UniProtKB - P14222 (PERF_HUMAN)
Protein
Perforin-1
Gene
PRF1
Organism
Homo sapiens (Human)
Status
Functioni
Pore-forming protein that plays a key role in secretory granule-dependent cell death, and in defense against virus-infected or neoplastic cells (PubMed:9058810, PubMed:9164947, PubMed:20889983, PubMed:21037563). 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 (PubMed:9058810). Can insert into the membrane of target cells in its calcium-bound form, oligomerize and form large pores (PubMed:20889983, PubMed:21037563). Promotes cytolysis and apoptosis of target cells by facilitating the uptake of cytotoxic granzymes (PubMed:20038786, PubMed:20225066, PubMed:32299851).7 Publications
Cofactori
Ca2+PROSITE-ProRule annotation
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sitei | 214 | Important for oligomerizationBy similarity | 1 | |
Sitei | 344 | Important for oligomerizationBy similarity | 1 | |
Metal bindingi | 436 | Calcium 1By similarity | 1 | |
Metal bindingi | 484 | Calcium 1By similarity | 1 | |
Metal bindingi | 486 | Calcium 2; via carbonyl oxygenBy similarity | 1 | |
Metal bindingi | 491 | Calcium 2By similarity | 1 |
GO - Molecular functioni
- calcium ion binding Source: UniProtKB
- identical protein binding Source: IntAct
- wide pore channel activity Source: UniProtKB
GO - Biological processi
- apoptotic process Source: ProtInc
- cellular defense response Source: ProtInc
- cytolysis Source: UniProtKB-KW
- defense response to tumor cell Source: UniProtKB
- defense response to virus Source: UniProtKB
- immune response to tumor cell Source: UniProtKB
- immunological synapse formation Source: UniProtKB
- positive regulation of killing of cells of other organism Source: UniProtKB
- protein homooligomerization Source: UniProtKB
- T cell mediated cytotoxicity Source: Ensembl
Keywordsi
Biological process | Cytolysis |
Ligand | Calcium, Metal-binding |
Enzyme and pathway databases
PathwayCommonsi | P14222 |
SIGNORi | P14222 |
Protein family/group databases
TCDBi | 1.C.39.2.8, the membrane attack complex/perforin (macpf) family |
Names & Taxonomyi
Protein namesi | Recommended name: Perforin-1Short name: P1 Alternative name(s): Cytolysin Lymphocyte pore-forming protein Short name: PFP |
Gene namesi | Name:PRF1 Synonyms:PFP |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
EuPathDBi | HostDB:ENSG00000180644.6 |
HGNCi | HGNC:9360, PRF1 |
MIMi | 170280, gene |
neXtProti | NX_P14222 |
Subcellular locationi
Plasma membrane
- Cell membrane 2 Publications; Multi-pass membrane protein 2 Publications
Endosome
- Endosome lumen 1 Publication
Extracellular region or secreted
Other locations
- Cytoplasmic granule lumen 1 Publication
Note: Stored in cytoplasmic granules of cytolytic T-lymphocytes and secreted into the cleft between T-lymphocyte and target cell (PubMed:20038786). Inserts into the cell membrane of target cells and forms pores (PubMed:20889983). Membrane insertion and pore formation requires a major conformation change (PubMed:20889983). May be taken up via endocytosis involving clathrin-coated vesicles and accumulate in a first time in large early endosomes (PubMed:20038786).2 Publications
Cytosol
- cytosol Source: HPA
Endosome
- endosome lumen Source: UniProtKB-SubCell
Extracellular region or secreted
- extracellular region Source: UniProtKB-SubCell
Lysosome
- cytolytic granule Source: UniProtKB
Plasma Membrane
- plasma membrane Source: UniProtKB-SubCell
Other locations
- integral component of membrane Source: UniProtKB
- membrane Source: UniProtKB
Keywords - Cellular componenti
Cell membrane, Endosome, Membrane, SecretedPathology & Biotechi
Involvement in diseasei
Familial hemophagocytic lymphohistiocytosis 2 (FHL2)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA rare disorder characterized by immune dysregulation with hypercytokinemia, defective function of natural killer cell, and massive infiltration of several organs by activated lymphocytes and macrophages. The clinical features of the disease include fever, hepatosplenomegaly, cytopenia, and less frequently neurological abnormalities ranging from irritability and hypotonia to seizures, cranial nerve deficits and ataxia.
Related information in OMIMFeature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_010772 | 50 | V → M in FHL2. 1 PublicationCorresponds to variant dbSNP:rs776299562EnsemblClinVar. | 1 | |
Natural variantiVAR_010744 | 183 | V → G in FHL2. 1 PublicationCorresponds to variant dbSNP:rs104894183EnsemblClinVar. | 1 | |
Natural variantiVAR_010774 | 224 | I → N in FHL2. 1 Publication | 1 | |
Natural variantiVAR_010745 | 225 | R → W in FHL2. 1 PublicationCorresponds to variant dbSNP:rs28933973EnsemblClinVar. | 1 | |
Natural variantiVAR_010746 | 252 | N → S in FHL2. 1 PublicationCorresponds to variant dbSNP:rs28933375EnsemblClinVar. | 1 | |
Natural variantiVAR_010747 | 279 | C → Y in FHL2. 1 PublicationCorresponds to variant dbSNP:rs104894182EnsemblClinVar. | 1 | |
Natural variantiVAR_010775 | 285 | Missing in FHL2. 1 Publication | 1 | |
Natural variantiVAR_010748 | 345 | P → L in FHL2. 1 PublicationCorresponds to variant dbSNP:rs28933374EnsemblClinVar. | 1 | |
Natural variantiVAR_010749 | 429 | G → E in FHL2. 1 PublicationCorresponds to variant dbSNP:rs104894181EnsemblClinVar. | 1 |
Keywords - Diseasei
Disease mutation, Familial hemophagocytic lymphohistiocytosisOrganism-specific databases
DisGeNETi | 5551 |
GeneReviewsi | PRF1 |
MalaCardsi | PRF1 |
MIMi | 603553, phenotype |
OpenTargetsi | ENSG00000180644 |
Orphaneti | 540, Familial hemophagocytic lymphohistiocytosis 391343, Fatal post-viral neurodegenerative disorder 88, Idiopathic aplastic anemia |
PharmGKBi | PA33732 |
Miscellaneous databases
Pharosi | P14222, Tchem |
Chemistry databases
ChEMBLi | CHEMBL5480 |
GuidetoPHARMACOLOGYi | 3100 |
Polymorphism and mutation databases
BioMutai | PRF1 |
DMDMi | 129819 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 21 | By similarityAdd BLAST | 21 | |
ChainiPRO_0000023609 | 22 – 555 | Perforin-1Add BLAST | 534 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Disulfide bondi | 23 ↔ 76 | By similarity | ||
Disulfide bondi | 31 ↔ 73 | By similarity | ||
Disulfide bondi | 102 ↔ 176 | By similarity | ||
Glycosylationi | 205 | N-linked (GlcNAc...) asparagine1 Publication | 1 | |
Disulfide bondi | 242 ↔ 408 | By similarity | ||
Disulfide bondi | 377 ↔ 393 | By similarity | ||
Disulfide bondi | 381 ↔ 395 | By similarity | ||
Disulfide bondi | 397 ↔ 407 | By similarity | ||
Disulfide bondi | 497 ↔ 510 | By similarity | ||
Disulfide bondi | 525 ↔ 534 | By similarity | ||
Glycosylationi | 549 | N-linked (GlcNAc...) asparagineSequence analysis | 1 |
Post-translational modificationi
N-glycosylated.By similarity
Keywords - PTMi
Disulfide bond, GlycoproteinProteomic databases
jPOSTi | P14222 |
MassIVEi | P14222 |
PaxDbi | P14222 |
PeptideAtlasi | P14222 |
PRIDEi | P14222 |
ProteomicsDBi | 53040 |
PTM databases
GlyGeni | P14222, 2 sites |
iPTMneti | P14222 |
PhosphoSitePlusi | P14222 |
Expressioni
Inductioni
Repressed by contact with target cells.1 Publication
Gene expression databases
Bgeei | ENSG00000180644, Expressed in granulocyte and 187 other tissues |
ExpressionAtlasi | P14222, baseline and differential |
Genevisiblei | P14222, HS |
Organism-specific databases
HPAi | ENSG00000180644, Tissue enhanced (blood, lymphoid tissue) |
Interactioni
Subunit structurei
Binary interactionsi
Hide detailsP14222
With | #Exp. | IntAct |
---|---|---|
CYSRT1 [A8MQ03] | 3 | EBI-724466,EBI-3867333 |
GZMB [P10144] | 3 | EBI-724466,EBI-2505785 |
KRT31 [Q15323] | 6 | EBI-724466,EBI-948001 |
NOTCH2NLC [P0DPK4] | 3 | EBI-724466,EBI-22310682 |
itself | 3 | EBI-724466,EBI-724466 |
GO - Molecular functioni
- identical protein binding Source: IntAct
Protein-protein interaction databases
BioGRIDi | 111542, 8 interactors |
DIPi | DIP-53288N |
IntActi | P14222, 7 interactors |
STRINGi | 9606.ENSP00000398568 |
Chemistry databases
BindingDBi | P14222 |
Miscellaneous databases
RNActi | P14222, protein |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 27 – 375 | MACPFPROSITE-ProRule annotationAdd BLAST | 349 | |
Domaini | 376 – 408 | EGF-likeAdd BLAST | 33 | |
Domaini | 397 – 519 | C2PROSITE-ProRule annotationAdd BLAST | 123 |
Domaini
The C2 domain mediates calcium-dependent binding to lipid membranes. A subsequent conformation change leads to membrane insertion of beta-hairpin structures and pore formation. The pore is formed by transmembrane beta-strands.By similarity
Sequence similaritiesi
Belongs to the complement C6/C7/C8/C9 family.Curated
Keywords - Domaini
EGF-like domain, Signal, Transmembrane, Transmembrane beta strandPhylogenomic databases
eggNOGi | ENOG502RQWS, Eukaryota |
GeneTreei | ENSGT00530000063725 |
HOGENOMi | CLU_039516_2_0_1 |
InParanoidi | P14222 |
OMAi | PAPCYTA |
OrthoDBi | 360042at2759 |
PhylomeDBi | P14222 |
TreeFami | TF330498 |
Family and domain databases
CDDi | cd04032, C2_Perforin, 1 hit |
Gene3Di | 2.60.40.150, 1 hit |
InterProi | View protein in InterPro IPR000008, C2_dom IPR035892, C2_domain_sf IPR020864, MACPF IPR020863, MACPF_CS IPR037300, Perforin-1_C2 |
Pfami | View protein in Pfam PF00168, C2, 1 hit PF01823, MACPF, 1 hit |
SMARTi | View protein in SMART SM00239, C2, 1 hit SM00457, MACPF, 1 hit |
PROSITEi | View protein in PROSITE PS50004, C2, 1 hit PS00279, MACPF_1, 1 hit PS51412, MACPF_2, 1 hit |
(1+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All
P14222-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MAARLLLLGI LLLLLPLPVP APCHTAARSE CKRSHKFVPG AWLAGEGVDV
60 70 80 90 100
TSLRRSGSFP VDTQRFLRPD GTCTLCENAL QEGTLQRLPL ALTNWRAQGS
110 120 130 140 150
GCQRHVTRAK VSSTEAVARD AARSIRNDWK VGLDVTPKPT SNVHVSVAGS
160 170 180 190 200
HSQAANFAAQ KTHQDQYSFS TDTVECRFYS FHVVHTPPLH PDFKRALGDL
210 220 230 240 250
PHHFNASTQP AYLRLISNYG THFIRAVELG GRISALTALR TCELALEGLT
260 270 280 290 300
DNEVEDCLTV EAQVNIGIHG SISAEAKACE EKKKKHKMTA SFHQTYRERH
310 320 330 340 350
SEVVGGHHTS INDLLFGIQA GPEQYSAWVN SLPGSPGLVD YTLEPLHVLL
360 370 380 390 400
DSQDPRREAL RRALSQYLTD RARWRDCSRP CPPGRQKSPR DPCQCVCHGS
410 420 430 440 450
AVTTQDCCPR QRGLAQLEVT FIQAWGLWGD WFTATDAYVK LFFGGQELRT
460 470 480 490 500
STVWDNNNPI WSVRLDFGDV LLATGGPLRL QVWDQDSGRD DDLLGTCDQA
510 520 530 540 550
PKSGSHEVRC NLNHGHLKFR YHARCLPHLG GGTCLDYVPQ MLLGEPPGNR
SGAVW
Computationally mapped potential isoform sequencesi
There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basketA0A1W2PR25 | A0A1W2PR25_HUMAN | Perforin-1 | PRF1 | 232 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 332 | L → V in CAA31612 (PubMed:3419519).Curated | 1 | |
Sequence conflicti | 426 | G → S in CAA31612 (PubMed:3419519).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_061504 | 4 | R → H. Corresponds to variant dbSNP:rs35418374EnsemblClinVar. | 1 | |
Natural variantiVAR_010772 | 50 | V → M in FHL2. 1 PublicationCorresponds to variant dbSNP:rs776299562EnsemblClinVar. | 1 | |
Natural variantiVAR_050482 | 91 | A → V. Corresponds to variant dbSNP:rs35947132EnsemblClinVar. | 1 | |
Natural variantiVAR_010773 | 123 | R → H1 PublicationCorresponds to variant dbSNP:rs139336186EnsemblClinVar. | 1 | |
Natural variantiVAR_029773 | 135 | V → M. Corresponds to variant dbSNP:rs12263572EnsemblClinVar. | 1 | |
Natural variantiVAR_010744 | 183 | V → G in FHL2. 1 PublicationCorresponds to variant dbSNP:rs104894183EnsemblClinVar. | 1 | |
Natural variantiVAR_010774 | 224 | I → N in FHL2. 1 Publication | 1 | |
Natural variantiVAR_010745 | 225 | R → W in FHL2. 1 PublicationCorresponds to variant dbSNP:rs28933973EnsemblClinVar. | 1 | |
Natural variantiVAR_010746 | 252 | N → S in FHL2. 1 PublicationCorresponds to variant dbSNP:rs28933375EnsemblClinVar. | 1 | |
Natural variantiVAR_010747 | 279 | C → Y in FHL2. 1 PublicationCorresponds to variant dbSNP:rs104894182EnsemblClinVar. | 1 | |
Natural variantiVAR_010775 | 285 | Missing in FHL2. 1 Publication | 1 | |
Natural variantiVAR_010748 | 345 | P → L in FHL2. 1 PublicationCorresponds to variant dbSNP:rs28933374EnsemblClinVar. | 1 | |
Natural variantiVAR_010749 | 429 | G → E in FHL2. 1 PublicationCorresponds to variant dbSNP:rs104894181EnsemblClinVar. | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | X13224 mRNA Translation: CAA31612.1 M28393 mRNA Translation: AAA60065.1 M31951 Genomic DNA Translation: AAA60167.1 AK312754 mRNA Translation: BAG35621.1 AL355344 Genomic DNA No translation available. CH471083 Genomic DNA Translation: EAW54407.1 BC047695 mRNA Translation: AAH47695.2 BC063043 mRNA Translation: AAH63043.1 AB209604 mRNA Translation: BAD92841.1 L40557 mRNA Translation: AAA63618.1 |
CCDSi | CCDS7305.1 |
PIRi | A45816, A37181 |
RefSeqi | NP_001076585.1, NM_001083116.1 NP_005032.2, NM_005041.4 |
Genome annotation databases
Ensembli | ENST00000373209; ENSP00000362305; ENSG00000180644 ENST00000441259; ENSP00000398568; ENSG00000180644 |
GeneIDi | 5551 |
KEGGi | hsa:5551 |
UCSCi | uc001jrf.5, human |
Keywords - Coding sequence diversityi
PolymorphismSimilar proteinsi
Cross-referencesi
Web resourcesi
PRF1base PRF1 mutation db |
Wikipedia Perforin entry |
Protein Spotlight Our hollow architecture - Issue 126 of February 2011 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | X13224 mRNA Translation: CAA31612.1 M28393 mRNA Translation: AAA60065.1 M31951 Genomic DNA Translation: AAA60167.1 AK312754 mRNA Translation: BAG35621.1 AL355344 Genomic DNA No translation available. CH471083 Genomic DNA Translation: EAW54407.1 BC047695 mRNA Translation: AAH47695.2 BC063043 mRNA Translation: AAH63043.1 AB209604 mRNA Translation: BAD92841.1 L40557 mRNA Translation: AAA63618.1 |
CCDSi | CCDS7305.1 |
PIRi | A45816, A37181 |
RefSeqi | NP_001076585.1, NM_001083116.1 NP_005032.2, NM_005041.4 |
3D structure databases
SMRi | P14222 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 111542, 8 interactors |
DIPi | DIP-53288N |
IntActi | P14222, 7 interactors |
STRINGi | 9606.ENSP00000398568 |
Chemistry databases
BindingDBi | P14222 |
ChEMBLi | CHEMBL5480 |
GuidetoPHARMACOLOGYi | 3100 |
Protein family/group databases
TCDBi | 1.C.39.2.8, the membrane attack complex/perforin (macpf) family |
PTM databases
GlyGeni | P14222, 2 sites |
iPTMneti | P14222 |
PhosphoSitePlusi | P14222 |
Polymorphism and mutation databases
BioMutai | PRF1 |
DMDMi | 129819 |
Proteomic databases
jPOSTi | P14222 |
MassIVEi | P14222 |
PaxDbi | P14222 |
PeptideAtlasi | P14222 |
PRIDEi | P14222 |
ProteomicsDBi | 53040 |
Protocols and materials databases
Antibodypediai | 3723, 569 antibodies |
Genome annotation databases
Ensembli | ENST00000373209; ENSP00000362305; ENSG00000180644 ENST00000441259; ENSP00000398568; ENSG00000180644 |
GeneIDi | 5551 |
KEGGi | hsa:5551 |
UCSCi | uc001jrf.5, human |
Organism-specific databases
CTDi | 5551 |
DisGeNETi | 5551 |
EuPathDBi | HostDB:ENSG00000180644.6 |
GeneCardsi | PRF1 |
GeneReviewsi | PRF1 |
HGNCi | HGNC:9360, PRF1 |
HPAi | ENSG00000180644, Tissue enhanced (blood, lymphoid tissue) |
MalaCardsi | PRF1 |
MIMi | 170280, gene 603553, phenotype |
neXtProti | NX_P14222 |
OpenTargetsi | ENSG00000180644 |
Orphaneti | 540, Familial hemophagocytic lymphohistiocytosis 391343, Fatal post-viral neurodegenerative disorder 88, Idiopathic aplastic anemia |
PharmGKBi | PA33732 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | ENOG502RQWS, Eukaryota |
GeneTreei | ENSGT00530000063725 |
HOGENOMi | CLU_039516_2_0_1 |
InParanoidi | P14222 |
OMAi | PAPCYTA |
OrthoDBi | 360042at2759 |
PhylomeDBi | P14222 |
TreeFami | TF330498 |
Enzyme and pathway databases
PathwayCommonsi | P14222 |
SIGNORi | P14222 |
Miscellaneous databases
BioGRID-ORCSi | 5551, 4 hits in 844 CRISPR screens |
GeneWikii | Perforin |
GenomeRNAii | 5551 |
Pharosi | P14222, Tchem |
PROi | PR:P14222 |
RNActi | P14222, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000180644, Expressed in granulocyte and 187 other tissues |
ExpressionAtlasi | P14222, baseline and differential |
Genevisiblei | P14222, HS |
Family and domain databases
CDDi | cd04032, C2_Perforin, 1 hit |
Gene3Di | 2.60.40.150, 1 hit |
InterProi | View protein in InterPro IPR000008, C2_dom IPR035892, C2_domain_sf IPR020864, MACPF IPR020863, MACPF_CS IPR037300, Perforin-1_C2 |
Pfami | View protein in Pfam PF00168, C2, 1 hit PF01823, MACPF, 1 hit |
SMARTi | View protein in SMART SM00239, C2, 1 hit SM00457, MACPF, 1 hit |
PROSITEi | View protein in PROSITE PS50004, C2, 1 hit PS00279, MACPF_1, 1 hit PS51412, MACPF_2, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | PERF_HUMAN | |
Accessioni | P14222Primary (citable) accession number: P14222 Secondary accession number(s): B2R6X4, Q59F57, Q86WX7 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | January 1, 1990 |
Last sequence update: | January 1, 1990 | |
Last modified: | December 2, 2020 | |
This is version 209 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- Human polymorphisms and disease mutations
Index of human polymorphisms and disease mutations - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - SIMILARITY comments
Index of protein domains and families - Protein Spotlight
Protein Spotlight articles and cited UniProtKB/Swiss-Prot entries - Human chromosome 10
Human chromosome 10: entries, gene names and cross-references to MIM - Human entries with polymorphisms or disease mutations
List of human entries with polymorphisms or disease mutations