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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

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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 IEA Ensembl GO_REF:0000107 NCBI chrNW_004624767:17,050,929...17,059,648
Ensembl chrNW_004624767:17,055,509...17,059,705 		JBrowse link
G Fas Fas cell surface death receptor acts_upstream_of_or_within
involved_in		 ISO
IEA		 (PMID:21052097) MGI
TreeGrafter		 PMID:21052097 GO_REF:0000118 NCBI chrNW_004624791:15,290,022...15,315,848
Ensembl chrNW_004624791:15,289,348...15,315,848 		JBrowse link
G Faslg Fas ligand involved_in ISO (PMID:11101870) BHF-UCL PMID:11101870 NCBI chrNW_004624771:9,031,978...9,038,760
Ensembl chrNW_004624771:9,032,016...9,038,825 		JBrowse link
G Mlkl mixed lineage kinase domain like pseudokinase involved_in ISO (PMID:22265413) UniProt PMID:22265413 NCBI chrNW_004624746:12,193,699...12,213,475 JBrowse link
G Ripk1 receptor interacting serine/threonine kinase 1 involved_in ISS
IEA		 UniProt
Ensembl		 GO_REF:0000024 GO_REF:0000107 NCBI chrNW_004624756:21,806,570...21,837,351
Ensembl chrNW_004624756:21,805,599...21,830,699 		JBrowse link
G Ripk3 receptor interacting serine/threonine kinase 3 involved_in ISO (PMID:22265413), (PMID:22817896) UniProt PMID:22265413 PMID:22817896 NCBI chrNW_004624820:8,165,546...8,169,172 JBrowse link
G Tlr3 toll like receptor 3 involved_in ISO (PMID:21737330) UniProt PMID:21737330 NCBI chrNW_004624769:16,925,969...16,945,250
Ensembl chrNW_004624769:16,925,984...16,941,196 		JBrowse link
G Tnf tumor necrosis factor involved_in
acts_upstream_of_or_within		 IEA
ISS
ISO		 (PMID:21368763)
(PMID:22037414)
(PMID:19498109)
(PMID:21052097)		 UniProt
MGI		 PMID:19498109 PMID:21052097 PMID:21368763 PMID:22037414 GO_REF:0000024 GO_REF:0000104 NCBI chrNW_004624754:24,623,059...24,625,647
Ensembl chrNW_004624754:24,623,425...24,625,531 		JBrowse link
Term paths to the root
Path 1
Term Annotations click to browse term
  biological_process 15135
    cellular process 14753
      signal transduction 5421
        necroptotic signaling pathway 8
Path 2
Term Annotations click to browse term
  biological_process 15135
    cellular process 14753
      cell death 1855
        programmed cell death 1855
          programmed necrotic cell death 49
            necroptotic process 36
              necroptotic signaling pathway 8
paths to the root