Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTN1IPNS)

• DOT Name: Pumilio homolog 3 (PUM3)
• Synonyms: HBV X-transactivated gene 5 protein; HBV XAg-transactivated protein 5; Minor histocompatibility antigen HA-8; HLA-HA8
• Gene Name: PUM3
• Related Disease:
  Acute graft versus host disease
  Advanced cancer
  Drug dependence
  Malaria
  Breast cancer
  Breast carcinoma
  Small-cell lung cancer
  Cone dystrophy with supernormal rod response
  High blood pressure
  Neoplasm
  Type-1 diabetes
• UniProt ID: PUM3_HUMAN
• PDB ID: 4WZR; 4WZW
• Pfam ID: PF08144
• Sequence:
  MEVKGKKQFTGKSTKTAQEKNRFHKNSDSGSSKTFPTRKVAKEGGPKVTSRNFEKSITKL
  GKKGVKQFKNKQQGDKSPKNKFQPANKFNKKRKFQPDGRSDESAAKKPKWDDFKKKKKEL
  KQSRQLSDKTNYDIVVRAKQMWEILRRKDCDKEKRVKLMSDLQKLIQGKIKTIAFAHDST
  RVIQCYIQYGNEEQRKQAFEELRDDLVELSKAKYSRNIVKKFLMYGSKPQIAEIIRSFKG
  HVRKMLRHAEASAIVEYAYNDKAILEQRNMLTEELYGNTFQLYKSADHRTLDKVLEVQPE
  KLELIMDEMKQILTPMAQKEAVIKHSLVHKVFLDFFTYAPPKLRSEMIEAIREAVVYLAH
  THDGARVAMHCLWHGTPKDRKVIVKTMKTYVEKVANGQYSHLVLLAAFDCIDDTKLVKQI
  IISEIISSLPSIVNDKYGRKVLLYLLSPRDPAHTVREIIEVLQKGDGNAHSKKDTEVRRR
  ELLESISPALLSYLQEHAQEVVLDKSACVLVSDILGSATGDVQPTMNAIASLAATGLHPG
  GKDGELHIAEHPAGHLVLKWLIEQDKKMKENGREGCFAKTLVEHVGMKNLKSWASVNRGA
  IILSSLLQSCDLEVANKVKAALKSLIPTLEKTKSTSKGIEILLEKLST
• Function: Inhibits the poly(ADP-ribosyl)ation activity of PARP1 and the degradation of PARP1 by CASP3 following genotoxic stress. Binds to double-stranded RNA or DNA without sequence specificity. Involved in development of the eye and of primordial germ cells.
• Tissue Specificity: Widely expressed.

Molecular Interaction Atlas (MIA) of This DOT

11 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute graft versus host disease	DIS8KLVM	Strong	Biomarker	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
Drug dependence	DIS9IXRC	Strong	Biomarker	[3]
Malaria	DISQ9Y50	Strong	Biomarker	[4]
Breast cancer	DIS7DPX1	moderate	Biomarker	[5]
Breast carcinoma	DIS2UE88	moderate	Biomarker	[5]
Small-cell lung cancer	DISK3LZD	moderate	Altered Expression	[6]
Cone dystrophy with supernormal rod response	DISHSXP5	Limited	CausalMutation	[7]
High blood pressure	DISY2OHH	Limited	Biomarker	[8]
Neoplasm	DISZKGEW	Limited	Altered Expression	[9]
Type-1 diabetes	DIS7HLUB	Limited	Genetic Variation	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Pumilio homolog 3 (PUM3).	[11]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Pumilio homolog 3 (PUM3).	[12]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Pumilio homolog 3 (PUM3).	[13]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Pumilio homolog 3 (PUM3).	[14]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Pumilio homolog 3 (PUM3).	[15]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Pumilio homolog 3 (PUM3).	[16]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Pumilio homolog 3 (PUM3).	[17]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Pumilio homolog 3 (PUM3).	[17]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol increases the expression of Pumilio homolog 3 (PUM3).	[18]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Pumilio homolog 3 (PUM3).	[19]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Pumilio homolog 3 (PUM3).	[20]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Pumilio homolog 3 (PUM3).	[21]

References

• [1] Disparity for a newly identified minor histocompatibility antigen, HA-8, correlates with acute graft-versus-host disease after haematopoietic stem cell transplantation from an HLA-identical sibling.Br J Haematol. 2003 Nov;123(4):671-5. doi: 10.1046/j.1365-2141.2003.04676.x.
• [2] Penicisulfuranol A, a novel C-terminal inhibitor disrupting molecular chaperone function of Hsp90 independent of ATP binding domain.Biochem Pharmacol. 2019 May;163:404-415. doi: 10.1016/j.bcp.2019.03.012. Epub 2019 Mar 8.
• [3] Neuropeptide PEN and Its Receptor GPR83: Distribution, Signaling, and Regulation.ACS Chem Neurosci. 2019 Apr 17;10(4):1884-1891. doi: 10.1021/acschemneuro.8b00559. Epub 2019 Feb 21.
• [4] Puf3 participates in ribosomal biogenesis in malaria parasites.J Cell Sci. 2018 Mar 26;131(6):jcs212597. doi: 10.1242/jcs.212597.
• [5] The influence of socio-cultural factors on breast cancer screening behaviors in Lagos, Nigeria.Ethn Health. 2019 Jul;24(5):544-559. doi: 10.1080/13557858.2017.1348489. Epub 2017 Jul 5.
• [6] Targeting the Somatostatin Receptor 2 with the Miniaturized Drug Conjugate, PEN-221: A Potent and Novel Therapeutic for the Treatment of Small Cell Lung Cancer.Mol Cancer Ther. 2019 Nov;18(11):1926-1936. doi: 10.1158/1535-7163.MCT-19-0022.
• [7] Molecular characteristics of four Japanese cases with KCNV2 retinopathy: report of novel disease-causing variants.Mol Vis. 2013 Jul 20;19:1580-90. Print 2013.
• [8] 'I believe high blood pressure can kill me:' using the PEN-3 Cultural Model to understand patients' perceptions of an intervention to control hypertension in Ghana.Ethn Health. 2019 Apr;24(3):257-270. doi: 10.1080/13557858.2017.1346178. Epub 2017 Jul 4.
• [9] Discovery of an SSTR2-Targeting Maytansinoid Conjugate (PEN-221) with Potent Activity in Vitro and in Vivo.J Med Chem. 2019 Mar 14;62(5):2708-2719. doi: 10.1021/acs.jmedchem.8b02036. Epub 2019 Feb 28.
• [10] Factors Affecting Self-Care Performance in Adolescents with Type I Diabetes According to the PEN-3 Cultural Model.Int J Endocrinol Metab. 2018 Sep 18;16(4):e62582. doi: 10.5812/ijem.62582. eCollection 2018 Oct.
• [11] Stem cell transcriptome responses and corresponding biomarkers that indicate the transition from adaptive responses to cytotoxicity. Chem Res Toxicol. 2017 Apr 17;30(4):905-922.
• [12] 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.
• [13] Retinoic acid-induced downmodulation of telomerase activity in human cancer cells. Exp Mol Pathol. 2005 Oct;79(2):108-17.
• [14] 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.
• [15] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [16] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [17] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [18] Identification of biomarkers and outcomes of endocrine disruption in human ovarian cortex using In Vitro Models. Toxicology. 2023 Feb;485:153425. doi: 10.1016/j.tox.2023.153425. Epub 2023 Jan 5.
• [19] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [20] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [21] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.