Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT90NDLY)

• DOT Name: Complement receptor type 2 (CR2)
• Synonyms: Cr2; Complement C3d receptor; Epstein-Barr virus receptor; EBV receptor; CD antigen CD21
• Gene Name: CR2
• Related Disease:
  Immunodeficiency, common variable, 7
  Common variable immunodeficiency
• UniProt ID: CR2_HUMAN
• PDB ID: 1GHQ; 1LY2; 1W2R; 1W2S; 2ATY; 2GSX; 3OED
• Pfam ID: PF00084
• Sequence:
  MGAAGLLGVFLALVAPGVLGISCGSPPPILNGRISYYSTPIAVGTVIRYSCSGTFRLIGE
  KSLLCITKDKVDGTWDKPAPKCEYFNKYSSCPEPIVPGGYKIRGSTPYRHGDSVTFACKT
  NFSMNGNKSVWCQANNMWGPTRLPTCVSVFPLECPALPMIHNGHHTSENVGSIAPGLSVT
  YSCESGYLLVGEKIINCLSSGKWSAVPPTCEEARCKSLGRFPNGKVKEPPILRVGVTANF
  FCDEGYRLQGPPSSRCVIAGQGVAWTKMPVCEEIFCPSPPPILNGRHIGNSLANVSYGSI
  VTYTCDPDPEEGVNFILIGESTLRCTVDSQKTGTWSGPAPRCELSTSAVQCPHPQILRGR
  MVSGQKDRYTYNDTVIFACMFGFTLKGSKQIRCNAQGTWEPSAPVCEKECQAPPNILNGQ
  KEDRHMVRFDPGTSIKYSCNPGYVLVGEESIQCTSEGVWTPPVPQCKVAACEATGRQLLT
  KPQHQFVRPDVNSSCGEGYKLSGSVYQECQGTIPWFMEIRLCKEITCPPPPVIYNGAHTG
  SSLEDFPYGTTVTYTCNPGPERGVEFSLIGESTIRCTSNDQERGTWSGPAPLCKLSLLAV
  QCSHVHIANGYKISGKEAPYFYNDTVTFKCYSGFTLKGSSQIRCKADNTWDPEIPVCEKE
  TCQHVRQSLQELPAGSRVELVNTSCQDGYQLTGHAYQMCQDAENGIWFKKIPLCKVIHCH
  PPPVIVNGKHTGMMAENFLYGNEVSYECDQGFYLLGEKKLQCRSDSKGHGSWSGPSPQCL
  RSPPVTRCPNPEVKHGYKLNKTHSAYSHNDIVYVDCNPGFIMNGSRVIRCHTDNTWVPGV
  PTCIKKAFIGCPPPPKTPNGNHTGGNIARFSPGMSILYSCDQGYLLVGEALLLCTHEGTW
  SQPAPHCKEVNCSSPADMDGIQKGLEPRKMYQYGAVVTLECEDGYMLEGSPQSQCQSDHQ
  WNPPLAVCRSRSLAPVLCGIAAGLILLTFLIVITLYVISKHRARNYYTDTSQKEAFHLEA
  REVYSVDPYNPAS
• Function: Receptor for complement C3, for the Epstein-Barr virus on human B-cells and T-cells and for HNRNPU. Participates in B lymphocytes activation ; (Microbial infection) Acts as a receptor for Epstein-Barr virus.
• Tissue Specificity: Mature B-lymphocytes, T-lymphocytes, pharyngeal epithelial cells, astrocytes and follicular dendritic cells of the spleen.
• KEGG Pathway:
  Complement and coagulation cascades (hsa04610)
  Hematopoietic cell lineage (hsa04640)
  B cell receptor sig.ling pathway (hsa04662)
  Epstein-Barr virus infection (hsa05169)
• Reactome Pathway: Regulation of Complement cascade (R-HSA-977606)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Immunodeficiency, common variable, 7	DISSHNT9	Definitive	Autosomal recessive	[1]
Common variable immunodeficiency	DISHE7JQ	Supportive	Autosomal dominant	[2]

4 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 Complement receptor type 2 (CR2).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate affects the expression of Complement receptor type 2 (CR2).	[4]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Complement receptor type 2 (CR2).	[5]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Complement receptor type 2 (CR2).	[5]

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 affects the methylation of Complement receptor type 2 (CR2).	[6]

References

• [1] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [2] Genetic CD21 deficiency is associated with hypogammaglobulinemia. J Allergy Clin Immunol. 2012 Mar;129(3):801-810.e6. doi: 10.1016/j.jaci.2011.09.027. Epub 2011 Oct 27.
• [3] Effect of mood stabilizers on gene expression in lymphoblastoid cells. J Neural Transm (Vienna). 2010 Feb;117(2):155-64.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [6] 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.