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FLASH GENE

Symbol

CASP2

contributors: mct - updated : 19-03-2015

HGNC name	caspase 2, apoptosis-related cysteine peptidase
HGNC id	1503

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Location	7q34      Physical location : 142.985.401 - 143.004.784
Synonym name	caspase 2, apoptosis-related cysteine protease (neural precursor cell expressed, developmentally down-regulated 2)
	NEDD2 apoptosis regulatory gene
	caspase 2, apoptosis-related cysteine protease
	ICH-1 protease
Synonym symbol(s)	ICH1, NEDD2, CASP-2, ICH-1L, ICH-1L/1S, PPP1R57
EC.number	3.4.22.55

DNA

TYPE	functioning gene
SPECIAL FEATURE
text	an element in 9, containing a decoy 3-acceptor site, inhibiting the inclusion of exon 9
STRUCTURE	19.38 kb     11 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

N

status

provisional

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_032982 11 - 4145 NP_116764 50.55 452 ubiquitous 1994 8087842 also called variant 1, ICH-1L, CASP2L pro-apoptotic excluding exon 9 promotes apoptosis RBM5 enhances the formation of proapoptotic Casp-2L NM_032983 10 - 3927 NP_116765 12 108 - 1994 8087842 variant 4 - - 2650 isoform 4 - 77 - 1994 8087842

EXPRESSION

Type	ubiquitous

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   thymus       highly Respiratory respiratory tract larynx     highly

cell lineage	neural precursor cell
cell lines
fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	a N terminal (Fas-associating protein with DEATH domain) FADD-like death effector domain
	a conserved QACXG pentapeptide active site motif

mono polymer

heteromer , tetramer

isoforms

Precursor

precursor producing two subunits,large (18kDa) and small (12kDa),that dimerize

HOMOLOGY

interspecies

ortholog to murine Nedd 2

intraspecies

paralog to CASP1

Homologene

FAMILY	caspase family of cysteinyl-aspartate specific proteases
	peptidase C14 family

CATEGORY

enzyme

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm,organelle,mitochondria,inner
	intracellular,cytoplasm,cytosolic
	intracellular,nucleus
text	procaspase 2 stored in the mitochondrial intermembrane space and released into cytosol after appropriate apoptotic stimuli
	has a unique ability to localize to the nucleus

basic FUNCTION	cysteine containing aspartate-specific protease, mammalian interleukin 1 beta convertase, promoting apoptosis
	splicing regulation of CASP-2L/CASP-2S may play an important role in neural development
	required in stress induced apoptosis for permeabilization of mitochondria
	potent inducer of NF-kappaB and p38 MAPK activation in a TRAF2-mediated way
	required for apoptosis induced by cytoskeletal disruption, having a context-dependent function
	role of caspase-2 as a tumor suppressor appears to be unique among mammalian caspases
	functions as an endogenous inhibitor of NFkappaB-dependent cell survival and this mechanism may contribute to tumor suppression
	changes of CASP2 and CASP5 activities could be indicative of their involvement in the cervical malignancy mechanisms
	its expression promotes growth arrest and chemotherapy resistance by a mechanism that depends on CASP2 and wild-type TP53
	initiator caspase, which has been implicated to function in apoptotic and non-apoptotic signalling pathways, including cell-cycle regulation, DNA-damage signalling and tumour suppression
	neuronally expressed developmentally down-regulated gene required for neuronal death induced by several stimuli, including NGF (nerve growth factor) deprivation and APP (
	highly conserved CASP2 is required for pore-forming toxins (PFT)-mediated apoptosis
	obligatory role as an initiator caspase during PFT-mediated apoptosis

CELLULAR PROCESS	cell life, cell death/apoptosis
	cell life, antiapoptosis

PHYSIOLOGICAL PROCESS

text	apoptotic or antiapoptotic depending upon cell lineage and stage of development

PATHWAY

metabolism

signaling

a component	complex with TRAF2, and RALBP1 that activates NF-kappaB and p38 MAPK through the caspase recruitment domain of caspase-2 independently of its proteolytic activity
	PIDDosome, which is an oligomeric signaling complex composed of PIDD1, CRADD and CASP2, can induce proximity-based dimerization and activation of CASP2

INTERACTION

DNA

RNA

small molecule

protein	interacts with NALP1
	interacts with TRAF1, TRAF2, and RALBP1
	MDM2 is a cleavage target of Caspase-2 and provide insight into a mechanism of Mdm2 inhibition that impacts TP53 dynamics upon genotoxic stress

cell & other

REGULATION

activated by

the TP53 target gene product PIDD (also known as LRDD) in a complex called the Caspase-2-PIDDosome

repressed by

RAS (RAS-induced down-regulation of CASP2 represents a novel mechanism by which oncogenic RAS protects malignant intestinal epithelial cells from anoikis, promotes their anchorage-independent growth, and allows them to form tumors)

Other	developmentally downregulated
	rgulated by RBM5 (CASP2 splicing regulation by RBM5 may contribute to its tumor suppressor activity)

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral         results in an increased ability of cells to acquire a transformed phenotype and become malignant, indicating that it is a tumor suppressor constitutional       loss of function promotes aberrant DNA-damage response and genetic instability, leading to defective TP53-mediated signalling and decreased trans-activation of TP53 target genes upon DNA damage constitutional       loss of function may play a role in promoting marrow adiposity under stress or disease conditions, but it is not required for T1-diabetes induced bone loss

Susceptibility

Variant & Polymorphism

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS

caspase-2(-/-) mouse embryonic fibroblasts (MEFs) show increased proliferation