| IED ID | IndEnz0002014100 |
| Enzyme Type ID | protease014100 |
| Protein Name |
Caspase-9 CASP-9 EC 3.4.22.62 Apoptotic protease Mch-6 Apoptotic protease-activating factor 3 APAF-3 ICE-like apoptotic protease 6 ICE-LAP6 Cleaved into: Caspase-9 subunit p35; Caspase-9 subunit p10 |
| Gene Name | CASP9 MCH6 |
| 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 | MDEADRRLLRRCRLRLVEELQVDQLWDALLSRELFRPHMIEDIQRAGSGSRRDQARQLIIDLETRGSQALPLFISCLEDTGQDMLASFLRTNRQAAKLSKPTLENLTPVVLRPEIRKPEVLRPETPRPVDIGSGGFGDVGALESLRGNADLAYILSMEPCGHCLIINNVNFCRESGLRTRTGSNIDCEKLRRRFSSLHFMVEVKGDLTAKKMVLALLELAQQDHGALDCCVVVILSHGCQASHLQFPGAVYGTDGCPVSVEKIVNIFNGTSCPSLGGKPKLFFIQACGGEQKDHGFEVASTSPEDESPGSNPEPDATPFQEGLRTFDQLDAISSLPTPSDIFVSYSTFPGFVSWRDPKSGSWYVETLDDIFEQWAHSEDLQSLLLRVANAVSVKGIYKQMPGCFNFLRKKLFFKTS |
| Enzyme Length | 416 |
| Uniprot Accession Number | P55211 |
| Absorption | |
| Active Site | ACT_SITE 237; /evidence=ECO:0000250; ACT_SITE 287; /evidence=ECO:0000250 |
| Activity Regulation | ACTIVITY REGULATION: Inhibited by the effector protein NleF that is produced by pathogenic E.coli; this inhibits apoptosis. {ECO:0000269|PubMed:23516580}. |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: Reaction=Strict requirement for an Asp residue at position P1 and with a marked preference for His at position P2. It has a preferred cleavage sequence of Leu-Gly-His-Asp-|-Xaa.; EC=3.4.22.62; Evidence={ECO:0000269|PubMed:23516580}; |
| DNA Binding | |
| EC Number | 3.4.22.62 |
| Enzyme Function | FUNCTION: Involved in the activation cascade of caspases responsible for apoptosis execution. Binding of caspase-9 to Apaf-1 leads to activation of the protease which then cleaves and activates caspase-3. Promotes DNA damage-induced apoptosis in a ABL1/c-Abl-dependent manner. Proteolytically cleaves poly(ADP-ribose) polymerase (PARP).; FUNCTION: Isoform 2 lacks activity is an dominant-negative inhibitor of caspase-9. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Active site (2); Alternative sequence (4); Beta strand (15); Chain (2); Domain (1); Helix (16); Modified residue (5); Mutagenesis (1); Natural variant (11); Propeptide (2); Region (1); Sequence conflict (6); Turn (5) |
| Keywords | 3D-structure;Alternative splicing;Apoptosis;Hydrolase;Phosphoprotein;Protease;Reference proteome;Thiol protease;Zymogen |
| Interact With | O14727; Q13490; Q96CA5; Q6PIA0; P42574; P43146; Q13418; P98170; Q8XAL7; Itself |
| Induction | |
| Subcellular Location | |
| Modified Residue | MOD_RES 125; /note="Phosphothreonine; by MAPK1"; /evidence="ECO:0000269|PubMed:12792650, ECO:0007744|PubMed:18669648"; MOD_RES 153; /note="Phosphotyrosine; by ABL1"; /evidence="ECO:0000269|PubMed:15657060"; MOD_RES 302; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:18669648"; MOD_RES 307; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:20068231"; MOD_RES 310; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:23186163" |
| Post Translational Modification | PTM: Cleavages at Asp-315 by granzyme B and at Asp-330 by caspase-3 generate the two active subunits. Caspase-8 and -10 can also be involved in these processing events.; PTM: Phosphorylated at Thr-125 by MAPK1/ERK2. Phosphorylation at Thr-125 is sufficient to block caspase-9 processing and subsequent caspase-3 activation. Phosphorylation on Tyr-153 by ABL1/c-Abl; occurs in the response of cells to DNA damage. {ECO:0000269|PubMed:12792650, ECO:0000269|PubMed:15657060}. |
| Signal Peptide | |
| Structure 3D | Electron microscopy (2); X-ray crystallography (8) |
| Cross Reference PDB | 1JXQ; 1NW9; 2AR9; 3D9T; 3V3K; 3YGS; 4RHW; 5JUY; 5WVC; 5WVE; |
| Mapped Pubmed ID | 10206961; 10329646; 10376594; 10929711; 11024045; 11084335; 11230124; 11242052; 11248093; 11257231; 11408476; 11701129; 11752425; 11801602; 11801603; 11870543; 11905052; 11919192; 12011067; 12021264; 12055227; 12096338; 12145703; 12372609; 12393263; 12393884; 12566444; 12620239; 12637514; 12732844; 12749848; 12782307; 12804035; 12824163; 12914932; 12954616; 14566819; 14684629; 14701803; 14747474; 14960576; 14982875; 14991812; 14993223; 15214043; 15220451; 15271982; 15280366; 15300255; 15473998; 15485395; 15485396; 15573119; 15629764; 15657349; 15674327; 15703181; 15811855; 15935070; 15941357; 16038259; 16181301; 16189514; 16242324; 16260615; 16287866; 16300929; 16337360; 16505307; 16505493; 16687442; 16689829; 16716256; 16888006; 16916640; 16936772; 17030903; 17071630; 17079734; 17285546; 17291493; 17299206; 17379327; 17437405; 17466630; 17504303; 17534194; 17626072; 17893147; 17899380; 18022362; 18054197; 18083711; 18086147; 18202770; 18297401; 18381704; 18415681; 18619610; 18632964; 18676680; 18723680; 18813792; 18840411; 18840507; 19016842; 19052714; 19058789; 19074885; 19081073; 19141860; 19153467; 19159073; 19170196; 19183163; 19219602; 19238172; 19269008; 19359048; 19412632; 19414860; 19465923; 19493480; 19494828; 19550122; 19573080; 19586613; 19625176; 19626422; 19655415; 19692168; 19724860; 19741144; 19770581; 19773279; 19789190; 19807657; 19826114; 19906200; 19909554; 19913121; 20013803; 20022954; 20042134; 20060927; 20071584; 20227371; 20227384; 20357690; 20379614; 20402676; 20453000; 20490276; 20494139; 20628086; 20644561; 20650551; 20661084; 20667824; 20800603; 20804486; 20855536; 20887385; 20959405; 20978129; 21045158; 21048031; 21078168; 21091209; 21117896; 21142842; 21178828; 21219631; 21266831; 21282934; 21284734; 21297999; 21382445; 21396853; 21461653; 21538054; 21555338; 21565459; 21612408; 21622622; 21637382; 21644232; 21659556; 21757755; 21785112; 21827945; 21868008; 21869827; 21944661; 21957492; 21988832; 22086301; 22120515; 22191568; 22306364; 22339913; 22573662; 22616010; 22679284; 22683311; 22926545; 22944165; 22974165; 22981751; 23038270; 23109891; 23203690; 23303631; 23396972; 23424205; 23443079; 23479167; 23572523; 23615977; 23645041; 23650375; 23652278; 23725396; 23867824; 24161344; 24346702; 24362031; 24367089; 24377517; 24405603; 24424093; 24427328; 24530529; 24592539; 24661197; 24839934; 24879622; 24980229; 25059065; 25214386; 25241761; 25313070; 25330190; 25356864; 25370148; 25416956; 25519916; 25569260; 25665064; 25815518; 26014377; 26024713; 26290316; 26323553; 26755433; 26984736; 27032384; 27046389; 27084536; 27141571; 27197231; 27245202; 27345387; 27425441; 27580936; 27618007; 27697150; 27748882; 27865841; 27899026; 27935156; 27942018; 28091912; 28111022; 28143931; 28298075; 28358701; 28870924; 28972559; 29066624; 29352212; 29352269; 29358613; 29365368; 29416675; 29500231; 29511177; 29561705; 29658604; 29842999; 29844931; 29845240; 30236204; 30843771; 30903678; 30907242; 31092436; 31329620; 31398407; 31673995; 31818185; 31877317; 31927634; 32105000; 32196578; 32210117; 32225068; 32397873; 32573644; 32816327; 32862582; 33933463; 34019244; 34288800; 9230442; 9390557; 9812896; 9922454; |
| Motif | |
| Gene Encoded By | |
| Mass | 46,281 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | |
| Cross Reference Brenda | 3.4.22.62; |