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FLASH GENE
Symbol ACKR3 contributors: mct - updated : 07-04-2015
HGNC name atypical chemokine receptor 3
HGNC id 23692
Location 2q37.3      Physical location : -
Synonym name
  • G-protein coupled receptor RDC1 homolog
  • chemokine orphan receptor 1
  • G-protein coupled receptor 159
  • chemokine (C-X-C motif) receptor 7
  • Synonym symbol(s) RDC1, GPR159, CMKOR1, CXC-R7, CXCR7, RDC-1
    DNA
    TYPE functioning gene
    STRUCTURE 12.62 kb     2 Exon(s)
    regulatory sequence Promoter
    text structure
  • HIC1-responsive element in the promoter (Van Rechem 2009)
  • NFKB is necessary for the high expression of ACKR3 gene and is recruited to the proximal promoter of the ACKR3 gene
  • MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    2 - 2114 41 362 - 2011 21418513
    EXPRESSION
    Type
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart    
    Digestivestomach    
    Nervousbrain     Homo sapiens
    Reproductivefemale systemovary   
    Respiratorylung    
    Urinarykidney    
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectivebone   
    visualeye   
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Blood/Hematopoieticbasophil
    Blood/Hematopoieticmonocyte
    Blood/Hematopoieticneutrophil
    Cardiovascularendothelial cell
    Lymphoid/ImmuneB cell
    Nervousneuron Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period embryo, fetal
    Text tissue, fetal liver cells
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • C terminus influences the ligand-uptake/degradation rate, G protein coupling, and receptor stability
  • intracellular tail of ACKR3 is a critical determinant of receptor trafficking, chemokine scavenging, and signaling
  • conjugated GlycoP
    HOMOLOGY
    interspecies homolog to murine Cxcr7 (92.8pc)
    homolog to rattus Cxcr7 (92.5pc)
    Homologene
    FAMILY
  • G-protein coupled receptor 1 family
  • CATEGORY receptor membrane G
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,endosome
    basic FUNCTION
  • having rhodopsin-like receptor activity
  • may be involved in G-protein coupled receptor protein signaling pathway
  • scavenger receptor for the SDF-1/CXCL12
  • involved in pathobiologic process including cell growth, survival, adhesion, tumor growth (Burns 2006)
  • acting as a coreceptor with CXCR4 for a restricted number of HIV isolates
  • is involved in various biological processes such as the control of adhesion, mobility, angiogenesis and cell survival
  • greater expression of CXCR7 in term placenta as compared to early stages thus may be having a role in the vertical transmission of HIV1 (Tripathi 2009)
  • role on the adhesion, proliferation and angiogenesis of endothelial progenitor cells
  • plays an important role in human cord blood derived endothelial progenitor cells (EPCs) in response to CXCL12
  • is essential for normal development, and promotes initiation and progression of diseases including cancer and autoimmunity
  • plays an important role on cell repair processing induced by CXCL12, and ACKR3 silencing attenuates cell adaptive response to acute CXCL12 stimulation after hypoxia
  • role in regulating the migration of plasmablasts during B-cell maturation
  • ACKR3 potentiates CXCR4 response and may contribute to the maintenance of leukemia by initiating cell recruitment to bone marrow niches that were once occupied by normal hematopoietic stem cells
  • is essential for the proper migration of interneuron precursors in the developing cerebral cortex
  • role for ACKR3 in oligodendrocyte progenitor cells (OPCs) maturation during remyelination and is a therapeutic strategy to promote remyelination in the adult central nervous system
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling signal transduction
  • melanocytes may have a unique mechanism of migration via CXCL12/ACKR3 signaling that is different from that of other cell types
  • a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • binding to ITAC
  • receptor for CXCL12 (Balabanian 2005)
  • both ACKR3 and CXCR4 are important for endothelial progenitor cells (EPCs) in response to CXCL12
  • may interact with CXCR4 at the intracellular level, possibly affecting CXCR4 trafficking and/or coupling to other proteins
  • ADRBK1 tightly controls ACKR3 signalling in astrocytes, but does not imprint the cell type-specific function of this chemokine receptor
  • CXCL12 protects neural progenitor cells (hNPCs) from apoptotic challenges through CXCR7- and CXCR4-mediated endocytotic signaling
  • is a primary ESR1-target gene
  • estrogen E2, through ESR1, directly down-regulates ACKR3 expression by interfering with NFKB1 transcription factor at the promoter level
  • can relay CXCL12 signaling in the cell
  • binds the chemokines CXCL12 and CXCL11
  • LHX6 directly binds to an ARX enhancer and to an intronic CXCR7 enhancer that remains active in mature interneurons
  • interfering with the CXCL12-scavenging activity of ACKR3 causes loss of CXCR4 function as a consequence of excessive CXCL12-mediated CXCR4 activation and degradation
  • cell & other
    REGULATION
    repressed by HIC1 (Van Rechem 2009)
    Other constitutive ubiquitination of ACKR3, that is a key modification responsible for the correct trafficking of ACKR3 from and to the plasma membrane
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral fusion      
    with HMGA2 in t(2;12)(q35;q13)in lipomas
    tumoral     --over  
    highly expressed in breast, lung and prostate cancers (Van Rechem 2009)
    tumoral        
    expression of CXCR7 increase as the tumors become more aggressive in prostate cancers (Wang 2008)
    tumoral        
    higher expression of CXCR7 is linked to early and metastatic recurrence in pathological stage I nonsmall cell lung cancer (Iwakiri 2009)
    tumoral     --over  
    in acute lymphoid leukemic cells compared with myeloid or normal hematopoietic cells and ACKR3 contributed to T-acute lymphoid leukemic cell migration induced by CXCL12
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target blocking of CXCR7 can be useful for therapeutic interference with CXCR4-mediated activation of integrins (Hartmann 2008)
    SystemTypeDisorderPubmed
    cancerreproductivebreast
    inhibition of NFKB1 signaling could be used in association with hormonotherapies to inhibit ACKR3 expression in breast cancer cells, thus limiting the proliferative and the pro-migrative effects of this receptor
    miscelleaneoushypertension 
    CXCR4 and ACKR3 as new pharmacological targets to control vasoreactivity and blood pressure
    ANIMAL & CELL MODELS