SC5A6_MOUSE
ID SC5A6_MOUSE Reviewed; 634 AA.
AC Q5U4D8; Q8BTU3;
DT 15-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 129.
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;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=BALB/cJ x C57BL/6J; TISSUE=Small intestine;
RA Balamurugan K., Said H.M.;
RT "Mus musculus small intestine sodium dependent multivitamin transporter.";
RL Submitted (MAR-2004) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J, and NOD; TISSUE=Embryo, and Thymus;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J;
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 [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19144319; DOI=10.1016/j.immuni.2008.11.006;
RA Trost M., English L., Lemieux S., Courcelles M., Desjardins M.,
RA Thibault P.;
RT "The phagosomal proteome in interferon-gamma-activated macrophages.";
RL Immunity 30:143-154(2009).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, and Kidney;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [7]
RP FUNCTION, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX PubMed=23104561; DOI=10.1152/ajpgi.00379.2012;
RA Ghosal A., Lambrecht N., Subramanya S.B., Kapadia R., Said H.M.;
RT "Conditional knockout of the Slc5a6 gene in mouse intestine impairs biotin
RT absorption.";
RL Am. J. Physiol. 304:G64-G71(2013).
RN [8]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=27492331; DOI=10.1152/ajpgi.00240.2016;
RA Sabui S., Bohl J.A., Kapadia R., Cogburn K., Ghosal A., Lambrecht N.W.,
RA Said H.M.;
RT "Role of the sodium-dependent multivitamin transporter (SMVT) in the
RT maintenance of intestinal mucosal integrity.";
RL Am. J. Physiol. 311:G561-G570(2016).
RN [9]
RP TISSUE SPECIFICITY.
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).
CC -!- FUNCTION: Sodium-dependent multivitamin transporter that transports
CC pantothenate, biotin and lipoate (By similarity). Required for biotin
CC and pantothenate uptake in the instestine (PubMed:23104561). Plays a
CC role in the maintenance of intestinal mucosa integrity, by providing
CC the gut mucosa with biotin (PubMed:27492331). May play a role in the
CC transport of biotin and pantothenate into the brain across the blood-
CC brain barrier (By similarity). May also be involved in the sodium-
CC dependent transport of iodide ions (By similarity).
CC {ECO:0000250|UniProtKB:Q9Y289, ECO:0000269|PubMed:23104561,
CC ECO:0000269|PubMed:27492331}.
CC -!- SUBUNIT: Interacts with PDZD11. {ECO:0000250|UniProtKB:Q9Y289}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q9Y289};
CC Multi-pass membrane protein {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Expressed in the intestinal mucosa, liver and
CC kidney (at protein level) (PubMed:23104561). Expressed in the colon
CC (PubMed:28052864). {ECO:0000269|PubMed:23104561,
CC ECO:0000269|PubMed:28052864}.
CC -!- DISRUPTION PHENOTYPE: Intestine-specific knockout leads to premature
CC lethality between the age of 6 and 10 weeks in around two-thirds of
CC mice due to acute peritonitis (PubMed:23104561). Growth retardation,
CC decreased bone density of the femoral and humoral head, decreased bone
CC length of the pelvic, tibial, and femoral bones, lethargic behavior,
CC hunched back posture, and decreased biotin status are observed
CC (PubMed:23104561). Abnormalities in the small bowel with shortened
CC villi and dysplasia, chronic active inflammation with focal
CC cryptitis/crypt abscesses in the cecum, an increase in the number of
CC neutrophils in the mucosa and low-grade adenomatous changes and
CC extensive submucosal edema (PubMed:23104561). Impaired carrier-mediated
CC biotin and pantothenate uptake in the jejunum (PubMed:23104561).
CC Reduced biotin levels in the liver (PubMed:23104561). Increase in gut
CC permeability and changes in the level of expression of tight junction
CC proteins in the cecum and colon (PubMed:27492331).
CC {ECO:0000269|PubMed:23104561, ECO:0000269|PubMed:27492331}.
CC -!- SIMILARITY: Belongs to the sodium:solute symporter (SSF) (TC 2.A.21)
CC family. {ECO:0000305}.
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DR EMBL; AY572835; AAS79366.1; -; mRNA.
DR EMBL; AK088682; BAC40502.1; -; mRNA.
DR EMBL; AK161633; BAE36503.1; -; mRNA.
DR EMBL; CH466524; EDL37322.1; -; Genomic_DNA.
DR EMBL; BC085132; AAH85132.1; -; mRNA.
DR EMBL; BC117852; AAI17853.1; -; mRNA.
DR EMBL; BC117853; AAI17854.1; -; mRNA.
DR CCDS; CCDS19169.1; -.
DR RefSeq; NP_001171092.1; NM_001177621.1.
DR RefSeq; NP_001171093.1; NM_001177622.1.
DR RefSeq; NP_808538.1; NM_177870.5.
DR RefSeq; XP_011239053.1; XM_011240751.1.
DR AlphaFoldDB; Q5U4D8; -.
DR SMR; Q5U4D8; -.
DR BioGRID; 236889; 1.
DR STRING; 10090.ENSMUSP00000110316; -.
DR GlyGen; Q5U4D8; 2 sites.
DR iPTMnet; Q5U4D8; -.
DR PhosphoSitePlus; Q5U4D8; -.
DR SwissPalm; Q5U4D8; -.
DR jPOST; Q5U4D8; -.
DR PaxDb; Q5U4D8; -.
DR PRIDE; Q5U4D8; -.
DR ProteomicsDB; 255347; -.
DR Antibodypedia; 52501; 197 antibodies from 29 providers.
DR DNASU; 330064; -.
DR Ensembl; ENSMUST00000080431; ENSMUSP00000079291; ENSMUSG00000006641.
DR Ensembl; ENSMUST00000114668; ENSMUSP00000110316; ENSMUSG00000006641.
DR Ensembl; ENSMUST00000202520; ENSMUSP00000143938; ENSMUSG00000006641.
DR Ensembl; ENSMUST00000202556; ENSMUSP00000143993; ENSMUSG00000006641.
DR GeneID; 330064; -.
DR KEGG; mmu:330064; -.
DR UCSC; uc008wwt.2; mouse.
DR CTD; 8884; -.
DR MGI; MGI:2660847; Slc5a6.
DR VEuPathDB; HostDB:ENSMUSG00000006641; -.
DR eggNOG; KOG2349; Eukaryota.
DR GeneTree; ENSGT00940000155731; -.
DR InParanoid; Q5U4D8; -.
DR OMA; YVFIHFI; -.
DR OrthoDB; 327628at2759; -.
DR PhylomeDB; Q5U4D8; -.
DR TreeFam; TF316728; -.
DR Reactome; R-MMU-196780; Biotin transport and metabolism.
DR Reactome; R-MMU-199220; Vitamin B5 (pantothenate) metabolism.
DR Reactome; R-MMU-425397; Transport of vitamins, nucleosides, and related molecules.
DR BioGRID-ORCS; 330064; 1 hit in 73 CRISPR screens.
DR ChiTaRS; Slc5a6; mouse.
DR PRO; PR:Q5U4D8; -.
DR Proteomes; UP000000589; Chromosome 5.
DR RNAct; Q5U4D8; protein.
DR Bgee; ENSMUSG00000006641; Expressed in choroid plexus of fourth ventricle and 133 other tissues.
DR ExpressionAtlas; Q5U4D8; baseline and differential.
DR Genevisible; Q5U4D8; MM.
DR GO; GO:0031526; C:brush border membrane; ISO:MGI.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0012506; C:vesicle membrane; ISO:MGI.
DR GO; GO:0015225; F:biotin transmembrane transporter activity; ISS:UniProtKB.
DR GO; GO:0015233; F:pantothenate transmembrane transporter activity; ISO:MGI.
DR GO; GO:0008523; F:sodium-dependent multivitamin transmembrane transporter activity; ISO:MGI.
DR GO; GO:0015293; F:symporter activity; IBA:GO_Central.
DR GO; GO:0090482; F:vitamin transmembrane transporter activity; ISS:UniProtKB.
DR GO; GO:1905135; P:biotin import across plasma membrane; ISS:UniProtKB.
DR GO; GO:0015878; P:biotin transport; ISO:MGI.
DR GO; GO:1904200; P:iodide transmembrane transport; ISS:UniProtKB.
DR GO; GO:0015887; P:pantothenate transmembrane transport; ISO:MGI.
DR GO; GO:0006814; P:sodium ion transport; IBA:GO_Central.
DR GO; GO:0150104; P:transport across blood-brain barrier; ISO:MGI.
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; Glycoprotein; Ion transport; Membrane;
KW Reference proteome; Sodium; Sodium transport; Symport; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1..634
FT /note="Sodium-dependent multivitamin transporter"
FT /id="PRO_0000105387"
FT TRANSMEM 23..43
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 65..85
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 100..120
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 142..162
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 175..195
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 207..227
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 255..275
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 295..315
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 350..370
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 403..423
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 427..447
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 455..475
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 526..546
FT /note="Helical"
FT /evidence="ECO:0000255"
FT CARBOHYD 488
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 497
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CONFLICT 25
FT /note="V -> D (in Ref. 4; AAH85132)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 634 AA; 68511 MW; 5C43F53C19F3F38E CRC64;
MSVASTAAPF HTTSGSSGAI STFSVVDYVV FGLLLVLSLV IGLYHACRGW GHHTVGELLM
ADRKMGCLPV ALSLLATFQS AVAILGAPAE IFRFGTQYWF LGCSYFLGLL IPAHIFIPVF
YRLHLTSAYE YLELRFNKAV RICGTVTFIF QMVIYMGVAL YAPSLALNAV TGFDLWLSVL
ALGIVCNIYT ALGGLKAVIW TDVFQTLVMF LGQLVVIIVG AARVGGLGHV WNVTSQHGLI
SGINLDPDPF VRHTFWTLAF GGVFMMLSLY GVNQAQVQRY LSSHSERAAV LSCYAVFPCQ
QVALCMSCLI GLVMFAYYNM YSMSPELKQA APDQLVLYFV MDLLKDMPGL PGLFVACLFS
GSLSTISSAF NSLATVTMED LIQPWFPQLT ETRAIMLSRG LAFAYGLVCL GMAYISSHLG
SVLQAALSIF GMVGGPLLGL FCLGLFFPCA NPLGAIVGLL TGLTMAFWIG IGSIVSRMSS
AVAPPPLNGS SSFLPANVTV AAVTTVMPST LSKPTGLQHF YSLSYLWYSA HNSTTVIVVG
LIVSLLTGGM RGRSLNPGTI YPVLPKLLAL LPLSCQKRLC WRSHSQDIPV IPNLFPEKMR
NGVLQDSTDK ERMAEDGLVH QPCSPTYVVQ ETSL
