Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTW9GS0U)

DOT Name Adenosine 5'-monophosphoramidase HINT2 (HINT2)
Synonyms EC 3.9.1.-; HINT-3; HIT-17kDa; Histidine triad nucleotide-binding protein 2, mitochondrial; HINT-2; PKCI-1-related HIT protein
Gene Name HINT2
Related Disease
Colorectal carcinoma ( )
Hepatocellular carcinoma ( )
Metastatic malignant neoplasm ( )
Neoplasm ( )
Non-small-cell lung cancer ( )
Ocular melanoma ( )
Pancreatic cancer ( )
Relapsing-remitting multiple sclerosis ( )
UniProt ID
HINT2_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
4INC; 4INI; 5KM5; 5KM8; 5KM9; 6YI0; 6YPR; 6YPX; 6YQD; 6YVP
EC Number
3.9.1.-
Pfam ID
PF01230
Sequence
MAAAVVLAAGLRAARRAVAATGVRGGQVRGAAGVTDGNEVAKAQQATPGGAAPTIFSRIL
DKSLPADILYEDQQCLVFRDVAPQAPVHFLVIPKKPIPRISQAEEEDQQLLGHLLLVAKQ
TAKAEGLGDGYRLVINDGKLGAQSVYHLHIHVLGGRQLQWPPG
Function
Exhibits adenosine 5'-monophosphoramidase activity, hydrolyzing purine nucleotide phosphoramidates with a single phosphate group such as adenosine 5'monophosphoramidate (AMP-NH2) to yield AMP and NH2. Hydrolyzes adenosine 5'-O-p-nitrophenylphosphoramidate (AMP-pNA). Hydrolyzes fluorogenic purine nucleoside tryptamine phosphoramidates in vitro. May be involved in steroid biosynthesis. May play a role in apoptosis.
Tissue Specificity High expression in liver and pancreas. Expression is significantly down-regulated in hepatocellular carcinoma (HCC) patients.
Reactome Pathway
RHOD GTPase cycle (R-HSA-9013405 )

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Colorectal carcinoma DIS5PYL0 Strong Biomarker [1]
Hepatocellular carcinoma DIS0J828 Strong Altered Expression [2]
Metastatic malignant neoplasm DIS86UK6 Strong Altered Expression [3]
Neoplasm DISZKGEW Strong Altered Expression [2]
Non-small-cell lung cancer DIS5Y6R9 Strong Altered Expression [3]
Ocular melanoma DISOHHFC Strong Altered Expression [4]
Pancreatic cancer DISJC981 Strong Altered Expression [5]
Relapsing-remitting multiple sclerosis DISSXFCF Strong Biomarker [6]
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⏷ Show the Full List of 8 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
11 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 Adenosine 5'-monophosphoramidase HINT2 (HINT2). [7]
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of Adenosine 5'-monophosphoramidase HINT2 (HINT2). [8]
Acetaminophen DMUIE76 Approved Acetaminophen increases the expression of Adenosine 5'-monophosphoramidase HINT2 (HINT2). [9]
Doxorubicin DMVP5YE Approved Doxorubicin increases the expression of Adenosine 5'-monophosphoramidase HINT2 (HINT2). [10]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate decreases the expression of Adenosine 5'-monophosphoramidase HINT2 (HINT2). [11]
Cisplatin DMRHGI9 Approved Cisplatin increases the expression of Adenosine 5'-monophosphoramidase HINT2 (HINT2). [12]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of Adenosine 5'-monophosphoramidase HINT2 (HINT2). [13]
Decitabine DMQL8XJ Approved Decitabine affects the expression of Adenosine 5'-monophosphoramidase HINT2 (HINT2). [14]
Zoledronate DMIXC7G Approved Zoledronate increases the expression of Adenosine 5'-monophosphoramidase HINT2 (HINT2). [15]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the expression of Adenosine 5'-monophosphoramidase HINT2 (HINT2). [16]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 increases the expression of Adenosine 5'-monophosphoramidase HINT2 (HINT2). [17]
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⏷ Show the Full List of 11 Drug(s)

References

1 HINT2 downregulation promotes colorectal carcinoma migration and metastasis.Oncotarget. 2017 Feb 21;8(8):13521-13531. doi: 10.18632/oncotarget.14587.
2 Clinical significance of down-regulated HINT2 in hepatocellular carcinoma.Medicine (Baltimore). 2019 Nov;98(48):e17815. doi: 10.1097/MD.0000000000017815.
3 WITHDRAWN: Upregulation of HINT2 Inhibits Non-Small Cell Lung Cancer Cell Invasion Via COX-2/PGE?Mediated Activation of -catenin Signaling.Oncol Res. 2017 Aug 11. doi: 10.3727/096504017X15021536183508. Online ahead of print.
4 m(6)A modification suppresses ocular melanoma through modulating HINT2 mRNA translation.Mol Cancer. 2019 Nov 14;18(1):161. doi: 10.1186/s12943-019-1088-x.
5 HINT2 triggers mitochondrial Ca(2+) influx by regulating the mitochondrial Ca(2+) uniporter (MCU) complex and enhances gemcitabine apoptotic effect in pancreatic cancer.Cancer Lett. 2017 Dec 28;411:106-116. doi: 10.1016/j.canlet.2017.09.020. Epub 2017 Sep 23.
6 Safety and efficacy of helminth treatment in relapsing-remitting multiple sclerosis: Results of the HINT 2 clinical trial.Mult Scler. 2019 Jan;25(1):81-91. doi: 10.1177/1352458517736377. Epub 2017 Oct 24.
7 Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
8 Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
9 Increased mitochondrial ROS formation by acetaminophen in human hepatic cells is associated with gene expression changes suggesting disruption of the mitochondrial electron transport chain. Toxicol Lett. 2015 Apr 16;234(2):139-50.
10 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.
11 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
12 Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
13 Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
14 Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
15 Zoledronate dysregulates fatty acid metabolism in renal tubular epithelial cells to induce nephrotoxicity. Arch Toxicol. 2018 Jan;92(1):469-485.
16 Label-free quantitative proteomic analysis identifies the oncogenic role of FOXA1 in BaP-transformed 16HBE cells. Toxicol Appl Pharmacol. 2020 Sep 15;403:115160. doi: 10.1016/j.taap.2020.115160. Epub 2020 Jul 25.
17 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.