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Protein

Caspase-3

Gene

Casp3

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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. 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: MGI
  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: MGI
  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: GO_Central
  21. positive regulation of apoptotic process Source: MGI
  22. positive regulation of neuron apoptotic process Source: MGI
  23. protein processing Source: MGI
  24. proteolysis Source: MGI
  25. regulation of apoptotic DNA fragmentation Source: MGI
  26. release of cytochrome c from mitochondria Source: MGI
  27. response to UV Source: MGI
  28. response to wounding Source: MGI
  29. sensory perception of sound Source: MGI
  30. T cell homeostasis Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protease, Thiol protease

Keywords - Biological processi

Apoptosis

Enzyme and pathway databases

BRENDAi3.4.22.56. 3474.
ReactomeiREACT_272089. Activation of caspases through apoptosome-mediated cleavage.
REACT_275864. Degradation of the extracellular matrix.
REACT_277640. Apoptotic cleavage of cellular proteins.
REACT_291081. Caspase-mediated cleavage of cytoskeletal proteins.
REACT_299111. Activation of DNA fragmentation factor.
REACT_301726. Signaling by Hippo.
REACT_311974. SMAC-mediated dissociation of IAP:caspase complexes.
REACT_313501. Role of DCC in regulating apoptosis.
REACT_324521. NADE modulates death signalling.
REACT_327578. Stimulation of the cell death response by PAK-2p34.
REACT_343176. Apoptotic cleavage of cell adhesion proteins.
REACT_350996. SMAC binds to IAPs.

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 Componenti: Chromosome 8

Organism-specific databases

MGIiMGI:107739. Casp3.

Subcellular locationi

GO - Cellular componenti

  1. cytoplasm Source: MGI
  2. cytosol Source: MGI
  3. nucleus Source: MGI
Complete GO annotation...

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

BgeeiP70677.
CleanExiMM_CASP3.
ExpressionAtlasiP70677. baseline and differential.
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. 15 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.
GeneTreeiENSGT00760000118912.
HOGENOMiHOG000231878.
HOVERGENiHBG050802.
InParanoidiP70677.
KOiK02187.
OMAiYASEYNM.
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

        10         20         30         40         50
MENNKTSVDS KSINNFEVKT IHGSKSVDSG IYLDSSYKMD YPEMGICIII
60 70 80 90 100
NNKNFHKSTG MSSRSGTDVD AANLRETFMG LKYQVRNKND LTREDILELM
110 120 130 140 150
DSVSKEDHSK RSSFVCVILS HGDEGVIYGT NGPVELKKLT SFFRGDYCRS
160 170 180 190 200
LTGKPKLFII QACRGTELDC GIETDSGTDE EMACQKIPVE ADFLYAYSTA
210 220 230 240 250
PGYYSWRNSK DGSWFIQSLC SMLKLYAHKL EFMHILTRVN RKVATEFESF
260 270
SLDSTFHAKK QIPCIVSMLT KELYFYH
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 (Ref. 6) Curated
Sequence conflicti231 – 2311E → Q in AAD09504 (Ref. 6) Curated
Sequence conflicti262 – 2621I → F in AAD09504 (Ref. 6) Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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:
EMBLi
GenBanki
DDBJi
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.

3D structure databases

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

Protein-protein interaction databases

BioGridi198497. 15 interactions.
DIPiDIP-44076N.
IntActiP70677. 9 interactions.
MINTiMINT-4050331.

Chemistry

BindingDBiP70677.
ChEMBLiCHEMBL5632.

Protein family/group databases

MEROPSiC14.003.

PTM databases

PhosphoSiteiP70677.

Proteomic databases

MaxQBiP70677.
PaxDbiP70677.
PRIDEiP70677.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi836.
MGIiMGI:107739. Casp3.

Phylogenomic databases

eggNOGiNOG279444.
GeneTreeiENSGT00760000118912.
HOGENOMiHOG000231878.
HOVERGENiHBG050802.
InParanoidiP70677.
KOiK02187.
OMAiYASEYNM.
OrthoDBiEOG7TTQ7K.
PhylomeDBiP70677.
TreeFamiTF102023.

Enzyme and pathway databases

BRENDAi3.4.22.56. 3474.
ReactomeiREACT_272089. Activation of caspases through apoptosome-mediated cleavage.
REACT_275864. Degradation of the extracellular matrix.
REACT_277640. Apoptotic cleavage of cellular proteins.
REACT_291081. Caspase-mediated cleavage of cytoskeletal proteins.
REACT_299111. Activation of DNA fragmentation factor.
REACT_301726. Signaling by Hippo.
REACT_311974. SMAC-mediated dissociation of IAP:caspase complexes.
REACT_313501. Role of DCC in regulating apoptosis.
REACT_324521. NADE modulates death signalling.
REACT_327578. Stimulation of the cell death response by PAK-2p34.
REACT_343176. Apoptotic cleavage of cell adhesion proteins.
REACT_350996. SMAC binds to IAPs.

Miscellaneous databases

ChiTaRSiCasp3. mouse.
NextBioi281052.
PROiP70677.
SOURCEiSearch...

Gene expression databases

BgeeiP70677.
CleanExiMM_CASP3.
ExpressionAtlasiP70677. baseline and differential.
GenevestigatoriP70677.

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]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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: April 1, 2015
This is version 145 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

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 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.