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Pathways
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ONTOLOGY REPORT - ANNOTATIONS

Term:necroptotic signaling pathway
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Accession:GO:0097527 term browser browse the term
Definition:The series of molecular signals which triggers the necroptotic death of a cell. The pathway starts with reception of a signal, is characterized by activation of receptor-interacting serine/threonine-protein kinase 1 and/or 3 (RIPK1/3, also called RIP1/3), and ends when the execution phase of necroptosis is triggered.
Comment:Gene products that may be annotated to this term include: 1) ligands such as TNF-alpha; 2) receptors such as TNFR (though care should be taken because TNF-alpha and TNFR may also be involved in non-necroptotic processes); 3) signaling molecules such as TNFR-associated death domain (TRADD), receptor-interacting protein kinase 1 (RIP1), cellular inhibitor of apoptosis 1 (cIAP1), cIAP2, TNFR-associated factor 2 (TRAF2) and TRAF5. Within the so-called complex I, RIP1 is polyubiquitinated by cIAPs, thereby providing a docking site for the recruitment of transforming growth factor beta (TGFbeta)-activated kinase 1 (TAK1), TAK1-binding protein 2 (TAB2) and TAB3 (which together deliver a pro-survival signal by activating the transcription factor NF-kB). In some pathophysiological and experimental settings, and in particular when caspase-8 is absent or when caspases are inhibited by pharmacological agents, cylindromatosis (CYLD)-deubiquitinated RIP1 engage in physical and functional interactions with its homolog RIP3, ultimately activating the execution of necrotic cell death. (The pathway downstream of RIPK3 remains largely unknown, although ROS generation, calcium overload, and the opening of the mitochondrial permeability transition pore have been implicated (PMID:22265414)). A necroptotic signaling pathway may also be induced by alkylating DNA damage (possibly by the overactivation of poly(ADP-ribose) polymerase 1, PARP1). This is sometimes referred to as PARP-dependent cell death or parthanatos; it is still being debated if it constitutes an independent cell death modality.
Synonyms:exact_synonym: necroptosis signaling pathway;   necroptotic signal transduction
 related_synonym: necroptosis signaling;   necroptotic signalling pathway


show annotations for term's descendants           Sort by:
necroptotic signaling pathway term browser
Symbol Object Name Qualifiers Evidence Notes Source PubMed Reference(s) RGD Reference(s) Position
G Fadd Fas associated via death domain involved_in ISO
IEA		 (PMID:11101870)
GO_REF:0000107		 RGD
Ensembl		 PMID:11101870 GO_REF:0000107 NCBI chr 1:199,743,200...199,745,746
Ensembl chr 1:199,739,994...199,745,653 		JBrowse link
G Fas Fas cell surface death receptor involved_in
acts_upstream_of_or_within		 ISO
IBA		 (PMID:16507998)
GO_REF:0000033
MGI:108212 (PMID:21052097)		 RGD
GO_Central		 PMID:16507998 PMID:21052097 GO_REF:0000033 NCBI chr 1:241,212,155...241,245,774
Ensembl chr 1:231,798,960...231,832,591 		JBrowse link
G Faslg Fas ligand involved_in ISO
IEA		 (PMID:11101870)
GO_REF:0000107		 RGD
Ensembl		 PMID:11101870 GO_REF:0000107 NCBI chr13:74,151,519...74,172,760
Ensembl chr13:74,154,954...74,162,215 		JBrowse link
G Mlkl mixed lineage kinase domain like pseudokinase involved_in ISO
IBA
IEA		 (PMID:22265413)
GO_REF:0000033
GO_REF:0000107		 RGD
GO_Central
Ensembl		 PMID:22265413 GO_REF:0000033 GO_REF:0000107 NCBI chr19:39,277,526...39,304,555
Ensembl chr19:39,276,785...39,304,502 		JBrowse link
G Ripk1 receptor interacting serine/threonine kinase 1 involved_in ISS
ISO
IBA
IEA		 GO_REF:0000024
(PMID:11101870), (PMID:16507998), (PMID:22265413), (PMID:22817896), (PMID:31827280)
(PMID:21876153), (PMID:31827281)
GO_REF:0000033
GO_REF:0000107		 UniProt
RGD
GO_Central
Ensembl		 PMID:11101870 PMID:16507998 PMID:21876153 PMID:22265413 PMID:22817896 More... GO_REF:0000024 GO_REF:0000033 GO_REF:0000107 NCBI chr17:30,839,639...30,871,824
Ensembl chr17:30,839,650...30,871,824 		JBrowse link
G Ripk3 receptor-interacting serine-threonine kinase 3 involved_in ISO
IEA		 (PMID:22265413), (PMID:22817896)
GO_REF:0000107		 RGD
Ensembl		 PMID:22265413 PMID:22817896 GO_REF:0000107 NCBI chr15:29,283,153...29,292,107
Ensembl chr15:29,283,145...29,292,121 		JBrowse link
G Tlr3 toll-like receptor 3 involved_in ISO
IEA		 (PMID:21737330)
GO_REF:0000107		 RGD
Ensembl		 PMID:21737330 GO_REF:0000107 NCBI chr16:46,821,980...46,837,900
Ensembl chr16:46,822,039...46,836,545 		JBrowse link
G Tnf tumor necrosis factor involved_in
acts_upstream_of_or_within		 ISO
ISS
IEA		 (PMID:11101870), (PMID:22265413), (PMID:22265414), (PMID:22817896)
GO_REF:0000024
GO_REF:0000104
MGI:108212|MGI:1197009|MGI:1261423|MGI:1336166|MGI:1346877|MGI:1921506|MGI:2154952 (PMID:19498109), (PMID:21052097), (PMID:21368763), (PMID:22037414)
GO_REF:0000107		 RGD
UniProt
Ensembl		 PMID:11101870 PMID:19498109 PMID:21052097 PMID:21368763 PMID:22037414 More... GO_REF:0000024 GO_REF:0000104 GO_REF:0000107 NCBI chr20:3,626,685...3,629,303
Ensembl chr20:3,622,011...3,624,629 		JBrowse link
Term paths to the root
Path 1
Term Annotations click to browse term
  biological_process 20558
    cellular process 19550
      signal transduction 7301
        necroptotic signaling pathway 8
Path 2
Term Annotations click to browse term
  biological_process 20558
    cellular process 19550
      cell death 2196
        programmed cell death 2196
          programmed necrotic cell death 59
            necroptotic process 44
              necroptotic signaling pathway 8
paths to the root