IED Industry Enzyme Database

Detail Information for IndEnz0002019072
IED ID IndEnz0002019072
Enzyme Type ID protease019072
Protein Name Caspase-3
CASP-3
EC 3.4.22.56
Apopain
Cysteine protease CPP32
CPP-32
Protein Yama
SREBP cleavage activity 1
SCA-1

Cleaved into: Caspase-3 subunit p17; Caspase-3 subunit p12
Gene Name CASP3 CPP32
Organism Homo sapiens (Human)
Taxonomic Lineage cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Euarchontoglires Primates Haplorrhini Simiiformes Catarrhini Hominoidea (apes) Hominidae (great apes) Homininae Homo Homo sapiens (Human)
Enzyme Sequence MENTENSVDSKSIKNLEPKIIHGSESMDSGISLDNSYKMDYPEMGLCIIINNKNFHKSTGMTSRSGTDVDAANLRETFRNLKYEVRNKNDLTREEIVELMRDVSKEDHSKRSSFVCVLLSHGEEGIIFGTNGPVDLKKITNFFRGDRCRSLTGKPKLFIIQACRGTELDCGIETDSGVDDDMACHKIPVEADFLYAYSTAPGYYSWRNSKDGSWFIQSLCAMLKQYADKLEFMHILTRVNRKVATEFESFSFDATFHAKKQIPCIVSMLTKELYFYH
Enzyme Length 277
Uniprot Accession Number P42574
Absorption
Active Site ACT_SITE 121; /evidence=ECO:0000250; ACT_SITE 163; /evidence=ECO:0000250
Activity Regulation ACTIVITY REGULATION: Inhibited by isatin sulfonamides.
Binding Site
Calcium Binding
catalytic Activity CATALYTIC ACTIVITY: Reaction=Strict requirement for an Asp residue at positions P1 and P4. It has a preferred cleavage sequence of Asp-Xaa-Xaa-Asp-|- with a hydrophobic amino-acid residue at P2 and a hydrophilic amino-acid residue at P3, although Val or Ala are also accepted at this position.; EC=3.4.22.56; Evidence={ECO:0000269|PubMed:23152800, ECO:0000269|PubMed:23845944, ECO:0000269|PubMed:30878284, ECO:0000269|PubMed:33725486};
DNA Binding
EC Number 3.4.22.56
Enzyme Function FUNCTION: Involved in the activation cascade of caspases responsible for apoptosis execution (PubMed:7596430). At the onset of apoptosis it proteolytically cleaves poly(ADP-ribose) polymerase (PARP) at a '216-Asp-|-Gly-217' bond (PubMed:7774019). Cleaves and activates sterol regulatory element binding proteins (SREBPs) between the basic helix-loop-helix leucine zipper domain and the membrane attachment domain. Cleaves and activates caspase-6, -7 and -9 (PubMed:7596430). Involved in the cleavage of huntingtin (PubMed:8696339). Triggers cell adhesion in sympathetic neurons through RET cleavage (PubMed:21357690). Cleaves and inhibits serine/threonine-protein kinase AKT1 in response to oxidative stress (PubMed:23152800). Acts as an inhibitor of type I interferon production during virus-induced apoptosis by mediating cleavage of antiviral proteins CGAS, IRF3 and MAVS, thereby preventing cytokine overproduction (PubMed:30878284). Cleaves XRCC4 and phospholipid scramblase proteins XKR4, XKR8 and XKR9, leading to promote phosphatidylserine exposure on apoptotic cell surface (PubMed:23845944, PubMed:33725486). {ECO:0000269|PubMed:21357690, ECO:0000269|PubMed:23152800, ECO:0000269|PubMed:23845944, ECO:0000269|PubMed:30878284, ECO:0000269|PubMed:33725486, ECO:0000269|PubMed:7596430, ECO:0000269|PubMed:7774019, ECO:0000269|PubMed:8696339}.
Temperature Dependency
PH Dependency
Pathway
nucleotide Binding
Features Active site (2); Beta strand (12); Chain (2); Helix (9); Modified residue (4); Natural variant (2); Propeptide (2); Sequence conflict (1); Turn (5)
Keywords 3D-structure;Acetylation;Apoptosis;Cytoplasm;Direct protein sequencing;Hydrolase;Phosphoprotein;Protease;Reference proteome;S-nitrosylation;Thiol protease;Zymogen
Interact With O43823; Q9Y243; P05067; P54252; P55212; P55211; Q14203-5; P42858; Q00987; O60551; P09874; Q5JUK2; P10599; Q9BYP7; P98170
Induction
Subcellular Location SUBCELLULAR LOCATION: Cytoplasm.
Modified Residue MOD_RES 1; /note="N-acetylmethionine"; /evidence="ECO:0007744|PubMed:19413330, ECO:0007744|PubMed:22223895"; MOD_RES 11; /note="N6-acetyllysine"; /evidence="ECO:0000250|UniProtKB:P70677"; MOD_RES 26; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:23186163"; MOD_RES 163; /note="S-nitrosocysteine; in inhibited form"; /evidence="ECO:0000269|PubMed:10213689"
Post Translational Modification PTM: Cleavage by granzyme B, caspase-6, caspase-8 and caspase-10 generates the two active subunits. Additional processing of the propeptides is likely due to the autocatalytic activity of the activated protease. Active heterodimers between the small subunit of caspase-7 protease and the large subunit of caspase-3 also occur and vice versa.; PTM: S-nitrosylated on its catalytic site cysteine in unstimulated human cell lines and denitrosylated upon activation of the Fas apoptotic pathway, associated with an increase in intracellular caspase activity. Fas therefore activates caspase-3 not only by inducing the cleavage of the caspase zymogen to its active subunits, but also by stimulating the denitrosylation of its active site thiol. {ECO:0000269|PubMed:10213689}.
Signal Peptide
Structure 3D X-ray crystallography (100)
Cross Reference PDB 1CP3; 1GFW; 1I3O; 1NME; 1NMQ; 1NMS; 1PAU; 1QX3; 1RE1; 1RHJ; 1RHK; 1RHM; 1RHQ; 1RHR; 1RHU; 2C1E; 2C2K; 2C2M; 2C2O; 2CDR; 2CJX; 2CJY; 2CNK; 2CNL; 2CNN; 2CNO; 2DKO; 2H5I; 2H5J; 2H65; 2J30; 2J31; 2J32; 2J33; 2XYG; 2XYH; 2XYP; 2XZD; 2XZT; 2Y0B; 3DEH; 3DEI; 3DEJ; 3DEK; 3EDQ; 3GJQ; 3GJR; 3GJS; 3GJT; 3H0E; 3ITN; 3KJF; 3PCX; 3PD0; 3PD1; 4DCJ; 4DCO; 4DCP; 4EHA; 4EHD; 4EHF; 4EHH; 4EHK; 4EHL; 4EHN; 4JJE; 4JQY; 4JQZ; 4JR0; 4PRY; 4PS0; 4QTX; 4QTY; 4QU0; 4QU5; 4QU8; 4QU9; 4QUA; 4QUB; 4QUD; 4QUE; 4QUG; 4QUH; 4QUI; 4QUJ; 4QUL; 5I9B; 5I9T; 5IAB; 5IAE; 5IAG; 5IAJ; 5IAK; 5IAN; 5IAR; 5IAS; 5IBC; 5IBP; 5IBR; 5IC4;
Mapped Pubmed ID 10082566; 10200466; 10206961; 10319819; 10454555; 10490026; 10564664; 10602493; 10608812; 10671544; 10672017; 10712510; 10713703; 10748026; 10823823; 10899937; 10921886; 11042212; 11053413; 11058115; 11076937; 11084335; 11106668; 11230124; 11242052; 11248093; 11257231; 11257232; 11261798; 11278283; 11278797; 11283607; 11313965; 11331419; 11387206; 11423904; 11437602; 11470874; 11500511; 11526478; 11550094; 11602184; 11689006; 11741893; 11787859; 11825902; 11830582; 11840332; 11866986; 11931755; 11960384; 11972398; 11981455; 11989976; 11992386; 12004072; 12011067; 12032677; 12036886; 12044963; 12055227; 12070005; 12070657; 12080079; 12107159; 12118383; 12124386; 12145703; 12149654; 12151338; 12169388; 12181128; 12186978; 12210761; 12228224; 12297281; 12390838; 12393869; 12393901; 12397210; 12483536; 12511568; 12515825; 12563278; 12566444; 12576296; 12576443; 12579342; 12581734; 12598529; 12605885; 12606589; 12611892; 12621124; 12643601; 12657644; 12677451; 12686427; 12700630; 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16689860; 16716256; 16781734; 16787777; 16791842; 16802364; 16808908; 16835231; 16866351; 16882668; 16884727; 16894574; 16931214; 16935258; 16948902; 16949642; 16955788; 16970398; 16977583; 16983089; 17013756; 17023557; 17038954; 17065568; 17071630; 17073446; 17080552; 17114647; 17118559; 17121821; 17123522; 17124493; 17130234; 17141888; 17143787; 17167422; 17172814; 17198755; 17217622; 17219053; 17235653; 17245643; 17261582; 17272816; 17297457; 17301822; 17321792; 17324936; 17379327; 17412564; 17413988; 17430778; 17436592; 17437405; 17462862; 17495975; 17498346; 17505517; 17525639; 17534194; 17544405; 17559062; 17597071; 17606719; 17606900; 17616526; 17645689; 17689858; 17698513; 17721932; 17724022; 17805550; 17880920; 17908973; 17950632; 17978580; 17981569; 17983802; 17989718; 18000616; 18047842; 18054197; 18055116; 18058802; 18060501; 18083346; 18086147; 18088367; 18154733; 18155705; 18155731; 18164959; 18171980; 18209072; 18211414; 18227733; 18256758; 18256791; 18296636; 18297401; 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29532884; 29601890; 29659498; 29680307; 29737550; 29750299; 29801534; 29842999; 29891674; 30019295; 30176316; 30207307; 30354994; 30371113; 30446907; 30604868; 30710195; 30725182; 30747227; 30794682; 30903678; 30908935; 30915355; 30918127; 31029152; 31038819; 31127027; 31268416; 31383790; 31392262; 31441002; 31498791; 31512106; 31587185; 31670857; 31673995; 31702036; 31799636; 31804757; 31856190; 31874420; 31884867; 31940955; 32109412; 32151194; 32188940; 32572905; 32573644; 32816327; 32985214; 33110232; 33165988; 33171188; 33180744; 33354577; 33448281; 33495811; 33500339; 33604948; 33689708; 33737560; 33856706; 33883691; 33920463; 34019244; 34021497; 34155600; 34256094; 34273529; 34278472; 34571081; 34727826; 7489707; 8804412; 8976194; 9108473; 9230442; 9252332; 9267021; 9323209; 9351817; 9367996; 9368003; 9390557; 9395403; 9422780; 9431985; 9525868; 9545236; 9624143; 9660939; 9685336; 9751706; 9786869; 9796814; 9799125; 9930654; 9973322;
Motif
Gene Encoded By
Mass 31,608
Kinetics
Metal Binding
Rhea ID
Cross Reference Brenda 3.4.22.56;