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2.A.30.4.2
Electroneutral NaCl symporter (Gitelman syndrome transporter)

Accession Number:P55017
Protein Name:NaCl Symporter aka SLC12A3
Length:1021
Molecular Weight:113125.00
Species:Homo sapiens (Human) [9606]
Number of TMSs:11
Location1 / Topology2 / Orientation3: Membrane1 / Multi-pass membrane protein2

Cross database links:

Genevestigator: P55017 P55017
eggNOG: prNOG15534 COG0531
HEGENOM: HBG446860 HOG000062855
RefSeq: NP_000330.2    NP_001119579.1    NP_001119580.1   
Entrez Gene ID: 6559   
Pfam: PF00324    PF08403   
OMIM: 263800  phenotype
600968  gene
KEGG: hsa:6559    hsa:6559   

Gene Ontology

GO:0016324 C:apical plasma membrane
GO:0005887 C:integral to plasma membrane
GO:0005624 C:membrane fraction
GO:0015378 F:sodium:chloride symporter activity
GO:0006821 P:chloride transport
GO:0006814 P:sodium ion transport
GO:0055085 P:transmembrane transport
GO:0035725 P:sodium ion transmembrane transport

References (39)

[1] “Gitelman's variant of Bartter's syndrome, inherited hypokalaemic alkalosis, is caused by mutations in the thiazide-sensitive Na-Cl cotransporter.”  Simon D.B.et.al.   8528245
[2] “Molecular cloning, expression pattern, and chromosomal localization of the human Na-Cl thiazide-sensitive cotransporter (SLC12A3).”  Mastroianni N.et.al.   8812482
[3] “The sequence and analysis of duplication-rich human chromosome 16.”  Martin J.et.al.   15616553
[4] “Novel molecular variants of the Na-Cl cotransporter gene are responsible for Gitelman syndrome.”  Mastroianni N.et.al.   8900229
[5] “Association of a mutation in thiazide-sensitive Na-Cl cotransporter with familial Gitelman's syndrome.”  Takeuchi K.et.al.   8954067
[6] “Novel mutations in the thiazide-sensitive NaCl cotransporter gene in patients with Gitelman syndrome with predominant localization to the C-terminal domain.”  Lemmink H.H.et.al.   9734597
[7] “Genetic variants of thiazide-sensitive NaCl-cotransporter in Gitelman's syndrome and primary hypertension.”  Melander O.et.al.   10988270
[8] “Novel mutations in thiazide-sensitive Na-Cl cotransporter gene of patients with Gitelman's syndrome.”  Monkawa T.et.al.   10616841
[9] “Gitelman's syndrome revisited: an evaluation of symptoms and health-related quality of life.”  Cruz D.N.et.al.   11168953
[10] “Severe hypomagnesaemia-induced hypocalcaemia in a patient with Gitelman's syndrome.”  Pantanetti P.et.al.   11940055
[11] “Two novel mutations of thiazide-sensitive Na-Cl cotrans porter (TSC) gene in two sporadic Japanese patients with Gitelman syndrome.”  Tajima T.et.al.   12008755
[12] “Identification of fifteen novel mutations in the SLC12A3 gene encoding the Na-Cl Co-transporter in Italian patients with Gitelman syndrome.”  Syren M.-L.et.al.   12112667
[13] “Four novel mutations in the thiazide-sensitive Na-Cl co-transporter gene in Japanese patients with Gitelman's syndrome.”  Maki N.et.al.   15069170
[14] “Phenotype and genotype analysis in Chinese patients with Gitelman's syndrome.”  Lin S.-H.et.al.   15687331
[15] “A novel mutation of the thiazide-sensitive sodium chloride cotransporter gene in a Japanese family with Gitelman syndrome.”  Terui K.et.al.   16429844
[16] “Novel mutations in the SLC12A3 gene causing Gitelman's syndrome in Swedes.”  Fava C.et.al.   17654016
[17] “Two novel genotypes of the thiazide-sensitive Na-Cl cotransporter (SLC12A3) gene in patients with Gitelman's syndrome.”  Aoi N.et.al.   17873326
[18] “Molecular variants of the thiazide-sensitive Na+-Cl- cotransporter in hypertensive families.”  Keszei A.P.et.al.   17885550
[19] “Gitelman's variant of Bartter's syndrome, inherited hypokalaemic alkalosis, is caused by mutations in the thiazide-sensitive Na-Cl cotransporter.”  Simon D.B.et.al.   8528245
[20] “Molecular cloning, expression pattern, and chromosomal localization of the human Na-Cl thiazide-sensitive cotransporter (SLC12A3).”  Mastroianni N.et.al.   8812482
[21] “Complete sequencing and characterization of 21,243 full-length human cDNAs.”  Ota T.et.al.   14702039
[22] “The sequence and analysis of duplication-rich human chromosome 16.”  Martin J.et.al.   15616553
[23] “Similar Effects of all WNK3 Variants upon SLC12 Cotransporters.”  Cruz-Rangel S.et.al.   21613606
[24] “Novel molecular variants of the Na-Cl cotransporter gene are responsible for Gitelman syndrome.”  Mastroianni N.et.al.   8900229
[25] “KLHL3 mutations cause familial hyperkalemic hypertension by impairing ion transport in the distal nephron.”  Louis-Dit-Picard H.et.al.   22406640
[26] “Association of a mutation in thiazide-sensitive Na-Cl cotransporter with familial Gitelman's syndrome.”  Takeuchi K.et.al.   8954067
[27] “Novel mutations in the thiazide-sensitive NaCl cotransporter gene in patients with Gitelman syndrome with predominant localization to the C-terminal domain.”  Lemmink H.H.et.al.   9734597
[28] “Genetic variants of thiazide-sensitive NaCl-cotransporter in Gitelman's syndrome and primary hypertension.”  Melander O.et.al.   10988270
[29] “Novel mutations in thiazide-sensitive Na-Cl cotransporter gene of patients with Gitelman's syndrome.”  Monkawa T.et.al.   10616841
[30] “Gitelman's syndrome revisited: an evaluation of symptoms and health-related quality of life.”  Cruz D.N.et.al.   11168953
[31] “Severe hypomagnesaemia-induced hypocalcaemia in a patient with Gitelman's syndrome.”  Pantanetti P.et.al.   11940055
[32] “Two novel mutations of thiazide-sensitive Na-Cl cotrans porter (TSC) gene in two sporadic Japanese patients with Gitelman syndrome.”  Tajima T.et.al.   12008755
[33] “Identification of fifteen novel mutations in the SLC12A3 gene encoding the Na-Cl Co-transporter in Italian patients with Gitelman syndrome.”  Syren M.-L.et.al.   12112667
[34] “Four novel mutations in the thiazide-sensitive Na-Cl co-transporter gene in Japanese patients with Gitelman's syndrome.”  Maki N.et.al.   15069170
[35] “Phenotype and genotype analysis in Chinese patients with Gitelman's syndrome.”  Lin S.-H.et.al.   15687331
[36] “A novel mutation of the thiazide-sensitive sodium chloride cotransporter gene in a Japanese family with Gitelman syndrome.”  Terui K.et.al.   16429844
[37] “Novel mutations in the SLC12A3 gene causing Gitelman's syndrome in Swedes.”  Fava C.et.al.   17654016
[38] “Two novel genotypes of the thiazide-sensitive Na-Cl cotransporter (SLC12A3) gene in patients with Gitelman's syndrome.”  Aoi N.et.al.   17873326
[39] “Molecular variants of the thiazide-sensitive Na+-Cl- cotransporter in hypertensive families.”  Keszei A.P.et.al.   17885550

External Searches:

  • Search: DB with
  • BLAST ExPASy (Swiss Institute of Bioinformatics (SIB) BLAST)
  • CDD Search (Conserved Domain Database)
  • Search COGs (Clusters of Orthologous Groups of proteins)
  • 2° Structure (Network Protein Sequence Analysis)

Analyze:

Predict TMSs (Predict number of transmembrane segments)
Window Size: Angle:  
FASTA formatted sequence
1:	MAELPTTETP GDATLCSGRF TISTLLSSDE PSPPAAYDSS HPSHLTHSST FCMRTFGYNT 
61:	IDVVPTYEHY ANSTQPGEPR KVRPTLADLH SFLKQEGRHL HALAFDSRPS HEMTDGLVEG 
121:	EAGTSSEKNP EEPVRFGWVK GVMIRCMLNI WGVILYLRLP WITAQAGIVL TWIIILLSVT 
181:	VTSITGLSIS AISTNGKVKS GGTYFLISRS LGPELGGSIG LIFAFANAVG VAMHTVGFAE 
241:	TVRDLLQEYG APIVDPINDI RIIGVVSVTV LLAISLAGME WESKAQVLFF LVIMVSFANY 
301:	LVGTLIPPSE DKASKGFFSY RADIFVQNLV PDWRGPDGTF FGMFSIFFPS ATGILAGANI 
361:	SGDLKDPAIA IPKGTLMAIF WTTISYLAIS ATIGSCVVRD ASGVLNDTVT PGWGACEGLA 
421:	CSYGWNFTEC TQQHSCHYGL INYYQTMSMV SGFAPLITAG IFGATLSSAL ACLVSAAKVF 
481:	QCLCEDQLYP LIGFFGKGYG KNKEPVRGYL LAYAIAVAFI IIAELNTIAP IISNFFLCSY 
541:	ALINFSCFHA SITNSPGWRP SFQYYNKWAA LFGAIISVVI MFLLTWWAAL IAIGVVLFLL 
601:	LYVIYKKPEV NWGSSVQAGS YNLALSYSVG LNEVEDHIKN YRPQCLVLTG PPNFRPALVD 
661:	FVGTFTRNLS LMICGHVLIG PHKQRMPELQ LIANGHTKWL NKRKIKAFYS DVIAEDLRRG 
721:	VQILMQAAGL GRMKPNILVV GFKKNWQSAH PATVEDYIGI LHDAFDFNYG VCVMRMREGL 
781:	NVSKMMQAHI NPVFDPAEDG KEASARVDPK ALVKEEQATT IFQSEQGKKT IDIYWLFDDG 
841:	GLTLLIPYLL GRKRRWSKCK IRVFVGGQIN RMDQERKAII SLLSKFRLGF HEVHILPDIN 
901:	QNPRAEHTKR FEDMIAPFRL NDGFKDEATV NEMRRDCPWK ISDEEITKNR VKSLRQVRLN 
961:	EIVLDYSRDA ALIVITLPIG RKGKCPSSLY MAWLETLSQD LRPPVILIRG NQENVLTFYC 
1021:	Q