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FLASH GENE

Symbol

CASP9

contributors: mct/npt/pgu - updated : 18-05-2014

HGNC name	caspase 9, apoptosis-related cysteine peptidase
HGNC id	1511

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

EXPRESSION

Type

widely

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Lymphoid/Immune lymph node       highly Reproductive female system uterus cervix   highly

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Blood / Hematopoietic

cells

System Cell Pubmed Species Stage Rna symbol Blood/Hematopoietic leukocyte

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

fetal

Text	brain, kidney, lung

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains

conjugated

ubiquitinated

mono polymer

heteromer , dimer

isoforms

Precursor

producing two subunits, large and small that dimerize

HOMOLOGY

interspecies	ortholog to murine Casp9
	ortholog to rattus casp9

Homologene

FAMILY

caspase family of cysteinyl-aspartate specific proteases

CATEGORY

enzyme

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm,organelle,mitochondria,interspace
	intracellular,cytoplasm,cytosolic
	intracellular,nucleus
text	procaspase 9 stored in mitochondrial intermembrane space released in the cytosol after appropriate apoptotic stimuli

basic FUNCTION	containing aspartate specific protease
	involved in the activation cascade of caspases responsible for apoptosis execution
	during apoptosis, the initiator caspase 9 is activated at the apoptosome after which it activates the executioner caspases 3 and 7 by proteolysis
	initial caspase in the mitochondrial apoptotic cascade

CELLULAR PROCESS	cell life, cell death/apoptosis

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component	two subunits, large and small that dimerize
	ATG7·CASP9 complex performs a dual function of linking CASP9 to the autophagic process while keeping in check its apoptotic activity

INTERACTION

DNA

RNA

small molecule

protein	cleaving and activating CASP3 and initiating apoptotic cascade after its activation
	oxidative modification of CASP9 facilitates its activation via disulfide-mediated interaction with APAF1
	BIRC2 cooperatively interacts with oligomerized processed CASP9 in the apoptosome and blocks procaspase-3 activation
	interacting with MAPK8 (MAPK8 activation was essential for CASP9 activation and nuclear translocation of cytochrome c) . CASP4 directly activates CASP9 by the processing of procaspase-9 at Asp-315 in ER stress-induced neuronal apoptosis
	after activation by CASP9, CASP3 inhibits ROS production and is required for efficient execution of apoptosis, while effector CASP7 is required for apoptotic cell detachment
	CASP3, CASP9, and MAPK14 interacted with SLIT1-ROBO2 signaling

cell & other

REGULATION

activated by

APAF1 cytochrome C multimeric complex

induced by	staurosporine that can induce caspase-9 activation and apoptosis independently of the apoptosome
		cellular oxidative state facilitates CASP9 activation

inhibited by

BIRC2, BIRC3, BIRC4 (XIAP)

Phosphorylated by

DYRK1A that phosphorylates CASP9 on threonine residue 125, and this phosphorylation event is crucial to protect retina cells from apoptotic cell death

Other	polyubiquitinated by BIRC4, while procaspase-9 was not
	PDCD6IP is a crucial mediator of Ca(2+) induced CASP9 activation

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional       gain of function in neurons of Alzheimer disease (before cleavage of tau and formation of neurofibrillary tangles)

Susceptibility

to modification of survival in non-small-cell lung cancer (NSCLC)

Variant & Polymorphism other	rs4645981 polymorphisms may affect survival in early-stage NSCLC

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS