Details of Drug Off-Target (DOT)

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

• DOT Name: Nucleolar MIF4G domain-containing protein 1 (NOM1)
• Synonyms: SGD1 homolog
• Gene Name: NOM1
• Related Disease:
  Preaxial polydactyly of fingers
  B-cell lymphoma
• UniProt ID: NOM1_HUMAN
• Pfam ID: PF02847 ; PF02854
• Sequence:
  MAASRSAGEAGPGGSQGRVVRMKRRGGRGPRRGPAGGGEKALKRLKLAVEEFVHATSEGE
  APGGCEGRGAPVSFRPGGRKSRKELRKEKRHLRKARRLQRTAGPEQGPGLGGRSGAEEAS
  GHRQDTEERARPAPSRDPSPPRKPRPSRVKAKATAATAKTRPSAAATAAARKRALLAANE
  EEDREIRKLERCLGLNKRKKKDGSSSVPLSFARDGLDYILGALESGKNSGLYDSSGEEEE
  DAGQTLPESDLESDSQDESEEEEEGDVEKEKKAQEAEAQSEDDDEDTEEEQGEEKEKGAQ
  EKRRGKRVRFAEDEEKSENSSEDGDITDKSLCGSGEKYIPPHVRQAEETVDFKKKEELER
  LKKHVKGLLNRLSEPNMASISGQLEELYMAHSRKDMNDTLTSALMGACVTASAMPSRLMM
  EHVLLVSILHHTVGIEVGAHFLEAVVRKFDAIYKYGSEGKECDNLFTVIAHLYNFHVVQS
  LLIFDILKKLIGTFTEKDIELILLMLKNVGFSLRKDDALSLKELITEAQTKASGAGSEFQ
  DQTRIRFMLETMLALKNNDMRKIPGYDPEPVEKLRKLQRALVRNAGSGSETQLRVSWDSV
  LSAEQTGRWWIVGSAWSGAPMIDNSHHTHLQKQLVGTVSSKILELARKQRMNTDIRRNIF
  CTIMTSEDFLDAFEKLLKLGLKDQQEREIIHVLMDCCLQEKTYNPFYAFLASKFCEYERR
  FQMTFQFSIWDKFRDLENLPATNFSNLVHLVAHLLKTKSLSLSILKVVEFSELDKPRVRF
  LRKVLSILLMETEVEDLSLIFTRVSDNPKLGVLREGLKLFISHFLLKNAQAHRSADEANV
  LREKADLATKCLQGKASLRM
• Function: Plays a role in targeting PPP1CA to the nucleolus.
• Tissue Specificity: Expressed in heart and skeletal muscle.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Preaxial polydactyly of fingers	DISXO6C9	Strong	Genetic Variation	[1]
B-cell lymphoma	DISIH1YQ	Limited	Biomarker	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Nucleolar MIF4G domain-containing protein 1 (NOM1).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Nucleolar MIF4G domain-containing protein 1 (NOM1).	[4]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Nucleolar MIF4G domain-containing protein 1 (NOM1).	[5]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil decreases the expression of Nucleolar MIF4G domain-containing protein 1 (NOM1).	[6]
Azacitidine	DMTA5OE	Approved	Azacitidine decreases the expression of Nucleolar MIF4G domain-containing protein 1 (NOM1).	[7]
Sodium phenylbutyrate	DMXLBCQ	Approved	Sodium phenylbutyrate decreases the expression of Nucleolar MIF4G domain-containing protein 1 (NOM1).	[8]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Nucleolar MIF4G domain-containing protein 1 (NOM1).	[9]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Nucleolar MIF4G domain-containing protein 1 (NOM1).	[11]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Nucleolar MIF4G domain-containing protein 1 (NOM1).	[13]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Nucleolar MIF4G domain-containing protein 1 (NOM1).	[15]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Nucleolar MIF4G domain-containing protein 1 (NOM1).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Nucleolar MIF4G domain-containing protein 1 (NOM1).	[12]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Nucleolar MIF4G domain-containing protein 1 (NOM1).	[14]

References

• [1] A physical and transcriptional map of the preaxial polydactyly locus on chromosome 7q36.Genomics. 1999 May 1;57(3):342-51. doi: 10.1006/geno.1999.5796.
• [2] Anaplastic lymphoma kinase-positive large B-cell lymphoma: an underrecognized aggressive lymphoma.Adv Hematol. 2012;2012:529572. doi: 10.1155/2012/529572. Epub 2012 Feb 26.
• [3] 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.
• [4] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [5] Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
• [6] Pharmacogenomic identification of novel determinants of response to chemotherapy in colon cancer. Cancer Res. 2006 Mar 1;66(5):2765-77.
• [7] The effect of DNA methylation inhibitor 5-Aza-2'-deoxycytidine on human endometrial stromal cells. Hum Reprod. 2010 Nov;25(11):2859-69.
• [8] Gene expression profile analysis of 4-phenylbutyrate treatment of IB3-1 bronchial epithelial cell line demonstrates a major influence on heat-shock proteins. Physiol Genomics. 2004 Jan 15;16(2):204-11.
• [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] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [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.
• [13] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.
• [14] 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.
• [15] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.