Details of Drug Off-Target (DOT)

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

DOT Name Tyrosine-protein kinase JAK2 (JAK2)
Synonyms EC 2.7.10.2; Janus kinase 2; JAK-2
Gene Name JAK2
Related Disease
Thrombocythemia 3 ( )
Thrombocythemia ( )
UniProt ID
JAK2_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
2B7A ; 2W1I ; 2XA4 ; 3E62 ; 3E63 ; 3E64 ; 3FUP ; 3IO7 ; 3IOK ; 3JY9 ; 3KCK ; 3KRR ; 3LPB ; 3Q32 ; 3RVG ; 3TJC ; 3TJD ; 3UGC ; 3ZMM ; 4AQC ; 4BBE ; 4BBF ; 4C61 ; 4C62 ; 4D0W ; 4D0X ; 4D1S ; 4E4M ; 4E6D ; 4E6Q ; 4F08 ; 4F09 ; 4FVP ; 4FVQ ; 4FVR ; 4GFM ; 4GMY ; 4HGE ; 4IVA ; 4JI9 ; 4JIA ; 4P7E ; 4YTC ; 4YTF ; 4YTH ; 4YTI ; 4Z32 ; 4ZIM ; 5AEP ; 5CF4 ; 5CF5 ; 5CF6 ; 5CF8 ; 5HEZ ; 5I4N ; 5L3A ; 5TQ3 ; 5TQ4 ; 5TQ5 ; 5TQ6 ; 5TQ7 ; 5TQ8 ; 5USY ; 5USZ ; 5UT0 ; 5UT1 ; 5UT2 ; 5UT3 ; 5UT4 ; 5UT5 ; 5UT6 ; 5WEV ; 5WIJ ; 5WIK ; 5WIL ; 5WIM ; 5WIN ; 6AAJ ; 6BBV ; 6BRW ; 6BS0 ; 6BSS ; 6D2I ; 6DRW ; 6E2P ; 6E2Q ; 6G3C ; 6M9H ; 6OAV ; 6OBB ; 6OBF ; 6OBL ; 6OCC ; 6TPD ; 6VGL ; 6VN8 ; 6VNB ; 6VNC ; 6VNE ; 6VNF ; 6VNG ; 6VNH ; 6VNI ; 6VNJ ; 6VNK ; 6VNL ; 6VNM ; 6VS3 ; 6VSN ; 6WTN ; 6WTO ; 6WTP ; 6WTQ ; 6X8E ; 6XJK ; 7F7W ; 7JYO ; 7JYQ ; 7LL4 ; 7LL5 ; 7Q7I ; 7Q7K ; 7Q7L ; 7Q7W ; 7REE ; 7RN6 ; 7T0P ; 7T1T ; 7TEU ; 7UYW ; 8B8N ; 8B8U ; 8B99 ; 8B9E ; 8B9H ; 8BA2 ; 8BA3 ; 8BA4 ; 8BAB ; 8BAK ; 8BM2 ; 8BPV ; 8BPW ; 8CZ9 ; 8EX0 ; 8EX1 ; 8EX2 ; 8EXK ; 8EYA ; 8EYB ; 8F88 ; 8G6Z ; 8G8O ; 8G8X
EC Number
2.7.10.2
Pfam ID
PF18379 ; PF18377 ; PF17887 ; PF07714 ; PF00017
Sequence
MGMACLTMTEMEGTSTSSIYQNGDISGNANSMKQIDPVLQVYLYHSLGKSEADYLTFPSG
EYVAEEICIAASKACGITPVYHNMFALMSETERIWYPPNHVFHIDESTRHNVLYRIRFYF
PRWYCSGSNRAYRHGISRGAEAPLLDDFVMSYLFAQWRHDFVHGWIKVPVTHETQEECLG
MAVLDMMRIAKENDQTPLAIYNSISYKTFLPKCIRAKIQDYHILTRKRIRYRFRRFIQQF
SQCKATARNLKLKYLINLETLQSAFYTEKFEVKEPGSGPSGEEIFATIIITGNGGIQWSR
GKHKESETLTEQDLQLYCDFPNIIDVSIKQANQEGSNESRVVTIHKQDGKNLEIELSSLR
EALSFVSLIDGYYRLTADAHHYLCKEVAPPAVLENIQSNCHGPISMDFAISKLKKAGNQT
GLYVLRCSPKDFNKYFLTFAVERENVIEYKHCLITKNENEEYNLSGTKKNFSSLKDLLNC
YQMETVRSDNIIFQFTKCCPPKPKDKSNLLVFRTNGVSDVPTSPTLQRPTHMNQMVFHKI
RNEDLIFNESLGQGTFTKIFKGVRREVGDYGQLHETEVLLKVLDKAHRNYSESFFEAASM
MSKLSHKHLVLNYGVCVCGDENILVQEFVKFGSLDTYLKKNKNCINILWKLEVAKQLAWA
MHFLEENTLIHGNVCAKNILLIREEDRKTGNPPFIKLSDPGISITVLPKDILQERIPWVP
PECIENPKNLNLATDKWSFGTTLWEICSGGDKPLSALDSQRKLQFYEDRHQLPAPKWAEL
ANLINNCMDYEPDFRPSFRAIIRDLNSLFTPDYELLTENDMLPNMRIGALGFSGAFEDRD
PTQFEERHLKFLQQLGKGNFGSVEMCRYDPLQDNTGEVVAVKKLQHSTEEHLRDFEREIE
ILKSLQHDNIVKYKGVCYSAGRRNLKLIMEYLPYGSLRDYLQKHKERIDHIKLLQYTSQI
CKGMEYLGTKRYIHRDLATRNILVENENRVKIGDFGLTKVLPQDKEYYKVKEPGESPIFW
YAPESLTESKFSVASDVWSFGVVLYELFTYIEKSKSPPAEFMRMIGNDKQGQMIVFHLIE
LLKNNGRLPRPDGCPDEIYMIMTECWNNNVNQRPSFRDLALRVDQIRDNMAG
Function
Non-receptor tyrosine kinase involved in various processes such as cell growth, development, differentiation or histone modifications. Mediates essential signaling events in both innate and adaptive immunity. In the cytoplasm, plays a pivotal role in signal transduction via its association with type I receptors such as growth hormone (GHR), prolactin (PRLR), leptin (LEPR), erythropoietin (EPOR), thrombopoietin (THPO); or type II receptors including IFN-alpha, IFN-beta, IFN-gamma and multiple interleukins. Following ligand-binding to cell surface receptors, phosphorylates specific tyrosine residues on the cytoplasmic tails of the receptor, creating docking sites for STATs proteins. Subsequently, phosphorylates the STATs proteins once they are recruited to the receptor. Phosphorylated STATs then form homodimer or heterodimers and translocate to the nucleus to activate gene transcription. For example, cell stimulation with erythropoietin (EPO) during erythropoiesis leads to JAK2 autophosphorylation, activation, and its association with erythropoietin receptor (EPOR) that becomes phosphorylated in its cytoplasmic domain. Then, STAT5 (STAT5A or STAT5B) is recruited, phosphorylated and activated by JAK2. Once activated, dimerized STAT5 translocates into the nucleus and promotes the transcription of several essential genes involved in the modulation of erythropoiesis. Part of a signaling cascade that is activated by increased cellular retinol and that leads to the activation of STAT5 (STAT5A or STAT5B). In addition, JAK2 mediates angiotensin-2-induced ARHGEF1 phosphorylation. Plays a role in cell cycle by phosphorylating CDKN1B. Cooperates with TEC through reciprocal phosphorylation to mediate cytokine-driven activation of FOS transcription. In the nucleus, plays a key role in chromatin by specifically mediating phosphorylation of 'Tyr-41' of histone H3 (H3Y41ph), a specific tag that promotes exclusion of CBX5 (HP1 alpha) from chromatin.
Tissue Specificity Ubiquitously expressed throughout most tissues.
KEGG Pathway
EGFR tyrosine ki.se inhibitor resistance (hsa01521 )
Chemokine sig.ling pathway (hsa04062 )
Efferocytosis (hsa04148 )
PI3K-Akt sig.ling pathway (hsa04151 )
Necroptosis (hsa04217 )
Sig.ling pathways regulating pluripotency of stem cells (hsa04550 )
JAK-STAT sig.ling pathway (hsa04630 )
Th1 and Th2 cell differentiation (hsa04658 )
Th17 cell differentiation (hsa04659 )
Cholinergic sy.pse (hsa04725 )
Prolactin sig.ling pathway (hsa04917 )
Adipocytokine sig.ling pathway (hsa04920 )
AGE-RAGE sig.ling pathway in diabetic complications (hsa04933 )
Growth hormone synthesis, secretion and action (hsa04935 )
Leishmaniasis (hsa05140 )
Toxoplasmosis (hsa05145 )
Tuberculosis (hsa05152 )
Hepatitis B (hsa05161 )
Influenza A (hsa05164 )
Kaposi sarcoma-associated herpesvirus infection (hsa05167 )
Herpes simplex virus 1 infection (hsa05168 )
Pathways in cancer (hsa05200 )
Chemical carcinogenesis - receptor activation (hsa05207 )
PD-L1 expression and PD-1 checkpoint pathway in cancer (hsa05235 )
Lipid and atherosclerosis (hsa05417 )
Reactome Pathway
MAPK3 (ERK1) activation (R-HSA-110056 )
MAPK1 (ERK2) activation (R-HSA-112411 )
Prolactin receptor signaling (R-HSA-1170546 )
Signaling by SCF-KIT (R-HSA-1433557 )
Signaling by Leptin (R-HSA-2586552 )
RMTs methylate histone arginines (R-HSA-3214858 )
Interleukin-3, Interleukin-5 and GM-CSF signaling (R-HSA-512988 )
RAF activation (R-HSA-5673000 )
RAF/MAP kinase cascade (R-HSA-5673001 )
Interleukin-4 and Interleukin-13 signaling (R-HSA-6785807 )
IL-6-type cytokine receptor ligand interactions (R-HSA-6788467 )
Signaling by moderate kinase activity BRAF mutants (R-HSA-6802946 )
Signaling by BRAF and RAF1 fusions (R-HSA-6802952 )
Paradoxical activation of RAF signaling by kinase inactive BRAF (R-HSA-6802955 )
Cyclin D associated events in G1 (R-HSA-69231 )
Interferon gamma signaling (R-HSA-877300 )
Regulation of IFNG signaling (R-HSA-877312 )
Interleukin-20 family signaling (R-HSA-8854691 )
Interleukin-35 Signalling (R-HSA-8984722 )
Signaling by Erythropoietin (R-HSA-9006335 )
Interleukin-12 signaling (R-HSA-9020591 )
Interleukin-23 signaling (R-HSA-9020933 )
Interleukin-27 signaling (R-HSA-9020956 )
Erythropoietin activates Phosphoinositide-3-kinase (PI3K) (R-HSA-9027276 )
Erythropoietin activates Phospholipase C gamma (PLCG) (R-HSA-9027277 )
Erythropoietin activates STAT5 (R-HSA-9027283 )
Erythropoietin activates RAS (R-HSA-9027284 )
Interleukin receptor SHC signaling (R-HSA-912526 )
Signaling downstream of RAS mutants (R-HSA-9649948 )
Signaling by RAF1 mutants (R-HSA-9656223 )
Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants (R-HSA-9670439 )
Signaling by CSF3 (G-CSF) (R-HSA-9674555 )
Potential therapeutics for SARS (R-HSA-9679191 )
Inactivation of CSF3 (G-CSF) signaling (R-HSA-9705462 )
IFNG signaling activates MAPKs (R-HSA-9732724 )
Growth hormone receptor signaling (R-HSA-982772 )
Factors involved in megakaryocyte development and platelet production (R-HSA-983231 )
Interleukin-6 signaling (R-HSA-1059683 )

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Thrombocythemia 3 DISNM1LK Strong Autosomal dominant [1]
Thrombocythemia DISL38J3 Supportive Autosomal dominant [2]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
This DOT Affected the Drug Response of 2 Drug(s)
Drug Name Drug ID Highest Status Interaction REF
Nicotine DMWX5CO Approved Tyrosine-protein kinase JAK2 (JAK2) increases the response to substance of Nicotine. [44]
Leptin DM5LY1H Investigative Tyrosine-protein kinase JAK2 (JAK2) increases the Ovarian cancer ADR of Leptin. [45]
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12 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate increases the methylation of Tyrosine-protein kinase JAK2 (JAK2). [3]
Arsenic DMTL2Y1 Approved Arsenic increases the phosphorylation of Tyrosine-protein kinase JAK2 (JAK2). [10]
Decitabine DMQL8XJ Approved Decitabine decreases the methylation of Tyrosine-protein kinase JAK2 (JAK2). [14]
Momelotinib DMF98Q0 Approved Momelotinib decreases the phosphorylation of Tyrosine-protein kinase JAK2 (JAK2). [22]
Resveratrol DM3RWXL Phase 3 Resveratrol decreases the phosphorylation of Tyrosine-protein kinase JAK2 (JAK2). [24]
Thymoquinone DMVDTR2 Phase 2/3 Thymoquinone decreases the phosphorylation of Tyrosine-protein kinase JAK2 (JAK2). [29]
Delphinidin DMS2WIN Phase 2 Delphinidin decreases the phosphorylation of Tyrosine-protein kinase JAK2 (JAK2). [31]
WP-1066 DMUGHWR Phase 1/2 WP-1066 decreases the phosphorylation of Tyrosine-protein kinase JAK2 (JAK2). [32]
Sphingosine-1-Phosphate DMJCQKA Phase 1 Sphingosine-1-Phosphate increases the phosphorylation of Tyrosine-protein kinase JAK2 (JAK2). [35]
EMODIN DMAEDQG Terminated EMODIN decreases the phosphorylation of Tyrosine-protein kinase JAK2 (JAK2). [38]
AG490 DM3WKO5 Terminated AG490 decreases the phosphorylation of Tyrosine-protein kinase JAK2 (JAK2). [39]
(E)-4-(3,5-dimethoxystyryl)phenol DMYXI2V Investigative (E)-4-(3,5-dimethoxystyryl)phenol decreases the phosphorylation of Tyrosine-protein kinase JAK2 (JAK2). [43]
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⏷ Show the Full List of 12 Drug(s)
36 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Ciclosporin DMAZJFX Approved Ciclosporin increases the expression of Tyrosine-protein kinase JAK2 (JAK2). [4]
Tretinoin DM49DUI Approved Tretinoin increases the expression of Tyrosine-protein kinase JAK2 (JAK2). [5]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Tyrosine-protein kinase JAK2 (JAK2). [6]
Cisplatin DMRHGI9 Approved Cisplatin decreases the expression of Tyrosine-protein kinase JAK2 (JAK2). [7]
Estradiol DMUNTE3 Approved Estradiol decreases the expression of Tyrosine-protein kinase JAK2 (JAK2). [8]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of Tyrosine-protein kinase JAK2 (JAK2). [9]
Quercetin DM3NC4M Approved Quercetin increases the expression of Tyrosine-protein kinase JAK2 (JAK2). [11]
Arsenic trioxide DM61TA4 Approved Arsenic trioxide increases the expression of Tyrosine-protein kinase JAK2 (JAK2). [12]
Hydrogen peroxide DM1NG5W Approved Hydrogen peroxide decreases the expression of Tyrosine-protein kinase JAK2 (JAK2). [13]
Zoledronate DMIXC7G Approved Zoledronate increases the expression of Tyrosine-protein kinase JAK2 (JAK2). [15]
Progesterone DMUY35B Approved Progesterone increases the expression of Tyrosine-protein kinase JAK2 (JAK2). [16]
Fulvestrant DM0YZC6 Approved Fulvestrant decreases the expression of Tyrosine-protein kinase JAK2 (JAK2). [17]
Diethylstilbestrol DMN3UXQ Approved Diethylstilbestrol increases the expression of Tyrosine-protein kinase JAK2 (JAK2). [17]
Melphalan DMOLNHF Approved Melphalan decreases the expression of Tyrosine-protein kinase JAK2 (JAK2). [18]
Mitoxantrone DMM39BF Approved Mitoxantrone decreases the expression of Tyrosine-protein kinase JAK2 (JAK2). [6]
Daunorubicin DMQUSBT Approved Daunorubicin decreases the expression of Tyrosine-protein kinase JAK2 (JAK2). [6]
Estrone DM5T6US Approved Estrone increases the expression of Tyrosine-protein kinase JAK2 (JAK2). [17]
Mestranol DMG3F94 Approved Mestranol increases the expression of Tyrosine-protein kinase JAK2 (JAK2). [17]
Tofacitinib DMBS370 Approved Tofacitinib decreases the activity of Tyrosine-protein kinase JAK2 (JAK2). [19]
Amlodipine DMBDAZV Approved Amlodipine increases the expression of Tyrosine-protein kinase JAK2 (JAK2). [20]
Paroxetine DM5PVQE Approved Paroxetine increases the expression of Tyrosine-protein kinase JAK2 (JAK2). [21]
Urethane DM7NSI0 Phase 4 Urethane increases the expression of Tyrosine-protein kinase JAK2 (JAK2). [23]
Curcumin DMQPH29 Phase 3 Curcumin decreases the expression of Tyrosine-protein kinase JAK2 (JAK2). [25]
Napabucasin DMDZ6Q3 Phase 3 Napabucasin decreases the expression of Tyrosine-protein kinase JAK2 (JAK2). [26]
Jakafi DMNORK8 Phase 3 Jakafi decreases the activity of Tyrosine-protein kinase JAK2 (JAK2). [27]
Genistein DM0JETC Phase 2/3 Genistein increases the expression of Tyrosine-protein kinase JAK2 (JAK2). [28]
Contigoside B DMX9V8K Phase 2/3 Contigoside B increases the expression of Tyrosine-protein kinase JAK2 (JAK2). [30]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the expression of Tyrosine-protein kinase JAK2 (JAK2). [33]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 decreases the expression of Tyrosine-protein kinase JAK2 (JAK2). [34]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 decreases the expression of Tyrosine-protein kinase JAK2 (JAK2). [36]
PMID25656651-Compound-5 DMAI95U Patented PMID25656651-Compound-5 decreases the activity of Tyrosine-protein kinase JAK2 (JAK2). [37]
HEXESTROL DM9AGWQ Withdrawn from market HEXESTROL increases the expression of Tyrosine-protein kinase JAK2 (JAK2). [17]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the expression of Tyrosine-protein kinase JAK2 (JAK2). [40]
Milchsaure DM462BT Investigative Milchsaure decreases the expression of Tyrosine-protein kinase JAK2 (JAK2). [41]
2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]PYRIDINE DMNQL17 Investigative 2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]PYRIDINE increases the expression of Tyrosine-protein kinase JAK2 (JAK2). [42]
Butanoic acid DMTAJP7 Investigative Butanoic acid decreases the expression of Tyrosine-protein kinase JAK2 (JAK2). [13]
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⏷ Show the Full List of 36 Drug(s)

References

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