SC5AB_RABIT
ID SC5AB_RABIT Reviewed; 674 AA.
AC Q28728; Q863B5;
DT 29-APR-2008, integrated into UniProtKB/Swiss-Prot.
DT 29-APR-2008, sequence version 2.
DT 03-AUG-2022, entry version 110.
DE RecName: Full=Sodium/myo-inositol cotransporter 2;
DE Short=Na(+)/myo-inositol cotransporter 2;
DE AltName: Full=Sodium-dependent glucose cotransporter;
DE AltName: Full=Sodium/glucose cotransporter KST1;
DE Short=rKST1;
DE AltName: Full=Sodium/myo-inositol transporter 2;
DE Short=SMIT2;
DE AltName: Full=Solute carrier family 5 member 11;
GN Name=SLC5A11 {ECO:0000250|UniProtKB:Q8WWX8};
GN Synonyms=KST1, SMIT2 {ECO:0000303|PubMed:15181167};
OS Oryctolagus cuniculus (Rabbit).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae; Oryctolagus.
OX NCBI_TaxID=9986;
RN [1] {ECO:0000305, ECO:0000312|EMBL:BAA03753.1}
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC TISSUE=Kidney {ECO:0000312|EMBL:BAA03753.1};
RX PubMed=8142451; DOI=10.1016/0005-2736(94)90110-4;
RA Hitomi K., Tsukagoshi N.;
RT "cDNA sequence for rkST1, a novel member of the sodium ion-dependent
RT glucose cotransporter family.";
RL Biochim. Biophys. Acta 1190:469-472(1994).
RN [2] {ECO:0000305, ECO:0000312|EMBL:AAP30856.1}
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES,
RP SUBCELLULAR LOCATION, AND INHIBITION.
RC TISSUE=Kidney cortex {ECO:0000312|EMBL:AAP30856.1};
RX PubMed=12133831; DOI=10.1074/jbc.m204321200;
RA Coady M.J., Wallendorff B., Gagnon D.G., Lapointe J.-Y.;
RT "Identification of a novel Na+/myo-inositol cotransporter.";
RL J. Biol. Chem. 277:35219-35224(2002).
RN [3] {ECO:0000305}
RP FUNCTION, ACTIVITY REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, SUBCELLULAR
RP LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=15181167; DOI=10.1113/jphysiol.2004.064311;
RA Bissonnette P., Coady M.J., Lapointe J.-Y.;
RT "Expression of the sodium-myo-inositol cotransporter SMIT2 at the apical
RT membrane of Madin-Darby canine kidney cells.";
RL J. Physiol. (Lond.) 558:759-768(2004).
RN [4] {ECO:0000305}
RP FUNCTION.
RX PubMed=15613375; DOI=10.1113/jphysiol.2004.076679;
RA Bourgeois F., Coady M.J., Lapointe J.-Y.;
RT "Determination of transport stoichiometry for two cation-coupled myo-
RT inositol cotransporters: SMIT2 and HMIT.";
RL J. Physiol. (Lond.) 563:333-343(2005).
RN [5] {ECO:0000305}
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=17932225; DOI=10.1152/ajpgi.00422.2007;
RA Aouameur R., Da Cal S., Bissonnette P., Coady M.J., Lapointe J.-Y.;
RT "SMIT2 mediates all myo-inositol uptake in apical membranes of rat small
RT intestine.";
RL Am. J. Physiol. 293:G1300-G1307(2007).
RN [6] {ECO:0000305}
RP FUNCTION, ACTIVITY REGULATION, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RX PubMed=17306760; DOI=10.1016/j.bbamem.2007.01.007;
RA Lahjouji K., Aouameur R., Bissonnette P., Coady M.J., Bichet D.G.,
RA Lapointe J.-Y.;
RT "Expression and functionality of the Na+/myo-inositol cotransporter SMIT2
RT in rabbit kidney.";
RL Biochim. Biophys. Acta 1768:1154-1159(2007).
CC -!- FUNCTION: Involved in the sodium-dependent cotransport of myo-inositol
CC (MI) with a Na(+):MI stoichiometry of 2:1. Exclusively responsible for
CC apical MI transport and absorption in intestine. Can also transport D-
CC chiro-inositol (DCI) but not L-fructose. Exhibits stereospecific
CC cotransport of both D-glucose and D-xylose. May induce apoptosis
CC through the TNF-alpha, PDCD1 pathway. May play a role in the regulation
CC of MI concentration in serum, involving reabsorption in at least the
CC proximal tubule of the kidney. {ECO:0000250|UniProtKB:Q8WWX8,
CC ECO:0000269|PubMed:12133831, ECO:0000269|PubMed:15181167,
CC ECO:0000269|PubMed:15613375, ECO:0000269|PubMed:17306760,
CC ECO:0000269|PubMed:17932225}.
CC -!- ACTIVITY REGULATION: MI transport activity stimulated five-fold under
CC 24 hour hypertonic shock conditions. MI inward currents were gradually
CC inhibited as increasing amounts of phlorizin were added to the
CC superfusion medium. When sodium is replaced by potassium, MI uptake is
CC dramatically reduced and in the presence of L-fucose or D-chiro-
CC inositol (DCI), the specific accumulation of tracer amounts of MI is
CC also reduced. {ECO:0000269|PubMed:15181167,
CC ECO:0000269|PubMed:17306760}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=120 uM for myoinositol (in Xenopus laevis oocytes)
CC {ECO:0000269|PubMed:12133831, ECO:0000269|PubMed:15181167};
CC KM=334 uM for myoinositol (in dog MDCK cells)
CC {ECO:0000269|PubMed:12133831, ECO:0000269|PubMed:15181167};
CC KM=130 uM for D-chiro-inositol {ECO:0000269|PubMed:12133831,
CC ECO:0000269|PubMed:15181167};
CC KM=30 mM for D-glucose {ECO:0000269|PubMed:12133831,
CC ECO:0000269|PubMed:15181167};
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000269|PubMed:12133831,
CC ECO:0000269|PubMed:15181167, ECO:0000269|PubMed:17306760}; Multi-pass
CC membrane protein {ECO:0000269|PubMed:12133831,
CC ECO:0000269|PubMed:15181167, ECO:0000269|PubMed:17306760}. Note=Located
CC on membrane of kidney brush border membrane vesicles (BBMVs) and apical
CC membrane of proximal convoluted tubules. {ECO:0000269|PubMed:12133831,
CC ECO:0000269|PubMed:15181167, ECO:0000269|PubMed:17306760}.
CC -!- TISSUE SPECIFICITY: Expressed in brain, lung and kidney. In the kidney,
CC strongly expressed in the cortex, at the luminal side of proximal
CC convoluted tubules and in BBMVs. Weaker expression observed in the
CC medulla (at protein level). {ECO:0000269|PubMed:15181167,
CC ECO:0000269|PubMed:17306760, ECO:0000269|PubMed:17932225,
CC ECO:0000269|PubMed:8142451}.
CC -!- SIMILARITY: Belongs to the sodium:solute symporter (SSF) (TC 2.A.21)
CC family. {ECO:0000255}.
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DR EMBL; D16226; BAA03753.1; -; mRNA.
DR EMBL; AF506029; AAP30856.1; -; mRNA.
DR RefSeq; NP_001075662.1; NM_001082193.2.
DR RefSeq; XP_008256041.1; XM_008257819.2.
DR RefSeq; XP_017197921.1; XM_017342432.1.
DR AlphaFoldDB; Q28728; -.
DR SMR; Q28728; -.
DR STRING; 9986.ENSOCUP00000005983; -.
DR PRIDE; Q28728; -.
DR GeneID; 100008981; -.
DR KEGG; ocu:100008981; -.
DR CTD; 115584; -.
DR eggNOG; KOG2349; Eukaryota.
DR HOGENOM; CLU_018808_9_2_1; -.
DR InParanoid; Q28728; -.
DR OMA; GWWGMRR; -.
DR OrthoDB; 243316at2759; -.
DR TreeFam; TF352855; -.
DR Proteomes; UP000001811; Unplaced.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0015293; F:symporter activity; IEA:UniProtKB-KW.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0008643; P:carbohydrate transport; IEA:UniProtKB-KW.
DR GO; GO:0032409; P:regulation of transporter activity; IEA:Ensembl.
DR GO; GO:0006814; P:sodium ion transport; IEA:UniProtKB-KW.
DR Gene3D; 1.20.1730.10; -; 1.
DR InterPro; IPR038377; Na/Glc_symporter_sf.
DR InterPro; IPR001734; Na/solute_symporter.
DR Pfam; PF00474; SSF; 1.
DR TIGRFAMs; TIGR00813; sss; 1.
DR PROSITE; PS50283; NA_SOLUT_SYMP_3; 1.
PE 1: Evidence at protein level;
KW Apoptosis; Ion transport; Membrane; Reference proteome; Sodium;
KW Sodium transport; Sugar transport; Symport; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1..674
FT /note="Sodium/myo-inositol cotransporter 2"
FT /id="PRO_0000331571"
FT TOPO_DOM 1..27
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 28..48
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 49..56
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 57..77
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 78..102
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 103..123
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 124..140
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 141..161
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 162..180
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 181..201
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 202..208
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 209..229
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 230..272
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 273..293
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 294..308
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 309..329
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 330..375
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 376..396
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 397..418
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 419..439
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 440..446
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 447..467
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 468..479
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 480..500
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 501..521
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 522..542
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 543..653
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 654..674
FT /note="Helical"
FT /evidence="ECO:0000255"
FT CONFLICT 164
FT /note="A -> T (in Ref. 1; BAA03753)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 674 AA; 73599 MW; 1827A7EC25C1F719 CRC64;
MESSTSSPQP PLSDPLDPFP QRSLEPGDIA VLVLYFLFVL AVGLWSTVKT KRDTVKGYFL
AGGDMVWWPV GASLFASNVG SGHFVGLAGS GAATGISVAA YEFNGMFSVL MLAWIFLPIY
IAGQVTTMPE YLRRRFGGSR IAITLAVLYL FIYIFTKISV DMYAGAIFIQ QSLHLDLYLS
VVGLLAVTAL YTVAGGLAAV IYTDALQTLI MLVGALTLMG YSFAAVGGME GLQEKYFLAL
PSNRSENSSC GLPREDAFHL FRDPLTSDLP WPGILFGMSI PSLWYWCTDQ VIVQRSLAAK
NLSHAKGGSL MAAYLKVLPL FIMVFPGMVS RILFPDQVAC ADPETCQRVC NNPSGCSDIA
YPKLVLELLP TGLRGLMMAV MVAALMSSLT SIFNSASTIF TMDLWNHVRP RASEKELMIV
GRVFVLLLVL VSVLWIPVVQ ASQGGQLFVY IQAISSYLQP PVAMVFVLGC FWKRANEKGA
FWGLVLGLLL GFIRLILDFI YVEPACHQPD ERPSVVKNVH YLYFSMILSS VTVLTVTVMS
LLTEPPSKEM ISHLTWFTRR DPVVQKAQVP AATPLPPALS HNGTAEANSA SIQLETIQEG
ASKAHSSDVT PKQSRVVRAL LWLCGMEGKS TEQAPRPAEP VLASIEENPV VKTLLDVNCL
LCICCAFFLW GYFA
