ID CCR2_RAT Reviewed; 373 AA. AC O55193; DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot. DT 01-JUN-1998, sequence version 1. DT 24-JAN-2024, entry version 149. DE RecName: Full=C-C chemokine receptor type 2; DE Short=C-C CKR-2; DE Short=CC-CKR-2; DE Short=CCR-2; DE Short=CCR2; DE AltName: CD_antigen=CD192; GN Name=Ccr2; Synonyms=Cmkbr2; 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], INDUCTION, AND TISSUE SPECIFICITY. RC STRAIN=Sprague-Dawley; RX PubMed=9655467; DOI=10.1016/s0165-5728(98)00005-8; RA Jiang Y., Salafranca M.N., Adhikari S., Xia Y., Feng L., Sonntag M.K., RA deFiebre C.M., Pennell N.A., Streit W.J., Harrison J.K.; RT "Chemokine receptor expression in cultured glia and rat experimental RT allergic encephalomyelitis."; RL J. Neuroimmunol. 86:1-12(1998). CC -!- FUNCTION: Key functional receptor for CCL2 but can also bind CCL7 and CC CCL12 (By similarity). Its binding with CCL2 on monocytes and CC macrophages mediates chemotaxis and migration induction through the CC activation of the PI3K cascade, the small G protein Rac and CC lamellipodium protrusion (By similarity). Also acts as a receptor for CC the beta-defensin DEFB106A/DEFB106B (By similarity). Regulates the CC expression of T-cell inflammatory cytokines and T-cell differentiation, CC promoting the differentiation of T-cells into T-helper 17 cells (Th17) CC during inflammation (By similarity). Facilitates the export of mature CC thymocytes by enhancing directional movement of thymocytes to CC sphingosine-1-phosphate stimulation and up-regulation of S1P1R CC expression; signals through the JAK-STAT pathway to regulate FOXO1 CC activity leading to an increased expression of S1P1R (By similarity). CC Plays an important role in mediating peripheral nerve injury-induced CC neuropathic pain (By similarity). Increases NMDA-mediated synaptic CC transmission in both dopamine D1 and D2 receptor-containing neurons, CC which may be caused by MAPK/ERK-dependent phosphorylation of CC GRIN2B/NMDAR2B (By similarity). Mediates the recruitment of macrophages CC and monocytes to the injury site following brain injury (By CC similarity). {ECO:0000250|UniProtKB:P41597, CC ECO:0000250|UniProtKB:P51683}. CC -!- SUBUNIT: Interacts with ARRB1 (By similarity). Interacts (via CC extracellular N-terminal region) with beta-defensin DEFB106A/DEFB106B; CC this interaction may preferentially require specific tyrosine sulfation CC on CCR2 (By similarity). Interacts with NUP85; the interaction is CC required for CCR2 clusters formation on the cell membrane and CCR2 CC signaling (By similarity). {ECO:0000250|UniProtKB:P41597}. CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P41597}; CC Multi-pass membrane protein {ECO:0000255}. Note=The chemoattractant CC receptors are distributed throughout the cell surface; after CC stimulation with a ligand, such as CCL2, they are rapidly recruited CC into microdomain clusters at the cell membrane. CC {ECO:0000250|UniProtKB:P41597}. CC -!- TISSUE SPECIFICITY: Expressed in lung, spleen, kidney, thymus and CC macrophages. {ECO:0000269|PubMed:9655467}. CC -!- INDUCTION: In animals in which experimental allergic encephalomyelitis CC (EAE) has been induced. {ECO:0000269|PubMed:9655467}. CC -!- PTM: N-glycosylated. {ECO:0000250|UniProtKB:P41597}. CC -!- PTM: Sulfation increases the affinity for both monomeric and dimeric CC CCL2 with stronger binding to the monomeric form (By similarity). CC Binding of sulfated CCR2 to CCL2 promotes conversion of CCL2 from dimer CC to monomer (By similarity). {ECO:0000250|UniProtKB:P41597}. CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family. CC {ECO:0000255|PROSITE-ProRule:PRU00521}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; U77349; AAC03242.1; -; Genomic_DNA. DR RefSeq; NP_068638.1; NM_021866.1. DR AlphaFoldDB; O55193; -. DR SMR; O55193; -. DR BindingDB; O55193; -. DR ChEMBL; CHEMBL1293204; -. DR PhosphoSitePlus; O55193; -. DR Ensembl; ENSRNOT00000100998.1; ENSRNOP00000095594.1; ENSRNOG00000063127.1. DR Ensembl; ENSRNOT00000114724.1; ENSRNOP00000081733.1; ENSRNOG00000063127.1. DR Ensembl; ENSRNOT00055003839; ENSRNOP00055002887; ENSRNOG00055002417. DR Ensembl; ENSRNOT00055003841; ENSRNOP00055002889; ENSRNOG00055002417. DR Ensembl; ENSRNOT00060040410; ENSRNOP00060033381; ENSRNOG00060023353. DR Ensembl; ENSRNOT00060040443; ENSRNOP00060033413; ENSRNOG00060023353. DR Ensembl; ENSRNOT00065001048; ENSRNOP00065000788; ENSRNOG00065000759. DR Ensembl; ENSRNOT00065001049; ENSRNOP00065000789; ENSRNOG00065000759. DR GeneID; 60463; -. DR KEGG; rno:60463; -. DR UCSC; RGD:620876; rat. DR AGR; RGD:620876; -. DR CTD; 729230; -. DR RGD; 620876; Ccr2. DR GeneTree; ENSGT01020000230359; -. DR InParanoid; O55193; -. DR OMA; YHIALGC; -. DR OrthoDB; 4604454at2759; -. DR PhylomeDB; O55193; -. DR TreeFam; TF330966; -. DR PRO; PR:O55193; -. DR Proteomes; UP000002494; Chromosome 8. DR GO; GO:0005737; C:cytoplasm; ISO:RGD. DR GO; GO:0030425; C:dendrite; IDA:RGD. DR GO; GO:0009897; C:external side of plasma membrane; ISO: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:0005886; C:plasma membrane; ISS:UniProtKB. DR GO; GO:0150001; C:primary dendrite; IDA:RGD. DR GO; GO:0016493; F:C-C chemokine receptor activity; ISO:RGD. DR GO; GO:0031727; F:CCR2 chemokine receptor binding; ISO:RGD. DR GO; GO:0035716; F:chemokine (C-C motif) ligand 12 binding; ISO:RGD. DR GO; GO:0035715; F:chemokine (C-C motif) ligand 2 binding; ISO:RGD. DR GO; GO:0071791; F:chemokine (C-C motif) ligand 5 binding; IBA:GO_Central. DR GO; GO:0035717; F:chemokine (C-C motif) ligand 7 binding; ISO:RGD. DR GO; GO:0019955; F:cytokine binding; ISO:RGD. DR GO; GO:0042802; F:identical protein binding; IPI:BHF-UCL. DR GO; GO:0001974; P:blood vessel remodeling; IEP:RGD. DR GO; GO:0019722; P:calcium-mediated signaling; IBA:GO_Central. DR GO; GO:0060326; P:cell chemotaxis; IBA:GO_Central. DR GO; GO:0006968; P:cellular defense response; ISO:RGD. DR GO; GO:0019725; P:cellular homeostasis; ISS:BHF-UCL. DR GO; GO:0070098; P:chemokine-mediated signaling pathway; IMP:RGD. DR GO; GO:0019221; P:cytokine-mediated signaling pathway; IMP:RGD. DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; IMP:RGD. DR GO; GO:0030097; P:hemopoiesis; ISO:RGD. DR GO; GO:0048873; P:homeostasis of number of cells within a tissue; ISO:RGD. DR GO; GO:0006959; P:humoral immune response; ISO:RGD. DR GO; GO:0006955; P:immune response; ISO:RGD. DR GO; GO:0006954; P:inflammatory response; ISO:RGD. DR GO; GO:0002437; P:inflammatory response to antigenic stimulus; IEP:RGD. DR GO; GO:0090594; P:inflammatory response to wounding; ISS:UniProtKB. DR GO; GO:0006874; P:intracellular calcium ion homeostasis; IDA:RGD. DR GO; GO:0061756; P:leukocyte adhesion to vascular endothelial cell; ISO:RGD. DR GO; GO:1905517; P:macrophage migration; ISS:UniProtKB. DR GO; GO:0002548; P:monocyte chemotaxis; ISO:RGD. DR GO; GO:0035696; P:monocyte extravasation; ISS:UniProtKB. DR GO; GO:0016525; P:negative regulation of angiogenesis; ISS:BHF-UCL. DR GO; GO:0043310; P:negative regulation of eosinophil degranulation; ISS:BHF-UCL. DR GO; GO:0002829; P:negative regulation of type 2 immune response; ISS:BHF-UCL. DR GO; GO:0097350; P:neutrophil clearance; ISO:RGD. DR GO; GO:0046641; P:positive regulation of alpha-beta T cell proliferation; ISS:BHF-UCL. DR GO; GO:2000464; P:positive regulation of astrocyte chemotaxis; ISS:BHF-UCL. DR GO; GO:2000451; P:positive regulation of CD8-positive, alpha-beta T cell extravasation; ISS:BHF-UCL. DR GO; GO:0120162; P:positive regulation of cold-induced thermogenesis; ISS:YuBioLab. DR GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; IBA:GO_Central. DR GO; GO:2000473; P:positive regulation of hematopoietic stem cell migration; ISS:BHF-UCL. DR GO; GO:0090265; P:positive regulation of immune complex clearance by monocytes and macrophages; ISS:BHF-UCL. DR GO; GO:0050729; P:positive regulation of inflammatory response; ISS:BHF-UCL. DR GO; GO:0032743; P:positive regulation of interleukin-2 production; ISS:BHF-UCL. DR GO; GO:1903238; P:positive regulation of leukocyte tethering or rolling; ISO:RGD. DR GO; GO:0090026; P:positive regulation of monocyte chemotaxis; ISS:UniProtKB. DR GO; GO:2000439; P:positive regulation of monocyte extravasation; ISS:BHF-UCL. DR GO; GO:1904783; P:positive regulation of NMDA glutamate receptor activity; IGI:ARUK-UCL. DR GO; GO:1900745; P:positive regulation of p38MAPK cascade; 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; ISS:BHF-UCL. DR GO; GO:0010820; P:positive regulation of T cell chemotaxis; ISS:BHF-UCL. DR GO; GO:0002827; P:positive regulation of T-helper 1 type immune response; ISS:BHF-UCL. DR GO; GO:2000412; P:positive regulation of thymocyte migration; ISS:UniProtKB. DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; IMP:RGD. DR GO; GO:0032729; P:positive regulation of type II interferon production; ISS:BHF-UCL. DR GO; GO:0050727; P:regulation of inflammatory response; ISS:UniProtKB. DR GO; GO:1905521; P:regulation of macrophage migration; ISO:RGD. DR GO; GO:0071675; P:regulation of mononuclear cell migration; ISO:RGD. DR GO; GO:0002724; P:regulation of T cell cytokine production; ISS:UniProtKB. DR GO; GO:0045580; P:regulation of T cell differentiation; ISS:UniProtKB. DR GO; GO:2000404; P:regulation of T cell migration; ISO:RGD. DR GO; GO:0010574; P:regulation of vascular endothelial growth factor production; ISS:BHF-UCL. DR GO; GO:0055093; P:response to hyperoxia; IEP:RGD. DR GO; GO:0001666; P:response to hypoxia; IEP:RGD. DR GO; GO:0019233; P:sensory perception of pain; ISS:UniProtKB. DR GO; GO:0035705; P:T-helper 17 cell chemotaxis; ISS:BHF-UCL. DR CDD; cd15184; 7tmA_CCR5_CCR2; 1. DR Gene3D; 1.20.1070.10; Rhodopsin 7-helix transmembrane proteins; 1. DR InterPro; IPR002237; Chemokine_CCR2. DR InterPro; IPR000355; Chemokine_rcpt. DR InterPro; IPR000276; GPCR_Rhodpsn. DR InterPro; IPR017452; GPCR_Rhodpsn_7TM. DR PANTHER; PTHR10489:SF928; C-C CHEMOKINE RECEPTOR TYPE 2; 1. DR PANTHER; PTHR10489; CELL ADHESION MOLECULE; 1. DR Pfam; PF00001; 7tm_1; 1. DR PRINTS; PR00657; CCCHEMOKINER. DR PRINTS; PR01107; CHEMOKINER2. DR PRINTS; PR00237; GPCRRHODOPSN. DR SMART; SM01381; 7TM_GPCR_Srsx; 1. DR SUPFAM; SSF81321; Family A G protein-coupled receptor-like; 1. DR PROSITE; PS00237; G_PROTEIN_RECEP_F1_1; 1. DR PROSITE; PS50262; G_PROTEIN_RECEP_F1_2; 1. PE 2: Evidence at transcript level; KW Cell membrane; Disulfide bond; G-protein coupled receptor; Glycoprotein; KW Inflammatory response; Membrane; Phosphoprotein; Receptor; KW Reference proteome; Transducer; Transmembrane; Transmembrane helix. FT CHAIN 1..373 FT /note="C-C chemokine receptor type 2" FT /id="PRO_0000069235" FT TOPO_DOM 1..60 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 61..81 FT /note="Helical; Name=1" FT /evidence="ECO:0000255" FT TOPO_DOM 82..91 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 92..112 FT /note="Helical; Name=2" FT /evidence="ECO:0000255" FT TOPO_DOM 113..128 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 129..149 FT /note="Helical; Name=3" FT /evidence="ECO:0000255" FT TOPO_DOM 150..170 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 171..191 FT /note="Helical; Name=4" FT /evidence="ECO:0000255" FT TOPO_DOM 192..220 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 221..241 FT /note="Helical; Name=5" FT /evidence="ECO:0000255" FT TOPO_DOM 242..256 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 257..277 FT /note="Helical; Name=6" FT /evidence="ECO:0000255" FT TOPO_DOM 278..301 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 302..322 FT /note="Helical; Name=7" FT /evidence="ECO:0000255" FT TOPO_DOM 323..373 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT MOD_RES 152 FT /note="Phosphotyrosine; by JAK2" FT /evidence="ECO:0000250|UniProtKB:P41597" FT DISULFID 126..203 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521" SQ SEQUENCE 373 AA; 42763 MW; 2E7BB012F5D6FD09 CRC64; MEDSNMLPQF IHGILSTSHS LFPRSIQELD EGATTPYDYD DGEPCHKTSV KQIGAWILPP LYSLVFIFGF VGNMLVIIIL ISCKKLKSMT DIYLFNLAIS DLLFLLTLPF WAHYAANEWV FGNIMCKLFT GLYHIGYFGG IFFIILLTID RYLAIVHAVF ALKARTVTFG VITSVVTWVV AVFASLPGII FTKSEQEDDQ HTCGPYFPTI WKNFQTIMRN ILSLILPLLV MVICYSGILH TLFRCRNEKK RHRAVRLIFA IMIVYFLFWT PYNIVLFLTT FQEFLGMSNC VVDMHLDQAM QVTETLGMTH CCVNPIIYAF VGEKFRRYLS IFFRKHIAKN LCKQCPVFYR ETADRVSSTF TPSTGEQEVS VGL //