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

DOT Name GTP-binding protein Rit1 (RIT1)
Synonyms EC 3.6.5.2; Ras-like protein expressed in many tissues; Ras-like without CAAX protein 1
Gene Name RIT1
Related Disease
Chronic obstructive pulmonary disease ( )
Noonan syndrome ( )
Noonan syndrome 8 ( )
Pneumonia ( )
Aarskog-Scott syndrome, X-linked ( )
Bladder cancer ( )
Carcinoma of esophagus ( )
Cockayne syndrome ( )
Cornelia de Lange syndrome ( )
Dubowitz syndrome ( )
Endometrial cancer ( )
Endometrial carcinoma ( )
Esophageal cancer ( )
Esophageal squamous cell carcinoma ( )
Hydrops fetalis ( )
Hypertrophic cardiomyopathy ( )
Melanocytic nevus ( )
Neoplasm ( )
Neoplasm of esophagus ( )
Prader-Willi syndrome ( )
Prostate cancer ( )
Prostate carcinoma ( )
Ptosis ( )
Robinow syndrome ( )
Seckel syndrome ( )
Silver-Russell syndrome ( )
Transitional cell carcinoma ( )
Triple negative breast cancer ( )
Urinary bladder cancer ( )
Urinary bladder neoplasm ( )
Crohn disease ( )
Hepatocellular carcinoma ( )
Lung adenocarcinoma ( )
Melanoma ( )
Carcinoma of liver and intrahepatic biliary tract ( )
Cardiomyopathy ( )
Liver cancer ( )
Adult lymphoma ( )
Advanced cancer ( )
Anxiety ( )
Anxiety disorder ( )
Clear cell renal carcinoma ( )
Cutaneous melanoma ( )
Inflammatory bowel disease ( )
Lymphoma ( )
Lymphoma, non-Hodgkin, familial ( )
Non-hodgkin lymphoma ( )
Pediatric lymphoma ( )
Renal cell carcinoma ( )
UniProt ID
RIT1_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
PDB ID
4KLZ
EC Number
3.6.5.2
Pfam ID
PF00071
Sequence
MDSGTRPVGSCCSSPAGLSREYKLVMLGAGGVGKSAMTMQFISHRFPEDHDPTIEDAYKI
RIRIDDEPANLDILDTAGQAEFTAMRDQYMRAGEGFIICYSITDRRSFHEVREFKQLIYR
VRRTDDTPVVLVGNKSDLKQLRQVTKEEGLALAREFSCPFFETSAAYRYYIDDVFHALVR
EIRRKEKEAVLAMEKKSKPKNSVWKRLKSPFRKKKDSVT
Function
Plays a crucial role in coupling NGF stimulation to the activation of both EPHB2 and MAPK14 signaling pathways and in NGF-dependent neuronal differentiation. Involved in ELK1 transactivation through the Ras-MAPK signaling cascade that mediates a wide variety of cellular functions, including cell proliferation, survival, and differentiation.
Tissue Specificity Expressed in many tissues.
Reactome Pathway
Signalling to p38 via RIT and RIN (R-HSA-187706 )

Molecular Interaction Atlas (MIA) of This DOT

49 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Chronic obstructive pulmonary disease DISQCIRF Definitive Genetic Variation [1]
Noonan syndrome DIS7Q7DN Definitive Autosomal dominant [2]
Noonan syndrome 8 DISSZJ2I Definitive Autosomal dominant [3]
Pneumonia DIS8EF3M Definitive Genetic Variation [1]
Aarskog-Scott syndrome, X-linked DISNHV62 Strong Biomarker [4]
Bladder cancer DISUHNM0 Strong Biomarker [5]
Carcinoma of esophagus DISS6G4D Strong Biomarker [6]
Cockayne syndrome DISW6GL2 Strong Biomarker [4]
Cornelia de Lange syndrome DISEQSXO Strong Biomarker [4]
Dubowitz syndrome DISRMNLQ Strong Biomarker [4]
Endometrial cancer DISW0LMR Strong Altered Expression [7]
Endometrial carcinoma DISXR5CY Strong Altered Expression [7]
Esophageal cancer DISGB2VN Strong Biomarker [6]
Esophageal squamous cell carcinoma DIS5N2GV Strong Biomarker [8]
Hydrops fetalis DISD9BBF Strong Genetic Variation [9]
Hypertrophic cardiomyopathy DISQG2AI Strong Biomarker [4]
Melanocytic nevus DISYS32D Strong Altered Expression [10]
Neoplasm DISZKGEW Strong Biomarker [11]
Neoplasm of esophagus DISOLKAQ Strong Biomarker [6]
Prader-Willi syndrome DISYWMLU Strong Biomarker [4]
Prostate cancer DISF190Y Strong Biomarker [12]
Prostate carcinoma DISMJPLE Strong Biomarker [12]
Ptosis DISJZNIY Strong Genetic Variation [13]
Robinow syndrome DISK1CNU Strong Biomarker [4]
Seckel syndrome DISEVUBA Strong Biomarker [4]
Silver-Russell syndrome DISSVJ1D Strong Biomarker [4]
Transitional cell carcinoma DISWVVDR Strong Biomarker [5]
Triple negative breast cancer DISAMG6N Strong Biomarker [11]
Urinary bladder cancer DISDV4T7 Strong Biomarker [5]
Urinary bladder neoplasm DIS7HACE Strong Biomarker [5]
Crohn disease DIS2C5Q8 moderate Genetic Variation [14]
Hepatocellular carcinoma DIS0J828 moderate Biomarker [15]
Lung adenocarcinoma DISD51WR moderate Genetic Variation [16]
Melanoma DIS1RRCY moderate Altered Expression [17]
Carcinoma of liver and intrahepatic biliary tract DIS8WA0W Disputed Biomarker [15]
Cardiomyopathy DISUPZRG Disputed Genetic Variation [18]
Liver cancer DISDE4BI Disputed Biomarker [15]
Adult lymphoma DISK8IZR Limited Altered Expression [19]
Advanced cancer DISAT1Z9 Limited Biomarker [20]
Anxiety DISIJDBA Limited Genetic Variation [21]
Anxiety disorder DISBI2BT Limited Genetic Variation [21]
Clear cell renal carcinoma DISBXRFJ Limited Biomarker [22]
Cutaneous melanoma DIS3MMH9 Limited Altered Expression [10]
Inflammatory bowel disease DISGN23E Limited Genetic Variation [23]
Lymphoma DISN6V4S Limited Altered Expression [19]
Lymphoma, non-Hodgkin, familial DISCXYIZ Limited Biomarker [24]
Non-hodgkin lymphoma DISS2Y8A Limited Biomarker [24]
Pediatric lymphoma DIS51BK2 Limited Altered Expression [19]
Renal cell carcinoma DISQZ2X8 Limited Biomarker [22]
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⏷ Show the Full List of 49 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
This DOT Affected the Drug Response of 1 Drug(s)
Drug Name Drug ID Highest Status Interaction REF
Fluorouracil DMUM7HZ Approved GTP-binding protein Rit1 (RIT1) affects the response to substance of Fluorouracil. [42]
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21 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 GTP-binding protein Rit1 (RIT1). [25]
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of GTP-binding protein Rit1 (RIT1). [26]
Tretinoin DM49DUI Approved Tretinoin decreases the expression of GTP-binding protein Rit1 (RIT1). [27]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate increases the expression of GTP-binding protein Rit1 (RIT1). [28]
Cisplatin DMRHGI9 Approved Cisplatin increases the expression of GTP-binding protein Rit1 (RIT1). [29]
Phenobarbital DMXZOCG Approved Phenobarbital affects the expression of GTP-binding protein Rit1 (RIT1). [30]
Bortezomib DMNO38U Approved Bortezomib increases the expression of GTP-binding protein Rit1 (RIT1). [31]
Diethylstilbestrol DMN3UXQ Approved Diethylstilbestrol increases the expression of GTP-binding protein Rit1 (RIT1). [32]
Rosiglitazone DMILWZR Approved Rosiglitazone increases the expression of GTP-binding protein Rit1 (RIT1). [29]
Azathioprine DMMZSXQ Approved Azathioprine increases the expression of GTP-binding protein Rit1 (RIT1). [33]
Cidofovir DMA13GD Approved Cidofovir increases the expression of GTP-binding protein Rit1 (RIT1). [29]
Ifosfamide DMCT3I8 Approved Ifosfamide increases the expression of GTP-binding protein Rit1 (RIT1). [29]
Clodronate DM9Y6X7 Approved Clodronate increases the expression of GTP-binding protein Rit1 (RIT1). [29]
Urethane DM7NSI0 Phase 4 Urethane increases the expression of GTP-binding protein Rit1 (RIT1). [34]
Dihydrotestosterone DM3S8XC Phase 4 Dihydrotestosterone increases the expression of GTP-binding protein Rit1 (RIT1). [35]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the expression of GTP-binding protein Rit1 (RIT1). [36]
Trichostatin A DM9C8NX Investigative Trichostatin A decreases the expression of GTP-binding protein Rit1 (RIT1). [37]
Formaldehyde DM7Q6M0 Investigative Formaldehyde increases the expression of GTP-binding protein Rit1 (RIT1). [38]
Sulforaphane DMQY3L0 Investigative Sulforaphane increases the expression of GTP-binding protein Rit1 (RIT1). [39]
methyl p-hydroxybenzoate DMO58UW Investigative methyl p-hydroxybenzoate decreases the expression of GTP-binding protein Rit1 (RIT1). [40]
N-(3-METHYLBUT-2-EN-1-YL)-9H-PURIN-6-AMINE DM2D4KY Investigative N-(3-METHYLBUT-2-EN-1-YL)-9H-PURIN-6-AMINE increases the expression of GTP-binding protein Rit1 (RIT1). [41]
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⏷ Show the Full List of 21 Drug(s)

References

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3 Gain-of-function mutations in RIT1 cause Noonan syndrome, a RAS/MAPK pathway syndrome. Am J Hum Genet. 2013 Jul 11;93(1):173-80. doi: 10.1016/j.ajhg.2013.05.021. Epub 2013 Jun 20.
4 New Noonan syndrome model mice with RIT1 mutation exhibit cardiac hypertrophy and susceptibility to -adrenergic stimulation-induced cardiac fibrosis.EBioMedicine. 2019 Apr;42:43-53. doi: 10.1016/j.ebiom.2019.03.014. Epub 2019 Mar 18.
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6 Targeting the overexpressed ROC1 induces G2 cell cycle arrest and apoptosis in esophageal cancer cells.Oncotarget. 2017 Apr 25;8(17):29125-29137. doi: 10.18632/oncotarget.16250.
7 Elevated expression of RIT1 correlates with poor prognosis in endometrial cancer.Int J Clin Exp Pathol. 2015 Sep 1;8(9):10315-24. eCollection 2015.
8 RIT1 suppresses esophageal squamous cell carcinoma growth and metastasis and predicts good prognosis.Cell Death Dis. 2018 Oct 22;9(11):1085. doi: 10.1038/s41419-018-0979-x.
9 Two cases of RIT1 associated Noonan syndrome: Further delineation of the clinical phenotype and review of the literature.Am J Med Genet A. 2016 Jul;170(7):1874-80. doi: 10.1002/ajmg.a.37657. Epub 2016 Apr 25.
10 Role of ROC1 protein in the control of cyclin D1 protein expression in skin melanomas.Pathol Res Pract. 2011 Mar 15;207(3):174-81. doi: 10.1016/j.prp.2011.01.001.
11 (212)Pb-Labeled Antibody 225.28 Targeted to Chondroitin Sulfate Proteoglycan 4 for Triple-Negative Breast Cancer Therapy in Mouse Models.Int J Mol Sci. 2018 Mar 21;19(4):925. doi: 10.3390/ijms19040925.
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13 Spectrum of mutations and genotype-phenotype analysis in Noonan syndrome patients with RIT1 mutations.Hum Genet. 2016 Feb;135(2):209-22. doi: 10.1007/s00439-015-1627-5. Epub 2015 Dec 29.
14 Association analyses identify 38 susceptibility loci for inflammatory bowel disease and highlight shared genetic risk across populations.Nat Genet. 2015 Sep;47(9):979-986. doi: 10.1038/ng.3359. Epub 2015 Jul 20.
15 HIF-1-induced RIT1 promotes liver cancer growth and metastasis and its deficiency increases sensitivity to sorafenib.Cancer Lett. 2019 Sep 28;460:96-107. doi: 10.1016/j.canlet.2019.06.016. Epub 2019 Jun 24.
16 Biochemical Classification of Disease-associated Mutants of RAS-like Protein Expressed in Many Tissues (RIT1).J Biol Chem. 2016 Jul 22;291(30):15641-52. doi: 10.1074/jbc.M116.714196. Epub 2016 May 18.
17 Autophagic UVRAG Promotes UV-Induced Photolesion Repair by Activation of the CRL4(DDB2) E3 Ligase.Mol Cell. 2016 May 19;62(4):507-19. doi: 10.1016/j.molcel.2016.04.014.
18 Mutations in RIT1 cause Noonan syndrome with possible juvenile myelomonocytic leukemia but are not involved in acute lymphoblastic leukemia.Eur J Hum Genet. 2016 Aug;24(8):1124-31. doi: 10.1038/ejhg.2015.273. Epub 2016 Jan 13.
19 Homozygous deletions and point mutations of the Rit1/Bcl11b gene in gamma-ray induced mouse thymic lymphomas.Biochem Biophys Res Commun. 2003 Feb 7;301(2):598-603. doi: 10.1016/s0006-291x(02)03069-3.
20 RIT1 oncoproteins escape LZTR1-mediated proteolysis.Science. 2019 Mar 15;363(6432):1226-1230. doi: 10.1126/science.aav1444.
21 Effects of implantable cardioverter/defibrillator shock and antitachycardia pacing on anxiety and quality of life: A MADIT-RIT substudy.Am Heart J. 2017 Jul;189:75-84. doi: 10.1016/j.ahj.2017.03.009. Epub 2017 Mar 20.
22 Inactivation of SAG or ROC1 E3 Ligase Inhibits Growth and Survival of Renal Cell Carcinoma Cells: Effect of BIM.Transl Oncol. 2019 Jun;12(6):810-818. doi: 10.1016/j.tranon.2019.03.002. Epub 2019 Apr 4.
23 Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease.Nature. 2012 Nov 1;491(7422):119-24. doi: 10.1038/nature11582.
24 Yttrium-90 ibritumomab tiuxetan (Zevalin) followed by BEAM (Z-BEAM) conditioning regimen and autologous stem cell transplantation (ASCT) in relapsed or refractory high-risk B-cell non-Hodgkin lymphoma (NHL): a single institution Italian experience.Ann Hematol. 2018 Sep;97(9):1619-1626. doi: 10.1007/s00277-018-3328-3. Epub 2018 Apr 16.
25 Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
26 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.
27 Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
28 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
29 Transcriptomics hit the target: monitoring of ligand-activated and stress response pathways for chemical testing. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):7-18.
30 Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
31 The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
32 Identification of biomarkers and outcomes of endocrine disruption in human ovarian cortex using In Vitro Models. Toxicology. 2023 Feb;485:153425. doi: 10.1016/j.tox.2023.153425. Epub 2023 Jan 5.
33 A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.
34 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
35 LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
36 Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
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38 Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
39 Sulforaphane-induced apoptosis in human leukemia HL-60 cells through extrinsic and intrinsic signal pathways and altering associated genes expression assayed by cDNA microarray. Environ Toxicol. 2017 Jan;32(1):311-328.
40 Transcriptome dynamics of alternative splicing events revealed early phase of apoptosis induced by methylparaben in H1299 human lung carcinoma cells. Arch Toxicol. 2020 Jan;94(1):127-140. doi: 10.1007/s00204-019-02629-w. Epub 2019 Nov 20.
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