Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT3FZDLX)

• DOT Name: ATP synthase subunit alpha, mitochondrial (ATP5F1A)
• Synonyms: ATP synthase F1 subunit alpha
• Gene Name: ATP5F1A
• Related Disease:
  Cognitive impairment
  Allergic asthma
  Alzheimer disease
  Asthma
  B-cell neoplasm
  Cardiac failure
  Colorectal carcinoma
  Congestive heart failure
  Depression
  Familial Alzheimer disease
  Head-neck squamous cell carcinoma
  Mitochondrial complex V (ATP synthase) deficiency nuclear type 4B
  Mitochondrial complex V (ATP synthase) deficiency, nuclear type 4A
  Mood disorder
  Non-small-cell lung cancer
  Obesity
  Postpartum depression
  Prostate cancer
  Prostate carcinoma
  Psoriasis
  Pulmonary hypertension
  Schizophrenia
  Clear cell renal carcinoma
  Mitochondrial disease
  Mitochondrial proton-transporting ATP synthase complex deficiency
  High blood pressure
  Adult glioblastoma
  Advanced cancer
  Amyotrophic lateral sclerosis
  Bacterial infection
  Combined oxidative phosphorylation deficiency 22
  Fetal growth restriction
  Frontotemporal dementia
  Glioblastoma multiforme
• UniProt ID: ATPA_HUMAN
• PDB ID: 8H9E; 8H9I; 8H9L; 8H9P; 8H9S; 8H9T; 8H9U; 8H9V
• Pfam ID: PF00006 ; PF00306 ; PF02874
• Sequence:
  MLSVRVAAAVVRALPRRAGLVSRNALGSSFIAARNFHASNTHLQKTGTAEMSSILEERIL
  GADTSVDLEETGRVLSIGDGIARVHGLRNVQAEEMVEFSSGLKGMSLNLEPDNVGVVVFG
  NDKLIKEGDIVKRTGAIVDVPVGEELLGRVVDALGNAIDGKGPIGSKTRRRVGLKAPGII
  PRISVREPMQTGIKAVDSLVPIGRGQRELIIGDRQTGKTSIAIDTIINQKRFNDGSDEKK
  KLYCIYVAIGQKRSTVAQLVKRLTDADAMKYTIVVSATASDAAPLQYLAPYSGCSMGEYF
  RDNGKHALIIYDDLSKQAVAYRQMSLLLRRPPGREAYPGDVFYLHSRLLERAAKMNDAFG
  GGSLTALPVIETQAGDVSAYIPTNVISITDGQIFLETELFYKGIRPAINVGLSVSRVGSA
  AQTRAMKQVAGTMKLELAQYREVAAFAQFGSDLDAATQQLLSRGVRLTELLKQGQYSPMA
  IEEQVAVIYAGVRGYLDKLEPSKITKFENAFLSHVVSQHQALLGTIRADGKISEQSDAKL
  KEIVTNFLAGFEA
• Function: Mitochondrial membrane ATP synthase (F(1)F(0) ATP synthase or Complex V) produces ATP from ADP in the presence of a proton gradient across the membrane which is generated by electron transport complexes of the respiratory chain. F-type ATPases consist of two structural domains, F(1) - containing the extramembraneous catalytic core, and F(0) - containing the membrane proton channel, linked together by a central stalk and a peripheral stalk. During catalysis, ATP synthesis in the catalytic domain of F(1) is coupled via a rotary mechanism of the central stalk subunits to proton translocation. Subunits alpha and beta form the catalytic core in F(1). Rotation of the central stalk against the surrounding alpha(3)beta(3) subunits leads to hydrolysis of ATP in three separate catalytic sites on the beta subunits. Subunit alpha does not bear the catalytic high-affinity ATP-binding sites. Binds the bacterial siderophore enterobactin and can promote mitochondrial accumulation of enterobactin-derived iron ions.
• Tissue Specificity: Fetal lung, heart, liver, gut and kidney. Expressed at higher levels in the fetal brain, retina and spinal cord.
• KEGG Pathway:
  Oxidative phosphorylation (hsa00190)
  Metabolic pathways (hsa01100)
  Thermogenesis (hsa04714)
  Alzheimer disease (hsa05010)
  Parkinson disease (hsa05012)
  Amyotrophic lateral sclerosis (hsa05014)
  Huntington disease (hsa05016)
  Prion disease (hsa05020)
  Pathways of neurodegeneration - multiple diseases (hsa05022)
  Chemical carcinogenesis - reactive oxygen species (hsa05208)
  Diabetic cardiomyopathy (hsa05415)
• Reactome Pathway:
  Formation of ATP by chemiosmotic coupling (R-HSA-163210)
  Cristae formation (R-HSA-8949613)
  Mitochondrial protein import (R-HSA-1268020)
• BioCyc Pathway: MetaCyc:HS07800-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

34 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cognitive impairment	DISH2ERD	Definitive	Biomarker	[1]
Allergic asthma	DISHF0H3	Strong	Altered Expression	[2]
Alzheimer disease	DISF8S70	Strong	Biomarker	[3]
Asthma	DISW9QNS	Strong	Genetic Variation	[4]
B-cell neoplasm	DISVY326	Strong	Altered Expression	[5]
Cardiac failure	DISDC067	Strong	Biomarker	[6]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[7]
Congestive heart failure	DIS32MEA	Strong	Biomarker	[6]
Depression	DIS3XJ69	Strong	Biomarker	[8]
Familial Alzheimer disease	DISE75U4	Strong	Biomarker	[9]
Head-neck squamous cell carcinoma	DISF7P24	Strong	Altered Expression	[10]
Mitochondrial complex V (ATP synthase) deficiency nuclear type 4B	DIS7G7VS	Strong	Autosomal recessive	[11]
Mitochondrial complex V (ATP synthase) deficiency, nuclear type 4A	DIS2Q29T	Strong	Autosomal dominant	[12]
Mood disorder	DISLVMWO	Strong	Genetic Variation	[13]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[14]
Obesity	DIS47Y1K	Strong	Biomarker	[15]
Postpartum depression	DIS08UKE	Strong	Biomarker	[16]
Prostate cancer	DISF190Y	Strong	Altered Expression	[17]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[17]
Psoriasis	DIS59VMN	Strong	Biomarker	[18]
Pulmonary hypertension	DIS1RSP5	Strong	Therapeutic	[19]
Schizophrenia	DISSRV2N	Strong	Biomarker	[20]
Clear cell renal carcinoma	DISBXRFJ	moderate	Biomarker	[21]
Mitochondrial disease	DISKAHA3	Moderate	Autosomal recessive	[11]
Mitochondrial proton-transporting ATP synthase complex deficiency	DISX6N3H	Supportive	Autosomal recessive	[22]
High blood pressure	DISY2OHH	Disputed	Biomarker	[23]
Adult glioblastoma	DISVP4LU	Limited	Altered Expression	[24]
Advanced cancer	DISAT1Z9	Limited	Genetic Variation	[24]
Amyotrophic lateral sclerosis	DISF7HVM	Limited	Biomarker	[25]
Bacterial infection	DIS5QJ9S	Limited	Biomarker	[26]
Combined oxidative phosphorylation deficiency 22	DIS0V261	Limited	Unknown	[27]
Fetal growth restriction	DIS5WEJ5	Limited	Biomarker	[28]
Frontotemporal dementia	DISKYHXL	Limited	Biomarker	[25]
Glioblastoma multiforme	DISK8246	Limited	Altered Expression	[24]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of ATP synthase subunit alpha, mitochondrial (ATP5F1A).	[29]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of ATP synthase subunit alpha, mitochondrial (ATP5F1A).	[30]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of ATP synthase subunit alpha, mitochondrial (ATP5F1A).	[31]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of ATP synthase subunit alpha, mitochondrial (ATP5F1A).	[32]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of ATP synthase subunit alpha, mitochondrial (ATP5F1A).	[33]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of ATP synthase subunit alpha, mitochondrial (ATP5F1A).	[35]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide decreases the expression of ATP synthase subunit alpha, mitochondrial (ATP5F1A).	[36]
Marinol	DM70IK5	Approved	Marinol decreases the expression of ATP synthase subunit alpha, mitochondrial (ATP5F1A).	[37]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of ATP synthase subunit alpha, mitochondrial (ATP5F1A).	[38]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of ATP synthase subunit alpha, mitochondrial (ATP5F1A).	[39]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of ATP synthase subunit alpha, mitochondrial (ATP5F1A).	[40]
Cannabidiol	DM0659E	Approved	Cannabidiol decreases the expression of ATP synthase subunit alpha, mitochondrial (ATP5F1A).	[41]
Cocaine	DMSOX7I	Approved	Cocaine affects the expression of ATP synthase subunit alpha, mitochondrial (ATP5F1A).	[42]
Acocantherin	DM7JT24	Approved	Acocantherin affects the expression of ATP synthase subunit alpha, mitochondrial (ATP5F1A).	[43]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of ATP synthase subunit alpha, mitochondrial (ATP5F1A).	[47]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of ATP synthase subunit alpha, mitochondrial (ATP5F1A).	[48]
chloropicrin	DMSGBQA	Investigative	chloropicrin decreases the expression of ATP synthase subunit alpha, mitochondrial (ATP5F1A).	[49]
AHPN	DM8G6O4	Investigative	AHPN decreases the expression of ATP synthase subunit alpha, mitochondrial (ATP5F1A).	[51]
Okadaic acid	DM47CO1	Investigative	Okadaic acid decreases the expression of ATP synthase subunit alpha, mitochondrial (ATP5F1A).	[52]

4 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Quercetin	DM3NC4M	Approved	Quercetin affects the binding of ATP synthase subunit alpha, mitochondrial (ATP5F1A).	[34]
Dihydroartemisinin	DMBXVMZ	Approved	Dihydroartemisinin affects the binding of ATP synthase subunit alpha, mitochondrial (ATP5F1A).	[44]
DNCB	DMDTVYC	Phase 2	DNCB affects the binding of ATP synthase subunit alpha, mitochondrial (ATP5F1A).	[45]
4-hydroxy-2-nonenal	DM2LJFZ	Investigative	4-hydroxy-2-nonenal affects the binding of ATP synthase subunit alpha, mitochondrial (ATP5F1A).	[9]

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 affects the methylation of ATP synthase subunit alpha, mitochondrial (ATP5F1A).	[46]

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