CCL2_RAT
ID CCL2_RAT Reviewed; 148 AA.
AC P14844; Q549R5;
DT 01-APR-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-APR-1990, sequence version 1.
DT 03-AUG-2022, entry version 165.
DE RecName: Full=C-C motif chemokine 2;
DE AltName: Full=Immediate-early serum-responsive protein JE;
DE AltName: Full=Monocyte chemoattractant protein 1;
DE AltName: Full=Monocyte chemotactic protein 1;
DE Short=MCP-1;
DE AltName: Full=Small-inducible cytokine A2;
DE Flags: Precursor;
GN Name=Ccl2; Synonyms=Je, Mcp1, Scya2;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=WAG/RIJ; TISSUE=Kidney;
RX PubMed=2106664; DOI=10.1093/nar/18.1.23;
RA Timmers H.T.M., Pronk G.J., Bos J.L., van der Eb A.J.;
RT "Analysis of the rat JE gene promoter identifies an AP-1 binding site
RT essential for basal expression but not for TPA induction.";
RL Nucleic Acids Res. 18:23-34(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=1704226; DOI=10.1016/0006-291x(91)91445-i;
RA Yoshimura T., Takeya M., Takahashi K.;
RT "Molecular cloning of rat monocyte chemoattractant protein-1 (MCP-1) and
RT its expression in rat spleen cells and tumor cell lines.";
RL Biochem. Biophys. Res. Commun. 174:504-509(1991).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Sprague-Dawley; TISSUE=Aortic smooth muscle;
RA Poon M., Taubman M.B.;
RT "Cloning of the full-length rat JE/MCP-1 cDNA.";
RL Submitted (APR-1998) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP SUBCELLULAR LOCATION, AND INDUCTION BY ENDOCANNABINOID ANANDAMIDE AND 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).
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 (By similarity). Increases NMDA-mediated synaptic transmission in
CC both dopamine D1 and D2 receptor-containing neurons, which may be
CC caused by MAPK/ERK-dependent phosphorylation of GRIN2B/NMDAR2B (By
CC similarity). {ECO:0000250|UniProtKB:P10148,
CC ECO:0000250|UniProtKB:P13500}.
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 -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:23955712}.
CC -!- INDUCTION: In pancreatic islets, secretion is stimulated by IL1B
CC (PubMed:23955712). In islets from Zucker diabetic fatty (ZDF) rats, but
CC not lean animals, secretion is also increased by endocannabinoid
CC anandamide/AEA (PubMed:23955712). {ECO:0000269|PubMed:23955712}.
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 -!- SIMILARITY: Belongs to the intercrine beta (chemokine CC) family.
CC {ECO:0000305}.
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DR EMBL; X17053; CAA34901.1; -; Genomic_DNA.
DR EMBL; M57441; AAA63496.1; -; mRNA.
DR EMBL; AF058786; AAC15187.1; -; mRNA.
DR PIR; S07723; S07723.
DR RefSeq; NP_113718.1; NM_031530.1.
DR AlphaFoldDB; P14844; -.
DR SMR; P14844; -.
DR STRING; 10116.ENSRNOP00000009448; -.
DR GlyGen; P14844; 1 site.
DR PhosphoSitePlus; P14844; -.
DR PaxDb; P14844; -.
DR Ensembl; ENSRNOT00000009448; ENSRNOP00000009448; ENSRNOG00000007159.
DR GeneID; 24770; -.
DR KEGG; rno:24770; -.
DR CTD; 6347; -.
DR RGD; 3645; Ccl2.
DR eggNOG; ENOG502S6ZP; Eukaryota.
DR GeneTree; ENSGT01050000244851; -.
DR HOGENOM; CLU_141716_1_0_1; -.
DR InParanoid; P14844; -.
DR OMA; PLTCCYS; -.
DR OrthoDB; 1575018at2759; -.
DR PhylomeDB; P14844; -.
DR TreeFam; TF339372; -.
DR PRO; PR:P14844; -.
DR Proteomes; UP000002494; Chromosome 10.
DR Bgee; ENSRNOG00000007159; Expressed in stomach and 16 other tissues.
DR Genevisible; P14844; RN.
DR GO; GO:0043679; C:axon terminus; IDA:RGD.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0030425; C:dendrite; IDA:RGD.
DR GO; GO:0030139; C:endocytic vesicle; IDA:RGD.
DR GO; GO:0005576; C:extracellular region; ISO:RGD.
DR GO; GO:0005615; C:extracellular space; IDA:RGD.
DR GO; GO:0043025; C:neuronal cell body; IDA:RGD.
DR GO; GO:0043204; C:perikaryon; IDA:RGD.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:RGD.
DR GO; GO:0005791; C:rough endoplasmic reticulum; IDA:RGD.
DR GO; GO:0045202; C:synapse; IDA:RGD.
DR GO; GO:0048020; F:CCR chemokine receptor binding; IBA:GO_Central.
DR GO; GO:0031727; F:CCR2 chemokine receptor binding; ISO:RGD.
DR GO; GO:0008009; F:chemokine activity; IDA:RGD.
DR GO; GO:0005125; F:cytokine activity; ISO:RGD.
DR GO; GO:0001664; F:G protein-coupled receptor binding; ISO:RGD.
DR GO; GO:0008201; F:heparin binding; IPI:RGD.
DR GO; GO:0007568; P:aging; IEP:RGD.
DR GO; GO:0031100; P:animal organ regeneration; IEP:RGD.
DR GO; GO:0043615; P:astrocyte cell migration; ISO:RGD.
DR GO; GO:0006874; P:cellular calcium ion homeostasis; IDA:RGD.
DR GO; GO:0071318; P:cellular response to ATP; IEP:RGD.
DR GO; GO:0071549; P:cellular response to dexamethasone stimulus; IEP:RGD.
DR GO; GO:0071392; P:cellular response to estradiol stimulus; IEP:RGD.
DR GO; GO:0071398; P:cellular response to fatty acid; IEP:RGD.
DR GO; GO:0044344; P:cellular response to fibroblast growth factor stimulus; ISO:RGD.
DR GO; GO:0071333; P:cellular response to glucose stimulus; IEP:RGD.
DR GO; GO:0071403; P:cellular response to high density lipoprotein particle stimulus; IEP:RGD.
DR GO; GO:0032869; P:cellular response to insulin stimulus; IEP:RGD.
DR GO; GO:0071346; P:cellular response to interferon-gamma; IEP:RGD.
DR GO; GO:0071347; P:cellular response to interleukin-1; IEP:RGD.
DR GO; GO:0071354; P:cellular response to interleukin-6; IEP:RGD.
DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IEP:RGD.
DR GO; GO:0071402; P:cellular response to lipoprotein particle stimulus; IEP:RGD.
DR GO; GO:0036006; P:cellular response to macrophage colony-stimulating factor stimulus; IEP:RGD.
DR GO; GO:0071407; P:cellular response to organic cyclic compound; ISO:RGD.
DR GO; GO:0036120; P:cellular response to platelet-derived growth factor stimulus; IEP:RGD.
DR GO; GO:0071300; P:cellular response to retinoic acid; IEP:RGD.
DR GO; GO:0071356; P:cellular response to tumor necrosis factor; IEP:RGD.
DR GO; GO:0071466; P:cellular response to xenobiotic stimulus; IEP:RGD.
DR GO; GO:0070098; P:chemokine-mediated signaling pathway; IMP:RGD.
DR GO; GO:0042466; P:chemokinesis; TAS:RGD.
DR GO; GO:0002544; P:chronic inflammatory response; IEP:RGD.
DR GO; GO:0019221; P:cytokine-mediated signaling pathway; IMP:RGD.
DR GO; GO:0007010; P:cytoskeleton organization; ISO:RGD.
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; IMP:RGD.
DR GO; GO:0035684; P:helper T cell extravasation; ISO:RGD.
DR GO; GO:0006954; P:inflammatory response; IEP:RGD.
DR GO; GO:0002523; P:leukocyte migration involved in inflammatory response; IMP:RGD.
DR GO; GO:0031663; P:lipopolysaccharide-mediated signaling pathway; ISO:RGD.
DR GO; GO:0048247; P:lymphocyte chemotaxis; IDA:RGD.
DR GO; GO:0048246; P:macrophage chemotaxis; IDA:RGD.
DR GO; GO:0000165; P:MAPK cascade; ISO:RGD.
DR GO; GO:0060135; P:maternal process involved in female pregnancy; IEP:RGD.
DR GO; GO:0060137; P:maternal process involved in parturition; IEP:RGD.
DR GO; GO:0002548; P:monocyte chemotaxis; ISO:RGD.
DR GO; GO:0016525; P:negative regulation of angiogenesis; ISO:RGD.
DR GO; GO:2000134; P:negative regulation of G1/S transition of mitotic cell cycle; ISO:RGD.
DR GO; GO:0034351; P:negative regulation of glial cell apoptotic process; ISO:RGD.
DR GO; GO:2000502; P:negative regulation of natural killer cell chemotaxis; ISO:RGD.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; ISO:RGD.
DR GO; GO:1905563; P:negative regulation of vascular endothelial cell proliferation; ISO:RGD.
DR GO; GO:0030593; P:neutrophil chemotaxis; IMP:RGD.
DR GO; GO:2000427; P:positive regulation of apoptotic cell clearance; ISO:RGD.
DR GO; GO:0090280; P:positive regulation of calcium ion import; ISO:RGD.
DR GO; GO:0045785; P:positive regulation of cell adhesion; IDA:RGD.
DR GO; GO:0022409; P:positive regulation of cell-cell adhesion; IDA:RGD.
DR GO; GO:0002693; P:positive regulation of cellular extravasation; IDA:RGD.
DR GO; GO:0032967; P:positive regulation of collagen biosynthetic process; IDA:RGD.
DR GO; GO:2000353; P:positive regulation of endothelial cell apoptotic process; ISO:RGD.
DR GO; GO:0001938; P:positive regulation of endothelial cell proliferation; IMP:RGD.
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; ISO:RGD.
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; ISO:RGD.
DR GO; GO:0001912; P:positive regulation of leukocyte mediated cytotoxicity; IMP:RGD.
DR GO; GO:0002687; P:positive regulation of leukocyte migration; IDA:RGD.
DR GO; GO:0010759; P:positive regulation of macrophage chemotaxis; IDA:RGD.
DR GO; GO:0090026; P:positive regulation of monocyte chemotaxis; IDA:RGD.
DR GO; GO:0051770; P:positive regulation of nitric-oxide synthase biosynthetic process; ISO:RGD.
DR GO; GO:1904783; P:positive regulation of NMDA glutamate receptor activity; IGI:ARUK-UCL.
DR GO; GO:0090314; P:positive regulation of protein targeting to membrane; IDA:RGD.
DR GO; GO:0050806; P:positive regulation of synaptic transmission; IDA:RGD.
DR GO; GO:0051968; P:positive regulation of synaptic transmission, glutamatergic; ISS:UniProtKB.
DR GO; GO:0050870; P:positive regulation of T cell activation; ISO:RGD.
DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; IMP:RGD.
DR GO; GO:0090303; P:positive regulation of wound healing; IMP:RGD.
DR GO; GO:0043491; P:protein kinase B signaling; ISO:RGD.
DR GO; GO:0008360; P:regulation of cell shape; ISO:RGD.
DR GO; GO:0010574; P:regulation of vascular endothelial growth factor production; ISO:RGD.
DR GO; GO:0014823; P:response to activity; IEP:RGD.
DR GO; GO:0043200; P:response to amino acid; IEP:RGD.
DR GO; GO:0046677; P:response to antibiotic; IEP:RGD.
DR GO; GO:0009617; P:response to bacterium; ISO:RGD.
DR GO; GO:1905237; P:response to cyclosporin A; IEP:RGD.
DR GO; GO:0045471; P:response to ethanol; IEP:RGD.
DR GO; GO:0010332; P:response to gamma radiation; IEP:RGD.
DR GO; GO:0051384; P:response to glucocorticoid; IEP:RGD.
DR GO; GO:0009408; P:response to heat; IDA:RGD.
DR GO; GO:0001666; P:response to hypoxia; IEP:RGD.
DR GO; GO:0032496; P:response to lipopolysaccharide; IEP:RGD.
DR GO; GO:0009612; P:response to mechanical stimulus; IEP:RGD.
DR GO; GO:0032570; P:response to progesterone; IEP:RGD.
DR GO; GO:0034612; P:response to tumor necrosis factor; IEP:RGD.
DR GO; GO:0033552; P:response to vitamin B3; IEP:RGD.
DR GO; GO:0009611; P:response to wounding; ISO:RGD.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEP:RGD.
DR GO; GO:0019233; P:sensory perception of pain; ISS:UniProtKB.
DR GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; IMP:RGD.
DR GO; GO:0048010; P:vascular endothelial growth factor receptor signaling pathway; IMP:RGD.
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 2: Evidence at transcript level;
KW Chemotaxis; Cytokine; Disulfide bond; Glycoprotein; Inflammatory response;
KW Pyrrolidone carboxylic acid; 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_0000005151"
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"
SQ SEQUENCE 148 AA; 16460 MW; 62D4C42BF4B11C9D CRC64;
MQVSVTLLGL LFTVAACSIH VLSQPDAVNA PLTCCYSFTG KMIPMSRLEN YKRITSSRCP
KEAVVFVTKL KREICADPNK EWVQKYIRKL DQNQVRSETT VFYKIASTLR TSAPLNVNLT
HKSEANASTL FSTTTSSTSV EVTSMTEN
