Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTR8M5TX)

• DOT Name: Immunoglobulin J chain (JCHAIN)
• Synonyms: Joining chain of multimeric IgA and IgM
• Gene Name: JCHAIN
• Related Disease:
  Atopic dermatitis
  B-cell acute lymphoblastic leukaemia
  B-cell neoplasm
  IgA nephropathy
  Liver cirrhosis
  Mediastinal large B-cell lymphoma
  Plasma cell myeloma
  Systemic lupus erythematosus
  Periodontitis
• UniProt ID: IGJ_HUMAN
• PDB ID: 6KXS; 6LX3; 6LXW; 6UE7; 6UE8; 6UE9; 6UEA; 7K0C; 7Y09; 7Y0H; 7Y0J; 7YG2; 7YSG; 7YTC; 7YTD; 8ADY; 8ADZ; 8AE0; 8AE2; 8AE3; 8BPE; 8BPF; 8GZN; 8SKU; 8SKV
• Pfam ID: PF15097
• Sequence:
  MKNHLLFWGVLAVFIKAVHVKAQEDERIVLVDNKCKCARITSRIIRSSEDPNEDIVERNI
  RIIVPLNNRENISDPTSPLRTRFVYHLSDLCKKCDPTEVELDNQIVTATQSNICDEDSAT
  ETCYTYDRNKCYTAVVPLVYGGETKMVETALTPDACYPD
• Function: Serves to link two monomer units of either IgM or IgA. In the case of IgM, the J chain-joined dimer is a nucleating unit for the IgM pentamer, and in the case of IgA it induces dimers and/or larger polymers. It also helps to bind these immunoglobulins to secretory component.
• Reactome Pathway:
  Scavenging of heme from plasma (R-HSA-2168880)
  Cell surface interactions at the vascular wall (R-HSA-202733)

Molecular Interaction Atlas (MIA) of This DOT

9 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Atopic dermatitis	DISTCP41	Strong	Altered Expression	[1]
B-cell acute lymphoblastic leukaemia	DISKLOKC	Strong	Altered Expression	[2]
B-cell neoplasm	DISVY326	Strong	Biomarker	[3]
IgA nephropathy	DISZ8MTK	Strong	Altered Expression	[4]
Liver cirrhosis	DIS4G1GX	Strong	Altered Expression	[5]
Mediastinal large B-cell lymphoma	DISAUA10	Strong	Biomarker	[3]
Plasma cell myeloma	DIS0DFZ0	Strong	Altered Expression	[6]
Systemic lupus erythematosus	DISI1SZ7	Strong	Altered Expression	[7]
Periodontitis	DISI9JOI	moderate	Biomarker	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Marinol	DM70IK5	Approved	Marinol decreases the expression of Immunoglobulin J chain (JCHAIN).	[9]
Demecolcine	DMCZQGK	Approved	Demecolcine decreases the expression of Immunoglobulin J chain (JCHAIN).	[10]
Hydroquinone	DM6AVR4	Approved	Hydroquinone decreases the expression of Immunoglobulin J chain (JCHAIN).	[11]
Coprexa	DMA0WEK	Phase 3	Coprexa increases the expression of Immunoglobulin J chain (JCHAIN).	[12]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Immunoglobulin J chain (JCHAIN).	[13]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Immunoglobulin J chain (JCHAIN).	[14]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Immunoglobulin J chain (JCHAIN).	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Octanal	DMTN0OK	Investigative	Octanal increases the methylation of Immunoglobulin J chain (JCHAIN).	[15]

References

• [1] Early cutaneous gene transcription changes in adult atopic dermatitis and potential clinical implications.Exp Dermatol. 2007 Jan;16(1):28-36. doi: 10.1111/j.1600-0625.2006.00504.x.
• [2] High expression of ID family and IGJ genes signature as predictor of low induction treatment response and worst survival in adult Hispanic patients with B-acute lymphoblastic leukemia.J Exp Clin Cancer Res. 2016 Apr 5;35:64. doi: 10.1186/s13046-016-0333-z.
• [3] J chain and myocyte enhancer factor 2B are useful in differentiating classical Hodgkin lymphoma from nodular lymphocyte predominant Hodgkin lymphoma and primary mediastinal large B-cell lymphoma.Hum Pathol. 2017 Oct;68:47-53. doi: 10.1016/j.humpath.2017.08.015. Epub 2017 Aug 26.
• [4] Increased dimeric IgA producing B cells in the bone marrow in IgA nephropathy determined by in situ hybridisation for J chain mRNA.J Clin Pathol. 1996 Jan;49(1):38-42. doi: 10.1136/jcp.49.1.38.
• [5] Quantitative analysis of core fucosylation of serum proteins in liver diseases by LC-MS-MRM.J Proteomics. 2018 Oct 30;189:67-74. doi: 10.1016/j.jprot.2018.02.003. Epub 2018 Feb 7.
• [6] Constitutively expressed Oct-2 prevents immunoglobulin gene silencing in myeloma x T cell hybrids.Immunity. 1994 Nov;1(8):623-34. doi: 10.1016/1074-7613(94)90034-5.
• [7] A proteomic study of peripheral blood mononuclear cells in systemic lupus erythematosus.Lupus. 2008 Sep;17(9):799-804. doi: 10.1177/0961203308089444.
• [8] Humoral immune responses in periodontal disease may have mucosal and systemic immune features.Clin Exp Immunol. 1999 Mar;115(3):534-41. doi: 10.1046/j.1365-2249.1999.00819.x.
• [9] Suppression by (9)-tetrahydrocannabinol of the primary immunoglobulin M response by human peripheral blood B cells is associated with impaired STAT3 activation. Toxicology. 2013 Aug 9;310:84-91. doi: 10.1016/j.tox.2013.05.009. Epub 2013 May 29.
• [10] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [11] Differently expressed long noncoding RNAs and mRNAs in TK6 cells exposed to low dose hydroquinone. Oncotarget. 2017 Oct 4;8(56):95554-95567. doi: 10.18632/oncotarget.21481. eCollection 2017 Nov 10.
• [12] Copper deprivation enhances the chemosensitivity of pancreatic cancer to rapamycin by mTORC1/2 inhibition. Chem Biol Interact. 2023 Sep 1;382:110546. doi: 10.1016/j.cbi.2023.110546. Epub 2023 Jun 7.
• [13] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [14] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [15] DNA Methylome Analysis of Saturated Aliphatic Aldehydes in Pulmonary Toxicity. Sci Rep. 2018 Jul 12;8(1):10497. doi: 10.1038/s41598-018-28813-z.