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Protein CCL4 PDB 1hum.png
Available structures
PDBOrtholog search: PDBe RCSB
AliasesCCL4, ACT2, AT744.1, G-26, HC21, LAG-1, LAG1, MIP-1-beta, MIP1B, MIP1B1, SCYA2, SCYA4, C-C motif chemokine ligand 4
External IDsOMIM: 182284 MGI: 98261 HomoloGene: 48153 GeneCards: CCL4
Gene location (Human)
Chromosome 17 (human)
Chr.Chromosome 17 (human)[1]
Chromosome 17 (human)
Genomic location for CCL4
Genomic location for CCL4
Band17q12Start36,103,590 bp[1]
End36,105,621 bp[1]
RNA expression pattern
PBB GE CCL4 204103 at fs.png
More reference expression data
RefSeq (mRNA)



RefSeq (protein)



Location (UCSC)Chr 17: 36.1 – 36.11 MbChr 11: 83.66 – 83.66 Mb
PubMed search[3][4]
View/Edit HumanView/Edit Mouse

Chemokine (C-C motif) ligand 4, also known as CCL4, is a protein which in humans is encoded by the CCL4 gene.[5]


CCL4, also known as Macrophage inflammatory protein-1β (MIP-1β) is a CC chemokine with specificity for CCR5 receptors. It is a chemoattractant for natural killer cells, monocytes and a variety of other immune cells.[6]

CCL4 is a major HIV-suppressive factor produced by CD8+ T cells.[7]

Perforin-low memory CD8+ T cells that normally synthesize MIP-1-beta.[8]

CCL4 is produced by: monocytes, B cells, T cells, fibroblasts, endothelial cells, and epithelial cells.[9]

Concentration of this chemokine has been shown to be inversely related with MicroRNA-125b. Concentration of CCL4 within the body increases with age, which may cause chronic inflammation and liver damage.[9][10]


CCL4 has been shown to interact with CCL3.[11]

CCL4 binds to G protein-Coupled Receptors CCR5 and CCR8.[9]

See also[edit]


  1. ^ a b c ENSG00000277943, ENSG00000275302 GRCh38: Ensembl release 89: ENSG00000275824, ENSG00000277943, ENSG00000275302 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000018930 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:".
  4. ^ "Mouse PubMed Reference:".
  5. ^ Irving SG, Zipfel PF, Balke J, McBride OW, Morton CC, Burd PR, Siebenlist U, Kelly K (June 1990). "Two inflammatory mediator cytokine genes are closely linked and variably amplified on chromosome 17q". Nucleic Acids Research. 18 (11): 3261–70. doi:10.1093/nar/18.11.3261. PMC 330932. PMID 1972563.
  6. ^ Bystry RS, Aluvihare V, Welch KA, Kallikourdis M, Betz AG (December 2001). "B cells and professional APCs recruit regulatory T cells via CCL4". Nature Immunology. 2 (12): 1126–32. doi:10.1038/ni735. PMID 11702067.
  7. ^ Cocchi F, DeVico AL, Garzino-Demo A, Arya SK, Gallo RC, Lusso P (December 1995). "Identification of RANTES, MIP-1 alpha, and MIP-1 beta as the major HIV-suppressive factors produced by CD8+ T cells". Science. 270 (5243): 1811–5. doi:10.1126/science.270.5243.1811. PMID 8525373.
  8. ^ Kamin-Lewis R, Abdelwahab SF, Trang C, Baker A, DeVico AL, Gallo RC, Lewis GK (July 2001). "Perforin-low memory CD8+ cells are the predominant T cells in normal humans that synthesize the beta -chemokine macrophage inflammatory protein-1beta". Proceedings of the National Academy of Sciences of the United States of America. 98 (16): 9283–8. doi:10.1073/pnas.161298998. PMC 55412. PMID 11470920.
  9. ^ a b c Morrison MD, Lundquist PG (April 1974). "Labyrinthine morphology and temperature in cryosurgery (guinea pig)". Acta Oto-Laryngologica. 77 (4): 261–73. doi:10.1111/acel.12294. PMC 4364832. PMID 25620312.
  10. ^ Morimoto T, Takagi H, Kondo T (January 1985). "Canine pancreatic allotransplantation with duodenum (pancreaticoduodenal transplantation) using cyclosporin A". Nagoya Journal of Medical Science. 47 (1–2): 57–66. doi:10.1074/jbc.M113.526780. PMC 3887178. PMID 24273171.
  11. ^ Guan E, Wang J, Norcross MA (April 2001). "Identification of human macrophage inflammatory proteins 1alpha and 1beta as a native secreted heterodimer". The Journal of Biological Chemistry. 276 (15): 12404–9. doi:10.1074/jbc.M006327200. PMID 11278300.

Further reading[edit]

  • Menten P, Wuyts A, Van Damme J (December 2002). "Macrophage inflammatory protein-1". Cytokine & Growth Factor Reviews. 13 (6): 455–81. doi:10.1016/S1359-6101(02)00045-X. PMID 12401480.
  • Muthumani K, Desai BM, Hwang DS, Choo AY, Laddy DJ, Thieu KP, Rao RG, Weiner DB (April 2004). "HIV-1 Vpr and anti-inflammatory activity". DNA and Cell Biology. 23 (4): 239–47. doi:10.1089/104454904773819824. PMID 15142381.
  • Conti L, Fantuzzi L, Del Cornò M, Belardelli F, Gessani S (2005). "Immunomodulatory effects of the HIV-1 gp120 protein on antigen presenting cells: implications for AIDS pathogenesis". Immunobiology. 209 (1–2): 99–115. doi:10.1016/j.imbio.2004.02.008. PMID 15481145.
  • Joseph AM, Kumar M, Mitra D (January 2005). "Nef: "necessary and enforcing factor" in HIV infection". Current HIV Research. 3 (1): 87–94. doi:10.2174/1570162052773013. PMID 15638726.
  • Zhao RY, Elder RT (March 2005). "Viral infections and cell cycle G2/M regulation". Cell Research. 15 (3): 143–9. doi:10.1038/ PMID 15780175.
  • Zhao RY, Bukrinsky M, Elder RT (April 2005). "HIV-1 viral protein R (Vpr) & host cellular responses". The Indian Journal of Medical Research. 121 (4): 270–86. PMID 15817944.
  • Li L, Li HS, Pauza CD, Bukrinsky M, Zhao RY (2006). "Roles of HIV-1 auxiliary proteins in viral pathogenesis and host-pathogen interactions". Cell Research. 15 (11–12): 923–34. doi:10.1038/ PMID 16354571.
  • King JE, Eugenin EA, Buckner CM, Berman JW (April 2006). "HIV tat and neurotoxicity". Microbes and Infection. 8 (5): 1347–57. doi:10.1016/j.micinf.2005.11.014. PMID 16697675.
  • Napolitano M, Modi WS, Cevario SJ, Gnarra JR, Seuanez HN, Leonard WJ (September 1991). "The gene encoding the Act-2 cytokine. Genomic structure, HTLV-I/Tax responsiveness of 5' upstream sequences, and chromosomal localization". The Journal of Biological Chemistry. 266 (26): 17531–6. PMID 1894635.
  • Irving SG, Zipfel PF, Balke J, McBride OW, Morton CC, Burd PR, Siebenlist U, Kelly K (June 1990). "Two inflammatory mediator cytokine genes are closely linked and variably amplified on chromosome 17q". Nucleic Acids Research. 18 (11): 3261–70. doi:10.1093/nar/18.11.3261. PMC 330932. PMID 1972563.
  • Baixeras E, Roman-Roman S, Jitsukawa S, Genevee C, Mechiche S, Viegas-Pequignot E, Hercend T, Triebel F (November 1990). "Cloning and expression of a lymphocyte activation gene (LAG-1)". Molecular Immunology. 27 (11): 1091–102. doi:10.1016/0161-5890(90)90097-J. PMID 2247088.
  • Lipes MA, Napolitano M, Jeang KT, Chang NT, Leonard WJ (December 1988). "Identification, cloning, and characterization of an immune activation gene". Proceedings of the National Academy of Sciences of the United States of America. 85 (24): 9704–8. doi:10.1073/pnas.85.24.9704. PMC 282843. PMID 2462251.
  • Brown KD, Zurawski SM, Mosmann TR, Zurawski G (January 1989). "A family of small inducible proteins secreted by leukocytes are members of a new superfamily that includes leukocyte and fibroblast-derived inflammatory agents, growth factors, and indicators of various activation processes". Journal of Immunology. 142 (2): 679–87. PMID 2521353.
  • Zipfel PF, Balke J, Irving SG, Kelly K, Siebenlist U (March 1989). "Mitogenic activation of human T cells induces two closely related genes which share structural similarities with a new family of secreted factors". Journal of Immunology. 142 (5): 1582–90. PMID 2521882.
  • Chang HC, Reinherz EL (June 1989). "Isolation and characterization of a cDNA encoding a putative cytokine which is induced by stimulation via the CD2 structure on human T lymphocytes". European Journal of Immunology. 19 (6): 1045–51. doi:10.1002/eji.1830190614. PMID 2568930.
  • Miller MD, Hata S, De Waal Malefyt R, Krangel MS (November 1989). "A novel polypeptide secreted by activated human T lymphocytes". Journal of Immunology. 143 (9): 2907–16. PMID 2809212.
  • Adams MD, Kerlavage AR, Fleischmann RD, Fuldner RA, Bult CJ, Lee NH, Kirkness EF, Weinstock KG, Gocayne JD, White O (September 1995). "Initial assessment of human gene diversity and expression patterns based upon 83 million nucleotides of cDNA sequence" (PDF). Nature. 377 (6547 Suppl): 3–174. PMID 7566098.
  • Post TW, Bozic CR, Rothenberg ME, Luster AD, Gerard N, Gerard C (December 1995). "Molecular characterization of two murine eosinophil beta chemokine receptors". Journal of Immunology. 155 (11): 5299–305. PMID 7594543.
  • Combadiere C, Ahuja SK, Murphy PM (July 1995). "Cloning and functional expression of a human eosinophil CC chemokine receptor". The Journal of Biological Chemistry. 270 (28): 16491–4. doi:10.1074/jbc.270.28.16491. PMID 7622448.
  • Paolini JF, Willard D, Consler T, Luther M, Krangel MS (September 1994). "The chemokines IL-8, monocyte chemoattractant protein-1, and I-309 are monomers at physiologically relevant concentrations". Journal of Immunology. 153 (6): 2704–17. PMID 8077676.

External links[edit]