Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTBFTUZ1)

• DOT Name: Mannan-binding lectin serine protease 2 (MASP2)
• Synonyms: EC 3.4.21.104; MBL-associated serine protease 2; Mannose-binding protein-associated serine protease 2; MASP-2
• Gene Name: MASP2
• Related Disease: Immunodeficiency due to MASP-2 deficiency
• UniProt ID: MASP2_HUMAN
• PDB ID: 1Q3X; 1SZB; 1ZJK; 3TVJ; 5JPM
• EC Number: 3.4.21.104
• Pfam ID: PF00431 ; PF07645 ; PF00084 ; PF00089
• Sequence:
  MRLLTLLGLLCGSVATPLGPKWPEPVFGRLASPGFPGEYANDQERRWTLTAPPGYRLRLY
  FTHFDLELSHLCEYDFVKLSSGAKVLATLCGQESTDTERAPGKDTFYSLGSSLDITFRSD
  YSNEKPFTGFEAFYAAEDIDECQVAPGEAPTCDHHCHNHLGGFYCSCRAGYVLHRNKRTC
  SALCSGQVFTQRSGELSSPEYPRPYPKLSSCTYSISLEEGFSVILDFVESFDVETHPETL
  CPYDFLKIQTDREEHGPFCGKTLPHRIETKSNTVTITFVTDESGDHTGWKIHYTSTAQPC
  PYPMAPPNGHVSPVQAKYILKDSFSIFCETGYELLQGHLPLKSFTAVCQKDGSWDRPMPA
  CSIVDCGPPDDLPSGRVEYITGPGVTTYKAVIQYSCEETFYTMKVNDGKYVCEADGFWTS
  SKGEKSLPVCEPVCGLSARTTGGRIYGGQKAKPGDFPWQVLILGGTTAAGALLYDNWVLT
  AAHAVYEQKHDASALDIRMGTLKRLSPHYTQAWSEAVFIHEGYTHDAGFDNDIALIKLNN
  KVVINSNITPICLPRKEAESFMRTDDIGTASGWGLTQRGFLARNLMYVDIPIVDHQKCTA
  AYEKPPYPRGSVTANMLCAGLESGGKDSCRGDSGGALVFLDSETERWFVGGIVSWGSMNC
  GEAGQYGVYTKVINYIPWIENIISDF
• Function: Serum protease that plays an important role in the activation of the complement system via mannose-binding lectin. After activation by auto-catalytic cleavage it cleaves C2 and C4, leading to their activation and to the formation of C3 convertase.
• Tissue Specificity: Plasma.
• KEGG Pathway:
  Complement and coagulation cascades (hsa04610)
  Staphylococcus aureus infection (hsa05150)
  Coro.virus disease - COVID-19 (hsa05171)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Immunodeficiency due to MASP-2 deficiency	DISVZ6G7	Strong	Autosomal recessive	[1]

4 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 Mannan-binding lectin serine protease 2 (MASP2).	[2]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Mannan-binding lectin serine protease 2 (MASP2).	[3]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone decreases the expression of Mannan-binding lectin serine protease 2 (MASP2).	[4]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Mannan-binding lectin serine protease 2 (MASP2).	[5]

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 decreases the methylation of Mannan-binding lectin serine protease 2 (MASP2).	[6]

References

• [1] The Gene Curation Coalition: A global effort to harmonize gene-disease evidence resources. Genet Med. 2022 Aug;24(8):1732-1742. doi: 10.1016/j.gim.2022.04.017. Epub 2022 May 4.
• [2] 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.
• [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] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [6] 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.