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Protein

Perforin-1

Gene

Prf1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Plays a key role in secretory granule-dependent cell death, and in defense against virus-infected or neoplastic cells. 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.5 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei213Important for oligomerization1
Sitei343Important for oligomerization1
Metal bindingi435Calcium 11 Publication1
Metal bindingi483Calcium 11 Publication1
Metal bindingi484Calcium 1; via carbonyl oxygen1 Publication1
Metal bindingi485Calcium 2; via carbonyl oxygen1 Publication1
Metal bindingi488Calcium 2; via carbonyl oxygen1 Publication1
Metal bindingi490Calcium 21 Publication1

GO - Molecular functioni

  • calcium ion binding Source: UniProtKB
  • identical protein binding Source: MGI
  • wide pore channel activity Source: UniProtKB

GO - Biological processi

Keywordsi

Biological processCytolysis
LigandCalcium, Metal-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Perforin-1
Short name:
P1
Alternative name(s):
Cytolysin
Lymphocyte pore-forming protein
Gene namesi
Name:Prf1
Synonyms:Pfp
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 10

Organism-specific databases

MGIiMGI:97551 Prf1

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell membrane, Endosome, Membrane, Secreted

Pathology & 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 keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi191D → K or V: Loss of cytotoxicity. 1 Publication1
Mutagenesisi191D → S: Strongly decreased cytotoxicity. 1 Publication1
Mutagenesisi213R → E or L: Strongly decreased cytotoxicity. 1 Publication1
Mutagenesisi343E → R: Strongly decreased cytotoxicity. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 202 PublicationsAdd BLAST20
ChainiPRO_000002361021 – 554Perforin-1Add BLAST534

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi22 ↔ 751 Publication
Disulfide bondi30 ↔ 721 Publication
Disulfide bondi101 ↔ 1751 Publication
Glycosylationi204N-linked (GlcNAc...) asparagine1 Publication1
Disulfide bondi241 ↔ 4071 Publication
Glycosylationi375N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi376 ↔ 3921 Publication
Disulfide bondi380 ↔ 3941 Publication
Disulfide bondi396 ↔ 4061 Publication
Disulfide bondi496 ↔ 5091 Publication
Disulfide bondi524 ↔ 5331 Publication
Glycosylationi548N-linked (GlcNAc...) asparagineSequence analysis1

Post-translational modificationi

N-glycosylated. The glycosylation sites are facing the interior of the pore.1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

EPDiP10820
MaxQBiP10820
PaxDbiP10820
PRIDEiP10820

PTM databases

iPTMnetiP10820
PhosphoSitePlusiP10820
SwissPalmiP10820

Expressioni

Tissue specificityi

Detected in cytotoxic T-lymphocytes and natural killer cells.3 Publications

Gene expression databases

BgeeiENSMUSG00000037202 Expressed in 46 organ(s), highest expression level in decidua
CleanExiMM_PRF1
ExpressionAtlasiP10820 baseline and differential
GenevisibleiP10820 MM

Interactioni

Subunit structurei

Monomer, as soluble protein. Homooligomer. Oligomerization is required for pore formation.2 Publications

GO - Molecular functioni

Protein-protein interaction databases

BioGridi202128, 1 interactor
DIPiDIP-59218N
IntActiP10820, 1 interactor
MINTiP10820
STRINGi10090.ENSMUSP00000041483

Structurei

Secondary structure

1554
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP10820
SMRiP10820
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP10820

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini26 – 374MACPFPROSITE-ProRule annotationAdd BLAST349
Domaini375 – 407EGF-likeAdd BLAST33
Domaini416 – 497C2PROSITE-ProRule annotationAdd BLAST82

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.

Sequence similaritiesi

Belongs to the complement C6/C7/C8/C9 family.Curated

Keywords - Domaini

EGF-like domain, Signal, Transmembrane, Transmembrane beta strand

Phylogenomic databases

eggNOGiENOG410IGJ0 Eukaryota
ENOG410XSHK LUCA
GeneTreeiENSGT00530000063725
HOGENOMiHOG000236309
HOVERGENiHBG008168
InParanoidiP10820
KOiK07818
OMAiNYGTHFI
OrthoDBiEOG091G03LE
PhylomeDBiP10820
TreeFamiTF330498

Family and domain databases

CDDicd04032 C2_Perforin, 1 hit
Gene3Di2.60.40.150, 1 hit
InterProiView protein in InterPro
IPR000008 C2_dom
IPR035892 C2_domain_sf
IPR020864 MACPF
IPR020863 MACPF_CS
IPR037300 Perforin-1_C2
PfamiView protein in Pfam
PF00168 C2, 1 hit
PF01823 MACPF, 1 hit
SMARTiView protein in SMART
SM00239 C2, 1 hit
SM00457 MACPF, 1 hit
PROSITEiView protein in PROSITE
PS50004 C2, 1 hit
PS00279 MACPF_1, 1 hit
PS51412 MACPF_2, 1 hit

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P10820-1 [UniParc]FASTAAdd to basket
« Hide
        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
Length:554
Mass (Da):62,081
Last modified:April 1, 1990 - v2
Checksum:i9E5964CE9FE8A0D8
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti3T → M in CAA31251 (PubMed:3261391).Curated1
Sequence conflicti176R → P in AAA39909 (PubMed:2783486).Curated1
Sequence conflicti229G → A in CAA31251 (PubMed:3261391).Curated1
Sequence conflicti229G → A in CAA42731 (Ref. 5) Curated1
Sequence conflicti435D → E in AAA39909 (PubMed:2783486).Curated1
Sequence conflicti543 – 550GDPPGNRS → EILQETAC in AAA39909 (PubMed:2783486).Curated8

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
CCDSiCCDS23875.1
PIRiJL0146 A31300
RefSeqiNP_035203.3, NM_011073.3
XP_006513433.1, XM_006513370.3
UniGeneiMm.240313

Genome annotation databases

EnsembliENSMUST00000035419; ENSMUSP00000041483; ENSMUSG00000037202
ENSMUST00000219375; ENSMUSP00000151354; ENSMUSG00000037202
GeneIDi18646
KEGGimmu:18646
UCSCiuc007ffv.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
CCDSiCCDS23875.1
PIRiJL0146 A31300
RefSeqiNP_035203.3, NM_011073.3
XP_006513433.1, XM_006513370.3
UniGeneiMm.240313

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3NSJX-ray2.75A21-554[»]
4Y1SX-ray1.61A410-535[»]
4Y1TX-ray2.67A410-535[»]
5UG6X-ray2.00A410-535[»]
5UG7X-ray1.80A410-535[»]
ProteinModelPortaliP10820
SMRiP10820
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi202128, 1 interactor
DIPiDIP-59218N
IntActiP10820, 1 interactor
MINTiP10820
STRINGi10090.ENSMUSP00000041483

PTM databases

iPTMnetiP10820
PhosphoSitePlusiP10820
SwissPalmiP10820

Proteomic databases

EPDiP10820
MaxQBiP10820
PaxDbiP10820
PRIDEiP10820

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000035419; ENSMUSP00000041483; ENSMUSG00000037202
ENSMUST00000219375; ENSMUSP00000151354; ENSMUSG00000037202
GeneIDi18646
KEGGimmu:18646
UCSCiuc007ffv.2 mouse

Organism-specific databases

CTDi5551
MGIiMGI:97551 Prf1

Phylogenomic databases

eggNOGiENOG410IGJ0 Eukaryota
ENOG410XSHK LUCA
GeneTreeiENSGT00530000063725
HOGENOMiHOG000236309
HOVERGENiHBG008168
InParanoidiP10820
KOiK07818
OMAiNYGTHFI
OrthoDBiEOG091G03LE
PhylomeDBiP10820
TreeFamiTF330498

Miscellaneous databases

EvolutionaryTraceiP10820
PROiPR:P10820
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000037202 Expressed in 46 organ(s), highest expression level in decidua
CleanExiMM_PRF1
ExpressionAtlasiP10820 baseline and differential
GenevisibleiP10820 MM

Family and domain databases

CDDicd04032 C2_Perforin, 1 hit
Gene3Di2.60.40.150, 1 hit
InterProiView protein in InterPro
IPR000008 C2_dom
IPR035892 C2_domain_sf
IPR020864 MACPF
IPR020863 MACPF_CS
IPR037300 Perforin-1_C2
PfamiView protein in Pfam
PF00168 C2, 1 hit
PF01823 MACPF, 1 hit
SMARTiView protein in SMART
SM00239 C2, 1 hit
SM00457 MACPF, 1 hit
PROSITEiView protein in PROSITE
PS50004 C2, 1 hit
PS00279 MACPF_1, 1 hit
PS51412 MACPF_2, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiPERF_MOUSE
AccessioniPrimary (citable) accession number: P10820
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 1, 1989
Last sequence update: April 1, 1990
Last modified: October 10, 2018
This is version 173 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. Protein Spotlight
    Protein Spotlight articles and cited UniProtKB/Swiss-Prot entries
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Main funding by: National Institutes of Health

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