UniProtKB - O00590 (ACKR2_HUMAN)
Atypical chemokine receptor 2
ACKR2
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.
2 PublicationsGO - Molecular functioni
- C-C chemokine binding Source: GO_Central
- C-C chemokine receptor activity Source: GO_Central
- chemokine receptor activity Source: ProtInc
- scavenger receptor activity Source: UniProtKB
GO - Biological processi
- calcium-mediated signaling Source: GO_Central
- cell chemotaxis Source: GO_Central
- immune response Source: GO_Central
- inflammatory response Source: UniProtKB-KW
- intracellular signal transduction Source: ProtInc
- positive regulation of cytosolic calcium ion concentration Source: GO_Central
Keywordsi
Molecular function | G-protein coupled receptor, Receptor, Transducer |
Biological process | Inflammatory response |
Enzyme and pathway databases
PathwayCommonsi | O00590 |
Reactomei | R-HSA-380108, Chemokine receptors bind chemokines |
SignaLinki | O00590 |
Names & Taxonomyi
Protein namesi | Recommended name: Atypical chemokine receptor 2Alternative name(s): C-C chemokine receptor D6 Chemokine receptor CCR-10 Chemokine receptor CCR-9 Chemokine-binding protein 2 Chemokine-binding protein D6 |
Gene namesi | Name:ACKR2 Synonyms:CCBP2, CCR10, CMKBR9, D6 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:1565, ACKR2 |
MIMi | 602648, gene |
neXtProti | NX_O00590 |
VEuPathDBi | HostDB:ENSG00000144648 |
Subcellular locationi
Endosome
Plasma membrane
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.
Cytoskeleton
- actin filament Source: UniProtKB
Cytosol
- cytosol Source: HPA
Endosome
- early endosome Source: UniProtKB-SubCell
- recycling endosome Source: UniProtKB-SubCell
Nucleus
- nuclear membrane Source: HPA
- nucleoplasm Source: HPA
Plasma Membrane
- external side of plasma membrane Source: GO_Central
- integral component of plasma membrane Source: ProtInc
- plasma membrane Source: UniProtKB
Other locations
- intracellular membrane-bounded organelle Source: HPA
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 1 – 50 | ExtracellularSequence analysisAdd BLAST | 50 | |
Transmembranei | 51 – 71 | Helical; Name=1Sequence analysisAdd BLAST | 21 | |
Topological domaini | 72 – 92 | CytoplasmicSequence analysisAdd BLAST | 21 | |
Transmembranei | 93 – 113 | Helical; Name=2Sequence analysisAdd BLAST | 21 | |
Topological domaini | 114 – 118 | ExtracellularSequence analysis | 5 | |
Transmembranei | 119 – 140 | Helical; Name=3Sequence analysisAdd BLAST | 22 | |
Topological domaini | 141 – 162 | CytoplasmicSequence analysisAdd BLAST | 22 | |
Transmembranei | 163 – 183 | Helical; Name=4Sequence analysisAdd BLAST | 21 | |
Topological domaini | 184 – 217 | ExtracellularSequence analysisAdd BLAST | 34 | |
Transmembranei | 218 – 238 | Helical; Name=5Sequence analysisAdd BLAST | 21 | |
Topological domaini | 239 – 250 | CytoplasmicSequence analysisAdd BLAST | 12 | |
Transmembranei | 251 – 271 | Helical; Name=6Sequence analysisAdd BLAST | 21 | |
Topological domaini | 272 – 293 | ExtracellularSequence analysisAdd BLAST | 22 | |
Transmembranei | 294 – 314 | Helical; Name=7Sequence analysisAdd BLAST | 21 | |
Topological domaini | 315 – 384 | CytoplasmicSequence analysisAdd BLAST | 70 |
Keywords - Cellular componenti
Cell membrane, Endosome, MembranePathology & Biotechi
Organism-specific databases
DisGeNETi | 1238 |
OpenTargetsi | ENSG00000144648 |
PharmGKBi | PA26139 |
Miscellaneous databases
Pharosi | O00590, Tbio |
Chemistry databases
ChEMBLi | CHEMBL4105988 |
Genetic variation databases
BioMutai | ACKR2 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000069219 | 1 – 384 | Atypical chemokine receptor 2Add BLAST | 384 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Glycosylationi | 19 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Disulfide bondi | 117 ↔ 195 | PROSITE-ProRule annotation |
Post-translational modificationi
Keywords - PTMi
Disulfide bond, Glycoprotein, PhosphoproteinProteomic databases
MassIVEi | O00590 |
PaxDbi | O00590 |
PeptideAtlasi | O00590 |
PRIDEi | O00590 |
ProteomicsDBi | 47990 |
PTM databases
GlyGeni | O00590, 1 site |
iPTMneti | O00590 |
PhosphoSitePlusi | O00590 |
Expressioni
Tissue specificityi
Inductioni
Gene expression databases
Bgeei | ENSG00000144648, Expressed in chorionic villus and 123 other tissues |
ExpressionAtlasi | O00590, baseline and differential |
Genevisiblei | O00590, HS |
Organism-specific databases
HPAi | ENSG00000144648, Tissue enhanced (liver, placenta) |
Interactioni
Binary interactionsi
O00590
GO - Molecular functioni
- C-C chemokine binding Source: GO_Central
Protein-protein interaction databases
BioGRIDi | 107643, 81 interactors |
IntActi | O00590, 9 interactors |
STRINGi | 9606.ENSP00000416996 |
Chemistry databases
BindingDBi | O00590 |
Miscellaneous databases
RNActi | O00590, protein |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 327 – 384 | C-terminal cytoplasmic tailAdd BLAST | 58 | |
Regioni | 363 – 384 | DisorderedSequence analysisAdd BLAST | 22 |
Domaini
Sequence similaritiesi
Keywords - Domaini
Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | KOG3656, Eukaryota |
GeneTreei | ENSGT01020000230359 |
InParanoidi | O00590 |
OMAi | IVHAQPH |
OrthoDBi | 791532at2759 |
PhylomeDBi | O00590 |
TreeFami | TF330966 |
Family and domain databases
InterProi | View protein in InterPro IPR033037, Ackr2 IPR000355, Chemokine_rcpt IPR001277, CXCR4/ACKR2 IPR000276, GPCR_Rhodpsn IPR017452, GPCR_Rhodpsn_7TM |
PANTHERi | PTHR10489:SF735, PTHR10489:SF735, 1 hit |
Pfami | View protein in Pfam PF00001, 7tm_1, 1 hit |
PRINTSi | PR00657, CCCHEMOKINER PR00645, CXCCHMKINER4 PR00237, GPCRRHODOPSN |
PROSITEi | View protein in PROSITE PS50262, G_PROTEIN_RECEP_F1_2, 1 hit |
(1+)i Sequence
Sequence statusi: Complete.
This entry has 1 described isoform and 4 potential isoforms that are computationally mapped.Show allAlign All
10 20 30 40 50
MAATASPQPL ATEDADSENS SFYYYDYLDE VAFMLCRKDA VVSFGKVFLP
60 70 80 90 100
VFYSLIFVLG LSGNLLLLMV LLRYVPRRRM VEIYLLNLAI SNLLFLVTLP
110 120 130 140 150
FWGISVAWHW VFGSFLCKMV STLYTINFYS GIFFISCMSL DKYLEIVHAQ
160 170 180 190 200
PYHRLRTRAK SLLLATIVWA VSLAVSIPDM VFVQTHENPK GVWNCHADFG
210 220 230 240 250
GHGTIWKLFL RFQQNLLGFL LPLLAMIFFY SRIGCVLVRL RPAGQGRALK
260 270 280 290 300
IAAALVVAFF VLWFPYNLTL FLHTLLDLQV FGNCEVSQHL DYALQVTESI
310 320 330 340 350
AFLHCCFSPI LYAFSSHRFR QYLKAFLAAV LGWHLAPGTA QASLSSCSES
360 370 380
SILTAQEEMT GMNDLGERQS ENYPNKEDVG NKSA
Computationally mapped potential isoform sequencesi
There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketV9GYB7 | V9GYB7_HUMAN | Atypical chemokine receptor 2 | ACKR2 | 233 | Annotation score: | ||
V9GYX0 | V9GYX0_HUMAN | Atypical chemokine receptor 2 | ACKR2 | 170 | Annotation score: | ||
V9GZ70 | V9GZ70_HUMAN | Atypical chemokine receptor 2 | ACKR2 | 142 | Annotation score: | ||
V9GYM0 | V9GYM0_HUMAN | Atypical chemokine receptor 2 | ACKR2 | 124 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 17 | S → A in AAB97728 (PubMed:9364936).Curated | 1 | |
Sequence conflicti | 161 | S → N in AAB97728 (PubMed:9364936).Curated | 1 | |
Sequence conflicti | 356 | Q → L in AAB97728 (PubMed:9364936).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_049379 | 41 | V → A. Corresponds to variant dbSNP:rs2228467Ensembl. | 1 | |
Natural variantiVAR_049380 | 248 | A → V. Corresponds to variant dbSNP:rs2228469Ensembl. | 1 | |
Natural variantiVAR_049381 | 311 | L → V. Corresponds to variant dbSNP:rs6779520Ensembl. | 1 | |
Natural variantiVAR_024252 | 373 | Y → S1 PublicationCorresponds to variant dbSNP:rs2228468Ensembl. | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | U94888 mRNA Translation: AAB97728.1 Y12815 mRNA Translation: CAA73346.1 AY262687 Genomic DNA Translation: AAP20651.1 BT006800 mRNA Translation: AAP35446.1 AK313561 mRNA Translation: BAG36335.1 BC008816 mRNA Translation: AAH08816.1 BC011631 mRNA Translation: AAH11631.1 BC020558 mRNA Translation: AAH20558.1 BC101629 mRNA Translation: AAI01630.1 BC112045 mRNA Translation: AAI12046.1 |
CCDSi | CCDS2706.1 |
RefSeqi | NP_001287.2, NM_001296.4 |
Genome annotation databases
Ensembli | ENST00000422265; ENSP00000416996; ENSG00000144648 ENST00000442925; ENSP00000396150; ENSG00000144648 |
GeneIDi | 1238 |
KEGGi | hsa:1238 |
MANE-Selecti | ENST00000422265.6; ENSP00000416996.1; NM_001296.5; NP_001287.2 |
UCSCi | uc003cme.4, human |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | U94888 mRNA Translation: AAB97728.1 Y12815 mRNA Translation: CAA73346.1 AY262687 Genomic DNA Translation: AAP20651.1 BT006800 mRNA Translation: AAP35446.1 AK313561 mRNA Translation: BAG36335.1 BC008816 mRNA Translation: AAH08816.1 BC011631 mRNA Translation: AAH11631.1 BC020558 mRNA Translation: AAH20558.1 BC101629 mRNA Translation: AAI01630.1 BC112045 mRNA Translation: AAI12046.1 |
CCDSi | CCDS2706.1 |
RefSeqi | NP_001287.2, NM_001296.4 |
3D structure databases
SMRi | O00590 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 107643, 81 interactors |
IntActi | O00590, 9 interactors |
STRINGi | 9606.ENSP00000416996 |
Chemistry databases
BindingDBi | O00590 |
ChEMBLi | CHEMBL4105988 |
Protein family/group databases
GPCRDBi | Search... |
PTM databases
GlyGeni | O00590, 1 site |
iPTMneti | O00590 |
PhosphoSitePlusi | O00590 |
Genetic variation databases
BioMutai | ACKR2 |
Proteomic databases
MassIVEi | O00590 |
PaxDbi | O00590 |
PeptideAtlasi | O00590 |
PRIDEi | O00590 |
ProteomicsDBi | 47990 |
Protocols and materials databases
Antibodypediai | 2896, 428 antibodies from 36 providers |
DNASUi | 1238 |
Genome annotation databases
Ensembli | ENST00000422265; ENSP00000416996; ENSG00000144648 ENST00000442925; ENSP00000396150; ENSG00000144648 |
GeneIDi | 1238 |
KEGGi | hsa:1238 |
MANE-Selecti | ENST00000422265.6; ENSP00000416996.1; NM_001296.5; NP_001287.2 |
UCSCi | uc003cme.4, human |
Organism-specific databases
CTDi | 1238 |
DisGeNETi | 1238 |
GeneCardsi | ACKR2 |
HGNCi | HGNC:1565, ACKR2 |
HPAi | ENSG00000144648, Tissue enhanced (liver, placenta) |
MIMi | 602648, gene |
neXtProti | NX_O00590 |
OpenTargetsi | ENSG00000144648 |
PharmGKBi | PA26139 |
VEuPathDBi | HostDB:ENSG00000144648 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG3656, Eukaryota |
GeneTreei | ENSGT01020000230359 |
InParanoidi | O00590 |
OMAi | IVHAQPH |
OrthoDBi | 791532at2759 |
PhylomeDBi | O00590 |
TreeFami | TF330966 |
Enzyme and pathway databases
PathwayCommonsi | O00590 |
Reactomei | R-HSA-380108, Chemokine receptors bind chemokines |
SignaLinki | O00590 |
Miscellaneous databases
BioGRID-ORCSi | 1238, 6 hits in 998 CRISPR screens |
ChiTaRSi | ACKR2, human |
GeneWikii | CCBP2 |
GenomeRNAii | 1238 |
Pharosi | O00590, Tbio |
PROi | PR:O00590 |
RNActi | O00590, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000144648, Expressed in chorionic villus and 123 other tissues |
ExpressionAtlasi | O00590, baseline and differential |
Genevisiblei | O00590, HS |
Family and domain databases
InterProi | View protein in InterPro IPR033037, Ackr2 IPR000355, Chemokine_rcpt IPR001277, CXCR4/ACKR2 IPR000276, GPCR_Rhodpsn IPR017452, GPCR_Rhodpsn_7TM |
PANTHERi | PTHR10489:SF735, PTHR10489:SF735, 1 hit |
Pfami | View protein in Pfam PF00001, 7tm_1, 1 hit |
PRINTSi | PR00657, CCCHEMOKINER PR00645, CXCCHMKINER4 PR00237, GPCRRHODOPSN |
PROSITEi | View protein in PROSITE PS50262, G_PROTEIN_RECEP_F1_2, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | ACKR2_HUMAN | |
Accessioni | O00590Primary (citable) accession number: O00590 Secondary accession number(s): B2R8Y8 Q96A02 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | June 20, 2001 |
Last sequence update: | May 2, 2002 | |
Last modified: | February 23, 2022 | |
This is version 184 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- 7-transmembrane G-linked receptors
List of 7-transmembrane G-linked receptor entries - Human chromosome 3
Human chromosome 3: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - SIMILARITY comments
Index of protein domains and families