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O08707

- ACKR2_MOUSE

UniProt

O08707 - ACKR2_MOUSE

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Protein
Atypical chemokine receptor 2
Gene
Ackr2, Ccbp2, D6
Organism
Mus musculus (Mouse)
Status
Reviewed - 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

  1. C-C chemokine binding Source: BHF-UCL
  2. C-C chemokine receptor activity Source: MGI
  3. C-X-C chemokine receptor activity Source: InterPro
  4. protein binding Source: MGI
  5. scavenger receptor activity Source: UniProtKB

GO - Biological processi

  1. chemokine-mediated signaling pathway Source: GOC
  2. chemotaxis Source: InterPro
  3. inflammatory response Source: UniProtKB-KW
  4. neutrophil activation Source: InterPro
  5. receptor-mediated endocytosis Source: GOC
  6. signal transduction Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

G-protein coupled receptor, Receptor, Transducer

Keywords - Biological processi

Inflammatory response

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: 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.

Topology

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

GO - Cellular componenti

  1. actin filament Source: UniProtKB
  2. early endosome Source: UniProtKB-SubCell
  3. integral component of membrane Source: UniProtKB-KW
  4. plasma membrane Source: UniProtKB
  5. recycling endosome Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Endosome, Membrane

PTM / Processingi

Molecule processing

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

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi17 – 171N-linked (GlcNAc...) Reviewed prediction
Disulfide bondi116 ↔ 194 By similarity

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.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni326 – 37853C-terminal cytoplasmic tail By similarity
Add
BLAST

Domaini

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

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG297330.
GeneTreeiENSGT00700000104251.
HOGENOMiHOG000234122.
HOVERGENiHBG106917.
InParanoidiQ8CEG1.
KOiK04187.
OMAiHCCFTPI.
OrthoDBiEOG7HMS1P.
TreeFamiTF330966.

Family and domain databases

Gene3Di1.20.1070.10. 1 hit.
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

MPTVASPLPL TTVGSENSSS IYDYDYLDDM TILVCRKDEV LSFGRVFLPV    50
VYSLIFVLGL AGNLLLLVVL LHSAPRRRTM ELYLLNLAVS NLLFVVTMPF 100
WAISVAWHWV FGSFLCKVIS TLYSINFYCG IFFITCMSLD KYLEIVHAQP 150
LHRPKAQFRN LLLIVMVWIT SLAISVPEMV FVQIHQTLDG VWHCYADFGG 200
HATIWKLYLR FQLNLLGFLL PLLAMIFFYS RIGCVLVRLR PPGQGRALRM 250
AAALVIVFFM LWFPYNLTLF LHSLLDLHVF GNCEISHRLD YTLQVTESLA 300
FSHCCFTPVL YAFCSHRFRR YLKAFLSVML RWHQAPGTPS SNHSESSRVT 350
AQEDVVSMND LGERQSEDSL NKGEMGNT 378
Length:378
Mass (Da):43,207
Last modified:July 27, 2011 - v2
Checksum:i1436D49E71698172
GO

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti266 – 2661N → Y in CAA73379. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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_006512203.1.
XP_006512267.1. XM_006512204.1.
UniGeneiMm.258105.
Mm.491478.

Genome annotation databases

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

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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 .
CCDSi CCDS23640.1.
RefSeqi NP_001263648.1. NM_001276719.1.
NP_067622.2. NM_021609.4.
XP_006512266.1. XM_006512203.1.
XP_006512267.1. XM_006512204.1.
UniGenei Mm.258105.
Mm.491478.

3D structure databases

ProteinModelPortali O08707.
SMRi O08707. Positions 39-319.
ModBasei Search...
MobiDBi Search...

Protein family/group databases

GPCRDBi Search...

PTM databases

PhosphoSitei O08707.

Proteomic databases

PRIDEi O08707.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000050327 ; ENSMUSP00000050119 ; ENSMUSG00000044534 .
GeneIDi 59289.
KEGGi mmu:59289.
UCSCi uc009sed.1. mouse.

Organism-specific databases

CTDi 1238.
MGIi MGI:1891697. Ackr2.

Phylogenomic databases

eggNOGi NOG297330.
GeneTreei ENSGT00700000104251.
HOGENOMi HOG000234122.
HOVERGENi HBG106917.
InParanoidi Q8CEG1.
KOi K04187.
OMAi HCCFTPI.
OrthoDBi EOG7HMS1P.
TreeFami TF330966.

Miscellaneous databases

NextBioi 314792.
PROi O08707.
SOURCEi Search...

Gene expression databases

Bgeei O08707.
CleanExi MM_CCBP2.
Genevestigatori O08707.

Family and domain databases

Gene3Di 1.20.1070.10. 1 hit.
InterProi IPR001277. Chemokine_CXCR4.
IPR000355. Chemokine_rcpt.
IPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
[Graphical view ]
PANTHERi PTHR24227. PTHR24227. 1 hit.
Pfami PF00001. 7tm_1. 1 hit.
[Graphical view ]
PRINTSi PR00657. CCCHEMOKINER.
PR00645. CXCCHMKINER4.
PR00237. GPCRRHODOPSN.
PROSITEi PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view ]
ProtoNeti Search...

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: July 9, 2014
This is version 112 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