ID   SC5A5_MOUSE             Reviewed;         618 AA.
AC   Q99PN0; B2RPX6;
DT   15-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT   01-JUN-2001, sequence version 1.
DT   27-MAR-2024, entry version 122.
DE   RecName: Full=Sodium/iodide cotransporter;
DE            Short=Na(+)/I(-) cotransporter;
DE   AltName: Full=Sodium-iodide symporter;
DE            Short=Na(+)/I(-) symporter;
DE   AltName: Full=Solute carrier family 5 member 5;
GN   Name=Slc5a5; Synonyms=Nis;
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=C57BL/6 X DBA/2;
RA   Perron B., Rodriguez A.-M., Leblanc G., Pourcher T.;
RT   "Cloning of the mouse sodium iodide symporter (mNIS) and its expression in
RT   the mammary gland.";
RL   Submitted (FEB-2000) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND TRANSPORTER ACTIVITY.
RC   STRAIN=BALB/cJ;
RX   PubMed=11716040; DOI=10.1089/105072501753210993;
RA   Pinke L.A., Dean D.S., Bergert E.R., Spitzweg C., Dutton C.M., Morris J.C.;
RT   "Cloning of the mouse sodium iodide symporter.";
RL   Thyroid 11:935-939(2001).
RN   [3]
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   [4]
RP   FUNCTION, TRANSPORTER ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, SUBCELLULAR
RP   LOCATION, SUBUNIT, AND GLYCOSYLATION.
RX   PubMed=18372236; DOI=10.1677/joe-07-0455;
RA   Dayem M., Basquin C., Navarro V., Carrier P., Marsault R., Chang P.,
RA   Huc S., Darrouzet E., Lindenthal S., Pourcher T.;
RT   "Comparison of expressed human and mouse sodium/iodide symporters reveals
RT   differences in transport properties and subcellular localization.";
RL   J. Endocrinol. 197:95-109(2008).
RN   [5]
RP   FUNCTION, TRANSPORTER ACTIVITY, AND ACTIVITY REGULATION.
RX   PubMed=32084174; DOI=10.1371/journal.pone.0229085;
RA   Concilio S.C., Zhekova H.R., Noskov S.Y., Russell S.J.;
RT   "Inter-species variation in monovalent anion substrate selectivity and
RT   inhibitor sensitivity in the sodium iodide symporter (NIS).";
RL   PLoS ONE 15:e0229085-e0229085(2020).
CC   -!- FUNCTION: Sodium:iodide symporter that mediates the transport of iodide
CC       into the thyroid gland (PubMed:11716040, PubMed:18372236,
CC       PubMed:32084174). Can also mediate the transport of chlorate,
CC       thiocynate, nitrate and selenocynate (By similarity).
CC       {ECO:0000250|UniProtKB:Q92911, ECO:0000269|PubMed:11716040,
CC       ECO:0000269|PubMed:18372236, ECO:0000269|PubMed:32084174}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=iodide(out) + 2 Na(+)(out) = iodide(in) + 2 Na(+)(in);
CC         Xref=Rhea:RHEA:71207, ChEBI:CHEBI:16382, ChEBI:CHEBI:29101;
CC         Evidence={ECO:0000269|PubMed:11716040, ECO:0000269|PubMed:18372236,
CC         ECO:0000269|PubMed:32084174};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=chlorate(out) + 2 Na(+)(out) = chlorate(in) + 2 Na(+)(in);
CC         Xref=Rhea:RHEA:71211, ChEBI:CHEBI:29101, ChEBI:CHEBI:49709;
CC         Evidence={ECO:0000250|UniProtKB:Q92911};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=2 Na(+)(out) + thiocyanate(out) = 2 Na(+)(in) +
CC         thiocyanate(in); Xref=Rhea:RHEA:71215, ChEBI:CHEBI:18022,
CC         ChEBI:CHEBI:29101; Evidence={ECO:0000250|UniProtKB:Q92911};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=2 Na(+)(out) + nitrate(out) = 2 Na(+)(in) + nitrate(in);
CC         Xref=Rhea:RHEA:71219, ChEBI:CHEBI:17632, ChEBI:CHEBI:29101;
CC         Evidence={ECO:0000250|UniProtKB:Q92911};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=2 Na(+)(out) + selenocyanate(out) = 2 Na(+)(in) +
CC         selenocyanate(in); Xref=Rhea:RHEA:71227, ChEBI:CHEBI:29101,
CC         ChEBI:CHEBI:29445; Evidence={ECO:0000250|UniProtKB:Q92911};
CC   -!- ACTIVITY REGULATION: Perchlorate inhibits iodide transport activity.
CC       {ECO:0000269|PubMed:32084174}.
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=26 uM for iodide {ECO:0000269|PubMed:18372236};
CC   -!- SUBUNIT: Homodimer; disulfide-linked (By similarity). Monomer
CC       (PubMed:18372236). Homooligomer (PubMed:18372236).
CC       {ECO:0000250|UniProtKB:Q92911, ECO:0000269|PubMed:18372236}.
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:18372236};
CC       Multi-pass membrane protein {ECO:0000255}. Cytoplasm
CC       {ECO:0000269|PubMed:18372236}.
CC   -!- PTM: Glycosylated. {ECO:0000269|PubMed:18372236}.
CC   -!- SIMILARITY: Belongs to the sodium:solute symporter (SSF) (TC 2.A.21)
CC       family. {ECO:0000305}.
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DR   EMBL; AF235001; AAK00232.1; -; mRNA.
DR   EMBL; AF380353; AAK59274.1; -; mRNA.
DR   EMBL; BC137650; AAI37651.1; -; mRNA.
DR   EMBL; BC137651; AAI37652.1; -; mRNA.
DR   CCDS; CCDS22385.1; -.
DR   AlphaFoldDB; Q99PN0; -.
DR   SMR; Q99PN0; -.
DR   STRING; 10090.ENSMUSP00000000809; -.
DR   GlyCosmos; Q99PN0; 2 sites, No reported glycans.
DR   GlyGen; Q99PN0; 2 sites.
DR   PhosphoSitePlus; Q99PN0; -.
DR   PaxDb; 10090-ENSMUSP00000000809; -.
DR   ProteomicsDB; 256605; -.
DR   AGR; MGI:2149330; -.
DR   MGI; MGI:2149330; Slc5a5.
DR   eggNOG; KOG2349; Eukaryota.
DR   InParanoid; Q99PN0; -.
DR   PhylomeDB; Q99PN0; -.
DR   Reactome; R-MMU-209968; Thyroxine biosynthesis.
DR   Reactome; R-MMU-428643; Organic anion transporters.
DR   PRO; PR:Q99PN0; -.
DR   Proteomes; UP000000589; Unplaced.
DR   RNAct; Q99PN0; Protein.
DR   GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR   GO; GO:0005634; C:nucleus; ISO:MGI.
DR   GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR   GO; GO:0015111; F:iodide transmembrane transporter activity; ISO:MGI.
DR   GO; GO:0015373; F:monoatomic anion:sodium symporter activity; ISO:MGI.
DR   GO; GO:0042803; F:protein homodimerization activity; ISO:MGI.
DR   GO; GO:0008507; F:sodium:iodide symporter activity; IDA:UniProtKB.
DR   GO; GO:0015293; F:symporter activity; IDA:MGI.
DR   GO; GO:1904322; P:cellular response to forskolin; ISO:MGI.
DR   GO; GO:1904401; P:cellular response to Thyroid stimulating hormone; ISO:MGI.
DR   GO; GO:1904200; P:iodide transmembrane transport; ISO:MGI.
DR   GO; GO:0015705; P:iodide transport; ISO:MGI.
DR   GO; GO:0006814; P:sodium ion transport; ISO:MGI.
DR   GO; GO:0006590; P:thyroid hormone generation; IEA:InterPro.
DR   CDD; cd11503; SLC5sbd_NIS; 1.
DR   Gene3D; 1.20.1730.10; Sodium/glucose cotransporter; 1.
DR   InterPro; IPR038377; Na/Glc_symporter_sf.
DR   InterPro; IPR001734; Na/solute_symporter.
DR   InterPro; IPR018212; Na/solute_symporter_CS.
DR   InterPro; IPR035689; SLC5A5.
DR   NCBIfam; TIGR00813; sss; 1.
DR   PANTHER; PTHR42985; SODIUM-COUPLED MONOCARBOXYLATE TRANSPORTER; 1.
DR   PANTHER; PTHR42985:SF11; SODIUM_IODIDE COTRANSPORTER; 1.
DR   Pfam; PF00474; SSF; 1.
DR   PROSITE; PS00456; NA_SOLUT_SYMP_1; 1.
DR   PROSITE; PS50283; NA_SOLUT_SYMP_3; 1.
PE   1: Evidence at protein level;
KW   Cell membrane; Cytoplasm; Disulfide bond; Glycoprotein; Ion transport;
KW   Membrane; Phosphoprotein; Reference proteome; Sodium; Sodium transport;
KW   Symport; Transmembrane; Transmembrane helix; Transport.
FT   CHAIN           1..618
FT                   /note="Sodium/iodide cotransporter"
FT                   /id="PRO_0000105384"
FT   TOPO_DOM        1..16
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        17..37
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        38..53
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        54..74
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        75..88
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        89..109
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        110..136
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        137..157
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        158..163
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        164..184
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        185..186
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        187..207
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        208..241
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        242..262
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        263..286
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        287..307
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        308..326
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        327..347
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        348..391
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        392..412
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        413..416
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        417..437
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        438..444
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        445..465
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        466..520
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        521..541
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        542..618
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   REGION          571..618
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   SITE            242
FT                   /note="Required for homodimerization"
FT                   /evidence="ECO:0000250|UniProtKB:Q92911"
FT   SITE            243
FT                   /note="Required for homodimerization"
FT                   /evidence="ECO:0000250|UniProtKB:Q92911"
FT   SITE            471
FT                   /note="Required for homodimerization"
FT                   /evidence="ECO:0000250|UniProtKB:Q92911"
FT   MOD_RES         551
FT                   /note="Phosphoserine; by PKA"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        485
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        497
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
SQ   SEQUENCE   618 AA;  65568 MW;  448AC5FE9AB5118E CRC64;
     MEGAEAGARA TFGPWDYGVF ATMLLVSTGI GLWVGLARGG QRSADDFFTG GRQLAAVPVG
     LSLAASFMSA VQVLGVPAEA ARYGLKFLWM CVGQLLNSLL TALLFLPIFY RLGLTSTYQY
     LELRFSRAVR LCGTLQYLVA TMLYTGIVIY APALILNQVT GLDIWASLLS TGIICTLYTT
     VGGMKAVVWT DVFQVVVMLV GFWVILARGV MLMGGPWNVL SLAQNHSRIN LMDFDPDPRS
     RYTFWTFVVG GSLVWLSMYG VNQAQVQRYV ACHTERKAKL ALLVNQLGLF LIVASAACCG
     IVMFVYYKDC DPLLTGRIAA PDQYMPLLVL DIFEDLPGVP GLFLACAYSG TLSTASTSIN
     AMAAVTVEDL IKPRMPSLAP RKLVFISKGL SFIYGSTCLT VAALSSLLGG GVLQGSFTVM
     GVISGPLLGA FTLGMLLPAC NTPGVLSGLT AGLAVSLWVA VGATLYPPGE QTMGVLPTSA
     AGCTNASVLP SPPGAANTSR GIPSSGMDSG RPAFADTFYA VSYLYYGALG TLTTMLCGAL
     ISYLTGPTKR SSLGPGLLWW DLARQTASVA PKEDTTTLED SLVKGPEDIP AATKKPPGFR
     PEAETHPLYL GHDVETNL
//