Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTX0F9QL)

DOT Name	Junctional adhesion molecule C (JAM3)
Synonyms	JAM-C; JAM-2; Junctional adhesion molecule 3; JAM-3
Gene Name	JAM3
Related Disease	Acute myelogenous leukaemia ( ) Autoimmune hepatitis ( ) B-cell neoplasm ( ) Glioma ( ) Hepatitis ( ) Primary biliary cholangitis ( ) Primary sclerosing cholangitis ( ) Acquired immune deficiency syndrome ( ) Advanced cancer ( ) Arthritis ( ) Atherosclerosis ( ) Cervical cancer ( ) Cervical carcinoma ( ) Colorectal carcinoma ( ) Isolated cleft lip ( ) Neoplasm ( ) Non-small-cell lung cancer ( ) Oligospermia ( ) Osteoarthritis ( ) Porencephaly-microcephaly-bilateral congenital cataract syndrome ( ) Renal carcinoma ( ) Renal cell carcinoma ( ) Rheumatoid arthritis ( ) Sciatic neuropathy ( ) leukaemia ( ) Leukemia ( ) Retinopathy ( ) Epithelial ovarian cancer ( ) Hypoplastic left heart syndrome ( ) Ovarian cancer ( ) Ovarian neoplasm ( ) Pneumonia ( )
UniProt ID	JAM3_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
Pfam ID	PF13927 ; PF07686
Sequence	MALRRPPRLRLCARLPDFFLLLLFRGCLIGAVNLKSSNRTPVVQEFESVELSCIITDSQT SDPRIEWKKIQDEQTTYVFFDNKIQGDLAGRAEILGKTSLKIWNVTRRDSALYRCEVVAR NDRKEIDEIVIELTVQVKPVTPVCRVPKAVPVGKMATLHCQESEGHPRPHYSWYRNDVPL PTDSRANPRFRNSSFHLNSETGTLVFTAVHKDDSGQYYCIASNDAGSARCEEQEMEVYDL NIGGIIGGVLVVLAVLALITLGICCAYRRGYFINNKQDGESYKNPGKPDGVNYIRTDEEG DFRHKSSFVI
Function	Junctional adhesion protein that mediates heterotypic cell-cell interactions with its cognate receptor JAM2 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 transmigration through the endothelium. 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 a counter-receptor for ITGAM, mediating leukocyte-platelet interactions and is involved in the regulation of transepithelial migration of polymorphonuclear neutrophils (PMN). Plays a role in angiogenesis. Plays a role in the regulation of cell migration (Probable). During myogenesis, it is involved in myocyte fusion; [Soluble form of JAM-C]: Promotes chemotaxis of vascular endothelial cells and stimulates angiogenesis.
Tissue Specificity	Detected on round and elongated spermatids (at protein level) . Highest expression in placenta, brain and kidney. Significant expression is detected on platelets. Expressed in intestinal mucosa cells. Expressed in the vascular endothelium. Found in serum (at protein level). Also detected in the synovial fluid of patients with rheumatoid arthritis, psoriatic arthritis or ostearthritis (at protein level).
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

32 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Acute myelogenous leukaemia	DISCSPTN	Definitive	Genetic Variation	[1]
Autoimmune hepatitis	DISOX03Q	Definitive	Altered Expression	[2]
B-cell neoplasm	DISVY326	Definitive	Altered Expression	[3]
Glioma	DIS5RPEH	Definitive	Altered Expression	[4]
Hepatitis	DISXXX35	Definitive	Biomarker	[2]
Primary biliary cholangitis	DIS43E0O	Definitive	Altered Expression	[2]
Primary sclerosing cholangitis	DISTH5WJ	Definitive	Biomarker	[2]
Acquired immune deficiency syndrome	DISL5UOX	Strong	Biomarker	[5]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[5]
Arthritis	DIST1YEL	Strong	Biomarker	[6]
Atherosclerosis	DISMN9J3	Strong	Altered Expression	[7]
Cervical cancer	DISFSHPF	Strong	Biomarker	[8]
Cervical carcinoma	DIST4S00	Strong	Biomarker	[8]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[9]
Isolated cleft lip	DIS2O2JV	Strong	Genetic Variation	[10]
Neoplasm	DISZKGEW	Strong	Altered Expression	[9]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[11]
Oligospermia	DIS6YJF3	Strong	Genetic Variation	[12]
Osteoarthritis	DIS05URM	Strong	Altered Expression	[6]
Porencephaly-microcephaly-bilateral congenital cataract syndrome	DIS173H2	Strong	Autosomal recessive	[13]
Renal carcinoma	DISER9XT	Strong	Biomarker	[14]
Renal cell carcinoma	DISQZ2X8	Strong	Biomarker	[14]
Rheumatoid arthritis	DISTSB4J	Strong	Altered Expression	[15]
Sciatic neuropathy	DISMGDKX	Strong	Biomarker	[16]
leukaemia	DISS7D1V	moderate	Biomarker	[17]
Leukemia	DISNAKFL	moderate	Biomarker	[17]
Retinopathy	DISB4B0F	moderate	Biomarker	[18]
Epithelial ovarian cancer	DIS56MH2	Limited	Biomarker	[19]
Hypoplastic left heart syndrome	DISSLFZ4	Limited	Biomarker	[20]
Ovarian cancer	DISZJHAP	Limited	Biomarker	[19]
Ovarian neoplasm	DISEAFTY	Limited	Biomarker	[19]
Pneumonia	DIS8EF3M	Limited	Altered Expression	[21]
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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Junctional adhesion molecule C (JAM3).	[22]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Junctional adhesion molecule C (JAM3).	[23]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Junctional adhesion molecule C (JAM3).	[24]
Gemcitabine	DMSE3I7	Approved	Gemcitabine decreases the expression of Junctional adhesion molecule C (JAM3).	[25]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Junctional adhesion molecule C (JAM3).	[26]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A increases the expression of Junctional adhesion molecule C (JAM3).	[28]
Tributylstannanyl	DMHN7CB	Investigative	Tributylstannanyl increases the expression of Junctional adhesion molecule C (JAM3).	[28]
Methyl Mercury Ion	DM6YEW4	Investigative	Methyl Mercury Ion increases the expression of Junctional adhesion molecule C (JAM3).	[28]
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⏷ Show the Full List of 8 Drug(s)

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 increases the methylation of Junctional adhesion molecule C (JAM3).	[27]
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References

1	JAM3 maintains leukemia-initiating cell self-renewal through LRP5/AKT/-catenin/CCND1 signaling.J Clin Invest. 2018 May 1;128(5):1737-1751. doi: 10.1172/JCI93198. Epub 2018 Mar 26.
2	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.
3	Junctional adhesion molecule C (JAM-C) distinguishes CD27+ germinal center B lymphocytes from non-germinal center cells and constitutes a new diagnostic tool for B-cell malignancies.Leukemia. 2007 Jun;21(6):1285-93. doi: 10.1038/sj.leu.2404689. Epub 2007 Apr 12.
4	Cooperative expression of junctional adhesion molecule-C and -B supports growth and invasion of glioma.Glia. 2010 Apr;58(5):524-37. doi: 10.1002/glia.20941.
5	Junctional adhesion molecule C (JAM-C) dimerization aids cancer cell migration and metastasis.Biochim Biophys Acta Mol Cell Res. 2018 Apr;1865(4):638-649. doi: 10.1016/j.bbamcr.2018.01.008. Epub 2018 Jan 31.
6	Expression and function of junctional adhesion molecule-C in human and experimental arthritis.Arthritis Res Ther. 2007;9(4):R65. doi: 10.1186/ar2223.
7	The role of junctional adhesion molecule-C (JAM-C) in oxidized LDL-mediated leukocyte recruitment.FASEB J. 2005 Dec;19(14):2078-80. doi: 10.1096/fj.05-4196fje. Epub 2005 Sep 29.
8	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.
9	JAM3 functions as a novel tumor suppressor and is inactivated by DNA methylation in colorectal cancer.Cancer Manag Res. 2019 Mar 27;11:2457-2470. doi: 10.2147/CMAR.S189937. eCollection 2019.
10	A genome-wide association study of cleft lip with and without cleft palate identifies risk variants near MAFB and ABCA4.Nat Genet. 2010 Jun;42(6):525-9. doi: 10.1038/ng.580. Epub 2010 May 2.
11	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.
12	Spermatozoa from infertile patients exhibit differences of DNA methylation associated with spermatogenesis-related processes: an array-based analysis.Reprod Biomed Online. 2016 Dec;33(6):709-719. doi: 10.1016/j.rbmo.2016.09.001. Epub 2016 Sep 15.
13	Cytogenetic analysis of primary neuroblastoma with del(1), del(14), hsr, and dmin chromosomes. Cancer Genet Cytogenet. 1991 Sep;55(2):231-4. doi: 10.1016/0165-4608(91)90082-6.
14	Jam3 promotes migration and suppresses apoptosis of renal carcinoma cell lines.Int J Mol Med. 2018 Nov;42(5):2923-2929. doi: 10.3892/ijmm.2018.3854. Epub 2018 Sep 4.
15	Junctional adhesion molecule C mediates leukocyte adhesion to rheumatoid arthritis synovium.Arthritis Rheum. 2008 Oct;58(10):3020-9. doi: 10.1002/art.23867.
16	The spatiotemporal localization of JAM-C following sciatic nerve crush in adult rats.Brain Behav. 2012 Jul;2(4):402-14. doi: 10.1002/brb3.63.
17	JAM-C Identifies Src Family Kinase-Activated Leukemia-Initiating Cells and Predicts Poor Prognosis in Acute Myeloid Leukemia.Cancer Res. 2017 Dec 1;77(23):6627-6640. doi: 10.1158/0008-5472.CAN-17-1223. Epub 2017 Sep 28.
18	Endothelial-specific deficiency of Junctional Adhesion Molecule-C promotes vessel normalisation in proliferative retinopathy.Thromb Haemost. 2015 Nov 25;114(6):1241-9. doi: 10.1160/TH15-01-0051. Epub 2015 Aug 27.
19	Endothelial cell junctional adhesion molecule C plays a key role in the development of tumors in a murine model of ovarian cancer.FASEB J. 2013 Oct;27(10):4244-53. doi: 10.1096/fj.13-230441. Epub 2013 Jul 3.
20	Narrowing the critical region within 11q24-qter for hypoplastic left heart and identification of a candidate gene, JAM3, expressed during cardiogenesis.Genomics. 2002 Apr;79(4):475-8. doi: 10.1006/geno.2002.6742.
21	Junctional adhesion molecule-C regulates the early influx of leukocytes into tissues during inflammation.J Immunol. 2005 May 15;174(10):6406-15. doi: 10.4049/jimmunol.174.10.6406.
22	Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
23	Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
24	Gene expression profile of human lymphoid CEM cells sensitive and resistant to glucocorticoid-evoked apoptosis. Genomics. 2003 Jun;81(6):543-55.
25	Gene expression profiling of breast cancer cells in response to gemcitabine: NF-kappaB pathway activation as a potential mechanism of resistance. Breast Cancer Res Treat. 2007 Apr;102(2):157-72.
26	Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
27	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.
28	Inhibition of CXCL12-mediated chemotaxis of Jurkat cells by direct immunotoxicants. Arch Toxicol. 2016 Jul;90(7):1685-94. doi: 10.1007/s00204-015-1585-7. Epub 2015 Aug 28.