Reviewed, UniProtKB/Swiss-Prot Q2PFV2 (CASP3_MACFA)

Names and origin

Protein names

Recommended name:
    Caspase-3
      Short name=CASP-3
    EC=3.4.22.56
Cleaved into the following 2 chains:
    1- Recommended name:
            Caspase-3 subunit p17
    2- Recommended name:
            Caspase-3 subunit p12

Gene names

Name:	CASP3
ORF Names:	QmoA-14231

Organism

Macaca fascicularis (Crab eating macaque) (Cynomolgus monkey)

Taxonomic identifier

9541 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Cercopithecidae › Cercopithecinae › Macaca

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. Involved in the cleavage of huntingtin 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 By similarity.
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
Gene Ontology (GO)
Biological process	apoptosis Inferred from electronic annotation. Source: UniProtKB-KW proteolysis Inferred from electronic annotation. Source: InterPro
Cellular component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	cysteine-type endopeptidase activity Inferred from electronic annotation. Source: InterPro
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_0000261332
	Propeptide	10 – 28	19	By similarity		PRO_0000261333
	Chain	29 – 175	147	Caspase-3 subunit p17		PRO_0000261334
	Chain	176 – 277	102	Caspase-3 subunit p12		PRO_0000261335
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	163	1	S-nitrosocysteine; in inhibited form By similarity

Sequences

	Sequence		Length	Mass (Da)
	Q2PFV2-1 [UniParc]. Last modified February 7, 2006. Version 1. Checksum: 6D60AB6FFB97FB7C	FASTA	277	31,286
	10 20 30 40 50 60 MENTENSVDS KSIKSLEPKI IHGSKSVDSG ISLDNSYKMD YPEMGLCIII NNKNFHKSTG 70 80 90 100 110 120 MASRSGTDVD AANLRETFIN LKYGVRNKND LTREEIVELM RNVSKEDHSK RSSFVCVLLS 130 140 150 160 170 180 HGEEGIIFGT NGPLDLKKIT SFFRGDCCRS LTGKPKLFII QACRGTELDC GIEADSGVED 190 200 210 220 230 240 DMACHKIPVE ADFLYAYSTA PGYYSWRNSK DGSWFIQSLC AMLKQYADKL EFMHILTRVN 250 260 270 RKVATEFESF SLDATFHAKK QIPCIVSMLT KELYFYH

References

[1]

"Analysis of gene expression in cynomolgus monkey tissues by macaque cDNA oligo-chips." Kobayashi M., Tanuma R., Hirata M., Osada N., Kusuda J., Sugano S., Hashimoto K. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Medulla oblongata.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AB220485 mRNA. Translation: BAE73018.1.
3D structure databases
ModBase	Search...
Protein family/group databases
MEROPS	C14.003.
Phylogenomic databases
HOVERGEN	Q2PFV2.
Enzyme and pathway databases
BRENDA	3.4.22.56. 3438.
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...

Entry information

Entry name

CASP3_MACFA

Accession

Primary (citable) accession number: Q2PFV2

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 28, 2006
Last sequence update:	February 7, 2006
Last modified:	June 16, 2009
This is version 26 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)