Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT1DH0N9)

• DOT Name: HLA class II histocompatibility antigen, DQ alpha 2 chain (HLA-DQA2)
• Synonyms: DX alpha chain; HLA class II histocompatibility antigen, DQ(6) alpha chain; HLA-DQA1; MHC class II DQA2
• Gene Name: HLA-DQA2
• Related Disease:
  Hepatitis B virus infection
  Narcolepsy
  Pneumonia
  Asthma
  Autoimmune disease
  Coeliac disease
  Cowden disease
  Cystic fibrosis
  Gastric cancer
  Graves disease
  Hepatitis C virus infection
  Hepatocellular carcinoma
  Lung adenocarcinoma
  Multiple sclerosis
  Myasthenia gravis
  Nasal polyp
  Oral cancer
  Psoriasis
  Rheumatic fever
  Rheumatic heart disease
  Rheumatoid arthritis
  Sarcoidosis
  Schizophrenia
  Squamous cell carcinoma
  Stomach cancer
  Systemic lupus erythematosus
  Thyroid gland carcinoma
  Type-1/2 diabetes
  Vitiligo
  Cutaneous lupus erythematosus
  Inflammatory bowel disease
  Cryohydrocytosis
  Small lymphocytic lymphoma
  Addison disease
  Lung cancer
  Lung carcinoma
  Lung squamous cell carcinoma
  Membranous glomerulonephritis
  Type-1 diabetes
• UniProt ID: DQA2_HUMAN
• Pfam ID: PF07654 ; PF00993
• Sequence:
  MILNKALLLGALALTAVMSPCGGEDIVADHVASYGVNFYQSHGPSGQYTHEFDGDEEFYV
  DLETKETVWQLPMFSKFISFDPQSALRNMAVGKHTLEFMMRQSNSTAATNEVPEVTVFSK
  FPVTLGQPNTLICLVDNIFPPVVNITWLSNGHSVTEGVSETSFLSKSDHSFFKISYLTFL
  PSADEIYDCKVEHWGLDEPLLKHWEPEIPAPMSELTETLVCALGLSVGLMGIVVGTVFII
  QGLRSVGASRHQGLL
• 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.
• Tissue Specificity: Restricted to skin Langerhans cells, although some expression at low levels may occur at the surface of B lymphoblastoid cells.
• 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

39 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hepatitis B virus infection	DISLQ2XY	Definitive	Genetic Variation	[1]
Narcolepsy	DISLCNLI	Definitive	Genetic Variation	[2]
Pneumonia	DIS8EF3M	Definitive	Biomarker	[3]
Asthma	DISW9QNS	Strong	Genetic Variation	[4]
Autoimmune disease	DISORMTM	Strong	Genetic Variation	[5]
Coeliac disease	DISIY60C	Strong	Genetic Variation	[5]
Cowden disease	DISMYKCE	Strong	Biomarker	[6]
Cystic fibrosis	DIS2OK1Q	Strong	Genetic Variation	[7]
Gastric cancer	DISXGOUK	Strong	Genetic Variation	[8]
Graves disease	DISU4KOQ	Strong	Genetic Variation	[9]
Hepatitis C virus infection	DISQ0M8R	Strong	Genetic Variation	[10]
Hepatocellular carcinoma	DIS0J828	Strong	Genetic Variation	[11]
Lung adenocarcinoma	DISD51WR	Strong	Genetic Variation	[12]
Multiple sclerosis	DISB2WZI	Strong	Genetic Variation	[13]
Myasthenia gravis	DISELRCI	Strong	Genetic Variation	[14]
Nasal polyp	DISLP3XE	Strong	Biomarker	[15]
Oral cancer	DISLD42D	Strong	Genetic Variation	[16]
Psoriasis	DIS59VMN	Strong	Genetic Variation	[17]
Rheumatic fever	DISLUF66	Strong	Genetic Variation	[18]
Rheumatic heart disease	DISCI8JQ	Strong	Genetic Variation	[19]
Rheumatoid arthritis	DISTSB4J	Strong	Genetic Variation	[20]
Sarcoidosis	DISE5B8Z	Strong	Genetic Variation	[21]
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[22]
Squamous cell carcinoma	DISQVIFL	Strong	Genetic Variation	[23]
Stomach cancer	DISKIJSX	Strong	Genetic Variation	[8]
Systemic lupus erythematosus	DISI1SZ7	Strong	Genetic Variation	[24]
Thyroid gland carcinoma	DISMNGZ0	Strong	Altered Expression	[25]
Type-1/2 diabetes	DISIUHAP	Strong	Genetic Variation	[26]
Vitiligo	DISR05SL	Strong	Genetic Variation	[27]
Cutaneous lupus erythematosus	DISOIX6L	moderate	Genetic Variation	[28]
Inflammatory bowel disease	DISGN23E	moderate	Genetic Variation	[29]
Cryohydrocytosis	DISMQHL3	Disputed	Biomarker	[30]
Small lymphocytic lymphoma	DIS30POX	Disputed	Genetic Variation	[31]
Addison disease	DIS7HNOH	Limited	Genetic Variation	[32]
Lung cancer	DISCM4YA	Limited	Genetic Variation	[33]
Lung carcinoma	DISTR26C	Limited	Genetic Variation	[34]
Lung squamous cell carcinoma	DISXPIBD	Limited	Genetic Variation	[34]
Membranous glomerulonephritis	DISFSUKQ	Limited	Genetic Variation	[35]
Type-1 diabetes	DIS7HLUB	Limited	Genetic Variation	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Sodium lauryl sulfate	DMLJ634	Approved	HLA class II histocompatibility antigen, DQ alpha 2 chain (HLA-DQA2) affects the response to substance of Sodium lauryl sulfate.	[38]

1 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic decreases the expression of HLA class II histocompatibility antigen, DQ alpha 2 chain (HLA-DQA2).	[36]

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, DQ alpha 2 chain (HLA-DQA2).	[37]

References

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