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Q92911 (SC5A5_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 134. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Sodium/iodide cotransporter

Short name=Na(+)/I(-) cotransporter
Alternative name(s):
Sodium-iodide symporter
Short name=Na(+)/I(-) symporter
Solute carrier family 5 member 5
Gene names
Name:SLC5A5
Synonyms:NIS
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length643 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Mediates iodide uptake in the thyroid gland.

Subcellular location

Membrane; Multi-pass membrane protein.

Tissue specificity

Expression is primarily in thyroid tissue, but also to a lower extent in mammary gland and ovary. Expression is reduced in tumors. Ref.1 Ref.2

Involvement in disease

Thyroid dyshormonogenesis 1 (TDH1) [MIM:274400]: A disorder characterized by the inability of the thyroid to maintain a concentration difference of readily exchangeable iodine between the plasma and the thyroid gland, leading to congenital hypothyroidism.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.6 Ref.7 Ref.8 Ref.9

Sequence similarities

Belongs to the sodium:solute symporter (SSF) (TC 2.A.21) family. [View classification]

Ontologies

Keywords
   Biological processIon transport
Sodium transport
Symport
Transport
   Cellular componentMembrane
   Coding sequence diversityPolymorphism
   DiseaseCongenital hypothyroidism
Disease mutation
   DomainTransmembrane
Transmembrane helix
   LigandSodium
   PTMGlycoprotein
Phosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcellular nitrogen compound metabolic process

Traceable author statement. Source: Reactome

cellular response to cAMP

Inferred from expression pattern PubMed 12021185. Source: UniProtKB

cellular response to gonadotropin stimulus

Inferred from expression pattern PubMed 12021185. Source: UniProtKB

iodide transport

Inferred from mutant phenotype PubMed 12021185. Source: UniProtKB

ion transport

Traceable author statement. Source: Reactome

small molecule metabolic process

Traceable author statement. Source: Reactome

thyroid hormone generation

Traceable author statement. Source: Reactome

transmembrane transport

Traceable author statement. Source: Reactome

transport

Traceable author statement Ref.1. Source: ProtInc

   Cellular_componentextracellular vesicular exosome

Inferred from direct assay PubMed 19199708. Source: UniProt

integral component of membrane

Traceable author statement PubMed 9388506. Source: ProtInc

nucleus

Inferred from direct assay PubMed 15961562. Source: UniProtKB

plasma membrane

Traceable author statement. Source: Reactome

   Molecular_functioniodide transmembrane transporter activity

Inferred from mutant phenotype PubMed 12021185. Source: UniProtKB

sodium:iodide symporter activity

Inferred from electronic annotation. Source: Ensembl

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 643643Sodium/iodide cotransporter
PRO_0000105383

Regions

Topological domain1 – 1616Extracellular Potential
Transmembrane17 – 3721Helical; Potential
Topological domain38 – 5316Cytoplasmic Potential
Transmembrane54 – 7421Helical; Potential
Topological domain75 – 8814Extracellular Potential
Transmembrane89 – 10921Helical; Potential
Topological domain110 – 13627Cytoplasmic Potential
Transmembrane137 – 15721Helical; Potential
Topological domain158 – 1636Extracellular Potential
Transmembrane164 – 18421Helical; Potential
Topological domain185 – 1862Cytoplasmic Potential
Transmembrane187 – 20721Helical; Potential
Topological domain208 – 24134Extracellular Potential
Transmembrane242 – 26221Helical; Potential
Topological domain263 – 28624Cytoplasmic Potential
Transmembrane287 – 30721Helical; Potential
Topological domain308 – 32619Extracellular Potential
Transmembrane327 – 34721Helical; Potential
Topological domain348 – 39144Cytoplasmic Potential
Transmembrane392 – 41221Helical; Potential
Topological domain413 – 4164Extracellular Potential
Transmembrane417 – 43721Helical; Potential
Topological domain438 – 4447Cytoplasmic Potential
Transmembrane445 – 46521Helical; Potential
Topological domain466 – 52560Extracellular Potential
Transmembrane526 – 54621Helical; Potential
Topological domain547 – 64397Cytoplasmic Potential

Amino acid modifications

Modified residue5561Phosphoserine; by PKA Potential
Glycosylation4891N-linked (GlcNAc...) Potential
Glycosylation5021N-linked (GlcNAc...) Potential

Natural variations

Natural variant931G → R in TDH1. Ref.7
VAR_010263
Natural variant1021A → P. Ref.2
VAR_010264
Natural variant2671Q → E in TDH1. Ref.8
VAR_010265
Natural variant2981C → G.
Corresponds to variant rs8108188 [ dbSNP | Ensembl ].
VAR_052490
Natural variant3541T → P in TDH1. Ref.6 Ref.7
VAR_010266
Natural variant3951G → R in TDH1. Ref.9
VAR_010267
Natural variant5361T → Q Requires 2 nucleotide substitutions. Ref.2
VAR_010268
Natural variant5431G → E in TDH1. Ref.7
VAR_010269
Natural variant5561S → Q Requires 2 nucleotide substitutions. Ref.2
VAR_010270

Sequences

Sequence LengthMass (Da)Tools
Q92911 [UniParc].

Last modified February 1, 1997. Version 1.
Checksum: 02D361A27B2FDA43

FASTA64368,666
        10         20         30         40         50         60 
MEAVETGERP TFGAWDYGVF ALMLLVSTGI GLWVGLARGG QRSAEDFFTG GRRLAALPVG 

        70         80         90        100        110        120 
LSLSASFMSA VQVLGVPSEA YRYGLKFLWM CLGQLLNSVL TALLFMPVFY RLGLTSTYEY 

       130        140        150        160        170        180 
LEMRFSRAVR LCGTLQYIVA TMLYTGIVIY APALILNQVT GLDIWASLLS TGIICTFYTA 

       190        200        210        220        230        240 
VGGMKAVVWT DVFQVVVMLS GFWVVLARGV MLVGGPRQVL TLAQNHSRIN LMDFNPDPRS 

       250        260        270        280        290        300 
RYTFWTFVVG GTLVWLSMYG VNQAQVQRYV ACRTEKQAKL ALLINQVGLF LIVSSAACCG 

       310        320        330        340        350        360 
IVMFVFYTDC DPLLLGRISA PDQYMPLLVL DIFEDLPGVP GLFLACAYSG TLSTASTSIN 

       370        380        390        400        410        420 
AMAAVTVEDL IKPRLRSLAP RKLVIISKGL SLIYGSACLT VAALSSLLGG GVLQGSFTVM 

       430        440        450        460        470        480 
GVISGPLLGA FILGMFLPAC NTPGVLAGLG AGLALSLWVA LGATLYPPSE QTMRVLPSSA 

       490        500        510        520        530        540 
ARCVALSVNA SGLLDPALLP ANDSSRAPSS GMDASRPALA DSFYAISYLY YGALGTLTTV 

       550        560        570        580        590        600 
LCGALISCLT GPTKRSTLAP GLLWWDLARQ TASVAPKEEV AILDDNLVKG PEELPTGNKK 

       610        620        630        640 
PPGFLPTNED RLFFLGQKEL EGAGSWTPCV GHDGGRDQQE TNL 

« Hide

References

« Hide 'large scale' references
[1]"Cloning of the human sodium iodide symporter."
Smanik P.A., Liu Q., Furminger T.L., Ryu K., Xing S., Mazzaferri E.L., Jhiang S.M.
Biochem. Biophys. Res. Commun. 226:339-345(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY.
Tissue: Thyroid.
[2]"Increased expression of the Na+/I- symporter in cultured human thyroid cells exposed to thyrotropin and in Graves' thyroid tissue."
Saito T., Endo T., Kawaguchi A., Ikeda M., Nakazato M., Kogai T., Onaya T.
J. Clin. Endocrinol. Metab. 82:3331-3336(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], INDUCTION, TISSUE SPECIFICITY, VARIANTS PRO-102; GLN-536 AND GLN-556.
Tissue: Thyroid.
[3]"The DNA sequence and biology of human chromosome 19."
Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., Carrano A.V. expand/collapse author list , Caoile C., Chan Y.M., Christensen M., Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., Rubin E.M., Lucas S.M.
Nature 428:529-535(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Brain.
[5]"Characterization of 3'UTR region of the human NIS cDNA."
Pauws E., Tol N.J., de Vijlder J.J.M., Ris-Stalpers C.
Submitted (APR-2000) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 528-643.
[6]"Congenital hypothyroidism caused by a mutation in the Na(+)/I(-) symporter."
Fujiwara H., Tatsumi K., Miki K., Harada T., Miyai K., Takai S., Amino N.
Nat. Genet. 16:124-125(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT TDH1 PRO-354.
[7]"Novel, missense and loss-of-function mutations in the sodium/iodide symporter gene causing iodide transport defect in three Japanese patients."
Kosugi S., Inoue S., Matsuda A., Jhiang S.M.
J. Clin. Endocrinol. Metab. 83:3373-3376(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS TDH1 ARG-93; PRO-354 AND GLU-543.
[8]"Congenital hypothyroidism due to mutations in the sodium/iodide symporter: identification of a nonsense mutation producing a downstream cryptic 3' splice site."
Pohlenz J., Rosenthal I.M., Weiss R.E., Jhiang S.M., Burant C., Refetoff S.
J. Clin. Invest. 101:1028-1035(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT TDH1 GLU-267.
[9]"A novel mutation in the sodium/iodide symporter gene in the largest family with iodide transport defect."
Kosugi S., Bhayana S., Dean H.J.
J. Clin. Endocrinol. Metab. 84:3248-3253(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT TDH1 ARG-395.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U66088 mRNA. Translation: AAB17378.1.
AC005796 Genomic DNA. Translation: AAC62827.1.
D87920 mRNA. Translation: BAA24835.1.
BC105047 mRNA. Translation: AAI05048.1.
BC105049 mRNA. Translation: AAI05050.1.
AF260700 mRNA. Translation: AAF70339.1.
CCDSCCDS12368.1.
PIRJC4974.
RefSeqNP_000444.1. NM_000453.2.
UniGeneHs.584804.

3D structure databases

ProteinModelPortalQ92911.
SMRQ92911. Positions 16-476.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid112419. 2 interactions.
STRING9606.ENSP00000222248.

Protein family/group databases

TCDB2.A.21.5.1. the solute:sodium symporter (sss) family.

PTM databases

PhosphoSiteQ92911.

Polymorphism databases

DMDM12643359.

Proteomic databases

PaxDbQ92911.
PeptideAtlasQ92911.
PRIDEQ92911.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000222248; ENSP00000222248; ENSG00000105641.
GeneID6528.
KEGGhsa:6528.
UCSCuc002nhr.4. human.

Organism-specific databases

CTD6528.
GeneCardsGC19P017982.
HGNCHGNC:11040. SLC5A5.
HPACAB022364.
HPA049055.
MIM274400. phenotype.
601843. gene.
neXtProtNX_Q92911.
Orphanet95716. Familial thyroid dyshormonogenesis.
PharmGKBPA35905.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0591.
HOGENOMHOG000261662.
HOVERGENHBG057280.
InParanoidQ92911.
KOK14385.
OMATFGAWDY.
OrthoDBEOG70PBX7.
PhylomeDBQ92911.
TreeFamTF316728.

Enzyme and pathway databases

ReactomeREACT_111217. Metabolism.
REACT_15518. Transmembrane transport of small molecules.
REACT_19419. Amino acid and oligopeptide SLC transporters.

Gene expression databases

ArrayExpressQ92911.
BgeeQ92911.
CleanExHS_SLC5A5.
GenevestigatorQ92911.

Family and domain databases

InterProIPR001734. Na/solute_symporter.
IPR018212. Na/solute_symporter_CS.
IPR019900. Na/solute_symporter_subgr.
[Graphical view]
PANTHERPTHR11819. PTHR11819. 1 hit.
PfamPF00474. SSF. 1 hit.
[Graphical view]
TIGRFAMsTIGR00813. sss. 1 hit.
PROSITEPS00456. NA_SOLUT_SYMP_1. 1 hit.
PS50283. NA_SOLUT_SYMP_3. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiSodium-iodide_symporter.
GenomeRNAi6528.
NextBio25399.
PROQ92911.
SOURCESearch...

Entry information

Entry nameSC5A5_HUMAN
AccessionPrimary (citable) accession number: Q92911
Secondary accession number(s): O43702, Q2M335, Q9NYB6
Entry history
Integrated into UniProtKB/Swiss-Prot: January 24, 2001
Last sequence update: February 1, 1997
Last modified: July 9, 2014
This is version 134 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 19

Human chromosome 19: entries, gene names and cross-references to MIM