PRF1

Domain

The C2 domain mediates calcium-dependent binding to lipid membranes. A subsequent conformation change leads to membrane insertion of beta-hairpin structures and pore formation. The pore is formed by transmembrane beta-strands.

Function

Pore-forming protein that plays a key role in secretory granule-dependent cell death, and in defense against virus-infected or neoplastic cells (PubMed:9058810, PubMed:9164947, PubMed:20889983, PubMed:21037563). 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 facilitating the uptake of cytotoxic granzymes (PubMed:20038786, PubMed:20225066, PubMed:32299851).

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

• Perforin-1
• P1
• Cytolysin
• Lymphocyte pore-forming protein
• PFP
• PRF1
• PFP

Database links

• entrezGene:5551
• omim:170280
• swissprot:P14222

Target type

Proteins

Primary research area

Immuno-oncology

Other research areas

• Immunology & Infectious Disease

Molecular weight

61377Da