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O89039 (ACKR3_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 108. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:Ackr3
Synonyms:Cmkor1, Cxcr7, Rdc1
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length362 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.6

Subunit structure

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

Subcellular location

Cell membrane; Multi-pass membrane protein. Cytoplasmperinuclear region. Early endosome By similarity. Recycling endosome By similarity. Note: Predominantly localizes to endocytic vesicles, and upon stimulation by the ligand is internalized via clathrin-coated pits in a beta-arrestin -dependent manner. Once internalized, the ligand dissociates from the receptor, and is targeted to degradation while the receptor is recycled back to the cell membrane By similarity. Ref.7

Tissue specificity

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. Ref.4 Ref.5 Ref.6 Ref.7

Developmental stage

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. Ref.4

Induction

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. Ref.5

Domain

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.

Post-translational modification

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.

Sequence similarities

Belongs to the G-protein coupled receptor 1 family. Atypical chemokine receptor subfamily.

Ontologies

Keywords
   Biological processCell adhesion
   Cellular componentCell membrane
Cytoplasm
Endosome
Membrane
   DomainTransmembrane
Transmembrane helix
   Molecular functionDevelopmental protein
G-protein coupled receptor
Receptor
Transducer
   PTMDisulfide bond
Glycoprotein
Phosphoprotein
Ubl conjugation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processangiogenesis

Inferred from electronic annotation. Source: InterPro

cell adhesion

Inferred from electronic annotation. Source: UniProtKB-KW

chemotaxis

Inferred from electronic annotation. Source: InterPro

negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage

Inferred from electronic annotation. Source: Ensembl

positive regulation of ERK1 and ERK2 cascade

Inferred from sequence or structural similarity. Source: UniProtKB

receptor internalization

Inferred from sequence or structural similarity. Source: UniProtKB

vasculogenesis

Inferred from electronic annotation. Source: InterPro

   Cellular_componentcell surface

Inferred from sequence or structural similarity. Source: UniProtKB

coated pit

Inferred from sequence or structural similarity. Source: UniProtKB

early endosome

Inferred from electronic annotation. Source: UniProtKB-SubCell

endosome

Inferred from sequence or structural similarity. Source: UniProtKB

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

perinuclear region of cytoplasm

Inferred from electronic annotation. Source: UniProtKB-SubCell

plasma membrane

Inferred from sequence or structural similarity. Source: UniProtKB

recycling endosome

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionC-X-C chemokine binding

Inferred from sequence or structural similarity. Source: UniProtKB

C-X-C chemokine receptor activity

Inferred from electronic annotation. Source: Ensembl

coreceptor activity

Inferred from electronic annotation. Source: InterPro

scavenger receptor activity

Inferred from sequence or structural similarity. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 362362Atypical chemokine receptor 3
PRO_0000070103

Regions

Topological domain1 – 4747Extracellular Potential
Transmembrane48 – 6821Helical; Name=1; Potential
Topological domain69 – 8113Cytoplasmic Potential
Transmembrane82 – 10221Helical; Name=2; Potential
Topological domain103 – 11816Extracellular Potential
Transmembrane119 – 13921Helical; Name=3; Potential
Topological domain140 – 16223Cytoplasmic Potential
Transmembrane163 – 18321Helical; Name=4; Potential
Topological domain184 – 21330Extracellular Potential
Transmembrane214 – 23421Helical; Name=5; Potential
Topological domain235 – 25218Cytoplasmic Potential
Transmembrane253 – 27321Helical; Name=6; Potential
Topological domain274 – 29623Extracellular Potential
Transmembrane297 – 31923Helical; Name=7; Potential
Topological domain320 – 36243Cytoplasmic Potential
Region324 – 36239C-terminal cytoplasmic tail By similarity

Amino acid modifications

Glycosylation131N-linked (GlcNAc...) Potential
Glycosylation221N-linked (GlcNAc...) Potential
Disulfide bond117 ↔ 196 By similarity

Experimental info

Sequence conflict171I → S in CAA09370. Ref.1
Sequence conflict1611R → L in CAA09370. Ref.1
Sequence conflict3611T → A in CAA09370. Ref.1

Sequences

Sequence LengthMass (Da)Tools
O89039 [UniParc].

Last modified January 25, 2012. Version 2.
Checksum: C47D1DD678697CFD

FASTA36241,650
        10         20         30         40         50         60 
MDVHLFDYVE PGNYSDINWP CNSSDCIVVD TVQCPAMPNK NVLLYTLSFI YIFIFVIGMI 

        70         80         90        100        110        120 
ANSVVVWVNI QAKTTGYDTH CYILNLAIAD LWVVITIPVW VVSLVQHNQW PMGELTCKIT 

       130        140        150        160        170        180 
HLIFSINLFG SIFFLACMSV DRYLSITYFT STSSYKKKMV RRVVCVLVWL LAFFVSLPDT 

       190        200        210        220        230        240 
YYLKTVTSAS NNETYCRSFY PEHSIKEWLI GMELVSVILG FAVPFTIIAI FYFLLARAMS 

       250        260        270        280        290        300 
ASGDQEKHSS RKIIFSYVVV FLVCWLPYHF VVLLDIFSIL HYIPFTCQLE NVLFTALHVT 

       310        320        330        340        350        360 
QCLSLVHCCV NPVLYSFINR NYRYELMKAF IFKYSAKTGL TKLIDASRVS ETEYSALEQN 


TK 

« Hide

References

« Hide 'large scale' references
[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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AJ010828 mRNA. Translation: CAA09370.1.
AF118816 mRNA. Translation: AAF34338.1.
CH473997 Genomic DNA. Translation: EDL92073.1.
CH473997 Genomic DNA. Translation: EDL92074.1.
RefSeqNP_445804.1. NM_053352.1.
XP_006245541.1. XM_006245479.1.
UniGeneRn.12959.

3D structure databases

ProteinModelPortalO89039.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING10116.ENSRNOP00000026558.

Chemistry

GuidetoPHARMACOLOGY80.

Protein family/group databases

GPCRDBSearch...

PTM databases

PhosphoSiteO89039.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSRNOT00000026558; ENSRNOP00000026558; ENSRNOG00000019622.
GeneID84348.
KEGGrno:84348.
UCSCRGD:620601. rat.

Organism-specific databases

CTD84348.
RGD620601. Cxcr7.

Phylogenomic databases

eggNOGNOG306050.
GeneTreeENSGT00720000108367.
HOGENOMHOG000261660.
HOVERGENHBG106832.
InParanoidQ9JLZ0.
KOK04304.
OMAYIPFTCQ.
OrthoDBEOG73FQMT.
TreeFamTF333489.

Gene expression databases

GenevestigatorO89039.

Family and domain databases

Gene3D1.20.1070.10. 1 hit.
InterProIPR001416. Chemokine_CXCR7.
IPR000355. Chemokine_rcpt.
IPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
[Graphical view]
PANTHERPTHR24227. PTHR24227. 1 hit.
PfamPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSPR00237. GPCRRHODOPSN.
PR00646. RDC1ORPHANR.
PROSITEPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio616647.
PROO89039.

Entry information

Entry nameACKR3_RAT
AccessionPrimary (citable) accession number: O89039
Secondary accession number(s): Q9JLZ0
Entry history
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: January 25, 2012
Last modified: April 16, 2014
This is version 108 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

7-transmembrane G-linked receptors

List of 7-transmembrane G-linked receptor entries