CASP3_RAT
ID CASP3_RAT Reviewed; 277 AA.
AC P55213; P70543; P97699; Q62993;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1997, sequence version 2.
DT 03-AUG-2022, entry version 188.
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=IRP;
DE AltName: Full=LICE;
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 Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=8761296;
RA Juan T.S.-C., McNiece I.K., Jenkins N.A., Gilbert D.J., Copeland N.G.,
RA Fletcher F.A.;
RT "Molecular characterization of mouse and rat CPP32 beta gene encoding a
RT cysteine protease resembling interleukin-1 beta converting enzyme and CED-
RT 3.";
RL Oncogene 13:749-755(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Brain;
RX PubMed=9030616; DOI=10.1523/jneurosci.17-05-01561.1997;
RA Ni B., Wu X., Du Y., Su Y., Hamilton-Byrd E., Rockey P.K., Rosteck P. Jr.,
RA Poirier G.G., Paul S.M.;
RT "Cloning and expression of a rat brain interleukin-1beta-converting enzyme
RT (ICE)-related protease (IRP) and its possible role in apoptosis of cultured
RT cerebellar granule neurons.";
RL J. Neurosci. 17:1561-1569(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Heart;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-264.
RA Yakovlev A.G.;
RT "Cloning of the rat cysteine protease p32-beta.";
RL Submitted (JUN-1996) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 30-241.
RC TISSUE=Ovary;
RX PubMed=7588240; DOI=10.1210/endo.136.11.7588240;
RA Flaws J.A., Kugu K., Trbovich A.M., Desanti A., Tilly K.I.,
RA Hirshfield A.N., Tilly J.L.;
RT "Interleukin-1 beta-converting enzyme-related proteases (IRPs) and
RT mammalian cell death: dissociation of IRP-induced oligonucleosomal
RT endonuclease activity from morphological apoptosis in granulosa cells of
RT the ovarian follicle.";
RL Endocrinology 136:5042-5053(1995).
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 -!- TISSUE SPECIFICITY: Expressed in heart, brain, liver, and muscle but
CC not in kidney or testis.
CC -!- DEVELOPMENTAL STAGE: Highly expressed in neuron-enriched regions of the
CC developing brain, but down-regulated to low levels in the adult brain.
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; U49930; AAC52765.1; -; mRNA.
DR EMBL; U84410; AAB41792.1; -; mRNA.
DR EMBL; BC081854; AAH81854.1; -; mRNA.
DR EMBL; U58656; AAB02722.1; -; mRNA.
DR EMBL; U34685; AAC52261.1; -; mRNA.
DR PIR; I67437; I67437.
DR RefSeq; NP_037054.1; NM_012922.2.
DR RefSeq; XP_006253192.1; XM_006253130.3.
DR AlphaFoldDB; P55213; -.
DR SMR; P55213; -.
DR BioGRID; 247437; 1.
DR ELM; P55213; -.
DR IntAct; P55213; 1.
DR MINT; P55213; -.
DR STRING; 10116.ENSRNOP00000014096; -.
DR ChEMBL; CHEMBL1075185; -.
DR MEROPS; C14.003; -.
DR iPTMnet; P55213; -.
DR PhosphoSitePlus; P55213; -.
DR jPOST; P55213; -.
DR PaxDb; P55213; -.
DR PRIDE; P55213; -.
DR DNASU; 25402; -.
DR Ensembl; ENSRNOT00000014095; ENSRNOP00000014096; ENSRNOG00000010475.
DR GeneID; 25402; -.
DR KEGG; rno:25402; -.
DR CTD; 836; -.
DR RGD; 2275; Casp3.
DR eggNOG; KOG3573; Eukaryota.
DR GeneTree; ENSGT00940000153232; -.
DR HOGENOM; CLU_036904_2_0_1; -.
DR InParanoid; P55213; -.
DR OMA; ADESYRM; -.
DR OrthoDB; 984395at2759; -.
DR PhylomeDB; P55213; -.
DR TreeFam; TF102023; -.
DR BRENDA; 3.4.22.56; 5301.
DR Reactome; R-RNO-111459; Activation of caspases through apoptosome-mediated cleavage.
DR Reactome; R-RNO-111465; Apoptotic cleavage of cellular proteins.
DR Reactome; R-RNO-111469; SMAC, XIAP-regulated apoptotic response.
DR Reactome; R-RNO-140342; Apoptosis induced DNA fragmentation.
DR Reactome; R-RNO-205025; NADE modulates death signalling.
DR Reactome; R-RNO-264870; Caspase-mediated cleavage of cytoskeletal proteins.
DR Reactome; R-RNO-351906; Apoptotic cleavage of cell adhesion proteins.
DR Reactome; R-RNO-418889; Caspase activation via Dependence Receptors in the absence of ligand.
DR Reactome; R-RNO-449836; Other interleukin signaling.
DR Reactome; R-RNO-5620971; Pyroptosis.
DR PRO; PR:P55213; -.
DR Proteomes; UP000002494; Chromosome 16.
DR Bgee; ENSRNOG00000010475; Expressed in duodenum and 20 other tissues.
DR Genevisible; P55213; RN.
DR GO; GO:0008303; C:caspase complex; ISO:RGD.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0005829; C:cytosol; IDA:RGD.
DR GO; GO:0031264; C:death-inducing signaling complex; IDA:RGD.
DR GO; GO:0045121; C:membrane raft; IDA:RGD.
DR GO; GO:0043025; C:neuronal cell body; IDA:RGD.
DR GO; GO:0005634; C:nucleus; ISO:RGD.
DR GO; GO:0004190; F:aspartic-type endopeptidase activity; ISO:RGD.
DR GO; GO:0004861; F:cyclin-dependent protein serine/threonine kinase inhibitor activity; ISO:RGD.
DR GO; GO:0004197; F:cysteine-type endopeptidase activity; ISO:RGD.
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:0097200; F:cysteine-type endopeptidase activity involved in execution phase of apoptosis; ISO:RGD.
DR GO; GO:0008234; F:cysteine-type peptidase activity; IDA:RGD.
DR GO; GO:0005123; F:death receptor binding; IPI:RGD.
DR GO; GO:0004175; F:endopeptidase activity; ISS:UniProtKB.
DR GO; GO:0008233; F:peptidase activity; ISO:RGD.
DR GO; GO:0016005; F:phospholipase A2 activator activity; IMP:RGD.
DR GO; GO:0002020; F:protease binding; IPI:RGD.
DR GO; GO:0044877; F:protein-containing complex binding; IPI:RGD.
DR GO; GO:0061713; P:anterior neural tube closure; ISO:RGD.
DR GO; GO:0006915; P:apoptotic process; IMP:RGD.
DR GO; GO:0007413; P:axonal fasciculation; IMP:RGD.
DR GO; GO:0001782; P:B cell homeostasis; ISO:RGD.
DR GO; GO:0045165; P:cell fate commitment; ISO:RGD.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; ISO:RGD.
DR GO; GO:0071407; P:cellular response to organic cyclic compound; IEP:RGD.
DR GO; GO:0071310; P:cellular response to organic substance; ISO:RGD.
DR GO; GO:0072734; P:cellular response to staurosporine; ISO:RGD.
DR GO; GO:1904019; P:epithelial cell apoptotic process; IEA:Ensembl.
DR GO; GO:0030218; P:erythrocyte differentiation; ISO:RGD.
DR GO; GO:0097194; P:execution phase of apoptosis; ISO:RGD.
DR GO; GO:0097191; P:extrinsic apoptotic signaling pathway; ISO:RGD.
DR GO; GO:0044346; P:fibroblast apoptotic process; IEA:Ensembl.
DR GO; GO:0034349; P:glial cell apoptotic process; IEP:RGD.
DR GO; GO:0007507; P:heart development; ISO:RGD.
DR GO; GO:0021766; P:hippocampus development; IEP:RGD.
DR GO; GO:0035556; P:intracellular signal transduction; IMP:RGD.
DR GO; GO:0008627; P:intrinsic apoptotic signaling pathway in response to osmotic stress; ISO:RGD.
DR GO; GO:0030216; P:keratinocyte differentiation; ISO:RGD.
DR GO; GO:0007611; P:learning or memory; IMP:RGD.
DR GO; GO:0071887; P:leukocyte apoptotic process; IEP:RGD.
DR GO; GO:0001554; P:luteolysis; IEP:RGD.
DR GO; GO:0046007; P:negative regulation of activated T cell proliferation; ISO:RGD.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISO:RGD.
DR GO; GO:0030889; P:negative regulation of B cell proliferation; ISO:RGD.
DR GO; GO:0045786; P:negative regulation of cell cycle; ISO:RGD.
DR GO; GO:0045736; P:negative regulation of cyclin-dependent protein serine/threonine kinase activity; ISO:RGD.
DR GO; GO:0051402; P:neuron apoptotic process; ISO:RGD.
DR GO; GO:0030182; P:neuron differentiation; IEP:RGD.
DR GO; GO:0048011; P:neurotrophin TRK receptor signaling pathway; ISO:RGD.
DR GO; GO:1902004; P:positive regulation of amyloid-beta formation; IDA:UniProtKB.
DR GO; GO:1902512; P:positive regulation of apoptotic DNA fragmentation; ISO:RGD.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IMP:RGD.
DR GO; GO:0043525; P:positive regulation of neuron apoptotic process; IMP:RGD.
DR GO; GO:0030163; P:protein catabolic process; IDA:RGD.
DR GO; GO:0016485; P:protein processing; ISO:RGD.
DR GO; GO:0006508; P:proteolysis; IDA:UniProtKB.
DR GO; GO:0031647; P:regulation of protein stability; IDA:UniProtKB.
DR GO; GO:0043200; P:response to amino acid; IEP:RGD.
DR GO; GO:0046677; P:response to antibiotic; IEP:RGD.
DR GO; GO:0032025; P:response to cobalt ion; IEP:RGD.
DR GO; GO:0032355; P:response to estradiol; IEP:RGD.
DR GO; GO:0051384; P:response to glucocorticoid; IEP:RGD.
DR GO; GO:0009749; P:response to glucose; IDA:RGD.
DR GO; GO:0042542; P:response to hydrogen peroxide; IDA:RGD.
DR GO; GO:0001666; P:response to hypoxia; IEP:RGD.
DR GO; GO:0032496; P:response to lipopolysaccharide; IEP:RGD.
DR GO; GO:0010038; P:response to metal ion; IEP:RGD.
DR GO; GO:0035094; P:response to nicotine; IEP:RGD.
DR GO; GO:0014070; P:response to organic cyclic compound; IEP:RGD.
DR GO; GO:0010033; P:response to organic substance; IEP:RGD.
DR GO; GO:0009411; P:response to UV; ISO:RGD.
DR GO; GO:0009611; P:response to wounding; ISO:RGD.
DR GO; GO:0010165; P:response to X-ray; IEP:RGD.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEP:RGD.
DR GO; GO:0007605; P:sensory perception of sound; ISO:RGD.
DR GO; GO:0051146; P:striated muscle cell differentiation; IEP:RGD.
DR GO; GO:0043029; P:T cell homeostasis; ISO:RGD.
DR GO; GO:0042060; P:wound healing; IEP:RGD.
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_0000004589"
FT PROPEP 10..28
FT /evidence="ECO:0000250"
FT /id="PRO_0000004590"
FT CHAIN 29..175
FT /note="Caspase-3 subunit p17"
FT /id="PRO_0000004591"
FT CHAIN 176..277
FT /note="Caspase-3 subunit p12"
FT /id="PRO_0000004592"
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"
FT CONFLICT 25..29
FT /note="KSMDS -> QVD (in Ref. 4; AAB02722)"
FT /evidence="ECO:0000305"
FT CONFLICT 170
FT /note="C -> S (in Ref. 5; AAC52261)"
FT /evidence="ECO:0000305"
FT CONFLICT 178
FT /note="T -> A (in Ref. 5; AAC52261)"
FT /evidence="ECO:0000305"
FT CONFLICT 182
FT /note="M -> V (in Ref. 5; AAC52261)"
FT /evidence="ECO:0000305"
FT CONFLICT 187
FT /note="I -> K (in Ref. 5; AAC52261)"
FT /evidence="ECO:0000305"
FT CONFLICT 190
FT /note="E -> G (in Ref. 2; AAB41792)"
FT /evidence="ECO:0000305"
FT CONFLICT 199
FT /note="T -> S (in Ref. 5; AAC52261)"
FT /evidence="ECO:0000305"
FT CONFLICT 211
FT /note="D -> G (in Ref. 5; AAC52261)"
FT /evidence="ECO:0000305"
FT CONFLICT 236
FT /note="L -> I (in Ref. 4; AAB02722)"
FT /evidence="ECO:0000305"
FT CONFLICT 245
FT /note="T -> M (in Ref. 2; AAB41792)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 277 AA; 31492 MW; ADABF418E2507402 CRC64;
MDNNETSVDS KSINNFETKT IHGSKSMDSG IYLDSSYKMD YPEMGLCIII NNKNFHKSTG
MSARNGTDVD AANLRETFMA LKYEVRNKND LTREEIMELM DSVSKEDHSK RSSFVCVILS
HGDEGVIFGT NGPVDLKKLT SFFRGDYCRS LTGKPKLFII QACRGTELDC GIETDSGTDD
DMACQKIPVE ADFLYAYSTA PGYYSWRNSR DGSWFIQSLC AMLKLYAHKL EFMHILTRVN
RKVATEFESF SLDATFHAKK QIPCIVSMLT KELYFYH
