General Information of Drug Off-Target (DOT) (ID: OT0VO6AY)

DOT Name NTF2-related export protein 1 (NXT1)
Synonyms Protein p15
Gene Name NXT1
Related Disease
Bladder cancer ( )
Chromosomal disorder ( )
Pancreatic cancer ( )
Transitional cell carcinoma ( )
Urinary bladder neoplasm ( )
Acute monocytic leukemia ( )
Adult T-cell leukemia/lymphoma ( )
Advanced cancer ( )
Astrocytoma ( )
Breast cancer ( )
Breast carcinoma ( )
Carcinoma of esophagus ( )
Colorectal carcinoma ( )
Follicular lymphoma ( )
Haematological malignancy ( )
Head-neck squamous cell carcinoma ( )
Hepatitis B virus infection ( )
Hepatitis C virus infection ( )
Hepatocellular carcinoma ( )
Leukemia ( )
Lymphoma ( )
Myelodysplastic syndrome ( )
Neoplasm of esophagus ( )
Non-small-cell lung cancer ( )
Ovarian neoplasm ( )
Plasma cell myeloma ( )
Promyelocytic leukaemia ( )
Prostate cancer ( )
Schistosomiasis ( )
Small lymphocytic lymphoma ( )
Squamous cell carcinoma ( )
T-cell acute lymphoblastic leukaemia ( )
T-cell lymphoma ( )
Urinary bladder cancer ( )
Acute lymphocytic leukaemia ( )
Acute myelogenous leukaemia ( )
Gastric cancer ( )
Lung adenocarcinoma ( )
Malignant mesothelioma ( )
Childhood acute lymphoblastic leukemia ( )
Acute leukaemia ( )
Carcinoma ( )
leukaemia ( )
Lymphoma, non-Hodgkin, familial ( )
Non-hodgkin lymphoma ( )
Retinoblastoma ( )
Stomach cancer ( )
T-cell leukaemia ( )
UniProt ID
NXT1_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
PDB ID
1JKG; 1JN5; 4WYK; 6E5U
Pfam ID
PF02136
Sequence
MASVDFKTYVDQACRAAEEFVNVYYTTMDKRRRLLSRLYMGTATLVWNGNAVSGQESLSE
FFEMLPSSEFQISVVDCQPVHDEATPSQTTVLVVICGSVKFEGNKQRDFNQNFILTAQAS
PSNTVWKIASDCFRFQDWAS
Function
Stimulator of protein export for NES-containing proteins. Also plays a role in the nuclear export of U1 snRNA, tRNA, and mRNA. The NXF1-NXT1 heterodimer is involved in the export of HSP70 mRNA in conjunction with ALYREF/THOC4 and THOC5.
KEGG Pathway
Ribosome biogenesis in eukaryotes (hsa03008 )
Nucleocytoplasmic transport (hsa03013 )
mR. surveillance pathway (hsa03015 )
Amyotrophic lateral sclerosis (hsa05014 )
Influenza A (hsa05164 )
Reactome Pathway
Transport of Mature mRNA derived from an Intron-Containing Transcript (R-HSA-159236 )

Molecular Interaction Atlas (MIA) of This DOT

48 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Bladder cancer DISUHNM0 Definitive Biomarker [1]
Chromosomal disorder DISM5BB5 Definitive Genetic Variation [2]
Pancreatic cancer DISJC981 Definitive Biomarker [3]
Transitional cell carcinoma DISWVVDR Definitive Altered Expression [1]
Urinary bladder neoplasm DIS7HACE Definitive Biomarker [1]
Acute monocytic leukemia DIS28NEL Strong Posttranslational Modification [4]
Adult T-cell leukemia/lymphoma DIS882XU Strong Biomarker [5]
Advanced cancer DISAT1Z9 Strong Biomarker [6]
Astrocytoma DISL3V18 Strong Genetic Variation [7]
Breast cancer DIS7DPX1 Strong Posttranslational Modification [8]
Breast carcinoma DIS2UE88 Strong Posttranslational Modification [8]
Carcinoma of esophagus DISS6G4D Strong Altered Expression [9]
Colorectal carcinoma DIS5PYL0 Strong Biomarker [10]
Follicular lymphoma DISVEUR6 Strong Posttranslational Modification [11]
Haematological malignancy DISCDP7W Strong Biomarker [12]
Head-neck squamous cell carcinoma DISF7P24 Strong Posttranslational Modification [13]
Hepatitis B virus infection DISLQ2XY Strong Biomarker [14]
Hepatitis C virus infection DISQ0M8R Strong Biomarker [14]
Hepatocellular carcinoma DIS0J828 Strong Altered Expression [15]
Leukemia DISNAKFL Strong Genetic Variation [16]
Lymphoma DISN6V4S Strong Biomarker [17]
Myelodysplastic syndrome DISYHNUI Strong Posttranslational Modification [18]
Neoplasm of esophagus DISOLKAQ Strong Altered Expression [9]
Non-small-cell lung cancer DIS5Y6R9 Strong Genetic Variation [19]
Ovarian neoplasm DISEAFTY Strong Posttranslational Modification [20]
Plasma cell myeloma DIS0DFZ0 Strong Posttranslational Modification [21]
Promyelocytic leukaemia DISYGG13 Strong Posttranslational Modification [22]
Prostate cancer DISF190Y Strong Genetic Variation [23]
Schistosomiasis DIS6PD44 Strong Genetic Variation [24]
Small lymphocytic lymphoma DIS30POX Strong Biomarker [25]
Squamous cell carcinoma DISQVIFL Strong Genetic Variation [26]
T-cell acute lymphoblastic leukaemia DIS17AI2 Strong Altered Expression [27]
T-cell lymphoma DISSXRTQ Strong Altered Expression [28]
Urinary bladder cancer DISDV4T7 Strong Biomarker [1]
Acute lymphocytic leukaemia DISPX75S moderate Posttranslational Modification [18]
Acute myelogenous leukaemia DISCSPTN moderate Posttranslational Modification [18]
Gastric cancer DISXGOUK moderate Biomarker [29]
Lung adenocarcinoma DISD51WR moderate Biomarker [30]
Malignant mesothelioma DISTHJGH moderate Biomarker [31]
Childhood acute lymphoblastic leukemia DISJ5D6U Disputed Posttranslational Modification [18]
Acute leukaemia DISDQFDI Limited Biomarker [18]
Carcinoma DISH9F1N Limited Biomarker [23]
leukaemia DISS7D1V Limited Genetic Variation [16]
Lymphoma, non-Hodgkin, familial DISCXYIZ Limited Biomarker [32]
Non-hodgkin lymphoma DISS2Y8A Limited Biomarker [32]
Retinoblastoma DISVPNPB Limited Altered Expression [33]
Stomach cancer DISKIJSX Limited Biomarker [29]
T-cell leukaemia DISJ6YIF Limited Genetic Variation [34]
------------------------------------------------------------------------------------
⏷ Show the Full List of 48 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
14 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate affects the expression of NTF2-related export protein 1 (NXT1). [35]
Ciclosporin DMAZJFX Approved Ciclosporin increases the expression of NTF2-related export protein 1 (NXT1). [36]
Estradiol DMUNTE3 Approved Estradiol increases the expression of NTF2-related export protein 1 (NXT1). [37]
Temozolomide DMKECZD Approved Temozolomide increases the expression of NTF2-related export protein 1 (NXT1). [38]
Marinol DM70IK5 Approved Marinol decreases the expression of NTF2-related export protein 1 (NXT1). [39]
Phenobarbital DMXZOCG Approved Phenobarbital affects the expression of NTF2-related export protein 1 (NXT1). [40]
Demecolcine DMCZQGK Approved Demecolcine decreases the expression of NTF2-related export protein 1 (NXT1). [41]
Urethane DM7NSI0 Phase 4 Urethane decreases the expression of NTF2-related export protein 1 (NXT1). [42]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the expression of NTF2-related export protein 1 (NXT1). [43]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 decreases the expression of NTF2-related export protein 1 (NXT1). [44]
Formaldehyde DM7Q6M0 Investigative Formaldehyde decreases the expression of NTF2-related export protein 1 (NXT1). [45]
Milchsaure DM462BT Investigative Milchsaure increases the expression of NTF2-related export protein 1 (NXT1). [46]
chloropicrin DMSGBQA Investigative chloropicrin decreases the expression of NTF2-related export protein 1 (NXT1). [47]
methyl p-hydroxybenzoate DMO58UW Investigative methyl p-hydroxybenzoate increases the expression of NTF2-related export protein 1 (NXT1). [48]
------------------------------------------------------------------------------------
⏷ Show the Full List of 14 Drug(s)

References

1 Deletions of p15 and p16 in schistosomal bladder cancer correlate with transforming growth factor-alpha expression.Clin Biochem. 2004 Dec;37(12):1098-104. doi: 10.1016/j.clinbiochem.2004.09.006.
2 Concomitant aberrant methylation of p15 and MGMT genes in acute myeloid leukemia: association with a particular immunophenotype of blast cells.Med Oncol. 2012 Dec;29(5):3547-56. doi: 10.1007/s12032-012-0289-6. Epub 2012 Jul 7.
3 Blind SELEX Approach Identifies RNA Aptamers That Regulate EMT and Inhibit Metastasis.Mol Cancer Res. 2017 Jul;15(7):811-820. doi: 10.1158/1541-7786.MCR-16-0462. Epub 2017 Apr 10.
4 KG-1 and KG-1a model the p15 CpG island methylation observed in acute myeloid leukemia patients.Leuk Res. 2001 Oct;25(10):917-25. doi: 10.1016/s0145-2126(01)00053-4.
5 Role of tumor suppressor genes in the development of adult T cell leukemia/lymphoma (ATLL).Leukemia. 2002 Jun;16(6):1069-85. doi: 10.1038/sj.leu.2402458.
6 Long Noncoding RNA ANRIL Regulates Proliferation of Non-small Cell Lung Cancer and Cervical Cancer Cells.Anticancer Res. 2015 Oct;35(10):5377-82.
7 Comparative genomic hybridization in glioma: a meta-analysis of 509 cases.Cancer Genet Cytogenet. 2002 Jun;135(2):147-59. doi: 10.1016/s0165-4608(01)00650-1.
8 Promoter hypermethylation of RAR2, DAPK, hMLH1, p14, and p15 is associated with progression of breast cancer: A PRISMA-compliant meta-analysis.Medicine (Baltimore). 2018 Dec;97(51):e13666. doi: 10.1097/MD.0000000000013666.
9 LncRNA SNHG7 promotes the proliferation of esophageal cancer cells and inhibits its apoptosis.Eur Rev Med Pharmacol Sci. 2018 May;22(9):2653-2661. doi: 10.26355/eurrev_201805_14961.
10 Long noncoding RNA BLACAT1 indicates a poor prognosis of colorectal cancer and affects cell proliferation by epigenetically silencing of p15.Cell Death Dis. 2017 Mar 9;8(3):e2665. doi: 10.1038/cddis.2017.83.
11 Frequent epigenetic inactivation of Rb1 in addition to p15 and p16 in mantle cell and follicular lymphoma.Hum Pathol. 2007 Dec;38(12):1849-57. doi: 10.1016/j.humpath.2007.05.009. Epub 2007 Sep 27.
12 Recent progress in molecular mechanisms of leukemogenesis: the cyclin-dependent kinase 4-inhibitor gene in human leukemias.Leukemia. 1997 Apr;11 Suppl 3:358-60.
13 Smoking and drinking can induce p15 methylation in the upper aerodigestive tract of healthy individuals and patients with head and neck squamous cell carcinoma.Cancer. 2004 Jul 1;101(1):125-32. doi: 10.1002/cncr.20323.
14 Aberrant promoter methylation profiles of tumor suppressor genes in hepatocellular carcinoma.Am J Pathol. 2003 Sep;163(3):1101-7. doi: 10.1016/S0002-9440(10)63469-4.
15 Depletion of histone demethylase KDM5B inhibits cell proliferation of hepatocellular carcinoma by regulation of cell cycle checkpoint proteins p15 and p27.J Exp Clin Cancer Res. 2016 Feb 25;35:37. doi: 10.1186/s13046-016-0311-5.
16 Regulation of DNA methylation and tumor suppression gene expression by miR-29b in leukemia patients and related mechanisms.Eur Rev Med Pharmacol Sci. 2018 Jan;22(1):158-165. doi: 10.26355/eurrev_201801_14113.
17 Different incidence and pattern of p15INK4b and p16INK4a promoter region hypermethylation in Hodgkin's and CD30-Positive non-Hodgkin's lymphomas.Am J Pathol. 2002 Sep;161(3):1007-13. doi: 10.1016/S0002-9440(10)64261-7.
18 Prognostic impact of p15 gene aberrations in acute leukemia.Leuk Lymphoma. 2017 Feb;58(2):257-265. doi: 10.1080/10428194.2016.1201574. Epub 2016 Jul 12.
19 Codeletion of p15 and p16 genes in primary non-small cell lung carcinoma.Cancer Res. 1995 Jul 15;55(14):2968-71.
20 Hypermethylation of P15, P16, and E-cadherin genes in ovarian cancer.Toxicol Ind Health. 2015 Oct;31(10):924-30. doi: 10.1177/0748233713484657. Epub 2013 Apr 9.
21 Aberrant promoter methylation of p15 (INKb) and p16 (INKa) genes may contribute to the pathogenesis of multiple myeloma: a meta-analysis.Tumour Biol. 2014 Sep;35(9):9035-43. doi: 10.1007/s13277-014-2054-2. Epub 2014 Jun 8.
22 p15(Ink4b) Loss of Expression by Promoter Hypermethylation Adds to Leukemogenesis and Confers a Poor Prognosis in Acute Promyelocytic Leukemia Patients.Cancer Res Treat. 2017 Jul;49(3):790-797. doi: 10.4143/crt.2016.108. Epub 2016 Dec 5.
23 Aneuploidy of chromosome 9 and the tumor suppressor genes p16(INK4) and p15(INK4B) detected by in situ hybridization in locally advanced prostate cancer.Eur Urol. 2000 Oct;38(4):475-82. doi: 10.1159/000020327.
24 Cell cycle regulators in bladder cancer: relationship to schistosomiasis.IUBMB Life. 2004 Sep;56(9):557-64. doi: 10.1080/15216540400013903.
25 CpG island methylation patterns in chronic lymphocytic leukemia.Leuk Lymphoma. 2009 Mar;50(3):419-26. doi: 10.1080/10428190902756594.
26 Epigenetic abnormalities in cutaneous squamous cell carcinomas: frequent inactivation of the RB1/p16 and p53 pathways.Br J Dermatol. 2006 Nov;155(5):999-1005. doi: 10.1111/j.1365-2133.2006.07487.x.
27 Universal inactivation of both p16 and p15 but not downstream components is an essential event in the pathogenesis of T-cell acute lymphoblastic leukemia.Clin Cancer Res. 2000 Apr;6(4):1219-28.
28 Frequent methylation silencing of p15(INK4b) (MTS2) and p16(INK4a) (MTS1) in B-cell and T-cell lymphomas.Blood. 1999 Sep 1;94(5):1773-81.
29 LncRNA SNHG17 promotes gastric cancer progression by epigenetically silencing of p15 and p57.J Cell Physiol. 2019 Apr;234(4):5163-5174. doi: 10.1002/jcp.27320. Epub 2018 Sep 6.
30 Association of p73 G4C14-to-A4T14 polymorphism at exon 2 with the response of human lung adenocarcinoma cell lines to chemotherapy.Cell Biol Int. 2010 Jan 25;34(2):185-8. doi: 10.1042/CBI20090148.
31 Fluorescence in situ hybridization in the definitive diagnosis of malignant mesothelioma in effusion cytology.Chest. 2010 Jul;138(1):137-44. doi: 10.1378/chest.09-1951. Epub 2010 Feb 5.
32 Frequent abnormalities of the p15 and p16 genes in mycosis fungoides and sezary syndrome.J Invest Dermatol. 2002 Mar;118(3):493-9. doi: 10.1046/j.0022-202x.2001.01682.x.
33 Biallelic deletions in INK4 in cutaneous melanoma are common and associated with decreased survival.Clin Cancer Res. 2005 Apr 15;11(8):2991-7. doi: 10.1158/1078-0432.CCR-04-1731.
34 Deletions of p15 and/or p16 genes as a poor-prognosis factor in adult T-cell leukemia.J Clin Oncol. 1997 May;15(5):1778-85. doi: 10.1200/JCO.1997.15.5.1778.
35 Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
36 Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
37 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
38 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.
39 THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
40 Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
41 Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
42 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
43 Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
44 Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
45 Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.
46 Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
47 Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.
48 Transcriptome dynamics of alternative splicing events revealed early phase of apoptosis induced by methylparaben in H1299 human lung carcinoma cells. Arch Toxicol. 2020 Jan;94(1):127-140. doi: 10.1007/s00204-019-02629-w. Epub 2019 Nov 20.