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Identification
HMDB Protein ID HMDBP01869
Secondary Accession Numbers
  • 7263
Name C-C motif chemokine 2
Synonyms
  1. HC11
  2. MCAF
  3. MCP-1
  4. Monocyte chemoattractant protein 1
  5. Monocyte chemotactic and activating factor
  6. Monocyte chemotactic protein 1
  7. Monocyte secretory protein JE
  8. Small-inducible cytokine A2
Gene Name CCL2
Protein Type Enzyme
Biological Properties
General Function Involved in chemokine activity
Specific Function Chemotactic factor that attracts monocytes and basophils but not neutrophils or eosinophils. Augments monocyte anti-tumor activity. Has been implicated in the pathogenesis of diseases characterized by monocytic infiltrates, like psoriasis, rheumatoid arthritis or atherosclerosis. May be involved in the recruitment of monocytes into the arterial wall during the disease process of atherosclerosis
Pathways Not Available
Reactions Not Available
GO Classification
Component
extracellular region
Function
cytokine activity
chemokine activity
binding
protein binding
receptor binding
Process
immune system process
immune response
Cellular Location
  1. Secreted
Gene Properties
Chromosome Location Chromosome:1
Locus 17q11.2-q12
SNPs CCL2
Gene Sequence
>300 bp
ATGAAAGTCTCTGCCGCCCTTCTGTGCCTGCTGCTCATAGCAGCCACCTTCATTCCCCAA
GGGCTCGCTCAGCCAGATGCAATCAATGCCCCAGTCACCTGCTGTTATAACTTCACCAAT
AGGAAGATCTCAGTGCAGAGGCTCGCGAGCTATAGAAGAATCACCAGCAGCAAGTGTCCC
AAAGAAGCTGTGATCTTCAAGACCATTGTGGCCAAGGAGATCTGTGCTGACCCCAAGCAG
AAGTGGGTTCAGGATTCCATGGACCACCTGGACAAGCAAACCCAAACTCCGAAGACTTGA
Protein Properties
Number of Residues 99
Molecular Weight 11024.9
Theoretical pI 9.72
Pfam Domain Function
Signals
  • 1-23
Transmembrane Regions
  • None
Protein Sequence
>C-C motif chemokine 2
MKVSAALLCLLLIAATFIPQGLAQPDAINAPVTCCYNFTNRKISVQRLASYRRITSSKCP
KEAVIFKTIVAKEICADPKQKWVQDSMDHLDKQTQTPKT
GenBank ID Protein 641145
UniProtKB/Swiss-Prot ID P13500
UniProtKB/Swiss-Prot Entry Name CCL2_HUMAN
PDB IDs
GenBank Gene ID A17786
GeneCard ID CCL2
GenAtlas ID CCL2
HGNC ID HGNC:10618
References
General References
  1. 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. [PubMed:14702039 ]
  2. 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. [PubMed:15489334 ]
  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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed:2518726 ]
  7. 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. [PubMed:2357211 ]
  8. Yoshimura T, Leonard EJ: Human monocyte chemoattractant protein-1 (MCP-1). Adv Exp Med Biol. 1991;305:47-56. [PubMed:1661560 ]
  9. 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. [PubMed:8107690 ]
  10. 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. [PubMed:10918580 ]
  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. [PubMed:2648385 ]
  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. [PubMed:2322286 ]
  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. [PubMed:2071154 ]
  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. [PubMed:8195247 ]
  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. [PubMed:8627182 ]
  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. [PubMed:8898111 ]
  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. [PubMed:9792674 ]
  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. [PubMed:9837883 ]
  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. [PubMed:10587439 ]
  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. [PubMed:10529171 ]
  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. [PubMed:15033992 ]
  22. 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. [PubMed:1857712 ]
  23. 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. [PubMed:8639605 ]
  24. 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. [PubMed:8989326 ]
  25. 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. [PubMed:16352737 ]