Details of Drug Off-Target (DOT)

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

• DOT Name: MHC class I polypeptide-related sequence A (MICA)
• Synonyms: MIC-A
• Gene Name: MICA
• Related Disease:
  Acute graft versus host disease
  Addison disease
  Advanced cancer
  Autoimmune disease
  Burkitt lymphoma
  Carcinoma of liver and intrahepatic biliary tract
  Chronic graft versus host disease
  Cytomegalovirus infection
  Epithelial neoplasm
  Epithelial ovarian cancer
  Glioma
  Head-neck squamous cell carcinoma
  Hepatitis A virus infection
  Hepatitis B virus infection
  Hepatitis C virus infection
  Leprosy
  Liver cancer
  Lung cancer
  Lung carcinoma
  Melanoma
  Multiple sclerosis
  Non-insulin dependent diabetes
  Non-small-cell lung cancer
  Primary sclerosing cholangitis
  Prostate cancer
  Prostate carcinoma
  Squamous cell carcinoma
  Tuberculosis
  Type-1/2 diabetes
  Uveitis
  Ulcerative colitis
  Bone osteosarcoma
  Clear cell renal carcinoma
  Crohn disease
  Gastric cancer
  Inflammatory bowel disease
  Mental disorder
  Neuroblastoma
  Osteosarcoma
  Renal cell carcinoma
  Rheumatoid arthritis
  Stomach cancer
• UniProt ID: MICA_HUMAN
• PDB ID: 1B3J; 1HYR; 7FI5; 7FI6; 7FI7; 7FI8; 7FI9
• Pfam ID: PF07654 ; PF00129
• Sequence:
  MGLGPVFLLLAGIFPFAPPGAAAEPHSLRYNLTVLSWDGSVQSGFLTEVHLDGQPFLRCD
  RQKCRAKPQGQWAEDVLGNKTWDRETRDLTGNGKDLRMTLAHIKDQKEGLHSLQEIRVCE
  IHEDNSTRSSQHFYYDGELFLSQNLETKEWTMPQSSRAQTLAMNVRNFLKEDAMKTKTHY
  HAMHADCLQELRRYLKSGVVLRRTVPPMVNVTRSEASEGNITVTCRASGFYPWNITLSWR
  QDGVSLSHDTQQWGDVLPDGNGTYQTWVATRICQGEEQRFTCYMEHSGNHSTHPVPSGKV
  LVLQSHWQTFHVSAVAAAAIFVIIIFYVRCCKKKTSAAEGPELVSLQVLDQHPVGTSDHR
  DATQLGFQPLMSDLGSTGSTEGA
• Function: Seems to have no role in antigen presentation. Acts as a stress-induced self-antigen that is recognized by gamma delta T-cells. Ligand for the KLRK1/NKG2D receptor. Binding to KLRK1 leads to cell lysis.
• Tissue Specificity: Widely expressed with the exception of the central nervous system where it is absent. Expressed predominantly in gastric epithelium and also in monocytes, keratinocytes, endothelial cells, fibroblasts and in the outer layer of Hassal's corpuscles within the medulla of normal thymus. In skin, expressed mainly in the keratin layers, basal cells, ducts and follicles. Also expressed in many, but not all, epithelial tumors of lung, breast, kidney, ovary, prostate and colon. In thyomas, overexpressed in cortical and medullar epithelial cells. Tumors expressing MICA display increased levels of gamma delta T-cells.
• KEGG Pathway:
  .tural killer cell mediated cytotoxicity (hsa04650)
  Kaposi sarcoma-associated herpesvirus infection (hsa05167)
• Reactome Pathway: Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell (R-HSA-198933)

Molecular Interaction Atlas (MIA) of This DOT

42 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute graft versus host disease	DIS8KLVM	Strong	Biomarker	[1]
Addison disease	DIS7HNOH	Strong	Biomarker	[2]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[3]
Autoimmune disease	DISORMTM	Strong	Biomarker	[4]
Burkitt lymphoma	DIS9D5XU	Strong	Altered Expression	[5]
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	Strong	Altered Expression	[6]
Chronic graft versus host disease	DIS1MM9J	Strong	Genetic Variation	[7]
Cytomegalovirus infection	DISCEMGC	Strong	Genetic Variation	[8]
Epithelial neoplasm	DIS0T594	Strong	Altered Expression	[9]
Epithelial ovarian cancer	DIS56MH2	Strong	Altered Expression	[10]
Glioma	DIS5RPEH	Strong	Altered Expression	[11]
Head-neck squamous cell carcinoma	DISF7P24	Strong	Altered Expression	[12]
Hepatitis A virus infection	DISUMFQV	Strong	Genetic Variation	[13]
Hepatitis B virus infection	DISLQ2XY	Strong	Biomarker	[14]
Hepatitis C virus infection	DISQ0M8R	Strong	Genetic Variation	[15]
Leprosy	DISAA4UI	Strong	Biomarker	[16]
Liver cancer	DISDE4BI	Strong	Altered Expression	[6]
Lung cancer	DISCM4YA	Strong	Biomarker	[17]
Lung carcinoma	DISTR26C	Strong	Biomarker	[17]
Melanoma	DIS1RRCY	Strong	Biomarker	[18]
Multiple sclerosis	DISB2WZI	Strong	Genetic Variation	[19]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Genetic Variation	[20]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[21]
Primary sclerosing cholangitis	DISTH5WJ	Strong	Genetic Variation	[22]
Prostate cancer	DISF190Y	Strong	Biomarker	[23]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[23]
Squamous cell carcinoma	DISQVIFL	Strong	Altered Expression	[24]
Tuberculosis	DIS2YIMD	Strong	Biomarker	[25]
Type-1/2 diabetes	DISIUHAP	Strong	Genetic Variation	[26]
Uveitis	DISV0RYS	Strong	Genetic Variation	[27]
Ulcerative colitis	DIS8K27O	Disputed	Biomarker	[28]
Bone osteosarcoma	DIST1004	Limited	Biomarker	[29]
Clear cell renal carcinoma	DISBXRFJ	Limited	Biomarker	[30]
Crohn disease	DIS2C5Q8	Limited	Altered Expression	[31]
Gastric cancer	DISXGOUK	Limited	Altered Expression	[32]
Inflammatory bowel disease	DISGN23E	Limited	Genetic Variation	[28]
Mental disorder	DIS3J5R8	Limited	Biomarker	[33]
Neuroblastoma	DISVZBI4	Limited	Biomarker	[34]
Osteosarcoma	DISLQ7E2	Limited	Biomarker	[29]
Renal cell carcinoma	DISQZ2X8	Limited	Biomarker	[30]
Rheumatoid arthritis	DISTSB4J	Limited	Genetic Variation	[35]
Stomach cancer	DISKIJSX	Limited	Altered Expression	[32]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Fluorouracil	DMUM7HZ	Approved	MHC class I polypeptide-related sequence A (MICA) affects the response to substance of Fluorouracil.	[55]

18 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 MHC class I polypeptide-related sequence A (MICA).	[36]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of MHC class I polypeptide-related sequence A (MICA).	[37]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of MHC class I polypeptide-related sequence A (MICA).	[38]
Doxorubicin	DMVP5YE	Approved	Doxorubicin affects the expression of MHC class I polypeptide-related sequence A (MICA).	[39]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of MHC class I polypeptide-related sequence A (MICA).	[40]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of MHC class I polypeptide-related sequence A (MICA).	[42]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of MHC class I polypeptide-related sequence A (MICA).	[43]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of MHC class I polypeptide-related sequence A (MICA).	[44]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of MHC class I polypeptide-related sequence A (MICA).	[40]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of MHC class I polypeptide-related sequence A (MICA).	[45]
Folic acid	DMEMBJC	Approved	Folic acid affects the expression of MHC class I polypeptide-related sequence A (MICA).	[46]
Malathion	DMXZ84M	Approved	Malathion increases the expression of MHC class I polypeptide-related sequence A (MICA).	[47]
Gefitinib	DM15F0X	Approved	Gefitinib increases the expression of MHC class I polypeptide-related sequence A (MICA).	[48]
Sulfasalazine	DMICA9H	Approved	Sulfasalazine decreases the expression of MHC class I polypeptide-related sequence A (MICA).	[49]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of MHC class I polypeptide-related sequence A (MICA).	[44]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of MHC class I polypeptide-related sequence A (MICA).	[50]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of MHC class I polypeptide-related sequence A (MICA).	[53]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of MHC class I polypeptide-related sequence A (MICA).	[54]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of MHC class I polypeptide-related sequence A (MICA).	[41]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of MHC class I polypeptide-related sequence A (MICA).	[51]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of MHC class I polypeptide-related sequence A (MICA).	[52]

References

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