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Protein

Perforin-1

Gene

Prf1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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
  • wide pore channel activity Source: UniProtKB

GO - Biological processi

  • cytolysis Source: UniProtKB
  • 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
  • protein homooligomerization Source: UniProtKB
Complete GO annotation...

Keywords - Biological processi

Cytolysis

Keywords - Ligandi

Calcium, 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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 10

Organism-specific databases

MGIiMGI:97551. Prf1.

Subcellular locationi

  • Cytoplasmic granule lumen
  • Secreted
  • Cell membrane; Multi-pass membrane protein
  • Endosome lumen By similarity

  • Note: Stored in cytoplasmic granules of cytolytic T-lymphocytes and secreted into the cleft between T-lymphocyte and target cell. 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.By similarity

GO - Cellular componenti

  • cytolytic granule Source: UniProtKB
  • cytoplasmic, membrane-bounded vesicle Source: MGI
  • endosome lumen Source: UniProtKB-SubCell
  • extracellular region Source: UniProtKB-SubCell
  • integral component of membrane Source: UniProtKB
  • membrane Source: MGI
  • plasma membrane Source: UniProtKB-SubCell
Complete GO annotation...

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...)1 Publication1
Disulfide bondi241 ↔ 4071 Publication
Glycosylationi375N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi376 ↔ 3921 Publication
Disulfide bondi380 ↔ 3941 Publication
Disulfide bondi396 ↔ 4061 Publication
Disulfide bondi496 ↔ 5091 Publication
Disulfide bondi524 ↔ 5331 Publication
Glycosylationi548N-linked (GlcNAc...)Sequence 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.
CleanExiMM_PRF1.
ExpressionAtlasiP10820. baseline and differential.
GenevisibleiP10820. MM.

Interactioni

Subunit structurei

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

Protein-protein interaction databases

BioGridi202128. 1 interactor.
DIPiDIP-59218N.
IntActiP10820. 1 interactor.
MINTiMINT-4107132.
STRINGi10090.ENSMUSP00000041483.

Structurei

Secondary structure

1554
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi22 – 25Combined sources4
Helixi27 – 31Combined sources5
Helixi40 – 42Combined sources3
Turni49 – 51Combined sources3
Beta strandi72 – 76Combined sources5
Turni78 – 82Combined sources5
Beta strandi84 – 87Combined sources4
Beta strandi91 – 96Combined sources6
Beta strandi106 – 110Combined sources5
Helixi113 – 121Combined sources9
Turni128 – 131Combined sources4
Turni140 – 143Combined sources4
Turni147 – 150Combined sources4
Helixi152 – 163Combined sources12
Beta strandi166 – 182Combined sources17
Helixi190 – 197Combined sources8
Helixi208 – 218Combined sources11
Beta strandi220 – 239Combined sources20
Helixi240 – 245Combined sources6
Helixi250 – 264Combined sources15
Helixi273 – 284Combined sources12
Helixi291 – 294Combined sources4
Beta strandi298 – 305Combined sources8
Helixi307 – 309Combined sources3
Beta strandi313 – 315Combined sources3
Helixi321 – 330Combined sources10
Turni331 – 333Combined sources3
Beta strandi336 – 344Combined sources9
Helixi345 – 348Combined sources4
Helixi355 – 369Combined sources15
Beta strandi384 – 386Combined sources3
Beta strandi394 – 397Combined sources4
Turni399 – 401Combined sources3
Helixi404 – 406Combined sources3
Beta strandi408 – 410Combined sources3
Beta strandi412 – 424Combined sources13
Beta strandi430 – 432Combined sources3
Beta strandi436 – 442Combined sources7
Beta strandi445 – 448Combined sources4
Beta strandi464 – 470Combined sources7
Turni471 – 473Combined sources3
Beta strandi477 – 483Combined sources7
Beta strandi486 – 488Combined sources3
Beta strandi491 – 498Combined sources8
Beta strandi502 – 510Combined sources9
Beta strandi512 – 524Combined sources13
Beta strandi528 – 530Combined sources3
Beta strandi541 – 543Combined sources3

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[»]
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
Contains 1 C2 domain.PROSITE-ProRule annotation
Contains 1 EGF-like domain.Curated
Contains 1 MACPF domain.PROSITE-ProRule annotation

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

Gene3Di2.60.40.150. 1 hit.
InterProiIPR000008. C2_dom.
IPR020864. MACPF.
IPR020863. MACPF_CS.
[Graphical view]
PfamiPF00168. C2. 1 hit.
PF01823. MACPF. 1 hit.
[Graphical view]
SMARTiSM00239. C2. 1 hit.
SM00457. MACPF. 1 hit.
[Graphical view]
SUPFAMiSSF49562. SSF49562. 1 hit.
PROSITEiPS50004. C2. 1 hit.
PS00279. MACPF_1. 1 hit.
PS51412. MACPF_2. 1 hit.
[Graphical view]

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.
GeneIDi18646.
KEGGimmu:18646.
UCSCiuc007ffv.2. mouse.

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[»]
ProteinModelPortaliP10820.
SMRiP10820.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi202128. 1 interactor.
DIPiDIP-59218N.
IntActiP10820. 1 interactor.
MINTiMINT-4107132.
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.
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.
PROiP10820.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000037202.
CleanExiMM_PRF1.
ExpressionAtlasiP10820. baseline and differential.
GenevisibleiP10820. MM.

Family and domain databases

Gene3Di2.60.40.150. 1 hit.
InterProiIPR000008. C2_dom.
IPR020864. MACPF.
IPR020863. MACPF_CS.
[Graphical view]
PfamiPF00168. C2. 1 hit.
PF01823. MACPF. 1 hit.
[Graphical view]
SMARTiSM00239. C2. 1 hit.
SM00457. MACPF. 1 hit.
[Graphical view]
SUPFAMiSSF49562. SSF49562. 1 hit.
PROSITEiPS50004. C2. 1 hit.
PS00279. MACPF_1. 1 hit.
PS51412. MACPF_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiPERF_MOUSE
AccessioniPrimary (citable) accession number: P10820
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 1, 1989
Last sequence update: April 1, 1990
Last modified: November 2, 2016
This is version 157 of the entry and version 2 of the sequence. [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. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. Protein Spotlight
    Protein Spotlight articles and cited UniProtKB/Swiss-Prot entries
  4. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.