Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTBML7XD)

• DOT Name: HAUS augmin-like complex subunit 1 (HAUS1)
• Synonyms: Coiled-coil domain-containing protein 5; Enhancer of invasion-cluster; HEI-C
• Gene Name: HAUS1
• Related Disease:
  Migraine disorder
  Obesity
• UniProt ID: HAUS1_HUMAN
• PDB ID: 7SQK
• Sequence:
  MEPQEERETQVAAWLKKIFGDHPIPQYEVNPRTTEILHHLSERNRVRDRDVYLVIEDLKQ
  KASEYESEAKYLQDLLMESVNFSPANLSSTGSRYLNALVDSAVALETKDTSLASFIPAVN
  DLTSDLFRTKSKSEEIKIELEKLEKNLTATLVLEKCLQEDVKKAELHLSTERAKVDNRRQ
  NMDFLKAKSEEFRFGIKAAEEQLSARGMDASLSHQSLVALSEKLARLKQQTIPLKKKLES
  YLDLMPNPSLAQVKIEEAKRELDSIEAELTRRVDMMEL
• Function: Contributes to mitotic spindle assembly, maintenance of centrosome integrity and completion of cytokinesis as part of the HAUS augmin-like complex.
• Tissue Specificity: Widely expressed. Expressed in pancreas, kidney, skeletal muscle, liver and heart. Weakly expressed in lung, brain and placenta.
• 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

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Migraine disorder	DISFCQTG	Strong	Genetic Variation	[1]
Obesity	DIS47Y1K	Strong	Biomarker	[2]

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 1 (HAUS1).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of HAUS augmin-like complex subunit 1 (HAUS1).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of HAUS augmin-like complex subunit 1 (HAUS1).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of HAUS augmin-like complex subunit 1 (HAUS1).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of HAUS augmin-like complex subunit 1 (HAUS1).	[7]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of HAUS augmin-like complex subunit 1 (HAUS1).	[8]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate decreases the expression of HAUS augmin-like complex subunit 1 (HAUS1).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of HAUS augmin-like complex subunit 1 (HAUS1).	[10]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of HAUS augmin-like complex subunit 1 (HAUS1).	[11]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of HAUS augmin-like complex subunit 1 (HAUS1).	[12]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of HAUS augmin-like complex subunit 1 (HAUS1).	[13]

References

• [1] Genome-wide meta-analysis identifies new susceptibility loci for migraine.Nat Genet. 2013 Aug;45(8):912-917. doi: 10.1038/ng.2676. Epub 2013 Jun 23.
• [2] Adapting the Healthy Eating Index 2010 for the Canadian Population: Evidence from the Canadian National Nutrition Survey.Nutrients. 2017 Aug 21;9(8):910. doi: 10.3390/nu9080910.
• [3] 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.
• [4] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [5] 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.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [8] 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.
• [9] Epigallocatechin-3-gallate (EGCG) protects against chromate-induced toxicity in vitro. Toxicol Appl Pharmacol. 2012 Jan 15;258(2):166-75.
• [10] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [11] 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.
• [12] Comprehensive analysis of transcriptomic changes induced by low and high doses of bisphenol A in HepG2 spheroids in vitro and rat liver in vivo. Environ Res. 2019 Jun;173:124-134. doi: 10.1016/j.envres.2019.03.035. Epub 2019 Mar 18.
• [13] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.