ID   CASP3_MACFA             Reviewed;         277 AA.
AC   Q2PFV2;
DT   28-NOV-2006, integrated into UniProtKB/Swiss-Prot.
DT   07-FEB-2006, sequence version 1.
DT   02-SEP-2026, entry version 102.
DE   RecName: Full=Caspase-3;
DE            Short=CASP-3;
DE            EC=3.4.22.56;
DE   Contains:
DE     RecName: Full=Caspase-3 subunit p17;
DE   Contains:
DE     RecName: Full=Caspase-3 subunit p12;
DE   Flags: Precursor;
GN   Name=CASP3; ORFNames=QmoA-14231;
OS   Macaca fascicularis (Crab-eating macaque) (Cynomolgus monkey).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini;
OC   Cercopithecidae; Cercopithecinae; Macaca.
OX   NCBI_TaxID=9541;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Medulla oblongata;
RA   Kobayashi M., Tanuma R., Hirata M., Osada N., Kusuda J., Sugano S.,
RA   Hashimoto K.;
RT   "Analysis of gene expression in cynomolgus monkey tissues by macaque cDNA
RT   oligo-chips.";
RL   Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
CC   -!- FUNCTION: Involved in the activation cascade of caspases responsible
CC       for apoptosis execution. At the onset of apoptosis, it proteolytically
CC       cleaves poly(ADP-ribose) polymerase PARP1 at a '216-Asp-|-Gly-217'
CC       bond. Cleaves and activates sterol regulatory element binding proteins
CC       (SREBPs) between the basic helix-loop-helix leucine zipper domain and
CC       the membrane attachment domain. Cleaves and activates caspase-6, -7 and
CC       -9 (CASP6, CASP7 and CASP9, respectively). Cleaves and inactivates
CC       interleukin-18 (IL18) (By similarity). Triggers cell adhesion in
CC       sympathetic neurons through RET cleavage (By similarity). Also involved
CC       in axon pruning during brain development (By similarity). Cleaves DSG2
CC       in response to apoptosis resulting in a loss of full length DSG2 at
CC       desmosome cell junctions and subsequent loss of cell-cell adhesion (By
CC       similarity). Also cleaves JUP in response to apoptosis (By similarity).
CC       Cleaves IL-1 beta between an Asp and an Ala, releasing the mature
CC       cytokine which is involved in a variety of inflammatory processes (By
CC       similarity). Cleaves and inhibits serine/threonine-protein kinase AKT1
CC       in response to oxidative stress. Acts as an inhibitor of type I
CC       interferon production during virus-induced apoptosis by mediating
CC       cleavage of antiviral proteins CGAS, IRF3 and MAVS, thereby preventing
CC       cytokine overproduction. Also involved in pyroptosis by mediating
CC       cleavage and activation of gasdermin-E (GSDME) (By similarity). Cleaves
CC       XRCC4 and phospholipid scramblase proteins XKR4, XKR8 and XKR9, leading
CC       to promote phosphatidylserine exposure on apoptotic cell surface (By
CC       similarity). Cleaves BIRC6 following inhibition of BIRC6-caspase
CC       binding by DIABLO/SMAC (By similarity). {ECO:0000250|UniProtKB:P42574,
CC       ECO:0000250|UniProtKB:P70677, ECO:0000250|UniProtKB:Q60431}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=Strict requirement for an Asp residue at positions P1 and P4.
CC         It has a preferred cleavage sequence of Asp-Xaa-Xaa-Asp-|- with a
CC         hydrophobic amino-acid residue at P2 and a hydrophilic amino-acid
CC         residue at P3, although Val or Ala are also accepted at this
CC         position.; EC=3.4.22.56; Evidence={ECO:0000250|UniProtKB:P42574};
CC   -!- ACTIVITY REGULATION: Inhibited by BIRC6; following inhibition of BIRC6-
CC       caspase binding by DIABLO/SMAC, BIRC6 is subjected to caspase cleavage,
CC       leading to an increase in active caspases.
CC       {ECO:0000250|UniProtKB:P42574}.
CC   -!- SUBUNIT: Heterotetramer that consists of two anti-parallel arranged
CC       heterodimers, each one formed by a 17 kDa (p17) and a 12 kDa (p12)
CC       subunit. Interacts with BIRC6/bruce. {ECO:0000250|UniProtKB:P42574}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P42574}.
CC   -!- PTM: Cleavage by granzyme B, caspase-6, caspase-8 and caspase-10
CC       generates the two active subunits. Additional processing of the
CC       propeptides is likely due to the autocatalytic activity of the
CC       activated protease. Active heterodimers between the small subunit of
CC       caspase-7 protease and the large subunit of caspase-3 also occur and
CC       vice versa. {ECO:0000250|UniProtKB:P42574}.
CC   -!- PTM: S-nitrosylated on its catalytic site cysteine in unstimulated cell
CC       lines and denitrosylated upon activation of the Fas apoptotic pathway,
CC       associated with an increase in intracellular caspase activity. Fas
CC       therefore activates caspase-3 not only by inducing the cleavage of the
CC       caspase zymogen to its active subunits, but also by stimulating the
CC       denitrosylation of its active site thiol.
CC       {ECO:0000250|UniProtKB:P42574}.
CC   -!- PTM: Ubiquitinated by BIRC6; this activity is inhibited by DIABLO/SMAC.
CC       {ECO:0000250|UniProtKB:P42574}.
CC   -!- SIMILARITY: Belongs to the peptidase C14A family. {ECO:0000305}.
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DR   EMBL; AB220485; BAE73018.1; -; mRNA.
DR   AlphaFoldDB; Q2PFV2; -.
DR   SMR; Q2PFV2; -.
DR   STRING; 9541.ENSMFAP00000031823; -.
DR   MEROPS; C14.003; -.
DR   eggNOG; KOG3573; Eukaryota.
DR   Proteomes; UP000233100; Unplaced.
DR   GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR   GO; GO:0031264; C:death-inducing signaling complex; IEA:TreeGrafter.
DR   GO; GO:0004197; F:cysteine-type endopeptidase activity; ISS:UniProtKB.
DR   GO; GO:0004175; F:endopeptidase activity; ISS:UniProtKB.
DR   GO; GO:0072734; P:cellular response to staurosporine; IEA:UniProtKB-ARBA.
DR   GO; GO:0030218; P:erythrocyte differentiation; IEA:TreeGrafter.
DR   GO; GO:0097194; P:execution phase of apoptosis; IEA:UniProtKB-ARBA.
DR   GO; GO:0030216; P:keratinocyte differentiation; IEA:TreeGrafter.
DR   GO; GO:0030182; P:neuron differentiation; IEA:TreeGrafter.
DR   GO; GO:1902004; P:positive regulation of amyloid-beta formation; ISS:UniProtKB.
DR   GO; GO:0043525; P:positive regulation of neuron apoptotic process; IEA:TreeGrafter.
DR   GO; GO:0051604; P:protein maturation; IEA:UniProtKB-ARBA.
DR   GO; GO:0006508; P:proteolysis; ISS:UniProtKB.
DR   GO; GO:0031647; P:regulation of protein stability; ISS:UniProtKB.
DR   GO; GO:0098883; P:synapse pruning; ISS:UniProtKB.
DR   CDD; cd00032; CASc; 1.
DR   FunFam; 3.30.70.1470:FF:000002; Caspase-3; 1.
DR   FunFam; 3.40.50.1460:FF:000001; Caspase-3 preproprotein; 1.
DR   Gene3D; 3.40.50.1460; -; 1.
DR   Gene3D; 3.30.70.1470; Caspase-like; 1.
DR   InterPro; IPR029030; Caspase-like_dom_sf.
DR   InterPro; IPR033139; Caspase_cys_AS.
DR   InterPro; IPR016129; Caspase_his_AS.
DR   InterPro; IPR002398; Pept_C14.
DR   InterPro; IPR011600; Pept_C14_caspase.
DR   InterPro; IPR002138; Pept_C14_p10.
DR   InterPro; IPR001309; Pept_C14_p20.
DR   InterPro; IPR015917; Pept_C14A.
DR   PANTHER; PTHR10454; CASPASE; 1.
DR   PANTHER; PTHR10454:SF198; CASPASE-3; 1.
DR   Pfam; PF00656; Peptidase_C14; 1.
DR   PRINTS; PR00376; IL1BCENZYME.
DR   SMART; SM00115; CASc; 1.
DR   SUPFAM; SSF52129; Caspase-like; 1.
DR   PROSITE; PS01122; CASPASE_CYS; 1.
DR   PROSITE; PS01121; CASPASE_HIS; 1.
DR   PROSITE; PS50207; CASPASE_P10; 1.
DR   PROSITE; PS50208; CASPASE_P20; 1.
PE   2: Evidence at transcript level;
KW   Acetylation; Apoptosis; Cytoplasm; Hydrolase; Phosphoprotein; Protease;
KW   Reference proteome; S-nitrosylation; Thiol protease; Ubl conjugation;
KW   Zymogen.
FT   PROPEP          1..9
FT                   /evidence="ECO:0000250|UniProtKB:P42574"
FT                   /id="PRO_0000261332"
FT   PROPEP          10..28
FT                   /evidence="ECO:0000250|UniProtKB:P42574"
FT                   /id="PRO_0000261333"
FT   CHAIN           29..175
FT                   /note="Caspase-3 subunit p17"
FT                   /evidence="ECO:0000250|UniProtKB:P42574"
FT                   /id="PRO_0000261334"
FT   CHAIN           176..277
FT                   /note="Caspase-3 subunit p12"
FT                   /evidence="ECO:0000250|UniProtKB:P42574"
FT                   /id="PRO_0000261335"
FT   ACT_SITE        121
FT                   /evidence="ECO:0000250|UniProtKB:P29466"
FT   ACT_SITE        163
FT                   /evidence="ECO:0000250|UniProtKB:P29466"
FT   MOD_RES         1
FT                   /note="N-acetylmethionine"
FT                   /evidence="ECO:0000250|UniProtKB:P42574"
FT   MOD_RES         11
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:P70677"
FT   MOD_RES         26
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P42574"
FT   MOD_RES         163
FT                   /note="S-nitrosocysteine; in inhibited form"
FT                   /evidence="ECO:0000250|UniProtKB:P42574"
SQ   SEQUENCE   277 AA;  31286 MW;  6D60AB6FFB97FB7C CRC64;
     MENTENSVDS KSIKSLEPKI IHGSKSVDSG ISLDNSYKMD YPEMGLCIII NNKNFHKSTG
     MASRSGTDVD AANLRETFIN LKYGVRNKND LTREEIVELM RNVSKEDHSK RSSFVCVLLS
     HGEEGIIFGT NGPLDLKKIT SFFRGDCCRS LTGKPKLFII QACRGTELDC GIEADSGVED
     DMACHKIPVE ADFLYAYSTA PGYYSWRNSK DGSWFIQSLC AMLKQYADKL EFMHILTRVN
     RKVATEFESF SLDATFHAKK QIPCIVSMLT KELYFYH
//