Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT9B447E)

DOT Name Small ubiquitin-related modifier 4 (SUMO4)
Synonyms SUMO-4; Small ubiquitin-like protein 4
Gene Name SUMO4
Related Disease
Diabetic retinopathy ( )
Amyloidosis ( )
Autoimmune disease ( )
Behcet disease ( )
Eclampsia ( )
Hepatocellular carcinoma ( )
Juvenile idiopathic arthritis ( )
Nephropathy ( )
Obesity ( )
Type-1/2 diabetes ( )
Uveitis ( )
Addison disease ( )
Graves disease ( )
Diabetic kidney disease ( )
Coronary atherosclerosis ( )
Coronary heart disease ( )
UniProt ID
SUMO4_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Pfam ID
PF11976
Sequence
MANEKPTEEVKTENNNHINLKVAGQDGSVVQFKIKRQTPLSKLMKAYCEPRGLSVKQIRF
RFGGQPISGTDKPAQLEMEDEDTIDVFQQPTGGVY
Function
Ubiquitin-like protein which can be covalently attached to target lysines as a monomer. Does not seem to be involved in protein degradation and may modulate protein subcellular localization, stability or activity. Upon oxidative stress, conjugates to various anti-oxidant enzymes, chaperones, and stress defense proteins. May also conjugate to NFKBIA, TFAP2A and FOS, negatively regulating their transcriptional activity, and to NR3C1, positively regulating its transcriptional activity. Covalent attachment to its substrates requires prior activation by the E1 complex SAE1-SAE2 and linkage to the E2 enzyme UBE2I.
Tissue Specificity Expressed mainly in adult and embryonic kidney. Expressed at various levels in immune tissues, with the highest expression in the lymph node and spleen.
KEGG Pathway
Nucleocytoplasmic transport (hsa03013 )
Fluid shear stress and atherosclerosis (hsa05418 )

Molecular Interaction Atlas (MIA) of This DOT

16 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Diabetic retinopathy DISHGUJM Definitive Genetic Variation [1]
Amyloidosis DISHTAI2 Strong Genetic Variation [2]
Autoimmune disease DISORMTM Strong Biomarker [3]
Behcet disease DISSYMBS Strong Genetic Variation [4]
Eclampsia DISWPO8U Strong Biomarker [5]
Hepatocellular carcinoma DIS0J828 Strong Altered Expression [6]
Juvenile idiopathic arthritis DISQZGBV Strong Genetic Variation [7]
Nephropathy DISXWP4P Strong Genetic Variation [8]
Obesity DIS47Y1K Strong Biomarker [9]
Type-1/2 diabetes DISIUHAP Strong Genetic Variation [10]
Uveitis DISV0RYS Strong Genetic Variation [4]
Addison disease DIS7HNOH moderate Genetic Variation [11]
Graves disease DISU4KOQ moderate Genetic Variation [11]
Diabetic kidney disease DISJMWEY Disputed Genetic Variation [8]
Coronary atherosclerosis DISKNDYU Limited Genetic Variation [12]
Coronary heart disease DIS5OIP1 Limited Genetic Variation [12]
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⏷ Show the Full List of 16 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
5 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 Small ubiquitin-related modifier 4 (SUMO4). [13]
Capsaicin DMGMF6V Approved Capsaicin increases the expression of Small ubiquitin-related modifier 4 (SUMO4). [14]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the expression of Small ubiquitin-related modifier 4 (SUMO4). [15]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 decreases the expression of Small ubiquitin-related modifier 4 (SUMO4). [16]
Milchsaure DM462BT Investigative Milchsaure increases the expression of Small ubiquitin-related modifier 4 (SUMO4). [17]
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References

1 A M55V polymorphism in the SUMO4 gene is associated with a reduced prevalence of diabetic retinopathy in patients with Type 1 diabetes.Exp Clin Endocrinol Diabetes. 2008 Jan;116(1):14-7. doi: 10.1055/s-2007-985357. Epub 2007 Oct 9.
2 Evidence for the role of small ubiquitin-like modifier 4 as a general autoimmunity locus in the Japanese population.J Clin Endocrinol Metab. 2006 Aug;91(8):3138-43. doi: 10.1210/jc.2006-0206. Epub 2006 May 30.
3 SUMO4 C438T polymorphism is associated with papulopustular skin lesion in Korean patients with Behet's disease.Rheumatol Int. 2012 Oct;32(10):3031-7. doi: 10.1007/s00296-011-2086-5. Epub 2011 Sep 8.
4 Uveitis genetics.Exp Eye Res. 2020 Jan;190:107853. doi: 10.1016/j.exer.2019.107853. Epub 2019 Oct 25.
5 SUMO-4: A novel functional candidate in the human placental protein SUMOylation machinery.PLoS One. 2017 May 17;12(5):e0178056. doi: 10.1371/journal.pone.0178056. eCollection 2017.
6 A M55V polymorphism in a novel SUMO gene (SUMO-4) differentially activates heat shock transcription factors and is associated with susceptibility to type I diabetes mellitus.J Biol Chem. 2004 Jun 25;279(26):27233-8. doi: 10.1074/jbc.M402273200. Epub 2004 Apr 29.
7 The type 1 diabetes susceptibility gene SUMO4 at IDDM5 is not associated with susceptibility to rheumatoid arthritis or juvenile idiopathic arthritis.Rheumatology (Oxford). 2005 Nov;44(11):1390-3. doi: 10.1093/rheumatology/kei041. Epub 2005 Sep 13.
8 SUMO4 163 G>A variation is associated with kidney disease in Indian subjects with type 2 diabetes.Mol Biol Rep. 2016 May;43(5):345-8. doi: 10.1007/s11033-016-3979-x. Epub 2016 Apr 7.
9 Expression-based network biology identifies alteration in key regulatory pathways of type 2 diabetes and associated risk/complications.PLoS One. 2009 Dec 7;4(12):e8100. doi: 10.1371/journal.pone.0008100.
10 Association of donor and recipient SUMO4 rs237025 genetic variant with new-onset diabetes mellitus after liver transplantation in a Chinese population.Gene. 2017 Sep 5;627:428-433. doi: 10.1016/j.gene.2017.06.060. Epub 2017 Jul 6.
11 No association of the codon 55 methionine to valine polymorphism in the SUMO4 gene with Graves' disease.Clin Endocrinol (Oxf). 2005 Mar;62(3):362-5. doi: 10.1111/j.1365-2265.2005.02224.x.
12 SUMO4 Met55Val polymorphism is associated with coronary heart disease in Japanese type 2 diabetes individuals.Diabetes Res Clin Pract. 2009 Jul;85(1):85-9. doi: 10.1016/j.diabres.2009.04.001. Epub 2009 May 1.
13 Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
14 A comparative proteomic analysis for capsaicin-induced apoptosis between human hepatocarcinoma (HepG2) and human neuroblastoma (SK-N-SH) cells. Proteomics. 2008 Nov;8(22):4748-67. doi: 10.1002/pmic.200800094.
15 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.
16 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.
17 Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.