Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT2OOLFJ)

• DOT Name: HAUS augmin-like complex subunit 2 (HAUS2)
• Synonyms: Centrosomal protein of 27 kDa; Cep27
• Gene Name: HAUS2
• UniProt ID: HAUS2_HUMAN
• PDB ID: 7SQK
• Pfam ID: PF15003
• Sequence:
  MAAANPWDPASAPNGAGLVLGHFIASGMVNQEMLNMSKKTVSCFVNFTRLQQITNIQAEI
  YQKNLEIELLKLEKDTADVVHPFFLAQKCHTLQSMNNHLEAVLKEKRSLRQRLLKPMCQE
  NLPIEAVYHRYMVHLLELAVTFIERLETHLETIRNIPHLAANLKKMNQALAKMDILVTET
  EELAENILKWRKQQNEVSSCIPKILAEESYLYKHDIIMPPLPFTSKVHVQTINAK
• 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 2 (HAUS2).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of HAUS augmin-like complex subunit 2 (HAUS2).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of HAUS augmin-like complex subunit 2 (HAUS2).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of HAUS augmin-like complex subunit 2 (HAUS2).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of HAUS augmin-like complex subunit 2 (HAUS2).	[5]
Estradiol	DMUNTE3	Approved	Estradiol affects the expression of HAUS augmin-like complex subunit 2 (HAUS2).	[6]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of HAUS augmin-like complex subunit 2 (HAUS2).	[7]
Demecolcine	DMCZQGK	Approved	Demecolcine decreases the expression of HAUS augmin-like complex subunit 2 (HAUS2).	[8]
GSK2110183	DMZHB37	Phase 2	GSK2110183 decreases the expression of HAUS augmin-like complex subunit 2 (HAUS2).	[9]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of HAUS augmin-like complex subunit 2 (HAUS2).	[10]
Torcetrapib	DMDHYM7	Discontinued in Phase 2	Torcetrapib increases the expression of HAUS augmin-like complex subunit 2 (HAUS2).	[11]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of HAUS augmin-like complex subunit 2 (HAUS2).	[8]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of HAUS augmin-like complex subunit 2 (HAUS2).	[12]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [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] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [6] Identification of novel low-dose bisphenol a targets in human foreskin fibroblast cells derived from hypospadias patients. PLoS One. 2012;7(5):e36711. doi: 10.1371/journal.pone.0036711. Epub 2012 May 4.
• [7] 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.
• [8] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [9] Novel ATP-competitive Akt inhibitor afuresertib suppresses the proliferation of malignant pleural mesothelioma cells. Cancer Med. 2017 Nov;6(11):2646-2659. doi: 10.1002/cam4.1179. Epub 2017 Sep 27.
• [10] 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.
• [11] Clarifying off-target effects for torcetrapib using network pharmacology and reverse docking approach. BMC Syst Biol. 2012 Dec 10;6:152.
• [12] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.