Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT2FHXQA)

DOT Name Inactive rhomboid protein 2 (RHBDF2)
Synonyms iRhom2; Rhomboid 5 homolog 2; Rhomboid family member 2; Rhomboid veinlet-like protein 5; Rhomboid veinlet-like protein 6
Gene Name RHBDF2
Related Disease
Palmoplantar keratoderma-esophageal carcinoma syndrome ( )
UniProt ID
RHDF2_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Pfam ID
PF12595 ; PF01694
Sequence
MASADKNGGSVSSVSSSRLQSRKPPNLSITIPPPEKETQAPGEQDSMLPEGFQNRRLKKS
QPRTWAAHTTACPPSFLPKRKNPAYLKSVSLQEPRSRWQESSEKRPGFRRQASLSQSIRK
GAAQWFGVSGDWEGQRQQWQRRSLHHCSMRYGRLKASCQRDLELPSQEAPSFQGTESPKP
CKMPKIVDPLARGRAFRHPEEMDRPHAPHPPLTPGVLSLTSFTSVRSGYSHLPRRKRMSV
AHMSLQAAAALLKGRSVLDATGQRCRVVKRSFAFPSFLEEDVVDGADTFDSSFFSKEEMS
SMPDDVFESPPLSASYFRGIPHSASPVSPDGVQIPLKEYGRAPVPGPRRGKRIASKVKHF
AFDRKKRHYGLGVVGNWLNRSYRRSISSTVQRQLESFDSHRPYFTYWLTFVHVIITLLVI
CTYGIAPVGFAQHVTTQLVLRNKGVYESVKYIQQENFWVGPSSIDLIHLGAKFSPCIRKD
GQIEQLVLRERDLERDSGCCVQNDHSGCIQTQRKDCSETLATFVKWQDDTGPPMDKSDLG
QKRTSGAVCHQDPRTCEEPASSGAHIWPDDITKWPICTEQARSNHTGFLHMDCEIKGRPC
CIGTKGSCEITTREYCEFMHGYFHEEATLCSQVHCLDKVCGLLPFLNPEVPDQFYRLWLS
LFLHAGVVHCLVSVVFQMTILRDLEKLAGWHRIAIIFILSGITGNLASAIFLPYRAEVGP
AGSQFGLLACLFVELFQSWPLLERPWKAFLNLSAIVLFLFICGLLPWIDNIAHIFGFLSG
LLLAFAFLPYITFGTSDKYRKRALILVSLLAFAGLFAALVLWLYIYPINWPWIEHLTCFP
FTSRFCEKYELDQVLH
Function
Regulates ADAM17 protease, a sheddase of the epidermal growth factor (EGF) receptor ligands and TNF, thereby plays a role in sleep, cell survival, proliferation, migration and inflammation. Does not exhibit any protease activity on its own.
Tissue Specificity Found in the epidermis and esophageal epithelium.
KEGG Pathway
TNF sig.ling pathway (hsa04668 )
Reactome Pathway
CD163 mediating an anti-inflammatory response (R-HSA-9662834 )

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Palmoplantar keratoderma-esophageal carcinoma syndrome DISS4NW9 Definitive Autosomal dominant [1]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
4 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 Inactive rhomboid protein 2 (RHBDF2). [2]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the methylation of Inactive rhomboid protein 2 (RHBDF2). [13]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 affects the phosphorylation of Inactive rhomboid protein 2 (RHBDF2). [15]
Coumarin DM0N8ZM Investigative Coumarin decreases the phosphorylation of Inactive rhomboid protein 2 (RHBDF2). [15]
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12 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of Inactive rhomboid protein 2 (RHBDF2). [3]
Tretinoin DM49DUI Approved Tretinoin decreases the expression of Inactive rhomboid protein 2 (RHBDF2). [4]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Inactive rhomboid protein 2 (RHBDF2). [5]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate increases the expression of Inactive rhomboid protein 2 (RHBDF2). [6]
Cisplatin DMRHGI9 Approved Cisplatin increases the expression of Inactive rhomboid protein 2 (RHBDF2). [7]
Estradiol DMUNTE3 Approved Estradiol increases the expression of Inactive rhomboid protein 2 (RHBDF2). [8]
Quercetin DM3NC4M Approved Quercetin increases the expression of Inactive rhomboid protein 2 (RHBDF2). [9]
Hydrogen peroxide DM1NG5W Approved Hydrogen peroxide affects the expression of Inactive rhomboid protein 2 (RHBDF2). [10]
Zoledronate DMIXC7G Approved Zoledronate increases the expression of Inactive rhomboid protein 2 (RHBDF2). [11]
Urethane DM7NSI0 Phase 4 Urethane decreases the expression of Inactive rhomboid protein 2 (RHBDF2). [12]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 increases the expression of Inactive rhomboid protein 2 (RHBDF2). [14]
Milchsaure DM462BT Investigative Milchsaure decreases the expression of Inactive rhomboid protein 2 (RHBDF2). [16]
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⏷ Show the Full List of 12 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 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.
3 Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
4 Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
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 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
7 Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
8 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.
9 Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
10 Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
11 Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
12 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
13 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.
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.
15 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.
16 Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.