KCNN4

Potassium channel, calcium activated intermediate/small conductance subfamily N alpha, member 4

Identifiers

KCNN4 ; IK; IK1; IKCA1; KCA4; KCa3.1; SK4; hIKCa1; hKCa4; hSK4

External IDs

OMIM: 602754 MGI: 1277957 HomoloGene: 1696 IUPHAR: 384 ChEMBL: 4305 GeneCards: KCNN4 Gene

Gene ontology
Molecular function	• protein binding • calmodulin binding • calcium-activated potassium channel activity • small conductance calcium-activated potassium channel activity • protein phosphatase binding • Intermediate conductance calcium-activated potassium channel activity
Cellular component	• plasma membrane • voltage-gated potassium channel complex • basolateral plasma membrane • apical plasma membrane • neuronal cell body • membrane raft
Biological process	• immune system process • potassium ion transport • calcium ion transport • cell volume homeostasis • defense response • synaptic transmission • stabilization of membrane potential • phospholipid translocation • saliva secretion • positive regulation of protein secretion • positive regulation of T cell receptor signaling pathway • potassium ion export • potassium ion transmembrane transport
Sources: Amigo / QuickGO

RNA expression pattern

More reference expression data

Orthologs

Species

Human

Mouse

RefSeq (mRNA)

RefSeq (protein)

Location (UCSC)

Chr 19:
43.77 – 43.78 Mb

Chr 7:
24.37 – 24.39 Mb

PubMed search

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.^[1]

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 depolarization, 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.^[1]

History

The channel activity was first described in 1958 by Gyorgi Gardos in human erythrocytes.^[2] The channels is also named Gardos channel because of its discoverer.

References

1 2 "Entrez Gene: KCNN4 potassium intermediate/small conductance calcium-activated channel, subfamily N, member 4".
↑ Gardos G (1958). "The function of calcium in the potassium permeability of human erythrocytes". Biochim. Biophys. Acta 30 (3): 653–4. doi:10.1016/0006-3002(58)90124-0. PMID 13618284.

Wei AD, Gutman GA, Aldrich R, Chandy KG, Grissmer S, Wulff H (2005). "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, Bond CT, Adelman JP, Maylie J (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.
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.
Logsdon NJ, Kang J, Togo JA, Christian EP, Aiyar J (1997). "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, Wu AC, Gargus JJ, Gutman GA, Dahl N, Mohrenweiser H, Chandy KG (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, Rauer H, Kalman K, Zhou J, Beckingham K, Chandy KG, Cahalan MD, Aiyar J (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, Baribaud F, Doms RW, Schols D, De Clercq E, Kotlikoff MI, Collman RG, Freedman BD (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.
Ghanshani S, Wulff H, Miller MJ, Rohm H, Neben A, Gutman GA, Cahalan MD, Chandy KG (2000). "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): 8151–6. doi:10.1073/pnas.97.14.8151. PMC 16685. PMID 10884437.
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, Werner S, Alzheimer C (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 (2002). "Calcium-activated potassium channel expression in human myometrium: effect of pregnancy". Proc. West. Pharmacol. Soc. 45: 184–6. PMID 12434576.
Syme CA, Hamilton KL, Jones HM, Gerlach AC, Giltinan L, Papworth GD, Watkins SC, Bradbury NA, Devor DC (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, Schreiber R, Seydewitz HH, Kuehr J, Brandis M, Kunzelmann K (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, Potapova O, Foye K, Wickrema A (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.
Bernard K, Bogliolo S, Soriani O, Ehrenfeld J (2003). "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.
Köhler 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.
Jones HM, Hamilton KL, Papworth GD, Syme CA, Watkins SC, Bradbury NA, Devor DC (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 (2004). "Modulation of Gardos channel activity by oxidants and oxygen tension: effects of 1-chloro-2,4-dinitrobenzene and phenazine methosulphate". Bioelectrochemistry 62 (2): 147–52. doi:10.1016/j.bioelechem.2003.07.008. PMID 15039018.
Lew VL, Tiffert T, Etzion Z, Perdomo D, Daw N, Macdonald L, Bookchin RM (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.

Membrane transport protein: ion channels (TC 1A)

Ca²⁺: Calcium channel

Ligand-gated	Inositol trisphosphate receptor 1 2 3 Ryanodine receptor 1 2 3

Voltage-gated	L-type/Ca_vα 1.1 1.2 1.3 1.4 N-type/Ca_vα2.2 P-type/Ca_vα 2.1 Q-type/Ca_vα2.1 R-type/Ca_vα2.3 T-type/Ca_vα 3.1 3.2 3.3 α₂δ-subunits 1 2 β-subunits β1 β2 β3 β4 γ-subunits γ1 γ2 γ3 γ4 Cation channels of sperm 1 2 3 4 Two-pore channel 1 2

Na⁺: Sodium channel

Constitutively active	Epithelial sodium channel α β γ δ

Proton-gated	Amiloride-sensitive cation channel 1 2 3 4

Voltage-gated	Na_vα 1.1 1.2 1.3 1.4 1.5 1.6 1.7 1.8 1.9 7A Na_vβ 1 2 3 4

K⁺: Potassium channel

Calcium-activated	BK channel α1 β1 β2 β3 β4 SK channel SK1 SK2 SK3 IK channel IK1 K_Ca 1.1 2.1 2.2 2.3 3.1 4.1 4.2 5.1

Inward-rectifier	K_ATP K_ir 1.1 2.1 2.2 2.3 2.4 2.6 GIRK/K_ir 3.1 3.2 3.3 3.4 K_ir 4.1 4.2 5.1 6.1 6.2 7.1

Tandem pore domain	K2P 1 2 3 4 5 6 7 9 10 12 13 15 16 17 18

Voltage-gated	K_vα1-6 1.1 1.2 1.3 1.4 1.5 1.6 1.7 1.8 2.1 2.2 3.1 3.2 3.3 3.4 4.1 4.2 4.3 5.1 6.1 6.2 6.3 6.4 K_vα7-12 7.1 7.2 7.3 7.4 7.5 8.1 8.2 9.1 9.2 9.3 10.1 10.2 11.1/hERG 11.2 11.3 12.1 12.2 12.3 K_vβ 1 2 3 KCNIP 1 2 3 4 minK/ISK minK/ISK-like MiRP 1 2 3 Shaker gene

Miscellaneous

Cl⁻: Chloride channel	Calcium-activated chloride channels Anoctamin ANO1 Bestrophin 1 2 Chloride Channel Accessory 1 2 3 4 CFTR CLCN 1 2 3 4 5 6 7 KA KB CLIC 1 2 3 4 5 6 L1 CLNS 1A 1B

H⁺: Proton channel	HVCN1

M⁺: CNG cation channel	α 1 2 3 4 β 1 2 3 HCN FC 1 2 3 4

M⁺: TRP cation channel	TRPA (1) TRPC 1 2 3 4 4AP 5 6 7 TRPM 1 2 3 4 5 6 7 8 TRPML 1 2 3 TRPN TRPP 1 2 TRPV 1 2 3 4 5 6

H₂O (+ solutes): Porin	Aquaporin 0 1 2 3 4 5 6 7 8 9 Voltage-dependent anion channel 1 2 3 General bacterial porin family

Cytoplasm: Gap junction	Connexin: A GJA1 GJA3 GJA4 GJA5 GJA8 GJA9 GJA10 B GJB1 GJB2 GJB3 GJB4 GJB5 GJB6 GJB7 C GJC1 GJC2 GJC3 D GJD2 GJD3 GJD4) Innexin

By gating mechanism

Ion channel class	Ligand-gated Light-gated Voltage-gated Stretch-activated

see also disorders

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KCNN4

Function

History

See also

References

Further reading