CCL2_MOUSE
ID CCL2_MOUSE Reviewed; 148 AA.
AC P10148; Q9QYD7;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1989, sequence version 1.
DT 03-AUG-2022, entry version 192.
DE RecName: Full=C-C motif chemokine 2;
DE AltName: Full=Monocyte chemoattractant protein 1;
DE AltName: Full=Monocyte chemotactic protein 1;
DE Short=MCP-1;
DE AltName: Full=Platelet-derived growth factor-inducible protein JE;
DE AltName: Full=Small-inducible cytokine A2;
DE Flags: Precursor;
GN Name=Ccl2; Synonyms=Je, Mcp1, Scya2;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2910858; DOI=10.1016/s0021-9258(19)84995-5;
RA Kawahara R.S., Deuel T.F.;
RT "Platelet-derived growth factor-inducible gene JE is a member of a family
RT of small inducible genes related to platelet factor 4.";
RL J. Biol. Chem. 264:679-682(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=3287374; DOI=10.1073/pnas.85.11.3738;
RA Rollins B.J., Morrison E.D., Stiles C.D.;
RT "Cloning and expression of JE, a gene inducible by platelet-derived growth
RT factor and whose product has cytokine-like properties.";
RL Proc. Natl. Acad. Sci. U.S.A. 85:3738-3742(1988).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], POLYMORPHISM, AND VARIANTS GLY-50 AND GLN-92.
RC STRAIN=B10.S/J, BALB/cJ, DBA/2J, NOD/LtJ, and SJL/J; TISSUE=Spleen;
RX PubMed=10438970;
RA Teuscher C., Butterfield R.J., Ma R.Z., Zachary J.F., Doerge R.W.,
RA Blankenhorn E.P.;
RT "Sequence polymorphisms in the chemokines Scya1 (TCA-3), Scya2 (monocyte
RT chemoattractant protein (MCP)-1), and Scya12 (MCP-5) are candidates for
RT eae7, a locus controlling susceptibility to monophasic
RT remitting/nonrelapsing experimental allergic encephalomyelitis.";
RL J. Immunol. 163:2262-2266(1999).
RN [4]
RP PROTEIN SEQUENCE OF 26-42.
RX PubMed=2065676; DOI=10.1111/j.1432-1033.1991.tb16113.x;
RA van Damme J., Decock B., Bertini R., Conings R., Lenaerts J.-P., Put W.,
RA Opdenakker G., Mantovani A.;
RT "Production and identification of natural monocyte chemotactic protein from
RT virally infected murine fibroblasts. Relationship with the product of the
RT mouse competence (JE) gene.";
RL Eur. J. Biochem. 199:223-229(1991).
RN [5]
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 [6]
RP FUNCTION, AND INDUCTION.
RX PubMed=29993042; DOI=10.1038/s41386-018-0115-8;
RA Wu X.B., Jing P.B., Zhang Z.J., Cao D.L., Gao M.H., Jiang B.C., Gao Y.J.;
RT "Chemokine receptor CCR2 contributes to neuropathic pain and the associated
RT depression via increasing NR2B-mediated currents in both D1 and D2 dopamine
RT receptor-containing medium spiny neurons in the nucleus accumbens shell.";
RL Neuropsychopharmacology 43:2320-2330(2018).
CC -!- FUNCTION: Acts as a ligand for C-C chemokine receptor CCR2 (By
CC similarity). Signals through binding and activation of CCR2 and induces
CC a strong chemotactic response and mobilization of intracellular calcium
CC ions (By similarity). Exhibits a chemotactic activity for monocytes and
CC basophils but not neutrophils or eosinophils (By similarity). Plays an
CC important role in mediating peripheral nerve injury-induced neuropathic
CC pain (PubMed:29993042). Increases NMDA-mediated synaptic transmission
CC in both dopamine D1 and D2 receptor-containing neurons, which may be
CC caused by MAPK/ERK-dependent phosphorylation of GRIN2B/NMDAR2B
CC (PubMed:29993042). {ECO:0000250|UniProtKB:P13500,
CC ECO:0000269|PubMed:29993042}.
CC -!- SUBUNIT: Monomer or homodimer; in equilibrium. Is tethered on
CC endothelial cells by glycosaminoglycan (GAG) side chains of
CC proteoglycans. Interacts with TNFAIP6 (via Link domain).
CC {ECO:0000250|UniProtKB:P13500}.
CC -!- INTERACTION:
CC P10148; E9M5R0: RHVP.R17; Xeno; NbExp=2; IntAct=EBI-16188285, EBI-16188152;
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:P13500}.
CC -!- INDUCTION: By platelet-derived growth factor (PubMed:23233732). Up-
CC regulated upon hypertonic conditions (PubMed:23233732). Up-regulated in
CC the dopamine D1 and D2 receptor-containing neurons of nucleus accumbens
CC shell after spinal nerve ligation (PubMed:29993042).
CC {ECO:0000269|PubMed:23233732, ECO:0000269|PubMed:29993042}.
CC -!- PTM: Processing at the N-terminus can regulate receptor and target cell
CC selectivity (By similarity). Deletion of the N-terminal residue
CC converts it from an activator of basophil to an eosinophil
CC chemoattractant (By similarity). {ECO:0000250|UniProtKB:P13500}.
CC -!- PTM: N-Glycosylated. {ECO:0000250|UniProtKB:P13500}.
CC -!- POLYMORPHISM: The polymorphisms in strain SJL/J may be associated with
CC severity of clinical symptoms of experimental allergic
CC encephalomyelitis, an animal model of multiple sclerosis, and
CC susceptibility to the monophasic remitting/nonrelapsing form of the
CC disease. {ECO:0000269|PubMed:10438970}.
CC -!- SIMILARITY: Belongs to the intercrine beta (chemokine CC) family.
CC {ECO:0000305}.
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DR EMBL; J04467; AAA37685.1; -; Genomic_DNA.
DR EMBL; M19681; AAA37684.1; -; Genomic_DNA.
DR EMBL; AF065929; AAF15379.1; -; mRNA.
DR EMBL; AF065930; AAF15380.1; -; mRNA.
DR EMBL; AF065931; AAF15381.1; -; mRNA.
DR EMBL; AF065932; AAF15382.1; -; mRNA.
DR EMBL; AF065933; AAF15383.1; -; mRNA.
DR CCDS; CCDS25139.1; -.
DR PIR; A30209; A30209.
DR PIR; S16226; S16226.
DR RefSeq; NP_035463.1; NM_011333.3.
DR AlphaFoldDB; P10148; -.
DR SMR; P10148; -.
DR BioGRID; 203121; 2.
DR DIP; DIP-61917N; -.
DR IntAct; P10148; 1.
DR STRING; 10090.ENSMUSP00000000193; -.
DR GlyGen; P10148; 1 site.
DR iPTMnet; P10148; -.
DR PhosphoSitePlus; P10148; -.
DR PaxDb; P10148; -.
DR PeptideAtlas; P10148; -.
DR PRIDE; P10148; -.
DR Antibodypedia; 4427; 1686 antibodies from 45 providers.
DR DNASU; 20296; -.
DR Ensembl; ENSMUST00000000193; ENSMUSP00000000193; ENSMUSG00000035385.
DR GeneID; 20296; -.
DR KEGG; mmu:20296; -.
DR UCSC; uc007kmp.1; mouse.
DR CTD; 6347; -.
DR MGI; MGI:98259; Ccl2.
DR VEuPathDB; HostDB:ENSMUSG00000035385; -.
DR eggNOG; ENOG502S6ZP; Eukaryota.
DR GeneTree; ENSGT01050000244851; -.
DR HOGENOM; CLU_141716_1_0_1; -.
DR InParanoid; P10148; -.
DR OMA; PLTCCYS; -.
DR OrthoDB; 1575018at2759; -.
DR PhylomeDB; P10148; -.
DR TreeFam; TF339372; -.
DR BioGRID-ORCS; 20296; 3 hits in 75 CRISPR screens.
DR ChiTaRS; Ccl2; mouse.
DR PRO; PR:P10148; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; P10148; protein.
DR Bgee; ENSMUSG00000035385; Expressed in endothelial cell of lymphatic vessel and 133 other tissues.
DR ExpressionAtlas; P10148; baseline and differential.
DR Genevisible; P10148; MM.
DR GO; GO:0043679; C:axon terminus; ISO:MGI.
DR GO; GO:0044299; C:C-fiber; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0030425; C:dendrite; ISO:MGI.
DR GO; GO:0030139; C:endocytic vesicle; ISO:MGI.
DR GO; GO:0005576; C:extracellular region; ISO:MGI.
DR GO; GO:0005615; C:extracellular space; IDA:MGI.
DR GO; GO:0043025; C:neuronal cell body; ISO:MGI.
DR GO; GO:0043204; C:perikaryon; ISO:MGI.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISO:MGI.
DR GO; GO:0005791; C:rough endoplasmic reticulum; ISO:MGI.
DR GO; GO:0045202; C:synapse; ISO:MGI.
DR GO; GO:0048020; F:CCR chemokine receptor binding; IBA:GO_Central.
DR GO; GO:0031727; F:CCR2 chemokine receptor binding; IPI:BHF-UCL.
DR GO; GO:0008009; F:chemokine activity; ISO:MGI.
DR GO; GO:0005125; F:cytokine activity; IDA:MGI.
DR GO; GO:0001664; F:G protein-coupled receptor binding; IDA:MGI.
DR GO; GO:0008201; F:heparin binding; ISO:MGI.
DR GO; GO:0007568; P:aging; IEA:Ensembl.
DR GO; GO:0001525; P:angiogenesis; TAS:BHF-UCL.
DR GO; GO:0031100; P:animal organ regeneration; IEA:Ensembl.
DR GO; GO:0043615; P:astrocyte cell migration; ISS:BHF-UCL.
DR GO; GO:0006874; P:cellular calcium ion homeostasis; ISO:MGI.
DR GO; GO:0071318; P:cellular response to ATP; IEA:Ensembl.
DR GO; GO:0071549; P:cellular response to dexamethasone stimulus; IEA:Ensembl.
DR GO; GO:0071392; P:cellular response to estradiol stimulus; IEA:Ensembl.
DR GO; GO:0071398; P:cellular response to fatty acid; IEA:Ensembl.
DR GO; GO:0071333; P:cellular response to glucose stimulus; IEA:Ensembl.
DR GO; GO:0071403; P:cellular response to high density lipoprotein particle stimulus; IEA:Ensembl.
DR GO; GO:0032869; P:cellular response to insulin stimulus; IEA:Ensembl.
DR GO; GO:0071346; P:cellular response to interferon-gamma; IDA:BHF-UCL.
DR GO; GO:0071347; P:cellular response to interleukin-1; IDA:BHF-UCL.
DR GO; GO:0071354; P:cellular response to interleukin-6; IEA:Ensembl.
DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IDA:BHF-UCL.
DR GO; GO:0036006; P:cellular response to macrophage colony-stimulating factor stimulus; IEA:Ensembl.
DR GO; GO:0071407; P:cellular response to organic cyclic compound; ISO:MGI.
DR GO; GO:0036120; P:cellular response to platelet-derived growth factor stimulus; IEA:Ensembl.
DR GO; GO:0071300; P:cellular response to retinoic acid; IEA:Ensembl.
DR GO; GO:0071356; P:cellular response to tumor necrosis factor; IDA:BHF-UCL.
DR GO; GO:0071466; P:cellular response to xenobiotic stimulus; IEA:Ensembl.
DR GO; GO:0070098; P:chemokine-mediated signaling pathway; ISO:MGI.
DR GO; GO:0002544; P:chronic inflammatory response; IEA:Ensembl.
DR GO; GO:0019221; P:cytokine-mediated signaling pathway; ISO:MGI.
DR GO; GO:0007010; P:cytoskeleton organization; ISO:MGI.
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:0008347; P:glial cell migration; ISO:MGI.
DR GO; GO:0035684; P:helper T cell extravasation; IDA:BHF-UCL.
DR GO; GO:0006954; P:inflammatory response; ISO:MGI.
DR GO; GO:0002523; P:leukocyte migration involved in inflammatory response; ISO:MGI.
DR GO; GO:0031663; P:lipopolysaccharide-mediated signaling pathway; ISO:MGI.
DR GO; GO:0048247; P:lymphocyte chemotaxis; ISO:MGI.
DR GO; GO:0048246; P:macrophage chemotaxis; ISS:BHF-UCL.
DR GO; GO:0000165; P:MAPK cascade; ISO:MGI.
DR GO; GO:0060135; P:maternal process involved in female pregnancy; IEA:Ensembl.
DR GO; GO:0060137; P:maternal process involved in parturition; IEA:Ensembl.
DR GO; GO:0002548; P:monocyte chemotaxis; ISO:MGI.
DR GO; GO:0035702; P:monocyte homeostasis; TAS:BHF-UCL.
DR GO; GO:0016525; P:negative regulation of angiogenesis; IMP:BHF-UCL.
DR GO; GO:2000134; P:negative regulation of G1/S transition of mitotic cell cycle; ISO:MGI.
DR GO; GO:0034351; P:negative regulation of glial cell apoptotic process; ISO:MGI.
DR GO; GO:2000502; P:negative regulation of natural killer cell chemotaxis; ISO:MGI.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; ISO:MGI.
DR GO; GO:1905563; P:negative regulation of vascular endothelial cell proliferation; ISO:MGI.
DR GO; GO:0030593; P:neutrophil chemotaxis; ISO:MGI.
DR GO; GO:2000427; P:positive regulation of apoptotic cell clearance; IDA:BHF-UCL.
DR GO; GO:0090280; P:positive regulation of calcium ion import; ISO:MGI.
DR GO; GO:0045785; P:positive regulation of cell adhesion; ISO:MGI.
DR GO; GO:0022409; P:positive regulation of cell-cell adhesion; ISO:MGI.
DR GO; GO:0002693; P:positive regulation of cellular extravasation; ISO:MGI.
DR GO; GO:0032967; P:positive regulation of collagen biosynthetic process; ISO:MGI.
DR GO; GO:2000353; P:positive regulation of endothelial cell apoptotic process; ISO:MGI.
DR GO; GO:0001938; P:positive regulation of endothelial cell proliferation; ISO:MGI.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IBA:GO_Central.
DR GO; GO:0010628; P:positive regulation of gene expression; IMP:ARUK-UCL.
DR GO; GO:0043547; P:positive regulation of GTPase activity; IBA:GO_Central.
DR GO; GO:0090265; P:positive regulation of immune complex clearance by monocytes and macrophages; IMP:BHF-UCL.
DR GO; GO:0001912; P:positive regulation of leukocyte mediated cytotoxicity; ISO:MGI.
DR GO; GO:0002687; P:positive regulation of leukocyte migration; ISO:MGI.
DR GO; GO:0010759; P:positive regulation of macrophage chemotaxis; IDA:BHF-UCL.
DR GO; GO:0090026; P:positive regulation of monocyte chemotaxis; IDA:UniProtKB.
DR GO; GO:0051770; P:positive regulation of nitric-oxide synthase biosynthetic process; IMP:BHF-UCL.
DR GO; GO:1904783; P:positive regulation of NMDA glutamate receptor activity; ISO:MGI.
DR GO; GO:0090314; P:positive regulation of protein targeting to membrane; ISO:MGI.
DR GO; GO:0050806; P:positive regulation of synaptic transmission; ISO:MGI.
DR GO; GO:0051968; P:positive regulation of synaptic transmission, glutamatergic; IDA:UniProtKB.
DR GO; GO:0050870; P:positive regulation of T cell activation; IMP:BHF-UCL.
DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; ISO:MGI.
DR GO; GO:0090303; P:positive regulation of wound healing; ISO:MGI.
DR GO; GO:0043491; P:protein kinase B signaling; ISO:MGI.
DR GO; GO:0008360; P:regulation of cell shape; ISO:MGI.
DR GO; GO:0010574; P:regulation of vascular endothelial growth factor production; IMP:BHF-UCL.
DR GO; GO:0014823; P:response to activity; IEA:Ensembl.
DR GO; GO:0043200; P:response to amino acid; IEA:Ensembl.
DR GO; GO:0046677; P:response to antibiotic; IEA:Ensembl.
DR GO; GO:0009617; P:response to bacterium; IEP:MGI.
DR GO; GO:1905237; P:response to cyclosporin A; IEA:Ensembl.
DR GO; GO:0045471; P:response to ethanol; IEA:Ensembl.
DR GO; GO:0010332; P:response to gamma radiation; IEA:Ensembl.
DR GO; GO:0009408; P:response to heat; ISO:MGI.
DR GO; GO:0001666; P:response to hypoxia; IEA:Ensembl.
DR GO; GO:0009612; P:response to mechanical stimulus; IEA:Ensembl.
DR GO; GO:0032570; P:response to progesterone; IEA:Ensembl.
DR GO; GO:0033552; P:response to vitamin B3; IEA:Ensembl.
DR GO; GO:0009611; P:response to wounding; IDA:MGI.
DR GO; GO:0019233; P:sensory perception of pain; IDA:UniProtKB.
DR GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; ISO:MGI.
DR GO; GO:0048010; P:vascular endothelial growth factor receptor signaling pathway; ISO:MGI.
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 Chemotaxis; Cytokine; Direct protein sequencing; Disulfide bond;
KW Glycoprotein; Inflammatory response; Pyrrolidone carboxylic acid;
KW Reference proteome; Secreted; Signal.
FT SIGNAL 1..23
FT /evidence="ECO:0000250"
FT CHAIN 24..148
FT /note="C-C motif chemokine 2"
FT /id="PRO_0000005149"
FT MOD_RES 24
FT /note="Pyrrolidone carboxylic acid"
FT /evidence="ECO:0000250|UniProtKB:P13500"
FT CARBOHYD 126
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 34..59
FT /evidence="ECO:0000250"
FT DISULFID 35..75
FT /evidence="ECO:0000250"
FT VARIANT 50
FT /note="S -> G (in strain: SJL/J)"
FT /evidence="ECO:0000269|PubMed:10438970"
FT VARIANT 92
FT /note="R -> Q (in strain: SJL/J)"
FT /evidence="ECO:0000269|PubMed:10438970"
SQ SEQUENCE 148 AA; 16326 MW; 29A5505FC6D94837 CRC64;
MQVPVMLLGL LFTVAGWSIH VLAQPDAVNA PLTCCYSFTS KMIPMSRLES YKRITSSRCP
KEAVVFVTKL KREVCADPKK EWVQTYIKNL DRNQMRSEPT TLFKTASALR SSAPLNVKLT
RKSEANASTT FSTTTSSTSV GVTSVTVN
