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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
  • scavenger receptor activity Source: UniProtKB

GO - Biological processi

  • chemotaxis Source: InterPro
  • inflammatory response Source: UniProtKB-KW
  • 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
Proteomesi
  • UP000000589 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)DescriptionActionsGraphical viewLength
Topological domaini1 – 49ExtracellularSequence analysisAdd BLAST49
Transmembranei50 – 70Helical; Name=1Sequence analysisAdd BLAST21
Topological domaini71 – 91CytoplasmicSequence analysisAdd BLAST21
Transmembranei92 – 112Helical; Name=2Sequence analysisAdd BLAST21
Topological domaini113 – 117ExtracellularSequence analysis5
Transmembranei118 – 139Helical; Name=3Sequence analysisAdd BLAST22
Topological domaini140 – 161CytoplasmicSequence analysisAdd BLAST22
Transmembranei162 – 182Helical; Name=4Sequence analysisAdd BLAST21
Topological domaini183 – 216ExtracellularSequence analysisAdd BLAST34
Transmembranei217 – 237Helical; Name=5Sequence analysisAdd BLAST21
Topological domaini238 – 249CytoplasmicSequence analysisAdd BLAST12
Transmembranei250 – 270Helical; Name=6Sequence analysisAdd BLAST21
Topological domaini271 – 292ExtracellularSequence analysisAdd BLAST22
Transmembranei293 – 313Helical; Name=7Sequence analysisAdd BLAST21
Topological domaini314 – 378CytoplasmicSequence analysisAdd BLAST65

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Endosome, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000692201 – 378Atypical chemokine receptor 2Add BLAST378

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi17N-linked (GlcNAc...)Sequence analysis1
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

PaxDbiO08707.
PRIDEiO08707.

PTM databases

PhosphoSitePlusiO08707.

Expressioni

Tissue specificityi

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

Gene expression databases

BgeeiENSMUSG00000044534.
CleanExiMM_CCBP2.
GenevisibleiO08707. MM.

Interactioni

GO - Molecular functioni

  • C-C chemokine binding Source: BHF-UCL

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000050119.

Structurei

3D structure databases

ProteinModelPortaliO08707.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni326 – 378C-terminal cytoplasmic tailBy similarityAdd BLAST53

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

eggNOGiKOG3656. Eukaryota.
ENOG410XRW9. LUCA.
GeneTreeiENSGT00760000118785.
HOGENOMiHOG000234122.
HOVERGENiHBG106917.
InParanoidiO08707.
KOiK04187.
OMAiHCCFTPI.
OrthoDBiEOG091G0FFG.
TreeFamiTF330966.

Family and domain databases

InterProiIPR033037. Ackr2.
IPR000355. Chemokine_rcpt.
IPR001277. CXCR4/ACKR2.
IPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
[Graphical view]
PANTHERiPTHR10489:SF735. PTHR10489:SF735. 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)DescriptionActionsGraphical viewLength
Sequence conflicti266N → Y in CAA73379 (PubMed:9139699).Curated1

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_006512203.3.
XP_006512267.1. XM_006512204.3.
UniGeneiMm.258105.
Mm.491478.

Genome annotation databases

EnsembliENSMUST00000050327; ENSMUSP00000050119; ENSMUSG00000044534.
GeneIDi59289.
KEGGimmu:59289.
UCSCiuc009sed.2. 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_006512203.3.
XP_006512267.1. XM_006512204.3.
UniGeneiMm.258105.
Mm.491478.

3D structure databases

ProteinModelPortaliO08707.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000050119.

Protein family/group databases

GPCRDBiSearch...

PTM databases

PhosphoSitePlusiO08707.

Proteomic databases

PaxDbiO08707.
PRIDEiO08707.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000050327; ENSMUSP00000050119; ENSMUSG00000044534.
GeneIDi59289.
KEGGimmu:59289.
UCSCiuc009sed.2. mouse.

Organism-specific databases

CTDi1238.
MGIiMGI:1891697. Ackr2.

Phylogenomic databases

eggNOGiKOG3656. Eukaryota.
ENOG410XRW9. LUCA.
GeneTreeiENSGT00760000118785.
HOGENOMiHOG000234122.
HOVERGENiHBG106917.
InParanoidiO08707.
KOiK04187.
OMAiHCCFTPI.
OrthoDBiEOG091G0FFG.
TreeFamiTF330966.

Miscellaneous databases

PROiO08707.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000044534.
CleanExiMM_CCBP2.
GenevisibleiO08707. MM.

Family and domain databases

InterProiIPR033037. Ackr2.
IPR000355. Chemokine_rcpt.
IPR001277. CXCR4/ACKR2.
IPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
[Graphical view]
PANTHERiPTHR10489:SF735. PTHR10489:SF735. 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...

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: November 30, 2016
This is version 131 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

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 one 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.