KCNH2

KCNH2
Dostupne strukture
PDB	Pretraga ortologa: PDBe RCSB
Spisak PDB ID kodova
	1BYW, 1UJL, 2L0W, 2L1M, 2L4R, 2LE7, 4HP9, 4HQA, 2N7G
Identifikatori
Aliasi	KCNH2
Vanjski ID-jevi	OMIM: 152427 MGI: 1341722 HomoloGene: 201 GeneCards: KCNH2
Lokacija gena (čovjek)
Hrom.	Hromosom 7 (čovjek)
Kraj	150,978,321 bp
Lokacija gena (miš)
Hrom.	Hromosom 5 (miš)
Kraj	24,556,602 bp
Obrazac RNK ekspresije
	; ; ; ;
	Više referentnih podataka o ekspresiji
Ontologija gena
Molekularna funkcija	• potassium channel activity; • protein homodimerization activity; • scaffold protein binding; • voltage-gated potassium channel activity involved in cardiac muscle cell action potential repolarization; • C3HC4-type RING finger domain binding; • voltage-gated ion channel activity; • ion channel activity; • GO:0001948, GO:0016582 vezivanje za proteine; • vezivanje identičnih proteina; • voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization; • voltage-gated potassium channel activity; • phosphorelay sensor kinase activity; • ubiquitin protein ligase binding; • delayed rectifier potassium channel activity; • inward rectifier potassium channel activity;
Ćelijska komponenta	• integral component of membrane; • membrana; • voltage-gated potassium channel complex; • ćelijska membrana; • cell surface; • perinuklearno područje citoplazme; • inward rectifier potassium channel complex; • integral component of plasma membrane;
Biološki proces	• membrane depolarization during action potential; • cardiac muscle contraction; • GO:0072468 Transdukcija signala; • regulation of membrane potential; • regulation of ion transmembrane transport; • ventricular cardiac muscle cell action potential; • ion transport; • potassium ion export across plasma membrane; • potassium ion transport; • membrane repolarization during action potential; • potassium ion homeostasis; • regulation of heart rate by hormone; • transmembrane transport; • potassium ion transmembrane transport; • positive regulation of potassium ion transmembrane transport; • phosphorelay signal transduction system; • regulation of membrane repolarization; • negative regulation of potassium ion transmembrane transport; • membrane repolarization during cardiac muscle cell action potential; • regulation of heart rate by cardiac conduction; • regulation of potassium ion transmembrane transport; • regulation of ventricular cardiac muscle cell membrane repolarization; • membrane repolarization during ventricular cardiac muscle cell action potential; • membrane repolarization; • negative regulation of potassium ion export across plasma membrane; • potassium ion import across plasma membrane; • cardiac conduction;
	Izvori:Amigo / QuickGO
Ortolozi
	3757
	16511
	ENSG00000055118
	ENSMUSG00000038319
	Q12809
	O35219
	NM_000238; NM_001204798; NM_172056; NM_172057
	NM_001294162; NM_013569
	NP_000229; NP_001191727; NP_742053; NP_742054
	NP_001281091; NP_038597
	Wikipodaci
Pogledaj/uredi – čovjek	Pogledaj/uredi – miš

Šablon:Lowercase title

hERG (KCNH2) jest gen koji je kod ljudi na hromosoma 7. Kodira protein poznat kao K_v11.1, alfa podjedinica kalijevog jonskog kanala. Ovaj ionski kanal (ponekad jednostavno označen kao 'hERG') je najpoznatiji po svom doprinosu srčanoj električnoj aktivnosti: hERG kanal posreduje u repolarizirajućoj I_Kr struji u srčanom akcijskom potencijalu, koja pomaže u koordinaciji otkucaja srca.

Kada je sposobnost ovog kanala da provodi električnu struju kroz ćelijsku membranu inhibirana ili ugrožena, bilo primjenom lijekova ili rijetkim mutacijama u nekim porodicama,^[5] može dovesti do potencijalno fatalnog poremećaja koji se naziva sindrom dugog QT intervala. Suprotno tome, genske mutacije koje povećavaju struju kroz ove kanale mogu dovesti do povezanog naslijeđenog poremećaja srčanog ritma zvanog sindrom kratkog QT.^[6] Brojni klinički uspješni lijekovi na tržištu imali su tendenciju da inhibiraju hERG, produžavajući QT i potencijalno dovodeći do fatalnog nepravilnosti otkucaja srca (komorska tahiaritmija zvana torsades de pointes). Ovo je učinilo inhibiciju hERG važnim anticiljem koji se mora izbjegavati tokom razvoja lijeka.^[7]

hERG je također povezan sa modulacijom funkcija nekih ćelija nervnog sistema ^[8] and with establishing and maintaining cancer-like features in leukemic cells.^[9]

Aminokiselinska sekvenca[uredi | uredi izvor]

Dužina polipeptidnog lanca je 1.159 aminokiselina, a molekulska težina 126.655 Da.^[7]

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
MPVRRGHVAP	QNTFLDTIIR	KFEGQSRKFI	IANARVENCA	VIYCNDGFCE
LCGYSRAEVM	QRPCTCDFLH	GPRTQRRAAA	QIAQALLGAE	ERKVEIAFYR
KDGSCFLCLV	DVVPVKNEDG	AVIMFILNFE	VVMEKDMVGS	PAHDTNHRGP
PTSWLAPGRA	KTFRLKLPAL	LALTARESSV	RSGGAGGAGA	PGAVVVDVDL
TPAAPSSESL	ALDEVTAMDN	HVAGLGPAEE	RRALVGPGSP	PRSAPGQLPS
PRAHSLNPDA	SGSSCSLART	RSRESCASVR	RASSADDIEA	MRAGVLPPPP
RHASTGAMHP	LRSGLLNSTS	DSDLVRYRTI	SKIPQITLNF	VDLKGDPFLA
SPTSDREIIA	PKIKERTHNV	TEKVTQVLSL	GADVLPEYKL	QAPRIHRWTI
LHYSPFKAVW	DWLILLLVIY	TAVFTPYSAA	FLLKETEEGP	PATECGYACQ
PLAVVDLIVD	IMFIVDILIN	FRTTYVNANE	EVVSHPGRIA	VHYFKGWFLI
DMVAAIPFDL	LIFGSGSEEL	IGLLKTARLL	RLVRVARKLD	RYSEYGAAVL
FLLMCTFALI	AHWLACIWYA	IGNMEQPHMD	SRIGWLHNLG	DQIGKPYNSS
GLGGPSIKDK	YVTALYFTFS	SLTSVGFGNV	SPNTNSEKIF	SICVMLIGSL
MYASIFGNVS	AIIQRLYSGT	ARYHTQMLRV	REFIRFHQIP	NPLRQRLEEY
FQHAWSYTNG	IDMNAVLKGF	PECLQADICL	HLNRSLLQHC	KPFRGATKGC
LRALAMKFKT	THAPPGDTLV	HAGDLLTALY	FISRGSIEIL	RGDVVVAILG
KNDIFGEPLN	LYARPGKSNG	DVRALTYCDL	HKIHRDDLLE	VLDMYPEFSD
HFWSSLEITF	NLRDTNMIPG	SPGSTELEGG	FSRQRKRKLS	FRRRTDKDTE
QPGEVSALGP	GRAGAGPSSR	GRPGGPWGES	PSSGPSSPES	SEDEGPGRSS
SPLRLVPFSS	PRPPGEPPGG	EPLMEDCEKS	SDTCNPLSGA	FSGVSNIFSF
WGDSRGRQYQ	ELPRCPAPTP	SLLNIPLSSP	GRRPRGDVES	RLDALQRQLN
RLETRLSADM	ATVLQLLQRQ	MTLVPPAYSA	VTTPGPGPTS	TSPLLPVSPL
PTLTLDSLSQ	VSQFMACEEL	PPGAPELPQE	GPTRRLSLPG	QLGALTSQPL
HRHGSDPGS

Struktura[uredi | uredi izvor]

Detaljna atomska struktura za hERG zasnovana na rendgenskoj kristalografiji još nije dostupna, ali strukture su nedavno riješene elektronskom mikroskopijom.^[10] U laboratoriji heterologno eksprimiran hERG kalijski kanal sastoji se od 4 identične alfa-podjedinice, koje formiraju pore kanala kroz plazmamembranu. Svaka hERG podjedinica sastoji se od po 6 transmembranskih alfa-heliksa, označenih s S1-S6, spirala pora koja se nalazi između S5 i S6, a citoplazmatski smještena N- i C-terminal. Heliks S4 sadrži pozitivno nabijen argininski ili lizinski aminokiselinski ostatak na svakoj 3. poziciji i smatra se da djeluje kao senzor osjetljiv na napon, koji omogućava kanalu da odgovori na promjene napona, promjenom konformacija između provodnih i neprovodnih stanja (zvanih 'pristajanje'). Između spirala S5 i S6, postoji vanćelijska petlja (poznata kao 'torola') i 'porina petlja', koja počinje i završava se vanćelijski, ali se uvlači u plazmamembranu; petlja pora za svaku od hERG podjedinica u jednom kanalu biti okrenuta prema pori koja provodi ione i susjedna je odgovarajućim petljama 3 druge podjedinice, a zajedno čine područje selektivnog filtera kanalske pore. Selektivnost sekvence, SVGFG, vrlo je slična onoj sadržanoj u bakterijskim KcsA kanalima.^[7] Iako potpuna kristalna struktura za hERG još nije dostupna, pronađena je struktura za citoplazmatski N-kraj, za koji se pokazalo da sadrži domen PAS (aminokiselina 26-135) koji usporava brzinu deaktivacije.^[11]

Funkcija[uredi | uredi izvor]

hERG formira glavni dio jednog od proteina ionskih kanala ('brza' odložena struja ispravljača (I_Kr) koji provodi kalijeve (kalij|K⁺]]) jone iz mišićnih ćelija srca (srčani miociti), a ova struja je kritična za pravilno određivanje vremena povratka u stanje mirovanja (repolarizacija) ćelijsku membranu tokom srčanog akciojskog potencijala.^[7] Ponekad, kada se govori o farmakološkim efektima lijekova, termini "hERG kanali" i "I"_Kr se koriste naizmjenično, ali, u tehničkom smislu, "hERG kanale" mogu napraviti samo u laboratoriji; formalno gledano, prirodni kanali u tijelu koji uključuju hERG nazivaju se imenom električne struje koja je izmjerena u tom tipu ćelije, tako da je, naprimjer, u srcu, ispravan naziv "I" '_Kr. Ova razlika u nomenklaturi postaje jasnija u kontroverzi oko toga da li kanali koji provode I_Kr uključuju druge podjedinice (npr. beta-podjedinice ^[12]) ili da li kanali uključuju mješavinu različitih tipova (izoformi) hERG-a,^[13] but, when the originally-discovered form of hERG^[14] se eksperimentalno prenosi u ćelije kojima je prethodno nedostajao hERG (tj. heterologna ekspresija), formira se kalijski ionski kanal, a ovaj kanal ima mnoge karakteristike srčane 'brze' odložene struje ispravljača (I_Kr),^[15]^[16]^[17] uključujući I_Kr-ovo unutrašnje ispravljanje koje rezultira u kanalu koji proizvodi 'paradoksalnu resurgentnu struju', kao odgovor na repolarizaciju membrane.^[18]

Genetika[uredi | uredi izvor]

Mutacije gubitka funkcije u ovom kanalu mogu dovesti do sindroma dugog QT (LQT2), dok mutacije povećanja funkcije mogu dovesti do sindroma kratkog QT. Oba klinička poremećaja proizlaze iz disfunkcije ionskih kanala (tzv. kanalopatija) koja može dovesti do rizika od potencijalno fatalnih srčanih aritmija (npr. torsades de pointes), zbog repolarizacijskih poremećaja srčanog akcijskog potencijala.^[15]^[19] Postoji mnogo više mutacija hERG-a opisanih za sindrom dugog QT nego za sindrom kratkog QT intervala.^[5]

Interakcije[uredi | uredi izvor]

Pokazalo se da HERG reaguje sa 14-3-3 epsilon proteinom, kodiranimgenom YWHAE.^[20]

Također pogledajte[uredi | uredi izvor]

Naponski-vođeni kalijev kanal

Reference[uredi | uredi izvor]

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000055118 - Ensembl, maj 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000038319 - 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 Hedley PL, Jørgensen P, Schlamowitz S, Wangari R, Moolman-Smook J, Brink PA, Kanters JK, Corfield VA, Christiansen M (2009). "The genetic basis of long QT and short QT syndromes: a mutation update". Hum. Mutat. 30 (11): 1486–511. doi:10.1002/humu.21106. PMID 19862833. S2CID 19122696.
^ Bjerregaard, Preben (2. 3. 2018). "The diagnosis and management of short QT syndrome". Heart Rhythm. 15 (8): 1261–1267. doi:10.1016/j.hrthm.2018.02.034. ISSN 1556-3871. PMID 29501667. S2CID 4519580.
^ ^a ^b ^c ^d Sanguinetti MC, Tristani-Firouzi M (mart 2006). "hERG potassium channels and cardiac arrhythmia". Nature. 440 (7083): 463–9. Bibcode:2006Natur.440..463S. doi:10.1038/nature04710. PMID 16554806. S2CID 929837.
^ Chiesa N, Rosati B, Arcangeli A, Olivotto M, Wanke E (juni 1997). "A novel role for HERG K+ channels: spike-frequency adaptation". J. Physiol. 501 (2): 313–8. doi:10.1111/j.1469-7793.1997.313bn.x. PMC 1159479. PMID 9192303. Overholt JL, Ficker E, Yang T, Shams H, Bright GR, Prabhakar NR (2000). Chemosensing at the carotid body. Involvement of a HERG-like potassium current in glomus cells. Adv. Exp. Med. Biol. Advances in Experimental Medicine and Biology. 475. str. 241–8. doi:10.1007/0-306-46825-5_22. ISBN 978-0-306-46367-9. PMID 10849664.
^ Arcangeli A (2005). "Expression and role of hERG channels in cancer cells". The hERG Cardiac Potassium Channel: Structure, Function and Long QT Syndrome. Novartis Found. Symp. Novartis Foundation Symposia. 266. str. 225–32, discussion 232–4. doi:10.1002/047002142X.ch17. ISBN 9780470021408. PMID 16050271.
^ Wang W, MacKinnon R (2017). "Cryo-EM Structure of the Open Human Ether-à-go-go-Related K+ Channel hERG". Cell. 169 (3): 422–430.e10. doi:10.1016/j.cell.2017.03.048. PMC 5484391. PMID 28431243.
^ Morais Cabral JH, Lee A, Cohen SL, Chait BT, Li M, Mackinnon R (novembar 1998). "Crystal structure and functional analysis of the HERG potassium channel N terminus: a eukaryotic PAS domain". Cell. 95 (5): 649–55. doi:10.1016/S0092-8674(00)81635-9. PMID 9845367. S2CID 15090987.
^ Weerapura M, Nattel S, Chartier D, Caballero R, Hébert TE (april 2002). "A comparison of currents carried by HERG, with and without coexpression of MiRP1, and the native rapid delayed rectifier current. Is MiRP1 the missing link?". J. Physiol. 540 (Pt 1): 15–27. doi:10.1113/jphysiol.2001.013296. PMC 2290231. PMID 11927665.Abbott GW, Goldstein SA (mart 2002). "Disease-associated mutations in KCNE potassium channel subunits (MiRPs) reveal promiscuous disruption of multiple currents and conservation of mechanism". FASEB J. 16 (3): 390–400. doi:10.1096/fj.01-0520hyp. PMID 11874988. S2CID 26205057.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.
^ Jones EM, Roti Roti EC, Wang J, Delfosse SA, Robertson GA (oktobar 2004). "Cardiac IKr channels minimally comprise hERG 1a and 1b subunits". J. Biol. Chem. 279 (43): 44690–4. doi:10.1074/jbc.M408344200. PMID 15304481.Robertson GA, Jones EM, Wang J (2005). "Gating and Assembly of Heteromeric hERG1a/1b Channels Underlying I Kr in the Heart". Gating and assembly of heteromeric hERG1a/1b channels underlying I(Kr) in the heart (PDF). Novartis Found. Symp. Novartis Foundation Symposia. 266. str. 4–15, discussion 15–8, 44–5. CiteSeerX 10.1.1.512.5443. doi:10.1002/047002142X.ch2. ISBN 9780470021408. PMID 16050259.
^ Warmke JW, Ganetzky B (april 1994). "A family of potassium channel genes related to eag in Drosophila and mammals". Proc. Natl. Acad. Sci. U.S.A. 91 (8): 3438–42. Bibcode:1994PNAS...91.3438W. doi:10.1073/pnas.91.8.3438. PMC 43592. PMID 8159766.Trudeau MC, Warmke JW, Ganetzky B, Robertson GA (juli 1995). "HERG, a human inward rectifier in the voltage-gated potassium channel family". Science. 269 (5220): 92–5. Bibcode:1995Sci...269...92T. doi:10.1126/science.7604285. PMID 7604285.Sanguinetti MC, Jiang C, Curran ME, Keating MT (april 1995). "A mechanistic link between an inherited and an acquired cardiac arrhythmia: HERG encodes the IKr potassium channel". Cell. 81 (2): 299–307. doi:10.1016/0092-8674(95)90340-2. PMID 7736582. S2CID 240044.
^ ^a ^b Sanguinetti MC, Jiang C, Curran ME, Keating MT (1995). "A mechanistic link between an inherited and an acquired cardiac arrhythmia: HERG encodes the IKr potassium channel". Cell. 81 (2): 299–307. doi:10.1016/0092-8674(95)90340-2. PMID 7736582. S2CID 240044.
^ Trudeau MC, Warmke JW, Ganetzky B, Robertson GA (juli 1995). "HERG, a human inward rectifier in the voltage-gated potassium channel family". Science. 269 (5220): 92–5. Bibcode:1995Sci...269...92T. doi:10.1126/science.7604285. PMID 7604285.
^ Robertson GA, Jones EM, Wang J (2005). "Gating and Assembly of Heteromeric hERG1a/1b Channels Underlying I Kr in the Heart". Gating and assembly of heteromeric hERG1a/1b channels underlying I(Kr) in the heart (PDF). Novartis Found. Symp. Novartis Foundation Symposia. 266. str. 4–15, discussion 15–8, 44–5. CiteSeerX 10.1.1.512.5443. doi:10.1002/047002142X.ch2. ISBN 9780470021408. PMID 16050259.
^ Robertson GA (mart 2000). "LQT2 : amplitude reduction and loss of selectivity in the tail that wags the HERG channel". Circ. Res. 86 (5): 492–3. doi:10.1161/01.res.86.5.492. PMID 10720408.
^ Moss AJ, Zareba W, Kaufman ES, Gartman E, Peterson DR, Benhorin J, Towbin JA, Keating MT, Priori SG, Schwartz PJ, Vincent GM, Robinson JL, Andrews ML, Feng C, Hall WJ, Medina A, Zhang L, Wang Z (2002). "Increased risk of arrhythmic events in long-QT syndrome with mutations in the pore region of the human ether-a-go-go-related gene potassium channel". Circulation. 105 (7): 794–9. doi:10.1161/hc0702.105124. PMID 11854117.
^ Kagan A, Melman YF, Krumerman A, McDonald TV (Apr 2002). "14-3-3 amplifies and prolongs adrenergic stimulation of HERG K+ channel activity". EMBO J. 21 (8): 1889–98. doi:10.1093/emboj/21.8.1889. PMC 125975. PMID 11953308.

Dopunska literatura[uredi | uredi izvor]

Vincent GM (1998). "The molecular genetics of the long QT syndrome: genes causing fainting and sudden death". Annu. Rev. Med. 49: 263–74. doi:10.1146/annurev.med.49.1.263. PMID 9509262.
Ackerman MJ (1998). "The long QT syndrome: ion channel diseases of the heart". Mayo Clin. Proc. 73 (3): 250–69. doi:10.4065/73.3.250. PMID 9511785.
Taglialatela M, Castaldo P, Pannaccione A, Giorgio G, Annunziato L (1998). "Human ether-a-gogo related gene (HERG) K+ channels as pharmacological targets: present and future implications". Biochem. Pharmacol. 55 (11): 1741–6. doi:10.1016/S0006-2952(98)00002-1. hdl:11566/37313. PMID 9714291.
Bjerregaard P, Gussak I (2005). "Short QT syndrome: mechanisms, diagnosis and treatment". Nat Clin Pract Cardiovasc Med. 2 (2): 84–7. doi:10.1038/ncpcardio0097. PMID 16265378. S2CID 10125533.
Gutman GA, Chandy KG, Grissmer S, Lazdunski M, McKinnon D, Pardo LA, Robertson GA, Rudy B, Sanguinetti MC, Stühmer W, Wang X (2005). "International Union of Pharmacology. LIII. Nomenclature and molecular relationships of voltage-gated potassium channels". Pharmacol. Rev. 57 (4): 473–508. doi:10.1124/pr.57.4.10. PMID 16382104. S2CID 219195192.

Vanjski linkovi[uredi | uredi izvor]

GeneReviews/NIH/NCBI/UW entry on Romano-Ward Syndrome
International Conference on Harmonization
Drosophila flybase entry for erg
Special K: Primate-specific Potassium Channel Variant Implicated in Schizophrenia - Schizophrenia Research Forum.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000055118 - Ensembl, maj 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000038319 - 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.

[Hedley-5] Hedley PL, Jørgensen P, Schlamowitz S, Wangari R, Moolman-Smook J, Brink PA, Kanters JK, Corfield VA, Christiansen M (2009). "The genetic basis of long QT and short QT syndromes: a mutation update". Hum. Mutat. 30 (11): 1486–511. doi:10.1002/humu.21106. PMID 19862833. S2CID 19122696.

[6] Bjerregaard, Preben (2. 3. 2018). "The diagnosis and management of short QT syndrome". Heart Rhythm. 15 (8): 1261–1267. doi:10.1016/j.hrthm.2018.02.034. ISSN 1556-3871. PMID 29501667. S2CID 4519580.

[Sanguinetti_MC,_Tristani-Firouzi_M_2006_463–9-7] Sanguinetti MC, Tristani-Firouzi M (mart 2006). "hERG potassium channels and cardiac arrhythmia". Nature. 440 (7083): 463–9. Bibcode:2006Natur.440..463S. doi:10.1038/nature04710. PMID 16554806. S2CID 929837.

[8] Chiesa N, Rosati B, Arcangeli A, Olivotto M, Wanke E (juni 1997). "A novel role for HERG K+ channels: spike-frequency adaptation". J. Physiol. 501 (2): 313–8. doi:10.1111/j.1469-7793.1997.313bn.x. PMC 1159479. PMID 9192303. Overholt JL, Ficker E, Yang T, Shams H, Bright GR, Prabhakar NR (2000). Chemosensing at the carotid body. Involvement of a HERG-like potassium current in glomus cells. Adv. Exp. Med. Biol. Advances in Experimental Medicine and Biology. 475. str. 241–8. doi:10.1007/0-306-46825-5_22. ISBN 978-0-306-46367-9. PMID 10849664.

[9] Arcangeli A (2005). "Expression and role of hERG channels in cancer cells". The hERG Cardiac Potassium Channel: Structure, Function and Long QT Syndrome. Novartis Found. Symp. Novartis Foundation Symposia. 266. str. 225–32, discussion 232–4. doi:10.1002/047002142X.ch17. ISBN 9780470021408. PMID 16050271.

[10] Wang W, MacKinnon R (2017). "Cryo-EM Structure of the Open Human Ether-à-go-go-Related K+ Channel hERG". Cell. 169 (3): 422–430.e10. doi:10.1016/j.cell.2017.03.048. PMC 5484391. PMID 28431243.

[pmid9845367-11] Morais Cabral JH, Lee A, Cohen SL, Chait BT, Li M, Mackinnon R (novembar 1998). "Crystal structure and functional analysis of the HERG potassium channel N terminus: a eukaryotic PAS domain". Cell. 95 (5): 649–55. doi:10.1016/S0092-8674(00)81635-9. PMID 9845367. S2CID 15090987.

[12] Weerapura M, Nattel S, Chartier D, Caballero R, Hébert TE (april 2002). "A comparison of currents carried by HERG, with and without coexpression of MiRP1, and the native rapid delayed rectifier current. Is MiRP1 the missing link?". J. Physiol. 540 (Pt 1): 15–27. doi:10.1113/jphysiol.2001.013296. PMC 2290231. PMID 11927665.Abbott GW, Goldstein SA (mart 2002). "Disease-associated mutations in KCNE potassium channel subunits (MiRPs) reveal promiscuous disruption of multiple currents and conservation of mechanism". FASEB J. 16 (3): 390–400. doi:10.1096/fj.01-0520hyp. PMID 11874988. S2CID 26205057.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.

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[pmid11953308-20] Kagan A, Melman YF, Krumerman A, McDonald TV (Apr 2002). "14-3-3 amplifies and prolongs adrenergic stimulation of HERG K+ channel activity". EMBO J. 21 (8): 1889–98. doi:10.1093/emboj/21.8.1889. PMC 125975. PMID 11953308.

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