Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT6DUAF3)

• DOT Name: UMP-CMP kinase (CMPK1)
• Synonyms: EC 2.7.4.14; Deoxycytidylate kinase; CK; dCMP kinase; Nucleoside-diphosphate kinase; EC 2.7.4.6; Uridine monophosphate/cytidine monophosphate kinase; UMP/CMP kinase; UMP/CMPK
• Gene Name: CMPK1
• UniProt ID: KCY_HUMAN
• PDB ID: 1TEV; 7E9V
• EC Number: 2.7.4.14; 2.7.4.6
• Pfam ID: PF00406
• Sequence:
  MKPLVVFVLGGPGAGKGTQCARIVEKYGYTHLSAGELLRDERKNPDSQYGELIEKYIKEG
  KIVPVEITISLLKREMDQTMAANAQKNKFLIDGFPRNQDNLQGWNKTMDGKADVSFVLFF
  DCNNEICIERCLERGKSSGRSDDNRESLEKRIQTYLQSTKPIIDLYEEMGKVKKIDASKS
  VDEVFDEVVQIFDKEG
• Function: Catalyzes the phosphorylation of pyrimidine nucleoside monophosphates at the expense of ATP. Plays an important role in de novo pyrimidine nucleotide biosynthesis. Has preference for UMP and CMP as phosphate acceptors. Also displays broad nucleoside diphosphate kinase activity.
• Tissue Specificity: Ubiquitously expressed.
• KEGG Pathway:
  Pyrimidine metabolism (hsa00240)
  Drug metabolism - other enzymes (hsa00983)
  Metabolic pathways (hsa01100)
  Nucleotide metabolism (hsa01232)
  Biosynthesis of cofactors (hsa01240)
• Reactome Pathway: Interconversion of nucleotide di- and triphosphates (R-HSA-499943)
• BioCyc Pathway: MetaCyc:HS08663-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Biotransformations of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Cidofovir	DMA13GD	Approved	UMP-CMP kinase (CMPK1) increases the phosphorylation of Cidofovir.	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of UMP-CMP kinase (CMPK1).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of UMP-CMP kinase (CMPK1).	[6]

5 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 UMP-CMP kinase (CMPK1).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of UMP-CMP kinase (CMPK1).	[3]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of UMP-CMP kinase (CMPK1).	[4]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of UMP-CMP kinase (CMPK1).	[5]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of UMP-CMP kinase (CMPK1).	[7]

References

• [1] 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.
• [2] 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.
• [3] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [4] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [5] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [6] 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.
• [7] 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.
• [8] Novel antiviral C5-substituted pyrimidine acyclic nucleoside phosphonates selected as human thymidylate kinase substrates. J Med Chem. 2011 Jan 13;54(1):222-32. doi: 10.1021/jm1011462. Epub 2010 Dec 3.