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Protein

Atypical chemokine receptor 2

Gene

Ackr2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -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
  • chemokine binding Source: GO_Central
  • scavenger receptor activity Source: UniProtKB

GO - Biological processi

Keywordsi

Molecular functionG-protein coupled receptor, Receptor, Transducer
Biological processInflammatory 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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 9

Organism-specific databases

MGIiMGI:1891697 Ackr2

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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

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...) asparagineSequence 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 Expressed in 117 organ(s), highest expression level in lung
CleanExiMM_CCBP2
ExpressionAtlasiO08707 baseline and differential
GenevisibleiO08707 MM

Interactioni

GO - Molecular functioni

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
GeneTreeiENSGT00930000150855
HOGENOMiHOG000234122
HOVERGENiHBG106917
InParanoidiO08707
KOiK04187
OMAiLWFPYNL
OrthoDBiEOG091G0FFG
TreeFamiTF330966

Family and domain databases

InterProiView protein in InterPro
IPR033037 Ackr2
IPR000355 Chemokine_rcpt
IPR001277 CXCR4/ACKR2
IPR000276 GPCR_Rhodpsn
IPR017452 GPCR_Rhodpsn_7TM
PANTHERiPTHR10489:SF735 PTHR10489:SF735, 1 hit
PfamiView protein in Pfam
PF00001 7tm_1, 1 hit
PRINTSiPR00657 CCCHEMOKINER
PR00645 CXCCHMKINER4
PR00237 GPCRRHODOPSN
PROSITEiView protein in PROSITE
PS50262 G_PROTEIN_RECEP_F1_2, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

This entry has 1 described isoform and 2 potential isoforms that are computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A1L1ST82A0A1L1ST82_MOUSE
Atypical chemokine receptor 2
Ackr2
67Annotation score:
A0A1L1SV85A0A1L1SV85_MOUSE
Atypical chemokine receptor 2
Ackr2
27Annotation score:

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
ENSMUST00000214340; ENSMUSP00000148966; ENSMUSG00000044534
GeneIDi59289
KEGGimmu:59289
UCSCiuc009sed.2 mouse

Similar proteinsi

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
ENSMUST00000214340; ENSMUSP00000148966; ENSMUSG00000044534
GeneIDi59289
KEGGimmu:59289
UCSCiuc009sed.2 mouse

Organism-specific databases

CTDi1238
MGIiMGI:1891697 Ackr2

Phylogenomic databases

eggNOGiKOG3656 Eukaryota
ENOG410XRW9 LUCA
GeneTreeiENSGT00930000150855
HOGENOMiHOG000234122
HOVERGENiHBG106917
InParanoidiO08707
KOiK04187
OMAiLWFPYNL
OrthoDBiEOG091G0FFG
TreeFamiTF330966

Miscellaneous databases

PROiPR:O08707
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000044534 Expressed in 117 organ(s), highest expression level in lung
CleanExiMM_CCBP2
ExpressionAtlasiO08707 baseline and differential
GenevisibleiO08707 MM

Family and domain databases

InterProiView protein in InterPro
IPR033037 Ackr2
IPR000355 Chemokine_rcpt
IPR001277 CXCR4/ACKR2
IPR000276 GPCR_Rhodpsn
IPR017452 GPCR_Rhodpsn_7TM
PANTHERiPTHR10489:SF735 PTHR10489:SF735, 1 hit
PfamiView protein in Pfam
PF00001 7tm_1, 1 hit
PRINTSiPR00657 CCCHEMOKINER
PR00645 CXCCHMKINER4
PR00237 GPCRRHODOPSN
PROSITEiView protein in PROSITE
PS50262 G_PROTEIN_RECEP_F1_2, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiACKR2_MOUSE
AccessioniPrimary (citable) accession number: O08707
Secondary accession number(s): Q8CEG1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: June 20, 2001
Last sequence update: July 27, 2011
Last modified: November 7, 2018
This is version 138 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

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

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