| 简介 | This gene encodes a protein with structural similarities to complement component C9 that is important in immunity. This protein forms membrane pores that allow the release of granzymes and subsequent cytolysis of target cells. Whether pore formation occurs in the plasma membrane of target cells or in an endosomal membrane inside target cells is subject to debate. Mutations in this gene are associated with a variety of human disease including diabetes, multiple sclerosis, lymphomas, autoimmune lymphoproliferative syndrome (ALPS), aplastic anemia, and familial hemophagocytic lymphohistiocytosis type 2 (FHL2), a rare and lethal autosomal recessive disorder of early childhood. [provided by RefSeq, Aug 2017]
Diseases associated with PRF1 include Hemophagocytic Lymphohistiocytosis, Familial, 2 and Lymphoma, Non-Hodgkin, Familial. Among its related pathways are Signaling by ALK fusions and activated point mutants and Granzyme Pathway. Gene Ontology (GO) annotations related to this gene include calcium ion binding and wide pore channel activity. An important paralog of this gene is CSMD3.
Pore-forming protein that plays a key role in granzyme-mediated programmed cell death, and in defense against virus-infected or neoplastic cells (PubMed:20889983, 21037563, 24558045, 9058810, 9164947).
Plays an important role in killing other cells that are recognized as non-self by the immune system, e.g.
in transplant rejection or some forms of autoimmune disease (PubMed:9058810).
Can insert into the membrane of target cells in its calcium-bound form, oligomerize and form large pores (PubMed:20889983, 21037563).
Promotes cytolysis and apoptosis of target cells by mediating the passage and uptake of cytotoxic granzymes (PubMed:20038786, 20225066, 24558045, 32299851).
Facilitates the delivery of cationic cargo protein, while anionic or neural proteins are not delivered efficiently (PubMed:24558045).
Perforin pores allow the release of mature caspase-7 (CASP7) into the extracellular milieu (By similarity).
Repressed by contact with target cells.
perforin70-75kDa,pore forming protein 1 (cytoplasmic granules of natural killer and cytotoxic T cell),crucial effector of T and NK cell-mediated cytolysis,highly homologous to complement component C9
Cytolytic granule {ECO:0000269 PubMed:20038786, 24088571}
Secreted 5
Cell membrane; Multi-pass membrane protein {ECO:0000269 PubMed:20889983, 21037563}5
Endosome lumen {ECO:0000269 PubMed:20038786}4
Note: Stored in cytolytic granules of cytolytic T-lymphocytes and secreted into the cleft between T-lymphocyte and target cell (PubMed:20038786). Inserts into the cell membrane of target cells and forms pores (PubMed:20889983). Membrane insertion and pore formation requires a major conformation change (PubMed:20889983). May be taken up via endocytosis involving clathrin-coated vesicles and accumulate in a first time in large early endosomes (PubMed:20038786) {ECO:0000269 PubMed:20038786, 20889983}
Quaternary structure:
Monomer, as soluble protein (PubMed:20889983, 21037563).
Homooligomer; homooligomerizes to form a pore-forming ring (PubMed:20889983, 21037563). |
|---|