Details of Drug Off-Target (DOT)

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

DOT Name C-C motif chemokine 4-like (CCL4L2)
Synonyms Lymphocyte activation gene 1 protein; LAG-1; Macrophage inflammatory protein 1-beta; MIP-1-beta; Monocyte adherence-induced protein 5-alpha; Small-inducible cytokine A4-like
Gene Name CCL4L2
Related Disease
Neoplasm ( )
Thyroid gland papillary carcinoma ( )
Type-1/2 diabetes ( )
Vascular disease ( )
Abdominal aortic aneurysm ( )
Adenoma ( )
Alzheimer disease ( )
Arteriosclerosis ( )
Atherosclerosis ( )
Breast carcinoma ( )
Colon cancer ( )
Colorectal carcinoma ( )
Crohn disease ( )
Dementia ( )
Depression ( )
Fatty liver disease ( )
Hepatitis ( )
Hepatitis B virus infection ( )
Hepatocellular carcinoma ( )
HIV infectious disease ( )
Huntington disease ( )
Immunodeficiency ( )
Inflammatory bowel disease ( )
Influenza ( )
Liver cirrhosis ( )
Liver failure ( )
Lung adenocarcinoma ( )
Lung cancer ( )
Lung carcinoma ( )
Lung squamous cell carcinoma ( )
Post-traumatic stress disorder ( )
Psoriasis ( )
Rheumatoid arthritis ( )
Systemic lupus erythematosus ( )
Tuberculosis ( )
Ulcerative colitis ( )
Myocardial ischemia ( )
Stroke ( )
Advanced cancer ( )
Amyotrophic lateral sclerosis ( )
Breast cancer ( )
Classic Hodgkin lymphoma ( )
Dengue ( )
Intellectual disability ( )
Malaria ( )
Melanoma ( )
Nasopharyngeal carcinoma ( )
Nervous system inflammation ( )
Pulmonary tuberculosis ( )
UniProt ID
CC4L_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
Pfam ID
PF00048
Sequence
MKLCVTVLSLLVLVAAFCSLALSAPMGSDPPTACCFSYTARKLPRNFVVDYYETSSLCSQ
PAVVFQTKRGKQVCADPSESWVQEYVYDLELN
Function Chemokine that induces chemotaxis of cells expressing CCR5 or CCR1. Inhibits HIV replication in peripheral blood monocytes that express CCR5.
Tissue Specificity Detected in B-cells.
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 )
Toll-like receptor sig.ling pathway (hsa04620 )
Cytosolic D.-sensing pathway (hsa04623 )
Human cytomegalovirus infection (hsa05163 )
Reactome Pathway
G alpha (i) signalling events (R-HSA-418594 )

Molecular Interaction Atlas (MIA) of This DOT

49 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Neoplasm DISZKGEW Definitive Biomarker [1]
Thyroid gland papillary carcinoma DIS48YMM Definitive Biomarker [2]
Type-1/2 diabetes DISIUHAP Definitive Altered Expression [3]
Vascular disease DISVS67S Definitive Biomarker [3]
Abdominal aortic aneurysm DISD06OF Strong Altered Expression [4]
Adenoma DIS78ZEV Strong Biomarker [5]
Alzheimer disease DISF8S70 Strong Altered Expression [6]
Arteriosclerosis DISK5QGC Strong Biomarker [7]
Atherosclerosis DISMN9J3 Strong Biomarker [7]
Breast carcinoma DIS2UE88 Strong Biomarker [8]
Colon cancer DISVC52G Strong Biomarker [9]
Colorectal carcinoma DIS5PYL0 Strong Biomarker [9]
Crohn disease DIS2C5Q8 Strong Altered Expression [10]
Dementia DISXL1WY Strong Altered Expression [11]
Depression DIS3XJ69 Strong Biomarker [12]
Fatty liver disease DIS485QZ Strong Biomarker [13]
Hepatitis DISXXX35 Strong Biomarker [14]
Hepatitis B virus infection DISLQ2XY Strong Biomarker [15]
Hepatocellular carcinoma DIS0J828 Strong Biomarker [5]
HIV infectious disease DISO97HC Strong Biomarker [16]
Huntington disease DISQPLA4 Strong Altered Expression [17]
Immunodeficiency DIS093I0 Strong Altered Expression [18]
Inflammatory bowel disease DISGN23E Strong Genetic Variation [19]
Influenza DIS3PNU3 Strong Altered Expression [20]
Liver cirrhosis DIS4G1GX Strong Biomarker [15]
Liver failure DISLGEL6 Strong Biomarker [21]
Lung adenocarcinoma DISD51WR Strong Biomarker [22]
Lung cancer DISCM4YA Strong Altered Expression [23]
Lung carcinoma DISTR26C Strong Altered Expression [23]
Lung squamous cell carcinoma DISXPIBD Strong Biomarker [22]
Post-traumatic stress disorder DISHL1EY Strong Biomarker [12]
Psoriasis DIS59VMN Strong Biomarker [24]
Rheumatoid arthritis DISTSB4J Strong Altered Expression [25]
Systemic lupus erythematosus DISI1SZ7 Strong Genetic Variation [26]
Tuberculosis DIS2YIMD Strong Biomarker [27]
Ulcerative colitis DIS8K27O Strong Altered Expression [10]
Myocardial ischemia DISFTVXF moderate Genetic Variation [28]
Stroke DISX6UHX moderate Genetic Variation [29]
Advanced cancer DISAT1Z9 Limited Biomarker [30]
Amyotrophic lateral sclerosis DISF7HVM Limited Altered Expression [31]
Breast cancer DIS7DPX1 Limited Altered Expression [32]
Classic Hodgkin lymphoma DISV1LU6 Limited Altered Expression [33]
Dengue DISKH221 Limited Altered Expression [34]
Intellectual disability DISMBNXP Limited Altered Expression [35]
Malaria DISQ9Y50 Limited Biomarker [36]
Melanoma DIS1RRCY Limited Altered Expression [37]
Nasopharyngeal carcinoma DISAOTQ0 Limited Genetic Variation [38]
Nervous system inflammation DISB3X5A Limited Genetic Variation [39]
Pulmonary tuberculosis DIS6FLUM Limited Genetic Variation [40]
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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
3 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of C-C motif chemokine 4-like (CCL4L2). [41]
Malathion DMXZ84M Approved Malathion increases the expression of C-C motif chemokine 4-like (CCL4L2). [42]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the expression of C-C motif chemokine 4-like (CCL4L2). [43]
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References

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2 Overexpression of LASS2 inhibits proliferation and causes G0/G1 cell cycle arrest in papillary thyroid cancer.Cancer Cell Int. 2018 Oct 1;18:151. doi: 10.1186/s12935-018-0649-1. eCollection 2018.
3 Inhibition of macrophage inflammatory protein-1 improves endothelial progenitor cell function and ischemia-induced angiogenesis in diabetes.Angiogenesis. 2019 Feb;22(1):53-65. doi: 10.1007/s10456-018-9636-3. Epub 2018 Jul 9.
4 Two C-C Family Chemokines, Eotaxin and RANTES, Are Novel Independent Plasma Biomarkers for Abdominal Aortic Aneurysm.J Am Heart Assoc. 2016 Apr 28;5(5):e002993. doi: 10.1161/JAHA.115.002993.
5 Repeated hepatocyte injury promotes hepatic tumorigenesis in hepatitis C virus transgenic mice.Cancer Sci. 2003 Aug;94(8):679-85. doi: 10.1111/j.1349-7006.2003.tb01502.x.
6 Polymorphonuclear Neutrophil Functions are Differentially Altered in Amnestic Mild Cognitive Impairment and Mild Alzheimer's Disease Patients.J Alzheimers Dis. 2017;60(1):23-42. doi: 10.3233/JAD-170124.
7 Chemokine receptor CCR5: from AIDS to atherosclerosis.Br J Pharmacol. 2011 Apr;162(7):1453-69. doi: 10.1111/j.1476-5381.2010.01147.x.
8 Cathepsin D specifically cleaves the chemokines macrophage inflammatory protein-1 alpha, macrophage inflammatory protein-1 beta, and SLC that are expressed in human breast cancer.Am J Pathol. 2003 Apr;162(4):1183-90. doi: 10.1016/s0002-9440(10)63914-4.
9 Subsite heterogeneity in the profiles of circulating cytokines in colorectal cancer.Cytokine. 2018 Oct;110:435-441. doi: 10.1016/j.cyto.2018.05.015. Epub 2018 May 23.
10 Inflammatory gene expression profiles in Crohn's disease and ulcerative colitis: a comparative analysis using a reverse transcriptase multiplex ligation-dependent probe amplification protocol.J Crohns Colitis. 2013 Sep;7(8):622-30. doi: 10.1016/j.crohns.2012.08.015. Epub 2012 Sep 24.
11 Human immunodeficiency virus type 1 infection alters chemokine beta peptide expression in human monocytes: implications for recruitment of leukocytes into brain and lymph nodes.Proc Natl Acad Sci U S A. 1996 Jan 23;93(2):700-4. doi: 10.1073/pnas.93.2.700.
12 The association between inflammatory markers (iNOS, HO-1, IL-33, MIP-1) and depression with and without posttraumatic stress disorder.Pharmacol Rep. 2018 Dec;70(6):1065-1072. doi: 10.1016/j.pharep.2018.06.001. Epub 2018 Jun 5.
13 Hepatocyte-specific deletion of LASS2 protects against diet-induced hepatic steatosis and insulin resistance.Free Radic Biol Med. 2018 May 20;120:330-341. doi: 10.1016/j.freeradbiomed.2018.04.003. Epub 2018 Apr 4.
14 Immunomodulative effects of mesenchymal stem cells derived from human embryonic stem cells in vivo and in vitro.J Zhejiang Univ Sci B. 2011 Jan;12(1):18-27. doi: 10.1631/jzus.B1000074.
15 Potential circulating biomarkers of circulating chemokines CCL5, MIP-1 and HA as for early detection of cirrhosis related to chronic HBV (hepatitis B virus) infection.BMC Infect Dis. 2019 Jun 14;19(1):523. doi: 10.1186/s12879-019-4130-0.
16 Genital inflammation and the risk of HIV acquisition in women.Clin Infect Dis. 2015 Jul 15;61(2):260-9. doi: 10.1093/cid/civ298. Epub 2015 Apr 21.
17 The cytokine and endocannabinoid systems are co-regulated by NF-B p65/RelA in cell culture and transgenic mouse models of Huntington's disease and in striatal tissue from Huntington's disease patients.J Neuroimmunol. 2014 Feb 15;267(1-2):61-72. doi: 10.1016/j.jneuroim.2013.12.008. Epub 2013 Dec 12.
18 Morphine exacerbates HIV-1 viral protein gp120 induced modulation of chemokine gene expression in U373 astrocytoma cells.Curr HIV Res. 2005 Jul;3(3):277-88. doi: 10.2174/1570162054368048.
19 Impact of Obesity on Short- and Intermediate-Term Outcomes in Inflammatory Bowel Diseases: Pooled Analysis of Placebo Arms of Infliximab Clinical Trials.Inflamm Bowel Dis. 2018 Sep 15;24(10):2278-2284. doi: 10.1093/ibd/izy135.
20 Comparison of influenza and SIV specific CD8 T cell responses in macaques.PLoS One. 2012;7(3):e32431. doi: 10.1371/journal.pone.0032431. Epub 2012 Mar 5.
21 Protective effect of recombinant human IL-1Ra on CCl4-induced acute liver injury in mice.World J Gastroenterol. 2010 Jun 14;16(22):2771-9. doi: 10.3748/wjg.v16.i22.2771.
22 High levels of CCL2 or CCL4 in the tumor microenvironment predict unfavorable survival in lung adenocarcinoma.Thorac Cancer. 2018 Jul;9(7):775-784. doi: 10.1111/1759-7714.12643. Epub 2018 May 2.
23 Occupational exposure to diesel engine exhaust and serum cytokine levels.Environ Mol Mutagen. 2018 Mar;59(2):144-150. doi: 10.1002/em.22142. Epub 2017 Oct 12.
24 Polymorphisms Associated with Age at Onset in Patients with Moderate-to-Severe Plaque Psoriasis.J Immunol Res. 2015;2015:101879. doi: 10.1155/2015/101879. Epub 2015 Nov 3.
25 Chemokine expression in rheumatoid arthritis (RA): evidence of RANTES and macrophage inflammatory protein (MIP)-1 beta production by synovial T cells.Clin Exp Immunol. 1995 Sep;101(3):398-407. doi: 10.1111/j.1365-2249.1995.tb03126.x.
26 Principal component analysis reveals disconnect between regulatory cytokines and disease activity in Systemic Lupus Erythematosus.Cytokine. 2019 Feb;114:67-73. doi: 10.1016/j.cyto.2018.10.013. Epub 2018 Dec 12.
27 Household contact investigation for the detection of tuberculosis in Vietnam: economic evaluation of a cluster-randomised trial.Lancet Glob Health. 2019 Mar;7(3):e376-e384. doi: 10.1016/S2214-109X(18)30520-5.
28 Exposure to air pollution and risk of hospitalization for cardiovascular diseases amongst Vietnamese adults: Case-crossover study.Sci Total Environ. 2020 Feb 10;703:134637. doi: 10.1016/j.scitotenv.2019.134637. Epub 2019 Nov 3.
29 Macrophage inflammatory protein-1beta induced cell adhesion with increased intracellular reactive oxygen species.J Mol Cell Cardiol. 2009 Jul;47(1):104-11. doi: 10.1016/j.yjmcc.2009.03.012. Epub 2009 Mar 26.
30 Likert vs PI-RADS v2: a comparison of two radiological scoring systems for detection of clinically significant prostate cancer.BJU Int. 2020 Jan;125(1):49-55. doi: 10.1111/bju.14916. Epub 2019 Nov 1.
31 Increased cerebrospinal fluid levels of cytokines monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1 (MIP-1) in patients with amyotrophic lateral sclerosis.Neurologia (Engl Ed). 2020 Apr;35(3):165-169. doi: 10.1016/j.nrl.2017.07.020. Epub 2017 Oct 11.
32 Equal Pro-inflammatory Profiles of CCLs, CXCLs, and Matrix Metalloproteinases in the Extracellular Microenvironment In Vivo in Human Dense Breast Tissue and Breast Cancer.Front Immunol. 2018 Jan 16;8:1994. doi: 10.3389/fimmu.2017.01994. eCollection 2017.
33 Epstein-Barr virus latent membrane protein-1 up-regulates cytokines and correlates with older age and poorer prognosis in Hodgkin lymphoma.Histopathology. 2017 Feb;70(3):442-455. doi: 10.1111/his.13085. Epub 2016 Nov 8.
34 Clinical Proteomics and Cytokine Profiling for Dengue Fever Disease Severity Biomarkers.OMICS. 2017 Nov;21(11):665-677. doi: 10.1089/omi.2017.0135. Epub 2017 Nov 1.
35 Mental retardation in Down syndrome: from gene dosage imbalance to molecular and cellular mechanisms.Neurosci Res. 2007 Dec;59(4):349-69. doi: 10.1016/j.neures.2007.08.007. Epub 2007 Aug 15.
36 A Time Series Analysis: Weather Factors, Human Migration and Malaria Cases in Endemic Area of Purworejo, Indonesia, 2005-2014.Iran J Public Health. 2018 Apr;47(4):499-509.
37 Human Melanoma-Derived Extracellular Vesicles Regulate Dendritic Cell Maturation.Front Immunol. 2017 Mar 29;8:358. doi: 10.3389/fimmu.2017.00358. eCollection 2017.
38 Decreased macrophage inflammatory protein (MIP)-1 and MIP-1 increase the risk of developing nasopharyngeal carcinoma.Cancer Commun (Lond). 2018 Apr 3;38(1):7. doi: 10.1186/s40880-018-0279-y.
39 Sequence polymorphisms in the chemokines Scya1 (TCA-3), Scya2 (monocyte chemoattractant protein (MCP)-1), and Scya12 (MCP-5) are candidates for eae7, a locus controlling susceptibility to monophasic remitting/nonrelapsing experimental allergic encephalomyelitis.J Immunol. 1999 Aug 15;163(4):2262-6.
40 CCL2, CCL3 and CCL4 gene polymorphisms in pulmonary tuberculosis patients of South India.Int J Immunogenet. 2014 Apr;41(2):98-104. doi: 10.1111/iji.12085. Epub 2013 Sep 3.
41 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.
42 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.
43 Genome-wide transcriptional and functional analysis of human T lymphocytes treated with benzo[alpha]pyrene. Int J Mol Sci. 2018 Nov 17;19(11).