KCNE2

KCNE2
Dostupne strukture
PDB	Pretraga ortologa: PDBe RCSB
Spisak PDB ID kodova
	2M0Q
Identifikatori
Aliasi	KCNE2
Vanjski ID-jevi	OMIM: 603796 MGI: 1891123 HomoloGene: 71688 GeneCards: KCNE2
Lokacija gena (čovjek)
Hrom.	Hromosom 21 (čovjek)
Kraj	34,371,381 bp
Lokacija gena (miš)
Hrom.	Hromosom 16 (miš)
Kraj	92,095,017 bp
Ontologija gena
Molekularna funkcija	• potassium channel activity; • protein homodimerization activity; • transmembrane transporter binding; • delayed rectifier potassium channel activity; • voltage-gated ion channel activity; • potassium channel regulator activity; • GO:0001948, GO:0016582 vezivanje za proteine; • voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization; • voltage-gated potassium channel activity; • inward rectifier potassium channel activity;
Ćelijska komponenta	• integral component of membrane; • membrana; • voltage-gated potassium channel complex; • ćelijska membrana; • Lizozom; • Endoplazmatski retikulum; • Golđijev aparat; • cell surface;
Biološki proces	• negative regulation of voltage-gated potassium channel activity; • tongue development; • regulation of inward rectifier potassium channel activity; • positive regulation of voltage-gated calcium channel activity; • regulation of ion transmembrane transport; • ventricular cardiac muscle cell action potential; • GO:0010260 starenje; • cardiac muscle cell action potential involved in contraction; • ion transport; • potassium ion transport; • membrane repolarization; • membrane repolarization during action potential; • regulation of delayed rectifier potassium channel activity; • cardiac conduction; • potassium ion transmembrane transport; • regulation of membrane repolarization; • positive regulation of proteasomal protein catabolic process; • regulation of heart rate by cardiac conduction; • regulation of potassium ion transmembrane transport; • regulation of cyclic nucleotide-gated ion channel activity; • negative regulation of delayed rectifier potassium channel activity; • regulation of ventricular cardiac muscle cell membrane repolarization; • membrane repolarization during ventricular cardiac muscle cell action potential; • GO:0015915 transport; • potassium ion export across plasma membrane; • potassium ion import across plasma membrane;
	Izvori:Amigo / QuickGO
Ortolozi
	9992
	246133
	ENSG00000159197
	ENSMUSG00000039672
	Q9Y6J6
	Q9D808
	NM_172201; NM_005136
	NM_134110; NM_001358372
	NP_751951
	NP_598871; NP_001345301
	Wikipodaci
Pogledaj/uredi – čovjek	Pogledaj/uredi – miš

Trodimenzijska animacija KCNE2

Član 2 naponski otvorenog kalijskog kanala potporodice E (KCNE2), znan i kao MinK-srodni peptid 1 (MiRP1), jest protein koji je kod ljudi kodiran genom KCNE2 sa hromosoma 21.^[5]^[6] MiRP1 je naponski usmjereni kalijev kanal, pomoćna podjedinica (beta podjedinica) povezana sa sindromom dugog QT.^[5] Sveprisutno je izražen u mnogim tkivima i tipovima ćelija.^[7] Zbog ovoga i svoje sposobnosti da regulira više različitih ionskih kanala, KCNE2 ima značajan uticaj na brojne tipove ćelija i tkiva.^[5]^[8] Ljudski KCNE2 je član petočlane porodice ljudskih KCNE gena. KCNE proteini sadrže jednu regiju koja se proteže kroz membranu, vanćelijski N– i unuraćelijski C-terminal. KCNE proteini široko su proučavani zbog njihove uloge u srcu i genetičkoj predispoziciji za naslijeđene srčane aritmije. Gen KCNE2 također sadrži jedan od 27 jednonikleotidnih polimorfizama (SNP), povezanih s povećanim rizikom od koronarne arterijske bolesti.^[9] U novije vrijeme, također su istražene uloge KCNE proteina u različitim ne-srčanim tkivima.

Otkriće

Steve Goldstein (tada na Univerzitetu Yale) koristio je strategiju pretraživanja BLAST, fokusirajući se na KCNE1 sekvence za koje se zna da su važne za funkciju, da identifikuje povezane ekspresijske oznake sekvence (EST) u NCBI bazi podataka. Koristeći sekvence iz ovih EST-ova, klonirani su KCNE2, 3 i 4.^[5]

Struktura

Aminokiselinska sekvenca

Dužina polipeptidnog lanca je 123 aminokiseline, a molekulska težina 14.472 Da.^[6]

C: Cistein

D: Asparaginska kiselina

E: Glutaminska kiselina

F: Fenilalanin

G: Glicin

H: Histidin

I: Izoleucin

K: Lizin

L: Leucin

M: Metionin

N: Asparagin

P: Prolin

Q: Glutamin

R: Arginin

S: Serin

T: Treonin

V: Valin

W: Triptofan

Y: Tirozin

10	20	30	40	50
MSTLSNFTQT	LEDVFRRIFI	TYMDNWRQNT	TAEQEALQAK	VDAENFYYVI
LYLMVMIGMF	SFIIVAILVS	TVKSKRREHS	NDPYHQYIVE	DWQEKYKSQI
LNLEESKATI	HENIGAAGFK	MSP

Gen

Gen KCNE2 nalazi se na hromosomu 21 na traci 21q22.11 i sadrži dva egzona.^[6] Pošto se ljudski KCNE2 nalazi ~79 kb od KCNE1 i u suprotnom smjeru, predlaže se da KCNE2 potiče od duplikacije gena.^[10]

Protein

Ovaj protein pripada porodici kalijskih kanala KCNE i jedan je od pet pojedinačnih transmembranskih domena pomoćnih podjedinica naponski vođenog kalijskog (Kv) kanala.^[11]^[12] Protein KCNE2 detektuje se najlakše u epitelu horoidnog pleksusa, na apikalnoj strani. KCNE2 tamo formira komplekse sa podjedinicom α kalijevog kanala reguliranog naponom, Kv1.3. Pored toga, KCNE2 formira recipročno regulisane tripartitne komplekse u epitelu horoidnog pleksusa sa KCNQ1 α podjedinicom i natrijum-ovisnim myo-inozitolskim transporterom, SMIT1. Kcne2 – /– miševi pokazuju povećanu osjetljivost na napade, smanjeno vrijeme nepokretnosti u testu ovjesa repa i smanjen sadržaj mio-inozitola u cerebrospinalnoj tekućini, u poređenju sa divljim tipom legla. Mega-doziranje mio-inozitola preokreće sve ove fenotipove, sugerirajući vezu između mio-inozitola i podložnosti napadima i promjenama ponašanja kod Kcne2–/– miševa.^[13]^[14]

Želučani epitel

KCNE2 je također visoko eksprimiran u parijetalnim ćelijama želučanog epitela, također sa apikalne strane. U ovim ćelijama, KCNQ1-KCNE2 K⁺ kanali, koji su konstitutivno aktivni, obezbeđuju kanal za vraćanje K⁺ iona nazad u lumen želuca. Ioni K⁺ ulaze u parijetalnu ćeliju kroz želučanu H⁺/K⁺-ATPazu, koja ih zamjenjuje za protone dok zakiseljava želudac. Dok su KCNQ1 kanali inhibirani niskim vančelijskim pH, aktivnost KCNQ1-KCNE2 kanala je povećana vanćelijskim protonima, što je idealna karakteristika za njihovu ulogu u parijetalnim ćelijama.^[15]^[16]^[17]

Epitel štitne žlijezde

KCNE2 formira konstitutivno aktivne K⁺ kanale sa KCNQ1 u bazolateralnoj membrani epitelnih ćelija štitaste žlijezde. Kcne2 – /– miševi pokazuju hipotireozu, posebno očiglednu tokom gestacija ili laktacija. KCNQ1-KCNE2 je neophodan za optimalan unos jodida u štitnjaču putem bazolateralnog natrij-jodid simportera (NIS). Jodid je potreban za biosintezu hormona štitnjače.^[18]^[19]

Srce

Prvobitno je otkriveno da KCNE2 reguliše funkciju hERG kanala. KCNE2 smanjuje makroskopsku i unitarnu struju kroz hERG i ubrzava deaktivaciju hERG-a. hERG generiše IKr, najistaknutiju repolarizirajuću struju u ljudskim komorskim kardiomiocitima. hERG i IKr su vrlo osjetljivi na blokadu nizom strukturno različitih farmakoloških agenasa. Ovo svojstvo znači da mnogi korišteni ili potencijalni lijekovi imaju sposobnost da ometaju repolarizaciju ljudskih srčanih komora , što dovodi do sindroma dugog QT intervala uzrokovanog lijekovima.^[5] KCNE2 također može regulirati aktiviranu hiperpolarizaciju, ciklički nukleotid-zavisni kanal (HCN) kanale pejsmejkera u ljudskom srcu i u srcima drugih vrsta, kao i naponski vođeni kalcijev kanal Cav1.2.^[20]^[21]

Kod miševa, mERG i KCNQ1, još jedna Kv α podjedinica, regulisana KCNE2, nisu ni uticajni ni visoko eksprimirani u komorama odraslih. Međutim, Kcne2 –/– miševi pokazuju produženje QT intervala na početku u dobi od sedam mjeseci ili ranije, ako su izazvani agensom za produžavanje QT intervala kao što je sevofluran. To je zato što je KCNE2 promiskuitetna regulatorna podjedinica koja formira komplekse sa Kv1.5 i Kv4.2 u komorskim miocitima odraslih miševa. KCNE2 povećava struje kroz Kv4.2 kanale i usporava njihovu inaktivaciju. KCNE2 je potreban da bi se Kv1.5 lokalizirao na interkaliranim diskovima mišjih komorskih miocita. Delecija Kcne2 kod miševa smanjuje prirodne struje koje se stvaraju u komorskim miocitima pomoću Kv4.2, odnosno Kv1.5, I_do i I_Kslow^[22]

Klinički značaj

Želučani epitel

Kcne2 –/– miševi pokazuju ahloridiju, želučanu hiperplaziju i pogrešan promet KCNQ1 u baznoj membrani parijetalne ćelije. Pogrešan promet nastaje zato što je KCNE3 pojačan u parijetalnim ćelijama Kcne2–/– miševa i otima KCNQ1, odvodeći ga do bazolateralne membrane. Kada su i Kcne2 i Kcne3 kod miševa deletirani, KCNQ1 se kreće do apikalne membrane parijetalne ćelije, ali je fenotip želuca još gori nego kod Kcne2–/– miševa, naglašavajući da je KCNQ1 zahtijeva kokonstituciju KCNE2 za funkcionalne atribute osim ciljanja u parijetalne ćelije. Kcne2–/– miševi također razvijaju gastritis cystica profunda i želučanu neoplaziju. Smanjenje KCNE2 kod ljudi je takođe primijećeno na mestima gastritis cystica profunda i želučanog adenokarcinoma.^[15]^[16]^[17]

Epitel štitne žlezde

Podaci dobijeni pozitronskom emisionom tomografijom pokazuju da je s KCNE2 poremećen unos 124I u štitnjaču. Delecija Kcne2 ne narušava organizaciju jodida nakon što ga preuzme NIS. Mladunci uzgojeni kod Kcne2–/– su posebno teško pogođeni jer dobijaju manje mlijeka (hipotireoza majki otežava izlučivanje mlijeka), a mlijeko koje dobijaju ima manjan T₄, a oni sami ne mogu adekvatno transportovati jodid u štitnjaču. Mladunci Kcne2–/– pokazuju zaostajanje u rastu, alopeciju, kardiomegaliju i smanjenu srčanu ejekcijsku frakciju, a sve to se ublažava suplementacijom hormona štitnjače kod mladunaca ili majki. Zamjena Kcne2–/– kod mladunaca sa Kcne2+/+ majki također ublažava ove fenotipove, naglašavajući uticaj genotipa majke u ovom slučaju.^[18]^[19]

Srce

Kao što je uočeno za hERG mutacije, i mutacije gubitka funkcije KCNE2 povezane su s naslijeđenim sindromom dugog QT intervala, a hERG-KCNE2 kanali koji nose mutacije pokazuju smanjenu aktivnost u poređenju sa kanalima divljeg tipa. Osim toga, neke mutacije KCNE2 i također češći polimorfizmi povezani su sa sindromom dugog QT intervala izazvanog lijekovima. U nekoliko slučajeva, specifične varijante KCNE2 sekvence povećavaju osjetljivost na inhibiciju hERG-KCNE2 kanala lijekom koji je izazvao produženje QT intervala kod pacijenta iz kojeg je izolirana varijanta gena.^[5]^[23] Sindrom dugog QT intervala predisponira za potencijalno smrtonosne komorske srčane aritmije, uključujući torsades de pointe, koje mogu degenerirati u komorsku fibrilaciju i iznenadnu srčanu smrt.^[5] Štaviše, varijacija gena KCNE2 može poremetiti funkciju kanala HCN1-KCNE2 i to potencijalno može doprinijeti srčanoj aritmogenezi.^[20] KCNE2 je također povezan s porodičnom pretkomorskom fibrilacijom, koja može uključivati prekomjernu struju KCNQ1-KCNE2, uzrokovanu mutacijama pojačanja funkcije KCNE2.^[24] ^[25]

Nedavno je u Kcne2–/– miševa otkrivena baterija vansrčanih efekata koji mogu doprinijeti srčanoj aritmogenezi kod Kcne2–/– miševa i potencijalno mogu doprinijeti ljudskim srčanim aritmijama ako se slični efekti uoče. Delecija Kcne2 kod miševa uzrokuje anemiju, netoleranciju na glukozu, dislipidemiju, hiperkalemiju i povišen serumski angiotenzin II. Neki ili svi od njih mogu doprinijeti predispoziciji za iznenadnu srčanu smrt kod Kcne2–/– miševa u kontekstu ishemije miokarda i postishemijsk aritmogeneze.^[26]

Klinički marker

Multilokusna studija genetičkog rizika zasnovana na kombinaciji od 27 lokusa, uključujući gen KCNE2, identificirala je osobe s povećanim rizikom za incidentne i rekurentne događaje koronarne arterijske bolesti, kao i povećanu kliničku korist od statinskih terapija. Zasnovana je na kohortnoj studiji (studija Malmo dijeta i raka) i četiri dodatna randomizirana kontrolirana ispitivanja kohorti primarne prevencije (JUPITER i ASCOT) i sekundarna prevencijasekundarne prevencije kohorte (CARE and PROVE IT-TIMI 22).^[9]

Takođe pogledajte

Reference

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000159197 - Ensembl, maj 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000039672 - Ensembl, maj 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.
^ ^a ^b ^c ^d ^e ^f ^g Abbott GW, Sesti F, Splawski I, Buck ME, Lehmann MH, Timothy KW, Keating MT, Goldstein SA (April 1999). "MiRP1 forms IKr potassium channels with HERG and is associated with cardiac arrhythmia". Cell. 97 (2): 175–87. doi:10.1016/S0092-8674(00)80728-X. PMID 10219239. S2CID 8507168.
^ ^a ^b ^c "KCNE2 potassium voltage-gated channel subfamily E regulatory subunit 2 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Pristupljeno 2016-10-10.
^ "BioGPS - your Gene Portal System". biogps.org. Pristupljeno 2016-10-10.
^ Abbott GW (2012). "KCNE2 and the K (+) channel: the tail wagging the dog". Channels. 6 (1): 1–10. doi:10.4161/chan.19126. PMC 3367673. PMID 22513486.
^ ^a ^b Mega JL, Stitziel NO, Smith JG, Chasman DI, Caulfield MJ, Devlin JJ, Nordio F, Hyde CL, Cannon CP, Sacks FM, Poulter NR, Sever PS, Ridker PM, Braunwald E, Melander O, Kathiresan S, Sabatine MS (June 2015). "Genetic risk, coronary heart disease events, and the clinical benefit of statin therapy: an analysis of primary and secondary prevention trials". Lancet. 385 (9984): 2264–71. doi:10.1016/S0140-6736(14)61730-X. PMC 4608367. PMID 25748612.
^ Abbott GW (September 2015). "The KCNE2 K⁺ channel regulatory subunit: Ubiquitous influence, complex pathobiology". Gene. 569 (2): 162–72. doi:10.1016/j.gene.2015.06.061. PMC 4917011. PMID 26123744.
^ "KCNE2 - Potassium voltage-gated channel subfamily E member 2 - Homo sapiens (Human) - KCNE2 gene & protein". www.uniprot.org. Pristupljeno 2016-10-10.
^ Abbott GW, Ramesh B, Srai SK (2008-01-01). "Secondary structure of the MiRP1 (KCNE2) potassium channel ancillary subunit". Protein and Peptide Letters. 15 (1): 63–75. doi:10.2174/092986608783330413. PMID 18221016.
^ Abbott GW, Tai KK, Neverisky DL, Hansler A, Hu Z, Roepke TK, Lerner DJ, Chen Q, Liu L, Zupan B, Toth M, Haynes R, Huang X, Demirbas D, Buccafusca R, Gross SS, Kanda VA, Berry GT (March 2014). "KCNQ1, KCNE2, and Na+-coupled solute transporters form reciprocally regulating complexes that affect neuronal excitability". Science Signaling. 7 (315): ra22. doi:10.1126/scisignal.2005025. PMC 4063528. PMID 24595108.
^ Roepke TK, Kanda VA, Purtell K, King EC, Lerner DJ, Abbott GW (December 2011). "KCNE2 forms potassium channels with KCNA3 and KCNQ1 in the choroid plexus epithelium". FASEB Journal. 25 (12): 4264–73. doi:10.1096/fj.11-187609. PMC 3236621. PMID 21859894.
^ ^a ^b Roepke TK, Anantharam A, Kirchhoff P, Busque SM, Young JB, Geibel JP, Lerner DJ, Abbott GW (August 2006). "The KCNE2 potassium channel ancillary subunit is essential for gastric acid secretion". The Journal of Biological Chemistry. 281 (33): 23740–7. doi:10.1074/jbc.M604155200. PMID 16754665.
^ ^a ^b Roepke TK, Purtell K, King EC, La Perle KM, Lerner DJ, Abbott GW (6 July 2010). "Targeted deletion of Kcne2 causes gastritis cystica profunda and gastric neoplasia". PLOS ONE. 5 (7): e11451. Bibcode:2010PLoSO...511451R. doi:10.1371/journal.pone.0011451. PMC 2897890. PMID 20625512.
^ ^a ^b Roepke TK, King EC, Purtell K, Kanda VA, Lerner DJ, Abbott GW (February 2011). "Genetic dissection reveals unexpected influence of beta subunits on KCNQ1 K+ channel polarized trafficking in vivo". FASEB Journal. 25 (2): 727–36. doi:10.1096/fj.10-173682. PMC 3023397. PMID 21084694.
^ ^a ^b Roepke TK, King EC, Reyna-Neyra A, Paroder M, Purtell K, Koba W, Fine E, Lerner DJ, Carrasco N, Abbott GW (October 2009). "Kcne2 deletion uncovers its crucial role in thyroid hormone biosynthesis". Nature Medicine. 15 (10): 1186–94. doi:10.1038/nm.2029. PMC 2790327. PMID 19767733.
^ ^a ^b Purtell K, Paroder-Belenitsky M, Reyna-Neyra A, Nicola JP, Koba W, Fine E, Carrasco N, Abbott GW (August 2012). "The KCNQ1-KCNE2 K⁺ channel is required for adequate thyroid I⁻ uptake". FASEB Journal. 26 (8): 3252–9. doi:10.1096/fj.12-206110. PMC 3405278. PMID 22549510.
^ ^a ^b Nawathe PA, Kryukova Y, Oren RV, Milanesi R, Clancy CE, Lu JT, Moss AJ, Difrancesco D, Robinson RB (September 2013). "An LQTS6 MiRP1 mutation suppresses pacemaker current and is associated with sinus bradycardia". Journal of Cardiovascular Electrophysiology. 24 (9): 1021–7. doi:10.1111/jce.12163. PMC 4059362. PMID 23631727.
^ Liu W, Deng J, Wang G, Zhang C, Luo X, Yan D, Su Q, Liu J (July 2014). "KCNE2 modulates cardiac L-type Ca(2+) channel". Journal of Molecular and Cellular Cardiology. 72: 208–18. doi:10.1016/j.yjmcc.2014.03.013. PMID 24681347.
^ Roepke TK, Kontogeorgis A, Ovanez C, Xu X, Young JB, Purtell K, Goldstein PA, Christini DJ, Peters NS, Akar FG, Gutstein DE, Lerner DJ, Abbott GW (October 2008). "Targeted deletion of kcne2 impairs ventricular repolarization via disruption of I(K,slow1) and I(to,f)". FASEB Journal. 22 (10): 3648–60. doi:10.1096/fj.08-110171. PMC 2537427. PMID 18603586.
^ Sesti F, Abbott GW, Wei J, Murray KT, Saksena S, Schwartz PJ, Priori SG, Roden DM, George AL, Goldstein SA (September 2000). "A common polymorphism associated with antibiotic-induced cardiac arrhythmia". Proceedings of the National Academy of Sciences of the United States of America. 97 (19): 10613–8. Bibcode:2000PNAS...9710613S. doi:10.1073/pnas.180223197. PMC 27073. PMID 10984545.
^ Yang Y, Xia M, Jin Q, Bendahhou S, Shi J, Chen Y, Liang B, Lin J, Liu Y, Liu B, Zhou Q, Zhang D, Wang R, Ma N, Su X, Niu K, Pei Y, Xu W, Chen Z, Wan H, Cui J, Barhanin J, Chen Y (November 2004). "Identification of a KCNE2 gain-of-function mutation in patients with familial atrial fibrillation". American Journal of Human Genetics. 75 (5): 899–905. doi:10.1086/425342. PMC 1182120. PMID 15368194.
^ Nielsen JB, Bentzen BH, Olesen MS, David JP, Olesen SP, Haunsø S, Svendsen JH, Schmitt N (2014). "Gain-of-function mutations in potassium channel subunit KCNE2 associated with early-onset lone atrial fibrillation". Biomarkers in Medicine. 8 (4): 557–70. doi:10.2217/bmm.13.137. PMID 24796621.
^ Hu Z, Kant R, Anand M, King EC, Krogh-Madsen T, Christini DJ, Abbott GW (February 2014). "Kcne2 deletion creates a multisystem syndrome predisposing to sudden cardiac death". Circulation: Cardiovascular Genetics. 7 (1): 33–42. doi:10.1161/CIRCGENETICS.113.000315. PMC 4917016. PMID 24403551.

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Um SY, McDonald TV (2007). Valdivia R (ured.). "Differential association between HERG and KCNE1 or KCNE2". PLOS ONE. 2 (9): e933. Bibcode:2007PLoSO...2..933U. doi:10.1371/journal.pone.0000933. PMC 1978535. PMID 17895974.
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Vanjski linkovi

GeneReviews/NIH/NCBI/UW entry on Romano-Ward Syndrome
KCNE2 protein, human na US National Library of Medicine Medical Subject Headings (MeSH)
KCNE2 lokacija ljudskog genoma UCSC Genome Browser.

KCNE2 detalji ljudskog genoma u UCSC Genome Browser.

Q9Y6J6

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000159197 - Ensembl, maj 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000039672 - Ensembl, maj 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.

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[7] "BioGPS - your Gene Portal System". biogps.org. Pristupljeno 2016-10-10.

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[:1-9] Mega JL, Stitziel NO, Smith JG, Chasman DI, Caulfield MJ, Devlin JJ, Nordio F, Hyde CL, Cannon CP, Sacks FM, Poulter NR, Sever PS, Ridker PM, Braunwald E, Melander O, Kathiresan S, Sabatine MS (June 2015). "Genetic risk, coronary heart disease events, and the clinical benefit of statin therapy: an analysis of primary and secondary prevention trials". Lancet. 385 (9984): 2264–71. doi:10.1016/S0140-6736(14)61730-X. PMC 4608367. PMID 25748612.

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[:4-15] Roepke TK, Anantharam A, Kirchhoff P, Busque SM, Young JB, Geibel JP, Lerner DJ, Abbott GW (August 2006). "The KCNE2 potassium channel ancillary subunit is essential for gastric acid secretion". The Journal of Biological Chemistry. 281 (33): 23740–7. doi:10.1074/jbc.M604155200. PMID 16754665.

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