SC5A4_HUMAN
ID SC5A4_HUMAN Reviewed; 659 AA.
AC Q9NY91; O15279;
DT 26-SEP-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 162.
DE RecName: Full=Solute carrier family 5 member 4 {ECO:0000303|PubMed:13130073};
GN Name=SLC5A4 {ECO:0000303|PubMed:13130073};
GN Synonyms=SAAT1, SGLT3 {ECO:0000303|PubMed:13130073};
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 [MRNA], FUNCTION, LACK OF SUGAR TRANSPORT ACTIVITY,
RP ACTIVITY REGULATION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RC TISSUE=Small intestine;
RX PubMed=13130073; DOI=10.1073/pnas.1733027100;
RA Diez-Sampedro A., Hirayama B.A., Osswald C., Gorboulev V., Baumgarten K.,
RA Volk C., Wright E.M., Koepsell H.;
RT "A glucose sensor hiding in a family of transporters.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:11753-11758(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=10591208; DOI=10.1038/990031;
RA Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., Clamp M.,
RA Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C.,
RA Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E.,
RA Bridgeman A.M., Buck D., Burgess J., Burrill W.D., Burton J., Carder C.,
RA Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G.,
RA Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V.,
RA Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M.,
RA Ellington A.G., Evans K.L., Fey J.M., Fleming K., French L., Garner A.A.,
RA Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C.,
RA Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., Hunt S.E.,
RA Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F.,
RA Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M.,
RA Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A.,
RA Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D.,
RA Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y.,
RA Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S.,
RA Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E.,
RA Swann R.M., Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L.,
RA Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L.,
RA Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N.,
RA Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., Shintani A.,
RA Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L.,
RA Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P.,
RA Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P.,
RA Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q.,
RA Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J.,
RA Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J.,
RA Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D.,
RA Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T.,
RA Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P.,
RA Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K.,
RA Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R.,
RA Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L.,
RA McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J.,
RA Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E.,
RA Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P.,
RA Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y.,
RA Wright H.;
RT "The DNA sequence of human chromosome 22.";
RL Nature 402:489-495(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 73-247.
RC TISSUE=Brain;
RA Poppe R., Koepsell H.;
RL Submitted (DEC-1995) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP FUNCTION, AND ACTIVITY REGULATION.
RX PubMed=17110502; DOI=10.1124/mol.106.030288;
RA Voss A.A., Diez-Sampedro A., Hirayama B.A., Loo D.D., Wright E.M.;
RT "Imino sugars are potent agonists of the human glucose sensor SGLT3.";
RL Mol. Pharmacol. 71:628-634(2007).
RN [5]
RP FUNCTION, LACK OF SUGAR TRANSPORT ACTIVITY, AND MUTAGENESIS OF GLU-457.
RX PubMed=20421923; DOI=10.1371/journal.pone.0010241;
RA Bianchi L., Diez-Sampedro A.;
RT "A single amino acid change converts the sugar sensor SGLT3 into a sugar
RT transporter.";
RL PLoS ONE 5:E10241-E10241(2010).
RN [6]
RP FUNCTION, LACK OF SUGAR TRANSPORT ACTIVITY, ACTIVITY REGULATION, AND TISSUE
RP SPECIFICITY.
RX PubMed=22766068; DOI=10.1016/j.ejphar.2012.06.033;
RA Kothinti R.K., Blodgett A.B., North P.E., Roman R.J., Tabatabai N.M.;
RT "A novel SGLT is expressed in the human kidney.";
RL Eur. J. Pharmacol. 690:77-83(2012).
CC -!- FUNCTION: Has electrogenic activity in response to glucose, and may
CC function as a glucose sensor (PubMed:13130073, PubMed:17110502,
CC PubMed:20421923, PubMed:22766068). Mediates influx of sodium ions into
CC the cell but does not transport sugars (PubMed:13130073,
CC PubMed:22766068). Also potently activated by imino sugars such as
CC deoxynojirimycin (DNJ) (PubMed:17110502, PubMed:20421923,
CC PubMed:22766068). {ECO:0000269|PubMed:13130073,
CC ECO:0000269|PubMed:17110502, ECO:0000269|PubMed:20421923,
CC ECO:0000269|PubMed:22766068}.
CC -!- ACTIVITY REGULATION: Inhibited by phlorizin.
CC {ECO:0000269|PubMed:13130073, ECO:0000269|PubMed:17110502,
CC ECO:0000269|PubMed:22766068}.
CC -!- INTERACTION:
CC Q9NY91; Q8NBJ4: GOLM1; NbExp=3; IntAct=EBI-12409133, EBI-712073;
CC Q9NY91; Q8N6L0: KASH5; NbExp=3; IntAct=EBI-12409133, EBI-749265;
CC Q9NY91; Q96HJ5: MS4A3; NbExp=3; IntAct=EBI-12409133, EBI-12806656;
CC Q9NY91; Q96Q45-2: TMEM237; NbExp=3; IntAct=EBI-12409133, EBI-10982110;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:13130073,
CC ECO:0000305|PubMed:17110502, ECO:0000305|PubMed:20421923,
CC ECO:0000305|PubMed:22766068}; Multi-pass membrane protein
CC {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Expressed in skeletal muscle, where it may localize
CC to the neuromuscular junction (at protein level) (PubMed:13130073).
CC Expressed in small intestine where it may localize to cholinergic
CC neurons of the submucosal plexus and myenteric plexus (at protein
CC level) (PubMed:13130073). Detected in kidney (at protein level)
CC (PubMed:22766068). {ECO:0000269|PubMed:13130073,
CC ECO:0000269|PubMed:22766068}.
CC -!- SIMILARITY: Belongs to the sodium:solute symporter (SSF) (TC 2.A.21)
CC family. {ECO:0000305}.
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DR EMBL; AJ133127; CAB81772.1; -; mRNA.
DR EMBL; AL008723; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; U41897; AAB61732.1; -; mRNA.
DR CCDS; CCDS13903.1; -.
DR RefSeq; NP_055042.1; NM_014227.2.
DR AlphaFoldDB; Q9NY91; -.
DR SMR; Q9NY91; -.
DR BioGRID; 112418; 35.
DR IntAct; Q9NY91; 4.
DR STRING; 9606.ENSP00000266086; -.
DR BindingDB; Q9NY91; -.
DR ChEMBL; CHEMBL1770047; -.
DR DrugCentral; Q9NY91; -.
DR TCDB; 2.A.21.3.18; the solute:sodium symporter (sss) family.
DR GlyGen; Q9NY91; 1 site.
DR iPTMnet; Q9NY91; -.
DR PhosphoSitePlus; Q9NY91; -.
DR BioMuta; SLC5A4; -.
DR DMDM; 17433306; -.
DR jPOST; Q9NY91; -.
DR MassIVE; Q9NY91; -.
DR PaxDb; Q9NY91; -.
DR PeptideAtlas; Q9NY91; -.
DR PRIDE; Q9NY91; -.
DR ProteomicsDB; 83196; -.
DR Antibodypedia; 11228; 109 antibodies from 24 providers.
DR DNASU; 6527; -.
DR Ensembl; ENST00000266086.6; ENSP00000266086.3; ENSG00000100191.6.
DR GeneID; 6527; -.
DR KEGG; hsa:6527; -.
DR MANE-Select; ENST00000266086.6; ENSP00000266086.3; NM_014227.3; NP_055042.1.
DR UCSC; uc003ami.4; human.
DR CTD; 6527; -.
DR DisGeNET; 6527; -.
DR GeneCards; SLC5A4; -.
DR HGNC; HGNC:11039; SLC5A4.
DR HPA; ENSG00000100191; Tissue enriched (intestine).
DR MIM; 618633; gene.
DR neXtProt; NX_Q9NY91; -.
DR OpenTargets; ENSG00000100191; -.
DR PharmGKB; PA35904; -.
DR VEuPathDB; HostDB:ENSG00000100191; -.
DR eggNOG; KOG2349; Eukaryota.
DR GeneTree; ENSGT00940000160846; -.
DR HOGENOM; CLU_018808_9_2_1; -.
DR InParanoid; Q9NY91; -.
DR OMA; CVKHCGI; -.
DR OrthoDB; 243316at2759; -.
DR PhylomeDB; Q9NY91; -.
DR TreeFam; TF352855; -.
DR PathwayCommons; Q9NY91; -.
DR Reactome; R-HSA-189200; Cellular hexose transport.
DR SignaLink; Q9NY91; -.
DR BioGRID-ORCS; 6527; 8 hits in 1060 CRISPR screens.
DR ChiTaRS; SLC5A4; human.
DR GeneWiki; SLC5A4; -.
DR GenomeRNAi; 6527; -.
DR Pharos; Q9NY91; Tchem.
DR PRO; PR:Q9NY91; -.
DR Proteomes; UP000005640; Chromosome 22.
DR RNAct; Q9NY91; protein.
DR Bgee; ENSG00000100191; Expressed in duodenum and 87 other tissues.
DR Genevisible; Q9NY91; HS.
DR GO; GO:0016021; C:integral component of membrane; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0005412; F:glucose:sodium symporter activity; IBA:GO_Central.
DR GO; GO:0006814; P:sodium ion transport; IBA:GO_Central.
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; PS00457; NA_SOLUT_SYMP_2; 1.
DR PROSITE; PS50283; NA_SOLUT_SYMP_3; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Glycoprotein; Ion transport; Membrane; Reference proteome;
KW Sodium; Sodium transport; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..659
FT /note="Solute carrier family 5 member 4"
FT /id="PRO_0000105376"
FT TOPO_DOM 1..28
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 29..47
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 48..64
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 65..85
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 86..105
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 106..126
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 127..171
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 172..191
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 192..208
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 209..229
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 230..270
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 271..291
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 292..314
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 315..334
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 335..423
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 424..443
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 444..455
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 456..476
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 477..526
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 527..547
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 548..637
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 638..658
FT /note="Helical"
FT /evidence="ECO:0000255"
FT REGION 573..592
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 248
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VARIANT 4
FT /note="T -> M (in dbSNP:rs16990065)"
FT /id="VAR_052489"
FT VARIANT 46
FT /note="A -> T (in dbSNP:rs2235171)"
FT /id="VAR_021997"
FT MUTAGEN 457
FT /note="E->Q: Confers sugar transport activity not found in
FT the wild-type protein. Increased sensitivity to inhibitor
FT phlorizin."
FT /evidence="ECO:0000269|PubMed:20421923"
FT CONFLICT 76
FT /note="A -> V (in Ref. 3; AAB61732)"
FT /evidence="ECO:0000305"
FT CONFLICT 106
FT /note="S -> P (in Ref. 3; AAB61732)"
FT /evidence="ECO:0000305"
FT CONFLICT 243
FT /note="V -> I (in Ref. 3; AAB61732)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 659 AA; 72456 MW; F8A34AED648B523A CRC64;
MASTVSPSTI AETPEPPPLS DHIRNAADIS VIVIYFLVVM AVGLWAMLKT NRGTIGGFFL
AGRDMAWWPM GASLFASNIG SNHYVGLAGT GAASGVATVT FEWTSSVMLL ILGWIFVPIY
IKSGVMTMPE YLKKRFGGER LQVYLSILSL FICVVLLISA DIFAGAIFIK LALGLDLYLA
IFILLAMTAV YTTTGGLASV IYTDTLQTII MLIGSFILMG FAFNEVGGYE SFTEKYVNAT
PSVVEGDNLT ISASCYTPRA DSFHIFRDAV TGDIPWPGII FGMPITALWY WCTNQVIVQR
CLCGKDMSHV KAACIMCAYL KLLPMFLMVM PGMISRILYT DMVACVVPSE CVKHCGVDVG
CTNYAYPTMV LELMPQGLRG LMLSVMLASL MSSLTSIFNS ASTLFTIDLY TKMRKQASEK
ELLIAGRIFV LLLTVVSIVW VPLVQVSQNG QLIHYTESIS SYLGPPIAAV FVLAIFCKRV
NEQGAFWGLM VGLAMGLIRM ITEFAYGTGS CLAPSNCPKI ICGVHYLYFS IVLFFGSMLV
TLGISLLTKP IPDVHLYRLC WVLRNSTEER IDIDAEEKSQ EETDDGVEED YPEKSRGCLK
KAYDLFCGLQ KGPKLTKEEE EALSKKLTDT SERPSWRTIV NINAILLLAV VVFIHGYYA
