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Unless otherwise stated all data on this page refer to the human proteins. Gene information is provided for human (Hs), mouse (Mm) and rat (Rn).
The SLC12 family of chloride transporters contribute to ion fluxes across a variety of tissues, particularly in the kidney and choroid plexus of the brain. Within this family, further subfamilies are identifiable: NKCC1, NKCC2 and NCC constitute a group of therapeutically-relevant transporters, targets for loop and thiazide diuretics. These 12 TM proteins exhibit cytoplasmic termini and an extended extracellular loop at TM7/8 and are kidney-specific (NKCC2 and NCC) or show a more widespread distribution (NKCC1). A second family, the K-Cl co-transporters are also 12 TM domain proteins with cytoplasmic termini, but with an extended extracellular loop at TM 5/6. CCC6 exhibits structural similarities with the K-Cl co-transporters, while CCC9 is divergent, with 11 TM domains and a cytoplasmic N-terminus and extracellular C-terminus.
NKCC2 (Kidney-specific Na-K-Cl symporter / SLC12A1) C Show summary »« Hide summary More detailed page
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NKCC1 (Basolateral Na-K-Cl symporter / SLC12A2) C Show summary »« Hide summary
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NCC (Na-Cl symporter / SLC12A3) C Show summary »« Hide summary More detailed page
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KCC1 (K-Cl cotransporter 1 / SLC12A4) C Show summary »« Hide summary
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KCC2 (K-Cl cotransporter 2 / SLC12A5) C Show summary »« Hide summary
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KCC3 (K-Cl cotransporter 3 / SLC12A6) C Show summary »« Hide summary
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KCC4 (K-Cl cotransporter 4 / SLC12A7) C Show summary »« Hide summary
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CCC9 (Cation-chloride cotransporter 9 / SLC12A8) C Show summary »« Hide summary
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CCC6 (Cation-chloride cotransporter 6 / SLC12A9) Show summary »« Hide summary
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* Key recommended reading is highlighted with an asterisk
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Hebert SC, Mount DB, Gamba G. (2004) Molecular physiology of cation-coupled Cl- cotransport: the SLC12 family. Pflugers Arch, 447 (5): 580-93. [PMID:12739168]
* Huang X, Dorhout Mees E, Vos P, Hamza S, Braam B. (2016) Everything we always wanted to know about furosemide but were afraid to ask. Am J Physiol Renal Physiol, 310 (10): F958-71. [PMID:26911852]
* Kahle KT, Khanna AR, Alper SL, Adragna NC, Lauf PK, Sun D, Delpire E. (2015) K-Cl cotransporters, cell volume homeostasis, and neurological disease. Trends Mol Med, 21 (8): 513-23. [PMID:26142773]
Kahle KT, Rinehart J, Lifton RP. (2010) Phosphoregulation of the Na-K-2Cl and K-Cl cotransporters by the WNK kinases. Biochim Biophys Acta, 1802 (12): 1150-8. [PMID:20637866]
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Lang F, Vallon V, Knipper M, Wangemann P. (2007) Functional significance of channels and transporters expressed in the inner ear and kidney. Am J Physiol, Cell Physiol, 293 (4): C1187-208. [PMID:17670895]
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* Martín-Aragón Baudel MA, Poole AV, Darlison MG. (2017) Chloride co-transporters as possible therapeutic targets for stroke. J Neurochem, 140 (2): 195-209. [PMID:27861901]
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Wagner CA, Devuyst O, Bourgeois S, Mohebbi N. (2009) Regulated acid-base transport in the collecting duct. Pflugers Arch, 458 (1): 137-56. [PMID:19277700]
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2. Grozio A, Mills KF, Yoshino J, Bruzzone S, Sociali G, Tokizane K, Lei HC, Cunningham R, Sasaki Y, Migaud ME et al.. (2019) Slc12a8 is a nicotinamide mononucleotide transporter. Nat Metab, 1 (1): 47-57. DOI: 10.1038/s42255-018-0009-4 [PMID:31131364]
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Database page citation:
SLC12 family of cation-coupled chloride transporters. Accessed on 02/12/2024. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=184.
Concise Guide to PHARMACOLOGY citation:
Alexander SPH, Fabbro D, Kelly E, Mathie AA, Peters JA, Veale EL, Armstrong JF, Faccenda E, Harding SD, Davies JA et al. (2023) The Concise Guide to PHARMACOLOGY 2023/24: Transporters. Br J Pharmacol. 180 Suppl 2:S374-469.
This work is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License
DIOA is able to differentiate KCC isoforms from NKCC and NCC transporters, but also inhibits CFTR [4].