Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTYOTM2B)

• DOT Name: Cytosolic Fe-S cluster assembly factor NUBP2 (NUBP2)
• Synonyms: Nucleotide-binding protein 2; NBP 2
• Gene Name: NUBP2
• Related Disease:
  Crouzon syndrome
  Jackson-Weiss syndrome
• UniProt ID: NUBP2_HUMAN
• Pfam ID: PF10609
• Sequence:
  MEAAAEPGNLAGVRHIILVLSGKGGVGKSTISTELALALRHAGKKVGILDVDLCGPSIPR
  MLGAQGRAVHQCDRGWAPVFLDREQSISLMSVGFLLEKPDEAVVWRGPKKNALIKQFVSD
  VAWGELDYLVVDTPPGTSDEHMATIEALRPYQPLGALVVTTPQAVSVGDVRRELTFCRKT
  GLRVMGIVENMSGFTCPHCTECTSVFSRGGGEELAQLAGVPFLGSVPLDPALMRTLEEGH
  DFIQEFPGSPAFAALTSIAQKILDATPACLP
• Function: Component of the cytosolic iron-sulfur (Fe/S) protein assembly (CIA) machinery. Required for maturation of extramitochondrial Fe-S proteins. The NUBP1-NUBP2 heterotetramer forms a Fe-S scaffold complex, mediating the de novo assembly of an Fe-S cluster and its transfer to target apoproteins. Negatively regulates cilium formation and structure.
• Tissue Specificity: Widely expressed with highest expression in skeletal muscle.
• Reactome Pathway: Cytosolic iron-sulfur cluster assembly (R-HSA-2564830)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Crouzon syndrome	DISIAVZU	moderate	Genetic Variation	[1]
Jackson-Weiss syndrome	DISRNZHH	moderate	Genetic Variation	[1]

1 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 Cytosolic Fe-S cluster assembly factor NUBP2 (NUBP2).	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Cytosolic Fe-S cluster assembly factor NUBP2 (NUBP2).	[3]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of Cytosolic Fe-S cluster assembly factor NUBP2 (NUBP2).	[4]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Cytosolic Fe-S cluster assembly factor NUBP2 (NUBP2).	[5]
Aspirin	DM672AH	Approved	Aspirin decreases the expression of Cytosolic Fe-S cluster assembly factor NUBP2 (NUBP2).	[6]
Mifepristone	DMGZQEF	Approved	Mifepristone increases the expression of Cytosolic Fe-S cluster assembly factor NUBP2 (NUBP2).	[7]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Cytosolic Fe-S cluster assembly factor NUBP2 (NUBP2).	[8]

References

• [1] Two craniosynostotic syndrome loci, Crouzon and Jackson-Weiss, map to chromosome 10q23-q26.Genomics. 1994 Jul 15;22(2):418-24. doi: 10.1006/geno.1994.1403.
• [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] 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.
• [4] Gene induction and apoptosis in human hepatocellular carci-noma cells SMMC-7721 exposed to 5-aza-2'-deoxycytidine. Chin Med J (Engl). 2007 Sep 20;120(18):1626-31.
• [5] Cannabis-induced cytotoxicity in leukemic cell lines: the role of the cannabinoid receptors and the MAPK pathway. Blood. 2005 Feb 1;105(3):1214-21. doi: 10.1182/blood-2004-03-1182. Epub 2004 Sep 28.
• [6] Effects of aspirin on metastasis-associated gene expression detected by cDNA microarray. Acta Pharmacol Sin. 2004 Oct;25(10):1327-33.
• [7] Mifepristone induced progesterone withdrawal reveals novel regulatory pathways in human endometrium. Mol Hum Reprod. 2007 Sep;13(9):641-54.
• [8] Environmental pollutant induced cellular injury is reflected in exosomes from placental explants. Placenta. 2020 Jan 1;89:42-49. doi: 10.1016/j.placenta.2019.10.008. Epub 2019 Oct 17.