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Protein

Atypical chemokine receptor 3

Gene

Ackr3

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 CXCL11 and CXCL12/SDF1. Chemokine binding does not activate G-protein-mediated signal transduction but instead induces beta-arrestin recruitment, leading to ligand internalization and activation of MAPK signaling pathway. Required for regulation of CXCR4 protein levels in migrating interneurons, thereby adapting their chemokine responsiveness. In glioma cells, transduces signals via MEK/ERK pathway, mediating resistance to apoptosis. Promotes cell growth and survival. Not involved in cell migration, adhesion or proliferation of normal hematopoietic progenitors but activated by CXCL11 in malignant hemapoietic cells, leading to phosphorylation of ERK1/2 (MAPK3/MAPK1) and enhanced cell adhesion and migration. Plays a regulatory role in CXCR4-mediated activation of cell surface integrins by CXCL12. Required for heart valve development.5 Publications

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Developmental protein, G-protein coupled receptor, Receptor, Transducer

Keywords - Biological processi

Cell adhesion

Enzyme and pathway databases

ReactomeiR-MMU-380108. Chemokine receptors bind chemokines.
R-MMU-418594. G alpha (i) signalling events.

Names & Taxonomyi

Protein namesi
Recommended name:
Atypical chemokine receptor 3
Alternative name(s):
C-X-C chemokine receptor type 7
Short name:
CXC-R7
Short name:
CXCR-7
Chemokine orphan receptor 1
G-protein coupled receptor RDC1 homolog
Short name:
RDC-1
Gene namesi
Name:Ackr3
Synonyms:Cmkor1, Cxcr7, Rdc1
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 1

Organism-specific databases

MGIiMGI:109562. Ackr3.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 47ExtracellularSequence analysisAdd BLAST47
Transmembranei48 – 68Helical; Name=1Sequence analysisAdd BLAST21
Topological domaini69 – 81CytoplasmicSequence analysisAdd BLAST13
Transmembranei82 – 102Helical; Name=2Sequence analysisAdd BLAST21
Topological domaini103 – 118ExtracellularSequence analysisAdd BLAST16
Transmembranei119 – 139Helical; Name=3Sequence analysisAdd BLAST21
Topological domaini140 – 162CytoplasmicSequence analysisAdd BLAST23
Transmembranei163 – 183Helical; Name=4Sequence analysisAdd BLAST21
Topological domaini184 – 213ExtracellularSequence analysisAdd BLAST30
Transmembranei214 – 234Helical; Name=5Sequence analysisAdd BLAST21
Topological domaini235 – 252CytoplasmicSequence analysisAdd BLAST18
Transmembranei253 – 273Helical; Name=6Sequence analysisAdd BLAST21
Topological domaini274 – 296ExtracellularSequence analysisAdd BLAST23
Transmembranei297 – 319Helical; Name=7Sequence analysisAdd BLAST23
Topological domaini320 – 362CytoplasmicSequence analysisAdd BLAST43

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Endosome, Membrane

Pathology & Biotechi

Disruption phenotypei

Lethal at perinatal stages, with most of the neonates dying within 24 hours. Mutants display slightly enlarged heart, but no clear effect on heart functionality is observed. Mutant mice display abnormalities in semilunar valves and ventricles, myocardial degeneration and fibrosis, as well as abnormal intracortical migration of interneurons and premature invasion of the cortical plate. According to PubMed:17804806, mutants display ventricular septal and atrial septal defects. According to PubMed:21246655, mutants display ventricular septal defects but no atrial septal defects. According to PubMed:18442043, no abnormalities in semilunar valve formation or ventricular septal defects are observed. No effect on hematopoiesis, neural development and gastrointestinal vascularization is observed. No apparent bone phenotype is observed.4 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000701021 – 362Atypical chemokine receptor 3Add BLAST362

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi13N-linked (GlcNAc...)Sequence analysis1
Glycosylationi22N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi117 ↔ 196PROSITE-ProRule annotation
Modified residuei347PhosphoserineCombined sources1
Modified residuei350PhosphoserineCombined sources1
Modified residuei355PhosphoserineCombined sources1

Post-translational modificationi

The Ser/Thr residues in the C-terminal cytoplasmic tail may be phosphorylated.By similarity
Ubiquitinated at the Lys residues in its C-terminal cytoplasmic tail and is essential for correct trafficking from and to the cell membrane. Deubiquitinated by CXCL12-stimulation in a reversible manner (By similarity).By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQBiP56485.
PaxDbiP56485.
PRIDEiP56485.

PTM databases

iPTMnetiP56485.
PhosphoSitePlusiP56485.

Expressioni

Tissue specificityi

Not detected in blood, liver, lung and heart, but high expression detected in several tumor cell lines (at protein level). Expressed in heart, spleen, kidney, lung, ovary, brain, testis, astrocytes, neutrophils and B-lymphocytes.3 Publications

Developmental stagei

Expression detected after E9.5 in the endothelial layer of the forming heart, neural tube, brain and septum transversum. At E10.5, expressed at high levels in the prosencephalon and in a part of the rhombencephalon and at lower levels in the neural tube, somites and heart. Detected in liver at E11 and E13, but not at E15 and E17. During heart development, expression detected mainly in endocardial cells and endocardial cushion mesenchymal cells in both outflow tract and atrioventricular canal regions and to a lesser degree in myocardial cells at E10.5, in the mesenchyme of the forming valves and in numerous microvessels in the myocardium at E12.5, and from E14.5 onward mainly in the microvasculature associated with myocardium, valves and great vessels. In developing telencephalon, observed at E11.5 in the ventral telencephalon in proliferative zones of the medial ganglionic eminence (MGE), in ventral part of the lateral ganglionic eminence (LGE) and in Cajal-Retzius (CR) neurons of dorsal telencephalon. At E12.5, detected in migrating olfactory tubercle neuron precursors and cortical interneurons, and in CR cells and subplate neurons of the cortex. At E13.5, observed in the germinal zone of MGE in the subpallium, in the marginal zone and cortical subventricular zone (SVZ) of the lateral cortex as well as in pyramidal cells and tangentially migrating interneurons. At postnatal stages, expressed in postnatal cortical plate and in migrating olfactory bulb interneurons in the striatal SVZ and rostral migratory stream.5 Publications

Gene expression databases

BgeeiENSMUSG00000044337.
CleanExiMM_CXCR7.
GenevisibleiP56485. MM.

Interactioni

Subunit structurei

Homodimer. Can form heterodimers with CXCR4; heterodimerization may regulate CXCR4 signaling activity (By similarity).Interacts with ARRB1 and ARRB2 (By similarity).By similarity

GO - Molecular functioni

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000069114.

Structurei

3D structure databases

ProteinModelPortaliP56485.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni324 – 362C-terminal cytoplasmic tailBy similarityAdd BLAST39

Domaini

The C-terminal cytoplasmic tail, plays a key role in: correct trafficking to the cell membrane, recruitment of beta-arrestin, ubiquitination, and in chemokine scavenging and signaling functions. The Ser/Thr residues and the Lys residues in the C-terminal cytoplasmic tail are essential for beta-arrestin recruitment and ubiquitination respectively (By similarity).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.
GeneTreeiENSGT00760000119055.
HOGENOMiHOG000261660.
HOVERGENiHBG106832.
InParanoidiP56485.
KOiK04304.
OMAiYIPFTCQ.
OrthoDBiEOG091G091W.
PhylomeDBiP56485.
TreeFamiTF333489.

Family and domain databases

InterProiIPR001416. ACKR3.
IPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
[Graphical view]
PANTHERiPTHR10489:SF682. PTHR10489:SF682. 1 hit.
PfamiPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSiPR00237. GPCRRHODOPSN.
PR00646. RDC1ORPHANR.
PROSITEiPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P56485-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MDVHLFDYAE PGNYSDINWP CNSSDCIVVD TVQCPTMPNK NVLLYTLSFI
60 70 80 90 100
YIFIFVIGMI ANSVVVWVNI QAKTTGYDTH CYILNLAIAD LWVVITIPVW
110 120 130 140 150
VVSLVQHNQW PMGELTCKIT HLIFSINLFG SIFFLACMSV DRYLSITYFT
160 170 180 190 200
GTSSYKKKMV RRVVCILVWL LAFFVSLPDT YYLKTVTSAS NNETYCRSFY
210 220 230 240 250
PEHSIKEWLI GMELVSVILG FAVPFTIIAI FYFLLARAMS ASGDQEKHSS
260 270 280 290 300
RKIIFSYVVV FLVCWLPYHF VVLLDIFSIL HYIPFTCQLE NVLFTALHVT
310 320 330 340 350
QCLSLVHCCV NPVLYSFINR NYRYELMKAF IFKYSAKTGL TKLIDASRVS
360
ETEYSALEQN TK
Length:362
Mass (Da):41,636
Last modified:May 10, 2004 - v2
Checksum:i7A0399DED5B73E66
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti97I → T in AAB71343 (PubMed:9510554).Curated1
Sequence conflicti185T → A in AAB71343 (PubMed:9510554).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF000236 mRNA. Translation: AAB71343.1.
AK031100 mRNA. Translation: BAC27252.1.
BC015254 mRNA. Translation: AAH15254.1.
CCDSiCCDS15152.1.
RefSeqiNP_001258536.1. NM_001271607.1.
NP_031748.2. NM_007722.4.
UniGeneiMm.491219.
Mm.6522.

Genome annotation databases

EnsembliENSMUST00000065587; ENSMUSP00000069114; ENSMUSG00000044337.
GeneIDi12778.
KEGGimmu:12778.
UCSCiuc007bzh.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF000236 mRNA. Translation: AAB71343.1.
AK031100 mRNA. Translation: BAC27252.1.
BC015254 mRNA. Translation: AAH15254.1.
CCDSiCCDS15152.1.
RefSeqiNP_001258536.1. NM_001271607.1.
NP_031748.2. NM_007722.4.
UniGeneiMm.491219.
Mm.6522.

3D structure databases

ProteinModelPortaliP56485.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000069114.

Protein family/group databases

GPCRDBiSearch...

PTM databases

iPTMnetiP56485.
PhosphoSitePlusiP56485.

Proteomic databases

MaxQBiP56485.
PaxDbiP56485.
PRIDEiP56485.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000065587; ENSMUSP00000069114; ENSMUSG00000044337.
GeneIDi12778.
KEGGimmu:12778.
UCSCiuc007bzh.2. mouse.

Organism-specific databases

CTDi57007.
MGIiMGI:109562. Ackr3.

Phylogenomic databases

eggNOGiKOG3656. Eukaryota.
ENOG410XRW9. LUCA.
GeneTreeiENSGT00760000119055.
HOGENOMiHOG000261660.
HOVERGENiHBG106832.
InParanoidiP56485.
KOiK04304.
OMAiYIPFTCQ.
OrthoDBiEOG091G091W.
PhylomeDBiP56485.
TreeFamiTF333489.

Enzyme and pathway databases

ReactomeiR-MMU-380108. Chemokine receptors bind chemokines.
R-MMU-418594. G alpha (i) signalling events.

Miscellaneous databases

PROiP56485.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000044337.
CleanExiMM_CXCR7.
GenevisibleiP56485. MM.

Family and domain databases

InterProiIPR001416. ACKR3.
IPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
[Graphical view]
PANTHERiPTHR10489:SF682. PTHR10489:SF682. 1 hit.
PfamiPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSiPR00237. GPCRRHODOPSN.
PR00646. RDC1ORPHANR.
PROSITEiPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiACKR3_MOUSE
AccessioniPrimary (citable) accession number: P56485
Secondary accession number(s): Q91WI0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: May 10, 2004
Last modified: November 30, 2016
This is version 136 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.