Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTTA5C3U)

• DOT Name: Aminoacyl tRNA synthase complex-interacting multifunctional protein 1 (AIMP1)
• Synonyms: Multisynthase complex auxiliary component p43
• Gene Name: AIMP1
• Related Disease:
  Intellectual disability
  Rheumatoid arthritis
  Adult glioblastoma
  Alzheimer disease
  Arteriosclerosis
  Atherosclerosis
  Bronchopulmonary dysplasia
  Carcinoma
  Colon cancer
  Colon carcinoma
  Colorectal carcinoma
  Gastric cancer
  Glioblastoma multiforme
  Glioma
  Hepatitis B virus infection
  Hepatitis C virus infection
  Hypomyelinating leukodystrophy 3
  Lung cancer
  Lung carcinoma
  Matthew-Wood syndrome
  Metastatic malignant neoplasm
  Neoplasm
  Pancreatic cancer
  Small lymphocytic lymphoma
  Stomach cancer
  Systemic lupus erythematosus
  Laryngeal squamous cell carcinoma
  Lupus nephritis
  Melanoma
  Nephritis
  Autosomal recessive non-syndromic intellectual disability
  Granular corneal dystrophy type II
  Leukodystrophy
  Myocardial infarction
  Nervous system inflammation
  Pulmonary emphysema
  Uveitis
• UniProt ID: AIMP1_HUMAN
• PDB ID: 1E7Z; 1EUJ; 1FL0; 4R3Z
• Pfam ID: PF01588
• Sequence:
  MANNDAVLKRLEQKGAEADQIIEYLKQQVSLLKEKAILQATLREEKKLRVENAKLKKEIE
  ELKQELIQAEIQNGVKQIPFPSGTPLHANSMVSENVIQSTAVTTVSSGTKEQIKGGTGDE
  KKAKEKIEKKGEKKEKKQQSIAGSADSKPIDVSRLDLRIGCIITARKHPDADSLYVEEVD
  VGEIAPRTVVSGLVNHVPLEQMQNRMVILLCNLKPAKMRGVLSQAMVMCASSPEKIEILA
  PPNGSVPGDRITFDAFPGEPDKELNPKKKIWEQIQPDLHTNDECVATYKGVPFEVKGKGV
  CRAQTMSNSGIK
• Function: Non-catalytic component of the multisynthase complex. Stimulates the catalytic activity of cytoplasmic arginyl-tRNA synthase. Binds tRNA. Possesses inflammatory cytokine activity. Negatively regulates TGF-beta signaling through stabilization of SMURF2 by binding to SMURF2 and inhibiting its SMAD7-mediated degradation. Involved in glucose homeostasis through induction of glucagon secretion at low glucose levels. Promotes dermal fibroblast proliferation and wound repair. Regulates KDELR1-mediated retention of HSP90B1/gp96 in the endoplasmic reticulum. Plays a role in angiogenesis by inducing endothelial cell migration at low concentrations and endothelian cell apoptosis at high concentrations. Induces maturation of dendritic cells and monocyte cell adhesion. Modulates endothelial cell responses by degrading HIF-1A through interaction with PSMA7.
• Reactome Pathway:
  Cytosolic tRNA aminoacylation (R-HSA-379716)
  Selenoamino acid metabolism (R-HSA-2408522)

Molecular Interaction Atlas (MIA) of This DOT

37 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Intellectual disability	DISMBNXP	Definitive	Genetic Variation	[1]
Rheumatoid arthritis	DISTSB4J	Definitive	Altered Expression	[2]
Adult glioblastoma	DISVP4LU	Strong	Biomarker	[3]
Alzheimer disease	DISF8S70	Strong	Biomarker	[4]
Arteriosclerosis	DISK5QGC	Strong	Biomarker	[5]
Atherosclerosis	DISMN9J3	Strong	Biomarker	[5]
Bronchopulmonary dysplasia	DISO0BY5	Strong	Altered Expression	[6]
Carcinoma	DISH9F1N	Strong	Biomarker	[7]
Colon cancer	DISVC52G	Strong	Altered Expression	[8]
Colon carcinoma	DISJYKUO	Strong	Altered Expression	[8]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[8]
Gastric cancer	DISXGOUK	Strong	Biomarker	[9]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[3]
Glioma	DIS5RPEH	Strong	Biomarker	[10]
Hepatitis B virus infection	DISLQ2XY	Strong	Biomarker	[11]
Hepatitis C virus infection	DISQ0M8R	Strong	Biomarker	[12]
Hypomyelinating leukodystrophy 3	DISJ0Y1E	Strong	Autosomal recessive	[13]
Lung cancer	DISCM4YA	Strong	Biomarker	[9]
Lung carcinoma	DISTR26C	Strong	Biomarker	[9]
Matthew-Wood syndrome	DISA7HR7	Strong	Biomarker	[14]
Metastatic malignant neoplasm	DIS86UK6	Strong	Altered Expression	[8]
Neoplasm	DISZKGEW	Strong	Biomarker	[15]
Pancreatic cancer	DISJC981	Strong	Altered Expression	[14]
Small lymphocytic lymphoma	DIS30POX	Strong	Altered Expression	[16]
Stomach cancer	DISKIJSX	Strong	Biomarker	[9]
Systemic lupus erythematosus	DISI1SZ7	Strong	Biomarker	[17]
Laryngeal squamous cell carcinoma	DIS9UUVF	moderate	Biomarker	[18]
Lupus nephritis	DISCVGPZ	moderate	Biomarker	[19]
Melanoma	DIS1RRCY	moderate	Altered Expression	[20]
Nephritis	DISQZQ70	moderate	Biomarker	[19]
Autosomal recessive non-syndromic intellectual disability	DISJWRZZ	Supportive	Autosomal recessive	[21]
Granular corneal dystrophy type II	DISAEE20	Limited	Biomarker	[22]
Leukodystrophy	DISVY1TT	Limited	Genetic Variation	[23]
Myocardial infarction	DIS655KI	Limited	Biomarker	[24]
Nervous system inflammation	DISB3X5A	Limited	Biomarker	[25]
Pulmonary emphysema	DIS5M7HZ	Limited	Biomarker	[26]
Uveitis	DISV0RYS	Limited	Biomarker	[25]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Aminoacyl tRNA synthase complex-interacting multifunctional protein 1 (AIMP1).	[27]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Aminoacyl tRNA synthase complex-interacting multifunctional protein 1 (AIMP1).	[28]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Aminoacyl tRNA synthase complex-interacting multifunctional protein 1 (AIMP1).	[29]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Aminoacyl tRNA synthase complex-interacting multifunctional protein 1 (AIMP1).	[30]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Aminoacyl tRNA synthase complex-interacting multifunctional protein 1 (AIMP1).	[32]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Aminoacyl tRNA synthase complex-interacting multifunctional protein 1 (AIMP1).	[33]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Aminoacyl tRNA synthase complex-interacting multifunctional protein 1 (AIMP1).	[34]
Selenium	DM25CGV	Approved	Selenium decreases the expression of Aminoacyl tRNA synthase complex-interacting multifunctional protein 1 (AIMP1).	[36]
Piroxicam	DMTK234	Approved	Piroxicam decreases the expression of Aminoacyl tRNA synthase complex-interacting multifunctional protein 1 (AIMP1).	[37]
Clozapine	DMFC71L	Approved	Clozapine increases the expression of Aminoacyl tRNA synthase complex-interacting multifunctional protein 1 (AIMP1).	[38]
Mifepristone	DMGZQEF	Approved	Mifepristone increases the expression of Aminoacyl tRNA synthase complex-interacting multifunctional protein 1 (AIMP1).	[39]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate decreases the expression of Aminoacyl tRNA synthase complex-interacting multifunctional protein 1 (AIMP1).	[40]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Aminoacyl tRNA synthase complex-interacting multifunctional protein 1 (AIMP1).	[36]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Aminoacyl tRNA synthase complex-interacting multifunctional protein 1 (AIMP1).	[42]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A increases the expression of Aminoacyl tRNA synthase complex-interacting multifunctional protein 1 (AIMP1).	[43]
Nickel chloride	DMI12Y8	Investigative	Nickel chloride decreases the expression of Aminoacyl tRNA synthase complex-interacting multifunctional protein 1 (AIMP1).	[44]
GW7604	DMCA4RM	Investigative	GW7604 increases the expression of Aminoacyl tRNA synthase complex-interacting multifunctional protein 1 (AIMP1).	[45]

3 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Quercetin	DM3NC4M	Approved	Quercetin increases the phosphorylation of Aminoacyl tRNA synthase complex-interacting multifunctional protein 1 (AIMP1).	[31]
Marinol	DM70IK5	Approved	Marinol increases the methylation of Aminoacyl tRNA synthase complex-interacting multifunctional protein 1 (AIMP1).	[35]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Aminoacyl tRNA synthase complex-interacting multifunctional protein 1 (AIMP1).	[41]

References

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