Wikipedia

ANK2

Ankirin-B, znan o kao ankirin-2, ke protein koji je kod ljudi kodiran genom ANK2 sa hromosoma 4.[2][3] Ankirin-B je sveprisutno eksprimiran, ali pokazuje visoku ekspresiju u srčanom mišiću. Ima bitnu ulogu u lokalizaciji i stabilizaciji membrane ionskih transportera i ionskih kanala u kardiomiocitima, kao i u strukturama kostamera. Mutacije u ankirinu-B uzrokuju dominantno naslijeđeni, sindeom srčane aritmije, poznat kao ankirin-B sindrom, kao i sindrom bolesnog sinusa; mutacije su takođe u manjem stepenu povezane sa hipertrofijskom kardiomiopatijom. Promjene u nivoima ekspresije ankirina-B primijećene su kod ljudi sa otkazivanjem srca.

ANK2
Dostupne strukture
PDBPretraga Human UniProta: PDBe RCSB
Spisak PDB ID kodova

4D8O, 4RLV, 4RLY

Identifikatori
AliasiANK2
Vanjski ID-jeviOMIM: 106410 HomoloGene: 81655 GeneCards: ANK2
Ontologija gena
Molekularna funkcija• protein-macromolecule adaptor activity
• spectrin binding
• transmembrane transporter binding
• ATPase binding
• structural constituent of cytoskeleton
• GO:0001948, GO:0016582 vezivanje za proteine
• vezivanje enzima
• protein kinase binding
• phosphorylation-dependent protein binding
Ćelijska komponenta• M band
• citoplazma
• citosol
• postsynaptic membrane
• membrana
• Interkalirani disk
• T-tubule
• sinapsa
• intracellular anatomical structure
• međućelijske veze
• basolateral plasma membrane
• Z disc
• apical plasma membrane
• Lipidni splav
• neuron projection
• Sarkolema
• A band
• citoskelet
• Kostamera
• mitohondrija
• Lizozom
• endozom
• early endosome
• reciklirajući endosom
• ćelijska membrana
• axon initial segment
Biološki proces• positive regulation of potassium ion transmembrane transporter activity
• protein localization to organelle
• positive regulation of cation channel activity
• regulation of cardiac muscle contraction by calcium ion signaling
• regulation of calcium ion transport
• regulation of protein stability
• regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion
• positive regulation of potassium ion transport
• regulation of release of sequestered calcium ion into cytosol
• SA node cell action potential
• protein stabilization
• ventricular cardiac muscle cell action potential
• cellular calcium ion homeostasis
• positive regulation of calcium ion transmembrane transporter activity
• nervous system development
• regulation of heart rate
• protein localization to M-band
• endoplasmic reticulum to Golgi vesicle-mediated transport
• regulation of cardiac muscle cell contraction
• protein localization to T-tubule
• GO:1901313 positive regulation of gene expression
• protein localization to cell surface
• paranodal junction assembly
• atrial cardiac muscle cell action potential
• sarcoplasmic reticulum calcium ion transport
• SA node cell to atrial cardiac muscle cell communication
• membrane depolarization during SA node cell action potential
• atrial cardiac muscle cell to AV node cell communication
• regulation of cardiac muscle contraction
• protein localization to endoplasmic reticulum
• response to methylmercury
• regulation of SA node cell action potential
• regulation of heart rate by cardiac conduction
• atrial septum development
• regulation of calcium ion transmembrane transporter activity
• GO:0072468 Transdukcija signala
• regulation of atrial cardiac muscle cell action potential
• T-tubule organization
• positive regulation of calcium ion transport
• regulation of ventricular cardiac muscle cell membrane repolarization
• cytoskeleton organization
• protein localization to plasma membrane
• Endocitoza
• protein transport
Izvori:Amigo / QuickGO
Ortolozi
VrsteČovjekMiš
Entrez

287

n/a

Ensembl

ENSG00000145362

n/a

UniProt

Q01484

n/a

RefSeq (mRNK)

NM_001127493
NM_001148
NM_020977

n/a

RefSeq (bjelančevina)
NP_001120965
NP_001139
NP_066187
NP_001341154
NP_001341157

NP_001341159
NP_001341160
NP_001341161
NP_001341164
NP_001341165
NP_001341166
NP_001341168
NP_001341169
NP_001341170
NP_001341171
NP_001341172
NP_001341173
NP_001341174
NP_001341175
NP_001341178
NP_001341181
NP_001341182
NP_001341183
NP_001341184
NP_001341185
NP_001341186
NP_001341187
NP_001341189
NP_001341190
NP_001341191
NP_001341193
NP_001341194
NP_001341195
NP_001341196
NP_001341197
NP_001341198
NP_001341199
NP_001341200
NP_001341201
NP_001341202
NP_001341203
NP_001341204
NP_001341205
NP_001341206
NP_001341207
NP_001341208
NP_001341209
NP_001341210
NP_001341211

n/a

Lokacija (UCSC)n/an/a
PubMed pretraga[1]n/a
Wikipodaci
Pogledaj/uredi – čovjek

Aminokiselinska sekvenca uredi

Dužina polipeptidnog lanca je 3.957 aminokiselina, a molekulska težina 433.715 Da.[4]

1020304050
MMNEDAAQKSDSGEKFNGSSQRRKRPKKSDSNASFLRAARAGNLDKVVEY
LKGGIDINTCNQNGLNALHLAAKEGHVGLVQELLGRGSSVDSATKKGNTA
LHIASLAGQAEVVKVLVKEGANINAQSQNGFTPLYMAAQENHIDVVKYLL
ENGANQSTATEDGFTPLAVALQQGHNQAVAILLENDTKGKVRLPALHIAA
RKDDTKSAALLLQNDHNADVQSKMMVNRTTESGFTPLHIAAHYGNVNVAT
LLLNRGAAVDFTARNGITPLHVASKRGNTNMVKLLLDRGGQIDAKTRDGL
TPLHCAARSGHDQVVELLLERGAPLLARTKNGLSPLHMAAQGDHVECVKH
LLQHKAPVDDVTLDYLTALHVAAHCGHYRVTKLLLDKRANPNARALNGFT
PLHIACKKNRIKVMELLVKYGASIQAITESGLTPIHVAAFMGHLNIVLLL
LQNGASPDVTNIRGETALHMAARAGQVEVVRCLLRNGALVDARAREEQTP
LHIASRLGKTEIVQLLLQHMAHPDAATTNGYTPLHISAREGQVDVASVLL
EAGAAHSLATKKGFTPLHVAAKYGSLDVAKLLLQRRAAADSAGKNGLTPL
HVAAHYDNQKVALLLLEKGASPHATAKNGYTPLHIAAKKNQMQIASTLLN
YGAETNIVTKQGVTPLHLASQEGHTDMVTLLLDKGANIHMSTKSGLTSLH
LAAQEDKVNVADILTKHGADQDAHTKLGYTPLIVACHYGNVKMVNFLLKQ
GANVNAKTKNGYTPLHQAAQQGHTHIINVLLQHGAKPNATTANGNTALAI
AKRLGYISVVDTLKVVTEEVTTTTTTITEKHKLNVPETMTEVLDVSDEEG
DDTMTGDGGEYLRPEDLKELGDDSLPSSQFLDGMNYLRYSLEGGRSDSLR
SFSSDRSHTLSHASYLRDSAVMDDSVVIPSHQVSTLAKEAERNSYRLSWG
TENLDNVALSSSPIHSGFLVSFMVDARGGAMRGCRHNGLRIIIPPRKCTA
PTRVTCRLVKRHRLATMPPMVEGEGLASRLIEVGPSGAQFLGKLHLPTAP
PPLNEGESLVSRILQLGPPGTKFLGPVIVEIPHFAALRGKERELVVLRSE
NGDSWKEHFCDYTEDELNEILNGMDEVLDSPEDLEKKRICRIITRDFPQY
FAVVSRIKQDSNLIGPEGGVLSSTVVPQVQAVFPEGALTKRIRVGLQAQP
MHSELVKKILGNKATFSPIVTLEPRRRKFHKPITMTIPVPKASSDVMLNG
FGGDAPTLRLLCSITGGTTPAQWEDITGTTPLTFVNECVSFTTNVSARFW
LIDCRQIQESVTFASQVYREIICVPYMAKFVVFAKSHDPIEARLRCFCMT
DDKVDKTLEQQENFAEVARSRDVEVLEGKPIYVDCFGNLVPLTKSGQHHI
FSFFAFKENRLPLFVKVRDTTQEPCGRLSFMKEPKSTRGLVHQAICNLNI
TLPIYTKESESDQEQEEEIDMTSEKNDETESTETSVLKSHLVNEVPVLAS
PDLLSEVSEMKQDLIKMTAILTTDVSDKAGSIKVKELVKAAEEEPGEPFE
IVERVKEDLEKVNEILRSGTCTRDESSVQSSRSERGLVEEEWVIVSDEEI
EEARQKAPLEITEYPCVEVRIDKEIKGKVEKDSTGLVNYLTDDLNTCVPL
PKEQLQTVQDKAGKKCEALAVGRSSEKEGKDIPPDETQSTQKQHKPSLGI
KKPVRRKLKEKQKQKEEGLQASAEKAELKKGSSEESLGEDPGLAPEPLPT
VKATSPLIEETPIGSIKDKVKALQKRVEDEQKGRSKLPIRVKGKEDVPKK
TTHRPHPAASPSLKSERHAPGSPSPKTERHSTLSSSAKTERHPPVSPSSK
TEKHSPVSPSAKTERHSPASSSSKTEKHSPVSPSTKTERHSPVSSTKTER
HPPVSPSGKTDKRPPVSPSGRTEKHPPVSPGRTEKRLPVSPSGRTDKHQP
VSTAGKTEKHLPVSPSGKTEKQPPVSPTSKTERIEETMSVRELMKAFQSG
QDPSKHKTGLFEHKSAKQKQPQEKGKVRVEKEKGPILTQREAQKTENQTI
KRGQRLPVTGTAESKRGVRVSSIGVKKEDAAGGKEKVLSHKIPEPVQSVP
EEESHRESEVPKEKMADEQGDMDLQISPDRKTSTDFSEVIKQELEDNDKY
QQFRLSEETEKAQLHLDQVLTSPFNTTFPLDYMKDEFLPALSLQSGALDG
SSESLKNEGVAGSPCGSLMEGTPQISSEESYKHEGLAETPETSPESLSFS
PKKSEEQTGETKESTKTETTTEIRSEKEHPTTKDITGGSEERGATVTEDS
ETSTESFQKEATLGSPKDTSPKRQDDCTGSCSVALAKETPTGLTEEAACD
EGQRTFGSSAHKTQTDSEVQESTATSDETKALPLPEASVKTDTGTESKPQ
GVIRSPQGLELALPSRDSEVLSAVADDSLAVSHKDSLEASPVLEDNSSHK
TPDSLEPSPLKESPCRDSLESSPVEPKMKAGIFPSHFPLPAAVAKTELLT
EVASVRSRLLRDPDGSAEDDSLEQTSLMESSGKSPLSPDTPSSEEVSYEV
TPKTTDVSTPKPAVIHECAEEDDSENGEKKRFTPEEEMFKMVTKIKMFDE
LEQEAKQKRDYKKEPKQEESSSSSDPDADCSVDVDEPKHTGSGEDESGVP
VLVTSESRKVSSSSESEPELAQLKKGADSGLLPEPVIRVQPPSPLPSSMD
SNSSPEEVQFQPVVSKQYTFKMNEDTQEEPGKSEEEKDSESHLAEDRHAV
STEAEDRSYDKLNRDTDQPKICDGHGCEAMSPSSSAAPVSSGLQSPTGDD
VDEQPVIYKESLALQGTHEKDTEGEELDVSRAESPQADCPSESFSSSSSL
PHCLVSEGKELDEDISATSSIQKTEVTKTDETFENLPKDCPSQDSSITTQ
TDRFSMDVPVSDLAENDEIYDPQITSPYENVPSQSFFSSEESKTQTDANH
TTSFHSSEVYSVTITSPVEDVVVASSSSGTVLSKESNFEGQDIKMESQQE
STLWEMQSDSVSSSFEPTMSATTTVVGEQISKVIITKTDVDSDSWSEIRE
DDEAFEARVKEEEQKIFGLMVDRQSQGTTPDTTPARTPTEEGTPTSEQNP
FLFQEGKLFEMTRSGAIDMTKRSYADESFHFFQIGQESREETLSEDVKEG
ATGADPLPLETSAESLALSESKETVDDEADLLPDDVSEEVEEIPASDAQL
NSQMGISASTETPTKEAVSVGTKDLPTVQTGDIPPLSGVKQISCPDSSEP
AVQVQLDFSTLTRSVYSDRGDDSPDSSPEEQKSVIEIPTAPMENVPFTES
KSKIPVRTMPTSTPAPPSAEYESSVSEDFLSSVDEENKADEAKPKSKLPV
KVPLQRVEQQLSDLDTSVQKTVAPQGQDMASIAPDNRSKSESDASSLDSK
TKCPVKTRSYTETETESRERAEELELESEEGATRPKILTSRLPVKSRSTT
SSCRGGTSPTKESKEHFFDLYRNSIEFFEEISDEASKLVDRLTQSEREQE
IVSDDESSSALEVSVIENLPPVETEHSVPEDIFDTRPIWDESIETLIERI
PDENGHDHAEDPQDEQERIEERLAYIADHLGFSWTELARELDFTEEQIHQ
IRIENPNSLQDQSHALLKYWLERDGKHATDTNLVECLTKINRMDIVHLME
TNTEPLQERISHSYAEIEQTITLDHSEGFSVLQEELCTAQHKQKEEQAVS
KESETCDHPPIVSEEDISVGYSTFQDGVPKTEGDSSATALFPQTHKEQVQ
QDFSGKMQDLPEESSLEYQQEYFVTTPGTETSETQKAMIVPSSPSKTPEE
VSTPAEEEKLYLQTPTSSERGGSPIIQEPEEPSEHREESSPRKTSLVIVE
SADNQPETCERLDEDAAFEKGDDMPEIPPETVTEEEYIDEHGHTVVKKVT
RKIIRRYVSSEGTEKEEIMVQGMPQEPVNIEEGDGYSKVIKRVVLKSDTE
QSEDNNE

Struktura uredi

Ankirin-B protein ima oko 220 kDa, sa nekoliko izoformi.[5] Gen ANK2 je veličine približno 560 kb i sastoji se od 53 egzona na ljudskom hromosomu 4; ANK2 se transkripcijski regulira putem preko 30 prerađenih varijani s promjenjivom ekspresijom izoformi u srčanom mišiću.[6][7][8] Ankirin-B je član ankirinske porodice proteina i modulairajući protein koji sadrži tri strukturna domena: N-terminalni domen sadrži multiplo ankirinsko ponavljanje; centralna regija sa visoko konzerviranim spektrinski vezujućim domenom sa domenom smrti, te C-terminalni regulatorni domen koji je posljednji konzervirani subjekt varijacije koji određuje aktivnost ankirina-B.[2][9][10]

Regija ankirina-B koja se veže za membranu sastoji se od 24 uzastopna ponavljanja ankirina , a domen vezivanja membrane za ankirine daje funkcionalne razlike među ankirinskih izoformi.[10] Iako je sveprisutno eksprimiran, ankirin-B pokazuje visoke nivoe ekspresije u srčanom mišiću, a eksprimiran je u 10 puta nižem nivou u skeletnim mišićima, što sugerira da ankirin-B u srčanum mišiću ima specifično prilagođenu funkciju.[11]

Funkcija uredi

Ankirin-B je član ankirinske porodice proteina. ankirin-1 se pokazao esencijalnim za normalnu funkciju eritrocita;[12] međutim, ankirin-B i ankirin-3 imaju bitnu ulogu u lokalizaciji i stabilizaciji membrane ionskih transportera i ionskih kanala u kardiomiocitima.[11][13]

Uvid u funkcioniranje ankirina-B dolazi iz studija koje koriste proteine himernog ankirina-B. Jedna studija pokazala je da domen smrti/C-terminal domen ankirina-B određuje i subćelijsku lokalizaciju, kao i aktivnost u obnavljanju normalnog receptora inozitol-trisfosfata i lokalizacije rinodinskog receptora i kardiomiocitne kontraktilnosti.[10] Dalja istraživanja pokazala su da su beta-ukosničke unutar domena ankirinskog ponavljanja domena ankirina-B potrebnog za interakciju sa receptora inozitol-trisfosfata, a smanjenje razine ankirina-B u neonatusnim kardiomiocitima smanjuje poluživot receptora inozitol-trisfosfata za tri puta i destabilizira njegovu pravilnu lokalizaciju ; svi ovi efekti su uklonjeni ponovnim uvođenjem ankirina-B.[14] Štaviše, specifična sekvenca u ankirinu-B (odsutna u drugim ankirinskim izoformama) savija se kao amfipatski alfa-heliks potreban je za normalne nivoe izmjenjivača natrij-kalcija, natrij- kalij ATPaza i receptora inozitol-trifosfata u kardiomiocitima, a regulirano je putem HDJ1/HSP40 vezivanja za ovu regiju.[15]

Dodatni uvid u funkciju ankirina-B došao je iz studija koje su koristile ankirin-B transgenih životinja. Ankirin-B iz kardiomiocita mišjeg genotipa (–/+) pokazali su nepravilne prostorne obrasce i periodičnost oslobađanja kalcija, kao i abnormalnu raspodjelu sarkomplazmatske mrežaste natrij-ATPaze, SERCA2 i rijanodinskih receptora, uz efekte koji su spašeni transfekcijom ankirina-B.[16] Efekti na rijanodinske receptore su također spašeni snažnim inhibitorom Ca2+/kalmodulin-ovisne protein-kinaze II, što sugerira da inhibicija Ca2+/kalmodulin-zavisne protein kinaze II takođe može biti potencijalna strategija liječenja.[17][18] Ovi miševi također pokazuju nekoliko elektrofizioloških abnormalnosti, uključujući bradikardiju, varijabilne otkucaje srca, duge QT-intervale, kateholaminergijsku polimorfnu ventrikularnu tahikardiju, sinkopu i iznenadnu srčanu smrt.[19] Mehanistička objašnjenja koja su u osnovi ovih efekata objašnjena su u kasnijoj studiji sprovedenoj na ankirinu-B (–/+) miševa, koja je pokazala da smanjenje ankirina-B menja transport natrija i kalcija i poboljšava spajanje otvora rijnodinskih receptora, što rezultira višom frekvencijom kalijevih iskri i talasima kalcija.[20]

Sada postaje jasno da ankirin-B postoji u biomolekulskom kompleksu sa natrij-kalij-ATPazom, natrij-kalcij izmjenjivačem i receptorom inozitol-trifosfata koji je lokalizovan u T-tubulama unutar diskretnih mikrodomena kardiomiocita koji se razlikuju od dijada formiranih od kompleksa dihidropiridinskog receptora sa rijanodinskim receptorimas. Aritmogena mutacija ljudskog ankirina-B (Glu1425Gly) blokira stvaranje ovog kompleksa, koji obezbjeđuje mehanizam iza srčane srčane aritmije kod pacijenata.[11] Studije iz drugih laboratorija bacile su svjetlo na potrebu ankirina-B u ciljanju i posttranslacijskoj stabilnosti natrij-kalcij izmjenjivača u kardiomiocitima , što je klinički važno jer je povećana ekspresija izmjenjivača natrij-kalcij faktor povezan sa aritmijom i srčanom insuficijencijom.[21] Ankyrin-B formira membranski kompleks sa ATP-osjetljivim kalijskim kanalima, koji je neophodan za normalan promet kanala i ciljanje kanala na membrane sarkolema; ova interakcija je također važna u odgovoru kardiomiocita na srčanu ishemiju i u regulaciji metabolizma.[22][23]

Također je identificirano da se ankirin-B povezuje na sarkomernim M-linijama i kostamerama u srčanom i seletnim mišićima. Egzon 43′ u ankirinu-B je specifično i pretežno eksprimiran u srčanom mišiću i sadrži ključne ostatke za moduliranje interakcija između ankirina-B i opskurina. Ova interakcija je također ključna za ciljanje protein-fosfataza 2A na srčanim M-linijama radi propagiranja signalnih paradigmi fosforilacije.[24] U skeletnim mišićima, ankirin-B stupa u interakciju sa dinaktinom-4 i sa β2-spektrom, što je potrebno za pravilnu lokalizaciju i funkcioniranje distrofinskog kompleksa i kostamernih struktura, kao i zaštita od ozljeda uzrokovanih vježbanjem[25]

Klinički značaj uredi

Mutacije u genu ANK2 povezane su sa dominantno naslijeđenim, srčanim aritmijom, sindromom poznatim kao ankirin-B sindrom, koji se ranije nazivao sindrom dugog QT-intervala, tip 4, koji se može opisati kao atipski aritmijski sindrom sa bradikardijom, atrijskm fibrilacijom, blokom provodljivosti, aritmijom i rizikom od iznenadne srčane smrti[26][27][28] Intenzivna istraga je u toku u vezi sa povezivanjem mutacija ANK2-a sa opsegom ozbiljnosti fenotipova srčanih tegoba, a početni dokazi sugeriraju da različiti stupnjevi gubitka funkcije ankirina-B mogu objasniti učinak bilo koje određene mutacije.[29][30][31][32][33][34][35][36][37][38]

U početku je otkriveno da mutacija Glu1425Gly u ANK2 uzrokuje dominantno naslijeđeni sindrom dugog QT, tip 4, srčanu aritmiju. Mehanističke osnove ove mutacije uključuju abnormalnu ekspresiju i ciljanje natrijeve pumpe, izmjenjivača natrij-kalcij i inozitol-1,4,5-trisfosfatne receptore na poprečne tubule, kao i rukovanje kalcijem, što dovodi do ekstra[[sistole a]].[39] Daljnja analiza mutacija ANK2 u regulatornom domenu ankirina-2, koja je specifična za izoformu ankirina-2, pokazala je da sindrom dugog QT nije dosljedna klinička manifestacija mutacije ANK2;[40] međutim, efekat na dinamiku Ca(2+) i lokalizaciju/ekspresiju izmjenjivača natrij-kalciju, natrij-kalij ATPaza i receptora inozitol-trifosfata u kardiomiocitima bila su konzistentna zapažanja. Ova studija pokazala je da su uobičajene patogene karakteristike svih mutacija "ANK2" abnormalna koordinacija panela povezanih ionskih kanala i transportera.[41] Additional mechanistic studies have shown that atrial cardiomyocytes lacking ankyrin-B have shortened action potentials, which can be explained by decreased voltage-dependent calcium channel expression, specifically Ca(v)1.3, which is responsible for low voltage-activated L-type Ca(2+) currents. Ankyrin-B directly associates with and is required for targeting Ca(v)1.3 to membranes.[42]

Mutacije ANK2 identificirane su također kod pacijenata sa disfunkcijom sinusnog čvora. Mehanicističke studije o efektima ovih mutacija na miševima pokazale su ozbiljnu bradikardiju i varijabilnost otkucaja srca, kao i disfunkciju u putevima prometa, baziranim na ankirinu B u primarnim i pomoćnim ćelijama pejsmejkera.[43][44][45] U velikoj studiji odnosa genotip-fenotip na 874 pacijenta sa hipertrofijskom kardiomiopatijom, pacijenti sa varijantama ANK2 pokazali su veću maksimalnu debljinu zida lijeve komore.[46]

Kod pacijenata sa ishemijskom i neishemijskom srčanom insuficijencijom, nivoi ankirina-B su promenjeni. Dalja mehanička studija je pokazala da reaktivne vrste kisika, unutarćelijski kalcij i kalpain reguliraju nivoe srčanog ankirina-B, a ankirin-B je neophodan za normalnu kardioprotekciju nakon reperfuzionih povreda.[47]

Interakcije uredi

Reference uredi

  1. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  2. ^ a b "Entrez Gene: ANK2 ankyrin 2, neuronal".
  3. ^ Schott JJ, Charpentier F, Peltier S, Foley P, Drouin E, Bouhour JB, Donnelly P, Vergnaud G, Bachner L, Moisan JP, et al. (novembar 1995). "Mapping of a gene for long QT syndrome to chromosome 4q25-27". Am. J. Hum. Genet. 57 (5): 1114–22. PMC 1801360. PMID 7485162.
  4. ^ "UniProt, Q01484" (jezik: engleski). Pristupljeno 21. 10. 2021.
  5. ^ "Protein sequences of human ANK2 (Uniprot ID Q01484)". UniProt. Pristupljeno 12. 7. 2015.
  6. ^ Wu, HC; Yamankurt, G; Luo, J; Subramaniam, J; Hashmi, SS; Hu, H; Cunha, SR (24. 6. 2015). "Identification and characterization of two ankyrin-B isoforms in mammalian heart". Cardiovascular Research. 107 (4): 466–77. doi:10.1093/cvr/cvv184. PMC 4540146. PMID 26109584.
  7. ^ van Oort, RJ; Altamirano, J; Lederer, WJ; Wehrens, XH (decembar 2008). "Alternative splicing: a key mechanism for ankyrin-B functional diversity?". Journal of Molecular and Cellular Cardiology. 45 (6): 709–11. doi:10.1016/j.yjmcc.2008.08.016. PMC 2606664. PMID 18838078.
  8. ^ Cunha, SR; Le Scouarnec, S; Schott, JJ; Mohler, PJ (decembar 2008). "Exon organization and novel alternative splicing of the human ANK2 gene: implications for cardiac function and human cardiac disease". Journal of Molecular and Cellular Cardiology. 45 (6): 724–34. doi:10.1016/j.yjmcc.2008.08.005. PMC 2630508. PMID 18790697.
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