SC5A5_HUMAN
ID SC5A5_HUMAN Reviewed; 643 AA.
AC Q92911; O43702; Q2M335; Q9NYB6;
DT 24-JAN-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1997, sequence version 1.
DT 03-AUG-2022, entry version 190.
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 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], AND TISSUE SPECIFICITY.
RC TISSUE=Thyroid;
RX PubMed=8806637; DOI=10.1006/bbrc.1996.1358;
RA Smanik P.A., Liu Q., Furminger T.L., Ryu K., Xing S., Mazzaferri E.L.,
RA Jhiang S.M.;
RT "Cloning of the human sodium iodide symporter.";
RL Biochem. Biophys. Res. Commun. 226:339-345(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], INDUCTION, TISSUE SPECIFICITY, AND VARIANTS
RP PRO-102; GLN-536 AND GLN-556.
RC TISSUE=Thyroid;
RX PubMed=9329364; DOI=10.1210/jcem.82.10.4269;
RA Saito T., Endo T., Kawaguchi A., Ikeda M., Nakazato M., Kogai T., Onaya T.;
RT "Increased expression of the Na+/I- symporter in cultured human thyroid
RT cells exposed to thyrotropin and in Graves' thyroid tissue.";
RL J. Clin. Endocrinol. Metab. 82:3331-3336(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [4]
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 [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 528-643.
RA Pauws E., Tol N.J., de Vijlder J.J.M., Ris-Stalpers C.;
RT "Characterization of 3'UTR region of the human NIS cDNA.";
RL Submitted (APR-2000) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP VARIANT TDH1 PRO-354.
RX PubMed=9171822; DOI=10.1038/ng0697-124;
RA Fujiwara H., Tatsumi K., Miki K., Harada T., Miyai K., Takai S., Amino N.;
RT "Congenital hypothyroidism caused by a mutation in the Na(+)/I(-)
RT symporter.";
RL Nat. Genet. 16:124-125(1997).
RN [7]
RP VARIANTS TDH1 ARG-93; PRO-354 AND GLU-543.
RX PubMed=9745458; DOI=10.1210/jcem.83.9.5245;
RA Kosugi S., Inoue S., Matsuda A., Jhiang S.M.;
RT "Novel, missense and loss-of-function mutations in the sodium/iodide
RT symporter gene causing iodide transport defect in three Japanese
RT patients.";
RL J. Clin. Endocrinol. Metab. 83:3373-3376(1998).
RN [8]
RP VARIANT TDH1 GLU-267.
RX PubMed=9486973; DOI=10.1172/jci1504;
RA Pohlenz J., Rosenthal I.M., Weiss R.E., Jhiang S.M., Burant C.,
RA Refetoff S.;
RT "Congenital hypothyroidism due to mutations in the sodium/iodide symporter:
RT identification of a nonsense mutation producing a downstream cryptic 3'
RT splice site.";
RL J. Clin. Invest. 101:1028-1035(1998).
RN [9]
RP VARIANT TDH1 ARG-395.
RX PubMed=10487695; DOI=10.1210/jcem.84.9.5971;
RA Kosugi S., Bhayana S., Dean H.J.;
RT "A novel mutation in the sodium/iodide symporter gene in the largest family
RT with iodide transport defect.";
RL J. Clin. Endocrinol. Metab. 84:3248-3253(1999).
CC -!- FUNCTION: Mediates iodide uptake in the thyroid gland.
CC -!- INTERACTION:
CC Q92911; A8MQ03: CYSRT1; NbExp=3; IntAct=EBI-12313867, EBI-3867333;
CC Q92911; P0DPK4: NOTCH2NLC; NbExp=3; IntAct=EBI-12313867, EBI-22310682;
CC -!- SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein.
CC -!- TISSUE SPECIFICITY: Expression is primarily in thyroid tissue, but also
CC to a lower extent in mammary gland and ovary. Expression is reduced in
CC tumors. {ECO:0000269|PubMed:8806637, ECO:0000269|PubMed:9329364}.
CC -!- DISEASE: Thyroid dyshormonogenesis 1 (TDH1) [MIM:274400]: A disorder
CC characterized by the inability of the thyroid to maintain a
CC concentration difference of readily exchangeable iodine between the
CC plasma and the thyroid gland, leading to congenital hypothyroidism.
CC {ECO:0000269|PubMed:10487695, ECO:0000269|PubMed:9171822,
CC ECO:0000269|PubMed:9486973, ECO:0000269|PubMed:9745458}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the sodium:solute symporter (SSF) (TC 2.A.21)
CC family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/SLC5A5ID44476ch19p13.html";
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DR EMBL; U66088; AAB17378.1; -; mRNA.
DR EMBL; AC005796; AAC62827.1; -; Genomic_DNA.
DR EMBL; D87920; BAA24835.1; -; mRNA.
DR EMBL; BC105047; AAI05048.1; -; mRNA.
DR EMBL; BC105049; AAI05050.1; -; mRNA.
DR EMBL; AF260700; AAF70339.1; -; mRNA.
DR CCDS; CCDS12368.1; -.
DR PIR; JC4974; JC4974.
DR RefSeq; NP_000444.1; NM_000453.2.
DR AlphaFoldDB; Q92911; -.
DR SMR; Q92911; -.
DR BioGRID; 112419; 157.
DR IntAct; Q92911; 11.
DR STRING; 9606.ENSP00000222248; -.
DR DrugBank; DB05382; Iodine.
DR DrugBank; DB09418; Potassium perchlorate.
DR TCDB; 2.A.21.5.1; the solute:sodium symporter (sss) family.
DR GlyGen; Q92911; 2 sites.
DR iPTMnet; Q92911; -.
DR PhosphoSitePlus; Q92911; -.
DR BioMuta; SLC5A5; -.
DR DMDM; 12643359; -.
DR MassIVE; Q92911; -.
DR PaxDb; Q92911; -.
DR PeptideAtlas; Q92911; -.
DR PRIDE; Q92911; -.
DR ProteomicsDB; 75594; -.
DR Antibodypedia; 14944; 574 antibodies from 31 providers.
DR DNASU; 6528; -.
DR Ensembl; ENST00000222248.4; ENSP00000222248.2; ENSG00000105641.4.
DR GeneID; 6528; -.
DR KEGG; hsa:6528; -.
DR MANE-Select; ENST00000222248.4; ENSP00000222248.2; NM_000453.3; NP_000444.1.
DR UCSC; uc002nhr.4; human.
DR CTD; 6528; -.
DR DisGeNET; 6528; -.
DR GeneCards; SLC5A5; -.
DR HGNC; HGNC:11040; SLC5A5.
DR HPA; ENSG00000105641; Group enriched (choroid plexus, salivary gland, stomach).
DR MalaCards; SLC5A5; -.
DR MIM; 274400; phenotype.
DR MIM; 601843; gene.
DR neXtProt; NX_Q92911; -.
DR OpenTargets; ENSG00000105641; -.
DR Orphanet; 95716; Familial thyroid dyshormonogenesis.
DR PharmGKB; PA35905; -.
DR VEuPathDB; HostDB:ENSG00000105641; -.
DR eggNOG; KOG2349; Eukaryota.
DR GeneTree; ENSGT00940000159489; -.
DR HOGENOM; CLU_018808_11_1_1; -.
DR InParanoid; Q92911; -.
DR OMA; FWFTIVL; -.
DR OrthoDB; 1180002at2759; -.
DR PhylomeDB; Q92911; -.
DR TreeFam; TF316728; -.
DR PathwayCommons; Q92911; -.
DR Reactome; R-HSA-209968; Thyroxine biosynthesis.
DR Reactome; R-HSA-428643; Organic anion transporters.
DR Reactome; R-HSA-5619096; Defective SLC5A5 causes thyroid dyshormonogenesis 1 (TDH1).
DR SignaLink; Q92911; -.
DR SIGNOR; Q92911; -.
DR BioGRID-ORCS; 6528; 11 hits in 1074 CRISPR screens.
DR ChiTaRS; SLC5A5; human.
DR GeneWiki; Sodium-iodide_symporter; -.
DR GenomeRNAi; 6528; -.
DR Pharos; Q92911; Tbio.
DR PRO; PR:Q92911; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; Q92911; protein.
DR Bgee; ENSG00000105641; Expressed in mucosa of stomach and 84 other tissues.
DR Genevisible; Q92911; HS.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:1903561; C:extracellular vesicle; HDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; TAS:ProtInc.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:ARUK-UCL.
DR GO; GO:0015111; F:iodide transmembrane transporter activity; IDA:ARUK-UCL.
DR GO; GO:0008507; F:sodium:iodide symporter activity; IBA:GO_Central.
DR GO; GO:0015293; F:symporter activity; IBA:GO_Central.
DR GO; GO:0071320; P:cellular response to cAMP; IEP:UniProtKB.
DR GO; GO:0071371; P:cellular response to gonadotropin stimulus; IEP:UniProtKB.
DR GO; GO:1904200; P:iodide transmembrane transport; IDA:ARUK-UCL.
DR GO; GO:0015705; P:iodide transport; IMP:UniProtKB.
DR GO; GO:0006811; P:ion transport; TAS:Reactome.
DR GO; GO:0006814; P:sodium ion transport; IBA:GO_Central.
DR GO; GO:0006590; P:thyroid hormone generation; TAS:Reactome.
DR GO; GO:0150104; P:transport across blood-brain barrier; NAS:ARUK-UCL.
DR CDD; cd11503; SLC5sbd_NIS; 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; IPR035689; SLC5A5.
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 Congenital hypothyroidism; Disease variant; Glycoprotein; Ion transport;
KW Membrane; Phosphoprotein; Reference proteome; Sodium; Sodium transport;
KW Symport; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..643
FT /note="Sodium/iodide cotransporter"
FT /id="PRO_0000105383"
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..525
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 526..546
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 547..643
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 623..643
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 556
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000255"
FT CARBOHYD 489
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 502
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VARIANT 93
FT /note="G -> R (in TDH1; dbSNP:rs121909178)"
FT /evidence="ECO:0000269|PubMed:9745458"
FT /id="VAR_010263"
FT VARIANT 102
FT /note="A -> P"
FT /evidence="ECO:0000269|PubMed:9329364"
FT /id="VAR_010264"
FT VARIANT 267
FT /note="Q -> E (in TDH1; dbSNP:rs121909176)"
FT /evidence="ECO:0000269|PubMed:9486973"
FT /id="VAR_010265"
FT VARIANT 298
FT /note="C -> G (in dbSNP:rs8108188)"
FT /id="VAR_052490"
FT VARIANT 354
FT /note="T -> P (in TDH1; dbSNP:rs121909174)"
FT /evidence="ECO:0000269|PubMed:9171822,
FT ECO:0000269|PubMed:9745458"
FT /id="VAR_010266"
FT VARIANT 395
FT /note="G -> R (in TDH1; dbSNP:rs121909180)"
FT /evidence="ECO:0000269|PubMed:10487695"
FT /id="VAR_010267"
FT VARIANT 536
FT /note="T -> Q (requires 2 nucleotide substitutions)"
FT /evidence="ECO:0000269|PubMed:9329364"
FT /id="VAR_010268"
FT VARIANT 543
FT /note="G -> E (in TDH1; dbSNP:rs121909179)"
FT /evidence="ECO:0000269|PubMed:9745458"
FT /id="VAR_010269"
FT VARIANT 556
FT /note="S -> Q (requires 2 nucleotide substitutions)"
FT /evidence="ECO:0000269|PubMed:9329364"
FT /id="VAR_010270"
SQ SEQUENCE 643 AA; 68666 MW; 02D361A27B2FDA43 CRC64;
MEAVETGERP TFGAWDYGVF ALMLLVSTGI GLWVGLARGG QRSAEDFFTG GRRLAALPVG
LSLSASFMSA VQVLGVPSEA YRYGLKFLWM CLGQLLNSVL TALLFMPVFY RLGLTSTYEY
LEMRFSRAVR LCGTLQYIVA TMLYTGIVIY APALILNQVT GLDIWASLLS TGIICTFYTA
VGGMKAVVWT DVFQVVVMLS GFWVVLARGV MLVGGPRQVL TLAQNHSRIN LMDFNPDPRS
RYTFWTFVVG GTLVWLSMYG VNQAQVQRYV ACRTEKQAKL ALLINQVGLF LIVSSAACCG
IVMFVFYTDC DPLLLGRISA PDQYMPLLVL DIFEDLPGVP GLFLACAYSG TLSTASTSIN
AMAAVTVEDL IKPRLRSLAP RKLVIISKGL SLIYGSACLT VAALSSLLGG GVLQGSFTVM
GVISGPLLGA FILGMFLPAC NTPGVLAGLG AGLALSLWVA LGATLYPPSE QTMRVLPSSA
ARCVALSVNA SGLLDPALLP ANDSSRAPSS GMDASRPALA DSFYAISYLY YGALGTLTTV
LCGALISCLT GPTKRSTLAP GLLWWDLARQ TASVAPKEEV AILDDNLVKG PEELPTGNKK
PPGFLPTNED RLFFLGQKEL EGAGSWTPCV GHDGGRDQQE TNL
