Details of Drug Off-Target (DOT)

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

DOT Name DENN domain-containing protein 5B (DENND5B)
Synonyms Rab6IP1-like protein
Gene Name DENND5B
Related Disease
Colon cancer ( )
Colorectal adenocarcinoma ( )
Colorectal cancer ( )
Colorectal cancer, susceptibility to, 1 ( )
Colorectal cancer, susceptibility to, 10 ( )
Colorectal cancer, susceptibility to, 12 ( )
Colorectal carcinoma ( )
Colorectal neoplasm ( )
Schizophrenia ( )
UniProt ID
DEN5B_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Pfam ID
PF03455 ; PF02141 ; PF01477 ; PF02759 ; PF03456
Sequence
MSGSCAAPGPGSGSSPAACRFAHYFVLCGIDADSGLEPDELAGENFDQSPLRRTFKSKVL
AHYPQNIEWNPFDQDAVNMLCMPKGLSFRTQTDNKDPQFHSFIITREDGSRTYGFVLTFY
EEVTSKQICTAMQTLYQMHNAEHYSSVYASSSCSMDSLASSLDEGDTTSLLKLQRYNSYD
ISRDTLYVSKSICLITPLPFMQACKKFLIQLYKAVTSQQPPPLPLESYIHNILYEVPLPP
PGRSLKFYGVYEPVICQRPGPSELPLSDYPLREAFELLGLENLVQVFTCVLLEMQILLYS
QDYQRLMTVAEGITTLLFPFQWQHVYVPILPASLLHFLDAPVPYLMGLQSKEGTDRSKLE
LPQEANLCFVDIDNHFIELPEEFPQFPNKVDFIQELSEVLVQFGIPPEGSLHCSESTSKL
KNMVLKDLVNDKKNGNVCTNNISMYELLKGNETIARLQALAKRTGVAVEKMDLSASLGEK
DKDLKLHCEEAELRDYQLNVQLREVFANRFTQMFADYEAFVIQTAQDMESWLTNREQMQN
FDKASFLSDQPEPYLPFLSRFIETQMFATFIDNKIMSQWEEKDPLLRVFDTRIDKIRLYN
VRAPTLRTSIYQKCSTLKEAAQSIEQRLMKMDHTAIHPHLLDMKIGQGKYEQGFFPKLQS
DVLATGPTSNNRWVSRSATAQRRKERLRQHSEHVGLDNDLREKYMQEARSLGKNLRQPKL
SDLSPAVIAQTNCKFVEGLLKECRMKTKRMLVEKMGHEAVELGHGEANITGLEENTLIAS
LCDLLERIWSHGLQVKQGKSALWSHLIQFQDREEKQEHLAESPVALGPERRKSDSGVMLP
TLRVSLIQDMRHIQNMSEIKTDVGRARAWIRLSLEKKLLSQHLKQLLSNQPLTKKLYKRY
AFLRCEEEREQFLYHLLSLNAVDYFCFTSVFTTIMIPYRSVIIPIKKLSNAIITSNPWIC
VSGELGDTGVMQIPKNLLEMTFECQNLGKLTTVQIGHDNSGLLAKWLVDCVMVRNEITGH
TYRFPCGRWLGKGIDDGSLERILIGELMTSASDEDLVKQCRTPPQQKSPTTARRLSITSL
TGKNNKPNAGQIQEGIGEAVNNIVKHFHKPEKERGSLTVLLCGENGLVAALEQVFHHGFK
SARIFHKNVFIWDFIEKVVAYFETTDQILDNEDDVLIQKSSCKTFCHYVNAINTAPRNIG
KDGKFQILVCLGTRDRLLPQWIPLLAECPAITRMYEESALLRDRMTVNSLIRILQTIQDF
TIVLEGSLIKGVDV
Function Guanine nucleotide exchange factor (GEF) which may activate RAB39A and/or RAB39B. Promotes the exchange of GDP to GTP, converting inactive GDP-bound Rab proteins into their active GTP-bound form.
Reactome Pathway
RAB GEFs exchange GTP for GDP on RABs (R-HSA-8876198 )

Molecular Interaction Atlas (MIA) of This DOT

9 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Colon cancer DISVC52G Strong Genetic Variation [1]
Colorectal adenocarcinoma DISPQOUB Strong Genetic Variation [1]
Colorectal cancer DISNH7P9 Strong Genetic Variation [1]
Colorectal cancer, susceptibility to, 1 DISZ794C Strong Genetic Variation [1]
Colorectal cancer, susceptibility to, 10 DISQXMYM Strong Genetic Variation [1]
Colorectal cancer, susceptibility to, 12 DIS4FXJX Strong Genetic Variation [1]
Colorectal carcinoma DIS5PYL0 Strong Genetic Variation [1]
Colorectal neoplasm DISR1UCN Strong Genetic Variation [1]
Schizophrenia DISSRV2N Strong Genetic Variation [2]
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⏷ Show the Full List of 9 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
7 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate decreases the expression of DENN domain-containing protein 5B (DENND5B). [3]
Tretinoin DM49DUI Approved Tretinoin decreases the expression of DENN domain-containing protein 5B (DENND5B). [4]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of DENN domain-containing protein 5B (DENND5B). [5]
Cisplatin DMRHGI9 Approved Cisplatin decreases the expression of DENN domain-containing protein 5B (DENND5B). [6]
Testosterone DM7HUNW Approved Testosterone decreases the expression of DENN domain-containing protein 5B (DENND5B). [7]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the mutagenesis of DENN domain-containing protein 5B (DENND5B). [8]
Trichostatin A DM9C8NX Investigative Trichostatin A increases the expression of DENN domain-containing protein 5B (DENND5B). [11]
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⏷ Show the Full List of 7 Drug(s)
2 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 decreases the phosphorylation of DENN domain-containing protein 5B (DENND5B). [9]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the methylation of DENN domain-containing protein 5B (DENND5B). [10]
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References

1 Large-Scale Genome-Wide Association Study of East Asians Identifies Loci Associated With Risk for Colorectal Cancer.Gastroenterology. 2019 Apr;156(5):1455-1466. doi: 10.1053/j.gastro.2018.11.066. Epub 2018 Dec 6.
2 Pleiotropic Meta-Analysis of Cognition, Education, and Schizophrenia Differentiates Roles of Early Neurodevelopmental and Adult Synaptic Pathways.Am J Hum Genet. 2019 Aug 1;105(2):334-350. doi: 10.1016/j.ajhg.2019.06.012.
3 Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
4 Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
5 Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
6 Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
7 The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
8 Exome-wide mutation profile in benzo[a]pyrene-derived post-stasis and immortal human mammary epithelial cells. Mutat Res Genet Toxicol Environ Mutagen. 2014 Dec;775-776:48-54. doi: 10.1016/j.mrgentox.2014.10.011. Epub 2014 Nov 4.
9 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.
10 DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
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.