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2.A.21.5.1
Sodium iodide symporter (NIS; also transports other monovalent anions including: ClO3-, SCN-, SeCN-, NO3-, Br-, BF4-, IO4- and BrO3-). It mediates electroneutral active transport of the environmental pollutant perchlorate (Dohan et al., 2007). Five beta-OH group-containing residues (Thr-351, Ser-353, Thr-354, Ser-356, and Thr-357) and Asn-360, all of which putatively face the same side of the helix in TMS IX, plus Asp-369, located in the membrane/cytosol interface, play key roles in NIS function and seem to be involved in Na+ binding/translocation (De la Vieja et al. 2007). Thr-354 is essential for iodide uptake (Tatsumi et al., 2010). The stoichiometry is Na+:I-= 2:1. The G39R mutant (congenital) is inactive. G93 is a pivot for the inwardly to outwardly conformational change (Paroder-Belenitsky et al., 2011).  The protein is present as a dimer (Huc-Brandt et al. 2011).  Functionally equivalent systems have been reviewed (Darrouzet et al. 2014). mutations cause congenital I- transport defects (ITD; Li et al. 2013).  The physiological, medical and mechanistic features of NIS have been reviewed (Portulano et al. 2014).

Accession Number:Q92911
Protein Name:SL55 aka SLC5A5 aka NIS
Length:643
Molecular Weight:68666.00
Species:Homo sapiens (Human) [9606]
Number of TMSs:13
Location1 / Topology2 / Orientation3: Membrane1 / Multi-pass membrane protein2
Substrate Sodium iodide, Chlorate, Thiocyanate, Selenium cyanide, nitrate, Br-, Tetrafluoroborate, Periodate, Bromate

Cross database links:

Genevestigator: Q92911 Q92911
eggNOG: prNOG04668 COG0591
HEGENOM: HBG446891 HOG000261662
RefSeq: NP_000444.1   
Entrez Gene ID: 6528   
Pfam: PF00474   
OMIM: 274400  phenotype
601843  gene
KEGG: hsa:6528    hsa:6528   

Gene Ontology

GO:0016021 C:integral to membrane
GO:0005886 C:plasma membrane
GO:0015111 F:iodide transmembrane transporter activity
GO:0006814 P:sodium ion transport
GO:0055085 P:transmembrane transport
GO:0005634 C:nucleus
GO:0008507 F:sodium:iodide symporter activity
GO:0071320 P:cellular response to cAMP
GO:0071371 P:cellular response to gonadotropin stimulus
GO:0006590 P:thyroid hormone generation

References (16)

[1] “Cloning of the human sodium iodide symporter.”  Smanik P.A.et.al.   8806637
[2] “Increased expression of the Na+/I- symporter in cultured human thyroid cells exposed to thyrotropin and in Graves' thyroid tissue.”  Saito T.et.al.   9329364
[3] “The DNA sequence and biology of human chromosome 19.”  Grimwood J.et.al.   15057824
[4] “The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).”  The MGC Project Teamet.al.   15489334
[5] “Congenital hypothyroidism caused by a mutation in the Na(+)/I(-) symporter.”  Fujiwara H.et.al.   9171822
[6] “Novel, missense and loss-of-function mutations in the sodium/iodide symporter gene causing iodide transport defect in three Japanese patients.”  Kosugi S.et.al.   9745458
[7] “Congenital hypothyroidism due to mutations in the sodium/iodide symporter: identification of a nonsense mutation producing a downstream cryptic 3' splice site.”  Pohlenz J.et.al.   9486973
[8] “A novel mutation in the sodium/iodide symporter gene in the largest family with iodide transport defect.”  Kosugi S.et.al.   10487695
[9] “Cloning of the human sodium iodide symporter.”  Smanik P.A.et.al.   8806637
[10] “Increased expression of the Na+/I- symporter in cultured human thyroid cells exposed to thyrotropin and in Graves' thyroid tissue.”  Saito T.et.al.   9329364
[11] “The DNA sequence and biology of human chromosome 19.”  Grimwood J.et.al.   15057824
[12] “The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).”  The MGC Project Teamet.al.   15489334
[13] “Congenital hypothyroidism caused by a mutation in the Na(+)/I(-) symporter.”  Fujiwara H.et.al.   9171822
[14] “Novel, missense and loss-of-function mutations in the sodium/iodide symporter gene causing iodide transport defect in three Japanese patients.”  Kosugi S.et.al.   9745458
[15] “Congenital hypothyroidism due to mutations in the sodium/iodide symporter: identification of a nonsense mutation producing a downstream cryptic 3' splice site.”  Pohlenz J.et.al.   9486973
[16] “A novel mutation in the sodium/iodide symporter gene in the largest family with iodide transport defect.”  Kosugi S.et.al.   10487695

External Searches:

  • Search: DB with
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  • Search COGs (Clusters of Orthologous Groups of proteins)
  • 2° Structure (Network Protein Sequence Analysis)

Analyze:

Predict TMSs (Predict number of transmembrane segments)
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FASTA formatted sequence 
1:	MEAVETGERP TFGAWDYGVF ALMLLVSTGI GLWVGLARGG QRSAEDFFTG GRRLAALPVG 
61:	LSLSASFMSA VQVLGVPSEA YRYGLKFLWM CLGQLLNSVL TALLFMPVFY RLGLTSTYEY 
121:	LEMRFSRAVR LCGTLQYIVA TMLYTGIVIY APALILNQVT GLDIWASLLS TGIICTFYTA 
181:	VGGMKAVVWT DVFQVVVMLS GFWVVLARGV MLVGGPRQVL TLAQNHSRIN LMDFNPDPRS 
241:	RYTFWTFVVG GTLVWLSMYG VNQAQVQRYV ACRTEKQAKL ALLINQVGLF LIVSSAACCG 
301:	IVMFVFYTDC DPLLLGRISA PDQYMPLLVL DIFEDLPGVP GLFLACAYSG TLSTASTSIN 
361:	AMAAVTVEDL IKPRLRSLAP RKLVIISKGL SLIYGSACLT VAALSSLLGG GVLQGSFTVM 
421:	GVISGPLLGA FILGMFLPAC NTPGVLAGLG AGLALSLWVA LGATLYPPSE QTMRVLPSSA 
481:	ARCVALSVNA SGLLDPALLP ANDSSRAPSS GMDASRPALA DSFYAISYLY YGALGTLTTV 
541:	LCGALISCLT GPTKRSTLAP GLLWWDLARQ TASVAPKEEV AILDDNLVKG PEELPTGNKK 
601:	PPGFLPTNED RLFFLGQKEL EGAGSWTPCV GHDGGRDQQE TNL