CCR2_MACMU
ID CCR2_MACMU Reviewed; 360 AA.
AC O18793;
DT 27-APR-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1999, sequence version 2.
DT 25-MAY-2022, entry version 116.
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: Full=Monocyte chemoattractant protein 1 receptor;
DE Short=MCP-1-R;
DE AltName: CD_antigen=CD192;
GN Name=CCR2; Synonyms=CMKBR2;
OS Macaca mulatta (Rhesus macaque).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini;
OC Cercopithecidae; Cercopithecinae; Macaca.
OX NCBI_TaxID=9544;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=11461684; DOI=10.1089/088922201750290104;
RA Margulies B.J., Hauer D.A., Clements J.E.;
RT "Identification and comparison of eleven rhesus macaque chemokine
RT receptors.";
RL AIDS Res. Hum. Retroviruses 17:981-986(2001).
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 -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=B;
CC IsoId=O18793-1; Sequence=Displayed;
CC Name=A;
CC IsoId=O18793-2; Sequence=Not described;
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}.
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DR EMBL; AF013958; AAD11572.1; -; mRNA.
DR RefSeq; NP_001027978.1; NM_001032806.1. [O18793-1]
DR AlphaFoldDB; O18793; -.
DR SMR; O18793; -.
DR GeneID; 574098; -.
DR KEGG; mcc:574098; -.
DR CTD; 729230; -.
DR InParanoid; O18793; -.
DR OrthoDB; 937138at2759; -.
DR Proteomes; UP000006718; Unplaced.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0009897; C:external side of plasma membrane; IBA:GO_Central.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0019957; F:C-C chemokine binding; IBA:GO_Central.
DR GO; GO:0016493; F:C-C chemokine receptor activity; IBA:GO_Central.
DR GO; GO:0001974; P:blood vessel remodeling; IEA:InterPro.
DR GO; GO:0019722; P:calcium-mediated signaling; IBA:GO_Central.
DR GO; GO:0060326; P:cell chemotaxis; IBA:GO_Central.
DR GO; GO:0006955; P:immune response; IBA:GO_Central.
DR GO; GO:0006954; P:inflammatory response; IBA:GO_Central.
DR GO; GO:0090594; P:inflammatory response to wounding; ISS:UniProtKB.
DR GO; GO:1905517; P:macrophage migration; ISS:UniProtKB.
DR GO; GO:0035696; P:monocyte extravasation; ISS:UniProtKB.
DR GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; IBA:GO_Central.
DR GO; GO:0090026; P:positive regulation of monocyte chemotaxis; ISS:UniProtKB.
DR GO; GO:0051968; P:positive regulation of synaptic transmission, glutamatergic; ISS:UniProtKB.
DR GO; GO:2000412; P:positive regulation of thymocyte migration; ISS:UniProtKB.
DR GO; GO:0050727; P:regulation of inflammatory response; ISS:UniProtKB.
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:0019233; P:sensory perception of pain; ISS:UniProtKB.
DR InterPro; IPR002237; Chemokine_CCR2.
DR InterPro; IPR000355; Chemokine_rcpt.
DR InterPro; IPR000276; GPCR_Rhodpsn.
DR InterPro; IPR017452; GPCR_Rhodpsn_7TM.
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 PROSITE; PS00237; G_PROTEIN_RECEP_F1_1; 1.
DR PROSITE; PS50262; G_PROTEIN_RECEP_F1_2; 1.
PE 2: Evidence at transcript level;
KW Alternative splicing; Cell membrane; Disulfide bond;
KW G-protein coupled receptor; Glycoprotein; Inflammatory response; Membrane;
KW Phosphoprotein; Receptor; Reference proteome; Sulfation; Transducer;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..360
FT /note="C-C chemokine receptor type 2"
FT /id="PRO_0000069233"
FT TOPO_DOM 1..42
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 43..70
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 71..80
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 81..100
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 101..114
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 115..136
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 137..153
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 154..178
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 179..206
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 207..226
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 227..243
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 244..268
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 269..285
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 286..309
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 310..360
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT MOD_RES 26
FT /note="Sulfotyrosine"
FT /evidence="ECO:0000250"
FT MOD_RES 139
FT /note="Phosphotyrosine; by JAK2"
FT /evidence="ECO:0000250|UniProtKB:P41597"
FT CARBOHYD 14
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 113..190
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521"
SQ SEQUENCE 360 AA; 41140 MW; 4B2552BCE913FE9F CRC64;
MLSTSRSRFI RNTNGSGEEV TTFFDYDYGA PCHKFDVKQI GAQLLPPLYS LVFIFGFVGN
MLVVLILINC KKLKSLTDIY LLNLAISDLL FLITLPLWAH SAANEWVFGN AMCKLFTGLY
HIGYLGGIFF IILLTIDRYL AIVHAVFALK ARTVTFGVVT SVITWLVAVF ASVPGIIFTK
CQEEDSVYIC GPYFPRGWNN FHTIMRNILG LVLPLLIMVI CYSGILKTLL RCRNEKKRHR
AVRLIFTIMI VYFLFWTPYN IVILLNTFQE FFGLSNCEST RQLDQATQVT ETLGMTHCCI
NPIIYAFVGE KFRRYLSMFF RKYITKRFCK QCPVFYRETV DGVTSTNTPS TAEQEVSVGL
