Q5IS54 (CASP3_PANTR) Reviewed, UniProtKB/Swiss-Prot

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. Caspase-3 subunit p17
2. Caspase-3 subunit p12

Gene names

Name:

CASP3

Organism

Pan troglodytes (Chimpanzee)

Taxonomic identifier

9598 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Pan

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. Triggers cell adhesion in sympathetic neurons through RET cleavage 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	Acetylation Phosphoprotein S-nitrosylation Zymogen
Gene Ontology (GO)
Biological process	proteolysis Inferred from electronic annotation. Source: UniProtKB-KW
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_0000004577
	Propeptide	10 – 28	19	By similarity		PRO_0000004578
	Chain	29 – 175	147	Caspase-3 subunit p17		PRO_0000004579
	Chain	176 – 277	102	Caspase-3 subunit p12		PRO_0000004580
Sites
	Active site	121	1	By similarity
	Active site	163	1	By similarity
Amino acid modifications
	Modified residue	1	1	N-acetylmethionine By similarity
	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

Sequences

	Sequence		Length	Mass (Da)
	Q5IS54 [UniParc]. Last modified February 15, 2005. Version 1. Checksum: 23B1CD3BCA3BF64A	FASTA	277	31,607
	10 20 30 40 50 60 MENTENSVDS KSIKNLEPKI IHGSQSMDSG ISLDNSYKMD YPEMGLCIII NNKNFHKSTG 70 80 90 100 110 120 MTSRSGTDVD AANLRETFRN LKYEVRNKND LTREEIVELM RDVSKEDHSK RSSFVCVLLS 130 140 150 160 170 180 HGEEGIIFGT NGPVDLKKIT NFFRGDRCRS LTGKPKLFII QACRGTELDC GIETDSGVDD 190 200 210 220 230 240 DMACHKIPVE ADFLYAYSTA PGYYSWRNSK DGSWFIQSLC AMLKQYADKL EFMHILTRVN 250 260 270 RKVATEFESF SFDATFHAKK QIPCIVSMLT KELYFYH

References

[1]	"Accelerated evolution of nervous system genes in the origin of Homo sapiens." Dorus S., Vallender E.J., Evans P.D., Anderson J.R., Gilbert S.L., Mahowald M., Wyckoff G.J., Malcom C.M., Lahn B.T. Cell 119:1027-1040(2004) [PubMed: 15620360] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].

Cross-references

Sequence databases
EMBL GenBank DDBJ	AY665274 mRNA. Translation: AAV74312.1.
RefSeq	NP_001012435.1. NM_001012433.1.
UniGene	Ptr.3233.
3D structure databases
ProteinModelPortal	Q5IS54.
SMR	Q5IS54. Positions 29-277.
ModBase	Search...
Protein-protein interaction databases
STRING	Q5IS54.
Protein family/group databases
MEROPS	C14.003.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSPTRT00000061788; ENSPTRP00000054330; ENSPTRG00000016640.
GeneID	461669.
KEGG	ptr:461669.
Organism-specific databases
CTD	836.
Phylogenomic databases
eggNOG	prNOG15513.
GeneTree	ENSGT00560000076782.
HOVERGEN	HBG050802.
InParanoid	Q5IS54.
OMA	CAMLKQY.
OrthoDB	EOG4CZBGR.
PhylomeDB	Q5IS54.
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]
KO	K02187.
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_PANTR

Accession

Primary (citable) accession number: Q5IS54

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 15, 2005
Last sequence update:	February 15, 2005
Last modified:	January 25, 2012
This is version 62 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program