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FLASH GENE
Symbol PF4 contributors: mct - updated : 25-01-2016
HGNC name platelet factor 4
HGNC id 8861
Location 4q13.3      Physical location : 74.846.795 - 74.847.715
Synonym name
  • chemokine (C-X-C motif) ligand 4
  • iroplact
  • oncostatin-A
    • Synonym symbol(s) CXCL4, SCYB4, MGC138298, PF-4
    DNA
    TYPE functioning gene
    SPECIAL FEATURE component of a cluster
    STRUCTURE 0.92 kb     3 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked Y status confirmed
    Map cen - IL8 - CXCL1 /PPBP /PF4 - CXCL5 /CXCL6 - CXCL2 /CXCL3 - CXCL11 - CXCL10 - CXCL9 - qter
    Text see IMC2@
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    3 - 476 10.7 101 - 2008 18648521
    EXPRESSION
    Type restricted
       expressed in (based on citations)
    organ(s)
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Blood/Hematopoieticplatelet Homo sapiens
    Lymphoid/Immunelymphocyte Homo sapiens
    cell lineage expressed during megakaryocytic differentiation
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
    mono polymer homomer , tetramer
    HOMOLOGY
    interspecies homolog to C.elegans F39H12.2
    Homologene
    FAMILY
  • platelet factor 4 family
  • intercrine alpha family (small cytokine C-X-C) (chemokine CXC)
    • CATEGORY signaling cytokine
    SUBCELLULAR LOCALIZATION extracellular
        intracellular
    intracellular,cytoplasm,cytosolic,granule
    text
  • released from the alpha-granules of activated platelets
  • stored in secretory granules and released in response to protein kinase C activation
    • basic FUNCTION
  • neutralizing the anticoagulant effect of heparin because it binds more strongly to heparin than to chondroitin-4-sulfate chains of the carrier molecule
  • chemotactic for neutrophils and monocytes
  • released during platelet aggregation
  • first chemokine described to inhibit neovascularization
  • can protect hematopoiesis from chemotherapy by enhancing cell viability and suppress tumor growth through anti-angiogenic pathway
  • playing a role in the modulation of monocyte-dependent T cell activation
  • potent inhibitor of tumor-induced angiogenesis
  • platelet-derived chemokine that promotes macrophage differentiation from monocyte
  • chemokine that binds to and neutralizes heparin and other negatively charged proteoglycans, but is also involved in angiogenesis and cancer development
  • (PF4 or CXCL4) and the erythrocyte Duffy-antigen receptor (ACKR1) are necessary for platelet-mediated killing of Plasmodium falciparum parasites
  • important mechanistic role for platelets and PF4 in vascular smooth muscle cell injury responses
  • regulates hematopoietic stem cells (HSCs) cycle activity
  • plays several roles in coagulation, angiogenesis control, immune system modulation and spread of cancer
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS immunity/defense
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • binding noncovalently to a proteoglycan molecule
  • binding to heparin with high affinity
  • interacting with integrin (integrins as novel receptors for PF4 that may contribute to its antiangiogenic effect)
  • may promote atherogenesis by suppressing CD163 in macrophages, which are then unable to upregulate the atheroprotective enzyme heme oxygenase-1 in response to hemoglobin
  • in contrast to stimulation of protein C activation, PF4 is shown here to inhibit activation of CPB2 by thrombin-THBD
  • FLI1, ELF1, and GABPA regulate PF4 gene expression through the -51 ETS site in megakaryocytes and implicate the differentiation stage-specific regulation of PF4 gene expression by multiple ETS factors
  • function in killing plasmodium for PF4 is critically dependent on ACKR1, which binds PF4
  • genetic disruption of ACKR1 expression inhibits binding of PF4 to parasitized cells and concomitantly prevents parasite killing by both human platelets and recombinant human PF4
  • RUNX1 activates endogenous PF4 expression in megakaryocytic differentiation
    • cell & other
    REGULATION
    activated by PREP1 and PREP1/PBX complexes with GATA-1 and ETS-1
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in early growth of liposarcoma, mammary adenocarcinoma, and osteosarcoma
    Susceptibility
    Variant & Polymorphism
    Candidate gene potential biomarker of early tumor presence
    Marker
    Therapy target several PF4 fragments and modified molecules exhibit antiangiogenesis properties and may become an alternative for further therapeutic angiogenesis
    ANIMAL & CELL MODELS
    NOA mice