Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT7CAG4A)

• DOT Name: Zinc finger protein 40 (HIVEP1)
• Synonyms: Cirhin interaction protein; CIRIP; Gate keeper of apoptosis-activating protein; GAAP; Human immunodeficiency virus type I enhancer-binding protein 1; HIV-EP1; Major histocompatibility complex-binding protein 1; MBP-1; Positive regulatory domain II-binding factor 1; PRDII-BF1
• Gene Name: HIVEP1
• Related Disease:
  Breast cancer
  Breast carcinoma
  Advanced cancer
  Dilated cardiomyopathy 1A
  Duchenne muscular dystrophy
  Endometrial cancer
  Endometrial carcinoma
  Muscular dystrophy
  Neoplasm
  Pachyonychia congenita 3
  Prostate cancer
  Prostate carcinoma
  Prostate neoplasm
  Vibrio cholerae infection
  Asthma
  Lung cancer
  Lung carcinoma
  Lung neoplasm
  Non-small-cell lung cancer
• UniProt ID: ZEP1_HUMAN
• PDB ID: 1BBO; 3ZNF; 4ZNF
• Pfam ID: PF00096
• Sequence:
  MPRTKQIHPRNLRDKIEEAQKELNGAEVSKKEILQAGVKGTSESLKGVKRKKIVAENHLK
  KIPKSPLRNPLQAKHKQNTEESSFAVLHSASESHKKQNYIPVKNGKQFTKQNGETPGIIA
  EASKSEESVSPKKPLFLQQPSELRRWRSEGADPAKFSDLDEQCDSSSLSSKTRTDNSECI
  SSHCGTTSPSYTNTAFDVLLKAMEPELSTLSQKGSPCAIKTEKLRPNKTARSPPKLKNSS
  MDAPNQTSQELVAESQSSCTSYTVHMSAAQKNEQGAMQSASHLYHQHEHFVPKSNQHNQQ
  LPGCSGFTGSLTNLQNQENAKLEQVYNIAVTSSVGLTSPSSRSQVTPQNQQMDSASPLSI
  SPANSTQSPPMPIYNSTHVASVVNQSVEQMCNLLLKDQKPKKQGKYICEYCNRACAKPSV
  LLKHIRSHTGERPYPCVTCGFSFKTKSNLYKHKKSHAHTIKLGLVLQPDAGGLFLSHESP
  KALSIHSDVEDSGESEEEGATDERQHDLGAMELQPVHIIKRMSNAETLLKSSFTPSSPEN
  VIGDFLLQDRSAESQAVTELPKVVVHHVTVSPLRTDSPKAMDPKPELSSAQKQKDLQVTN
  VQPLSANMSQGGVSRLETNENSHQKGDMNPLEGKQDSHVGTVHAQLQRQQATDYSQEQQG
  KLLSPRSLGSTDSGYFSRSESADQTVSPPTPFARRLPSTEQDSGRSNGPSAALVTTSTPS
  ALPTGEKALLLPGQMRPPLATKTLEERISKLISDNEALVDDKQLDSVKPRRTSLSRRGSI
  DSPKSYIFKDSFQFDLKPVGRRTSSSSDIPKSPFTPTEKSKQVFLLSVPSLDCLPITRSN
  SMPTTGYSAVPANIIPPPHPLRGSQSFDDKIGAFYDDVFVSGPNAPVPQSGHPRTLVRQA
  AIEDSSANESHVLGTGQSLDESHQGCHAAGEAMSVRSKALAQGPHIEKKKSHQGRGTMFE
  CETCRNRYRKLENFENHKKFYCSELHGPKTKVAMREPEHSPVPGGLQPQILHYRVAGSSG
  IWEQTPQIRKRRKMKSVGDDEELQQNESGTSPKSSEGLQFQNALGCNPSLPKHNVTIRSD
  QQHKNIQLQNSHIHLVARGPEQTMDPKLSTIMEQQISSAAQDKIELQRHGTGISVIQHTN
  SLSRPNSFDKPEPFERASPVSFQELNRTGKSGSLKVIGISQEESHPSRDGSHPHQLALSD
  ALRGELQESSRKSPSERHVLGQPSRLVRQHNIQVPEILVTEEPDRDLEAQCHDQEKSEKF
  SWPQRSETLSKLPTEKLPPKKKRLRLAEIEHSSTESSFDSTLSRSLSRESSLSHTSSFSA
  SLDIEDVSKTEASPKIDFLNKAEFLMIPAGLNTLNVPGCHREMRRTASEQINCTQTSMEV
  SDLRSKSFDCGSITPPQTTPLTELQPPSSPSRVGVTGHVPLLERRRGPLVRQISLNIAPD
  SHLSPVHPTSFQNTALPSVNAVPYQGPQLTSTSLAEFSANTLHSQTQVKDLQAETSNSSS
  TNVFPVQQLCDINLLNQIHAPPSHQSTQLSLQVSTQGSKPDKNSVLSGSSKSEDCFAPKY
  QLHCQVFTSGPSCSSNPVHSLPNQVISDPVGTDHCVTSATLPTKLIDSMSNSHPLLPPEL
  RPLGSQVQKVPSSFMLPIRLQSSVPAYCFATLTSLPQILVTQDLPNQPICQTNHSVVPIS
  EEQNSVPTLQKGHQNALPNPEKEFLCENVFSEMSQNSSLSESLPITQKISVGRLSPQQES
  SASSKRMLSPANSLDIAMEKHQKRAKDENGAVCATDVRPLEALSSRVNEASKQKKPILVR
  QVCTTEPLDGVMLEKDVFSQPEISNEAVNLTNVLPADNSSTGCSKFVVIEPISELQEFEN
  IKSSTSLTLTVRSSPAPSENTHISPLKCTDNNQERKSPGVKNQGDKVNIQEQSQQPVTSL
  SLFNIKDTQQLAFPSLKTTTNFTWCYLLRQKSLHLPQKDQKTSAYTDWTVSASNPNPLGL
  PTKVALALLNSKQNTGKSLYCQAITTHSKSDLLVYSSKWKSSLSKRALGNQKSTVVEFSN
  KDASEINSEQDKENSLIKSEPRRIKIFDGGYKSNEEYVYVRGRGRGKYICEECGIRCKKP
  SMLKKHIRTHTDVRPYHCTYCNFSFKTKGNLTKHMKSKAHSKKCVDLGVSVGLIDEQDTE
  ESDEKQRFSYERSGYDLEESDGPDEDDNENEDDDEDSQAESVLSATPSVTASPQHLPSRS
  SLQDPVSTDEDVRITDCFSGVHTDPMDVLPRALLTRMTVLSTAQSDYNRKTLSPGKARQR
  AARDENDTIPSVDTSRSPCHQMSVDYPESEEILRSSMAGKAVAITQSPSSVRLPPAAAEH
  SPQTAAGMPSVASPHPDPQEQKQQITLQPTPGLPSPHTHLFSHLPLHSQQQSRTPYNMVP
  VGGIHVVPAGLTYSTFVPLQAGPVQLTIPAVSVVHRTLGTHRNTVTEVSGTTNPAGVAEL
  SSVVPCIPIGQIRVPGLQNLSTPGLQSLPSLSMETVNIVGLANTNMAPQVHPPGLALNAV
  GLQVLTANPSSQSSPAPQAHIPGLQILNIALPTLIPSVSQVAVDAQGAPEMPASQSKACE
  TQPKQTSVASANQVSRTESPQGLPTVQRENAKKVLNPPAPAGDHARLDGLSKMDTEKAAS
  ANHVKPKPELTSIQGQPASTSQPLLKAHSEVFTKPSGQQTLSPDRQVPRPTALPRRQPTV
  HFSDVSSDDDEDRLVIAT
• Function: This protein specifically binds to the DNA sequence 5'-GGGACTTTCC-3' which is found in the enhancer elements of numerous viral promoters such as those of SV40, CMV, or HIV-1. In addition, related sequences are found in the enhancer elements of a number of cellular promoters, including those of the class I MHC, interleukin-2 receptor, and interferon-beta genes. It may act in T-cell activation. Involved in activating HIV-1 gene expression. Isoform 2 and isoform 3 also bind to the IPCS (IRF1 and p53 common sequence) DNA sequence in the promoter region of interferon regulatory factor 1 and p53 genes and are involved in transcription regulation of these genes. Isoform 2 does not activate HIV-1 gene expression. Isoform 2 and isoform 3 may be involved in apoptosis.

Molecular Interaction Atlas (MIA) of This DOT

19 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast cancer	DIS7DPX1	Definitive	Biomarker	[1]
Breast carcinoma	DIS2UE88	Definitive	Biomarker	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
Dilated cardiomyopathy 1A	DIS0RK9Z	Strong	Altered Expression	[3]
Duchenne muscular dystrophy	DISRQ3NV	Strong	Biomarker	[4]
Endometrial cancer	DISW0LMR	Strong	Biomarker	[5]
Endometrial carcinoma	DISXR5CY	Strong	Biomarker	[5]
Muscular dystrophy	DISJD6P7	Strong	Biomarker	[4]
Neoplasm	DISZKGEW	Strong	Genetic Variation	[6]
Pachyonychia congenita 3	DISZLC6C	Strong	Altered Expression	[7]
Prostate cancer	DISF190Y	Strong	Biomarker	[7]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[7]
Prostate neoplasm	DISHDKGQ	Strong	Biomarker	[8]
Vibrio cholerae infection	DISW7E3U	Strong	Biomarker	[9]
Asthma	DISW9QNS	Disputed	Biomarker	[10]
Lung cancer	DISCM4YA	Disputed	Altered Expression	[11]
Lung carcinoma	DISTR26C	Disputed	Altered Expression	[11]
Lung neoplasm	DISVARNB	Disputed	Biomarker	[11]
Non-small-cell lung cancer	DIS5Y6R9	Disputed	Biomarker	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Zinc finger protein 40 (HIVEP1).	[12]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Zinc finger protein 40 (HIVEP1).	[22]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Zinc finger protein 40 (HIVEP1).	[22]
Hexadecanoic acid	DMWUXDZ	Investigative	Hexadecanoic acid increases the phosphorylation of Zinc finger protein 40 (HIVEP1).	[25]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Zinc finger protein 40 (HIVEP1).	[13]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Zinc finger protein 40 (HIVEP1).	[14]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Zinc finger protein 40 (HIVEP1).	[15]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Zinc finger protein 40 (HIVEP1).	[16]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Zinc finger protein 40 (HIVEP1).	[17]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate increases the expression of Zinc finger protein 40 (HIVEP1).	[18]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Zinc finger protein 40 (HIVEP1).	[19]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Zinc finger protein 40 (HIVEP1).	[20]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Zinc finger protein 40 (HIVEP1).	[21]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Zinc finger protein 40 (HIVEP1).	[19]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Zinc finger protein 40 (HIVEP1).	[23]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Zinc finger protein 40 (HIVEP1).	[24]
geraniol	DMS3CBD	Investigative	geraniol increases the expression of Zinc finger protein 40 (HIVEP1).	[26]

References

• [1] Negative transcriptional control of ERBB2 gene by MBP-1 and HDAC1: diagnostic implications in breast cancer.BMC Cancer. 2013 Feb 19;13:81. doi: 10.1186/1471-2407-13-81.
• [2] MBP-1 inhibits breast cancer growth and metastasis in immunocompetent mice.Cancer Res. 2009 Dec 15;69(24):9354-9. doi: 10.1158/0008-5472.CAN-09-2974.
• [3] Myc promoter-binding protein-1 (MBP-1) is a novel potential prognostic marker in invasive ductal breast carcinoma.PLoS One. 2010 Sep 23;5(9):e12961. doi: 10.1371/journal.pone.0012961.
• [4] Major basic protein-1 promotes fibrosis of dystrophic muscle and attenuates the cellular immune response in muscular dystrophy.Hum Mol Genet. 2008 Aug 1;17(15):2280-92. doi: 10.1093/hmg/ddn129. Epub 2008 Apr 21.
• [5] X chromosome-linked long noncoding RNA lnc-XLEC1 regulates c-Myc-dependent cell growth by collaborating with MBP-1 in endometrial cancer.Int J Cancer. 2019 Aug 15;145(4):927-940. doi: 10.1002/ijc.32166. Epub 2019 Feb 23.
• [6] Novel roles of holocarboxylase synthetase in gene regulation and intermediary metabolism.Nutr Rev. 2014 Jun;72(6):369-76. doi: 10.1111/nure.12103. Epub 2014 Mar 28.
• [7] Knockdown of MBP-1 in human prostate cancer cells delays cell cycle progression.J Biol Chem. 2006 Aug 18;281(33):23652-7. doi: 10.1074/jbc.M602930200. Epub 2006 Jun 8.
• [8] Carboxyl-terminal repressor domain of MBP-1 is sufficient for regression of prostate tumor growth in nude mice.Cancer Res. 2005 Feb 1;65(3):718-21.
• [9] Low concentrations mono-butyl phthalate stimulates steroidogenesis by facilitating steroidogenic acute regulatory protein expression in mouse Leydig tumor cells (MLTC-1).Chem Biol Interact. 2006 Dec 1;164(1-2):15-24. doi: 10.1016/j.cbi.2006.08.022. Epub 2006 Sep 1.
• [10] Charcot-Leyden crystal protein/galectin-10 is a surrogate biomarker of eosinophilic airway inflammation in asthma.Biomark Med. 2019 Jun;13(9):715-724. doi: 10.2217/bmm-2018-0280. Epub 2019 Jun 3.
• [11] Tumor-suppressive effects of MBP-1 in non-small cell lung cancer cells.Cancer Res. 2006 Dec 15;66(24):11907-12. doi: 10.1158/0008-5472.CAN-06-2754.
• [12] 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.
• [13] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [14] 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.
• [15] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [16] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [17] Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
• [18] Epigallocatechin-3-gallate (EGCG) protects against chromate-induced toxicity in vitro. Toxicol Appl Pharmacol. 2012 Jan 15;258(2):166-75.
• [19] Gene expression profiling in Ishikawa cells: a fingerprint for estrogen active compounds. Toxicol Appl Pharmacol. 2009 Apr 1;236(1):85-96.
• [20] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [21] 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.
• [22] 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.
• [23] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.
• [24] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [25] Functional lipidomics: Palmitic acid impairs hepatocellular carcinoma development by modulating membrane fluidity and glucose metabolism. Hepatology. 2017 Aug;66(2):432-448. doi: 10.1002/hep.29033. Epub 2017 Jun 16.
• [26] Geraniol suppresses prostate cancer growth through down-regulation of E2F8. Cancer Med. 2016 Oct;5(10):2899-2908.