Reviewed, UniProtKB/Swiss-Prot P55213 (CASP3_RAT)

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
    Yama protein
    SREBP cleavage activity 1
      Short name=SCA-1
    LICE
    IRP
Cleaved into the following 2 chains:
    1- Recommended name:
            Caspase-3 subunit p17
    2- Recommended name:
            Caspase-3 subunit p12

Gene names

Name:	Casp3
Synonyms:	Cpp32

Organism

Rattus norvegicus (Rat)

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

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

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 transcript 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 By similarity.
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.
Subcellular location	Cytoplasm.
Tissue specificity	Expressed in heart, brain, liver, and muscle but not in kidney or testis.
Developmental stage	Highly expressed in neuron-enriched regions of the developing brain, but down-regulated to low levels in the adult brain.
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	Acetylation Phosphoprotein S-nitrosylation Zymogen
Gene Ontology (GO)
Biological process	apoptosis Inferred from electronic annotation. Source: UniProtKB-KW hippocampus development Inferred from expression pattern. Source: RGD induction of apoptosis Traceable author statement. Source: RGD intracellular signaling cascade Inferred from mutant phenotype. Source: RGD learning or memory Inferred from mutant phenotype. Source: RGD neuron differentiation Inferred from expression pattern. Source: RGD positive regulation of neuron apoptosis Inferred from mutant phenotype. Source: RGD proteolysis Inferred from direct assay. Source: RGD response to X-ray Inferred from expression pattern. Source: RGD response to amino acid stimulus Inferred from expression pattern. Source: RGD response to antibiotic Inferred from expression pattern. Source: RGD response to cobalt ion Inferred from expression pattern. Source: RGD response to drug Inferred from expression pattern. Source: RGD response to estradiol stimulus Inferred from expression pattern. Source: RGD response to glucocorticoid stimulus Inferred from expression pattern. Source: RGD response to glucose stimulus Inferred from direct assay. Source: RGD response to hydrogen peroxide Inferred from direct assay. Source: RGD response to hypoxia Inferred from expression pattern. Source: RGD response to lipopolysaccharide Inferred from expression pattern. Source: RGD response to nicotine Inferred from expression pattern. Source: RGD wound healing Inferred from expression pattern. Source: RGD
Cellular component	cytosol Inferred from direct assay. Source: RGD soluble fraction Inferred from direct assay. Source: RGD
Molecular function	cysteine-type endopeptidase activity Inferred from electronic annotation. Source: InterPro phospholipase A2 activator activity Inferred from mutant phenotype. Source: RGD
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Propeptide	1 – 9	9	By similarity		PRO_0000004589
	Propeptide	10 – 28	19	By similarity		PRO_0000004590
	Chain	29 – 175	147	Caspase-3 subunit p17		PRO_0000004591
	Chain	176 – 277	102	Caspase-3 subunit p12		PRO_0000004592
Sites
	Active site	121	1	By similarity
	Active site	163	1	By similarity
Amino acid modifications
	Modified residue	26	1	Phosphoserine By similarity
	Modified residue	82	1	N6-acetyllysine By similarity
	Modified residue	163	1	S-nitrosocysteine; in inhibited form By similarity
Experimental info
	Sequence conflict	25 – 29	5	KSMDS → QVD in AAB02722. Ref.4
	Sequence conflict	170	1	C → S in AAC52261. Ref.5
	Sequence conflict	178	1	T → A in AAC52261. Ref.5
	Sequence conflict	182	1	M → V in AAC52261. Ref.5
	Sequence conflict	187	1	I → K in AAC52261. Ref.5
	Sequence conflict	190	1	E → G in AAB41792. Ref.2
	Sequence conflict	199	1	T → S in AAC52261. Ref.5
	Sequence conflict	211	1	D → G in AAC52261. Ref.5
	Sequence conflict	236	1	L → I in AAB02722. Ref.4
	Sequence conflict	245	1	T → M in AAB41792. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	P55213-1 [UniParc]. Last modified November 1, 1997. Version 2. Checksum: ADABF418E2507402	FASTA	277	31,492
	10 20 30 40 50 60 MDNNETSVDS KSINNFETKT IHGSKSMDSG IYLDSSYKMD YPEMGLCIII NNKNFHKSTG 70 80 90 100 110 120 MSARNGTDVD AANLRETFMA LKYEVRNKND LTREEIMELM DSVSKEDHSK RSSFVCVILS 130 140 150 160 170 180 HGDEGVIFGT NGPVDLKKLT SFFRGDYCRS LTGKPKLFII QACRGTELDC GIETDSGTDD 190 200 210 220 230 240 DMACQKIPVE ADFLYAYSTA PGYYSWRNSR DGSWFIQSLC AMLKLYAHKL EFMHILTRVN 250 260 270 RKVATEFESF SLDATFHAKK QIPCIVSMLT KELYFYH

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: 8761296] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Cloning and expression of a rat brain interleukin-1beta-converting enzyme (ICE)-related protease (IRP) and its possible role in apoptosis of cultured cerebellar granule neurons." Ni B., Wu X., Du Y., Su Y., Hamilton-Byrd E., Rockey P.K., Rosteck P. Jr., Poirier G.G., Paul S.M. J. Neurosci. 17:1561-1569(1997) [PubMed: 9030616] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Brain.
[3]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Heart.
[4]	"Cloning of the rat cysteine protease p32-beta." Yakovlev A.G. Submitted (JUN-1996) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-264.
[5]	"Interleukin-1 beta-converting enzyme-related proteases (IRPs) and mammalian cell death: dissociation of IRP-induced oligonucleosomal endonuclease activity from morphological apoptosis in granulosa cells of the ovarian follicle." Flaws J.A., Kugu K., Trbovich A.M., Desanti A., Tilly K.I., Hirshfield A.N., Tilly J.L. Endocrinology 136:5042-5053(1995) [PubMed: 7588240] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 30-241. Tissue: Ovary.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	U49930 mRNA. Translation: AAC52765.1. U84410 mRNA. Translation: AAB41792.1. BC081854 mRNA. Translation: AAH81854.1. U58656 mRNA. Translation: AAB02722.1. U34685 mRNA. Translation: AAC52261.1.
IPI	IPI00215220.
PIR	I67437.
RefSeq	NP_037054.1.
UniGene	Rn.10562
3D structure databases
HSSP	HSSP built from PDB template 1PAU based on UniProtKB P42574.
ModBase	Search...
Protein-protein interaction databases
STRING	P55213.
Protein family/group databases
MEROPS	C14.003.
PTM databases
PhosphoSite	P55213.
Genome annotation databases
Ensembl	ENSRNOT00000014095; ENSRNOP00000014096; ENSRNOG00000010475; Rattus norvegicus. [Genome view]
GeneID	25402.
KEGG	rno:25402.
NMPDR	fig|10116.3.peg.12437.
UCSC	NM_012922. rat.
Organism-specific databases
CTD	25402.
RGD	2275. Casp3.
Phylogenomic databases
HOVERGEN	P55213.
OMA	HGEEGII.
Enzyme and pathway databases
BRENDA	3.4.22.56. 248.
Gene expression databases
ArrayExpress	P55213.
Genevestigator	P55213.
GermOnline	ENSRNOG00000010475. Rattus norvegicus.
Family and domain databases
InterPro	IPR015470. Caspase_3_related. 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:SF30. Casp3_like. 1 hit. PTHR10454. Pept_C14_p45. 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 Resources
NextBio	606497.

Entry information

Entry name

CASP3_RAT

Accession

Primary (citable) accession number: P55213
Secondary accession number(s): P70543, P97699, Q62993

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	November 1, 1997
Last modified:	November 3, 2009
This is version 85 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)