Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT5C4VVU)

• DOT Name: Nucleotidyltransferase MB21D2 (MB21D2)
• Synonyms: EC 2.7.7.-; Mab-21 domain-containing protein 2; hMB21D2
• Gene Name: MB21D2
• Related Disease:
  Autoimmune disease
  Autoimmune disease, susceptibility to, 6
  Hypothyroidism
  STAT3-related early-onset multisystem autoimmune disease
• UniProt ID: M21D2_HUMAN
• PDB ID: 7LT1
• EC Number: 2.7.7.-
• Pfam ID: PF03281 ; PF20266
• Sequence:
  MKMAAPTANKAASLGCNNKPAFPELDFRSGARVEELNKLIQEFTKHDQREYDDQRALEIH
  TAKDFIFSMLGMVQKLDQKLPVANEYLLLSGGVREGVVDLDLDELNVYARGTDYDMDFTL
  LVPALKLHDRNQPVTLDMRHSALCHSWLSLRLFDEGTISKWKDCCTIVDHINGATNYFFS
  PTKVADWFYDSISIVLSEIQKKPQRGMPKVEKVEKNGTIISIILGVGSSRMLYDIVPVVS
  FKGWPAVAQSWLMENHFWDGKITEEEVISGFYLVPACSYKGKKDNEWRLSFARSEVQLKK
  CISSSLMQAYQACKAIIIKLLSRPKAISPYHLRSMMLWACDRLPANYLAQEDYAAHFLLG
  LIDDLQHCLVNKMCPNYFIPQCNMLEHLSEETVMLHARKLSSVRSDPAEHLRTAIEHVKA
  ANRLTLELQRRGSTTSIPSPQSDGGDPNQPDDRLAKKLQQLVTENPGKSISVFINPDDVT
  RPHFRIDDKFF
• Function: Probable nucleotidyltransferase that catalyzes the formation of cyclic dinucleotide second messenger in response to some unknown stimulus.

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Autoimmune disease	DISORMTM	Strong	Genetic Variation	[1]
Autoimmune disease, susceptibility to, 6	DISHNUXI	Strong	Genetic Variation	[1]
Hypothyroidism	DISR0H6D	Strong	Genetic Variation	[1]
STAT3-related early-onset multisystem autoimmune disease	DISAXTN7	Strong	Genetic Variation	[1]

9 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 Nucleotidyltransferase MB21D2 (MB21D2).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Nucleotidyltransferase MB21D2 (MB21D2).	[3]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Nucleotidyltransferase MB21D2 (MB21D2).	[4]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Nucleotidyltransferase MB21D2 (MB21D2).	[5]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Nucleotidyltransferase MB21D2 (MB21D2).	[6]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Nucleotidyltransferase MB21D2 (MB21D2).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Nucleotidyltransferase MB21D2 (MB21D2).	[3]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Nucleotidyltransferase MB21D2 (MB21D2).	[9]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Nucleotidyltransferase MB21D2 (MB21D2).	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of Nucleotidyltransferase MB21D2 (MB21D2).	[7]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Nucleotidyltransferase MB21D2 (MB21D2).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Nucleotidyltransferase MB21D2 (MB21D2).	[7]

References

• [1] Leveraging Polygenic Functional Enrichment to Improve GWAS Power.Am J Hum Genet. 2019 Jan 3;104(1):65-75. doi: 10.1016/j.ajhg.2018.11.008. Epub 2018 Dec 27.
• [2] 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.
• [3] 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.
• [4] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [5] 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.
• [6] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [7] 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.
• [8] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [9] 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.
• [10] 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.
• [11] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.