Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT6DX554)

• DOT Name: PR domain-containing protein 11 (PRDM11)
• Synonyms: EC 2.1.1.-
• Gene Name: PRDM11
• Related Disease:
  Hyperthyroidism
  Meningococcal disease
  Neoplasm
  Panic disorder
  B-cell lymphoma
• UniProt ID: PRD11_HUMAN
• PDB ID: 3RAY
• EC Number: 2.1.1.-
• Pfam ID: PF21549
• Sequence:
  MLKMAEPIASLMIVECRACLRCSPLFLYQREKDRMTENMKECLAQTNAAVGDMVTVVKTE
  VCSPLRDQEYGQPCSRRPDSSAMEVEPKKLKGKRDLIVPKSFQQVDFWFCESCQEYFVDE
  CPNHGPPVFVSDTPVPVGIPDRAALTIPQGMEVVKDTSGESDVRCVNEVIPKGHIFGPYE
  GQISTQDKSAGFFSWLIVDKNNRYKSIDGSDETKANWMRYVVISREEREQNLLAFQHSER
  IYFRACRDIRPGEWLRVWYSEDYMKRLHSMSQETIHRNLARGEKRLQREKSEQVLDNPED
  LRGPIHLSVLRQGKSPYKRGFDEGDVHPQAKKKKIDLIFKDVLEASLESAKVEAHQLALS
  TSLVIRKVPKYQDDAYSQCATTMTHGVQNIGQTQGEGDWKVPQGVSKEPGQLEDEEEEPS
  SFKADSPAEASLASDPHELPTTSFCPNCIRLKKKVRELQAELDMLKSGKLPEPPVLPPQV
  LELPEFSDPAGKLVWMRLLSEGRVRSGLCGG
• Function: May be involved in transcription regulation.
• Tissue Specificity: Highly expressed in lung, including bronchial epithelial cells and airway smooth muscle cells, as well as in peripheral blood mononuclear cells. In tonsils, expressed in B-cell types, including naive B-cells, centroblasts, centrocytes and memory B-cells (at protein level). In benign hyperplastic lymph nodes, expressed in germinal center cells in both the dark and light zones, as well as in scattered cells in the mantle zone and the interfollicular area (at protein level).

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hyperthyroidism	DISX87ZH	Strong	Genetic Variation	[1]
Meningococcal disease	DISGDM2Z	Strong	Genetic Variation	[2]
Neoplasm	DISZKGEW	Strong	Altered Expression	[3]
Panic disorder	DISD3VNY	Strong	Genetic Variation	[4]
B-cell lymphoma	DISIH1YQ	Limited	Biomarker	[3]

4 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-containing protein 11 (PRDM11).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of PR domain-containing protein 11 (PRDM11).	[10]
TAK-243	DM4GKV2	Phase 1	TAK-243 decreases the sumoylation of PR domain-containing protein 11 (PRDM11).	[11]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of PR domain-containing protein 11 (PRDM11).	[12]

4 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-containing protein 11 (PRDM11).	[6]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of PR domain-containing protein 11 (PRDM11).	[7]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of PR domain-containing protein 11 (PRDM11).	[8]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of PR domain-containing protein 11 (PRDM11).	[9]

References

• [1] Genome-wide analyses identify a role for SLC17A4 and AADAT in thyroid hormone regulation.Nat Commun. 2018 Oct 26;9(1):4455. doi: 10.1038/s41467-018-06356-1.
• [2] Genome-wide association study identifies variants in the CFH region associated with host susceptibility to meningococcal disease.Nat Genet. 2010 Sep;42(9):772-6. doi: 10.1038/ng.640. Epub 2010 Aug 8.
• [3] Loss of PRDM11 promotes MYC-driven lymphomagenesis.Blood. 2015 Feb 19;125(8):1272-81. doi: 10.1182/blood-2014-03-560805. Epub 2014 Dec 12.
• [4] Genome-wide association study of panic disorder in the Japanese population.J Hum Genet. 2009 Feb;54(2):122-6. doi: 10.1038/jhg.2008.17. Epub 2009 Jan 23.
• [5] 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.
• [6] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [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] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [9] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [10] 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.
• [11] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
• [12] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.