SC5A6_HUMAN
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 03-AUG-2022, entry version 163.
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 NERIB, VARIANTS NERIB ARG-94--635-LEU DEL AND LEU-123,
RP CHARACTERIZATION OF VARIANTS NERIB 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 NERIB 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).
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}; Multi-pass membrane protein
CC {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: Neurodegeneration, infantile-onset, biotin-responsive (NERIB)
CC [MIM:618973]: An autosomal recessive disorder characterized by early
CC infantile onset, progressive neurodegeneration, global developmental
CC delay, and developmental regression with loss of early motor and
CC cognitive milestones. Additional variable features include seizures,
CC ataxia, spasticity, peripheral neuropathy, immune defects, and
CC osteopenia. Treatment with biotin, pantothenic acid, and lipoate may
CC result in clinical improvement. {ECO:0000269|PubMed:27904971,
CC ECO:0000269|PubMed:31754459}. 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}.
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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; 270.
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 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 PRIDE; Q9Y289; -.
DR ProteomicsDB; 85700; -.
DR Antibodypedia; 52501; 197 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 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 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; 327628at2759; -.
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; 8 hits in 1075 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:0005887; C:integral component of plasma membrane; TAS:ProtInc.
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 Gene3D; 1.20.1730.10; -; 1.
DR InterPro; IPR038377; Na/Glc_symporter_sf.
DR InterPro; IPR001734; Na/solute_symporter.
DR InterPro; IPR018212; Na/solute_symporter_CS.
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; Reference proteome; Sodium; Sodium transport;
KW 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 NERIB; reduced membrane localization;
FT impaired biotin transport; dbSNP:rs994218778)"
FT /evidence="ECO:0000269|PubMed:27904971"
FT /id="VAR_084535"
FT VARIANT 123
FT /note="R -> L (in NERIB; reduced membrane localization;
FT impaired biotin transport)"
FT /evidence="ECO:0000269|PubMed:27904971"
FT /id="VAR_084536"
FT VARIANT 400
FT /note="R -> T (in NERIB; impaired biotin transport;
FT dbSNP:rs370950187)"
FT /evidence="ECO:0000269|PubMed:31754459"
FT /id="VAR_084537"
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
