Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZR4GBH)

• DOT Name: Hormonally up-regulated neu tumor-associated kinase (HUNK)
• Synonyms: EC 2.7.11.1; B19; Serine/threonine-protein kinase MAK-V
• Gene Name: HUNK
• Related Disease:
  Breast neoplasm
  Her2-receptor negative breast cancer
  HER2/NEU overexpressing breast cancer
  Metastatic malignant neoplasm
  Neoplasm
  Adenocarcinoma
  Polyp
  Hemoglobinopathy
• UniProt ID: HUNK_HUMAN
• EC Number: 2.7.11.1
• Pfam ID: PF00069
• Sequence:
  MPAAAGDGLLGEPAAPGGGGGAEDAARPAAACEGSFLPAWVSGVPRERLRDFQHHKRVGN
  YLIGSRKLGEGSFAKVREGLHVLTGEKVAIKVIDKKRAKKDTYVTKNLRREGQIQQMIRH
  PNITQLLDILETENSYYLVMELCPGGNLMHKIYEKKRLEESEARRYIRQLISAVEHLHRA
  GVVHRDLKIENLLLDEDNNIKLIDFGLSNCAGILGYSDPFSTQCGSPAYAAPELLARKKY
  GPKIDVWSIGVNMYAMLTGTLPFTVEPFSLRALYQKMVDKEMNPLPTQLSTGAISFLRSL
  LEPDPVKRPNIQQALANRWLNENYTGKVPCNVTYPNRISLEDLSPSVVLHMTEKLGYKNS
  DVINTVLSNRACHILAIYFLLNKKLERYLSGKSDIQDSLCYKTRLYQIEKYRAPKESYEA
  SLDTWTRDLEFHAVQDKKPKEQEKRGDFLHRPFSKKLDKNLPSHKQPSGSLMTQIQNTKA
  LLKDRKASKSSFPDKDSFGCRNIFRKTSDSNCVASSSMEFIPVPPPRTPRIVKKPEPHQP
  GPGSTGIPHKEDPLMLDMVRSFESVDRDDHVEVLSPSHHYRILNSPVSLARRNSSERTLS
  PGLPSGSMSPLHTPLHPTLVSFAHEDKNSPPKEEGLCCPPPVPSNGPMQPLGSPNCVKSR
  GRFPMMGIGQMLRKRHQSLQPSADRPLEASLPPLQPLAPVNLAFDMADGVKTQC

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast neoplasm	DISNGJLM	Strong	Biomarker	[1]
Her2-receptor negative breast cancer	DISS605N	Strong	Biomarker	[2]
HER2/NEU overexpressing breast cancer	DISYKID5	Strong	Biomarker	[2]
Metastatic malignant neoplasm	DIS86UK6	Strong	Altered Expression	[3]
Neoplasm	DISZKGEW	Strong	Biomarker	[4]
Adenocarcinoma	DIS3IHTY	moderate	Biomarker	[5]
Polyp	DISRSLYF	moderate	Biomarker	[5]
Hemoglobinopathy	DISCT4GX	Limited	Biomarker	[6]

2 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 Hormonally up-regulated neu tumor-associated kinase (HUNK).	[7]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Hormonally up-regulated neu tumor-associated kinase (HUNK).	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Hormonally up-regulated neu tumor-associated kinase (HUNK).	[8]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Hormonally up-regulated neu tumor-associated kinase (HUNK).	[9]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Hormonally up-regulated neu tumor-associated kinase (HUNK).	[10]
Belinostat	DM6OC53	Phase 2	Belinostat decreases the expression of Hormonally up-regulated neu tumor-associated kinase (HUNK).	[11]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Hormonally up-regulated neu tumor-associated kinase (HUNK).	[13]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Hormonally up-regulated neu tumor-associated kinase (HUNK).	[14]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Hormonally up-regulated neu tumor-associated kinase (HUNK).	[15]

References

• [1] [Proteinkinase MAK-V/Hunk as a possible dianostic and prognostic marker of human breast carcinoma].Arkh Patol. 2004 Sep-Oct;66(5):6-9.
• [2] Staurosporine, an inhibitor of hormonally up-regulated neu-associated kinase.Oncotarget. 2018 Nov 13;9(89):35962-35973. doi: 10.18632/oncotarget.26311. eCollection 2018 Nov 13.
• [3] HUNK suppresses metastasis of basal type breast cancers by disrupting the interaction between PP2A and cofilin-1.Proc Natl Acad Sci U S A. 2010 Feb 9;107(6):2622-7. doi: 10.1073/pnas.0914492107. Epub 2010 Jan 22.
• [4] Regulation of cell survival by HUNK mediates breast cancer resistance to HER2 inhibitors.Breast Cancer Res Treat. 2015 Jan;149(1):91-8. doi: 10.1007/s10549-014-3227-9. Epub 2014 Dec 17.
• [5] Detection of parvovirus B19 nucleic acids and expression of viral VP1/VP2 antigen in human colon carcinoma.Am J Gastroenterol. 2007 Jul;102(7):1489-98. doi: 10.1111/j.1572-0241.2007.01240.x. Epub 2007 Apr 24.
• [6] Persistent B19 infection in immunocompetent individuals: implications for transfusion safety.Blood. 2005 Oct 15;106(8):2890-5. doi: 10.1182/blood-2005-03-1053. Epub 2005 Jun 23.
• [7] 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.
• [8] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [9] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [10] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [11] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [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] Loss of TRIM33 causes resistance to BET bromodomain inhibitors through MYC- and TGF-beta-dependent mechanisms. Proc Natl Acad Sci U S A. 2016 Aug 2;113(31):E4558-66.
• [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] Bisphenol A Exposure Changes the Transcriptomic and Proteomic Dynamics of Human Retinoblastoma Y79 Cells. Genes (Basel). 2021 Feb 11;12(2):264. doi: 10.3390/genes12020264.