Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTWB4R1Y)

• DOT Name: Ankyrin-2 (ANK2)
• Synonyms: ANK-2; Ankyrin-B; Brain ankyrin; Non-erythroid ankyrin
• Gene Name: ANK2
• Related Disease:
  Complex neurodevelopmental disorder
  Neuroblastoma
  Neurodevelopmental disorder
  Andersen-Tawil syndrome
  Arrhythmia
  Atrial fibrillation
  Autism
  Autism spectrum disorder
  Autosomal recessive early-onset Parkinson disease 6
  Beta thalassemia
  Cardiac arrhythmia, ankyrin-B-related
  Cardiac disease
  Cardiac failure
  Cardiovascular disease
  Congestive heart failure
  Epilepsy
  Myocardial infarction
  Neurodegenerative disease
  Obesity
  Oligospermia
  Parkinson disease
  Sinoatrial node disorder
  Spinocerebellar ataxia type 5
  Stroke
  Venous thromboembolism
  Ventricular tachycardia
  Acute myelogenous leukaemia
  Brugada syndrome
  Catecholaminergic polymorphic ventricular tachycardia
  Long QT syndrome
  Catecholaminergic polymorphic ventricular tachycardia 1
  Heart arrhythmia
  Non-insulin dependent diabetes
• UniProt ID: ANK2_HUMAN
• PDB ID: 4D8O; 4RLV; 4RLY; 5Y4D; 5Y4E; 5Y4F; 5YIR; 5YIS; 6KZJ; 6M3Q
• Pfam ID: PF00023 ; PF12796 ; PF13637 ; PF00531 ; PF17809 ; PF00791
• Sequence:
  MMNEDAAQKSDSGEKFNGSSQRRKRPKKSDSNASFLRAARAGNLDKVVEYLKGGIDINTC
  NQNGLNALHLAAKEGHVGLVQELLGRGSSVDSATKKGNTALHIASLAGQAEVVKVLVKEG
  ANINAQSQNGFTPLYMAAQENHIDVVKYLLENGANQSTATEDGFTPLAVALQQGHNQAVA
  ILLENDTKGKVRLPALHIAARKDDTKSAALLLQNDHNADVQSKMMVNRTTESGFTPLHIA
  AHYGNVNVATLLLNRGAAVDFTARNGITPLHVASKRGNTNMVKLLLDRGGQIDAKTRDGL
  TPLHCAARSGHDQVVELLLERGAPLLARTKNGLSPLHMAAQGDHVECVKHLLQHKAPVDD
  VTLDYLTALHVAAHCGHYRVTKLLLDKRANPNARALNGFTPLHIACKKNRIKVMELLVKY
  GASIQAITESGLTPIHVAAFMGHLNIVLLLLQNGASPDVTNIRGETALHMAARAGQVEVV
  RCLLRNGALVDARAREEQTPLHIASRLGKTEIVQLLLQHMAHPDAATTNGYTPLHISARE
  GQVDVASVLLEAGAAHSLATKKGFTPLHVAAKYGSLDVAKLLLQRRAAADSAGKNGLTPL
  HVAAHYDNQKVALLLLEKGASPHATAKNGYTPLHIAAKKNQMQIASTLLNYGAETNIVTK
  QGVTPLHLASQEGHTDMVTLLLDKGANIHMSTKSGLTSLHLAAQEDKVNVADILTKHGAD
  QDAHTKLGYTPLIVACHYGNVKMVNFLLKQGANVNAKTKNGYTPLHQAAQQGHTHIINVL
  LQHGAKPNATTANGNTALAIAKRLGYISVVDTLKVVTEEVTTTTTTITEKHKLNVPETMT
  EVLDVSDEEGDDTMTGDGGEYLRPEDLKELGDDSLPSSQFLDGMNYLRYSLEGGRSDSLR
  SFSSDRSHTLSHASYLRDSAVMDDSVVIPSHQVSTLAKEAERNSYRLSWGTENLDNVALS
  SSPIHSGFLVSFMVDARGGAMRGCRHNGLRIIIPPRKCTAPTRVTCRLVKRHRLATMPPM
  VEGEGLASRLIEVGPSGAQFLGKLHLPTAPPPLNEGESLVSRILQLGPPGTKFLGPVIVE
  IPHFAALRGKERELVVLRSENGDSWKEHFCDYTEDELNEILNGMDEVLDSPEDLEKKRIC
  RIITRDFPQYFAVVSRIKQDSNLIGPEGGVLSSTVVPQVQAVFPEGALTKRIRVGLQAQP
  MHSELVKKILGNKATFSPIVTLEPRRRKFHKPITMTIPVPKASSDVMLNGFGGDAPTLRL
  LCSITGGTTPAQWEDITGTTPLTFVNECVSFTTNVSARFWLIDCRQIQESVTFASQVYRE
  IICVPYMAKFVVFAKSHDPIEARLRCFCMTDDKVDKTLEQQENFAEVARSRDVEVLEGKP
  IYVDCFGNLVPLTKSGQHHIFSFFAFKENRLPLFVKVRDTTQEPCGRLSFMKEPKSTRGL
  VHQAICNLNITLPIYTKESESDQEQEEEIDMTSEKNDETESTETSVLKSHLVNEVPVLAS
  PDLLSEVSEMKQDLIKMTAILTTDVSDKAGSIKVKELVKAAEEEPGEPFEIVERVKEDLE
  KVNEILRSGTCTRDESSVQSSRSERGLVEEEWVIVSDEEIEEARQKAPLEITEYPCVEVR
  IDKEIKGKVEKDSTGLVNYLTDDLNTCVPLPKEQLQTVQDKAGKKCEALAVGRSSEKEGK
  DIPPDETQSTQKQHKPSLGIKKPVRRKLKEKQKQKEEGLQASAEKAELKKGSSEESLGED
  PGLAPEPLPTVKATSPLIEETPIGSIKDKVKALQKRVEDEQKGRSKLPIRVKGKEDVPKK
  TTHRPHPAASPSLKSERHAPGSPSPKTERHSTLSSSAKTERHPPVSPSSKTEKHSPVSPS
  AKTERHSPASSSSKTEKHSPVSPSTKTERHSPVSSTKTERHPPVSPSGKTDKRPPVSPSG
  RTEKHPPVSPGRTEKRLPVSPSGRTDKHQPVSTAGKTEKHLPVSPSGKTEKQPPVSPTSK
  TERIEETMSVRELMKAFQSGQDPSKHKTGLFEHKSAKQKQPQEKGKVRVEKEKGPILTQR
  EAQKTENQTIKRGQRLPVTGTAESKRGVRVSSIGVKKEDAAGGKEKVLSHKIPEPVQSVP
  EEESHRESEVPKEKMADEQGDMDLQISPDRKTSTDFSEVIKQELEDNDKYQQFRLSEETE
  KAQLHLDQVLTSPFNTTFPLDYMKDEFLPALSLQSGALDGSSESLKNEGVAGSPCGSLME
  GTPQISSEESYKHEGLAETPETSPESLSFSPKKSEEQTGETKESTKTETTTEIRSEKEHP
  TTKDITGGSEERGATVTEDSETSTESFQKEATLGSPKDTSPKRQDDCTGSCSVALAKETP
  TGLTEEAACDEGQRTFGSSAHKTQTDSEVQESTATSDETKALPLPEASVKTDTGTESKPQ
  GVIRSPQGLELALPSRDSEVLSAVADDSLAVSHKDSLEASPVLEDNSSHKTPDSLEPSPL
  KESPCRDSLESSPVEPKMKAGIFPSHFPLPAAVAKTELLTEVASVRSRLLRDPDGSAEDD
  SLEQTSLMESSGKSPLSPDTPSSEEVSYEVTPKTTDVSTPKPAVIHECAEEDDSENGEKK
  RFTPEEEMFKMVTKIKMFDELEQEAKQKRDYKKEPKQEESSSSSDPDADCSVDVDEPKHT
  GSGEDESGVPVLVTSESRKVSSSSESEPELAQLKKGADSGLLPEPVIRVQPPSPLPSSMD
  SNSSPEEVQFQPVVSKQYTFKMNEDTQEEPGKSEEEKDSESHLAEDRHAVSTEAEDRSYD
  KLNRDTDQPKICDGHGCEAMSPSSSAAPVSSGLQSPTGDDVDEQPVIYKESLALQGTHEK
  DTEGEELDVSRAESPQADCPSESFSSSSSLPHCLVSEGKELDEDISATSSIQKTEVTKTD
  ETFENLPKDCPSQDSSITTQTDRFSMDVPVSDLAENDEIYDPQITSPYENVPSQSFFSSE
  ESKTQTDANHTTSFHSSEVYSVTITSPVEDVVVASSSSGTVLSKESNFEGQDIKMESQQE
  STLWEMQSDSVSSSFEPTMSATTTVVGEQISKVIITKTDVDSDSWSEIREDDEAFEARVK
  EEEQKIFGLMVDRQSQGTTPDTTPARTPTEEGTPTSEQNPFLFQEGKLFEMTRSGAIDMT
  KRSYADESFHFFQIGQESREETLSEDVKEGATGADPLPLETSAESLALSESKETVDDEAD
  LLPDDVSEEVEEIPASDAQLNSQMGISASTETPTKEAVSVGTKDLPTVQTGDIPPLSGVK
  QISCPDSSEPAVQVQLDFSTLTRSVYSDRGDDSPDSSPEEQKSVIEIPTAPMENVPFTES
  KSKIPVRTMPTSTPAPPSAEYESSVSEDFLSSVDEENKADEAKPKSKLPVKVPLQRVEQQ
  LSDLDTSVQKTVAPQGQDMASIAPDNRSKSESDASSLDSKTKCPVKTRSYTETETESRER
  AEELELESEEGATRPKILTSRLPVKSRSTTSSCRGGTSPTKESKEHFFDLYRNSIEFFEE
  ISDEASKLVDRLTQSEREQEIVSDDESSSALEVSVIENLPPVETEHSVPEDIFDTRPIWD
  ESIETLIERIPDENGHDHAEDPQDEQERIEERLAYIADHLGFSWTELARELDFTEEQIHQ
  IRIENPNSLQDQSHALLKYWLERDGKHATDTNLVECLTKINRMDIVHLMETNTEPLQERI
  SHSYAEIEQTITLDHSEGFSVLQEELCTAQHKQKEEQAVSKESETCDHPPIVSEEDISVG
  YSTFQDGVPKTEGDSSATALFPQTHKEQVQQDFSGKMQDLPEESSLEYQQEYFVTTPGTE
  TSETQKAMIVPSSPSKTPEEVSTPAEEEKLYLQTPTSSERGGSPIIQEPEEPSEHREESS
  PRKTSLVIVESADNQPETCERLDEDAAFEKGDDMPEIPPETVTEEEYIDEHGHTVVKKVT
  RKIIRRYVSSEGTEKEEIMVQGMPQEPVNIEEGDGYSKVIKRVVLKSDTEQSEDNNE
• Function: Plays an essential role in the localization and membrane stabilization of ion transporters and ion channels in several cell types, including cardiomyocytes, as well as in striated muscle cells. In skeletal muscle, required for proper localization of DMD and DCTN4 and for the formation and/or stability of a special subset of microtubules associated with costameres and neuromuscular junctions. In cardiomyocytes, required for coordinate assembly of Na/Ca exchanger, SLC8A1/NCX1, Na/K ATPases ATP1A1 and ATP1A2 and inositol 1,4,5-trisphosphate (InsP3) receptors at sarcoplasmic reticulum/sarcolemma sites. Required for expression and targeting of SPTBN1 in neonatal cardiomyocytes and for the regulation of neonatal cardiomyocyte contraction rate. In the inner segment of rod photoreceptors, required for the coordinated expression of the Na/K ATPase, Na/Ca exchanger and beta-2-spectrin (SPTBN1). Plays a role in endocytosis and intracellular protein transport. Associates with phosphatidylinositol 3-phosphate (PI3P)-positive organelles and binds dynactin to promote long-range motility of cells. Recruits RABGAP1L to (PI3P)-positive early endosomes, where RABGAP1L inactivates RAB22A, and promotes polarized trafficking to the leading edge of the migrating cells. Part of the ANK2/RABGAP1L complex which is required for the polarized recycling of fibronectin receptor ITGA5 ITGB1 to the plasma membrane that enables continuous directional cell migration.
• Tissue Specificity: Present in plasma membrane of neurons as well as glial cells throughout the brain. Expressed in fetal brain and in temporal cortex of adult brain. Also expressed in the inner segments of rod photoreceptors in retina.
• KEGG Pathway:
  Cytoskeleton in muscle cells (hsa04820)
  Proteoglycans in cancer (hsa05205)
• Reactome Pathway:
  COPI-mediated anterograde transport (R-HSA-6807878)
  Interaction between L1 and Ankyrins (R-HSA-445095)

Molecular Interaction Atlas (MIA) of This DOT

33 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Complex neurodevelopmental disorder	DISB9AFI	Definitive	Autosomal dominant	[1]
Neuroblastoma	DISVZBI4	Definitive	Altered Expression	[2]
Neurodevelopmental disorder	DIS372XH	Definitive	Biomarker	[3]
Andersen-Tawil syndrome	DIS3IWZ7	Strong	Biomarker	[4]
Arrhythmia	DISFF2NI	Strong	Biomarker	[5]
Atrial fibrillation	DIS15W6U	Strong	Biomarker	[6]
Autism	DISV4V1Z	Strong	Genetic Variation	[7]
Autism spectrum disorder	DISXK8NV	Strong	Genetic Variation	[7]
Autosomal recessive early-onset Parkinson disease 6	DISHVLD5	Strong	Biomarker	[8]
Beta thalassemia	DIS5RCQK	Strong	Genetic Variation	[9]
Cardiac arrhythmia, ankyrin-B-related	DISGGN33	Strong	Autosomal dominant	[10]
Cardiac disease	DISVO1I5	Strong	Genetic Variation	[11]
Cardiac failure	DISDC067	Strong	Altered Expression	[12]
Cardiovascular disease	DIS2IQDX	Strong	Biomarker	[13]
Congestive heart failure	DIS32MEA	Strong	Altered Expression	[12]
Epilepsy	DISBB28L	Strong	Biomarker	[14]
Myocardial infarction	DIS655KI	Strong	Biomarker	[15]
Neurodegenerative disease	DISM20FF	Strong	Biomarker	[16]
Obesity	DIS47Y1K	Strong	Biomarker	[17]
Oligospermia	DIS6YJF3	Strong	Posttranslational Modification	[18]
Parkinson disease	DISQVHKL	Strong	Biomarker	[8]
Sinoatrial node disorder	DISYJI6J	Strong	Genetic Variation	[19]
Spinocerebellar ataxia type 5	DISPYXJ0	Strong	Biomarker	[20]
Stroke	DISX6UHX	Strong	Biomarker	[21]
Venous thromboembolism	DISUR7CR	Strong	Genetic Variation	[22]
Ventricular tachycardia	DISIBXJ3	Strong	Genetic Variation	[23]
Acute myelogenous leukaemia	DISCSPTN	moderate	Genetic Variation	[24]
Brugada syndrome	DISSGN0E	Disputed	Autosomal dominant	[1]
Catecholaminergic polymorphic ventricular tachycardia	DISSAS1A	Disputed	Autosomal dominant	[1]
Long QT syndrome	DISMKWS3	Disputed	Autosomal dominant	[1]
Catecholaminergic polymorphic ventricular tachycardia 1	DISKGB3F	Limited	Genetic Variation	[13]
Heart arrhythmia	DISLKUNL	Limited	Autosomal dominant	[25]
Non-insulin dependent diabetes	DISK1O5Z	Limited	Genetic Variation	[26]

This DOT Affected the Drug Response of 3 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Temozolomide	DMKECZD	Approved	Ankyrin-2 (ANK2) affects the response to substance of Temozolomide.	[49]
DTI-015	DMXZRW0	Approved	Ankyrin-2 (ANK2) affects the response to substance of DTI-015.	[49]
Lovastatin	DM9OZWQ	Approved	Ankyrin-2 (ANK2) decreases the response to substance of Lovastatin.	[50]

22 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Ankyrin-2 (ANK2).	[27]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Ankyrin-2 (ANK2).	[28]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Ankyrin-2 (ANK2).	[29]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Ankyrin-2 (ANK2).	[30]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Ankyrin-2 (ANK2).	[31]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Ankyrin-2 (ANK2).	[32]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Ankyrin-2 (ANK2).	[33]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Ankyrin-2 (ANK2).	[35]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Ankyrin-2 (ANK2).	[36]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Ankyrin-2 (ANK2).	[37]
Phenobarbital	DMXZOCG	Approved	Phenobarbital increases the expression of Ankyrin-2 (ANK2).	[38]
Isotretinoin	DM4QTBN	Approved	Isotretinoin increases the expression of Ankyrin-2 (ANK2).	[39]
Mitoxantrone	DMM39BF	Approved	Mitoxantrone decreases the expression of Ankyrin-2 (ANK2).	[31]
Daunorubicin	DMQUSBT	Approved	Daunorubicin decreases the expression of Ankyrin-2 (ANK2).	[31]
Beta-carotene	DM0RXBT	Approved	Beta-carotene increases the expression of Ankyrin-2 (ANK2).	[40]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Ankyrin-2 (ANK2).	[41]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Ankyrin-2 (ANK2).	[42]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Ankyrin-2 (ANK2).	[43]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Ankyrin-2 (ANK2).	[45]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Ankyrin-2 (ANK2).	[46]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Ankyrin-2 (ANK2).	[47]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of Ankyrin-2 (ANK2).	[48]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Ankyrin-2 (ANK2).	[34]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Ankyrin-2 (ANK2).	[44]

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