Details of Drug Off-Target (DOT)

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

• DOT Name: Death-associated protein kinase 2 (DAPK2)
• Synonyms: DAP kinase 2; EC 2.7.11.1; DAP-kinase-related protein 1; DRP-1
• Gene Name: DAPK2
• Related Disease:
  Cerebral infarction
  Acute myelogenous leukaemia
  Adult glioblastoma
  Advanced cancer
  Alzheimer disease
  Atherosclerosis
  Atrichia with papular lesions
  Autosomal dominant optic atrophy, classic form
  Breast cancer
  Breast carcinoma
  Cardiac failure
  Cardiomyopathy
  Charlevoix-Saguenay spastic ataxia
  Colon cancer
  Colon carcinoma
  Colorectal carcinoma
  Congestive heart failure
  Epithelial ovarian cancer
  Gastric cancer
  Glioblastoma multiforme
  Glioma
  Head-neck squamous cell carcinoma
  Hepatocellular carcinoma
  Huntington disease
  Hyperglycemia
  Lung cancer
  Lung carcinoma
  Neoplasm
  Non-insulin dependent diabetes
  Obesity
  Ovarian cancer
  Ovarian neoplasm
  Parkinson disease
  Promyelocytic leukaemia
  Prostate cancer
  Prostate carcinoma
  Pulmonary arterial hypertension
  Status epilepticus seizure
  Stomach cancer
  Subarachnoid hemorrhage
  Type-1/2 diabetes
  Amyotrophic lateral sclerosis
  Diabetic kidney disease
  High blood pressure
  Melanoma
  Myocardial infarction
  Neuroblastoma
  Pancreatic cancer
  Pulmonary fibrosis
• UniProt ID: DAPK2_HUMAN
• PDB ID: 1WMK; 1WRZ; 1Z9X; 1ZUZ; 1ZWS; 2A27; 2A2A; 2CKE; 6PAW; 7A6R; 7A6Y
• EC Number: 2.7.11.1
• Pfam ID: PF00069
• Sequence:
  MFQASMRSPNMEPFKQQKVEDFYDIGEELGSGQFAIVKKCREKSTGLEYAAKFIKKRQSR
  ASRRGVSREEIEREVSILRQVLHHNVITLHDVYENRTDVVLILELVSGGELFDFLAQKES
  LSEEEATSFIKQILDGVNYLHTKKIAHFDLKPENIMLLDKNIPIPHIKLIDFGLAHEIED
  GVEFKNIFGTPEFVAPEIVNYEPLGLEADMWSIGVITYILLSGASPFLGDTKQETLANIT
  AVSYDFDEEFFSQTSELAKDFIRKLLVKETRKRLTIQEALRHPWITPVDNQQAMVRRESV
  VNLENFRKQYVRRRWKLSFSIVSLCNHLTRSLMKKVHLRPDEDLRNCESDTEEDIARRKA
  LHPRRRSSTS
• Function: Calcium/calmodulin-dependent serine/threonine kinase involved in multiple cellular signaling pathways that trigger cell survival, apoptosis, and autophagy. Regulates both type I apoptotic and type II autophagic cell death signals, depending on the cellular setting. The former is caspase-dependent, while the latter is caspase-independent and is characterized by the accumulation of autophagic vesicles. Acts as a mediator of anoikis and a suppressor of beta-catenin-dependent anchorage-independent growth of malignant epithelial cells. May play a role in granulocytic maturation. Regulates granulocytic motility by controlling cell spreading and polarization ; Isoform 2 is not regulated by calmodulin. It can phosphorylate MYL9. It can induce membrane blebbing and autophagic cell death.
• Tissue Specificity: Expressed in neutrophils and eosinophils . Isoform 2 is expressed in embryonic stem cells (at protein level). Isoform 1 is ubiquitously expressed in all tissue types examined with high levels in heart, lung and skeletal muscle.
• KEGG Pathway:
  Autophagy - animal (hsa04140)
  Pathways in cancer (hsa05200)
  Bladder cancer (hsa05219)
• Reactome Pathway: Caspase activation via Dependence Receptors in the absence of ligand (R-HSA-418889)

Molecular Interaction Atlas (MIA) of This DOT

49 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cerebral infarction	DISR1WNP	Definitive	Biomarker	[1]
Acute myelogenous leukaemia	DISCSPTN	Strong	Altered Expression	[2]
Adult glioblastoma	DISVP4LU	Strong	Biomarker	[3]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[4]
Alzheimer disease	DISF8S70	Strong	Biomarker	[5]
Atherosclerosis	DISMN9J3	Strong	Biomarker	[6]
Atrichia with papular lesions	DIS80CUB	Strong	Biomarker	[2]
Autosomal dominant optic atrophy, classic form	DISXUAV9	Strong	Posttranslational Modification	[7]
Breast cancer	DIS7DPX1	Strong	Biomarker	[8]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[8]
Cardiac failure	DISDC067	Strong	Biomarker	[9]
Cardiomyopathy	DISUPZRG	Strong	Altered Expression	[10]
Charlevoix-Saguenay spastic ataxia	DISE8X81	Strong	Biomarker	[11]
Colon cancer	DISVC52G	Strong	Altered Expression	[12]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[13]
Colorectal carcinoma	DIS5PYL0	Strong	Posttranslational Modification	[14]
Congestive heart failure	DIS32MEA	Strong	Biomarker	[9]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[15]
Gastric cancer	DISXGOUK	Strong	Biomarker	[16]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[3]
Glioma	DIS5RPEH	Strong	Biomarker	[17]
Head-neck squamous cell carcinoma	DISF7P24	Strong	Altered Expression	[4]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[18]
Huntington disease	DISQPLA4	Strong	Biomarker	[19]
Hyperglycemia	DIS0BZB5	Strong	Biomarker	[1]
Lung cancer	DISCM4YA	Strong	Altered Expression	[20]
Lung carcinoma	DISTR26C	Strong	Altered Expression	[20]
Neoplasm	DISZKGEW	Strong	Altered Expression	[21]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Biomarker	[22]
Obesity	DIS47Y1K	Strong	Biomarker	[23]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[15]
Ovarian neoplasm	DISEAFTY	Strong	Biomarker	[15]
Parkinson disease	DISQVHKL	Strong	Biomarker	[24]
Promyelocytic leukaemia	DISYGG13	Strong	Biomarker	[2]
Prostate cancer	DISF190Y	Strong	Altered Expression	[25]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[25]
Pulmonary arterial hypertension	DISP8ZX5	Strong	Biomarker	[26]
Status epilepticus seizure	DISY3BIC	Strong	Biomarker	[27]
Stomach cancer	DISKIJSX	Strong	Biomarker	[16]
Subarachnoid hemorrhage	DISI7I8Y	Strong	Biomarker	[28]
Type-1/2 diabetes	DISIUHAP	Strong	Biomarker	[29]
Amyotrophic lateral sclerosis	DISF7HVM	moderate	Genetic Variation	[30]
Diabetic kidney disease	DISJMWEY	moderate	Biomarker	[31]
High blood pressure	DISY2OHH	moderate	Biomarker	[32]
Melanoma	DIS1RRCY	Limited	Biomarker	[33]
Myocardial infarction	DIS655KI	Limited	Biomarker	[34]
Neuroblastoma	DISVZBI4	Limited	Biomarker	[35]
Pancreatic cancer	DISJC981	Limited	Altered Expression	[36]
Pulmonary fibrosis	DISQKVLA	Limited	Biomarker	[37]

2 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 Death-associated protein kinase 2 (DAPK2).	[38]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Death-associated protein kinase 2 (DAPK2).	[51]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Death-associated protein kinase 2 (DAPK2).	[39]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Death-associated protein kinase 2 (DAPK2).	[40]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Death-associated protein kinase 2 (DAPK2).	[41]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Death-associated protein kinase 2 (DAPK2).	[42]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Death-associated protein kinase 2 (DAPK2).	[43]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Death-associated protein kinase 2 (DAPK2).	[2]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Death-associated protein kinase 2 (DAPK2).	[45]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Death-associated protein kinase 2 (DAPK2).	[45]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Death-associated protein kinase 2 (DAPK2).	[46]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of Death-associated protein kinase 2 (DAPK2).	[47]
Menthol	DMG2KW7	Approved	Menthol decreases the expression of Death-associated protein kinase 2 (DAPK2).	[48]
Phenytoin	DMNOKBV	Approved	Phenytoin decreases the expression of Death-associated protein kinase 2 (DAPK2).	[49]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene increases the expression of Death-associated protein kinase 2 (DAPK2).	[39]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of Death-associated protein kinase 2 (DAPK2).	[50]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Death-associated protein kinase 2 (DAPK2).	[52]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Death-associated protein kinase 2 (DAPK2).	[53]

References

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