Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTPMGIU4)

• DOT Name: Microtubule-associated proteins 1A/1B light chain 3A (MAP1LC3A)
• Synonyms: Autophagy-related protein LC3 A; Autophagy-related ubiquitin-like modifier LC3 A; MAP1 light chain 3-like protein 1; MAP1A/MAP1B light chain 3 A; MAP1A/MAP1B LC3 A; Microtubule-associated protein 1 light chain 3 alpha
• Gene Name: MAP1LC3A
• Related Disease:
  Esophageal squamous cell carcinoma
  Glioblastoma multiforme
  Rheumatoid arthritis
  Adenocarcinoma
  Advanced cancer
  Alzheimer disease
  Breast cancer
  Choroid plexus carcinoma
  Clear cell renal carcinoma
  Coronary atherosclerosis
  Diabetic kidney disease
  Glaucoma/ocular hypertension
  Hepatitis C virus infection
  Hepatocellular carcinoma
  Interstitial cystitis
  Lafora disease
  Lung adenocarcinoma
  Lung squamous cell carcinoma
  Mucopolysaccharidosis
  Mucopolysaccharidosis type IIIA
  Myocardial infarction
  Neoplasm
  Neurodegenerative disease
  Non-insulin dependent diabetes
  Non-small-cell lung cancer
  Vibrio cholerae infection
  Carcinoma
  Inclusion body myositis
  Intracerebral hemorrhage
  Medullary thyroid gland carcinoma
  Triple negative breast cancer
  Undifferentiated carcinoma
  Coronary heart disease
  High blood pressure
  Digestive system neoplasm
  Gastric cancer
  Ischemia
  Parkinson disease
  Stomach cancer
• UniProt ID: MLP3A_HUMAN
• PDB ID: 3ECI; 3WAL; 3WAN; 4ZDV; 5CX3; 5DPR; 6TBE; 7R9W; 7R9Z; 7RA0
• Pfam ID: PF02991
• Sequence:
  MPSDRPFKQRRSFADRCKEVQQIRDQHPSKIPVIIERYKGEKQLPVLDKTKFLVPDHVNM
  SELVKIIRRRLQLNPTQAFFLLVNQHSMVSVSTPIADIYEQEKDEDGFLYMVYASQETFG
  F
• Function: Ubiquitin-like modifier involved in formation of autophagosomal vacuoles (autophagosomes). While LC3s are involved in elongation of the phagophore membrane, the GABARAP/GATE-16 subfamily is essential for a later stage in autophagosome maturation. Through its interaction with the reticulophagy receptor TEX264, participates in the remodeling of subdomains of the endoplasmic reticulum into autophagosomes upon nutrient stress, which then fuse with lysosomes for endoplasmic reticulum turnover.
• Tissue Specificity: Most abundant in heart, brain, liver, skeletal muscle and testis but absent in thymus and peripheral blood leukocytes.
• KEGG Pathway:
  Mitophagy - animal (hsa04137)
  Autophagy - animal (hsa04140)
  Ferroptosis (hsa04216)
  Apelin sig.ling pathway (hsa04371)
  NOD-like receptor sig.ling pathway (hsa04621)
  Amyotrophic lateral sclerosis (hsa05014)
  Pathways of neurodegeneration - multiple diseases (hsa05022)
  Shigellosis (hsa05131)
  Kaposi sarcoma-associated herpesvirus infection (hsa05167)
• Reactome Pathway:
  PINK1-PRKN Mediated Mitophagy (R-HSA-5205685)
  Receptor Mediated Mitophagy (R-HSA-8934903)
  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
Esophageal squamous cell carcinoma	DIS5N2GV	Definitive	Altered Expression	[1]
Glioblastoma multiforme	DISK8246	Definitive	Altered Expression	[2]
Rheumatoid arthritis	DISTSB4J	Definitive	Altered Expression	[3]
Adenocarcinoma	DIS3IHTY	Strong	Altered Expression	[4]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[5]
Alzheimer disease	DISF8S70	Strong	Biomarker	[6]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[7]
Choroid plexus carcinoma	DISQ04MQ	Strong	Biomarker	[8]
Clear cell renal carcinoma	DISBXRFJ	Strong	Biomarker	[9]
Coronary atherosclerosis	DISKNDYU	Strong	Biomarker	[10]
Diabetic kidney disease	DISJMWEY	Strong	Biomarker	[11]
Glaucoma/ocular hypertension	DISLBXBY	Strong	Biomarker	[12]
Hepatitis C virus infection	DISQ0M8R	Strong	Biomarker	[13]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[14]
Interstitial cystitis	DIS7CAJA	Strong	Altered Expression	[15]
Lafora disease	DIS83JHH	Strong	Biomarker	[16]
Lung adenocarcinoma	DISD51WR	Strong	Biomarker	[17]
Lung squamous cell carcinoma	DISXPIBD	Strong	Altered Expression	[4]
Mucopolysaccharidosis	DISB083T	Strong	Biomarker	[18]
Mucopolysaccharidosis type IIIA	DISP7DR6	Strong	Biomarker	[18]
Myocardial infarction	DIS655KI	Strong	Altered Expression	[19]
Neoplasm	DISZKGEW	Strong	Biomarker	[20]
Neurodegenerative disease	DISM20FF	Strong	Biomarker	[21]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Therapeutic	[22]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[20]
Vibrio cholerae infection	DISW7E3U	Strong	Biomarker	[23]
Carcinoma	DISH9F1N	moderate	Biomarker	[24]
Inclusion body myositis	DISZXXG5	moderate	Biomarker	[25]
Intracerebral hemorrhage	DISC81BT	moderate	Biomarker	[26]
Medullary thyroid gland carcinoma	DISHBL3K	moderate	Altered Expression	[27]
Triple negative breast cancer	DISAMG6N	moderate	Biomarker	[28]
Undifferentiated carcinoma	DISIAZST	moderate	Altered Expression	[27]
Coronary heart disease	DIS5OIP1	Disputed	Biomarker	[10]
High blood pressure	DISY2OHH	Disputed	Biomarker	[29]
Digestive system neoplasm	DISPOJCT	Limited	Altered Expression	[30]
Gastric cancer	DISXGOUK	Limited	Altered Expression	[31]
Ischemia	DIS5XOOY	Limited	Biomarker	[32]
Parkinson disease	DISQVHKL	Limited	Altered Expression	[33]
Stomach cancer	DISKIJSX	Limited	Altered Expression	[31]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Microtubule-associated proteins 1A/1B light chain 3A (MAP1LC3A).	[34]
Marinol	DM70IK5	Approved	Marinol increases the lipidation of Microtubule-associated proteins 1A/1B light chain 3A (MAP1LC3A).	[44]
Thymoquinone	DMVDTR2	Phase 2/3	Thymoquinone increases the lipidation of Microtubule-associated proteins 1A/1B light chain 3A (MAP1LC3A).	[48]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Microtubule-associated proteins 1A/1B light chain 3A (MAP1LC3A).	[51]
PMID25656651-Compound-5	DMAI95U	Patented	PMID25656651-Compound-5 increases the lipidation of Microtubule-associated proteins 1A/1B light chain 3A (MAP1LC3A).	[53]
Resorcinol	DMM37C0	Investigative	Resorcinol increases the lipidation of Microtubule-associated proteins 1A/1B light chain 3A (MAP1LC3A).	[44]

18 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 Microtubule-associated proteins 1A/1B light chain 3A (MAP1LC3A).	[35]
Doxorubicin	DMVP5YE	Approved	Doxorubicin affects the expression of Microtubule-associated proteins 1A/1B light chain 3A (MAP1LC3A).	[36]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Microtubule-associated proteins 1A/1B light chain 3A (MAP1LC3A).	[37]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Microtubule-associated proteins 1A/1B light chain 3A (MAP1LC3A).	[38]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Microtubule-associated proteins 1A/1B light chain 3A (MAP1LC3A).	[39]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Microtubule-associated proteins 1A/1B light chain 3A (MAP1LC3A).	[40]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Microtubule-associated proteins 1A/1B light chain 3A (MAP1LC3A).	[41]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Microtubule-associated proteins 1A/1B light chain 3A (MAP1LC3A).	[43]
Trovafloxacin	DM6AN32	Approved	Trovafloxacin increases the expression of Microtubule-associated proteins 1A/1B light chain 3A (MAP1LC3A).	[46]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Microtubule-associated proteins 1A/1B light chain 3A (MAP1LC3A).	[36]
Chloroquine	DMSI5CB	Phase 3 Trial	Chloroquine increases the expression of Microtubule-associated proteins 1A/1B light chain 3A (MAP1LC3A).	[47]
Apilimod dimesylate	DM4N2O0	Phase 2	Apilimod dimesylate increases the expression of Microtubule-associated proteins 1A/1B light chain 3A (MAP1LC3A).	[50]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Microtubule-associated proteins 1A/1B light chain 3A (MAP1LC3A).	[52]
Clioquinol	DM746BZ	Withdrawn from market	Clioquinol increases the expression of Microtubule-associated proteins 1A/1B light chain 3A (MAP1LC3A).	[54]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Microtubule-associated proteins 1A/1B light chain 3A (MAP1LC3A).	[55]
Paraquat	DMR8O3X	Investigative	Paraquat increases the expression of Microtubule-associated proteins 1A/1B light chain 3A (MAP1LC3A).	[56]
Cordycepin	DM72Y01	Investigative	Cordycepin increases the expression of Microtubule-associated proteins 1A/1B light chain 3A (MAP1LC3A).	[57]
Bafilomycin A1	DMUNK59	Investigative	Bafilomycin A1 increases the expression of Microtubule-associated proteins 1A/1B light chain 3A (MAP1LC3A).	[58]

2 Drug(s) Affected the Biochemical Pathways of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the metabolism of Microtubule-associated proteins 1A/1B light chain 3A (MAP1LC3A).	[42]
BEZ235	DMKBRDL	Phase 2	BEZ235 increases the metabolism of Microtubule-associated proteins 1A/1B light chain 3A (MAP1LC3A).	[49]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Capsaicin	DMGMF6V	Approved	Capsaicin affects the localization of Microtubule-associated proteins 1A/1B light chain 3A (MAP1LC3A).	[45]

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