C-C motif chemokine 2

Details

Name
C-C motif chemokine 2
Synonyms
  • HC11
  • 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 Name
CCL2
UniProtKB Entry
P13500Swiss-Prot
Organism
Humans
NCBI Taxonomy ID
9606
Amino acid sequence
>lcl|BSEQ0010732|C-C motif chemokine 2
MKVSAALLCLLLIAATFIPQGLAQPDAINAPVTCCYNFTNRKISVQRLASYRRITSSKCP
KEAVIFKTIVAKEICADPKQKWVQDSMDHLDKQTQTPKT
Number of residues
99
Molecular Weight
11024.87
Theoretical pI
9.72
GO Classification
Functions
CCR2 chemokine receptor binding / chemokine activity / protein kinase activity
Processes
angiogenesis / astrocyte cell migration / cell adhesion / cell surface receptor signaling pathway / cellular homeostasis / cellular response to fibroblast growth factor stimulus / cellular response to interleukin-1 / cellular response to lipopolysaccharide / cellular response to tumor necrosis factor / chemokine-mediated signaling pathway / chemotaxis / cytokine-mediated signaling pathway / cytoskeleton organization / eosinophil chemotaxis / helper T cell extravasation / humoral immune response / inflammatory response / macrophage chemotaxis / monocyte chemotaxis / negative regulation of glial cell apoptotic process / negative regulation of natural killer cell chemotaxis / negative regulation of neuron apoptotic process / positive regulation of apoptotic cell clearance / positive regulation of calcium ion import / positive regulation of nitric-oxide synthase biosynthetic process / positive regulation of T cell activation / protein phosphorylation / regulation of cell shape / response to bacterium / signal transduction / viral genome replication
Components
extracellular region / extracellular space
General Function
Acts as a ligand for C-C chemokine receptor CCR2 (PubMed:10529171, PubMed:10587439, PubMed:9837883). Signals through binding and activation of CCR2 and induces a strong chemotactic response and mobilization of intracellular calcium ions (PubMed:10587439, PubMed:9837883). Exhibits a chemotactic activity for monocytes and basophils but not neutrophils or eosinophils (PubMed:8195247, PubMed:8627182, PubMed:9792674). May be involved in the recruitment of monocytes into the arterial wall during the disease process of atherosclerosis (PubMed:8107690)
Specific Function
Ccr chemokine receptor binding
Pfam Domain Function
Signal Regions
1-23
Transmembrane Regions
Not Available
Cellular Location
Secreted
Gene sequence
>lcl|BSEQ0010733|C-C motif chemokine 2 (CCL2)
ATGAAAGTCTCTGCCGCCCTTCTGTGCCTGCTGCTCATAGCAGCCACCTTCATTCCCCAA
GGGCTCGCTCAGCCAGATGCAATCAATGCCCCAGTCACCTGCTGTTATAACTTCACCAAT
AGGAAGATCTCAGTGCAGAGGCTCGCGAGCTATAGAAGAATCACCAGCAGCAAGTGTCCC
AAAGAAGCTGTGATCTTCAAGACCATTGTGGCCAAGGAGATCTGTGCTGACCCCAAGCAG
AAGTGGGTTCAGGATTCCATGGACCACCTGGACAAGCAAACCCAAACTCCGAAGACTTGA
Chromosome Location
17
Locus
17q12
External Identifiers
ResourceLink
UniProtKB IDP13500
UniProtKB Entry NameCCL2_HUMAN
GenBank Protein ID307163
GenBank Gene IDM24545
GeneCard IDCCL2
GenAtlas IDCCL2
HGNC IDHGNC:10618
PDB ID(s)1DOK, 1DOL, 1DOM, 1DON, 1ML0, 2BDN, 2NZ1, 3IFD, 4DN4, 4R8I, 4ZK9, 7SO0, 7XA3, 8FJ0
KEGG IDhsa:6347
NCBI Gene ID6347
General References
  1. 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. [Article]
  2. 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. [Article]
  3. 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. [Article]
  4. 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. [Article]
  5. 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. [Article]
  6. Yoshimura T, Leonard EJ: Human monocyte chemoattractant protein-1 (MCP-1). Adv Exp Med Biol. 1991;305:47-56. [Article]
  7. 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. [Article]
  8. 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. [Article]
  9. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. [Article]
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  11. 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. [Article]
  12. 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. [Article]
  13. 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. [Article]
  14. 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. [Article]
  15. 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. [Article]
  16. 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. [Article]
  17. 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. [Article]
  18. 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. [Article]
  19. 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. [Article]
  20. 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. [Article]
  21. 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. [Article]
  22. 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. [Article]
  23. 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. [Article]
  24. 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. [Article]
  25. 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. [Article]
  26. 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. [Article]

Associated Data

Bio-Entities
Bio-EntityType
C-C motif chemokine 2 (Humans)protein
primary
Drug Relations
DrugDrug groupPharmacological action?TypeActionsDetails
MimosineexperimentalyestargetinhibitorDetails
DanazolapprovedunknowntargetinhibitorDetails
Chondroitin sulfateapproved, investigational, nutraceuticalunknowntargetDetails
BindaritinvestigationalyestargetinhibitorDetails