Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTNYA92F)

• DOT Name: Calmodulin-1 (CALM2)
• Gene Name: CALM2
• Related Disease:
  Acute myelogenous leukaemia
  Chronic renal failure
  Familial long QT syndrome
  Long QT syndrome
  Long QT syndrome 14
  Long QT syndrome 15
  Schizophrenia
  T-cell acute lymphoblastic leukaemia
  Acute leukaemia
  Adult glioblastoma
  Advanced cancer
  Alzheimer disease
  Anxiety
  Anxiety disorder
  Arrhythmia
  Bipolar disorder
  Breast carcinoma
  Carcinoma
  Cardiac arrest
  Catecholaminergic polymorphic ventricular tachycardia
  Catecholaminergic polymorphic ventricular tachycardia 4
  Cerebral cavernous malformation
  Cocaine addiction
  Colon cancer
  Colon carcinoma
  Colorectal carcinoma
  Delirium
  Glioblastoma multiforme
  Glioma
  Long QT syndrome 16
  Non-hodgkin lymphoma
  Prostate cancer
  Small-cell lung cancer
  Systemic lupus erythematosus
  X-linked hydrocephalus with stenosis of the aqueduct of Sylvius
  Breast cancer
  Brugada syndrome
  Catecholaminergic polymorphic ventricular tachycardia 1
  leukaemia
  Lymphoma
  Acute lymphocytic leukaemia
  Childhood acute lymphoblastic leukemia
  Hepatitis C virus infection
  Leukemia
  Lung cancer
  Lymphoma, non-Hodgkin, familial
  Neuroblastoma
  Prostate carcinoma
  Renal carcinoma
• UniProt ID: CALM1_HUMAN
• PDB ID: 1CDL ; 1CLL ; 1CTR ; 1IWQ ; 1J7O ; 1J7P ; 1K90 ; 1K93 ; 1L7Z ; 1LVC ; 1NKF ; 1PK0 ; 1S26 ; 1SK6 ; 1SW8 ; 1UP5 ; 1WRZ ; 1XFU ; 1XFV ; 1XFW ; 1XFX ; 1XFY ; 1XFZ ; 1Y6W ; 1YR5 ; 1YRT ; 1YRU ; 1ZOT ; 1ZUZ ; 2BE6 ; 2F3Y ; 2F3Z ; 2HF5 ; 2I08 ; 2JZI ; 2K0E ; 2K0F ; 2K0J ; 2K61 ; 2KNE ; 2KUG ; 2KUH ; 2L53 ; 2L7L ; 2LGF ; 2LL6 ; 2LL7 ; 2LQC ; 2LQP ; 2LV6 ; 2M0J ; 2M0K ; 2M55 ; 2MG5 ; 2N27 ; 2N6A ; 2N77 ; 2N8J ; 2R28 ; 2V01 ; 2V02 ; 2VAY ; 2W73 ; 2WEL ; 2X0G ; 2Y4V ; 3BYA ; 3DVE ; 3DVJ ; 3DVK ; 3DVM ; 3EVV ; 3EWT ; 3EWV ; 3G43 ; 3HR4 ; 3J41 ; 3O77 ; 3O78 ; 3OXQ ; 3SUI ; 3UCT ; 3UCW ; 3UCY ; 4BW7 ; 4BW8 ; 4BYF ; 4DCK ; 4DJC ; 4GOW ; 4JPZ ; 4JQ0 ; 4L79 ; 4LZX ; 4M1L ; 4OVN ; 4Q57 ; 4Q5U ; 4UMO ; 4UPU ; 4V0C ; 5COC ; 5DBR ; 5DOW ; 5DSU ; 5GGM ; 5I0I ; 5J03 ; 5J8H ; 5JQA ; 5JTH ; 5K7L ; 5K8Q ; 5OEO ; 5TP5 ; 5TP6 ; 5V02 ; 5V03 ; 5V7X ; 5WBX ; 5WC5 ; 6B8L ; 6B8M ; 6B8N ; 6B8P ; 6B8Q ; 6BUT ; 6C1D ; 6C1G ; 6C1H ; 6CNM ; 6CNN ; 6CNO ; 6DAD ; 6DAE ; 6DAF ; 6DAH ; 6E2F ; 6E2G ; 6EEB ; 6FEG ; 6FEH ; 6GDK ; 6GDL ; 6HCS ; 6HR1 ; 6JI8 ; 6JII ; 6JIU ; 6JIY ; 6JRS ; 6JV2 ; 6K4K ; 6K4L ; 6K4R ; 6M2W ; 6M7H ; 6MUD ; 6MUE ; 6N5W ; 6O5G ; 6OS4 ; 6PAW ; 6PBX ; 6PBY ; 6TV7 ; 6U39 ; 6U3A ; 6U3B ; 6U3D ; 6UZZ ; 6V00 ; 6V01 ; 6X32 ; 6X33 ; 6X35 ; 6X36 ; 6XXX ; 6XY3 ; 6XYR ; 6Y4P ; 6Y94 ; 6Y95 ; 6YA9 ; 6YNS ; 6YNU ; 6ZBI ; 7AUG ; 7BF1 ; 7BF2 ; 7KL5 ; 7L8V ; 7PSZ ; 7PU9 ; 7SHQ ; 7SX3 ; 7SX4 ; 7T2Q ; 7TCI ; 7TCP ; 7TZC ; 7U9T ; 7UA3 ; 7UA4 ; 7VMB ; 7VUO ; 7VUR ; 7VUS ; 7VUT ; 7VUU ; 7VVD ; 7VVH ; 7WJI ; 7WR3 ; 7WR4 ; 7WR5 ; 7WZS ; 7XN4 ; 7XN5 ; 7XN6 ; 7ZRP ; 7ZRQ ; 8AHS ; 8B6Q ; 8BFG ; 8DGH ; 8DGK ; 8DUJ ; 8DVE ; 8EOW ; 8EP0 ; 8EP1 ; 8FNY ; 8FO6 ; 8GM4 ; 8GM5 ; 8J00 ; 8J03 ; 8J04 ; 8J05 ; 8J07 ; 8SIK ; 8SIM ; 8SIN ; 8UXL ; 8UXM
• Pfam ID: PF13499
• Sequence:
  MADQLTEEQIAEFKEAFSLFDKDGDGTITTKELGTVMRSLGQNPTEAELQDMINEVDADG
  NGTIDFPEFLTMMARKMKDTDSEEEIREAFRVFDKDGNGYISAAELRHVMTNLGEKLTDE
  EVDEMIREADIDGDGQVNYEEFVQMMTAK
• Function: Calmodulin acts as part of a calcium signal transduction pathway by mediating the control of a large number of enzymes, ion channels, aquaporins and other proteins through calcium-binding. Calcium-binding is required for the activation of calmodulin. Among the enzymes to be stimulated by the calmodulin-calcium complex are a number of protein kinases, such as myosin light-chain kinases and calmodulin-dependent protein kinase type II (CaMK2), and phosphatases. Together with CCP110 and centrin, is involved in a genetic pathway that regulates the centrosome cycle and progression through cytokinesis. Is a regulator of voltage-dependent L-type calcium channels. Mediates calcium-dependent inactivation of CACNA1C. Positively regulates calcium-activated potassium channel activity of KCNN2. Forms a potassium channel complex with KCNQ1 and regulates electrophysiological activity of the channel via calcium-binding. Acts as a sensor to modulate the endoplasmic reticulum contacts with other organelles mediated by VMP1:ATP2A2 ; (Microbial infection) Required for Legionella pneumophila SidJ glutamylase activity; (Microbial infection) Required for C.violaceum CopC and S.flexneri OspC3 arginine ADP-riboxanase activity.
• KEGG Pathway:
  Ras sig.ling pathway (hsa04014)
  Rap1 sig.ling pathway (hsa04015)
  Calcium sig.ling pathway (hsa04020)
  cGMP-PKG sig.ling pathway (hsa04022)
  cAMP sig.ling pathway (hsa04024)
  Phosphatidylinositol sig.ling system (hsa04070)
  Oocyte meiosis (hsa04114)
  Cellular senescence (hsa04218)
  Adrenergic sig.ling in cardiomyocytes (hsa04261)
  Vascular smooth muscle contraction (hsa04270)
  Apelin sig.ling pathway (hsa04371)
  C-type lectin receptor sig.ling pathway (hsa04625)
  Circadian entrainment (hsa04713)
  Long-term potentiation (hsa04720)
  Neurotrophin sig.ling pathway (hsa04722)
  Dopaminergic sy.pse (hsa04728)
  Olfactory transduction (hsa04740)
  Phototransduction (hsa04744)
  Inflammatory mediator regulation of TRP channels (hsa04750)
  Insulin sig.ling pathway (hsa04910)
  GnRH sig.ling pathway (hsa04912)
  Estrogen sig.ling pathway (hsa04915)
  Melanogenesis (hsa04916)
  Oxytocin sig.ling pathway (hsa04921)
  Glucagon sig.ling pathway (hsa04922)
  Renin secretion (hsa04924)
  Aldosterone synthesis and secretion (hsa04925)
  Salivary secretion (hsa04970)
  Gastric acid secretion (hsa04971)
  Alzheimer disease (hsa05010)
  Parkinson disease (hsa05012)
  Pathways of neurodegeneration - multiple diseases (hsa05022)
  Amphetamine addiction (hsa05031)
  Alcoholism (hsa05034)
  Pertussis (hsa05133)
  Tuberculosis (hsa05152)
  Human cytomegalovirus infection (hsa05163)
  Kaposi sarcoma-associated herpesvirus infection (hsa05167)
  Human immunodeficiency virus 1 infection (hsa05170)
  Pathways in cancer (hsa05200)
  Glioma (hsa05214)
  Lipid and atherosclerosis (hsa05417)
  Fluid shear stress and atherosclerosis (hsa05418)
• Reactome Pathway:
  Calmodulin induced events (R-HSA-111933)
  Cam-PDE 1 activation (R-HSA-111957)
  CaM pathway (R-HSA-111997)
  Platelet degranulation (R-HSA-114608)
  Translocation of SLC2A4 (GLUT4) to the plasma membrane (R-HSA-1445148)
  Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation (R-HSA-1474151)
  PKA activation (R-HSA-163615)
  DARPP-32 events (R-HSA-180024)
  Synthesis of IP3 and IP4 in the cytosol (R-HSA-1855204)
  Calcineurin activates NFAT (R-HSA-2025928)
  eNOS activation (R-HSA-203615)
  Transcriptional activation of mitochondrial biogenesis (R-HSA-2151201)
  Inactivation, recovery and regulation of the phototransduction cascade (R-HSA-2514859)
  Stimuli-sensing channels (R-HSA-2672351)
  FCERI mediated Ca+2 mobilization (R-HSA-2871809)
  Ca2+ pathway (R-HSA-4086398)
  Reduction of cytosolic Ca++ levels (R-HSA-418359)
  Sodium/Calcium exchangers (R-HSA-425561)
  Unblocking of NMDA receptors, glutamate binding and activation (R-HSA-438066)
  CREB1 phosphorylation through the activation of Adenylate Cyclase (R-HSA-442720)
  CREB1 phosphorylation through the activation of CaMKII/CaMKK/CaMKIV cascasde (R-HSA-442729)
  Ras activation upon Ca2+ influx through NMDA receptor (R-HSA-442982)
  Smooth Muscle Contraction (R-HSA-445355)
  Activation of Ca-permeable Kainate Receptor (R-HSA-451308)
  Uptake and function of anthrax toxins (R-HSA-5210891)
  VEGFR2 mediated vascular permeability (R-HSA-5218920)
  VEGFR2 mediated cell proliferation (R-HSA-5218921)
  Phase 0 - rapid depolarisation (R-HSA-5576892)
  Ion homeostasis (R-HSA-5578775)
  CLEC7A (Dectin-1) induces NFAT activation (R-HSA-5607763)
  RHO GTPases activate IQGAPs (R-HSA-5626467)
  RHO GTPases activate PAKs (R-HSA-5627123)
  RAF activation (R-HSA-5673000)
  RAF/MAP kinase cascade (R-HSA-5673001)
  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)
  Glycogen breakdown (glycogenolysis) (R-HSA-70221)
  Protein methylation (R-HSA-8876725)
  Extra-nuclear estrogen signaling (R-HSA-9009391)
  Loss of phosphorylation of MECP2 at T308 (R-HSA-9022535)
  Regulation of MECP2 expression and activity (R-HSA-9022692)
  Ion transport by P-type ATPases (R-HSA-936837)
  Negative regulation of NMDA receptor-mediated neuronal transmission (R-HSA-9617324)
  Activation of RAC1 downstream of NMDARs (R-HSA-9619229)
  Activation of AMPK downstream of NMDARs (R-HSA-9619483)
  Long-term potentiation (R-HSA-9620244)
  RAS processing (R-HSA-9648002)
  Signaling downstream of RAS mutants (R-HSA-9649948)
  Signaling by RAF1 mutants (R-HSA-9656223)
  FCGR3A-mediated IL10 synthesis (R-HSA-9664323)
  Antigen activates B Cell Receptor (BCR) leading to generation of second messengers (R-HSA-983695)
  CaMK IV-mediated phosphorylation of CREB (R-HSA-111932)

Molecular Interaction Atlas (MIA) of This DOT

49 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute myelogenous leukaemia	DISCSPTN	Definitive	Biomarker	[1]
Chronic renal failure	DISGG7K6	Definitive	Genetic Variation	[2]
Familial long QT syndrome	DISRNNCY	Definitive	Autosomal dominant	[3]
Long QT syndrome	DISMKWS3	Definitive	Autosomal dominant	[4]
Long QT syndrome 14	DISD1WD5	Definitive	Autosomal dominant	[3]
Long QT syndrome 15	DISQXPO1	Definitive	Autosomal dominant	[3]
Schizophrenia	DISSRV2N	Definitive	Altered Expression	[5]
T-cell acute lymphoblastic leukaemia	DIS17AI2	Definitive	Biomarker	[6]
Acute leukaemia	DISDQFDI	Strong	Biomarker	[7]
Adult glioblastoma	DISVP4LU	Strong	Altered Expression	[8]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[9]
Alzheimer disease	DISF8S70	Strong	Biomarker	[10]
Anxiety	DISIJDBA	Strong	Biomarker	[11]
Anxiety disorder	DISBI2BT	Strong	Biomarker	[12]
Arrhythmia	DISFF2NI	Strong	Biomarker	[3]
Bipolar disorder	DISAM7J2	Strong	Biomarker	[13]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[14]
Carcinoma	DISH9F1N	Strong	Biomarker	[14]
Cardiac arrest	DIS9DIA4	Strong	Genetic Variation	[15]
Catecholaminergic polymorphic ventricular tachycardia	DISSAS1A	Strong	Autosomal dominant	[16]
Catecholaminergic polymorphic ventricular tachycardia 4	DIS56S7C	Strong	Autosomal dominant	[16]
Cerebral cavernous malformation	DISLKNYA	Strong	Biomarker	[17]
Cocaine addiction	DISHTRXG	Strong	Biomarker	[18]
Colon cancer	DISVC52G	Strong	Biomarker	[19]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[19]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[20]
Delirium	DIS2OKP1	Strong	Biomarker	[21]
Glioblastoma multiforme	DISK8246	Strong	Altered Expression	[8]
Glioma	DIS5RPEH	Strong	Biomarker	[22]
Long QT syndrome 16	DISOJNAT	Strong	Autosomal dominant	[16]
Non-hodgkin lymphoma	DISS2Y8A	Strong	Biomarker	[23]
Prostate cancer	DISF190Y	Strong	Altered Expression	[24]
Small-cell lung cancer	DISK3LZD	Strong	Biomarker	[25]
Systemic lupus erythematosus	DISI1SZ7	Strong	Biomarker	[26]
X-linked hydrocephalus with stenosis of the aqueduct of Sylvius	DIS6QXIR	Strong	Genetic Variation	[27]
Breast cancer	DIS7DPX1	moderate	Biomarker	[14]
Brugada syndrome	DISSGN0E	moderate	GermlineCausalMutation	[15]
Catecholaminergic polymorphic ventricular tachycardia 1	DISKGB3F	moderate	Biomarker	[28]
leukaemia	DISS7D1V	moderate	Biomarker	[29]
Lymphoma	DISN6V4S	moderate	Biomarker	[30]
Acute lymphocytic leukaemia	DISPX75S	Limited	Biomarker	[6]
Childhood acute lymphoblastic leukemia	DISJ5D6U	Limited	Genetic Variation	[31]
Hepatitis C virus infection	DISQ0M8R	Limited	Biomarker	[32]
Leukemia	DISNAKFL	Limited	Biomarker	[33]
Lung cancer	DISCM4YA	Limited	Altered Expression	[34]
Lymphoma, non-Hodgkin, familial	DISCXYIZ	Limited	Biomarker	[23]
Neuroblastoma	DISVZBI4	Limited	Biomarker	[35]
Prostate carcinoma	DISMJPLE	Limited	Altered Expression	[24]
Renal carcinoma	DISER9XT	Limited	Biomarker	[36]

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Afatinib	DMTKD7Q	Approved	Calmodulin-1 (CALM2) affects the response to substance of Afatinib.	[71]
Afimoxifene	DMFORDT	Phase 2	Calmodulin-1 (CALM2) decreases the response to substance of Afimoxifene.	[72]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Calmodulin-1 (CALM2).	[37]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Calmodulin-1 (CALM2).	[45]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Calmodulin-1 (CALM2).	[61]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of Calmodulin-1 (CALM2).	[63]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Calmodulin-1 (CALM2).	[38]
Acetaminophen	DMUIE76	Approved	Acetaminophen affects the expression of Calmodulin-1 (CALM2).	[39]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Calmodulin-1 (CALM2).	[40]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Calmodulin-1 (CALM2).	[41]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Calmodulin-1 (CALM2).	[42]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Calmodulin-1 (CALM2).	[43]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Calmodulin-1 (CALM2).	[44]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Calmodulin-1 (CALM2).	[46]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Calmodulin-1 (CALM2).	[47]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Calmodulin-1 (CALM2).	[48]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Calmodulin-1 (CALM2).	[49]
Marinol	DM70IK5	Approved	Marinol increases the expression of Calmodulin-1 (CALM2).	[50]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Calmodulin-1 (CALM2).	[51]
Selenium	DM25CGV	Approved	Selenium increases the expression of Calmodulin-1 (CALM2).	[52]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Calmodulin-1 (CALM2).	[53]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of Calmodulin-1 (CALM2).	[54]
Aspirin	DM672AH	Approved	Aspirin increases the expression of Calmodulin-1 (CALM2).	[55]
Etoposide	DMNH3PG	Approved	Etoposide increases the expression of Calmodulin-1 (CALM2).	[56]
Diclofenac	DMPIHLS	Approved	Diclofenac affects the expression of Calmodulin-1 (CALM2).	[48]
Piroxicam	DMTK234	Approved	Piroxicam decreases the expression of Calmodulin-1 (CALM2).	[57]
Cocaine	DMSOX7I	Approved	Cocaine decreases the expression of Calmodulin-1 (CALM2).	[18]
Sulindac	DM2QHZU	Approved	Sulindac decreases the expression of Calmodulin-1 (CALM2).	[55]
Phenytoin	DMNOKBV	Approved	Phenytoin decreases the expression of Calmodulin-1 (CALM2).	[59]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Calmodulin-1 (CALM2).	[60]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Calmodulin-1 (CALM2).	[52]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Calmodulin-1 (CALM2).	[62]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Calmodulin-1 (CALM2).	[64]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Calmodulin-1 (CALM2).	[65]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of Calmodulin-1 (CALM2).	[66]
Deguelin	DMXT7WG	Investigative	Deguelin decreases the expression of Calmodulin-1 (CALM2).	[67]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate decreases the expression of Calmodulin-1 (CALM2).	[68]
Glyphosate	DM0AFY7	Investigative	Glyphosate decreases the expression of Calmodulin-1 (CALM2).	[69]
Phencyclidine	DMQBEYX	Investigative	Phencyclidine decreases the expression of Calmodulin-1 (CALM2).	[18]
Okadaic acid	DM47CO1	Investigative	Okadaic acid decreases the expression of Calmodulin-1 (CALM2).	[70]

References

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