ID   CCL2_CANLF              Reviewed;         101 AA.
AC   P52203;
DT   01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-1996, sequence version 1.
DT   25-MAY-2022, entry version 122.
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=Small-inducible cytokine A2;
DE   Flags: Precursor;
GN   Name=CCL2; Synonyms=MCP1, SCYA2;
OS   Canis lupus familiaris (Dog) (Canis familiaris).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Laurasiatheria; Carnivora; Caniformia; Canidae; Canis.
OX   NCBI_TaxID=9615;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, INDUCTION, AND TISSUE SPECIFICITY.
RC   TISSUE=Jugular vein endothelial cell;
RX   PubMed=9024159; DOI=10.1161/01.cir.95.3.693;
RA   Kumar A.G., Ballantyne C.M., Michael L.H., Kukielka G.L., Youker K.A.,
RA   Lindsey M.L., Hawkins H.K., Birdsall H.H., Mackay C.R., Larosa G.J.,
RA   Rossen R.D., Smith C.W., Entman M.L.;
RT   "Induction of monocyte chemoattractant protein-1 in the small veins of the
RT   ischemic and reperfused canine myocardium.";
RL   Circulation 95:693-700(1997).
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). May play a significant role in monocyte trafficking into
CC       the reperfused myocardium (PubMed:9024159).
CC       {ECO:0000250|UniProtKB:P10148, ECO:0000250|UniProtKB:P13500,
CC       ECO:0000269|PubMed:9024159}.
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:0000250|UniProtKB:P13500}.
CC   -!- TISSUE SPECIFICITY: Endothelium of small veins and intrafascicular
CC       veins, and infiltrating leukocytes. {ECO:0000269|PubMed:9024159}.
CC   -!- INDUCTION: By TNF-alpha. {ECO:0000269|PubMed:9024159}.
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; U29653; AAA84911.1; -; mRNA.
DR   RefSeq; NP_001003297.1; NM_001003297.1.
DR   AlphaFoldDB; P52203; -.
DR   SMR; P52203; -.
DR   STRING; 9612.ENSCAFP00000027107; -.
DR   PaxDb; P52203; -.
DR   GeneID; 403981; -.
DR   KEGG; cfa:403981; -.
DR   CTD; 6347; -.
DR   eggNOG; ENOG502S6ZP; Eukaryota.
DR   InParanoid; P52203; -.
DR   OrthoDB; 1575018at2759; -.
DR   Proteomes; UP000002254; Unplaced.
DR   GO; GO:0005615; C:extracellular space; IEA:UniProtKB-KW.
DR   GO; GO:0008009; F:chemokine activity; IEA:InterPro.
DR   GO; GO:0006955; P:immune response; IEA:InterPro.
DR   GO; GO:0006954; P:inflammatory response; IEA:UniProtKB-KW.
DR   GO; GO:0051968; P:positive regulation of synaptic transmission, glutamatergic; ISS:UniProtKB.
DR   GO; GO:0019233; P:sensory perception of pain; ISS:UniProtKB.
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; Inflammatory response;
KW   Pyrrolidone carboxylic acid; Reference proteome; Secreted; Signal.
FT   SIGNAL          1..23
FT                   /evidence="ECO:0000250"
FT   CHAIN           24..101
FT                   /note="C-C motif chemokine 2"
FT                   /id="PRO_0000005143"
FT   MOD_RES         24
FT                   /note="Pyrrolidone carboxylic acid"
FT                   /evidence="ECO:0000250|UniProtKB:P13500"
FT   DISULFID        34..59
FT                   /evidence="ECO:0000250"
FT   DISULFID        35..75
FT                   /evidence="ECO:0000250"
SQ   SEQUENCE   101 AA;  11121 MW;  CDD7E2B1901A7267 CRC64;
     MKVSAALLCL LLIAAALTTQ VLTQPDAIIS PVTCCYTLTN KKISIQRLAS YKRVTSSKCP
     KEAVIFKTVL NKEICADPKQ KWVQDSMAHL DKKSQTQTAK P