Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTITK5E6)

DOT Name CD180 antigen (CD180)
Synonyms Lymphocyte antigen 64; Radioprotective 105 kDa protein; CD antigen CD180
Gene Name CD180
Related Disease
Craniosynostosis ( )
Diffuse systemic sclerosis ( )
Immune system disorder ( )
Lupus ( )
Lyme disease ( )
Metabolic disorder ( )
Nasal polyp ( )
Obesity ( )
Small lymphocytic lymphoma ( )
Systemic lupus erythematosus ( )
Tuberculosis ( )
Arteriosclerosis ( )
Atherosclerosis ( )
Myocardial infarction ( )
Plasma cell myeloma ( )
Parkinson disease ( )
Primary biliary cholangitis ( )
Cardiovascular disease ( )
Neoplasm ( )
UniProt ID
CD180_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
3B2D
Pfam ID
PF18831 ; PF13855
Sequence
MAFDVSCFFWVVLFSAGCKVITSWDQMCIEKEANKTYNCENLGLSEIPDTLPNTTEFLEF
SFNFLPTIHNRTFSRLMNLTFLDLTRCQINWIHEDTFQSHHQLSTLVLTGNPLIFMAETS
LNGPKSLKHLFLIQTGISNLEFIPVHNLENLESLYLGSNHISSIKFPKDFPARNLKVLDF
QNNAIHYISREDMRSLEQAINLSLNFNGNNVKGIELGAFDSTIFQSLNFGGTPNLSVIFN
GLQNSTTQSLWLGTFEDIDDEDISSAMLKGLCEMSVESLNLQEHRFSDISSTTFQCFTQL
QELDLTATHLKGLPSGMKGLNLLKKLVLSVNHFDQLCQISAANFPSLTHLYIRGNVKKLH
LGVGCLEKLGNLQTLDLSHNDIEASDCCSLQLKNLSHLQTLNLSHNEPLGLQSQAFKECP
QLELLDLAFTRLHINAPQSPFQNLHFLQVLNLTYCFLDTSNQHLLAGLPVLRHLNLKGNH
FQDGTITKTNLLQTVGSLEVLILSSCGLLSIDQQAFHSLGKMSHVDLSHNSLTCDSIDSL
SHLKGIYLNLAANSINIISPRLLPILSQQSTINLSHNPLDCTCSNIHFLTWYKENLHKLE
GSEETTCANPPSLRGVKLSDVKLSCGITAIGIFFLIVFLLLLAILLFFAVKYLLRWKYQH
I
Function
May cooperate with MD-1 and TLR4 to mediate the innate immune response to bacterial lipopolysaccharide (LPS) in B-cells. Leads to NF-kappa-B activation. Also involved in the life/death decision of B-cells.
Tissue Specificity Expressed mainly on mature peripherical B cells. Detected in spleen, lymph node and appendix. Not detected in pre-B and -T cells.
Reactome Pathway
Toll Like Receptor 4 (TLR4) Cascade (R-HSA-166016 )

Molecular Interaction Atlas (MIA) of This DOT

19 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Craniosynostosis DIS6J405 Strong Altered Expression [1]
Diffuse systemic sclerosis DISYF5LP Strong Altered Expression [2]
Immune system disorder DISAEGPH Strong Biomarker [3]
Lupus DISOKJWA Strong Biomarker [4]
Lyme disease DISO70G5 Strong Biomarker [5]
Metabolic disorder DIS71G5H Strong Biomarker [6]
Nasal polyp DISLP3XE Strong Biomarker [1]
Obesity DIS47Y1K Strong Biomarker [6]
Small lymphocytic lymphoma DIS30POX Strong Biomarker [7]
Systemic lupus erythematosus DISI1SZ7 Strong Biomarker [4]
Tuberculosis DIS2YIMD Strong Biomarker [8]
Arteriosclerosis DISK5QGC moderate Biomarker [9]
Atherosclerosis DISMN9J3 moderate Biomarker [9]
Myocardial infarction DIS655KI moderate Biomarker [9]
Plasma cell myeloma DIS0DFZ0 moderate Altered Expression [10]
Parkinson disease DISQVHKL Disputed Biomarker [11]
Primary biliary cholangitis DIS43E0O Disputed Altered Expression [12]
Cardiovascular disease DIS2IQDX Limited Biomarker [9]
Neoplasm DISZKGEW Limited Biomarker [13]
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⏷ Show the Full List of 19 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
3 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Marinol DM70IK5 Approved Marinol increases the expression of CD180 antigen (CD180). [14]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 decreases the expression of CD180 antigen (CD180). [16]
Sulforaphane DMQY3L0 Investigative Sulforaphane decreases the expression of CD180 antigen (CD180). [17]
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1 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the methylation of CD180 antigen (CD180). [15]
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References

1 Discordant frequencies of tissue-resident and circulating CD180-negative B cells in chronic rhinosinusitis.Int Forum Allergy Rhinol. 2017 Jun;7(6):609-614. doi: 10.1002/alr.21924. Epub 2017 Feb 25.
2 Toll-Like Receptor Mediated Activation of Natural Autoantibody Producing B Cell Subpopulations in an Autoimmune Disease Model.Int J Mol Sci. 2019 Dec 6;20(24):6152. doi: 10.3390/ijms20246152.
3 Inhibition of myeloid differentiation 1 specifically in colon with antisense oligonucleotide exacerbates dextran sodium sulfate-induced colitis.J Cell Biochem. 2019 Oct;120(10):16888-16899. doi: 10.1002/jcb.28947. Epub 2019 May 19.
4 CD180 Ligation Inhibits TLR7- and TLR9-Mediated Activation of Macrophages and Dendritic Cells Through the Lyn-SHP-1/2 Axis in Murine Lupus.Front Immunol. 2018 Nov 15;9:2643. doi: 10.3389/fimmu.2018.02643. eCollection 2018.
5 A multi-omic analysis reveals the regulatory role of CD180 during the response of macrophages to Borrelia burgdorferi.Emerg Microbes Infect. 2018 Mar 7;7(1):19. doi: 10.1038/s41426-017-0018-5.
6 The radioprotective 105/MD-1 complex contributes to diet-induced obesity and adipose tissue inflammation.Diabetes. 2012 May;61(5):1199-209. doi: 10.2337/db11-1182. Epub 2012 Mar 6.
7 The interplay of CD150 and CD180 receptor pathways contribute to the pathobiology of chronic lymphocytic leukemia B cells by selective inhibition of Akt and MAPK signaling.PLoS One. 2017 Oct 5;12(10):e0185940. doi: 10.1371/journal.pone.0185940. eCollection 2017.
8 The N-terminal peptide moiety of the Mycobacterium tuberculosis 19 kDa lipoprotein harbors RP105-agonistic properties.J Leukoc Biol. 2018 Feb;103(2):311-319. doi: 10.1002/JLB.2MA0517-190RR. Epub 2018 Jan 9.
9 The Role of RP105 in Cardiovascular Disease through Regulating TLR4 and PI3K Signaling Pathways.Curr Med Sci. 2019 Apr;39(2):185-189. doi: 10.1007/s11596-019-2017-3. Epub 2019 Apr 23.
10 Myeloma Cells Are Activated in Bone Marrow Microenvironment by the CD180/MD-1 Complex, Which Senses Lipopolysaccharide.Cancer Res. 2018 Apr 1;78(7):1766-1778. doi: 10.1158/0008-5472.CAN-17-2446. Epub 2018 Jan 23.
11 Down-regulation of B cell-related genes in peripheral blood leukocytes of Parkinson's disease patients with and without GBA mutations.Mol Genet Metab. 2016 Feb;117(2):179-85. doi: 10.1016/j.ymgme.2015.09.005. Epub 2015 Sep 14.
12 Altered expression of TLR homolog RP105 on monocytes hypersensitive to LPS in patients with primary biliary cirrhosis.J Hepatol. 2007 Sep;47(3):404-11. doi: 10.1016/j.jhep.2007.03.012. Epub 2007 Apr 3.
13 Identification of CCR2 and CD180 as Robust Pharmacodynamic Tumor and Blood Biomarkers for Clinical Use with BRD4/BET Inhibitors.Clin Cancer Res. 2017 Feb 15;23(4):1025-1035. doi: 10.1158/1078-0432.CCR-16-1658. Epub 2017 Jan 10.
14 Single-cell Transcriptome Mapping Identifies Common and Cell-type Specific Genes Affected by Acute Delta9-tetrahydrocannabinol in Humans. Sci Rep. 2020 Feb 26;10(1):3450. doi: 10.1038/s41598-020-59827-1.
15 Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
16 Targeting MYC dependence in cancer by inhibiting BET bromodomains. Proc Natl Acad Sci U S A. 2011 Oct 4;108(40):16669-74. doi: 10.1073/pnas.1108190108. Epub 2011 Sep 26.
17 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.