Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT6H0EWF)

DOT Name Inhibitor of growth protein 2 (ING2)
Synonyms Inhibitor of growth 1-like protein; ING1Lp; p32; p33ING2
Gene Name ING2
Related Disease
Adenocarcinoma ( )
Respiratory syncytial virus infection ( )
Squamous cell carcinoma ( )
Acute lymphocytic leukaemia ( )
Advanced cancer ( )
Autoimmune disease ( )
Bladder cancer ( )
Bone osteosarcoma ( )
Brain cancer ( )
Breast cancer ( )
Breast carcinoma ( )
Breast neoplasm ( )
Colon cancer ( )
Colon carcinoma ( )
Colorectal carcinoma ( )
Glioma ( )
Head-neck squamous cell carcinoma ( )
Hepatitis C virus infection ( )
Hepatocellular carcinoma ( )
Lung cancer ( )
Lung carcinoma ( )
Lung neoplasm ( )
Meningioma ( )
Obesity ( )
Osteosarcoma ( )
Triple negative breast cancer ( )
Urinary bladder cancer ( )
Urinary bladder neoplasm ( )
Fetal growth restriction ( )
Melanoma ( )
Sarcoma ( )
Soft tissue sarcoma ( )
Type-1/2 diabetes ( )
Prostate cancer ( )
Prostate carcinoma ( )
Neuroblastoma ( )
Non-small-cell lung cancer ( )
Timothy syndrome ( )
Tourette syndrome ( )
Tuberous sclerosis ( )
UniProt ID
ING2_HUMAN
3D Structure
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2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
Pfam ID
PF12998
Sequence
MLGQQQQQLYSSAALLTGERSRLLTCYVQDYLECVESLPHDMQRNVSVLRELDNKYQETL
KEIDDVYEKYKKEDDLNQKKRLQQLLQRALINSQELGDEKIQIVTQMLELVENRARQMEL
HSQCFQDPAESERASDKAKMDSSQPERSSRRPRRQRTSESRDLCHMANGIEDCDDQPPKE
KKSKSAKKKKRSKAKQEREASPVEFAIDPNEPTYCLCNQVSYGEMIGCDNEQCPIEWFHF
SCVSLTYKPKGKWYCPKCRGDNEKTMDKSTEKTKKDRRSR
Function
Seems to be involved in p53/TP53 activation and p53/TP53-dependent apoptotic pathways, probably by enhancing acetylation of p53/TP53. Component of a mSin3A-like corepressor complex, which is probably involved in deacetylation of nucleosomal histones. ING2 activity seems to be modulated by binding to phosphoinositides (PtdInsPs).
Tissue Specificity Widely expressed. Higher expressed in colon-cancer tumor than in normal colon tissues.
Reactome Pathway
PI5P Regulates TP53 Acetylation (R-HSA-6811555 )
SUMOylation of transcription cofactors (R-HSA-3899300 )

Molecular Interaction Atlas (MIA) of This DOT

40 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Adenocarcinoma DIS3IHTY Definitive Altered Expression [1]
Respiratory syncytial virus infection DIS7FWHY Definitive Biomarker [2]
Squamous cell carcinoma DISQVIFL Definitive Biomarker [1]
Acute lymphocytic leukaemia DISPX75S Strong Biomarker [3]
Advanced cancer DISAT1Z9 Strong Altered Expression [4]
Autoimmune disease DISORMTM Strong Biomarker [5]
Bladder cancer DISUHNM0 Strong Genetic Variation [6]
Bone osteosarcoma DIST1004 Strong Biomarker [7]
Brain cancer DISBKFB7 Strong Altered Expression [8]
Breast cancer DIS7DPX1 Strong Altered Expression [9]
Breast carcinoma DIS2UE88 Strong Altered Expression [9]
Breast neoplasm DISNGJLM Strong Biomarker [10]
Colon cancer DISVC52G Strong Altered Expression [11]
Colon carcinoma DISJYKUO Strong Altered Expression [11]
Colorectal carcinoma DIS5PYL0 Strong Biomarker [12]
Glioma DIS5RPEH Strong Biomarker [13]
Head-neck squamous cell carcinoma DISF7P24 Strong Biomarker [14]
Hepatitis C virus infection DISQ0M8R Strong Genetic Variation [15]
Hepatocellular carcinoma DIS0J828 Strong Biomarker [16]
Lung cancer DISCM4YA Strong Altered Expression [17]
Lung carcinoma DISTR26C Strong Altered Expression [17]
Lung neoplasm DISVARNB Strong Altered Expression [17]
Meningioma DISPT4TG Strong Genetic Variation [18]
Obesity DIS47Y1K Strong Biomarker [19]
Osteosarcoma DISLQ7E2 Strong Biomarker [7]
Triple negative breast cancer DISAMG6N Strong Altered Expression [10]
Urinary bladder cancer DISDV4T7 Strong Genetic Variation [6]
Urinary bladder neoplasm DIS7HACE Strong Genetic Variation [6]
Fetal growth restriction DIS5WEJ5 moderate Altered Expression [20]
Melanoma DIS1RRCY moderate Altered Expression [21]
Sarcoma DISZDG3U moderate Biomarker [22]
Soft tissue sarcoma DISSN8XB moderate Biomarker [22]
Type-1/2 diabetes DISIUHAP moderate Biomarker [19]
Prostate cancer DISF190Y Disputed Biomarker [23]
Prostate carcinoma DISMJPLE Disputed Biomarker [23]
Neuroblastoma DISVZBI4 Limited Genetic Variation [24]
Non-small-cell lung cancer DIS5Y6R9 Limited Biomarker [25]
Timothy syndrome DISBXBZP Limited Biomarker [26]
Tourette syndrome DISX9D54 Limited Biomarker [26]
Tuberous sclerosis DISEMUGZ Limited Biomarker [26]
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⏷ Show the Full List of 40 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
10 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate increases the expression of Inhibitor of growth protein 2 (ING2). [27]
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of Inhibitor of growth protein 2 (ING2). [28]
Tretinoin DM49DUI Approved Tretinoin decreases the expression of Inhibitor of growth protein 2 (ING2). [29]
Acetaminophen DMUIE76 Approved Acetaminophen increases the expression of Inhibitor of growth protein 2 (ING2). [30]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate decreases the expression of Inhibitor of growth protein 2 (ING2). [31]
Temozolomide DMKECZD Approved Temozolomide decreases the expression of Inhibitor of growth protein 2 (ING2). [32]
Diethylstilbestrol DMN3UXQ Approved Diethylstilbestrol decreases the expression of Inhibitor of growth protein 2 (ING2). [33]
Urethane DM7NSI0 Phase 4 Urethane decreases the expression of Inhibitor of growth protein 2 (ING2). [34]
Formaldehyde DM7Q6M0 Investigative Formaldehyde decreases the expression of Inhibitor of growth protein 2 (ING2). [36]
Milchsaure DM462BT Investigative Milchsaure affects the expression of Inhibitor of growth protein 2 (ING2). [37]
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⏷ Show the Full List of 10 Drug(s)
1 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 decreases the sumoylation of Inhibitor of growth protein 2 (ING2). [35]
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References

1 Decreased expression of ING2 gene and its clinicopathological significance in Chinese NSCLC patients.Neoplasma. 2014;61(4):468-75. doi: 10.4149/neo_2014_058.
2 Mitochondrial protein p32/HAPB1/gC1qR/C1qbp is required for efficient respiratory syncytial virus production.Biochem Biophys Res Commun. 2017 Aug 5;489(4):460-465. doi: 10.1016/j.bbrc.2017.05.171. Epub 2017 May 30.
3 miR-153-3p Suppresses Inhibitor of Growth Protein 2 Expression to Function as Tumor Suppressor in Acute Lymphoblastic Leukemia.Technol Cancer Res Treat. 2019 Jan-Dec;18:1533033819852990. doi: 10.1177/1533033819852990.
4 Efficacy of a novel LyP-1-containing self-microemulsifying drug delivery system (SMEDDS) for active targeting to breast cancer.Eur J Pharm Biopharm. 2019 Mar;136:138-146. doi: 10.1016/j.ejpb.2019.01.017. Epub 2019 Jan 22.
5 Mitochondrial p32/C1qbp Is a Critical Regulator of Dendritic Cell Metabolism and Maturation.Cell Rep. 2018 Nov 13;25(7):1800-1815.e4. doi: 10.1016/j.celrep.2018.10.057.
6 Comprehensive pathway-based interrogation of genetic variations in the nucleotide excision DNA repair pathway and risk of bladder cancer.Cancer. 2012 Jan 1;118(1):205-15. doi: 10.1002/cncr.26224. Epub 2011 Jun 20.
7 Prognostic scoring system for osteosarcoma using network-regularized high-dimensional Cox-regression analysis and potential therapeutic targets.J Cell Physiol. 2019 Aug;234(8):13851-13857. doi: 10.1002/jcp.28065. Epub 2019 Jan 3.
8 Mitochondrial p32 is upregulated in Myc expressing brain cancers and mediates glutamine addiction.Oncotarget. 2015 Jan 20;6(2):1157-70. doi: 10.18632/oncotarget.2708.
9 Suberoylanilide hydroxamic acid (SAHA)-induced dynamics of a human histone deacetylase protein interaction network.Mol Cell Proteomics. 2014 Nov;13(11):3114-25. doi: 10.1074/mcp.M113.037127. Epub 2014 Jul 29.
10 Application of polymersomes engineered to target p32 protein for detection of small breast tumors in mice.Oncotarget. 2018 Apr 10;9(27):18682-18697. doi: 10.18632/oncotarget.24588. eCollection 2018 Apr 10.
11 ING2 is upregulated in colon cancer and increases invasion by enhanced MMP13 expression.Int J Cancer. 2009 Sep 15;125(6):1306-15. doi: 10.1002/ijc.24437.
12 ING2, a tumor associated gene, enhances PAI? and HSPA1A expression with HDAC1 and mSin3A through the PHD domain and Cterminal.Mol Med Rep. 2017 Nov;16(5):7367-7374. doi: 10.3892/mmr.2017.7553. Epub 2017 Sep 20.
13 A novel small molecule inhibitor of p32 mitochondrial protein overexpressed in glioma.J Transl Med. 2017 Oct 18;15(1):210. doi: 10.1186/s12967-017-1312-7.
14 Frequent deletion of ING2 locus at 4q35.1 associates with advanced tumor stage in head and neck squamous cell carcinoma.J Cancer Res Clin Oncol. 2009 May;135(5):703-13. doi: 10.1007/s00432-008-0507-y. Epub 2008 Nov 8.
15 Impact of novel NS5A resistance-associated substitutions of hepatitis C virus detected in treatment-experienced patients.Sci Rep. 2019 Apr 5;9(1):5722. doi: 10.1038/s41598-019-42114-z.
16 Analysis of loss of heterozygosity on chromosome 4q in hepatocellular carcinoma using high-throughput SNP array.Oncol Rep. 2010 Feb;23(2):445-55.
17 Alterations in novel candidate tumor suppressor genes, ING1 and ING2 in human lung cancer.Oncol Rep. 2006 Mar;15(3):545-9.
18 Search for mutations of the hRAD54 gene in sporadic meningiomas with deletion at 1p32.Mol Carcinog. 1999 Apr;24(4):300-4. doi: 10.1002/(sici)1098-2744(199904)24:4<300::aid-mc8>3.0.co;2-g.
19 p32 regulates ER stress and lipid homeostasis by down-regulating GCS1 expression.FASEB J. 2018 Jul;32(7):3892-3902. doi: 10.1096/fj.201701004RR. Epub 2018 Feb 20.
20 A role for the mitochondrial-associated protein p32 in regulation of trophoblast proliferation.Mol Hum Reprod. 2014 Aug;20(8):745-55. doi: 10.1093/molehr/gau039. Epub 2014 May 29.
21 Nuclear ING2 expression is reduced in human cutaneous melanomas.Br J Cancer. 2006 Jul 3;95(1):80-6. doi: 10.1038/sj.bjc.6603205. Epub 2006 Jun 6.
22 Targeted disruption of Ing2 results in defective spermatogenesis and development of soft-tissue sarcomas.PLoS One. 2010 Nov 19;5(11):e15541. doi: 10.1371/journal.pone.0015541.
23 A novel crosstalk between the tumor suppressors ING1 and ING2 regulates androgen receptor signaling.J Mol Med (Berl). 2016 Oct;94(10):1167-1179. doi: 10.1007/s00109-016-1440-1. Epub 2016 Jun 16.
24 Prognostic relevance of genetic alterations in the p32 region of chromosome 1 in neuroblastoma.Eur J Cancer. 1997 Oct;33(12):1983-5. doi: 10.1016/s0959-8049(97)00239-6.
25 Exploiting ING2 Epigenetic Modulation as a Therapeutic Opportunity for Non-Small Cell Lung Cancer.Cancers (Basel). 2019 Oct 21;11(10):1601. doi: 10.3390/cancers11101601.
26 Tactile stimulation partially prevents neurodevelopmental changes in visual tract caused by early iron deficiency.Brain Res. 2017 Feb 15;1657:130-139. doi: 10.1016/j.brainres.2016.12.003. Epub 2016 Dec 9.
27 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.
28 Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
29 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.
30 Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
31 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
32 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.
33 Identification of biomarkers and outcomes of endocrine disruption in human ovarian cortex using In Vitro Models. Toxicology. 2023 Feb;485:153425. doi: 10.1016/j.tox.2023.153425. Epub 2023 Jan 5.
34 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
35 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.
36 Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.
37 Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.