Perforin-1

Mammalian protein found in Homo sapiens
PRF1
Identifiers
AliasesPRF1, FLH2, HPLH2, P1, PFN1, PFP, perforin 1
External IDsOMIM: 170280 MGI: 97551 HomoloGene: 3698 GeneCards: PRF1
Gene location (Human)
Chromosome 10 (human)
Chr.Chromosome 10 (human)[1]
Chromosome 10 (human)
Genomic location for PRF1
Genomic location for PRF1
Band10q22.1Start70,597,348 bp[1]
End70,602,759 bp[1]
Gene location (Mouse)
Chromosome 10 (mouse)
Chr.Chromosome 10 (mouse)[2]
Chromosome 10 (mouse)
Genomic location for PRF1
Genomic location for PRF1
Band10 B4|10 32.18 cMStart61,133,612 bp[2]
End61,140,459 bp[2]
RNA expression pattern
Bgee
HumanMouse (ortholog)
Top expressed in
  • blood

  • spleen

  • bone marrow cells

  • lymph node

  • superficial temporal artery

  • upper lobe of left lung

  • right lung

  • lower lobe of lung

  • periodontal fiber

  • palpebral conjunctiva
Top expressed in
  • blood

  • spleen

  • lymph node

  • subcutaneous adipose tissue

  • thymus

  • right lung

  • mucosa of small intestine

  • uterus

  • right ventricle

  • right lung lobe
More reference expression data
BioGPS
More reference expression data
Gene ontology
Molecular function
  • protein binding
  • metal ion binding
  • calcium ion binding
  • wide pore channel activity
  • identical protein binding
Cellular component
  • integral component of membrane
  • extracellular region
  • endosome
  • plasma membrane
  • endosome lumen
  • membrane
  • cytosol
  • cytoplasmic vesicle
  • cytolytic granule
Biological process
  • cellular defense response
  • immunological synapse formation
  • cytolysis
  • apoptotic process
  • transmembrane transport
  • positive regulation of killing of cells of other organism
  • defense response to tumor cell
  • immune response to tumor cell
  • protein homooligomerization
  • defense response to virus
  • T cell mediated cytotoxicity
Sources:Amigo / QuickGO
Orthologs
SpeciesHumanMouse
Entrez

5551

18646

Ensembl

ENSG00000180644

ENSMUSG00000037202

UniProt

P14222

P10820

RefSeq (mRNA)

NM_005041
NM_001083116

NM_011073

RefSeq (protein)

NP_001076585
NP_005032

NP_035203

Location (UCSC)Chr 10: 70.6 – 70.6 MbChr 10: 61.13 – 61.14 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Perforin-1 is a protein that in humans is encoded by the PRF1 gene and the Prf1 gene in mice.[5][6][7]

Function

Perforin is a pore forming cytolytic protein found in the granules of cytotoxic T lymphocytes (CTLs) and natural killer cells (NK cells). Upon degranulation, perforin molecules translocate to the target cell with the help of calreticulin, which works as a chaperone protein to prevent perforin from degrading. Perforin then binds to the target cell's plasma membrane via membrane phospholipids while phosphatidylcholine binds calcium ions to increase perforin's affinity to the membrane.[8] Perforin 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, into the target cell.[9] The lytic membrane-inserting part of perforin is the MACPF domain.[10] This region shares homology with cholesterol-dependent cytolysins from Gram-positive bacteria.[11]

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.[7] 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.[12]

Clinical significance

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.[7]

Interactions

Perforin has been shown to interact with calreticulin.[13]

See also

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000180644 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000037202 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ 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.
  6. ^ 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. S2CID 35292868.
  7. ^ a b c "Entrez Gene: PRF1 perforin 1 (pore forming protein)".
  8. ^ Osińska, Iwona et al. “Perforin: an important player in immune response.” Central-European journal of immunology vol. 39,1 (2014): 109-15. doi:10.5114/ceji.2014.42135
  9. ^ 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.
  10. ^ 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. Bibcode:1986Natur.322..831T. doi:10.1038/322831a0. PMID 2427956. S2CID 4330219.
  11. ^ 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. Bibcode:2007Sci...317.1548R. doi:10.1126/science.1144706. PMID 17717151. S2CID 20372720.
  12. ^ 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.
  13. ^ 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

  • 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.
  • Peitsch MC, Amiguet P, Guy R, et al. (1990). "Localization and molecular modelling of the membrane-inserted domain of the ninth component of human complement and perforin". Mol. Immunol. 27 (7): 589–602. doi:10.1016/0161-5890(90)90001-G. PMID 2395434.
  • Young JD, Hengartner H, Podack ER, Cohn ZA (1986). "Purification and characterization of a cytolytic pore-forming protein from granules of cloned lymphocytes with natural killer activity". Cell. 44 (6): 849–59. doi:10.1016/0092-8674(86)90007-3. PMID 2420467. S2CID 30182487.
  • Young JD, Cohn ZA, Podack ER (1986). "The ninth component of complement and the pore-forming protein (perforin 1) from cytotoxic T cells: structural, immunological, and functional similarities". Science. 233 (4760): 184–90. doi:10.1126/science.2425429. PMID 2425429.
  • Lichtenheld MG, Podack ER (1990). "Structure of the human perforin gene. A simple gene organization with interesting potential regulatory sequences". J. Immunol. 143 (12): 4267–74. doi:10.4049/jimmunol.143.12.4267. PMID 2480391. S2CID 8326644.
  • Shinkai Y, Takio K, Okumura K (1988). "Homology of perforin to the ninth component of complement (C9)". Nature. 334 (6182): 525–7. Bibcode:1988Natur.334..525S. doi:10.1038/334525a0. PMID 3261391. S2CID 4348928.
  • Lichtenheld MG, Olsen KJ, Lu P, et al. (1988). "Structure and function of human perforin". Nature. 335 (6189): 448–51. Bibcode:1988Natur.335..448L. doi:10.1038/335448a0. PMID 3419519. S2CID 4359028.
  • Goebel WS, Schloemer RH, Brahmi Z (1996). "Target cell-induced perforin mRNA turnover in NK3.3 cells is mediated by multiple elements within the mRNA coding region". Mol. Immunol. 33 (4–5): 341–9. doi:10.1016/0161-5890(95)00155-7. PMID 8676885.
  • Nöske K, Bilzer T, Planz O, Stitz L (1998). "Virus-Specific CD4+ T Cells Eliminate Borna Disease Virus from the Brain via Induction of Cytotoxic CD8+ T Cells". J. Virol. 72 (5): 4387–95. doi:10.1128/JVI.72.5.4387-4395.1998. PMC 109669. PMID 9557729.
  • Andrin C, Pinkoski MJ, Burns K, et al. (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.
  • Yu CR, Ortaldo JR, Curiel RE, et al. (1999). "Role of a STAT binding site in the regulation of the human perforin promoter". J. Immunol. 162 (5): 2785–90. doi:10.4049/jimmunol.162.5.2785. PMID 10072525. S2CID 26096007.
  • Stepp SE, Dufourcq-Lagelouse R, Le Deist F, et al. (1999). "Perforin gene defects in familial hemophagocytic lymphohistiocytosis". Science. 286 (5446): 1957–9. doi:10.1126/science.286.5446.1957. PMID 10583959.
  • Takahashi T, Nieda M, Koezuka Y, et al. (2000). "Analysis of human V alpha 24+ CD4+ NKT cells activated by alpha-glycosylceramide-pulsed monocyte-derived dendritic cells". J. Immunol. 164 (9): 4458–64. doi:10.4049/jimmunol.164.9.4458. PMID 10779745.
  • Badovinac VP, Tvinnereim AR, Harty JT (2000). "Regulation of antigen-specific CD8+ T cell homeostasis by perforin and interferon-gamma". Science. 290 (5495): 1354–8. Bibcode:2000Sci...290.1354B. doi:10.1126/science.290.5495.1354. PMID 11082062.
  • Göransdotter Ericson K, Fadeel B, Nilsson-Ardnor S, et al. (2001). "Spectrum of Perforin Gene Mutations in Familial Hemophagocytic Lymphohistiocytosis". Am. J. Hum. Genet. 68 (3): 590–7. doi:10.1086/318796. PMC 1274472. PMID 11179007.
  • Clementi R, zur Stadt U, Savoldi G, et al. (2002). "Six novel mutations in the PRF1 gene in children with haemophagocytic lymphohistiocytosis". J. Med. Genet. 38 (9): 643–6. doi:10.1136/jmg.38.9.643. PMC 1734943. PMID 11565555.
  • Ambach A, Bonnekoh B, Gollnick H (2001). "Perforin granule release from cytotoxic lymphocytes ex vivo is inhibited by ciclosporin but not by methotrexate". Skin Pharmacol. Appl. Skin Physiol. 14 (5): 249–60. doi:10.1159/000056355. PMID 11586066. S2CID 30142804.

External links

Perforin-1 at NLM Genetics Home Reference