Caspase-3 precursor - Mus musculus (Mouse)

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P70677 (CASP3_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified May 1, 2013. Version 124. History...

Clusters with 100%, 90%, 50% identity |

Documents (3) |

Third-party data

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Names·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents Customize order

Names and origin

Protein names

Recommended 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

Gene names

Name:	Casp3
Synonyms:	Cpp32

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	277 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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 process	Apoptosis
Cellular component	Cytoplasm
Molecular function	Hydrolase Protease Thiol protease
PTM	Phosphoprotein S-nitrosylation Zymogen
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	B cell homeostasis Inferred from mutant phenotype PubMed 12970760. Source: MGI T cell homeostasis Inferred from mutant phenotype PubMed 12970760. Source: MGI apoptotic DNA fragmentation Inferred from mutant phenotype PubMed 16469926. Source: MGI cell fate commitment Inferred from mutant phenotype PubMed 15068794. Source: MGI cellular response to organic substance Inferred from direct assay PubMed 12606450. Source: MGI extrinsic apoptotic signaling pathway via death domain receptors Inferred from mutant phenotype PubMed 12970760. Source: MGI heart development Inferred from genetic interaction PubMed 16469926. Source: MGI induction of apoptosis Inferred from direct assay PubMed 12944902 PubMed 14645204 PubMed 15456877 PubMed 15728238 PubMed 18590716. 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: Compara 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 nuclear fragmentation involved in apoptotic nuclear change Inferred from electronic annotation. Source: Compara positive regulation of neuron apoptotic process Inferred from direct assay PubMed 15231831. Source: MGI protein processing Inferred from direct assay PubMed 15231831. Source: MGI proteolysis Inferred from electronic annotation. Source: UniProtKB-KW release of cytochrome c from mitochondria Inferred from genetic interaction PubMed 16469926. Source: MGI response to DNA damage stimulus Inferred from direct assay PubMed 11092819. 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_component	cytoplasm Inferred from direct assay PubMed 12477715. Source: MGI cytosol Inferred from electronic annotation. Source: Compara mitochondrion Inferred from electronic annotation. Source: Compara nucleus Inferred from electronic annotation. Source: Compara
Molecular_function	aspartic-type endopeptidase activity Inferred from direct assay PubMed 15231831. 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
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Parp1	P11103	3	EBI-1790419,EBI-642213
Rps18	P62270	5	EBI-1790419,EBI-352460
THAP11	Q96EK4	2	EBI-1790419,EBI-1790529	From a different organism.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Propeptide

1 – 9

By similarity

PRO_0000004573

Propeptide

10 – 28

By similarity

PRO_0000004574

Chain

29 – 175

147

Caspase-3 subunit p17

PRO_0000004575

Chain

176 – 277

102

Caspase-3 subunit p12

PRO_0000004576

Sites

Active site

121

By similarity

Active site

163

By similarity

Amino acid modifications

Modified residue

Phosphoserine Ref.7

Modified residue

163

S-nitrosocysteine; in inhibited form By similarity

Experimental info

Sequence conflict

63 – 65

SRS → ARN in AAD09504. Ref.6

Sequence conflict

231

E → Q in AAD09504. Ref.6

Sequence conflict

262

I → F in AAD09504. Ref.6

Sequences

Sequence

Length

Mass (Da)

Tools

P70677 [UniParc].

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

FASTA

277

31,475

        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' referencesShow '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, MASS SPECTROMETRY. Tissue: Embryonic brain.
+	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.
IPI	IPI00308498.
PIR	JC5410.
RefSeq	NP_033940.1. NM_009810.2.
UniGene	Mm.34405.
3D structure databases
ProteinModelPortal	P70677.
SMR	P70677. Positions 29-277.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-44076N.
IntAct	P70677. 8 interactions.
MINT	MINT-4050331.
Protein family/group databases
MEROPS	C14.003.
PTM databases
PhosphoSite	P70677.
Proteomic databases
PaxDb	P70677.
PRIDE	P70677.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000093517; ENSMUSP00000091238; ENSMUSG00000031628.
GeneID	12367.
KEGG	mmu:12367.
UCSC	uc009lql.1. mouse.
Organism-specific databases
CTD	836.
MGI	MGI:107739. Casp3.
Phylogenomic databases
eggNOG	NOG279444.
GeneTree	ENSGT00700000104277.
HOGENOM	HOG000231878.
HOVERGEN	HBG050802.
InParanoid	P70677.
KO	K02187.
OMA	SSFVCVL.
OrthoDB	EOG4CZBGR.
Enzyme and pathway databases
BRENDA	3.4.22.56. 3474.
Reactome	REACT_100962. Apoptosis.
Gene expression databases
ArrayExpress	P70677.
Bgee	P70677.
CleanEx	MM_CASP3.
Genevestigator	P70677.
GermOnline	ENSMUSG00000031628. Mus musculus.
Family and domain databases
InterPro	IPR015470. Caspase_3. IPR011600. Pept_C14_cat. IPR001309. Pept_C14_ICE_p20. IPR016129. Pept_C14_ICE_p20_AS. IPR002138. Pept_C14_p10. IPR002398. Pept_C14_p45. IPR015917. Pept_C14_p45_core. [Graphical view]
PANTHER	PTHR10454. PTHR10454. 1 hit. PTHR10454:SF30. PTHR10454:SF30. 1 hit.
Pfam	PF00656. Peptidase_C14. 1 hit. [Graphical view]
PRINTS	PR00376. IL1BCENZYME.
SMART	SM00115. CASc. 1 hit. [Graphical view]
PROSITE	PS01122. CASPASE_CYS. 1 hit. PS01121. CASPASE_HIS. 1 hit. PS50207. CASPASE_P10. 1 hit. PS50208. CASPASE_P20. 1 hit. [Graphical view]
ProtoNet	Search...
Other
BindingDB	P70677.
ChEMBL	CHEMBL5632.
NextBio	281052.
SOURCE	Search...

Entry information

Entry name

CASP3_MOUSE

Accession

Primary (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:	May 1, 2013
This is version 124 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Relevant documents

Peptidase families

Classification of peptidase families and list of entries

MGD cross-references

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

SIMILARITY comments

Index of protein domains and families

Names·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents

Preferred order of sections

Names and origin

Cleaved into the following 2 chains:

Protein attributes

General annotation (Comments)

Ontologies

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Sequence annotation (Features)

Molecule processing

Sites

Amino acid modifications

Experimental info

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

Protein family/group databases

PTM databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Gene expression databases

Family and domain databases

Other

Entry information

Relevant documents