Perforin (PRF1) Antibody – Mouse Monoclonal

The protein encoded by this gene has structural and functional similarities to complement component 9 (C9). Like C9, this protein creates transmembrane tubules and is capable of lysing non-specifically a variety of target cells. This protein is one of the main cytolytic proteins of cytolytic granules, and it is known to be a key effector molecule for T-cell- and natural killer-cell-mediated cytolysis. Defects in this gene cause familial hemophagocytic lymphohistiocytosis type 2 (HPLH2), a rare and lethal autosomal recessive disorder of early childhood. Alternative splicing results in multiple transcript variants encoding the same protein. [provided by RefSeq, Jul 2008]

Function: Plays a key role in secretory granule-dependent cell death, and in defense against virus-infected or neoplastic cells. 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. Can insert into the membrane of target cells in its calcium-bound form, oligomerize and form large pores. Promotes cytolysis and apoptosis of target cells by facilitating the uptake of cytotoxic granzymes. Ref.10 Ref.11 Ref.13 Ref.14 Ref.15 Ref.17

Subunit structure: Monomer, as sobluble protein. Homooligomer. Oligomerization is required for pore formation. Ref.14 Ref.17

Subcellular location: Cytoplasmic granule lumen. Secreted. Cell membrane; Multi-pass membrane protein. Endosome lumen. Note: Stored in cytoplasmic granules of cytolytic T-lymphocytes and secreted into the cleft between T-lymphocyte and target cell. Inserts into the cell membrane of target cells and forms pores. Membrane insertion and pore formation requires a major conformation change. May be taken up via endocytosis involving clathrin-coated vesicles and accumulate in a first time in large early endosomes. Ref.13 Ref.14 Ref.17

Induction: Repressed by contact with target cells. Ref.9

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. Ref.16

Post-translational modification: N-glycosylated

By similarity.

Involvement in disease: Familial hemophagocytic lymphohistiocytosis 2 (FHL2) [MIM:603553]: 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.Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.18 Ref.19

Sequence similarities: Belongs to the complement C6/C7/C8/C9 family.Contains 1 C2 domain.Contains 1 EGF-like domain.Contains 1 MACPF domain.