PRF1
GeneName
PRF1
Summary
PRF1, also known as perforin, is a 61 kDa cytolytic protein that plays a pivotal role in the immune response, particularly in the cytotoxic activity of T cells and natural killer (NK) cells. It is expressed in cytolytic granules and is secreted at the immunological synapse to form pores in target cell membranes, facilitating the entry of granzymes and inducing apoptosis in infected or malignant cells. PRF1 is involved in various biological processes, including the defense response to tumour cells and viruses, as well as the regulation of programmed cell death. Its activity is associated with structures such as the cytosol, endosome lumen, and extracellular region.
Importance
PRF1 is relevant to: - Cancer immunotherapy, as it is essential for the cytotoxic activity of T cells against tumour cells - Viral infections, due to its role in the immune response against virus-infected cells - Understanding the mechanisms of cell-mediated cytotoxicity, which can inform therapeutic strategies for enhancing immune responses - Investigating immune deficiencies and disorders, as mutations in PRF1 are linked to familial hemophagocytic lymphohistiocytosis
Top Products
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Abcam Product Citation Summary
The data indicates that PRF1 is being studied in the context of hepatitis B virus infection, particularly in serum from chronic HBV-infected patients and human cell supernatants. Additionally, PRF1 detection has been performed in human T cell blasts, suggesting its relevance in immune responses.
Abcam Product Citation Table
Domain
Perforin consists of three domains: (1) the MACPF domain, which includes the central machinery of pore formation, (2) the EGF-like domain, which forms a 'shelf-like' assembly connecting the MACPF and C2 domains, and (3) the C2 domain, which mediates calcium-dependent binding to lipid membranes. The C2 domain is critical for initial calcium-dependent interaction with lipid membranes of the target cell: calcium-binding causes a significant structural rearrangement, leading to oligomerization and deployment of the two transmembrane beta-strands (named CH1/TMH1 and CH2/TMH2) that enter the membrane as amphipathic beta-hairpins. The third calcium-binding site (Ca(2+) 3), which constitutes the weakest affinity site, triggers structural rearrangements in the C2 domain that facilitate its interaction with lipid membranes.
Function
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, PubMed:21037563, PubMed:24558045, PubMed:9058810, PubMed: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, PubMed:21037563). Promotes cytolysis and apoptosis of target cells by mediating the passage and uptake of cytotoxic granzymes (PubMed:20038786, PubMed:20225066, PubMed:24558045, PubMed: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).
Involvement in disease
Hemophagocytic lymphohistiocytosis, familial, 2
FHL2
A rare disorder characterized by immune dysregulation with hypercytokinemia, defective function of natural killer cell, and massive infiltration of several organs by activated lymphocytes and macrophages. The clinical features of the disease include fever, hepatosplenomegaly, cytopenia, and less frequently neurological abnormalities ranging from irritability and hypotonia to seizures, cranial nerve deficits and ataxia.
None
The disease is caused by variants affecting the gene represented in this entry.
Post-translational modifications
N-glycosylated.
Sequence Similarities
Belongs to the complement C6/C7/C8/C9 family.
Cellular localization
- Cytolytic granule
- Secreted
- Cell membrane
- Multi-pass membrane protein
- Endosome lumen
- 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).
Alternative names
PFP, PRF1, Perforin-1, P1, Cytolysin, Lymphocyte pore-forming protein
Database links
swissprot:P14222 entrezGene:5551 omim:170280
Other research areas
- Immunology & Infectious Disease