Browse PRF1

Summary
SymbolPRF1
Nameperforin 1 (pore forming protein)
Aliases PFP; HPLH2; Perforin; perforin 1 (preforming protein); FLH2; cytolysin; lymphocyte pore forming protein; lym ......
Chromosomal Location10q22
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Basic function annotation.
> Subcellular Location, Domain and Function
> Gene Ontology
> KEGG and Reactome Pathway
> Subcellular Location, Domain and Function
 
Subcellular Location Cytoplasmic granule lumen. Secreted. Cell membrane; Multi-pass membrane protein. Endosome lumen. Note=Stored in cytoplasmic granules of cytolytic T-lymphocytes and secreted into the cleft between T-lymphocyte and target cell. Inserts into the cell membrane of target cells and forms pores. Membrane insertion and pore formation requires a major conformation change. May be taken up via endocytosis involving clathrin-coated vesicles and accumulate in a first time in large early endosomes.
Domain PF00168 C2 domain
PF01823 MAC/Perforin domain
Function

Plays a key role in secretory granule-dependent cell death, and in defense against virus-infected or neoplastic cells. Plays an important role in killing other cells that are recognized as non-self by the immune system, e.g. in transplant rejection or some forms of autoimmune disease. Can insert into the membrane of target cells in its calcium-bound form, oligomerize and form large pores. Promotes cytolysis and apoptosis of target cells by facilitating the uptake of cytotoxic granzymes.

> Gene Ontology
 
Biological Process GO:0001771 immunological synapse formation
GO:0002347 response to tumor cell
GO:0002357 defense response to tumor cell
GO:0002418 immune response to tumor cell
GO:0006968 cellular defense response
GO:0008037 cell recognition
GO:0009615 response to virus
GO:0009988 cell-cell recognition
GO:0019835 cytolysis
GO:0051259 protein oligomerization
GO:0051260 protein homooligomerization
GO:0051607 defense response to virus
GO:0098542 defense response to other organism
Molecular Function GO:0015267 channel activity
GO:0022803 passive transmembrane transporter activity
GO:0022829 wide pore channel activity
Cellular Component GO:0005775 vacuolar lumen
GO:0031904 endosome lumen
GO:0044194 cytolytic granule
GO:0044440 endosomal part
> KEGG and Reactome Pathway
 
KEGG hsa04210 Apoptosis
hsa04650 Natural killer cell mediated cytotoxicity
Reactome -
Summary
SymbolPRF1
Nameperforin 1 (pore forming protein)
Aliases PFP; HPLH2; Perforin; perforin 1 (preforming protein); FLH2; cytolysin; lymphocyte pore forming protein; lym ......
Chromosomal Location10q22
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between PRF1 and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.
> Text Mining
 
  Literatures describing the relation between PRF1 and anti-tumor immunity in human cancer.
PMID Cancer type Relation to immunity Evidence sentences
26423796LymphomaPromote immunity (NK cell function)ALT-803 is a superagonist IL-15 mutant and IL-15Rα-Fc fusion complex that activates the IL-15 receptor constitutively expressed on natural killer (NK) cells. ALT-803 augmented cytotoxicity and the expression of granzyme B and perforin, providing one potential mechanism for this enhanced functionality.
23440424NeuroblastomaPromote immunityThe final products contained more than 90% CD56(+) cells and could kill neuroblastoma cells effectively that were originally highly resistant to nonprocessed NK cells. Mechanistically, cytolysis of neuroblastoma was mediated through natural cytotoxicity receptor (NCR), DNAX accessory molecule-1 (DNAM-1; CD226), perforin, and granzyme B.
16651448LeukemiaPromote immunity (T cell function)The cytokine interleukin (IL)-12 promotes CD8(+) T-cell cytotoxicity and, with IL-18, synergistically up-regulates IFN-gamma release. We have shown that culturing CD8(+) T cells ex vivo with IL-12 and IL-18 enhanced antitumor responses in vivo and in vitro using a model of C1498/ovalbumin, a murine acute myeloid leukemia cell line expressing the antigen ovalbumin. Maximal IFN-gamma release occurred after T-cell culture with IL-12 and IL-18. Tumor-specific in vitro cytotoxicity was enhanced by IL-12, unaffected by addition of IL-18, and abrogated in perforin-deficient T cells irrespective of cytokine exposure.
22419581MyelomaPromote immunity (NK cell function)Expanded natural killer cells killed both allogeneic and autologous primary myeloma cells avidly via a perforin-mediated mechanism in which the activating receptor NKG2D, natural cytotoxicity receptors, and DNAX-accessory molecule-1 played a central role. The transferred, expanded natural killer cells proliferated in vivo in an interleukin-2 dose-dependent fashion, persisted up to 4 weeks, were readily detectable in the human bone, inhibited myeloma growth and protected bone from myeloma-induced osteolysis.
24698324MelanomaPromote immunityWhen immunodeficient mice were injected with miR-150(-/-) NK cells, there was a significant reduction in tumor growth and metastasis of B16F10 melanoma. We report that miR-150 binds to 3' untranslated regions of mouse and human Prf1, posttranscriptionally downregulating its expression. Mouse wild-type NK cells displayed downregulated miR-150 expression in response to IL-15, which led to corresponding repression and induction of Prf1 during rest and after IL-15 activation, respectively.
19202127Renal Cell Carcinoma; Lung CarcinomaPromote immunity (NK cell function)Bioluminescence imaging of mice with established tumors showed treatment with bortezomib and syngeneic NK cells reduced tumor growth and prolonged survival compared with controls receiving bortezomib or NK cells alone. In contrast, tumor progression was not delayed when animals received bortezomib and perforin-deficient NK cells, showing drug-induced augmentation in NK-cell cytotoxicity was mediated through perforin/granzyme.
29668066colon adenocarcinomaPromote immunityThey display several NK cell-associated receptors, carry granules containing cytotoxic effector molecules, and swiftly upregulate perforin and granzymes upon activation.
23851682Lung Adenocarcinoma; Non-Small Cell Lung CarcinomaPromote immunity (infiltration)Because mice bearing early NSCLC treated with anti-CD25 mAb exhibited increased tumor cell death associated with infiltration by CD8(+) T cells expressing elevated levels of granzyme A, granzyme B, perforin, and IFN-γ, we therefore evaluated carboplatin combination therapy resulting in a significantly extended survival beyond that observed with chemotherapy alone, indicating that Treg depletion in combination with cytotoxic therapy may be beneficial as a treatment strategy for advanced NSCLC.
20145137Breast CarcinomaPromote immunity (T cell function)In allogeneic MLTR, antiestrogen-treated MCF-7 cells caused downregulation of the effector molecules granzyme B, perforin, and Fas ligand in CD8(+) T cells, and suppressed the generation of cytotoxic effector cells in a TGFbeta-dependent manner.
17545627Breast AdenocarcinomaPromote immunityInterestingly, perforin significantly delayed the onset of mammary tumorigenesis and reduced the number of mammary tumors without improving survival. This data suggests that perforin may mediate some suppression of epithelial carcinogenesis by intervening early in the tumor development process.
25125657melanomaPromote immunity(T cell function)Here, we show that CCDC134 is differentially expressed on resting and activated immune cells and that it promotes CD8(+) T-cell activation, proliferation, and cytotoxicity by augmenting expression of the T-cell effector molecules IFNγ, TNFα, granzyme B, and perforin
21908738MyelomaPromote immunityMHC class I expression on myeloma cells and contact with T cells were required for CD8(+) T cell divisions and DP-T cell development. DP-T cells present in myeloma-infiltrated bones contained a higher proportion of cells expressing cytotoxic mediators IFN-gamma and/or perforin compared with single-positive CD8(+) T cells, acquired the capacity to degranulate as measured by CD107 expression, and contributed to an elevated perforin level seen in the myeloma-infiltrated bones.
17015756colon carcinomaPromote immunityNotably, redirected CD4+ T cells mediate cytolysis of CEA+ tumor cells with high efficiencies. Lysis by redirected CD4+ T cells is independent of death receptor signaling via TNF-alpha or Fas, but mediated by perforin and granzyme because cytolysis is inhibited by blocking the release of cytotoxic granules, but not by blocking of Fas ligand or TNF-alpha.
Summary
SymbolPRF1
Nameperforin 1 (pore forming protein)
Aliases PFP; HPLH2; Perforin; perforin 1 (preforming protein); FLH2; cytolysin; lymphocyte pore forming protein; lym ......
Chromosomal Location10q22
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.
> High-throughput Screening
  Statistical results of PRF1 in screening data sets for detecting immune reponses.
PMID Screening System Cancer Type Cell Line Data Set Statistical Results Relation to immunity
29301958CRISPR-Cas9 melanomaB16F10Pmel-1 T cell NA/NSNA/NS
29301958CRISPR-Cas9 melanomaB16F10OT-1 T cell NA/NSNA/NS
28783722CRISPR-Cas9 melanomaMel6242CT-CRISPR NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX+Anti-PD1 NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX NA/NSNA/NS
25691366RNAiBreast cancerMCF7Luc-CTL assay NA/NSNA/NS
24476824shRNAmelanomaB16Primary screen NA/NSNA/NS
24476824shRNAmelanomaB16Secondary screen NA/NSNA/NS
Summary
SymbolPRF1
Nameperforin 1 (pore forming protein)
Aliases PFP; HPLH2; Perforin; perforin 1 (preforming protein); FLH2; cytolysin; lymphocyte pore forming protein; lym ......
Chromosomal Location10q22
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets.
> Expression difference between responders and non-responders
> Mutation difference between responders and non-responders
> Expression difference between responders and non-responders
 
Points in the above scatter plot represent the expression difference of PRF1 in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)1412-0.4760.344
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)650.0720.956
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)87-0.8810.401
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160.6720.261
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59-0.2570.855
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 471.8480.292
729033130MelanomaallAnti-PD-1 (nivolumab) 26230.7560.225
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 15110.8370.426
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 11120.6430.579
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 481.6120.168
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 280.7580.68
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 682300.2480.277
> Mutation difference between responders and non-responders
 
Points in the above scatter plot represent the mutation difference of PRF1 in various data sets.
No PMID Cancer type Group Drug # Res # NRes % Mut/Res % Mut/NRes % Diff (R vs NR) Pval Anno
125765070Non-small cell lung cancer (NSCLC)allAnti-PD-1 (pembrolizumab) 14170001
225765070Non-small cell lung cancer (NSCLC)smokingAnti-PD-1 (pembrolizumab) 1030001
325765070Non-small cell lung cancer (NSCLC)non-smokingAnti-PD-1 (pembrolizumab) 4140001
426359337MelanomaallAnti-CTLA-4 (ipilimumab) 27733.74.1-0.41
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 0140001
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 27593.75.1-1.41
726997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)21174.804.81
826997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)860001
926997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)13117.707.71
1028552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 91611.1011.10.36
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590001
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 47250250.364
1329033130MelanomaallAnti-PD-1 (nivolumab) 382703.7-3.70.415
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 22130001
1529033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 161407.1-7.10.467
1629301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 11130001
1729301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 610001
1829301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 5120001
Summary
SymbolPRF1
Nameperforin 1 (pore forming protein)
Aliases PFP; HPLH2; Perforin; perforin 1 (preforming protein); FLH2; cytolysin; lymphocyte pore forming protein; lym ......
Chromosomal Location10q22
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of PRF1. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.
> Lymphocyte
 
Summary
SymbolPRF1
Nameperforin 1 (pore forming protein)
Aliases PFP; HPLH2; Perforin; perforin 1 (preforming protein); FLH2; cytolysin; lymphocyte pore forming protein; lym ......
Chromosomal Location10q22
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of PRF1. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by PRF1.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolPRF1
Nameperforin 1 (pore forming protein)
Aliases PFP; HPLH2; Perforin; perforin 1 (preforming protein); FLH2; cytolysin; lymphocyte pore forming protein; lym ......
Chromosomal Location10q22
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of PRF1. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolPRF1
Nameperforin 1 (pore forming protein)
Aliases PFP; HPLH2; Perforin; perforin 1 (preforming protein); FLH2; cytolysin; lymphocyte pore forming protein; lym ......
Chromosomal Location10q22
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of PRF1 expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolPRF1
Nameperforin 1 (pore forming protein)
Aliases PFP; HPLH2; Perforin; perforin 1 (preforming protein); FLH2; cytolysin; lymphocyte pore forming protein; lym ......
Chromosomal Location10q22
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between PRF1 and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolPRF1
Nameperforin 1 (pore forming protein)
Aliases PFP; HPLH2; Perforin; perforin 1 (preforming protein); FLH2; cytolysin; lymphocyte pore forming protein; lym ......
Chromosomal Location10q22
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting PRF1 collected from DrugBank database.
> Drugs from DrugBank database
 

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