Details of Drug Off-Target (DOT)

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

• DOT Name: HAUS augmin-like complex subunit 8 (HAUS8)
• Synonyms: HEC1/NDC80-interacting centrosome-associated protein 1; Sarcoma antigen NY-SAR-48
• Gene Name: HAUS8
• Related Disease:
  Malignant soft tissue neoplasm
  Sarcoma
• UniProt ID: HAUS8_HUMAN
• PDB ID: 7SQK
• Sequence:
  MADSSGRGAGKPATGPTNSSSAKKKDKRVQGGRVIESRYLQYEKKTTQKAPAGDGSQTRG
  KMSEGGRKSSLLQKSKADSSGVGKGDLQSTLLEGHGTAPPDLDLSAINDKSIVKKTPQLA
  KTISKKPESTSFSAPRKKSPDLSEAMEMMESQTLLLTLLSVKMENNLAEFERRAEKNLLI
  MCKEKEKLQKKAHELKRRLLLSQRKRELADVLDAQIEMLSPFEAVATRFKEQYRTFATAL
  DTTRHELPVRSIHLEGDGQQLLDALQHELVTTQRLLGELDVGDSEENVQVLDLLSELKDV
  TAKKDLELRRSFAQVLELSAEASKEAALANQEVWEETQGMAPPSRWYFNQDSACRESGGA
  PKNTPLSEDDNPGASSAPAQATFISPSEDFSSSSQAEVPPSLSRSGRDLS
• 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

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Malignant soft tissue neoplasm	DISTC6NO	Strong	Biomarker	[1]
Sarcoma	DISZDG3U	Strong	Biomarker	[1]

10 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 8 (HAUS8).	[2]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of HAUS augmin-like complex subunit 8 (HAUS8).	[3]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of HAUS augmin-like complex subunit 8 (HAUS8).	[4]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of HAUS augmin-like complex subunit 8 (HAUS8).	[5]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of HAUS augmin-like complex subunit 8 (HAUS8).	[6]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of HAUS augmin-like complex subunit 8 (HAUS8).	[6]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of HAUS augmin-like complex subunit 8 (HAUS8).	[8]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of HAUS augmin-like complex subunit 8 (HAUS8).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of HAUS augmin-like complex subunit 8 (HAUS8).	[11]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of HAUS augmin-like complex subunit 8 (HAUS8).	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of HAUS augmin-like complex subunit 8 (HAUS8).	[7]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of HAUS augmin-like complex subunit 8 (HAUS8).	[10]

References

• [1] Hice1, a novel microtubule-associated protein required for maintenance of spindle integrity and chromosomal stability in human cells.Mol Cell Biol. 2008 Jun;28(11):3652-62. doi: 10.1128/MCB.01923-07. Epub 2008 Mar 24.
• [2] Stem cell transcriptome responses and corresponding biomarkers that indicate the transition from adaptive responses to cytotoxicity. Chem Res Toxicol. 2017 Apr 17;30(4):905-922.
• [3] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [4] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [5] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [6] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [7] Effect of aflatoxin B(1), benzo[a]pyrene, and methapyrilene on transcriptomic and epigenetic alterations in human liver HepaRG cells. Food Chem Toxicol. 2018 Nov;121:214-223. doi: 10.1016/j.fct.2018.08.034. Epub 2018 Aug 26.
• [8] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [9] 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.
• [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] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [12] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.