Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTIKQF3U)

DOT Name NSFL1 cofactor p47 (NSFL1C)
Synonyms UBX domain-containing protein 2C; p97 cofactor p47
Gene Name NSFL1C
Related Disease
Adult T-cell leukemia/lymphoma ( )
Chronic granulomatous disease ( )
Human T-lymphotropic virus 1 infectious disease ( )
Immunodeficiency ( )
Schizophrenia ( )
Vibrio cholerae infection ( )
Advanced cancer ( )
Asthma ( )
Malaria ( )
Type-1/2 diabetes ( )
UniProt ID
NSF1C_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
1SS6
Pfam ID
PF08059 ; PF14555 ; PF00789
Sequence
MAAERQEALREFVAVTGAEEDRARFFLESAGWDLQIALASFYEDGGDEDIVTISQATPSS
VSRGTAPSDNRVTSFRDLIHDQDEDEEEEEGQRFYAGGSERSGQQIVGPPRKKSPNELVD
DLFKGAKEHGAVAVERVTKSPGETSKPRPFAGGGYRLGAAPEEESAYVAGEKRQHSSQDV
HVVLKLWKSGFSLDNGELRSYQDPSNAQFLESIRRGEVPAELRRLAHGGQVNLDMEDHRD
EDFVKPKGAFKAFTGEGQKLGSTAPQVLSTSSPAQQAENEAKASSSILIDESEPTTNIQI
RLADGGRLVQKFNHSHRISDIRLFIVDARPAMAATSFILMTTFPNKELADESQTLKEANL
LNAVIVQRLT
Function
Reduces the ATPase activity of VCP. Necessary for the fragmentation of Golgi stacks during mitosis and for VCP-mediated reassembly of Golgi stacks after mitosis. May play a role in VCP-mediated formation of transitional endoplasmic reticulum (tER). Inhibits the activity of CTSL (in vitro). Together with UBXN2B/p37, regulates the centrosomal levels of kinase AURKA/Aurora A during mitotic progression by promoting AURKA removal from centrosomes in prophase. Also, regulates spindle orientation during mitosis.
KEGG Pathway
Protein processing in endoplasmic reticulum (hsa04141 )
Reactome Pathway
RHOH GTPase cycle (R-HSA-9013407 )

Molecular Interaction Atlas (MIA) of This DOT

10 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Adult T-cell leukemia/lymphoma DIS882XU Strong Altered Expression [1]
Chronic granulomatous disease DIS9ZR24 Strong Genetic Variation [2]
Human T-lymphotropic virus 1 infectious disease DISN5C4M Strong Biomarker [1]
Immunodeficiency DIS093I0 Strong Biomarker [3]
Schizophrenia DISSRV2N Strong Altered Expression [4]
Vibrio cholerae infection DISW7E3U Strong Biomarker [5]
Advanced cancer DISAT1Z9 moderate Biomarker [6]
Asthma DISW9QNS Limited Altered Expression [7]
Malaria DISQ9Y50 Limited Biomarker [8]
Type-1/2 diabetes DISIUHAP Limited Altered Expression [9]
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⏷ Show the Full List of 10 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
8 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 NSFL1 cofactor p47 (NSFL1C). [10]
Ciclosporin DMAZJFX Approved Ciclosporin increases the expression of NSFL1 cofactor p47 (NSFL1C). [11]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of NSFL1 cofactor p47 (NSFL1C). [12]
Temozolomide DMKECZD Approved Temozolomide increases the expression of NSFL1 cofactor p47 (NSFL1C). [15]
Benzatropine DMF7EXL Approved Benzatropine decreases the expression of NSFL1 cofactor p47 (NSFL1C). [16]
Tocopherol DMBIJZ6 Phase 2 Tocopherol increases the expression of NSFL1 cofactor p47 (NSFL1C). [17]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the expression of NSFL1 cofactor p47 (NSFL1C). [18]
Bisphenol A DM2ZLD7 Investigative Bisphenol A increases the expression of NSFL1 cofactor p47 (NSFL1C). [19]
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⏷ Show the Full List of 8 Drug(s)
3 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Arsenic DMTL2Y1 Approved Arsenic increases the ubiquitination of NSFL1 cofactor p47 (NSFL1C). [13]
Quercetin DM3NC4M Approved Quercetin decreases the phosphorylation of NSFL1 cofactor p47 (NSFL1C). [14]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 affects the phosphorylation of NSFL1 cofactor p47 (NSFL1C). [14]
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References

1 Degradation of p47 by autophagy contributes to CADM1 overexpression in ATLL cells through the activation of NF-B.Sci Rep. 2019 Mar 5;9(1):3491. doi: 10.1038/s41598-019-39424-7.
2 Aberrant [correction of Abberant] cytosolic calcium ion mobilization in chronic granulomatous disease neutrophils.Inflammation. 2004 Jun;28(3):133-8. doi: 10.1023/b:ifla.0000039559.96659.d9.
3 p47 licenses activation of the immune deficiency pathway in the tick Ixodes scapularis.Proc Natl Acad Sci U S A. 2019 Jan 2;116(1):205-210. doi: 10.1073/pnas.1808905116. Epub 2018 Dec 17.
4 Prefrontal cortex shotgun proteome analysis reveals altered calcium homeostasis and immune system imbalance in schizophrenia.Eur Arch Psychiatry Clin Neurosci. 2009 Apr;259(3):151-63. doi: 10.1007/s00406-008-0847-2. Epub 2009 Jan 22.
5 A Recombinant 47-kDa Outer Membrane Protein Induces an Immune Response against Orientia tsutsugamushi Strain Boryong.Am J Trop Med Hyg. 2017 Jul;97(1):30-37. doi: 10.4269/ajtmh.15-0771.
6 Loss of the eukaryotic initiation factor 3f in melanoma.Mol Carcinog. 2008 Oct;47(10):806-13. doi: 10.1002/mc.20436.
7 CaMKII is essential for the proasthmatic effects of oxidation.Sci Transl Med. 2013 Jul 24;5(195):195ra97. doi: 10.1126/scitranslmed.3006135.
8 Plasmodium P47: a key gene for malaria transmission by mosquito vectors.Curr Opin Microbiol. 2017 Dec;40:168-174. doi: 10.1016/j.mib.2017.11.029. Epub 2017 Dec 8.
9 Euterpe oleracea Mart. seed extract protects against renal injury in diabetic and spontaneously hypertensive rats: role of inflammation and oxidative stress.Eur J Nutr. 2018 Mar;57(2):817-832. doi: 10.1007/s00394-016-1371-1. Epub 2017 Jan 20.
10 Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
11 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.
12 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.
13 Quantitative Assessment of Arsenite-Induced Perturbation of Ubiquitinated Proteome. Chem Res Toxicol. 2022 Sep 19;35(9):1589-1597. doi: 10.1021/acs.chemrestox.2c00197. Epub 2022 Aug 22.
14 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.
15 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.
16 Cannabidiol Displays Proteomic Similarities to Antipsychotics in Cuprizone-Exposed Human Oligodendrocytic Cell Line MO3.13. Front Mol Neurosci. 2021 May 28;14:673144. doi: 10.3389/fnmol.2021.673144. eCollection 2021.
17 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.
18 New insights into BaP-induced toxicity: role of major metabolites in transcriptomics and contribution to hepatocarcinogenesis. Arch Toxicol. 2016 Jun;90(6):1449-58.
19 Low-dose Bisphenol A exposure alters the functionality and cellular environment in a human cardiomyocyte model. Environ Pollut. 2023 Oct 15;335:122359. doi: 10.1016/j.envpol.2023.122359. Epub 2023 Aug 9.