Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTQXCYB1)

• DOT Name: C-C motif chemokine 3-like 1 (CCL3L1)
• Synonyms: G0/G1 switch regulatory protein 19-2; LD78-beta(1-70); PAT 464.2; Small-inducible cytokine A3-like 1; Tonsillar lymphocyte LD78 beta protein
• Gene Name: CCL3L1
• Related Disease:
  Malaria
  Acquired immune deficiency syndrome
  Autoimmune disease
  Haemophilia A
  Hemophilia
  Hepatitis B virus infection
  Hepatitis C virus infection
  Osteoarthritis
  Papillon-Lefevre disease
  Systemic lupus erythematosus
  Tuberculosis
  Vasculitis
  Viral hepatitis
  Lupus
  Lupus nephritis
  Acute myelogenous leukaemia
  Ankylosing spondylitis
  Asthma
  Immune system disorder
  Neoplasm
  Type-1 diabetes
• UniProt ID: CL3L1_HUMAN
• Pfam ID: PF00048
• Sequence:
  MQVSTAALAVLLCTMALCNQVLSAPLAADTPTACCFSYTSRQIPQNFIADYFETSSQCSK
  PSVIFLTKRGRQVCADPSEEWVQKYVSDLELSA
• Function: Chemotactic for lymphocytes and monocytes. Is a ligand for CCR1, CCR3 and CCR5. Is an inhibitor of HIV-1-infection. The processed form LD78-beta(3-70) shows a 20-fold to 30-fold higher chemotactic activity and is a very potent inhibitor of HIV-1-infection. LD78-beta(3-70) is also a ligand for CCR1, CCR3 and CCR5.
• KEGG Pathway:
  Cytokine-cytokine receptor interaction (hsa04060)
  Viral protein interaction with cytokine and cytokine receptor (hsa04061)
  Chemokine sig.ling pathway (hsa04062)
  Toll-like receptor sig.ling pathway (hsa04620)
  Chagas disease (hsa05142)
  Human cytomegalovirus infection (hsa05163)
  Rheumatoid arthritis (hsa05323)
  Lipid and atherosclerosis (hsa05417)
• Reactome Pathway:
  Interleukin-10 signaling (R-HSA-6783783)
  Chemokine receptors bind chemokines (R-HSA-380108)

Molecular Interaction Atlas (MIA) of This DOT

21 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Malaria	DISQ9Y50	Definitive	Genetic Variation	[1]
Acquired immune deficiency syndrome	DISL5UOX	Strong	Genetic Variation	[2]
Autoimmune disease	DISORMTM	Strong	Biomarker	[3]
Haemophilia A	DIS0RQ2E	Strong	Biomarker	[4]
Hemophilia	DIS1S8P6	Strong	Biomarker	[4]
Hepatitis B virus infection	DISLQ2XY	Strong	Genetic Variation	[5]
Hepatitis C virus infection	DISQ0M8R	Strong	Biomarker	[6]
Osteoarthritis	DIS05URM	Strong	Biomarker	[7]
Papillon-Lefevre disease	DIS3R7KX	Strong	Biomarker	[8]
Systemic lupus erythematosus	DISI1SZ7	Strong	Genetic Variation	[9]
Tuberculosis	DIS2YIMD	Strong	Genetic Variation	[10]
Vasculitis	DISQRKDX	Strong	Genetic Variation	[11]
Viral hepatitis	DISVT5Q7	Strong	Genetic Variation	[6]
Lupus	DISOKJWA	moderate	Genetic Variation	[12]
Lupus nephritis	DISCVGPZ	moderate	Genetic Variation	[12]
Acute myelogenous leukaemia	DISCSPTN	Limited	Biomarker	[13]
Ankylosing spondylitis	DISRC6IR	Limited	Genetic Variation	[14]
Asthma	DISW9QNS	Limited	Genetic Variation	[15]
Immune system disorder	DISAEGPH	Limited	Biomarker	[15]
Neoplasm	DISZKGEW	Limited	Altered Expression	[16]
Type-1 diabetes	DIS7HLUB	Limited	Biomarker	[17]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of C-C motif chemokine 3-like 1 (CCL3L1).	[18]
Arsenic	DMTL2Y1	Approved	Arsenic decreases the expression of C-C motif chemokine 3-like 1 (CCL3L1).	[19]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of C-C motif chemokine 3-like 1 (CCL3L1).	[20]
Marinol	DM70IK5	Approved	Marinol increases the expression of C-C motif chemokine 3-like 1 (CCL3L1).	[21]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of C-C motif chemokine 3-like 1 (CCL3L1).	[22]
Selenium	DM25CGV	Approved	Selenium increases the expression of C-C motif chemokine 3-like 1 (CCL3L1).	[23]
Malathion	DMXZ84M	Approved	Malathion increases the expression of C-C motif chemokine 3-like 1 (CCL3L1).	[24]
Pioglitazone	DMKJ485	Approved	Pioglitazone decreases the expression of C-C motif chemokine 3-like 1 (CCL3L1).	[25]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of C-C motif chemokine 3-like 1 (CCL3L1).	[26]
Eugenol	DM7US1H	Patented	Eugenol increases the expression of C-C motif chemokine 3-like 1 (CCL3L1).	[27]

References

• [1] CCL3L1 copy number and susceptibility to malaria.Infect Genet Evol. 2012 Jul;12(5):1147-54. doi: 10.1016/j.meegid.2012.03.021. Epub 2012 Mar 30.
• [2] CCL3L1-CCR5 genotype improves the assessment of AIDS Risk in HIV-1-infected individuals.PLoS One. 2008 Sep 8;3(9):e3165. doi: 10.1371/journal.pone.0003165.
• [3] Accuracy and differential bias in copy number measurement of CCL3L1 in association studies with three auto-immune disorders.BMC Genomics. 2011 Aug 18;12:418. doi: 10.1186/1471-2164-12-418.
• [4] Copy number variations of CCL3L1 and long-term prognosis of HIV-1 infection in asymptomatic HIV-infected Japanese with hemophilia.Immunogenetics. 2007 Oct;59(10):793-8. doi: 10.1007/s00251-007-0252-4. Epub 2007 Sep 14.
• [5] Polymorphisms of CCL3L1/CCR5 genes and recurrence of hepatitis B in liver transplant recipients.Hepatobiliary Pancreat Dis Int. 2011 Dec;10(6):593-8. doi: 10.1016/s1499-3872(11)60101-x.
• [6] Lower copy numbers of the chemokine CCL3L1 gene in patients with chronic hepatitis C.J Hepatol. 2010 Feb;52(2):153-9. doi: 10.1016/j.jhep.2009.11.001. Epub 2009 Nov 27.
• [7] Molecular characterization of articular cartilage from young adults with femoroacetabular impingement.J Bone Joint Surg Am. 2013 Aug 21;95(16):1457-64. doi: 10.2106/JBJS.L.00497.
• [8] Proteolysis of macrophage inflammatory protein-1alpha isoforms LD78beta and LD78alpha by neutrophil-derived serine proteases.J Biol Chem. 2005 Apr 29;280(17):17415-21. doi: 10.1074/jbc.M500340200. Epub 2005 Feb 22.
• [9] Association of copy number variation in the FCGR3B gene with risk of autoimmune diseases.Genes Immun. 2010 Mar;11(2):155-60. doi: 10.1038/gene.2009.71. Epub 2009 Sep 10.
• [10] CCL3L1 copy number, CCR5 genotype and susceptibility to tuberculosis.BMC Med Genet. 2014 Jan 9;15:5. doi: 10.1186/1471-2350-15-5.
• [11] Genetic variations in the receptor-ligand pair CCR5 and CCL3L1 are important determinants of susceptibility to Kawasaki disease.J Infect Dis. 2005 Jul 15;192(2):344-9. doi: 10.1086/430953. Epub 2005 Jun 8.
• [12] CCL3L1 gene-containing segmental duplications and polymorphisms in CCR5 affect risk of systemic lupus erythaematosus.Ann Rheum Dis. 2008 Aug;67(8):1076-83. doi: 10.1136/ard.2007.078048. Epub 2007 Oct 30.
• [13] Synthesis of a novel cytokine and its gene (LD78) expressions in hematopoietic fresh tumor cells and cell lines.J Clin Invest. 1989 Dec;84(6):1707-12. doi: 10.1172/JCI114353.
• [14] Association study of copy number variants in CCL3L1, FCGR3A and FCGR3B genes with risk of ankylosing spondylitis in a West Algerian population.Int J Immunogenet. 2019 Dec;46(6):437-443. doi: 10.1111/iji.12454. Epub 2019 Aug 21.
• [15] Copy number variation of CCL3L1 influences asthma risk by modulating IL-10 expression.Clin Chim Acta. 2011 Nov 20;412(23-24):2100-4. doi: 10.1016/j.cca.2011.07.017. Epub 2011 Jul 26.
• [16] Chemokine gene transfection into tumour cells reduced tumorigenicity in nude mice in association with neutrophilic infiltration.Br J Cancer. 1995 Sep;72(3):708-14. doi: 10.1038/bjc.1995.398.
• [17] Evidence for an influence of chemokine ligand 3-like 1 (CCL3L1) gene copy number on susceptibility to rheumatoid arthritis.Ann Rheum Dis. 2008 Mar;67(3):409-13. doi: 10.1136/ard.2007.075028. Epub 2007 Jun 29.
• [18] RNA sequence analysis of inducible pluripotent stem cell-derived cardiomyocytes reveals altered expression of DNA damage and cell cycle genes in response to doxorubicin. Toxicol Appl Pharmacol. 2018 Oct 1;356:44-53.
• [19] Gene expression profiles in peripheral lymphocytes by arsenic exposure and skin lesion status in a Bangladeshi population. Cancer Epidemiol Biomarkers Prev. 2006 Jul;15(7):1367-75. doi: 10.1158/1055-9965.EPI-06-0106.
• [20] The contribution of methotrexate exposure and host factors on transcriptional variance in human liver. Toxicol Sci. 2007 Jun;97(2):582-94.
• [21] Inhibiting Heat Shock Proteins Can Potentiate the Cytotoxic Effect of Cannabidiol in Human Glioma Cells. Anticancer Res. 2015 Nov;35(11):5827-37.
• [22] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [23] Changes in gene expression profiles in response to selenium supplementation among individuals with arsenic-induced pre-malignant skin lesions. Toxicol Lett. 2007 Mar 8;169(2):162-76. doi: 10.1016/j.toxlet.2007.01.006. Epub 2007 Jan 19.
• [24] 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.
• [25] Peroxisome proliferator activated receptor gamma (PPAR-gama) ligand pioglitazone regulated gene networks in term human primary trophoblast cells. Reprod Toxicol. 2018 Oct;81:99-107.
• [26] Genome-wide transcriptional and functional analysis of human T lymphocytes treated with benzo[alpha]pyrene. Int J Mol Sci. 2018 Nov 17;19(11).
• [27] Prediction of the contact sensitizing potential of chemicals using analysis of gene expression changes in human THP-1 monocytes. Toxicol Lett. 2010 Nov 10;199(1):51-9.