Details of Drug Off-Target (DOT)

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

• DOT Name: Junctional adhesion molecule B (JAM2)
• Synonyms: JAM-B; Junctional adhesion molecule 2; JAM-2; Vascular endothelial junction-associated molecule; VE-JAM; CD antigen CD322
• Gene Name: JAM2
• Related Disease:
  Hepatitis
  Alzheimer disease
  Basal ganglia calcification, idiopathic, 8, autosomal recessive
  Cervical cancer
  Cervical carcinoma
  Colon cancer
  Colon carcinoma
  Non-small-cell lung cancer
  Psoriasis
  Psoriatic arthritis
  Bilateral striopallidodentate calcinosis
  Nervous system inflammation
• UniProt ID: JAM2_HUMAN
• Pfam ID: PF13927 ; PF07686
• Sequence:
  MARRSRHRLLLLLLRYLVVALGYHKAYGFSAPKDQQVVTAVEYQEAILACKTPKKTVSSR
  LEWKKLGRSVSFVYYQQTLQGDFKNRAEMIDFNIRIKNVTRSDAGKYRCEVSAPSEQGQN
  LEEDTVTLEVLVAPAVPSCEVPSSALSGTVVELRCQDKEGNPAPEYTWFKDGIRLLENPR
  LGSQSTNSSYTMNTKTGTLQFNTVSKLDTGEYSCEARNSVGYRRCPGKRMQVDDLNISGI
  IAAVVVVALVISVCGLGVCYAQRKGYFSKETSFQKSNSSSKATTMSENDFKHTKSFII
• Function: Junctional adhesion protein that mediates heterotypic cell-cell interactions with its cognate receptor JAM3 to regulate different cellular processes. Plays a role in homing and mobilization of hematopoietic stem and progenitor cells within the bone marrow. At the surface of bone marrow stromal cells, it contributes to the retention of the hematopoietic stem and progenitor cells expressing JAM3. Plays a central role in leukocytes extravasation by facilitating not only transmigration but also tethering and rolling of leukocytes along the endothelium. Tethering and rolling of leukocytes are dependent on the binding by JAM2 of the integrin alpha-4/beta-1. Plays a role in spermatogenesis where JAM2 and JAM3, which are respectively expressed by Sertoli and germ cells, mediate an interaction between both cell types and play an essential role in the anchorage of germ cells onto Sertoli cells and the assembly of cell polarity complexes during spermatid differentiation. Also functions as an inhibitory somatodendritic cue that prevents the myelination of non-axonal parts of neurons. During myogenesis, it is involved in myocyte fusion. May also play a role in angiogenesis.
• Tissue Specificity: Highly expressed in heart, placenta, lung, foreskin and lymph node . Prominently expressed on high endothelial venules and also present on the endothelia of other vessels (at protein level) . Also expressed in the brain in the caudate nuclei .
• KEGG Pathway:
  Cell adhesion molecules (hsa04514)
  Tight junction (hsa04530)
  Leukocyte transendothelial migration (hsa04670)
  Epithelial cell sig.ling in Helicobacter pylori infection (hsa05120)
• Reactome Pathway:
  Integrin cell surface interactions (R-HSA-216083)
  Cell surface interactions at the vascular wall (R-HSA-202733)

Molecular Interaction Atlas (MIA) of This DOT

12 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hepatitis	DISXXX35	Definitive	Biomarker	[1]
Alzheimer disease	DISF8S70	Strong	Genetic Variation	[2]
Basal ganglia calcification, idiopathic, 8, autosomal recessive	DISRP7TU	Strong	Autosomal recessive	[3]
Cervical cancer	DISFSHPF	Strong	Biomarker	[4]
Cervical carcinoma	DIST4S00	Strong	Biomarker	[4]
Colon cancer	DISVC52G	Strong	Biomarker	[5]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[5]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[6]
Psoriasis	DIS59VMN	Strong	Biomarker	[7]
Psoriatic arthritis	DISLWTG2	Strong	Biomarker	[7]
Bilateral striopallidodentate calcinosis	DISNZJTB	Supportive	Autosomal dominant	[3]
Nervous system inflammation	DISB3X5A	Limited	Biomarker	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Junctional adhesion molecule B (JAM2).	[9]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Junctional adhesion molecule B (JAM2).	[10]
Estradiol	DMUNTE3	Approved	Estradiol affects the expression of Junctional adhesion molecule B (JAM2).	[11]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Junctional adhesion molecule B (JAM2).	[13]
Dexamethasone	DMMWZET	Approved	Dexamethasone decreases the expression of Junctional adhesion molecule B (JAM2).	[14]
Cannabidiol	DM0659E	Approved	Cannabidiol decreases the expression of Junctional adhesion molecule B (JAM2).	[15]
Cytarabine	DMZD5QR	Approved	Cytarabine increases the expression of Junctional adhesion molecule B (JAM2).	[16]
Permethrin	DMZ0Q1G	Approved	Permethrin increases the expression of Junctional adhesion molecule B (JAM2).	[17]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Junctional adhesion molecule B (JAM2).	[19]
Nitrobenzanthrone	DMN6L70	Investigative	Nitrobenzanthrone affects the expression of Junctional adhesion molecule B (JAM2).	[20]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Junctional adhesion molecule B (JAM2).	[12]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Junctional adhesion molecule B (JAM2).	[18]

References

• [1] Junctional adhesion molecules JAM-B and JAM-C promote autoimmune-mediated liver fibrosis in mice.J Autoimmun. 2018 Jul;91:83-96. doi: 10.1016/j.jaut.2018.05.001. Epub 2018 May 9.
• [2] Linking Genetics of Brain Changes to Alzheimer's Disease: Sparse Whole Genome Association Scan of Regional MRI Volumes in the ADNI and AddNeuroMed Cohorts.J Alzheimers Dis. 2015;45(3):851-64. doi: 10.3233/JAD-142214.
• [3] Biallelic loss-of-function mutations in JAM2 cause primary familial brain calcification. Brain. 2020 Feb 1;143(2):491-502. doi: 10.1093/brain/awz392.
• [4] MicroRNA-374b inhibits cervical cancer cell proliferation and induces apoptosis through the p38/ERK signaling pathway by binding to JAM-2.J Cell Physiol. 2018 Sep;233(9):7379-7390. doi: 10.1002/jcp.26574. Epub 2018 Mar 25.
• [5] Transcriptome profiling analysis reveals biomarkers in colon cancer samples of various differentiation.Oncol Lett. 2018 Jul;16(1):48-54. doi: 10.3892/ol.2018.8668. Epub 2018 May 8.
• [6] MicroRNA-374b inhibits the tumor growth and promotes apoptosis in non-small cell lung cancer tissue through the p38/ERK signaling pathway by targeting JAM-2.J Thorac Dis. 2018 Sep;10(9):5489-5498. doi: 10.21037/jtd.2018.09.93.
• [7] Human leukocyte antigen (HLA)-C polymorphisms are associated with a decreased risk of rheumatoid arthritis.Mol Biol Rep. 2014 Jun;41(6):4103-8. doi: 10.1007/s11033-014-3280-9. Epub 2014 Feb 25.
• [8] Lack of junctional adhesion molecule (JAM)-B ameliorates experimental autoimmune encephalomyelitis.Brain Behav Immun. 2018 Oct;73:3-20. doi: 10.1016/j.bbi.2018.06.014. Epub 2018 Jun 18.
• [9] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [10] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [11] Research resource: STR DNA profile and gene expression comparisons of human BG-1 cells and a BG-1/MCF-7 clonal variant. Mol Endocrinol. 2014 Dec;28(12):2072-81.
• [12] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [13] Gene expression profile induced by arsenic trioxide in chronic lymphocytic leukemia cells reveals a central role for heme oxygenase-1 in apoptosis and regulation of matrix metalloproteinase-9. Oncotarget. 2016 Dec 13;7(50):83359-83377.
• [14] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [15] Cannabidiol Activates Neuronal Precursor Genes in Human Gingival Mesenchymal Stromal Cells. J Cell Biochem. 2017 Jun;118(6):1531-1546. doi: 10.1002/jcb.25815. Epub 2016 Dec 29.
• [16] Cytosine arabinoside induces ectoderm and inhibits mesoderm expression in human embryonic stem cells during multilineage differentiation. Br J Pharmacol. 2011 Apr;162(8):1743-56.
• [17] Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
• [18] 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.
• [19] Targeting MYCN in neuroblastoma by BET bromodomain inhibition. Cancer Discov. 2013 Mar;3(3):308-23.
• [20] 3-Nitrobenzanthrone promotes malignant transformation in human lung epithelial cells through the epiregulin-signaling pathway. Cell Biol Toxicol. 2022 Oct;38(5):865-887. doi: 10.1007/s10565-021-09612-1. Epub 2021 May 25.