Details of Drug Off-Target (DOT)

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

• DOT Name: ATP synthase subunit a (ATP6)
• Synonyms: F-ATPase protein 6
• Gene Name: ATP6
• Related Disease:
  Adenocarcinoma
  Autoimmune disease
  Deafness
  Intellectual disability
  Periodic paralysis with later-onset distal motor neuropathy
  Systemic lupus erythematosus
  Ataxia-telangiectasia
  Bone osteosarcoma
  Breast cancer
  Breast carcinoma
  Cardiomyopathy
  Charcot marie tooth disease
  Childhood acute lymphoblastic leukemia
  Demyelinating polyneuropathy
  Essential hypertension
  IgA nephropathy
  Leber hereditary optic neuropathy
  Leigh syndrome
  Maternally-inherited Leigh syndrome
  MELAS syndrome
  Mitochondrial encephalomyopathy
  Mitochondrial myopathy
  Mitochondrial proton-transporting ATP synthase complex deficiency
  Multiple sclerosis
  Myopathy
  Nephropathy
  Obesity
  Osteoporosis
  Osteosarcoma
  Peripheral neuropathy
  Polyneuropathy
  Retinitis pigmentosa
  Retinopathy
  Trichohepatoenteric syndrome
  Female hypogonadism
  Amyotrophic lateral sclerosis
  Fetal growth restriction
  Nervous system disease
  Prostate cancer
  Prostate carcinoma
  Type-1/2 diabetes
• UniProt ID: ATP6_HUMAN
• PDB ID: 8H9F; 8H9J; 8H9M; 8H9Q; 8H9S; 8H9T; 8H9U; 8H9V
• Pfam ID: PF00119
• Sequence:
  MNENLFASFIAPTILGLPAAVLIILFPPLLIPTSKYLINNRLITTQQWLIKLTSKQMMTM
  HNTKGRTWSLMLVSLIIFIATTNLLGLLPHSFTPTTQLSMNLAMAIPLWAGTVIMGFRSK
  IKNALAHFLPQGTPTPLIPMLVIIETISLLIQPMALAVRLTANITAGHLLMHLIGSATLA
  MSTINLPSTLIIFTILILLTILEIAVALIQAYVFTLLVSLYLHDNT
• 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. Key component of the proton channel; it may play a direct role in the translocation of protons across the membrane.
• 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:
  Cristae formation (R-HSA-8949613)
  Formation of ATP by chemiosmotic coupling (R-HSA-163210)
• BioCyc Pathway: MetaCyc:HS00024-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

41 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adenocarcinoma	DIS3IHTY	Definitive	Genetic Variation	[1]
Autoimmune disease	DISORMTM	Definitive	Genetic Variation	[2]
Deafness	DISKCLH4	Definitive	Genetic Variation	[3]
Intellectual disability	DISMBNXP	Definitive	Genetic Variation	[4]
Periodic paralysis with later-onset distal motor neuropathy	DIS0GEC0	Definitive	GermlineCausalMutation	[5]
Systemic lupus erythematosus	DISI1SZ7	Definitive	Genetic Variation	[2]
Ataxia-telangiectasia	DISP3EVR	Strong	Genetic Variation	[6]
Bone osteosarcoma	DIST1004	Strong	Genetic Variation	[7]
Breast cancer	DIS7DPX1	Strong	Genetic Variation	[8]
Breast carcinoma	DIS2UE88	Strong	Genetic Variation	[8]
Cardiomyopathy	DISUPZRG	Strong	Genetic Variation	[9]
Charcot marie tooth disease	DIS3BT2L	Strong	Genetic Variation	[10]
Childhood acute lymphoblastic leukemia	DISJ5D6U	Strong	Genetic Variation	[11]
Demyelinating polyneuropathy	DIS7IO4W	Strong	Genetic Variation	[12]
Essential hypertension	DIS7WI98	Strong	Genetic Variation	[13]
IgA nephropathy	DISZ8MTK	Strong	Genetic Variation	[14]
Leber hereditary optic neuropathy	DIS7Y2EE	Strong	Genetic Variation	[15]
Leigh syndrome	DISWQU45	Strong	Genetic Variation	[16]
Maternally-inherited Leigh syndrome	DISGE06V	Strong	Genetic Variation	[17]
MELAS syndrome	DIS81Z3S	Strong	CausalMutation	[18]
Mitochondrial encephalomyopathy	DISA6PTN	Strong	Genetic Variation	[19]
Mitochondrial myopathy	DIS9SA7V	Strong	Genetic Variation	[9]
Mitochondrial proton-transporting ATP synthase complex deficiency	DISX6N3H	Strong	GermlineCausalMutation	[4]
Multiple sclerosis	DISB2WZI	Strong	Genetic Variation	[2]
Myopathy	DISOWG27	Strong	Genetic Variation	[9]
Nephropathy	DISXWP4P	Strong	Genetic Variation	[20]
Obesity	DIS47Y1K	Strong	Genetic Variation	[21]
Osteoporosis	DISF2JE0	Strong	Genetic Variation	[22]
Osteosarcoma	DISLQ7E2	Strong	Genetic Variation	[7]
Peripheral neuropathy	DIS7KN5G	Strong	Biomarker	[23]
Polyneuropathy	DISB9G3W	Strong	Genetic Variation	[24]
Retinitis pigmentosa	DISCGPY8	Strong	Genetic Variation	[25]
Retinopathy	DISB4B0F	Strong	Genetic Variation	[26]
Trichohepatoenteric syndrome	DISL3ODF	Strong	Genetic Variation	[27]
Female hypogonadism	DISWASB4	moderate	Genetic Variation	[28]
Amyotrophic lateral sclerosis	DISF7HVM	Limited	Biomarker	[29]
Fetal growth restriction	DIS5WEJ5	Limited	Biomarker	[30]
Nervous system disease	DISJ7GGT	Limited	Genetic Variation	[16]
Prostate cancer	DISF190Y	Limited	Biomarker	[31]
Prostate carcinoma	DISMJPLE	Limited	Biomarker	[31]
Type-1/2 diabetes	DISIUHAP	Limited	Biomarker	[32]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Tributylstannanyl	DMHN7CB	Investigative	ATP synthase subunit a (ATP6) increases the response to substance of Tributylstannanyl.	[50]

1 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 ATP synthase subunit a (ATP6).	[33]

17 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 a (ATP6).	[34]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of ATP synthase subunit a (ATP6).	[35]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of ATP synthase subunit a (ATP6).	[37]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of ATP synthase subunit a (ATP6).	[38]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide decreases the expression of ATP synthase subunit a (ATP6).	[39]
Marinol	DM70IK5	Approved	Marinol increases the expression of ATP synthase subunit a (ATP6).	[40]
Ethinyl estradiol	DMODJ40	Approved	Ethinyl estradiol increases the expression of ATP synthase subunit a (ATP6).	[41]
Zidovudine	DM4KI7O	Approved	Zidovudine increases the expression of ATP synthase subunit a (ATP6).	[42]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of ATP synthase subunit a (ATP6).	[43]
Fialuridine	DMCIGRB	Phase 2	Fialuridine decreases the expression of ATP synthase subunit a (ATP6).	[44]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of ATP synthase subunit a (ATP6).	[45]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of ATP synthase subunit a (ATP6).	[46]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A increases the expression of ATP synthase subunit a (ATP6).	[47]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate decreases the expression of ATP synthase subunit a (ATP6).	[48]
[3H]methyltrienolone	DMTSGOW	Investigative	[3H]methyltrienolone increases the expression of ATP synthase subunit a (ATP6).	[49]
Hydroxyestradiol	DMJXQME	Investigative	Hydroxyestradiol increases the expression of ATP synthase subunit a (ATP6).	[41]
2-hydroxy-17beta-estradiol	DMM9Z0B	Investigative	2-hydroxy-17beta-estradiol increases the expression of ATP synthase subunit a (ATP6).	[41]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Estradiol	DMUNTE3	Approved	Estradiol affects the binding of ATP synthase subunit a (ATP6).	[36]

References

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