Details of Drug Off-Target (DOT)

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

DOT Name NK-tumor recognition protein (NKTR)
Synonyms NK-TR protein; Natural-killer cells cyclophilin-related protein; Peptidyl-prolyl cis-trans isomerase NKTR; PPIase; EC 5.2.1.8; Rotamase
Gene Name NKTR
Related Disease
Neoplasm ( )
Abdominal aortic aneurysm ( )
Abscess ( )
Amyotrophic lateral sclerosis type 1 ( )
Analgesia ( )
Gastric disease ( )
Non-small-cell lung cancer ( )
Parkinson disease ( )
Retinoblastoma ( )
UniProt ID
NKTR_HUMAN
3D Structure
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2D Sequence (FASTA)
Download
3D Structure (PDB)
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PDB ID
2HE9
EC Number
5.2.1.8
Pfam ID
PF00160
Sequence
MGAQDRPQCHFDIEINREPVGRIMFQLFSDICPKTCKNFLCLCSGEKGLGKTTGKKLCYK
GSTFHRVVKNFMIQGGDFSEGNGKGGESIYGGYFKDENFILKHDRAFLLSMANRGKHTNG
SQFFITTKPAPHLDGVHVVFGLVISGFEVIEQIENLKTDAASRPYADVRVIDCGVLATKS
IKDVFEKKRKKPTHSEGSDSSSNSSSSSESSSESELEHERSRRRKHKRRPKVKRSKKRRK
EASSSEEPRNKHAMNPKGHSERSDTNEKRSVDSSAKREKPVVRPEEIPPVPENRFLLRRD
MPVVTAEPEPKIPDVAPIVSDQKPSVSKSGRKIKGRGTIRYHTPPRSRSCSESDDDDSSE
TPPHWKEEMQRLRAYRPPSGEKWSKGDKLSDPCSSRWDERSLSQRSRSWSYNGYYSDLST
ARHSGHHKKRRKEKKVKHKKKGKKQKHCRRHKQTKKRRILIPSDIESSKSSTRRMKSSCD
RERSSRSSSLSSHHSSKRDWSKSDKDVQSSLTHSSRDSYRSKSHSQSYSRGSSRSRTASK
SSSHSRSRSKSRSSSKSGHRKRASKSPRKTASQLSENKPVKTEPLRATMAQNENVVVQPV
VAENIPVIPLSDSPPPSRWKPGQKPWKPSYERIQEMKAKTTHLLPIQSTYSLANIKETGS
SSSYHKREKNSESDQSTYSKYSDRSSESSPRSRSRSSRSRSYSRSYTRSRSLASSHSRSR
SPSSRSHSRNKYSDHSQCSRSSSYTSISSDDGRRAKRRLRSSGKKNSVSHKKHSSSSEKT
LHSKYVKGRDRSSCVRKYSESRSSLDYSSDSEQSSVQATQSAQEKEKQGQMERTHNKQEK
NRGEEKSKSERECPHSKKRTLKENLSDHLRNGSKPKRKNYAGSKWDSESNSERDVTKNSK
NDSHPSSDKEEGEATSDSESEVSEIHIKVKPTTKSSTNTSLPDDNGAWKSSKQRTSTSDS
EGSCSNSENNRGKPQKHKHGSKENLKREHTKKVKEKLKGKKDKKHKAPKRKQAFHWQPPL
EFGEEEEEEIDDKQVTQESKEKKVSENNETIKDNILKTEKSSEEDLSGKHDTVTVSSDLD
QFTKDDSKLSISPTALNTEENVACLQNIQHVEESVPNGVEDVLQTDDNMEICTPDRSSPA
KVEETSPLGNARLDTPDINIVLKQDMATEHPQAEVVKQESSMSESKVLGEVGKQDSSSAS
LASAGESTGKKEVAEKSQINLIDKKWKPLQGVGNLAAPNAATSSAVEVKVLTTVPEMKPQ
GLRIEIKSKNKVRPGSLFDEVRKTARLNRRPRNQESSSDEQTPSRDDDSQSRSPSRSRSK
SETKSRHRTRSVSYSHSRSRSRSSTSSYRSRSYSRSRSRGWYSRGRTRSRSSSYRSYKSH
RTSSRSRSRSSSYDPHSRSRSYTYDSYYSRSRSRSRSQRSDSYHRGRSYNRRSRSCRSYG
SDSESDRSYSHHRSPSESSRYS
Function
PPIase that catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides and may therefore assist protein folding. Component of a putative tumor-recognition complex involved in the function of NK cells.

Molecular Interaction Atlas (MIA) of This DOT

9 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Neoplasm DISZKGEW Definitive Biomarker [1]
Abdominal aortic aneurysm DISD06OF Strong Biomarker [2]
Abscess DISAP982 Strong Biomarker [3]
Amyotrophic lateral sclerosis type 1 DIS5A2M0 Strong Biomarker [4]
Analgesia DISK3TVI Strong Biomarker [5]
Gastric disease DISNZNTG Strong Biomarker [6]
Non-small-cell lung cancer DIS5Y6R9 Strong Biomarker [7]
Parkinson disease DISQVHKL Strong Biomarker [8]
Retinoblastoma DISVPNPB Strong Biomarker [9]
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⏷ Show the Full List of 9 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
5 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 NK-tumor recognition protein (NKTR). [10]
Arsenic DMTL2Y1 Approved Arsenic affects the methylation of NK-tumor recognition protein (NKTR). [14]
TAK-243 DM4GKV2 Phase 1 TAK-243 decreases the sumoylation of NK-tumor recognition protein (NKTR). [20]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 affects the phosphorylation of NK-tumor recognition protein (NKTR). [21]
Coumarin DM0N8ZM Investigative Coumarin affects the phosphorylation of NK-tumor recognition protein (NKTR). [21]
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13 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Acetaminophen DMUIE76 Approved Acetaminophen increases the expression of NK-tumor recognition protein (NKTR). [11]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate affects the expression of NK-tumor recognition protein (NKTR). [12]
Cisplatin DMRHGI9 Approved Cisplatin decreases the expression of NK-tumor recognition protein (NKTR). [13]
Arsenic trioxide DM61TA4 Approved Arsenic trioxide decreases the expression of NK-tumor recognition protein (NKTR). [15]
Vorinostat DMWMPD4 Approved Vorinostat decreases the expression of NK-tumor recognition protein (NKTR). [16]
Marinol DM70IK5 Approved Marinol increases the expression of NK-tumor recognition protein (NKTR). [17]
Selenium DM25CGV Approved Selenium decreases the expression of NK-tumor recognition protein (NKTR). [18]
Testosterone enanthate DMB6871 Approved Testosterone enanthate affects the expression of NK-tumor recognition protein (NKTR). [19]
Tocopherol DMBIJZ6 Phase 2 Tocopherol decreases the expression of NK-tumor recognition protein (NKTR). [18]
Geldanamycin DMS7TC5 Discontinued in Phase 2 Geldanamycin increases the expression of NK-tumor recognition protein (NKTR). [22]
Bisphenol A DM2ZLD7 Investigative Bisphenol A increases the expression of NK-tumor recognition protein (NKTR). [23]
Milchsaure DM462BT Investigative Milchsaure increases the expression of NK-tumor recognition protein (NKTR). [24]
CH-223191 DMMJZYC Investigative CH-223191 increases the expression of NK-tumor recognition protein (NKTR). [25]
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⏷ Show the Full List of 13 Drug(s)

References

1 A First-in-Human Study and Biomarker Analysis of NKTR-214, a Novel IL2R-Biased Cytokine, in Patients with Advanced or Metastatic Solid Tumors.Cancer Discov. 2019 Jun;9(6):711-721. doi: 10.1158/2159-8290.CD-18-1495. Epub 2019 Apr 15.
2 Differential gene expression in human abdominal aortic aneurysm and aortic occlusive disease.Oncotarget. 2015 May 30;6(15):12984-96. doi: 10.18632/oncotarget.3848.
3 Novel Regulation of Alpha-Toxin and the Phenol-Soluble Modulins by Peptidyl-Prolyl cis/trans Isomerase Enzymes in Staphylococcus aureus.Toxins (Basel). 2019 Jun 16;11(6):343. doi: 10.3390/toxins11060343.
4 The role of immunophilins in mutant superoxide dismutase-1linked familial amyotrophic lateral sclerosis.Proc Natl Acad Sci U S A. 1999 Mar 16;96(6):3251-6. doi: 10.1073/pnas.96.6.3251.
5 SUMMIT-07: a randomized trial of NKTR-181, a new molecular entity, full mu-opioid receptor agonist for chronic low-back pain.Pain. 2019 Jun;160(6):1374-1382. doi: 10.1097/j.pain.0000000000001517.
6 Differential Proteomic Analysis Reveals Protein Networks and Pathways that May Contribute to Helicobacter pylori FKBP-Type PPIase-Associated Gastric Diseases.Proteomics Clin Appl. 2018 May;12(3):e1700127. doi: 10.1002/prca.201700127. Epub 2017 Dec 5.
7 Analysis of gene expression profiles of non-small cell lung cancer at different stages reveals significantly altered biological functions and candidate genes.Oncol Rep. 2017 Mar;37(3):1736-1746. doi: 10.3892/or.2017.5380. Epub 2017 Jan 17.
8 The Molecular Basis of the Interaction of CyclophilinA with -Synuclein.Angew Chem Int Ed Engl. 2020 Mar 27;59(14):5643-5646. doi: 10.1002/anie.201914878. Epub 2020 Jan 29.
9 Deletion of a splice donor site ablates expression of the following exon and produces an unphosphorylated RB protein unable to bind SV40 T antigen.Cell Growth Differ. 1990 Jan;1(1):17-25.
10 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.
11 Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
12 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
13 Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
14 Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
15 Chronic occupational exposure to arsenic induces carcinogenic gene signaling networks and neoplastic transformation in human lung epithelial cells. Toxicol Appl Pharmacol. 2012 Jun 1;261(2):204-16.
16 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.
17 Delta9-tetrahydrocannabinol inhibits cytotrophoblast cell proliferation and modulates gene transcription. Mol Hum Reprod. 2006 May;12(5):321-33. doi: 10.1093/molehr/gal036. Epub 2006 Apr 5.
18 Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
19 Transcriptional profiling of testosterone-regulated genes in the skeletal muscle of human immunodeficiency virus-infected men experiencing weight loss. J Clin Endocrinol Metab. 2007 Jul;92(7):2793-802. doi: 10.1210/jc.2006-2722. Epub 2007 Apr 17.
20 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.
21 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.
22 Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration. Arch Toxicol. 2016 Jan;90(1):159-80.
23 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.
24 Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
25 Adaptive changes in global gene expression profile of lung carcinoma A549 cells acutely exposed to distinct types of AhR ligands. Toxicol Lett. 2018 Aug;292:162-174.