Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTI0SMF2)

• DOT Name: Serine/threonine-protein kinase haspin (HASPIN)
• Synonyms: EC 2.7.11.1; Germ cell-specific gene 2 protein; H-haspin; Haploid germ cell-specific nuclear protein kinase
• Gene Name: HASPIN
• Related Disease:
  Neoplasm
  Pancreatic cancer
• UniProt ID: HASP_HUMAN
• PDB ID: 2VUW; 2WB8; 3DLZ; 3E7V; 3F2N; 3FMD; 3IQ7; 4OUC; 4QTC; 5HTB; 5HTC; 6G34; 6G35; 6G36; 6G37; 6G38; 6G39; 6G3A; 6Z56; 6Z57; 6Z58; 6Z59; 6Z5A; 6Z5B; 6Z5C; 6Z5D; 6Z5E; 7AVQ; 7OPS; 7SQM
• EC Number: 2.7.11.1
• Pfam ID: PF12330
• Sequence:
  MAASLPGPGSRLFRTYGAADGRRQRRPGREAAQWFPPQDRRRFFNSSGSSDASIGDPSQS
  DDPDDPDDPDFPGSPVRRRRRRPGGRVPKDRPSLTVTPKRWKLRARPSLTVTPRRLGLRA
  RPPQKCSTPCGPLRLPPFPSRDSGRLSPDLSVCGQPRDGDELGISASLFSSLASPCPGSP
  TPRDSVISIGTSACLVAASAVPSGLHLPEVSLDRASLPCSQEEATGGAKDTRMVHQTRAS
  LRSVLFGLMNSGTPEDSEFRADGKNMRESCCKRKLVVGNGPEGPGLSSTGKRRATGQDSC
  QERGLQEAVRREHQEASVPKGRIVPRGIDRLERTRSSRKSKHQEATETSLLHSHRFKKGQ
  KLGKDSFPTQDLTPLQNVCFWTKTRASFSFHKKKIVTDVSEVCSIYTTATSLSGSLLSEC
  SNRPVMNRTSGAPSSWHSSSMYLLSPLNTLSISNKKASDAEKVYGECSQKGPVPFSHCLP
  TEKLQRCEKIGEGVFGEVFQTIADHTPVAIKIIAIEGPDLVNGSHQKTFEEILPEIIISK
  ELSLLSGEVCNRTEGFIGLNSVHCVQGSYPPLLLKAWDHYNSTKGSANDRPDFFKDDQLF
  IVLEFEFGGIDLEQMRTKLSSLATAKSILHQLTASLAVAEASLRFEHRDLHWGNVLLKKT
  SLKKLHYTLNGKSSTIPSCGLQVSIIDYTLSRLERDGIVVFCDVSMDEDLFTGDGDYQFD
  IYRLMKKENNNRWGEYHPYSNVLWLHYLTDKMLKQMTFKTKCNTPAMKQIKRKIQEFHRT
  MLNFSSATDLLCQHSLFK
• Function: Serine/threonine-protein kinase that phosphorylates histone H3 at 'Thr-3' (H3T3ph) during mitosis. May act through H3T3ph to both position and modulate activation of AURKB and other components of the chromosomal passenger complex (CPC) at centromeres to ensure proper chromatid cohesion, metaphase alignment and normal progression through the cell cycle.
• Tissue Specificity: Strongly expressed in testis. Also present in thymus and bone marrow and low levels observed in prostate, intestine, lung, spleen and lymph node. Expressed in fetal skin, liver, kidney and small intestine and also in proliferating but not non-proliferating cell lines.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Neoplasm	DISZKGEW	moderate	Altered Expression	[1]
Pancreatic cancer	DISJC981	moderate	Biomarker	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Serine/threonine-protein kinase haspin (HASPIN).	[2]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Serine/threonine-protein kinase haspin (HASPIN).	[3]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Serine/threonine-protein kinase haspin (HASPIN).	[3]
Demecolcine	DMCZQGK	Approved	Demecolcine decreases the expression of Serine/threonine-protein kinase haspin (HASPIN).	[4]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of Serine/threonine-protein kinase haspin (HASPIN).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Serine/threonine-protein kinase haspin (HASPIN).	[6]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Serine/threonine-protein kinase haspin (HASPIN).	[7]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Serine/threonine-protein kinase haspin (HASPIN).	[8]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Serine/threonine-protein kinase haspin (HASPIN).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Serine/threonine-protein kinase haspin (HASPIN).	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Serine/threonine-protein kinase haspin (HASPIN).	[9]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Serine/threonine-protein kinase haspin (HASPIN).	[12]

References

• [1] Haspin knockdown can inhibit progression and development of pancreatic cancer in vitro and vivo.Exp Cell Res. 2019 Dec 1;385(1):111605. doi: 10.1016/j.yexcr.2019.111605. Epub 2019 Sep 4.
• [2] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [3] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [4] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [5] Effects of ciglitazone and troglitazone on the proliferation of human stomach cancer cells. World J Gastroenterol. 2009 Jan 21;15(3):310-20.
• [6] 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.
• [7] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [8] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [9] 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.
• [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] 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] 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.