ACKR2_RAT
ID ACKR2_RAT Reviewed; 382 AA.
AC O09027;
DT 20-JUN-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1997, sequence version 1.
DT 25-MAY-2022, entry version 131.
DE RecName: Full=Atypical chemokine receptor 2;
DE AltName: Full=C-C chemokine receptor D6;
DE AltName: Full=CCR10-related receptor;
DE AltName: Full=Chemokine-binding protein 2;
DE AltName: Full=Chemokine-binding protein D6;
GN Name=Ackr2; Synonyms=Ccbp2, Ccr10rr, D6;
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 [MRNA].
RC STRAIN=Sprague-Dawley;
RX PubMed=9324304; DOI=10.1089/dna.1997.16.1023;
RA Bonini J.A., Steiner D.F.;
RT "Molecular cloning and expression of a novel rat CC-chemokine receptor
RT (rCCR10rR) that binds MCP-1 and MIP-1beta with high affinity.";
RL DNA Cell Biol. 16:1023-1030(1997).
CC -!- FUNCTION: Atypical chemokine receptor that controls chemokine levels
CC and localization via high-affinity chemokine binding that is uncoupled
CC from classic ligand-driven signal transduction cascades, resulting
CC instead in chemokine sequestration, degradation, or transcytosis. Also
CC known as interceptor (internalizing receptor) or chemokine-scavenging
CC receptor or chemokine decoy receptor. Acts as a receptor for chemokines
CC including CCL2, CCL3, CCL3L1, CCL4, CCL5, CCL7, CCL8, CCL11, CCL13,
CC CCL17, CCL22, CCL23, CCL24, SCYA2/MCP-1, SCY3/MIP-1-alpha, SCYA5/RANTES
CC and SCYA7/MCP-3. Upon active ligand stimulation, activates a beta-
CC arrestin 1 (ARRB1)-dependent, G protein-independent signaling pathway
CC that results in the phosphorylation of the actin-binding protein
CC cofilin (CFL1) through a RAC1-PAK1-LIMK1 signaling pathway. Activation
CC of this pathway results in up-regulation of ACKR2 from endosomal
CC compartment to cell membrane, increasing its efficiency in chemokine
CC uptake and degradation. By scavenging chemokines in tissues, on the
CC surfaces of lymphatic vessels, and in placenta, plays an essential role
CC in the resolution (termination) of the inflammatory response and in the
CC regulation of adaptive immune responses. Plays a major role in the
CC immune silencing of macrophages during the resolution of inflammation.
CC Acts as a regulator of inflammatory leukocyte interactions with
CC lymphatic endothelial cells (LECs) and is required for immature/mature
CC dendritic cells discrimination by LECs.
CC -!- SUBCELLULAR LOCATION: Early endosome {ECO:0000250}. Recycling endosome
CC {ECO:0000250}. Cell membrane; Multi-pass membrane protein.
CC Note=Predominantly localizes to endocytic vesicles, and upon
CC stimulation by the ligand is internalized via clathrin-coated pits.
CC Once internalized, the ligand dissociates from the receptor, and is
CC targeted to degradation while the receptor is recycled back to the cell
CC membrane (By similarity). {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Predominantly expressed in spleen.
CC -!- DOMAIN: The C-terminal cytoplasmic tail controls its phosphorylation,
CC stability, intracellular trafficking itinerary, and chemokine
CC scavenging properties. {ECO:0000250}.
CC -!- PTM: Phosphorylated on serine residues in the C-terminal cytoplasmic
CC tail. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
CC Atypical chemokine receptor subfamily. {ECO:0000255|PROSITE-
CC ProRule:PRU00521}.
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DR EMBL; U92803; AAB61572.1; -; mRNA.
DR AlphaFoldDB; O09027; -.
DR SMR; O09027; -.
DR STRING; 10116.ENSRNOP00000026343; -.
DR GlyGen; O09027; 1 site.
DR PhosphoSitePlus; O09027; -.
DR PaxDb; O09027; -.
DR UCSC; RGD:620323; rat.
DR RGD; 620323; Ackr2.
DR eggNOG; KOG3656; Eukaryota.
DR InParanoid; O09027; -.
DR PhylomeDB; O09027; -.
DR Reactome; R-RNO-380108; Chemokine receptors bind chemokines.
DR PRO; PR:O09027; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005884; C:actin filament; ISS:UniProtKB.
DR GO; GO:0005769; C:early endosome; IEA:UniProtKB-SubCell.
DR GO; GO:0009897; C:external side of plasma membrane; IBA:GO_Central.
DR GO; GO:0005887; C:integral component of plasma membrane; IEA:InterPro.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0055037; C:recycling endosome; IEA:UniProtKB-SubCell.
DR GO; GO:0019957; F:C-C chemokine binding; ISO:RGD.
DR GO; GO:0016493; F:C-C chemokine receptor activity; ISO:RGD.
DR GO; GO:0004950; F:chemokine receptor activity; ISO:RGD.
DR GO; GO:0005044; F:scavenger receptor activity; ISS:UniProtKB.
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; IEA:UniProtKB-KW.
DR GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; IBA:GO_Central.
DR GO; GO:0007165; P:signal transduction; ISO:RGD.
DR InterPro; IPR033037; Ackr2.
DR InterPro; IPR000355; Chemokine_rcpt.
DR InterPro; IPR001277; CXCR4/ACKR2.
DR InterPro; IPR000276; GPCR_Rhodpsn.
DR InterPro; IPR017452; GPCR_Rhodpsn_7TM.
DR PANTHER; PTHR10489:SF735; PTHR10489:SF735; 1.
DR Pfam; PF00001; 7tm_1; 1.
DR PRINTS; PR00657; CCCHEMOKINER.
DR PRINTS; PR00645; CXCCHMKINER4.
DR PRINTS; PR00237; GPCRRHODOPSN.
DR PROSITE; PS50262; G_PROTEIN_RECEP_F1_2; 1.
PE 2: Evidence at transcript level;
KW Cell membrane; Disulfide bond; Endosome; G-protein coupled receptor;
KW Glycoprotein; Inflammatory response; Membrane; Phosphoprotein; Receptor;
KW Reference proteome; Transducer; Transmembrane; Transmembrane helix.
FT CHAIN 1..382
FT /note="Atypical chemokine receptor 2"
FT /id="PRO_0000069221"
FT TOPO_DOM 1..49
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 50..70
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 71..92
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 93..113
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 114..118
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 119..140
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 141..162
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 163..183
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 184..217
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 218..238
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 239..250
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 251..271
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 272..293
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 294..314
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 315..382
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 327..382
FT /note="C-terminal cytoplasmic tail"
FT /evidence="ECO:0000250"
FT CARBOHYD 17
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 117..195
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521"
SQ SEQUENCE 382 AA; 43293 MW; E8714CE23DB96772 CRC64;
MPTIASPLPL ATTGPENGSS IYDYDYLDDV TVLVCSKDEV LSFGRVFLPV VYSLIFVLGL
AGNLLLLVVL LHSVPQRRRM IELYLLNLAV SNLLFVVTMP FWAISVAWHW VFGSFLCKVV
STLYSINFYC GIFFITCMSL DKYLEIVHAQ PLHRPKTRFR NLLLIVMVWI TALAVSVPEM
VFVKVHQTLD GVWHCYADFG GHATIWKLYL RFQMNLLGFL FPLLAMIFFY SRIGCVLVRL
RPPGQGRALR MAAALVVVFF LLWFPYNLTL FLHSLLDLHV FGNCKISHRL DYMLQVTESL
AFSHCCFTPV LYAFSSHSFR QYLKAVLSVV LRRHQAPGTA HAPPCSHSES SRVTAQEDVV
SMNDLGERQA DISLNKGEIG NN
