InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: PRF1

Summary

InnateDB Protein

IDBP-77453.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

PRF1

Protein Name

perforin 1 (pore forming protein)

Synonyms

FLH2; HPLH2; P1; PFN1; PFP;

Species

Homo sapiens

Ensembl Protein

ENSP00000362305

InnateDB Gene

IDBG-77451 (PRF1)

Protein Structure

UniProt Annotation

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. {ECO:0000269PubMed:20038786, ECO:0000269PubMed:20225066, ECO:0000269PubMed:20889983, ECO:0000269PubMed:21037563, ECO:0000269PubMed:9058810, ECO:0000269PubMed:9164947}.

Subcellular Localization

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.

Disease Associations

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. {ECO:0000269PubMed:10583959, ECO:0000269PubMed:11179007}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Tissue Specificity

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 7 experimentally validated interaction(s) in this database.
They are also associated with 5 interaction(s) predicted by orthology.

Experimentally validated
Total	7 [view]
Protein-Protein	7 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	5 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0005509	calcium ion binding
GO:0005515	protein binding
GO:0022829	wide pore channel activity

Biological Process

GO:0002357	defense response to tumor cell
GO:0002418	immune response to tumor cell
GO:0006915	apoptotic process
GO:0006968	cellular defense response
GO:0019835	cytolysis
GO:0051260	protein homooligomerization
GO:0051607	defense response to virus
GO:0055085	transmembrane transport

Cellular Component

GO:0005576	extracellular region
GO:0005886	plasma membrane
GO:0016020	membrane
GO:0016021	integral component of membrane
GO:0031904	endosome lumen
GO:0044194	cytolytic granule