Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZE5Q7R)

DOT Name HLA class II histocompatibility antigen, DO alpha chain (HLA-DOA)
Synonyms MHC DN-alpha; MHC DZ alpha; MHC class II antigen DOA
Gene Name HLA-DOA
Related Disease
B-cell neoplasm ( )
Multiple sclerosis ( )
Non-insulin dependent diabetes ( )
Advanced cancer ( )
Autoimmune disease ( )
Bladder cancer ( )
Bone sarcoma ( )
Cervical cancer ( )
Cervical carcinoma ( )
Chronic hepatitis B virus infection ( )
Colon carcinoma ( )
Colorectal carcinoma ( )
Ewing sarcoma ( )
Familial prostate carcinoma ( )
Gastric cancer ( )
Graves disease ( )
Hepatitis B virus infection ( )
Hepatocellular carcinoma ( )
Hydatidiform mole ( )
Idiopathic thrombocytopenic purpura ( )
Metastatic melanoma ( )
Neoplasm ( )
Non-small-cell lung cancer ( )
Osteosarcoma ( )
Pancreatic cancer ( )
Primary biliary cholangitis ( )
Prostate cancer, hereditary, 1 ( )
Psoriasis ( )
Rheumatoid arthritis ( )
Stomach cancer ( )
Systemic lupus erythematosus ( )
Urinary bladder cancer ( )
Urinary bladder neoplasm ( )
Vitiligo ( )
Breast cancer ( )
Breast carcinoma ( )
Epithelial ovarian cancer ( )
Ovarian cancer ( )
Ovarian neoplasm ( )
Bone osteosarcoma ( )
Acute myelogenous leukaemia ( )
Addison disease ( )
Atopic dermatitis ( )
Lung cancer ( )
Lung carcinoma ( )
Melanoma ( )
Metastatic malignant neoplasm ( )
UniProt ID
DOA_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
PDB ID
4I0P
Pfam ID
PF07654 ; PF00993
Sequence
MALRAGLVLGFHTLMTLLSPQEAGATKADHMGSYGPAFYQSYGASGQFTHEFDEEQLFSV
DLKKSEAVWRLPEFGDFARFDPQGGLAGIAAIKAHLDILVERSNRSRAINVPPRVTVLPK
SRVELGQPNILICIVDNIFPPVINITWLRNGQTVTEGVAQTSFYSQPDHLFRKFHYLPFV
PSAEDVYDCQVEHWGLDAPLLRHWELQVPIPPPDAMETLVCALGLAIGLVGFLVGTVLII
MGTYVSSVPR
Function Important modulator in the HLA class II restricted antigen presentation pathway by interaction with the HLA-DM molecule in B-cells. Modifies peptide exchange activity of HLA-DM.
KEGG Pathway
Phagosome (hsa04145 )
Cell adhesion molecules (hsa04514 )
Antigen processing and presentation (hsa04612 )
Hematopoietic cell lineage (hsa04640 )
Th1 and Th2 cell differentiation (hsa04658 )
Th17 cell differentiation (hsa04659 )
Intesti.l immune network for IgA production (hsa04672 )
Type I diabetes mellitus (hsa04940 )
Leishmaniasis (hsa05140 )
Toxoplasmosis (hsa05145 )
Staphylococcus aureus infection (hsa05150 )
Tuberculosis (hsa05152 )
Influenza A (hsa05164 )
Human T-cell leukemia virus 1 infection (hsa05166 )
Herpes simplex virus 1 infection (hsa05168 )
Epstein-Barr virus infection (hsa05169 )
Asthma (hsa05310 )
Autoimmune thyroid disease (hsa05320 )
Inflammatory bowel disease (hsa05321 )
Systemic lupus erythematosus (hsa05322 )
Rheumatoid arthritis (hsa05323 )
Allograft rejection (hsa05330 )
Graft-versus-host disease (hsa05332 )
Viral myocarditis (hsa05416 )
Reactome Pathway
MHC class II antigen presentation (R-HSA-2132295 )

Molecular Interaction Atlas (MIA) of This DOT

47 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
B-cell neoplasm DISVY326 Definitive Altered Expression [1]
Multiple sclerosis DISB2WZI Definitive Altered Expression [2]
Non-insulin dependent diabetes DISK1O5Z Definitive Biomarker [3]
Advanced cancer DISAT1Z9 Strong Altered Expression [4]
Autoimmune disease DISORMTM Strong Biomarker [5]
Bladder cancer DISUHNM0 Strong Genetic Variation [6]
Bone sarcoma DIS95A0A Strong Genetic Variation [7]
Cervical cancer DISFSHPF Strong Genetic Variation [8]
Cervical carcinoma DIST4S00 Strong Genetic Variation [8]
Chronic hepatitis B virus infection DISHL4NT Strong Genetic Variation [9]
Colon carcinoma DISJYKUO Strong Biomarker [10]
Colorectal carcinoma DIS5PYL0 Strong Genetic Variation [11]
Ewing sarcoma DISQYLV3 Strong Genetic Variation [12]
Familial prostate carcinoma DISL9KNO Strong Biomarker [13]
Gastric cancer DISXGOUK Strong Altered Expression [14]
Graves disease DISU4KOQ Strong Biomarker [15]
Hepatitis B virus infection DISLQ2XY Strong Genetic Variation [16]
Hepatocellular carcinoma DIS0J828 Strong Genetic Variation [17]
Hydatidiform mole DISKNP7O Strong Biomarker [18]
Idiopathic thrombocytopenic purpura DISFKGJU Strong Genetic Variation [19]
Metastatic melanoma DISSL43L Strong Biomarker [20]
Neoplasm DISZKGEW Strong Altered Expression [21]
Non-small-cell lung cancer DIS5Y6R9 Strong Biomarker [22]
Osteosarcoma DISLQ7E2 Strong Genetic Variation [7]
Pancreatic cancer DISJC981 Strong Genetic Variation [23]
Primary biliary cholangitis DIS43E0O Strong Genetic Variation [24]
Prostate cancer, hereditary, 1 DISE2P4L Strong Biomarker [13]
Psoriasis DIS59VMN Strong Genetic Variation [25]
Rheumatoid arthritis DISTSB4J Strong Genetic Variation [26]
Stomach cancer DISKIJSX Strong Altered Expression [14]
Systemic lupus erythematosus DISI1SZ7 Strong Biomarker [27]
Urinary bladder cancer DISDV4T7 Strong Genetic Variation [6]
Urinary bladder neoplasm DIS7HACE Strong Genetic Variation [6]
Vitiligo DISR05SL Strong Genetic Variation [25]
Breast cancer DIS7DPX1 moderate Genetic Variation [28]
Breast carcinoma DIS2UE88 moderate Genetic Variation [28]
Epithelial ovarian cancer DIS56MH2 moderate Biomarker [29]
Ovarian cancer DISZJHAP moderate Biomarker [29]
Ovarian neoplasm DISEAFTY moderate Biomarker [29]
Bone osteosarcoma DIST1004 Disputed Genetic Variation [30]
Acute myelogenous leukaemia DISCSPTN Limited Biomarker [31]
Addison disease DIS7HNOH Limited Genetic Variation [32]
Atopic dermatitis DISTCP41 Limited Altered Expression [33]
Lung cancer DISCM4YA Limited Biomarker [34]
Lung carcinoma DISTR26C Limited Biomarker [34]
Melanoma DIS1RRCY Limited Biomarker [35]
Metastatic malignant neoplasm DIS86UK6 Limited Biomarker [36]
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⏷ Show the Full List of 47 Disease(s)
Molecular Interaction Atlas (MIA) 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
Valproate DMCFE9I Approved Valproate increases the expression of HLA class II histocompatibility antigen, DO alpha chain (HLA-DOA). [37]
Carbamazepine DMZOLBI Approved Carbamazepine affects the expression of HLA class II histocompatibility antigen, DO alpha chain (HLA-DOA). [38]
Bortezomib DMNO38U Approved Bortezomib decreases the expression of HLA class II histocompatibility antigen, DO alpha chain (HLA-DOA). [39]
Gefitinib DM15F0X Approved Gefitinib affects the expression of HLA class II histocompatibility antigen, DO alpha chain (HLA-DOA). [38]
Saquinavir DMG814N Approved Saquinavir affects the expression of HLA class II histocompatibility antigen, DO alpha chain (HLA-DOA). [38]
Indapamide DMGN1PW Approved Indapamide affects the expression of HLA class II histocompatibility antigen, DO alpha chain (HLA-DOA). [38]
SNDX-275 DMH7W9X Phase 3 SNDX-275 increases the expression of HLA class II histocompatibility antigen, DO alpha chain (HLA-DOA). [40]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the expression of HLA class II histocompatibility antigen, DO alpha chain (HLA-DOA). [41]
Acetaldehyde DMJFKG4 Investigative Acetaldehyde increases the expression of HLA class II histocompatibility antigen, DO alpha chain (HLA-DOA). [43]
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⏷ Show the Full List of 9 Drug(s)
1 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Bisphenol A DM2ZLD7 Investigative Bisphenol A increases the methylation of HLA class II histocompatibility antigen, DO alpha chain (HLA-DOA). [42]
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References

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10 Differential expression of S19 ribosomal protein, laminin-binding protein, and human lymphocyte antigen class I messenger RNAs associated with colon carcinoma progression and differentiation.Cancer Res. 1992 Feb 15;52(4):791-6.
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13 Association analyses of more than 140,000 men identify 63 new prostate cancer susceptibility loci.Nat Genet. 2018 Jul;50(7):928-936. doi: 10.1038/s41588-018-0142-8. Epub 2018 Jun 11.
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18 Genetic analysis of hydatidiform moles utilizing the oligonucleotide-DNA typing of the HLA-DRB gene.Placenta. 1994 Jul;15(5):541-9. doi: 10.1016/s0143-4004(05)80422-9.
19 Association of cytotoxic T-lymphocyte antigen 4 gene with immune thrombocytopenia in Chinese Han children.Hematology. 2019 Dec;24(1):123-128. doi: 10.1080/10245332.2018.1530179. Epub 2018 Oct 14.
20 Checkpoint immunotherapy by nivolumab for treatment of metastatic melanoma.J Cancer Res Ther. 2018 Oct-Dec;14(6):1167-1175. doi: 10.4103/jcrt.JCRT_1290_16.
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25 Lack of association between cytotoxic T-lymphocyte antigen-4+49A/G polymorphism and psoriasis and vitiligo: A meta-analysis of case-control studies.Gene. 2015 Sep 1;568(2):196-202. doi: 10.1016/j.gene.2015.05.051. Epub 2015 May 24.
26 Contribution of a Non-classical HLA Gene, HLA-DOA, to the Risk of Rheumatoid Arthritis.Am J Hum Genet. 2016 Aug 4;99(2):366-74. doi: 10.1016/j.ajhg.2016.06.019.
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31 Prognostic value of lymphocyte surface markers in acute myeloid leukemia.Blood. 1991 May 15;77(10):2242-50.
32 Polymorphisms in the cytotoxic T lymphocyte antigen-4 gene region confer susceptibility to Addison's disease.J Clin Endocrinol Metab. 2004 Jul;89(7):3474-6. doi: 10.1210/jc.2003-031854.
33 The Major Orphan Forms of Ichthyosis Are Characterized by Systemic T-Cell Activation and Th-17/Tc-17/Th-22/Tc-22 Polarization in Blood.J Invest Dermatol. 2018 Oct;138(10):2157-2167. doi: 10.1016/j.jid.2018.03.1523. Epub 2018 Apr 14.
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36 Altered frequency and function of spleen CTLA-4+Tim-3+ T cells are associated with miscarriage?"Wang S. Sun F
37 Stem cell transcriptome responses and corresponding biomarkers that indicate the transition from adaptive responses to cytotoxicity. Chem Res Toxicol. 2017 Apr 17;30(4):905-922.
38 Systems pharmacological analysis of drugs inducing stevens-johnson syndrome and toxic epidermal necrolysis. Chem Res Toxicol. 2015 May 18;28(5):927-34. doi: 10.1021/tx5005248. Epub 2015 Apr 3.
39 The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
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41 Inter- and intra-laboratory study to determine the reproducibility of toxicogenomics datasets. Toxicology. 2011 Nov 28;290(1):50-8.
42 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.
43 Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.