CCL2_HUMAN
ID CCL2_HUMAN Reviewed; 99 AA.
AC P13500; B2R4V3; Q9UDF3;
DT 01-JAN-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1990, sequence version 1.
DT 03-AUG-2022, entry version 245.
DE RecName: Full=C-C motif chemokine 2;
DE AltName: Full=HC11;
DE AltName: Full=Monocyte chemoattractant protein 1;
DE AltName: Full=Monocyte chemotactic and activating factor;
DE Short=MCAF;
DE AltName: Full=Monocyte chemotactic protein 1;
DE Short=MCP-1;
DE AltName: Full=Monocyte secretory protein JE;
DE AltName: Full=Small-inducible cytokine A2;
DE Flags: Precursor;
GN Name=CCL2; Synonyms=MCP1, SCYA2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2923622; DOI=10.1016/0006-291x(89)92430-3;
RA Furutani Y., Nomura H., Notake M., Oyamada Y., Fukui T., Yamada M.,
RA Larsen C.G., Oppenheim J.J., Matsushima K.;
RT "Cloning and sequencing of the cDNA for human monocyte chemotactic and
RT activating factor (MCAF).";
RL Biochem. Biophys. Res. Commun. 159:249-255(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], SUBCELLULAR LOCATION,
RP GLYCOSYLATION, AND TISSUE SPECIFICITY.
RX PubMed=2513477; DOI=10.1128/mcb.9.11.4687-4695.1989;
RA Rollins B.J., Stier P., Ernst T., Wong G.G.;
RT "The human homolog of the JE gene encodes a monocyte secretory protein.";
RL Mol. Cell. Biol. 9:4687-4695(1989).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Glial tumor;
RX PubMed=2465924; DOI=10.1016/0014-5793(89)80590-3;
RA Yoshimura T., Yuhki N., Moore S.K., Appella E., Lerman M.I., Leonard E.J.;
RT "Human monocyte chemoattractant protein-1 (MCP-1). Full-length cDNA
RT cloning, expression in mitogen-stimulated blood mononuclear leukocytes, and
RT sequence similarity to mouse competence gene JE.";
RL FEBS Lett. 244:487-493(1989).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2518726; DOI=10.1093/intimm/1.4.388;
RA Chang H.C., Hsu F., Freeman G.J., Griffin J.D., Reinherz E.L.;
RT "Cloning and expression of a gamma-interferon-inducible gene in monocytes:
RT a new member of a cytokine gene family.";
RL Int. Immunol. 1:388-397(1989).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2357211; DOI=10.1016/0006-291x(90)90338-n;
RA Shyy Y.J., Li Y.S., Kolattukudy P.E.;
RT "Structure of human monocyte chemotactic protein gene and its regulation by
RT TPA.";
RL Biochem. Biophys. Res. Commun. 169:346-351(1990).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=1661560; DOI=10.1007/978-1-4684-6009-4_6;
RA Yoshimura T., Leonard E.J.;
RT "Human monocyte chemoattractant protein-1 (MCP-1).";
RL Adv. Exp. Med. Biol. 305:47-56(1991).
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA], AND FUNCTION.
RX PubMed=8107690; DOI=10.1007/bf01772208;
RA Li Y.S., Shyy Y.J., Wright J.G., Valente A.J., Cornhill J.F.,
RA Kolattukudy P.E.;
RT "The expression of monocyte chemotactic protein (MCP-1) in human vascular
RT endothelium in vitro and in vivo.";
RL Mol. Cell. Biochem. 126:61-68(1993).
RN [8]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=10918580; DOI=10.1038/sj.onc.1203643;
RA Finzer P., Soto U., Delius H., Patzelt A., Poustka A., Coy J.F.,
RA zur Hausen H., Roesl F.;
RT "Differential transcriptional regulation of the monocyte-chemoattractant
RT protein-1 (MCP-1) gene in tumorigenic and non-tumorigenic HPV 18 positive
RT cells: the role of the chromatin structure and AP-1 composition.";
RL Oncogene 19:3235-3244(2000).
RN [9]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Caput D., Ferrara P., Miloux B., Minty A., Vita N.;
RT "Protein with cytokine activity, recombinant DNA, expression vector and
RT hosts for obtaining it.";
RL Patent number EP0488900, 03-JUN-1992.
RN [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [11]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RG SeattleSNPs variation discovery resource;
RL Submitted (JUN-2002) to the EMBL/GenBank/DDBJ databases.
RN [12]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Urinary bladder;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [13]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [14]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Pancreas;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [15]
RP PROTEIN SEQUENCE OF 24-99, AND PYROGLUTAMATE FORMATION AT GLN-24.
RX PubMed=2648385; DOI=10.1073/pnas.86.6.1850;
RA Robinson E.A., Yoshimura T., Leonard E.J., Tanaka S., Griffin P.R.,
RA Shabanowitz J., Hunt D.F., Appella E.;
RT "Complete amino acid sequence of a human monocyte chemoattractant, a
RT putative mediator of cellular immune reactions.";
RL Proc. Natl. Acad. Sci. U.S.A. 86:1850-1854(1989).
RN [16]
RP PROTEIN SEQUENCE OF 29-53 AND 82-92.
RX PubMed=2322286; DOI=10.1016/0006-291x(90)90609-q;
RA Decock B., Conings R., Lenaerts J.-P., Biliau A., van Damme J.;
RT "Identification of the monocyte chemotactic protein from human osteosarcoma
RT cells and monocytes: detection of a novel N-terminally processed form.";
RL Biochem. Biophys. Res. Commun. 167:904-909(1990).
RN [17]
RP GENE STRUCTURE.
RX PubMed=2071154; DOI=10.1016/0888-7543(91)90338-f;
RA Rollins B.J., Morton C.C., Ledbetter D.H., Eddy R.L. Jr., Shows T.B.;
RT "Assignment of the human small inducible cytokine A2 gene, SCYA2 (encoding
RT JE or MCP-1), to 17q11.2-12: evolutionary relatedness of cytokines
RT clustered at the same locus.";
RL Genomics 10:489-492(1991).
RN [18]
RP FUNCTION, AND MUTAGENESIS.
RX PubMed=8195247; DOI=10.1016/s0021-9258(17)40768-x;
RA Zhang Y.J., Rutledge B.J., Rollins B.J.;
RT "Structure/activity analysis of human monocyte chemoattractant protein-1
RT (MCP-1) by mutagenesis. Identification of a mutated protein that inhibits
RT MCP-1-mediated monocyte chemotaxis.";
RL J. Biol. Chem. 269:15918-15924(1994).
RN [19]
RP FUNCTION, AND EFFECT OF DELETION OF N-TERMINAL RESIDUES.
RX PubMed=8627182; DOI=10.1084/jem.183.2.681;
RA Weber M., Uguccioni M., Baggiolini M., Clark-Lewis I., Dahinden C.A.;
RT "Deletion of the NH2-terminal residue converts monocyte chemotactic protein
RT 1 from an activator of basophil mediator release to an eosinophil
RT chemoattractant.";
RL J. Exp. Med. 183:681-685(1996).
RN [20]
RP SUBUNIT.
RX PubMed=8898111; DOI=10.1016/0014-5793(96)01024-1;
RA Kim K.-S., Rajarathnam K., Clark-Lewis I., Sykes B.D.;
RT "Structural characterization of a monomeric chemokine: monocyte
RT chemoattractant protein-3.";
RL FEBS Lett. 395:277-282(1996).
RN [21]
RP FUNCTION, GAG BINDING SITES LYS-81 AND HIS-89, AND MUTAGENESIS OF LYS-81;
RP HIS-89 AND 95-GLN--THR-99.
RX PubMed=9792674; DOI=10.1074/jbc.273.45.29641;
RA Chakravarty L., Rogers L., Quach T., Breckenridge S., Kolattukudy P.E.;
RT "Lysine 58 and histidine 66 at the C-terminal alpha-helix of monocyte
RT chemoattractant protein-1 are essential for glycosaminoglycan binding.";
RL J. Biol. Chem. 273:29641-29647(1998).
RN [22]
RP FUNCTION, HOMODIMERIZATION, AND MUTAGENESIS OF PRO-31; VAL-32; THR-33 AND
RP TYR-36.
RX PubMed=9837883; DOI=10.1074/jbc.273.50.33157;
RA Paavola C.D., Hemmerich S., Grunberger D., Polsky I., Bloom A.,
RA Freedman R., Mulkins M., Bhakta S., McCarley D., Wiesent L., Wong B.,
RA Jarnagin K., Handel T.M.;
RT "Monomeric monocyte chemoattractant protein-1 (MCP-1) binds and activates
RT the MCP-1 receptor CCR2B.";
RL J. Biol. Chem. 273:33157-33165(1998).
RN [23]
RP FUNCTION, AND MUTAGENESIS OF 25-PRO--PRO-31; ASP-26; ILE-28; ASN-29;
RP PRO-31; VAL-32 AND THR-33.
RX PubMed=10587439; DOI=10.1021/bi9912239;
RA Jarnagin K., Grunberger D., Mulkins M., Wong B., Hemmerich S., Paavola C.,
RA Bloom A., Bhakta S., Diehl F., Freedman R., McCarley D., Polsky I.,
RA Ping-Tsou A., Kosaka A., Handel T.M.;
RT "Identification of surface residues of the monocyte chemotactic protein 1
RT that affect signaling through the receptor CCR2.";
RL Biochemistry 38:16167-16177(1999).
RN [24]
RP FUNCTION, IMPORTANCE OF TYR-36; ARG-47; LYS-58; LYS-61 AND LYS-72 FOR
RP RECEPTOR BINDING, AND MUTAGENESIS.
RX PubMed=10529171; DOI=10.1021/bi991029m;
RA Hemmerich S., Paavola C., Bloom A., Bhakta S., Freedman R., Grunberger D.,
RA Krstenansky J., Lee S., McCarley D., Mulkins M., Wong B., Pease J.,
RA Mizoue L., Mirzadegan T., Polsky I., Thompson K., Handel T.M., Jarnagin K.;
RT "Identification of residues in the monocyte chemotactic protein-1 that
RT contact the MCP-1 receptor, CCR2.";
RL Biochemistry 38:13013-13025(1999).
RN [25]
RP GAG BINDING SITES ARG-41; LYS-42 AND ARG-47, MUTAGENESIS, AND SUBUNIT.
RX PubMed=15033992; DOI=10.1074/jbc.m311224200;
RA Lau E.K., Paavola C.D., Johnson Z., Gaudry J.-P., Geretti E., Borlat F.,
RA Kungl A.J., Proudfoot A.E., Handel T.M.;
RT "Identification of the glycosaminoglycan binding site of the CC chemokine,
RT MCP-1: implications for structure and function in vivo.";
RL J. Biol. Chem. 279:22294-22305(2004).
RN [26]
RP INDUCTION BY OSMOTIC STRESS.
RX PubMed=23233732; DOI=10.1194/jlr.m033365;
RA Ueno M., Shen W.J., Patel S., Greenberg A.S., Azhar S., Kraemer F.B.;
RT "Fat-specific protein 27 modulates nuclear factor of activated T cells 5
RT and the cellular response to stress.";
RL J. Lipid Res. 54:734-743(2013).
RN [27]
RP SUBCELLULAR LOCATION, AND INDUCTION BY IL1B.
RX PubMed=23955712; DOI=10.1038/nm.3265;
RA Jourdan T., Godlewski G., Cinar R., Bertola A., Szanda G., Liu J., Tam J.,
RA Han T., Mukhopadhyay B., Skarulis M.C., Ju C., Aouadi M., Czech M.P.,
RA Kunos G.;
RT "Activation of the Nlrp3 inflammasome in infiltrating macrophages by
RT endocannabinoids mediates beta cell loss in type 2 diabetes.";
RL Nat. Med. 19:1132-1140(2013).
RN [28]
RP TISSUE SPECIFICITY.
RX PubMed=23765988; DOI=10.1002/jcp.24418;
RA Caballero-Campo P., Buffone M.G., Benencia F., Conejo-Garcia J.R.,
RA Rinaudo P.F., Gerton G.L.;
RT "A role for the chemokine receptor CCR6 in mammalian sperm motility and
RT chemotaxis.";
RL J. Cell. Physiol. 229:68-78(2014).
RN [29]
RP 3D-STRUCTURE MODELING.
RX PubMed=1857712; DOI=10.1093/protein/4.3.263;
RA Gronenborn A.M., Clore G.M.;
RT "Modeling the three-dimensional structure of the monocyte chemo-attractant
RT and activating protein MCAF/MCP-1 on the basis of the solution structure of
RT interleukin-8.";
RL Protein Eng. 4:263-269(1991).
RN [30]
RP STRUCTURE BY NMR.
RX PubMed=8639605; DOI=10.1021/bi9602270;
RA Handel T.M., Domaille P.J.;
RT "Heteronuclear (1H, 13C, 15N) NMR assignments and solution structure of the
RT monocyte chemoattractant protein-1 (MCP-1) dimer.";
RL Biochemistry 35:6569-6584(1996).
RN [31]
RP X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS), AND SUBUNIT.
RX PubMed=8989326; DOI=10.1038/nsb0197-64;
RA Lubkowski J., Bujacz G., Domaille P.J., Handel T.M., Wlodawer A.;
RT "The structure of MCP-1 in two crystal forms provides a rare example of
RT variable quaternary interactions.";
RL Nat. Struct. Biol. 4:64-69(1997).
RN [32]
RP INVOLVEMENT IN MYCOBACTERIUM TUBERCULOSIS SUSCEPTIBILITY.
RX PubMed=16352737; DOI=10.1084/jem.20050126;
RA Flores-Villanueva P.O., Ruiz-Morales J.A., Song C.-H., Flores L.M.,
RA Jo E.-K., Montano M., Barnes P.F., Selman M., Granados J.;
RT "A functional promoter polymorphism in monocyte chemoattractant protein-1
RT is associated with increased susceptibility to pulmonary tuberculosis.";
RL J. Exp. Med. 202:1649-1658(2005).
RN [33]
RP INTERACTION WITH TNFAIP6, AND MUTAGENESIS OF 41-ARG-LYS-42.
RX PubMed=27044744; DOI=10.1074/jbc.m116.720953;
RA Dyer D.P., Salanga C.L., Johns S.C., Valdambrini E., Fuster M.M.,
RA Milner C.M., Day A.J., Handel T.M.;
RT "The Anti-inflammatory Protein TSG-6 Regulates Chemokine Function by
RT Inhibiting Chemokine/Glycosaminoglycan Interactions.";
RL J. Biol. Chem. 291:12627-12640(2016).
CC -!- FUNCTION: Acts as a ligand for C-C chemokine receptor CCR2
CC (PubMed:9837883, PubMed:10587439, PubMed:10529171). Signals through
CC binding and activation of CCR2 and induces a strong chemotactic
CC response and mobilization of intracellular calcium ions
CC (PubMed:9837883, PubMed:10587439). Exhibits a chemotactic activity for
CC monocytes and basophils but not neutrophils or eosinophils
CC (PubMed:8627182, PubMed:9792674, PubMed:8195247). May be involved in
CC the recruitment of monocytes into the arterial wall during the disease
CC process of atherosclerosis (PubMed:8107690).
CC {ECO:0000269|PubMed:10529171, ECO:0000269|PubMed:10587439,
CC ECO:0000269|PubMed:8107690, ECO:0000269|PubMed:8195247,
CC ECO:0000269|PubMed:8627182, ECO:0000269|PubMed:9792674,
CC ECO:0000269|PubMed:9837883}.
CC -!- SUBUNIT: Monomer or homodimer; in equilibrium (PubMed:8898111,
CC PubMed:9837883, PubMed:15033992, PubMed:8989326). Is tethered on
CC endothelial cells by glycosaminoglycan (GAG) side chains of
CC proteoglycans (PubMed:9792674). Interacts with TNFAIP6 (via Link
CC domain). {ECO:0000269|PubMed:15033992, ECO:0000269|PubMed:27044744,
CC ECO:0000269|PubMed:8898111, ECO:0000269|PubMed:8989326,
CC ECO:0000269|PubMed:9792674, ECO:0000269|PubMed:9837883}.
CC -!- INTERACTION:
CC P13500; P13501: CCL5; NbExp=2; IntAct=EBI-1034732, EBI-2848366;
CC P13500; P80075: CCL8; NbExp=2; IntAct=EBI-1034732, EBI-16803830;
CC P13500; P02776: PF4; NbExp=2; IntAct=EBI-1034732, EBI-2565740;
CC P13500; P78317: RNF4; NbExp=3; IntAct=EBI-1034732, EBI-2340927;
CC P13500; Q9Y320: TMX2; NbExp=3; IntAct=EBI-1034732, EBI-6447886;
CC P13500; Q2F862; Xeno; NbExp=5; IntAct=EBI-1034732, EBI-16161937;
CC PRO_0000005146; P98066: TNFAIP6; NbExp=2; IntAct=EBI-11711396, EBI-11700693;
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:23955712,
CC ECO:0000269|PubMed:2513477}.
CC -!- TISSUE SPECIFICITY: Expressed in the seminal plasma, endometrial fluid
CC and follicular fluid (at protein level) (PubMed:23765988). Expressed in
CC monocytes (PubMed:2513477). {ECO:0000269|PubMed:23765988,
CC ECO:0000269|PubMed:2513477}.
CC -!- INDUCTION: Up-regulated upon hypertonic conditions (PubMed:23233732).
CC In pancreatic islets, secretion is stimulated by IL1B
CC (PubMed:23955712). {ECO:0000269|PubMed:23233732,
CC ECO:0000269|PubMed:23955712}.
CC -!- PTM: Processing at the N-terminus can regulate receptor and target cell
CC selectivity (PubMed:8627182). Deletion of the N-terminal residue
CC converts it from an activator of basophil to an eosinophil
CC chemoattractant (PubMed:8627182). {ECO:0000269|PubMed:8627182}.
CC -!- PTM: N-Glycosylated. {ECO:0000269|PubMed:2513477}.
CC -!- POLYMORPHISM: Genetic variations in CCL2 determine Mycobacterium
CC tuberculosis susceptibility [MIM:607948].
CC {ECO:0000269|PubMed:16352737}.
CC -!- SIMILARITY: Belongs to the intercrine beta (chemokine CC) family.
CC {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Wikipedia; Note=CCL2 entry;
CC URL="https://en.wikipedia.org/wiki/CCL2";
CC -!- WEB RESOURCE: Name=SeattleSNPs;
CC URL="http://pga.gs.washington.edu/data/scya2/";
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DR EMBL; M24545; AAA18164.1; -; mRNA.
DR EMBL; M28225; AAA60308.1; -; Genomic_DNA.
DR EMBL; M28223; AAA60308.1; JOINED; Genomic_DNA.
DR EMBL; M28224; AAA60308.1; JOINED; Genomic_DNA.
DR EMBL; M28226; AAA60309.1; -; mRNA.
DR EMBL; M31626; AAA36330.1; -; Genomic_DNA.
DR EMBL; M30816; AAA36330.1; JOINED; Genomic_DNA.
DR EMBL; M31625; AAA36330.1; JOINED; Genomic_DNA.
DR EMBL; X14768; CAA32876.1; -; mRNA.
DR EMBL; M37719; AAA18102.1; -; Genomic_DNA.
DR EMBL; S71513; AAB20651.1; -; mRNA.
DR EMBL; S69738; AAB29926.1; -; mRNA.
DR EMBL; Y18933; CAC14049.1; -; Genomic_DNA.
DR EMBL; A17786; CAA01352.1; -; mRNA.
DR EMBL; BT007329; AAP35993.1; -; mRNA.
DR EMBL; AF519531; AAM54046.1; -; Genomic_DNA.
DR EMBL; AK311960; BAG34900.1; -; mRNA.
DR EMBL; CH471147; EAW80212.1; -; Genomic_DNA.
DR EMBL; BC009716; AAH09716.1; -; mRNA.
DR CCDS; CCDS11277.1; -.
DR PIR; A35474; A60299.
DR RefSeq; NP_002973.1; NM_002982.3.
DR PDB; 1DOK; X-ray; 1.85 A; A/B=24-99.
DR PDB; 1DOL; X-ray; 2.40 A; A=24-99.
DR PDB; 1DOM; NMR; -; A/B=24-99.
DR PDB; 1DON; NMR; -; A/B=24-99.
DR PDB; 1ML0; X-ray; 2.80 A; D=24-99.
DR PDB; 2BDN; X-ray; 2.53 A; A=24-99.
DR PDB; 2NZ1; X-ray; 2.50 A; D/E/Y=24-99.
DR PDB; 3IFD; X-ray; 1.90 A; A=24-99.
DR PDB; 4DN4; X-ray; 2.80 A; M=24-99.
DR PDB; 4R8I; X-ray; 2.05 A; A=24-99.
DR PDB; 4ZK9; X-ray; 2.60 A; B=24-99.
DR PDB; 7SO0; X-ray; 1.74 A; B=24-99.
DR PDBsum; 1DOK; -.
DR PDBsum; 1DOL; -.
DR PDBsum; 1DOM; -.
DR PDBsum; 1DON; -.
DR PDBsum; 1ML0; -.
DR PDBsum; 2BDN; -.
DR PDBsum; 2NZ1; -.
DR PDBsum; 3IFD; -.
DR PDBsum; 4DN4; -.
DR PDBsum; 4R8I; -.
DR PDBsum; 4ZK9; -.
DR PDBsum; 7SO0; -.
DR AlphaFoldDB; P13500; -.
DR SMR; P13500; -.
DR BioGRID; 112251; 31.
DR DIP; DIP-5838N; -.
DR IntAct; P13500; 17.
DR STRING; 9606.ENSP00000225831; -.
DR BindingDB; P13500; -.
DR ChEMBL; CHEMBL1649052; -.
DR DrugBank; DB09301; Chondroitin sulfate.
DR DrugBank; DB01406; Danazol.
DR DrugBank; DB01055; Mimosine.
DR DrugCentral; P13500; -.
DR GlyGen; P13500; 1 site.
DR BioMuta; CCL2; -.
DR DMDM; 126842; -.
DR MassIVE; P13500; -.
DR PaxDb; P13500; -.
DR PeptideAtlas; P13500; -.
DR PRIDE; P13500; -.
DR ProteomicsDB; 52921; -.
DR ABCD; P13500; 30 sequenced antibodies.
DR Antibodypedia; 4427; 1686 antibodies from 45 providers.
DR DNASU; 6347; -.
DR Ensembl; ENST00000225831.4; ENSP00000225831.4; ENSG00000108691.9.
DR GeneID; 6347; -.
DR KEGG; hsa:6347; -.
DR MANE-Select; ENST00000225831.4; ENSP00000225831.4; NM_002982.4; NP_002973.1.
DR UCSC; uc002hhy.4; human.
DR CTD; 6347; -.
DR DisGeNET; 6347; -.
DR GeneCards; CCL2; -.
DR HGNC; HGNC:10618; CCL2.
DR HPA; ENSG00000108691; Tissue enhanced (urinary).
DR MalaCards; CCL2; -.
DR MIM; 158105; gene.
DR MIM; 607948; phenotype.
DR neXtProt; NX_P13500; -.
DR OpenTargets; ENSG00000108691; -.
DR PharmGKB; PA130413151; -.
DR VEuPathDB; HostDB:ENSG00000108691; -.
DR eggNOG; ENOG502S6ZP; Eukaryota.
DR GeneTree; ENSGT01050000244851; -.
DR HOGENOM; CLU_141716_1_0_1; -.
DR InParanoid; P13500; -.
DR OMA; PITCCYT; -.
DR OrthoDB; 1575018at2759; -.
DR PhylomeDB; P13500; -.
DR TreeFam; TF334888; -.
DR PathwayCommons; P13500; -.
DR Reactome; R-HSA-380108; Chemokine receptors bind chemokines.
DR Reactome; R-HSA-380994; ATF4 activates genes in response to endoplasmic reticulum stress.
DR Reactome; R-HSA-6783783; Interleukin-10 signaling.
DR Reactome; R-HSA-6785807; Interleukin-4 and Interleukin-13 signaling.
DR SignaLink; P13500; -.
DR SIGNOR; P13500; -.
DR BioGRID-ORCS; 6347; 11 hits in 1077 CRISPR screens.
DR ChiTaRS; CCL2; human.
DR EvolutionaryTrace; P13500; -.
DR GeneWiki; CCL2; -.
DR GenomeRNAi; 6347; -.
DR Pharos; P13500; Tchem.
DR PRO; PR:P13500; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; P13500; protein.
DR Bgee; ENSG00000108691; Expressed in vena cava and 173 other tissues.
DR ExpressionAtlas; P13500; baseline and differential.
DR Genevisible; P13500; HS.
DR GO; GO:0005576; C:extracellular region; IDA:BHF-UCL.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0048020; F:CCR chemokine receptor binding; IBA:GO_Central.
DR GO; GO:0031727; F:CCR2 chemokine receptor binding; ISS:BHF-UCL.
DR GO; GO:0008009; F:chemokine activity; IBA:GO_Central.
DR GO; GO:0004672; F:protein kinase activity; TAS:ProtInc.
DR GO; GO:0005102; F:signaling receptor binding; TAS:ProtInc.
DR GO; GO:0001525; P:angiogenesis; TAS:BHF-UCL.
DR GO; GO:0009887; P:animal organ morphogenesis; TAS:ProtInc.
DR GO; GO:0043615; P:astrocyte cell migration; IDA:BHF-UCL.
DR GO; GO:0007155; P:cell adhesion; TAS:ProtInc.
DR GO; GO:0007166; P:cell surface receptor signaling pathway; TAS:ProtInc.
DR GO; GO:0019725; P:cellular homeostasis; TAS:BHF-UCL.
DR GO; GO:0044344; P:cellular response to fibroblast growth factor stimulus; IEP:UniProtKB.
DR GO; GO:0071346; P:cellular response to interferon-gamma; IEP:UniProtKB.
DR GO; GO:0071347; P:cellular response to interleukin-1; IEP:UniProtKB.
DR GO; GO:0071222; P:cellular response to lipopolysaccharide; ISS:BHF-UCL.
DR GO; GO:0071407; P:cellular response to organic cyclic compound; IDA:UniProtKB.
DR GO; GO:0071356; P:cellular response to tumor necrosis factor; IEP:UniProtKB.
DR GO; GO:0070098; P:chemokine-mediated signaling pathway; IBA:GO_Central.
DR GO; GO:0006935; P:chemotaxis; TAS:ProtInc.
DR GO; GO:0019221; P:cytokine-mediated signaling pathway; IDA:BHF-UCL.
DR GO; GO:0007010; P:cytoskeleton organization; IDA:UniProtKB.
DR GO; GO:0048245; P:eosinophil chemotaxis; IBA:GO_Central.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0007187; P:G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger; TAS:ProtInc.
DR GO; GO:0035684; P:helper T cell extravasation; ISS:BHF-UCL.
DR GO; GO:0006959; P:humoral immune response; TAS:ProtInc.
DR GO; GO:0006954; P:inflammatory response; IDA:UniProtKB.
DR GO; GO:0031663; P:lipopolysaccharide-mediated signaling pathway; IDA:UniProtKB.
DR GO; GO:0048247; P:lymphocyte chemotaxis; IBA:GO_Central.
DR GO; GO:0048246; P:macrophage chemotaxis; IDA:BHF-UCL.
DR GO; GO:0000165; P:MAPK cascade; IMP:UniProtKB.
DR GO; GO:0002548; P:monocyte chemotaxis; IDA:BHF-UCL.
DR GO; GO:2000134; P:negative regulation of G1/S transition of mitotic cell cycle; IMP:BHF-UCL.
DR GO; GO:0034351; P:negative regulation of glial cell apoptotic process; IDA:UniProtKB.
DR GO; GO:2000502; P:negative regulation of natural killer cell chemotaxis; IDA:UniProtKB.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; IDA:UniProtKB.
DR GO; GO:1905563; P:negative regulation of vascular endothelial cell proliferation; IMP:BHF-UCL.
DR GO; GO:0030593; P:neutrophil chemotaxis; IBA:GO_Central.
DR GO; GO:2000427; P:positive regulation of apoptotic cell clearance; ISS:BHF-UCL.
DR GO; GO:0090280; P:positive regulation of calcium ion import; IDA:BHF-UCL.
DR GO; GO:2000353; P:positive regulation of endothelial cell apoptotic process; IMP:BHF-UCL.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IBA:GO_Central.
DR GO; GO:0043547; P:positive regulation of GTPase activity; IBA:GO_Central.
DR GO; GO:0051770; P:positive regulation of nitric-oxide synthase biosynthetic process; ISS:BHF-UCL.
DR GO; GO:1904783; P:positive regulation of NMDA glutamate receptor activity; ISS:ARUK-UCL.
DR GO; GO:0051968; P:positive regulation of synaptic transmission, glutamatergic; ISS:UniProtKB.
DR GO; GO:0050870; P:positive regulation of T cell activation; ISS:BHF-UCL.
DR GO; GO:0043491; P:protein kinase B signaling; IMP:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; TAS:ProtInc.
DR GO; GO:0007259; P:receptor signaling pathway via JAK-STAT; TAS:ProtInc.
DR GO; GO:0008360; P:regulation of cell shape; IDA:UniProtKB.
DR GO; GO:0009617; P:response to bacterium; NAS:BHF-UCL.
DR GO; GO:0019233; P:sensory perception of pain; ISS:UniProtKB.
DR GO; GO:0007165; P:signal transduction; NAS:ProtInc.
DR GO; GO:0019079; P:viral genome replication; TAS:ProtInc.
DR InterPro; IPR039809; Chemokine_b/g/d.
DR InterPro; IPR000827; Chemokine_CC_CS.
DR InterPro; IPR001811; Chemokine_IL8-like_dom.
DR InterPro; IPR036048; Interleukin_8-like_sf.
DR PANTHER; PTHR12015; PTHR12015; 1.
DR Pfam; PF00048; IL8; 1.
DR SMART; SM00199; SCY; 1.
DR SUPFAM; SSF54117; SSF54117; 1.
DR PROSITE; PS00472; SMALL_CYTOKINES_CC; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Chemotaxis; Cytokine; Direct protein sequencing;
KW Disulfide bond; Glycoprotein; Inflammatory response;
KW Pyrrolidone carboxylic acid; Reference proteome; Secreted; Signal.
FT SIGNAL 1..23
FT /evidence="ECO:0000269|PubMed:2648385"
FT CHAIN 24..99
FT /note="C-C motif chemokine 2"
FT /id="PRO_0000005146"
FT SITE 31
FT /note="Involved in dimerization"
FT SITE 36
FT /note="Involved in dimerization, receptor binding and
FT signaling"
FT SITE 41
FT /note="Involved in GAG binding"
FT SITE 42
FT /note="Involved in GAG binding"
FT SITE 47
FT /note="Involved in GAG binding and receptor binding"
FT SITE 58
FT /note="Involved in dimerization"
FT SITE 61
FT /note="Involved in dimerization"
FT SITE 72
FT /note="Involved in GAG binding and receptor binding"
FT SITE 81
FT /note="Involved in GAG binding"
FT SITE 89
FT /note="Involved in GAG binding"
FT MOD_RES 24
FT /note="Pyrrolidone carboxylic acid"
FT /evidence="ECO:0000269|PubMed:1661560,
FT ECO:0000269|PubMed:2648385"
FT CARBOHYD 37
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 34..59
FT DISULFID 35..75
FT MUTAGEN 24..91
FT /note="Missing: 83% reduction in activity."
FT MUTAGEN 24..85
FT /note="Missing: 90% reduction in activity."
FT MUTAGEN 24
FT /note="Missing: Loss of activity."
FT MUTAGEN 25..31
FT /note="Missing: Loss of signaling."
FT /evidence="ECO:0000269|PubMed:10587439"
FT MUTAGEN 26
FT /note="D->A: Reduction in activity."
FT /evidence="ECO:0000269|PubMed:10587439"
FT MUTAGEN 28
FT /note="I->A: Slight reduction in activity."
FT /evidence="ECO:0000269|PubMed:10587439"
FT MUTAGEN 29
FT /note="N->A: 50% reduction in activity."
FT /evidence="ECO:0000269|PubMed:10587439"
FT MUTAGEN 31
FT /note="P->A: Loss of dimerization; slight reduction of
FT activity."
FT /evidence="ECO:0000269|PubMed:10587439,
FT ECO:0000269|PubMed:9837883"
FT MUTAGEN 32
FT /note="V->A: Slight reduction in activity."
FT /evidence="ECO:0000269|PubMed:10587439,
FT ECO:0000269|PubMed:9837883"
FT MUTAGEN 32
FT /note="V->E: Slight reduction in affinity."
FT /evidence="ECO:0000269|PubMed:10587439,
FT ECO:0000269|PubMed:9837883"
FT MUTAGEN 33
FT /note="T->A: Slight reduction in activity."
FT /evidence="ECO:0000269|PubMed:10587439,
FT ECO:0000269|PubMed:9837883"
FT MUTAGEN 33
FT /note="T->E: Slight reduction in affinity."
FT /evidence="ECO:0000269|PubMed:10587439,
FT ECO:0000269|PubMed:9837883"
FT MUTAGEN 36
FT /note="Y->A: Loss of activity."
FT /evidence="ECO:0000269|PubMed:9837883"
FT MUTAGEN 41..42
FT /note="RK->AA: Abolishes binding to Link domain of
FT TNFAIP6."
FT /evidence="ECO:0000269|PubMed:27044744"
FT MUTAGEN 47
FT /note="R->F: 95% reduction in activity; strong reduction of
FT receptor binding."
FT MUTAGEN 50
FT /note="S->Q: 40% reduction in activity."
FT MUTAGEN 51
FT /note="Y->D: Loss of activity."
FT MUTAGEN 53
FT /note="R->L: Loss of activity."
FT MUTAGEN 79
FT /note="K->A: No effect on heparin binding."
FT MUTAGEN 81
FT /note="K->A: Strongly reduces heparin binding."
FT /evidence="ECO:0000269|PubMed:9792674"
FT MUTAGEN 89
FT /note="H->A: Strongly reduces heparin binding."
FT /evidence="ECO:0000269|PubMed:9792674"
FT MUTAGEN 91
FT /note="D->L: 90% reduction in activity."
FT MUTAGEN 95..99
FT /note="Missing: No effect on heparin binding."
FT /evidence="ECO:0000269|PubMed:9792674"
FT HELIX 25..29
FT /evidence="ECO:0007829|PDB:1DOK"
FT STRAND 32..34
FT /evidence="ECO:0007829|PDB:1DOK"
FT HELIX 45..47
FT /evidence="ECO:0007829|PDB:1DOK"
FT STRAND 48..54
FT /evidence="ECO:0007829|PDB:1DOK"
FT STRAND 59..61
FT /evidence="ECO:0007829|PDB:1DOK"
FT STRAND 63..68
FT /evidence="ECO:0007829|PDB:1DOK"
FT STRAND 73..76
FT /evidence="ECO:0007829|PDB:1DOK"
FT STRAND 78..80
FT /evidence="ECO:0007829|PDB:4ZK9"
FT HELIX 81..92
FT /evidence="ECO:0007829|PDB:1DOK"
FT STRAND 93..95
FT /evidence="ECO:0007829|PDB:1DON"
SQ SEQUENCE 99 AA; 11025 MW; 45EC72361435302F CRC64;
MKVSAALLCL LLIAATFIPQ GLAQPDAINA PVTCCYNFTN RKISVQRLAS YRRITSSKCP
KEAVIFKTIV AKEICADPKQ KWVQDSMDHL DKQTQTPKT
