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Gene Review

CCL3L1  -  chemokine (C-C motif) ligand 3-like 1

Homo sapiens

Synonyms: 464.2, D17S1718, G0S19-2, LD78, LD78-beta(1-70), ...
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Disease relevance of CCL3L1


High impact information on CCL3L1

  • Specific haplotypes encompassing the CCR5 and CCR2 loci, and the copy number of the CCL3L1 gene, have also been convincingly correlated with delayed progression [6].
  • Analysis of the CCL3-L1 gene for association with HIV-1 susceptibility and disease progression [7].
  • Sequences homologous to uCOM are found in the promoters of other inducible genes, coding for proteases, cytokines and chemokines: for example, in the promoter of the MIP-1alpha/LD78 chemokine gene, a 15/18 nucleotides identity is found in a region mediating positive and negative functions in TPA induction [8].
  • Furthermore, AMD3451 inhibited CXCL12- and CCL3L1-induced endocytosis in CXCR4- and CCR5-transfected cells [9].
  • However, the magnitude of the reduced risk of KD associated with the CCR5- Delta 32 allele and certain CCR5 haplotypes was significantly greater in individuals who also possessed a high copy number of the gene encoding CCL3L1, the most potent CCR5 ligand [2].

Biological context of CCL3L1


Anatomical context of CCL3L1


Associations of CCL3L1 with chemical compounds

  • A proline at position 2 (CCL3L1) provides for high potency and efficacy but the isoform with a serine at position 2 (CCL3(2-70)) is as efficacious in some assays showing that the proline is not the only determinant of high efficacy [11].

Other interactions of CCL3L1

  • Here, using real-time PCR we have shown that CCL3-L1 and a novel CCL4 isoform (termed CCL4-L1) can vary from 1-6 copies per diploid genome (pdg) in Caucasians and are occasionally completely absent [1].
  • We suggest that the CUS-G0S19-3 sequence was generated by recombination between a G0S19-2 gene and a member of a novel CUS-associated gene family [17].
  • Furthermore, it was confirmed that HM145 is a functional receptor for LD78, one of the C-C chemokines, as revealed by the measurement of decrease of cAMP accumulation as well as calcium influx using stable transfectants [18].
  • These data suggest that increased expression of the CCL3L1, CCR3 and CCR5 chemokine-receptors system is involved in brain tumorigenesis, especially in the progression of glioblastoma [12].
  • The same doses of LD78 suppressed the formation of neutrophil, macrophage, and megakaryocytic colonies which were supported by human interleukin-3 and erythropoietin; however, LD78 did not affect colony formation by either non-phagocytic mononuclear cells or sorted CD34+ cells [15].

Analytical, diagnostic and therapeutic context of CCL3L1


  1. Gene copy number regulates the production of the human chemokine CCL3-L1. Townson, J.R., Barcellos, L.F., Nibbs, R.J. Eur. J. Immunol. (2002) [Pubmed]
  2. Genetic variations in the receptor-ligand pair CCR5 and CCL3L1 are important determinants of susceptibility to Kawasaki disease. Burns, J.C., Shimizu, C., Gonzalez, E., Kulkarni, H., Patel, S., Shike, H., Sundel, R.S., Newburger, J.W., Ahuja, S.K. J. Infect. Dis. (2005) [Pubmed]
  3. Susceptibility to HIV/AIDS: an individual characteristic we can measure? Jülg, B., Goebel, F.D. Infection (2005) [Pubmed]
  4. Postgenomic up-regulation of CCL3L1 expression in HTLV-2-infected persons curtails HIV-1 replication. Pilotti, E., Elviri, L., Vicenzi, E., Bertazzoni, U., Re, M.C., Allibardi, S., Poli, G., Casoli, C. Blood (2007) [Pubmed]
  5. Lower copy numbers of the chemokine CCL3L1 gene in patients with chronic hepatitis C. Grünhage, F., Nattermann, J., Gressner, O.A., Wasmuth, H.E., Hellerbrand, C., Sauerbruch, T., Spengler, U., Lammert, F. J. Hepatol. (2010) [Pubmed]
  6. Genetics of resistance to HIV infection: Role of co-receptors and co-receptor ligands. Arenzana-Seisdedos, F., Parmentier, M. Semin. Immunol. (2006) [Pubmed]
  7. Analysis of the CCL3-L1 gene for association with HIV-1 susceptibility and disease progression. Bugeja, M.J., Booth, D.R., Bennetts, B.H., Guerin, J., Kaldor, J.M., Stewart, G.J. AIDS (2004) [Pubmed]
  8. Functional characterization of COM, a DNA region required for cooperation between AP-1 sites in urokinase gene transcription. De Cesare, D., Palazzolo, M., Blasi, F. Oncogene (1996) [Pubmed]
  9. Inhibition of human immunodeficiency virus replication by a dual CCR5/CXCR4 antagonist. Princen, K., Hatse, S., Vermeire, K., Aquaro, S., De Clercq, E., Gerlach, L.O., Rosenkilde, M., Schwartz, T.W., Skerlj, R., Bridger, G., Schols, D. J. Virol. (2004) [Pubmed]
  10. CCL3L1 and CCL4L1 chemokine genes are located in a segmental duplication at chromosome 17q12. Modi, W.S. Genomics (2004) [Pubmed]
  11. Diverse signalling by different chemokines through the chemokine receptor CCR5. Mueller, A., Mahmoud, N.G., Strange, P.G. Biochem. Pharmacol. (2006) [Pubmed]
  12. Up-regulation of CC chemokine, CCL3L1, and receptors, CCR3, CCR5 in human glioblastoma that promotes cell growth. Kouno, J., Nagai, H., Nagahata, T., Onda, M., Yamaguchi, H., Adachi, K., Takahashi, H., Teramoto, A., Emi, M. J. Neurooncol. (2004) [Pubmed]
  13. Chemokine-protease interactions in cancer. Van Damme, J., Struyf, S., Opdenakker, G. Semin. Cancer Biol. (2004) [Pubmed]
  14. T-cell chemotactic activity of cytokine LD78: a comparative study with interleukin-8, a chemotactic factor for the T-cell CD45RA+ phenotype. Tanaka, J., Nomiyama, H., Yamamoto, T., Hamada, F., Kambara, T. Int. Arch. Allergy Immunol. (1993) [Pubmed]
  15. Suppressive effect of LD78 on the proliferation of human hemopoietic progenitors. Shiozaki, H., Ide, T., Nakao, J., Imamura, T., Nakamura, M., Shimada, K., Miura, Y., Suda, T. Jpn. J. Cancer Res. (1992) [Pubmed]
  16. The inhibitory effect of human macrophage inflammatory protein-1 alpha (LD78) on acute myeloid leukemia cells in vitro. Basara, N., Stosić-Grujicić, S., Sefer, D., Ivanović, Z., Antunović, P., Milenković, P. Stem Cells (1996) [Pubmed]
  17. The third human homolog of a murine gene encoding an inhibitor of stem cell proliferation is truncated and linked to a CpG island-containing upstream sequence. Russell, L., Forsdyke, D.R. DNA Cell Biol. (1993) [Pubmed]
  18. Molecular cloning of cDNAs encoding a LD78 receptor and putative leukocyte chemotactic peptide receptors. Nomura, H., Nielsen, B.W., Matsushima, K. Int. Immunol. (1993) [Pubmed]
  19. The normal copy of the G0S19-3-associated, CpG island-containing, upstream sequence is downstream of G0S19-2/MIP1alpha in association with a TRE17 oncogene. Heximer, S.P., Ernst, B.D., Russell, L., Forsdyke, D.R. DNA Cell Biol. (1998) [Pubmed]
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