Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT0QNNY1)

DOT Name DENN domain-containing protein 5A (DENND5A)
Synonyms Rab6-interacting protein 1; Rab6IP1
Gene Name DENND5A
Related Disease
Developmental and epileptic encephalopathy, 49 ( )
Tourette syndrome ( )
UniProt ID
DEN5A_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
MSGGGGGGGSAPSRFADYFVICGLDTETGLEPDELSALCQYIQASKARDGASPFISSTTE
GENFEQTPLRRTFKSKVLARYPENVEWNPFDQDAVGMLCMPKGLAFKTQADPREPQFHAF
IITREDGSRTFGFALTFYEEVTSKQICSAMQTLYHMHNAEYDVLHAPPADDRDQSSMEDG
EDTPVTKLQRFNSYDISRDTLYVSKCICLITPMSFMKACRSVLEQLHQAVTSPQPPPLPL
ESYIYNVLYEVPLPPPGRSLKFSGVYGPIICQRPSTNELPLFDFPVKEVFELLGVENVFQ
LFTCALLEFQILLYSQHYQRLMTVAETITALMFPFQWQHVYVPILPASLLHFLDAPVPYL
MGLHSNGLDDRSKLELPQEANLCFVDIDNHFIELPEDLPQFPNKLEFVQEVSEILMAFGI
PPEGNLHCSESASKLKRLRASELVSDKRNGNIAGSPLHSYELLKENETIARLQALVKRTG
VSLEKLEVREDPSSNKDLKVQCDEEELRIYQLNIQIREVFANRFTQMFADYEVFVIQPSQ
DKESWFTNREQMQNFDKASFLSDQPEPYLPFLSRFLETQMFASFIDNKIMCHDDDDKDPV
LRVFDSRVDKIRLLNVRTPTLRTSMYQKCTTVDEAEKAIELRLAKIDHTAIHPHLLDMKI
GQGKYEPGFFPKLQSDVLSTGPASNKWTKRNAPAQWRRKDRQKQHTEHLRLDNDQREKYI
QEARTMGSTIRQPKLSNLSPSVIAQTNWKFVEGLLKECRNKTKRMLVEKMGREAVELGHG
EVNITGVEENTLIASLCDLLERIWSHGLQVKQGKSALWSHLLHYQDNRQRKLTSGSLSTS
GILLDSERRKSDASSLMPPLRISLIQDMRHIQNIGEIKTDVGKARAWVRLSMEKKLLSRH
LKQLLSDHELTKKLYKRYAFLRCDDEKEQFLYHLLSFNAVDYFCFTNVFTTILIPYHILI
VPSKKLGGSMFTANPWICISGELGETQIMQIPRNVLEMTFECQNLGKLTTVQIGHDNSGL
YAKWLVEYVMVRNEITGHTYKFPCGRWLGKGMDDGSLERILVGELLTSQPEVDERPCRTP
PLQQSPSVIRRLVTISPNNKPKLNTGQIQESIGEAVNGIVKHFHKPEKERGSLTLLLCGE
CGLVSALEQAFQHGFKSPRLFKNVFIWDFLEKAQTYYETLEKNEVVPEENWHTRARNFCR
FVTAINNTPRNIGKDGKFQMLVCLGARDHLLHHWIALLADCPITAHMYEDVALIKDHTLV
NSLIRVLQTLQEFNITLETSLVKGIDI
Function
Guanine nucleotide exchange factor (GEF) which may activate RAB6A and RAB39A and/or RAB39B. Promotes the exchange of GDP to GTP, converting inactive GDP-bound Rab proteins into their active GTP-bound form. Involved in the negative regulation of neurite outgrowth.
Reactome Pathway
RAB GEFs exchange GTP for GDP on RABs (R-HSA-8876198 )

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Developmental and epileptic encephalopathy, 49 DIS1LYUH Strong Autosomal recessive [1]
Tourette syndrome DISX9D54 No Known Unknown [1]
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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
Ciclosporin DMAZJFX Approved Ciclosporin increases the expression of DENN domain-containing protein 5A (DENND5A). [2]
Tretinoin DM49DUI Approved Tretinoin increases the expression of DENN domain-containing protein 5A (DENND5A). [3]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of DENN domain-containing protein 5A (DENND5A). [4]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate increases the expression of DENN domain-containing protein 5A (DENND5A). [5]
Cisplatin DMRHGI9 Approved Cisplatin increases the expression of DENN domain-containing protein 5A (DENND5A). [6]
Estradiol DMUNTE3 Approved Estradiol increases the expression of DENN domain-containing protein 5A (DENND5A). [2]
Demecolcine DMCZQGK Approved Demecolcine increases the expression of DENN domain-containing protein 5A (DENND5A). [7]
Isotretinoin DM4QTBN Approved Isotretinoin increases the expression of DENN domain-containing protein 5A (DENND5A). [8]
Aspirin DM672AH Approved Aspirin increases the expression of DENN domain-containing protein 5A (DENND5A). [9]
Tocopherol DMBIJZ6 Phase 2 Tocopherol increases the expression of DENN domain-containing protein 5A (DENND5A). [10]
APR-246 DMNFADH Phase 2 APR-246 affects the expression of DENN domain-containing protein 5A (DENND5A). [11]
Leflunomide DMR8ONJ Phase 1 Trial Leflunomide increases the expression of DENN domain-containing protein 5A (DENND5A). [13]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 decreases the expression of DENN domain-containing protein 5A (DENND5A). [14]
Formaldehyde DM7Q6M0 Investigative Formaldehyde increases the expression of DENN domain-containing protein 5A (DENND5A). [7]
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⏷ Show the Full List of 14 Drug(s)
1 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the methylation of DENN domain-containing protein 5A (DENND5A). [12]
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References

1 The Gene Curation Coalition: A global effort to harmonize gene-disease evidence resources. Genet Med. 2022 Aug;24(8):1732-1742. doi: 10.1016/j.gim.2022.04.017. Epub 2022 May 4.
2 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.
3 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.
4 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.
5 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
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 Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
8 Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 2009 May;1(3):177-87.
9 Expression profile analysis of colon cancer cells in response to sulindac or aspirin. Biochem Biophys Res Commun. 2002 Mar 29;292(2):498-512.
10 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.
11 Mutant p53 reactivation by PRIMA-1MET induces multiple signaling pathways converging on apoptosis. Oncogene. 2010 Mar 4;29(9):1329-38. doi: 10.1038/onc.2009.425. Epub 2009 Nov 30.
12 Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
13 Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
14 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.