Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTOM3GHH)

• DOT Name: Pecanex-like protein 3 (PCNX3)
• Synonyms: Pecanex homolog protein 3
• Gene Name: PCNX3
• Related Disease:
  Non-small-cell lung cancer
  Coronary heart disease
  Systemic lupus erythematosus
• UniProt ID: PCX3_HUMAN
• Pfam ID: PF05041
• Sequence:
  MGSQVLQILRQGVWASLTGGWFFDPHQSTFSNCFHLYVWIFLLIFPFLLYMVLPPSLMVA
  GVYCLVVAVIFATIKTVNYRLHAMFDQGEIVEKRSSTMGELEEEPAQGDSNPPRDPGVEM
  TVFRKVSSTPPVRCSSQHSVFGFNQVSELLPRMEDSGPLRDIKELVREQGSNNVIVTSAD
  REMLKLSSQEKLIGDLPQTPPGAVPDPSLASTDSSEPSPLAGDGAPWSGSSMADTPMSPL
  LKGSLSQELSKSFLTLTQPDRALVRTSSRREQRRGAGGYQPLDRRGSGEPTPQKAGSSDS
  CFSGTDRETLSSFKSEKTNSTHLDSPPGGPAPEGSDTDPPSEAELPASPDAGVPSDDTLR
  SFDTVIGAGTPPGLAEPLLVVRPKDLALLRPSKRQPPLRRHSPPGRAPRRPLLEGGGFFE
  DEDTSEGSELSPASSLRSQRRYSTDSSSSTSCYSPESSRGAAGGPRKRRAPHGAEEGTAV
  PPKRPYGTQRTPSTASAKTHARVLSMDGAGGDVLRPPLAGCKAELEAQVGVEQAASEPVV
  LPAEARRGPAANQPGWRGELQEEGAVGGAAEETGRRDRSSSVRRTQAIRRRHNAGSNPTP
  PASVMGSPPSSLQEAQRGRAASHSRALTLPSALHFASSLLLTRAGANVHEACTFDDTSEG
  AVHYFYDESGVRRSYTFGLAGGGYENPVGQQGEQTANGAWDRHSHSSSFHSADVPEATGG
  LNLLQPRPVVLQGMQVRRVPLEIPEEQTLMEEAPPRAQHSYKYWLLPGRWTSVRYERLAL
  LALLDRTRGVLENIFGVGLSSLVAFLGYLLLLKGFFTDIWVFQFCLVIASCQYSLLKSVQ
  PDAASPMHGHNWVIAYSRPVYFCICCLLIWLLDALGSAQPFPPVSLYGLTLFSASFFFCA
  RDVATVFTLCFPFVFLLGLLPQVNTCLMYLLEQIDMHGFGGTAATSPLTAVFSLSRSLLA
  AALLYGFCLGAIKTPWPEQHVPVLFSVFCGLLVALSYHLSRQSSDPTVLWSLIRSKLFPE
  LEERSLETARAEPPDPLPDKMRQSVREVLHSDLVMCVVIAVLTFAISASTVFIALKSVLG
  FVLYALAGAVGFFTHYLLPQLRKQLPWFCLSQPVLKPLEYSQYEVRGAAQVMWFEKLYAG
  LQCVEKYLIYPAVVLNALTVDAHTVVSHPDKYCFYCRALLMTVAGLKLLRSAFCCPPQQY
  LTLAFTVLLFHFDYPRLSQGFLLDYFLMSLLCSKLWDLLYKLRFVLTYIAPWQITWGSAF
  HAFAQPFAVPHSAMLFVQALLSGLFSTPLNPLLGSAVFIMSYARPLKFWERDYNTKRVDH
  SNTRLVTQLDRNPGADDNNLNSIFYEHLTRSLQHTLCGDLVLGRWGNYGPGDCFVLASDY
  LNALVHLIEVGNGLVTFQLRGLEFRGTYCQQREVEAITEGVEEDEGCCCCEPGHLPRVLS
  FNAAFGQRWLAWEVTASKYVLEGYSISDNNAASMLQVFDLRKILITYYVKSIIYYVSRSP
  KLEVWLSHEGITAALRPVRVPGYADSDPTFSLSVDEDYDLRLSGLSLPSFCAVHLEWIQY
  CASRRSQPVDQDWNSPLVTLCFGLCVLGRRALGTASHSMSASLEPFLYGLHALFKGDFRI
  TSPRDEWVFADMDLLHRVVAPGVRMALKLHQDHFTSPDEYEEPAALYDAIAANEERLVIS
  HEGDPAWRSAILSNTPSLLALRHVLDDASDEYKIIMLNRRHLSFRVIKVNRECVRGLWAG
  QQQELVFLRNRNPERGSIQNAKQALRNMINSSCDQPLGYPIYVSPLTTSLAGSHPQLRAL
  WGGPISLGAIAHWLLRTWERLHKGCGAGCNSGGNVDDSDCSGGGGLTSLSNNPPVAHPTP
  ENTAGNGDQPLPPGPGWGPRSSLSGSGDGRPPPLLQWPPPRLPGPPPASPIPTEGPRTSR
  PPGPGLLSSEGPSGKWSLGGRKGLGGSDGEPASGSPKGGTPKSQAPLDLSLSLSLSLSPD
  VSTEASPPRASQDIPCLDSSAPESGTPMGALGDWPAPIEERESPAAQPLLEHQY

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[1]
Coronary heart disease	DIS5OIP1	moderate	Genetic Variation	[2]
Systemic lupus erythematosus	DISI1SZ7	Limited	Biomarker	[3]

3 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 Pecanex-like protein 3 (PCNX3).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Pecanex-like protein 3 (PCNX3).	[9]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Pecanex-like protein 3 (PCNX3).	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Pecanex-like protein 3 (PCNX3).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Pecanex-like protein 3 (PCNX3).	[6]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Pecanex-like protein 3 (PCNX3).	[7]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Pecanex-like protein 3 (PCNX3).	[8]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Pecanex-like protein 3 (PCNX3).	[10]
KOJIC ACID	DMP84CS	Investigative	KOJIC ACID decreases the expression of Pecanex-like protein 3 (PCNX3).	[12]

References

• [1] Pecanex functions as a competitive endogenous RNA of S-phase kinase associated protein 2 in lung cancer.Cancer Lett. 2017 Oct 10;406:36-46. doi: 10.1016/j.canlet.2017.07.030. Epub 2017 Aug 5.
• [2] Identification of 64 Novel Genetic Loci Provides an Expanded View on the Genetic Architecture of Coronary Artery Disease.Circ Res. 2018 Feb 2;122(3):433-443. doi: 10.1161/CIRCRESAHA.117.312086. Epub 2017 Dec 6.
• [3] High-density genotyping of immune-related loci identifies new SLE risk variants in individuals with Asian ancestry.Nat Genet. 2016 Mar;48(3):323-30. doi: 10.1038/ng.3496. Epub 2016 Jan 25.
• [4] 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.
• [5] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [6] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [7] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [8] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [9] Effect of aflatoxin B(1), benzo[a]pyrene, and methapyrilene on transcriptomic and epigenetic alterations in human liver HepaRG cells. Food Chem Toxicol. 2018 Nov;121:214-223. doi: 10.1016/j.fct.2018.08.034. Epub 2018 Aug 26.
• [10] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [11] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [12] Toxicogenomics of kojic acid on gene expression profiling of a375 human malignant melanoma cells. Biol Pharm Bull. 2006 Apr;29(4):655-69.