Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTXDJR9T)

• DOT Name: B-cell receptor CD22 (CD22)
• Synonyms: B-lymphocyte cell adhesion molecule; BL-CAM; Sialic acid-binding Ig-like lectin 2; Siglec-2; T-cell surface antigen Leu-14; CD antigen CD22
• Gene Name: CD22
• UniProt ID: CD22_HUMAN
• PDB ID: 5VKJ; 5VKM; 5VL3; 7O52
• Pfam ID: PF08205 ; PF13895 ; PF13927
• Sequence:
  MHLLGPWLLLLVLEYLAFSDSSKWVFEHPETLYAWEGACVWIPCTYRALDGDLESFILFH
  NPEYNKNTSKFDGTRLYESTKDGKVPSEQKRVQFLGDKNKNCTLSIHPVHLNDSGQLGLR
  MESKTEKWMERIHLNVSERPFPPHIQLPPEIQESQEVTLTCLLNFSCYGYPIQLQWLLEG
  VPMRQAAVTSTSLTIKSVFTRSELKFSPQWSHHGKIVTCQLQDADGKFLSNDTVQLNVKH
  TPKLEIKVTPSDAIVREGDSVTMTCEVSSSNPEYTTVSWLKDGTSLKKQNTFTLNLREVT
  KDQSGKYCCQVSNDVGPGRSEEVFLQVQYAPEPSTVQILHSPAVEGSQVEFLCMSLANPL
  PTNYTWYHNGKEMQGRTEEKVHIPKILPWHAGTYSCVAENILGTGQRGPGAELDVQYPPK
  KVTTVIQNPMPIREGDTVTLSCNYNSSNPSVTRYEWKPHGAWEEPSLGVLKIQNVGWDNT
  TIACAACNSWCSWASPVALNVQYAPRDVRVRKIKPLSEIHSGNSVSLQCDFSSSHPKEVQ
  FFWEKNGRLLGKESQLNFDSISPEDAGSYSCWVNNSIGQTASKAWTLEVLYAPRRLRVSM
  SPGDQVMEGKSATLTCESDANPPVSHYTWFDWNNQSLPYHSQKLRLEPVKVQHSGAYWCQ
  GTNSVGKGRSPLSTLTVYYSPETIGRRVAVGLGSCLAILILAICGLKLQRRWKRTQSQQG
  LQENSSGQSFFVRNKKVRRAPLSEGPHSLGCYNPMMEDGISYTTLRFPEMNIPRTGDAES
  SEMQRPPPDCDDTVTYSALHKRQVGDYENVIPDFPEDEGIHYSELIQFGVGERPQAQENV
  DYVILKH
• Function: Mediates B-cell B-cell interactions. May be involved in the localization of B-cells in lymphoid tissues. Binds sialylated glycoproteins; one of which is CD45. Preferentially binds to alpha-2,6-linked sialic acid. The sialic acid recognition site can be masked by cis interactions with sialic acids on the same cell surface. Upon ligand induced tyrosine phosphorylation in the immune response seems to be involved in regulation of B-cell antigen receptor signaling. Plays a role in positive regulation through interaction with Src family tyrosine kinases and may also act as an inhibitory receptor by recruiting cytoplasmic phosphatases via their SH2 domains that block signal transduction through dephosphorylation of signaling molecules.
• Tissue Specificity: B-lymphocytes.
• KEGG Pathway:
  Cell adhesion molecules (hsa04514)
  Hematopoietic cell lineage (hsa04640)
  B cell receptor sig.ling pathway (hsa04662)
• Reactome Pathway:
  CD22 mediated BCR regulation (R-HSA-5690714)
  Antigen activates B Cell Receptor (BCR) leading to generation of second messengers (R-HSA-983695)
  Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell (R-HSA-198933)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of B-cell receptor CD22 (CD22).	[1]
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of B-cell receptor CD22 (CD22).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of B-cell receptor CD22 (CD22).	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of B-cell receptor CD22 (CD22).	[2]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of B-cell receptor CD22 (CD22).	[3]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of B-cell receptor CD22 (CD22).	[4]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of B-cell receptor CD22 (CD22).	[5]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of B-cell receptor CD22 (CD22).	[7]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene affects the expression of B-cell receptor CD22 (CD22).	[8]
Bryostatin-1	DM1JOXY	Phase 2	Bryostatin-1 increases the expression of B-cell receptor CD22 (CD22).	[9]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of B-cell receptor CD22 (CD22).	[11]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of B-cell receptor CD22 (CD22).	[12]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of B-cell receptor CD22 (CD22).	[13]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of B-cell receptor CD22 (CD22).	[14]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A increases the expression of B-cell receptor CD22 (CD22).	[15]
KOJIC ACID	DMP84CS	Investigative	KOJIC ACID decreases the expression of B-cell receptor CD22 (CD22).	[16]

References

• [1] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [2] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [3] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [4] Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
• [5] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [6] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [7] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [8] Differential modulation of PI3-kinase/Akt pathway during all-trans retinoic acid- and Am80-induced HL-60 cell differentiation revealed by DNA microarray analysis. Biochem Pharmacol. 2004 Dec 1;68(11):2177-86.
• [9] Phase II trial of bryostatin 1 in patients with relapsed low-grade non-Hodgkin's lymphoma and chronic lymphocytic leukemia. Clin Cancer Res. 2000 Mar;6(3):825-8.
• [10] 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.
• [11] Discovery and characterization of super-enhancer-associated dependencies in diffuse large B cell lymphoma. Cancer Cell. 2013 Dec 9;24(6):777-90. doi: 10.1016/j.ccr.2013.11.003.
• [12] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [13] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [14] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.
• [15] Linking site-specific loss of histone acetylation to repression of gene expression by the mycotoxin ochratoxin A. Arch Toxicol. 2018 Feb;92(2):995-1014.
• [16] Toxicogenomics of kojic acid on gene expression profiling of a375 human malignant melanoma cells. Biol Pharm Bull. 2006 Apr;29(4):655-69.