Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT7KZMP2)

• DOT Name: HLA class II histocompatibility antigen, DR alpha chain (HLA-DRA)
• Synonyms: MHC class II antigen DRA
• Gene Name: HLA-DRA
• Related Disease:
  Acute lymphocytic leukaemia
  Bacteremia
  Childhood acute lymphoblastic leukemia
  Classic Hodgkin lymphoma
  Colorectal carcinoma
  Crohn disease
  Hepatitis B virus infection
  Sarcoidosis
  Adult glioblastoma
  Advanced cancer
  Alcohol dependence
  Alzheimer disease
  Autoimmune disease
  Bipolar disorder
  Breast cancer
  Breast carcinoma
  Disorder of orbital region
  Epstein barr virus infection
  Fuchs' endothelial dystrophy
  Glioblastoma multiforme
  Haemophilia A
  Heparin-induced thrombocytopenia
  Hepatocellular carcinoma
  IgA nephropathy
  Inflammatory bowel disease
  Keratoconjunctivitis sicca
  Latent tuberculosis infection
  Narcolepsy
  Nasal polyp
  Non-insulin dependent diabetes
  Polyp
  Prediabetes syndrome
  Primary biliary cholangitis
  Rheumatoid arthritis
  Rosacea
  Schizophrenia
  Sjogren syndrome
  Systemic lupus erythematosus
  Systemic sclerosis
  Toxic shock syndrome
  Tuberculosis
  Type-1 diabetes
  Ulcerative colitis
  Pemphigus vulgaris
  Posterior uveitis
  Asthma
  Multiple sclerosis
  Parkinson disease
• UniProt ID: DRA_HUMAN
• PDB ID: 1A6A ; 1AQD ; 1BX2 ; 1D5M ; 1D5X ; 1D5Z ; 1D6E ; 1DLH ; 1FV1 ; 1FYT ; 1H15 ; 1HQR ; 1HXY ; 1J8H ; 1JWM ; 1JWS ; 1JWU ; 1KG0 ; 1KLG ; 1KLU ; 1LO5 ; 1PYW ; 1R5I ; 1SEB ; 1SJE ; 1SJH ; 1T5W ; 1T5X ; 1YMM ; 1ZGL ; 2FSE ; 2G9H ; 2IAM ; 2IAN ; 2ICW ; 2IPK ; 2OJE ; 2Q6W ; 2SEB ; 2WBJ ; 2XN9 ; 3C5J ; 3L6F ; 3O6F ; 3PDO ; 3PGC ; 3PGD ; 3QXA ; 3QXD ; 3S4S ; 3S5L ; 3T0E ; 4AEN ; 4AH2 ; 4C56 ; 4E41 ; 4FQX ; 4GBX ; 4H1L ; 4H25 ; 4H26 ; 4I5B ; 4IS6 ; 4MCY ; 4MCZ ; 4MD0 ; 4MD4 ; 4MD5 ; 4MDI ; 4MDJ ; 4OV5 ; 4X5W ; 4X5X ; 4Y19 ; 4Y1A ; 5JLZ ; 5LAX ; 5NI9 ; 5NIG ; 5V4M ; 5V4N ; 6ATF ; 6ATI ; 6ATZ ; 6BIJ ; 6BIL ; 6BIN ; 6BIR ; 6BIV ; 6BIX ; 6BIY ; 6BIZ ; 6CPL ; 6CPN ; 6CPO ; 6CQJ ; 6CQL ; 6CQN ; 6CQQ ; 6CQR ; 6NIX ; 6QZA ; 6QZC ; 6QZD ; 6R0E ; 6V0Y ; 6V13 ; 6V15 ; 6V18 ; 6V19 ; 6V1A ; 7N19 ; 7NZE ; 7O00 ; 7YX9 ; 7YXB ; 7Z0Q ; 8CMB ; 8CMC ; 8CMD ; 8CME ; 8CMF ; 8CMG ; 8CMH ; 8CMI ; 8EUQ
• Pfam ID: PF07654 ; PF00993
• Sequence:
  MAISGVPVLGFFIIAVLMSAQESWAIKEEHVIIQAEFYLNPDQSGEFMFDFDGDEIFHVD
  MAKKETVWRLEEFGRFASFEAQGALANIAVDKANLEIMTKRSNYTPITNVPPEVTVLTNS
  PVELREPNVLICFIDKFTPPVVNVTWLRNGKPVTTGVSETVFLPREDHLFRKFHYLPFLP
  STEDVYDCRVEHWGLDEPLLKHWEFDAPSPLPETTENVVCALGLTVGLVGIIIGTIFIIK
  GLRKSNAAERRGPL
• Function: An alpha chain of antigen-presenting major histocompatibility complex class II (MHCII) molecule. In complex with the beta chain HLA-DRB, displays antigenic peptides on professional antigen presenting cells (APCs) for recognition by alpha-beta T cell receptor (TCR) on HLA-DR-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.
• Tissue Specificity: Expressed in professional APCs: 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

48 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute lymphocytic leukaemia	DISPX75S	Definitive	Genetic Variation	[1]
Bacteremia	DIS6N9RZ	Definitive	Altered Expression	[2]
Childhood acute lymphoblastic leukemia	DISJ5D6U	Definitive	Genetic Variation	[1]
Classic Hodgkin lymphoma	DISV1LU6	Definitive	Genetic Variation	[3]
Colorectal carcinoma	DIS5PYL0	Definitive	Altered Expression	[4]
Crohn disease	DIS2C5Q8	Definitive	Genetic Variation	[5]
Hepatitis B virus infection	DISLQ2XY	Definitive	Genetic Variation	[6]
Sarcoidosis	DISE5B8Z	Definitive	Genetic Variation	[7]
Adult glioblastoma	DISVP4LU	Strong	Altered Expression	[8]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[9]
Alcohol dependence	DIS4ZSCO	Strong	Genetic Variation	[10]
Alzheimer disease	DISF8S70	Strong	Altered Expression	[11]
Autoimmune disease	DISORMTM	Strong	Biomarker	[12]
Bipolar disorder	DISAM7J2	Strong	Biomarker	[13]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[14]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[14]
Disorder of orbital region	DISH0ECJ	Strong	Biomarker	[15]
Epstein barr virus infection	DISOO0WT	Strong	Genetic Variation	[16]
Fuchs' endothelial dystrophy	DISL7TXC	Strong	Biomarker	[17]
Glioblastoma multiforme	DISK8246	Strong	Altered Expression	[8]
Haemophilia A	DIS0RQ2E	Strong	Genetic Variation	[18]
Heparin-induced thrombocytopenia	DISAKJKZ	Strong	Genetic Variation	[19]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[20]
IgA nephropathy	DISZ8MTK	Strong	Biomarker	[21]
Inflammatory bowel disease	DISGN23E	Strong	Biomarker	[22]
Keratoconjunctivitis sicca	DISNOENH	Strong	Biomarker	[15]
Latent tuberculosis infection	DIS6R1EH	Strong	Biomarker	[23]
Narcolepsy	DISLCNLI	Strong	Genetic Variation	[24]
Nasal polyp	DISLP3XE	Strong	Genetic Variation	[25]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Altered Expression	[26]
Polyp	DISRSLYF	Strong	Genetic Variation	[25]
Prediabetes syndrome	DISH2I53	Strong	Biomarker	[27]
Primary biliary cholangitis	DIS43E0O	Strong	Genetic Variation	[28]
Rheumatoid arthritis	DISTSB4J	Strong	Genetic Variation	[29]
Rosacea	DIS02PWG	Strong	Genetic Variation	[30]
Schizophrenia	DISSRV2N	Strong	Biomarker	[13]
Sjogren syndrome	DISUBX7H	Strong	Genetic Variation	[31]
Systemic lupus erythematosus	DISI1SZ7	Strong	Genetic Variation	[32]
Systemic sclerosis	DISF44L6	Strong	Genetic Variation	[33]
Toxic shock syndrome	DISX5S53	Strong	Biomarker	[34]
Tuberculosis	DIS2YIMD	Strong	Biomarker	[23]
Type-1 diabetes	DIS7HLUB	Strong	Genetic Variation	[35]
Ulcerative colitis	DIS8K27O	Strong	Genetic Variation	[36]
Pemphigus vulgaris	DISENR62	moderate	Genetic Variation	[37]
Posterior uveitis	DISIBJSM	moderate	Genetic Variation	[38]
Asthma	DISW9QNS	Limited	Biomarker	[39]
Multiple sclerosis	DISB2WZI	Limited	Genetic Variation	[1]
Parkinson disease	DISQVHKL	Limited	Genetic Variation	[40]

22 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, DR alpha chain (HLA-DRA).	[41]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of HLA class II histocompatibility antigen, DR alpha chain (HLA-DRA).	[42]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of HLA class II histocompatibility antigen, DR alpha chain (HLA-DRA).	[43]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of HLA class II histocompatibility antigen, DR alpha chain (HLA-DRA).	[44]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of HLA class II histocompatibility antigen, DR alpha chain (HLA-DRA).	[45]
Arsenic	DMTL2Y1	Approved	Arsenic decreases the expression of HLA class II histocompatibility antigen, DR alpha chain (HLA-DRA).	[46]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of HLA class II histocompatibility antigen, DR alpha chain (HLA-DRA).	[47]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of HLA class II histocompatibility antigen, DR alpha chain (HLA-DRA).	[48]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of HLA class II histocompatibility antigen, DR alpha chain (HLA-DRA).	[49]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of HLA class II histocompatibility antigen, DR alpha chain (HLA-DRA).	[50]
Selenium	DM25CGV	Approved	Selenium increases the expression of HLA class II histocompatibility antigen, DR alpha chain (HLA-DRA).	[51]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of HLA class II histocompatibility antigen, DR alpha chain (HLA-DRA).	[52]
Bortezomib	DMNO38U	Approved	Bortezomib decreases the expression of HLA class II histocompatibility antigen, DR alpha chain (HLA-DRA).	[53]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone decreases the expression of HLA class II histocompatibility antigen, DR alpha chain (HLA-DRA).	[54]
Ursodeoxycholic acid	DMCUT21	Approved	Ursodeoxycholic acid increases the expression of HLA class II histocompatibility antigen, DR alpha chain (HLA-DRA).	[55]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of HLA class II histocompatibility antigen, DR alpha chain (HLA-DRA).	[56]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene increases the expression of HLA class II histocompatibility antigen, DR alpha chain (HLA-DRA).	[57]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of HLA class II histocompatibility antigen, DR alpha chain (HLA-DRA).	[58]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of HLA class II histocompatibility antigen, DR alpha chain (HLA-DRA).	[51]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of HLA class II histocompatibility antigen, DR alpha chain (HLA-DRA).	[56]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of HLA class II histocompatibility antigen, DR alpha chain (HLA-DRA).	[60]
Chrysin	DM7V2LG	Investigative	Chrysin decreases the expression of HLA class II histocompatibility antigen, DR alpha chain (HLA-DRA).	[58]

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 decreases the methylation of HLA class II histocompatibility antigen, DR alpha chain (HLA-DRA).	[59]

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