Affinage

PRF1

Perforin-1 · UniProt P14222

Round 2 corrected
Length
555 aa
Mass
61.4 kDa
Annotated
2026-04-28
130 papers in source corpus 21 papers cited in narrative 21 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

Perforin-1 (PRF1) is a Ca²⁺-dependent pore-forming protein of cytotoxic lymphocytes that serves as the essential membrane-disrupting effector enabling granzyme delivery to target cells, thereby mediating immune killing and lymphocyte homeostasis. Stored in cytotoxic granules as part of macromolecular complexes with granzyme B and serglycin, perforin is exocytosed at the immune synapse, where its C-terminal C2 domain binds target membranes in a Ca²⁺-dependent manner and its MACPF/CDC domain oligomerizes to form ~160 Å transmembrane pores; these pores trigger Ca²⁺-dependent endocytosis of granzyme–serglycin complexes into enlarged endosomes ("gigantosomes"), from which perforin forms secondary pores to release granzymes into the cytosol, initiating apoptosis or, through granzyme B cleavage of gasdermin E, pyroptosis (PMID:2420467, PMID:21037563, PMID:11911826, PMID:21685908, PMID:32188940). Loss-of-function PRF1 mutations cause familial hemophagocytic lymphohistiocytosis type 2 (FHL2), while hypomorphic mutations such as A91V predispose to late-onset HLH and hematological malignancies (PMID:10583959, PMID:11179007, PMID:27622035). Perforin also controls CD8⁺ T cell homeostasis independently of its antimicrobial effector role and cooperates with granulysin to kill intracellular Mycobacterium tuberculosis (PMID:11082062, PMID:9756476).

Mechanistic history

Synthesis pass · year-by-year structured walk · 10 steps
  1. 1986 High

    Establishing the fundamental pore-forming activity: purified perforin was shown to form Ca²⁺-dependent ~160 Å transmembrane pores and large nonselective ion channels, providing the molecular basis for cytotoxic lymphocyte killing activity.

    Evidence Protein purification from cytolytic granules; planar lipid bilayer electrophysiology; liposome leakage; electron microscopy

    PMID:2420467 PMID:2425429

    Open questions at the time
    • Mechanism of oligomerization and pore assembly unknown
    • In vivo relevance not yet demonstrated genetically
    • Lipid selectivity of membrane binding uncharacterized
  2. 1988 High

    Cloning human and mouse perforin cDNAs revealed homology to complement C9 in the MACPF domain, establishing that cytotoxic lymphocyte killing uses a pore-forming module shared with innate immunity and restricted to killer-type cells.

    Evidence cDNA cloning; RNA blot analysis; sequence comparison between perforin and C9

    PMID:2592021 PMID:3261391 PMID:3419519

    Open questions at the time
    • Domain boundaries and three-dimensional structure unknown
    • No functional mutagenesis of homology region
  3. 1998 High

    Demonstrating that perforin functions beyond direct cytolysis: perforin was required to deliver granulysin into cells harboring intracellular M. tuberculosis, establishing its role as a general translocator for granule effectors in antimicrobial defense.

    Evidence CTL killing assays against intracellular M. tuberculosis; granulysin-dependent and perforin-dependent killing reconstitution

    PMID:9756476

    Open questions at the time
    • Mechanism of intracellular delivery to pathogen-containing compartments unresolved
    • Relative contributions of perforin pore vs. endosomal pathway for granulysin delivery unknown
  4. 1999 High

    Identifying perforin deficiency as the genetic cause of familial hemophagocytic lymphohistiocytosis type 2 established that perforin-mediated cytotoxicity is essential for immune homeostasis, not just pathogen clearance.

    Evidence PRF1 gene sequencing in FHL families; absent perforin immunostaining; defective NK/CTL cytotoxicity

    PMID:10583959 PMID:11179007

    Open questions at the time
    • Precise mechanism by which perforin deficiency triggers hyperinflammation not defined
    • Genotype-phenotype spectrum for hypomorphic alleles incomplete
  5. 2000 High

    Perforin-deficient mice showed uncontrolled CD8⁺ T cell expansion after infection, revealing that perforin regulates lymphocyte homeostasis through a mechanism independent of its antimicrobial role, explaining the immunoregulatory failure in FHL.

    Evidence Perforin-KO mice infected with Listeria monocytogenes; flow cytometry tracking antigen-specific CD8⁺ T cells

    PMID:11082062

    Open questions at the time
    • Whether perforin acts on T cells directly (fratricide) or through APC killing is unresolved
    • Relative importance of this pathway vs. Fas/FasL in vivo uncertain
  6. 2002 High

    Demonstrating that granzyme B, perforin, and serglycin exist as preformed macromolecular complexes in granules resolved how effector molecules are co-delivered: serglycin serves as a scaffold, perforin as translocator, and granzyme B as the apoptotic effector.

    Evidence Co-immunoprecipitation; gel filtration; cytotoxicity and membrane permeabilization assays

    PMID:11911826

    Open questions at the time
    • Stoichiometry of the complex undefined
    • Whether serglycin is required for pore formation in vivo unknown
  7. 2010 High

    The crystal structure of monomeric perforin and cryo-EM reconstruction of the pore revealed that the MACPF domain is oriented inside-out relative to CDCs, the C2 domain mediates Ca²⁺-dependent membrane docking, and >50 FHL mutations mapped onto the structure, providing the first atomic framework for understanding disease and pore assembly.

    Evidence X-ray crystallography of murine perforin; cryo-EM pore reconstruction; mapping of FHL mutations

    PMID:21037563

    Open questions at the time
    • High-resolution pore structure at near-atomic resolution not yet achieved
    • Conformational intermediates during oligomerization unresolved
  8. 2011 High

    Live-cell imaging revealed a two-step delivery mechanism: perforin pores at the plasma membrane trigger Ca²⁺-dependent endocytosis of perforin–granzyme complexes into gigantosomes, from which secondary perforin pores release granzymes into the cytosol, resolving the long-standing question of how granzymes access cytosolic substrates.

    Evidence Live-cell time-lapse microscopy; Ca²⁺ flux measurements; endosomal fractionation; fluorescent granzyme tracking

    PMID:20530211 PMID:21685908

    Open questions at the time
    • Molecular signals governing gigantosome formation incompletely defined
    • Role of acid sphingomyelinase pathway in vivo during CTL attack not confirmed
  9. 2013 High

    Real-time imaging at the immune synapse showed perforin pores assemble within 30 seconds and are repaired within 20–80 seconds, yet this window suffices for lethal granzyme delivery and caspase activation within 2 minutes, defining the kinetic constraints of the killing mechanism.

    Evidence Time-lapse microscopy of immune synapse; biochemical permeabilization and caspase activation assays in primary human CTLs

    PMID:23377437

    Open questions at the time
    • Whether pore repair is target cell type-dependent unknown
    • Contribution of endosomal vs. direct plasma membrane pathway in this rapid killing not quantified
  10. 2020 High

    Perforin was shown to be required for granzyme B–mediated cleavage of gasdermin E in target cells, linking the perforin pathway to pyroptosis (not only apoptosis) and establishing perforin release levels as a determinant of pyroptosis-driven cytokine release syndrome in CAR T cell therapy.

    Evidence Perforin-KO mouse tumor models; GSDME knockout; granzyme B cleavage assays; CAR T cell co-culture with caspase inhibitors

    PMID:31953257 PMID:32188940

    Open questions at the time
    • Whether perforin pores are needed for GSDME cleavage in all tumor types unresolved
    • Therapeutic strategies to modulate perforin release for CRS mitigation not established

Open questions

Synthesis pass · forward-looking unresolved questions
  • A near-atomic resolution structure of the full perforin pore, the conformational pathway from monomer to assembled ring, and the precise mechanism by which perforin selectively spares the effector CTL/NK cell remain major unresolved questions.
  • No high-resolution cryo-EM pore structure at near-atomic resolution
  • Self-protection mechanism of killer cells not molecularly defined
  • Relative quantitative contributions of direct plasma membrane pore vs. endosomal pathway in different target cell types unresolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 3 GO:0005215 transporter activity 3 GO:0008289 lipid binding 2
Localization
GO:0005886 plasma membrane 3 GO:0005576 extracellular region 2 GO:0031410 cytoplasmic vesicle 2 GO:0005768 endosome 1
Pathway
R-HSA-168256 Immune System 6 R-HSA-5357801 Programmed Cell Death 4 R-HSA-1643685 Disease 3
Partners
GNLYGSDMEGZMBSRGN
Complex memberships
Granzyme B–serglycin–perforin granule complex

Evidence

Reading pass · 21 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1986 Perforin (PFP) was purified from granules of cloned NK-like cytolytic cells and shown to form Ca2+-dependent transmembrane pores of ~160 Å diameter in target cell membranes, depolarizing cells and making lipid vesicles leaky; the protein formed large (averaging ~400 pS), voltage-insensitive, nonselective ion channels in planar bilayers, functionally and morphologically similar to lesions formed by intact NK cells. Protein purification from cytolytic granules; planar lipid bilayer electrophysiology; liposome leakage assays; electron microscopy of membrane lesions Cell High 2420467
1986 Structural and functional homologies between perforin (PFP) and complement component C9 were demonstrated: monospecific antibodies to purified C9 and PFP showed cross-reactivity, and both proteins polymerize to form tubular membrane lesions (100 Å for C9, 160 Å for PFP) that create stable, nonselective, voltage-insensitive aqueous pores; perforin polymerization requires Ca2+. Immunological cross-reactivity assays; electron microscopy; planar lipid bilayer electrophysiology; Zn2+-induced polymerization of C9 Science High 2425429
1988 Human perforin cDNA was isolated; the deduced amino acid sequence showed 68.4% similarity to mouse perforin and confirmed structural homology to complement component C9 at functionally conserved regions; perforin expression was restricted to killer-type cells (NK cells and cytotoxic T lymphocytes) among cell lines tested. cDNA cloning and sequencing; RNA blot analysis; sequence comparison Nature High 2592021 3261391 3419519
1988 Mouse perforin cDNA was cloned and sequenced; the deduced primary structure has homology with C9 at their respective functionally conserved regions, providing direct molecular evidence that a killer-cell-specific protein evolutionarily linked to C9 is involved in cell-mediated cytolysis. cDNA library screening with oligonucleotide probes derived from N-terminal amino acid sequencing; sequence analysis Nature High 3261391
1989 Human perforin (PFP) gene was mapped to chromosome 17q11-21 by in situ hybridization, and perforin mRNA was found to be expressed preferentially in killer-type cells and large granular lymphocytes. cDNA isolation; RNA blot analysis; in situ hybridization for chromosomal mapping Immunogenetics High 2592021
1998 Granulysin in combination with perforin decreased the viability of intracellular Mycobacterium tuberculosis; the ability of CTLs to kill intracellular M. tuberculosis was dependent on the presence of granulysin in cytotoxic granules, defining a mechanism by which T cells directly contribute to immunity against intracellular pathogens requiring perforin to deliver granulysin. CTL killing assays; granulysin-deficient cell functional studies; intracellular killing assays with M. tuberculosis Science High 9756476
1999 Loss-of-function mutations in the perforin gene (PRF1) were identified as the cause of 10q21-22-linked familial hemophagocytic lymphohistiocytosis (FHL); homozygous nonsense and missense mutations in PRF1 were found in FHL patients, cultured lymphocytes had defective cytotoxic activity, and immunostaining revealed little or no perforin in granules, demonstrating that perforin-based effector systems are required for down-regulation of cellular immune activation. Gene sequencing; NK/CTL cytotoxicity assays; immunostaining of granules Science High 10583959
2000 Perforin-deficient mice exhibited increased expansion and decreased death of antigen-specific CD8+ T cells after Listeria monocytogenes infection, demonstrating that perforin controls CD8+ T cell expansion (homeostasis) independently of its antimicrobial effector role; IFN-γ controlled immunodominance and the death phase by a separate mechanism. Perforin-deficient and IFN-γ-deficient mouse infection model; flow cytometry of antigen-specific CD8+ T cells Science High 11082062
2002 Granzyme B (GrB) and perforin coexist as multimolecular complexes with the proteoglycan serglycin in cytotoxic granules; cytotoxic cells secrete macromolecular GrB-serglycin complexes; monomeric perforin and perforin-serglycin complexes mediate cytosolic delivery of macromolecular GrB-serglycin without producing detectable plasma membrane pores, indicating a multimeric modular delivery system (serglycin=scaffold, perforin=translocator, granzyme=effector). Co-immunoprecipitation; gel filtration; cytotoxicity assays; membrane permeabilization assays Immunity High 11911826
2010 The X-ray crystal structure of monomeric murine perforin was determined and a cryo-electron microscopy reconstruction of the entire perforin pore was obtained. Perforin is a thin 'key-shaped' molecule comprising: an N-terminal MACPF/CDC domain, an EGF domain forming a central shelf with the C-terminal sequence, and a C-terminal C2 domain that mediates initial Ca2+-dependent membrane binding. The MACPF domain orientation in the perforin pore is inside-out relative to CDC subunit arrangement, revealing remarkable mechanistic flexibility in the MACPF/CDC fold. More than 50 FHL-linked perforin mutations mapped onto this structure. X-ray crystallography; cryo-electron microscopy reconstruction; structure-function mapping of disease mutations Nature High 21037563
2010 Acid sphingomyelinase (ASM) is released extracellularly when cells are wounded by perforin in the presence of Ca2+; ASM-deficient cells undergo lysosomal exocytosis after wounding but are defective in injury-dependent endocytosis and plasma membrane repair; exogenous recombinant ASM restores endocytosis and resealing, demonstrating that conversion of plasma membrane sphingomyelin to ceramide by ASM promotes internalization of perforin lesions. Cell wounding assays; ASM-deficient cells; rescue with recombinant ASM; endocytosis and membrane resealing assays Journal of Cell Biology High 20530211
2011 Perforin induces a transient Ca2+ flux in the target cell triggering endocytosis of both perforin and granzymes into enlarged endosomes ('gigantosomes'); perforin then forms pores in the gigantosome membrane, allowing endosomal cargo including granzymes to be gradually released into the cytosol; after ~15 min gigantosomes rupture releasing remaining contents. This two-step mechanism (plasma membrane pore → endocytosis → endosomal pore → cytosolic release) delivers granzymes to the target cell cytosol. Live-cell time-lapse microscopy; Ca2+ flux measurements; endosomal fractionation; fluorescent granzyme tracking Nature Immunology High 21685908
2013 Using biochemical approaches combined with time-lapse microscopy of human primary cytotoxic lymphocytes, perforin pores were shown to assemble on the target cell plasma membrane within 30 seconds of recognition, enabling rapid diffusion of extracellular granzymes into the target cell through transient plasma membrane pores that are repaired within 20–80 seconds; even this short exposure is sufficient for delivery of lethal amounts of granzymes, with caspase-dependent apoptosis initiated within 2 minutes. Time-lapse live microscopy of immune synapse; biochemical Ca2+ flux and permeabilization assays; caspase activation assays Blood High 23377437
2012 In a cohort of HLH patients with complete loss of perforin, Rab27a, or syntaxin-11, disease severity (age at onset) differed significantly with a gradient: perforin deficiency caused earliest onset, followed by Rab27a, then syntaxin-11. A syntaxin-11-deficient mouse model showed that HLH severity was not fully correlated with differences in cytotoxic activity but that antigen presentation capacity also differed, suggesting cytotoxic effectors have immune-regulatory roles beyond controlling viral replication. Patient cohort comparison; Stx11−/− mouse model with LCMV infection; lymphocyte degranulation assays; rescue with human STX11 expression Blood High 23160464
2018 miR-30e was shown to directly target PRF1 mRNA and negatively regulate perforin expression in peripheral blood NK cells and decidual NK cells; up-regulation of miR-30e suppressed NK cell cytotoxicity and shifted cytokine production toward IL-4/IL-10 (Th2) by reducing perforin levels, contributing to immune tolerance at the maternal-fetal interface. miRNA mimic/inhibitor transfection; PCR and Western blot for miR-30e and PRF1; flow cytometry for cytotoxicity and cytokine expression; ELISA Biomedicine & Pharmacotherapy Medium 30551399
2020 In perforin-deficient mice, the tumor suppressive activity of GSDME was abrogated: GSDME expression in tumor cells normally promotes anti-tumor immunity via killer cytotoxic lymphocytes (NK and CD8+ T cells), and this function is lost when perforin is absent, demonstrating that perforin is required downstream of GSDME-mediated pyroptosis for anti-tumor immune activation. Additionally, granzyme B from killer cells directly cleaves GSDME at the same caspase-3 site to trigger caspase-independent pyroptosis in target cells. Perforin-deficient mouse tumor models; GSDME knockout/overexpression; granzyme B cleavage assays in vitro; lymphocyte depletion experiments Nature High 32188940
2020 CAR T cells activate caspase 3 in target cells through release of granzyme B, which cleaves gasdermin E (GSDME), triggering pyroptosis; the quantity of perforin/granzyme B released by CAR T cells (rather than conventional CD8+ T cells) is critical for inducing target cell pyroptosis and the subsequent cytokine release syndrome, defining perforin release level as a key determinant of pyroptosis-mediated CRS. CAR T cell co-culture assays; granzyme B measurement; GSDME knockout models; caspase inhibitor experiments; patient correlations Science Immunology High 31953257
2001 Comprehensive mutational analysis of the PRF1 coding region in FHL patients identified missense, nonsense, and deletion mutations spread across the gene; the W374X nonsense mutation at codon 374 was identified as the most common perforin mutation, found in approximately 30% of Turkish FHL patients. All identified mutations associated with absent or severely reduced perforin in granules and absent NK/CTL cytotoxic activity, establishing genotype-phenotype correlations. Gene sequencing of all exons; NK cytotoxicity assays; immunostaining; linkage analysis American Journal of Human Genetics High 11179007
2006 Missense mutations in RAB27A (Ala87Pro) and hMunc13-4/UNC13D (Leu403Pro) were shown to prevent formation of a stable hMunc13-4/Rab27a complex in vitro using a mammalian two-hybrid system, functionally characterizing these FHL-related missense mutations in the granule exocytosis pathway that delivers perforin to targets. Mammalian two-hybrid system; large-scale PRF1/UNC13D/STX11 sequencing; functional complex formation assay Human Mutation Medium 16278825
2012 The PRF1 A91V missense mutation (compound heterozygous with G149S) was shown to result in low perforin expression levels and impaired NK cell-mediated cytotoxicity, which was partially reconstituted after incubation with IL-2, demonstrating that this hypomorphic mutation reduces but does not abolish perforin function and can predispose to later-onset FHL2. Flow cytometry for intracellular perforin; NK cell cytotoxicity assays; IL-2 stimulation rescue Human Immunology Medium 23073290
2016 Missense perforin mutations A91V and R410W were shown to cause protein misfolding and partial loss of perforin activity, linking partial PRF1 loss-of-function to hereditary cancer predisposition including hematological malignancies and some solid tumors across three generations of a family. Sequencing; protein misfolding assessment; functional perforin activity assays; family pedigree analysis Oncoimmunology Medium 27622035

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2005 A human protein-protein interaction network: a resource for annotating the proteome. Cell 1704 16169070
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2020 Gasdermin E suppresses tumour growth by activating anti-tumour immunity. Nature 1315 32188940
2014 A proteome-scale map of the human interactome network. Cell 977 25416956
1999 Perforin gene defects in familial hemophagocytic lymphohistiocytosis. Science (New York, N.Y.) 940 10583959
2020 A reference map of the human binary protein interactome. Nature 849 32296183
2002 HIV-specific CD8+ T cell proliferation is coupled to perforin expression and is maintained in nonprogressors. Nature immunology 835 12368910
1998 An antimicrobial activity of cytolytic T cells mediated by granulysin. Science (New York, N.Y.) 791 9756476
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2020 Gasdermin E-mediated target cell pyroptosis by CAR T cells triggers cytokine release syndrome. Science immunology 469 31953257
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2005 Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes. Genome research 409 16344560
1988 Structure and function of human perforin. Nature 354 3419519
1986 Purification and characterization of a cytolytic pore-forming protein from granules of cloned lymphocytes with natural killer activity. Cell 345 2420467
2000 Regulation of antigen-specific CD8+ T cell homeostasis by perforin and interferon-gamma. Science (New York, N.Y.) 334 11082062
2002 The P1' specificity of tobacco etch virus protease. Biochemical and biophysical research communications 330 12074568
2010 The structural basis for membrane binding and pore formation by lymphocyte perforin. Nature 324 21037563
2011 Hypomorphic mutations in PRF1, MUNC13-4, and STXBP2 are associated with adult-onset familial HLH. Blood 318 21881043
2010 Exocytosis of acid sphingomyelinase by wounded cells promotes endocytosis and plasma membrane repair. The Journal of cell biology 290 20530211
1986 The ninth component of complement and the pore-forming protein (perforin 1) from cytotoxic T cells: structural, immunological, and functional similarities. Science (New York, N.Y.) 281 2425429
2010 Perforin expression directly ex vivo by HIV-specific CD8 T-cells is a correlate of HIV elite control. PLoS pathogens 270 20523897
1988 Homology of perforin to the ninth component of complement (C9). Nature 266 3261391
2011 Perforin pores in the endosomal membrane trigger the release of endocytosed granzyme B into the cytosol of target cells. Nature immunology 240 21685908
2004 Genome of bacteriophage P1. Journal of bacteriology 225 15489417
2007 Genetic susceptibility to respiratory syncytial virus bronchiolitis is predominantly associated with innate immune genes. The Journal of infectious diseases 223 17703412
2006 Mutation spectrum in children with primary hemophagocytic lymphohistiocytosis: molecular and functional analyses of PRF1, UNC13D, STX11, and RAB27A. Human mutation 223 16278825
2002 Cytotoxic cell granule-mediated apoptosis: perforin delivers granzyme B-serglycin complexes into target cells without plasma membrane pore formation. Immunity 208 11911826
2013 Perforin forms transient pores on the target cell plasma membrane to facilitate rapid access of granzymes during killer cell attack. Blood 207 23377437
2001 Spectrum of perforin gene mutations in familial hemophagocytic lymphohistiocytosis. American journal of human genetics 195 11179007
2005 Increase in activated CD8+ T lymphocytes expressing perforin and granzyme B correlates with disease activity in patients with systemic lupus erythematosus. Arthritis and rheumatism 193 15641052
2023 Structural basis of NINJ1-mediated plasma membrane rupture in cell death. Nature 191 37198476
2009 Mutations in the perforin gene can be linked to macrophage activation syndrome in patients with systemic onset juvenile idiopathic arthritis. Rheumatology (Oxford, England) 183 20019066
1988 An Ultrabithorax protein binds sequences near its own and the Antennapedia P1 promoters. Cell 164 2904838
1996 The role of MCM/P1 proteins in the licensing of DNA replication. Trends in biochemical sciences 159 8882583
1999 P1 ParA interacts with the P1 partition complex at parS and an ATP-ADP switch controls ParA activities. The EMBO journal 142 10064607
1987 Cloning and sequence analysis of cytadhesin P1 gene from Mycoplasma pneumoniae. Infection and immunity 124 3119495
2011 Impact of ectoenzymes on p2 and p1 receptor signaling. Advances in pharmacology (San Diego, Calif.) 113 21586362
1999 Intracellular localization of P1 ParB protein depends on ParA and parS. Proceedings of the National Academy of Sciences of the United States of America 99 10611311
1999 Environmental signals controlling sexual development of the corn Smut fungus Ustilago maydis through the transcriptional regulator Prf1. The Plant cell 94 10402430
1998 Corepression of the P1 addiction operon by Phd and Doc. Journal of bacteriology 93 9829946
2009 PFP: Automated prediction of gene ontology functional annotations with confidence scores using protein sequence data. Proteins 91 18655063
1977 Replication of prophage P1 during the cell cycle of Escherichia coli. Molecular & general genetics : MGG 91 325389
1987 Two DNA antirestriction systems of bacteriophage P1, darA, and darB: characterization of darA- phages. Virology 87 3029954
2004 PTEN regulates Mdm2 expression through the P1 promoter. The Journal of biological chemistry 84 15090541
2003 PKA and MAPK phosphorylation of Prf1 allows promoter discrimination in Ustilago maydis. The EMBO journal 84 14592979
2002 Solution structure of a luteoviral P1-P2 frameshifting mRNA pseudoknot. Journal of molecular biology 76 12225754
2012 Distinct severity of HLH in both human and murine mutants with complete loss of cytotoxic effector PRF1, RAB27A, and STX11. Blood 72 23160464
2008 Characterization of PRF1, STX11 and UNC13D genotype-phenotype correlations in familial hemophagocytic lymphohistiocytosis. British journal of haematology 72 18710388
1970 Morphological variants of coliphage P1. Journal of virology 72 4193834
2000 Proteins complexed to the P1 adhesin of Mycoplasma pneumoniae. Microbiology (Reading, England) 67 10746778
1983 The conformation around the peptide bond between the P1- and P2-positions is important for catalytic activity of some proline-specific proteases. Biochimica et biophysica acta 66 6340741
1989 Molecular cloning and chromosomal assignment of a human perforin (PFP) gene. Immunogenetics 56 2592021
1987 Both P1 and P2 protamine genes are expressed in mouse, hamster, and rat. Biology of reproduction 54 3676400
2008 Host-specific effect of P1 exchange between two potyviruses. Molecular plant pathology 53 18705848
2001 Small changes in the regulation of one Arabidopsis profilin isovariant, PRF1, alter seedling development. The Plant cell 53 11340190
2015 Binding forces of Streptococcus mutans P1 adhesin. ACS nano 52 25671413
2002 Architecture of Fis-activated transcription complexes at the Escherichia coli rrnB P1 and rrnE P1 promoters. Journal of molecular biology 51 11866514
2017 DNA methylation of the RUNX2 P1 promoter mediates MMP13 transcription in chondrocytes. Scientific reports 48 28798419
2010 Micrococcin P1: structure, biology and synthesis. Natural product reports 48 20179875
1995 The tripartite immunity system of phages P1 and P7. FEMS microbiology reviews 48 7669337
2016 Pyrophosphate: fructose-6-phosphate 1-phosphotransferase (PFP) regulates carbon metabolism during grain filling in rice. Plant cell reports 45 26993329
2010 Partitioning of P1 plasmids by gradual distribution of the ATPase ParA. Molecular microbiology 44 21091504
2013 The PAF complex and Prf1/Rtf1 delineate distinct Cdk9-dependent pathways regulating transcription elongation in fission yeast. PLoS genetics 43 24385927
1990 The c4 repressors of bacteriophages P1 and P7 are antisense RNAs. Cell 43 1696181
1996 Three functions of bacteriophage P1 involved in cell lysis. Journal of bacteriology 42 8576044
2017 The multicomponent antirestriction system of phage P1 is linked to capsid morphogenesis. Molecular microbiology 40 28509398
1987 P1 plasmid replication requires methylated DNA. The EMBO journal 39 2826133
2015 Spectrum of Atypical Clinical Presentations in Patients with Biallelic PRF1 Missense Mutations. Pediatric blood & cancer 36 26184781
2011 Screening the PRF1, UNC13D, STX11, SH2D1A, XIAP, and ITK gene mutations in Chinese children with Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis. Pediatric blood & cancer 36 21674762
2002 Loop-inserted and thermostabilized structure of P1-P1' cleaved ovalbumin mutant R339T. Journal of molecular biology 36 11779232
1993 Linkage of human spermatid-specific basic nuclear protein genes. Definition and evolution of the P1-->P2-->TP2 locus. The Journal of biological chemistry 36 8428967
1998 Cloning and expression of diadenosine 5',5'''-P1,P4-tetraphosphate hydrolase from Lupinus angustifolius L. The Biochemical journal 35 9425114
1984 Stimulation of DNA synthesis by microinjection of diadenosine 5',5''-P1, P4-tetraphosphate (Ap4A) into Xenopus laevis oocytes. Developmental biology 35 6724135
2002 Genetic polymorphism of cytochrome P450 1A1 (Cyp1A1) and glutathione transferases (M1, T1 and P1) among Africans. Clinical chemistry and laboratory medicine 34 12435115
1989 Isolation, characterization, and inactivation of the APA1 gene encoding yeast diadenosine 5',5'''-P1,P4-tetraphosphate phosphorylase. Journal of bacteriology 34 2556364
2019 Phylo-PFP: improved automated protein function prediction using phylogenetic distance of distantly related sequences. Bioinformatics (Oxford, England) 33 30165572
2011 P1 peptidase--a mysterious protein of family Potyviridae. Journal of biosciences 33 21451259
2008 Pheromone-regulated target genes respond differentially to MAPK phosphorylation of transcription factor Prf1. Molecular microbiology 33 18627457
2005 The high-mobility-group domain transcription factor Rop1 is a direct regulator of prf1 in Ustilago maydis. Eukaryotic cell 33 15701800
1996 Characterization and phylogeny of the pfp gene of Amycolatopsis methanolica encoding PPi-dependent phosphofructokinase. Journal of bacteriology 33 8550409
2020 A Pd1-Ps-P1 Feedback Loop Controls Pubescence Density in Soybean. Molecular plant 32 33065270
2010 Uptake of Hydrocarbon by Pseudomonas fluorescens (P1) and Pseudomonas putida (K1) Strains in the Presence of Surfactants: A Cell Surface Modification. Water, air, and soil pollution 32 21258434
2006 Patients of African ancestry with hemophagocytic lymphohistiocytosis share a common haplotype of PRF1 with a 50delT mutation. The Journal of pediatrics 31 16860143
1994 Interaction of human P1 and P2 protamines with DNA. Biochemical and biophysical research communications 31 8024562
1990 Structure of the ecdysone-inducible P1 gene of Drosophila melanogaster. Journal of molecular biology 30 1696317
1989 The superimmunity gene sim of bacteriophage P1 causes superinfection exclusion. Virology 30 2763457
2018 Effect of miR-30e regulating NK cell activities on immune tolerance of maternal-fetal interface by targeting PRF1. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 27 30551399
2016 Transcriptional Auto-Regulation of RUNX1 P1 Promoter. PloS one 26 26901859
1989 Three additional operators, Op21, Op68, and Op88, of bacteriophage P1. Evidence for control of the P1 dam methylase by Op68. The Journal of biological chemistry 26 2536753
2020 PRF1 mutation alters immune system activation, inflammation, and risk of autoimmunity. Multiple sclerosis (Houndmills, Basingstoke, England) 25 33566725
2010 Phosphorylation of DCC by ERK2 is facilitated by direct docking of the receptor P1 domain to the kinase. Structure (London, England : 1993) 25 21070949
2006 Detection of inflamed atherosclerotic lesions with diadenosine-5',5'''-P1,P4-tetraphosphate (Ap4A) and positron-emission tomography. Proceedings of the National Academy of Sciences of the United States of America 25 17038498
1985 Transfection by genomic DNA of cytochrome P1-450 enzymatic activity and inducibility. Molecular and cellular biology 25 3990691
2009 Hap2 regulates the pheromone response transcription factor prf1 in Ustilago maydis. Molecular microbiology 24 19400774
2008 BACE1 inhibitors: optimization by replacing the P1' residue with non-acidic moiety. Bioorganic & medicinal chemistry letters 24 18249539
1992 Transcriptional control via translational repression by c4 antisense RNA of bacteriophages P1 and P7. Genes & development 24 1459462
2023 Domain-PFP allows protein function prediction using function-aware domain embedding representations. Communications biology 23 37907681
2019 Morphological Changes and Expressions of AOX1A, CYP81D8, and Putative PFP Genes in a Large Set of Commercial Maize Hybrids Under Extreme Waterlogging. Frontiers in plant science 23 30778365
2016 Missense mutations in the perforin (PRF1) gene as a cause of hereditary cancer predisposition. Oncoimmunology 23 27622035
2014 PFP/ESG: automated protein function prediction servers enhanced with Gene Ontology visualization tool. Bioinformatics (Oxford, England) 23 25273111
2008 Requirements for surface expression and function of adhesin P1 from Streptococcus mutans. Infection and immunity 23 18362133
2001 Complete nucleotide sequence of the mycoplasma virus P1 genome. Plasmid 23 11322826
1992 C1 repressor of phage P1 is inactivated by noncovalent binding of P1 Coi protein. The Journal of biological chemistry 23 1740459
1988 The c1 repressor of bacteriophage P1. Isolation and characterization of the repressor protein. The Journal of biological chemistry 23 2826478
1980 Mutations in coliphage p1 affecting host cell lysis. Journal of virology 23 16789200
1989 Organization of the immunity region immI of bacteriophage P1 and synthesis of the P1 antirepressor. Journal of molecular biology 22 2585500
1989 Protein-DNA interactions in regulation of P1 plasmid replication. Journal of bacteriology 21 2644199
2008 P1 nuclease cleavage is dependent on length of the mismatches in DNA. DNA repair 20 18524693
2018 Mycoplasma pneumoniae induces allergy by producing P1-specific immunoglobulin E. Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology 19 29555351
2012 Evaluation of function predictions by PFP, ESG,and PSI-BLAST for moonlighting proteins. BMC proceedings 19 23173871
2003 The involvement of diadenosine 5',5"'-P1,P4-tetraphosphate in cell cycle arrest and regulation of apoptosis. Biochemical pharmacology 19 12504798
2002 Neisseria gonorrhoeae porin P1.B induces endosome exocytosis and a redistribution of Lamp1 to the plasma membrane. Infection and immunity 19 12379671
1997 Epitope specificity of murine and human bactericidal antibodies against PorA P1.7,16 induced with experimental meningococcal group B vaccines. FEMS immunology and medical microbiology 19 9093834
1994 Substrate specificity of porcine renin: P1', P1, and P3 residues of renin substrates are crucial for activity. Biochemistry 19 7981226
2005 Crystal structure of an Anti-meningococcal subtype P1.4 PorA antibody provides basis for peptide-vaccine design. Journal of molecular biology 18 16038932
2020 Neurologic Manifestations as Initial Clinical Presentation of Familial Hemophagocytic Lymphohistiocytosis Type2 Due to PRF1 Mutation in Chinese Pediatric Patients. Frontiers in genetics 17 32194620
2016 Collectin CL-P1 utilizes C-reactive protein for complement activation. Biochimica et biophysica acta 17 26922829
1995 A YAC-, P1-, and cosmid-based physical map of the BRCA1 region on chromosome 17q21. Genomics 17 7774927
2012 Functional impact of A91V mutation of the PRF1 perforin gene. Human immunology 16 23073290
1990 Reductive trapping of substrate to methylamine oxidase from Arthrobacter P1. FEBS letters 16 2155832
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2012 Paramutagenicity of a p1 epiallele in maize. TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik 15 22986680
1990 A bacteriophage P1-encoded modulator protein affects the P1 c1 repression system. The Journal of biological chemistry 15 2211715
1990 Increased capsaicin content in PFP-resistant cells of chili pepper (Capsicum annuum L.). Plant cell reports 15 24232685
1989 Organization of the bacteriophage P1 tail-fibre operon. Gene 15 2526777
1983 SOS induction by P1 Km miniplasmids. Journal of bacteriology 15 6223918
2014 A novel PRF1 gene mutation in a fatal neonate case with type 2 familial hemophagocytic lymphohistiocytosis. Korean journal of pediatrics 14 24578718
1996 P1-purinoceptor-mediated vasodilatation and vasoconstriction in hypoxia. Journal of autonomic pharmacology 14 9131417