Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT9ZVFRZ)

• DOT Name: FMR1-interacting protein NUFIP1 (NUFIP1)
• Synonyms: Nuclear FMR1-interacting protein 1; Nuclear FMRP-interacting protein 1
• Gene Name: NUFIP1
• Related Disease: Isolated congenital microcephaly
• UniProt ID: NUFP1_HUMAN
• PDB ID: 5L85
• Pfam ID: PF10453
• Sequence:
  MAEPTSDFETPIGWHASPELTPTLGPLSDTAPPRDSWMFWAMLPPPPPPLTSSLPAAGSK
  PSSESQPPMEAQSLPGAPPPFDAQILPGAQPPFDAQSPLDSQPQPSGQPWNFHASTSWYW
  RQSSDRFPRHQKSFNPAVKNSYYPRKYDAKFTDFSLPPSRKQKKKKRKEPVFHFFCDTCD
  RGFKNQEKYDKHMSEHTKCPELDCSFTAHEKIVQFHWRNMHAPGMKKIKLDTPEEIARWR
  EERRKNYPTLANIERKKKLKLEKEKRGAVLTTTQYGKMKGMSRHSQMAKIRSPGKNHKWK
  NDNSRQRAVTGSGSHLCDLKLEGPPEANADPLGVLINSDSESDKEEKPQHSVIPKEVTPA
  LCSLMSSYGSLSGSESEPEETPIKTEADVLAENQVLDSSAPKSPSQDVKATVRNFSEAKS
  ENRKKSFEKTNPKRKKDYHNYQTLFEPRTHHPYLLEMLLAPDIRHERNVILQCVRYIIKK
  DFFGLDTNSAKSKDV
• Function: Binds RNA.
• Tissue Specificity: Expressed in spleen, thymus, prostate, testis, ovary, small intestine, colon, peripheral blood leukocyte, heart, brain, placenta, lung, liver, skeletal muscle, kidney, and pancreas.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Isolated congenital microcephaly	DISUXHZ6	moderate	Genetic Variation	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of FMR1-interacting protein NUFIP1 (NUFIP1).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of FMR1-interacting protein NUFIP1 (NUFIP1).	[3]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of FMR1-interacting protein NUFIP1 (NUFIP1).	[4]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of FMR1-interacting protein NUFIP1 (NUFIP1).	[5]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of FMR1-interacting protein NUFIP1 (NUFIP1).	[6]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of FMR1-interacting protein NUFIP1 (NUFIP1).	[8]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of FMR1-interacting protein NUFIP1 (NUFIP1).	[9]

1 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 FMR1-interacting protein NUFIP1 (NUFIP1).	[7]

References

• [1] Genotype-phenotype correlations in patients with retinoblastoma and interstitial 13q deletions.Eur J Hum Genet. 2011 Sep;19(9):947-58. doi: 10.1038/ejhg.2011.58. Epub 2011 Apr 20.
• [2] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [3] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [4] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [5] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [6] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [7] 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.
• [8] 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.
• [9] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.