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Protein

Atypical chemokine receptor 2

Gene

ACKR2

Organism
Homo sapiens (Human)
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.2 Publications

GO - Molecular functioni

  • C-C chemokine receptor activity Source: Ensembl
  • chemokine receptor activity Source: ProtInc
  • scavenger receptor activity Source: UniProtKB

GO - Biological processi

  • chemotaxis Source: ProtInc
  • G-protein coupled receptor signaling pathway Source: ProtInc
  • immune response Source: ProtInc
  • inflammatory response Source: UniProtKB-KW
  • multicellular organism development Source: ProtInc
Complete GO annotation...

Keywords - Molecular functioni

G-protein coupled receptor, Receptor, Transducer

Keywords - Biological processi

Inflammatory response

Enzyme and pathway databases

BioCyciZFISH:ENSG00000144648-MONOMER.
ZFISH:ENSG00000172348-MONOMER.

Names & Taxonomyi

Protein namesi
Recommended name:
Atypical chemokine receptor 2
Alternative 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
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 3

Organism-specific databases

HGNCiHGNC:1565. ACKR2.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 50ExtracellularSequence analysisAdd BLAST50
Transmembranei51 – 71Helical; Name=1Sequence analysisAdd BLAST21
Topological domaini72 – 92CytoplasmicSequence analysisAdd BLAST21
Transmembranei93 – 113Helical; Name=2Sequence analysisAdd BLAST21
Topological domaini114 – 118ExtracellularSequence analysis5
Transmembranei119 – 140Helical; Name=3Sequence analysisAdd BLAST22
Topological domaini141 – 162CytoplasmicSequence analysisAdd BLAST22
Transmembranei163 – 183Helical; Name=4Sequence analysisAdd BLAST21
Topological domaini184 – 217ExtracellularSequence analysisAdd BLAST34
Transmembranei218 – 238Helical; Name=5Sequence analysisAdd BLAST21
Topological domaini239 – 250CytoplasmicSequence analysisAdd BLAST12
Transmembranei251 – 271Helical; Name=6Sequence analysisAdd BLAST21
Topological domaini272 – 293ExtracellularSequence analysisAdd BLAST22
Transmembranei294 – 314Helical; Name=7Sequence analysisAdd BLAST21
Topological domaini315 – 384CytoplasmicSequence analysisAdd BLAST70

GO - Cellular componenti

  • actin filament Source: UniProtKB
  • early endosome Source: UniProtKB-SubCell
  • integral component of plasma membrane Source: ProtInc
  • plasma membrane Source: UniProtKB
  • recycling endosome Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Endosome, Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi1238.
OpenTargetsiENSG00000144648.
PharmGKBiPA26139.

Polymorphism and mutation databases

BioMutaiCCBP2.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000692191 – 384Atypical chemokine receptor 2Add BLAST384

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi19N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi117 ↔ 195PROSITE-ProRule annotation

Post-translational modificationi

Phosphorylated on serine residues in the C-terminal cytoplasmic tail.1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiO00590.
PeptideAtlasiO00590.
PRIDEiO00590.

PTM databases

iPTMnetiO00590.
PhosphoSitePlusiO00590.

Expressioni

Tissue specificityi

Found in endothelial cells lining afferent lymphatics in dermis and lymph nodes. Also found in lymph nodes subcapsular and medullary sinuses, tonsillar lymphatic sinuses and lymphatics in mucosa and submucosa of small and large intestine and appendix. Also found in some malignant vascular tumors. Expressed at high levels in Kaposi sarcoma-related pathologies. Expressed on apoptotic neutrophils (at protein level). Expressed primarily in placenta and fetal liver, and found at very low levels in the lung and lymph node.3 Publications

Inductioni

By interleukin-6 and interferon-gamma.1 Publication

Gene expression databases

BgeeiENSG00000144648.
CleanExiHS_CCBP2.
HS_CCR10.
ExpressionAtlasiO00590. baseline and differential.
GenevisibleiO00590. HS.

Organism-specific databases

HPAiHPA013819.

Interactioni

Protein-protein interaction databases

BioGridi107643. 9 interactors.
MINTiMINT-6631488.
STRINGi9606.ENSP00000273145.

Structurei

3D structure databases

ProteinModelPortaliO00590.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni327 – 384C-terminal cytoplasmic tailAdd BLAST58

Domaini

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

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.
InParanoidiO00590.
KOiK04187.
OMAiHCCFTPI.
OrthoDBiEOG091G0FFG.
PhylomeDBiO00590.
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.

O00590-1 [UniParc]FASTAAdd to basket

« Hide

        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
Length:384
Mass (Da):43,443
Last modified:May 2, 2002 - v2
Checksum:i464C5703C1DE9A6A
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti17S → A in AAB97728 (PubMed:9364936).Curated1
Sequence conflicti161S → N in AAB97728 (PubMed:9364936).Curated1
Sequence conflicti356Q → L in AAB97728 (PubMed:9364936).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_04937941V → A.Corresponds to variant rs2228467dbSNPEnsembl.1
Natural variantiVAR_049380248A → V.Corresponds to variant rs2228469dbSNPEnsembl.1
Natural variantiVAR_049381311L → V.Corresponds to variant rs6779520dbSNPEnsembl.1
Natural variantiVAR_024252373Y → S.1 PublicationCorresponds to variant rs2228468dbSNPEnsembl.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.
CCDSiCCDS2706.1.
RefSeqiNP_001287.2. NM_001296.4.
UniGeneiHs.146346.

Genome annotation databases

EnsembliENST00000422265; ENSP00000416996; ENSG00000144648.
ENST00000442925; ENSP00000396150; ENSG00000144648.
GeneIDi1238.
KEGGihsa:1238.
UCSCiuc003cme.4. human.

Keywords - Coding sequence diversityi

Polymorphism

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.
CCDSiCCDS2706.1.
RefSeqiNP_001287.2. NM_001296.4.
UniGeneiHs.146346.

3D structure databases

ProteinModelPortaliO00590.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi107643. 9 interactors.
MINTiMINT-6631488.
STRINGi9606.ENSP00000273145.

Protein family/group databases

GPCRDBiSearch...

PTM databases

iPTMnetiO00590.
PhosphoSitePlusiO00590.

Polymorphism and mutation databases

BioMutaiCCBP2.

Proteomic databases

PaxDbiO00590.
PeptideAtlasiO00590.
PRIDEiO00590.

Protocols and materials databases

DNASUi1238.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000422265; ENSP00000416996; ENSG00000144648.
ENST00000442925; ENSP00000396150; ENSG00000144648.
GeneIDi1238.
KEGGihsa:1238.
UCSCiuc003cme.4. human.

Organism-specific databases

CTDi1238.
DisGeNETi1238.
GeneCardsiACKR2.
HGNCiHGNC:1565. ACKR2.
HPAiHPA013819.
MIMi602648. gene.
neXtProtiNX_O00590.
OpenTargetsiENSG00000144648.
PharmGKBiPA26139.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3656. Eukaryota.
ENOG410XRW9. LUCA.
GeneTreeiENSGT00760000118785.
HOGENOMiHOG000234122.
HOVERGENiHBG106917.
InParanoidiO00590.
KOiK04187.
OMAiHCCFTPI.
OrthoDBiEOG091G0FFG.
PhylomeDBiO00590.
TreeFamiTF330966.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000144648-MONOMER.
ZFISH:ENSG00000172348-MONOMER.

Miscellaneous databases

ChiTaRSiACKR2. human.
GeneWikiiCCBP2.
GenomeRNAii1238.
PROiO00590.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000144648.
CleanExiHS_CCBP2.
HS_CCR10.
ExpressionAtlasiO00590. baseline and differential.
GenevisibleiO00590. HS.

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_HUMAN
AccessioniPrimary (citable) accession number: O00590
Secondary accession number(s): B2R8Y8
, O00537, Q53YA1, Q86UN9, Q96A02
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 20, 2001
Last sequence update: May 2, 2002
Last modified: November 30, 2016
This is version 151 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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

Complete proteome, Reference proteome

Documents

  1. 7-transmembrane G-linked receptors
    List of 7-transmembrane G-linked receptor entries
  2. Human chromosome 3
    Human chromosome 3: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. 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.