Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTYTP3SU)

• DOT Name: PR domain zinc finger protein 15 (PRDM15)
• Synonyms: EC 2.1.1.-; PR domain-containing protein 15; Zinc finger protein 298
• Gene Name: PRDM15
• Related Disease: Lymphoma
• UniProt ID: PRD15_HUMAN
• EC Number: 2.1.1.-
• Pfam ID: PF21549 ; PF00096
• Sequence:
  MPRRRPPASGAAQFPERIATRSPDPIPLCTFQRQPRAAPVQPPCRLFFVTFAGCGHRWRS
  ESKPGWISRSRSGIALRAARPPGSSPPRPAAPRPPPPGGVVAEAPGDVVIPRPRVQPMRV
  ARGGPWTPNPAFREAESWSQIGNQRVSEQLLETSLGNEVSDTEPLSPASAGLRRNPALPP
  GPFAQNFSWGNQENLPPALGKIANGGGTGAGKAECGYETESHLLEPHEIPLNVNTHKFSD
  CEFPYEFCTVCFSPFKLLGMSGVEGVWNQHSRSASMHTFLNHSATGIREAGCRKDMPVSE
  MAEDGSEEIMFIWCEDCSQYHDSECPELGPVVMVKDSFVLSRARSWPASGHVHTQAGQGM
  RGYEDRDRADPQQLPEAVPAGLVRRLSGQQLPCRSTLTWGRLCHLVAQGRSSLPPNLEIR
  RLEDGAEGVFAITQLVKRTQFGPFESRRVAKWEKESAFPLKVFQKDGHPVCFDTSNEDDC
  NWMMLVRPAAEAEHQNLTAYQHGSDVYFTTSRDIPPGTELRVWYAAFYAKKMDKPMLKQA
  GSGVHAAGTPENSAPVESEPSQWACKVCSATFLELQLLNEHLLGHLEQAKSLPPGSQSEA
  AAPEKEQDTPRGEPPAVPESENVATKEQKKKPRRGRKPKVSKAEQPLVIVEDKEPTEQVA
  EIITEVPPDEPVSATPDERIMELVLGKLATTTTDTSSVPKFTHHQNNTITLKRSLILSSR
  HGIRRKLIKQLGEHKRVYQCNICSKIFQNSSNLSRHVRSHGDKLFKCEECAKLFSRKESL
  KQHVSYKHSRNEVDGEYRYRCGTCEKTFRIESALEFHNCRTDDKTFQCEMCFRFFSTNSN
  LSKHKKKHGDKKFACEVCSKMFYRKDVMLDHQRRHLEGVRRVKREDLEAGGENLVRYKKE
  PSGCPVCGKVFSCRSNMNKHLLTHGDKKYTCEICGRKFFRVDVLRDHIHVHFKDIALMDD
  HQREEFIGKIGISSEENDDNSDESADSEPHKYSCKRCQLTFGRGKEYLKHIMEVHKEKGY
  GCSICNRRFALKATYHAHMVIHRENLPDPNVQKYIHPCEICGRIFNSIGNLERHKLIHTG
  VKSHACEQCGKSFARKDMLKEHMRVHDNVREYLCAECGKGMKTKHALRHHMKLHKGIKEY
  ECKECHRRFAQKVNMLKHCKRHTGIKDFMCELCGKTFSERNTMETHKLIHTVGKQWTCSV
  CDKKYVTEYMLQKHVQLTHDKVEAQSCQLCGTKVSTRASMSRHMRRKHPEVLAVRIDDLD
  HLPETTTIDASSIGIVQPELTLEQEDLAEGKHGKAAKRSHKRKQKPEEEAGAPVPEDATF
  SEYSEKETEFTGSVGDETNSAVQSIQQVVVTLGDPNVTTPSSSVGLTNITVTPITTAAAT
  QFTNLQPVAVGHLTTPERQLQLDNSILTVTFDTVSGSAMLHNRQNDVQIHPQPEASNPQS
  VAHFINLTTLVNSITPLGSQLSDQHPLTWRAVPQTDVLPPSQPQAPPQQAAQPQVQAEQQ
  QQQMYSY
• Function: Sequence-specific DNA-binding transcriptional regulator. Plays a role as a molecular node in a transcriptional network regulating embryonic development and cell fate decision. Stimulates the expression of upstream key transcriptional activators and repressors of the Wnt/beta-catenin and MAPK/ERK pathways, respectively, that are essential for naive pluripotency and self-renewal maintenance of embryonic stem cells (ESCs). Specifically promotes SPRY1 and RSPO1 transcription activation through recognition and direct binding of a specific DNA sequence in their promoter regions. Involved in early embryo development. Also plays a role in induced pluripotent stem cells (iPSCs) reprogramming.
• Tissue Specificity: Detected in all tissues examined.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Lymphoma	DISN6V4S	Limited	Altered Expression	[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 PR domain zinc finger protein 15 (PRDM15).	[2]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of PR domain zinc finger protein 15 (PRDM15).	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of PR domain zinc finger protein 15 (PRDM15).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of PR domain zinc finger protein 15 (PRDM15).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of PR domain zinc finger protein 15 (PRDM15).	[5]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of PR domain zinc finger protein 15 (PRDM15).	[7]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of PR domain zinc finger protein 15 (PRDM15).	[8]
GALLICACID	DM6Y3A0	Investigative	GALLICACID decreases the expression of PR domain zinc finger protein 15 (PRDM15).	[9]

References

• [1] Genome-wide analysis of immune system genes by expressed sequence Tag profiling.J Immunol. 2013 Jun 1;190(11):5578-87. doi: 10.4049/jimmunol.1203471. Epub 2013 Apr 24.
• [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] 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.
• [5] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [6] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [7] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [8] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.
• [9] Gene expression profile analysis of gallic acid-induced cell death process. Sci Rep. 2021 Aug 18;11(1):16743. doi: 10.1038/s41598-021-96174-1.