Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTB2HOIZ)

• DOT Name: HAUS augmin-like complex subunit 7 (HAUS7)
• Synonyms: 26S proteasome-associated UCH37-interacting protein 1; UCHL5-interacting protein; X-linked protein STS1769
• Gene Name: HAUS7
• Related Disease:
  Oligospermia
  Alopecia
• UniProt ID: HAUS7_HUMAN
• PDB ID: 7SQK
• Sequence:
  MAGQDAGCGRGGDDYSEDEGDSSVSRAAVEVFGKLKDLNCPFLEGLYITEPKTIQELLCS
  PSEYRLEILEWMCTRVWPSLQDRFSSLKGVPTEVKIQEMTKLGHELMLCAPDDQELLKGC
  ACAQKQLHFMDQLLDTIRSLTIGCSSCSSLMEHFEDTREKNEALLGELFSSPHLQMLLNP
  ECDPWPLDMQPLLNKQSDDWQWASASAKSEEEEKLAELARQLQESAAKLHALRTEYFAQH
  EQGAAAGAADISTLDQKLRLVTSDFHQLILAFLQVYDDELGECCQRPGPDLHPCGPIIQA
  THQNLTSYSQLLQVVMAVADTSAKAVETVKKQQGEQICWGGSSSVMSLATKMNELMEK
• Function: Contributes to mitotic spindle assembly, maintenance of centrosome integrity and completion of cytokinesis as part of the HAUS augmin-like complex.
• Tissue Specificity: Detected in spleen, thymus, testis, ovary, small intestine and colon, with highest levels of expression in testis and ovary.
• 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
Oligospermia	DIS6YJF3	Strong	Genetic Variation	[1]
Alopecia	DIS37HU4	Limited	Genetic Variation	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of HAUS augmin-like complex subunit 7 (HAUS7).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the methylation of HAUS augmin-like complex subunit 7 (HAUS7).	[4]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of HAUS augmin-like complex subunit 7 (HAUS7).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of HAUS augmin-like complex subunit 7 (HAUS7).	[12]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of HAUS augmin-like complex subunit 7 (HAUS7).	[13]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of HAUS augmin-like complex subunit 7 (HAUS7).	[5]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of HAUS augmin-like complex subunit 7 (HAUS7).	[7]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of HAUS augmin-like complex subunit 7 (HAUS7).	[8]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of HAUS augmin-like complex subunit 7 (HAUS7).	[8]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of HAUS augmin-like complex subunit 7 (HAUS7).	[9]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of HAUS augmin-like complex subunit 7 (HAUS7).	[10]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of HAUS augmin-like complex subunit 7 (HAUS7).	[11]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of HAUS augmin-like complex subunit 7 (HAUS7).	[14]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of HAUS augmin-like complex subunit 7 (HAUS7).	[15]

References

• [1] A novel mutation in HAUS7 results in severe oligozoospermia in two brothers.Gene. 2018 Jan 10;639:106-110. doi: 10.1016/j.gene.2017.10.014. Epub 2017 Oct 7.
• [2] Genetic prediction of male pattern baldness.PLoS Genet. 2017 Feb 14;13(2):e1006594. doi: 10.1371/journal.pgen.1006594. eCollection 2017 Feb.
• [3] 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.
• [4] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [7] 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.
• [8] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [9] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [10] Effects of ciglitazone and troglitazone on the proliferation of human stomach cancer cells. World J Gastroenterol. 2009 Jan 21;15(3):310-20.
• [11] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [12] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [13] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
• [14] 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.
• [15] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.