CASP3_RABIT
ID CASP3_RABIT Reviewed; 277 AA.
AC Q8MJC3;
DT 11-OCT-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 1.
DT 25-MAY-2022, entry version 117.
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 Contains:
DE RecName: Full=Caspase-3 subunit p17;
DE Contains:
DE RecName: Full=Caspase-3 subunit p12;
DE Flags: Precursor;
GN Name=CASP3;
OS Oryctolagus cuniculus (Rabbit).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae; Oryctolagus.
OX NCBI_TaxID=9986;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=9575916; DOI=10.1152/ajpheart.1998.274.4.h1132;
RA Wang H., Keiser J.A.;
RT "Molecular characterization of rabbit CPP32 and its function in vascular
RT smooth muscle cell apoptosis.";
RL Am. J. Physiol. 274:H1132-H1140(1998).
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; AF506008; AAM47195.1; -; mRNA.
DR RefSeq; NP_001075586.1; NM_001082117.1.
DR AlphaFoldDB; Q8MJC3; -.
DR SMR; Q8MJC3; -.
DR STRING; 9986.ENSOCUP00000005723; -.
DR MEROPS; C14.003; -.
DR GeneID; 100008840; -.
DR KEGG; ocu:100008840; -.
DR CTD; 836; -.
DR eggNOG; KOG3573; Eukaryota.
DR InParanoid; Q8MJC3; -.
DR Proteomes; UP000001811; 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_0000004585"
FT PROPEP 10..28
FT /evidence="ECO:0000250"
FT /id="PRO_0000004586"
FT CHAIN 29..175
FT /note="Caspase-3 subunit p17"
FT /evidence="ECO:0000250"
FT /id="PRO_0000004587"
FT CHAIN 176..277
FT /note="Caspase-3 subunit p12"
FT /evidence="ECO:0000250"
FT /id="PRO_0000004588"
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; 31653 MW; 7BA4B12E6D43629A CRC64;
MENNETSVDA KSIKNLETQT IHGSKSMDSG KYLDNSYKMD YPEMGLCIII NNKNFHKNTG
MSSRSGTDVN AANLGETFMN LKYEVRNKND LTREEIMELM YNVSKEDHSK RSSFICVILS
HGDEGVIYGT NGPIELKKLT SFFRGDYCRS LTGKPKLFII QACRGTELDS GIETDSGVDY
DMACQKIPVE ADFLYAYSTA PGYYSWRNSE EGSWFIQSLC AMLKEYAHKL EFMHILTRVN
RKVATEFESY SLDATFHAKK QIPCIVSMLT KELYFYH
