Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTMLEJ67)

DOT Name Mitogen-activated protein kinase-binding protein 1 (MAPKBP1)
Synonyms JNK-binding protein 1; JNKBP-1
Gene Name MAPKBP1
Related Disease
Nephronophthisis 20 ( )
Normal pressure hydrocephalus ( )
Nephronophthisis ( )
Late-onset nephronophthisis ( )
Nephronophthisis 1 ( )
UniProt ID
MABP1_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Pfam ID
PF00400
Sequence
MAVEGSTITSRIKNLLRSPSIKLRRSKAGNRREDLSSKVTLEKVLGITVSGGRGLACDPR
SGLVAYPAGCVVVLFNPRKHKQHHILNSSRKTITALAFSPDGKYLVTGESGHMPAVRVWD
VAEHSQVAELQEHKYGVACVAFSPSAKYIVSVGYQHDMIVNVWAWKKNIVVASNKVSSRV
TAVSFSEDCSYFVTAGNRHIKFWYLDDSKTSKVNATVPLLGRSGLLGELRNNLFTDVACG
RGKKADSTFCITSSGLLCEFSDRRLLDKWVELRNIDSFTTTVAHCISVSQDYIFCGCADG
TVRLFNPSNLHFLSTLPRPHALGTDIASVTEASRLFSGVANARYPDTIALTFDPTNQWLS
CVYNDHSIYVWDVRDPKKVGKVYSALYHSSCVWSVEVYPEVKDSNQACLPPSSFITCSSD
NTIRLWNTESSGVHGSTLHRNILSSDLIKIIYVDGNTQALLDTELPGGDKADASLLDPRV
GIRSVCVSPNGQHLASGDRMGTLRVHELQSLSEMLKVEAHDSEILCLEYSKPDTGLKLLA
SASRDRLIHVLDAGREYSLQQTLDEHSSSITAVKFAASDGQVRMISCGADKSIYFRTAQK
SGDGVQFTRTHHVVRKTTLYDMDVEPSWKYTAIGCQDRNIRIFNISSGKQKKLFKGSQGE
DGTLIKVQTDPSGIYIATSCSDKNLSIFDFSSGECVATMFGHSEIVTGMKFSNDCKHLIS
VSGDSCIFVWRLSSEMTISMRQRLAELRQRQRGGKQQGPSSPQRASGPNRHQAPSMLSPG
PALSSDSDKEGEDEGTEEELPALPVLAKSTKKALASVPSPALPRSLSHWEMSRAQESVGF
LDPAPAANPGPRRRGRWVQPGVELSVRSMLDLRQLETLAPSLQDPSQDSLAIIPSGPRKH
GQEALETSLTSQNEKPPRPQASQPCSYPHIIRLLSQEEGVFAQDLEPAPIEDGIVYPEPS
DNPTMDTSEFQVQAPARGTLGRVYPGSRSSEKHSPDSACSVDYSSSCLSSPEHPTEDSES
TEPLSVDGISSDLEEPAEGDEEEEEEEGGMGPYGLQEGSPQTPDQEQFLKQHFETLASGA
APGAPVQVPERSESRSISSRFLLQVQTRPLREPSPSSSSLALMSRPAQVPQASGEQPRGN
GANPPGAPPEVEPSSGNPSPQQAASVLLPRCRLNPDSSWAPKRVATASPFSGLQKAQSVH
SLVPQERHEASLQAPSPGALLSREIEAQDGLGSLPPADGRPSRPHSYQNPTTSSMAKISR
SISVGENLGLVAEPQAHAPIRVSPLSKLALPSRAHLVLDIPKPLPDRPTLAAFSPVTKGR
APGEAEKPGFPVGLGKAHSTTERWACLGEGTTPKPRTECQAHPGPSSPCAQQLPVSSLFQ
GPENLQPPPPEKTPNPMECTKPGAALSQDSEPAVSLEQCEQLVAELRGSVRQAVRLYHSV
AGCKMPSAEQSRIAQLLRDTFSSVRQELEAVAGAVLSSPGSSPGAVGAEQTQALLEQYSE
LLLRAVERRMERKL
Function Negative regulator of NOD2 function. It down-regulates NOD2-induced processes such as activation of NF-kappa-B signaling, IL8 secretion and antibacterial response. Involved in JNK signaling pathway.
Tissue Specificity Expressed in intestinal mucosa, where it is detected in epithelial cells, endothelial cells, smooth muscle cells and immune cells, such as lymphocytes . Expressed in kidney .

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Nephronophthisis 20 DIS5ILXC Strong Autosomal recessive [1]
Normal pressure hydrocephalus DISOEFO9 Strong Genetic Variation [2]
Nephronophthisis DISXU4HY moderate Genetic Variation [2]
Late-onset nephronophthisis DIS8G9LN Supportive Autosomal recessive [2]
Nephronophthisis 1 DIS7QNQ3 Supportive Autosomal recessive [2]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
1 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate increases the methylation of Mitogen-activated protein kinase-binding protein 1 (MAPKBP1). [3]
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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 Mitogen-activated protein kinase-binding protein 1 (MAPKBP1). [4]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Mitogen-activated protein kinase-binding protein 1 (MAPKBP1). [5]
Cisplatin DMRHGI9 Approved Cisplatin decreases the expression of Mitogen-activated protein kinase-binding protein 1 (MAPKBP1). [6]
Quercetin DM3NC4M Approved Quercetin increases the expression of Mitogen-activated protein kinase-binding protein 1 (MAPKBP1). [7]
Urethane DM7NSI0 Phase 4 Urethane increases the expression of Mitogen-activated protein kinase-binding protein 1 (MAPKBP1). [8]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 increases the expression of Mitogen-activated protein kinase-binding protein 1 (MAPKBP1). [9]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 decreases the expression of Mitogen-activated protein kinase-binding protein 1 (MAPKBP1). [10]
Trichostatin A DM9C8NX Investigative Trichostatin A decreases the expression of Mitogen-activated protein kinase-binding protein 1 (MAPKBP1). [11]
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⏷ Show the Full List of 8 Drug(s)

References

1 Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
2 Mutations in MAPKBP1 Cause Juvenile or Late-Onset Cilia-Independent Nephronophthisis. Am J Hum Genet. 2017 Feb 2;100(2):323-333. doi: 10.1016/j.ajhg.2016.12.011. Epub 2017 Jan 12.
3 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.
4 Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
5 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.
6 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.
7 Quercetin induced cell apoptosis and altered gene expression in AGS human gastric cancer cells. Environ Toxicol. 2018 Nov;33(11):1168-1181. doi: 10.1002/tox.22623. Epub 2018 Aug 27.
8 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
9 Targeting MYCN in neuroblastoma by BET bromodomain inhibition. Cancer Discov. 2013 Mar;3(3):308-23.
10 Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
11 From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.