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FLASH GENE
Symbol CCR5 contributors: mct - updated : 29-05-2020
HGNC name chemokine (C-C motif) receptor 5
HGNC id 1606
Location 3p21.31      Physical location : 46.411.632 - 46.417.690
Synonym name
  • small inducible cytokine (CCL3, CCL4, CCL5) common receptor
  • CD195 antigen
  • HIV-1 fusion coreceptor
  • chemokine receptor CCR5
  • chemokine recptor CCR5 Delta32
  • Synonym symbol(s) CMKBR5, CKR-5, CC-CKR-5, CKR5, CD195, FLJ78003, IDDM22
    DNA
    TYPE functioning gene
    SPECIAL FEATURE component of a cluster
    text member of a chemokine receptor gene cluster
    STRUCTURE 6.06 kb     3 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status confirmed
    RNA
    TRANSCRIPTS type messenger
    text differing in their 5'utr by alternative splicing of exon 2 and exon 3
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    3 initiation site 3686 40.5 352 lymphocytes - 8663314
    3 initiation site 3451 - 352 - - 8663314
    - - - - - - 2015 25918237
  • 32 bp deletion in the CCR5 gene
  • CCR5-delta32 patients are at higher risk than the normal population of a fatal outcome in influenza infection
  • EXPRESSION
    Type restricted
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Lymphoid/Immunelymph node    
     thymus    
    Urinarykidney    
    Visualeye    
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Lymphoid    
    Muscularstriatumskeletal  
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Blood/Hematopoieticleukocyte Homo sapiens
    Lymphoid/Immunemacrophage Homo sapiens
    Lymphoid/ImmuneT cell Homo sapiens
    cell lineage
    cell lines promyeloblastic cell line
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • five transmembrane domains (TM3-TM6) sufficient for the function
  • HOMOLOGY
    Homologene
    FAMILY
  • G-protein coupled receptor 1 family
  • CATEGORY receptor
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,endosome
    basic FUNCTION
  • mediating macrophage-tropic strains of HIV-1 entry in CD4+ T lymphocytes
  • during human T cell activation by antigen-presenting cells, recruited into the immunological synapse, where they deliver costimulatory signals
  • important in the recruitment of T-helper cells to the synovium, where they accumulate, drive the inflammatory process and the consequent synovitis and joint destruction
  • CXCR4 and the related CCR5 serve as co-receptors for HIV-1 viral particles, facilitating their entry into cells
  • is a novel link between obesity, adipose tissue inflammation, and insulin resistance
  • acts as the principal coreceptor during HIV-1 transmission and early stages of infection
  • is the major coreceptor for human immunodeficiency virus (HIV)
  • CCR5 is a host factor required for Dengue virus (DENV-2) replication in human macrophages
  • plays an important role in neuroplasticity, learning and memory, and CCR5 has a role in the cognitive deficits caused by HIV
  • critical role for CCR5 not only in the recruitment but also in the activation of myeloid-derived suppressor cells (MDSCs) in tumor lesions
  • is a critical molecule for Treg-mediated blood-brain barrier protection and a potential target to optimize Treg therapy for stroke
  • governs DNA damage repair and breast cancer stem cell expansion
  • CCR5 was required for maintenance of the mesenchymal phenotype of metastatic melanoma cells
  • critical role of CCR5 expressed by melanoma cells in cancer progression
  • is a chemokine receptor that is not expressed on neutrophils and inflammatory monocytes under homeostatic conditions
  • CCR5 plays an important role for the migration of the inflammatory monocytes to infection focus during sepsis, having protective role in sepsis
  • CCR2 and CCR5 are required for collaboration between macrophages and pulmonary-artery smooth muscle cells (PASMCs) to initiate and amplify PASMC migration and proliferation during pulmonary arterial hypertension (PAH) development
  • expression levels of CCR1, CCR5 were higher in bone marrow mast cell progenitors (MCp) than in the peripheral blood, suggesting that CCR1 and CCR5 may mediate retention in the bone marrow
  • is a pivotal regulator of macrophage trafficking in the kidneys in response to an inflammatory cascade
  • CELLULAR PROCESS cell life, differentiation
    PHYSIOLOGICAL PROCESS immunity/defense
    text granulocyte
    PATHWAY
    metabolism
    signaling signal transduction
    cell-cell signaling
    a component
  • DARC hetero-oligomerizes with the CC chemokine receptor CCR5 (DARC-CCR5 interaction impairs chemotaxis and calcium flux through CCR5)
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interacting with PRAF2
  • interaction between CXCR4 and CCR5 to exert specific biological functions and modulate T lymphocyte responses, and cooperation between receptors represents one key strategy for the functional plasticity of chemokines
  • interacting with TPST2 (involved in tyrosine sulfation of CCR5 N-terminal peptide)
  • interacting with arrestins (arrestins may serve as scaffolding proteins linking CCR5 to multiple downstream signaling molecules in a biologically important primary cell type)
  • NUP85 binds to the C-terminal region of CCR5 and enhances CCR5-mediated cellular chemotaxis
  • CCL4 is a novel key mediator, and the peripheral CCL4-CCR5 axis contributes to neuropathic pain
  • NUP85 binds to chemokine receptors CCR2 and CCR5, and amplifies chemotactic signals in leucocytes
  • NUP85 is a cytoplasmic protein that binds to the membrane-proximal C-terminal regions (Pro-Cs) of chemokine receptors, CCR2 and CCR5
  • interaction between CCL5 and CCR5 plays an active role in recruiting leukocytes into target sites
  • cell & other
    REGULATION
    activated by IL-10 (associated with increased migration of microglia in response to macrophage inflammatory protein-1 beta)
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Susceptibility
  • to AIDS lymphoma
  • to HIV disease progression, resistance or non progressive infections
  • to West Nile virus (Omim 610379)
  • to juvenile idiopathic arthritis (JIA)
  • to multiple sclerosis (MS)
  • Variant & Polymorphism other
  • reduced risk of AIDS lymphoma with the CCR5-delta 32 mutation
  • CCR5Delta32 is a functional variant, significantly associated with protection from developing JIA
  • CCR5 delta32 mutation can be considered as a risk factor for MS
  • Candidate gene
    Marker
  • CCR5 and CCL5 are potential markers for metastatic Pancreatic cancer (PC) cancer
  • Therapy target
    SystemTypeDisorderPubmed
    cancerdigestivestomach
    therapeutic strategies to inhibit the CCL5/CCR5 axis in different ways in the treatment of Gastric cancer
    cancerskin 
    novel strategies of melanoma treatment could be based on blocking CCR5/CCR5 ligand interactions
    cancerdigestivepancreas
    blocking CCR5/CCL5 axis might prove beneficial to prevent metastasis and provide a more therapeutic strategy to control PC progression
    immunologyinfectious 
    targeting CCR5 might represent a therapeutic strategy for dengue fever
    ANIMAL & CELL MODELS