Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTS63HG5)

• DOT Name: Mannose-binding protein C (MBL2)
• Synonyms: MBP-C; Collectin-1; MBP1; Mannan-binding protein; Mannose-binding lectin
• Gene Name: MBL2
• UniProt ID: MBL2_HUMAN
• PDB ID: 1HUP
• Pfam ID: PF01391 ; PF00059
• Sequence:
  MSLFPSLPLLLLSMVAASYSETVTCEDAQKTCPAVIACSSPGINGFPGKDGRDGTKGEKG
  EPGQGLRGLQGPPGKLGPPGNPGPSGSPGPKGQKGDPGKSPDGDSSLAASERKALQTEMA
  RIKKWLTFSLGKQVGNKFFLTNGEIMTFEKVKALCVKFQASVATPRNAAENGAIQNLIKE
  EAFLGITDEKTEGQFVDLTGNRLTYTNWNEGEPNNAGSDEDCVLLLKNGQWNDVPCSTSH
  LAVCEFPI
• Function: Calcium-dependent lectin involved in innate immune defense. Binds mannose, fucose and N-acetylglucosamine on different microorganisms and activates the lectin complement pathway. Binds to late apoptotic cells, as well as to apoptotic blebs and to necrotic cells, but not to early apoptotic cells, facilitating their uptake by macrophages. May bind DNA. Upon SARS coronavirus-2/SARS-CoV-2 infection, activates the complement lectin pathway which leads to the inhibition SARS-CoV-2 infection and a reduction of the induced inflammatory response.
• Tissue Specificity: Plasma protein produced mainly in the liver.
• KEGG Pathway:
  Phagosome (hsa04145)
  Complement and coagulation cascades (hsa04610)
  Staphylococcus aureus infection (hsa05150)
  Coro.virus disease - COVID-19 (hsa05171)
• Reactome Pathway:
  Initial triggering of complement (R-HSA-166663)
  SARS-CoV-2 activates/modulates innate and adaptive immune responses (R-HSA-9705671)
  Lectin pathway of complement activation (R-HSA-166662)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Bortezomib	DMNO38U	Approved	Mannose-binding protein C (MBL2) increases the response to substance of Bortezomib.	[9]

9 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 Mannose-binding protein C (MBL2).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Mannose-binding protein C (MBL2).	[2]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Mannose-binding protein C (MBL2).	[3]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Mannose-binding protein C (MBL2).	[2]
Troglitazone	DM3VFPD	Approved	Troglitazone increases the expression of Mannose-binding protein C (MBL2).	[4]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone increases the expression of Mannose-binding protein C (MBL2).	[4]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of Mannose-binding protein C (MBL2).	[5]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Mannose-binding protein C (MBL2).	[6]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Mannose-binding protein C (MBL2).	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Mannose-binding protein C (MBL2).	[7]

References

• [1] 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.
• [2] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [3] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [4] Transcriptomic analysis of untreated and drug-treated differentiated HepaRG cells over a 2-week period. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):27-35.
• [5] A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.
• [6] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [7] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [8] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [9] Mechanisms of peripheral neuropathy associated with bortezomib and vincristine in patients with newly diagnosed multiple myeloma: a prospective analysis of data from the HOVON-65/GMMG-HD4 trial. Lancet Oncol. 2010 Nov;11(11):1057-65. doi: 10.1016/S1470-2045(10)70206-0. Epub 2010 Sep 21.