Details of Drug Off-Target (DOT)

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
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]
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Molecular Interaction Atlas (MIA)

MIA Detail

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]
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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.