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FLASH GENE
Symbol PRF1 contributors: mct - updated : 27-06-2012
HGNC name perforin 1 (pore forming protein)
HGNC id 9360
Corresponding disease
HPLH2 hemophagocytic lymphohistiocytosis, familial, 2
Location 10q22.1      Physical location : 72.357.104 - 72.362.531
Synonym name
  • cytolysin
  • lymphocyte pore forming protein
  • perforin 1 (preforming protein)
    • Synonym symbol(s) PFP, HPLH2, P1, FLH2, MGC65093, PFN1, PFN
    DNA
    TYPE functioning gene
    STRUCTURE 5.43 kb     3 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    Map cen - D10S1665 - D10S529 - D10S1688 - [D10S537 - D10S676 ] - D10S1650 - D10S218 - D10S1694 - qter
    Text [PRF1 ]
    RNA
    TRANSCRIPTS type messenger
    text two transcripts encode the same protein
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    3 - 2529 59.2 555 - 2009 18927437
    3 - 2555 59.2 555 - 2009 18927437
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Lymphoid/Immuneactivated B lymphocyte Homo sapiens
    Lymphoid/Immunenatural killer Homo sapiens
    Lymphoid/ImmuneT cell
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a N-terminal membrane attack complex perforin-like (MACPF)/cholesterol dependent cytolysin (CDC) domain
  • a Mac/perforin domain
  • an epidermal growth factor-like domain (EGF), that together with the extreme C-terminal sequence, forms a central shelf-like structure
  • a C2 domain at the C terminus, which is needed for calcium-dependent binding to lipid membranes
  • extreme C terminus essential for rapid trafficking from the endoplasmic reticulum to the Golgi compartment
    • HOMOLOGY
    intraspecies homolog to complement component C9
    Homologene
    FAMILY
  • complement C6/C7/C8/C9 family
    • CATEGORY immunity/defense , structural protein
    SUBCELLULAR LOCALIZATION extracellular
        plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,lumen
    intracellular,cytoplasm,organelle,Golgi
    intracellular,cytoplasm,organelle,endosome
    intracellular,cytoplasm,cytosolic,granule
    intracellular,nucleus
    text
  • N-linked glycosylation of perforin was critical for transport from the Golgi to secretory granules
    • basic FUNCTION
  • crucial effector of T and NK cell-mediated cytolysis
  • plays a key role in immune surveillance and immune homeostasis
  • involved in down regulation of cellular immune activation
  • involved in cell-mediated cytotoxicity
  • pore-forming protein engaged mainly in mediating target T cell death and is employed by cytotoxic T lymphocytes (CTLs) and natural killer cells
  • plays a negative role in regulating CD4(+) T cell activation and immune response by affecting TCR-dependent Ca(2+) signaling
  • its permeabilizing activity, but not binding to lipid membranes, is affected by pH
  • oligomerizes to form pores that deliver the pro-apoptopic granzymes into the cytosol of the target cell
  • forms heterogeneous pores through a multistep mechanism
  • PRF1-dependent cytotoxicity has an immunoregulatory role that is distinguishable from its pathogen clearance function and limits T-cell activation in the physiologic context by suppressing antigen presentation
  • rapidly induces plasma membrane phospholipid flip-flop
  • FCGR3A and PRF1 may participate in the pathogenesis and progression of primary biliary cirrhosis (PBC)
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
    cell & other
    REGULATION
    induced by IL12A in NK cell line and regulated by STAT4
    Other regulated by DNA methylation and chromatin structure in T cells
    ASSOCIATED DISORDERS
    corresponding disease(s) HPLH2
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional       loss of function
    help explain the aberrant proliferation and activation of cytotoxic T cells and may represent genetic risk factors for bone marrow failure
    constitutional     --over  
    in SCLE (subacute cutaneous lupus erythematosus) CD4(+) T cells, and demethylation of the perforin promoter region was seen in CD4(+) T cells from patients with SCLE
    Susceptibility
  • to autism spectrum disorder
  • to acquired aplastic anemia
  • to multiple sclerosis
    • Variant & Polymorphism other
  • non synonymous mutations associated to acquired aplastic anemia
  • A91V (polymorphism resulting in both presynaptic and postsynaptic defects in function) increasing the risk of multiple sclerosis
    • Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS