SC5A3_HUMAN
ID SC5A3_HUMAN Reviewed; 718 AA.
AC P53794; O43489;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 23-FEB-2022, sequence version 3.
DT 03-AUG-2022, entry version 174.
DE RecName: Full=Sodium/myo-inositol cotransporter {ECO:0000305};
DE Short=Na(+)/myo-inositol cotransporter;
DE AltName: Full=Sodium/myo-inositol transporter 1;
DE Short=SMIT1;
DE AltName: Full=Solute carrier family 5 member 3;
GN Name=SLC5A3 {ECO:0000312|HGNC:HGNC:11038};
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], AND VARIANT LYS-566.
RC TISSUE=Placenta;
RX PubMed=7789985; DOI=10.1016/0888-7543(95)80052-n;
RA Berry G.T., Mallee J.J., Kwon H.M., Rim J.S., Mulla W.R., Muenke M.,
RA Spinner N.B.;
RT "The human osmoregulatory Na+/myo-inositol cotransporter gene (SLC5A3):
RT molecular cloning and localization to chromosome 21.";
RL Genomics 25:507-513(1995).
RN [2]
RP SEQUENCE REVISION TO 50 AND 566.
RA Berry G.T., Mallee J.J., Kwon H.M., Rim J.S., Mulla W.R., Muenke M.,
RA Spinner N.B.;
RL Submitted (APR-2004) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT THR-50.
RX PubMed=9441750; DOI=10.1006/geno.1997.5055;
RA Mallee J.J., Atta M.G., Lorica V., Rim J.S., Kwon H.M., Lucente A.D.,
RA Wang Y., Berry G.T.;
RT "The structural organization of the human Na+/myo-inositol cotransporter
RT (SLC5A3) gene and characterization of the promoter.";
RL Genomics 46:459-465(1997).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=10830953; DOI=10.1038/35012518;
RA Hattori M., Fujiyama A., Taylor T.D., Watanabe H., Yada T., Park H.-S.,
RA Toyoda A., Ishii K., Totoki Y., Choi D.-K., Groner Y., Soeda E., Ohki M.,
RA Takagi T., Sakaki Y., Taudien S., Blechschmidt K., Polley A., Menzel U.,
RA Delabar J., Kumpf K., Lehmann R., Patterson D., Reichwald K., Rump A.,
RA Schillhabel M., Schudy A., Zimmermann W., Rosenthal A., Kudoh J.,
RA Shibuya K., Kawasaki K., Asakawa S., Shintani A., Sasaki T., Nagamine K.,
RA Mitsuyama S., Antonarakis S.E., Minoshima S., Shimizu N., Nordsiek G.,
RA Hornischer K., Brandt P., Scharfe M., Schoen O., Desario A., Reichelt J.,
RA Kauer G., Bloecker H., Ramser J., Beck A., Klages S., Hennig S.,
RA Riesselmann L., Dagand E., Wehrmeyer S., Borzym K., Gardiner K.,
RA Nizetic D., Francis F., Lehrach H., Reinhardt R., Yaspo M.-L.;
RT "The DNA sequence of human chromosome 21.";
RL Nature 405:311-319(2000).
RN [5]
RP INDUCTION.
RX PubMed=21679696; DOI=10.1016/j.bbrc.2011.06.001;
RA Kage-Nakadai E., Uehara T., Mitani S.;
RT "H+/myo-inositol transporter genes, hmit-1.1 and hmit-1.2, have roles in
RT the osmoprotective response in Caenorhabditis elegans.";
RL Biochem. Biophys. Res. Commun. 410:471-477(2011).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-594 AND SER-632, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
CC -!- FUNCTION: Prevents intracellular accumulation of high concentrations of
CC myo-inositol (an osmolyte) that result in impairment of cellular
CC function.
CC -!- SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein.
CC -!- INDUCTION: Induced by hyperosmotic stress.
CC {ECO:0000269|PubMed:21679696}.
CC -!- SIMILARITY: Belongs to the sodium:solute symporter (SSF) (TC 2.A.21)
CC family. {ECO:0000305}.
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DR EMBL; L38500; AAC41747.2; -; Genomic_DNA.
DR EMBL; AF027153; AAC39548.1; -; Genomic_DNA.
DR EMBL; AP001719; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS33549.1; -.
DR PIR; A56851; A56851.
DR AlphaFoldDB; P53794; -.
DR IntAct; P53794; 12.
DR MINT; P53794; -.
DR STRING; 9606.ENSP00000370543; -.
DR DrugBank; DB13178; Inositol.
DR TCDB; 2.A.21.3.14; the solute:sodium symporter (sss) family.
DR GlyGen; P53794; 1 site.
DR iPTMnet; P53794; -.
DR PhosphoSitePlus; P53794; -.
DR BioMuta; SLC5A3; -.
DR DMDM; 3334498; -.
DR EPD; P53794; -.
DR jPOST; P53794; -.
DR MassIVE; P53794; -.
DR MaxQB; P53794; -.
DR PaxDb; P53794; -.
DR PeptideAtlas; P53794; -.
DR PRIDE; P53794; -.
DR ProteomicsDB; 56620; -.
DR Antibodypedia; 8029; 209 antibodies from 28 providers.
DR DNASU; 6526; -.
DR Ensembl; ENST00000381151.5; ENSP00000370543.3; ENSG00000198743.7.
DR UCSC; uc002yto.4; human.
DR GeneCards; SLC5A3; -.
DR HGNC; HGNC:11038; SLC5A3.
DR HPA; ENSG00000198743; Tissue enhanced (brain, choroid plexus).
DR MIM; 600444; gene.
DR neXtProt; NX_P53794; -.
DR PharmGKB; PA35903; -.
DR VEuPathDB; HostDB:ENSG00000198743; -.
DR eggNOG; KOG2349; Eukaryota.
DR HOGENOM; CLU_018808_9_2_1; -.
DR InParanoid; P53794; -.
DR OrthoDB; 243316at2759; -.
DR PhylomeDB; P53794; -.
DR TreeFam; TF352855; -.
DR PathwayCommons; P53794; -.
DR Reactome; R-HSA-429593; Inositol transporters.
DR SignaLink; P53794; -.
DR Pharos; P53794; Tbio.
DR PRO; PR:P53794; -.
DR Proteomes; UP000005640; Chromosome 21.
DR RNAct; P53794; protein.
DR Bgee; ENSG00000198743; Expressed in renal medulla and 208 other tissues.
DR Genevisible; P53794; HS.
DR GO; GO:0016021; C:integral component of membrane; IBA:GO_Central.
DR GO; GO:0005887; C:integral component of plasma membrane; TAS:ProtInc.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:ARUK-UCL.
DR GO; GO:0005886; C:plasma membrane; IDA:ARUK-UCL.
DR GO; GO:0008076; C:voltage-gated potassium channel complex; IEA:Ensembl.
DR GO; GO:0015150; F:fucose transmembrane transporter activity; ISS:ARUK-UCL.
DR GO; GO:0005412; F:glucose:sodium symporter activity; ISS:ARUK-UCL.
DR GO; GO:0005365; F:myo-inositol transmembrane transporter activity; ISS:ARUK-UCL.
DR GO; GO:0005367; F:myo-inositol:sodium symporter activity; ISS:ARUK-UCL.
DR GO; GO:0015146; F:pentose transmembrane transporter activity; ISS:ARUK-UCL.
DR GO; GO:0015166; F:polyol transmembrane transporter activity; ISS:ARUK-UCL.
DR GO; GO:0015459; F:potassium channel regulator activity; IDA:ARUK-UCL.
DR GO; GO:0044325; F:transmembrane transporter binding; IPI:ARUK-UCL.
DR GO; GO:0015756; P:fucose transmembrane transport; ISS:ARUK-UCL.
DR GO; GO:1904659; P:glucose transmembrane transport; ISS:ARUK-UCL.
DR GO; GO:0006020; P:inositol metabolic process; IBA:GO_Central.
DR GO; GO:1904679; P:myo-inositol import across plasma membrane; ISS:ARUK-UCL.
DR GO; GO:0015798; P:myo-inositol transport; ISS:ARUK-UCL.
DR GO; GO:0015750; P:pentose transmembrane transport; ISS:ARUK-UCL.
DR GO; GO:0007422; P:peripheral nervous system development; IEA:Ensembl.
DR GO; GO:0015791; P:polyol transmembrane transport; ISS:ARUK-UCL.
DR GO; GO:0043085; P:positive regulation of catalytic activity; ISS:ARUK-UCL.
DR GO; GO:1905477; P:positive regulation of protein localization to membrane; ISS:ARUK-UCL.
DR GO; GO:1903428; P:positive regulation of reactive oxygen species biosynthetic process; ISS:ARUK-UCL.
DR GO; GO:0043576; P:regulation of respiratory gaseous exchange; IEA:Ensembl.
DR GO; GO:0032409; P:regulation of transporter activity; IEA:Ensembl.
DR GO; GO:0150104; P:transport across blood-brain barrier; NAS:ARUK-UCL.
DR CDD; cd11491; SLC5sbd_SMIT; 1.
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 InterPro; IPR042731; SMIT.
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 Glycoprotein; Ion transport; Membrane; Phosphoprotein; Reference proteome;
KW Sodium; Sodium transport; Symport; Transmembrane; Transmembrane helix;
KW Transport.
FT CHAIN 1..718
FT /note="Sodium/myo-inositol cotransporter"
FT /id="PRO_0000105381"
FT TOPO_DOM 1..9
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 10..29
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 30..38
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 39..57
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 58..86
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 87..110
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 111..123
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 124..144
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 145..157
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 158..183
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 184..186
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 187..205
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 206..303
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 304..324
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 325..353
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 354..376
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 377..406
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 407..430
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 431..443
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 444..462
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 463..510
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 511..532
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 533..695
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 696..716
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 717..718
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT SITE 24
FT /note="Implicated in sodium coupling"
FT /evidence="ECO:0000250"
FT SITE 285
FT /note="Implicated in sodium coupling"
FT /evidence="ECO:0000250"
FT MOD_RES 594
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 632
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT CARBOHYD 232
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VARIANT 50
FT /note="A -> T (in dbSNP:rs8129891)"
FT /evidence="ECO:0000269|PubMed:7789985,
FT ECO:0000269|PubMed:9441750"
FT /id="VAR_061875"
FT VARIANT 566
FT /note="Q -> K (in dbSNP:rs4817617)"
FT /evidence="ECO:0000269|PubMed:7789985"
FT /id="VAR_061876"
FT CONFLICT 31
FT /note="S -> C (in Ref. 1; AAC41747)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 718 AA; 79664 MW; 1CC015C061F57C1A CRC64;
MRAVLDTADI AIVALYFILV MCIGFFAMWK SNRSTVSGYF LAGRSMTWVA IGASLFVSNI
GSEHFIGLAG SGAASGFAVG AWEFNALLLL QLLGWVFIPI YIRSGVYTMP EYLSKRFGGH
RIQVYFAALS LILYIFTKLS VDLYSGALFI QESLGWNLYV SVILLIGMTA LLTVTGGLVA
VIYTDTLQAL LMIIGALTLM IISIMEIGGF EEVKRRYMLA SPDVTSILLT YNLSNTNSCN
VSPKKEALKM LRNPTDEDVP WPGFILGQTP ASVWYWCADQ VIVQRVLAAK NIAHAKGSTL
MAGFLKLLPM FIIVVPGMIS RILFTDDIAC INPEHCMLVC GSRAGCSNIA YPRLVMKLVP
VGLRGLMMAV MIAALMSDLD SIFNSASTIF TLDVYKLIRK SASSRELMIV GRIFVAFMVV
ISIAWVPIIV EMQGGQMYLY IQEVADYLTP PVAALFLLAI FWKRCNEQGA FYGGMAGFVL
GAVRLILAFA YRAPECDQPD NRPGFIKDIH YMYVATGLFW VTGLITVIVS LLTPPPTKEQ
IRTTTFWSKK NLVVKENCSP KEEPYQMQEK SILRCSENNE TINHIIPNGK SEDSIKGLQP
EDVNLLVTCR EEGNPVASLG HSEAETPVDA YSNGQAALMG EKERKKETDD GGRYWKFIDW
FCGFKSKSLS KRSLRDLMEE EAVCLQMLEE TRQVKVILNI GLFAVCSLGI FMFVYFSL
