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perforin-1; P1; lymphocyte pore-forming protein; PFP; cytolysin (PRF1 PFP)

Function: - perforin functions in T-cell mediated cell lysis by polymerizing into large non-specific pores in the target cell plasma membrane [2] - in the presence of Ca+2, binds to target cell membranes - inserts into target cell membranes & forms pores, & thus contributes to cytolysis & apoptosis of target cells - the Fas/FasL & perforin/granzyme systems account for cytotoxic T-cell induced apoptosis [3] Structure: - monomer, homooligomer - oligomerization is required for pore formation - belongs to the complement C6/C7/C8/C9 family - contains 1 C2 domain - contains 1 EGF-like domain - contains 1 MACPF domain - the N-terminus of perforin is important in the initial pore formation, whereas the putative alpha-helix may be involved in subsequent polymerization of perforin into large pores through which granzymes may pass Compartment: - cytoplasmic granule lumen, secreted, cell membrane - released from cytoplasmic granules of cytolytic T-lymphocytes - inserts into the cell membrane of target cells & forms pores - membrane insertion & pore formation requires a major conformation change Expression: repressed by contact with target cells Pathology: - defects in PRF1 are the cause of familial hemophagocytic lymphohistiocytosis type 2 Laboratory: - perforin Ag in tissue - perforin in leukocytes Comparative biology: - perforin deficient mice are viable & fertile & have normal numbers of CD8+ T cells & NK cells which do not lyse virus- infected or allogeneic cells or NK target cells in vitro [4]

General

Ca+2 binding protein glycoprotein membrane protein oligomerizing protein

Properties

SIZE: entity length = 555 aa MW = 61 kD COMPARTMENT: cytoplasm MOTIF: signal sequence {1-21} MACPF {27-375} MOTIF: transmembrane domain {188-204} N-glycosylation site {N205} transmembrane domain {212-231} arginine residue {214} cysteine residue {C257} MODIFICATION: cysteine residue {C279} cysteine residue {C279} MODIFICATION: cysteine residue {C257} glutamate residue {344} EGF domain {376-408} C2 domain {416-498} MOTIF: binding site FOR-BINDING-OF: phospholipid Ca+2-binding site N-glycosylation site {N549}

References

  1. Persechini PM et al Channel-forming activity of the perforin N-terminus and a putative alpha-helical region homologous with complement C9. Biochemistry. 1992 Jun 2;31(21):5017-21. PMID: 1599928
  2. Ojcius DM et al Cytolytic and ion channel-forming properties of the N terminus of lymphocyte perforin. Proc Natl Acad Sci U S A. 1991 Jun 1;88(11):4621-5. PMID: 1711204
  3. Kagi D, Vignaux F, Ledermann B et al Fas and perforin pathways as major mechanisms of T cell- mediated cytotoxicity. Science. 1994 Jul 22;265(5171):528-30. PMID: 7518614
  4. Kagi D, Ledermann B et al Cytotoxicity mediated by T cells and natural killer cells is greatly impaired in perforin-deficient mice. Nature. 1994 May 5;369(6475):31-7. PMID: 8164737
  5. UniProt :accession P14222
  6. PRF1base; Note: PRF1 mutation db http://bioinf.uta.fi/PRF1base/
  7. GeneReviews https://www.genecards.org/cgi-bin/carddisp.pl?gene=PRF1
  8. Wikipedia; Note: perforin entry http://en.wikipedia.org/wiki/perforin

Databases & Figures

OMIM correlations MORBIDMAP 170280 UniProt P14222 PFAM correlations Entrez Gene 5551 Kegg hsa:5551 Contents of Cytotoxic T-cell Granules