UniProtKB - P10820 (PERF_MOUSE)
Protein
Perforin-1
Gene
Prf1
Organism
Mus musculus (Mouse)
Status
Functioni
Plays a key role in secretory granule-dependent cell death, and in defense against virus-infected or neoplastic cells (PubMed:19446473, PubMed:21037563, PubMed:3261391, PubMed:7526382, PubMed:8164737). Can insert into the membrane of target cells in its calcium-bound form, oligomerize and form large pores (PubMed:19446473, PubMed:21037563, PubMed:3261391, PubMed:7526382, PubMed:8164737). Promotes cytolysis and apoptosis of target cells by facilitating the uptake of cytotoxic granzymes (PubMed:19446473, PubMed:21037563, PubMed:3261391, PubMed:7526382, PubMed:8164737).5 Publications
Cofactori
Ca2+PROSITE-ProRule annotation1 Publication
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sitei | 213 | Important for oligomerization1 Publication | 1 | |
Sitei | 343 | Important for oligomerization1 Publication | 1 | |
Metal bindingi | 435 | Calcium 11 Publication | 1 | |
Metal bindingi | 483 | Calcium 11 Publication | 1 | |
Metal bindingi | 484 | Calcium 1; via carbonyl oxygen1 Publication | 1 | |
Metal bindingi | 485 | Calcium 2; via carbonyl oxygen1 Publication | 1 | |
Metal bindingi | 488 | Calcium 2; via carbonyl oxygen1 Publication | 1 | |
Metal bindingi | 490 | Calcium 21 Publication | 1 |
GO - Molecular functioni
- calcium ion binding Source: UniProtKB
- identical protein binding Source: MGI
- wide pore channel activity Source: UniProtKB
GO - Biological processi
- apoptotic process Source: MGI
- circadian rhythm Source: MGI
- 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: MGI
- positive regulation of killing of cells of other organism Source: MGI
- protein homooligomerization Source: UniProtKB
- T cell mediated cytotoxicity Source: MGI
Keywordsi
Biological process | Cytolysis |
Ligand | Calcium, Metal-binding |
Names & Taxonomyi
Protein namesi | Recommended name: Perforin-1Short name: P1 Alternative name(s): Cytolysin Lymphocyte pore-forming protein |
Gene namesi | Name:Prf1 Synonyms:Pfp |
Organismi | Mus musculus (Mouse) |
Taxonomic identifieri | 10090 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus |
Proteomesi |
|
Organism-specific databases
MGIi | MGI:97551, Prf1 |
Subcellular locationi
Plasma membrane
- Cell membrane 2 Publications; Multi-pass membrane protein 2 Publications
Endosome
- Endosome lumen By similarity
Extracellular region or secreted
- Secreted 2 Publications
Other locations
- Cytoplasmic granule lumen 2 Publications
Note: Stored in cytoplasmic granules of cytolytic T-lymphocytes and secreted into the cleft between T-lymphocyte and target cell (PubMed:2040805, PubMed:8164737). May be taken up via endocytosis involving clathrin-coated vesicles and accumulate in a first time in large early endosomes (By similarity). Inserts into the cell membrane of target cells and forms pores. Membrane insertion and pore formation requires a major conformation change (PubMed:19446473, PubMed:21037563).By similarity4 Publications
Cytosol
- cytosol Source: MGI
Endosome
- endosome lumen Source: UniProtKB-SubCell
Extracellular region or secreted
- extracellular space Source: MGI
Lysosome
- cytolytic granule Source: UniProtKB
Plasma Membrane
- plasma membrane Source: UniProtKB-SubCell
Other locations
- cytoplasmic vesicle Source: MGI
- integral component of membrane Source: UniProtKB
Keywords - Cellular componenti
Cell membrane, Endosome, Membrane, SecretedPathology & Biotechi
Disruption phenotypei
Mice are viable and fertile, but die of virus infections that are normally efficiently dealt with by the immune system. They cannot eliminate lymphocytic choriomeningitis virus, but die of the infection. Young mice are abnormally susceptible to mouse hepatitis virus. Cytolytic activity towards tumor cells and transplants is also severely reduced.2 Publications
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 191 | D → K or V: Loss of cytotoxicity. 1 Publication | 1 | |
Mutagenesisi | 191 | D → S: Strongly decreased cytotoxicity. 1 Publication | 1 | |
Mutagenesisi | 213 | R → E or L: Strongly decreased cytotoxicity. 1 Publication | 1 | |
Mutagenesisi | 343 | E → R: Strongly decreased cytotoxicity. 1 Publication | 1 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 20 | 2 PublicationsAdd BLAST | 20 | |
ChainiPRO_0000023610 | 21 – 554 | Perforin-1Add BLAST | 534 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Disulfide bondi | 22 ↔ 75 | 1 Publication | ||
Disulfide bondi | 30 ↔ 72 | 1 Publication | ||
Disulfide bondi | 101 ↔ 175 | 1 Publication | ||
Glycosylationi | 204 | N-linked (GlcNAc...) asparagine1 Publication | 1 | |
Disulfide bondi | 241 ↔ 407 | 1 Publication | ||
Glycosylationi | 375 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Disulfide bondi | 376 ↔ 392 | 1 Publication | ||
Disulfide bondi | 380 ↔ 394 | 1 Publication | ||
Disulfide bondi | 396 ↔ 406 | 1 Publication | ||
Disulfide bondi | 496 ↔ 509 | 1 Publication | ||
Disulfide bondi | 524 ↔ 533 | 1 Publication | ||
Glycosylationi | 548 | N-linked (GlcNAc...) asparagineSequence analysis | 1 |
Post-translational modificationi
N-glycosylated. The glycosylation sites are facing the interior of the pore.1 Publication
Keywords - PTMi
Disulfide bond, GlycoproteinProteomic databases
EPDi | P10820 |
MaxQBi | P10820 |
PaxDbi | P10820 |
PRIDEi | P10820 |
ProteomicsDBi | 287675 |
PTM databases
GlyGeni | P10820, 3 sites |
iPTMneti | P10820 |
PhosphoSitePlusi | P10820 |
SwissPalmi | P10820 |
Expressioni
Tissue specificityi
Detected in cytotoxic T-lymphocytes and natural killer cells.3 Publications
Gene expression databases
Bgeei | ENSMUSG00000037202, Expressed in decidua and 61 other tissues |
Genevisiblei | P10820, MM |
Interactioni
Subunit structurei
Monomer, as soluble protein. Homooligomer. Oligomerization is required for pore formation.
2 PublicationsGO - Molecular functioni
- identical protein binding Source: MGI
Protein-protein interaction databases
BioGRIDi | 202128, 2 interactors |
DIPi | DIP-59218N |
IntActi | P10820, 1 interactor |
MINTi | P10820 |
STRINGi | 10090.ENSMUSP00000041483 |
Miscellaneous databases
RNActi | P10820, protein |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
SMRi | P10820 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | P10820 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 26 – 374 | MACPFPROSITE-ProRule annotationAdd BLAST | 349 | |
Domaini | 375 – 407 | EGF-likeAdd BLAST | 33 | |
Domaini | 395 – 513 | C2PROSITE-ProRule annotationAdd BLAST | 119 |
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.1 Publication
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 | P10820 |
OMAi | PAPCYTA |
OrthoDBi | 360042at2759 |
PhylomeDBi | P10820 |
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 |
i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
P10820-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MATCLFLLGL FLLLPRPVPA PCYTATRSEC KQKHKFVPGV WMAGEGMDVT
60 70 80 90 100
TLRRSGSFPV NTQRFLRPDR TCTLCKNSLM RDATQRLPVA ITHWRPHSSH
110 120 130 140 150
CQRNVAAAKV HSTEGVAREA AANINNDWRV GLDVNPRPEA NMRASVAGSH
160 170 180 190 200
SKVANFAAEK TYQDQYNFNS DTVECRMYSF RLVQKPPLHL DFKKALRALP
210 220 230 240 250
RNFNSSTEHA YHRLISSYGT HFITAVDLGG RISVLTALRT CQLTLNGLTA
260 270 280 290 300
DEVGDCLNVE AQVSIGAQAS VSSEYKACEE KKKQHKMATS FHQTYRERHV
310 320 330 340 350
EVLGGPLDST HDLLFGNQAT PEQFSTWTAS LPSNPGLVDY SLEPLHTLLE
360 370 380 390 400
EQNPKREALR QAISHYIMSR ARWQNCSRPC RSGQHKSSHD SCQCECQDSK
410 420 430 440 450
VTNQDCCPRQ RGLAHLVVSN FRAEHLWGDY TTATDAYLKV FFGGQEFRTG
460 470 480 490 500
VVWNNNNPRW TDKMDFENVL LSTGGPLRVQ VWDADYGWDD DLLGSCDRSP
510 520 530 540 550
HSGFHEVTCE LNHGRVKFSY HAKCLPHLTG GTCLEYAPQG LLGDPPGNRS
GAVW
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 3 | T → M in CAA31251 (PubMed:3261391).Curated | 1 | |
Sequence conflicti | 176 | R → P in AAA39909 (PubMed:2783486).Curated | 1 | |
Sequence conflicti | 229 | G → A in CAA31251 (PubMed:3261391).Curated | 1 | |
Sequence conflicti | 229 | G → A in CAA42731 (Ref. 5) Curated | 1 | |
Sequence conflicti | 435 | D → E in AAA39909 (PubMed:2783486).Curated | 1 | |
Sequence conflicti | 543 – 550 | GDPPGNRS → EILQETAC in AAA39909 (PubMed:2783486).Curated | 8 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | M23182 mRNA Translation: AAA39910.1 X51340, X51446 Genomic DNA Translation: CAA35721.1 X12760 mRNA Translation: CAA31251.1 J04148 mRNA Translation: AAA39909.1 X60165 mRNA Translation: CAA42731.1 M95527 Genomic DNA Translation: AAB01574.1 |
CCDSi | CCDS23875.1 |
PIRi | JL0146, A31300 |
RefSeqi | NP_035203.3, NM_011073.3 XP_006513433.1, XM_006513370.3 |
Genome annotation databases
Ensembli | ENSMUST00000035419; ENSMUSP00000041483; ENSMUSG00000037202 ENSMUST00000219375; ENSMUSP00000151354; ENSMUSG00000037202 |
GeneIDi | 18646 |
KEGGi | mmu:18646 |
UCSCi | uc007ffv.2, mouse |
Similar proteinsi
Cross-referencesi
Web resourcesi
Protein Spotlight Our hollow architecture - Issue 126 of February 2011 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | M23182 mRNA Translation: AAA39910.1 X51340, X51446 Genomic DNA Translation: CAA35721.1 X12760 mRNA Translation: CAA31251.1 J04148 mRNA Translation: AAA39909.1 X60165 mRNA Translation: CAA42731.1 M95527 Genomic DNA Translation: AAB01574.1 |
CCDSi | CCDS23875.1 |
PIRi | JL0146, A31300 |
RefSeqi | NP_035203.3, NM_011073.3 XP_006513433.1, XM_006513370.3 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
3NSJ | X-ray | 2.75 | A | 21-554 | [»] | |
4Y1S | X-ray | 1.61 | A | 410-535 | [»] | |
4Y1T | X-ray | 2.67 | A | 410-535 | [»] | |
5UG6 | X-ray | 2.00 | A | 410-535 | [»] | |
5UG7 | X-ray | 1.80 | A | 410-535 | [»] | |
SMRi | P10820 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 202128, 2 interactors |
DIPi | DIP-59218N |
IntActi | P10820, 1 interactor |
MINTi | P10820 |
STRINGi | 10090.ENSMUSP00000041483 |
PTM databases
GlyGeni | P10820, 3 sites |
iPTMneti | P10820 |
PhosphoSitePlusi | P10820 |
SwissPalmi | P10820 |
Proteomic databases
EPDi | P10820 |
MaxQBi | P10820 |
PaxDbi | P10820 |
PRIDEi | P10820 |
ProteomicsDBi | 287675 |
Protocols and materials databases
Antibodypediai | 3723, 578 antibodies |
Genome annotation databases
Ensembli | ENSMUST00000035419; ENSMUSP00000041483; ENSMUSG00000037202 ENSMUST00000219375; ENSMUSP00000151354; ENSMUSG00000037202 |
GeneIDi | 18646 |
KEGGi | mmu:18646 |
UCSCi | uc007ffv.2, mouse |
Organism-specific databases
CTDi | 5551 |
MGIi | MGI:97551, Prf1 |
Phylogenomic databases
eggNOGi | ENOG502RQWS, Eukaryota |
GeneTreei | ENSGT00530000063725 |
HOGENOMi | CLU_039516_2_0_1 |
InParanoidi | P10820 |
OMAi | PAPCYTA |
OrthoDBi | 360042at2759 |
PhylomeDBi | P10820 |
TreeFami | TF330498 |
Miscellaneous databases
BioGRID-ORCSi | 18646, 1 hit in 52 CRISPR screens |
EvolutionaryTracei | P10820 |
PROi | PR:P10820 |
RNActi | P10820, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSMUSG00000037202, Expressed in decidua and 61 other tissues |
Genevisiblei | P10820, MM |
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_MOUSE | |
Accessioni | P10820Primary (citable) accession number: P10820 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | July 1, 1989 |
Last sequence update: | April 1, 1990 | |
Last modified: | April 7, 2021 | |
This is version 185 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
3D-structure, Direct protein sequencing, Reference proteomeDocuments
- MGD cross-references
Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families - Protein Spotlight
Protein Spotlight articles and cited UniProtKB/Swiss-Prot entries