ID   CASP3_MESAU             Reviewed;         277 AA.
AC   Q60431;
DT   01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1996, sequence version 1.
DT   25-MAY-2022, entry version 122.
DE   RecName: Full=Caspase-3;
DE            Short=CASP-3;
DE            EC=3.4.22.56;
DE   AltName: Full=Apopain;
DE   AltName: Full=Cysteine protease CPP32;
DE            Short=CPP-32;
DE   AltName: Full=Protein Yama;
DE   AltName: Full=SREBP cleavage activity 1;
DE            Short=SCA-1;
DE   Contains:
DE     RecName: Full=Caspase-3 subunit p17;
DE   Contains:
DE     RecName: Full=Caspase-3 subunit p12;
DE   Flags: Precursor;
GN   Name=CASP3; Synonyms=CPP32;
OS   Mesocricetus auratus (Golden hamster).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea;
OC   Cricetidae; Cricetinae; Mesocricetus.
OX   NCBI_TaxID=10036;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Brain;
RX   PubMed=8605870; DOI=10.1002/j.1460-2075.1996.tb00438.x;
RA   Wang X., Zelenski N.G., Yang J., Sakai J., Brown M.S., Goldstein J.L.;
RT   "Cleavage of sterol regulatory element binding proteins (SREBPs) by CPP32
RT   during apoptosis.";
RL   EMBO J. 15:1012-1020(1996).
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 (PARP) 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. Triggers cell adhesion in sympathetic neurons through RET cleavage
CC       (By similarity). Cleaves IL-1 beta between an Asp and an Ala, releasing
CC       the mature cytokine which is involved in a variety of inflammatory
CC       processes (By similarity). Cleaves and inhibits serine/threonine-
CC       protein kinase AKT1 in response to oxidative stress. Acts as an
CC       inhibitor of type I interferon production during virus-induced
CC       apoptosis by mediating cleavage of antiviral proteins CGAS, IRF3 and
CC       MAVS, thereby preventing cytokine overproduction. Cleaves XRCC4 and
CC       phospholipid scramblase proteins XKR4, XKR8 and XKR9, leading to
CC       promote phosphatidylserine exposure on apoptotic cell surface (By
CC       similarity). {ECO:0000250|UniProtKB:P42574,
CC       ECO:0000250|UniProtKB:P70677}.
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   -!- 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}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm.
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 (By similarity). {ECO:0000250}.
CC   -!- PTM: S-nitrosylated on its catalytic site cysteine in unstimulated
CC       human cell lines and denitrosylated upon activation of the Fas
CC       apoptotic pathway, associated with an increase in intracellular caspase
CC       activity. Fas therefore activates caspase-3 not only by inducing the
CC       cleavage of the caspase zymogen to its active subunits, but also by
CC       stimulating the denitrosylation of its active site thiol (By
CC       similarity). {ECO:0000250}.
CC   -!- SIMILARITY: Belongs to the peptidase C14A family. {ECO:0000305}.
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DR   EMBL; U27463; AAB01511.1; -; mRNA.
DR   PIR; S64710; S64710.
DR   RefSeq; NP_001268511.1; NM_001281582.1.
DR   AlphaFoldDB; Q60431; -.
DR   SMR; Q60431; -.
DR   DIP; DIP-987N; -.
DR   MEROPS; C14.003; -.
DR   GeneID; 101828960; -.
DR   CTD; 836; -.
DR   OrthoDB; 984395at2759; -.
DR   Proteomes; UP000189706; Unplaced.
DR   GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR   GO; GO:0097153; F:cysteine-type endopeptidase activity involved in apoptotic process; ISS:UniProtKB.
DR   GO; GO:0097199; F:cysteine-type endopeptidase activity involved in apoptotic signaling pathway; ISS:UniProtKB.
DR   GO; GO:0004175; F:endopeptidase activity; ISS:UniProtKB.
DR   GO; GO:1902004; P:positive regulation of amyloid-beta formation; ISS:UniProtKB.
DR   GO; GO:0006508; P:proteolysis; ISS:UniProtKB.
DR   GO; GO:0031647; P:regulation of protein stability; ISS:UniProtKB.
DR   CDD; cd00032; CASc; 1.
DR   InterPro; IPR015471; Casp3/7.
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; IPR002138; Pept_C14_p10.
DR   InterPro; IPR001309; Pept_C14_p20.
DR   InterPro; IPR015917; Pept_C14A.
DR   PANTHER; PTHR10454; PTHR10454; 1.
DR   PANTHER; PTHR10454:SF31; PTHR10454:SF31; 1.
DR   PRINTS; PR00376; IL1BCENZYME.
DR   SMART; SM00115; CASc; 1.
DR   SUPFAM; SSF52129; SSF52129; 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; Zymogen.
FT   PROPEP          1..9
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000004561"
FT   PROPEP          10..28
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000004562"
FT   CHAIN           29..175
FT                   /note="Caspase-3 subunit p17"
FT                   /id="PRO_0000004563"
FT   CHAIN           176..277
FT                   /note="Caspase-3 subunit p12"
FT                   /id="PRO_0000004564"
FT   ACT_SITE        121
FT                   /evidence="ECO:0000250"
FT   ACT_SITE        163
FT                   /evidence="ECO:0000250"
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;  31612 MW;  0BF3A4590A2828A3 CRC64;
     MENNETSVDS KSIKNFEVKT IHGSKSMDSG IYLDSSYKMD YPEMGVCIII NNKNFHKSTG
     MTPRSGTDVD AAKLRETFMA LKYEVRNKND LTREEIVELM KNASKEDHSK RSSFVCVILS
     HGDEGVIFGT DGPIDLKKLT SYFRGDYCRS LIGKPKLFII QACRGTELDC GIETDSGTED
     DMTCQKIPVE ADFLYAYSTA PGYYSWRNPK DGSWFIQSLC SMLKLYAHKL EFMHILTRVN
     RKVATEFESF SLDSTFHAKK QIPCIVSMLT KELYFYH