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; MGI: 2153182; HomoloGene: 23150; GeneCards: KCNN2; OMA:KCNN2 - orthologs
Gene location (Human) Chr. Chromosome 5 (human) Band 5q22.3 Start 114,055,926 bp End 114,496,500 bp
Gene location (Mouse) Chr. Chromosome 18 (mouse) Band 18|18 B3-C Start 45,268,860 bp End 45,686,024 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in secondary oocyte right adrenal gland right adrenal cortex left adrenal gland left adrenal cortex Region I of hippocampus proper Brodmann area 23 middle temporal gyrus gonad testicle Top expressed in adrenal gland dentate gyrus of hippocampal formation granule cell primary visual cortex cerebellar cortex subiculum Region I of hippocampus proper hippocampus proper lateral geniculate nucleus primary motor cortex superior frontal gyrus More reference expression data BioGPS 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 soma plasma membrane Z discdkac 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 Species Human Mouse Entrez 3781 140492 Ensembl ENSG00000080709 ENSMUSG00000054477 UniProt Q9H2S1 P58390 RefSeq (mRNA) NM_001278204 NM_021614 NM_170775 NM_001372233 NM_080465 NM_001312905 RefSeq (protein) NP_001265133 NP_067627 NP_740721 NP_001359162 NP_001299834 NP_536713 Location (UCSC) Chr 5: 114.06 – 114.5 Mb Chr 18: 45.27 – 45.69 Mb PubMed search
Wikidata
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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.

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.

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. 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.

See also

• SK channel
• Voltage-gated potassium channel

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. 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.

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