Sodium/iodide cotransporter - Homo sapiens (Human)

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Q92911 (SC5A5_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified May 1, 2013. Version 123. History...

Clusters with 100%, 90%, 50% identity |

Documents (5) |

Third-party data

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Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·Documents Customize order

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	643 AA.
Sequence status	Complete.
Protein existence	Evidence 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 process	Ion transport Sodium transport Symport Transport
Cellular component	Membrane
Coding sequence diversity	Polymorphism
Disease	Congenital hypothyroidism Disease mutation
Domain	Transmembrane Transmembrane helix
Ligand	Sodium
PTM	Glycoprotein Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cellular 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 thyroid hormone generation Traceable author statement. Source: Reactome
Cellular_component	integral to 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_function	iodide transmembrane transporter activity Inferred from mutant phenotype PubMed 12021185. Source: UniProtKB sodium:iodide symporter activity Inferred from electronic annotation. Source: Compara
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 643

643

Sodium/iodide cotransporter

PRO_0000105383

Regions

Topological domain

1 – 16

Extracellular Potential

Transmembrane

17 – 37

Helical; Potential

Topological domain

38 – 53

Cytoplasmic Potential

Transmembrane

54 – 74

Helical; Potential

Topological domain

75 – 88

Extracellular Potential

Transmembrane

89 – 109

Helical; Potential

Topological domain

110 – 136

Cytoplasmic Potential

Transmembrane

137 – 157

Helical; Potential

Topological domain

158 – 163

Extracellular Potential

Transmembrane

164 – 184

Helical; Potential

Topological domain

185 – 186

Cytoplasmic Potential

Transmembrane

187 – 207

Helical; Potential

Topological domain

208 – 241

Extracellular Potential

Transmembrane

242 – 262

Helical; Potential

Topological domain

263 – 286

Cytoplasmic Potential

Transmembrane

287 – 307

Helical; Potential

Topological domain

308 – 326

Extracellular Potential

Transmembrane

327 – 347

Helical; Potential

Topological domain

348 – 391

Cytoplasmic Potential

Transmembrane

392 – 412

Helical; Potential

Topological domain

413 – 416

Extracellular Potential

Transmembrane

417 – 437

Helical; Potential

Topological domain

438 – 444

Cytoplasmic Potential

Transmembrane

445 – 465

Helical; Potential

Topological domain

466 – 525

Extracellular Potential

Transmembrane

526 – 546

Helical; Potential

Topological domain

547 – 643

Cytoplasmic Potential

Amino acid modifications

Modified residue

556

Phosphoserine; by PKA Potential

Glycosylation

489

N-linked (GlcNAc...) Potential

Glycosylation

502

N-linked (GlcNAc...) Potential

Natural variations

Natural variant

G → R in TDH1. Ref.7

VAR_010263

Natural variant

102

A → P. Ref.2

VAR_010264

Natural variant

267

Q → E in TDH1. Ref.8

VAR_010265

Natural variant

298

C → G.
Corresponds to variant rs8108188 [ dbSNP | Ensembl ].

VAR_052490

Natural variant

354

T → P in TDH1. Ref.6 Ref.7

VAR_010266

Natural variant

395

G → R in TDH1. Ref.9

VAR_010267

Natural variant

536

T → Q Requires 2 nucleotide substitutions. Ref.2

VAR_010268

Natural variant

543

G → E in TDH1. Ref.7

VAR_010269

Natural variant

556

S → Q Requires 2 nucleotide substitutions. Ref.2

VAR_010270

Sequences

Sequence

Length

Mass (Da)

Tools

Q92911 [UniParc].

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

FASTA

643

68,666

        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' referencesShow '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. 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.

Web resources

GeneReviews

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.
IPI	IPI00024248.
PIR	JC4974.
RefSeq	NP_000444.1. NM_000453.2.
UniGene	Hs.584804.
3D structure databases
ProteinModelPortal	Q92911.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000222248.
Protein family/group databases
TCDB	2.A.21.5.1. solute:sodium symporter (SSS) family.
PTM databases
PhosphoSite	Q92911.
Polymorphism databases
DMDM	12643359.
Proteomic databases
PaxDb	Q92911.
PeptideAtlas	Q92911.
PRIDE	Q92911.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000222248; ENSP00000222248; ENSG00000105641.
GeneID	6528.
KEGG	hsa:6528.
UCSC	uc002nhr.4. human.
Organism-specific databases
CTD	6528.
GeneCards	GC19P017982.
HGNC	HGNC:11040. SLC5A5.
HPA	CAB022364.
MIM	274400. phenotype. 601843. gene.
neXtProt	NX_Q92911.
Orphanet	95716. Familial thyroid dyshormonogenesis.
PharmGKB	PA35905.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0591.
HOGENOM	HOG000261662.
HOVERGEN	HBG057280.
InParanoid	Q92911.
KO	K14385.
OMA	ATFGAWD.
OrthoDB	EOG48WC1K.
PhylomeDB	Q92911.
Enzyme and pathway databases
Reactome	REACT_111217. Metabolism. REACT_15518. Transmembrane transport of small molecules. REACT_19419. Amino acid and oligopeptide SLC transporters.
Gene expression databases
ArrayExpress	Q92911.
Bgee	Q92911.
CleanEx	HS_SLC5A5.
Genevestigator	Q92911.
GermOnline	ENSG00000105641. Homo sapiens.
Family and domain databases
InterPro	IPR001734. Na/solute_symporter. IPR018212. Na/solute_symporter_CS. IPR019900. Na/solute_symporter_subgr. [Graphical view]
PANTHER	PTHR11819. PTHR11819. 1 hit.
Pfam	PF00474. SSF. 1 hit. [Graphical view]
TIGRFAMs	TIGR00813. sss. 1 hit.
PROSITE	PS00456. NA_SOLUT_SYMP_1. 1 hit. PS00457. NA_SOLUT_SYMP_2. False negative. PS50283. NA_SOLUT_SYMP_3. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	6528.
NextBio	25399.
SOURCE	Search...

Entry information

Entry name

SC5A5_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 123 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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

Human chromosome 19

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

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

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

SIMILARITY comments

Index of protein domains and families

Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·Documents

Preferred order of sections

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Sequence annotation (Features)

Molecule processing

Regions

Amino acid modifications

Natural variations

Sequences

References

Web resources

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

Protein family/group databases

PTM databases

Polymorphism databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Gene expression databases

Family and domain databases

Other

Entry information

Relevant documents