Details of Drug Off-Target (DOT)

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

DOT Name	Lupus La protein (SSB)
Synonyms	La autoantigen; La ribonucleoprotein; Sjoegren syndrome type B antigen; SS-B
Gene Name	SSB
Related Disease	Peeling skin syndrome 1 ( ) Potocki-Shaffer syndrome ( ) Systemic sclerosis ( ) Adult lymphoma ( ) Ataxia-telangiectasia ( ) Atrioventricular block ( ) Cardiac disease ( ) Cardiac failure ( ) Cardiovascular disease ( ) Congestive heart failure ( ) Cytomegalovirus infection ( ) Dengue ( ) Hematologic disease ( ) Hepatitis B virus infection ( ) Hepatitis C virus infection ( ) Hereditary angioedema ( ) Keratoconjunctivitis sicca ( ) Leukopenia ( ) Lupus ( ) Lymphoma ( ) Pediatric lymphoma ( ) Sjogren syndrome ( ) Stroke ( ) Subacute cutaneous lupus erythematosus ( ) Syphilis ( ) Xerophthalmia ( ) Autoimmune disease ( ) Epstein barr virus infection ( ) Graves disease ( ) MALT lymphoma ( ) Thyroiditis ( ) Female hypogonadism ( ) Rheumatoid arthritis ( )
UniProt ID	LA_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
PDB ID	1OWX; 1S79; 1S7A; 1YTY; 1ZH5; 2VOD; 2VON; 2VOO; 2VOP
Pfam ID	PF05383 ; PF00076 ; PF08777
Sequence	MAENGDNEKMAALEAKICHQIEYYFGDFNLPRDKFLKEQIKLDEGWVPLEIMIKFNRLNR LTTDFNVIVEALSKSKAELMEISEDKTKIRRSPSKPLPEVTDEYKNDVKNRSVYIKGFPT DATLDDIKEWLEDKGQVLNIQMRRTLHKAFKGSIFVVFDSIESAKKFVETPGQKYKETDL LILFKDDYFAKKNEERKQNKVEAKLRAKQEQEAKQKLEEDAEMKSLEEKIGCLLKFSGDL DDQTCREDLHILFSNHGEIKWIDFVRGAKEGIILFKEKAKEALGKAKDANNGNLQLRNKE VTWEVLEGEVEKEALKKIIEDQQESLNKWKSKGRRFKGKGKGNKAAQPGSGKGKVQFQGK KTKFASDDEHDEHDENGATGPVKRAREETDKEEPASKQQKTENGAGDQ
Function	Binds to the 3' poly(U) terminus of nascent RNA polymerase III transcripts, protecting them from exonuclease digestion and facilitating their folding and maturation. In case of Coxsackievirus B3 infection, binds to the viral internal ribosome entry site (IRES) and stimulates the IRES-mediated translation.
KEGG Pathway	Systemic lupus erythematosus (hsa05322 )
Reactome Pathway	RNA Polymerase III Abortive And Retractive Initiation (R-HSA-749476 ) RNA Polymerase III Transcription Termination (R-HSA-73980 )

Molecular Interaction Atlas (MIA) of This DOT

33 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Peeling skin syndrome 1	DIS35574	Definitive	Altered Expression	[1]
Potocki-Shaffer syndrome	DISKGU59	Definitive	Altered Expression	[1]
Systemic sclerosis	DISF44L6	Definitive	Altered Expression	[1]
Adult lymphoma	DISK8IZR	Strong	Genetic Variation	[2]
Ataxia-telangiectasia	DISP3EVR	Strong	Biomarker	[3]
Atrioventricular block	DIS8YLE6	Strong	Biomarker	[4]
Cardiac disease	DISVO1I5	Strong	Biomarker	[4]
Cardiac failure	DISDC067	Strong	Genetic Variation	[5]
Cardiovascular disease	DIS2IQDX	Strong	Biomarker	[6]
Congestive heart failure	DIS32MEA	Strong	Genetic Variation	[5]
Cytomegalovirus infection	DISCEMGC	Strong	Altered Expression	[7]
Dengue	DISKH221	Strong	Biomarker	[8]
Hematologic disease	DIS9XD9A	Strong	Biomarker	[9]
Hepatitis B virus infection	DISLQ2XY	Strong	Biomarker	[10]
Hepatitis C virus infection	DISQ0M8R	Strong	Biomarker	[11]
Hereditary angioedema	DIS8X53J	Strong	Biomarker	[12]
Keratoconjunctivitis sicca	DISNOENH	Strong	Biomarker	[13]
Leukopenia	DISJMBMM	Strong	Biomarker	[14]
Lupus	DISOKJWA	Strong	Altered Expression	[15]
Lymphoma	DISN6V4S	Strong	Genetic Variation	[2]
Pediatric lymphoma	DIS51BK2	Strong	Genetic Variation	[2]
Sjogren syndrome	DISUBX7H	Strong	Biomarker	[16]
Stroke	DISX6UHX	Strong	Genetic Variation	[5]
Subacute cutaneous lupus erythematosus	DIS6XDK0	Strong	Biomarker	[17]
Syphilis	DISJ73BS	Strong	Biomarker	[18]
Xerophthalmia	DIS5B72B	Strong	Biomarker	[13]
Autoimmune disease	DISORMTM	moderate	Biomarker	[19]
Epstein barr virus infection	DISOO0WT	moderate	Biomarker	[20]
Graves disease	DISU4KOQ	moderate	Biomarker	[21]
MALT lymphoma	DIS1AVVE	moderate	Biomarker	[21]
Thyroiditis	DISTCV24	moderate	Biomarker	[21]
Female hypogonadism	DISWASB4	Limited	Biomarker	[22]
Rheumatoid arthritis	DISTSB4J	Limited	Biomarker	[23]
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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

9 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Lupus La protein (SSB).	[24]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Lupus La protein (SSB).	[25]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Lupus La protein (SSB).	[26]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol decreases the expression of Lupus La protein (SSB).	[27]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of Lupus La protein (SSB).	[28]
Aminoglutethimide	DMWFHMZ	Approved	Aminoglutethimide decreases the expression of Lupus La protein (SSB).	[29]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Lupus La protein (SSB).	[31]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Lupus La protein (SSB).	[32]
Deguelin	DMXT7WG	Investigative	Deguelin increases the expression of Lupus La protein (SSB).	[33]
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⏷ Show the Full List of 9 Drug(s)

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Lupus La protein (SSB).	[30]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Lupus La protein (SSB).	[30]
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References

1	Hypokalaemia in Sjgren's syndrome: the missing piece.Clin Med (Lond). 2017 Feb;17(1):40-42. doi: 10.7861/clinmedicine.17-1-40.
2	STAT4, TRAF3IP2, IL10, and HCP5 Polymorphisms in Sjgren's Syndrome: Association with Disease Susceptibility and Clinical Aspects.J Immunol Res. 2019 Feb 10;2019:7682827. doi: 10.1155/2019/7682827. eCollection 2019.
3	The development of ataxia telangiectasia mutated kinase inhibitors.Mini Rev Med Chem. 2014;14(10):805-11.
4	An expanded phenotype of maternal SSA/SSB antibody-associated fetal cardiac disease.J Matern Fetal Neonatal Med. 2009 Mar;22(3):233-8. doi: 10.1080/14767050802488220.
5	Food groups and risk of coronary heart disease, stroke and heart failure: A systematic review and dose-response meta-analysis of prospective studies.Crit Rev Food Sci Nutr. 2019;59(7):1071-1090. doi: 10.1080/10408398.2017.1392288. Epub 2017 Nov 7.
6	Concomitant Ro/SSA and La/SSB antibodies are biomarkers for the risk of venous thromboembolism and cerebral infarction in primary Sjgren's syndrome.J Intern Med. 2019 Oct;286(4):458-468. doi: 10.1111/joim.12941. Epub 2019 Jun 17.
7	Human cytomegalovirus induces the endoplasmic reticulum chaperone BiP through increased transcription and activation of translation by using the BiP internal ribosome entry site.J Virol. 2010 Nov;84(21):11479-86. doi: 10.1128/JVI.01330-10. Epub 2010 Aug 25.
8	La protein binds to NS5 and NS3 and to the 5' and 3' ends of Dengue 4 virus RNA.Virus Res. 2004 Jun 15;102(2):141-50. doi: 10.1016/j.virusres.2004.01.024.
9	Glutathione S-transferase genotype and risk of systemic lupus erythematosus in Koreans.Lupus. 2005;14(5):381-4. doi: 10.1191/0961203305lu2100oa.
10	Functional characterization of the interaction between human La and hepatitis B virus RNA.J Biol Chem. 2004 Oct 15;279(42):43437-47. doi: 10.1074/jbc.M402227200. Epub 2004 Aug 9.
11	Anti-SSB/La antibody is negatively associated with HLA-DR2 in chronic hepatitis C infection.Clin Rheumatol. 2008 Mar;27(3):365-8. doi: 10.1007/s10067-007-0783-y. Epub 2007 Nov 9.
12	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.
13	Clinical and immunological parameters of Sjgren's syndrome.Autoimmun Rev. 2018 Oct;17(10):1053-1064. doi: 10.1016/j.autrev.2018.05.005. Epub 2018 Aug 10.
14	Impact of the leucocyte immunoglobulin-like receptor A3 (LILRA3) on susceptibility and subphenotypes of systemic lupus erythematosus and Sjgren's syndrome.Ann Rheum Dis. 2015 Nov;74(11):2070-5. doi: 10.1136/annrheumdis-2013-204441. Epub 2014 Jun 6.
15	Increased levels of anti-dsDNA antibodies in immune complexes before treatment with belimumab associate with clinical response in patients with systemic lupus erythematosus.Arthritis Res Ther. 2019 Nov 29;21(1):259. doi: 10.1186/s13075-019-2056-y.
16	Antigen-driven selection of antibodies against SSA, SSB and the centromere 'complex', including a novel antigen, MIS12 complex, in human salivary glands.Ann Rheum Dis. 2020 Jan;79(1):150-158. doi: 10.1136/annrheumdis-2019-215862. Epub 2019 Oct 14.
17	Clinical relevance of antibodies to Ro/SS-A and La/SS-B in subacute cutaneous lupus erythematosus and related conditions.Immunol Invest. 1993 Apr;22(3):189-203. doi: 10.3109/08820139309063402.
18	Null alleles of the fourth component of complement and HLA haplotypes in familial systemic lupus erythematosus.Immunogenetics. 1985;21(4):299-311. doi: 10.1007/BF00430796.
19	La/SSB chimeric autoantibody receptor modified NK92MI cells for targeted therapy of autoimmune disease.Clin Immunol. 2018 Jul;192:40-49. doi: 10.1016/j.clim.2018.04.006. Epub 2018 Apr 16.
20	Epstein-Barr virus as an etiological agent in primary Sjgren's syndrome.Med Hypotheses. 1987 Apr;22(4):373-86. doi: 10.1016/0306-9877(87)90033-8.
21	Autoimmunity and extranodal lymphocytic infiltrates in lymphoproliferative disorders.J Intern Med. 1999 Mar;245(3):277-86. doi: 10.1046/j.1365-2796.1999.0443f.x.
22	A truncating MEIOB mutation responsible for familial primary ovarian insufficiency abolishes its interaction with its partner SPATA22 and their recruitment to DNA double-strand breaks.EBioMedicine. 2019 Apr;42:524-531. doi: 10.1016/j.ebiom.2019.03.075. Epub 2019 Apr 15.
23	Association of increased frequencies of HLA-DPB1*05:01 with the presence of anti-Ro/SS-A and anti-La/SS-B antibodies in Japanese rheumatoid arthritis and systemic lupus erythematosus patients.PLoS One. 2013;8(1):e53910. doi: 10.1371/journal.pone.0053910. Epub 2013 Jan 8.
24	Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
25	Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
26	Proteomics-based identification of differentially abundant proteins from human keratinocytes exposed to arsenic trioxide. J Proteomics Bioinform. 2014 Jul;7(7):166-178.
27	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.
28	Transcriptional profiling of testosterone-regulated genes in the skeletal muscle of human immunodeficiency virus-infected men experiencing weight loss. J Clin Endocrinol Metab. 2007 Jul;92(7):2793-802. doi: 10.1210/jc.2006-2722. Epub 2007 Apr 17.
29	Proteomic profile of aminoglutethimide-induced apoptosis in HL-60 cells: role of myeloperoxidase and arylamine free radicals. Chem Biol Interact. 2015 Sep 5;239:129-38.
30	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.
31	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.
32	Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
33	Neurotoxicity and underlying cellular changes of 21 mitochondrial respiratory chain inhibitors. Arch Toxicol. 2021 Feb;95(2):591-615. doi: 10.1007/s00204-020-02970-5. Epub 2021 Jan 29.