeq; XP_006712191.1; XM_006712128.1. DR RefSeq; XP_006712192.1; XM_006712129.1. DR RefSeq; XP_006712193.1; XM_006712130.1. DR AlphaFoldDB; Q9Y289; -. DR SMR; Q9Y289; -. DR BioGRID; 114403; 271. DR IntAct; Q9Y289; 7. DR MINT; Q9Y289; -. DR STRING; 9606.ENSP00000310208; -. DR DrugBank; DB00121; Biotin. DR DrugBank; DB08872; Gabapentin enacarbil. DR DrugBank; DB00166; Lipoic acid. DR TCDB; 2.A.21.5.7; the solute:sodium symporter (sss) family. DR GlyCosmos; Q9Y289; 3 sites, No reported glycans. DR GlyGen; Q9Y289; 3 sites. DR iPTMnet; Q9Y289; -. DR PhosphoSitePlus; Q9Y289; -. DR SwissPalm; Q9Y289; -. DR BioMuta; SLC5A6; -. DR DMDM; 229462745; -. DR EPD; Q9Y289; -. DR jPOST; Q9Y289; -. DR MassIVE; Q9Y289; -. DR MaxQB; Q9Y289; -. DR PaxDb; Q9Y289; -. DR PeptideAtlas; Q9Y289; -. DR ProteomicsDB; 85700; -. DR Antibodypedia; 52501; 200 antibodies from 29 providers. DR DNASU; 8884; -. DR Ensembl; ENST00000310574.8; ENSP00000310208.3; ENSG00000138074.15. DR Ensembl; ENST00000408041.5; ENSP00000384853.1; ENSG00000138074.15. DR GeneID; 8884; -. DR KEGG; hsa:8884; -. DR MANE-Select; ENST00000310574.8; ENSP00000310208.3; NM_021095.4; NP_066918.2. DR UCSC; uc002rjd.4; human. DR AGR; HGNC:11041; -. DR CTD; 8884; -. DR DisGeNET; 8884; -. DR GeneCards; SLC5A6; -. DR HGNC; HGNC:11041; SLC5A6. DR HPA; ENSG00000138074; Tissue enhanced (liver). DR MalaCards; SLC5A6; -. DR MIM; 604024; gene. DR MIM; 618973; phenotype. DR MIM; 619903; phenotype. DR neXtProt; NX_Q9Y289; -. DR OpenTargets; ENSG00000138074; -. DR PharmGKB; PA379; -. DR VEuPathDB; HostDB:ENSG00000138074; -. DR eggNOG; KOG2349; Eukaryota. DR GeneTree; ENSGT00940000155731; -. DR HOGENOM; CLU_018808_11_1_1; -. DR InParanoid; Q9Y289; -. DR OMA; YVFIHFI; -. DR OrthoDB; 3078791at2759; -. DR PhylomeDB; Q9Y289; -. DR TreeFam; TF316728; -. DR PathwayCommons; Q9Y289; -. DR Reactome; R-HSA-196780; Biotin transport and metabolism. DR Reactome; R-HSA-199220; Vitamin B5 (pantothenate) metabolism. DR Reactome; R-HSA-425397; Transport of vitamins, nucleosides, and related molecules. DR SignaLink; Q9Y289; -. DR BioGRID-ORCS; 8884; 10 hits in 1155 CRISPR screens. DR ChiTaRS; SLC5A6; human. DR GeneWiki; SLC5A6; -. DR GenomeRNAi; 8884; -. DR Pharos; Q9Y289; Tbio. DR PRO; PR:Q9Y289; -. DR Proteomes; UP000005640; Chromosome 2. DR RNAct; Q9Y289; protein. DR Bgee; ENSG00000138074; Expressed in right lobe of liver and 141 other tissues. DR ExpressionAtlas; Q9Y289; baseline and differential. DR Genevisible; Q9Y289; HS. DR GO; GO:0016324; C:apical plasma membrane; ISS:ARUK-UCL. DR GO; GO:0009925; C:basal plasma membrane; ISS:ARUK-UCL. DR GO; GO:0016323; C:basolateral plasma membrane; ISS:ARUK-UCL. DR GO; GO:0031526; C:brush border membrane; IEA:Ensembl. DR GO; GO:0016020; C:membrane; TAS:ProtInc. DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB. DR GO; GO:0012506; C:vesicle membrane; IEA:Ensembl. DR GO; GO:0015225; F:biotin transmembrane transporter activity; IDA:UniProtKB. DR GO; GO:0015233; F:pantothenate transmembrane transporter activity; IMP:ARUK-UCL. DR GO; GO:0008523; F:sodium-dependent multivitamin transmembrane transporter activity; IBA:GO_Central. DR GO; GO:0015293; F:symporter activity; IBA:GO_Central. DR GO; GO:0090482; F:vitamin transmembrane transporter activity; IDA:UniProtKB. DR GO; GO:1905135; P:biotin import across plasma membrane; IDA:UniProtKB. DR GO; GO:0015878; P:biotin transport; IBA:GO_Central. DR GO; GO:1904200; P:iodide transmembrane transport; IDA:UniProtKB. DR GO; GO:0015887; P:pantothenate transmembrane transport; IMP:ARUK-UCL. DR GO; GO:0006814; P:sodium ion transport; IBA:GO_Central. DR GO; GO:0150104; P:transport across blood-brain barrier; IMP:ARUK-UCL. DR CDD; cd11504; SLC5sbd_SMVT; 1. DR Gene3D; 1.20.1730.10; Sodium/glucose cotransporter; 1. DR InterPro; IPR038377; Na/Glc_symporter_sf. DR InterPro; IPR001734; Na/solute_symporter. DR InterPro; IPR018212; Na/solute_symporter_CS. DR PANTHER; PTHR42985; SODIUM-COUPLED MONOCARBOXYLATE TRANSPORTER; 1. DR PANTHER; PTHR42985:SF2; SODIUM-DEPENDENT MULTIVITAMIN TRANSPORTER; 1. DR Pfam; PF00474; SSF; 1. DR TIGRFAMs; TIGR00813; sss; 1. DR PROSITE; PS00456; NA_SOLUT_SYMP_1; 1. DR PROSITE; PS50283; NA_SOLUT_SYMP_3; 1. PE 1: Evidence at protein level; KW Biotin; Cell membrane; Disease variant; Glycoprotein; Ion transport; KW Membrane; Neurodegeneration; Neuropathy; Reference proteome; Sodium; KW Sodium transport; Symport; Transmembrane; Transmembrane helix; Transport. FT CHAIN 1..635 FT /note="Sodium-dependent multivitamin transporter" FT /id="PRO_0000105386" FT TRANSMEM 24..44 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 68..88 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 101..121 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 143..163 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 176..196 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 199..219 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 256..276 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 297..317 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 336..356 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 396..416 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 428..448 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 456..476 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 528..548 FT /note="Helical" FT /evidence="ECO:0000255" FT CARBOHYD 138 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 489 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 498 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT VARIANT 94..635 FT /note="Missing (in SMVTD and COMNB; reduced membrane FT localization; impaired biotin transport; FT dbSNP:rs994218778)" FT /evidence="ECO:0000269|PubMed:27904971, FT ECO:0000269|PubMed:35013551" FT /id="VAR_084535" FT VARIANT 123 FT /note="R -> L (in SMVTD; reduced membrane localization; FT impaired biotin transport)" FT /evidence="ECO:0000269|PubMed:27904971" FT /id="VAR_084536" FT VARIANT 162 FT /note="Y -> C (in COMNB; no effect on membrane FT localization)" FT /evidence="ECO:0000269|PubMed:35013551" FT /id="VAR_087446" FT VARIANT 400 FT /note="R -> T (in SMVTD; impaired biotin transport; FT dbSNP:rs370950187)" FT /evidence="ECO:0000269|PubMed:31754459" FT /id="VAR_084537" FT VARIANT 429 FT /note="S -> G (in COMNB; no effect on membrane FT localization)" FT /evidence="ECO:0000269|PubMed:35013551" FT /id="VAR_087447" FT VARIANT 481 FT /note="S -> F (in dbSNP:rs1395)" FT /evidence="ECO:0000269|PubMed:10329687, FT ECO:0000269|PubMed:10334869, ECO:0000269|PubMed:14702039, FT ECO:0000269|Ref.5" FT /id="VAR_052491" FT VARIANT 492 FT /note="S -> N (in dbSNP:rs1064845)" FT /id="VAR_052492" FT MUTAGEN 68 FT /note="C->A: No effect on biotin transport." FT /evidence="ECO:0000269|PubMed:22015582" FT MUTAGEN 78 FT /note="T->A: Reduced membrane localization. Decrease in FT biotin transport." FT /evidence="ECO:0000269|PubMed:28052864" FT MUTAGEN 104 FT /note="C->A: No effect on biotin transport." FT /evidence="ECO:0000269|PubMed:22015582" FT MUTAGEN 128 FT /note="S->A: No effect on biotin transport." FT /evidence="ECO:0000269|PubMed:28052864" FT MUTAGEN 138 FT /note="N->A: Reduced protein levels. Decrease in biotin FT transport." FT /evidence="ECO:0000269|PubMed:21570947" FT MUTAGEN 144 FT /note="C->A: No effect on biotin transport." FT /evidence="ECO:0000269|PubMed:22015582" FT MUTAGEN 187 FT /note="C->A: No effect on biotin transport." FT /evidence="ECO:0000269|PubMed:22015582" FT MUTAGEN 242 FT /note="S->A: No effect on biotin transport." FT /evidence="ECO:0000269|PubMed:28052864" FT MUTAGEN 283 FT /note="S->A: No effect on protein levels or membrane FT localization." FT /evidence="ECO:0000269|PubMed:21570947" FT MUTAGEN 286 FT /note="T->A: Resistant to phorbol 12-myristate 13-acetate FT (PMA)-induced inhibition of biotin transport. No effect on FT protein levels or membrane localization." FT /evidence="ECO:0000269|PubMed:21570947" FT MUTAGEN 294 FT /note="C->A: Reduced membrane localization." FT /evidence="ECO:0000269|PubMed:22015582" FT MUTAGEN 294 FT /note="C->A: Reduced membrane localization. Decrease in FT biotin transport." FT /evidence="ECO:0000269|PubMed:22015582" FT MUTAGEN 294 FT /note="C->S,M: Decrease in biotin transport." FT /evidence="ECO:0000269|PubMed:22015582" FT MUTAGEN 309 FT /note="C->A: No effect on biotin transport." FT /evidence="ECO:0000269|PubMed:22015582" FT MUTAGEN 358 FT /note="C->A: No effect on biotin transport." FT /evidence="ECO:0000269|PubMed:22015582" FT MUTAGEN 366 FT /note="T->A: No effect on biotin transport." FT /evidence="ECO:0000269|PubMed:28052864" FT MUTAGEN 410 FT /note="C->A: No effect on biotin transport." FT /evidence="ECO:0000269|PubMed:22015582" FT MUTAGEN 443 FT /note="C->A: No effect on biotin transport." FT /evidence="ECO:0000269|PubMed:22015582" FT MUTAGEN 450 FT /note="C->A: No effect on biotin transport." FT /evidence="ECO:0000269|PubMed:22015582" FT MUTAGEN 489 FT /note="N->A: Slight decrease in protein levels. Decrease in FT biotin transport." FT /evidence="ECO:0000269|PubMed:21570947" FT MUTAGEN 498 FT /note="N->A: No effect on biotin transport." FT /evidence="ECO:0000269|PubMed:21570947" FT MUTAGEN 534 FT /note="N->A: No effect on biotin transport." FT /evidence="ECO:0000269|PubMed:21570947" FT MUTAGEN 577 FT /note="C->A: No effect on biotin transport." FT /evidence="ECO:0000269|PubMed:22015582" FT MUTAGEN 583 FT /note="C->A: No effect on biotin transport." FT /evidence="ECO:0000269|PubMed:22015582" FT MUTAGEN 627 FT /note="T->A: No effect on biotin transport." FT /evidence="ECO:0000269|PubMed:28052864" FT MUTAGEN 628 FT /note="C->A,S: Decrease in biotin transport." FT /evidence="ECO:0000269|PubMed:22015582" SQ SEQUENCE 635 AA; 68642 MW; 52A6E40DB337134F CRC64; MSVGVSTSAP LSPTSGTSVG MSTFSIMDYV VFVLLLVLSL AIGLYHACRG WGRHTVGELL MADRKMGCLP VALSLLATFQ SAVAILGVPS EIYRFGTQYW FLGCCYFLGL LIPAHIFIPV FYRLHLTSAY EYLELRFNKT VRVCGTVTFI FQMVIYMGVV LYAPSLALNA VTGFDLWLSV LALGIVCTVY TALGGLKAVI WTDVFQTLVM FLGQLAVIIV GSAKVGGLGR VWAVASQHGR ISGFELDPDP FVRHTFWTLA FGGVFMMLSL YGVNQAQVQR YLSSRTEKAA VLSCYAVFPF QQVSLCVGCL IGLVMFAYYQ EYPMSIQQAQ AAPDQFVLYF VMDLLKGLPG LPGLFIACLF SGSLSTISSA FNSLATVTME DLIRPWFPEF SEARAIMLSR GLAFGYGLLC LGMAYISSQM GPVLQAAISI FGMVGGPLLG LFCLGMFFPC ANPPGAVVGL LAGLVMAFWI GIGSIVTSMG SSMPPSPSNG SSFSLPTNLT VATVTTLMPL TTFSKPTGLQ RFYSLSYLWY SAHNSTTVIV VGLIVSLLTG RMRGRSLNPA TIYPVLPKLL SLLPLSCQKR LHCRSYGQDH LDTGLFPEKP RNGVLGDSRD KEAMALDGTA YQGSSSTCIL QETSL //