C-C motif chemokine 2


NameC-C motif chemokine 2
SynonymsHC11 MCAF MCP-1 MCP1 Monocyte chemoattractant protein 1 Monocyte chemotactic and activating factor Monocyte chemotactic protein 1 Monocyte secretory protein JE SCYA2 Small-inducible cytokine A2
Gene NameCCL2
OrganismHuman
Amino acid sequence
>lcl|BSEQ0010732|C-C motif chemokine 2
MKVSAALLCLLLIAATFIPQGLAQPDAINAPVTCCYNFTNRKISVQRLASYRRITSSKCP
KEAVIFKTIVAKEICADPKQKWVQDSMDHLDKQTQTPKT
Number of residues99
Molecular Weight11024.87
Theoretical pI9.72
GO Classification
Functions
    heparin binding
    receptor binding
    chemokine activity
    CCR2 chemokine receptor binding
    protein kinase activity
Processes
    negative regulation of glial cell apoptotic process
    chemotaxis
    cellular response to platelet-derived growth factor stimulus
    negative regulation of neuron apoptotic process
    response to bacterium
    cell adhesion
    cellular response to ATP
    cellular homeostasis
    negative regulation of natural killer cell chemotaxis
    positive regulation of calcium ion import
    organ morphogenesis
    cellular response to organic cyclic compound
    positive regulation of GTPase activity
    cellular response to high density lipoprotein particle stimulus
    positive regulation of apoptotic cell clearance
    cellular response to fibroblast growth factor stimulus
    positive regulation of ERK1 and ERK2 cascade
    response to gamma radiation
    G-protein coupled receptor signaling pathway
    response to antibiotic
    protein kinase B signaling
    cellular response to interferon-gamma
    positive regulation of cellular extravasation
    cellular response to retinoic acid
    response to mechanical stimulus
    JAK-STAT cascade
    positive regulation of synaptic transmission
    cell surface receptor signaling pathway
    angiogenesis
    cellular response to interleukin-6
    monocyte chemotaxis
    positive regulation of immune complex clearance by monocytes and macrophages
    cellular response to tumor necrosis factor
    endoplasmic reticulum unfolded protein response
    maternal process involved in parturition
    positive regulation of collagen biosynthetic process
    viral genome replication
    cellular response to insulin stimulus
    eosinophil chemotaxis
    response to heat
    positive regulation of leukocyte mediated cytotoxicity
    cellular protein metabolic process
    PERK-mediated unfolded protein response
    cellular response to macrophage colony-stimulating factor stimulus
    response to wounding
    helper T cell extravasation
    positive regulation of macrophage chemotaxis
    MAPK cascade
    response to amino acid
    chemokine-mediated signaling pathway
    neutrophil chemotaxis
    cellular response to lipopolysaccharide
    aging
    leukocyte migration involved in inflammatory response
    positive regulation of nitric-oxide synthase biosynthetic process
    protein phosphorylation
    cellular response to drug
    positive regulation of tumor necrosis factor production
    cytoskeleton organization
    humoral immune response
    cytokine-mediated signaling pathway
    cellular response to dexamethasone stimulus
    lymphocyte chemotaxis
    organ regeneration
    positive regulation of T cell activation
    response to hypoxia
    positive regulation of monocyte chemotaxis
    response to activity
    cellular response to interleukin-1
    inflammatory response
    cellular calcium ion homeostasis
    maternal process involved in female pregnancy
    macrophage chemotaxis
    response to progesterone
    regulation of vascular endothelial growth factor production
    vascular endothelial growth factor receptor signaling pathway
    transforming growth factor beta receptor signaling pathway
    G-protein coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger
    signal transduction
    regulation of cell shape
    lipopolysaccharide-mediated signaling pathway
    positive regulation of endothelial cell proliferation
    negative regulation of angiogenesis
    positive regulation of protein targeting to membrane
    response to vitamin B3
    response to ethanol
    astrocyte cell migration
Components
    dendrite
    perinuclear region of cytoplasm
    synapse
    extracellular region
    endocytic vesicle
    rough endoplasmic reticulum
    extracellular space
    C-fiber
    axon terminus
    perikaryon
General FunctionNone
Specific FunctionNone
Transmembrane Regions
GenBank Protein ID307163
UniProtKB IDP13500
UniProtKB Entry NameCCL2_HUMAN
Cellular LocationSecreted
Gene sequence
>lcl|BSEQ0010733|C-C motif chemokine 2 (CCL2)
ATGAAAGTCTCTGCCGCCCTTCTGTGCCTGCTGCTCATAGCAGCCACCTTCATTCCCCAA
GGGCTCGCTCAGCCAGATGCAATCAATGCCCCAGTCACCTGCTGTTATAACTTCACCAAT
AGGAAGATCTCAGTGCAGAGGCTCGCGAGCTATAGAAGAATCACCAGCAGCAAGTGTCCC
AAAGAAGCTGTGATCTTCAAGACCATTGTGGCCAAGGAGATCTGTGCTGACCCCAAGCAG
AAGTGGGTTCAGGATTCCATGGACCACCTGGACAAGCAAACCCAAACTCCGAAGACTTGA
GenBank Gene IDM24545
GeneCard IDNone
GenAtlas IDCCL2
HGNC IDHGNC:10618
Chromosome LocationNone
Locus17q11.2-q12
References
  1. Shyy YJ, Li YS, Kolattukudy PE: Structure of human monocyte chemotactic protein gene and its regulation by TPA. Biochem Biophys Res Commun. 1990 Jun 15;169(2):346-51.[2357211 ]
  2. Yoshimura T, Leonard EJ: Human monocyte chemoattractant protein-1 (MCP-1). Adv Exp Med Biol. 1991;305:47-56.[1661560 ]
  3. Furutani Y, Nomura H, Notake M, Oyamada Y, Fukui T, Yamada M, Larsen CG, Oppenheim JJ, Matsushima K: Cloning and sequencing of the cDNA for human monocyte chemotactic and activating factor (MCAF). Biochem Biophys Res Commun. 1989 Feb 28;159(1):249-55.[2923622 ]
  4. Rollins BJ, Stier P, Ernst T, Wong GG: The human homolog of the JE gene encodes a monocyte secretory protein. Mol Cell Biol. 1989 Nov;9(11):4687-95.[2513477 ]
  5. Yoshimura T, Yuhki N, Moore SK, Appella E, Lerman MI, Leonard EJ: Human monocyte chemoattractant protein-1 (MCP-1). Full-length cDNA cloning, expression in mitogen-stimulated blood mononuclear leukocytes, and sequence similarity to mouse competence gene JE. FEBS Lett. 1989 Feb 27;244(2):487-93.[2465924 ]
  6. Chang HC, Hsu F, Freeman GJ, Griffin JD, Reinherz EL: Cloning and expression of a gamma-interferon-inducible gene in monocytes: a new member of a cytokine gene family. Int Immunol. 1989;1(4):388-97.[2518726 ]
  7. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7.[15489334 ]
  8. Robinson EA, Yoshimura T, Leonard EJ, Tanaka S, Griffin PR, Shabanowitz J, Hunt DF, Appella E: Complete amino acid sequence of a human monocyte chemoattractant, a putative mediator of cellular immune reactions. Proc Natl Acad Sci U S A. 1989 Mar;86(6):1850-4.[2648385 ]
  9. Decock B, Conings R, Lenaerts JP, Billiau A, Van Damme J: Identification of the monocyte chemotactic protein from human osteosarcoma cells and monocytes: detection of a novel N-terminally processed form. Biochem Biophys Res Commun. 1990 Mar 30;167(3):904-9.[2322286 ]
  10. Rollins BJ, Morton CC, Ledbetter DH, Eddy RL Jr, Shows TB: Assignment of the human small inducible cytokine A2 gene, SCYA2 (encoding JE or MCP-1), to 17q11.2-12: evolutionary relatedness of cytokines clustered at the same locus. Genomics. 1991 Jun;10(2):489-92.[2071154 ]
  11. Zhang YJ, Rutledge BJ, Rollins BJ: Structure/activity analysis of human monocyte chemoattractant protein-1 (MCP-1) by mutagenesis. Identification of a mutated protein that inhibits MCP-1-mediated monocyte chemotaxis. J Biol Chem. 1994 Jun 3;269(22):15918-24.[8195247 ]
  12. Weber M, Uguccioni M, Baggiolini M, Clark-Lewis I, Dahinden CA: Deletion of the NH2-terminal residue converts monocyte chemotactic protein 1 from an activator of basophil mediator release to an eosinophil chemoattractant. J Exp Med. 1996 Feb 1;183(2):681-5.[8627182 ]
  13. Kim KS, Rajarathnam K, Clark-Lewis I, Sykes BD: Structural characterization of a monomeric chemokine: monocyte chemoattractant protein-3. FEBS Lett. 1996 Oct 21;395(2-3):277-82.[8898111 ]
  14. Chakravarty L, Rogers L, Quach T, Breckenridge S, Kolattukudy PE: Lysine 58 and histidine 66 at the C-terminal alpha-helix of monocyte chemoattractant protein-1 are essential for glycosaminoglycan binding. J Biol Chem. 1998 Nov 6;273(45):29641-7.[9792674 ]
  15. Paavola CD, Hemmerich S, Grunberger D, Polsky I, Bloom A, Freedman R, Mulkins M, Bhakta S, McCarley D, Wiesent L, Wong B, Jarnagin K, Handel TM: Monomeric monocyte chemoattractant protein-1 (MCP-1) binds and activates the MCP-1 receptor CCR2B. J Biol Chem. 1998 Dec 11;273(50):33157-65.[9837883 ]
  16. Jarnagin K, Grunberger D, Mulkins M, Wong B, Hemmerich S, Paavola C, Bloom A, Bhakta S, Diehl F, Freedman R, McCarley D, Polsky I, Ping-Tsou A, Kosaka A, Handel TM: Identification of surface residues of the monocyte chemotactic protein 1 that affect signaling through the receptor CCR2. Biochemistry. 1999 Dec 7;38(49):16167-77.[10587439 ]
  17. Hemmerich S, Paavola C, Bloom A, Bhakta S, Freedman R, Grunberger D, Krstenansky J, Lee S, McCarley D, Mulkins M, Wong B, Pease J, Mizoue L, Mirzadegan T, Polsky I, Thompson K, Handel TM, Jarnagin K: Identification of residues in the monocyte chemotactic protein-1 that contact the MCP-1 receptor, CCR2. Biochemistry. 1999 Oct 5;38(40):13013-25.[10529171 ]
  18. Lau EK, Paavola CD, Johnson Z, Gaudry JP, Geretti E, Borlat F, Kungl AJ, Proudfoot AE, Handel TM: Identification of the glycosaminoglycan binding site of the CC chemokine, MCP-1: implications for structure and function in vivo. J Biol Chem. 2004 May 21;279(21):22294-305. Epub 2004 Mar 18.[15033992 ]
  19. Ueno M, Shen WJ, Patel S, Greenberg AS, Azhar S, Kraemer FB: Fat-specific protein 27 modulates nuclear factor of activated T cells 5 and the cellular response to stress. J Lipid Res. 2013 Mar;54(3):734-43. doi: 10.1194/jlr.M033365. Epub 2012 Dec 11.[23233732 ]
  20. Gronenborn AM, Clore GM: Modeling the three-dimensional structure of the monocyte chemo-attractant and activating protein MCAF/MCP-1 on the basis of the solution structure of interleukin-8. Protein Eng. 1991 Feb;4(3):263-9.[1857712 ]
  21. Flores-Villanueva PO, Ruiz-Morales JA, Song CH, Flores LM, Jo EK, Montano M, Barnes PF, Selman M, Granados J: A functional promoter polymorphism in monocyte chemoattractant protein-1 is associated with increased susceptibility to pulmonary tuberculosis. J Exp Med. 2005 Dec 19;202(12):1649-58. Epub 2005 Dec 13.[16352737 ]
  22. Li YS, Shyy YJ, Wright JG, Valente AJ, Cornhill JF, Kolattukudy PE: The expression of monocyte chemotactic protein (MCP-1) in human vascular endothelium in vitro and in vivo. Mol Cell Biochem. 1993 Sep 8;126(1):61-8.[8107690 ]
  23. Finzer P, Soto U, Delius H, Patzelt A, Coy JF, Poustka A, zur Hausen H, Rosl F: Differential transcriptional regulation of the monocyte-chemoattractant protein-1 (MCP-1) gene in tumorigenic and non-tumorigenic HPV 18 positive cells: the role of the chromatin structure and AP-1 composition. Oncogene. 2000 Jul 6;19(29):3235-44.[10918580 ]
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  25. Handel TM, Domaille PJ: Heteronuclear (1H, 13C, 15N) NMR assignments and solution structure of the monocyte chemoattractant protein-1 (MCP-1) dimer. Biochemistry. 1996 May 28;35(21):6569-84.[8639605 ]
  26. Lubkowski J, Bujacz G, Boque L, Domaille PJ, Handel TM, Wlodawer A: The structure of MCP-1 in two crystal forms provides a rare example of variable quaternary interactions. Nat Struct Biol. 1997 Jan;4(1):64-9.[8989326 ]

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FRCD ID Name Exact Mass Structure



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Spiroxamine




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