Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT50NR57)

DOT Name Serine/threonine-protein kinase PINK1, mitochondrial (PINK1)
Synonyms EC 2.7.11.1; BRPK; PTEN-induced putative kinase protein 1
Gene Name PINK1
Related Disease
Autosomal recessive early-onset Parkinson disease 6 ( )
Parkinson disease ( )
Adenocarcinoma ( )
Advanced cancer ( )
Alzheimer disease ( )
Amyloidosis ( )
Arteriosclerosis ( )
Atherosclerosis ( )
Autoimmune disease ( )
Autosomal recessive early-onset Parkinson disease 7 ( )
Breast carcinoma ( )
Carcinoma ( )
Cardiac failure ( )
Cardiovascular disease ( )
Cerebral infarction ( )
Chronic obstructive pulmonary disease ( )
Colorectal carcinoma ( )
Congestive heart failure ( )
Dementia ( )
Depression ( )
Dysautonomia ( )
Dystonia ( )
Esophageal squamous cell carcinoma ( )
Hepatitis C virus infection ( )
Late-onset Parkinson disease ( )
Lung adenocarcinoma ( )
Lung cancer ( )
Lung carcinoma ( )
Major depressive disorder ( )
Mental disorder ( )
Movement disorder ( )
Neoplasm ( )
Nervous system disease ( )
Neuroblastoma ( )
Pulmonary fibrosis ( )
Squamous cell carcinoma ( )
Type-1/2 diabetes ( )
Breast cancer ( )
Hepatocellular carcinoma ( )
Neuralgia ( )
Neurodegenerative disease ( )
Pancreatic cancer ( )
Young-onset Parkinson disease ( )
Amyotrophic lateral sclerosis ( )
Chronic kidney disease ( )
Juvenile-onset Parkinson disease ( )
Lewy body dementia ( )
Melanoma ( )
Non-small-cell lung cancer ( )
Osteoarthritis ( )
Parkinsonian disorder ( )
Renal fibrosis ( )
UniProt ID
PINK1_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
EC Number
2.7.11.1
Pfam ID
PF00069
Sequence
MAVRQALGRGLQLGRALLLRFTGKPGRAYGLGRPGPAAGCVRGERPGWAAGPGAEPRRVG
LGLPNRLRFFRQSVAGLAARLQRQFVVRAWGCAGPCGRAVFLAFGLGLGLIEEKQAESRR
AVSACQEIQAIFTQKSKPGPDPLDTRRLQGFRLEEYLIGQSIGKGCSAAVYEATMPTLPQ
NLEVTKSTGLLPGRGPGTSAPGEGQERAPGAPAFPLAIKMMWNISAGSSSEAILNTMSQE
LVPASRVALAGEYGAVTYRKSKRGPKQLAPHPNIIRVLRAFTSSVPLLPGALVDYPDVLP
SRLHPEGLGHGRTLFLVMKNYPCTLRQYLCVNTPSPRLAAMMLLQLLEGVDHLVQQGIAH
RDLKSDNILVELDPDGCPWLVIADFGCCLADESIGLQLPFSSWYVDRGGNGCLMAPEVST
ARPGPRAVIDYSKADAWAVGAIAYEIFGLVNPFYGQGKAHLESRSYQEAQLPALPESVPP
DVRQLVRALLQREASKRPSARVAANVLHLSLWGEHILALKNLKLDKMVGWLLQQSAATLL
ANRLTEKCCVETKMKMLFLANLECETLCQAALLLCSWRAAL
Function
Serine/threonine-protein kinase which protects against mitochondrial dysfunction during cellular stress by phosphorylating mitochondrial proteins such as PRKN and DNM1L, to coordinate mitochondrial quality control mechanisms that remove and replace dysfunctional mitochondrial components. Depending on the severity of mitochondrial damage and/or dysfunction, activity ranges from preventing apoptosis and stimulating mitochondrial biogenesis to regulating mitochondrial dynamics and eliminating severely damaged mitochondria via mitophagy. Mediates the translocation and activation of PRKN at the outer membrane (OMM) of dysfunctional/depolarized mitochondria. At the OMM of damaged mitochondria, phosphorylates pre-existing polyubiquitin chains at 'Ser-65', the PINK1-phosphorylated polyubiquitin then recruits PRKN from the cytosol to the OMM where PRKN is fully activated by phosphorylation at 'Ser-65' by PINK1. In damaged mitochondria, mediates the decision between mitophagy or preventing apoptosis by promoting PRKN-dependent poly- or monoubiquitination of VDAC1; polyubiquitination of VDAC1 by PRKN promotes mitophagy, while monoubiquitination of VDAC1 by PRKN decreases mitochondrial calcium influx which ultimately inhibits apoptosis. When cellular stress results in irreversible mitochondrial damage, functions with PRKN to promote clearance of damaged mitochondria via selective autophagy (mitophagy). The PINK1-PRKN pathway also promotes fission of damaged mitochondria by phosphorylating and thus promoting the PRKN-dependent degradation of mitochondrial proteins involved in fission such as MFN2. This prevents the refusion of unhealthy mitochondria with the mitochondrial network or initiates mitochondrial fragmentation facilitating their later engulfment by autophagosomes. Also promotes mitochondrial fission independently of PRKN and ATG7-mediated mitophagy, via the phosphorylation and activation of DNM1L. Regulates motility of damaged mitochondria by promoting the ubiquitination and subsequent degradation of MIRO1 and MIRO2; in motor neurons, this likely inhibits mitochondrial intracellular anterograde transport along the axons which probably increases the chance of the mitochondria undergoing mitophagy in the soma. Required for ubiquinone reduction by mitochondrial complex I by mediating phosphorylation of complex I subunit NDUFA10. Phosphorylates LETM1, positively regulating its mitochondrial calcium transport activity.
Tissue Specificity
Highly expressed in heart, skeletal muscle and testis, and at lower levels in brain, placenta, liver, kidney, pancreas, prostate, ovary and small intestine. Present in the embryonic testis from an early stage of development.
KEGG Pathway
Mitophagy - animal (hsa04137 )
Parkinson disease (hsa05012 )
Amyotrophic lateral sclerosis (hsa05014 )
Pathways of neurodegeneration - multiple diseases (hsa05022 )
Reactome Pathway
FOXO-mediated transcription of cell death genes (R-HSA-9614657 )
PINK1-PRKN Mediated Mitophagy (R-HSA-5205685 )

Molecular Interaction Atlas (MIA) of This DOT

52 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Autosomal recessive early-onset Parkinson disease 6 DISHVLD5 Definitive Autosomal recessive [1]
Parkinson disease DISQVHKL Definitive Autosomal recessive [2]
Adenocarcinoma DIS3IHTY Strong Altered Expression [3]
Advanced cancer DISAT1Z9 Strong Biomarker [4]
Alzheimer disease DISF8S70 Strong Biomarker [5]
Amyloidosis DISHTAI2 Strong Altered Expression [6]
Arteriosclerosis DISK5QGC Strong Biomarker [7]
Atherosclerosis DISMN9J3 Strong Biomarker [7]
Autoimmune disease DISORMTM Strong Biomarker [8]
Autosomal recessive early-onset Parkinson disease 7 DISQVZFT Strong Biomarker [9]
Breast carcinoma DIS2UE88 Strong Genetic Variation [10]
Carcinoma DISH9F1N Strong Altered Expression [11]
Cardiac failure DISDC067 Strong Biomarker [12]
Cardiovascular disease DIS2IQDX Strong Biomarker [13]
Cerebral infarction DISR1WNP Strong Altered Expression [14]
Chronic obstructive pulmonary disease DISQCIRF Strong Biomarker [15]
Colorectal carcinoma DIS5PYL0 Strong Altered Expression [16]
Congestive heart failure DIS32MEA Strong Biomarker [12]
Dementia DISXL1WY Strong Genetic Variation [17]
Depression DIS3XJ69 Strong Biomarker [18]
Dysautonomia DISF4MT6 Strong Biomarker [19]
Dystonia DISJLFGW Strong Genetic Variation [20]
Esophageal squamous cell carcinoma DIS5N2GV Strong Altered Expression [21]
Hepatitis C virus infection DISQ0M8R Strong Biomarker [22]
Late-onset Parkinson disease DIS9IOUI Strong Genetic Variation [23]
Lung adenocarcinoma DISD51WR Strong Biomarker [3]
Lung cancer DISCM4YA Strong Biomarker [3]
Lung carcinoma DISTR26C Strong Biomarker [3]
Major depressive disorder DIS4CL3X Strong Biomarker [24]
Mental disorder DIS3J5R8 Strong Biomarker [25]
Movement disorder DISOJJ2D Strong Biomarker [26]
Neoplasm DISZKGEW Strong Biomarker [27]
Nervous system disease DISJ7GGT Strong Biomarker [28]
Neuroblastoma DISVZBI4 Strong Biomarker [29]
Pulmonary fibrosis DISQKVLA Strong Biomarker [30]
Squamous cell carcinoma DISQVIFL Strong Altered Expression [3]
Type-1/2 diabetes DISIUHAP Strong Biomarker [31]
Breast cancer DIS7DPX1 moderate Genetic Variation [10]
Hepatocellular carcinoma DIS0J828 moderate Altered Expression [32]
Neuralgia DISWO58J moderate Biomarker [33]
Neurodegenerative disease DISM20FF moderate Biomarker [34]
Pancreatic cancer DISJC981 moderate Biomarker [35]
Young-onset Parkinson disease DIS05LFS Supportive Autosomal recessive [36]
Amyotrophic lateral sclerosis DISF7HVM Limited Biomarker [37]
Chronic kidney disease DISW82R7 Limited Altered Expression [38]
Juvenile-onset Parkinson disease DISNT5BI Limited Biomarker [39]
Lewy body dementia DISAE66J Limited Biomarker [40]
Melanoma DIS1RRCY Limited Biomarker [41]
Non-small-cell lung cancer DIS5Y6R9 Limited Biomarker [42]
Osteoarthritis DIS05URM Limited Biomarker [43]
Parkinsonian disorder DISHGY45 Limited Genetic Variation [44]
Renal fibrosis DISMHI3I Limited Altered Expression [45]
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⏷ Show the Full List of 52 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
31 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate increases the expression of Serine/threonine-protein kinase PINK1, mitochondrial (PINK1). [46]
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of Serine/threonine-protein kinase PINK1, mitochondrial (PINK1). [47]
Acetaminophen DMUIE76 Approved Acetaminophen increases the expression of Serine/threonine-protein kinase PINK1, mitochondrial (PINK1). [48]
Doxorubicin DMVP5YE Approved Doxorubicin increases the expression of Serine/threonine-protein kinase PINK1, mitochondrial (PINK1). [49]
Cisplatin DMRHGI9 Approved Cisplatin affects the expression of Serine/threonine-protein kinase PINK1, mitochondrial (PINK1). [50]
Temozolomide DMKECZD Approved Temozolomide decreases the expression of Serine/threonine-protein kinase PINK1, mitochondrial (PINK1). [51]
Arsenic trioxide DM61TA4 Approved Arsenic trioxide increases the expression of Serine/threonine-protein kinase PINK1, mitochondrial (PINK1). [47]
Hydrogen peroxide DM1NG5W Approved Hydrogen peroxide decreases the expression of Serine/threonine-protein kinase PINK1, mitochondrial (PINK1). [52]
Calcitriol DM8ZVJ7 Approved Calcitriol increases the expression of Serine/threonine-protein kinase PINK1, mitochondrial (PINK1). [53]
Decitabine DMQL8XJ Approved Decitabine affects the expression of Serine/threonine-protein kinase PINK1, mitochondrial (PINK1). [50]
Rosiglitazone DMILWZR Approved Rosiglitazone increases the expression of Serine/threonine-protein kinase PINK1, mitochondrial (PINK1). [54]
Ethanol DMDRQZU Approved Ethanol decreases the expression of Serine/threonine-protein kinase PINK1, mitochondrial (PINK1). [55]
Capsaicin DMGMF6V Approved Capsaicin increases the expression of Serine/threonine-protein kinase PINK1, mitochondrial (PINK1). [56]
Sorafenib DMS8IFC Approved Sorafenib increases the expression of Serine/threonine-protein kinase PINK1, mitochondrial (PINK1). [57]
Melatonin DMKWFBT Approved Melatonin increases the expression of Serine/threonine-protein kinase PINK1, mitochondrial (PINK1). [58]
Urethane DM7NSI0 Phase 4 Urethane increases the expression of Serine/threonine-protein kinase PINK1, mitochondrial (PINK1). [59]
Tocopherol DMBIJZ6 Phase 2 Tocopherol increases the expression of Serine/threonine-protein kinase PINK1, mitochondrial (PINK1). [60]
GSK2110183 DMZHB37 Phase 2 GSK2110183 increases the expression of Serine/threonine-protein kinase PINK1, mitochondrial (PINK1). [61]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 increases the expression of Serine/threonine-protein kinase PINK1, mitochondrial (PINK1). [63]
THAPSIGARGIN DMDMQIE Preclinical THAPSIGARGIN increases the expression of Serine/threonine-protein kinase PINK1, mitochondrial (PINK1). [64]
Trichostatin A DM9C8NX Investigative Trichostatin A affects the expression of Serine/threonine-protein kinase PINK1, mitochondrial (PINK1). [65]
Milchsaure DM462BT Investigative Milchsaure decreases the expression of Serine/threonine-protein kinase PINK1, mitochondrial (PINK1). [66]
Coumestrol DM40TBU Investigative Coumestrol decreases the expression of Serine/threonine-protein kinase PINK1, mitochondrial (PINK1). [67]
Sulforaphane DMQY3L0 Investigative Sulforaphane decreases the expression of Serine/threonine-protein kinase PINK1, mitochondrial (PINK1). [68]
Acetaldehyde DMJFKG4 Investigative Acetaldehyde decreases the expression of Serine/threonine-protein kinase PINK1, mitochondrial (PINK1). [55]
Deguelin DMXT7WG Investigative Deguelin decreases the expression of Serine/threonine-protein kinase PINK1, mitochondrial (PINK1). [69]
Paraquat DMR8O3X Investigative Paraquat increases the expression of Serine/threonine-protein kinase PINK1, mitochondrial (PINK1). [70]
D-glucose DMMG2TO Investigative D-glucose increases the expression of Serine/threonine-protein kinase PINK1, mitochondrial (PINK1). [71]
Benzoquinone DMNBA0G Investigative Benzoquinone increases the expression of Serine/threonine-protein kinase PINK1, mitochondrial (PINK1). [73]
OLEANOLIC_ACID DMWDMJ3 Investigative OLEANOLIC_ACID increases the expression of Serine/threonine-protein kinase PINK1, mitochondrial (PINK1). [74]
[3H]CP55940 DMU7FC5 Investigative [3H]CP55940 increases the expression of Serine/threonine-protein kinase PINK1, mitochondrial (PINK1). [75]
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⏷ Show the Full List of 31 Drug(s)
1 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the methylation of Serine/threonine-protein kinase PINK1, mitochondrial (PINK1). [62]
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1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT
Drug Name Drug ID Highest Status Interaction REF
Chlorpyrifos DMKPUI6 Investigative Chlorpyrifos increases the stability of Serine/threonine-protein kinase PINK1, mitochondrial (PINK1). [72]
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References

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