ACKR2_MOUSE
ID ACKR2_MOUSE Reviewed; 378 AA.
AC O08707; Q8CEG1;
DT 20-JUN-2001, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 158.
DE RecName: Full=Atypical chemokine receptor 2;
DE AltName: Full=C-C chemokine receptor D6;
DE AltName: Full=Chemokine-binding protein 2;
DE AltName: Full=Chemokine-binding protein D6;
GN Name=Ackr2; Synonyms=Ccbp2, D6;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=C3H/HeJ;
RX PubMed=9139699; DOI=10.1074/jbc.272.19.12495;
RA Nibbs R.J., Wylie S.M., Pragnell I.B., Graham G.J.;
RT "Cloning and characterization of a novel murine beta chemokine receptor,
RT D6. Comparison to three other related macrophage inflammatory protein-
RT 1alpha receptors, CCR-1, CCR-3, and CCR-5.";
RL J. Biol. Chem. 272:12495-12504(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J, and NOD;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=22651933; DOI=10.1096/fj.11-194894;
RA Pashover-Schallinger E., Aswad M., Schif-Zuck S., Shapiro H., Singer P.,
RA Ariel A.;
RT "The atypical chemokine receptor D6 controls macrophage efferocytosis and
RT cytokine secretion during the resolution of inflammation.";
RL FASEB J. 26:3891-3900(2012).
RN [6]
RP REVIEW.
RX PubMed=23125030; DOI=10.1002/path.4123;
RA Graham G.J., Locati M.;
RT "Regulation of the immune and inflammatory responses by the 'atypical'
RT chemokine receptor D6.";
RL J. Pathol. 229:168-175(2013).
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. {ECO:0000269|PubMed:22651933}.
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: Expressed on apoptotic neutrophils (at protein
CC level). {ECO:0000269|PubMed:22651933}.
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; Y12879; CAA73379.1; -; mRNA.
DR EMBL; AK028281; BAC25855.1; -; mRNA.
DR EMBL; AK145960; BAE26786.1; -; mRNA.
DR EMBL; AK147166; BAE27731.1; -; mRNA.
DR EMBL; AK157140; BAE33976.1; -; mRNA.
DR EMBL; CH466587; EDL09123.1; -; Genomic_DNA.
DR EMBL; BC113146; AAI13147.1; -; mRNA.
DR CCDS; CCDS23640.1; -.
DR RefSeq; NP_001263648.1; NM_001276719.1.
DR RefSeq; NP_067622.2; NM_021609.4.
DR RefSeq; XP_006512266.1; XM_006512203.3.
DR RefSeq; XP_006512267.1; XM_006512204.3.
DR AlphaFoldDB; O08707; -.
DR SMR; O08707; -.
DR STRING; 10090.ENSMUSP00000050119; -.
DR GlyGen; O08707; 1 site.
DR PhosphoSitePlus; O08707; -.
DR PaxDb; O08707; -.
DR PRIDE; O08707; -.
DR ProteomicsDB; 285934; -.
DR Antibodypedia; 2896; 433 antibodies from 36 providers.
DR DNASU; 59289; -.
DR Ensembl; ENSMUST00000050327; ENSMUSP00000050119; ENSMUSG00000044534.
DR Ensembl; ENSMUST00000214340; ENSMUSP00000148966; ENSMUSG00000044534.
DR GeneID; 59289; -.
DR KEGG; mmu:59289; -.
DR UCSC; uc009sed.2; mouse.
DR CTD; 1238; -.
DR MGI; MGI:1891697; Ackr2.
DR VEuPathDB; HostDB:ENSMUSG00000044534; -.
DR eggNOG; KOG3656; Eukaryota.
DR GeneTree; ENSGT01050000244811; -.
DR HOGENOM; CLU_009579_8_3_1; -.
DR InParanoid; O08707; -.
DR OMA; IVHAQPH; -.
DR OrthoDB; 791532at2759; -.
DR PhylomeDB; O08707; -.
DR TreeFam; TF330966; -.
DR Reactome; R-MMU-380108; Chemokine receptors bind chemokines.
DR BioGRID-ORCS; 59289; 1 hit in 73 CRISPR screens.
DR ChiTaRS; Ackr2; mouse.
DR PRO; PR:O08707; -.
DR Proteomes; UP000000589; Chromosome 9.
DR RNAct; O08707; protein.
DR Bgee; ENSMUSG00000044534; Expressed in right lung lobe and 98 other tissues.
DR ExpressionAtlas; O08707; baseline and differential.
DR Genevisible; O08707; MM.
DR GO; GO:0005884; C:actin filament; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
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:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0031965; C:nuclear membrane; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
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; IPI:BHF-UCL.
DR GO; GO:0016493; F:C-C chemokine receptor activity; IDA:MGI.
DR GO; GO:0004950; F:chemokine receptor activity; ISO:MGI.
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; IDA:MGI.
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 1: Evidence at protein 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..378
FT /note="Atypical chemokine receptor 2"
FT /id="PRO_0000069220"
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..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..117
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 118..139
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 140..161
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 162..182
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 183..216
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 217..237
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 238..249
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 250..270
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 271..292
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 293..313
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 314..378
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 326..378
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 116..194
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521"
FT CONFLICT 266
FT /note="N -> Y (in Ref. 1; CAA73379)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 378 AA; 43207 MW; 1436D49E71698172 CRC64;
MPTVASPLPL TTVGSENSSS IYDYDYLDDM TILVCRKDEV LSFGRVFLPV VYSLIFVLGL
AGNLLLLVVL LHSAPRRRTM ELYLLNLAVS NLLFVVTMPF WAISVAWHWV FGSFLCKVIS
TLYSINFYCG IFFITCMSLD KYLEIVHAQP LHRPKAQFRN LLLIVMVWIT SLAISVPEMV
FVQIHQTLDG VWHCYADFGG HATIWKLYLR FQLNLLGFLL PLLAMIFFYS RIGCVLVRLR
PPGQGRALRM AAALVIVFFM LWFPYNLTLF LHSLLDLHVF GNCEISHRLD YTLQVTESLA
FSHCCFTPVL YAFCSHRFRR YLKAFLSVML RWHQAPGTPS SNHSESSRVT AQEDVVSMND
LGERQSEDSL NKGEMGNT
