Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT3ROU4J)

DOT Name Antigen-presenting glycoprotein CD1d (CD1D)
Synonyms R3G1; CD antigen CD1d
Gene Name CD1D
Related Disease
Colitis ( )
Inflammatory bowel disease ( )
Neoplasm ( )
X-linked lymphoproliferative syndrome ( )
Acute lymphocytic leukaemia ( )
Advanced cancer ( )
Asthma ( )
Autoimmune disease ( )
Bacterial infection ( )
Breast neoplasm ( )
Choriocarcinoma ( )
Clear cell renal carcinoma ( )
Gaucher disease ( )
Hepatitis B virus infection ( )
Hepatitis C virus infection ( )
Hepatocellular carcinoma ( )
Liver cirrhosis ( )
Lung cancer ( )
Lung neoplasm ( )
Lymphoma ( )
Medulloblastoma ( )
Melanoma ( )
Multiple sclerosis ( )
Non-small-cell lung cancer ( )
Plasma cell myeloma ( )
Prostate cancer ( )
Prostate carcinoma ( )
Psoriasis ( )
Renal cell carcinoma ( )
Rheumatoid arthritis ( )
Skin disease ( )
Small lymphocytic lymphoma ( )
Systemic lupus erythematosus ( )
Chronic obstructive pulmonary disease ( )
Gastric cancer ( )
Nervous system inflammation ( )
Neuroblastoma ( )
Stomach cancer ( )
Type-1/2 diabetes ( )
Adult lymphoma ( )
Allergic contact dermatitis ( )
Breast cancer ( )
Breast carcinoma ( )
Lung carcinoma ( )
Obesity ( )
Pediatric lymphoma ( )
T-cell lymphoma ( )
Type-1 diabetes ( )
UniProt ID
CD1D_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
PDB ID
1ZT4; 2PO6; 3HUJ; 3SDX; 3TZV; 3U0P; 3VWJ; 3VWK; 4EN3; 4LHU; 4MNG; 4MQ7; 4WO4; 4WW2; 4WWK; 6V7Y; 6V7Z; 6V80
Pfam ID
PF07654 ; PF16497
Sequence
MGCLLFLLLWALLQAWGSAEVPQRLFPLRCLQISSFANSSWTRTDGLAWLGELQTHSWSN
DSDTVRSLKPWSQGTFSDQQWETLQHIFRVYRSSFTRDVKEFAKMLRLSYPLELQVSAGC
EVHPGNASNNFFHVAFQGKDILSFQGTSWEPTQEAPLWVNLAIQVLNQDKWTRETVQWLL
NGTCPQFVSGLLESGKSELKKQVKPKAWLSRGPSPGPGRLLLVCHVSGFYPKPVWVKWMR
GEQEQQGTQPGDILPNADETWYLRATLDVVAGEAAGLSCRVKHSSLEGQDIVLYWGGSYT
SMGLIALAVLACLLFLLIVGFTSRFKRQTSYQGVL
Function Antigen-presenting protein that binds self and non-self glycolipids and presents them to T-cell receptors on natural killer T-cells.
Tissue Specificity Expressed on cortical thymocytes, on certain T-cell leukemias, and in various other tissues.
KEGG Pathway
Tight junction (hsa04530 )
Hematopoietic cell lineage (hsa04640 )
Amoebiasis (hsa05146 )
Reactome Pathway
Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell (R-HSA-198933 )

Molecular Interaction Atlas (MIA) of This DOT

48 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Colitis DISAF7DD Definitive Biomarker [1]
Inflammatory bowel disease DISGN23E Definitive Genetic Variation [1]
Neoplasm DISZKGEW Definitive Biomarker [2]
X-linked lymphoproliferative syndrome DISA7MJ4 Definitive Biomarker [3]
Acute lymphocytic leukaemia DISPX75S Strong Altered Expression [4]
Advanced cancer DISAT1Z9 Strong Altered Expression [5]
Asthma DISW9QNS Strong Biomarker [6]
Autoimmune disease DISORMTM Strong Altered Expression [7]
Bacterial infection DIS5QJ9S Strong Biomarker [8]
Breast neoplasm DISNGJLM Strong Biomarker [9]
Choriocarcinoma DISDBVNL Strong Biomarker [10]
Clear cell renal carcinoma DISBXRFJ Strong Altered Expression [11]
Gaucher disease DISTW5JG Strong Biomarker [12]
Hepatitis B virus infection DISLQ2XY Strong Altered Expression [13]
Hepatitis C virus infection DISQ0M8R Strong Biomarker [14]
Hepatocellular carcinoma DIS0J828 Strong Altered Expression [13]
Liver cirrhosis DIS4G1GX Strong Biomarker [15]
Lung cancer DISCM4YA Strong Altered Expression [16]
Lung neoplasm DISVARNB Strong Altered Expression [2]
Lymphoma DISN6V4S Strong Biomarker [17]
Medulloblastoma DISZD2ZL Strong Altered Expression [18]
Melanoma DIS1RRCY Strong Biomarker [5]
Multiple sclerosis DISB2WZI Strong Biomarker [19]
Non-small-cell lung cancer DIS5Y6R9 Strong Altered Expression [16]
Plasma cell myeloma DIS0DFZ0 Strong Biomarker [20]
Prostate cancer DISF190Y Strong Biomarker [21]
Prostate carcinoma DISMJPLE Strong Biomarker [21]
Psoriasis DIS59VMN Strong Biomarker [22]
Renal cell carcinoma DISQZ2X8 Strong Altered Expression [11]
Rheumatoid arthritis DISTSB4J Strong Altered Expression [23]
Skin disease DISDW8R6 Strong Biomarker [22]
Small lymphocytic lymphoma DIS30POX Strong Biomarker [24]
Systemic lupus erythematosus DISI1SZ7 Strong Biomarker [25]
Chronic obstructive pulmonary disease DISQCIRF moderate Altered Expression [26]
Gastric cancer DISXGOUK moderate Biomarker [27]
Nervous system inflammation DISB3X5A moderate Altered Expression [28]
Neuroblastoma DISVZBI4 moderate Biomarker [29]
Stomach cancer DISKIJSX moderate Biomarker [27]
Type-1/2 diabetes DISIUHAP moderate Biomarker [30]
Adult lymphoma DISK8IZR Limited Biomarker [31]
Allergic contact dermatitis DISFFVF9 Limited Biomarker [32]
Breast cancer DIS7DPX1 Limited Biomarker [33]
Breast carcinoma DIS2UE88 Limited Biomarker [33]
Lung carcinoma DISTR26C Limited Biomarker [5]
Obesity DIS47Y1K Limited Biomarker [34]
Pediatric lymphoma DIS51BK2 Limited Biomarker [31]
T-cell lymphoma DISSXRTQ Limited Biomarker [35]
Type-1 diabetes DIS7HLUB Limited Altered Expression [36]
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⏷ Show the Full List of 48 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 Antigen-presenting glycoprotein CD1d (CD1D). [37]
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of Antigen-presenting glycoprotein CD1d (CD1D). [38]
Tretinoin DM49DUI Approved Tretinoin increases the expression of Antigen-presenting glycoprotein CD1d (CD1D). [39]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Antigen-presenting glycoprotein CD1d (CD1D). [40]
Estradiol DMUNTE3 Approved Estradiol decreases the expression of Antigen-presenting glycoprotein CD1d (CD1D). [38]
Arsenic trioxide DM61TA4 Approved Arsenic trioxide decreases the expression of Antigen-presenting glycoprotein CD1d (CD1D). [41]
Carbamazepine DMZOLBI Approved Carbamazepine affects the expression of Antigen-presenting glycoprotein CD1d (CD1D). [42]
Methotrexate DM2TEOL Approved Methotrexate increases the expression of Antigen-presenting glycoprotein CD1d (CD1D). [43]
Rosiglitazone DMILWZR Approved Rosiglitazone increases the expression of Antigen-presenting glycoprotein CD1d (CD1D). [44]
Amphotericin B DMTAJQE Approved Amphotericin B decreases the expression of Antigen-presenting glycoprotein CD1d (CD1D). [45]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 decreases the expression of Antigen-presenting glycoprotein CD1d (CD1D). [47]
PMID27336223-Compound-5 DM6E50A Patented PMID27336223-Compound-5 increases the expression of Antigen-presenting glycoprotein CD1d (CD1D). [44]
PMID27336223-Compound-11 DMBN6KU Patented PMID27336223-Compound-11 increases the expression of Antigen-presenting glycoprotein CD1d (CD1D). [48]
Trichostatin A DM9C8NX Investigative Trichostatin A increases the expression of Antigen-presenting glycoprotein CD1d (CD1D). [37]
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⏷ Show the Full List of 14 Drug(s)
2 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 Antigen-presenting glycoprotein CD1d (CD1D). [46]
Bisphenol A DM2ZLD7 Investigative Bisphenol A increases the methylation of Antigen-presenting glycoprotein CD1d (CD1D). [49]
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References

1 CD1d Modulates Colonic Inflammation in NOD2-/- Mice by Altering the Intestinal Microbial Composition Comprising Acetatifactor muris.J Crohns Colitis. 2019 Aug 14;13(8):1081-1091. doi: 10.1093/ecco-jcc/jjz025.
2 CD1d highly expressed on DCs reduces lung tumor burden by enhancing antitumor immunity.Oncol Rep. 2019 May;41(5):2679-2688. doi: 10.3892/or.2019.7037. Epub 2019 Feb 28.
3 Patients with X-linked lymphoproliferative disease due to BIRC4 mutation have normal invariant natural killer T-cell populations.Clin Immunol. 2009 Jul;132(1):116-23. doi: 10.1016/j.clim.2009.03.517. Epub 2009 Apr 23.
4 A soluble form of CTLA-4 is present in paediatric patients with acute lymphoblastic leukaemia and correlates with CD1d+ expression.PLoS One. 2012;7(9):e44654. doi: 10.1371/journal.pone.0044654. Epub 2012 Sep 25.
5 Increased cytoplasmatic expression of cancer immune surveillance receptor CD1d in anaplastic thyroid carcinomas.Cancer Med. 2019 Nov;8(16):7065-7073. doi: 10.1002/cam4.2573. Epub 2019 Sep 27.
6 -Lactosylceramide Protects Against iNKT-Mediated Murine Airway Hyperreactivity and Liver Injury Through Competitive Inhibition of Cd1d Binding.Front Chem. 2019 Nov 28;7:811. doi: 10.3389/fchem.2019.00811. eCollection 2019.
7 Excessive interferon- signaling in autoimmunity alters glycosphingolipid processing in B cells.J Autoimmun. 2018 May;89:53-62. doi: 10.1016/j.jaut.2017.11.004. Epub 2017 Nov 27.
8 Acidification-dependent activation of CD1d-restricted natural killer T cells is intact in cystic fibrosis.Immunology. 2010 Jun;130(2):288-95. doi: 10.1111/j.1365-2567.2009.03234.x. Epub 2010 Jan 19.
9 CD1d-expressing breast cancer cells modulate NKT cell-mediated antitumor immunity in a murine model of breast cancer metastasis.PLoS One. 2011;6(6):e20702. doi: 10.1371/journal.pone.0020702. Epub 2011 Jun 13.
10 A possible coagulation-independent mechanism for pregnancy loss involving (2) glycoprotein 1-dependent antiphospholipid antibodies and CD1d.Am J Reprod Immunol. 2012 Jan;67(1):54-65. doi: 10.1111/j.1600-0897.2011.01028.x. Epub 2011 Jun 20.
11 CD1d expression in renal cell carcinoma is associated with higher relapse rates, poorer cancer-specific and overall survival.J Clin Pathol. 2015 Mar;68(3):200-5. doi: 10.1136/jclinpath-2014-202735. Epub 2014 Dec 4.
12 Lipid Antigen Presentation by CD1b and CD1d in Lysosomal Storage Disease Patients.Front Immunol. 2019 Jun 4;10:1264. doi: 10.3389/fimmu.2019.01264. eCollection 2019.
13 Elevated Hepatic CD1d Levels Coincide with Invariant NKT Cell Defects in Chronic Hepatitis B Virus Infection.J Immunol. 2018 May 15;200(10):3530-3538. doi: 10.4049/jimmunol.1701801. Epub 2018 Apr 11.
14 Hepatic CD1d expression in hepatitis C virus infection and recognition by resident proinflammatory CD1d-reactive T cells.J Immunol. 2004 Aug 1;173(3):2159-66. doi: 10.4049/jimmunol.173.3.2159.
15 Human CD1d-glycolipid tetramers generated by in vitro oxidative refolding chromatography.Proc Natl Acad Sci U S A. 2001 Mar 13;98(6):3294-8. doi: 10.1073/pnas.051604498.
16 Epigenetic induction of CD1d expression primes lung cancer cells for killing by invariant natural killer T cells.Oncoimmunology. 2018 Feb 12;7(6):e1428156. doi: 10.1080/2162402X.2018.1428156. eCollection 2018.
17 Enhanced Anti-lymphoma Activity of CAR19-iNKT Cells Underpinned by Dual CD19 and CD1d Targeting.Cancer Cell. 2018 Oct 8;34(4):596-610.e11. doi: 10.1016/j.ccell.2018.08.017.
18 Therapeutic implications of CD1d expression and tumor-infiltrating macrophages in pediatric medulloblastomas.J Neurooncol. 2014 Nov;120(2):293-301. doi: 10.1007/s11060-014-1572-5. Epub 2014 Aug 13.
19 Expression of CD1d by astrocytes corresponds with relative activity in multiple sclerosis lesions.Brain Pathol. 2020 Jan;30(1):26-35. doi: 10.1111/bpa.12733. Epub 2019 Jun 6.
20 Regulation of multiple myeloma survival and progression by CD1d.Blood. 2009 Mar 12;113(11):2498-507. doi: 10.1182/blood-2008-06-161281. Epub 2008 Dec 3.
21 Bimodal CD40/Fas-Dependent Crosstalk between iNKT Cells and Tumor-Associated Macrophages Impairs Prostate Cancer Progression.Cell Rep. 2018 Mar 13;22(11):3006-3020. doi: 10.1016/j.celrep.2018.02.058.
22 A central role for transcription factor C/EBP-beta in regulating CD1d gene expression in human keratinocytes.J Immunol. 2009 Aug 1;183(3):1657-66. doi: 10.4049/jimmunol.0900057. Epub 2009 Jul 10.
23 Low levels of soluble CD1d protein alters NKT cell function in patients with rheumatoid arthritis.Int J Mol Med. 2009 Oct;24(4):481-6. doi: 10.3892/ijmm_00000256.
24 Invariant NKT cells contribute to chronic lymphocytic leukemia surveillance and prognosis.Blood. 2017 Jun 29;129(26):3440-3451. doi: 10.1182/blood-2016-11-751065. Epub 2017 May 2.
25 Decreased CD1d level is associated with CD86 over-expression in B cells from systemic lupus erythematosus.Acta Biochim Biophys Sin (Shanghai). 2017 Apr 1;49(4):328-337. doi: 10.1093/abbs/gmx011.
26 Deficiency of innate-like T lymphocytes in chronic obstructive pulmonary disease.Respir Res. 2017 Nov 28;18(1):197. doi: 10.1186/s12931-017-0671-1.
27 Utilization of invariant natural killer T cells for gastric cancer treatment.Future Oncol. 2018 Aug;14(20):2053-2066. doi: 10.2217/fon-2017-0724. Epub 2018 Jul 27.
28 Abrogation of Endogenous Glycolipid Antigen Presentation on Myelin-Laden Macrophages by D-Sphingosine Ameliorates the Pathogenesis of Experimental Autoimmune Encephalomyelitis.Front Immunol. 2019 Mar 19;10:404. doi: 10.3389/fimmu.2019.00404. eCollection 2019.
29 Valpha24-invariant NKT cells mediate antitumor activity via killing of tumor-associated macrophages.J Clin Invest. 2009 Jun;119(6):1524-36. doi: 10.1172/JCI37869.
30 The enlarged population of marginal zone/CD1d(high) B lymphocytes in nonobese diabetic mice maps to diabetes susceptibility region Idd11.J Immunol. 2005 Apr 15;174(8):4821-7. doi: 10.4049/jimmunol.174.8.4821.
31 Id2 Collaborates with Id3 To Suppress Invariant NKT and Innate-like Tumors.J Immunol. 2017 Apr 15;198(8):3136-3148. doi: 10.4049/jimmunol.1601935. Epub 2017 Mar 3.
32 CD1d-dependent, iNKT-cell cytotoxicity against keratinocytes in allergic contact dermatitis.Exp Dermatol. 2012 Dec;21(12):915-20. doi: 10.1111/exd.12036.
33 A Potent CD1d-binding Glycolipid for iNKT-Cell-based Therapy Against Human Breast Cancer.Anticancer Res. 2019 Feb;39(2):549-555. doi: 10.21873/anticanres.13147.
34 Adipocyte CD1d determines adipose inflammation and insulin resistance in obesity.Adipocyte. 2018;7(2):129-136. doi: 10.1080/21623945.2018.1440928. Epub 2018 Mar 6.
35 Evolving Strategies for the Treatment of T-Cell Lymphoma: A Systematic Review and Recent Patents.Recent Pat Anticancer Drug Discov. 2018;13(3):308-340. doi: 10.2174/1574892813666180517102801.
36 Role of regulatory invariant CD1d-restricted natural killer T-cells in protection against type 1 diabetes.Immunol Res. 2005;31(3):177-88. doi: 10.1385/IR:31:3:177.
37 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.
38 Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
39 Retinoic acid-induced downmodulation of telomerase activity in human cancer cells. Exp Mol Pathol. 2005 Oct;79(2):108-17.
40 Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
41 Arsenic suppresses gene expression in promyelocytic leukemia cells partly through Sp1 oxidation. Blood. 2005 Jul 1;106(1):304-10.
42 Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
43 The contribution of methotrexate exposure and host factors on transcriptional variance in human liver. Toxicol Sci. 2007 Jun;97(2):582-94.
44 PPARgamma controls CD1d expression by turning on retinoic acid synthesis in developing human dendritic cells. J Exp Med. 2006 Oct 2;203(10):2351-62.
45 Differential expression of microRNAs and their predicted targets in renal cells exposed to amphotericin B and its complex with copper (II) ions. Toxicol Mech Methods. 2017 Sep;27(7):537-543. doi: 10.1080/15376516.2017.1333554. Epub 2017 Jun 8.
46 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.
47 BET bromodomain inhibition as a novel strategy for reactivation of HIV-1. J Leukoc Biol. 2012 Dec;92(6):1147-54. doi: 10.1189/jlb.0312165. Epub 2012 Jul 16.
48 In vitro modulation of TLR-2, CD1d and IL-10 by adapalene on normal human skin and acne inflammatory lesions. Exp Dermatol. 2007 Jun;16(6):500-6. doi: 10.1111/j.1600-0625.2007.00552.x.
49 DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.