Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT6XBWN0)

DOT Name Aspartate aminotransferase, mitochondrial (GOT2)
Synonyms
mAspAT; EC 2.6.1.1; EC 2.6.1.7; Fatty acid-binding protein; FABP-1; Glutamate oxaloacetate transaminase 2; Kynurenine aminotransferase 4; Kynurenine aminotransferase IV; Kynurenine--oxoglutarate transaminase 4; Kynurenine--oxoglutarate transaminase IV; Plasma membrane-associated fatty acid-binding protein; FABPpm; Transaminase A
Gene Name GOT2
Related Disease
Acute kidney injury ( )
Chronic kidney disease ( )
Adenocarcinoma ( )
Arteriosclerosis ( )
Atherosclerosis ( )
Colon cancer ( )
Colorectal carcinoma ( )
Crohn disease ( )
Developmental and epileptic encephalopathy, 82 ( )
Endometrial carcinoma ( )
Hepatitis C virus infection ( )
Hepatocellular carcinoma ( )
High blood pressure ( )
Intellectual disability ( )
Isolated congenital microcephaly ( )
Lymphoma ( )
Malignant glioma ( )
Matthew-Wood syndrome ( )
Neoplasm ( )
Non-insulin dependent diabetes ( )
Pancreatic cancer ( )
Pediatric lymphoma ( )
Plasma cell myeloma ( )
Psoriasis ( )
Renal cell carcinoma ( )
Schizophrenia ( )
Thyroid cancer ( )
Thyroid gland carcinoma ( )
Thyroid gland undifferentiated (anaplastic) carcinoma ( )
Thyroid tumor ( )
Type-1/2 diabetes ( )
Advanced cancer ( )
Carcinoma ( )
Cardiovascular disease ( )
Clear cell renal carcinoma ( )
Obesity ( )
Non-alcoholic fatty liver disease ( )
B-cell lymphoma ( )
Breast cancer ( )
Breast carcinoma ( )
Chronic obstructive pulmonary disease ( )
Coeliac disease ( )
Glioblastoma multiforme ( )
Triple negative breast cancer ( )
UniProt ID
AATM_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
PDB ID
5AX8
EC Number
2.6.1.1; 2.6.1.7
Pfam ID
PF00155
Sequence
MALLHSGRVLPGIAAAFHPGLAAAASARASSWWTHVEMGPPDPILGVTEAFKRDTNSKKM
NLGVGAYRDDNGKPYVLPSVRKAEAQIAAKNLDKEYLPIGGLAEFCKASAELALGENSEV
LKSGRFVTVQTISGTGALRIGASFLQRFFKFSRDVFLPKPTWGNHTPIFRDAGMQLQGYR
YYDPKTCGFDFTGAVEDISKIPEQSVLLLHACAHNPTGVDPRPEQWKEIATVVKKRNLFA
FFDMAYQGFASGDGDKDAWAVRHFIEQGINVCLCQSYAKNMGLYGERVGAFTMVCKDADE
AKRVESQLKILIRPMYSNPPLNGARIAAAILNTPDLRKQWLQEVKVMADRIIGMRTQLVS
NLKKEGSTHNWQHITDQIGMFCFTGLKPEQVERLIKEFSIYMTKDGRISVAGVTSSNVGY
LAHAIHQVTK
Function
Catalyzes the irreversible transamination of the L-tryptophan metabolite L-kynurenine to form kynurenic acid (KA). As a member of the malate-aspartate shuttle, it has a key role in the intracellular NAD(H) redox balance. Is important for metabolite exchange between mitochondria and cytosol, and for amino acid metabolism. Facilitates cellular uptake of long-chain free fatty acids.
KEGG Pathway
Arginine biosynthesis (hsa00220 )
Alanine, aspartate and glutamate metabolism (hsa00250 )
Cysteine and methionine metabolism (hsa00270 )
Arginine and proline metabolism (hsa00330 )
Tyrosine metabolism (hsa00350 )
Phenylalanine metabolism (hsa00360 )
Phenylalanine, tyrosine and tryptophan biosynthesis (hsa00400 )
Metabolic pathways (hsa01100 )
Carbon metabolism (hsa01200 )
2-Oxocarboxylic acid metabolism (hsa01210 )
Biosynthesis of amino acids (hsa01230 )
Fat digestion and absorption (hsa04975 )
Reactome Pathway
Glyoxylate metabolism and glycine degradation (R-HSA-389661 )
Gluconeogenesis (R-HSA-70263 )
Aspartate and asparagine metabolism (R-HSA-8963693 )
Glutamate and glutamine metabolism (R-HSA-8964539 )
Degradation of cysteine and homocysteine (R-HSA-1614558 )
BioCyc Pathway
MetaCyc:HS04858-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

44 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Acute kidney injury DISXZG0T Definitive Biomarker [1]
Chronic kidney disease DISW82R7 Definitive Altered Expression [2]
Adenocarcinoma DIS3IHTY Strong Biomarker [3]
Arteriosclerosis DISK5QGC Strong Genetic Variation [4]
Atherosclerosis DISMN9J3 Strong Genetic Variation [4]
Colon cancer DISVC52G Strong Altered Expression [3]
Colorectal carcinoma DIS5PYL0 Strong Genetic Variation [5]
Crohn disease DIS2C5Q8 Strong Biomarker [6]
Developmental and epileptic encephalopathy, 82 DISEVPN9 Strong Autosomal recessive [7]
Endometrial carcinoma DISXR5CY Strong Altered Expression [8]
Hepatitis C virus infection DISQ0M8R Strong Altered Expression [9]
Hepatocellular carcinoma DIS0J828 Strong Altered Expression [10]
High blood pressure DISY2OHH Strong Genetic Variation [11]
Intellectual disability DISMBNXP Strong Biomarker [12]
Isolated congenital microcephaly DISUXHZ6 Strong Biomarker [12]
Lymphoma DISN6V4S Strong Altered Expression [13]
Malignant glioma DISFXKOV Strong Biomarker [14]
Matthew-Wood syndrome DISA7HR7 Strong Altered Expression [15]
Neoplasm DISZKGEW Strong Altered Expression [16]
Non-insulin dependent diabetes DISK1O5Z Strong Genetic Variation [4]
Pancreatic cancer DISJC981 Strong Biomarker [15]
Pediatric lymphoma DIS51BK2 Strong Altered Expression [13]
Plasma cell myeloma DIS0DFZ0 Strong Altered Expression [17]
Psoriasis DIS59VMN Strong Biomarker [18]
Renal cell carcinoma DISQZ2X8 Strong Altered Expression [19]
Schizophrenia DISSRV2N Strong Altered Expression [20]
Thyroid cancer DIS3VLDH Strong Biomarker [21]
Thyroid gland carcinoma DISMNGZ0 Strong Biomarker [21]
Thyroid gland undifferentiated (anaplastic) carcinoma DISYBB1W Strong Biomarker [22]
Thyroid tumor DISLVKMD Strong Biomarker [21]
Type-1/2 diabetes DISIUHAP Strong Biomarker [23]
Advanced cancer DISAT1Z9 moderate Altered Expression [24]
Carcinoma DISH9F1N moderate Altered Expression [25]
Cardiovascular disease DIS2IQDX moderate Biomarker [26]
Clear cell renal carcinoma DISBXRFJ moderate Biomarker [27]
Obesity DIS47Y1K moderate Biomarker [28]
Non-alcoholic fatty liver disease DISDG1NL Disputed Genetic Variation [11]
B-cell lymphoma DISIH1YQ Limited Altered Expression [13]
Breast cancer DIS7DPX1 Limited Altered Expression [29]
Breast carcinoma DIS2UE88 Limited Altered Expression [29]
Chronic obstructive pulmonary disease DISQCIRF Limited Altered Expression [30]
Coeliac disease DISIY60C Limited Altered Expression [31]
Glioblastoma multiforme DISK8246 Limited Biomarker [32]
Triple negative breast cancer DISAMG6N Limited Biomarker [29]
------------------------------------------------------------------------------------
⏷ Show the Full List of 44 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
This DOT Affected the Drug Response of 1 Drug(s)
Drug Name Drug ID Highest Status Interaction REF
Ciprofloxacin XR DM2NLS9 Approved Aspartate aminotransferase, mitochondrial (GOT2) increases the Acute hepatic failure ADR of Ciprofloxacin XR. [46]
------------------------------------------------------------------------------------
12 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 Aspartate aminotransferase, mitochondrial (GOT2). [33]
Tretinoin DM49DUI Approved Tretinoin decreases the expression of Aspartate aminotransferase, mitochondrial (GOT2). [34]
Doxorubicin DMVP5YE Approved Doxorubicin affects the expression of Aspartate aminotransferase, mitochondrial (GOT2). [35]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of Aspartate aminotransferase, mitochondrial (GOT2). [36]
Arsenic DMTL2Y1 Approved Arsenic increases the expression of Aspartate aminotransferase, mitochondrial (GOT2). [37]
Arsenic trioxide DM61TA4 Approved Arsenic trioxide increases the expression of Aspartate aminotransferase, mitochondrial (GOT2). [38]
Niclosamide DMJAGXQ Approved Niclosamide increases the expression of Aspartate aminotransferase, mitochondrial (GOT2). [40]
Epigallocatechin gallate DMCGWBJ Phase 3 Epigallocatechin gallate decreases the expression of Aspartate aminotransferase, mitochondrial (GOT2). [41]
Genistein DM0JETC Phase 2/3 Genistein increases the expression of Aspartate aminotransferase, mitochondrial (GOT2). [42]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 decreases the expression of Aspartate aminotransferase, mitochondrial (GOT2). [41]
THAPSIGARGIN DMDMQIE Preclinical THAPSIGARGIN decreases the expression of Aspartate aminotransferase, mitochondrial (GOT2). [44]
[3H]methyltrienolone DMTSGOW Investigative [3H]methyltrienolone increases the expression of Aspartate aminotransferase, mitochondrial (GOT2). [45]
------------------------------------------------------------------------------------
⏷ Show the Full List of 12 Drug(s)
3 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Fulvestrant DM0YZC6 Approved Fulvestrant increases the methylation of Aspartate aminotransferase, mitochondrial (GOT2). [39]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene affects the methylation of Aspartate aminotransferase, mitochondrial (GOT2). [43]
Bisphenol A DM2ZLD7 Investigative Bisphenol A increases the methylation of Aspartate aminotransferase, mitochondrial (GOT2). [39]
------------------------------------------------------------------------------------

References

1 Cisplatin binding and inactivation of mitochondrial glutamate oxaloacetate transaminase in cisplatin-induced rat nephrotoxicity.Biosci Biotechnol Biochem. 2013;77(8):1645-9. doi: 10.1271/bbb.130172. Epub 2013 Aug 7.
2 Intestinal fatty acid-binding protein levels in patients with chronic renal failure.J Surg Res. 2018 Oct;230:94-100. doi: 10.1016/j.jss.2018.04.057. Epub 2018 May 25.
3 Tissue and cell-specific patterns of expression of rat liver and intestinal fatty acid binding protein during development and in experimental colonic and small intestinal adenocarcinomas.Lab Invest. 1993 Jun;68(6):663-75.
4 Intestinal fatty acid binding protein Ala54Thr polymorphism is associated with peripheral atherosclerosis combined with type 2 diabetes mellitus.J Diabetes. 2017 Sep;9(9):821-826. doi: 10.1111/1753-0407.12496. Epub 2016 Dec 9.
5 Gene Polymorphisms of ADIPOQ +45T>G, UCP2 -866G>A, and FABP2 Ala54Thr on the Risk of Colorectal Cancer: A Matched Case-Control Study.PLoS One. 2013 Jun 27;8(6):e67275. doi: 10.1371/journal.pone.0067275. Print 2013.
6 Parallel Changes in Harvey-Bradshaw Index, TNF, and Intestinal Fatty Acid Binding Protein in Response to Infliximab in Crohn's Disease.Gastroenterol Res Pract. 2017;2017:1745918. doi: 10.1155/2017/1745918. Epub 2017 Oct 23.
7 Targeted Exome Sequencing of Krebs Cycle Genes Reveals Candidate Cancer-Predisposing Mutations in Pheochromocytomas and Paragangliomas. Clin Cancer Res. 2017 Oct 15;23(20):6315-6324. doi: 10.1158/1078-0432.CCR-16-2250. Epub 2017 Jul 18.
8 Reversed glucose and fatty acids transporter expression in human endometrial cancer.Horm Metab Res. 2012 Jun;44(6):436-41. doi: 10.1055/s-0031-1301301. Epub 2012 Feb 20.
9 HCV-RNA and anti-HCV IgM in Egyptian subjects bearing IgG anti-HCV antibodies.Jpn J Infect Dis. 1999 Jun;52(3):113-6.
10 Altered epidermal fatty acid-binding protein expression in hepatocellular carcinoma predicts unfavorable outcomes.Cancer Manag Res. 2018 Nov 23;10:6275-6284. doi: 10.2147/CMAR.S181555. eCollection 2018.
11 Serum aminotransferases in nonalcoholic fatty liver disease are a signature of liver metabolic perturbations at the amino acid and Krebs cycle level.Am J Clin Nutr. 2016 Feb;103(2):422-34. doi: 10.3945/ajcn.115.118695. Epub 2016 Jan 20.
12 Bi-allelic GOT2 Mutations Cause a Treatable Malate-Aspartate Shuttle-Related Encephalopathy.Am J Hum Genet. 2019 Sep 5;105(3):534-548. doi: 10.1016/j.ajhg.2019.07.015. Epub 2019 Aug 15.
13 Cooperative STAT/NF-B signaling regulates lymphoma metabolic reprogramming and aberrant GOT2 expression.Nat Commun. 2018 Apr 17;9(1):1514. doi: 10.1038/s41467-018-03803-x.
14 Interaction of brain fatty acid-binding protein with the polyunsaturated fatty acid environment as a potential determinant of poor prognosis in malignant glioma.Prog Lipid Res. 2013 Oct;52(4):562-70. doi: 10.1016/j.plipres.2013.08.004. Epub 2013 Aug 24.
15 Mitochondrial glutamine metabolism via GOT2 supports pancreatic cancer growth through senescence inhibition.Cell Death Dis. 2018 Jan 19;9(2):55. doi: 10.1038/s41419-017-0089-1.
16 Inhibition of oncogenic Src induces FABP4-mediated lipolysis via PPAR activation exerting cancer growth suppression.EBioMedicine. 2019 Mar;41:134-145. doi: 10.1016/j.ebiom.2019.02.015. Epub 2019 Feb 10.
17 Development and characterization of two human tumor sublines expressing high-grade resistance to the cyanoguanidine CHS 828.Anticancer Drugs. 2004 Jan;15(1):45-54. doi: 10.1097/00001813-200401000-00008.
18 Liver fatty acid-binding protein might be a predictive marker of clinical response to systemic treatment in psoriasis.Arch Dermatol Res. 2019 Jul;311(5):389-397. doi: 10.1007/s00403-019-01917-w. Epub 2019 Apr 16.
19 Detection of transcript for brain-type fatty Acid-binding protein in tumor and urine of patients with renal cell carcinoma.Urology. 2007 Feb;69(2):236-40. doi: 10.1016/j.urology.2006.09.060.
20 Fatty acid composition and fatty acid binding protein expression in the postmortem frontal cortex of patients with schizophrenia: A case-control study.Schizophr Res. 2016 Mar;171(1-3):225-32. doi: 10.1016/j.schres.2016.01.014. Epub 2016 Jan 17.
21 Targeting the proteasome as a promising therapeutic strategy in thyroid cancer.J Surg Oncol. 2012 Mar 15;105(4):357-64. doi: 10.1002/jso.22113. Epub 2011 Oct 17.
22 Synergy of a herpes oncolytic virus and paclitaxel for anaplastic thyroid cancer.Clin Cancer Res. 2008 Mar 1;14(5):1519-28. doi: 10.1158/1078-0432.CCR-07-4628.
23 Computational prediction and experimental validation associating FABP-1 and pancreatic adenocarcinoma with diabetes.BMC Gastroenterol. 2011 Jan 20;11:5. doi: 10.1186/1471-230X-11-5.
24 A novel fatty acid-binding protein 5-estrogen-related receptor signaling pathway promotes cell growth and energy metabolism in prostate cancer cells.Oncotarget. 2018 Aug 3;9(60):31753-31770. doi: 10.18632/oncotarget.25878. eCollection 2018 Aug 3.
25 Hepatic adenomas with synchronous or metachronous fibrolamellar carcinomas: both are characterized by LFABP loss.Mod Pathol. 2016 Jun;29(6):607-15. doi: 10.1038/modpathol.2016.59. Epub 2016 Mar 25.
26 Human liver fatty acid binding protein (hFABP1) gene is regulated by liver-enriched transcription factors HNF3 and C/EBP.Biochimie. 2012 Feb;94(2):384-92. doi: 10.1016/j.biochi.2011.08.006. Epub 2011 Aug 16.
27 Study of FABP's interactome and detecting new molecular targets in clear cell renal cell carcinoma.J Cell Physiol. 2020 Apr;235(4):3776-3789. doi: 10.1002/jcp.29272. Epub 2019 Oct 10.
28 Metabolic Syndrome is Associated with Ceramide Accumulation in Visceral Adipose Tissue of Women with Morbid Obesity.Obesity (Silver Spring). 2019 Mar;27(3):444-453. doi: 10.1002/oby.22405. Epub 2019 Feb 5.
29 Preventing BRCA1/ZBRK1 repressor complex binding to the GOT2 promoter results in accelerated aspartate biosynthesis and promotion of cell proliferation.Mol Oncol. 2019 Apr;13(4):959-977. doi: 10.1002/1878-0261.12466. Epub 2019 Mar 1.
30 Impaired Skeletal Muscle Kynurenine Metabolism in Patients with Chronic Obstructive Pulmonary Disease.J Clin Med. 2019 Jun 26;8(7):915. doi: 10.3390/jcm8070915.
31 Serum zonulin is elevated in IBS and correlates with stool frequency in IBS-D.United European Gastroenterol J. 2019 Jun;7(5):709-715. doi: 10.1177/2050640619826419. Epub 2019 Jan 19.
32 -3 and -6 Fatty Acids Modulate Conventional and Atypical Protein Kinase C Activities in a Brain Fatty Acid Binding Protein Dependent Manner in Glioblastoma Multiforme.Nutrients. 2018 Apr 6;10(4):454. doi: 10.3390/nu10040454.
33 Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
34 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.
35 Expression Profiling of Human Pluripotent Stem Cell-Derived Cardiomyocytes Exposed to Doxorubicin-Integration and Visualization of Multi-Omics Data. Toxicol Sci. 2018 May 1;163(1):182-195. doi: 10.1093/toxsci/kfy012.
36 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.
37 Nucleophosmin in the pathogenesis of arsenic-related bladder carcinogenesis revealed by quantitative proteomics. Toxicol Appl Pharmacol. 2010 Jan 15;242(2):126-35. doi: 10.1016/j.taap.2009.09.016. Epub 2009 Oct 7.
38 Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
39 DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
40 Growth inhibition of ovarian tumor-initiating cells by niclosamide. Mol Cancer Ther. 2012 Aug;11(8):1703-12.
41 Comparative proteomics reveals concordant and discordant biochemical effects of caffeine versus epigallocatechin-3-gallate in human endothelial cells. Toxicol Appl Pharmacol. 2019 Sep 1;378:114621. doi: 10.1016/j.taap.2019.114621. Epub 2019 Jun 10.
42 Quantitative proteomics and transcriptomics addressing the estrogen receptor subtype-mediated effects in T47D breast cancer cells exposed to the phytoestrogen genistein. Mol Cell Proteomics. 2011 Jan;10(1):M110.002170.
43 Effect of aflatoxin B(1), benzo[a]pyrene, and methapyrilene on transcriptomic and epigenetic alterations in human liver HepaRG cells. Food Chem Toxicol. 2018 Nov;121:214-223. doi: 10.1016/j.fct.2018.08.034. Epub 2018 Aug 26.
44 Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
45 Androgen-dependent regulation of medium and long chain fatty acids uptake in prostate cancer. Prostate. 2007 Sep 1;67(12):1330-8. doi: 10.1002/pros.20609.
46 ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.