CASP3_PIG
ID CASP3_PIG Reviewed; 277 AA.
AC Q95ND5;
DT 11-OCT-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 25-MAY-2022, entry version 120.
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;
OS Sus scrofa (Pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus.
OX NCBI_TaxID=9823;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=11440638; DOI=10.1089/107999001750277880;
RA Muneta Y., Shimojima Y., Mori Y.;
RT "Porcine caspase-3: its cloning and activity during apoptosis of PK15 cells
RT induced by porcine Fas ligand.";
RL J. Interferon Cytokine Res. 21:409-415(2001).
RN [2]
RP INTERACTION WITH ASFV INHIBITOR OF APOPTOSIS PROTEIN.
RX PubMed=11222676; DOI=10.1128/jvi.75.6.2535-2543.2001;
RA Nogal M.L., Gonzalez de Buitrago G., Rodriguez C., Cubelos B.,
RA Carrascosa A.L., Salas M.L., Revilla Y.;
RT "African swine fever virus IAP homologue inhibits caspase activation and
RT promotes cell survival in mammalian cells.";
RL J. Virol. 75:2535-2543(2001).
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 (By similarity). Interacts with BIRC6/bruce (By similarity).
CC {ECO:0000250}.
CC -!- SUBUNIT: (Microbial infection) Subunit p17 interacts with African swine
CC fever virus (ASFV) inhibitor of apoptosis protein.
CC {ECO:0000269|PubMed:11222676}.
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; AB029345; BAB55544.1; -; mRNA.
DR RefSeq; NP_999296.1; NM_214131.1.
DR AlphaFoldDB; Q95ND5; -.
DR SMR; Q95ND5; -.
DR STRING; 9823.ENSSSCP00000016724; -.
DR MEROPS; C14.003; -.
DR PaxDb; Q95ND5; -.
DR PeptideAtlas; Q95ND5; -.
DR PRIDE; Q95ND5; -.
DR GeneID; 397244; -.
DR KEGG; ssc:397244; -.
DR CTD; 836; -.
DR eggNOG; KOG3573; Eukaryota.
DR InParanoid; Q95ND5; -.
DR OrthoDB; 984395at2759; -.
DR Proteomes; UP000008227; Unplaced.
DR Proteomes; UP000314985; Unplaced.
DR GO; GO:0005737; C:cytoplasm; IDA:AgBase.
DR GO; GO:0005634; C:nucleus; IDA:AgBase.
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:0006915; P:apoptotic process; IBA:GO_Central.
DR GO; GO:0030218; P:erythrocyte differentiation; IBA:GO_Central.
DR GO; GO:0030216; P:keratinocyte differentiation; IBA:GO_Central.
DR GO; GO:0030182; P:neuron differentiation; IBA:GO_Central.
DR GO; GO:1902004; P:positive regulation of amyloid-beta formation; ISS:UniProtKB.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IBA:GO_Central.
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 1: Evidence at protein level;
KW Acetylation; Apoptosis; Cytoplasm; Host-virus interaction; Hydrolase;
KW Phosphoprotein; Protease; Reference proteome; S-nitrosylation;
KW Thiol protease; Zymogen.
FT PROPEP 1..9
FT /evidence="ECO:0000250"
FT /id="PRO_0000004581"
FT PROPEP 10..28
FT /evidence="ECO:0000250"
FT /id="PRO_0000004582"
FT CHAIN 29..175
FT /note="Caspase-3 subunit p17"
FT /evidence="ECO:0000250"
FT /id="PRO_0000004583"
FT CHAIN 176..277
FT /note="Caspase-3 subunit p12"
FT /evidence="ECO:0000250"
FT /id="PRO_0000004584"
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; 31379 MW; 616C0F56141B012B CRC64;
MENNKTSVDS KSIKTLETKI LHGSKSMDSG ISLDVSYKMD YPEMGLCIII NNKNFDKNTG
MACRSGTDVD AANLRETFTN LKYEVRNKND LTREEILELM HSVSKEDHSK RSSFICVLLS
HGEEGKIFGT NGPVDLKKLT SFFRGDCCRT LTGKPKLFII QACRGTELDC GIETDSGTED
DMACQKIPVE ADFLYAYSTA PGYYSWRNSK DGSWFIQSLC AALKQYVHKL ELMHILTRVN
RKVAVEFESF STDSTFHAKK QIPCIVSMLT KELYFYH
