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P10820

- PERF_MOUSE

UniProt

P10820 - PERF_MOUSE

Protein

Perforin-1

Gene

Prf1

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 139 (01 Oct 2014)
      Sequence version 2 (01 Apr 1990)
      Previous versions | rss
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    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)LengthDescriptionGraphical viewFeature identifierActions
    Sitei213 – 2131Important for oligomerization
    Sitei343 – 3431Important for oligomerization
    Metal bindingi435 – 4351Calcium 11 Publication
    Metal bindingi483 – 4831Calcium 11 Publication
    Metal bindingi484 – 4841Calcium 1; via carbonyl oxygen1 Publication
    Metal bindingi485 – 4851Calcium 2; via carbonyl oxygen1 Publication
    Metal bindingi488 – 4881Calcium 2; via carbonyl oxygen1 Publication
    Metal bindingi490 – 4901Calcium 21 Publication

    GO - Molecular functioni

    1. calcium ion binding Source: UniProtKB
    2. wide pore channel activity Source: UniProtKB

    GO - Biological processi

    1. cytolysis Source: UniProtKB
    2. defense response to tumor cell Source: UniProtKB
    3. defense response to virus Source: UniProtKB
    4. immune response to tumor cell Source: UniProtKB
    5. protein homooligomerization Source: UniProtKB
    6. transmembrane transport Source: GOC

    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
    ProteomesiUP000000589: 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

    1. cytolytic granule Source: UniProtKB
    2. cytoplasmic membrane-bounded vesicle Source: MGI
    3. endosome lumen Source: UniProtKB-SubCell
    4. extracellular region Source: UniProtKB-SubCell
    5. integral component of membrane Source: UniProtKB
    6. plasma membrane Source: UniProtKB-SubCell

    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)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi191 – 1911D → K or V: Loss of cytotoxicity. 1 Publication
    Mutagenesisi191 – 1911D → S: Strongly decreased cytotoxicity. 1 Publication
    Mutagenesisi213 – 2131R → E or L: Strongly decreased cytotoxicity. 1 Publication
    Mutagenesisi343 – 3431E → R: Strongly decreased cytotoxicity. 1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 20202 PublicationsAdd
    BLAST
    Chaini21 – 554534Perforin-1PRO_0000023610Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Disulfide bondi22 ↔ 751 Publication
    Disulfide bondi30 ↔ 721 Publication
    Disulfide bondi101 ↔ 1751 Publication
    Glycosylationi204 – 2041N-linked (GlcNAc...)1 Publication
    Disulfide bondi241 ↔ 4071 Publication
    Glycosylationi375 – 3751N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi376 ↔ 3921 Publication
    Disulfide bondi380 ↔ 3941 Publication
    Disulfide bondi396 ↔ 4061 Publication
    Disulfide bondi496 ↔ 5091 Publication
    Disulfide bondi524 ↔ 5331 Publication
    Glycosylationi548 – 5481N-linked (GlcNAc...)Sequence Analysis

    Post-translational modificationi

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

    Keywords - PTMi

    Disulfide bond, Glycoprotein

    Proteomic databases

    PaxDbiP10820.
    PRIDEiP10820.

    Expressioni

    Tissue specificityi

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

    Gene expression databases

    ArrayExpressiP10820.
    BgeeiP10820.
    CleanExiMM_PRF1.
    GenevestigatoriP10820.

    Interactioni

    Subunit structurei

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

    Protein-protein interaction databases

    BioGridi202128. 1 interaction.
    DIPiDIP-59218N.
    IntActiP10820. 1 interaction.
    MINTiMINT-4107132.

    Structurei

    Secondary structure

    1
    554
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi22 – 254
    Helixi27 – 315
    Helixi40 – 423
    Turni49 – 513
    Beta strandi72 – 765
    Turni78 – 825
    Beta strandi84 – 874
    Beta strandi91 – 966
    Beta strandi106 – 1105
    Helixi113 – 1219
    Turni128 – 1314
    Turni140 – 1434
    Turni147 – 1504
    Helixi152 – 16312
    Beta strandi166 – 18217
    Helixi190 – 1978
    Helixi208 – 21811
    Beta strandi220 – 23920
    Helixi240 – 2456
    Helixi250 – 26415
    Helixi273 – 28412
    Helixi291 – 2944
    Beta strandi298 – 3058
    Helixi307 – 3093
    Beta strandi313 – 3153
    Helixi321 – 33010
    Turni331 – 3333
    Beta strandi336 – 3449
    Helixi345 – 3484
    Helixi355 – 36915
    Beta strandi384 – 3863
    Beta strandi394 – 3974
    Turni399 – 4013
    Helixi404 – 4063
    Beta strandi408 – 4103
    Beta strandi413 – 42513
    Beta strandi436 – 4427
    Beta strandi445 – 4484
    Beta strandi464 – 4707
    Turni471 – 4733
    Beta strandi477 – 4837
    Beta strandi486 – 4883
    Beta strandi491 – 4988
    Beta strandi502 – 5109
    Beta strandi512 – 52413
    Beta strandi528 – 5303
    Beta strandi541 – 5433

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    3NSJX-ray2.75A21-554[»]
    ProteinModelPortaliP10820.
    SMRiP10820. Positions 21-551.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP10820.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini26 – 374349MACPFPROSITE-ProRule annotationAdd
    BLAST
    Domaini375 – 40733EGF-likeAdd
    BLAST
    Domaini416 – 49782C2PROSITE-ProRule annotationAdd
    BLAST

    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

    eggNOGiNOG39137.
    GeneTreeiENSGT00530000063725.
    HOGENOMiHOG000236309.
    HOVERGENiHBG008168.
    InParanoidiP10820.
    KOiK07818.
    OMAiNYGTHFI.
    OrthoDBiEOG7SJD49.
    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

    MATCLFLLGL FLLLPRPVPA PCYTATRSEC KQKHKFVPGV WMAGEGMDVT    50
    TLRRSGSFPV NTQRFLRPDR TCTLCKNSLM RDATQRLPVA ITHWRPHSSH 100
    CQRNVAAAKV HSTEGVAREA AANINNDWRV GLDVNPRPEA NMRASVAGSH 150
    SKVANFAAEK TYQDQYNFNS DTVECRMYSF RLVQKPPLHL DFKKALRALP 200
    RNFNSSTEHA YHRLISSYGT HFITAVDLGG RISVLTALRT CQLTLNGLTA 250
    DEVGDCLNVE AQVSIGAQAS VSSEYKACEE KKKQHKMATS FHQTYRERHV 300
    EVLGGPLDST HDLLFGNQAT PEQFSTWTAS LPSNPGLVDY SLEPLHTLLE 350
    EQNPKREALR QAISHYIMSR ARWQNCSRPC RSGQHKSSHD SCQCECQDSK 400
    VTNQDCCPRQ RGLAHLVVSN FRAEHLWGDY TTATDAYLKV FFGGQEFRTG 450
    VVWNNNNPRW TDKMDFENVL LSTGGPLRVQ VWDADYGWDD DLLGSCDRSP 500
    HSGFHEVTCE LNHGRVKFSY HAKCLPHLTG GTCLEYAPQG LLGDPPGNRS 550
    GAVW 554
    Length:554
    Mass (Da):62,081
    Last modified:April 1, 1990 - v2
    Checksum:i9E5964CE9FE8A0D8
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti3 – 31T → M in CAA31251. (PubMed:3261391)Curated
    Sequence conflicti176 – 1761R → P in AAA39909. (PubMed:2783486)Curated
    Sequence conflicti229 – 2291G → A in CAA31251. (PubMed:3261391)Curated
    Sequence conflicti229 – 2291G → A in CAA42731. 1 PublicationCurated
    Sequence conflicti435 – 4351D → E in AAA39909. (PubMed:2783486)Curated
    Sequence conflicti543 – 5508GDPPGNRS → EILQETAC in AAA39909. (PubMed:2783486)Curated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    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_006513370.1.
    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:
    EMBL
    GenBank
    DDBJ
    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_006513370.1.
    UniGenei Mm.240313.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    3NSJ X-ray 2.75 A 21-554 [» ]
    ProteinModelPortali P10820.
    SMRi P10820. Positions 21-551.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 202128. 1 interaction.
    DIPi DIP-59218N.
    IntActi P10820. 1 interaction.
    MINTi MINT-4107132.

    Proteomic databases

    PaxDbi P10820.
    PRIDEi P10820.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000035419 ; ENSMUSP00000041483 ; ENSMUSG00000037202 .
    GeneIDi 18646.
    KEGGi mmu:18646.
    UCSCi uc007ffv.2. mouse.

    Organism-specific databases

    CTDi 5551.
    MGIi MGI:97551. Prf1.

    Phylogenomic databases

    eggNOGi NOG39137.
    GeneTreei ENSGT00530000063725.
    HOGENOMi HOG000236309.
    HOVERGENi HBG008168.
    InParanoidi P10820.
    KOi K07818.
    OMAi NYGTHFI.
    OrthoDBi EOG7SJD49.
    PhylomeDBi P10820.
    TreeFami TF330498.

    Miscellaneous databases

    EvolutionaryTracei P10820.
    NextBioi 294644.
    PROi P10820.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P10820.
    Bgeei P10820.
    CleanExi MM_PRF1.
    Genevestigatori P10820.

    Family and domain databases

    Gene3Di 2.60.40.150. 1 hit.
    InterProi IPR000008. C2_dom.
    IPR020864. MACPF.
    IPR020863. MACPF_CS.
    [Graphical view ]
    Pfami PF00168. C2. 1 hit.
    PF01823. MACPF. 1 hit.
    [Graphical view ]
    SMARTi SM00239. C2. 1 hit.
    SM00457. MACPF. 1 hit.
    [Graphical view ]
    SUPFAMi SSF49562. SSF49562. 1 hit.
    PROSITEi PS50004. C2. 1 hit.
    PS00279. MACPF_1. 1 hit.
    PS51412. MACPF_2. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. 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. Cited for: FUNCTION, DISRUPTION PHENOTYPE.
    11. Cited for: SUBUNIT, FUNCTION, SUBCELLULAR LOCATION, MUTAGENESIS OF ASP-191; ARG-213 AND GLU-343.
    12. 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.

    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: October 1, 2014
    This is version 139 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

    External Data

    Dasty 3