Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTCPF9NF)

• DOT Name: B-lymphocyte antigen CD19 (CD19)
• Synonyms: B-lymphocyte surface antigen B4; Differentiation antigen CD19; T-cell surface antigen Leu-12; CD antigen CD19
• Gene Name: CD19
• Related Disease:
  Immunodeficiency, common variable, 3
  Common variable immunodeficiency
• UniProt ID: CD19_HUMAN
• PDB ID: 6AL5; 7JIC; 7URV; 7URX
• Sequence:
  MPPPRLLFFLLFLTPMEVRPEEPLVVKVEEGDNAVLQCLKGTSDGPTQQLTWSRESPLKP
  FLKLSLGLPGLGIHMRPLAIWLFIFNVSQQMGGFYLCQPGPPSEKAWQPGWTVNVEGSGE
  LFRWNVSDLGGLGCGLKNRSSEGPSSPSGKLMSPKLYVWAKDRPEIWEGEPPCLPPRDSL
  NQSLSQDLTMAPGSTLWLSCGVPPDSVSRGPLSWTHVHPKGPKSLLSLELKDDRPARDMW
  VMETGLLLPRATAQDAGKYYCHRGNLTMSFHLEITARPVLWHWLLRTGGWKVSAVTLAYL
  IFCLCSLVGILHLQRALVLRRKRKRMTDPTRRFFKVTPPPGSGPQNQYGNVLSLPTPTSG
  LGRAQRWAAGLGGTAPSYGNPSSDVQADGALGSRSPPGVGPEEEEGEGYEEPDSEEDSEF
  YENDSNLGQDQLSQDGSGYENPEDEPLGPEDEDSFSNAESYENEDEELTQPVARTMDFLS
  PHGSAWDPSREATSLGSQSYEDMRGILYAAPQLRSIRGQPGPNHEEDADSYENMDNPDGP
  DPAWGGGGRMGTWSTR
• Function: Functions as a coreceptor for the B-cell antigen receptor complex (BCR) on B-lymphocytes. Decreases the threshold for activation of downstream signaling pathways and for triggering B-cell responses to antigens. Activates signaling pathways that lead to the activation of phosphatidylinositol 3-kinase and the mobilization of intracellular Ca(2+) stores. Is not required for early steps during B cell differentiation in the blood marrow. Required for normal differentiation of B-1 cells. Required for normal B cell differentiation and proliferation in response to antigen challenges. Required for normal levels of serum immunoglobulins, and for production of high-affinity antibodies in response to antigen challenge.
• Tissue Specificity: Detected on marginal zone and germinal center B cells in lymph nodes . Detected on blood B cells (at protein level) .
• KEGG Pathway:
  PI3K-Akt sig.ling pathway (hsa04151)
  Hematopoietic cell lineage (hsa04640)
  B cell receptor sig.ling pathway (hsa04662)
  Epstein-Barr virus infection (hsa05169)
  Primary immunodeficiency (hsa05340)
• Reactome Pathway:
  Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell (R-HSA-198933)
  Constitutive Signaling by Aberrant PI3K in Cancer (R-HSA-2219530)
  PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling (R-HSA-6811558)
  Regulation of Complement cascade (R-HSA-977606)
  Antigen activates B Cell Receptor (BCR) leading to generation of second messengers (R-HSA-983695)
  PIP3 activates AKT signaling (R-HSA-1257604)

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, 3	DIS0RJE3	Definitive	Autosomal recessive	[1]
Common variable immunodeficiency	DISHE7JQ	Supportive	Autosomal dominant	[2]

2 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-lymphocyte antigen CD19 (CD19).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of B-lymphocyte antigen CD19 (CD19).	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of B-lymphocyte antigen CD19 (CD19).	[4]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of B-lymphocyte antigen CD19 (CD19).	[5]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of B-lymphocyte antigen CD19 (CD19).	[6]
GSK618334	DMJPXZ4	Phase 1	GSK618334 decreases the expression of B-lymphocyte antigen CD19 (CD19).	[8]
Deguelin	DMXT7WG	Investigative	Deguelin decreases the expression of B-lymphocyte antigen CD19 (CD19).	[9]
CATECHIN	DMY38SB	Investigative	CATECHIN increases the expression of B-lymphocyte antigen CD19 (CD19).	[10]

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] Clinical Practice Guidelines for Rare Diseases: The Orphanet Database. PLoS One. 2017 Jan 18;12(1):e0170365. doi: 10.1371/journal.pone.0170365. eCollection 2017.
• [3] 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.
• [4] The contribution of methotrexate exposure and host factors on transcriptional variance in human liver. Toxicol Sci. 2007 Jun;97(2):582-94.
• [5] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [6] 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.
• [7] 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.
• [8] Phase IIa trial of fingolimod for amyotrophic lateral sclerosis demonstrates acceptable acute safety and tolerability. Muscle Nerve. 2017 Dec;56(6):1077-1084. doi: 10.1002/mus.25733. Epub 2017 Aug 29.
• [9] Neurotoxicity and underlying cellular changes of 21 mitochondrial respiratory chain inhibitors. Arch Toxicol. 2021 Feb;95(2):591-615. doi: 10.1007/s00204-020-02970-5. Epub 2021 Jan 29.
• [10] Epicatechin and a cocoa polyphenolic extract modulate gene expression in human Caco-2 cells. J Nutr. 2004 Oct;134(10):2509-16.