Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT1ZU6JB)

DOT Name Protein NPAT (NPAT)
Synonyms Nuclear protein of the ataxia telangiectasia mutated locus; Nuclear protein of the ATM locus; p220
Gene Name NPAT
Related Disease
Cervical cancer ( )
Cervical carcinoma ( )
Ataxia-telangiectasia ( )
Classic Hodgkin lymphoma ( )
Language disorder ( )
Small lymphocytic lymphoma ( )
Neoplasm ( )
UniProt ID
NPAT_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Pfam ID
PF15712
Sequence
MLLPSDVARLVLGYLQQENLISTCQTFILESSDLKEYAEHCTDEGFIPACLLSLFGKNLT
TILNEYVAMKTKETSNNVPAIMSSLWKKLDHTLSQIRSMQSSPRFAGSQRARTRTGIAEI
KRQRKLASQTAPASAELLTLPYLSGQFTTPPSTGTQVTRPSGQISDPSRSYFVVVNHSQS
QDTVTTGEALNVIPGAQEKKAHASLMSPGRRKSESQRKSTTLSGPHSTIRNFQDPNAFAV
EKQMVIENAREKILSNKSLQEKLAENINKFLTSDNNIAQVPKQTDNNPTEPETSIDEFLG
LPSEIHMSEEAIQDILEQTESDPAFQALFDLFDYGKTKNNKNISQSISSQPMESNPSIVL
ADETNLAVKGSFETEESDGQSGQPAFCTSYQNDDPLNALKNSNNHDVLRQEDQENFSQIS
TSIQKKAFKTAVPTEQKCDIDITFESVPNLNDFNQRGNSNAECNPHCAELYTNQMSTETE
MAIGIEKNSLSSNVPSESQLQPDQPDIPITSFVSLGCEANNENLILSGKSSQLLSQDTSL
TGKPSKKSQFCENSNDTVKLKINFHGSKSSDSSEVHKSKIEINVLEPVMSQLSNCQDNSC
LQSEILPVSVESSHLNVSGQVEIHLGDSLSSTKQPSNDSASVELNHTENEAQASKSENSQ
EPSSSVKEENTIFLSLGGNANCEKVALTPPEGTPVENSHSLPPESVCSSVGDSHPESQNT
DDKPSSNNSAEIDASNIVSLKVIISDDPFVSSDTELTSAVSSINGENLPTIILSSPTKSP
TKNAELVKCLSSEETVGAVVYAEVGDSASMEQSLLTFKSEDSAVNNTQNEDGIAFSANVT
PCVSKDGGYIQLMPATSTAFGNSNNILIATCVTDPTALGTSVSQSNVVVLPGNSAPMTAQ
PLPPQLQTPPRSNSVFAVNQAVSPNFSQGSAIIIASPVQPVLQGMVGMIPVSVVGQNGNN
FSTPPRQVLHMPLTAPVCNRSIPQFPVPPKSQKAQGLRNKPCIGKQVNNLVDSSGHSVGC
HAQKTEVSDKSIATDLGKKSEETTVPFPEESIVPAAKPCHRRVLCFDSTTAPVANTQGPN
HKMVSQNKERNAVSFPNLDSPNVSSTLKPPSNNAIKREKEKPPLPKILSKSESAISRHTT
IRETQSEKKVSPTEIVLESFHKATANKENELCSDVERQKNPENSKLSIGQQNGGLRSEKS
IASLQEMTKKQGTSSNNKNVLSVGTAVKDLKQEQTKSASSLITTEMLQDIQRHSSVSRLA
DSSDLPVPRTPGSGAGEKHKEEPIDIIKAPSSRRFSEDSSTSKVMVPPVTPDLPACSPAS
ETGSENSVNMAAHTLMILSRAAISRTTSATPLKDNTQQFRASSRSTTKKRKIEELDERER
NSRPSSKNLTNSSIPMKKKKIKKKKLPSSFPAGMDVDKFLLSLHYDE
Function
Required for progression through the G1 and S phases of the cell cycle and for S phase entry. Activates transcription of the histone H2A, histone H2B, histone H3 and histone H4 genes in conjunction with MIZF. Also positively regulates the ATM, MIZF and PRKDC promoters. Transcriptional activation may be accomplished at least in part by the recruitment of the NuA4 histone acetyltransferase (HAT) complex to target gene promoters.
Tissue Specificity Ubiquitously expressed.

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Cervical cancer DISFSHPF Definitive Genetic Variation [1]
Cervical carcinoma DIST4S00 Definitive Genetic Variation [1]
Ataxia-telangiectasia DISP3EVR Strong Biomarker [2]
Classic Hodgkin lymphoma DISV1LU6 Strong Genetic Variation [3]
Language disorder DISTLKP7 Strong Biomarker [2]
Small lymphocytic lymphoma DIS30POX Strong Biomarker [4]
Neoplasm DISZKGEW Limited Altered Expression [5]
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⏷ Show the Full List of 7 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
2 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 Protein NPAT (NPAT). [6]
TAK-243 DM4GKV2 Phase 1 TAK-243 increases the sumoylation of Protein NPAT (NPAT). [12]
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8 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 Protein NPAT (NPAT). [7]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Protein NPAT (NPAT). [8]
Vorinostat DMWMPD4 Approved Vorinostat increases the expression of Protein NPAT (NPAT). [9]
Zoledronate DMIXC7G Approved Zoledronate increases the expression of Protein NPAT (NPAT). [10]
Clorgyline DMCEUJD Approved Clorgyline increases the expression of Protein NPAT (NPAT). [11]
Trichostatin A DM9C8NX Investigative Trichostatin A affects the expression of Protein NPAT (NPAT). [13]
Formaldehyde DM7Q6M0 Investigative Formaldehyde decreases the expression of Protein NPAT (NPAT). [14]
Milchsaure DM462BT Investigative Milchsaure decreases the expression of Protein NPAT (NPAT). [15]
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⏷ Show the Full List of 8 Drug(s)

References

1 Genetic variants of NPAT-ATM and AURKA are associated with an early adverse reaction in the gastrointestinal tract of patients with cervical cancer treated with pelvic radiation therapy.Int J Radiat Oncol Biol Phys. 2011 Nov 15;81(4):1144-52. doi: 10.1016/j.ijrobp.2010.09.012. Epub 2010 Nov 2.
2 Runs of homozygosity associated with speech delay in autism in a taiwanese han population: evidence for the recessive model.PLoS One. 2013 Aug 16;8(8):e72056. doi: 10.1371/journal.pone.0072056. eCollection 2013.
3 Exome sequencing reveals germline NPAT mutation as a candidate risk factor for Hodgkin lymphoma.Blood. 2011 Jul 21;118(3):493-8. doi: 10.1182/blood-2011-03-341560. Epub 2011 May 11.
4 Analysis of 11q22-q23 deletion target genes in B-cell chronic lymphocytic leukaemia: evidence for a pathogenic role of NPAT, CUL5, and PPP2R1B.Eur J Cancer. 2007 May;43(8):1328-35. doi: 10.1016/j.ejca.2007.02.005. Epub 2007 Apr 20.
5 Global methylation pattern of genes in androgen-sensitive and androgen-independent prostate cancer cells.Mol Cancer Ther. 2010 Jan;9(1):33-45. doi: 10.1158/1535-7163.MCT-09-0486. Epub 2010 Jan 6.
6 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.
7 Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
8 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.
9 A genomic approach to predict synergistic combinations for breast cancer treatment. Pharmacogenomics J. 2013 Feb;13(1):94-104. doi: 10.1038/tpj.2011.48. Epub 2011 Nov 15.
10 The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
11 Anti-oncogenic and pro-differentiation effects of clorgyline, a monoamine oxidase A inhibitor, on high grade prostate cancer cells. BMC Med Genomics. 2009 Aug 20;2:55. doi: 10.1186/1755-8794-2-55.
12 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.
13 A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.
14 Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.
15 Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.