View source for Kv1.1

{{Short description|Protein-coding gene in the species Homo sapiens}}
{{cs1 config|name-list-style=vanc|display-authors=6}}
{{distinguish|KV-1}}
{{Infobox_gene}}

'''Potassium voltage-gated channel subfamily A member 1''' also known as '''K<sub>v</sub>1.1''' is a [[shaker gene|shaker related]] [[voltage-gated potassium channel]] that in humans is encoded by the ''KCNA1'' [[gene]].<ref name="pmid1349297">{{cite journal | vauthors = Curran ME, Landes GM, Keating MT | title = Molecular cloning, characterization, and genomic localization of a human potassium channel gene | journal = Genomics | volume = 12 | issue = 4 | pages = 729–737 | date = April 1992 | pmid = 1349297 | doi = 10.1016/0888-7543(92)90302-9 }}</ref><ref name="pmid8821794">{{cite journal | vauthors = Albrecht B, Weber K, Pongs O | title = Characterization of a voltage-activated K-channel gene cluster on human chromosome 12p13 | journal = Receptors & Channels | volume = 3 | issue = 3 | pages = 213–220 | year = 1995 | pmid = 8821794 }}</ref><ref name="pmid16382104">{{cite journal | vauthors = Gutman GA, Chandy KG, Grissmer S, Lazdunski M, McKinnon D, Pardo LA, Robertson GA, Rudy B, Sanguinetti MC, Stühmer W, Wang X | title = International Union of Pharmacology. LIII. Nomenclature and molecular relationships of voltage-gated potassium channels | journal = Pharmacological Reviews | volume = 57 | issue = 4 | pages = 473–508 | date = December 2005 | pmid = 16382104 | doi = 10.1124/pr.57.4.10 | s2cid = 219195192 }}</ref> [[Isaacs syndrome]] is a result of an [[autoimmune]] reaction against the K<sub>v</sub>1.1 ion channel.<ref name="pmid9616766">{{cite journal | vauthors = Newsom-Davis J | title = Autoimmune neuromyotonia (Isaacs' syndrome): an antibody-mediated potassium channelopathy | journal = Annals of the New York Academy of Sciences | volume = 835 | issue = 1 | pages = 111–119 | date = December 1997 | pmid = 9616766 | doi = 10.1111/j.1749-6632.1997.tb48622.x | s2cid = 13231594 | bibcode = 1997NYASA.835..111N }}{{Dead link|date=February 2020 |bot=InternetArchiveBot |fix-attempted=yes }}</ref>

== Genomics ==

The gene is located on the Watson (plus) strand of the short arm of [[chromosome 12]] (12p13.32). The gene itself is 8,348 bases in length and encodes a protein of 495 amino acids (predicted molecular weight 56.466 kilo[[Dalton (unit)|dalton]]s).

== Alternative names ==

The recommended name for this protein is potassium voltage-gated channel subfamily A member 1 but a number of alternatives have been used in the literature including HuK1 (human K<sup>+</sup> channel I), RBK1 (rubidium potassium channel 1), MBK ([[mouse brain]] K<sup>+</sup> channel), voltage gated potassium channel HBK1, voltage gated potassium channel subunit K<sub>v</sub>1.1, voltage-gated K<sup>+</sup> channel HuKI and AEMK (associated with [[myokymia]] with periodic ataxia).

== Structure ==

The [[protein]] is believed to have six domains (S1-S6) with the loop between S5 and S6 forming the channel pore. This region also has a conserved selectivity filter motif. The functional channel is a homotetramer. The N-terminus of the protein associates with β subunits. These subunits regulate channel inactivation as well as its expression. The [[C-terminus]] is associated with a [[PDZ domain]] protein involved in channel targeting.<ref name="entrez">{{cite web | title = Entrez Gene: KCNA1 potassium voltage-gated channel | url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=3736}}</ref><ref>{{cite web|url=https://www.uniprot.org/uniprot/Q09470#section_comments|title=KCNA1 - Potassium voltage-gated channel subfamily A member 1 - Homo sapiens (Human) - KCNA1 gene & protein|website=www.uniprot.org}}</ref>

== Function ==

The protein functions as a potassium selective channel through which the potassium ion may pass in consensus with the electrochemical gradient. They play a role in repolarisation of membranes.<ref name="entrez"/>

== RNA editing ==

The pre-mRNA of this protein is subject to [[RNA editing]].<ref name="pmid15361858">{{cite journal | vauthors = Bhalla T, Rosenthal JJ, Holmgren M, Reenan R | title = Control of human potassium channel inactivation by editing of a small mRNA hairpin | journal = Nature Structural & Molecular Biology | volume = 11 | issue = 10 | pages = 950–956 | date = October 2004 | pmid = 15361858 | doi = 10.1038/nsmb825 | s2cid = 34081059 }}</ref>

=== Type ===

'''A to I''' RNA editing is catalyzed by a family of [[adenosine deaminase]]s acting on RNA (ADARs) that specifically recognize adenosines within double-stranded regions of pre-mRNAs (e.g. [[Potassium channel RNA editing signal]]) and deaminate them to [[inosine]]. Inosines are recognised as guanosine by the cells translational machinery. There are three members of the ADAR family ADARs 1-3 with [[ADAR|ADAR1]]  and [[ADARB1|ADAR2]] being the only enzymatically active members. [[ADARB2|ADAR3]] is thought to have a regulatory role in the brain. ADAR1 and ADAR2 are widely expressed in tissues while ADAR3 is restricted to the brain. The double stranded regions of RNA are formed by base-pairing between residues in the region close to the editing site with residues usually in a neighboring intron but can sometimes be an exonic sequence too. The region that base pairs with the editing region is known as an Editing Complementary Sequence (ECS).

=== Location ===

The modified residue is found at amino acid 400 of the final protein. This is located in the sixth [[transmembrane protein|transmembrane]] region found, which corresponds to the inner vestibule of the pore. A stem loop hairpin structure mediates the RNA editing. [[ADARB1|ADAR2]] is likely to be the preferred editing enzyme at the I/V site. Editing results in a codon alteration from ATT to GTT, resulting in an amino acid change from [[isoleucine]] to [[valine]]. ADAR2 enzyme is the major editing enzyme. The MFOLD programme predicted that the minimum region required for editing would form an imperfect inverted repeat [[stem-loop|hairpin]]. This region is composed of a 114 base pairs. Similar regions have been identified in mouse and rat. The edited adenosine is found in a 6-base pair duplex region. Mutation experiment in the region near the 6-base pair duplex have shown that the specific bases in this region were also essential for editing to occur. The region required for editing is unusual in that the hairpin structure is formed by [[exon]]ic sequences only. In the majority of A to I editing the ECS is found within an [[intron]]ic sequence.<ref name="pmid15361858"/>

=== Conservation ===
The editing is highly conserved having been observed in squid, fruit fly, mouse, and rat.<ref name="pmid15361858"/>

=== Regulation ===
Editing levels vary in different tissues: 17% in the [[caudate nucleus]], 68% in the [[spinal cord]], and 77% in the [[Medulla oblongata|medulla]].<ref name="pmid12907802">{{cite journal | vauthors = Hoopengardner B, Bhalla T, Staber C, Reenan R | title = Nervous system targets of RNA editing identified by comparative genomics | journal = Science | volume = 301 | issue = 5634 | pages = 832–836 | date = August 2003 | pmid = 12907802 | doi = 10.1126/science.1086763 | s2cid = 782642 | bibcode = 2003Sci...301..832H }}</ref>

=== Consequences ===

==== Structure ====

Editing results in a codon (I/V) change from (ATT) to (GTT) resulting in translation of a [[valine]] instead of an [[isoleucine]] at the position of the editing site. Valine has a larger side-chain. RNA editing at this position occurs at a highly conserved ion conducting pore of the channel.  This may affect the channels role in the process of fast inactivation.<ref name="BhallaRosenthal2004">{{cite journal | vauthors = Bhalla T, Rosenthal JJ, Holmgren M, Reenan R | title = Control of human potassium channel inactivation by editing of a small mRNA hairpin | journal = Nature Structural & Molecular Biology | volume = 11 | issue = 10 | pages = 950–956 | date = October 2004 | pmid = 15361858 | doi = 10.1038/nsmb825 | s2cid = 34081059 }}</ref>

==== Function ====

Voltage-dependent potassium channels modulate excitability by opening and closing a potassium selective pore in response to voltage. The flow of potassium ions is interrupted by interaction of an [[ball and chain inactivation|inactivating particle]], an auxiliary protein in humans but an intrinsic part of the channel in other species. The I to V amino acid change is thought to disrupt the hydrophobic interaction between the inactivating particle and the pore lining. This interrupts the process of fast inactivation. Activation kinetics are unaffected by RNA editing.<ref name="pmid15361858"/> Changes in inactivation kinetics affect the duration and frequency of the action potential. An edited channel passes more current and has a shorter action potential than the non-edited type due to the inability of the inactivating particle to interact with the residue in the ion-conducting pore of the channel. This was determined by electrophysiology analysis.<ref name="Bezanilla2004">{{cite journal | vauthors = Bezanilla F | title = RNA editing of a human potassium channel modifies its inactivation | journal = Nature Structural & Molecular Biology | volume = 11 | issue = 10 | pages = 915–916 | date = October 2004 | pmid = 15452561 | doi = 10.1038/nsmb1004-915 | s2cid = 40545616 | doi-access = free }}</ref> The length of time the membrane is depolarised is decreased, which also reduces the efficiency of transmitter release.<ref name="pmid12907802"/> Since editing can cause amino acid changes in 1- 4 in potassium channel tetramers, it can have a wide variety of effects on channel inactivation.

=== Dysregulation ===

Changes in the process of fast inactivation are known to have behavioral and neurological consequences in vivo.<ref name="pmid15361858"/>

== Clinical ==

Mutations in this gene cause [[episodic ataxia]] type 1.

== See also ==
*[[GABRA3]] - a channel subunit which undergoes similar RNA editing

== References ==
{{Reflist|2}}

== Further reading ==
{{refbegin | 2}}
* {{cite journal | vauthors = Grunnet M, Rasmussen HB, Hay-Schmidt A, Rosenstierne M, Klaerke DA, Olesen SP, Jespersen T | title = KCNE4 is an inhibitory subunit to Kv1.1 and Kv1.3 potassium channels | journal = Biophysical Journal | volume = 85 | issue = 3 | pages = 1525–1537 | date = September 2003 | pmid = 12944270 | pmc = 1303329 | doi = 10.1016/S0006-3495(03)74585-8 | bibcode = 2003BpJ....85.1525G }}
* {{cite journal | vauthors = Nie DY, Zhou ZH, Ang BT, Teng FY, Xu G, Xiang T, Wang CY, Zeng L, Takeda Y, Xu TL, Ng YK, Faivre-Sarrailh C, Popko B, Ling EA, Schachner M, Watanabe K, Pallen CJ, Tang BL, Xiao ZC | title = Nogo-A at CNS paranodes is a ligand of Caspr: possible regulation of K(+) channel localization | journal = The EMBO Journal | volume = 22 | issue = 21 | pages = 5666–5678 | date = November 2003 | pmid = 14592966 | pmc = 275427 | doi = 10.1093/emboj/cdg570 }}
* {{cite journal | vauthors = Imbrici P, Cusimano A, D'Adamo MC, De Curtis A, Pessia M | title = Functional characterization of an episodic ataxia type-1 mutation occurring in the S1 segment of hKv1.1 channels | journal = Pflugers Archiv | volume = 446 | issue = 3 | pages = 373–379 | date = June 2003 | pmid = 12799903 | doi = 10.1007/s00424-002-0962-2 | s2cid = 21478393 }}
* {{cite journal | vauthors = Glaudemans B, van der Wijst J, Scola RH, Lorenzoni PJ, Heister A, van der Kemp AW, Knoers NV, Hoenderop JG, Bindels RJ | title = A missense mutation in the Kv1.1 voltage-gated potassium channel-encoding gene KCNA1 is linked to human autosomal dominant hypomagnesemia | journal = The Journal of Clinical Investigation | volume = 119 | issue = 4 | pages = 936–942 | date = April 2009 | pmid = 19307729 | pmc = 2662556 | doi = 10.1172/JCI36948 }}
* {{cite journal | vauthors = Shook SJ, Mamsa H, Jen JC, Baloh RW, Zhou L | title = Novel mutation in KCNA1 causes episodic ataxia with paroxysmal dyspnea | journal = Muscle & Nerve | volume = 37 | issue = 3 | pages = 399–402 | date = March 2008 | pmid = 17912752 | doi = 10.1002/mus.20904 | s2cid = 26175513 }}
* {{cite journal | vauthors = Gubitosi-Klug RA, Mancuso DJ, Gross RW | title = The human Kv1.1 channel is palmitoylated, modulating voltage sensing: Identification of a palmitoylation consensus sequence | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 102 | issue = 17 | pages = 5964–5968 | date = April 2005 | pmid = 15837928 | pmc = 1087951 | doi = 10.1073/pnas.0501999102 | doi-access = free | bibcode = 2005PNAS..102.5964G }}
* {{cite journal | vauthors = Zhang ZH, Rhodes KJ, Childers WE, Argentieri TM, Wang Q | title = Disinactivation of N-type inactivation of voltage-gated K channels by an erbstatin analogue | journal = The Journal of Biological Chemistry | volume = 279 | issue = 28 | pages = 29226–29230 | date = July 2004 | pmid = 15136567 | doi = 10.1074/jbc.M403290200 | doi-access = free }}
* {{cite journal | vauthors = Kimura K, Wakamatsu A, Suzuki Y, Ota T, Nishikawa T, Yamashita R, Yamamoto J, Sekine M, Tsuritani K, Wakaguri H, Ishii S, Sugiyama T, Saito K, Isono Y, Irie R, Kushida N, Yoneyama T, Otsuka R, Kanda K, Yokoi T, Kondo H, Wagatsuma M, Murakawa K, Ishida S, Ishibashi T, Takahashi-Fujii A, Tanase T, Nagai K, Kikuchi H, Nakai K, Isogai T, Sugano S | title = Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes | journal = Genome Research | volume = 16 | issue = 1 | pages = 55–65 | date = January 2006 | pmid = 16344560 | pmc = 1356129 | doi = 10.1101/gr.4039406 }}
* {{cite journal | vauthors = Jow F, Zhang ZH, Kopsco DC, Carroll KC, Wang K | title = Functional coupling of intracellular calcium and inactivation of voltage-gated Kv1.1/Kvbeta1.1 A-type K+ channels | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 101 | issue = 43 | pages = 15535–15540 | date = October 2004 | pmid = 15486093 | pmc = 524431 | doi = 10.1073/pnas.0402081101 | doi-access = free | bibcode = 2004PNAS..10115535J }}
* {{cite journal | vauthors = Imbrici P, Grottesi A, D'Adamo MC, Mannucci R, Tucker SJ, Pessia M | title = Contribution of the central hydrophobic residue in the PXP motif of voltage-dependent K+ channels to S6 flexibility and gating properties | journal = Channels | volume = 3 | issue = 1 | pages = 39–45 | year = 2009 | pmid = 19202350 | doi = 10.4161/chan.3.1.7548 | doi-access = free }}
* {{cite journal | vauthors = Kinali M, Jungbluth H, Eunson LH, Sewry CA, Manzur AY, Mercuri E, Hanna MG, Muntoni F | title = Expanding the phenotype of potassium channelopathy: severe neuromyotonia and skeletal deformities without prominent Episodic Ataxia | journal = Neuromuscular Disorders | volume = 14 | issue = 10 | pages = 689–693 | date = October 2004 | pmid = 15351427 | doi = 10.1016/j.nmd.2004.06.007 | s2cid = 44972020 }}
* {{cite journal | vauthors = Demos MK, Macri V, Farrell K, Nelson TN, Chapman K, Accili E, Armstrong L | title = A novel KCNA1 mutation associated with global delay and persistent cerebellar dysfunction | journal = Movement Disorders | volume = 24 | issue = 5 | pages = 778–782 | date = April 2009 | pmid = 19205071 | doi = 10.1002/mds.22467 | s2cid = 25655998 }}
* {{cite journal | vauthors = Imbrici P, Gualandi F, D'Adamo MC, Masieri MT, Cudia P, De Grandis D, Mannucci R, Nicoletti I, Tucker SJ, Ferlini A, Pessia M | title = A novel KCNA1 mutation identified in an Italian family affected by episodic ataxia type 1 | journal = Neuroscience | volume = 157 | issue = 3 | pages = 577–587 | date = December 2008 | pmid = 18926884 | doi = 10.1016/j.neuroscience.2008.09.022 | s2cid = 15772885 }}
* {{cite journal | vauthors = Tan KM, Lennon VA, Klein CJ, Boeve BF, Pittock SJ | title = Clinical spectrum of voltage-gated potassium channel autoimmunity | journal = Neurology | volume = 70 | issue = 20 | pages = 1883–1890 | date = May 2008 | pmid = 18474843 | doi = 10.1212/01.wnl.0000312275.04260.a0 | s2cid = 34815377 }}
* {{cite journal | vauthors = Chen H, von Hehn C, Kaczmarek LK, Ment LR, Pober BR, Hisama FM | title = Functional analysis of a novel potassium channel (KCNA1) mutation in hereditary myokymia | journal = Neurogenetics | volume = 8 | issue = 2 | pages = 131–135 | date = April 2007 | pmid = 17136396 | pmc = 1820748 | doi = 10.1007/s10048-006-0071-z }}
* {{cite journal | vauthors = Strausberg RL, Feingold EA, Grouse LH, Derge JG, Klausner RD, Collins FS, Wagner L, Shenmen CM, Schuler GD, Altschul SF, Zeeberg B, Buetow KH, Schaefer CF, Bhat NK, Hopkins RF, Jordan H, Moore T, Max SI, Wang J, Hsieh F, Diatchenko L, Marusina K, Farmer AA, Rubin GM, Hong L, Stapleton M, Soares MB, Bonaldo MF, Casavant TL, Scheetz TE, Brownstein MJ, Usdin TB, Toshiyuki S, Carninci P, Prange C, Raha SS, Loquellano NA, Peters GJ, Abramson RD, Mullahy SJ, Bosak SA, McEwan PJ, McKernan KJ, Malek JA, Gunaratne PH, Richards S, Worley KC, Hale S, Garcia AM, Gay LJ, Hulyk SW, Villalon DK, Muzny DM, Sodergren EJ, Lu X, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madan A, Young AC, Shevchenko Y, Bouffard GG, Blakesley RW, Touchman JW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Krzywinski MI, Skalska U, Smailus DE, Schnerch A, Schein JE, Jones SJ, Marra MA | title = Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 99 | issue = 26 | pages = 16899–16903 | date = December 2002 | pmid = 12477932 | pmc = 139241 | doi = 10.1073/pnas.242603899 | doi-access = free | bibcode = 2002PNAS...9916899M }}
* {{cite journal | vauthors = Gutman GA, Chandy KG, Grissmer S, Lazdunski M, McKinnon D, Pardo LA, Robertson GA, Rudy B, Sanguinetti MC, Stühmer W, Wang X | title = International Union of Pharmacology. LIII. Nomenclature and molecular relationships of voltage-gated potassium channels | journal = Pharmacological Reviews | volume = 57 | issue = 4 | pages = 473–508 | date = December 2005 | pmid = 16382104 | doi = 10.1124/pr.57.4.10 | s2cid = 219195192 }}
* {{cite journal | vauthors = Lee H, Wang H, Jen JC, Sabatti C, Baloh RW, Nelson SF | title = A novel mutation in KCNA1 causes episodic ataxia without myokymia | journal = Human Mutation | volume = 24 | issue = 6 | pages = 536 | date = December 2004 | pmid = 15532032 | doi = 10.1002/humu.9295 | s2cid = 2542180 | doi-access = free }}
* {{cite journal | vauthors = Gu C, Jan YN, Jan LY | title = A conserved domain in axonal targeting of Kv1 (Shaker) voltage-gated potassium channels | journal = Science | volume = 301 | issue = 5633 | pages = 646–649 | date = August 2003 | pmid = 12893943 | doi = 10.1126/science.1086998 | s2cid = 9924760 | bibcode = 2003Sci...301..646G }}
{{refend}}

== External links ==
* [https://www.ncbi.nlm.nih.gov/books/NBK25442/  GeneReviews/NCBI/NIH/UW entry on Episodic Ataxia Type 1, Episodic Ataxia with Myokymia, Hereditary Cerebellar Ataxia with Neuromyotonia]
* {{MeshName|Kv1.1+Potassium+Channel}}
* {{MeshName|KCNA1+protein,+human}}

{{PDB Gallery|geneid=3736}}
{{Ion channels|g3}}

[[Category:Ion channels]]