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Not to be confused with Porphyrin.
Perforin 1 (pore forming protein)
The structure of a MACPF domain containing protein Plu-MACPF: PDB: 2QP2[1] The MACPF domain is in cyan/pink. Another domain, the ? prism domain is in orange. Two calcium atoms are in grey.
Symbols PRF1 ; FLH2; HPLH2; P1; PFN1; PFP
External IDs OMIM170280 MGI97551 HomoloGene3698 ChEMBL: 5480 GeneCards: PRF1 Gene
RNA expression pattern
PBB GE PRF1 214617 at tn.png
More reference expression data
Species Human Mouse
Entrez 5551 18646
Ensembl ENSG00000180644 ENSMUSG00000037202
UniProt P14222 P10820
RefSeq (mRNA) NM_001083116 NM_011073
RefSeq (protein) NP_001076585 NP_035203
Location (UCSC) Chr 10:
70.6 – 70.6 Mb
Chr 10:
61.3 – 61.3 Mb
PubMed search [1] [2]

Perforin-1 is a protein that in humans is encoded by the PRF1 gene and the Prf1 gene in mice.[2][3][4]


Perforin is a pore forming cytolytic protein found in the granules of Cytotoxic T lymphocytes (CTLs) and NK cells. Upon degranulation, perforin binds to the target cell's plasma membrane, and oligomerises in a Ca2+ dependent manner to form pores on the target cell. The pore formed allows for the passive diffusion of a family of pro-apoptotic proteases, known as the granzymes in to the target cell.[5] The lytic membrane-inserting part of perforin is the MACPF domain.[6] This region shares homology with cholesterol-dependent cytolysins from Gram-positive bacteria.[1]

Perforin 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.[4] Perforin is thought to act by creating holes in the plasma membrane which triggers an influx of calcium and initiates membrane repair mechanisms. These repair mechanisms bring perforin and granzymes into early endosomes.[7]

Clinical significance[edit]

Homozygous inheritance of defective PRF1 alleles result in the development of familial hemophagocytic lymphohistiocytosis type 2 (FHL2), a rare and lethal autosomal recessive disorder of infancy.[4]


Perforin has been shown to interact with calreticulin.[8]

See also[edit]


  1. ^ a b Rosado CJ, Buckle AM, Law RH, Butcher RE, Kan WT, Bird CH, Ung K, Browne KA, Baran K, Bashtannyk-Puhalovich TA, Faux NG, Wong W, Porter CJ, Pike RN, Ellisdon AM, Pearce MC, Bottomley SP, Emsley J, Smith AI, Rossjohn J, Hartland EL, Voskoboinik I, Trapani JA, Bird PI, Dunstone MA, Whisstock JC (2007). "A common fold mediates vertebrate defense and bacterial attack". Science 317 (5844): 1548–51. doi:10.1126/science.1144706. PMID 17717151. 
  2. ^ Fink TM, Zimmer M, Weitz S, Tschopp J, Jenne DE, Lichter P (Sep 1992). "Human perforin (PRF1) maps to 10q22, a region that is syntenic with mouse chromosome 10". Genomics 13 (4): 1300–2. doi:10.1016/0888-7543(92)90050-3. PMID 1505959. 
  3. ^ Shinkai Y, Yoshida MC, Maeda K, Kobata T, Maruyama K, Yodoi J, Yagita H, Okumura K (Jan 1990). "Molecular cloning and chromosomal assignment of a human perforin (PFP) gene". Immunogenetics 30 (6): 452–7. doi:10.1007/BF02421177. PMID 2592021. 
  4. ^ a b c "Entrez Gene: PRF1 perforin 1 (pore forming protein)". 
  5. ^ Trapani JA (1996). "Target cell apoptosis induced by cytotoxic T cells and natural killer cells involves synergy between the pore-forming protein, perforin, and the serine protease, granzyme B". Australian and New Zealand journal of medicine 25 (6): 793–9. doi:10.1111/j.1445-5994.1995.tb02883.x. PMID 8770355. 
  6. ^ Tschopp J, Masson D, Stanley KK (1986). "Structural/functional similarity between proteins involved in complement- and cytotoxic T-lymphocyte-mediated cytolysis". Nature 322 (6082): 831–4. doi:10.1038/322831a0. PMID 2427956. 
  7. ^ Thiery J, Keefe D, Boulant S, Boucrot E, Walch M, Martinvalet D, Goping IS, Bleackley RC, Kirchhausen T, Lieberman J (2011). "Perforin pores in the endosomal membrane trigger the release of endocytosed granzyme B into the cytosol of target cells". Nat. Immunol. 12 (8): 770–7. doi:10.1038/ni.2050. PMC 3140544. PMID 21685908. 
  8. ^ Andrin C, Pinkoski MJ, Burns K, et al. (July 1998). "Interaction between a Ca2+-binding protein calreticulin and perforin, a component of the cytotoxic T-cell granules". Biochemistry 37 (29): 10386–94. doi:10.1021/bi980595z. PMID 9671507. 

Further reading[edit]

External links[edit]

Perforin at NLM Genetics Home Reference