Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTW8JHU2)

• DOT Name: HLA class II histocompatibility antigen, DP beta 1 chain (HLA-DPB1)
• Synonyms: HLA class II histocompatibility antigen, DP(W4) beta chain; MHC class II antigen DPB1
• Gene Name: HLA-DPB1
• Related Disease:
  Behcet disease
  Acute lymphocytic leukaemia
  Advanced cancer
  Angioedema
  Ankylosing spondylitis
  Asthma
  Autoimmune disease
  Autoimmune hepatitis
  Cervical cancer
  Chronic hepatitis B virus infection
  Chronic obstructive pulmonary disease
  Classic Hodgkin lymphoma
  Dermatomyositis
  Follicular lymphoma
  Graves disease
  Haematological malignancy
  Hashimoto thyroiditis
  Hepatitis C virus infection
  IgA nephropathy
  Irritant contact dermatitis
  Juvenile idiopathic arthritis
  Knee osteoarthritis
  leukaemia
  Narcolepsy
  Osteoarthritis
  Pemphigus
  Pulmonary tuberculosis
  Urticaria
  Lymphoma
  Scleroderma
  Childhood acute lymphoblastic leukemia
  Glioblastoma multiforme
  Anca-associated vasculitis
  Autism
  Cervical carcinoma
  Chronic graft versus host disease
  Endometriosis
  Inflammatory bowel disease
  Myelodysplastic syndrome
  Neoplasm
  Pulmonary fibrosis
  Sjogren syndrome
  Systemic sclerosis
  Type-1/2 diabetes
  Uterine cervix neoplasm
  Vasculitis
• UniProt ID: DPB1_HUMAN
• PDB ID: 3LQZ; 4P4K; 4P4R; 4P57; 4P5K; 4P5M; 7T2A; 7T2B; 7T2C; 7T2D
• Pfam ID: PF07654 ; PF00969
• Sequence:
  MMVLQVSAAPRTVALTALLMVLLTSVVQGRATPENYLFQGRQECYAFNGTQRFLERYIYN
  REEFARFDSDVGEFRAVTELGRPAAEYWNSQKDILEEKRAVPDRMCRHNYELGGPMTLQR
  RVQPRVNVSPSKKGPLQHHNLLVCHVTDFYPGSIQVRWFLNGQEETAGVVSTNLIRNGDW
  TFQILVMLEMTPQQGDVYTCQVEHTSLDSPVTVEWKAQSDSARSKTLTGAGGFVLGLIIC
  GVGIFMHRRSKKVQRGSA
• Function: Binds peptides derived from antigens that access the endocytic route of antigen presenting cells (APC) and presents them on the cell surface for recognition by the CD4 T-cells. The peptide binding cleft accommodates peptides of 10-30 residues. The peptides presented by MHC class II molecules are generated mostly by degradation of proteins that access the endocytic route, where they are processed by lysosomal proteases and other hydrolases. Exogenous antigens that have been endocytosed by the APC are thus readily available for presentation via MHC II molecules, and for this reason this antigen presentation pathway is usually referred to as exogenous. As membrane proteins on their way to degradation in lysosomes as part of their normal turn-over are also contained in the endosomal/lysosomal compartments, exogenous antigens must compete with those derived from endogenous components. Autophagy is also a source of endogenous peptides, autophagosomes constitutively fuse with MHC class II loading compartments. In addition to APCs, other cells of the gastrointestinal tract, such as epithelial cells, express MHC class II molecules and CD74 and act as APCs, which is an unusual trait of the GI tract. To produce a MHC class II molecule that presents an antigen, three MHC class II molecules (heterodimers of an alpha and a beta chain) associate with a CD74 trimer in the ER to form a heterononamer. Soon after the entry of this complex into the endosomal/lysosomal system where antigen processing occurs, CD74 undergoes a sequential degradation by various proteases, including CTSS and CTSL, leaving a small fragment termed CLIP (class-II-associated invariant chain peptide). The removal of CLIP is facilitated by HLA-DM via direct binding to the alpha-beta-CLIP complex so that CLIP is released. HLA-DM stabilizes MHC class II molecules until primary high affinity antigenic peptides are bound. The MHC II molecule bound to a peptide is then transported to the cell membrane surface. In B-cells, the interaction between HLA-DM and MHC class II molecules is regulated by HLA-DO. Primary dendritic cells (DCs) also to express HLA-DO. Lysosomal microenvironment has been implicated in the regulation of antigen loading into MHC II molecules, increased acidification produces increased proteolysis and efficient peptide loading.
• 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

46 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Behcet disease	DISSYMBS	Definitive	Genetic Variation	[1]
Acute lymphocytic leukaemia	DISPX75S	Strong	Genetic Variation	[2]
Advanced cancer	DISAT1Z9	Strong	Genetic Variation	[3]
Angioedema	DIS90QDN	Strong	Biomarker	[4]
Ankylosing spondylitis	DISRC6IR	Strong	Genetic Variation	[5]
Asthma	DISW9QNS	Strong	Biomarker	[6]
Autoimmune disease	DISORMTM	Strong	Biomarker	[7]
Autoimmune hepatitis	DISOX03Q	Strong	Genetic Variation	[8]
Cervical cancer	DISFSHPF	Strong	Genetic Variation	[9]
Chronic hepatitis B virus infection	DISHL4NT	Strong	Genetic Variation	[10]
Chronic obstructive pulmonary disease	DISQCIRF	Strong	Biomarker	[11]
Classic Hodgkin lymphoma	DISV1LU6	Strong	Biomarker	[12]
Dermatomyositis	DIS50C5O	Strong	Genetic Variation	[13]
Follicular lymphoma	DISVEUR6	Strong	Genetic Variation	[14]
Graves disease	DISU4KOQ	Strong	Genetic Variation	[15]
Haematological malignancy	DISCDP7W	Strong	Biomarker	[16]
Hashimoto thyroiditis	DIS77CDF	Strong	Biomarker	[17]
Hepatitis C virus infection	DISQ0M8R	Strong	Genetic Variation	[18]
IgA nephropathy	DISZ8MTK	Strong	Genetic Variation	[19]
Irritant contact dermatitis	DIS62JY3	Strong	Biomarker	[20]
Juvenile idiopathic arthritis	DISQZGBV	Strong	Genetic Variation	[21]
Knee osteoarthritis	DISLSNBJ	Strong	Genetic Variation	[22]
leukaemia	DISS7D1V	Strong	Genetic Variation	[23]
Narcolepsy	DISLCNLI	Strong	Genetic Variation	[24]
Osteoarthritis	DIS05URM	Strong	Genetic Variation	[22]
Pemphigus	DISZAZ6M	Strong	Altered Expression	[25]
Pulmonary tuberculosis	DIS6FLUM	Strong	Genetic Variation	[26]
Urticaria	DIS9WQAI	Strong	Biomarker	[27]
Lymphoma	DISN6V4S	moderate	Biomarker	[28]
Scleroderma	DISVQ342	moderate	Biomarker	[29]
Childhood acute lymphoblastic leukemia	DISJ5D6U	Disputed	Biomarker	[30]
Glioblastoma multiforme	DISK8246	Disputed	Genetic Variation	[31]
Anca-associated vasculitis	DISU3CNU	Limited	Genetic Variation	[32]
Autism	DISV4V1Z	Limited	Genetic Variation	[7]
Cervical carcinoma	DIST4S00	Limited	Genetic Variation	[9]
Chronic graft versus host disease	DIS1MM9J	Limited	Biomarker	[33]
Endometriosis	DISX1AG8	Limited	Biomarker	[34]
Inflammatory bowel disease	DISGN23E	Limited	Genetic Variation	[35]
Myelodysplastic syndrome	DISYHNUI	Limited	Genetic Variation	[36]
Neoplasm	DISZKGEW	Limited	Altered Expression	[37]
Pulmonary fibrosis	DISQKVLA	Limited	Genetic Variation	[29]
Sjogren syndrome	DISUBX7H	Limited	Genetic Variation	[38]
Systemic sclerosis	DISF44L6	Limited	Genetic Variation	[39]
Type-1/2 diabetes	DISIUHAP	Limited	Genetic Variation	[40]
Uterine cervix neoplasm	DIS0BYVV	Limited	Biomarker	[41]
Vasculitis	DISQRKDX	Limited	Biomarker	[42]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Aspirin	DM672AH	Approved	HLA class II histocompatibility antigen, DP beta 1 chain (HLA-DPB1) increases the Urticaria ADR of Aspirin.	[4]

13 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, DP beta 1 chain (HLA-DPB1).	[43]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of HLA class II histocompatibility antigen, DP beta 1 chain (HLA-DPB1).	[44]
Arsenic	DMTL2Y1	Approved	Arsenic decreases the expression of HLA class II histocompatibility antigen, DP beta 1 chain (HLA-DPB1).	[45]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of HLA class II histocompatibility antigen, DP beta 1 chain (HLA-DPB1).	[46]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of HLA class II histocompatibility antigen, DP beta 1 chain (HLA-DPB1).	[47]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of HLA class II histocompatibility antigen, DP beta 1 chain (HLA-DPB1).	[48]
Isotretinoin	DM4QTBN	Approved	Isotretinoin increases the expression of HLA class II histocompatibility antigen, DP beta 1 chain (HLA-DPB1).	[50]
Bortezomib	DMNO38U	Approved	Bortezomib decreases the expression of HLA class II histocompatibility antigen, DP beta 1 chain (HLA-DPB1).	[51]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of HLA class II histocompatibility antigen, DP beta 1 chain (HLA-DPB1).	[52]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of HLA class II histocompatibility antigen, DP beta 1 chain (HLA-DPB1).	[54]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of HLA class II histocompatibility antigen, DP beta 1 chain (HLA-DPB1).	[55]
Butanoic acid	DMTAJP7	Investigative	Butanoic acid increases the expression of HLA class II histocompatibility antigen, DP beta 1 chain (HLA-DPB1).	[56]
Nitrobenzanthrone	DMN6L70	Investigative	Nitrobenzanthrone decreases the expression of HLA class II histocompatibility antigen, DP beta 1 chain (HLA-DPB1).	[57]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Folic acid	DMEMBJC	Approved	Folic acid affects the methylation of HLA class II histocompatibility antigen, DP beta 1 chain (HLA-DPB1).	[49]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of HLA class II histocompatibility antigen, DP beta 1 chain (HLA-DPB1).	[53]

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