Perforin-1 is a protein

Protein

Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...

 that in humans is encoded by the PRF1 gene

Gene

A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...

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Function

Perforin is a cytolytic

Cytolysis

Cytolysis, or osmotic lysis, occurs when a cell bursts due to an osmotic imbalance that has caused excess water to move into the cell. It occurs in a hypotonic environment, where water diffuses into the cell and causes its volume to increase. If the volume of water exceeds the cell membrane's...

 protein found in the granules of CD8 T-cells

T cell

T cells or T lymphocytes belong to a group of white blood cells known as lymphocytes, and play a central role in cell-mediated immunity. They can be distinguished from other lymphocytes, such as B cells and natural killer cells , by the presence of a T cell receptor on the cell surface. They are...

 and NK cells

Natural killer cell

Natural killer cells are a type of cytotoxic lymphocyte that constitute a major component of the innate immune system. NK cells play a major role in the rejection of tumors and cells infected by viruses...

. Upon degranulation

Degranulation

Degranulation is a cellular process that releases antimicrobial cytotoxic molecules from secretory vesicles called granules found inside some cells...

, perforin inserts itself into the target cell's plasma membrane, forming a pore. The lytic membrane-inserting part of perforin is the MACPF

MACPF

The MACPF protein superfamily is named after a domain that is common to the Membrane Attack Complex proteins of complement and perforin . Many members of this protein family are important eukaryote pore forming toxins....

 domain. This region shares homology with cholesterol-dependent cytolysin

Cytolysin

Cytolysin refers to the substance or antibody elaborated by microorganisms, plants or animals that is specifically toxic to individual cells, in many cases causing their dissolution through lysis. Cytolysins that have a specific action for certain cells are named accordingly...

s from Gram-positive bacteria.

Perforin has structural and functional similarities to complement component 9

Complement component 9

Complement component 9 is a protein involved in the complement system....

 (C9). Like C9, this protein creates transmembrane tubule

Tubule

A tubule is a very small tube or fistular structure.A system of surface-connected membranes in muscle that enables a nerve impulse to travel to the interior of the muscle fibre.In anatomy, a tubule is a minute tube lined with glandular epithelium....

s 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.

Clinical significance

Defects in this gene cause familial hemophagocytic lymphohistiocytosis

Hemophagocytic lymphohistiocytosis

Hemophagocytic lymphohistiocytosis , also known as hemophagocytic syndrome, is an uncommon hematologic disorder that, typically, clinically manifests as fever, hepatosplenomegaly, lymphadenopathy, jaundice and rash, with laboratory findings of lymphocytosis and histiocytosis, and the pathologic...

 type 2 (HPLH2), a rare and lethal autosomal recessive disorder of early childhood.

Interactions

Perforin has been shown to interact

Protein-protein interaction

Protein–protein interactions occur when two or more proteins bind together, often to carry out their biological function. Many of the most important molecular processes in the cell such as DNA replication are carried out by large molecular machines that are built from a large number of protein...

 with Calreticulin

Calreticulin

Calreticulin also known as calregulin, CRP55, CaBP3, calsequestrin-like protein, and endoplasmic reticulum resident protein 60 is a protein that in humans is encoded by the CALR gene....

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