Details of Drug Off-Target (DOT)

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

DOT Name T-cell surface glycoprotein CD8 alpha chain (CD8A)
Synonyms T-lymphocyte differentiation antigen T8/Leu-2; CD antigen CD8a
Gene Name CD8A
Related Disease
Respiratory syncytial virus infection ( )
Tuberculosis ( )
Abdominal aortic aneurysm ( )
Acute megakaryoblastic leukemia ( )
Advanced cancer ( )
Alzheimer disease ( )
Autoimmune disease ( )
Brain cancer ( )
Breast cancer ( )
Breast neoplasm ( )
Coeliac disease ( )
Craniosynostosis ( )
Gastric cancer ( )
Glioblastoma multiforme ( )
Glioma ( )
Hepatitis C virus infection ( )
Hepatocellular carcinoma ( )
Immunodeficiency ( )
leukaemia ( )
Leukemia ( )
Marinesco-Sjogren syndrome ( )
Meningioma ( )
Multiple sclerosis ( )
Neoplasm ( )
Obesity ( )
Recessive X-linked ichthyosis ( )
Sjogren syndrome ( )
Small lymphocytic lymphoma ( )
Stomach cancer ( )
Susceptibility to respiratory infections associated with CD8alpha chain mutation ( )
Systemic lupus erythematosus ( )
Triple negative breast cancer ( )
Chronic obstructive pulmonary disease ( )
Colorectal carcinoma ( )
Fetal growth restriction ( )
Type-1/2 diabetes ( )
Bladder transitional cell carcinoma ( )
Lymphoma ( )
Melanoma ( )
Neuroblastoma ( )
Timothy syndrome ( )
Tourette syndrome ( )
Tuberous sclerosis ( )
UniProt ID
CD8A_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
PDB ID
1AKJ; 1CD8; 1Q69; 2HP4; 3QZW; 7UMG; 7UVF; 8EW6
Pfam ID
PF07686
Sequence
MALPVTALLLPLALLLHAARPSQFRVSPLDRTWNLGETVELKCQVLLSNPTSGCSWLFQP
RGAAASPTFLLYLSQNKPKAAEGLDTQRFSGKRLGDTFVLTLSDFRRENEGYYFCSALSN
SIMYFSHFVPVFLPAKPTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFA
CDIYIWAPLAGTCGVLLLSLVITLYCNHRNRRRVCKCPRPVVKSGDKPSLSARYV
Function
Integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses. In T-cells, functions primarily as a coreceptor for MHC class I molecule:peptide complex. The antigens presented by class I peptides are derived from cytosolic proteins while class II derived from extracellular proteins. Interacts simultaneously with the T-cell receptor (TCR) and the MHC class I proteins presented by antigen presenting cells (APCs). In turn, recruits the Src kinase LCK to the vicinity of the TCR-CD3 complex. LCK then initiates different intracellular signaling pathways by phosphorylating various substrates ultimately leading to lymphokine production, motility, adhesion and activation of cytotoxic T-lymphocytes (CTLs). This mechanism enables CTLs to recognize and eliminate infected cells and tumor cells. In NK-cells, the presence of CD8A homodimers at the cell surface provides a survival mechanism allowing conjugation and lysis of multiple target cells. CD8A homodimer molecules also promote the survival and differentiation of activated lymphocytes into memory CD8 T-cells.
Tissue Specificity
CD8 on thymus-derived T-cells usually consists of a disulfide-linked alpha/CD8A and a beta/CD8B chain. Less frequently, CD8 can be expressed as a CD8A homodimer. A subset of natural killer cells, memory T-cells, intraepithelial lymphocytes, monocytes and dendritic cells expresses CD8A homodimers. Expressed at the cell surface of plasmacytoid dendritic cells upon herpes simplex virus-1 stimulation.
KEGG Pathway
Cell adhesion molecules (hsa04514 )
Antigen processing and presentation (hsa04612 )
Hematopoietic cell lineage (hsa04640 )
T cell receptor sig.ling pathway (hsa04660 )
Yersinia infection (hsa05135 )
Primary immunodeficiency (hsa05340 )
Reactome Pathway
Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell (R-HSA-198933 )

Molecular Interaction Atlas (MIA) of This DOT

43 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Respiratory syncytial virus infection DIS7FWHY Definitive Biomarker [1]
Tuberculosis DIS2YIMD Definitive Altered Expression [2]
Abdominal aortic aneurysm DISD06OF Strong Altered Expression [3]
Acute megakaryoblastic leukemia DIS0JX3M Strong Genetic Variation [4]
Advanced cancer DISAT1Z9 Strong Altered Expression [5]
Alzheimer disease DISF8S70 Strong Biomarker [6]
Autoimmune disease DISORMTM Strong Biomarker [7]
Brain cancer DISBKFB7 Strong Altered Expression [8]
Breast cancer DIS7DPX1 Strong Altered Expression [9]
Breast neoplasm DISNGJLM Strong Biomarker [10]
Coeliac disease DISIY60C Strong Altered Expression [11]
Craniosynostosis DIS6J405 Strong Biomarker [12]
Gastric cancer DISXGOUK Strong Biomarker [13]
Glioblastoma multiforme DISK8246 Strong Biomarker [14]
Glioma DIS5RPEH Strong Biomarker [15]
Hepatitis C virus infection DISQ0M8R Strong Genetic Variation [16]
Hepatocellular carcinoma DIS0J828 Strong Altered Expression [17]
Immunodeficiency DIS093I0 Strong Biomarker [18]
leukaemia DISS7D1V Strong Biomarker [19]
Leukemia DISNAKFL Strong Biomarker [19]
Marinesco-Sjogren syndrome DISKEU0B Strong Biomarker [20]
Meningioma DISPT4TG Strong Genetic Variation [21]
Multiple sclerosis DISB2WZI Strong Biomarker [22]
Neoplasm DISZKGEW Strong Altered Expression [23]
Obesity DIS47Y1K Strong Biomarker [24]
Recessive X-linked ichthyosis DISZY56W Strong Biomarker [25]
Sjogren syndrome DISUBX7H Strong Biomarker [26]
Small lymphocytic lymphoma DIS30POX Strong Altered Expression [27]
Stomach cancer DISKIJSX Strong Biomarker [13]
Susceptibility to respiratory infections associated with CD8alpha chain mutation DIS0IOGZ Strong Autosomal recessive [28]
Systemic lupus erythematosus DISI1SZ7 Strong Altered Expression [29]
Triple negative breast cancer DISAMG6N Strong Altered Expression [10]
Chronic obstructive pulmonary disease DISQCIRF moderate Biomarker [30]
Colorectal carcinoma DIS5PYL0 moderate Biomarker [31]
Fetal growth restriction DIS5WEJ5 moderate Altered Expression [32]
Type-1/2 diabetes DISIUHAP moderate Biomarker [24]
Bladder transitional cell carcinoma DISNL46A Limited Genetic Variation [33]
Lymphoma DISN6V4S Limited Altered Expression [34]
Melanoma DIS1RRCY Limited Biomarker [33]
Neuroblastoma DISVZBI4 Limited Genetic Variation [35]
Timothy syndrome DISBXBZP Limited Biomarker [36]
Tourette syndrome DISX9D54 Limited Biomarker [36]
Tuberous sclerosis DISEMUGZ Limited Biomarker [36]
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⏷ Show the Full List of 43 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
6 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Cisplatin DMRHGI9 Approved Cisplatin decreases the expression of T-cell surface glycoprotein CD8 alpha chain (CD8A). [37]
Methotrexate DM2TEOL Approved Methotrexate decreases the expression of T-cell surface glycoprotein CD8 alpha chain (CD8A). [39]
Cytarabine DMZD5QR Approved Cytarabine increases the expression of T-cell surface glycoprotein CD8 alpha chain (CD8A). [40]
Aspirin DM672AH Approved Aspirin decreases the expression of T-cell surface glycoprotein CD8 alpha chain (CD8A). [41]
GSK618334 DMJPXZ4 Phase 1 GSK618334 decreases the expression of T-cell surface glycoprotein CD8 alpha chain (CD8A). [43]
Acetaldehyde DMJFKG4 Investigative Acetaldehyde increases the expression of T-cell surface glycoprotein CD8 alpha chain (CD8A). [44]
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⏷ Show the Full List of 6 Drug(s)
2 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 T-cell surface glycoprotein CD8 alpha chain (CD8A). [38]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene affects the methylation of T-cell surface glycoprotein CD8 alpha chain (CD8A). [42]
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References

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