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O09027

- ACKR2_RAT

UniProt

O09027 - ACKR2_RAT

Protein

Atypical chemokine receptor 2

Gene

Ackr2

Organism
Rattus norvegicus (Rat)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at transcript leveli
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    • History
      Entry version 103 (01 Oct 2014)
      Sequence version 1 (01 Jul 1997)
      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 including CCL2, CCL3, CCL3L1, CCL4, CCL5, CCL7, CCL8, CCL11, CCL13, CCL17, CCL22, CCL23, CCL24, SCYA2/MCP-1, SCY3/MIP-1-alpha, SCYA5/RANTES and SCYA7/MCP-3. Upon active ligand stimulation, activates a beta-arrestin 1 (ARRB1)-dependent, G protein-independent signaling pathway that results in the phosphorylation of the actin-binding protein cofilin (CFL1) through a RAC1-PAK1-LIMK1 signaling pathway. Activation of this pathway results in up-regulation of ACKR2 from endosomal compartment to cell membrane, increasing its efficiency in chemokine uptake and degradation. By scavenging chemokines in tissues, on the surfaces of lymphatic vessels, and in placenta, plays an essential role in the resolution (termination) of the inflammatory response and in the regulation of adaptive immune responses. Plays a major role in the immune silencing of macrophages during the resolution of inflammation. Acts as a regulator of inflammatory leukocyte interactions with lymphatic endothelial cells (LECs) and is required for immature/mature dendritic cells discrimination by LECs.

    GO - Molecular functioni

    1. C-X-C chemokine receptor activity Source: InterPro
    2. scavenger receptor activity Source: UniProtKB

    GO - Biological processi

    1. chemotaxis Source: InterPro
    2. inflammatory response Source: UniProtKB-KW
    3. neutrophil activation Source: InterPro
    4. receptor-mediated endocytosis Source: GOC

    Keywords - Molecular functioni

    G-protein coupled receptor, Receptor, Transducer

    Keywords - Biological processi

    Inflammatory response

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Atypical chemokine receptor 2
    Alternative name(s):
    C-C chemokine receptor D6
    CCR10-related receptor
    Chemokine-binding protein 2
    Chemokine-binding protein D6
    Gene namesi
    Name:Ackr2
    Synonyms:Ccbp2, Ccr10rr, D6
    OrganismiRattus norvegicus (Rat)
    Taxonomic identifieri10116 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
    ProteomesiUP000002494: Unplaced

    Organism-specific databases

    RGDi620323. Ackr2.

    Subcellular locationi

    Early endosome By similarity. Recycling endosome By similarity. Cell membrane; Multi-pass membrane protein
    Note: Predominantly localizes to endocytic vesicles, and upon stimulation by the ligand is internalized via clathrin-coated pits. 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. actin filament Source: UniProtKB
    2. early endosome Source: UniProtKB-SubCell
    3. integral component of membrane Source: UniProtKB-KW
    4. plasma membrane Source: UniProtKB
    5. recycling endosome Source: UniProtKB-SubCell

    Keywords - Cellular componenti

    Cell membrane, Endosome, Membrane

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 382382Atypical chemokine receptor 2PRO_0000069221Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Glycosylationi17 – 171N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi117 ↔ 195PROSITE-ProRule annotation

    Post-translational modificationi

    Phosphorylated on serine residues in the C-terminal cytoplasmic tail.By similarity

    Keywords - PTMi

    Disulfide bond, Glycoprotein, Phosphoprotein

    PTM databases

    PhosphoSiteiO09027.

    Expressioni

    Tissue specificityi

    Predominantly expressed in spleen.

    Gene expression databases

    GenevestigatoriO09027.

    Interactioni

    Protein-protein interaction databases

    STRINGi10116.ENSRNOP00000026343.

    Structurei

    3D structure databases

    ProteinModelPortaliO09027.
    ModBaseiSearch...
    MobiDBiSearch...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini1 – 4949ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini71 – 9222CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini114 – 1185ExtracellularSequence Analysis
    Topological domaini141 – 16222CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini184 – 21734ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini239 – 25012CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini272 – 29322ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini315 – 38268CytoplasmicSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei50 – 7021Helical; Name=1Sequence AnalysisAdd
    BLAST
    Transmembranei93 – 11321Helical; Name=2Sequence AnalysisAdd
    BLAST
    Transmembranei119 – 14022Helical; Name=3Sequence AnalysisAdd
    BLAST
    Transmembranei163 – 18321Helical; Name=4Sequence AnalysisAdd
    BLAST
    Transmembranei218 – 23821Helical; Name=5Sequence AnalysisAdd
    BLAST
    Transmembranei251 – 27121Helical; Name=6Sequence AnalysisAdd
    BLAST
    Transmembranei294 – 31421Helical; Name=7Sequence AnalysisAdd
    BLAST

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni327 – 38256C-terminal cytoplasmic tailBy similarityAdd
    BLAST

    Domaini

    The C-terminal cytoplasmic tail controls its phosphorylation, stability, intracellular trafficking itinerary, and chemokine scavenging properties.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

    eggNOGiNOG297330.
    HOGENOMiHOG000234122.
    HOVERGENiHBG106917.
    InParanoidiO09027.
    PhylomeDBiO09027.

    Family and domain databases

    Gene3Di1.20.1070.10. 1 hit.
    InterProiIPR001277. Chemokine_CXCR4.
    IPR000355. Chemokine_rcpt.
    IPR000276. GPCR_Rhodpsn.
    IPR017452. GPCR_Rhodpsn_7TM.
    [Graphical view]
    PANTHERiPTHR24227. PTHR24227. 1 hit.
    PfamiPF00001. 7tm_1. 1 hit.
    [Graphical view]
    PRINTSiPR00657. CCCHEMOKINER.
    PR00645. CXCCHMKINER4.
    PR00237. GPCRRHODOPSN.
    PROSITEiPS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    O09027-1 [UniParc]FASTAAdd to Basket

    « Hide

    MPTIASPLPL ATTGPENGSS IYDYDYLDDV TVLVCSKDEV LSFGRVFLPV    50
    VYSLIFVLGL AGNLLLLVVL LHSVPQRRRM IELYLLNLAV SNLLFVVTMP 100
    FWAISVAWHW VFGSFLCKVV STLYSINFYC GIFFITCMSL DKYLEIVHAQ 150
    PLHRPKTRFR NLLLIVMVWI TALAVSVPEM VFVKVHQTLD GVWHCYADFG 200
    GHATIWKLYL RFQMNLLGFL FPLLAMIFFY SRIGCVLVRL RPPGQGRALR 250
    MAAALVVVFF LLWFPYNLTL FLHSLLDLHV FGNCKISHRL DYMLQVTESL 300
    AFSHCCFTPV LYAFSSHSFR QYLKAVLSVV LRRHQAPGTA HAPPCSHSES 350
    SRVTAQEDVV SMNDLGERQA DISLNKGEIG NN 382
    Length:382
    Mass (Da):43,293
    Last modified:July 1, 1997 - v1
    Checksum:iE8714CE23DB96772
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U92803 mRNA. Translation: AAB61572.1.
    UniGeneiRn.10771.
    Rn.234526.

    Genome annotation databases

    UCSCiRGD:620323. rat.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U92803 mRNA. Translation: AAB61572.1 .
    UniGenei Rn.10771.
    Rn.234526.

    3D structure databases

    ProteinModelPortali O09027.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    STRINGi 10116.ENSRNOP00000026343.

    Protein family/group databases

    GPCRDBi Search...

    PTM databases

    PhosphoSitei O09027.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    UCSCi RGD:620323. rat.

    Organism-specific databases

    RGDi 620323. Ackr2.

    Phylogenomic databases

    eggNOGi NOG297330.
    HOGENOMi HOG000234122.
    HOVERGENi HBG106917.
    InParanoidi O09027.
    PhylomeDBi O09027.

    Miscellaneous databases

    PROi O09027.

    Gene expression databases

    Genevestigatori O09027.

    Family and domain databases

    Gene3Di 1.20.1070.10. 1 hit.
    InterProi IPR001277. Chemokine_CXCR4.
    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 PR00657. CCCHEMOKINER.
    PR00645. CXCCHMKINER4.
    PR00237. GPCRRHODOPSN.
    PROSITEi PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Molecular cloning and expression of a novel rat CC-chemokine receptor (rCCR10rR) that binds MCP-1 and MIP-1beta with high affinity."
      Bonini J.A., Steiner D.F.
      DNA Cell Biol. 16:1023-1030(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Strain: Sprague-Dawley.

    Entry informationi

    Entry nameiACKR2_RAT
    AccessioniPrimary (citable) accession number: O09027
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: June 20, 2001
    Last sequence update: July 1, 1997
    Last modified: October 1, 2014
    This is version 103 of the entry and version 1 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