Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTJFD4P5)

DOT Name Small ubiquitin-related modifier 1 (SUMO1)
Synonyms SUMO-1; GAP-modifying protein 1; GMP1; SMT3 homolog 3; Sentrin; Ubiquitin-homology domain protein PIC1; Ubiquitin-like protein SMT3C; Smt3C; Ubiquitin-like protein UBL1
Gene Name SUMO1
Related Disease
Adult glioblastoma ( )
Cleft lip/palate ( )
Glioblastoma multiforme ( )
Isolated cleft palate ( )
Squamous cell carcinoma ( )
Amyotrophic lateral sclerosis ( )
Arteriosclerosis ( )
Atherosclerosis ( )
Bone osteosarcoma ( )
Breast cancer ( )
Breast carcinoma ( )
Cardiac failure ( )
Clear cell renal carcinoma ( )
Colon cancer ( )
Colon carcinoma ( )
Congestive heart failure ( )
Cytomegalovirus infection ( )
Hepatocellular carcinoma ( )
Isolated cleft lip ( )
Leukemia ( )
Lung adenocarcinoma ( )
Lung cancer ( )
Lung carcinoma ( )
Myocardial infarction ( )
Neoplasm ( )
Osteosarcoma ( )
Progressive multifocal leukoencephalopathy ( )
Promyelocytic leukaemia ( )
Prostate neoplasm ( )
Rheumatoid arthritis ( )
Advanced cancer ( )
Gastric cancer ( )
Neuroblastoma ( )
Non-small-cell lung cancer ( )
Stomach cancer ( )
Acute myelogenous leukaemia ( )
Alzheimer disease ( )
Endometrial cancer ( )
Endometrial carcinoma ( )
Glioma ( )
Hepatitis C virus infection ( )
Liver cancer ( )
Lymphoma ( )
Orofacial cleft 10 ( )
Orofacial cleft 5 ( )
Prostate cancer ( )
Prostate carcinoma ( )
UniProt ID
SUMO1_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
PDB ID
1A5R ; 1TGZ ; 1WYW ; 1Y8R ; 1Z5S ; 2ASQ ; 2BF8 ; 2G4D ; 2IO2 ; 2IY0 ; 2IY1 ; 2KQS ; 2LAS ; 2MW5 ; 2N1A ; 2N1V ; 2PE6 ; 2UYZ ; 2VRR ; 3KYC ; 3KYD ; 3RZW ; 3UIP ; 4WJN ; 4WJO ; 4WJP ; 4WJQ ; 5AEK ; 5B7A ; 5ELJ ; 5GHD ; 6EOP ; 6EOT ; 6J4I ; 6JXU ; 6JXV ; 6K5T ; 6TRW ; 6UYO ; 6UYP ; 6UYQ ; 6UYR ; 6UYS ; 6UYT ; 6UYU ; 6UYV ; 6UYX ; 6UYY ; 6UYZ ; 6V7P ; 6V7Q ; 6V7R ; 6V7S ; 6WW3 ; 6XOG ; 6XOH ; 6XOI ; 8DJH ; 8DJI ; 8ODR
Pfam ID
PF11976
Sequence
MSDQEAKPSTEDLGDKKEGEYIKLKVIGQDSSEIHFKVKMTTHLKKLKESYCQRQGVPMN
SLRFLFEGQRIADNHTPKELGMEEEDVIEVYQEQTGGHSTV
Function
Ubiquitin-like protein that can be covalently attached to proteins as a monomer or a lysine-linked polymer. Covalent attachment via an isopeptide bond to its substrates requires prior activation by the E1 complex SAE1-SAE2 and linkage to the E2 enzyme UBE2I, and can be promoted by E3 ligases such as PIAS1-4, RANBP2 or CBX4. This post-translational modification on lysine residues of proteins plays a crucial role in a number of cellular processes such as nuclear transport, DNA replication and repair, mitosis and signal transduction. Involved for instance in targeting RANGAP1 to the nuclear pore complex protein RANBP2. Covalently attached to the voltage-gated potassium channel KCNB1; this modulates the gating characteristics of KCNB1. Polymeric SUMO1 chains are also susceptible to polyubiquitination which functions as a signal for proteasomal degradation of modified proteins. May also regulate a network of genes involved in palate development. Covalently attached to ZFHX3.
KEGG Pathway
Nucleocytoplasmic transport (hsa03013 )
Fluid shear stress and atherosclerosis (hsa05418 )
Reactome Pathway
SUMO is transferred from E1 to E2 (UBE2I, UBC9) (R-HSA-3065678 )
SUMO is proteolytically processed (R-HSA-3065679 )
SUMOylation of DNA damage response and repair proteins (R-HSA-3108214 )
SUMOylation of transcription factors (R-HSA-3232118 )
SUMOylation of ubiquitinylation proteins (R-HSA-3232142 )
SUMOylation of transcription cofactors (R-HSA-3899300 )
SUMOylation of SUMOylation proteins (R-HSA-4085377 )
SUMOylation of intracellular receptors (R-HSA-4090294 )
SUMOylation of chromatin organization proteins (R-HSA-4551638 )
SUMOylation of RNA binding proteins (R-HSA-4570464 )
SUMOylation of DNA replication proteins (R-HSA-4615885 )
SUMOylation of DNA methylation proteins (R-HSA-4655427 )
SUMOylation of immune response proteins (R-HSA-4755510 )
Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks (R-HSA-5693565 )
Formation of Incision Complex in GG-NER (R-HSA-5696395 )
Regulation of IFNG signaling (R-HSA-877312 )
Negative regulation of activity of TFAP2 (AP-2) family transcription factors (R-HSA-8866904 )
Postmitotic nuclear pore complex (NPC) reformation (R-HSA-9615933 )
Maturation of nucleoprotein (R-HSA-9683610 )
Maturation of nucleoprotein (R-HSA-9694631 )
SUMOylation of nuclear envelope proteins (R-HSA-9793242 )
PKR-mediated signaling (R-HSA-9833482 )
SUMO is conjugated to E1 (UBA2 (R-HSA-3065676 )
BioCyc Pathway
MetaCyc:ENSG00000116030-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

47 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Adult glioblastoma DISVP4LU Definitive Biomarker [1]
Cleft lip/palate DIS14IG3 Definitive Genetic Variation [2]
Glioblastoma multiforme DISK8246 Definitive Biomarker [1]
Isolated cleft palate DISV80CD Definitive Biomarker [3]
Squamous cell carcinoma DISQVIFL Definitive Biomarker [4]
Amyotrophic lateral sclerosis DISF7HVM Strong Biomarker [5]
Arteriosclerosis DISK5QGC Strong Biomarker [6]
Atherosclerosis DISMN9J3 Strong Biomarker [6]
Bone osteosarcoma DIST1004 Strong Altered Expression [7]
Breast cancer DIS7DPX1 Strong Biomarker [8]
Breast carcinoma DIS2UE88 Strong Biomarker [8]
Cardiac failure DISDC067 Strong Altered Expression [9]
Clear cell renal carcinoma DISBXRFJ Strong Altered Expression [10]
Colon cancer DISVC52G Strong Biomarker [11]
Colon carcinoma DISJYKUO Strong Biomarker [11]
Congestive heart failure DIS32MEA Strong Altered Expression [9]
Cytomegalovirus infection DISCEMGC Strong Altered Expression [12]
Hepatocellular carcinoma DIS0J828 Strong Biomarker [13]
Isolated cleft lip DIS2O2JV Strong Genetic Variation [14]
Leukemia DISNAKFL Strong Biomarker [15]
Lung adenocarcinoma DISD51WR Strong Altered Expression [16]
Lung cancer DISCM4YA Strong Biomarker [16]
Lung carcinoma DISTR26C Strong Biomarker [16]
Myocardial infarction DIS655KI Strong Altered Expression [17]
Neoplasm DISZKGEW Strong Biomarker [18]
Osteosarcoma DISLQ7E2 Strong Altered Expression [7]
Progressive multifocal leukoencephalopathy DISX02WS Strong Biomarker [19]
Promyelocytic leukaemia DISYGG13 Strong Altered Expression [20]
Prostate neoplasm DISHDKGQ Strong Altered Expression [21]
Rheumatoid arthritis DISTSB4J Strong Altered Expression [22]
Advanced cancer DISAT1Z9 moderate Biomarker [16]
Gastric cancer DISXGOUK moderate Posttranslational Modification [23]
Neuroblastoma DISVZBI4 moderate Biomarker [24]
Non-small-cell lung cancer DIS5Y6R9 moderate Biomarker [16]
Stomach cancer DISKIJSX moderate Posttranslational Modification [23]
Acute myelogenous leukaemia DISCSPTN Disputed Altered Expression [25]
Alzheimer disease DISF8S70 Limited Biomarker [26]
Endometrial cancer DISW0LMR Limited Altered Expression [27]
Endometrial carcinoma DISXR5CY Limited Altered Expression [27]
Glioma DIS5RPEH Limited Biomarker [28]
Hepatitis C virus infection DISQ0M8R Limited Biomarker [29]
Liver cancer DISDE4BI Limited Altered Expression [30]
Lymphoma DISN6V4S Limited Altered Expression [31]
Orofacial cleft 10 DISO5G3Z Limited Unknown [3]
Orofacial cleft 5 DISXH76T Limited Autosomal dominant [3]
Prostate cancer DISF190Y Limited Biomarker [32]
Prostate carcinoma DISMJPLE Limited Biomarker [32]
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⏷ Show the Full List of 47 Disease(s)
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
Valproate DMCFE9I Approved Valproate increases the expression of Small ubiquitin-related modifier 1 (SUMO1). [33]
Tretinoin DM49DUI Approved Tretinoin decreases the expression of Small ubiquitin-related modifier 1 (SUMO1). [34]
Acetaminophen DMUIE76 Approved Acetaminophen increases the expression of Small ubiquitin-related modifier 1 (SUMO1). [35]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Small ubiquitin-related modifier 1 (SUMO1). [36]
Estradiol DMUNTE3 Approved Estradiol decreases the expression of Small ubiquitin-related modifier 1 (SUMO1). [37]
Arsenic trioxide DM61TA4 Approved Arsenic trioxide decreases the expression of Small ubiquitin-related modifier 1 (SUMO1). [38]
Progesterone DMUY35B Approved Progesterone increases the expression of Small ubiquitin-related modifier 1 (SUMO1). [39]
Bortezomib DMNO38U Approved Bortezomib increases the expression of Small ubiquitin-related modifier 1 (SUMO1). [40]
Aspirin DM672AH Approved Aspirin decreases the expression of Small ubiquitin-related modifier 1 (SUMO1). [41]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the expression of Small ubiquitin-related modifier 1 (SUMO1). [42]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the expression of Small ubiquitin-related modifier 1 (SUMO1). [44]
Formaldehyde DM7Q6M0 Investigative Formaldehyde decreases the expression of Small ubiquitin-related modifier 1 (SUMO1). [45]
AHPN DM8G6O4 Investigative AHPN decreases the expression of Small ubiquitin-related modifier 1 (SUMO1). [46]
THIOCTIC ACID DMNFCXW Investigative THIOCTIC ACID increases the expression of Small ubiquitin-related modifier 1 (SUMO1). [47]
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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
TAK-243 DM4GKV2 Phase 1 TAK-243 increases the sumoylation of Small ubiquitin-related modifier 1 (SUMO1). [43]
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References

1 SUMO1 modification stabilizes CDK6 protein and drives the cell cycle and glioblastoma progression.Nat Commun. 2014 Jun 23;5:4234. doi: 10.1038/ncomms5234.
2 Sumoylation in Craniofacial Disorders.Adv Exp Med Biol. 2017;963:323-335. doi: 10.1007/978-3-319-50044-7_19.
3 SUMO1 haploinsufficiency leads to cleft lip and palate. Science. 2006 Sep 22;313(5794):1751. doi: 10.1126/science.1128406.
4 Evaluation of the expression of p53, MDM2, and SUMO-1 in oral lichen planus.Oral Dis. 2013 Nov;19(8):775-80. doi: 10.1111/odi.12068. Epub 2013 Jan 28.
5 Mutation of the caspase-3 cleavage site in the astroglial glutamate transporter EAAT2 delays disease progression and extends lifespan in the SOD1-G93A mouse model of ALS.Exp Neurol. 2017 Jun;292:145-153. doi: 10.1016/j.expneurol.2017.03.014. Epub 2017 Mar 22.
6 SUMO-specific protease 2 (SENP2) suppresses keratinocyte migration by targeting NDR1 for de-SUMOylation.FASEB J. 2019 Jan;33(1):163-174. doi: 10.1096/fj.201800353R. Epub 2018 Jul 3.
7 Overexpression of SENP1 reduces the stemness capacity of osteosarcoma stem cells and increases their sensitivity to HSVtk/GCV.Int J Oncol. 2018 Nov;53(5):2010-2020. doi: 10.3892/ijo.2018.4537. Epub 2018 Aug 23.
8 Effect of the knockdown of death-associated protein 1 expression on cell adhesion, growth and migration in breast cancer cells.Oncol Rep. 2015 Mar;33(3):1450-8. doi: 10.3892/or.2014.3686. Epub 2014 Dec 22.
9 miR-146a Suppresses SUMO1 Expression and Induces Cardiac Dysfunction in Maladaptive Hypertrophy.Circ Res. 2018 Aug 31;123(6):673-685. doi: 10.1161/CIRCRESAHA.118.312751.
10 SENP1 promotes proliferation of clear cell renal cell carcinoma through activation of glycolysis.Oncotarget. 2016 Dec 6;7(49):80435-80449. doi: 10.18632/oncotarget.12606.
11 Over-expression of small ubiquitin-related modifier-1 and sumoylated p53 in colon cancer.Cell Biochem Biophys. 2013;67(3):1081-7. doi: 10.1007/s12013-013-9612-x.
12 Small ubiquitin-related modifier (SUMO) pathway-mediated enhancement of human cytomegalovirus replication correlates with a recruitment of SUMO-1/3 proteins to viral replication compartments.J Gen Virol. 2013 Jun;94(Pt 6):1373-1384. doi: 10.1099/vir.0.051078-0. Epub 2013 Feb 13.
13 NRF2 SUMOylation promotes de novo serine synthesis and maintains HCC tumorigenesis.Cancer Lett. 2019 Dec 1;466:39-48. doi: 10.1016/j.canlet.2019.09.010. Epub 2019 Sep 20.
14 SUMO1 genetic polymorphisms may contribute to the risk of nonsyndromic cleft lip with or without palate: a meta-analysis.Genet Test Mol Biomarkers. 2014 Sep;18(9):616-24. doi: 10.1089/gtmb.2014.0056. Epub 2014 Aug 11.
15 SUMO-dependent compartmentalization in promyelocytic leukemia protein nuclear bodies prevents the access of LRH-1 to chromatin.Mol Cell Biol. 2005 Jun;25(12):5095-105. doi: 10.1128/MCB.25.12.5095-5105.2005.
16 SUMO1 promotes the proliferation and invasion of non-small cell lung cancer cells by regulating NF-B.Thorac Cancer. 2019 Jan;10(1):33-40. doi: 10.1111/1759-7714.12895. Epub 2018 Nov 4.
17 Pharmacological inhibition of SUMO-1 with ginkgolic acid alleviates cardiac fibrosis induced by myocardial infarction in mice.Toxicol Appl Pharmacol. 2018 Apr 15;345:1-9. doi: 10.1016/j.taap.2018.03.006. Epub 2018 Mar 7.
18 SUMO1 modification of KHSRP regulates tumorigenesis by preventing the TL-G-Rich miRNA biogenesis.Mol Cancer. 2017 Oct 11;16(1):157. doi: 10.1186/s12943-017-0724-6.
19 PML nuclear body-residing proteins sequentially associate with HPV genome after infectious nuclear delivery.PLoS Pathog. 2019 Feb 25;15(2):e1007590. doi: 10.1371/journal.ppat.1007590. eCollection 2019 Feb.
20 SUMO1 negatively regulates the transcriptional activity of EVI1 and significantly increases its co-localization with EVI1 after treatment with arsenic trioxide.Biochim Biophys Acta. 2013 Oct;1833(10):2357-68. doi: 10.1016/j.bbamcr.2013.06.003. Epub 2013 Jun 13.
21 Induction of the SUMO-specific protease 1 transcription by the androgen receptor in prostate cancer cells.J Biol Chem. 2007 Dec 28;282(52):37341-9. doi: 10.1074/jbc.M706978200. Epub 2007 Oct 11.
22 Evaluation of SUMO1 and POU2AF1 in whole blood from rheumatoid arthritis patients and at risk relatives.Int J Immunogenet. 2019 Apr;46(2):59-66. doi: 10.1111/iji.12414. Epub 2019 Jan 25.
23 SUMO-1 Gene Silencing Inhibits Proliferation and Promotes Apoptosis of Human Gastric Cancer SGC-7901 Cells.Cell Physiol Biochem. 2017;41(3):987-998. doi: 10.1159/000460836. Epub 2017 Feb 21.
24 Antisense palmitoyl protein thioesterase 1 (PPT1) treatment inhibits PPT1 activity and increases cell death in LA-N-5 neuroblastoma cells.J Neurosci Res. 2000 Oct 15;62(2):234-40. doi: 10.1002/1097-4547(20001015)62:2<234::AID-JNR8>3.0.CO;2-8.
25 SUMOylation of insulin-like growth factor 1 receptor, promotes proliferation in acute myeloid leukemia.Cancer Lett. 2015 Feb 1;357(1):297-306. doi: 10.1016/j.canlet.2014.11.052. Epub 2014 Nov 28.
26 Metal Binding by GMP-1 and Its Pyrimido [1, 2]benzimidazole Analogs Confirms Protection Against Amyloid- Associated Neurotoxicity.J Alzheimers Dis. 2020;73(2):695-705. doi: 10.3233/JAD-190695.
27 Prostaglandin E2 (PGE2) promotes proliferation and invasion by enhancing SUMO-1 activity via EP4 receptor in endometrial cancer.Tumour Biol. 2016 Sep;37(9):12203-12211. doi: 10.1007/s13277-016-5087-x. Epub 2016 May 26.
28 SUMO-1 marks subdomains within glial cytoplasmic inclusions of multiple system atrophy.Neurosci Lett. 2005 Jun 10-17;381(1-2):74-9. doi: 10.1016/j.neulet.2005.02.013. Epub 2005 Mar 2.
29 SUMO1 depletion prevents lipid droplet accumulation and HCV replication.Arch Virol. 2016 Jan;161(1):141-8. doi: 10.1007/s00705-015-2628-3. Epub 2015 Oct 8.
30 Connexin 43 SUMOylation improves gap junction functions between liver cancer stem cells and enhances their sensitivity to HSVtk/GCV.Int J Oncol. 2018 Mar;52(3):872-880. doi: 10.3892/ijo.2018.4263. Epub 2018 Feb 1.
31 Epstein-Barr Virus Latent Membrane Protein-1 Induces the Expression of SUMO-1 and SUMO-2/3 in LMP1-positive Lymphomas and Cells.Sci Rep. 2019 Jan 18;9(1):208. doi: 10.1038/s41598-018-36312-4.
32 Important role of SUMOylation of Spliceosome factors in prostate cancer cells.J Proteome Res. 2014 Aug 1;13(8):3571-82. doi: 10.1021/pr4012848. Epub 2014 Jul 24.
33 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.
34 Pharmacogenomic analysis of acute promyelocytic leukemia cells highlights CYP26 cytochrome metabolism in differential all-trans retinoic acid sensitivity. Blood. 2007 May 15;109(10):4450-60.
35 Caffeine disrupts ataxia telangiectasia mutated gene-related pathways and exacerbates acetaminophen toxicity in human fetal immortalized hepatocytes. Toxicology. 2021 Jun 15;457:152811. doi: 10.1016/j.tox.2021.152811. Epub 2021 May 7.
36 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.
37 Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
38 Arsenic trioxide induces different gene expression profiles of genes related to growth and apoptosis in glioma cells dependent on the p53 status. Mol Biol Rep. 2008 Sep;35(3):421-9.
39 Coordinate up-regulation of TMEM97 and cholesterol biosynthesis genes in normal ovarian surface epithelial cells treated with progesterone: implications for pathogenesis of ovarian cancer. BMC Cancer. 2007 Dec 11;7:223.
40 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.
41 Expression profile analysis of colon cancer cells in response to sulindac or aspirin. Biochem Biophys Res Commun. 2002 Mar 29;292(2):498-512.
42 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.
43 Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
44 Alternatives for the worse: Molecular insights into adverse effects of bisphenol a and substitutes during human adipocyte differentiation. Environ Int. 2021 Nov;156:106730. doi: 10.1016/j.envint.2021.106730. Epub 2021 Jun 27.
45 Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
46 ST1926, a novel and orally active retinoid-related molecule inducing apoptosis in myeloid leukemia cells: modulation of intracellular calcium homeostasis. Blood. 2004 Jan 1;103(1):194-207.
47 -Lipoic acid (-LA) inhibits the transcriptional activity of interferon regulatory factor 1 (IRF-1) via SUMOylation. Toxicol In Vitro. 2014 Oct;28(7):1242-8. doi: 10.1016/j.tiv.2014.06.003. Epub 2014 Jun 26.