KCNN4

KCNN4
Identifiers
Aliases	KCNN4 , IK1, IKCA1, KCA4, KCa3.1, SK4, hIKCa1, hKCa4, hSK4, IK, DHS2, potassium calcium-activated channel subfamily N member 4
External IDs	OMIM: 602754 MGI: 1277957 HomoloGene: 1696 GeneCards: KCNN4
Gene location (Human)
Chr.	Chromosome 19 (human)
End	43,780,976 bp
Gene location (Mouse)
Chr.	Chromosome 7 (mouse)
End	24,086,115 bp
RNA expression pattern
	Top expressed in
	parotid gland; ; minor salivary gland; ; trachea; ; skin of abdomen; ; placenta; ; lymph node; ; rectum; ; appendix; ; spleen; ; right uterine tube;
	Top expressed in
	parotid gland; ; Paneth cell; ; lacrimal gland; ; submandibular gland; ; crypt of lieberkuhn of small intestine; ; thymus; ; lymph node; ; blood; ; Epithelium of stomach; ; spleen;
	More reference expression data
	More reference expression data
Gene ontology
Molecular function	protein binding ; protein phosphatase binding ; calcium-activated potassium channel activity ; potassium channel activity ; calmodulin binding ; small conductance calcium-activated potassium channel activity ; Intermediate conductance calcium-activated potassium channel activity ;
Cellular component	integral component of membrane ; membrane ; voltage-gated potassium channel complex ; plasma membrane ; vesicle ; neuronal cell body ; neuron projection ;
Biological process	calcium ion transport ; positive regulation of protein secretion ; cell volume homeostasis ; potassium ion transport ; saliva secretion ; ion transport ; positive regulation of T cell receptor signaling pathway ; immune system process ; defense response ; phospholipid translocation ; stabilization of membrane potential ; potassium ion transmembrane transport ;
	Sources:Amigo / QuickGO
Orthologs
	3783
	16534
	ENSG00000104783
	ENSMUSG00000054342
	O15554
	O89109
	NM_002250
	NM_001163510 ; NM_008433
	NP_002241
	NP_001156982 ; NP_032459
	Wikidata
View/Edit Human	View/Edit Mouse

Last updated January 12, 2023

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.^[5]

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.^[5]

History

The channel activity was first described in 1958 by György Gárdos in human erythrocytes.^[6] The channel is also named Gardos channel because of its discoverer.

Related Research Articles

Calcium-activated potassium channels are potassium channels gated by calcium, or that are structurally or phylogenetically related to calcium gated channels. They were first discovered in 1958 by Gardos who saw that calcium levels inside of a cell could affect the permeability of potassium through that cell membrane. Then in 1970, Meech was the first to observe that intracellular calcium could trigger potassium currents. In humans they are divided into three subtypes: large conductance or BK channels, which have very high conductance which range from 100 to 300 pS, intermediate conductance or IK channels, with intermediate conductance ranging from 25 to 100 pS, and small conductance or SK channels with small conductances from 2-25 pS.

K_v7.3 (KvLQT3) is a potassium channel protein coded for by the gene KCNQ3.

SK3 also known as K_Ca2.3 is a protein that in humans is encoded by the KCNN3 gene.

Calcium-activated potassium channel subunit alpha-1 also known as large conductance calcium-activated potassium channel, subfamily M, alpha member 1 (K_Ca1.1), or BK channel alpha subunit, is a voltage gated potassium channel encoded by the KCNMA1 gene and characterized by their large conductance of potassium ions (K+) through cell membranes.

Potassium voltage-gated channel subfamily D member 2 is a protein that in humans is encoded by the KCND2 gene. It contributes to the cardiac transient outward potassium current (I_to1), the main contributing current to the repolarizing phase 1 of the cardiac action potential.

Calcium/calmodulin-dependent protein kinase type 1 is an enzyme that in humans is encoded by the CAMK1 gene.

Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 is a protein that in humans is encoded by the GNG2 gene.

G protein-activated inward rectifier potassium channel 2 is a protein that in humans is encoded by the KCNJ6 gene. Mutation in KCNJ6 gene has been proposed to be the cause of Keppen-Lubinsky Syndrome (KPLBS).

Chloride channel accessory 1 is a protein that in humans is encoded by the CLCA1 gene.

Potassium voltage-gated channel, shaker-related subfamily, member 3, also known as KCNA3 or K_v1.3, is a protein that in humans is encoded by the KCNA3 gene.

Chloride channel accessory 2 is a protein that in humans is encoded by the CLCA2 gene.

Calcium-activated potassium channel subunit beta-2 is a protein that in humans is encoded by the KCNMB2 gene.

Calcium-activated potassium channel subunit beta-3 is a protein that in humans is encoded by the KCNMB3 gene.

Potassium intermediate/small conductance calcium-activated channel, subfamily N, member 2, also known as KCNN2, is a protein which in humans is encoded by the KCNN2 gene. KCNN2 is an ion channel protein also known as K_Ca2.2.

Potassium voltage-gated channel subfamily KQT member 5 is a protein that in humans is encoded by the KCNQ5 gene.

Potassium intermediate/small conductance calcium-activated channel, subfamily N, member 1 , also known as KCNN1 is a human gene encoding the K_Ca2.1 protein.

Calcium-activated potassium channel subunit beta-4 is a protein that in humans is encoded by the KCNMB4 gene.

Potassium voltage-gated channel subfamily G member 3 is a protein that in humans is encoded by the KCNG3 gene. The protein encoded by this gene is a voltage-gated potassium channel subunit.

Potassium channel, subfamily U, member 1, also known as KCNU1, is a gene encoding the K_Ca5.1 protein.

Stichodactyla toxin is a 35-residue basic peptide from the sea anemone Stichodactyla helianthus that blocks a number of potassium channels. Related peptides form a conserved family of protein domains known as the ShkT domain. Another well-studied toxin of the family is BgK from Bunodosoma granulifera.

References

1 2 3 GRCh38: Ensembl release 89: ENSG00000104783 - Ensembl, May 2017
1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000054342 - Ensembl, May 2017
↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
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. S2CID 8290401.
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. Bibcode:1997PNAS...9411651I. 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. Bibcode:1997PNAS...9411013J. 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. Bibcode:2000PNAS...97.4832L. 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. Bibcode:2000PNAS...97.8151W. 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. Bibcode:2003PNAS..100.7366H. 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. S2CID 20530729.
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.

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[refGRCh38Ensembl-1] 1 2 3 GRCh38: Ensembl release 89: ENSG00000104783 - Ensembl, May 2017

[refGRCm38Ensembl-2] 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000054342 - Ensembl, May 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[entrez-5] 1 2 "Entrez Gene: KCNN4 potassium intermediate/small conductance calcium-activated channel, subfamily N, member 4".

[pmid13618284-6] 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.

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KCNN4

Contents

Function

History

See also

Related Research Articles

References

Further reading