Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTMZ1T7J)

• DOT Name: T-cell surface glycoprotein CD8 beta chain (CD8B)
• Synonyms: CD antigen CD8b
• Gene Name: CD8B
• Related Disease:
  Advanced cancer
  Gastric cancer
  Glioblastoma multiforme
  Hepatitis C virus infection
  Hepatocellular carcinoma
  Juvenile idiopathic arthritis
  leukaemia
  Leukemia
  Lupus
  Progressive supranuclear palsy
  Small lymphocytic lymphoma
  Stomach cancer
  Systemic lupus erythematosus
  Lyme disease
  Lymphoma
  Neoplasm
  Schizophrenia
• UniProt ID: CD8B_HUMAN
• Pfam ID: PF07686
• Sequence:
  MRPRLWLLLAAQLTVLHGNSVLQQTPAYIKVQTNKMVMLSCEAKISLSNMRIYWLRQRQA
  PSSDSHHEFLALWDSAKGTIHGEEVEQEKIAVFRDASRFILNLTSVKPEDSGIYFCMIVG
  SPELTFGKGTQLSVVDFLPTTAQPTKKSTLKKRVCRLPRPETQKGPLCSPITLGLLVAGV
  LVLLVSLGVAIHLCCRRRRARLRFMKQFYK
• 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. A palmitoylation site in the cytoplasmic tail of CD8B chain contributes to partitioning of CD8 into the plasma membrane lipid rafts where signaling proteins are enriched. Once LCK recruited, it initiates different intracellular signaling pathways by phosphorylating various substrates ultimately leading to lymphokine production, motility, adhesion and activation of cytotoxic T-lymphocytes (CTLs). Additionally, plays a critical role in thymic selection of CD8+ T-cells.
• Tissue Specificity: Isoform 1, isoform 3, isoform 5, isoform 6, isoform 7 and isoform 8 are expressed in both thymus and peripheral CD8+ T-cells. Expression of isoform 1 is higher in thymus CD8+ T-cells than in peripheral CD8+ T-cells. Expression of isoform 6 is higher in peripheral CD8+ T-cells than in thymus CD8+ T-cells.
• 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)
  Nef Mediated CD8 Down-regulation (R-HSA-182218)

Molecular Interaction Atlas (MIA) of This DOT

17 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[1]
Gastric cancer	DISXGOUK	Strong	Biomarker	[2]
Glioblastoma multiforme	DISK8246	Strong	Altered Expression	[3]
Hepatitis C virus infection	DISQ0M8R	Strong	Altered Expression	[4]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[5]
Juvenile idiopathic arthritis	DISQZGBV	Strong	Biomarker	[6]
leukaemia	DISS7D1V	Strong	Biomarker	[7]
Leukemia	DISNAKFL	Strong	Biomarker	[7]
Lupus	DISOKJWA	Strong	Biomarker	[8]
Progressive supranuclear palsy	DISO5KRQ	Strong	Genetic Variation	[9]
Small lymphocytic lymphoma	DIS30POX	Strong	Altered Expression	[10]
Stomach cancer	DISKIJSX	Strong	Biomarker	[2]
Systemic lupus erythematosus	DISI1SZ7	Strong	Biomarker	[8]
Lyme disease	DISO70G5	moderate	Biomarker	[11]
Lymphoma	DISN6V4S	Limited	Altered Expression	[12]
Neoplasm	DISZKGEW	Limited	Biomarker	[13]
Schizophrenia	DISSRV2N	Limited	Biomarker	[14]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Fluorouracil	DMUM7HZ	Approved	Fluorouracil decreases the expression of T-cell surface glycoprotein CD8 beta chain (CD8B).	[15]
Manganese	DMKT129	Investigative	Manganese increases the expression of T-cell surface glycoprotein CD8 beta chain (CD8B).	[17]

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 increases the methylation of T-cell surface glycoprotein CD8 beta chain (CD8B).	[16]

References

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• [2] Mycoplasma hyorhinis infection in gastric carcinoma and its effects on the malignant phenotypes of gastric cancer cells.BMC Gastroenterol. 2010 Nov 10;10:132. doi: 10.1186/1471-230X-10-132.
• [3] FGL2 promotes tumor progression in the CNS by suppressing CD103(+) dendritic cell differentiation.Nat Commun. 2019 Jan 25;10(1):448. doi: 10.1038/s41467-018-08271-x.
• [4] Contradictory intrahepatic immune responses activated in high-load hepatitis C virus livers compared with low-load livers.Arch Virol. 2018 Apr;163(4):855-865. doi: 10.1007/s00705-017-3675-8. Epub 2017 Dec 16.
• [5] Mycoplasma infection promotes tumor progression via interaction of the mycoplasmal protein p37 and epithelial cell adhesion molecule in hepatocellular carcinoma.Cancer Lett. 2019 Jul 10;454:44-52. doi: 10.1016/j.canlet.2019.04.007. Epub 2019 Apr 10.
• [6] Gene expression signatures in polyarticular juvenile idiopathic arthritis demonstrate disease heterogeneity and offer a molecular classification of disease subsets.Arthritis Rheum. 2009 Jul;60(7):2113-23. doi: 10.1002/art.24534.
• [7] Comparative sequence analysis of a region on human chromosome 13q14, frequently deleted in B-cell chronic lymphocytic leukemia, and its homologous region on mouse chromosome 14.Genomics. 2000 Dec 15;70(3):327-34. doi: 10.1006/geno.2000.6386.
• [8] cAMP responsive element modulator (CREM) mediates chromatin remodeling of CD8 during the generation of CD3+ CD4- CD8- T cells.J Biol Chem. 2014 Jan 24;289(4):2361-70. doi: 10.1074/jbc.M113.523605. Epub 2013 Dec 2.
• [9] Identification of common variants influencing risk of the tauopathy progressive supranuclear palsy.Nat Genet. 2011 Jun 19;43(7):699-705. doi: 10.1038/ng.859.
• [10] Nucleotide sequence, transcription map, and mutation analysis of the 13q14 chromosomal region deleted in B-cell chronic lymphocytic leukemia.Blood. 2001 Apr 1;97(7):2098-104. doi: 10.1182/blood.v97.7.2098.
• [11] The Borrelia burgdorferi 37-kilodalton immunoblot band (P37) used in serodiagnosis of early lyme disease is the flaA gene product.J Clin Microbiol. 1999 Mar;37(3):548-52. doi: 10.1128/JCM.37.3.548-552.1999.
• [12] The phenotypic diversity of peripheral T-cell lymphomas: the Southeastern Cancer Study Group experience.Hum Pathol. 1986 Jun;17(6):567-74. doi: 10.1016/s0046-8177(86)80128-9.
• [13] Exclusion of Leu1 and Leu2 genes as tumor suppressor genes in 13q14.3-deleted B-CLL.Leukemia. 1999 Oct;13(10):1630-2. doi: 10.1038/sj.leu.2401525.
• [14] Transcription of PIK3CD in human brain and schizophrenia: regulation by proinflammatory cytokines.Hum Mol Genet. 2019 Oct 1;28(19):3188-3198. doi: 10.1093/hmg/ddz144.
• [15] Dissecting progressive stages of 5-fluorouracil resistance in vitro using RNA expression profiling. Int J Cancer. 2004 Nov 1;112(2):200-12. doi: 10.1002/ijc.20401.
• [16] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [17] Gene expression profiling of human primary astrocytes exposed to manganese chloride indicates selective effects on several functions of the cells. Neurotoxicology. 2007 May;28(3):478-89.