Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT2RMGGB)

• DOT Name: Protein hinderin (KIAA1328)
• Gene Name: KIAA1328
• UniProt ID: K1328_HUMAN
• Pfam ID: PF15369
• Sequence:
  MADVAGPSRPSAAAFWSRDFSDEEQSVVYVPGISAEGNVRSRHKLMSPKADVKLKTSRVT
  DASISMESLKGTGDSVDEQNSCRGEIKSASLKDLCLEDKRRIANLIKELARVSEEKEVTE
  ERLKAEQESFEKKIRQLEEQNELIIKEREALQLQYRECQELLSLYQKYLSEQQEKLTMSL
  SELGAARMQEQQVSSRKSTLQCSSVELDGSYLSIARPQTYYQTKQRPKSAVQDSASESLI
  AFRNNSLKPVTLHHPKDDLDKIPSETTTCNCESPGRKPAVPTEKMPQEELHMKECPHLKP
  TPSQCCGHRLAADRVHDSHPTNMTPQHPKTHPESCSYCRLSWASLVHGGGALQPIETLKK
  QISEDRKQQLMLQKMELEIEKERLQHLLAQQETKLLLKQQQLHQSRLDYNCLLKSNCDGW
  LLGTSSSIKKHQDPPNSGENRKERKTVGFHSHMKDDAQWSCQKKDTCRPQRGTVTGVRKD
  ASTSPMPTGSLKDFVTTASPSLQHTTSRYETSLLDLVQSLSPNSAPKPQRYPSREAGAWN
  HGTFRLSPLKSTRKKMGMHRTPEELEENQILEDIFFI
• Function: Competes with SMC1 for binding to SMC3. May affect the availability of SMC3 to engage in the formation of multimeric protein complexes.
• Tissue Specificity: Widely expressed.

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Protein hinderin (KIAA1328).	[1]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Protein hinderin (KIAA1328).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Protein hinderin (KIAA1328).	[3]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Protein hinderin (KIAA1328).	[6]

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 Protein hinderin (KIAA1328).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Protein hinderin (KIAA1328).	[5]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of Protein hinderin (KIAA1328).	[7]

References

• [1] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [2] 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.
• [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] 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.
• [5] 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.
• [6] 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.
• [7] 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.