Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTJ02XFL)

• DOT Name: Outer mitochondrial transmembrane helix translocase (ATAD1)
• Synonyms: EC 7.4.2.-; ATPase family AAA domain-containing protein 1; hATAD1; Thorase
• Gene Name: ATAD1
• Related Disease:
  Bladder cancer
  Myocardial infarction
  Plasmodium vivax malaria
  Urinary bladder neoplasm
  Acute leukaemia
  Acute lymphocytic leukaemia
  Anemia
  Arthrogryposis
  Breast cancer
  Breast carcinoma
  Coeliac disease
  Duchenne muscular dystrophy
  Endometrial cancer
  Endometrial carcinoma
  Familial adenomatous polyposis
  Gallbladder cancer
  Gastric cancer
  Hepatocellular carcinoma
  Hereditary nonpolyposis colon cancer
  Hyperekplexia 4
  Hyperlipidemia
  Hyperlipidemia, familial combined, LPL related
  Inclusion body myopathy with Paget disease of bone and frontotemporal dementia type 1
  Lynch syndrome
  Nephrotic syndrome
  Parkinson disease
  Plasma cell myeloma
  Polycystic ovarian syndrome
  Small lymphocytic lymphoma
  Stomach cancer
  Ulcerative colitis
  Urinary bladder cancer
  Amyotrophic lateral sclerosis
  Coronary heart disease
  Plasmodium falciparum malaria
  Hereditary hyperekplexia
  Acute myelogenous leukaemia
  Cervical cancer
  Cervical carcinoma
  Colorectal carcinoma
  Fabry disease
  Myelodysplastic syndrome
  Neoplasm
  Pancreatic cancer
  Rectal carcinoma
  Tuberculosis
• UniProt ID: ATAD1_HUMAN
• PDB ID: 7UPR; 7UPT
• EC Number: 7.4.2.-
• Pfam ID: PF00004 ; PF17862
• Sequence:
  MVHAEAFSRPLSRNEVVGLIFRLTIFGAVTYFTIKWMVDAIDPTRKQKVEAQKQAEKLMK
  QIGVKNVKLSEYEMSIAAHLVDPLNMHVTWSDIAGLDDVITDLKDTVILPIKKKHLFENS
  RLLQPPKGVLLYGPPGCGKTLIAKATAKEAGCRFINLQPSTLTDKWYGESQKLAAAVFSL
  AIKLQPSIIFIDEIDSFLRNRSSSDHEATAMMKAQFMSLWDGLDTDHSCQVIVMGATNRP
  QDLDSAIMRRMPTRFHINQPALKQREAILKLILKNENVDRHVDLLEVAQETDGFSGSDLK
  EMCRDAALLCVREYVNSTSEESHDEDEIRPVQQQDLHRAIEKMKKSKDAAFQNVLTHVCL
  D
• Function: Outer mitochondrial translocase required to remove mislocalized tail-anchored transmembrane proteins on mitochondria. Specifically recognizes and binds tail-anchored transmembrane proteins: acts as a dislocase that mediates the ATP-dependent extraction of mistargeted tail-anchored transmembrane proteins from the mitochondrion outer membrane. Also plays a critical role in regulating the surface expression of AMPA receptors (AMPAR), thereby regulating synaptic plasticity and learning and memory. Required for NMDA-stimulated AMPAR internalization and inhibition of GRIA1 and GRIA2 recycling back to the plasma membrane; these activities are ATPase-dependent.
• Reactome Pathway: Class I peroxisomal membrane protein import (R-HSA-9603798)

Molecular Interaction Atlas (MIA) of This DOT

46 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Bladder cancer	DISUHNM0	Definitive	Genetic Variation	[1]
Myocardial infarction	DIS655KI	Definitive	Genetic Variation	[2]
Plasmodium vivax malaria	DISPU3H9	Definitive	Biomarker	[3]
Urinary bladder neoplasm	DIS7HACE	Definitive	Genetic Variation	[1]
Acute leukaemia	DISDQFDI	Strong	Genetic Variation	[4]
Acute lymphocytic leukaemia	DISPX75S	Strong	Genetic Variation	[5]
Anemia	DISTVL0C	Strong	Biomarker	[6]
Arthrogryposis	DISC81CM	Strong	Genetic Variation	[7]
Breast cancer	DIS7DPX1	Strong	Genetic Variation	[8]
Breast carcinoma	DIS2UE88	Strong	Genetic Variation	[8]
Coeliac disease	DISIY60C	Strong	Genetic Variation	[9]
Duchenne muscular dystrophy	DISRQ3NV	Strong	Genetic Variation	[10]
Endometrial cancer	DISW0LMR	Strong	Genetic Variation	[11]
Endometrial carcinoma	DISXR5CY	Strong	Genetic Variation	[11]
Familial adenomatous polyposis	DISW53RE	Strong	Biomarker	[12]
Gallbladder cancer	DISXJUAF	Strong	Genetic Variation	[13]
Gastric cancer	DISXGOUK	Strong	Genetic Variation	[14]
Hepatocellular carcinoma	DIS0J828	Strong	Genetic Variation	[14]
Hereditary nonpolyposis colon cancer	DISPA49R	Strong	Genetic Variation	[15]
Hyperekplexia 4	DIS5CD4T	Strong	Autosomal recessive	[16]
Hyperlipidemia	DIS61J3S	Strong	Biomarker	[17]
Hyperlipidemia, familial combined, LPL related	DISL1CE3	Strong	Biomarker	[18]
Inclusion body myopathy with Paget disease of bone and frontotemporal dementia type 1	DISHQXXA	Strong	Biomarker	[19]
Lynch syndrome	DIS3IW5F	Strong	Genetic Variation	[15]
Nephrotic syndrome	DISSPSC2	Strong	Biomarker	[20]
Parkinson disease	DISQVHKL	Strong	Genetic Variation	[21]
Plasma cell myeloma	DIS0DFZ0	Strong	Genetic Variation	[5]
Polycystic ovarian syndrome	DISZ2BNG	Strong	Genetic Variation	[22]
Small lymphocytic lymphoma	DIS30POX	Strong	Biomarker	[23]
Stomach cancer	DISKIJSX	Strong	Genetic Variation	[14]
Ulcerative colitis	DIS8K27O	Strong	Genetic Variation	[24]
Urinary bladder cancer	DISDV4T7	Strong	Genetic Variation	[1]
Amyotrophic lateral sclerosis	DISF7HVM	moderate	Genetic Variation	[25]
Coronary heart disease	DIS5OIP1	moderate	Genetic Variation	[26]
Plasmodium falciparum malaria	DIS3Q9KF	moderate	Genetic Variation	[27]
Hereditary hyperekplexia	DIS9YXFE	Supportive	Autosomal dominant	[7]
Acute myelogenous leukaemia	DISCSPTN	Limited	Biomarker	[28]
Cervical cancer	DISFSHPF	Limited	Genetic Variation	[29]
Cervical carcinoma	DIST4S00	Limited	Genetic Variation	[29]
Colorectal carcinoma	DIS5PYL0	Limited	Genetic Variation	[14]
Fabry disease	DISUUQJF	Limited	Genetic Variation	[30]
Myelodysplastic syndrome	DISYHNUI	Limited	Posttranslational Modification	[28]
Neoplasm	DISZKGEW	Limited	Genetic Variation	[31]
Pancreatic cancer	DISJC981	Limited	Posttranslational Modification	[32]
Rectal carcinoma	DIS8FRR7	Limited	Genetic Variation	[33]
Tuberculosis	DIS2YIMD	Limited	Biomarker	[34]

3 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 Outer mitochondrial transmembrane helix translocase (ATAD1).	[35]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Outer mitochondrial transmembrane helix translocase (ATAD1).	[41]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Outer mitochondrial transmembrane helix translocase (ATAD1).	[41]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Outer mitochondrial transmembrane helix translocase (ATAD1).	[36]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Outer mitochondrial transmembrane helix translocase (ATAD1).	[37]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Outer mitochondrial transmembrane helix translocase (ATAD1).	[38]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Outer mitochondrial transmembrane helix translocase (ATAD1).	[39]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Outer mitochondrial transmembrane helix translocase (ATAD1).	[40]

References

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