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FLASH GENE
Symbol ACKR2 contributors: mct - updated : 18-12-2013
HGNC name chemokine binding protein 2
HGNC id 1565
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • seven transmembrane segments (7TM) receptor
  • conserved 58-AA C terminus, with a serine cluster controling the constitutive phosphorylation, high stability, and intracellular trafficking itinerary of the receptor, but indispensable for scavenging because it prevents initial chemokine engagement of ACKR2 from inhibiting subsequent chemokine uptake
    • HOMOLOGY
    interspecies homolog to murine Cmkbr9
    Homologene
    FAMILY
  • G protein coupled receptor superfamily (family 1)
  • beta chemokine receptor
  • chemokine decoy receptor family
    • CATEGORY immunity/defense , receptor membrane G
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,endosome
    basic FUNCTION
  • plays a nonredundant role in the protection against fetal loss caused by systemic inflammation and antiphospholipid antibodies
  • heptahelical receptor that suppresses inflammation and tumorigenesis by scavenging extracellular pro-inflammatory CC chemokines
  • plays a negative role in the growth and metastasis of breast cancer
  • role of the chemokine scavenger receptor D6 in balancing inflammation and immune activation
  • key regulator of lymphatic function and a novel, and indispensable, contributor to the integration of innate and adaptive immune responses
  • scavenger activity in acute inflammation, and may have additional roles in chronic inflammatory conditions possibly promoting immune activation
  • is able to bind and drive to degradative compartments most inflammatory CC chemokines and is able to convey G-protein independent signaling events to optimize its scavenging activity
  • specifically involved in regulating the ability of lymphatic endothelial cells (LEC) to discriminate between mature and immature dendritic cells (DCs) 1)
  • essential regulator of inflammatory leukocyte interactions with LECs and is required for immature/mature DC discrimination by LECs 1)
    • CELLULAR PROCESS cell communication
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling signal transduction
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • with affinity binding for monocyte chemoattractant protein 1 (SCYA2) and 2 (SCYA8)
  • CCL2 binding to primary adult human astrocytes is CCR2-independent and is likely to be mediated via the ACKR2 decoy chemokine receptor
  • control of CCR2 ligands by ACKR2 regulates the traffic of Ly6C(high) monocytes and controls their immunosuppressive potential
  • engagement of ACKR2 by its ligands activates a ARRB1-dependent, G protein-independent signaling pathway that results in the phosphorylation of the actin-binding protein cofilin through the RAC1-PAK1-LIMK1 cascade
    • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --over  
    in patients with COPD as compared with both smoker and nonsmoker control subjects
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • mice lacking D6 expression in the nonhematopoietic compartment have a selective increase in the number of Ly6C(high) monocytes in the circulation and in secondary lymphoid tissues