Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTLGM5A8)

• DOT Name: RNA-binding protein RO60 (RO60)
• Synonyms: 60 kDa SS-A/Ro ribonucleoprotein; 60 kDa Ro protein; 60 kDa ribonucleoprotein Ro; RoRNP; Ro 60 kDa autoantigen; Ro60 autoantigen; Sjoegren syndrome antigen A2; Sjoegren syndrome type A antigen; SS-A; TROVE domain family member 2
• Gene Name: RO60
• Related Disease:
  Peeling skin syndrome 1
  Potocki-Shaffer syndrome
  Advanced cancer
  Astrocytoma
  Breast cancer
  Breast carcinoma
  Chagas disease
  Colitis
  Cutaneous lupus erythematosus
  Hepatitis
  Hepatitis A virus infection
  Hereditary angioedema
  Idiopathic inflammatory myopathy
  Idiopathic thrombocytopenic purpura
  Inflammatory bowel disease
  Keratoconjunctivitis sicca
  Myositis disease
  Ocular motor apraxia, Cogan type
  Relapsing-remitting multiple sclerosis
  Rheumatoid arthritis
  Sjogren syndrome
  Thrombocytopenia
  Trichohepatoenteric syndrome
  Xerophthalmia
  Autoimmune polyendocrine syndrome type 1
  Gastroesophageal reflux disease
  Overactive bladder
  Pulmonary disease
  Pure red-cell aplasia
  Mixed connective tissue disease
  Autoimmune disease
  Matthew-Wood syndrome
  Pancreatic ductal carcinoma
  Systemic sclerosis
• UniProt ID: RO60_HUMAN
• Pfam ID: PF05731
• Sequence:
  MEESVNQMQPLNEKQIANSQDGYVWQVTDMNRLHRFLCFGSEGGTYYIKEQKLGLENAEA
  LIRLIEDGRGCEVIQEIKSFSQEGRTTKQEPMLFALAICSQCSDISTKQAAFKAVSEVCR
  IPTHLFTFIQFKKDLKESMKCGMWGRALRKAIADWYNEKGGMALALAVTKYKQRNGWSHK
  DLLRLSHLKPSSEGLAIVTKYITKGWKEVHELYKEKALSVETEKLLKYLEAVEKVKRTRD
  ELEVIHLIEEHRLVREHLLTNHLKSKEVWKALLQEMPLTALLRNLGKMTANSVLEPGNSE
  VSLVCEKLCNEKLLKKARIHPFHILIALETYKTGHGLRGKLKWRPDEEILKALDAAFYKT
  FKTVEPTGKRFLLAVDVSASMNQRVLGSILNASTVAAAMCMVVTRTEKDSYVVAFSDEMV
  PCPVTTDMTLQQVLMAMSQIPAGGTDCSLPMIWAQKTNTPADVFIVFTDNETFAGGVHPA
  IALREYRKKMDIPAKLIVCGMTSNGFTIADPDDRGMLDMCGFDTGALDVIRNFTLDMI
• Function: RNA-binding protein that binds to misfolded non-coding RNAs, pre-5S rRNA, and several small cytoplasmic RNA molecules known as Y RNAs. Binds to endogenous Alu retroelements which are induced by type I interferon and stimulate porinflammatory cytokine secretion. Regulates the expression of Alu retroelements as well as inflammatory genes. May play roles in cilia formation and/or maintenance.
• KEGG Pathway: Systemic lupus erythematosus (hsa05322)

Molecular Interaction Atlas (MIA) of This DOT

34 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Peeling skin syndrome 1	DIS35574	Definitive	Genetic Variation	[1]
Potocki-Shaffer syndrome	DISKGU59	Definitive	Genetic Variation	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
Astrocytoma	DISL3V18	Strong	Biomarker	[3]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[4]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[4]
Chagas disease	DIS8KNVF	Strong	Biomarker	[5]
Colitis	DISAF7DD	Strong	Biomarker	[6]
Cutaneous lupus erythematosus	DISOIX6L	Strong	Genetic Variation	[7]
Hepatitis	DISXXX35	Strong	Biomarker	[8]
Hepatitis A virus infection	DISUMFQV	Strong	Biomarker	[8]
Hereditary angioedema	DIS8X53J	Strong	Biomarker	[9]
Idiopathic inflammatory myopathy	DISGB1BZ	Strong	Altered Expression	[10]
Idiopathic thrombocytopenic purpura	DISFKGJU	Strong	Biomarker	[11]
Inflammatory bowel disease	DISGN23E	Strong	Altered Expression	[6]
Keratoconjunctivitis sicca	DISNOENH	Strong	Biomarker	[12]
Myositis disease	DISCIXF0	Strong	Biomarker	[13]
Ocular motor apraxia, Cogan type	DIS32GGL	Strong	Biomarker	[14]
Relapsing-remitting multiple sclerosis	DISSXFCF	Strong	Biomarker	[15]
Rheumatoid arthritis	DISTSB4J	Strong	Biomarker	[2]
Sjogren syndrome	DISUBX7H	Strong	Biomarker	[16]
Thrombocytopenia	DISU61YW	Strong	Biomarker	[11]
Trichohepatoenteric syndrome	DISL3ODF	Strong	Biomarker	[17]
Xerophthalmia	DIS5B72B	Strong	Biomarker	[12]
Autoimmune polyendocrine syndrome type 1	DISWJP8J	moderate	Genetic Variation	[18]
Gastroesophageal reflux disease	DISQ8G5S	moderate	Biomarker	[19]
Overactive bladder	DISQR5TD	moderate	Biomarker	[19]
Pulmonary disease	DIS6060I	moderate	Biomarker	[19]
Pure red-cell aplasia	DIST91OT	moderate	Biomarker	[20]
Mixed connective tissue disease	DISXX0H8	Disputed	Genetic Variation	[21]
Autoimmune disease	DISORMTM	Limited	Biomarker	[22]
Matthew-Wood syndrome	DISA7HR7	Limited	Altered Expression	[23]
Pancreatic ductal carcinoma	DIS26F9Q	Limited	Altered Expression	[23]
Systemic sclerosis	DISF44L6	Limited	Altered Expression	[24]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of RNA-binding protein RO60 (RO60).	[25]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of RNA-binding protein RO60 (RO60).	[28]

19 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 RNA-binding protein RO60 (RO60).	[26]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of RNA-binding protein RO60 (RO60).	[26]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of RNA-binding protein RO60 (RO60).	[27]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of RNA-binding protein RO60 (RO60).	[29]
Selenium	DM25CGV	Approved	Selenium decreases the expression of RNA-binding protein RO60 (RO60).	[30]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of RNA-binding protein RO60 (RO60).	[31]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone decreases the expression of RNA-binding protein RO60 (RO60).	[26]
Indomethacin	DMSC4A7	Approved	Indomethacin decreases the expression of RNA-binding protein RO60 (RO60).	[32]
Cidofovir	DMA13GD	Approved	Cidofovir decreases the expression of RNA-binding protein RO60 (RO60).	[26]
Fenofibrate	DMFKXDY	Approved	Fenofibrate decreases the expression of RNA-binding protein RO60 (RO60).	[26]
Ifosfamide	DMCT3I8	Approved	Ifosfamide decreases the expression of RNA-binding protein RO60 (RO60).	[26]
Clodronate	DM9Y6X7	Approved	Clodronate decreases the expression of RNA-binding protein RO60 (RO60).	[26]
Epanova	DMHEAGL	Approved	Epanova increases the expression of RNA-binding protein RO60 (RO60).	[33]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of RNA-binding protein RO60 (RO60).	[34]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of RNA-binding protein RO60 (RO60).	[30]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of RNA-binding protein RO60 (RO60).	[35]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of RNA-binding protein RO60 (RO60).	[36]
Nickel chloride	DMI12Y8	Investigative	Nickel chloride decreases the expression of RNA-binding protein RO60 (RO60).	[37]
crotylaldehyde	DMTWRQI	Investigative	crotylaldehyde decreases the expression of RNA-binding protein RO60 (RO60).	[38]

References

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• [2] Clinical associations of the positive anti Ro52 without Ro60 autoantibodies: undifferentiated connective tissue diseases.J Clin Pathol. 2018 Jan;71(1):12-19. doi: 10.1136/jclinpath-2015-203587. Epub 2017 Jun 29.
• [3] Expression Profile of MiR-128 in the Astrocytoma Patients and Cell Lines.Mol Neurobiol. 2016 Sep;53(7):4631-7. doi: 10.1007/s12035-015-9401-1. Epub 2015 Aug 26.
• [4] 17-beta-estradiol increases expression of 52-kDa and 60-kDa SS-A/Ro autoantigens in human keratinocytes and breast cancer cell line MCF-7.J Invest Dermatol. 1996 Oct;107(4):610-4. doi: 10.1111/1523-1747.ep12584194.
• [5] Seroprevalence and geographical distribution of sero-positive blood donors to Trypanosoma cruzi at the central blood bank of the National Medical Center "La Raza".Transfusion. 2019 Feb;59(2):639-647. doi: 10.1111/trf.15074. Epub 2018 Dec 5.
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• [8] Immune responses to Ro60 and its peptides in mice. I. The nature of the immunogen and endogenous autoantigen determine the specificities of the induced autoantibodies.J Exp Med. 1999 Feb 1;189(3):531-40. doi: 10.1084/jem.189.3.531.
• [9] Association of Sjgren's syndrome with hereditary angioneurotic edema: report of a case.Clin Immunol Immunopathol. 1997 Jul;84(1):95-7. doi: 10.1006/clin.1997.4347.
• [10] Anti-Ro52 antibodies frequently co-occur with anti-Jo-1 antibodies in sera from patients with idiopathic inflammatory myopathy.Clin Exp Immunol. 1997 Jul;109(1):32-40. doi: 10.1046/j.1365-2249.1997.4081308.x.
• [11] Thrombocytopenia in the neonatal lupus syndrome.Arch Dermatol. 1988 Apr;124(4):560-3.
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• [14] Congenital heart block and immune mediated sensorineural hearing loss: possible cross reactivity of immune response.Lupus. 2017 Jul;26(8):835-840. doi: 10.1177/0961203316682099. Epub 2016 Dec 5.
• [15] Defective structural RNA processing in relapsing-remitting multiple sclerosis.Genome Biol. 2015 Mar 25;16(1):58. doi: 10.1186/s13059-015-0629-x.
• [16] Ro60 and Y RNAs: structure, functions, and roles in autoimmunity.Crit Rev Biochem Mol Biol. 2019 Apr;54(2):133-152. doi: 10.1080/10409238.2019.1608902. Epub 2019 May 14.
• [17] Neonatal lupus erythematosus occurring in one fraternal twin. Serologic and immunogenetic studies.Arthritis Rheum. 1985 Mar;28(3):271-5. doi: 10.1002/art.1780280306.
• [18] Profiling Autoantibodies against Salivary Proteins in Sicca Conditions.J Dent Res. 2019 Jul;98(7):772-778. doi: 10.1177/0022034519850564. Epub 2019 May 16.
• [19] Prevalence and clinical characteristics of overactive bladder in systemic sclerosis.Mod Rheumatol. 2020 Mar;30(2):327-331. doi: 10.1080/14397595.2019.1589913. Epub 2019 Apr 1.
• [20] Lupus enteritis during pregnancy: A case-based review.Mod Rheumatol. 2017 Nov;27(6):1089-1092. doi: 10.3109/14397595.2015.1055642. Epub 2015 Aug 18.
• [21] Interferons (IFN-A/-B/-G) Genetic Variants in Patients with Mixed Connective Tissue Disease (MCTD).J Clin Med. 2019 Nov 21;8(12):2046. doi: 10.3390/jcm8122046.
• [22] Diagnostic Utility of Separate Anti-Ro60 and Anti-Ro52/TRIM21 Antibody Detection in Autoimmune Diseases.Front Immunol. 2019 Mar 12;10:444. doi: 10.3389/fimmu.2019.00444. eCollection 2019.
• [23] Ro60/SSA levels are increased and promote the progression of pancreatic ductal adenocarcinoma.Biochem Biophys Res Commun. 2018 Jan 22;495(4):2519-2524. doi: 10.1016/j.bbrc.2017.12.124. Epub 2017 Dec 22.
• [24] Autoantibodies are present before the clinical diagnosis of systemic sclerosis.PLoS One. 2019 Mar 26;14(3):e0214202. doi: 10.1371/journal.pone.0214202. eCollection 2019.
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• [29] Minimal peroxide exposure of neuronal cells induces multifaceted adaptive responses. PLoS One. 2010 Dec 17;5(12):e14352. doi: 10.1371/journal.pone.0014352.
• [30] 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.
• [31] 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.
• [32] Mechanisms of indomethacin-induced alterations in the choline phospholipid metabolism of breast cancer cells. Neoplasia. 2006 Sep;8(9):758-71.
• [33] Differential effects of omega-3 and omega-6 Fatty acids on gene expression in breast cancer cells. Breast Cancer Res Treat. 2007 Jan;101(1):7-16. doi: 10.1007/s10549-006-9269-x. Epub 2006 Jul 6.
• [34] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [35] Low-dose Bisphenol A exposure alters the functionality and cellular environment in a human cardiomyocyte model. Environ Pollut. 2023 Oct 15;335:122359. doi: 10.1016/j.envpol.2023.122359. Epub 2023 Aug 9.
• [36] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [37] The contact allergen nickel triggers a unique inflammatory and proangiogenic gene expression pattern via activation of NF-kappaB and hypoxia-inducible factor-1alpha. J Immunol. 2007 Mar 1;178(5):3198-207.
• [38] Gene expression profile and cytotoxicity of human bronchial epithelial cells exposed to crotonaldehyde. Toxicol Lett. 2010 Aug 16;197(2):113-22.