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Details on Person UniProt:P55211 CASP9

Class:Id	ReferenceGeneProduct:57034
_chainChangeLog	propeptide:1- added on Fri February 6 2015;chain:-315 added on Fri February 6 2015;propeptide:316-330 added on Fri February 6 2015;chain:331-416 added on Fri February 6 2015
_displayName	UniProt:P55211 CASP9
_timestamp	2025-02-21 18:44:54
chain	propeptide:1- chain:-315 propeptide:316-330 chain:331-416
checksum	78E0180DF2A3BDD2
comment	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 effector caspases caspase-3 (CASP3) or caspase-7 (CASP7). Promotes DNA damage-induced apoptosis in a ABL1/c-Abl-dependent manner. Proteolytically cleaves poly(ADP-ribose) polymerase (PARP). Cleaves BIRC6 following inhibition of BIRC6-caspase binding by DIABLO/SMAC (PubMed:36758105, PubMed:36758106).FUNCTION Lacks activity is an dominant-negative inhibitor of caspase-9.CATALYTIC ACTIVITY 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.ACTIVITY REGULATION Inhibited by the effector protein NleF that is produced by pathogenic E.coli; this inhibits apoptosis (PubMed:23516580). Inhibited by BIRC6; following inhibition of BIRC6-caspase binding by DIABLO/SMAC, BIRC6 is subjected to caspase cleavage, leading to an increase in active caspases (PubMed:36758105, PubMed:36758106).SUBUNIT Heterotetramer that consists of two anti-parallel arranged heterodimers, each one formed by a 35 kDa (p35) and a 10 kDa (p10) subunit. Caspase-9 and APAF1 bind to each other via their respective NH2-terminal CED-3 homologous domains in the presence of cytochrome C and ATP. Interacts (inactive form) with EFHD2. Interacts with HAX1. Interacts with BIRC2/c-IAP1, XIAP/BIRC4, BIRC5/survivin, BIRC6/bruce and BIRC7/livin. Interacts with ABL1 (via SH3 domain); the interaction is direct and increases in the response of cells to genotoxic stress and ABL1/c-Abl activation. Interacts with BCL2L10 (PubMed:19255499). Interacts with NleF from pathogenic E.coli.INTERACTION Ubiquitous, with highest expression in the heart, moderate expression in liver, skeletal muscle, and pancreas. Low levels in all other tissues. Within the heart, specifically expressed in myocytes.DEVELOPMENTAL STAGE Expressed at low levels in fetal heart, at moderate levels in neonate heart, and at high levels in adult heart.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.PTM (Microbial infection) ADP-riboxanation by C.violaceum CopC blocks CASP9 processing, preventing CASP9 activation and ability to mediate intrinsic apoptosis.PTM Ubiquitinated by BIRC6; this activity is inhibited by DIABLO/SMAC.MISCELLANEOUS May function as an endogenous apoptotic inhibitor, inhibits the BAX-mediated cleavage of procaspase-3.SIMILARITY Belongs to the peptidase C14A family.ONLINE INFORMATION Caspase-9 entry
description	recommendedName: Caspase-9 shortName: CASP-9 ecNumber evidence="14 17 18"3.4.22.62 alternativeName: Apoptotic protease Mch-6 alternativeName: Apoptotic protease-activating factor 3 shortName: APAF-3 alternativeName: ICE-like apoptotic protease 6 shortName: ICE-LAP6 component recommendedName: Caspase-9 subunit p35 /component component recommendedName: Caspase-9 subunit p10 /component
geneName	CASP9 MCH6
identifier	P55211
isSequenceChanged	FALSE
keyword	3D-structure Alternative splicing Apoptosis Hydrolase Phosphoprotein Protease Proteomics identification Reference proteome Thiol protease Ubl conjugation Zymogen
modified	[InstanceEdit:9836292] Weiser, Joel, 2023-05-25 [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9926675] Weiser, Joel, 2024-11-03 [InstanceEdit:9939033] Weiser, Joel, 2025-02-21
name	CASP9
referenceDatabase	[ReferenceDatabase:2] UniProt
referenceGene	[ReferenceDNASequence:8992341] ENSEMBL:ENSG00000132906 CASP9 [Homo sapiens]
secondaryIdentifier	CASP9_HUMAN B4E1A3 O95348 Q53Y70 Q5JRU9 Q5UGI1 Q92852 Q9BQ62 Q9UEQ3 Q9UIJ8
sequenceLength	416
species	[Species:48887] Homo sapiens
(isoformParent)	[ReferenceIsoform:148680] UniProt:P55211-2 CASP9 [Homo sapiens] [ReferenceIsoform:404437] UniProt:P55211-1 CASP9 [Homo sapiens] [ReferenceIsoform:8977748] UniProt:P55211-3 CASP9 [Homo sapiens] [ReferenceIsoform:8977749] UniProt:P55211-4 CASP9 [Homo sapiens]
(referenceEntity)	[EntityWithAccessionedSequence:57033] CASP9(1-416) [cytosol] [Homo sapiens] [EntityWithAccessionedSequence:141638] CASP9(?-315) [cytosol] [Homo sapiens] [EntityWithAccessionedSequence:141639] CASP9(331-416) [cytosol] [Homo sapiens] [EntityWithAccessionedSequence:198636] p-S196-CASP9(1-416) [cytosol] [Homo sapiens] [EntityWithAccessionedSequence:9627087] p-T412-CASP9(1-416) [cytosol] [Homo sapiens]
(referenceSequence)	[ModifiedResidue:198639] O-phospho-L-serine at 196 [ModifiedResidue:9627074] O-phospho-L-threonine at 412
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No pathways have been reviewed or authored by UniProt:P55211 CASP9 (57034)