Submit Data |  Help |  Video Tutorials |  News |  Publications |  FTP Download |  REST API |  Citing RGD |  Contact   

ONTOLOGY REPORT - ANNOTATIONS


Term:necroptotic signaling pathway
go back to main search page
Accession:GO:0097527 term browser browse the term
Definition:A 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 Evidence Notes Source PubMed Reference(s) RGD Reference(s) Position
G Fadd Fas associated via death domain ISO (PMID:11101870) RGD PMID:11101870 NCBI chr 1:217,746,176...217,748,581
Ensembl chr 1:217,742,929...217,748,628
JBrowse link
G Fas Fas cell surface death receptor ISO
IBA
MGI:MGI:108212 (MGI:MGI:5315337|PMID:21052097)
PMID:21873635
(PMID:16507998)
RGD PMID:16507998, PMID:21052097, PMID:21873635 MGI:MGI:5315337, RGD:13792537 NCBI chr 1:252,589,785...252,624,790
Ensembl chr 1:252,589,785...252,624,790
JBrowse link
G Faslg Fas ligand ISO (PMID:11101870) RGD PMID:11101870 NCBI chr13:79,696,811...79,717,581
Ensembl chr13:79,698,445...79,705,705
JBrowse link
G LOC103694380 tumor necrosis factor-like ISS GO_REF:0000024 UniProt GO_REF:0000024 NCBI chr20:4,855,792...4,858,447
Ensembl chr20:4,855,829...4,858,447
JBrowse link
G Mlkl mixed lineage kinase domain like pseudokinase ISO (PMID:22265413)
(MGI:MGI:5516182|PMID:22265413)
RGD PMID:22265413 MGI:MGI:5516182 NCBI chr19:43,508,416...43,535,050
Ensembl chr19:43,506,976...43,528,851
JBrowse link
G Ripk1 receptor interacting serine/threonine kinase 1 ISS
ISO
GO_REF:0000024
(MGI:MGI:5291865|PMID:21876153), (MGI:MGI:6401044|PMID:31827281)
(PMID:11101870), (PMID:16507998), (PMID:22265413), (PMID:22817896), (PMID:31827280)
UniProt
RGD
PMID:11101870, PMID:16507998, PMID:21876153, PMID:22265413, PMID:22817896, PMID:31827280, PMID:31827281 GO_REF:0000024, MGI:MGI:5291865, MGI:MGI:6401044 NCBI chr17:31,537,580...31,569,904
Ensembl chr17:31,537,591...31,569,904
JBrowse link
G Ripk3 receptor-interacting serine-threonine kinase 3 ISO (PMID:22265413), (PMID:22817896) RGD PMID:22265413, PMID:22817896 NCBI chr15:34,470,796...34,479,741
Ensembl chr15:34,470,796...34,479,741
JBrowse link
G Tlr3 toll-like receptor 3 ISO (PMID:21737330) RGD PMID:21737330 NCBI chr16:50,016,466...50,031,011
Ensembl chr16:50,016,857...50,031,214
JBrowse link
G Tnf tumor necrosis factor ISS
ISO
GO_REF:0000024
MGI:MGI:108212|MGI:MGI:1197009|MGI:MGI:1261423|MGI:MGI:1336166|MGI:MGI:1346877|MGI:MGI:1921506|MGI:MGI:2154952 (MGI:MGI:4947443|PMID:21368763), (MGI:MGI:5306844|PMID:22037414), (MGI:MGI:5315337|PMID:21052097), (MGI:MGI:5510543|PMID:19498109)
(PMID:11101870), (PMID:22265413), (PMID:22265414), (PMID:22817896)
UniProt
RGD
PMID:11101870, PMID:19498109, PMID:21052097, PMID:21368763, PMID:22037414, PMID:22265413, PMID:22265414, PMID:22817896 GO_REF:0000024, MGI:MGI:4947443, MGI:MGI:5306844, MGI:MGI:5315337, MGI:MGI:5510543 NCBI chr20:5,189,382...5,192,000
Ensembl chr20:5,189,390...5,192,000
JBrowse link

Term paths to the root
Path 1
Term Annotations click to browse term
  biological_process 20014
    cellular process 18788
      signal transduction 7015
        necroptotic signaling pathway 9
Path 2
Term Annotations click to browse term
  biological_process 20014
    cellular process 18788
      cell death 2154
        necrotic cell death 62
          programmed necrotic cell death 45
            necroptotic process 35
              necroptotic signaling pathway 9
paths to the root

NHLBI Logo

RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.