Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTD9PAZJ)

• DOT Name: PR domain zinc finger protein 4 (PRDM4)
• Synonyms: EC 2.1.1.-; PR domain-containing protein 4
• Gene Name: PRDM4
• Related Disease:
  Gonorrhea
  Metastatic prostate carcinoma
  Obesity
• UniProt ID: PRDM4_HUMAN
• PDB ID: 2L9Z; 3DB5
• EC Number: 2.1.1.-
• Pfam ID: PF21549 ; PF00096 ; PF18445
• Sequence:
  MHHRMNEMNLSPVGMEQLTSSSVSNALPVSGSHLGLAASPTHSAIPAPGLPVAIPNLGPS
  LSSLPSALSLMLPMGIGDRGVMCGLPERNYTLPPPPYPHLESSYFRTILPGILSYLADRP
  PPQYIHPNSINVDGNTALSITNNPSALDPYQSNGNVGLEPGIVSIDSRSVNTHGAQSLHP
  SDGHEVALDTAITMENVSRVTSPISTDGMAEELTMDGVAGEHSQIPNGSRSHEPLSVDSV
  SNNLAADAVGHGGVIPMHGNGLELPVVMETDHIASRVNGMSDSALSDSIHTVAMSTNSVS
  VALSTSHNLASLESVSLHEVGLSLEPVAVSSITQEVAMGTGHVDVSSDSLSFVSPSLQME
  DSNSNKENMATLFTIWCTLCDRAYPSDCPEHGPVTFVPDTPIESRARLSLPKQLVLRQSI
  VGAEVGVWTGETIPVRTCFGPLIGQQSHSMEVAEWTDKAVNHIWKIYHNGVLEFCIITTD
  ENECNWMMFVRKARNREEQNLVAYPHDGKIFFCTSQDIPPENELLFYYSRDYAQQIGVPE
  HPDVHLCNCGKECNSYTEFKAHLTSHIHNHLPTQGHSGSHGPSHSKERKWKCSMCPQAFI
  SPSKLHVHFMGHMGMKPHKCDFCSKAFSDPSNLRTHLKIHTGQKNYRCTLCDKSFTQKAH
  LESHMVIHTGEKNLKCDYCDKLFMRRQDLKQHVLIHTQERQIKCPKCDKLFLRTNHLKKH
  LNSHEGKRDYVCEKCTKAYLTKYHLTRHLKTCKGPTSSSSAPEEEEEDDSEEEDLADSVG
  TEDCRINSAVYSADESLSAHK
• Function: May function as a transcription factor involved in cell differentiation.
• Tissue Specificity: Expressed in many tissues. Highly expressed in ovary, testis, pancreas, brain, heart and prostate.
• KEGG Pathway: Neurotrophin sig.ling pathway (hsa04722)
• Reactome Pathway: p75NTR negatively regulates cell cycle via SC1 (R-HSA-193670)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Gonorrhea	DISQ5AO6	Strong	Biomarker	[1]
Metastatic prostate carcinoma	DISVBEZ9	Strong	Altered Expression	[2]
Obesity	DIS47Y1K	Strong	Altered Expression	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of PR domain zinc finger protein 4 (PRDM4).	[4]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of PR domain zinc finger protein 4 (PRDM4).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of PR domain zinc finger protein 4 (PRDM4).	[6]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of PR domain zinc finger protein 4 (PRDM4).	[7]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of PR domain zinc finger protein 4 (PRDM4).	[8]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of PR domain zinc finger protein 4 (PRDM4).	[9]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of PR domain zinc finger protein 4 (PRDM4).	[10]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of PR domain zinc finger protein 4 (PRDM4).	[4]
Paclitaxel	DMLB81S	Approved	Paclitaxel decreases the expression of PR domain zinc finger protein 4 (PRDM4).	[11]
Piroxicam	DMTK234	Approved	Piroxicam decreases the expression of PR domain zinc finger protein 4 (PRDM4).	[12]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of PR domain zinc finger protein 4 (PRDM4).	[13]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of PR domain zinc finger protein 4 (PRDM4).	[15]
geraniol	DMS3CBD	Investigative	geraniol increases the expression of PR domain zinc finger protein 4 (PRDM4).	[16]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of PR domain zinc finger protein 4 (PRDM4).	[14]

References

• [1] Identification of recurrence-related genes by integrating microRNA and gene expression profiling of gastric cancer.Int J Oncol. 2012 Dec;41(6):2166-74. doi: 10.3892/ijo.2012.1637. Epub 2012 Sep 24.
• [2] PRDM4 mediates YAP-induced cell invasion by activating leukocyte-specific integrin 2 expression.EMBO Rep. 2018 Jun;19(6):e45180. doi: 10.15252/embr.201745180. Epub 2018 Apr 17.
• [3] PI3Ka-Akt1-mediated Prdm4 induction in adipose tissue increases energy expenditure, inhibits weight gain, and improves insulin resistance in diet-induced obese mice.Cell Death Dis. 2018 Aug 29;9(9):876. doi: 10.1038/s41419-018-0904-3.
• [4] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [5] 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.
• [6] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [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] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [9] Persistent and non-persistent changes in gene expression result from long-term estrogen exposure of MCF-7 breast cancer cells. J Steroid Biochem Mol Biol. 2011 Feb;123(3-5):140-50.
• [10] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [11] Proteomic analysis of anti-cancer effects by paclitaxel treatment in cervical cancer cells. Gynecol Oncol. 2005 Jul;98(1):45-53. doi: 10.1016/j.ygyno.2005.04.010.
• [12] Apoptosis induced by piroxicam plus cisplatin combined treatment is triggered by p21 in mesothelioma. PLoS One. 2011;6(8):e23569.
• [13] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [14] 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.
• [15] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.
• [16] Geraniol suppresses prostate cancer growth through down-regulation of E2F8. Cancer Med. 2016 Oct;5(10):2899-2908.