| 穿孔素1 Perforin 1 | |||
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| 标识 | |||
| 代号 | PRF1; FLH2; HPLH2; P1; PFN1; PFP | ||
| 扩展标识 | 遗传学：170280 鼠基因：97551 同源基因：3698 ChEMBL: 5480 GeneCards: PRF1 Gene | ||
| RNA表达模式 | |||
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| 更多表达数据 | |||
| 直系同源体 | |||
| 物种 | 人类 | 小鼠 | |
| Entrez | 5551 | 18646 | |
| Ensembl | ENSG00000180644 | ENSMUSG00000037202 | |
| UniProt | P14222 | P10820 | |
| mRNA序列 | NM_001083116 | NM_011073 | |
| 蛋白序列 | NP_001076585 | NP_035203 | |
| 基因位置 |
Chr 10: 72.36 – 72.36 Mb |
Chr 10: 61.3 – 61.3 Mb |
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| PubMed查询 | [1] | [2] | |
穿孔素（英語：Perforin）是人體內一類由PRF1基因编码的蛋白質。
功能
穿孔素是一種由细胞毒性T细胞或自然殺傷細胞分泌的細胞溶解蛋白質。它們會插入靶細胞的細胞膜中，並形成孔隙。穿孔素的MACPF域能夠促使細胞溶解。該域與革蘭氏陽性菌的膽固醇依賴性溶細胞素有一定的同源型。
穿孔素在結構上和功能上與補體成分9（C9）具有一些共同點。比如說，穿孔素可以像補體成分9那樣在細胞膜上形成能夠非特異性地裂解多種靶細胞的孔洞。穿孔素是促細胞溶解顆粒中的一種主要促細胞裂解蛋白，在由T細胞和天然殺傷細胞介導的細胞溶解中起關鍵作用。它通過在細胞膜上產生孔洞，從而讓鈣離子大量流入細胞，使得靶細胞啓動細胞膜的修復機制。上述的修復機制可讓穿孔素和顆粒酶進入早期內涵體。
臨床意義
有缺陷的PRF1等位基因純合會導致2型噬血細胞综合癥，一種罕見的致死性幼年期常染色體隱性遺傳病。
相互作用
參見
參考
拓展閱讀
- Trapani JA. 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. 1996, 25 (6): 793–9. PMID 8770355. doi:10.1111/j.1445-5994.1995.tb02883.x.
- Peitsch MC, Amiguet P, Guy R; et al. Localization and molecular modelling of the membrane-inserted domain of the ninth component of human complement and perforin. Mol. Immunol. 1990, 27 (7): 589–602. PMID 2395434. doi:10.1016/0161-5890(90)90001-G.
- Young JD, Hengartner H, Podack ER, Cohn ZA. Purification and characterization of a cytolytic pore-forming protein from granules of cloned lymphocytes with natural killer activity. Cell. 1986, 44 (6): 849–59. PMID 2420467. doi:10.1016/0092-8674(86)90007-3.
- Young JD, Cohn ZA, Podack ER. The ninth component of complement and the pore-forming protein (perforin 1) from cytotoxic T cells: structural, immunological, and functional similarities. Science. 1986, 233 (4760): 184–90. PMID 2425429. doi:10.1126/science.2425429.
- Lichtenheld MG, Podack ER. Structure of the human perforin gene. A simple gene organization with interesting potential regulatory sequences. J. Immunol. 1990, 143 (12): 4267–74. PMID 2480391.
- Shinkai Y, Takio K, Okumura K. Homology of perforin to the ninth component of complement (C9). Nature. 1988, 334 (6182): 525–7. PMID 3261391. doi:10.1038/334525a0.
- Lichtenheld MG, Olsen KJ, Lu P; et al. Structure and function of human perforin. Nature. 1988, 335 (6189): 448–51. PMID 3419519. doi:10.1038/335448a0.
- Goebel WS, Schloemer RH, Brahmi Z. Target cell-induced perforin mRNA turnover in NK3.3 cells is mediated by multiple elements within the mRNA coding region. Mol. Immunol. 1996, 33 (4–5): 341–9. PMID 8676885. doi:10.1016/0161-5890(95)00155-7.
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Nöske K, Bilzer T, Planz O, Stitz L. Virus-Specific CD4+ T Cells Eliminate Borna Disease Virus from the Brain via Induction of Cytotoxic CD8+ T Cells. J. Virol. 1998, 72 (5): 4387–95. PMC 109669
. PMID 9557729.
- Andrin C, Pinkoski MJ, Burns K; et al. Interaction between a Ca2+-binding protein calreticulin and perforin, a component of the cytotoxic T-cell granules. Biochemistry. 1998, 37 (29): 10386–94. PMID 9671507. doi:10.1021/bi980595z.
- Yu CR, Ortaldo JR, Curiel RE; et al. Role of a STAT binding site in the regulation of the human perforin promoter. J. Immunol. 1999, 162 (5): 2785–90. PMID 10072525.
- Stepp SE, Dufourcq-Lagelouse R, Le Deist F; et al. Perforin gene defects in familial hemophagocytic lymphohistiocytosis. Science. 1999, 286 (5446): 1957–9. PMID 10583959. doi:10.1126/science.286.5446.1957.
- Takahashi T, Nieda M, Koezuka Y; et al. Analysis of human V alpha 24+ CD4+ NKT cells activated by alpha-glycosylceramide-pulsed monocyte-derived dendritic cells. J. Immunol. 2000, 164 (9): 4458–64. PMID 10779745. doi:10.4049/jimmunol.164.9.4458.
- Badovinac VP, Tvinnereim AR, Harty JT. Regulation of antigen-specific CD8+ T cell homeostasis by perforin and interferon-gamma. Science. 2000, 290 (5495): 1354–8. PMID 11082062. doi:10.1126/science.290.5495.1354.
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Göransdotter Ericson K, Fadeel B, Nilsson-Ardnor S; et al. Spectrum of Perforin Gene Mutations in Familial Hemophagocytic Lymphohistiocytosis. Am. J. Hum. Genet. 2001, 68 (3): 590–7. PMC 1274472 . PMID 11179007. doi:10.1086/318796.
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Clementi R, zur Stadt U, Savoldi G; et al. Six novel mutations in the PRF1 gene in children with haemophagocytic lymphohistiocytosis. J. Med. Genet. 2002, 38 (9): 643–6. PMC 1734943 . PMID 11565555. doi:10.1136/jmg.38.9.643.
- Ambach A, Bonnekoh B, Gollnick H. Perforin granule release from cytotoxic lymphocytes ex vivo is inhibited by ciclosporin but not by methotrexate. Skin Pharmacol. Appl. Skin Physiol. 2001, 14 (5): 249–60. PMID 11586066. doi:10.1159/000056355.
外部連結
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