KCNA2 explained

Potassium voltage-gated channel subfamily A member 2 also known as K_v1.2 is a protein that in humans is encoded by the KCNA2 gene.^{[1] [2]}

Function

Potassium channels represent the most complex class of voltage-gated ion channels from both functional and structural standpoints. Their diverse functions include regulating neurotransmitter release, heart rate, insulin secretion, neuronal excitability, epithelial electrolyte transport, smooth muscle contraction, and cell volume. Four sequence-related potassium channel genes - shaker, shaw, shab, and shal - have been identified in Drosophila, and each has been shown to have human homolog(s). This gene encodes a member of the potassium channel, voltage-gated, shaker-related subfamily. This member contains six membrane-spanning domains with a shaker-type repeat in the fourth segment. It belongs to the delayed rectifier class, members of which allow nerve cells to efficiently repolarize following an action potential. The coding region of this gene is intronless, and the gene is clustered with genes KCNA3 and KCNA10 on chromosome 1.

Interactions

KCNA2 has been shown to interact with KCNA4,^[3] DLG4,^[4] PTPRA,^[5] KCNAB2,^{[3] [6]} RHOA^[7] and Cortactin.^[8]

Clinical

Mutations in this gene have been associated with hereditary spastic paraplegia.^[9]

See also

• Voltage-gated potassium channel
• Pandinotoxin

Further reading

• Paulmichl M, Nasmith P, Hellmiss R, Reed K, Boyle WA, Nerbonne JM, Peralta EG, Clapham DE . Cloning and expression of a rat cardiac delayed rectifier potassium channel . Proceedings of the National Academy of Sciences of the United States of America . 88 . 17 . 7892–5 . September 1991 . 1715584 . 52410 . 10.1073/pnas.88.17.7892 . 1991PNAS...88.7892P . free .
• Grissmer S, Dethlefs B, Wasmuth JJ, Goldin AL, Gutman GA, Cahalan MD, Chandy KG . Expression and chromosomal localization of a lymphocyte K+ channel gene . Proceedings of the National Academy of Sciences of the United States of America . 87 . 23 . 9411–5 . December 1990 . 2251283 . 55175 . 10.1073/pnas.87.23.9411 . 1990PNAS...87.9411G . free .
• McKinnon D . Isolation of a cDNA clone coding for a putative second potassium channel indicates the existence of a gene family . The Journal of Biological Chemistry . 264 . 14 . 8230–6 . May 1989 . 10.1016/S0021-9258(18)83173-8 . 2722779 . free .
• Kim E, Niethammer M, Rothschild A, Jan YN, Sheng M . Clustering of Shaker-type K+ channels by interaction with a family of membrane-associated guanylate kinases . Nature . 378 . 6552 . 85–8 . November 1995 . 7477295 . 10.1038/378085a0 . 1995Natur.378...85K . 4362906 .
• Klocke R, Roberds SL, Tamkun MM, Gronemeier M, Augustin A, Albrecht B, Pongs O, Jockusch H . Chromosomal mapping in the mouse of eight K(+)-channel genes representing the four Shaker-like subfamilies Shaker, Shab, Shaw, and Shal . Genomics . 18 . 3 . 568–74 . December 1993 . 7905852 . 10.1016/S0888-7543(05)80358-1 .
• Ramaswami M, Tanouy M, Mathew MK . Facile formation of heteromultimeric potassium channels by expression of cloned human cDNAs . Indian Journal of Biochemistry & Biophysics . 31 . 4 . 254–60 . August 1994 . 8002006 .
• Nakahira K, Shi G, Rhodes KJ, Trimmer JS . Selective interaction of voltage-gated K+ channel beta-subunits with alpha-subunits . The Journal of Biological Chemistry . 271 . 12 . 7084–9 . March 1996 . 8636142 . 10.1074/jbc.271.12.7084 . free .
• Adda S, Fleischmann BK, Freedman BD, Yu M, Hay DW, Kotlikoff MI . Expression and function of voltage-dependent potassium channel genes in human airway smooth muscle . The Journal of Biological Chemistry . 271 . 22 . 13239–43 . May 1996 . 8662756 . 10.1074/jbc.271.22.13239 . free .
• Bonaldo MF, Lennon G, Soares MB . Normalization and subtraction: two approaches to facilitate gene discovery . Genome Research . 6 . 9 . 791–806 . September 1996 . 8889548 . 10.1101/gr.6.9.791 . free .
• Kim E, Sheng M . Differential K+ channel clustering activity of PSD-95 and SAP97, two related membrane-associated putative guanylate kinases . Neuropharmacology . 35 . 7 . 993–1000 . 1997 . 8938729 . 10.1016/0028-3908(96)00093-7 . 23755452 .
• Cachero TG, Morielli AD, Peralta EG . The small GTP-binding protein RhoA regulates a delayed rectifier potassium channel . Cell . 93 . 6 . 1077–85 . June 1998 . 9635436 . 10.1016/S0092-8674(00)81212-X . 13943167 . free .
• Tsai W, Morielli AD, Cachero TG, Peralta EG . Receptor protein tyrosine phosphatase alpha participates in the m1 muscarinic acetylcholine receptor-dependent regulation of Kv1.2 channel activity . The EMBO Journal . 18 . 1 . 109–18 . January 1999 . 9878055 . 1171107 . 10.1093/emboj/18.1.109 .
• Coleman SK, Newcombe J, Pryke J, Dolly JO . Subunit composition of Kv1 channels in human CNS . Journal of Neurochemistry . 73 . 2 . 849–58 . August 1999 . 10428084 . 10.1046/j.1471-4159.1999.0730849.x . free .
• D'Adamo MC, Imbrici P, Sponcichetti F, Pessia M . Mutations in the KCNA1 gene associated with episodic ataxia type-1 syndrome impair heteromeric voltage-gated K(+) channel function . FASEB Journal . 13 . 11 . 1335–45 . August 1999 . 10428758 . 10.1096/fasebj.13.11.1335. 12876970 . free .
• Wade GR, Laurier LG, Preiksaitis HG, Sims SM . Delayed rectifier and Ca(2+)-dependent K(+) currents in human esophagus: roles in regulating muscle contraction . The American Journal of Physiology . 277 . 4 Pt 1 . G885–95 . October 1999 . 10516156 . 10.1152/ajpgi.1999.277.4.g885.
• Poliak S, Gollan L, Martinez R, Custer A, Einheber S, Salzer JL, Trimmer JS, Shrager P, Peles E . Caspr2, a new member of the neurexin superfamily, is localized at the juxtaparanodes of myelinated axons and associates with K+ channels . Neuron . 24 . 4 . 1037–47 . December 1999 . 10624965 . 10.1016/S0896-6273(00)81049-1 . 12444497 . free .
• Manganas LN, Trimmer JS . Subunit composition determines Kv1 potassium channel surface expression . The Journal of Biological Chemistry . 275 . 38 . 29685–93 . September 2000 . 10896669 . 10.1074/jbc.M005010200 . free .
• Kuryshev YA, Wible BA, Gudz TI, Ramirez AN, Brown AM . KChAP/Kvbeta1.2 interactions and their effects on cardiac Kv channel expression . American Journal of Physiology. Cell Physiology . 281 . 1 . C290–9 . July 2001 . 11401852 . 10.1152/ajpcell.2001.281.1.c290 . 2308556 .
• Byron KL, Lucchesi PA . Signal transduction of physiological concentrations of vasopressin in A7r5 vascular smooth muscle cells. A role for PYK2 and tyrosine phosphorylation of K+ channels in the stimulation of Ca2+ spiking . The Journal of Biological Chemistry . 277 . 9 . 7298–307 . March 2002 . 11739373 . 10.1074/jbc.M104726200 . free .

Notes and References

1. Gutman GA, Chandy KG, Grissmer S, Lazdunski M, McKinnon D, Pardo LA, Robertson GA, Rudy B, Sanguinetti MC, Stühmer W, Wang X . International Union of Pharmacology. LIII. Nomenclature and molecular relationships of voltage-gated potassium channels . Pharmacological Reviews . 57 . 4 . 473–508 . December 2005 . 16382104 . 10.1124/pr.57.4.10 . 219195192 .
2. Web site: Entrez Gene: KCNA2 potassium voltage-gated channel, shaker-related subfamily, member 2.
3. Coleman SK, Newcombe J, Pryke J, Dolly JO . Subunit composition of Kv1 channels in human CNS . Journal of Neurochemistry . 73 . 2 . 849–58 . August 1999 . 10428084 . 10.1046/j.1471-4159.1999.0730849.x . free .
4. Eldstrom J, Doerksen KW, Steele DF, Fedida D . N-terminal PDZ-binding domain in Kv1 potassium channels . FEBS Letters . 531 . 3 . 529–37 . November 2002 . 12435606 . 10.1016/S0014-5793(02)03572-X . 40689829 . 2002FEBSL.531..529E .
5. Tsai W, Morielli AD, Cachero TG, Peralta EG . Receptor protein tyrosine phosphatase alpha participates in the m1 muscarinic acetylcholine receptor-dependent regulation of Kv1.2 channel activity . The EMBO Journal . 18 . 1 . 109–18 . January 1999 . 9878055 . 1171107 . 10.1093/emboj/18.1.109 .
6. Nakahira K, Shi G, Rhodes KJ, Trimmer JS . Selective interaction of voltage-gated K+ channel beta-subunits with alpha-subunits . The Journal of Biological Chemistry . 271 . 12 . 7084–9 . March 1996 . 8636142 . 10.1074/jbc.271.12.7084 . free .
7. Cachero TG, Morielli AD, Peralta EG . The small GTP-binding protein RhoA regulates a delayed rectifier potassium channel . Cell . 93 . 6 . 1077–85 . June 1998 . 9635436 . 10.1016/S0092-8674(00)81212-X . 13943167 . free .
8. Hattan D, Nesti E, Cachero TG, Morielli AD . Tyrosine phosphorylation of Kv1.2 modulates its interaction with the actin-binding protein cortactin . The Journal of Biological Chemistry . 277 . 41 . 38596–606 . October 2002 . 12151401 . 10.1074/jbc.M205005200 . free .
9. Helbig KL, Hedrich UB, Shinde DN, Krey I, Teichmann AC, Hentschel J, Schubert J, Chamberlin AC, Huether R, Lu HM, Alcaraz WA, Tang S, Jungbluth C, Dugan SL, Vainionpää L, Karle KN, Synofzik M, Schöls L, Schüle R, Lehesjoki AE, Helbig I, Lerche H, Lemke JR . A recurrent mutation in KCNA2 as a novel cause of hereditary spastic paraplegia and ataxia . Annals of Neurology . 80 . 4 . October 2016 . 638–642 . 27543892 . 5129488 . 10.1002/ana.24762 .