Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTFIO49N)

• DOT Name: HAUS augmin-like complex subunit 4 (HAUS4)
• Gene Name: HAUS4
• UniProt ID: HAUS4_HUMAN
• PDB ID: 7SQK
• Pfam ID: PF14735
• Sequence:
  MASGDFCSPGEGMEILQQVCSKQLPPCNLSKEDLLQNPYFSKLLLNLSQHVDESGLSLTL
  AKEQAQAWKEVRLHKTTWLRSEILHRVIQELLVDYYVKIQDTNVTSEDKKFHETLEQRLL
  VTELMRLLGPSQEREIPPLLGLEKADLLELMPLSEDFVWMRARLQQEVEEQLKKKCFTLL
  CYYDPNSDADSETVKAAKVWKLAEVLVGEQQQCQDAKSQQKEQMLLLEKKSAAYSQVLLR
  CLTLLQRLLQEHRLKTQSELDRINAQYLEVKCGAMILKLRMEELKILSDTYTVEKVEVHR
  LIRDRLEGAIHLQEQDMENSRQVLNSYEVLGEEFDRLVKEYTVLKQATENKRWALQEFSK
  VYR
• Function: Contributes to mitotic spindle assembly, maintenance of centrosome integrity and completion of cytokinesis as part of the HAUS augmin-like complex.
• 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

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of HAUS augmin-like complex subunit 4 (HAUS4).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of HAUS augmin-like complex subunit 4 (HAUS4).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of HAUS augmin-like complex subunit 4 (HAUS4).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of HAUS augmin-like complex subunit 4 (HAUS4).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of HAUS augmin-like complex subunit 4 (HAUS4).	[5]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of HAUS augmin-like complex subunit 4 (HAUS4).	[6]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of HAUS augmin-like complex subunit 4 (HAUS4).	[7]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of HAUS augmin-like complex subunit 4 (HAUS4).	[7]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of HAUS augmin-like complex subunit 4 (HAUS4).	[8]
Selenium	DM25CGV	Approved	Selenium increases the expression of HAUS augmin-like complex subunit 4 (HAUS4).	[9]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of HAUS augmin-like complex subunit 4 (HAUS4).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of HAUS augmin-like complex subunit 4 (HAUS4).	[2]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of HAUS augmin-like complex subunit 4 (HAUS4).	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of HAUS augmin-like complex subunit 4 (HAUS4).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of HAUS augmin-like complex subunit 4 (HAUS4).	[11]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [2] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [3] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [4] 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.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] 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.
• [7] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [8] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [9] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [10] 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.
• [11] 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.
• [12] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.