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Protein

Caspase-3

Gene

Casp3

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript leveli

Functioni

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).By similarity

Catalytic activityi

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.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei121By similarity1
Active sitei163By similarity1

GO - Molecular functioni

  • aspartic-type endopeptidase activity Source: Ensembl
  • cysteine-type endopeptidase activity involved in execution phase of apoptosis Source: GO_Central
  • cysteine-type peptidase activity Source: RGD
  • death receptor binding Source: RGD
  • phospholipase A2 activator activity Source: RGD
  • protease binding Source: RGD
  • protein complex binding Source: RGD

GO - Biological processi

  • apoptotic process Source: RGD
  • cellular response to organic cyclic compound Source: RGD
  • erythrocyte differentiation Source: GO_Central
  • execution phase of apoptosis Source: GO_Central
  • glial cell apoptotic process Source: RGD
  • hippocampus development Source: RGD
  • intracellular signal transduction Source: RGD
  • keratinocyte differentiation Source: GO_Central
  • learning or memory Source: RGD
  • negative regulation of apoptotic process Source: Ensembl
  • neuron differentiation Source: RGD
  • neurotrophin TRK receptor signaling pathway Source: Ensembl
  • positive regulation of apoptotic process Source: RGD
  • positive regulation of neuron apoptotic process Source: RGD
  • proteolysis Source: RGD
  • response to amino acid Source: RGD
  • response to antibiotic Source: RGD
  • response to cobalt ion Source: RGD
  • response to drug Source: RGD
  • response to estradiol Source: RGD
  • response to glucocorticoid Source: RGD
  • response to glucose Source: RGD
  • response to hydrogen peroxide Source: RGD
  • response to hypoxia Source: RGD
  • response to lipopolysaccharide Source: RGD
  • response to metal ion Source: RGD
  • response to nicotine Source: RGD
  • response to organic cyclic compound Source: RGD
  • response to organic substance Source: RGD
  • response to X-ray Source: RGD
  • wound healing Source: RGD
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protease, Thiol protease

Keywords - Biological processi

Apoptosis

Enzyme and pathway databases

BRENDAi3.4.22.56. 5301.
ReactomeiR-RNO-111459. Activation of caspases through apoptosome-mediated cleavage.
R-RNO-111465. Apoptotic cleavage of cellular proteins.
R-RNO-2028269. Signaling by Hippo.
R-RNO-205025. NADE modulates death signalling.
R-RNO-211227. Activation of DNA fragmentation factor.
R-RNO-264870. Caspase-mediated cleavage of cytoskeletal proteins.
R-RNO-351906. Apoptotic cleavage of cell adhesion proteins.
R-RNO-418889. Ligand-independent caspase activation via DCC.
R-RNO-449147. Signaling by Interleukins.

Protein family/group databases

MEROPSiC14.003.

Names & Taxonomyi

Protein namesi
Recommended name:
Caspase-3 (EC:3.4.22.56)
Short name:
CASP-3
Alternative name(s):
Apopain
Cysteine protease CPP32
Short name:
CPP-32
IRP
LICE
Protein Yama
SREBP cleavage activity 1
Short name:
SCA-1
Cleaved into the following 2 chains:
Gene namesi
Name:Casp3
Synonyms:Cpp32
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 16

Organism-specific databases

RGDi2275. Casp3.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: RGD
  • cytosol Source: RGD
  • death-inducing signaling complex Source: RGD
  • membrane raft Source: RGD
  • nucleus Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Chemistry databases

ChEMBLiCHEMBL1075185.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
PropeptideiPRO_00000045891 – 9By similarity9
PropeptideiPRO_000000459010 – 28By similarityAdd BLAST19
ChainiPRO_000000459129 – 175Caspase-3 subunit p17Add BLAST147
ChainiPRO_0000004592176 – 277Caspase-3 subunit p12Add BLAST102

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineBy similarity1
Modified residuei11N6-acetyllysineBy similarity1
Modified residuei26PhosphoserineBy similarity1
Modified residuei163S-nitrosocysteine; in inhibited formBy similarity1

Post-translational modificationi

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).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).By similarity

Keywords - PTMi

Acetylation, Phosphoprotein, S-nitrosylation, Zymogen

Proteomic databases

PaxDbiP55213.
PRIDEiP55213.

PTM databases

iPTMnetiP55213.
PhosphoSitePlusiP55213.

Expressioni

Tissue specificityi

Expressed in heart, brain, liver, and muscle but not in kidney or testis.

Developmental stagei

Highly expressed in neuron-enriched regions of the developing brain, but down-regulated to low levels in the adult brain.

Gene expression databases

BgeeiENSRNOG00000010475.
GenevisibleiP55213. RN.

Interactioni

Subunit structurei

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

GO - Molecular functioni

  • death receptor binding Source: RGD
  • protease binding Source: RGD
  • protein complex binding Source: RGD

Protein-protein interaction databases

IntActiP55213. 1 interactor.
MINTiMINT-2635470.
STRINGi10116.ENSRNOP00000014096.

Structurei

3D structure databases

ProteinModelPortaliP55213.
SMRiP55213.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the peptidase C14A family.Curated

Phylogenomic databases

eggNOGiKOG3573. Eukaryota.
ENOG410ZQIE. LUCA.
GeneTreeiENSGT00760000118912.
HOGENOMiHOG000231878.
HOVERGENiHBG050802.
InParanoidiP55213.
KOiK02187.
OMAiNHKHRGL.
OrthoDBiEOG091G05YD.
PhylomeDBiP55213.
TreeFamiTF102023.

Family and domain databases

CDDicd00032. CASc. 1 hit.
Gene3Di3.40.50.1460. 1 hit.
InterProiIPR029030. Caspase-like_dom.
IPR015470. Caspase_3.
IPR033139. Caspase_cys_AS.
IPR016129. Caspase_his_AS.
IPR002138. Pept_C14_p10.
IPR001309. Pept_C14_p20.
IPR015917. Pept_C14A.
[Graphical view]
PANTHERiPTHR10454:SF30. PTHR10454:SF30. 1 hit.
PRINTSiPR00376. IL1BCENZYME.
SMARTiSM00115. CASc. 1 hit.
[Graphical view]
SUPFAMiSSF52129. SSF52129. 1 hit.
PROSITEiPS01122. CASPASE_CYS. 1 hit.
PS01121. CASPASE_HIS. 1 hit.
PS50207. CASPASE_P10. 1 hit.
PS50208. CASPASE_P20. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P55213-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MDNNETSVDS KSINNFETKT IHGSKSMDSG IYLDSSYKMD YPEMGLCIII
60 70 80 90 100
NNKNFHKSTG MSARNGTDVD AANLRETFMA LKYEVRNKND LTREEIMELM
110 120 130 140 150
DSVSKEDHSK RSSFVCVILS HGDEGVIFGT NGPVDLKKLT SFFRGDYCRS
160 170 180 190 200
LTGKPKLFII QACRGTELDC GIETDSGTDD DMACQKIPVE ADFLYAYSTA
210 220 230 240 250
PGYYSWRNSR DGSWFIQSLC AMLKLYAHKL EFMHILTRVN RKVATEFESF
260 270
SLDATFHAKK QIPCIVSMLT KELYFYH
Length:277
Mass (Da):31,492
Last modified:November 1, 1997 - v2
Checksum:iADABF418E2507402
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti25 – 29KSMDS → QVD in AAB02722 (Ref. 4) Curated5
Sequence conflicti170C → S in AAC52261 (PubMed:7588240).Curated1
Sequence conflicti178T → A in AAC52261 (PubMed:7588240).Curated1
Sequence conflicti182M → V in AAC52261 (PubMed:7588240).Curated1
Sequence conflicti187I → K in AAC52261 (PubMed:7588240).Curated1
Sequence conflicti190E → G in AAB41792 (PubMed:9030616).Curated1
Sequence conflicti199T → S in AAC52261 (PubMed:7588240).Curated1
Sequence conflicti211D → G in AAC52261 (PubMed:7588240).Curated1
Sequence conflicti236L → I in AAB02722 (Ref. 4) Curated1
Sequence conflicti245T → M in AAB41792 (PubMed:9030616).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
PIRiI67437.
RefSeqiNP_037054.1. NM_012922.2.
XP_006253192.1. XM_006253130.3.
UniGeneiRn.10562.

Genome annotation databases

EnsembliENSRNOT00000014095; ENSRNOP00000014096; ENSRNOG00000010475.
GeneIDi25402.
KEGGirno:25402.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
PIRiI67437.
RefSeqiNP_037054.1. NM_012922.2.
XP_006253192.1. XM_006253130.3.
UniGeneiRn.10562.

3D structure databases

ProteinModelPortaliP55213.
SMRiP55213.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiP55213. 1 interactor.
MINTiMINT-2635470.
STRINGi10116.ENSRNOP00000014096.

Chemistry databases

ChEMBLiCHEMBL1075185.

Protein family/group databases

MEROPSiC14.003.

PTM databases

iPTMnetiP55213.
PhosphoSitePlusiP55213.

Proteomic databases

PaxDbiP55213.
PRIDEiP55213.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000014095; ENSRNOP00000014096; ENSRNOG00000010475.
GeneIDi25402.
KEGGirno:25402.

Organism-specific databases

CTDi836.
RGDi2275. Casp3.

Phylogenomic databases

eggNOGiKOG3573. Eukaryota.
ENOG410ZQIE. LUCA.
GeneTreeiENSGT00760000118912.
HOGENOMiHOG000231878.
HOVERGENiHBG050802.
InParanoidiP55213.
KOiK02187.
OMAiNHKHRGL.
OrthoDBiEOG091G05YD.
PhylomeDBiP55213.
TreeFamiTF102023.

Enzyme and pathway databases

BRENDAi3.4.22.56. 5301.
ReactomeiR-RNO-111459. Activation of caspases through apoptosome-mediated cleavage.
R-RNO-111465. Apoptotic cleavage of cellular proteins.
R-RNO-2028269. Signaling by Hippo.
R-RNO-205025. NADE modulates death signalling.
R-RNO-211227. Activation of DNA fragmentation factor.
R-RNO-264870. Caspase-mediated cleavage of cytoskeletal proteins.
R-RNO-351906. Apoptotic cleavage of cell adhesion proteins.
R-RNO-418889. Ligand-independent caspase activation via DCC.
R-RNO-449147. Signaling by Interleukins.

Miscellaneous databases

PROiP55213.

Gene expression databases

BgeeiENSRNOG00000010475.
GenevisibleiP55213. RN.

Family and domain databases

CDDicd00032. CASc. 1 hit.
Gene3Di3.40.50.1460. 1 hit.
InterProiIPR029030. Caspase-like_dom.
IPR015470. Caspase_3.
IPR033139. Caspase_cys_AS.
IPR016129. Caspase_his_AS.
IPR002138. Pept_C14_p10.
IPR001309. Pept_C14_p20.
IPR015917. Pept_C14A.
[Graphical view]
PANTHERiPTHR10454:SF30. PTHR10454:SF30. 1 hit.
PRINTSiPR00376. IL1BCENZYME.
SMARTiSM00115. CASc. 1 hit.
[Graphical view]
SUPFAMiSSF52129. SSF52129. 1 hit.
PROSITEiPS01122. CASPASE_CYS. 1 hit.
PS01121. CASPASE_HIS. 1 hit.
PS50207. CASPASE_P10. 1 hit.
PS50208. CASPASE_P20. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiCASP3_RAT
AccessioniPrimary (citable) accession number: P55213
Secondary accession number(s): P70543, P97699, Q62993
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: November 1, 1997
Last modified: November 30, 2016
This is version 152 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Peptidase families
    Classification of peptidase families and list of entries
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.