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Q924I3

- ACKR4_MOUSE

UniProt

Q924I3 - ACKR4_MOUSE

Protein

Atypical chemokine receptor 4

Gene

Ackr4

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 4 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 97 (01 Oct 2014)
      Sequence version 1 (01 Dec 2001)
      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 CCL2, CCL8, CCL13, CCL19, CCL21 and CCL25. Chemokine-binding does not activate G-protein-mediated signal transduction but instead induces beta-arrestin recruitment, leading to ligand internalization. Plays an important role in controlling the migration of immune and cancer cells that express chemokine receptors CCR7 and CCR9, by reducing the availability of CCL19, CCL21, and CCL25 through internalization. Negatively regulates CXCR3-induced chemotaxis. Regulates T-cell development in the thymus and inhibits spontaneous autoimmunity.2 Publications

    GO - Molecular functioni

    1. chemokine receptor activity Source: UniProtKB
    2. scavenger receptor activity Source: InterPro

    GO - Biological processi

    1. chemokine-mediated signaling pathway Source: GOC
    2. chemotaxis Source: InterPro

    Keywords - Molecular functioni

    G-protein coupled receptor, Receptor, Transducer

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Atypical chemokine receptor 4
    Alternative name(s):
    C-C chemokine receptor type 11
    Short name:
    C-C CKR-11
    Short name:
    CC-CKR-11
    Short name:
    CCR-11
    CC chemokine receptor-like 1
    Short name:
    CCRL1
    CCX CKR
    Gene namesi
    Name:Ackr4
    Synonyms:Ccr11, Ccrl1
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 9

    Organism-specific databases

    MGIiMGI:2181676. Ackr4.

    Subcellular locationi

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

    Keywords - Cellular componenti

    Cell membrane, Endosome, Membrane

    Pathology & Biotechi

    Disruption phenotypei

    Mice have a larger thymus with relatively fewer cortical thymic epithelial cells and this is associated with severe reductions in cortical CCL25 distribution and accumulation of DN2 thymocyte precursor cells in the medulla. The downstream effects materialize in reduced proportions of DN3 cells and significantly reduced numbers of cortical DN3 cells. Aberrant thymocyte development culminates in increased prevalence of spontaneous autoimmune-like disease, characterized by lymphocytic infiltration of peripheral organs.1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 350350Atypical chemokine receptor 4PRO_0000069297Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Glycosylationi6 – 61N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi19 – 191N-linked (GlcNAc...)Sequence Analysis

    Post-translational modificationi

    The Ser/Thr residues in the C-terminal cytoplasmic tail may be phosphorylated.By similarity

    Keywords - PTMi

    Glycoprotein, Phosphoprotein

    Proteomic databases

    PRIDEiQ924I3.

    PTM databases

    PhosphoSiteiQ924I3.

    Expressioni

    Tissue specificityi

    Expressed in lung, heart, spleen, skeletal muscle, testis, astrocytes and microglia. Expressed by cortical thymic epithelial cells.3 Publications

    Gene expression databases

    BgeeiQ924I3.
    CleanExiMM_CCRL1.
    GenevestigatoriQ924I3.

    Interactioni

    Subunit structurei

    Forms heteromers with CXCR3. Interacts with ARRB1 and ARRB2 By similarity.By similarity

    Structurei

    3D structure databases

    ProteinModelPortaliQ924I3.
    SMRiQ924I3. Positions 39-322.
    ModBaseiSearch...
    MobiDBiSearch...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini1 – 4141ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini63 – 7715CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini100 – 11415ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini136 – 15419CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini176 – 19924ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini221 – 24020CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini262 – 28928ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini311 – 35040CytoplasmicSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei42 – 6221Helical; Name=1Sequence AnalysisAdd
    BLAST
    Transmembranei78 – 9922Helical; Name=2Sequence AnalysisAdd
    BLAST
    Transmembranei115 – 13521Helical; Name=3Sequence AnalysisAdd
    BLAST
    Transmembranei155 – 17521Helical; Name=4Sequence AnalysisAdd
    BLAST
    Transmembranei200 – 22021Helical; Name=5Sequence AnalysisAdd
    BLAST
    Transmembranei241 – 26121Helical; Name=6Sequence AnalysisAdd
    BLAST
    Transmembranei290 – 31021Helical; Name=7Sequence AnalysisAdd
    BLAST

    Family & Domainsi

    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

    eggNOGiNOG148788.
    GeneTreeiENSGT00730000110640.
    HOGENOMiHOG000234122.
    HOVERGENiHBG106917.
    InParanoidiQ924I3.
    KOiK04186.
    OMAiLEICIGF.
    OrthoDBiEOG7GJ6DG.
    PhylomeDBiQ924I3.
    TreeFamiTF330966.

    Family and domain databases

    Gene3Di1.20.1070.10. 1 hit.
    InterProiIPR005383. Chemokine_CCRL1.
    IPR000355. Chemokine_rcpt.
    IPR000276. GPCR_Rhodpsn.
    IPR017452. GPCR_Rhodpsn_7TM.
    [Graphical view]
    PANTHERiPTHR24227. PTHR24227. 1 hit.
    PTHR24227:SF35. PTHR24227:SF35. 1 hit.
    PfamiPF00001. 7tm_1. 1 hit.
    [Graphical view]
    PRINTSiPR00657. CCCHEMOKINER.
    PR01558. CHEMOKINER11.
    PR00237. GPCRRHODOPSN.
    PROSITEiPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
    PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Q924I3-1 [UniParc]FASTAAdd to Basket

    « Hide

    MALELNQSAE YYYEENEMNY THDYSQYEVI CIKEEVRQFA KVFLPAFFTV    50
    AFVTGLAGNS VVVAIYAYYK KQRTKTDVYI LNLAVADLLL LITLPFWAVN 100
    AVHGWILGKM MCKVTSALYT VNFVSGMQFL ACISIDRYWA ITKAPSQSGA 150
    GRPCWIICCC VWMAAILLSI PQLVFYTVNQ NARCTPIFPH HLGTSLKASI 200
    QMLEIGIGFV VPFLIMGVCY ASTARALIKM PNIKKSRPLR VLLAVVVVFI 250
    VTQLPYNVVK FCQAIDAIYL LITSCDMSKR MDVAIQVTES IALFHSCLNP 300
    ILYVFMGASF KNYIMKVAKK YGSWRRQRQN VEEIPFDSEG PTEPTSSFTI 350
    Length:350
    Mass (Da):39,531
    Last modified:December 1, 2001 - v1
    Checksum:iC5F7D9DC949CECCF
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti50 – 501V → M in BAC27061. (PubMed:16141072)Curated
    Sequence conflicti287 – 2871V → L in AAL68400. (PubMed:11981810)Curated
    Sequence conflicti287 – 2871V → L in AAL68962. (PubMed:11981810)Curated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF306532 mRNA. Translation: AAK81712.1.
    AY072796 mRNA. Translation: AAL68400.1.
    AY072938 mRNA. Translation: AAL68962.1.
    AK030643 mRNA. Translation: BAC27061.1.
    AK042430 mRNA. Translation: BAC31258.1.
    CCDSiCCDS23459.1.
    RefSeqiNP_663746.2. NM_145700.2.
    XP_006511797.1. XM_006511734.1.
    XP_006511798.1. XM_006511735.1.
    UniGeneiMm.269254.

    Genome annotation databases

    EnsembliENSMUST00000076147; ENSMUSP00000075507; ENSMUSG00000079355.
    GeneIDi252837.
    KEGGimmu:252837.
    UCSCiuc009rhh.2. mouse.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF306532 mRNA. Translation: AAK81712.1 .
    AY072796 mRNA. Translation: AAL68400.1 .
    AY072938 mRNA. Translation: AAL68962.1 .
    AK030643 mRNA. Translation: BAC27061.1 .
    AK042430 mRNA. Translation: BAC31258.1 .
    CCDSi CCDS23459.1.
    RefSeqi NP_663746.2. NM_145700.2.
    XP_006511797.1. XM_006511734.1.
    XP_006511798.1. XM_006511735.1.
    UniGenei Mm.269254.

    3D structure databases

    ProteinModelPortali Q924I3.
    SMRi Q924I3. Positions 39-322.
    ModBasei Search...
    MobiDBi Search...

    Protein family/group databases

    GPCRDBi Search...

    PTM databases

    PhosphoSitei Q924I3.

    Proteomic databases

    PRIDEi Q924I3.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000076147 ; ENSMUSP00000075507 ; ENSMUSG00000079355 .
    GeneIDi 252837.
    KEGGi mmu:252837.
    UCSCi uc009rhh.2. mouse.

    Organism-specific databases

    CTDi 51554.
    MGIi MGI:2181676. Ackr4.

    Phylogenomic databases

    eggNOGi NOG148788.
    GeneTreei ENSGT00730000110640.
    HOGENOMi HOG000234122.
    HOVERGENi HBG106917.
    InParanoidi Q924I3.
    KOi K04186.
    OMAi LEICIGF.
    OrthoDBi EOG7GJ6DG.
    PhylomeDBi Q924I3.
    TreeFami TF330966.

    Miscellaneous databases

    NextBioi 387341.
    PROi Q924I3.
    SOURCEi Search...

    Gene expression databases

    Bgeei Q924I3.
    CleanExi MM_CCRL1.
    Genevestigatori Q924I3.

    Family and domain databases

    Gene3Di 1.20.1070.10. 1 hit.
    InterProi IPR005383. Chemokine_CCRL1.
    IPR000355. Chemokine_rcpt.
    IPR000276. GPCR_Rhodpsn.
    IPR017452. GPCR_Rhodpsn_7TM.
    [Graphical view ]
    PANTHERi PTHR24227. PTHR24227. 1 hit.
    PTHR24227:SF35. PTHR24227:SF35. 1 hit.
    Pfami PF00001. 7tm_1. 1 hit.
    [Graphical view ]
    PRINTSi PR00657. CCCHEMOKINER.
    PR01558. CHEMOKINER11.
    PR00237. GPCRRHODOPSN.
    PROSITEi PS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
    PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Astrocytes express functional chemokine receptors."
      Dorf M.E., Berman M.A., Tanabe S., Heesen M., Luo Y.
      J. Neuroimmunol. 111:109-121(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY.
      Strain: BALB/c.
    2. "Characterization of mouse CCX-CKR, a receptor for the lymphocyte-attracting chemokines TECK/mCCL25, SLC/mCCL21 and MIP-3beta/mCCL19: comparison to human CCX-CKR."
      Townson J.R., Nibbs R.J.
      Eur. J. Immunol. 32:1230-1241(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION IN CHEMOKINES BINDING, TISSUE SPECIFICITY.
    3. "RANTES and eotaxin stimulate chemotaxis, chemokine/cytokine synthesis, and receptor modulation in murine astrocytes."
      Luo Y., Berman M.A., Fischer F.R., Abromson-Leeman S.R., Kuziel W.A., Gerard C., Dorf M.E.
      Submitted (SEP-2000) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Strain: BALB/c.
    4. "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.
      Tissue: Head and Thymus.
    5. "CCX-CKR deficiency alters thymic stroma impairing thymocyte development and promoting autoimmunity."
      Bunting M.D., Comerford I., Seach N., Hammett M.V., Asquith D.L., Koerner H., Boyd R.L., Nibbs R.J., McColl S.R.
      Blood 121:118-128(2013) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, DISRUPTION PHENOTYPE, TISSUE SPECIFICITY.

    Entry informationi

    Entry nameiACKR4_MOUSE
    AccessioniPrimary (citable) accession number: Q924I3
    Secondary accession number(s): Q8C0M1, Q8QZW9
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: July 5, 2005
    Last sequence update: December 1, 2001
    Last modified: October 1, 2014
    This is version 97 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. 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