KCNN2

KCNN2
Identifiers
Aliases	KCNN2 , KCa2.2, SK2, SKCA2, SKCa 2, hSK2, potassium calcium-activated channel subfamily N member 2, DYT34, NEDMAB
External IDs	OMIM: 605879 HomoloGene: 23150 GeneCards: KCNN2
Gene location (Human)
Chr.	Chromosome 5 (human)
End	114,496,500 bp
RNA expression pattern
	Top expressed in
	secondary oocyte; ; right adrenal gland; ; left adrenal gland; ; Region I of hippocampus proper; ; Brodmann area 23; ; middle temporal gyrus; ; right lobe of liver; ; cerebellar vermis; ; right ventricle; ; spinal cord;
	n/a
	More reference expression data
	More reference expression data
Gene ontology
Molecular function	protein homodimerization activity ; protein domain specific binding ; calcium-activated potassium channel activity ; calmodulin binding ; alpha-actinin binding ; protein binding ; small conductance calcium-activated potassium channel activity ;
Cellular component	integral component of membrane ; membrane ; cell surface ; neuronal cell body ; plasma membrane ; Z disc ; dendritic spine ; neuron projection ;
Biological process	ion transport ; potassium ion transport ; regulation of potassium ion transmembrane transport ; potassium ion transmembrane transport ; membrane repolarization during atrial cardiac muscle cell action potential ;
	Sources:Amigo / QuickGO
Orthologs
	3781
	n/a
	ENSG00000080709
	n/a
	Q9H2S1
	n/a
	NM_001278204 ; NM_021614 ; NM_170775 ; NM_001372233
	n/a
	NP_001265133 ; NP_067627 ; NP_740721 ; NP_001359162
	n/a
	Wikidata
View/Edit Human

Last updated August 13, 2023

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.^[3] KCNN2 is an ion channel protein also known as K_Ca2.2.^[4]

Function

Action potentials in vertebrate neurons are followed by an afterhyperpolarization (AHP) that may persist for several seconds and may have profound consequences for the firing pattern of the neuron. Each component of the AHP is kinetically distinct and is mediated by different calcium-activated potassium channels. The K_Ca2.2 protein is activated before membrane hyperpolarization and is thought to regulate neuronal excitability by contributing to the slow component of synaptic AHP. K_Ca2.2 is an integral membrane protein that forms a voltage-independent calcium-activated channel with three other calmodulin-binding subunits. This protein is a member of the calcium-activated potassium channel family. Two transcript variants encoding different isoforms have been found for the KCNN2 gene.^[4]

In a 2009 study, SK2 (KCNN2) potassium channel was overexpressed in the basolateral amygdala using a herpes simplex viral system. This reduced anxiety and stress-induced corticosterone secretion at a systemic level. SK2 overexpression also reduced dendritic arborization of the amygdala neurons.^[5] In a 2015 study, it was found that UBE3A, the protein maternally deleted in Angelman syndrome, marks KCNN2 for degradation in the hippocampus, and that UBE3A deficiency is associated with an increase in KCNN2 levels. KCNN2 operates through a negative feedback loop to reduce glutamatergic NMDA receptor activation when it itself is activated by that same receptor. Angelman syndrome therefore leads to a reduction in glutamatergic NMDA receptor activation, which impairs long-term potentiation of hippocampal neurons and thus fear conditioning.^[6]

Related Research Articles

BK channels (big potassium), are large conductance calcium-activated potassium channels, also known as Maxi-K, slo1, or Kca1.1. BK channels are voltage-gated potassium channels that conduct large amounts of potassium ions (K⁺) across the cell membrane, hence their name, big potassium. These channels can be activated (opened) by either electrical means, or by increasing Ca²⁺ concentrations in the cell. BK channels help regulate physiological processes, such as circadian behavioral rhythms and neuronal excitability. BK channels are also involved in many processes in the body, as it is a ubiquitous channel. They have a tetrameric structure that is composed of a transmembrane domain, voltage sensing domain, potassium channel domain, and a cytoplasmic C-terminal domain, with many X-ray structures for reference. Their function is to repolarize the membrane potential by allowing for potassium to flow outward, in response to a depolarization or increase in calcium levels.

Potassium channels are the most widely distributed type of ion channel found in virtually all organisms. They form potassium-selective pores that span cell membranes. Potassium channels are found in most cell types and control a wide variety of cell functions.

<span class="mw-page-title-main">Repolarization</span>

In neuroscience, repolarization refers to the change in membrane potential that returns it to a negative value just after the depolarization phase of an action potential which has changed the membrane potential to a positive value. The repolarization phase usually returns the membrane potential back to the resting membrane potential. The efflux of potassium (K⁺) ions results in the falling phase of an action potential. The ions pass through the selectivity filter of the K⁺ channel pore.

Calcium signaling is the use of calcium ions (Ca²⁺) to communicate and drive intracellular processes often as a step in signal transduction. Ca²⁺ is important for cellular signalling, for once it enters the cytosol of the cytoplasm it exerts allosteric regulatory effects on many enzymes and proteins. Ca²⁺ can act in signal transduction resulting from activation of ion channels or as a second messenger caused by indirect signal transduction pathways such as G protein-coupled receptors.

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.

The K_ir2.1 inward-rectifier potassium channel is a lipid-gated ion channel encoded by the KCNJ2 gene.

SK channels are a subfamily of calcium-activated potassium channels. They are so called because of their small single channel conductance in the order of 10 pS. SK channels are a type of ion channel allowing potassium cations to cross the cell membrane and are activated (opened) by an increase in the concentration of intracellular calcium through N-type calcium channels. Their activation limits the firing frequency of action potentials and is important for regulating afterhyperpolarization in the neurons of the central nervous system as well as many other types of electrically excitable cells. This is accomplished through the hyperpolarizing leak of positively charged potassium ions along their concentration gradient into the extracellular space. This hyperpolarization causes the membrane potential to become more negative. SK channels are thought to be involved in synaptic plasticity and therefore play important roles in learning and memory.

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

The transmembrane cation channel superfamily was defined in InterPro and Pfam as the family of tetrameric ion channels. These include the sodium, potassium, calcium, ryanodine receptor, HCN, CNG, CatSper, and TRP channels. This large group of ion channels apparently includes families 1.A.1, 1.A.2, 1.A.3, and 1.A.4 of the TCDB transporter classification.

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

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.

Potassium voltage-gated channel, Shab-related subfamily, member 1, also known as KCNB1 or K_v2.1, is a protein that, in humans, is encoded by the KCNB1 gene.

Potassium channel subfamily K member 3 is a protein that in humans is encoded by the KCNK3 gene.

Potassium channel subfamily K member 4 is a protein that in humans is encoded by the KCNK4 gene. KCNK4 protein channels are also called TRAAK channels.

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

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.

Potassium channel subfamily T, member 1, also known as KCNT1 is a human gene that encodes the K_Ca4.1 protein. K_Ca4.1 is a member of the calcium-activated potassium channel protein family

References

1 2 3 GRCh38: Ensembl release 89: ENSG00000080709 - Ensembl, May 2017
↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑ Wei AD, Gutman GA, Aldrich R, Chandy KG, Grissmer S, Wulff H (December 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.
1 2 "Entrez Gene: KCNN2 potassium intermediate/small conductance calcium-activated channel, subfamily N, member 2".
↑ Mitra R, Ferguson D, Sapolsky RM (February 2009). "SK2 potassium channel over-expression in basolateral amygdala reduces anxiety, stress-induced corticosterone and dendritic arborization". Mol. Psychiatry. 14 (9): 847–55, 827. doi:10.1038/mp.2009.9. PMC 2763614 . PMID 19204724.
↑ Sun, Jiandong; Zhu, Guoqi; Liu, Yan; Standley, Steve; Ji, Angela; Tunuguntla, Rashmi; Wang, Yubin; Claus, Chad; Luo, Yun; Baudry, Michel; Bi, Xiaoning (2015-07-21). "UBE3A Regulates Synaptic Plasticity and Learning and Memory by Controlling SK2 Channel Endocytosis". Cell Reports. 12 (3): 449–461. doi:10.1016/j.celrep.2015.06.023. ISSN 2211-1247. PMC 4520703 . PMID 26166566.

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. S2CID 8290401.
Jäger H, Adelman JP, Grissmer S (2000). "SK2 encodes the apamin-sensitive Ca²⁺-activated K⁺ channels in the human leukemic T cell line, Jurkat". FEBS Lett. 469 (2–3): 196–202. doi: 10.1016/S0014-5793(00)01236-9 . PMID 10713270. S2CID 44455392.
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. Bibcode:2000PNAS...97.4832L. doi: 10.1073/pnas.090521697 . PMC 18318 . PMID 10758170.
Desai R, Peretz A, Idelson H, et al. (2001). "Ca²⁺-activated K⁺ channels in human leukemic Jurkat T cells. Molecular cloning, biochemical and functional characterization". J. Biol. Chem. 275 (51): 39954–63. doi: 10.1074/jbc.M001562200 . PMID 10991935.
Rimini R, Rimland JM, Terstappen GC (2001). "Quantitative expression analysis of the small conductance calcium-activated potassium channels, SK1, SK2 and SK3, in human brain". Brain Res. Mol. Brain Res. 85 (1–2): 218–20. doi: 10.1016/S0169-328X(00)00255-2 . PMID 11146124.
Schumacher MA, Rivard AF, Bächinger HP, Adelman JP (2001). "Structure of the gating domain of a Ca²⁺-activated K⁺ channel complexed with Ca²⁺/calmodulin". Nature. 410 (6832): 1120–4. Bibcode:2001Natur.410.1120S. doi:10.1038/35074145. PMID 11323678. S2CID 205016620.
Miller MJ, Rauer H, Tomita H, et al. (2001). "Nuclear localization and dominant-negative suppression by a mutant SKCa3 N-terminal channel fragment identified in a patient with schizophrenia". J. Biol. Chem. 276 (30): 27753–6. doi: 10.1074/jbc.C100221200 . PMID 11395478.
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. Bibcode:2002PNAS...9916899M. doi: 10.1073/pnas.242603899 . PMC 139241 . PMID 12477932.
Piotrowska AP, Solari V, Puri P (2003). "Distribution of Ca²⁺-activated K channels, SK2 and SK3, in the normal and Hirschsprung's disease bowel". J. Pediatr. Surg. 38 (6): 978–83. doi:10.1016/S0022-3468(03)00138-6. PMID 12778407.
Xu Y, Tuteja D, Zhang Z, et al. (2004). "Molecular identification and functional roles of a Ca²⁺-activated K⁺ channel in human and mouse hearts". J. Biol. Chem. 278 (49): 49085–94. doi: 10.1074/jbc.M307508200 . PMID 13679367.
Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. doi: 10.1038/ng1285 . PMID 14702039.
Feranchak AP, Doctor RB, Troetsch M, et al. (2004). "Calcium-dependent regulation of secretion in biliary epithelial cells: the role of apamin-sensitive SK channels". Gastroenterology. 127 (3): 903–13. doi:10.1053/j.gastro.2004.06.047. PMID 15362045.
Tajima N, Schönherr K, Niedling S, et al. (2006). "Ca²⁺-activated K⁺ channels in human melanoma cells are up-regulated by hypoxia involving hypoxia-inducible factor-1α and the von Hippel-Lindau protein". J. Physiol. 571 (Pt 2): 349–59. doi:10.1113/jphysiol.2005.096818. PMC 1796787 . PMID 16396931.
Lu L, Zhang Q, Timofeyev V, et al. (2007). "Molecular coupling of a Ca²⁺-activated K⁺ channel to L-type Ca²⁺ channels via alpha-actinin2". Circ. Res. 100 (1): 112–20. doi: 10.1161/01.RES.0000253095.44186.72 . PMID 17110593.
Morimoto T, Ohya S, Hayashi H, et al. (2007). "Cell-cycle-dependent regulation of Ca²⁺-activated K⁺ channel in Jurkat T-lymphocyte". J. Pharmacol. Sci. 104 (1): 94–8. doi: 10.1254/jphs.SC0070032 . PMID 17452806.
Dolga AM, Terpolilli N, Kepura F, et al. (2011). "KCa2 channels activation prevents [Ca²⁺]i deregulation and reduces neuronal death following glutamate toxicity and cerebral ischemia". Cell Death Dis. 2 (e147): e147. doi:10.1038/cddis.2011.30. PMC 3122061 . PMID 21509037.

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[refGRCh38Ensembl-1] 1 2 3 GRCh38: Ensembl release 89: ENSG00000080709 - Ensembl, May 2017

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

[pmid16382103-3] Wei AD, Gutman GA, Aldrich R, Chandy KG, Grissmer S, Wulff H (December 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.

[entrez-4] 1 2 "Entrez Gene: KCNN2 potassium intermediate/small conductance calcium-activated channel, subfamily N, member 2".

[pmid19204724-5] Mitra R, Ferguson D, Sapolsky RM (February 2009). "SK2 potassium channel over-expression in basolateral amygdala reduces anxiety, stress-induced corticosterone and dendritic arborization". Mol. Psychiatry. 14 (9): 847–55, 827. doi:10.1038/mp.2009.9. PMC 2763614 . PMID 19204724.

[6] Sun, Jiandong; Zhu, Guoqi; Liu, Yan; Standley, Steve; Ji, Angela; Tunuguntla, Rashmi; Wang, Yubin; Claus, Chad; Luo, Yun; Baudry, Michel; Bi, Xiaoning (2015-07-21). "UBE3A Regulates Synaptic Plasticity and Learning and Memory by Controlling SK2 Channel Endocytosis". Cell Reports. 12 (3): 449–461. doi:10.1016/j.celrep.2015.06.023. ISSN 2211-1247. PMC 4520703 . PMID 26166566.

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KCNN2

Contents

Function

See also

Related Research Articles

References

Further reading