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P10820 (PERF_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 3, 2013. Version 129. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Perforin-1
Short name=P1
Alternative name(s):
Cytolysin
Lymphocyte pore-forming protein
Gene names
Name:Prf1
Synonyms:Pfp
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length554 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.3 Ref.9 Ref.10 Ref.11 Ref.12

Subunit structure

Monomer, as sobluble protein. Homooligomer. Oligomerization is required for pore formation. Ref.11 Ref.12

Subcellular location

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. Ref.3 Ref.8 Ref.9 Ref.11 Ref.12

Tissue specificity

Detected in cytotoxic T-lymphocytes and natural killer cells. Ref.3 Ref.4 Ref.8

Domain

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.

Post-translational modification

N-glycosylated. The glycosylation sites are facing the interior of the pore. Ref.12

Disruption phenotype

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. Ref.9 Ref.10

Sequence similarities

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

Contains 1 C2 domain.

Contains 1 EGF-like domain.

Contains 1 MACPF domain.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2020 Ref.3 Ref.7
Chain21 – 554534Perforin-1
PRO_0000023610

Regions

Domain26 – 374349MACPF
Domain375 – 40733EGF-like
Domain416 – 49782C2

Sites

Metal binding4351Calcium 1
Metal binding4831Calcium 1
Metal binding4841Calcium 1; via carbonyl oxygen
Metal binding4851Calcium 2; via carbonyl oxygen
Metal binding4881Calcium 2; via carbonyl oxygen
Metal binding4901Calcium 2
Site2131Important for oligomerization
Site3431Important for oligomerization

Amino acid modifications

Glycosylation2041N-linked (GlcNAc...) Ref.12
Glycosylation3751N-linked (GlcNAc...) Potential
Glycosylation5481N-linked (GlcNAc...) Potential
Disulfide bond22 ↔ 75 Ref.12
Disulfide bond30 ↔ 72 Ref.12
Disulfide bond101 ↔ 175 Ref.12
Disulfide bond241 ↔ 407 Ref.12
Disulfide bond376 ↔ 392 Ref.12
Disulfide bond380 ↔ 394 Ref.12
Disulfide bond396 ↔ 406 Ref.12
Disulfide bond496 ↔ 509 Ref.12
Disulfide bond524 ↔ 533 Ref.12

Experimental info

Mutagenesis1911D → K or V: Loss of cytotoxicity. Ref.11
Mutagenesis1911D → S: Strongly decreased cytotoxicity. Ref.11
Mutagenesis2131R → E or L: Strongly decreased cytotoxicity. Ref.11
Mutagenesis3431E → R: Strongly decreased cytotoxicity. Ref.11
Sequence conflict31T → M in CAA31251. Ref.3
Sequence conflict1761R → P in AAA39909. Ref.4
Sequence conflict2291G → A in CAA31251. Ref.3
Sequence conflict2291G → A in CAA42731. Ref.5
Sequence conflict4351D → E in AAA39909. Ref.4
Sequence conflict543 – 5508GDPPGNRS → EILQETAC in AAA39909. Ref.4

Secondary structure

1 ........................................................................................... 554
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P10820 [UniParc].

Last modified April 1, 1990. Version 2.
Checksum: 9E5964CE9FE8A0D8

FASTA55462,081
        10         20         30         40         50         60 
MATCLFLLGL FLLLPRPVPA PCYTATRSEC KQKHKFVPGV WMAGEGMDVT TLRRSGSFPV 

        70         80         90        100        110        120 
NTQRFLRPDR TCTLCKNSLM RDATQRLPVA ITHWRPHSSH CQRNVAAAKV HSTEGVAREA 

       130        140        150        160        170        180 
AANINNDWRV GLDVNPRPEA NMRASVAGSH SKVANFAAEK TYQDQYNFNS DTVECRMYSF 

       190        200        210        220        230        240 
RLVQKPPLHL DFKKALRALP RNFNSSTEHA YHRLISSYGT HFITAVDLGG RISVLTALRT 

       250        260        270        280        290        300 
CQLTLNGLTA DEVGDCLNVE AQVSIGAQAS VSSEYKACEE KKKQHKMATS FHQTYRERHV 

       310        320        330        340        350        360 
EVLGGPLDST HDLLFGNQAT PEQFSTWTAS LPSNPGLVDY SLEPLHTLLE EQNPKREALR 

       370        380        390        400        410        420 
QAISHYIMSR ARWQNCSRPC RSGQHKSSHD SCQCECQDSK VTNQDCCPRQ RGLAHLVVSN 

       430        440        450        460        470        480 
FRAEHLWGDY TTATDAYLKV FFGGQEFRTG VVWNNNNPRW TDKMDFENVL LSTGGPLRVQ 

       490        500        510        520        530        540 
VWDADYGWDD DLLGSCDRSP HSGFHEVTCE LNHGRVKFSY HAKCLPHLTG GTCLEYAPQG 

       550 
LLGDPPGNRS GAVW

« Hide

References

[1]"The structure of the mouse lymphocyte pore-forming protein perforin."
Kwon B.S., Wakulchik M., Liu C.C., Persechini P.M., Trapani J.A., Haq A.K., Kim Y., Young J.D.-E.
Biochem. Biophys. Res. Commun. 158:1-10(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"Genomic organization of the mouse pore-forming protein (perforin) gene and localization to chromosome 10. Similarities to and differences from C9."
Trapani J.A., Kwon B.S., Kozak C.A., Chintamaneni C., Young J.D., Dupont B.
J. Exp. Med. 171:545-557(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]"Homology of perforin to the ninth component of complement (C9)."
Shinkai Y., Takio K., Okumura K.
Nature 334:525-527(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF N-TERMINUS, FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[4]"Cloning, analysis, and expression of murine perforin 1 cDNA, a component of cytolytic T-cell granules with homology to complement component C9."
Lowrey D.M., Aebischer Y., Olsen K., Lichtenheld M., Rupp F., Hengartner H., Podack E.R.
Proc. Natl. Acad. Sci. U.S.A. 86:247-251(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY.
[5]Mueller C., Lowin B., Tschopp J.
Submitted (NOV-1992) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Strain: C57BL/6.
[6]"Structure and function of the murine perforin promoter and upstream region. Reciprocal gene activation or silencing in perforin positive and negative cells."
Lichtenheld M.G., Podack E.R.
J. Immunol. 149:2619-2626(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-117.
Strain: BALB/c.
[7]"The primary structure of the lymphocyte pore-forming protein perforin: partial amino acid sequencing and determination of isoelectric point."
Persechini P.M., Young J.D.-E.
Biochem. Biophys. Res. Commun. 156:740-745(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 21-52; 76-96; 160-187; 255-278; 312-328; 400-420 AND 439-464.
[8]"Subcellular localization of perforin and serine esterase in lymphokine-activated killer cells and cytotoxic T cells by immunogold labeling."
Ojcius D.M., Zheng L.M., Sphicas E.C., Zychlinsky A., Young J.D.-E.
J. Immunol. 146:4427-4432(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[9]"Cytotoxicity mediated by T cells and natural killer cells is greatly impaired in perforin-deficient mice."
Kagi D., Ledermann B., Burki K., Seiler P., Odermatt B., Olsen K.J., Podack E.R., Zinkernagel R.M., Hengartner H.
Nature 369:31-37(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, DISRUPTION PHENOTYPE.
[10]"Immune function in mice lacking the perforin gene."
Walsh C.M., Matloubian M., Liu C.C., Ueda R., Kurahara C.G., Christensen J.L., Huang M.T., Young J.D., Ahmed R., Clark W.R.
Proc. Natl. Acad. Sci. U.S.A. 91:10854-10858(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, DISRUPTION PHENOTYPE.
[11]"The molecular basis for perforin oligomerization and transmembrane pore assembly."
Baran K., Dunstone M., Chia J., Ciccone A., Browne K.A., Clarke C.J.P., Lukoyanova N., Saibil H., Whisstock J.C., Voskoboinik I., Trapani J.A.
Immunity 30:684-695(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBUNIT, FUNCTION, SUBCELLULAR LOCATION, MUTAGENESIS OF ASP-191; ARG-213 AND GLU-343.
[12]"The structural basis for membrane binding and pore formation by lymphocyte perforin."
Law R.H., Lukoyanova N., Voskoboinik I., Caradoc-Davies T.T., Baran K., Dunstone M.A., D'Angelo M.E., Orlova E.V., Coulibaly F., Verschoor S., Browne K.A., Ciccone A., Kuiper M.J., Bird P.I., Trapani J.A., Saibil H.R., Whisstock J.C.
Nature 468:447-451(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.75 ANGSTROMS) OF 21-554 OF MUTANT GLU-213 IN COMPLEX WITH CALCIUM, ELECTRON MICROSCOPY OF PORE COMPLEX, FUNCTION, SUBCELLULAR LOCATION, SUBUNIT, GLYCOSYLATION AT ASN-204, DISULFIDE BONDS, CALCIUM-BINDING.
+Additional computationally mapped references.

Web resources

Protein Spotlight

Our hollow architecture - Issue 126 of February 2011

Cross-references

Sequence databases

EMBL
GenBank
DDBJ		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.
IPIIPI00308993.
PIRA31300. JL0146.
RefSeqNP_035203.3. NM_011073.3.
UniGeneMm.240313.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3NSJX-ray2.75A21-554[»]
ProteinModelPortalP10820.
SMRP10820. Positions 21-551.
ModBaseSearch...

Protein-protein interaction databases

DIPDIP-59218N.

Proteomic databases

PaxDbP10820.
PRIDEP10820.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000035419; ENSMUSP00000041483; ENSMUSG00000037202.
GeneID18646.
KEGGmmu:18646.

Organism-specific databases

CTD5551.
MGIMGI:97551. Prf1.

Phylogenomic databases

eggNOGNOG39137.
GeneTreeENSGT00530000063725.
HOGENOMHOG000236309.
HOVERGENHBG008168.
InParanoidP10820.
KOK07818.
OMASNYGTHF.
OrthoDBEOG42NJ0B.

Gene expression databases

ArrayExpressP10820.
BgeeP10820.
CleanExMM_PRF1.
GenevestigatorP10820.
GermOnlineENSMUSG00000037202. Mus musculus.

Family and domain databases

InterProIPR000008. C2_Ca-dep.
IPR008973. C2_Ca/lipid-bd_dom_CaLB.
IPR018029. C2_membr_targeting.
IPR020864. MACPF.
IPR020863. MACPF_CS.
[Graphical view]
PfamPF00168. C2. 1 hit.
PF01823. MACPF. 1 hit.
[Graphical view]
SMARTSM00239. C2. 1 hit.
SM00457. MACPF. 1 hit.
[Graphical view]
SUPFAMSSF49562. C2_CaLB. 1 hit.
PROSITEPS50004. C2. 1 hit.
PS00022. EGF_1. False negative.
PS01186. EGF_2. False negative.
PS50026. EGF_3. False negative.
PS00279. MACPF_1. 1 hit.
PS51412. MACPF_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP10820.
NextBio294644.
SOURCESearch...

Entry information

Entry namePERF_MOUSE
AccessionPrimary (citable) accession number: P10820
Entry history
Integrated into UniProtKB/Swiss-Prot: July 1, 1989
Last sequence update: April 1, 1990
Last modified: April 3, 2013
This is version 129 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

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

to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·Documents