Details of Drug Off-Target (DOT)

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

• DOT Name: HAUS augmin-like complex subunit 3 (HAUS3)
• Gene Name: HAUS3
• Related Disease:
  Advanced cancer
  Hepatocellular carcinoma
  Neoplasm
• UniProt ID: HAUS3_HUMAN
• PDB ID: 6PTB; 6PTE; 7SQK
• Pfam ID: PF14932
• Sequence:
  MSCGNEFVETLKKIGYPKADNLNGEDFDWLFEGVEDESFLKWFCGNVNEQNVLSERELEA
  FSILQKSGKPILEGAALDEALKTCKTSDLKTPRLDDKELEKLEDEVQTLLKLKNLKIQRR
  NKCQLMASVTSHKSLRLNAKEEEATKKLKQSQGILNAMITKISNELQALTDEVTQLMMFF
  RHSNLGQGTNPLVFLSQFSLEKYLSQEEQSTAALTLYTKKQFFQGIHEVVESSNEDNFQL
  LDIQTPSICDNQEILEERRLEMARLQLAYICAQHQLIHLKASNSSMKSSIKWAEESLHSL
  TSKAVDKENLDAKISSLTSEIMKLEKEVTQIKDRSLPAVVRENAQLLNMPVVKGDFDLQI
  AKQDYYTARQELVLNQLIKQKASFELLQLSYEIELRKHRDIYRQLENLVQELSQSNMMLY
  KQLEMLTDPSVSQQINPRNTIDTKDYSTHRLYQVLEGENKKKELFLTHGNLEEVAEKLKQ
  NISLVQDQLAVSAQEHSFFLSKRNKDVDMLCDTLYQGGNQLLLSDQELTEQFHKVESQLN
  KLNHLLTDILADVKTKRKTLANNKLHQMEREFYVYFLKDEDYLKDIVENLETQSKIKAVS
  LED
• 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

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[1]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[1]
Neoplasm	DISZKGEW	Strong	Altered Expression	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of HAUS augmin-like complex subunit 3 (HAUS3).	[2]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of HAUS augmin-like complex subunit 3 (HAUS3).	[10]

11 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 HAUS augmin-like complex subunit 3 (HAUS3).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of HAUS augmin-like complex subunit 3 (HAUS3).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of HAUS augmin-like complex subunit 3 (HAUS3).	[5]
Estradiol	DMUNTE3	Approved	Estradiol affects the expression of HAUS augmin-like complex subunit 3 (HAUS3).	[6]
Arsenic	DMTL2Y1	Approved	Arsenic affects the expression of HAUS augmin-like complex subunit 3 (HAUS3).	[7]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of HAUS augmin-like complex subunit 3 (HAUS3).	[3]
Selenium	DM25CGV	Approved	Selenium decreases the expression of HAUS augmin-like complex subunit 3 (HAUS3).	[8]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of HAUS augmin-like complex subunit 3 (HAUS3).	[9]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of HAUS augmin-like complex subunit 3 (HAUS3).	[8]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde decreases the expression of HAUS augmin-like complex subunit 3 (HAUS3).	[11]
OXYQUINOLINE	DMZVS9Y	Investigative	OXYQUINOLINE decreases the expression of HAUS augmin-like complex subunit 3 (HAUS3).	[3]

References

• [1] High Expression of Human AugminComplex Submit 3 Indicates Poor Prognosis and Associates with Tumor Progression in Hepatocellular Carcinoma.J Cancer. 2019 Feb 23;10(6):1434-1443. doi: 10.7150/jca.28317. eCollection 2019.
• [2] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [3] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [4] 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.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [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] Drinking-water arsenic exposure modulates gene expression in human lymphocytes from a U.S. population. Environ Health Perspect. 2008 Apr;116(4):524-31. doi: 10.1289/ehp.10861.
• [8] 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.
• [9] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [10] 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.
• [11] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.