Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTQ2UJMH)

DOT Name C-C motif chemokine 19 (CCL19)
Synonyms
Beta-chemokine exodus-3; CK beta-11; Epstein-Barr virus-induced molecule 1 ligand chemokine; EBI1 ligand chemokine; ELC; Macrophage inflammatory protein 3 beta; MIP-3-beta; Small-inducible cytokine A19
Gene Name CCL19
Related Disease
Advanced cancer ( )
Multiple sclerosis ( )
Prostate cancer ( )
Prostate carcinoma ( )
Tuberculosis ( )
Adult lymphoma ( )
Allergic contact dermatitis ( )
Allergy ( )
Alzheimer disease ( )
Autoimmune disease ( )
Breast cancer ( )
Breast carcinoma ( )
Cardiac failure ( )
Cervical cancer ( )
Cervical carcinoma ( )
Colorectal carcinoma ( )
Congestive heart failure ( )
Endometriosis ( )
Epithelial ovarian cancer ( )
Hepatocellular carcinoma ( )
HIV infectious disease ( )
Lung cancer ( )
Lung carcinoma ( )
Lymphoma ( )
Metastatic malignant neoplasm ( )
Myocardial infarction ( )
Neoplasm ( )
Non-alcoholic fatty liver disease ( )
Non-small-cell lung cancer ( )
Obesity ( )
Ovarian cancer ( )
Pediatric lymphoma ( )
Pneumonia ( )
Pneumonitis ( )
Psoriasis ( )
Rheumatoid arthritis ( )
Small lymphocytic lymphoma ( )
Systemic lupus erythematosus ( )
Systemic sclerosis ( )
Asthma ( )
Lung adenocarcinoma ( )
Stroke ( )
Acute myelogenous leukaemia ( )
Arteriosclerosis ( )
Atherosclerosis ( )
Benign prostatic hyperplasia ( )
Coronary atherosclerosis ( )
Coronary heart disease ( )
Crohn disease ( )
UniProt ID
CCL19_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
PDB ID
2MP1; 7STA
Pfam ID
PF00048
Sequence
MALLLALSLLVLWTSPAPTLSGTNDAEDCCLSVTQKPIPGYIVRNFHYLLIKDGCRVPAV
VFTTLRGRQLCAPPDQPWVERIIQRLQRTSAKMKRRSS
Function
May play a role not only in inflammatory and immunological responses but also in normal lymphocyte recirculation and homing. May play an important role in trafficking of T-cells in thymus, and T-cell and B-cell migration to secondary lymphoid organs. Binds to chemokine receptor CCR7. Recombinant CCL19 shows potent chemotactic activity for T-cells and B-cells but not for granulocytes and monocytes. Binds to atypical chemokine receptor ACKR4 and mediates the recruitment of beta-arrestin (ARRB1/2) to ACKR4.
Tissue Specificity Expressed at high levels in the lymph nodes, thymus and appendix. Intermediate levels seen in colon and trachea, while low levels found in spleen, small intestine, lung, kidney and stomach.
KEGG Pathway
Cytokine-cytokine receptor interaction (hsa04060 )
Viral protein interaction with cytokine and cytokine receptor (hsa04061 )
Chemokine sig.ling pathway (hsa04062 )
NF-kappa B sig.ling pathway (hsa04064 )
Reactome Pathway
G alpha (i) signalling events (R-HSA-418594 )
Interleukin-10 signaling (R-HSA-6783783 )
Chemokine receptors bind chemokines (R-HSA-380108 )

Molecular Interaction Atlas (MIA) of This DOT

49 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Advanced cancer DISAT1Z9 Definitive Biomarker [1]
Multiple sclerosis DISB2WZI Definitive Biomarker [2]
Prostate cancer DISF190Y Definitive Altered Expression [3]
Prostate carcinoma DISMJPLE Definitive Altered Expression [3]
Tuberculosis DIS2YIMD Definitive Altered Expression [4]
Adult lymphoma DISK8IZR Strong Biomarker [5]
Allergic contact dermatitis DISFFVF9 Strong Altered Expression [6]
Allergy DIS48ZAP Strong Biomarker [7]
Alzheimer disease DISF8S70 Strong Biomarker [8]
Autoimmune disease DISORMTM Strong Biomarker [9]
Breast cancer DIS7DPX1 Strong Biomarker [10]
Breast carcinoma DIS2UE88 Strong Biomarker [10]
Cardiac failure DISDC067 Strong Altered Expression [11]
Cervical cancer DISFSHPF Strong Biomarker [12]
Cervical carcinoma DIST4S00 Strong Biomarker [12]
Colorectal carcinoma DIS5PYL0 Strong Biomarker [13]
Congestive heart failure DIS32MEA Strong Altered Expression [11]
Endometriosis DISX1AG8 Strong Biomarker [14]
Epithelial ovarian cancer DIS56MH2 Strong Biomarker [15]
Hepatocellular carcinoma DIS0J828 Strong Altered Expression [16]
HIV infectious disease DISO97HC Strong Biomarker [17]
Lung cancer DISCM4YA Strong Biomarker [18]
Lung carcinoma DISTR26C Strong Altered Expression [18]
Lymphoma DISN6V4S Strong Biomarker [5]
Metastatic malignant neoplasm DIS86UK6 Strong Posttranslational Modification [10]
Myocardial infarction DIS655KI Strong Genetic Variation [19]
Neoplasm DISZKGEW Strong Biomarker [5]
Non-alcoholic fatty liver disease DISDG1NL Strong Biomarker [20]
Non-small-cell lung cancer DIS5Y6R9 Strong Altered Expression [21]
Obesity DIS47Y1K Strong Altered Expression [22]
Ovarian cancer DISZJHAP Strong Biomarker [23]
Pediatric lymphoma DIS51BK2 Strong Biomarker [5]
Pneumonia DIS8EF3M Strong Biomarker [24]
Pneumonitis DIS88E0K Strong Biomarker [24]
Psoriasis DIS59VMN Strong Biomarker [25]
Rheumatoid arthritis DISTSB4J Strong Biomarker [26]
Small lymphocytic lymphoma DIS30POX Strong Biomarker [27]
Systemic lupus erythematosus DISI1SZ7 Strong Biomarker [28]
Systemic sclerosis DISF44L6 Strong Altered Expression [29]
Asthma DISW9QNS moderate Biomarker [30]
Lung adenocarcinoma DISD51WR moderate Altered Expression [31]
Stroke DISX6UHX moderate Altered Expression [32]
Acute myelogenous leukaemia DISCSPTN Limited Genetic Variation [33]
Arteriosclerosis DISK5QGC Limited Biomarker [34]
Atherosclerosis DISMN9J3 Limited Biomarker [34]
Benign prostatic hyperplasia DISI3CW2 Limited Biomarker [3]
Coronary atherosclerosis DISKNDYU Limited Biomarker [34]
Coronary heart disease DIS5OIP1 Limited Biomarker [34]
Crohn disease DIS2C5Q8 Limited Biomarker [35]
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⏷ Show the Full List of 49 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
9 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of C-C motif chemokine 19 (CCL19). [36]
Arsenic DMTL2Y1 Approved Arsenic decreases the expression of C-C motif chemokine 19 (CCL19). [37]
Methotrexate DM2TEOL Approved Methotrexate decreases the expression of C-C motif chemokine 19 (CCL19). [38]
Aspirin DM672AH Approved Aspirin increases the expression of C-C motif chemokine 19 (CCL19). [39]
Malathion DMXZ84M Approved Malathion increases the expression of C-C motif chemokine 19 (CCL19). [40]
Capecitabine DMTS85L Approved Capecitabine decreases the expression of C-C motif chemokine 19 (CCL19). [41]
Eugenol DM7US1H Patented Eugenol increases the expression of C-C motif chemokine 19 (CCL19). [42]
Formaldehyde DM7Q6M0 Investigative Formaldehyde increases the expression of C-C motif chemokine 19 (CCL19). [43]
Phencyclidine DMQBEYX Investigative Phencyclidine increases the expression of C-C motif chemokine 19 (CCL19). [44]
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⏷ Show the Full List of 9 Drug(s)

References

1 CCR7 Sulfotyrosine Enhances CCL21 Binding.Int J Mol Sci. 2017 Aug 25;18(9):1857. doi: 10.3390/ijms18091857.
2 CCL19 is constitutively expressed in the CNS, up-regulated in neuroinflammation, active and also inactive multiple sclerosis lesions.J Neuroimmunol. 2007 Oct;190(1-2):72-9. doi: 10.1016/j.jneuroim.2007.07.024. Epub 2007 Sep 6.
3 The effect of CCL19/CCR7 on the proliferation and migration of cell in prostate cancer.Tumour Biol. 2015 Jan;36(1):329-35. doi: 10.1007/s13277-014-2642-1. Epub 2014 Sep 26.
4 Discriminative expression of whole blood genes in HIV patients with latent and active TB in Ethiopia.Tuberculosis (Edinb). 2016 Sep;100:25-31. doi: 10.1016/j.tube.2016.06.003. Epub 2016 Jun 13.
5 Age-Related Gliosis Promotes Central Nervous System Lymphoma through CCL19-Mediated Tumor Cell Retention.Cancer Cell. 2019 Sep 16;36(3):250-267.e9. doi: 10.1016/j.ccell.2019.08.001.
6 Gene expression time course in the human skin during elicitation of allergic contact dermatitis.J Invest Dermatol. 2007 Nov;127(11):2585-95. doi: 10.1038/sj.jid.5700902. Epub 2007 Jun 28.
7 Expansion of CD4(+) CD25(+) and CD25(-) T-Bet, GATA-3, Foxp3 and RORt cells in allergic inflammation, local lung distribution and chemokine gene expression.PLoS One. 2011;6(5):e19889. doi: 10.1371/journal.pone.0019889. Epub 2011 May 19.
8 NK Cells are Activated in Amnestic Mild Cognitive Impairment but not in Mild Alzheimer's Disease Patients.J Alzheimers Dis. 2015;46(1):93-107. doi: 10.3233/JAD-143054.
9 Expression of CCR7 and its ligands CCL19/CCL21 in muscles of polymyositis.J Neurol Sci. 2006 Nov 15;249(2):158-65. doi: 10.1016/j.jns.2006.06.021. Epub 2006 Aug 2.
10 CCR7 mediates human breast cancer cell invasion, migration by inducing epithelial-mesenchymal transition and suppressing apoptosis through AKT pathway.Cancer Med. 2017 May;6(5):1062-1071. doi: 10.1002/cam4.1039. Epub 2017 Apr 4.
11 Homeostatic Chemokines and Prognosisin Patients With Acute Coronary Syndromes.J Am Coll Cardiol. 2019 Aug 13;74(6):774-782. doi: 10.1016/j.jacc.2019.06.030.
12 Increased CCL19 expression is associated with progression in cervical cancer.Oncotarget. 2017 May 18;8(43):73817-73825. doi: 10.18632/oncotarget.17982. eCollection 2017 Sep 26.
13 CCL19 suppresses angiogenesis through promoting miR-206 and inhibiting Met/ERK/Elk-1/HIF-1/VEGF-A pathway in colorectal cancer.Cell Death Dis. 2018 Sep 24;9(10):974. doi: 10.1038/s41419-018-1010-2.
14 CCL19/CCR7 contributes to the pathogenesis of endometriosis via PI3K/Akt pathway by regulating the proliferation and invasion of ESCs.Am J Reprod Immunol. 2017 Nov;78(5). doi: 10.1111/aji.12744. Epub 2017 Aug 30.
15 Crk-like adapter protein regulates CCL19/CCR7-mediated epithelial-to-mesenchymal transition via ERK signaling pathway in epithelial ovarian carcinomas.Med Oncol. 2015 Mar;32(3):47. doi: 10.1007/s12032-015-0494-1. Epub 2015 Jan 31.
16 The effect of chemokine CC motif ligand 19 on the proliferation and migration of hepatocellular carcinoma.Tumour Biol. 2014 Dec;35(12):12575-81. doi: 10.1007/s13277-014-2578-5. Epub 2014 Sep 16.
17 Selective miRNA Modulation Fails to Activate HIV Replication in InVitro Latency Models.Mol Ther Nucleic Acids. 2019 Sep 6;17:323-336. doi: 10.1016/j.omtn.2019.06.006. Epub 2019 Jun 20.
18 CCL19-producing fibroblastic stromal cells restrain lung carcinoma growth by promoting local antitumor T-cell responses.J Allergy Clin Immunol. 2018 Oct;142(4):1257-1271.e4. doi: 10.1016/j.jaci.2017.12.998. Epub 2018 Jan 31.
19 Sequence variation in promoter regions of genes for CC chemokine ligands (CCL)19 and 21 in Czech patients with myocardial infarction.Mol Biol Rep. 2014 May;41(5):3163-8. doi: 10.1007/s11033-014-3175-9. Epub 2014 Feb 4.
20 Inhibition of CCL19 benefits nonalcoholic fatty liver disease by inhibiting TLR4/NFBp65 signaling.Mol Med Rep. 2018 Nov;18(5):4635-4642. doi: 10.3892/mmr.2018.9490. Epub 2018 Sep 14.
21 An assessment of the relationship between the expression of CCR7/CCL19 axis and selected regulatory miRNAs in non-small cell lung cancer.Mol Biol Rep. 2019 Oct;46(5):5389-5396. doi: 10.1007/s11033-019-04993-3. Epub 2019 Aug 28.
22 Adipose tissue expression of CCL19 chemokine is positively associated with insulin resistance.Diabetes Metab Res Rev. 2019 Feb;35(2):e3087. doi: 10.1002/dmrr.3087. Epub 2018 Nov 8.
23 Anti-tumor responses induced by chemokine CCL19 transfected into an ovarian carcinoma model via fiber-mutant adenovirus vector.Biol Pharm Bull. 2005 Jun;28(6):1066-70. doi: 10.1248/bpb.28.1066.
24 CCL21 as a Potential Serum Biomarker for Pulmonary Arterial Hypertension in Systemic Sclerosis.Arthritis Rheumatol. 2018 Oct;70(10):1644-1653. doi: 10.1002/art.40534. Epub 2018 Aug 30.
25 Inhibition of CCR7/CCL19 axis in lesional skin is a critical event for clinical remission induced by TNF blockade in patients with psoriasis.Am J Pathol. 2013 Aug;183(2):413-21. doi: 10.1016/j.ajpath.2013.04.021. Epub 2013 May 31.
26 Stimulation of osteoclast migration and bone resorption by C-C chemokine ligands 19 and 21.Exp Mol Med. 2017 Jul 21;49(7):e358. doi: 10.1038/emm.2017.100.
27 Mutations in NOTCH1 PEST domain orchestrate CCL19-driven homing of chronic lymphocytic leukemia cells by modulating the tumor suppressor gene DUSP22.Leukemia. 2017 Sep;31(9):1882-1893. doi: 10.1038/leu.2016.383. Epub 2016 Dec 26.
28 Longitudinal association of type 1 interferon-induced chemokines with disease activity in systemic lupus erythematosus.Sci Rep. 2018 Feb 19;8(1):3268. doi: 10.1038/s41598-018-20203-9.
29 Global chemokine expression in systemic sclerosis (SSc): CCL19 expression correlates with vascular inflammation in SSc skin.Ann Rheum Dis. 2014 Oct;73(10):1864-72. doi: 10.1136/annrheumdis-2012-202814. Epub 2013 Jul 19.
30 Expression and pathological significance of CC chemokine receptor 7 and its ligands in the airway of asthmatic rats exposed to cigarette smoke.J Thorac Dis. 2018 Sep;10(9):5459-5467. doi: 10.21037/jtd.2018.08.124.
31 High CC chemokine receptor 7 expression improves postoperative prognosis of lung adenocarcinoma patients.Br J Cancer. 2013 Sep 3;109(5):1100-8. doi: 10.1038/bjc.2013.440. Epub 2013 Aug 6.
32 Ischemic stroke damages the intestinal mucosa and induces alteration of the intestinal lymphocytes and CCL19 mRNA in rats.Neurosci Lett. 2017 Sep 29;658:165-170. doi: 10.1016/j.neulet.2017.08.061. Epub 2017 Aug 30.
33 Genome-wide haplotype association study identify the FGFR2 gene as a risk gene for acute myeloid leukemia.Oncotarget. 2017 Jan 31;8(5):7891-7899. doi: 10.18632/oncotarget.13631.
34 Contribution of homeostatic chemokines CCL19 and CCL21 and their receptor CCR7 to coronary artery disease.Arterioscler Thromb Vasc Biol. 2014 Sep;34(9):1933-41. doi: 10.1161/ATVBAHA.113.303081. Epub 2014 Jul 2.
35 Augmented expression of secondary lymphoid tissue chemokine and EBI1 ligand chemokine in Crohn's disease.J Clin Pathol. 2005 Oct;58(10):1057-63. doi: 10.1136/jcp.2004.024828.
36 Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
37 Pattern of expression of apoptosis and inflammatory genes in humans exposed to arsenic and/or fluoride. Sci Total Environ. 2010 Jan 15;408(4):760-7. doi: 10.1016/j.scitotenv.2009.11.016. Epub 2009 Dec 4.
38 The contribution of methotrexate exposure and host factors on transcriptional variance in human liver. Toxicol Sci. 2007 Jun;97(2):582-94.
39 Expression profile analysis of colon cancer cells in response to sulindac or aspirin. Biochem Biophys Res Commun. 2002 Mar 29;292(2):498-512.
40 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.
41 Gene expression responses reflecting 5-FU-induced toxicity: Comparison between patient colon tissue and 3D human colon organoids. Toxicol Lett. 2022 Dec 1;371:17-24. doi: 10.1016/j.toxlet.2022.09.013. Epub 2022 Sep 29.
42 Chemicals with weak skin sensitizing properties can be identified using low-density microarrays on immature dendritic cells. Toxicol Lett. 2007 Nov 1;174(1-3):98-109. doi: 10.1016/j.toxlet.2007.08.015. Epub 2007 Sep 5.
43 Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
44 Differential response of Mono Mac 6, BEAS-2B, and Jurkat cells to indoor dust. Environ Health Perspect. 2007 Sep;115(9):1325-32.