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O89039

- ACKR3_RAT

UniProt

O89039 - ACKR3_RAT

Protein

Atypical chemokine receptor 3

Gene

Ackr3

Organism
Rattus norvegicus (Rat)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 109 (01 Oct 2014)
      Sequence version 2 (25 Jan 2012)
      Previous versions | rss
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    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

    1. coreceptor activity Source: InterPro
    2. C-X-C chemokine binding Source: UniProtKB
    3. C-X-C chemokine receptor activity Source: Ensembl
    4. scavenger receptor activity Source: UniProtKB

    GO - Biological processi

    1. angiogenesis Source: InterPro
    2. cell adhesion Source: UniProtKB-KW
    3. chemotaxis Source: InterPro
    4. negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage Source: Ensembl
    5. positive regulation of ERK1 and ERK2 cascade Source: UniProtKB
    6. receptor internalization Source: UniProtKB
    7. vasculogenesis Source: InterPro

    Keywords - Molecular functioni

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

    Keywords - Biological processi

    Cell adhesion

    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: Chromosome 9

    Organism-specific databases

    RGDi620601. Cxcr7.

    Subcellular locationi

    Cell membrane 1 Publication; Multi-pass membrane protein 1 Publication. Cytoplasmperinuclear region 1 Publication. 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.By similarity

    GO - Cellular componenti

    1. cell surface Source: UniProtKB
    2. coated pit Source: UniProtKB
    3. early endosome Source: UniProtKB-SubCell
    4. endosome Source: UniProtKB
    5. integral component of membrane Source: UniProtKB-KW
    6. perinuclear region of cytoplasm Source: UniProtKB-SubCell
    7. plasma membrane Source: UniProtKB
    8. recycling endosome Source: UniProtKB-SubCell

    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

    GenevestigatoriO89039.

    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...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini1 – 4747ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini69 – 8113CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini103 – 11816ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini140 – 16223CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini184 – 21330ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini235 – 25218CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini274 – 29623ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini320 – 36243CytoplasmicSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei48 – 6821Helical; Name=1Sequence AnalysisAdd
    BLAST
    Transmembranei82 – 10221Helical; Name=2Sequence AnalysisAdd
    BLAST
    Transmembranei119 – 13921Helical; Name=3Sequence AnalysisAdd
    BLAST
    Transmembranei163 – 18321Helical; Name=4Sequence AnalysisAdd
    BLAST
    Transmembranei214 – 23421Helical; Name=5Sequence AnalysisAdd
    BLAST
    Transmembranei253 – 27321Helical; Name=6Sequence AnalysisAdd
    BLAST
    Transmembranei297 – 31923Helical; Name=7Sequence AnalysisAdd
    BLAST

    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.
    GeneTreeiENSGT00720000108367.
    HOGENOMiHOG000261660.
    HOVERGENiHBG106832.
    InParanoidiQ9JLZ0.
    KOiK04304.
    OMAiYIPFTCQ.
    OrthoDBiEOG73FQMT.
    TreeFamiTF333489.

    Family and domain databases

    Gene3Di1.20.1070.10. 1 hit.
    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

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    MDVHLFDYVE PGNYSDINWP CNSSDCIVVD TVQCPAMPNK NVLLYTLSFI    50
    YIFIFVIGMI ANSVVVWVNI QAKTTGYDTH CYILNLAIAD LWVVITIPVW 100
    VVSLVQHNQW PMGELTCKIT HLIFSINLFG SIFFLACMSV DRYLSITYFT 150
    STSSYKKKMV RRVVCVLVWL LAFFVSLPDT YYLKTVTSAS NNETYCRSFY 200
    PEHSIKEWLI GMELVSVILG FAVPFTIIAI FYFLLARAMS ASGDQEKHSS 250
    RKIIFSYVVV FLVCWLPYHF VVLLDIFSIL HYIPFTCQLE NVLFTALHVT 300
    QCLSLVHCCV NPVLYSFINR NYRYELMKAF IFKYSAKTGL TKLIDASRVS 350
    ETEYSALEQN TK 362
    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. 1 PublicationCurated
    Sequence conflicti161 – 1611R → L in CAA09370. 1 PublicationCurated
    Sequence conflicti361 – 3611T → A in CAA09370. 1 PublicationCurated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    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_006245479.1.
    UniGeneiRn.12959.

    Genome annotation databases

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

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AJ010828 mRNA. Translation: CAA09370.1 .
    AF118816 mRNA. Translation: AAF34338.1 .
    CH473997 Genomic DNA. Translation: EDL92073.1 .
    CH473997 Genomic DNA. Translation: EDL92074.1 .
    RefSeqi NP_445804.1. NM_053352.1.
    XP_006245541.1. XM_006245479.1.
    UniGenei Rn.12959.

    3D structure databases

    ProteinModelPortali O89039.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    STRINGi 10116.ENSRNOP00000026558.

    Chemistry

    GuidetoPHARMACOLOGYi 80.

    Protein family/group databases

    GPCRDBi Search...

    PTM databases

    PhosphoSitei O89039.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSRNOT00000026558 ; ENSRNOP00000026558 ; ENSRNOG00000019622 .
    GeneIDi 84348.
    KEGGi rno:84348.
    UCSCi RGD:620601. rat.

    Organism-specific databases

    CTDi 84348.
    RGDi 620601. Cxcr7.

    Phylogenomic databases

    eggNOGi NOG306050.
    GeneTreei ENSGT00720000108367.
    HOGENOMi HOG000261660.
    HOVERGENi HBG106832.
    InParanoidi Q9JLZ0.
    KOi K04304.
    OMAi YIPFTCQ.
    OrthoDBi EOG73FQMT.
    TreeFami TF333489.

    Miscellaneous databases

    NextBioi 616647.
    PROi O89039.

    Gene expression databases

    Genevestigatori O89039.

    Family and domain databases

    Gene3Di 1.20.1070.10. 1 hit.
    InterProi IPR001416. Chemokine_CXCR7.
    IPR000355. Chemokine_rcpt.
    IPR000276. GPCR_Rhodpsn.
    IPR017452. GPCR_Rhodpsn_7TM.
    [Graphical view ]
    PANTHERi PTHR24227. PTHR24227. 1 hit.
    Pfami PF00001. 7tm_1. 1 hit.
    [Graphical view ]
    PRINTSi PR00237. GPCRRHODOPSN.
    PR00646. RDC1ORPHANR.
    PROSITEi PS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
    PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    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: October 1, 2014
    This is version 109 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