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O08707 (ACKR2_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 112. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Atypical chemokine receptor 2
Alternative name(s):
C-C chemokine receptor D6
Chemokine-binding protein 2
Chemokine-binding protein D6
Gene names
Name:Ackr2
Synonyms:Ccbp2, D6
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length378 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Atypical chemokine receptor that controls chemokine levels and localization via high-affinity chemokine binding that is uncoupled from classic ligand-driven signal transduction cascades, resulting instead in chemokine sequestration, degradation, or transcytosis. Also known as interceptor (internalizing receptor) or chemokine-scavenging receptor or chemokine decoy receptor. Acts as a receptor for chemokines including CCL2, CCL3, CCL3L1, CCL4, CCL5, CCL7, CCL8, CCL11, CCL13, CCL17, CCL22, CCL23, CCL24, SCYA2/MCP-1, SCY3/MIP-1-alpha, SCYA5/RANTES and SCYA7/MCP-3. Upon active ligand stimulation, activates a beta-arrestin 1 (ARRB1)-dependent, G protein-independent signaling pathway that results in the phosphorylation of the actin-binding protein cofilin (CFL1) through a RAC1-PAK1-LIMK1 signaling pathway. Activation of this pathway results in up-regulation of ACKR2 from endosomal compartment to cell membrane, increasing its efficiency in chemokine uptake and degradation. By scavenging chemokines in tissues, on the surfaces of lymphatic vessels, and in placenta, plays an essential role in the resolution (termination) of the inflammatory response and in the regulation of adaptive immune responses. Plays a major role in the immune silencing of macrophages during the resolution of inflammation. Acts as a regulator of inflammatory leukocyte interactions with lymphatic endothelial cells (LECs) and is required for immature/mature dendritic cells discrimination by LECs. Ref.5

Subcellular location

Early endosome By similarity. Recycling endosome By similarity. Cell membrane; Multi-pass membrane protein. Note: Predominantly localizes to endocytic vesicles, and upon stimulation by the ligand is internalized via clathrin-coated pits. Once internalized, the ligand dissociates from the receptor, and is targeted to degradation while the receptor is recycled back to the cell membrane By similarity.

Tissue specificity

Expressed on apoptotic neutrophils (at protein level). Ref.5

Domain

The C-terminal cytoplasmic tail controls its phosphorylation, stability, intracellular trafficking itinerary, and chemokine scavenging properties By similarity.

Post-translational modification

Phosphorylated on serine residues in the C-terminal cytoplasmic tail By similarity.

Sequence similarities

Belongs to the G-protein coupled receptor 1 family. Atypical chemokine receptor subfamily.

Ontologies

Keywords
   Biological processInflammatory response
   Cellular componentCell membrane
Endosome
Membrane
   DomainTransmembrane
Transmembrane helix
   Molecular functionG-protein coupled receptor
Receptor
Transducer
   PTMDisulfide bond
Glycoprotein
Phosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processchemokine-mediated signaling pathway

Inferred from direct assay Ref.1. Source: GOC

chemotaxis

Inferred from electronic annotation. Source: InterPro

inflammatory response

Inferred from electronic annotation. Source: UniProtKB-KW

neutrophil activation

Inferred from electronic annotation. Source: InterPro

receptor-mediated endocytosis

Inferred from sequence or structural similarity. Source: GOC

signal transduction

Inferred from direct assay Ref.1. Source: MGI

   Cellular_componentactin filament

Inferred from sequence or structural similarity. Source: UniProtKB

early endosome

Inferred from electronic annotation. Source: UniProtKB-SubCell

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

plasma membrane

Inferred from sequence or structural similarity. Source: UniProtKB

recycling endosome

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionC-C chemokine binding

Inferred from physical interaction Ref.1. Source: BHF-UCL

C-C chemokine receptor activity

Inferred from direct assay Ref.1. Source: MGI

C-X-C chemokine receptor activity

Inferred from electronic annotation. Source: InterPro

protein binding

Inferred from physical interaction Ref.1. Source: MGI

scavenger receptor activity

Inferred from sequence or structural similarity. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 378378Atypical chemokine receptor 2
PRO_0000069220

Regions

Topological domain1 – 4949Extracellular Potential
Transmembrane50 – 7021Helical; Name=1; Potential
Topological domain71 – 9121Cytoplasmic Potential
Transmembrane92 – 11221Helical; Name=2; Potential
Topological domain113 – 1175Extracellular Potential
Transmembrane118 – 13922Helical; Name=3; Potential
Topological domain140 – 16122Cytoplasmic Potential
Transmembrane162 – 18221Helical; Name=4; Potential
Topological domain183 – 21634Extracellular Potential
Transmembrane217 – 23721Helical; Name=5; Potential
Topological domain238 – 24912Cytoplasmic Potential
Transmembrane250 – 27021Helical; Name=6; Potential
Topological domain271 – 29222Extracellular Potential
Transmembrane293 – 31321Helical; Name=7; Potential
Topological domain314 – 37865Cytoplasmic Potential
Region326 – 37853C-terminal cytoplasmic tail By similarity

Amino acid modifications

Glycosylation171N-linked (GlcNAc...) Potential
Disulfide bond116 ↔ 194 By similarity

Experimental info

Sequence conflict2661N → Y in CAA73379. Ref.1

Sequences

Sequence LengthMass (Da)Tools
O08707 [UniParc].

Last modified July 27, 2011. Version 2.
Checksum: 1436D49E71698172

FASTA37843,207
        10         20         30         40         50         60 
MPTVASPLPL TTVGSENSSS IYDYDYLDDM TILVCRKDEV LSFGRVFLPV VYSLIFVLGL 

        70         80         90        100        110        120 
AGNLLLLVVL LHSAPRRRTM ELYLLNLAVS NLLFVVTMPF WAISVAWHWV FGSFLCKVIS 

       130        140        150        160        170        180 
TLYSINFYCG IFFITCMSLD KYLEIVHAQP LHRPKAQFRN LLLIVMVWIT SLAISVPEMV 

       190        200        210        220        230        240 
FVQIHQTLDG VWHCYADFGG HATIWKLYLR FQLNLLGFLL PLLAMIFFYS RIGCVLVRLR 

       250        260        270        280        290        300 
PPGQGRALRM AAALVIVFFM LWFPYNLTLF LHSLLDLHVF GNCEISHRLD YTLQVTESLA 

       310        320        330        340        350        360 
FSHCCFTPVL YAFCSHRFRR YLKAFLSVML RWHQAPGTPS SNHSESSRVT AQEDVVSMND 

       370 
LGERQSEDSL NKGEMGNT 

« Hide

References

« Hide 'large scale' references
[1]"Cloning and characterization of a novel murine beta chemokine receptor, D6. Comparison to three other related macrophage inflammatory protein-1alpha receptors, CCR-1, CCR-3, and CCR-5."
Nibbs R.J., Wylie S.M., Pragnell I.B., Graham G.J.
J. Biol. Chem. 272:12495-12504(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Strain: C3H.
[2]"The transcriptional landscape of the mammalian genome."
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. expand/collapse author list , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Strain: C57BL/6J and NOD.
[3]Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[5]"The atypical chemokine receptor D6 controls macrophage efferocytosis and cytokine secretion during the resolution of inflammation."
Pashover-Schallinger E., Aswad M., Schif-Zuck S., Shapiro H., Singer P., Ariel A.
FASEB J. 26:3891-3900(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, TISSUE SPECIFICITY.
[6]"Regulation of the immune and inflammatory responses by the 'atypical' chemokine receptor D6."
Graham G.J., Locati M.
J. Pathol. 229:168-175(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
Y12879 mRNA. Translation: CAA73379.1.
AK028281 mRNA. Translation: BAC25855.1.
AK145960 mRNA. Translation: BAE26786.1.
AK147166 mRNA. Translation: BAE27731.1.
AK157140 mRNA. Translation: BAE33976.1.
CH466587 Genomic DNA. Translation: EDL09123.1.
BC113146 mRNA. Translation: AAI13147.1.
CCDSCCDS23640.1.
RefSeqNP_001263648.1. NM_001276719.1.
NP_067622.2. NM_021609.4.
XP_006512266.1. XM_006512203.1.
XP_006512267.1. XM_006512204.1.
UniGeneMm.258105.
Mm.491478.

3D structure databases

ProteinModelPortalO08707.
SMRO08707. Positions 39-319.
ModBaseSearch...
MobiDBSearch...

Protein family/group databases

GPCRDBSearch...

PTM databases

PhosphoSiteO08707.

Proteomic databases

PRIDEO08707.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000050327; ENSMUSP00000050119; ENSMUSG00000044534.
GeneID59289.
KEGGmmu:59289.
UCSCuc009sed.1. mouse.

Organism-specific databases

CTD1238.
MGIMGI:1891697. Ackr2.

Phylogenomic databases

eggNOGNOG297330.
GeneTreeENSGT00700000104251.
HOGENOMHOG000234122.
HOVERGENHBG106917.
InParanoidQ8CEG1.
KOK04187.
OMAHCCFTPI.
OrthoDBEOG7HMS1P.
TreeFamTF330966.

Gene expression databases

BgeeO08707.
CleanExMM_CCBP2.
GenevestigatorO08707.

Family and domain databases

Gene3D1.20.1070.10. 1 hit.
InterProIPR001277. Chemokine_CXCR4.
IPR000355. Chemokine_rcpt.
IPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
[Graphical view]
PANTHERPTHR24227. PTHR24227. 1 hit.
PfamPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSPR00657. CCCHEMOKINER.
PR00645. CXCCHMKINER4.
PR00237. GPCRRHODOPSN.
PROSITEPS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio314792.
PROO08707.
SOURCESearch...

Entry information

Entry nameACKR2_MOUSE
AccessionPrimary (citable) accession number: O08707
Secondary accession number(s): Q8CEG1
Entry history
Integrated into UniProtKB/Swiss-Prot: June 20, 2001
Last sequence update: July 27, 2011
Last modified: July 9, 2014
This is version 112 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot

7-transmembrane G-linked receptors

List of 7-transmembrane G-linked receptor entries