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Protein

Atypical chemokine receptor 3

Gene

Ackr3

Organism
Rattus norvegicus (Rat)
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.1 Publication

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionDevelopmental protein, G-protein coupled receptor, Receptor, Transducer
Biological processCell adhesion

Enzyme and pathway databases

ReactomeiR-RNO-380108. Chemokine receptors bind chemokines.
R-RNO-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
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 9

Organism-specific databases

RGDi620601. Ackr3.

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 – 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

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Endosome, Membrane

Pathology & Biotechi

Chemistry databases

GuidetoPHARMACOLOGYi80.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000701031 – 362Atypical chemokine receptor 3Add BLAST362

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi13N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi22N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi117 ↔ 196PROSITE-ProRule annotation
Modified residuei347PhosphoserineBy similarity1
Modified residuei350PhosphoserineCombined sources1
Modified residuei355PhosphoserineBy similarity1

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

PaxDbiO89039.

PTM databases

iPTMnetiO89039.
PhosphoSitePlusiO89039.

Expressioni

Tissue specificityi

Expressed in vascular smooth muscle cells (at protein level). In brain, expressed in blood vessels, pyramidal cells in hippocampal subfield CA3, mature dentate gyrus granule cells, ventricle walls, olfactory bulb, accumbens shell, supraoptic, lateroanterior and ventromedial hypothalamic nuclei, medial region of thalamus, and motor nuclei, central gray and raphe magnus nucleus of brain stem. Detected in primary neurons, GABAergic neurons, astrocytes, cerebral cortex, ventral striatum and choroid plexus. Not detected in mesencephalon.4 Publications

Developmental stagei

Expressed in the ventral and dorsal parts of telencephalon at all developmental stages of brain analyzed (E14 to P56). Strong expression detected in the cranial connective tissue surrounding the brain at E14-E15. In the cortex, expressed mainly in the marginal zone at preplate stage (E14), with expression increasing strongly in the marginal zone/layer I between E15 and E18 and declining rapidly in layer I after P0. Expression emerges in the lateral part of cortical plate at E15 and increases in the medial and lateral parts between E15 and E17. Expression not detected in the cortical ventricular and subventricular zones at the early embryonic stages but emerges at E18. Expressed in GABAergic precursors and in some reelin-expressing Cajal-Ratzius cells, in neurons forming the cortical plate and sparsely in the developing dentate gyrus and cerebellar external germinal layer. In the ventral telencephalon, expressed in the germinative zone of the ganglionic eminences and in GABAergic neurons forming the caudate putamen between E14 and E18.1 Publication

Inductioni

By ischemia. Up-regulated in the cingulate, retrosplenial and frontal areas of the cortex ipsilateral to middle cerebral artery occlusion (MCAO) by 163% at 6 hours, 220% at 2 days and 89% at 4 days after ischemia-onset, with expression reduced back to control level at 10 days after MCAO. Expression is almost undetectable in the infarct area between days 2 and 10 after MCAO.1 Publication

Gene expression databases

BgeeiENSRNOG00000019622.
GenevisibleiO89039. RN.

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

STRINGi10116.ENSRNOP00000026558.

Structurei

3D structure databases

ProteinModelPortaliO89039.
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.
InParanoidiO89039.
KOiK04304.
OMAiYIPFTCQ.
OrthoDBiEOG091G091W.
TreeFamiTF333489.

Family and domain databases

CDDicd14987. 7tmA_ACKR3_CXCR7. 1 hit.
InterProiView protein in InterPro
IPR001416. ACKR3.
IPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
PANTHERiPTHR10489:SF750. PTHR10489:SF750. 1 hit.
PfamiView protein in Pfam
PF00001. 7tm_1. 1 hit.
PRINTSiPR00237. GPCRRHODOPSN.
PR00646. RDC1ORPHANR.
PROSITEiView protein in PROSITE
PS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.

Sequencei

Sequence statusi: Complete.

O89039-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MDVHLFDYVE PGNYSDINWP CNSSDCIVVD TVQCPAMPNK 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
STSSYKKKMV RRVVCVLVWL 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):41,650
Last modified:January 25, 2012 - v2
Checksum:iC47D1DD678697CFD
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti17I → S in CAA09370 (Ref. 1) Curated1
Sequence conflicti161R → L in CAA09370 (Ref. 1) Curated1
Sequence conflicti361T → A in CAA09370 (Ref. 1) Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ010828 mRNA. Translation: CAA09370.1.
AF118816 mRNA. Translation: AAF34338.1.
CH473997 Genomic DNA. Translation: EDL92073.1.
CH473997 Genomic DNA. Translation: EDL92074.1.
RefSeqiNP_445804.1. NM_053352.1.
XP_006245541.1. XM_006245479.3.
UniGeneiRn.12959.

Genome annotation databases

EnsembliENSRNOT00000026558; ENSRNOP00000026558; ENSRNOG00000019622.
GeneIDi84348.
KEGGirno:84348.
UCSCiRGD:620601. rat.

Similar proteinsi

Entry informationi

Entry nameiACKR3_RAT
AccessioniPrimary (citable) accession number: O89039
Secondary accession number(s): Q9JLZ0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: January 25, 2012
Last modified: August 30, 2017
This is version 126 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. 7-transmembrane G-linked receptors
    List of 7-transmembrane G-linked receptor entries
  2. SIMILARITY comments
    Index of protein domains and families