Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTJRO09Y)

• DOT Name: Ubiquitin-like protein ATG12 (ATG12)
• Synonyms: Autophagy-related protein 12; APG12-like
• Gene Name: ATG12
• Related Disease:
  Adenocarcinoma
  Carcinoid tumor
  Advanced cancer
  Alzheimer disease
  Bladder cancer
  Carcinoma
  Cervical cancer
  Cervical carcinoma
  Chondrosarcoma
  Colorectal carcinoma
  Cystic fibrosis
  Hepatocellular carcinoma
  HIV infectious disease
  Leukocyte adhesion deficiency type 1
  Lupus
  Multiple sclerosis
  Non-small-cell lung cancer
  Pancreatic cancer
  Parkinson disease
  Prostate cancer
  Prostate carcinoma
  Pulmonary fibrosis
  Systemic lupus erythematosus
  Urinary bladder cancer
  Urinary bladder neoplasm
  Uveal Melanoma
  Alopecia
  B-cell neoplasm
  Breast cancer
  Breast carcinoma
  Head-neck squamous cell carcinoma
  Osteoarthritis
  Autosomal dominant cerebellar ataxia type II
  Bone osteosarcoma
  Gastric cancer
  Neoplasm
  Osteosarcoma
  Spinocerebellar ataxia type 3
  Stomach cancer
• UniProt ID: ATG12_HUMAN
• PDB ID: 4GDK; 4GDL; 4NAW
• Pfam ID: PF04110
• Sequence:
  MAEEPQSVLQLPTSIAAGGEGLTDVSPETTTPEPPSSAAVSPGTEEPAGDTKKKIDILLK
  AVGDTPIMKTKKWAVERTRTIQGLIDFIKKFLKLVASEQLFIYVNQSFAPSPDQEVGTLY
  ECFGSDGKLVLHYCKSQAWG
• Function: Ubiquitin-like protein involved in autophagy vesicles formation. Conjugation with ATG5 through a ubiquitin-like conjugating system involving also ATG7 as an E1-like activating enzyme and ATG10 as an E2-like conjugating enzyme, is essential for its function. The ATG12-ATG5 conjugate acts as an E3-like enzyme which is required for lipidation of ATG8 family proteins and their association to the vesicle membranes; (Microbial infection) May act as a proviral factor. In association with ATG5, negatively regulates the innate antiviral immune response by impairing the type I IFN production pathway upon vesicular stomatitis virus (VSV) infection. Required for the translation of incoming hepatitis C virus (HCV) RNA and, thereby, for the initiation of HCV replication, but not required once infection is established.
• Tissue Specificity: Ubiquitous.
• KEGG Pathway:
  FoxO sig.ling pathway (hsa04068)
  Autophagy - other (hsa04136)
  Autophagy - animal (hsa04140)
  NOD-like receptor sig.ling pathway (hsa04621)
  RIG-I-like receptor sig.ling pathway (hsa04622)
  Shigellosis (hsa05131)
• Reactome Pathway:
  PINK1-PRKN Mediated Mitophagy (R-HSA-5205685)
  Receptor Mediated Mitophagy (R-HSA-8934903)
  Negative regulators of DDX58/IFIH1 signaling (R-HSA-936440)
  Macroautophagy (R-HSA-1632852)

Molecular Interaction Atlas (MIA) of This DOT

39 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adenocarcinoma	DIS3IHTY	Definitive	Genetic Variation	[1]
Carcinoid tumor	DISMNRDC	Definitive	Biomarker	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
Alzheimer disease	DISF8S70	Strong	Biomarker	[3]
Bladder cancer	DISUHNM0	Strong	Genetic Variation	[4]
Carcinoma	DISH9F1N	Strong	Genetic Variation	[5]
Cervical cancer	DISFSHPF	Strong	Biomarker	[6]
Cervical carcinoma	DIST4S00	Strong	Biomarker	[6]
Chondrosarcoma	DIS4I7JB	Strong	Biomarker	[7]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[8]
Cystic fibrosis	DIS2OK1Q	Strong	Genetic Variation	[9]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[10]
HIV infectious disease	DISO97HC	Strong	Altered Expression	[11]
Leukocyte adhesion deficiency type 1	DISA1J7W	Strong	Biomarker	[12]
Lupus	DISOKJWA	Strong	Altered Expression	[13]
Multiple sclerosis	DISB2WZI	Strong	Biomarker	[14]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[15]
Pancreatic cancer	DISJC981	Strong	Altered Expression	[16]
Parkinson disease	DISQVHKL	Strong	Altered Expression	[17]
Prostate cancer	DISF190Y	Strong	Genetic Variation	[18]
Prostate carcinoma	DISMJPLE	Strong	Genetic Variation	[18]
Pulmonary fibrosis	DISQKVLA	Strong	Altered Expression	[19]
Systemic lupus erythematosus	DISI1SZ7	Strong	Altered Expression	[13]
Urinary bladder cancer	DISDV4T7	Strong	Genetic Variation	[4]
Urinary bladder neoplasm	DIS7HACE	Strong	Genetic Variation	[4]
Uveal Melanoma	DISA7ZGL	Strong	Biomarker	[20]
Alopecia	DIS37HU4	moderate	Biomarker	[21]
B-cell neoplasm	DISVY326	moderate	Biomarker	[21]
Breast cancer	DIS7DPX1	moderate	Altered Expression	[22]
Breast carcinoma	DIS2UE88	moderate	Altered Expression	[22]
Head-neck squamous cell carcinoma	DISF7P24	moderate	Genetic Variation	[23]
Osteoarthritis	DIS05URM	moderate	Biomarker	[24]
Autosomal dominant cerebellar ataxia type II	DIS0PM39	Limited	Biomarker	[25]
Bone osteosarcoma	DIST1004	Limited	Biomarker	[26]
Gastric cancer	DISXGOUK	Limited	Altered Expression	[27]
Neoplasm	DISZKGEW	Limited	Biomarker	[2]
Osteosarcoma	DISLQ7E2	Limited	Biomarker	[26]
Spinocerebellar ataxia type 3	DISQBQID	Limited	Altered Expression	[28]
Stomach cancer	DISKIJSX	Limited	Altered Expression	[27]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Staurosporine	DM0E9BR	Investigative	Ubiquitin-like protein ATG12 (ATG12) affects the response to substance of Staurosporine.	[55]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Ubiquitin-like protein ATG12 (ATG12).	[29]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Ubiquitin-like protein ATG12 (ATG12).	[30]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Ubiquitin-like protein ATG12 (ATG12).	[31]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Ubiquitin-like protein ATG12 (ATG12).	[32]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the expression of Ubiquitin-like protein ATG12 (ATG12).	[33]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Ubiquitin-like protein ATG12 (ATG12).	[34]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Ubiquitin-like protein ATG12 (ATG12).	[35]
Selenium	DM25CGV	Approved	Selenium decreases the expression of Ubiquitin-like protein ATG12 (ATG12).	[36]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Ubiquitin-like protein ATG12 (ATG12).	[37]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil decreases the expression of Ubiquitin-like protein ATG12 (ATG12).	[38]
Hydroquinone	DM6AVR4	Approved	Hydroquinone increases the expression of Ubiquitin-like protein ATG12 (ATG12).	[39]
Artesunate	DMR27C8	Approved	Artesunate increases the expression of Ubiquitin-like protein ATG12 (ATG12).	[40]
Trovafloxacin	DM6AN32	Approved	Trovafloxacin increases the expression of Ubiquitin-like protein ATG12 (ATG12).	[41]
Chloramphenicol	DMFXEWT	Approved	Chloramphenicol increases the expression of Ubiquitin-like protein ATG12 (ATG12).	[42]
Thymoquinone	DMVDTR2	Phase 2/3	Thymoquinone decreases the expression of Ubiquitin-like protein ATG12 (ATG12).	[43]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Ubiquitin-like protein ATG12 (ATG12).	[36]
Tetrandrine	DMAOJBX	Phase 1	Tetrandrine increases the expression of Ubiquitin-like protein ATG12 (ATG12).	[44]
GSK618334	DMJPXZ4	Phase 1	GSK618334 increases the expression of Ubiquitin-like protein ATG12 (ATG12).	[45]
Torcetrapib	DMDHYM7	Discontinued in Phase 2	Torcetrapib increases the expression of Ubiquitin-like protein ATG12 (ATG12).	[46]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Ubiquitin-like protein ATG12 (ATG12).	[47]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Ubiquitin-like protein ATG12 (ATG12).	[48]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate increases the expression of Ubiquitin-like protein ATG12 (ATG12).	[49]
Paraquat	DMR8O3X	Investigative	Paraquat increases the expression of Ubiquitin-like protein ATG12 (ATG12).	[50]
Glyphosate	DM0AFY7	Investigative	Glyphosate increases the expression of Ubiquitin-like protein ATG12 (ATG12).	[51]
acrolein	DMAMCSR	Investigative	acrolein increases the expression of Ubiquitin-like protein ATG12 (ATG12).	[52]
Cordycepin	DM72Y01	Investigative	Cordycepin affects the expression of Ubiquitin-like protein ATG12 (ATG12).	[53]
Galangin	DM5TQ2O	Investigative	Galangin increases the expression of Ubiquitin-like protein ATG12 (ATG12).	[54]

References

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