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Protein

Caspase-3

Gene

CASP3

Organism
Canis lupus familiaris (Dog) (Canis familiaris)
Status
Reviewed-Annotation score: Annotation score: 3 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

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protease, Thiol protease

Keywords - Biological processi

Apoptosis

Enzyme and pathway databases

BRENDAi3.4.22.56. 1153.
ReactomeiR-CFA-111459. Activation of caspases through apoptosome-mediated cleavage.
R-CFA-111465. Apoptotic cleavage of cellular proteins.
R-CFA-2028269. Signaling by Hippo.
R-CFA-205025. NADE modulates death signalling.
R-CFA-211227. Activation of DNA fragmentation factor.
R-CFA-264870. Caspase-mediated cleavage of cytoskeletal proteins.
R-CFA-351906. Apoptotic cleavage of cell adhesion proteins.
R-CFA-418889. Ligand-independent caspase activation via DCC.
R-CFA-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
Cleaved into the following 2 chains:
Gene namesi
Name:CASP3
OrganismiCanis lupus familiaris (Dog) (Canis familiaris)
Taxonomic identifieri9615 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCarnivoraCaniformiaCanidaeCanis
Proteomesi
  • UP000002254 Componenti: Chromosome 16

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
PropeptideiPRO_00000045571 – 9By similarity9
PropeptideiPRO_000000455810 – 28By similarityAdd BLAST19
ChainiPRO_000000455929 – 175Caspase-3 subunit p17By similarityAdd BLAST147
ChainiPRO_0000004560176 – 277Caspase-3 subunit p12By similarityAdd 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, -8 and -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

PaxDbiQ8MKI5.

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

Protein-protein interaction databases

STRINGi9615.ENSCAFP00000038581.

Structurei

3D structure databases

ProteinModelPortaliQ8MKI5.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the peptidase C14A family.Curated

Phylogenomic databases

eggNOGiKOG3573. Eukaryota.
ENOG410ZQIE. LUCA.
GeneTreeiENSGT00760000118912.
HOGENOMiHOG000231878.
HOVERGENiHBG050802.
InParanoidiQ8MKI5.
KOiK02187.

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.

Q8MKI5-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MENTENSVDA KSFKNAETKI LHGSKSMDSG MSFDNSYKMD YPEMGLCIII
60 70 80 90 100
NNKNFHKSTG MAPRSGTDVD AANLRETFTN LKYEVRNKND LTCEEILELM
110 120 130 140 150
NSVSKEDHSK RSSFVCVLLS HGDEGIIFGT NGPVDLRKVT GFFRGDYCRS
160 170 180 190 200
LTGKPKLFII QACRGTELDC GIETDSGIED DMACQKIPVE ADFLYAYSTA
210 220 230 240 250
PGYYSWRNSK DGSWFIQSLC AMLKLYAHKL EFMHILTRVN RKVATEFESF
260 270
SLDSAFHGKK QIPCIVSMLT KELYLYH
Length:277
Mass (Da):31,335
Last modified:October 1, 2002 - v1
Checksum:i7094C76D868BDAB9
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB085580 mRNA. Translation: BAB92962.1.
RefSeqiNP_001003042.1. NM_001003042.1.
UniGeneiCfa.84.

Genome annotation databases

EnsembliENSCAFT00000012385; ENSCAFP00000011475; ENSCAFG00000007750.
GeneIDi403567.
KEGGicfa:403567.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB085580 mRNA. Translation: BAB92962.1.
RefSeqiNP_001003042.1. NM_001003042.1.
UniGeneiCfa.84.

3D structure databases

ProteinModelPortaliQ8MKI5.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9615.ENSCAFP00000038581.

Protein family/group databases

MEROPSiC14.003.

Proteomic databases

PaxDbiQ8MKI5.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSCAFT00000012385; ENSCAFP00000011475; ENSCAFG00000007750.
GeneIDi403567.
KEGGicfa:403567.

Organism-specific databases

CTDi836.

Phylogenomic databases

eggNOGiKOG3573. Eukaryota.
ENOG410ZQIE. LUCA.
GeneTreeiENSGT00760000118912.
HOGENOMiHOG000231878.
HOVERGENiHBG050802.
InParanoidiQ8MKI5.
KOiK02187.

Enzyme and pathway databases

BRENDAi3.4.22.56. 1153.
ReactomeiR-CFA-111459. Activation of caspases through apoptosome-mediated cleavage.
R-CFA-111465. Apoptotic cleavage of cellular proteins.
R-CFA-2028269. Signaling by Hippo.
R-CFA-205025. NADE modulates death signalling.
R-CFA-211227. Activation of DNA fragmentation factor.
R-CFA-264870. Caspase-mediated cleavage of cytoskeletal proteins.
R-CFA-351906. Apoptotic cleavage of cell adhesion proteins.
R-CFA-418889. Ligand-independent caspase activation via DCC.
R-CFA-449147. Signaling by Interleukins.

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_CANLF
AccessioniPrimary (citable) accession number: Q8MKI5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 11, 2004
Last sequence update: October 1, 2002
Last modified: November 30, 2016
This is version 108 of the entry and version 1 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.