Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTI1P52G)

• DOT Name: Protein SFI1 homolog (SFI1)
• Synonyms: hSFI1
• Gene Name: SFI1
• Related Disease:
  Intellectual disability
  Diabetic kidney disease
  Isolated cleft lip
  Non-insulin dependent diabetes
  Schizophrenia
  Chronic renal failure
  End-stage renal disease
  Neoplasm
• UniProt ID: SFI1_HUMAN
• PDB ID: 2K2I
• Sequence:
  MKNLLTEKCISSHNFHQKVIKQRMEKKVDSRYFKDGAVKKPYSAKTLSNKKSSASFGIRR
  ELPSTSHLVQYRGTHTCTRQGRLRELRIRCVARKFLYLWIRMTFGRVFPSKARFYYEQRL
  LRKVFEEWKEEWWVFQHEWKLCVRADCHYRYYLYNLMFQTWKTYVRQQQEMRNKYIRAEV
  HDAKQKMRQAWKSWLIYVVVRRTKLQMQTTALEFRQRIILRVWWSTWRQRLGQVRVSRAL
  HASALKHRALSLQVQAWSQWREQLLYVQKEKQKVVSAVKHHQHWQKRRFLKAWLEYLQVR
  RVKRQQNEMAERFHHVTVLQIYFCDWQQAWERRESLYAHHAQVEKLARKMALRRAFTHWK
  HYMLLCAEEAAQFEMAEEHHRHSQLYFCFRALKDNVTHAHLQQIRRNLAHQQHGVTLLHR
  FWNLWRSQIEQKKERELLPLLHAAWDHYRIALLCKCIELWLQYTQKRRYKQLLQARADGH
  FQQRALPAAFHTWNRLWRWRHQENVLSARATRFHRETLEKQVFSLWRQKMFQHRENRLAE
  RMAILHAERQLLYRSWFMWHQQAAARHQEQEWQTVACAHHRHGRLKKAFCLWRESAQGLR
  TERTGRVRAAEFHMAQLLRWAWSQWRECLALRGAERQKLMRADLHHQHSVLHRALQAWVT
  YQGRVRSILREVAARESQHNRQLLRGALRRWKENTMARVDEAKKTFQASTHYRRTICSKV
  LVQWREAVSVQMYYRQQEDCAIWEAQKVLDRGCLRTWFQRWWDCSRRSAQQRLQLERAVQ
  HHHRQLLLEGLARWKTHHLQCVRKRLLHRQSTQLLAQRLSRTCFRQWRQQLAARRQEQRA
  TVRALWFWAFSLQAKVWATWLAFVLERRRKKARLQWALQAYQGQLLQEGATRLLRFAASM
  KASRQQLQAQQQVQAAHSLHRAVRRCATLWKQKVLGRGGKPQPLAAIAPSRKVTFEGPLL
  NRIAAGAGDGTLETKRPQASRPLGALGRLAAEEPHALELNTAHSARKQPRRPHFLLEPAQ
  SQRPQKPQEHGLGMAQPAAPSLTRPFLAEAPTALVPHSPLPGALSSAPGPKQPPTASTGP
  ELLLLPLSSFMPCGAAAPARVSAQRATPRDKPPVPSSLASVPDPHLLLPGDFSATRAGPG
  LSTAGSLDLEAELEEIQQQLLHYQTTKQNLWSCRRQASSLRRWLELNREEPGPEDQEVEQ
  QVQKELEQVEMQIQLLAEELQAQRQPIGACVARIQALRQALC
• Function: Plays a role in the dynamic structure of centrosome-associated contractile fibers via its interaction with CETN2.
• Reactome Pathway:
  Loss of Nlp from mitotic centrosomes (R-HSA-380259)
  Recruitment of mitotic centrosome proteins and complexes (R-HSA-380270)
  Loss of proteins required for interphase microtubule organization from the centrosome (R-HSA-380284)
  Recruitment of NuMA to mitotic centrosomes (R-HSA-380320)
  Anchoring of the basal body to the plasma membrane (R-HSA-5620912)
  AURKA Activation by TPX2 (R-HSA-8854518)
  Regulation of PLK1 Activity at G2/M Transition (R-HSA-2565942)

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Intellectual disability	DISMBNXP	Definitive	Biomarker	[1]
Diabetic kidney disease	DISJMWEY	Strong	Genetic Variation	[2]
Isolated cleft lip	DIS2O2JV	Strong	Genetic Variation	[3]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Genetic Variation	[4]
Schizophrenia	DISSRV2N	Strong	Altered Expression	[5]
Chronic renal failure	DISGG7K6	moderate	Biomarker	[2]
End-stage renal disease	DISXA7GG	moderate	Biomarker	[2]
Neoplasm	DISZKGEW	Limited	Biomarker	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Protein SFI1 homolog (SFI1).	[7]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Protein SFI1 homolog (SFI1).	[8]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate affects the expression of Protein SFI1 homolog (SFI1).	[9]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Protein SFI1 homolog (SFI1).	[10]

References

• [1] SFI1 promotes centriole duplication by recruiting USP9X to stabilize the microcephaly protein STIL.J Cell Biol. 2019 Jul 1;218(7):2185-2197. doi: 10.1083/jcb.201803041. Epub 2019 Jun 13.
• [2] A genome-wide association study for diabetic nephropathy genes in African Americans.Kidney Int. 2011 Mar;79(5):563-72. doi: 10.1038/ki.2010.467. Epub 2010 Dec 8.
• [3] Genome-wide analyses of non-syndromic cleft lip with palate identify 14 novel loci and genetic heterogeneity.Nat Commun. 2017 Feb 24;8:14364. doi: 10.1038/ncomms14364.
• [4] Exome sequencing of 20,791cases of type 2 diabetes and 24,440controls.Nature. 2019 Jun;570(7759):71-76. doi: 10.1038/s41586-019-1231-2. Epub 2019 May 22.
• [5] Dietary glucoraphanin prevents the onset of psychosis in the adult offspring after maternal immune activation.Sci Rep. 2018 Feb 1;8(1):2158. doi: 10.1038/s41598-018-20538-3.
• [6] The development of a bicistronic plasmid DNA vaccine for B-cell lymphoma.Vaccine. 2002 Jan 31;20(9-10):1400-11. doi: 10.1016/s0264-410x(01)00464-9.
• [7] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [8] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [9] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [10] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.