Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT8EJRD8)

• DOT Name: Bifunctional peptidase and (JMJD7)
• Synonyms: 3S)-lysyl hydroxylase JMJD7 (EC 1.14.11.63; EC 3.4.-.-; JmjC domain-containing protein 7; Jumonji domain-containing protein 7; L-lysine (3S)-hydroxylase JMJD7
• Gene Name: JMJD7
• Related Disease:
  Breast cancer
  Breast carcinoma
• UniProt ID: JMJD7_HUMAN
• PDB ID: 5NFN; 5NFO
• EC Number: 1.14.11.63; 3.4.-.-
• Pfam ID: PF13621
• Sequence:
  MAEAALEAVRSELREFPAAARELCVPLAVPYLDKPPTPLHFYRDWVCPNRPCIIRNALQH
  WPALQKWSLPYFRATVGSTEVSVAVTPDGYADAVRGDRFMMPAERRLPLSFVLDVLEGRA
  QHPGVLYVQKQCSNLPSELPQLLPDLESHVPWASEALGKMPDAVNFWLGEAAAVTSLHKD
  HYENLYCVVSGEKHFLFHPPSDRPFIPYELYTPATYQLTEEGTFKVVDEEAMEKVPWIPL
  DPLAPDLARYPSYSQAQALRCTVRAGEMLYLPALWFHHVQQSQGCIAVNFWYDMEYDLKY
  SYFQLLDSLTKASGLD
• Function: Bifunctional enzyme that acts both as an endopeptidase and 2-oxoglutarate-dependent monooxygenase. Endopeptidase that cleaves histones N-terminal tails at the carboxyl side of methylated arginine or lysine residues, to generate 'tailless nucleosomes', which may trigger transcription elongation. Preferentially recognizes and cleaves monomethylated and dimethylated arginine residues of histones H2, H3 and H4. After initial cleavage, continues to digest histones tails via its aminopeptidase activity. Additionally, may play a role in protein biosynthesis by modifying the translation machinery. Acts as a Fe(2+) and 2-oxoglutarate-dependent monooxygenase, catalyzing (S)-stereospecific hydroxylation at C-3 of 'Lys-22' of DRG1 and 'Lys-21' of DRG2 translation factors (TRAFAC), promoting their interaction with ribonucleic acids (RNA).
• Reactome Pathway: Protein hydroxylation (R-HSA-9629569)
• BioCyc Pathway: MetaCyc:G66-32545-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast cancer	DIS7DPX1	Strong	Biomarker	[1]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[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 Bifunctional peptidase and (JMJD7).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Bifunctional peptidase and (JMJD7).	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic increases the expression of Bifunctional peptidase and (JMJD7).	[3]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Bifunctional peptidase and (JMJD7).	[4]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Bifunctional peptidase and (JMJD7).	[6]

References

• [1] Clipping of arginine-methylated histone tails by JMJD5 and JMJD7.Proc Natl Acad Sci U S A. 2017 Sep 12;114(37):E7717-E7726. doi: 10.1073/pnas.1706831114. Epub 2017 Aug 28.
• [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] Arsenic alters transcriptional responses to Pseudomonas aeruginosa infection and decreases antimicrobial defense of human airway epithelial cells. Toxicol Appl Pharmacol. 2017 Sep 15;331:154-163.
• [4] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [5] 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.
• [6] 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.