INTRINSIC APOPTOTIC PATHWAY (PW:0000104)

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Description

Apoptosis, or programmed cell death, removes excess or damaged cells to maintain tissue homeostasis. The two major apoptotic pathways, the extrinsic, triggered by ligands activating the death receptors and the intrinsic (mitochondrial), triggered by intracellular stresses, converge on the activation of executioner caspases. In the intrinsic pathway, the Bcl-2 family of pro- and anti-apoptotic proteins controls the life-to-death switch. Structurally, they share the Bcl homology BH domain. Most pr

Pathway Diagram:

Ariadne Genomics Inc. caspase targets pro-survival Bcl BH3-only Bcl Bax Casp3 ---> caspase targets Casp7 ---> caspase targets Casp3 ---> caspase targets Casp7 ---> caspase targets Casp9 ---> Casp7 Casp9 ---> Casp3 Casp9 ---- Xiap Htra2 ---> released_Htra2 released_Diablo ---- Xiap Casp3 ---- Xiap Casp7 ---- Xiap BH3-only Bcl ---- pro-survival Bcl Apaf1 ---- released_Cycs Diablo ---> released_Diablo Apaf1 ---- Casp9 Cycs ---> released_Cycs released_Htra2 ---> Xiap intracellular stresses Bok ---- pro-survival Bcl Bax ---- pro-survival Bcl Bak1 ---- pro-survival Bcl released_Diablo released_Htra2 Bak1 Bok Htra2 Diablo Xiap Casp3 Casp7 intracellular stresses --+> BH3-only Bcl BH3-only Bcl ---| pro-survival Bcl pro-survival Bcl ---| Bak1 pro-survival Bcl ---| Bax pro-survival Bcl ---| Bok apoptosome --+> Casp9 released_Htra2 ---| Xiap released_Diablo ---| Xiap Xiap ---| Casp7 Xiap ---| Casp3 Casp9 --+> Casp3 Casp9 --+> Casp7 Xiap ---| Casp9 Apaf1 released_Cycs ATP dATP Cycs apoptosome Casp9
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Genes in Pathway:

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intrinsic apoptotic pathway term browser
Symbol Object Name JBrowse Chr Start Stop Reference
G Apaf1 apoptotic peptidase activating factor 1 JBrowse link 7 31,699,309 31,784,192 RGD:2313998
G Bad BCL2-associated agonist of cell death JBrowse link 1 222,198,516 222,207,459 RGD:1579966
RGD:2314029
G Bad_v1 BCL2-associated agonist of cell death, variant 1 RGD:1579966
G Bad_v2 BCL2-associated agonist of cell death, variant 2 RGD:1579966
G Bak1 BCL2-antagonist/killer 1 JBrowse link 20 5,609,620 5,618,899 RGD:2313963
RGD:2313975
G Bax BCL2 associated X, apoptosis regulator JBrowse link 1 101,451,801 101,457,207 RGD:1579966
RGD:2314140
RGD:2313998
RGD:2313975
RGD:2313963
G Bax_v1 BCL2 associated X, apoptosis regulator, variant 1 RGD:1579966
G Bax_v2 BCL2 associated X, apoptosis regulator, variant 2 RGD:1579966
G Bbc3 Bcl-2 binding component 3 JBrowse link 1 78,261,491 78,267,802 RGD:2313994
RGD:2314029
G Bcl2 BCL2, apoptosis regulator JBrowse link 13 26,605,426 26,769,374 RGD:1579966
RGD:2314140
RGD:2313998
RGD:2313975
G Bcl2a1 BCL2-related protein A1 JBrowse link 8 96,551,424 96,559,527 RGD:2313975
G Bcl2l1 Bcl2-like 1 JBrowse link 3 148,259,594 148,314,191 RGD:1579966
RGD:2314140
RGD:2313975
G Bcl2l11 BCL2 like 11 JBrowse link 3 120,726,906 120,764,192 RGD:2314029
G Bcl2l2 Bcl2-like 2 JBrowse link 15 33,543,774 33,549,165 RGD:2313963
RGD:2313975
G Bid BH3 interacting domain death agonist JBrowse link 4 153,439,812 153,465,247 RGD:2313998
RGD:2314029
RGD:2314002
G Bik BCL2-interacting killer JBrowse link 7 124,390,924 124,410,449 RGD:2314029
G Bmf Bcl2 modifying factor JBrowse link 3 110,303,515 110,324,125 RGD:2314029
G Bnip1 BCL2 interacting protein 1 JBrowse link 10 16,677,077 16,689,321 RGD:634759
RGD:2314029
G Bnip3 BCL2 interacting protein 3 JBrowse link 1 211,248,098 211,265,282 RGD:2314028
RGD:2314029
G Bnip3l BCL2 interacting protein 3 like JBrowse link 15 43,643,897 43,667,123 RGD:2314029
G Bok BOK, BCL2 family apoptosis regulator JBrowse link 9 100,829,593 100,840,498 RGD:70678
RGD:2313975
G Casp3 caspase 3 JBrowse link 16 48,845,011 48,863,249 RGD:71121
RGD:2314390
RGD:2314187
RGD:2314002
RGD:2313998
RGD:2313963
G Casp7 caspase 7 JBrowse link 1 277,190,557 277,242,779 RGD:2314187
G Casp9 caspase 9 JBrowse link 5 160,356,211 160,373,774 RGD:2313963
RGD:2314390
RGD:2314187
RGD:2314002
RGD:2313998
G Cycs cytochrome c, somatic JBrowse link 4 80,331,226 80,333,326 RGD:2313963
RGD:2313998
G Fas Fas cell surface death receptor JBrowse link 1 252,589,785 252,624,790 RGD:1626509
G Hrk harakiri, BCL2 interacting protein JBrowse link 12 44,008,879 44,029,211 RGD:70327
RGD:2314029
RGD:2290488
G Htra2 HtrA serine peptidase 2 JBrowse link 4 113,883,671 113,886,833 RGD:2314385
G Mcl1 MCL1, BCL2 family apoptosis regulator JBrowse link 2 197,786,212 197,788,992 RGD:70678
RGD:2313975
G Pmaip1 phorbol-12-myristate-13-acetate-induced protein 1 JBrowse link 18 62,159,128 62,179,635 RGD:2314029
RGD:2314140
G Xiap X-linked inhibitor of apoptosis JBrowse link X 128,409,425 128,455,786 RGD:2314390

Additional Elements in Pathway:

(includes Gene Groups, Small Molecules, Other Pathways..etc.)
Object TypePathway ObjectPathway Object Description
Gene Groupcaspase targetsseveral genes identified as caspase substrates
Functional Classpro-survival Bclthe members of the Bcl family that are anti-apoptotic
Functional ClassBH3-only Bclthe members of the pro-apoptotic Bcl family with only the BH3 domain

Pathway Gene Annotations

Pathway Annotations Associated with Genes in the intrinsic apoptotic pathway
Pathway TermsGene Symbols
acute myeloid leukemia pathwayBad
adenosine signaling pathwayBad
allograft rejection pathwayFas
Alzheimer disease pathwayApaf1 , Bad , Bid , Casp3 , Casp7 , Casp9 , Cycs , Fas
amyotrophic lateral sclerosis disease pathwayApaf1 , Bad , Bax , Bcl2 , Bcl2l1 , Bid , Casp3 , Casp9 , Cycs
apoptotic cell death pathwayApaf1 , Bad , Bax , Bcl2 , Bcl2l1 , Bid , Casp3 , Casp7 , Casp9 , Cycs , Fas , Xiap
autoimmune thyroid disease pathwayFas
Bone morphogenetic proteins signaling pathwayXiap
cardiolipin metabolic pathwayCycs
ceramide signaling pathwayBad , Bax , Bcl2 , Bcl2l1 , Bid , Casp9 , Cycs
chronic myeloid leukemia pathwayBad , Bcl2l1
colorectal cancer pathwayBad , Bax , Bcl2 , Casp3 , Casp9 , Cycs
cytokine mediated signaling pathwayFas
electron transport chain pathwayCycs
endometrial cancer pathwayBad , Casp9
Endoplasmic Reticulum-associated degradation pathwayBak1 , Bax , Bcl2
Entamoeba histolyca infection pathwayCasp3
epidermal growth factor/neuregulin signaling pathwayBad
erythropoietin signaling pathwayBcl2 , Bcl2l1
extrinsic apoptotic pathwayCasp3 , Casp7 , Fas
FasL mediated signaling pathwayBid , Casp3 , Casp7 , Fas
glutathione metabolic pathwayCasp7
glutathione synthase deficiency pathwayCasp7
glutathionuria disease pathwayCasp7
graft-versus-host disease pathwayFas
hepatitis C virus infection pathwayBad
Huntington disease pathwayApaf1 , Bax , Bbc3 , Casp3 , Casp9 , Cycs
hypoxia inducible factor pathwayBnip3 , Mcl1
influenza A virus infection pathwayCasp9 , Cycs , Fas
insulin signaling pathwayBad
insulin-like growth factor signaling pathwayBad
interleukin-2 signaling pathwayBcl2
interleukin-3 signaling pathwayBcl2l1
interleukin-6 signaling pathwayMcl1
intrinsic apoptotic pathwayApaf1 , Bad , Bad_v1 , Bad_v2 , Bak1 , Bax , Bax_v1 , Bax_v2 , Bbc3 , Bcl2 , Bcl2a1 , Bcl2l1 , Bcl2l11 , Bcl2l2 , Bid , Bik , Bmf , Bnip1 , Bnip3 , Bnip3l , Bok , Casp3 , Casp7 , Casp9 , Cycs , Fas , Hrk , Htra2 , Mcl1 , Pmaip1 , Xiap
Jak-Stat signaling pathwayBcl2l1
measles infection pathwayBbc3 , Fas
melanoma pathwayBad
mitochondrial autophagy pathwayBnip3 , Bnip3l
mitogen activated protein kinase signaling pathwayCasp3 , Fas
mTOR signaling pathwayBnip3 , Cycs
Mycobacterium tuberculosis infection pathwayApaf1 , Bad , Bax , Bcl2 , Bid , Casp3 , Casp9 , Cycs
myocarditis pathwayBid , Casp3 , Casp9 , Cycs
neurotrophic factor signaling pathwayBad , Bax , Bcl2
NOD-like receptor signaling pathwayXiap
non-small cell lung cancer pathwayBad , Casp9
p53 signaling pathwayApaf1 , Bax , Bbc3 , Bid , Casp3 , Casp9 , Cycs , Fas , Pmaip1
pancreatic cancer pathwayBad , Bcl2l1 , Casp9
Parkinson disease pathwayApaf1 , Casp3 , Casp9 , Cycs , Htra2
phosphatidylinositol 3-kinase-Akt signaling pathwayBad , Casp9
prion diseases pathwayBax
prostate cancer pathwayBad , Bcl2 , Casp9
small cell lung cancer pathwayApaf1 , Bcl2 , Bcl2l1 , Casp9 , Cycs , Xiap
syndecan signaling pathwayBax , Casp3
titanium dioxide nanoparticle response pathwayBax , Casp3 , Fas
Toxoplasma gondii infection pathwayBad , Bcl2 , Bcl2l1 , Casp3 , Casp9 , Cycs , Xiap
Trail mediated signaling pathwayBid , Casp3 , Casp7
transforming growth factor-beta Smad dependent signaling pathwayXiap
Trypanosoma brucei infection pathwayFas
Trypanosoma cruzi infection pathwayFas
type 1 diabetes mellitus pathwayFas
ubiquitin/proteasome degradation pathwayXiap
vascular endothelial growth factor signaling pathwayBad , Casp9
Phenotype Annotations Associated with Genes in the intrinsic apoptotic pathway

References Associated with the intrinsic apoptotic pathway:

Ontology Path Diagram:

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