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 02-SEP-2026, entry version 206. 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 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). Triggers cell adhesion in sympathetic neurons CC through RET cleavage (By similarity). Also involved in axon pruning CC during brain development (By similarity). Cleaves DSG2 in response to CC apoptosis resulting in a loss of full length DSG2 at desmosome cell CC junctions and subsequent loss of cell-cell adhesion (By similarity). CC Also cleaves JUP in response to apoptosis (By similarity). Cleaves IL-1 CC beta between an Asp and an Ala, releasing the mature cytokine which is CC involved in a variety of inflammatory processes (By similarity). CC Cleaves and inhibits serine/threonine-protein kinase AKT1 in response CC to oxidative stress. Acts as an inhibitor of type I interferon CC production during virus-induced apoptosis by mediating cleavage of CC antiviral proteins CGAS, IRF3 and MAVS, thereby preventing cytokine CC overproduction. Also involved in pyroptosis by mediating cleavage and CC activation of gasdermin-E (GSDME) (By similarity). Cleaves XRCC4 and CC phospholipid scramblase proteins XKR4, XKR8 and XKR9, leading to CC 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}. 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 -!- 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. {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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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_001423828.1; NM_001436899.1. DR RefSeq; NP_001423829.1; NM_001436900.1. DR RefSeq; NP_037054.1; NM_012922.3. DR AlphaFoldDB; P55213; -. DR SMR; P55213; -. DR BioGRID; 247437; 1. DR ELM; P55213; -. DR FunCoup; P55213; 2466. 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; 10116-ENSRNOP00000014096; -. DR DNASU; 25402; -. DR Ensembl; ENSRNOT00000014095.7; ENSRNOP00000014096.3; ENSRNOG00000010475.7. DR Ensembl; ENSRNOT00055019386; ENSRNOP00055015619; ENSRNOG00055011427. DR Ensembl; ENSRNOT00060012174; ENSRNOP00060009190; ENSRNOG00060007399. DR Ensembl; ENSRNOT00065025146; ENSRNOP00065019686; ENSRNOG00065015182. DR GeneID; 25402; -. DR KEGG; rno:25402; -. DR AGR; RGD:2275; -. 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; HFTANHC; -. DR OrthoDB; 6116485at2759; -. DR PhylomeDB; P55213; -. 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-2028269; Signaling by Hippo. 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 cell types or tissues. DR ExpressionAtlas; P55213; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IDA:RGD. DR GO; GO:0005829; C:cytosol; ISO:RGD. DR GO; GO:0031264; C:death-inducing signaling complex; IDA:RGD. DR GO; GO:0098978; C:glutamatergic synapse; ISO:RGD. DR GO; GO:0043025; C:neuronal cell body; IDA:RGD. DR GO; GO:0005634; C:nucleus; ISO:RGD. DR GO; GO:0014069; C:postsynaptic density; 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; ISS:UniProtKB. 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:0008047; F:enzyme activator activity; IBA:GO_Central. 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; ISO: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:0072734; P:cellular response to staurosporine; ISO:RGD. DR GO; GO:0006974; P:DNA damage response; ISO:RGD. DR GO; GO:0030218; P:erythrocyte differentiation; ISO:RGD. DR GO; GO:0097194; P:execution phase of apoptosis; ISO:RGD. 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:0097193; P:intrinsic apoptotic signaling pathway; ISO: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: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:0001818; P:negative regulation of cytokine production; 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:0140639; P:positive regulation of pyroptotic inflammatory response; ISO:RGD. DR GO; GO:0030163; P:protein catabolic process; IDA:RGD. DR GO; GO:0051604; P:protein maturation; ISO:RGD. DR GO; GO:0016485; P:protein processing; ISO:RGD. DR GO; GO:0006508; P:proteolysis; IDA:UniProtKB. DR GO; GO:0070269; P:pyroptotic inflammatory response; ISO:RGD. DR GO; GO:0043523; P:regulation of neuron apoptotic process; IEP:RGD. DR GO; GO:0032880; P:regulation of protein localization; ISO:RGD. DR GO; GO:0031647; P:regulation of protein stability; IDA:UniProtKB. DR GO; GO:0098693; P:regulation of synaptic vesicle cycle; ISO:RGD. DR GO; GO:0043200; P:response to amino acid; IEP:RGD. DR GO; GO:0072347; P:response to anesthetic; IEP:RGD. DR GO; GO:0010996; P:response to auditory stimulus; ISO: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:0045471; P:response to ethanol; 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:1990418; P:response to insulin-like growth factor stimulus; 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: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:0036269; P:swimming behavior; IEP:RGD. DR GO; GO:0098883; P:synapse pruning; ISS:UniProtKB. DR GO; GO:0043029; P:T cell homeostasis; ISO:RGD. DR CDD; cd00032; CASc; 1. DR FunFam; 3.40.50.1460:FF:000001; Caspase-3 preproprotein; 1. DR Gene3D; 3.40.50.1460; -; 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_0000004589" FT PROPEP 10..28 FT /evidence="ECO:0000250|UniProtKB:P42574" FT /id="PRO_0000004590" FT CHAIN 29..175 FT /note="Caspase-3 subunit p17" FT /evidence="ECO:0000250|UniProtKB:P42574" FT /id="PRO_0000004591" FT CHAIN 176..277 FT /note="Caspase-3 subunit p12" FT /evidence="ECO:0000250|UniProtKB:P42574" FT /id="PRO_0000004592" 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" 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 //