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P70677 (CASP3_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 137. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Caspase-3

Short name=CASP-3
EC=3.4.22.56
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:

  1. Caspase-3 subunit p17
  2. Caspase-3 subunit p12
Gene names
Name:Casp3
Synonyms:Cpp32
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length277 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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.

Catalytic activity

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.

Subunit structure

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

Subcellular location

Cytoplasm.

Tissue specificity

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

Post-translational modification

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.

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.

Sequence similarities

Belongs to the peptidase C14A family.

Ontologies

Keywords
   Biological processApoptosis
   Cellular componentCytoplasm
   Molecular functionHydrolase
Protease
Thiol protease
   PTMAcetylation
Phosphoprotein
S-nitrosylation
Zymogen
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processB cell homeostasis

Inferred from mutant phenotype PubMed 12970760. Source: MGI

T cell homeostasis

Inferred from mutant phenotype PubMed 12970760. Source: MGI

apoptotic process

Inferred from direct assay PubMed 12847083PubMed 17901126. Source: MGI

cell fate commitment

Inferred from mutant phenotype PubMed 15068794. Source: MGI

cellular response to DNA damage stimulus

Inferred from direct assay PubMed 11092819. Source: MGI

cellular response to organic substance

Inferred from direct assay PubMed 12606450. Source: MGI

erythrocyte differentiation

Inferred from Biological aspect of Ancestor. Source: RefGenome

execution phase of apoptosis

Inferred from direct assay PubMed 12124386PubMed 15456877. Source: MGI

extrinsic apoptotic signaling pathway in absence of ligand

Inferred from direct assay PubMed 12124386. Source: MGI

extrinsic apoptotic signaling pathway via death domain receptors

Inferred from mutant phenotype PubMed 12970760. Source: MGI

glial cell apoptotic process

Inferred from mutant phenotype PubMed 11549719. Source: MGI

heart development

Inferred from genetic interaction PubMed 16469926. Source: MGI

intrinsic apoptotic signaling pathway in response to oxidative stress

Inferred from direct assay PubMed 12954857. Source: MGI

keratinocyte differentiation

Inferred from mutant phenotype PubMed 15068794. Source: MGI

negative regulation of B cell proliferation

Inferred from mutant phenotype PubMed 12970760. Source: MGI

negative regulation of activated T cell proliferation

Inferred from mutant phenotype PubMed 12970760. Source: MGI

negative regulation of apoptotic process

Inferred from electronic annotation. Source: Ensembl

negative regulation of cell cycle

Inferred from mutant phenotype PubMed 12970760. Source: MGI

negative regulation of cyclin-dependent protein serine/threonine kinase activity

Inferred from mutant phenotype PubMed 12970760. Source: MGI

neuron apoptotic process

Inferred from direct assay PubMed 12427836. Source: MGI

neuron differentiation

Inferred from Biological aspect of Ancestor. Source: RefGenome

positive regulation of apoptotic process

Inferred from mutant phenotype PubMed 9512515. Source: MGI

positive regulation of neuron apoptotic process

Inferred from direct assay PubMed 15231831. Source: MGI

protein processing

Inferred from direct assay PubMed 15231831. Source: MGI

regulation of apoptotic DNA fragmentation

Inferred from mutant phenotype PubMed 16469926. Source: MGI

release of cytochrome c from mitochondria

Inferred from genetic interaction PubMed 16469926. Source: MGI

response to UV

Inferred from direct assay PubMed 11092819. Source: MGI

response to wounding

Inferred from direct assay PubMed 14507967. Source: MGI

sensory perception of sound

Inferred from mutant phenotype PubMed 11374883. Source: MGI

   Cellular_componentcytoplasm

Inferred from direct assay PubMed 12477715PubMed 23861879. Source: MGI

cytosol

Traceable author statement. Source: Reactome

mitochondrion

Inferred from electronic annotation. Source: Ensembl

nucleus

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionaspartic-type endopeptidase activity

Inferred from direct assay PubMed 15231831PubMed 23727203. Source: MGI

cyclin-dependent protein serine/threonine kinase inhibitor activity

Inferred from mutant phenotype PubMed 12970760. Source: MGI

cysteine-type endopeptidase activity

Inferred from direct assay PubMed 19759058. Source: UniProtKB

cysteine-type endopeptidase activity involved in apoptotic process

Inferred from direct assay PubMed 16183742PubMed 24378336. Source: MGI

cysteine-type endopeptidase activity involved in execution phase of apoptosis

Inferred from direct assay PubMed 12124386. Source: MGI

cysteine-type peptidase activity

Inferred from direct assay PubMed 17544522. Source: MGI

peptidase activity

Inferred from direct assay PubMed 12427836PubMed 12954857PubMed 13679151PubMed 14561754. Source: MGI

protein binding

Inferred from physical interaction PubMed 17124493PubMed 18585351PubMed 19759058. Source: IntAct

serine-type endopeptidase activity

Traceable author statement. Source: Reactome

Complete GO annotation...

Binary interactions

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Propeptide1 – 99 By similarity
PRO_0000004573
Propeptide10 – 2819 By similarity
PRO_0000004574
Chain29 – 175147Caspase-3 subunit p17
PRO_0000004575
Chain176 – 277102Caspase-3 subunit p12
PRO_0000004576

Sites

Active site1211 By similarity
Active site1631 By similarity

Amino acid modifications

Modified residue11N-acetylmethionine By similarity
Modified residue111N6-acetyllysine Ref.9
Modified residue261Phosphoserine Ref.7 Ref.8
Modified residue1631S-nitrosocysteine; in inhibited form By similarity

Experimental info

Sequence conflict63 – 653SRS → ARN in AAD09504. Ref.6
Sequence conflict2311E → Q in AAD09504. Ref.6
Sequence conflict2621I → F in AAD09504. Ref.6

Sequences

Sequence LengthMass (Da)Tools
P70677 [UniParc].

Last modified February 1, 1997. Version 1.
Checksum: CE91598F74826605

FASTA27731,475
        10         20         30         40         50         60 
MENNKTSVDS KSINNFEVKT IHGSKSVDSG IYLDSSYKMD YPEMGICIII NNKNFHKSTG 

        70         80         90        100        110        120 
MSSRSGTDVD AANLRETFMG LKYQVRNKND LTREDILELM DSVSKEDHSK RSSFVCVILS 

       130        140        150        160        170        180 
HGDEGVIYGT NGPVELKKLT SFFRGDYCRS LTGKPKLFII QACRGTELDC GIETDSGTDE 

       190        200        210        220        230        240 
EMACQKIPVE ADFLYAYSTA PGYYSWRNSK DGSWFIQSLC SMLKLYAHKL EFMHILTRVN 

       250        260        270 
RKVATEFESF SLDSTFHAKK QIPCIVSMLT KELYFYH 

« Hide

References

« Hide 'large scale' references
[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]"Characterization of seven murine caspase family members."
van de Craen M., Vandenabeele P., Declercq W., van den Brande I., van Loo G., Molemans F., Schotte P., van Criekinge W., Beyaert R., Fiers W.
FEBS Lett. 403:61-69(1997) [PubMed] [Europe PMC] [Abstract]
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]"Phosphoproteomic analysis of the developing mouse brain."
Ballif B.A., Villen J., Beausoleil S.A., Schwartz D., Gygi S.P.
Mol. Cell. Proteomics 3:1093-1101(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-26, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Embryonic brain.
[8]"Large-scale phosphorylation analysis of mouse liver."
Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007) [PubMed] [Europe PMC] [Abstract]
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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS22294.1.
PIRJC5410.
RefSeqNP_001271338.1. NM_001284409.1.
NP_033940.1. NM_009810.3.
UniGeneMm.34405.

3D structure databases

ProteinModelPortalP70677.
SMRP70677. Positions 29-277.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid198497. 14 interactions.
DIPDIP-44076N.
IntActP70677. 9 interactions.
MINTMINT-4050331.

Chemistry

BindingDBP70677.
ChEMBLCHEMBL5632.

Protein family/group databases

MEROPSC14.003.

PTM databases

PhosphoSiteP70677.

Proteomic databases

MaxQBP70677.
PaxDbP70677.
PRIDEP70677.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000093517; ENSMUSP00000091238; ENSMUSG00000031628.
GeneID12367.
KEGGmmu:12367.
UCSCuc009lql.1. mouse.

Organism-specific databases

CTD836.
MGIMGI:107739. Casp3.

Phylogenomic databases

eggNOGNOG279444.
GeneTreeENSGT00740000114863.
HOGENOMHOG000231878.
HOVERGENHBG050802.
InParanoidP70677.
KOK02187.
OMASSFVCVL.
OrthoDBEOG7TTQ7K.
PhylomeDBP70677.
TreeFamTF102023.

Enzyme and pathway databases

BRENDA3.4.22.56. 3474.

Gene expression databases

ArrayExpressP70677.
BgeeP70677.
CleanExMM_CASP3.
GenevestigatorP70677.

Family and domain databases

Gene3D3.40.50.1460. 1 hit.
InterProIPR029030. 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]
PANTHERPTHR10454:SF30. PTHR10454:SF30. 1 hit.
PfamPF00656. Peptidase_C14. 1 hit.
[Graphical view]
PRINTSPR00376. IL1BCENZYME.
SMARTSM00115. CASc. 1 hit.
[Graphical view]
PROSITEPS01122. CASPASE_CYS. 1 hit.
PS01121. CASPASE_HIS. 1 hit.
PS50207. CASPASE_P10. 1 hit.
PS50208. CASPASE_P20. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio281052.
PROP70677.
SOURCESearch...

Entry information

Entry nameCASP3_MOUSE
AccessionPrimary (citable) accession number: P70677
Secondary accession number(s): O08668, Q8CHV5, Q9QWI4
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: February 1, 1997
Last modified: July 9, 2014
This is version 137 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot