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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

Complete GO annotation...

Keywords - Molecular functioni

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

Keywords - Biological processi

Cell adhesion

Enzyme and pathway databases

ReactomeiREACT_278843. Chemokine receptors bind chemokines.
REACT_339234. 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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
ProteomesiUP000002494 Componenti: Chromosome 9

Organism-specific databases

RGDi620601. Ackr3.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 4747ExtracellularSequence AnalysisAdd
BLAST
Transmembranei48 – 6821Helical; Name=1Sequence AnalysisAdd
BLAST
Topological domaini69 – 8113CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei82 – 10221Helical; Name=2Sequence AnalysisAdd
BLAST
Topological domaini103 – 11816ExtracellularSequence AnalysisAdd
BLAST
Transmembranei119 – 13921Helical; Name=3Sequence AnalysisAdd
BLAST
Topological domaini140 – 16223CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei163 – 18321Helical; Name=4Sequence AnalysisAdd
BLAST
Topological domaini184 – 21330ExtracellularSequence AnalysisAdd
BLAST
Transmembranei214 – 23421Helical; Name=5Sequence AnalysisAdd
BLAST
Topological domaini235 – 25218CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei253 – 27321Helical; Name=6Sequence AnalysisAdd
BLAST
Topological domaini274 – 29623ExtracellularSequence AnalysisAdd
BLAST
Transmembranei297 – 31923Helical; Name=7Sequence AnalysisAdd
BLAST
Topological domaini320 – 36243CytoplasmicSequence AnalysisAdd
BLAST

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Endosome, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 362362Atypical chemokine receptor 3PRO_0000070103Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi13 – 131N-linked (GlcNAc...)Sequence Analysis
Glycosylationi22 – 221N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi117 ↔ 196PROSITE-ProRule annotation

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

PTM databases

PhosphoSiteiO89039.

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

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

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000026558.

Structurei

3D structure databases

ProteinModelPortaliO89039.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni324 – 36239C-terminal cytoplasmic tailBy similarityAdd
BLAST

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

eggNOGiNOG306050.
GeneTreeiENSGT00760000119055.
HOGENOMiHOG000261660.
HOVERGENiHBG106832.
InParanoidiO89039.
KOiK04304.
OMAiYIPFTCQ.
OrthoDBiEOG73FQMT.
TreeFamiTF333489.

Family and domain databases

InterProiIPR001416. Chemokine_CXCR7.
IPR000355. Chemokine_rcpt.
IPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
[Graphical view]
PANTHERiPTHR24227. PTHR24227. 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.

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)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti17 – 171I → S in CAA09370 (Ref. 1) Curated
Sequence conflicti161 – 1611R → L in CAA09370 (Ref. 1) Curated
Sequence conflicti361 – 3611T → A in CAA09370 (Ref. 1) Curated

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_006245479.2.
XP_008765521.1. XM_008767299.1.
XP_008765522.1. XM_008767300.1.
UniGeneiRn.12959.

Genome annotation databases

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

Cross-referencesi

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_006245479.2.
XP_008765521.1. XM_008767299.1.
XP_008765522.1. XM_008767300.1.
UniGeneiRn.12959.

3D structure databases

ProteinModelPortaliO89039.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000026558.

Chemistry

GuidetoPHARMACOLOGYi80.

Protein family/group databases

GPCRDBiSearch...

PTM databases

PhosphoSiteiO89039.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi57007.
RGDi620601. Ackr3.

Phylogenomic databases

eggNOGiNOG306050.
GeneTreeiENSGT00760000119055.
HOGENOMiHOG000261660.
HOVERGENiHBG106832.
InParanoidiO89039.
KOiK04304.
OMAiYIPFTCQ.
OrthoDBiEOG73FQMT.
TreeFamiTF333489.

Enzyme and pathway databases

ReactomeiREACT_278843. Chemokine receptors bind chemokines.
REACT_339234. G alpha (i) signalling events.

Miscellaneous databases

NextBioi616647.
PROiO89039.

Gene expression databases

GenevisibleiO89039. RN.

Family and domain databases

InterProiIPR001416. Chemokine_CXCR7.
IPR000355. Chemokine_rcpt.
IPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
[Graphical view]
PANTHERiPTHR24227. PTHR24227. 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...

Publicationsi

« Hide 'large scale' publications
  1. "Investigation of the role of rat RDC-1 as a putative calcitonin gene-related peptide receptor."
    Mirtella A., Lowe S.R., Bartlett T.J., Drake W., Clark A.J.
    Submitted (SEP-1998) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Strain: Sprague-Dawley.
    Tissue: Lung.
  2. Xie P., Fu A.K.Y., Ip N.Y.
    Submitted (JAN-1999) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Muscle.
  3. Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.
    Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  4. "Regional and cellular localization of the CXCl12/SDF-1 chemokine receptor CXCR7 in the developing and adult rat brain."
    Schonemeier B., Kolodziej A., Schulz S., Jacobs S., Hoellt V., Stumm R.
    J. Comp. Neurol. 510:207-220(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: TISSUE SPECIFICITY, DEVELOPMENTAL STAGE.
  5. "Enhanced expression of the CXCl12/SDF-1 chemokine receptor CXCR7 after cerebral ischemia in the rat brain."
    Schonemeier B., Schulz S., Hoellt V., Stumm R.
    J. Neuroimmunol. 198:39-45(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: TISSUE SPECIFICITY, INDUCTION.
  6. "Beta-arrestin- but not G protein-mediated signaling by the 'decoy' receptor CXCR7."
    Rajagopal S., Kim J., Ahn S., Craig S., Lam C.M., Gerard N.P., Gerard C., Lefkowitz R.J.
    Proc. Natl. Acad. Sci. U.S.A. 107:628-632(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, TISSUE SPECIFICITY.
  7. "CXCR7 protein expression in human adult brain and differentiated neurons."
    Shimizu S., Brown M., Sengupta R., Penfold M.E., Meucci O.
    PLoS ONE 6:E20680-E20680(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.

Entry informationi

Entry nameiACKR3_RAT
AccessioniPrimary (citable) accession number: O89039
Secondary accession number(s): Q9JLZ0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: January 25, 2012
Last modified: June 24, 2015
This is version 114 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. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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 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.