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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 ISO (PMID:11101870) RGD PMID:11101870 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)
PMID:21873635
MGI:108212 (MGI:5315337|PMID:21052097)
RGD PMID:16507998 PMID:21052097 PMID:21873635 MGI:5315337, RGD:13792537 NCBI chr 1:231,798,963...231,832,591
Ensembl chr 1:231,798,960...231,832,591
JBrowse link
G Faslg Fas ligand involved_in ISO (PMID:11101870) RGD PMID:11101870 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 (PMID:22265413)
(MGI:5516182|PMID:22265413)
RGD PMID:22265413 MGI:5516182 NCBI chr19:39,278,123...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
GO_REF:0000024
(PMID:11101870), (PMID:16507998), (PMID:22265413), (PMID:22817896), (PMID:31827280)
(MGI:5291865|PMID:21876153), (MGI:6401044|PMID:31827281)
UniProt
RGD
PMID:11101870 PMID:16507998 PMID:21876153 PMID:22265413 PMID:22817896 More... GO_REF:0000024 MGI:5291865 MGI:6401044 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 (PMID:22265413), (PMID:22817896) RGD PMID:22265413 PMID:22817896 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 (PMID:21737330) RGD PMID:21737330 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
(PMID:11101870), (PMID:22265413), (PMID:22265414), (PMID:22817896)
GO_REF:0000024
MGI:108212|MGI:1197009|MGI:1261423|MGI:1336166|MGI:1346877|MGI:1921506|MGI:2154952 (MGI:4947443|PMID:21368763), (MGI:5306844|PMID:22037414), (MGI:5315337|PMID:21052097), (MGI:5510543|PMID:19498109)
RGD
UniProt
PMID:11101870 PMID:19498109 PMID:21052097 PMID:21368763 PMID:22037414 More... GO_REF:0000024 MGI:4947443 MGI:5306844 MGI:5315337 MGI:5510543 NCBI chr20:3,622,011...3,624,629
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 20099
    cellular process 18695
      signal transduction 7110
        necroptotic signaling pathway 8
Path 2
Term Annotations click to browse term
  biological_process 20099
    cellular process 18695
      cell death 2261
        necrotic cell death 75
          programmed necrotic cell death 55
            necroptotic process 45
              necroptotic signaling pathway 8
paths to the root