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O08707

- ACKR2_MOUSE

UniProt

O08707 - ACKR2_MOUSE

Protein

Atypical chemokine receptor 2

Gene

Ackr2

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 113 (01 Oct 2014)
      Sequence version 2 (27 Jul 2011)
      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.1 Publication

    GO - Molecular functioni

    1. C-C chemokine binding Source: BHF-UCL
    2. C-C chemokine receptor activity Source: MGI
    3. C-X-C chemokine receptor activity Source: InterPro
    4. protein binding Source: MGI
    5. scavenger receptor activity Source: UniProtKB

    GO - Biological processi

    1. chemokine-mediated signaling pathway Source: GOC
    2. chemotaxis Source: InterPro
    3. inflammatory response Source: UniProtKB-KW
    4. neutrophil activation Source: InterPro
    5. receptor-mediated endocytosis Source: GOC
    6. signal transduction Source: MGI

    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
    Chemokine-binding protein 2
    Chemokine-binding protein D6
    Gene namesi
    Name:Ackr2
    Synonyms:Ccbp2, D6
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 9

    Organism-specific databases

    MGIiMGI:1891697. 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 – 378378Atypical chemokine receptor 2PRO_0000069220Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Glycosylationi17 – 171N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi116 ↔ 194PROSITE-ProRule annotation

    Post-translational modificationi

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

    Keywords - PTMi

    Disulfide bond, Glycoprotein, Phosphoprotein

    Proteomic databases

    PRIDEiO08707.

    PTM databases

    PhosphoSiteiO08707.

    Expressioni

    Tissue specificityi

    Expressed on apoptotic neutrophils (at protein level).1 Publication

    Gene expression databases

    BgeeiO08707.
    CleanExiMM_CCBP2.
    GenevestigatoriO08707.

    Structurei

    3D structure databases

    ProteinModelPortaliO08707.
    SMRiO08707. Positions 39-319.
    ModBaseiSearch...
    MobiDBiSearch...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini1 – 4949ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini71 – 9121CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini113 – 1175ExtracellularSequence Analysis
    Topological domaini140 – 16122CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini183 – 21634ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini238 – 24912CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini271 – 29222ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini314 – 37865CytoplasmicSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei50 – 7021Helical; Name=1Sequence AnalysisAdd
    BLAST
    Transmembranei92 – 11221Helical; Name=2Sequence AnalysisAdd
    BLAST
    Transmembranei118 – 13922Helical; Name=3Sequence AnalysisAdd
    BLAST
    Transmembranei162 – 18221Helical; Name=4Sequence AnalysisAdd
    BLAST
    Transmembranei217 – 23721Helical; Name=5Sequence AnalysisAdd
    BLAST
    Transmembranei250 – 27021Helical; Name=6Sequence AnalysisAdd
    BLAST
    Transmembranei293 – 31321Helical; Name=7Sequence AnalysisAdd
    BLAST

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni326 – 37853C-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.
    GeneTreeiENSGT00700000104251.
    HOGENOMiHOG000234122.
    HOVERGENiHBG106917.
    InParanoidiQ8CEG1.
    KOiK04187.
    OMAiHCCFTPI.
    OrthoDBiEOG7HMS1P.
    TreeFamiTF330966.

    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.

    O08707-1 [UniParc]FASTAAdd to Basket

    « Hide

    MPTVASPLPL TTVGSENSSS IYDYDYLDDM TILVCRKDEV LSFGRVFLPV    50
    VYSLIFVLGL AGNLLLLVVL LHSAPRRRTM ELYLLNLAVS NLLFVVTMPF 100
    WAISVAWHWV FGSFLCKVIS TLYSINFYCG IFFITCMSLD KYLEIVHAQP 150
    LHRPKAQFRN LLLIVMVWIT SLAISVPEMV FVQIHQTLDG VWHCYADFGG 200
    HATIWKLYLR FQLNLLGFLL PLLAMIFFYS RIGCVLVRLR PPGQGRALRM 250
    AAALVIVFFM LWFPYNLTLF LHSLLDLHVF GNCEISHRLD YTLQVTESLA 300
    FSHCCFTPVL YAFCSHRFRR YLKAFLSVML RWHQAPGTPS SNHSESSRVT 350
    AQEDVVSMND LGERQSEDSL NKGEMGNT 378
    Length:378
    Mass (Da):43,207
    Last modified:July 27, 2011 - v2
    Checksum:i1436D49E71698172
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti266 – 2661N → Y in CAA73379. (PubMed:9139699)Curated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    Y12879 mRNA. Translation: CAA73379.1.
    AK028281 mRNA. Translation: BAC25855.1.
    AK145960 mRNA. Translation: BAE26786.1.
    AK147166 mRNA. Translation: BAE27731.1.
    AK157140 mRNA. Translation: BAE33976.1.
    CH466587 Genomic DNA. Translation: EDL09123.1.
    BC113146 mRNA. Translation: AAI13147.1.
    CCDSiCCDS23640.1.
    RefSeqiNP_001263648.1. NM_001276719.1.
    NP_067622.2. NM_021609.4.
    XP_006512266.1. XM_006512203.1.
    XP_006512267.1. XM_006512204.1.
    UniGeneiMm.258105.
    Mm.491478.

    Genome annotation databases

    EnsembliENSMUST00000050327; ENSMUSP00000050119; ENSMUSG00000044534.
    GeneIDi59289.
    KEGGimmu:59289.
    UCSCiuc009sed.1. mouse.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    Y12879 mRNA. Translation: CAA73379.1 .
    AK028281 mRNA. Translation: BAC25855.1 .
    AK145960 mRNA. Translation: BAE26786.1 .
    AK147166 mRNA. Translation: BAE27731.1 .
    AK157140 mRNA. Translation: BAE33976.1 .
    CH466587 Genomic DNA. Translation: EDL09123.1 .
    BC113146 mRNA. Translation: AAI13147.1 .
    CCDSi CCDS23640.1.
    RefSeqi NP_001263648.1. NM_001276719.1.
    NP_067622.2. NM_021609.4.
    XP_006512266.1. XM_006512203.1.
    XP_006512267.1. XM_006512204.1.
    UniGenei Mm.258105.
    Mm.491478.

    3D structure databases

    ProteinModelPortali O08707.
    SMRi O08707. Positions 39-319.
    ModBasei Search...
    MobiDBi Search...

    Protein family/group databases

    GPCRDBi Search...

    PTM databases

    PhosphoSitei O08707.

    Proteomic databases

    PRIDEi O08707.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000050327 ; ENSMUSP00000050119 ; ENSMUSG00000044534 .
    GeneIDi 59289.
    KEGGi mmu:59289.
    UCSCi uc009sed.1. mouse.

    Organism-specific databases

    CTDi 1238.
    MGIi MGI:1891697. Ackr2.

    Phylogenomic databases

    eggNOGi NOG297330.
    GeneTreei ENSGT00700000104251.
    HOGENOMi HOG000234122.
    HOVERGENi HBG106917.
    InParanoidi Q8CEG1.
    KOi K04187.
    OMAi HCCFTPI.
    OrthoDBi EOG7HMS1P.
    TreeFami TF330966.

    Miscellaneous databases

    NextBioi 314792.
    PROi O08707.
    SOURCEi Search...

    Gene expression databases

    Bgeei O08707.
    CleanExi MM_CCBP2.
    Genevestigatori O08707.

    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. "Cloning and characterization of a novel murine beta chemokine receptor, D6. Comparison to three other related macrophage inflammatory protein-1alpha receptors, CCR-1, CCR-3, and CCR-5."
      Nibbs R.J., Wylie S.M., Pragnell I.B., Graham G.J.
      J. Biol. Chem. 272:12495-12504(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Strain: C3H.
    2. "The transcriptional landscape of the mammalian genome."
      Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
      , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
      Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Strain: C57BL/6J and NOD.
    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. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    5. "The atypical chemokine receptor D6 controls macrophage efferocytosis and cytokine secretion during the resolution of inflammation."
      Pashover-Schallinger E., Aswad M., Schif-Zuck S., Shapiro H., Singer P., Ariel A.
      FASEB J. 26:3891-3900(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, TISSUE SPECIFICITY.
    6. "Regulation of the immune and inflammatory responses by the 'atypical' chemokine receptor D6."
      Graham G.J., Locati M.
      J. Pathol. 229:168-175(2013) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW.

    Entry informationi

    Entry nameiACKR2_MOUSE
    AccessioniPrimary (citable) accession number: O08707
    Secondary accession number(s): Q8CEG1
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: June 20, 2001
    Last sequence update: July 27, 2011
    Last modified: October 1, 2014
    This is version 113 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. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    3. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3