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P70677

- CASP3_MOUSE

UniProt

P70677 - CASP3_MOUSE

Protein

Caspase-3

Gene

Casp3

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 1 (01 Feb 1997)
      Previous versions | rss
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    Functioni

    Involved in the activation cascade of caspases responsible for apoptosis execution. At the onset of apoptosis it proteolytically cleaves poly(ADP-ribose) polymerase (PARP) at a '216-Asp-|-Gly-217' bond. Cleaves and activates sterol regulatory element binding proteins (SREBPs) between the basic helix-loop-helix leucine zipper domain and the membrane attachment domain. Cleaves and activates caspase-6, -7 and -9. Triggers cell adhesion in sympathetic neurons through RET cleavage By similarity. Cleaves IL-1 beta between an Asp and an Ala, releasing the mature cytokine which is involved in a variety of inflammatory processes.By similarity

    Catalytic activityi

    Strict requirement for an Asp residue at positions P1 and P4. It has a preferred cleavage sequence of Asp-Xaa-Xaa-Asp-|- with a hydrophobic amino-acid residue at P2 and a hydrophilic amino-acid residue at P3, although Val or Ala are also accepted at this position.

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Active sitei121 – 1211By similarity
    Active sitei163 – 1631By similarity

    GO - Molecular functioni

    1. aspartic-type endopeptidase activity Source: MGI
    2. cyclin-dependent protein serine/threonine kinase inhibitor activity Source: MGI
    3. cysteine-type endopeptidase activity Source: UniProtKB
    4. cysteine-type endopeptidase activity involved in apoptotic process Source: MGI
    5. cysteine-type endopeptidase activity involved in execution phase of apoptosis Source: MGI
    6. cysteine-type peptidase activity Source: MGI
    7. peptidase activity Source: MGI
    8. protein binding Source: IntAct
    9. serine-type endopeptidase activity Source: Reactome

    GO - Biological processi

    1. apoptotic process Source: MGI
    2. B cell homeostasis Source: MGI
    3. cell fate commitment Source: MGI
    4. cellular response to DNA damage stimulus Source: MGI
    5. cellular response to organic substance Source: MGI
    6. erythrocyte differentiation Source: RefGenome
    7. execution phase of apoptosis Source: MGI
    8. extrinsic apoptotic signaling pathway in absence of ligand Source: MGI
    9. extrinsic apoptotic signaling pathway via death domain receptors Source: MGI
    10. glial cell apoptotic process Source: MGI
    11. heart development Source: MGI
    12. intrinsic apoptotic signaling pathway in response to oxidative stress Source: MGI
    13. keratinocyte differentiation Source: MGI
    14. negative regulation of activated T cell proliferation Source: MGI
    15. negative regulation of apoptotic process Source: Ensembl
    16. negative regulation of B cell proliferation Source: MGI
    17. negative regulation of cell cycle Source: MGI
    18. negative regulation of cyclin-dependent protein serine/threonine kinase activity Source: MGI
    19. neuron apoptotic process Source: MGI
    20. neuron differentiation Source: RefGenome
    21. positive regulation of apoptotic process Source: MGI
    22. positive regulation of neuron apoptotic process Source: MGI
    23. protein processing Source: MGI
    24. regulation of apoptotic DNA fragmentation Source: MGI
    25. release of cytochrome c from mitochondria Source: MGI
    26. response to UV Source: MGI
    27. response to wounding Source: MGI
    28. sensory perception of sound Source: MGI
    29. T cell homeostasis Source: MGI

    Keywords - Molecular functioni

    Hydrolase, Protease, Thiol protease

    Keywords - Biological processi

    Apoptosis

    Enzyme and pathway databases

    BRENDAi3.4.22.56. 3474.
    ReactomeiREACT_196537. Signaling by Hippo.
    REACT_199052. Degradation of the extracellular matrix.
    REACT_205002. Activation of DNA fragmentation factor.
    REACT_210562. Caspase-mediated cleavage of cytoskeletal proteins.
    REACT_210754. NADE modulates death signalling.
    REACT_211941. Stimulation of the cell death response by PAK-2p34.
    REACT_212869. Apoptotic cleavage of cell adhesion proteins.
    REACT_224460. Apoptotic cleavage of cellular proteins.
    REACT_225157. Activation of caspases through apoptosome-mediated cleavage.

    Protein family/group databases

    MEROPSiC14.003.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Caspase-3 (EC:3.4.22.56)
    Short name:
    CASP-3
    Alternative name(s):
    Apopain
    Cysteine protease CPP32
    Short name:
    CPP-32
    LICE
    Protein Yama
    SREBP cleavage activity 1
    Short name:
    SCA-1
    Cleaved into the following 2 chains:
    Gene namesi
    Name:Casp3
    Synonyms:Cpp32
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 8

    Organism-specific databases

    MGIiMGI:107739. Casp3.

    Subcellular locationi

    GO - Cellular componenti

    1. cytoplasm Source: MGI
    2. cytosol Source: Reactome
    3. mitochondrion Source: Ensembl
    4. nucleus Source: Ensembl

    Keywords - Cellular componenti

    Cytoplasm

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Propeptidei1 – 99By similarityPRO_0000004573
    Propeptidei10 – 2819By similarityPRO_0000004574Add
    BLAST
    Chaini29 – 175147Caspase-3 subunit p17PRO_0000004575Add
    BLAST
    Chaini176 – 277102Caspase-3 subunit p12PRO_0000004576Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei1 – 11N-acetylmethionineBy similarity
    Modified residuei11 – 111N6-acetyllysine1 Publication
    Modified residuei26 – 261Phosphoserine2 Publications
    Modified residuei163 – 1631S-nitrosocysteine; in inhibited formBy similarity

    Post-translational modificationi

    Cleavage by granzyme B, caspase-6, caspase-8 and caspase-10 generates the two active subunits. Additional processing of the propeptides is likely due to the autocatalytic activity of the activated protease. Active heterodimers between the small subunit of caspase-7 protease and the large subunit of caspase-3 also occur and vice versa By similarity.By similarity
    S-nitrosylated on its catalytic site cysteine in unstimulated human cell lines and denitrosylated upon activation of the Fas apoptotic pathway, associated with an increase in intracellular caspase activity. Fas therefore activates caspase-3 not only by inducing the cleavage of the caspase zymogen to its active subunits, but also by stimulating the denitrosylation of its active site thiol By similarity.By similarity

    Keywords - PTMi

    Acetylation, Phosphoprotein, S-nitrosylation, Zymogen

    Proteomic databases

    MaxQBiP70677.
    PaxDbiP70677.
    PRIDEiP70677.

    PTM databases

    PhosphoSiteiP70677.

    Expressioni

    Tissue specificityi

    Highest expression in spleen, lung, liver, kidney and heart. Lower expression in brain, skeletal muscle and testis.

    Gene expression databases

    ArrayExpressiP70677.
    BgeeiP70677.
    CleanExiMM_CASP3.
    GenevestigatoriP70677.

    Interactioni

    Subunit structurei

    Heterotetramer that consists of two anti-parallel arranged heterodimers, each one formed by a 17 kDa (p17) and a 12 kDa (p12) subunit. Interacts with BIRC6/bruce.By similarity

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    HttP428592EBI-1790419,EBI-5327353
    Parp1P111033EBI-1790419,EBI-642213
    Rps18P622705EBI-1790419,EBI-352460
    THAP11Q96EK42EBI-1790419,EBI-1790529From a different organism.

    Protein-protein interaction databases

    BioGridi198497. 14 interactions.
    DIPiDIP-44076N.
    IntActiP70677. 9 interactions.
    MINTiMINT-4050331.

    Structurei

    3D structure databases

    ProteinModelPortaliP70677.
    SMRiP70677. Positions 29-277.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the peptidase C14A family.Curated

    Phylogenomic databases

    eggNOGiNOG279444.
    GeneTreeiENSGT00740000114863.
    HOGENOMiHOG000231878.
    HOVERGENiHBG050802.
    InParanoidiP70677.
    KOiK02187.
    OMAiSSFVCVL.
    OrthoDBiEOG7TTQ7K.
    PhylomeDBiP70677.
    TreeFamiTF102023.

    Family and domain databases

    Gene3Di3.40.50.1460. 1 hit.
    InterProiIPR029030. Caspase-like_dom.
    IPR015470. Caspase_3.
    IPR011600. Pept_C14_caspase.
    IPR001309. Pept_C14_ICE_p20.
    IPR016129. Pept_C14_ICE_p20_AS.
    IPR002138. Pept_C14_p10.
    IPR015917. Pept_C14A_p45_core.
    [Graphical view]
    PANTHERiPTHR10454:SF30. PTHR10454:SF30. 1 hit.
    PfamiPF00656. Peptidase_C14. 1 hit.
    [Graphical view]
    PRINTSiPR00376. IL1BCENZYME.
    SMARTiSM00115. CASc. 1 hit.
    [Graphical view]
    PROSITEiPS01122. CASPASE_CYS. 1 hit.
    PS01121. CASPASE_HIS. 1 hit.
    PS50207. CASPASE_P10. 1 hit.
    PS50208. CASPASE_P20. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

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

    P70677-1 [UniParc]FASTAAdd to Basket

    « Hide

    MENNKTSVDS KSINNFEVKT IHGSKSVDSG IYLDSSYKMD YPEMGICIII    50
    NNKNFHKSTG MSSRSGTDVD AANLRETFMG LKYQVRNKND LTREDILELM 100
    DSVSKEDHSK RSSFVCVILS HGDEGVIYGT NGPVELKKLT SFFRGDYCRS 150
    LTGKPKLFII QACRGTELDC GIETDSGTDE EMACQKIPVE ADFLYAYSTA 200
    PGYYSWRNSK DGSWFIQSLC SMLKLYAHKL EFMHILTRVN RKVATEFESF 250
    SLDSTFHAKK QIPCIVSMLT KELYFYH 277
    Length:277
    Mass (Da):31,475
    Last modified:February 1, 1997 - v1
    Checksum:iCE91598F74826605
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti63 – 653SRS → ARN in AAD09504. 1 PublicationCurated
    Sequence conflicti231 – 2311E → Q in AAD09504. 1 PublicationCurated
    Sequence conflicti262 – 2621I → F in AAD09504. 1 PublicationCurated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U54803, U54802 Genomic DNA. Translation: AAC52768.1.
    U49929 mRNA. Translation: AAC52764.1.
    D86352 mRNA. Translation: BAA21727.1.
    Y13086 mRNA. Translation: CAA73528.1.
    U19522 mRNA. Translation: AAC53196.1.
    BC038825 mRNA. Translation: AAH38825.2.
    U63720 mRNA. Translation: AAD09504.1.
    CCDSiCCDS22294.1.
    PIRiJC5410.
    RefSeqiNP_001271338.1. NM_001284409.1.
    NP_033940.1. NM_009810.3.
    UniGeneiMm.34405.

    Genome annotation databases

    EnsembliENSMUST00000093517; ENSMUSP00000091238; ENSMUSG00000031628.
    GeneIDi12367.
    KEGGimmu:12367.
    UCSCiuc009lql.1. mouse.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U54803 , U54802 Genomic DNA. Translation: AAC52768.1 .
    U49929 mRNA. Translation: AAC52764.1 .
    D86352 mRNA. Translation: BAA21727.1 .
    Y13086 mRNA. Translation: CAA73528.1 .
    U19522 mRNA. Translation: AAC53196.1 .
    BC038825 mRNA. Translation: AAH38825.2 .
    U63720 mRNA. Translation: AAD09504.1 .
    CCDSi CCDS22294.1.
    PIRi JC5410.
    RefSeqi NP_001271338.1. NM_001284409.1.
    NP_033940.1. NM_009810.3.
    UniGenei Mm.34405.

    3D structure databases

    ProteinModelPortali P70677.
    SMRi P70677. Positions 29-277.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 198497. 14 interactions.
    DIPi DIP-44076N.
    IntActi P70677. 9 interactions.
    MINTi MINT-4050331.

    Chemistry

    BindingDBi P70677.
    ChEMBLi CHEMBL5632.

    Protein family/group databases

    MEROPSi C14.003.

    PTM databases

    PhosphoSitei P70677.

    Proteomic databases

    MaxQBi P70677.
    PaxDbi P70677.
    PRIDEi P70677.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000093517 ; ENSMUSP00000091238 ; ENSMUSG00000031628 .
    GeneIDi 12367.
    KEGGi mmu:12367.
    UCSCi uc009lql.1. mouse.

    Organism-specific databases

    CTDi 836.
    MGIi MGI:107739. Casp3.

    Phylogenomic databases

    eggNOGi NOG279444.
    GeneTreei ENSGT00740000114863.
    HOGENOMi HOG000231878.
    HOVERGENi HBG050802.
    InParanoidi P70677.
    KOi K02187.
    OMAi SSFVCVL.
    OrthoDBi EOG7TTQ7K.
    PhylomeDBi P70677.
    TreeFami TF102023.

    Enzyme and pathway databases

    BRENDAi 3.4.22.56. 3474.
    Reactomei REACT_196537. Signaling by Hippo.
    REACT_199052. Degradation of the extracellular matrix.
    REACT_205002. Activation of DNA fragmentation factor.
    REACT_210562. Caspase-mediated cleavage of cytoskeletal proteins.
    REACT_210754. NADE modulates death signalling.
    REACT_211941. Stimulation of the cell death response by PAK-2p34.
    REACT_212869. Apoptotic cleavage of cell adhesion proteins.
    REACT_224460. Apoptotic cleavage of cellular proteins.
    REACT_225157. Activation of caspases through apoptosome-mediated cleavage.

    Miscellaneous databases

    NextBioi 281052.
    PROi P70677.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P70677.
    Bgeei P70677.
    CleanExi MM_CASP3.
    Genevestigatori P70677.

    Family and domain databases

    Gene3Di 3.40.50.1460. 1 hit.
    InterProi IPR029030. Caspase-like_dom.
    IPR015470. Caspase_3.
    IPR011600. Pept_C14_caspase.
    IPR001309. Pept_C14_ICE_p20.
    IPR016129. Pept_C14_ICE_p20_AS.
    IPR002138. Pept_C14_p10.
    IPR015917. Pept_C14A_p45_core.
    [Graphical view ]
    PANTHERi PTHR10454:SF30. PTHR10454:SF30. 1 hit.
    Pfami PF00656. Peptidase_C14. 1 hit.
    [Graphical view ]
    PRINTSi PR00376. IL1BCENZYME.
    SMARTi SM00115. CASc. 1 hit.
    [Graphical view ]
    PROSITEi PS01122. CASPASE_CYS. 1 hit.
    PS01121. CASPASE_HIS. 1 hit.
    PS50207. CASPASE_P10. 1 hit.
    PS50208. CASPASE_P20. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Molecular characterization of mouse and rat CPP32 beta gene encoding a cysteine protease resembling interleukin-1 beta converting enzyme and CED-3."
      Juan T.S.-C., McNiece I.K., Jenkins N.A., Gilbert D.J., Copeland N.G., Fletcher F.A.
      Oncogene 13:749-755(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
    2. "Specific expression of CPP32 in sensory neurons of mouse embryos and activation of CPP32 in the apoptosis induced by a withdrawal of NGF."
      Mukasa T., Urase K., Momoi M.Y., Kimura I., Momoi T.
      Biochem. Biophys. Res. Commun. 231:770-774(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    3. Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Strain: C3H/An.
    4. Fernandes-Alnemri T., Litwack G., Alnemri E.S.
      Submitted (MAY-1997) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Tissue: Brain.
    5. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Strain: FVB/N.
      Tissue: Mammary gland.
    6. "Multiple pathways of apoptosis converging on the CPP32 protease."
      Denis F., Alam A., Cohen L., Hartgers F., Braun M., Martinez O., Fortin J.-P., Sekaly R.-P.
      Submitted (JUL-1996) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 58-277.
    7. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-26, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Embryonic brain.
    8. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-26, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Liver.
    9. "SIRT5-mediated lysine desuccinylation impacts diverse metabolic pathways."
      Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y., Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.
      Mol. Cell 50:919-930(2013) [PubMed] [Europe PMC] [Abstract]
      Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-11, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Embryonic fibroblast.

    Entry informationi

    Entry nameiCASP3_MOUSE
    AccessioniPrimary (citable) accession number: P70677
    Secondary accession number(s): O08668, Q8CHV5, Q9QWI4
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: November 1, 1997
    Last sequence update: February 1, 1997
    Last modified: October 1, 2014
    This is version 139 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. Peptidase families
      Classification of peptidase families and list of entries
    3. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3