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Protein

Caspase-3

Gene

Casp3

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: -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
  • cyclin-dependent protein serine/threonine kinase inhibitor 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-containing complex binding Source: RGD

GO - Biological processi

  • apoptotic process Source: RGD
  • B cell homeostasis Source: Ensembl
  • cell fate commitment Source: Ensembl
  • cellular response to DNA damage stimulus Source: Ensembl
  • cellular response to organic cyclic compound Source: RGD
  • cellular response to staurosporine Source: Ensembl
  • erythrocyte differentiation Source: GO_Central
  • execution phase of apoptosis Source: GO_Central
  • glial cell apoptotic process Source: RGD
  • heart development Source: Ensembl
  • hippocampus development Source: RGD
  • intracellular signal transduction Source: RGD
  • intrinsic apoptotic signaling pathway in response to osmotic stress Source: Ensembl
  • keratinocyte differentiation Source: GO_Central
  • learning or memory Source: RGD
  • negative regulation of activated T cell proliferation Source: Ensembl
  • negative regulation of apoptotic process Source: Ensembl
  • negative regulation of B cell proliferation Source: Ensembl
  • negative regulation of cyclin-dependent protein serine/threonine kinase activity Source: Ensembl
  • neuron 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
  • protein processing Source: Ensembl
  • 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 UV Source: Ensembl
  • response to X-ray Source: RGD
  • sensory perception of sound Source: Ensembl
  • T cell homeostasis Source: Ensembl
  • wound healing Source: RGD

Keywordsi

Molecular functionHydrolase, Protease, Thiol protease
Biological processApoptosis

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-449836 Other interleukin signaling

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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 16

Organism-specific databases

RGDi2275 Casp3

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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-protein interaction databases

ELMiP55213
IntActiP55213, 1 interactor
MINTiP55213
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
OMAiVDDDMAC
OrthoDBiEOG091G05YD
PhylomeDBiP55213
TreeFamiTF102023

Family and domain databases

CDDicd00032 CASc, 1 hit
InterProiView protein in InterPro
IPR015471 Casp3/7
IPR029030 Caspase-like_dom_sf
IPR033139 Caspase_cys_AS
IPR016129 Caspase_his_AS
IPR002138 Pept_C14_p10
IPR001309 Pept_C14_p20
IPR015917 Pept_C14A
PANTHERiPTHR10454:SF31 PTHR10454:SF31, 1 hit
PRINTSiPR00376 IL1BCENZYME
SMARTiView protein in SMART
SM00115 CASc, 1 hit
SUPFAMiSSF52129 SSF52129, 1 hit
PROSITEiView protein in PROSITE
PS01122 CASPASE_CYS, 1 hit
PS01121 CASPASE_HIS, 1 hit
PS50207 CASPASE_P10, 1 hit
PS50208 CASPASE_P20, 1 hit

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

Similar proteinsi

Entry informationi

Entry nameiCASP3_RAT
AccessioniPrimary (citable) accession number: P55213
Secondary accession number(s): P70543, P97699, Q62993
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: November 1, 1997
Last modified: July 18, 2018
This is version 164 of the entry and version 2 of the sequence. See 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

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