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Protein

Atypical chemokine receptor 2

Gene

Ackr2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.1 Publication

GO - Molecular functioni

  • C-C chemokine binding Source: BHF-UCL
  • C-C chemokine receptor activity Source: MGI
  • C-X-C chemokine receptor activity Source: InterPro
  • scavenger receptor activity Source: UniProtKB

GO - Biological processi

  • chemokine-mediated signaling pathway Source: GOC
  • chemotaxis Source: InterPro
  • inflammatory response Source: UniProtKB-KW
  • neutrophil activation Source: InterPro
  • receptor-mediated endocytosis Source: MGI
  • signal transduction Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

G-protein coupled receptor, Receptor, Transducer

Keywords - Biological processi

Inflammatory response

Enzyme and pathway databases

ReactomeiREACT_288802. Chemokine receptors bind chemokines.

Names & Taxonomyi

Protein namesi
Recommended name:
Atypical chemokine receptor 2
Alternative name(s):
C-C chemokine receptor D6
Chemokine-binding protein 2
Chemokine-binding protein D6
Gene namesi
Name:Ackr2
Synonyms:Ccbp2, D6
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589 Componenti: Chromosome 9

Organism-specific databases

MGIiMGI:1891697. Ackr2.

Subcellular locationi

  • 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).By similarity

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 4949ExtracellularSequence AnalysisAdd
BLAST
Transmembranei50 – 7021Helical; Name=1Sequence AnalysisAdd
BLAST
Topological domaini71 – 9121CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei92 – 11221Helical; Name=2Sequence AnalysisAdd
BLAST
Topological domaini113 – 1175ExtracellularSequence Analysis
Transmembranei118 – 13922Helical; Name=3Sequence AnalysisAdd
BLAST
Topological domaini140 – 16122CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei162 – 18221Helical; Name=4Sequence AnalysisAdd
BLAST
Topological domaini183 – 21634ExtracellularSequence AnalysisAdd
BLAST
Transmembranei217 – 23721Helical; Name=5Sequence AnalysisAdd
BLAST
Topological domaini238 – 24912CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei250 – 27021Helical; Name=6Sequence AnalysisAdd
BLAST
Topological domaini271 – 29222ExtracellularSequence AnalysisAdd
BLAST
Transmembranei293 – 31321Helical; Name=7Sequence AnalysisAdd
BLAST
Topological domaini314 – 37865CytoplasmicSequence AnalysisAdd
BLAST

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Endosome, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 378378Atypical chemokine receptor 2PRO_0000069220Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi17 – 171N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi116 ↔ 194PROSITE-ProRule annotation

Post-translational modificationi

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

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

PRIDEiO08707.

PTM databases

PhosphoSiteiO08707.

Expressioni

Tissue specificityi

Expressed on apoptotic neutrophils (at protein level).1 Publication

Gene expression databases

BgeeiO08707.
CleanExiMM_CCBP2.
GenevestigatoriO08707.

Structurei

3D structure databases

ProteinModelPortaliO08707.
SMRiO08707. Positions 39-319.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni326 – 37853C-terminal cytoplasmic tailBy similarityAdd
BLAST

Domaini

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

Sequence similaritiesi

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

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG297330.
GeneTreeiENSGT00760000118785.
HOGENOMiHOG000234122.
HOVERGENiHBG106917.
InParanoidiO08707.
KOiK04187.
OMAiHCCFTPI.
OrthoDBiEOG7HMS1P.
TreeFamiTF330966.

Family and domain databases

InterProiIPR001277. Chemokine_CXCR4.
IPR000355. Chemokine_rcpt.
IPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
[Graphical view]
PANTHERiPTHR24227. PTHR24227. 1 hit.
PfamiPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSiPR00657. CCCHEMOKINER.
PR00645. CXCCHMKINER4.
PR00237. GPCRRHODOPSN.
PROSITEiPS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

O08707-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MPTVASPLPL TTVGSENSSS IYDYDYLDDM TILVCRKDEV LSFGRVFLPV
60 70 80 90 100
VYSLIFVLGL AGNLLLLVVL LHSAPRRRTM ELYLLNLAVS NLLFVVTMPF
110 120 130 140 150
WAISVAWHWV FGSFLCKVIS TLYSINFYCG IFFITCMSLD KYLEIVHAQP
160 170 180 190 200
LHRPKAQFRN LLLIVMVWIT SLAISVPEMV FVQIHQTLDG VWHCYADFGG
210 220 230 240 250
HATIWKLYLR FQLNLLGFLL PLLAMIFFYS RIGCVLVRLR PPGQGRALRM
260 270 280 290 300
AAALVIVFFM LWFPYNLTLF LHSLLDLHVF GNCEISHRLD YTLQVTESLA
310 320 330 340 350
FSHCCFTPVL YAFCSHRFRR YLKAFLSVML RWHQAPGTPS SNHSESSRVT
360 370
AQEDVVSMND LGERQSEDSL NKGEMGNT
Length:378
Mass (Da):43,207
Last modified:July 27, 2011 - v2
Checksum:i1436D49E71698172
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti266 – 2661N → Y in CAA73379 (PubMed:9139699).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS23640.1.
RefSeqiNP_001263648.1. NM_001276719.1.
NP_067622.2. NM_021609.4.
XP_006512266.1. XM_006512203.2.
XP_006512267.1. XM_006512204.2.
UniGeneiMm.258105.
Mm.491478.

Genome annotation databases

EnsembliENSMUST00000050327; ENSMUSP00000050119; ENSMUSG00000044534.
GeneIDi59289.
KEGGimmu:59289.
UCSCiuc009sed.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS23640.1.
RefSeqiNP_001263648.1. NM_001276719.1.
NP_067622.2. NM_021609.4.
XP_006512266.1. XM_006512203.2.
XP_006512267.1. XM_006512204.2.
UniGeneiMm.258105.
Mm.491478.

3D structure databases

ProteinModelPortaliO08707.
SMRiO08707. Positions 39-319.
ModBaseiSearch...
MobiDBiSearch...

Protein family/group databases

GPCRDBiSearch...

PTM databases

PhosphoSiteiO08707.

Proteomic databases

PRIDEiO08707.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000050327; ENSMUSP00000050119; ENSMUSG00000044534.
GeneIDi59289.
KEGGimmu:59289.
UCSCiuc009sed.1. mouse.

Organism-specific databases

CTDi1238.
MGIiMGI:1891697. Ackr2.

Phylogenomic databases

eggNOGiNOG297330.
GeneTreeiENSGT00760000118785.
HOGENOMiHOG000234122.
HOVERGENiHBG106917.
InParanoidiO08707.
KOiK04187.
OMAiHCCFTPI.
OrthoDBiEOG7HMS1P.
TreeFamiTF330966.

Enzyme and pathway databases

ReactomeiREACT_288802. Chemokine receptors bind chemokines.

Miscellaneous databases

NextBioi314792.
PROiO08707.
SOURCEiSearch...

Gene expression databases

BgeeiO08707.
CleanExiMM_CCBP2.
GenevestigatoriO08707.

Family and domain databases

InterProiIPR001277. Chemokine_CXCR4.
IPR000355. Chemokine_rcpt.
IPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
[Graphical view]
PANTHERiPTHR24227. PTHR24227. 1 hit.
PfamiPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSiPR00657. CCCHEMOKINER.
PR00645. CXCCHMKINER4.
PR00237. GPCRRHODOPSN.
PROSITEiPS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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.
    , 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.

Entry informationi

Entry nameiACKR2_MOUSE
AccessioniPrimary (citable) accession number: O08707
Secondary accession number(s): Q8CEG1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 20, 2001
Last sequence update: July 27, 2011
Last modified: April 1, 2015
This is version 118 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. 7-transmembrane G-linked receptors
    List of 7-transmembrane G-linked receptor entries
  2. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.