Details of Drug Off-Target (DOT)

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

• DOT Name: Properdin (CFP)
• Synonyms: Complement factor P
• Gene Name: CFP
• Related Disease: Properdin deficiency, X-linked
• UniProt ID: PROP_HUMAN
• PDB ID: 1W0R; 1W0S; 6RUR; 6RUS; 6RUV; 6RV6; 6S08; 6S0A; 6S0B; 6SEJ; 7B26; 7NOZ
• Pfam ID: PF00090 ; PF18487
• Sequence:
  MITEGAQAPRLLLPPLLLLLTLPATGSDPVLCFTQYEESSGKCKGLLGGGVSVEDCCLNT
  AFAYQKRSGGLCQPCRSPRWSLWSTWAPCSVTCSEGSQLRYRRCVGWNGQCSGKVAPGTL
  EWQLQACEDQQCCPEMGGWSGWGPWEPCSVTCSKGTRTRRRACNHPAPKCGGHCPGQAQE
  SEACDTQQVCPTHGAWATWGPWTPCSASCHGGPHEPKETRSRKCSAPEPSQKPPGKPCPG
  LAYEQRRCTGLPPCPVAGGWGPWGPVSPCPVTCGLGQTMEQRTCNHPVPQHGGPFCAGDA
  TRTHICNTAVPCPVDGEWDSWGEWSPCIRRNMKSISCQEIPGQQSRGRTCRGRKFDGHRC
  AGQQQDIRHCYSIQHCPLKGSWSEWSTWGLCMPPCGPNPTRARQRLCTPLLPKYPPTVSM
  VEGQGEKNVTFWGRPLPRCEELQGQKLVVEEKRPCLHVPACKDPEEEEL
• Function: A positive regulator of the alternate pathway (AP) of complement. It binds to and stabilizes the C3- and C5-convertase enzyme complexes. Inhibits CFI-CFH mediated degradation of Complement C3 beta chain (C3b).
• KEGG Pathway: Herpes simplex virus 1 infection (hsa05168)
• Reactome Pathway:
  Activation of C3 and C5 (R-HSA-174577)
  Defective B3GALTL causes PpS (R-HSA-5083635)
  O-glycosylation of TSR domain-containing proteins (R-HSA-5173214)
  Neutrophil degranulation (R-HSA-6798695)
  Regulation of Complement cascade (R-HSA-977606)
  Alternative complement activation (R-HSA-173736)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Properdin deficiency, X-linked	DIS443C8	Strong	X-linked	[1]

2 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 Properdin (CFP).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Properdin (CFP).	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Properdin (CFP).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Properdin (CFP).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Properdin (CFP).	[5]
Arsenic	DMTL2Y1	Approved	Arsenic increases the expression of Properdin (CFP).	[6]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Properdin (CFP).	[7]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of Properdin (CFP).	[8]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Properdin (CFP).	[10]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of Properdin (CFP).	[11]

References

• [1] Properdin deficiency: molecular basis and disease association. Mol Immunol. 1999 Sep-Oct;36(13-14):863-7. doi: 10.1016/s0161-5890(99)00107-8.
• [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] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [6] Arsenic alters transcriptional responses to Pseudomonas aeruginosa infection and decreases antimicrobial defense of human airway epithelial cells. Toxicol Appl Pharmacol. 2017 Sep 15;331:154-163.
• [7] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [8] Computational discovery of niclosamide ethanolamine, a repurposed drug candidate that reduces growth of hepatocellular carcinoma cells initro and in mice by inhibiting cell division cycle 37 signaling. Gastroenterology. 2017 Jun;152(8):2022-2036.
• [9] 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.
• [10] 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.
• [11] Sulforaphane-induced apoptosis in human leukemia HL-60 cells through extrinsic and intrinsic signal pathways and altering associated genes expression assayed by cDNA microarray. Environ Toxicol. 2017 Jan;32(1):311-328.