KCNN4

Potassium intermediate/small conductance calcium-activated channel, subfamily N, member 4
Identifiers
Symbols	KCNN4; IK1; IKCA1; KCA4; KCa3.1; SK4; hIKCa1; hKCa4; hSK4
External IDs	OMIM: 602754 MGI: 1277957 HomoloGene: 1696 IUPHAR: KCa3.1 GeneCards: KCNN4 Gene
Gene Ontology Molecular function • ion channel activity • protein binding • calmodulin binding • calcium-activated potassium channel activity Cellular component • voltage-gated potassium channel complex • membrane • integral to membrane Biological process • ion transport • potassium ion transport • cell volume homeostasis • defense response • phospholipid translocation • saliva secretion • positive regulation of protein secretion Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	3783	16534
Ensembl	ENSG00000104783	ENSMUSG00000054342
UniProt	O15554	Q8C2E0
RefSeq (mRNA)	NM_002250	NM_008433
RefSeq (protein)	NP_002241	NP_032459
Location (UCSC)	Chr 19: 44.27 – 44.29 Mb	Chr 7: 25.16 – 25.17 Mb
PubMed search	[1]	[2]

Potassium intermediate/small conductance calcium-activated channel, subfamily N, member 4, also known as KCNN4, is a human gene encoding the K_Ca3.1 protein.

Function

The K_Ca3.1 protein is part of a potentially heterotetrameric voltage-independent potassium channel that is activated by intracellular calcium. Activation is followed by membrane hyperpolarization, which promotes calcium influx. The encoded protein may be part of the predominant calcium-activated potassium channel in T-lymphocytes. This gene is similar to other KCNN family potassium channel genes, but it differs enough to possibly be considered as part of a new subfamily.

See also

• SK channel
• Voltage-gated potassium channel
• Senicapoc

Further reading

• Wei AD, Gutman GA, Aldrich R, et al. (2006). "International Union of Pharmacology. LII. Nomenclature and molecular relationships of calcium-activated potassium channels.". Pharmacol. Rev. 57 (4): 463–72. doi:10.1124/pr.57.4.9. PMID 16382103. 
• Ishii TM, Silvia C, Hirschberg B, et al. (1997). "A human intermediate conductance calcium-activated potassium channel.". Proc. Natl. Acad. Sci. U.S.A. 94 (21): 11651–6. doi:10.1073/pnas.94.21.11651. PMC 23567. PMID 9326665. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=23567. 
• Joiner WJ, Wang LY, Tang MD, Kaczmarek LK (1997). "hSK4, a member of a novel subfamily of calcium-activated potassium channels.". Proc. Natl. Acad. Sci. U.S.A. 94 (20): 11013–8. doi:10.1073/pnas.94.20.11013. PMC 23566. PMID 9380751. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=23566. 
• Logsdon NJ, Kang J, Togo JA, et al. (1998). "A novel gene, hKCa4, encodes the calcium-activated potassium channel in human T lymphocytes.". J. Biol. Chem. 272 (52): 32723–6. doi:10.1074/jbc.272.52.32723. PMID 9407042. 
• Ghanshani S, Coleman M, Gustavsson P, et al. (1998). "Human calcium-activated potassium channel gene KCNN4 maps to chromosome 19q13.2 in the region deleted in diamond-blackfan anemia.". Genomics 51 (1): 160–1. doi:10.1006/geno.1998.5333. PMID 9693050. 
• Fanger CM, Ghanshani S, Logsdon NJ, et al. (1999). "Calmodulin mediates calcium-dependent activation of the intermediate conductance KCa channel, IKCa1.". J. Biol. Chem. 274 (9): 5746–54. doi:10.1074/jbc.274.9.5746. PMID 10026195. 
• Liu QH, Williams DA, McManus C, et al. (2000). "HIV-1 gp120 and chemokines activate ion channels in primary macrophages through CCR5 and CXCR4 stimulation.". Proc. Natl. Acad. Sci. U.S.A. 97 (9): 4832–7. doi:10.1073/pnas.090521697. PMC 18318. PMID 10758170. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=18318. 
• Ghanshani S, Wulff H, Miller MJ, et al. (2001). "Up-regulation of the IKCa1 potassium channel during T-cell activation. Molecular mechanism and functional consequences.". J. Biol. Chem. 275 (47): 37137–49. doi:10.1074/jbc.M003941200. PMID 10961988. 
• Wulff H, Miller MJ, Hansel W, Grissmer S, Cahalan MD, Chandy KG (2000). "Design of a potent and selective inhibitor of the intermediate-conductance Ca2+-activated K+ channel, IKCa1: a potential immunosuppressant.". Proc Natl Acad Sci U S A. 97 (14): 8151–8156. doi:10.1073/pnas.97.14.8151. PMC 16685. PMID 10884437. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=16685. 
• Wulff H, Gutman GA, Cahalan MD, Chandy KG (2001). "Delineation of the clotrimazole/TRAM-34 binding site on the intermediate conductance calcium-activated potassium channel, IKCa1.". J. Biol. Chem. 276 (34): 32040–5. doi:10.1074/jbc.M105231200. PMID 11425865. 
• Koegel H, Kaesler S, Burgstahler R, et al. (2003). "Unexpected down-regulation of the hIK1 Ca2+-activated K+ channel by its opener 1-ethyl-2-benzimidazolinone in HaCaT keratinocytes. Inverse effects on cell growth and proliferation.". J. Biol. Chem. 278 (5): 3323–30. doi:10.1074/jbc.M208914200. PMID 12421833. 
• Mazzone JN, Kaiser RA, Buxton IL (2003). "Calcium-activated potassium channel expression in human myometrium: effect of pregnancy.". Proc. West. Pharmacol. Soc. 45: 184–6. PMID 12434576. 
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=139241. 
• Syme CA, Hamilton KL, Jones HM, et al. (2003). "Trafficking of the Ca2+-activated K+ channel, hIK1, is dependent upon a C-terminal leucine zipper.". J. Biol. Chem. 278 (10): 8476–86. doi:10.1074/jbc.M210072200. PMID 12493744. 
• Hamilton KL, Syme CA, Devor DC (2003). "Molecular localization of the inhibitory arachidonic acid binding site to the pore of hIK1.". J. Biol. Chem. 278 (19): 16690–7. doi:10.1074/jbc.M212959200. PMID 12609997. 
• Mall M, Gonska T, Thomas J, et al. (2003). "Modulation of Ca2+-activated Cl- secretion by basolateral K+ channels in human normal and cystic fibrosis airway epithelia.". Pediatr. Res. 53 (4): 608–18. doi:10.1203/01.PDR.0000057204.51420.DC. PMID 12612194. 
• Hoffman JF, Joiner W, Nehrke K, et al. (2003). "The hSK4 (KCNN4) isoform is the Ca2+-activated K+ channel (Gardos channel) in human red blood cells.". Proc. Natl. Acad. Sci. U.S.A. 100 (12): 7366–71. doi:10.1073/pnas.1232342100. PMC 165881. PMID 12773623. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=165881. 
• Bernard K, Bogliolo S, Soriani O, Ehrenfeld J (2004). "Modulation of calcium-dependent chloride secretion by basolateral SK4-like channels in a human bronchial cell line.". J. Membr. Biol. 196 (1): 15–31. doi:10.1007/s00232-003-0621-3. PMID 14724753. 
• Kohler R, Wulff H, Eichler I, Kneifel M, Neumann D, Knorr A, Grgic I, Kämpfe D, Si H, Wibawa J, Real R, Borner K, Brakemeier S, Orzechowski HD, Reusch HP, Paul M, Chandy KG, Hoyer J (2003). "Blockade of the intermediate-conductance calcium-activated potassium channel as a new therapeutic strategy for restenosis.". Circulation 108 (9): 1119–25. doi:10.1161/01.CIR.0000086464.04719.DD. PMID 12939222. 
• Toyama K, Wulff H, Chandy KG, Azam P, Raman G, Saito T, Fujiwara Y, Mattson DL, Das S, Melvin JE, Pratt PF, Hatoum OA, Gutterman DD, Harder DR, Miura H. (2008). "The intermediate-conductance calcium-activated potassium channel KCa3.1 contributes to atherogenesis in mice and humans.". J Clin Invest. 118 (9): 3025–37. doi:10.1172/JCI30836. PMC 2496961. PMID 18688283. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2496961. 
• Jones HM, Hamilton KL, Papworth GD, et al. (2004). "Role of the NH2 terminus in the assembly and trafficking of the intermediate conductance Ca2+-activated K+ channel hIK1.". J. Biol. Chem. 279 (15): 15531–40. doi:10.1074/jbc.M400069200. PMID 14754884. 
• Gibson JS, Muzyamba MC (2005). "Modulation of Gardos channel activity by oxidants and oxygen tension: effects of 1-chloro-2,4-dinitrobenzene and phenazine methosulphate.". Bioelectrochemistry (Amsterdam, Netherlands) 62 (2): 147–52. doi:10.1016/j.bioelechem.2003.07.008. PMID 15039018. 
• Lew VL, Tiffert T, Etzion Z, et al. (2005). "Distribution of dehydration rates generated by maximal Gardos-channel activation in normal and sickle red blood cells.". Blood 105 (1): 361–7. doi:10.1182/blood-2004-01-0125. PMID 15339840. 

This article incorporates text from the United States National Library of Medicine, which is in the public domain.