Solute carrier family 12 member 3
Details
- Name
- Solute carrier family 12 member 3
- Synonyms
- Na-Cl cotransporter
- Na-Cl symporter
- NCC
- Thiazide-sensitive sodium-chloride cotransporter
- TSC
- Gene Name
- SLC12A3
- Organism
- Humans
- Amino acid sequence
>lcl|BSEQ0021968|Solute carrier family 12 member 3 MAELPTTETPGDATLCSGRFTISTLLSSDEPSPPAAYDSSHPSHLTHSSTFCMRTFGYNT IDVVPTYEHYANSTQPGEPRKVRPTLADLHSFLKQEGRHLHALAFDSRPSHEMTDGLVEG EAGTSSEKNPEEPVRFGWVKGVMIRCMLNIWGVILYLRLPWITAQAGIVLTWIIILLSVT VTSITGLSISAISTNGKVKSGGTYFLISRSLGPELGGSIGLIFAFANAVGVAMHTVGFAE TVRDLLQEYGAPIVDPINDIRIIAVVSVTVLLAISLAGMEWESKAQVLFFLVIMVSFANY LVGTLIPPSEDKASKGFFSYRADIFVQNLVPDWRGPDGTFFGMFSIFFPSATGILAGANI SGDLKDPAIAIPKGTLMAIFWTTISYLAISATIGSCVVRDASGVLNDTVTPGWGACEGLA CSYGWNFTECTQQHSCHYGLINYYQTMSMVSGFAPLITAGIFGATLSSALACLVSAAKVF QCLCEDQLYPLIGFFGKGYGKNKEPVRGYLLAYAIAVAFIIIAELNTIAPIISNFFLCSY ALINFSCFHASITNSPGWRPSFQYYNKWAALFGAIISVVIMFLLTWWAALIAIGVVLFLL LYVIYKKPEVNWGSSVQAGSYNLALSYSVGLNEVEDHIKNYRPQCLVLTGPPNFRPALVD FVGTFTRNLSLMICGHVLIGPHKQRMPELQLIANGHTKWLNKRKIKAFYSDVIAEDLRRG VQILMQAAGLGRMKPNILVVGFKKNWQSAHPATVEDYIGILHDAFDFNYGVCVMRMREGL NVSKMMQAHINPVFDPAEDGKEASARVDPKALVKEEQATTIFQSEQGKKTIDIYWLFDDG GLTLLIPYLLGRKRRWSKCKIRVFVGGQINRMDQERKAIISLLSKFRLGFHEVHILPDIN QNPRAEHTKRFEDMIAPFRLNDGFKDEATVNEMRRDCPWKISDEEITKNRVKSLRQVRLN EIVLDYSRDAALIVITLPIGRKGKCPSSLYMAWLETLSQDLRPPVILIRGNQENVLTFYC Q
- Number of residues
- 1021
- Molecular Weight
- 113138.04
- Theoretical pI
- 7.94
- GO Classification
- Functionspotassium / potassium ion symporter activity / sodium / sodium ion transmembrane transporter activity / transporter activityProcessescell volume homeostasis / chloride ion homeostasis / chloride transmembrane transport / ion transport / potassium ion homeostasis / potassium ion import / sodium ion homeostasis / sodium ion transmembrane transport / sodium ion transport / transmembrane transport / transportComponentsapical plasma membrane / cytosol / extracellular exosome / integral component of plasma membrane / membrane / plasma membrane
- General Function
- Transporter activity
- Specific Function
- Key mediator of sodium and chloride reabsorption in this nephron segment, accounting for a significant fraction of renal sodium reabsorption.
- Pfam Domain Function
- Transmembrane Regions
- 136-156 159-179 219-239 262-282 287-307 340-360 378-398 453-473 512-532 535-555 578-598 661-681
- Cellular Location
- Cell membrane
- Gene sequence
>lcl|BSEQ0021969|Solute carrier family 12 member 3 (SLC12A3) ATGGCAGAACTGCCCACAACAGAGACGCCTGGGGACGCCACTTTGTGCAGCGGGCGCTTC ACCATCAGCACACTGCTGAGCAGTGATGAGCCCTCTCCACCAGCTGCCTATGACAGCAGC CACCCCAGCCACCTGACCCACAGCAGCACCTTCTGCATGCGCACCTTTGGCTACAACACG ATCGATGTGGTGCCCACATATGAGCACTATGCCAACAGCACCCAGCCTGGTGAGCCCCGG AAGGTCCGGCCCACACTGGCTGACCTGCACTCCTTCCTCAAGCAGGAAGGCAGACACCTG CATGCCCTGGCCTTTGACAGCCGGCCCAGCCACGAGATGACTGATGGGCTGGTGGAGGGC GAGGCAGGCACCAGCAGCGAGAAGAACCCCGAGGAGCCAGTGCGCTTCGGCTGGGTCAAG GGGGTGATGATTCGTTGCATGCTCAACATTTGGGGCGTGATCCTCTACCTGCGGCTGCCC TGGATTACGGCCCAGGCAGGCATCGTCCTGACCTGGATCATCATCCTGCTGTCGGTCACG GTGACCTCCATCACAGGCCTCTCCATCTCAGCCATCTCCACCAATGGCAAGGTCAAGTCA GGTGGCACCTACTTCCTCATCTCCCGGAGTCTGGGCCCAGAGCTTGGGGGCTCCATCGGC CTCATTTTCGCTTTCGCCAATGCCGTGGGTGTGGCCATGCACACGGTGGGCTTTGCAGAG ACCGTGCGGGACCTGCTCCAGGAGTATGGGGCACCCATCGTGGACCCCATTAACGACATC CGCATCATTGGCGTGGTCTCGGTCACTGTGCTGCTGGCCATCTCCCTGGCTGGCATGGAG TGGGAGTCCAAGGCCCAGGTGCTGTTCTTCCTTGTCATCATGGTCTCCTTTGCCAACTAT TTAGTGGGGACGCTGATCCCCCCATCTGAGGACAAGGCCTCCAAAGGCTTCTTCAGCTAC CGGGCGGACATTTTTGTCCAGAACTTGGTGCCTGACTGGCGGGGTCCAGATGGCACCTTC TTCGGAATGTTCTCCATCTTCTTCCCCTCGGCCACAGGCATCCTGGCAGGGGCCAACATA TCTGGTGACCTCAAGGACCCTGCTATAGCCATCCCCAAGGGGACCCTCATGGCCATTTTC TGGACGACCATTTCCTACCTGGCCATCTCAGCCACCATTGGCTCCTGCGTGGTGCGTGAT GCCTCTGGGGTCCTGAATGACACAGTGACCCCTGGCTGGGGTGCCTGCGAGGGGCTGGCC TGCAGCTATGGCTGGAACTTCACCGAGTGCACCCAGCAGCACAGCTGCCACTACGGCCTC ATCAACTATTACCAGACCATGAGCATGGTGTCAGGCTTCGCGCCCCTGATCACGGCTGGC ATCTTCGGGGCCACCCTCTCCTCTGCCCTGGCCTGCCTTGTCTCTGCTGCCAAAGTCTTC CAGTGCCTTTGCGAGGACCAGCTGTACCCACTGATCGGCTTCTTCGGCAAAGGCTATGGC AAGAACAAGGAGCCCGTGCGTGGCTACCTGCTGGCCTACGCCATCGCTGTGGCCTTCATC ATCATCGCTGAGCTCAACACCATAGCCCCCATCATTTCCAACTTCTTCCTCTGCTCCTAT GCCCTCATCAACTTCAGCTGCTTCCACGCCTCCATCACCAACTCGCCTGGGTGGAGACCT TCATTCCAATACTACAACAAGTGGGCGGCGCTGTTTGGGGCTATCATCTCCGTGGTCATC ATGTTCCTCCTCACCTGGTGGGCGGCCCTCATCGCCATTGGCGTGGTGCTCTTCCTCCTG CTCTATGTCATCTACAAGAAGCCAGAGGTAAATTGGGGCTCCTCGGTACAGGCTGGCTCC TACAACCTGGCCCTCAGCTACTCGGTGGGCCTCAATGAGGTGGAAGACCACATCAAGAAC TACCGCCCCCAGTGCCTGGTGCTCACGGGGCCCCCCAACTTCCGCCCGGCCCTGGTGGAC TTTGTGGGCACCTTCACCCGGAACCTCAGCCTGATGATCTGTGGCCACGTGCTCATCGGA CCCCACAAGCAGAGGATGCCTGAGCTCCAGCTCATCGCCAACGGGCACACCAAGTGGCTG AACAAGAGGAAGATCAAGGCCTTCTACTCGGATGTCATTGCCGAGGACCTCCGCAGAGGC GTCCAGATCCTCATGCAGGCCGCAGGTCTCGGGAGAATGAAGCCCAACATTCTGGTGGTT GGGTTCAAGAAGAACTGGCAGTCGGCTCACCCGGCCACAGTGGAAGACTACATTGGCATC CTCCATGATGCCTTTGATTTCAACTATGGCGTGTGTGTCATGAGGATGCGGGAGGGACTC AACGTGTCCAAGATGATGCAGGCGCACATTAACCCCGTGTTTGACCCAGCGGAGGACGGG AAGGAAGCCAGCGCCAGAGGTGCCAGGCCATCAGTCTCTGGCGCTTTGGACCCCAAGGCC CTGGTGAAGGAGGAGCAGGCCACCACCATCTTCCAGTCGGAGCAGGGCAAGAAGACCATA GACATCTACTGGCTCTTTGACGATGGAGGCCTCACCCTCCTCATTCCCTATCTCCTTGGC CGCAAGAGGAGGTGGAGCAAATGCAAGATCCGTGTGTTCGTAGGCGGCCAGATTAACAGG ATGGACCAGGAGAGAAAGGCGATCATTTCTCTGCTGAGCAAGTTCCGACTGGGATTCCAT GAAGTCCACATCCTCCCTGACATCAACCAGAACCCTCGGGCTGAGCACACCAAGAGGTTT GAGGACATGATTGCACCCTTCCGTCTGAATGATGGCTTCAAGGATGAGGCCACTGTCAAC GAGATGCGGCGGGACTGCCCCTGGAAGATCTCAGATGAGGAGATTACGAAGAACAGAGTC AAGTCCCTTCGGCAGGTGAGGCTGAATGAGATTGTGCTGGATTACTCCCGAGACGCTGCT CTCATCGTCATCACTTTGCCCATAGGGAGGAAGGGGAAGTGCCCCAGCTCGCTGTACATG GCCTGGCTGGAGACCCTGTCCCAGGACCTCAGACCTCCAGTCATCCTGATCCGAGGAAAC CAGGAAAACGTGCTCACCTTTTACTGCCAGTAA
- Chromosome Location
- 16
- Locus
- 16q13
- External Identifiers
Resource Link UniProtKB ID P55017 UniProtKB Entry Name S12A3_HUMAN GenBank Protein ID 1172161 GenBank Gene ID U44128 GenAtlas ID SLC12A3 HGNC ID HGNC:10912 - General References
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- Mastroianni N, De Fusco M, Zollo M, Arrigo G, Zuffardi O, Bettinelli A, Ballabio A, Casari G: Molecular cloning, expression pattern, and chromosomal localization of the human Na-Cl thiazide-sensitive cotransporter (SLC12A3). Genomics. 1996 Aug 1;35(3):486-93. [Article]
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- Cruz-Rangel S, Melo Z, Vazquez N, Meade P, Bobadilla NA, Pasantes-Morales H, Gamba G, Mercado A: Similar effects of all WNK3 variants on SLC12 cotransporters. Am J Physiol Cell Physiol. 2011 Sep;301(3):C601-8. doi: 10.1152/ajpcell.00070.2011. Epub 2011 May 25. [Article]
- Mastroianni N, Bettinelli A, Bianchetti M, Colussi G, De Fusco M, Sereni F, Ballabio A, Casari G: Novel molecular variants of the Na-Cl cotransporter gene are responsible for Gitelman syndrome. Am J Hum Genet. 1996 Nov;59(5):1019-26. [Article]
- Louis-Dit-Picard H, Barc J, Trujillano D, Miserey-Lenkei S, Bouatia-Naji N, Pylypenko O, Beaurain G, Bonnefond A, Sand O, Simian C, Vidal-Petiot E, Soukaseum C, Mandet C, Broux F, Chabre O, Delahousse M, Esnault V, Fiquet B, Houillier P, Bagnis CI, Koenig J, Konrad M, Landais P, Mourani C, Niaudet P, Probst V, Thauvin C, Unwin RJ, Soroka SD, Ehret G, Ossowski S, Caulfield M, Bruneval P, Estivill X, Froguel P, Hadchouel J, Schott JJ, Jeunemaitre X: KLHL3 mutations cause familial hyperkalemic hypertension by impairing ion transport in the distal nephron. Nat Genet. 2012 Mar 11;44(4):456-60, S1-3. doi: 10.1038/ng.2218. [Article]
- Takeuchi K, Kure S, Kato T, Taniyama Y, Takahashi N, Ikeda Y, Abe T, Narisawa K, Muramatsu Y, Abe K: Association of a mutation in thiazide-sensitive Na-Cl cotransporter with familial Gitelman's syndrome. J Clin Endocrinol Metab. 1996 Dec;81(12):4496-9. [Article]
- Lemmink HH, Knoers NV, Karolyi L, van Dijk H, Niaudet P, Antignac C, Guay-Woodford LM, Goodyer PR, Carel JC, Hermes A, Seyberth HW, Monnens LA, van den Heuvel LP: Novel mutations in the thiazide-sensitive NaCl cotransporter gene in patients with Gitelman syndrome with predominant localization to the C-terminal domain. Kidney Int. 1998 Sep;54(3):720-30. [Article]
- Melander O, Orho-Melander M, Bengtsson K, Lindblad U, Rastam L, Groop L, Hulthen UL: Genetic variants of thiazide-sensitive NaCl-cotransporter in Gitelman's syndrome and primary hypertension. Hypertension. 2000 Sep;36(3):389-94. [Article]
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- Cruz DN, Shaer AJ, Bia MJ, Lifton RP, Simon DB: Gitelman's syndrome revisited: an evaluation of symptoms and health-related quality of life. Kidney Int. 2001 Feb;59(2):710-7. [Article]
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- Syren ML, Tedeschi S, Cesareo L, Bellantuono R, Colussi G, Procaccio M, Ali A, Domenici R, Malberti F, Sprocati M, Sacco M, Miglietti N, Edefonti A, Sereni F, Casari G, Coviello DA, Bettinelli A: Identification of fifteen novel mutations in the SLC12A3 gene encoding the Na-Cl Co-transporter in Italian patients with Gitelman syndrome. Hum Mutat. 2002 Jul;20(1):78. [Article]
- Maki N, Komatsuda A, Wakui H, Ohtani H, Kigawa A, Aiba N, Hamai K, Motegi M, Yamaguchi A, Imai H, Sawada K: Four novel mutations in the thiazide-sensitive Na-Cl co-transporter gene in Japanese patients with Gitelman's syndrome. Nephrol Dial Transplant. 2004 Jul;19(7):1761-6. Epub 2004 Apr 6. [Article]
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Drug Relations
- Drug Relations
DrugBank ID Name Drug group Pharmacological action? Actions Details DB00436 Bendroflumethiazide approved yes inhibitor Details DB00562 Benzthiazide approved yes inhibitor Details DB00880 Chlorothiazide approved, vet_approved yes inhibitor Details DB00999 Hydrochlorothiazide approved, vet_approved yes inhibitor Details DB01021 Trichlormethiazide approved, vet_approved yes inhibitor Details DB00524 Metolazone approved yes inhibitor Details DB01324 Polythiazide approved yes inhibitor Details DB01325 Quinethazone approved yes inhibitor Details DB00808 Indapamide approved yes inhibitor Details