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

DOT Name HLA class II histocompatibility antigen, DRB1 beta chain (HLA-DRB1)
Synonyms Human leukocyte antigen DRB1; HLA-DRB1
Gene Name HLA-DRB1
UniProt ID
DRB1_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
1A6A ; 1AQD ; 1BX2 ; 1D5M ; 1D5X ; 1D5Z ; 1D6E ; 1DLH ; 1FYT ; 1HXY ; 1J8H ; 1JWM ; 1JWS ; 1JWU ; 1KG0 ; 1KLG ; 1KLU ; 1LO5 ; 1PYW ; 1R5I ; 1SEB ; 1SJE ; 1SJH ; 1T5W ; 1T5X ; 1YMM ; 2FSE ; 2G9H ; 2IAM ; 2IAN ; 2ICW ; 2IPK ; 2OJE ; 2SEB ; 2WBJ ; 2XN9 ; 3L6F ; 3O6F ; 3PDO ; 3PGC ; 3PGD ; 3QXA ; 3QXD ; 3S4S ; 3S5L ; 3T0E ; 4AEN ; 4AH2 ; 4C56 ; 4E41 ; 4FQX ; 4GBX ; 4I5B ; 4IS6 ; 4MCY ; 4MCZ ; 4MD0 ; 4MD4 ; 4MD5 ; 4MDI ; 4MDJ ; 4OV5 ; 4X5W ; 4X5X ; 4Y19 ; 4Y1A ; 5JLZ ; 5LAX ; 5NI9 ; 5NIG ; 6BIJ ; 6BIL ; 6BIN ; 6BIR ; 6BIV ; 6BIX ; 6BIY ; 6BIZ ; 6CPL ; 6CPN ; 6CPO ; 6CQJ ; 6CQL ; 6CQN ; 6CQQ ; 6CQR ; 6HBY ; 6NIX ; 6QZA ; 6QZC ; 6QZD ; 6R0E ; 6V0Y ; 6V13 ; 6V15 ; 6V18 ; 6V19 ; 6V1A
Pfam ID
PF07654 ; PF00969
Sequence
MVCLKLPGGSCMTALTVTLMVLSSPLALSGDTRPRFLWQPKRECHFFNGTERVRFLDRYF
YNQEESVRFDSDVGEFRAVTELGRPDAEYWNSQKDILEQARAAVDTYCRHNYGVVESFTV
QRRVQPKVTVYPSKTQPLQHHNLLVCSVSGFYPGSIEVRWFLNGQEEKAGMVSTGLIQNG
DWTFQTLVMLETVPRSGEVYTCQVEHPSVTSPLTVEWRARSESAQSKMLSGVGGFVLGLL
FLGAGLFIYFRNQKGHSGLQPTGFLS
Function
A beta chain of antigen-presenting major histocompatibility complex class II (MHCII) molecule. In complex with the alpha chain HLA-DRA, displays antigenic peptides on professional antigen presenting cells (APCs) for recognition by alpha-beta T cell receptor (TCR) on HLA-DRB1-restricted CD4-positive T cells. This guides antigen-specific T-helper effector functions, both antibody-mediated immune response and macrophage activation, to ultimately eliminate the infectious agents and transformed cells. Typically presents extracellular peptide antigens of 10 to 30 amino acids that arise from proteolysis of endocytosed antigens in lysosomes. In the tumor microenvironment, presents antigenic peptides that are primarily generated in tumor-resident APCs likely via phagocytosis of apoptotic tumor cells or macropinocytosis of secreted tumor proteins. Presents peptides derived from intracellular proteins that are trapped in autolysosomes after macroautophagy, a mechanism especially relevant for T cell selection in the thymus and central immune tolerance. The selection of the immunodominant epitopes follows two processing modes: 'bind first, cut/trim later' for pathogen-derived antigenic peptides and 'cut first, bind later' for autoantigens/self-peptides. The anchor residue at position 1 of the peptide N-terminus, usually a large hydrophobic residue, is essential for high affinity interaction with MHCII molecules ; Allele DRB1*01:01: Displays an immunodominant epitope derived from Bacillus anthracis pagA/protective antigen, PA (KLPLYISNPNYKVNVYAVT), to both naive and PA-specific memory CD4-positive T cells. Presents immunodominant HIV-1 gag peptide (FRDYVDRFYKTLRAEQASQE) on infected dendritic cells for recognition by TRAV24-TRBV2 TCR on CD4-positive T cells and controls viral load. May present to T-helper 1 cells several HRV-16 epitopes derived from capsid proteins VP1 (PRFSLPFLSIASAYYMFYDG) and VP2 (PHQFINLRSNNSATLIVPYV), contributing to viral clearance. Displays commonly recognized peptides derived from IAV external protein HA (PKYVKQNTLKLAT and SNGNFIAPEYAYKIVK) and from internal proteins M, NP and PB1, with M-derived epitope (GLIYNRMGAVTTEV) being the most immunogenic. Presents a self-peptide derived from COL4A3 (GWISLWKGFSF) to TCR (TRAV14 biased) on CD4-positive, FOXP3-positive regulatory T cells and mediates immune tolerance to self. May present peptides derived from oncofetal trophoblast glycoprotein TPBG 5T4, known to be recognized by both T-helper 1 and regulatory T cells. Displays with low affinity a self-peptide derived from MBP (VHFFKNIVTPRTP) ; Allele DRB1*03:01: May present to T-helper 1 cells an HRV-16 epitope derived from capsid protein VP2 (NEKQPSDDNWLNFDGTLLGN), contributing to viral clearance. Displays self-peptides derived from retinal SAG (NRERRGIALDGKIKHE) and thyroid TG (LSSVVVDPSIRHFDV). Presents viral epitopes derived from HHV-6B gH/U48 and U85 antigens to polyfunctional CD4-positive T cells with cytotoxic activity implicated in control of HHV-6B infection. Presents several immunogenic epitopes derived from C. tetani neurotoxin tetX, playing a role in immune recognition and long-term protection ; Allele DRB1*04:01: Presents an immunodominant bacterial epitope derived from M. tuberculosis esxB/culture filtrate antigen CFP-10 (EISTNIRQAGVQYSR), eliciting CD4-positive T cell effector functions such as IFNG production and cytotoxic activity. May present to T-helper 1 cells an HRV-16 epitope derived from capsid protein VP2 (NEKQPSDDNWLNFDGTLLGN), contributing to viral clearance. Presents tumor epitopes derived from melanoma-associated TYR antigen (QNILLSNAPLGPQFP and DYSYLQDSDPDSFQD), triggering CD4-positive T cell effector functions such as GMCSF production. Displays preferentially citrullinated self-peptides derived from VIM (GVYATR/citSSAVR and SAVRAR/citSSVPGVR) and ACAN (VVLLVATEGR/ CitVRVNSAYQDK). Displays self-peptides derived from COL2A1 ; Allele DRB1*04:02: Displays native or citrullinated self-peptides derived from VIM; Allele DRB1*04:04: May present to T-helper 1 cells several HRV-16 epitopes derived from capsid proteins VP1 (HIVMQYMYVPPGAPIPTTRN) and VP2 (RGDSTITSQDVANAVVGYGV), contributing to viral clearance. Displays preferentially citrullinated self-peptides derived from VIM (SAVRAR/citSSVPGVR) ; Allele DRB1*04:05: May present to T-helper 1 cells an immunogenic epitope derived from tumor-associated antigen WT1 (KRYFKLSHLQMHSRKH), likely providing for effective antitumor immunity in a wide range of solid and hematological malignancies; Allele DRB1*05:01: Presents an immunodominant HIV-1 gag peptide (FRDYVDRFYKTLRAEQASQE) on infected dendritic cells for recognition by TRAV24-TRBV2 TCR on CD4-positive T cells and controls viral load; Allele DRB1*07:01: Upon EBV infection, presents latent antigen EBNA2 peptide (PRSPTVFYNIPPMPLPPSQL) to CD4-positive T cells, driving oligoclonal expansion and selection of a dominant virus-specific memory T cell subset with cytotoxic potential to directly eliminate virus-infected B cells. May present to T-helper 1 cells several HRV-16 epitopes derived from capsid proteins VP1 (PRFSLPFLSIASAYYMFYDG) and VP2 (VPYVNAVPMDSMVRHNNWSL), contributing to viral clearance. In the context of tumor immunesurveillance, may present to T-helper 1 cells an immunogenic epitope derived from tumor-associated antigen WT1 (MTEYKLVVVGAVGVGKSALTIQLI), likely providing for effective antitumor immunity in a wide range of solid and hematological malignancies. In metastatic epithelial tumors, presents to intratumoral CD4-positive T cells a KRAS neoantigen (MTEYKLVVVGAVGVGKSALTIQLI) carrying G12V hotspot driver mutation and may mediate tumor regression ; Allele DRB1*11:01: Displays an immunodominant HIV-1 gag peptide (FRDYVDRFYKTLRAEQASQE) on infected dendritic cells for recognition by TRAV24-TRBV2 TCR on CD4-positive T cells and controls viral load. May present to T-helper 1 cells an HRV-16 epitope derived from capsid protein VP2 (SDRIIQITRGDSTITSQDVA), contributing to viral clearance. Presents several immunogenic epitopes derived from C. tetani neurotoxin tetX, playing a role in immune recognition and longterm protection. In the context of tumor immunesurveillance, may present tumor-derived neoantigens to CD4-positive T cells and trigger anti-tumor helper functions ; Allele DRB1*13:01: Presents viral epitopes derived from HHV-6B antigens to polyfunctional CD4-positive T cells implicated in control of HHV-6B infection; Allele DRB1*15:01: May present to T-helper 1 cells an HRV-16 epitope derived from capsid protein VP2 (SNNSATLIVPYVNAVPMDSM), contributing to viral clearance. Displays a self-peptide derived from MBP (ENPVVHFFKNIVTPR). May present to T-helper 1 cells an immunogenic epitope derived from tumor-associated antigen WT1 (KRYFKLSHLQMHSRKH), likely providing for effective antitumor immunity in a wide range of solid and hematological malignancies; Allele DRB1*15:02: Displays an immunodominant HIV-1 gag peptide (FRDYVDRFYKTLRAEQASQE) on infected dendritic cells for recognition by TRAV24-TRBV2 TCR on CD4-positive T cells and controls viral load. May present to T-helper 1 cells an immunogenic epitope derived from tumor-associated antigen WT1 (KRYFKLSHLQMHSRKH), likely providing for effective antitumor immunity in a wide range of solid and hematological malignancies ; (Microbial infection) Acts as a receptor for Epstein-Barr virus on lymphocytes.
Tissue Specificity Expressed in professional APCs: monocyte/macrophages, dendritic cells and B cells (at protein level) . Expressed in thymic epithelial cells (at protein level) .
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
Phosphorylation of CD3 and TCR zeta chains (R-HSA-202427 )
Translocation of ZAP-70 to Immunological synapse (R-HSA-202430 )
Generation of second messenger molecules (R-HSA-202433 )
MHC class II antigen presentation (R-HSA-2132295 )
PD-1 signaling (R-HSA-389948 )
Interferon gamma signaling (R-HSA-877300 )
Downstream TCR signaling (R-HSA-202424 )

Molecular Interaction Atlas (MIA) of This DOT

Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
This DOT Affected the Drug Response of 5 Drug(s)
Drug Name Drug ID Highest Status Interaction REF
Azathioprine DMMZSXQ Approved HLA class II histocompatibility antigen, DRB1 beta chain (HLA-DRB1) affects the response to substance of Azathioprine. [15]
Aspirin DM672AH Approved HLA class II histocompatibility antigen, DRB1 beta chain (HLA-DRB1) affects the response to substance of Aspirin. [16]
Penicillamine DM40EF6 Approved HLA class II histocompatibility antigen, DRB1 beta chain (HLA-DRB1) increases the response to substance of Penicillamine. [18]
Mercaptopurine DMTM2IK Approved HLA class II histocompatibility antigen, DRB1 beta chain (HLA-DRB1) affects the response to substance of Mercaptopurine. [15]
Lumiracoxib DM1S4AG Approved HLA class II histocompatibility antigen, DRB1 beta chain (HLA-DRB1) affects the response to substance of Lumiracoxib. [19]
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This DOT Affected the Regulation of Drug Effects of 1 Drug(s)
Drug Name Drug ID Highest Status Interaction REF
Nitric Oxide DM1RBYG Approved HLA class II histocompatibility antigen, DRB1 beta chain (HLA-DRB1) increases the abundance of Nitric Oxide. [17]
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19 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate affects the expression of HLA class II histocompatibility antigen, DRB1 beta chain (HLA-DRB1). [1]
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of HLA class II histocompatibility antigen, DRB1 beta chain (HLA-DRB1). [2]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of HLA class II histocompatibility antigen, DRB1 beta chain (HLA-DRB1). [3]
Estradiol DMUNTE3 Approved Estradiol increases the expression of HLA class II histocompatibility antigen, DRB1 beta chain (HLA-DRB1). [4]
Arsenic DMTL2Y1 Approved Arsenic affects the expression of HLA class II histocompatibility antigen, DRB1 beta chain (HLA-DRB1). [5]
Temozolomide DMKECZD Approved Temozolomide decreases the expression of HLA class II histocompatibility antigen, DRB1 beta chain (HLA-DRB1). [6]
Triclosan DMZUR4N Approved Triclosan decreases the expression of HLA class II histocompatibility antigen, DRB1 beta chain (HLA-DRB1). [7]
Zoledronate DMIXC7G Approved Zoledronate increases the expression of HLA class II histocompatibility antigen, DRB1 beta chain (HLA-DRB1). [8]
Dexamethasone DMMWZET Approved Dexamethasone decreases the expression of HLA class II histocompatibility antigen, DRB1 beta chain (HLA-DRB1). [9]
Irinotecan DMP6SC2 Approved Irinotecan increases the expression of HLA class II histocompatibility antigen, DRB1 beta chain (HLA-DRB1). [10]
Diclofenac DMPIHLS Approved Diclofenac affects the expression of HLA class II histocompatibility antigen, DRB1 beta chain (HLA-DRB1). [11]
Gefitinib DM15F0X Approved Gefitinib affects the expression of HLA class II histocompatibility antigen, DRB1 beta chain (HLA-DRB1). [11]
Ciprofloxacin XR DM2NLS9 Approved Ciprofloxacin XR affects the expression of HLA class II histocompatibility antigen, DRB1 beta chain (HLA-DRB1). [11]
Hydrochlorothiazide DMUSZHD Approved Hydrochlorothiazide affects the expression of HLA class II histocompatibility antigen, DRB1 beta chain (HLA-DRB1). [11]
Clindamycin DM15HL8 Approved Clindamycin affects the expression of HLA class II histocompatibility antigen, DRB1 beta chain (HLA-DRB1). [11]
Metronidazole DMTIVEN Approved Metronidazole affects the expression of HLA class II histocompatibility antigen, DRB1 beta chain (HLA-DRB1). [11]
Cefepime DMHVWIK Approved Cefepime affects the expression of HLA class II histocompatibility antigen, DRB1 beta chain (HLA-DRB1). [11]
PMID26394986-Compound-22 DM43Z1G Patented PMID26394986-Compound-22 affects the expression of HLA class II histocompatibility antigen, DRB1 beta chain (HLA-DRB1). [11]
Milchsaure DM462BT Investigative Milchsaure decreases the expression of HLA class II histocompatibility antigen, DRB1 beta chain (HLA-DRB1). [14]
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⏷ Show the Full List of 19 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 decreases the methylation of HLA class II histocompatibility antigen, DRB1 beta chain (HLA-DRB1). [12]
Bisphenol A DM2ZLD7 Investigative Bisphenol A increases the methylation of HLA class II histocompatibility antigen, DRB1 beta chain (HLA-DRB1). [13]
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References

1 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.
2 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.
3 Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
4 Epidermal growth factor receptor signalling in human breast cancer cells operates parallel to estrogen receptor alpha signalling and results in tamoxifen insensitive proliferation. BMC Cancer. 2014 Apr 23;14:283.
5 Drinking-water arsenic exposure modulates gene expression in human lymphocytes from a U.S. population. Environ Health Perspect. 2008 Apr;116(4):524-31. doi: 10.1289/ehp.10861.
6 Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
7 Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
8 Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
9 Sulfur mustard alkylates steroid hormones and impacts hormone function in vitro. Arch Toxicol. 2019 Nov;93(11):3141-3152. doi: 10.1007/s00204-019-02571-x. Epub 2019 Sep 12.
10 Clinical determinants of response to irinotecan-based therapy derived from cell line models. Clin Cancer Res. 2008 Oct 15;14(20):6647-55.
11 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.
12 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.
13 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.
14 Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
15 HLA-DQA1-HLA-DRB1 variants confer susceptibility to pancreatitis induced by thiopurine immunosuppressants. Nat Genet. 2014 Oct;46(10):1131-4. doi: 10.1038/ng.3093. Epub 2014 Sep 14.
16 Genetic and ethnic risk factors associated with drug hypersensitivity. Curr Opin Allergy Clin Immunol. 2010 Aug;10(4):280-90. doi: 10.1097/ACI.0b013e32833b1eb3.
17 Activation of nitric oxide signaling by the rheumatoid arthritis shared epitope. Arthritis Rheum. 2006 Nov;54(11):3423-32. doi: 10.1002/art.22178.
18 HLA-DR antigens and proteinuria induced by aurothioglucose and D-penicillamine in patients with rheumatoid arthritis. J Rheumatol. 1983 Dec;10(6):948-53.
19 A genome-wide study identifies HLA alleles associated with lumiracoxib-related liver injury. Nat Genet. 2010 Aug;42(8):711-4. doi: 10.1038/ng.632. Epub 2010 Jul 18.