Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTM4ECDK)

• DOT Name: Microtubule-associated proteins 1A/1B light chain 3C (MAP1LC3C)
• Synonyms: Autophagy-related protein LC3 C; Autophagy-related ubiquitin-like modifier LC3 C; MAP1 light chain 3-like protein 3; MAP1A/MAP1B light chain 3 C; MAP1A/MAP1B LC3 C; Microtubule-associated protein 1 light chain 3 gamma
• Gene Name: MAP1LC3C
• Related Disease:
  Cerebellar ataxia, intellectual disability, and dysequilibrium syndrome 2
  Colorectal carcinoma
  Neoplasm
  Kidney cancer
  Renal carcinoma
  Breast cancer
  Breast carcinoma
  Lung cancer
  Lung squamous cell carcinoma
  Advanced cancer
• UniProt ID: MLP3C_HUMAN
• PDB ID: 2NCN; 3VVW; 3WAM; 3WAP; 5DPW
• Pfam ID: PF02991
• Sequence:
  MPPPQKIPSVRPFKQRKSLAIRQEEVAGIRAKFPNKIPVVVERYPRETFLPPLDKTKFLV
  PQELTMTQFLSIIRSRMVLRATEAFYLLVNNKSLVSMSATMAEIYRDYKDEDGFVYMTYA
  SQETFGCLESAAPRDGSSLEDRPCNPL
• Function: Ubiquitin-like modifier that plays a crucial role in antibacterial autophagy (xenophagy) through the selective binding of CALCOCO2. Recruits all ATG8 family members to infecting bacteria such as S.typhimurium. May also play a role in aggrephagy, the macroautophagic degradation of ubiquitinated and aggregated proteins.
• Tissue Specificity: Most abundant in placenta, lung and ovary.
• 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: Macroautophagy (R-HSA-1632852)

Molecular Interaction Atlas (MIA) of This DOT

10 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cerebellar ataxia, intellectual disability, and dysequilibrium syndrome 2	DISUFWJU	Strong	Biomarker	[1]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[2]
Neoplasm	DISZKGEW	Strong	Biomarker	[2]
Kidney cancer	DISBIPKM	moderate	Altered Expression	[3]
Renal carcinoma	DISER9XT	moderate	Altered Expression	[3]
Breast cancer	DIS7DPX1	Disputed	Biomarker	[3]
Breast carcinoma	DIS2UE88	Disputed	Biomarker	[3]
Lung cancer	DISCM4YA	Disputed	Biomarker	[3]
Lung squamous cell carcinoma	DISXPIBD	Disputed	Altered Expression	[3]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[4]

1 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 3C (MAP1LC3C).	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Microtubule-associated proteins 1A/1B light chain 3C (MAP1LC3C).	[6]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Microtubule-associated proteins 1A/1B light chain 3C (MAP1LC3C).	[7]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Microtubule-associated proteins 1A/1B light chain 3C (MAP1LC3C).	[6]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Microtubule-associated proteins 1A/1B light chain 3C (MAP1LC3C).	[7]
Trovafloxacin	DM6AN32	Approved	Trovafloxacin increases the expression of Microtubule-associated proteins 1A/1B light chain 3C (MAP1LC3C).	[8]
Belinostat	DM6OC53	Phase 2	Belinostat increases the expression of Microtubule-associated proteins 1A/1B light chain 3C (MAP1LC3C).	[7]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Microtubule-associated proteins 1A/1B light chain 3C (MAP1LC3C).	[9]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Microtubule-associated proteins 1A/1B light chain 3C (MAP1LC3C).	[10]

References

• [1] The BEACH-containing protein WDR81 coordinates p62 and LC3C to promote aggrephagy.J Cell Biol. 2017 May 1;216(5):1301-1320. doi: 10.1083/jcb.201608039. Epub 2017 Apr 12.
• [2] The Influence of Tumor Microenvironment on ATG4D Gene Expression in Colorectal Cancer Patients.Med Oncol. 2018 Oct 29;35(12):159. doi: 10.1007/s12032-018-1220-6.
• [3] Cross-cancer profiling of molecular alterations within the human autophagy interaction network.Autophagy. 2015;11(9):1668-87. doi: 10.1080/15548627.2015.1067362.
• [4] Autophagosome Proteins LC3A, LC3B and LC3C Have Distinct Subcellular Distribution Kinetics and Expression in Cancer Cell Lines.PLoS One. 2015 Sep 17;10(9):e0137675. doi: 10.1371/journal.pone.0137675. eCollection 2015.
• [5] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [6] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [7] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [8] TNF enhances trovafloxacin-induced in vitro hepatotoxicity by inhibiting protective autophagy. Toxicol Lett. 2021 May 15;342:73-84. doi: 10.1016/j.toxlet.2021.02.009. Epub 2021 Feb 17.
• [9] Loss of TRIM33 causes resistance to BET bromodomain inhibitors through MYC- and TGF-beta-dependent mechanisms. Proc Natl Acad Sci U S A. 2016 Aug 2;113(31):E4558-66.
• [10] Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration. Arch Toxicol. 2016 Jan;90(1):159-80.