RIPK1 (receptor-interacting serine/threonine-protein kinase 1) is a cytoplasmic signaling protein with an N-terminal Ser/Thr kinase domain, an intermediate domain containing a RIP homotypic interaction motif (RHIM), and a C-terminal death domain. Recruited via its death domain to ligated TNFR1 (through TRADD), FAS and other death receptors, and via its RHIM to TRIF (TLR3/4) and ZBP1, RIPK1 acts as a molecular switch between survival, inflammation and cell death. In the TNFR1 signaling complex (complex I) it functions as a kinase-independent scaffold: ubiquitinated by cIAP1/2 and LUBAC, it recruits the TAK1 and IKK complexes to drive canonical NF-kappaB and MAPK activation and pro-survival gene expression, and its scaffold function also restrains caspase-8-mediated apoptosis and RIPK3/MLKL-mediated necroptosis. When NF-kappaB signaling or IKK/MK2/TBK1 phosphorylation checkpoints fail, RIPK1 dissociates into cytosolic death complexes; death-domain dimerization activates its kinase, and autophosphorylated RIPK1 promotes assembly of complex IIa/the ripoptosome (RIPK1-FADD-caspase-8) driving RIPK1-dependent apoptosis, or, when caspase-8 is inactive, RHIM-mediated hetero-amyloid assembly with RIPK3 (the necrosome), in which RIPK3 phosphorylates MLKL to execute necroptosis. Caspase-8 cleavage of RIPK1 after Asp324 limits these responses; non-cleavable variants cause an autoinflammatory disease, and biallelic loss-of-function causes immunodeficiency with intestinal inflammation.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000165 MAPK cascade | IEA GO_REF:0000108 | KEEP AS NON CORE | Summary: IEA inferred by inter-ontology logic from the IBA JUN kinase kinase kinase activity annotation. Reason: RIPK1 contributes to TNF-induced JNK/p38 MAPK activation (e.g. via phosphorylation of DAB2IP/AIP1 and ASK1 activation), so participation in MAPK signaling is defensible, but the inference route (RIPK1 as a JNKKK) is not supported; MAPK activation is peripheral to its core TNFR1 survival/death functions. Supporting Evidence: PMID:17389591 RIP1 (the Ser/Thr protein kinase receptor-interacting protein) associates with the GAP domain of AIP1 and mediates TNF-induced AIP1 phosphorylation at Ser-604 and JNK/p38 activation |
| GO:0002947 tumor necrosis factor receptor superfamily complex | NAS PMID:36179048 Novel biochemical, structural, and systems insights into inf... | ACCEPT | Summary: RIPK1 is a component of the TNFR1 signaling complex (complex I, TNF-RSC), mapped by contextual interaction proteomics. Reason: RIPK1 is recruited by TRADD to ligand-bound TNFR1 and is a core component of complex I, where it is ubiquitinated and acts as a scaffold for IKK/TAK1 recruitment. Supporting Evidence: PMID:36179048 We used this approach to generate an integrated model of the formation principles and architecture of a large signalosome, the TNF-receptor signaling complex (TNF-RSC) PMID:8612133 RIP is a serine-threonine kinase that is recruited by TRADD to TNFR1 in a TNF-dependent process PMID:12887920 The initial plasma membrane bound complex (complex I) consists of TNFR1, the adaptor TRADD, the kinase RIP1, and TRAF2 and rapidly signals activation of NF-kappa B |
| GO:0004672 protein kinase activity | IDA PMID:15001576 TRAF7 potentiates MEKK3-induced AP1 and CHOP activation and ... | ACCEPT | Summary: Protein kinase activity (IDA, PMID:15001576). Reason: RIPK1 is an active Ser/Thr protein kinase (autophosphorylation, RIPK3 and DAB2IP phosphorylation; inhibited by necrostatins). The more specific protein serine/threonine kinase activity term is also annotated; this general term is correct. Supporting Evidence: PMID:8612133 RIP is a serine-threonine kinase that is recruited by TRADD to TNFR1 in a TNF-dependent process PMID:23473668 Necrostatins, a series of small-molecule inhibitors, suppress necroptosis by specifically inhibiting RIP1 kinase activity |
| GO:0004672 protein kinase activity | IDA PMID:22265413 Mixed lineage kinase domain-like protein mediates necrosis s... | ACCEPT | Summary: Protein kinase activity (IDA, PMID:22265413). Reason: RIPK1 is an active Ser/Thr protein kinase (autophosphorylation, RIPK3 and DAB2IP phosphorylation; inhibited by necrostatins). The more specific protein serine/threonine kinase activity term is also annotated; this general term is correct. Supporting Evidence: PMID:8612133 RIP is a serine-threonine kinase that is recruited by TRADD to TNFR1 in a TNF-dependent process PMID:23473668 Necrostatins, a series of small-molecule inhibitors, suppress necroptosis by specifically inhibiting RIP1 kinase activity |
| GO:0004672 protein kinase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Protein kinase activity (IEA, GO_REF:0000120). Reason: RIPK1 is an active Ser/Thr protein kinase (autophosphorylation, RIPK3 and DAB2IP phosphorylation; inhibited by necrostatins). The more specific protein serine/threonine kinase activity term is also annotated; this general term is correct. Supporting Evidence: PMID:8612133 RIP is a serine-threonine kinase that is recruited by TRADD to TNFR1 in a TNF-dependent process PMID:23473668 Necrostatins, a series of small-molecule inhibitors, suppress necroptosis by specifically inhibiting RIP1 kinase activity |
| GO:0004672 protein kinase activity | IMP PMID:22817896 The RIP1/RIP3 necrosome forms a functional amyloid signaling... | ACCEPT | Summary: Protein kinase activity (IMP, PMID:22817896). Reason: RIPK1 is an active Ser/Thr protein kinase (autophosphorylation, RIPK3 and DAB2IP phosphorylation; inhibited by necrostatins). The more specific protein serine/threonine kinase activity term is also annotated; this general term is correct. Supporting Evidence: PMID:22817896 Mutations in the RHIMs of RIP1 and RIP3 that are defective in the interaction compromise cluster formation, kinase activation, and programmed necrosis in vivo |
| GO:0004674 protein serine/threonine kinase activity | IDA PMID:23473668 Structural basis of RIP1 inhibition by necrostatins. | ACCEPT | Summary: Protein serine/threonine kinase activity (IDA, PMID:23473668). Reason: Core molecular function. RIPK1 autophosphorylates (S14/15, S20, S161, S166) and phosphorylates RIPK3 and DAB2IP; kinase activity is required for RIPK1-dependent apoptosis and necroptosis but dispensable for its scaffold/NF-kB function. Supporting Evidence: PMID:8612133 RIP is a serine-threonine kinase that is recruited by TRADD to TNFR1 in a TNF-dependent process PMID:23473668 Necrostatins, a series of small-molecule inhibitors, suppress necroptosis by specifically inhibiting RIP1 kinase activity |
| GO:0004674 protein serine/threonine kinase activity | IDA PMID:8612133 TNF-dependent recruitment of the protein kinase RIP to the T... | ACCEPT | Summary: Protein serine/threonine kinase activity (IDA, PMID:8612133). Reason: Core molecular function. RIPK1 autophosphorylates (S14/15, S20, S161, S166) and phosphorylates RIPK3 and DAB2IP; kinase activity is required for RIPK1-dependent apoptosis and necroptosis but dispensable for its scaffold/NF-kB function. Supporting Evidence: PMID:8612133 RIP is a serine-threonine kinase that is recruited by TRADD to TNFR1 in a TNF-dependent process PMID:23473668 Necrostatins, a series of small-molecule inhibitors, suppress necroptosis by specifically inhibiting RIP1 kinase activity |
| GO:0004674 protein serine/threonine kinase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Protein serine/threonine kinase activity (IEA, GO_REF:0000120). Reason: Core molecular function. RIPK1 autophosphorylates (S14/15, S20, S161, S166) and phosphorylates RIPK3 and DAB2IP; kinase activity is required for RIPK1-dependent apoptosis and necroptosis but dispensable for its scaffold/NF-kB function. Supporting Evidence: PMID:8612133 RIP is a serine-threonine kinase that is recruited by TRADD to TNFR1 in a TNF-dependent process PMID:23473668 Necrostatins, a series of small-molecule inhibitors, suppress necroptosis by specifically inhibiting RIP1 kinase activity |
| GO:0004674 protein serine/threonine kinase activity | IMP PMID:30988283 Serine 25 phosphorylation inhibits RIPK1 kinase-dependent ce... | ACCEPT | Summary: Protein serine/threonine kinase activity (IMP, PMID:30988283). Reason: Core molecular function. RIPK1 autophosphorylates (S14/15, S20, S161, S166) and phosphorylates RIPK3 and DAB2IP; kinase activity is required for RIPK1-dependent apoptosis and necroptosis but dispensable for its scaffold/NF-kB function. Supporting Evidence: PMID:30988283 We identify phosphorylation of RIPK1 on Ser25 by IKKs as a key mechanism directly inhibiting RIPK1 kinase activity |
| GO:0004674 protein serine/threonine kinase activity | IMP PMID:31827280 A dominant autoinflammatory disease caused by non-cleavable ... | ACCEPT | Summary: Protein serine/threonine kinase activity (IMP, PMID:31827280). Reason: Core molecular function. RIPK1 autophosphorylates (S14/15, S20, S161, S166) and phosphorylates RIPK3 and DAB2IP; kinase activity is required for RIPK1-dependent apoptosis and necroptosis but dispensable for its scaffold/NF-kB function. Supporting Evidence: PMID:31827280 Impaired cleavage of RIPK1 D324 variants by caspase-8 sensitized patients' peripheral blood mononuclear cells to RIPK1 activation, apoptosis and necroptosis induced by TNF |
| GO:0004674 protein serine/threonine kinase activity | TAS Reactome:R-HSA-5213464 | ACCEPT | Summary: Protein serine/threonine kinase activity (TAS, Reactome:R-HSA-5213464). Reason: Core molecular function. RIPK1 autophosphorylates (S14/15, S20, S161, S166) and phosphorylates RIPK3 and DAB2IP; kinase activity is required for RIPK1-dependent apoptosis and necroptosis but dispensable for its scaffold/NF-kB function. Supporting Evidence: Reactome:R-HSA-5213464 RIPK1 interaction with RIPK3 further potentiates their kinase activation |
| GO:0004674 protein serine/threonine kinase activity | TAS Reactome:R-HSA-5213466 | ACCEPT | Summary: Protein serine/threonine kinase activity (TAS, Reactome:R-HSA-5213466). Reason: Core molecular function. RIPK1 autophosphorylates (S14/15, S20, S161, S166) and phosphorylates RIPK3 and DAB2IP; kinase activity is required for RIPK1-dependent apoptosis and necroptosis but dispensable for its scaffold/NF-kB function. Supporting Evidence: Reactome:R-HSA-5213466 RIPK1:RIPK3 complex formation further |
| GO:0004706 JUN kinase kinase kinase activity | IBA GO_REF:0000033 | MARK AS OVER ANNOTATED | Summary: IBA: JUN kinase kinase kinase activity propagated from the PANTHER node. Reason: RIPK1 is a Ser/Thr kinase, but there is no evidence that it directly phosphorylates the JNK kinases MAP2K4/MAP2K7. RIPK1's contribution to JNK activation is indirect (phosphorylation of DAB2IP leading to ASK1 activation), so a JNKKK activity term over-states its catalytic role; protein serine/threonine kinase activity is the appropriate MF. Propagation Review Root cause: PROPAGATION BAD Failure modes: WRONG ORTHOLOG OR PARALOG FUNCTIONAL DIVERGENCE Sources checked: PANTHER:PTN001147669 SUPPORTS SOURCE BUT NOT TARGET Ancestral node carrying the JNKKK IBD; its experimental descendants are mixed-lineage kinases. RIPK1 belongs to the RIP kinase subfamily of the TKL group, whose characterized members act in death-receptor and innate immune signaling rather than as MAP3Ks for MAP2K4/7. UniProtKB:Q16584 Β· MAP3K11 SUPPORTS SOURCE BUT NOT TARGET MLK3 is a bona fide JNKKK; its activity does not extend to the RIPK subfamily. FB:FBgn0030018 SUPPORTS SOURCE BUT NOT TARGET Drosophila MLK-family donor; supports the MLK clade, not RIPK1. Supporting Evidence: PMID:17389591 RIP1 (the Ser/Thr protein kinase receptor-interacting protein) associates with the GAP domain of AIP1 and mediates TNF-induced AIP1 phosphorylation at Ser-604 and JNK/p38 activation |
| GO:0004722 protein serine/threonine phosphatase activity | IEA GO_REF:0000107 | REMOVE | Summary: IEA (Ensembl Compara) protein serine/threonine phosphatase activity. Reason: RIPK1 is a protein kinase with no phosphatase domain or activity. In the necrosome the phosphatase activity belongs to PGAM5, which is recruited to RIPK1/RIPK3 complexes; the electronic transfer misattributes it. Supporting Evidence: PMID:22265414 We report the identification of RIP1- and RIP3-containing protein complexes that form specifically in response to necrosis induction |
| GO:0005123 death receptor binding | IEA GO_REF:0000107 | ACCEPT | Summary: Death receptor binding (IEA). Reason: RIPK1's death domain binds the intracellular death domain of FAS (and weakly TNFR1); this is a real and characteristic DD-DD interaction of RIPK1. Supporting Evidence: PMID:7538908 we have identified two gene products that associate with the intracellular domain of Fas: Fas itself, and a novel 74 kDa protein we have named RIP |
| GO:0005123 death receptor binding | IPI PMID:7538908 RIP: a novel protein containing a death domain that interact... | ACCEPT | Summary: Death receptor binding (IPI). Reason: RIPK1's death domain binds the intracellular death domain of FAS (and weakly TNFR1); this is a real and characteristic DD-DD interaction of RIPK1. Supporting Evidence: PMID:7538908 we have identified two gene products that associate with the intracellular domain of Fas: Fas itself, and a novel 74 kDa protein we have named RIP |
| GO:0005515 protein binding | IPI PMID:10356400 The interaction of p62 with RIP links the atypical PKCs to N... | REMOVE | Summary: IPI-based protein binding annotation from PMID:10356400; the reported partner(s) in this context: SQSTM1/p62 (links RIP to atypical PKCs in NF-kB activation). Reason: Generic protein binding is uninformative and does not describe RIPK1's molecular activity; removal does not dispute the interaction. RIPK1's informative functions (protein serine/threonine kinase activity, signaling adaptor/scaffold activity in TNFR1 complex I, death domain binding, RHIM-mediated binding to RIPK3) are captured by other annotations in this review. |
| GO:0005515 protein binding | IPI PMID:12884866 Caspase-8 and caspase-10 activate NF-kappaB through RIP, NIK... | REMOVE | Summary: IPI-based protein binding annotation from PMID:12884866; the reported partner(s) in this context: prodomain-only caspase-8/-10 isoforms. Reason: Generic protein binding is uninformative and does not describe RIPK1's molecular activity; removal does not dispute the interaction. RIPK1's informative functions (protein serine/threonine kinase activity, signaling adaptor/scaffold activity in TNFR1 complex I, death domain binding, RHIM-mediated binding to RIPK3) are captured by other annotations in this review. |
| GO:0005515 protein binding | IPI PMID:12884866 Caspase-8 and caspase-10 activate NF-kappaB through RIP, NIK... | REMOVE | Summary: IPI-based protein binding annotation from PMID:12884866; the reported partner(s) in this context: prodomain-only caspase-8/-10 isoforms. Reason: Generic protein binding is uninformative and does not describe RIPK1's molecular activity; removal does not dispute the interaction. RIPK1's informative functions (protein serine/threonine kinase activity, signaling adaptor/scaffold activity in TNFR1 complex I, death domain binding, RHIM-mediated binding to RIPK3) are captured by other annotations in this review. |
| GO:0005515 protein binding | IPI PMID:12887920 Induction of TNF receptor I-mediated apoptosis via two seque... | REMOVE | Summary: IPI-based protein binding annotation from PMID:12887920; the reported partner(s) in this context: TNFR1 complex I/complex II components. Reason: Generic protein binding is uninformative and does not describe RIPK1's molecular activity; removal does not dispute the interaction. RIPK1's informative functions (protein serine/threonine kinase activity, signaling adaptor/scaffold activity in TNFR1 complex I, death domain binding, RHIM-mediated binding to RIPK3) are captured by other annotations in this review. |
| GO:0005515 protein binding | IPI PMID:14653779 The inhibitor ABIN-2 disrupts the interaction of receptor-in... | REMOVE | Summary: IPI-based protein binding annotation from PMID:14653779; the reported partner(s) in this context: IKBKG/NEMO (RIP-NEMO interaction blocked by ABIN-2). Reason: Generic protein binding is uninformative and does not describe RIPK1's molecular activity; removal does not dispute the interaction. RIPK1's informative functions (protein serine/threonine kinase activity, signaling adaptor/scaffold activity in TNFR1 complex I, death domain binding, RHIM-mediated binding to RIPK3) are captured by other annotations in this review. |
| GO:0005515 protein binding | IPI PMID:16127453 IPS-1, an adaptor triggering RIG-I- and Mda5-mediated type I... | REMOVE | Summary: IPI-based protein binding annotation from PMID:16127453; the reported partner(s) in this context: MAVS/IPS-1. Reason: Generic protein binding is uninformative and does not describe RIPK1's molecular activity; removal does not dispute the interaction. RIPK1's informative functions (protein serine/threonine kinase activity, signaling adaptor/scaffold activity in TNFR1 complex I, death domain binding, RHIM-mediated binding to RIPK3) are captured by other annotations in this review. |
| GO:0005515 protein binding | IPI PMID:16611992 Competitive control of independent programs of tumor necrosi... | REMOVE | Summary: IPI-based protein binding annotation from PMID:16611992; the reported partner(s) in this context: TRADD/TNFR1 signaling complex components. Reason: Generic protein binding is uninformative and does not describe RIPK1's molecular activity; removal does not dispute the interaction. RIPK1's informative functions (protein serine/threonine kinase activity, signaling adaptor/scaffold activity in TNFR1 complex I, death domain binding, RHIM-mediated binding to RIPK3) are captured by other annotations in this review. |
| GO:0005515 protein binding | IPI PMID:17047155 Caspase-8 prevents sustained activation of NF-kappaB in mono... | REMOVE | Summary: IPI-based protein binding annotation from PMID:17047155; the reported partner(s) in this context: caspase-8/FADD/FLIP complex in differentiating monocytes. Reason: Generic protein binding is uninformative and does not describe RIPK1's molecular activity; removal does not dispute the interaction. RIPK1's informative functions (protein serine/threonine kinase activity, signaling adaptor/scaffold activity in TNFR1 complex I, death domain binding, RHIM-mediated binding to RIPK3) are captured by other annotations in this review. |
| GO:0005515 protein binding | IPI PMID:17389591 RIP1-mediated AIP1 phosphorylation at a 14-3-3-binding site ... | REMOVE | Summary: IPI-based protein binding annotation from PMID:17389591; the reported partner(s) in this context: DAB2IP/AIP1 (RIPK1 substrate). Reason: Generic protein binding is uninformative and does not describe RIPK1's molecular activity; removal does not dispute the interaction. RIPK1's informative functions (protein serine/threonine kinase activity, signaling adaptor/scaffold activity in TNFR1 complex I, death domain binding, RHIM-mediated binding to RIPK3) are captured by other annotations in this review. |
| GO:0005515 protein binding | IPI PMID:17449468 RBCK1 negatively regulates tumor necrosis factor- and interl... | REMOVE | Summary: IPI-based protein binding annotation from PMID:17449468; the reported partner(s) in this context: RBCK1/HOIL-1. Reason: Generic protein binding is uninformative and does not describe RIPK1's molecular activity; removal does not dispute the interaction. RIPK1's informative functions (protein serine/threonine kinase activity, signaling adaptor/scaffold activity in TNFR1 complex I, death domain binding, RHIM-mediated binding to RIPK3) are captured by other annotations in this review. |
| GO:0005515 protein binding | IPI PMID:18022363 IAP antagonists target cIAP1 to induce TNFalpha-dependent ap... | REMOVE | Summary: IPI-based protein binding annotation from PMID:18022363; the reported partner(s) in this context: cIAP1 (BIRC2). Reason: Generic protein binding is uninformative and does not describe RIPK1's molecular activity; removal does not dispute the interaction. RIPK1's informative functions (protein serine/threonine kinase activity, signaling adaptor/scaffold activity in TNFR1 complex I, death domain binding, RHIM-mediated binding to RIPK3) are captured by other annotations in this review. |
| GO:0005515 protein binding | IPI PMID:18029035 Involvement of Ymer in suppression of NF-kappaB activation b... | REMOVE | Summary: IPI-based protein binding annotation from PMID:18029035; the reported partner(s) in this context: Ymer/CCDC50 via K63 chains on RIP1. Reason: Generic protein binding is uninformative and does not describe RIPK1's molecular activity; removal does not dispute the interaction. RIPK1's informative functions (protein serine/threonine kinase activity, signaling adaptor/scaffold activity in TNFR1 complex I, death domain binding, RHIM-mediated binding to RIPK3) are captured by other annotations in this review. |
| GO:0005515 protein binding | IPI PMID:18067272 Casein kinase 1alpha interacts with RIP1 and regulates NF-ka... | REMOVE | Summary: IPI-based protein binding annotation from PMID:18067272; the reported partner(s) in this context: casein kinase 1 alpha (CSNK1A1). Reason: Generic protein binding is uninformative and does not describe RIPK1's molecular activity; removal does not dispute the interaction. RIPK1's informative functions (protein serine/threonine kinase activity, signaling adaptor/scaffold activity in TNFR1 complex I, death domain binding, RHIM-mediated binding to RIPK3) are captured by other annotations in this review. |
| GO:0005515 protein binding | IPI PMID:18485876 TNF-alpha induces two distinct caspase-8 activation pathways... | REMOVE | Summary: IPI-based protein binding annotation from PMID:18485876; the reported partner(s) in this context: FADD and caspase-8 in complex II. Reason: Generic protein binding is uninformative and does not describe RIPK1's molecular activity; removal does not dispute the interaction. RIPK1's informative functions (protein serine/threonine kinase activity, signaling adaptor/scaffold activity in TNFR1 complex I, death domain binding, RHIM-mediated binding to RIPK3) are captured by other annotations in this review. |
| GO:0005515 protein binding | IPI PMID:19060883 ABIN-1 is a ubiquitin sensor that restricts cell death and s... | REMOVE | Summary: IPI-based protein binding annotation from PMID:19060883; the reported partner(s) in this context: ABIN-1 (TNIP1)-containing TNF signaling complexes. Reason: Generic protein binding is uninformative and does not describe RIPK1's molecular activity; removal does not dispute the interaction. RIPK1's informative functions (protein serine/threonine kinase activity, signaling adaptor/scaffold activity in TNFR1 complex I, death domain binding, RHIM-mediated binding to RIPK3) are captured by other annotations in this review. |
| GO:0005515 protein binding | IPI PMID:19524512 Receptor interacting protein kinase-3 determines cellular ne... | REMOVE | Summary: IPI-based protein binding annotation from PMID:19524512; the reported partner(s) in this context: RIPK3. Reason: Generic protein binding is uninformative and does not describe RIPK1's molecular activity; removal does not dispute the interaction. RIPK1's informative functions (protein serine/threonine kinase activity, signaling adaptor/scaffold activity in TNFR1 complex I, death domain binding, RHIM-mediated binding to RIPK3) are captured by other annotations in this review. |
| GO:0005515 protein binding | IPI PMID:19524512 Receptor interacting protein kinase-3 determines cellular ne... | REMOVE | Summary: IPI-based protein binding annotation from PMID:19524512; the reported partner(s) in this context: RIPK3. Reason: Generic protein binding is uninformative and does not describe RIPK1's molecular activity; removal does not dispute the interaction. RIPK1's informative functions (protein serine/threonine kinase activity, signaling adaptor/scaffold activity in TNFR1 complex I, death domain binding, RHIM-mediated binding to RIPK3) are captured by other annotations in this review. |
| GO:0005515 protein binding | IPI PMID:19524513 Phosphorylation-driven assembly of the RIP1-RIP3 complex reg... | REMOVE | Summary: IPI-based protein binding annotation from PMID:19524513; the reported partner(s) in this context: RIPK3. Reason: Generic protein binding is uninformative and does not describe RIPK1's molecular activity; removal does not dispute the interaction. RIPK1's informative functions (protein serine/threonine kinase activity, signaling adaptor/scaffold activity in TNFR1 complex I, death domain binding, RHIM-mediated binding to RIPK3) are captured by other annotations in this review. |
| GO:0005515 protein binding | IPI PMID:19524513 Phosphorylation-driven assembly of the RIP1-RIP3 complex reg... | REMOVE | Summary: IPI-based protein binding annotation from PMID:19524513; the reported partner(s) in this context: RIPK3. Reason: Generic protein binding is uninformative and does not describe RIPK1's molecular activity; removal does not dispute the interaction. RIPK1's informative functions (protein serine/threonine kinase activity, signaling adaptor/scaffold activity in TNFR1 complex I, death domain binding, RHIM-mediated binding to RIPK3) are captured by other annotations in this review. |
| GO:0005515 protein binding | IPI PMID:19524513 Phosphorylation-driven assembly of the RIP1-RIP3 complex reg... | REMOVE | Summary: IPI-based protein binding annotation from PMID:19524513; the reported partner(s) in this context: RIPK3. Reason: Generic protein binding is uninformative and does not describe RIPK1's molecular activity; removal does not dispute the interaction. RIPK1's informative functions (protein serine/threonine kinase activity, signaling adaptor/scaffold activity in TNFR1 complex I, death domain binding, RHIM-mediated binding to RIPK3) are captured by other annotations in this review. |
| GO:0005515 protein binding | IPI PMID:19524513 Phosphorylation-driven assembly of the RIP1-RIP3 complex reg... | REMOVE | Summary: IPI-based protein binding annotation from PMID:19524513; the reported partner(s) in this context: RIPK3. Reason: Generic protein binding is uninformative and does not describe RIPK1's molecular activity; removal does not dispute the interaction. RIPK1's informative functions (protein serine/threonine kinase activity, signaling adaptor/scaffold activity in TNFR1 complex I, death domain binding, RHIM-mediated binding to RIPK3) are captured by other annotations in this review. |
| GO:0005515 protein binding | IPI PMID:19781631 Proteinase-activated receptor-2 mediated inhibition of TNFal... | REMOVE | Summary: IPI-based protein binding annotation from PMID:19781631; the reported partner(s) in this context: TNF signaling components in a PAR2 study. Reason: Generic protein binding is uninformative and does not describe RIPK1's molecular activity; removal does not dispute the interaction. RIPK1's informative functions (protein serine/threonine kinase activity, signaling adaptor/scaffold activity in TNFR1 complex I, death domain binding, RHIM-mediated binding to RIPK3) are captured by other annotations in this review. |
| GO:0005515 protein binding | IPI PMID:21383699 Annexin-1 interacts with NEMO and RIP1 to constitutively act... | REMOVE | Summary: IPI-based protein binding annotation from PMID:21383699; the reported partner(s) in this context: ANXA1 and NEMO. Reason: Generic protein binding is uninformative and does not describe RIPK1's molecular activity; removal does not dispute the interaction. RIPK1's informative functions (protein serine/threonine kinase activity, signaling adaptor/scaffold activity in TNFR1 complex I, death domain binding, RHIM-mediated binding to RIPK3) are captured by other annotations in this review. |
| GO:0005515 protein binding | IPI PMID:21383699 Annexin-1 interacts with NEMO and RIP1 to constitutively act... | REMOVE | Summary: IPI-based protein binding annotation from PMID:21383699; the reported partner(s) in this context: ANXA1 and NEMO. Reason: Generic protein binding is uninformative and does not describe RIPK1's molecular activity; removal does not dispute the interaction. RIPK1's informative functions (protein serine/threonine kinase activity, signaling adaptor/scaffold activity in TNFR1 complex I, death domain binding, RHIM-mediated binding to RIPK3) are captured by other annotations in this review. |
| GO:0005515 protein binding | IPI PMID:21458669 NEMO and RIP1 control cell fate in response to extensive DNA... | REMOVE | Summary: IPI-based protein binding annotation from PMID:21458669; the reported partner(s) in this context: NEMO/FADD/caspase-8 after DNA damage. Reason: Generic protein binding is uninformative and does not describe RIPK1's molecular activity; removal does not dispute the interaction. RIPK1's informative functions (protein serine/threonine kinase activity, signaling adaptor/scaffold activity in TNFR1 complex I, death domain binding, RHIM-mediated binding to RIPK3) are captured by other annotations in this review. |
| GO:0005515 protein binding | IPI PMID:21458669 NEMO and RIP1 control cell fate in response to extensive DNA... | REMOVE | Summary: IPI-based protein binding annotation from PMID:21458669; the reported partner(s) in this context: NEMO/FADD/caspase-8 after DNA damage. Reason: Generic protein binding is uninformative and does not describe RIPK1's molecular activity; removal does not dispute the interaction. RIPK1's informative functions (protein serine/threonine kinase activity, signaling adaptor/scaffold activity in TNFR1 complex I, death domain binding, RHIM-mediated binding to RIPK3) are captured by other annotations in this review. |
| GO:0005515 protein binding | IPI PMID:21458669 NEMO and RIP1 control cell fate in response to extensive DNA... | REMOVE | Summary: IPI-based protein binding annotation from PMID:21458669; the reported partner(s) in this context: NEMO/FADD/caspase-8 after DNA damage. Reason: Generic protein binding is uninformative and does not describe RIPK1's molecular activity; removal does not dispute the interaction. RIPK1's informative functions (protein serine/threonine kinase activity, signaling adaptor/scaffold activity in TNFR1 complex I, death domain binding, RHIM-mediated binding to RIPK3) are captured by other annotations in this review. |
| GO:0005515 protein binding | IPI PMID:21525013 TWEAK induces apoptosis through a death-signaling complex co... | REMOVE | Summary: IPI-based protein binding annotation from PMID:21525013; the reported partner(s) in this context: FADD and caspase-8 (TWEAK-induced death complex). Reason: Generic protein binding is uninformative and does not describe RIPK1's molecular activity; removal does not dispute the interaction. RIPK1's informative functions (protein serine/threonine kinase activity, signaling adaptor/scaffold activity in TNFR1 complex I, death domain binding, RHIM-mediated binding to RIPK3) are captured by other annotations in this review. |
| GO:0005515 protein binding | IPI PMID:21525013 TWEAK induces apoptosis through a death-signaling complex co... | REMOVE | Summary: IPI-based protein binding annotation from PMID:21525013; the reported partner(s) in this context: FADD and caspase-8 (TWEAK-induced death complex). Reason: Generic protein binding is uninformative and does not describe RIPK1's molecular activity; removal does not dispute the interaction. RIPK1's informative functions (protein serine/threonine kinase activity, signaling adaptor/scaffold activity in TNFR1 complex I, death domain binding, RHIM-mediated binding to RIPK3) are captured by other annotations in this review. |
| GO:0005515 protein binding | IPI PMID:21810480 AWP1 binds to tumor necrosis factor receptor-associated fact... | REMOVE | Summary: IPI-based protein binding annotation from PMID:21810480; the reported partner(s) in this context: TRAF2-associated proteins (AWP1/ZFAND6 study). Reason: Generic protein binding is uninformative and does not describe RIPK1's molecular activity; removal does not dispute the interaction. RIPK1's informative functions (protein serine/threonine kinase activity, signaling adaptor/scaffold activity in TNFR1 complex I, death domain binding, RHIM-mediated binding to RIPK3) are captured by other annotations in this review. |
| GO:0005515 protein binding | IPI PMID:21887730 Control of NOD2 and Rip2-dependent innate immune activation ... | REMOVE | Summary: IPI-based protein binding annotation from PMID:21887730; the reported partner(s) in this context: ARHGEF2/GEF-H1. Reason: Generic protein binding is uninformative and does not describe RIPK1's molecular activity; removal does not dispute the interaction. RIPK1's informative functions (protein serine/threonine kinase activity, signaling adaptor/scaffold activity in TNFR1 complex I, death domain binding, RHIM-mediated binding to RIPK3) are captured by other annotations in this review. |
| GO:0005515 protein binding | IPI PMID:21931591 cIAP1/2 are direct E3 ligases conjugating diverse types of u... | REMOVE | Summary: IPI-based protein binding annotation from PMID:21931591; the reported partner(s) in this context: cIAP1, cIAP2 and XIAP. Reason: Generic protein binding is uninformative and does not describe RIPK1's molecular activity; removal does not dispute the interaction. RIPK1's informative functions (protein serine/threonine kinase activity, signaling adaptor/scaffold activity in TNFR1 complex I, death domain binding, RHIM-mediated binding to RIPK3) are captured by other annotations in this review. |
| GO:0005515 protein binding | IPI PMID:21931591 cIAP1/2 are direct E3 ligases conjugating diverse types of u... | REMOVE | Summary: IPI-based protein binding annotation from PMID:21931591; the reported partner(s) in this context: cIAP1, cIAP2 and XIAP. Reason: Generic protein binding is uninformative and does not describe RIPK1's molecular activity; removal does not dispute the interaction. RIPK1's informative functions (protein serine/threonine kinase activity, signaling adaptor/scaffold activity in TNFR1 complex I, death domain binding, RHIM-mediated binding to RIPK3) are captured by other annotations in this review. |
| GO:0005515 protein binding | IPI PMID:22173242 RIP1 is required for IAP inhibitor-mediated sensitization of... | REMOVE | Summary: IPI-based protein binding annotation from PMID:22173242; the reported partner(s) in this context: FADD and caspase-8. Reason: Generic protein binding is uninformative and does not describe RIPK1's molecular activity; removal does not dispute the interaction. RIPK1's informative functions (protein serine/threonine kinase activity, signaling adaptor/scaffold activity in TNFR1 complex I, death domain binding, RHIM-mediated binding to RIPK3) are captured by other annotations in this review. |
| GO:0005515 protein binding | IPI PMID:22265413 Mixed lineage kinase domain-like protein mediates necrosis s... | REMOVE | Summary: IPI-based protein binding annotation from PMID:22265413; the reported partner(s) in this context: RIPK3/MLKL necrosome components. Reason: Generic protein binding is uninformative and does not describe RIPK1's molecular activity; removal does not dispute the interaction. RIPK1's informative functions (protein serine/threonine kinase activity, signaling adaptor/scaffold activity in TNFR1 complex I, death domain binding, RHIM-mediated binding to RIPK3) are captured by other annotations in this review. |
| GO:0005515 protein binding | IPI PMID:22265414 The mitochondrial phosphatase PGAM5 functions at the converg... | REMOVE | Summary: IPI-based protein binding annotation from PMID:22265414; the reported partner(s) in this context: PGAM5/RIPK3/MLKL necrosome components. Reason: Generic protein binding is uninformative and does not describe RIPK1's molecular activity; removal does not dispute the interaction. RIPK1's informative functions (protein serine/threonine kinase activity, signaling adaptor/scaffold activity in TNFR1 complex I, death domain binding, RHIM-mediated binding to RIPK3) are captured by other annotations in this review. |
| GO:0005515 protein binding | IPI PMID:22274400 Pick your poison: the Ripoptosome, a cell death platform reg... | REMOVE | Summary: IPI-based protein binding annotation from PMID:22274400; the reported partner(s) in this context: ripoptosome components. Reason: Generic protein binding is uninformative and does not describe RIPK1's molecular activity; removal does not dispute the interaction. RIPK1's informative functions (protein serine/threonine kinase activity, signaling adaptor/scaffold activity in TNFR1 complex I, death domain binding, RHIM-mediated binding to RIPK3) are captured by other annotations in this review. |
| GO:0005515 protein binding | IPI PMID:22817896 The RIP1/RIP3 necrosome forms a functional amyloid signaling... | REMOVE | Summary: IPI-based protein binding annotation from PMID:22817896; the reported partner(s) in this context: RIPK3 (RHIM-RHIM hetero-amyloid). Reason: Generic protein binding is uninformative and does not describe RIPK1's molecular activity; removal does not dispute the interaction. RIPK1's informative functions (protein serine/threonine kinase activity, signaling adaptor/scaffold activity in TNFR1 complex I, death domain binding, RHIM-mediated binding to RIPK3) are captured by other annotations in this review. |
| GO:0005515 protein binding | IPI PMID:22817896 The RIP1/RIP3 necrosome forms a functional amyloid signaling... | REMOVE | Summary: IPI-based protein binding annotation from PMID:22817896; the reported partner(s) in this context: RIPK3 (RHIM-RHIM hetero-amyloid). Reason: Generic protein binding is uninformative and does not describe RIPK1's molecular activity; removal does not dispute the interaction. RIPK1's informative functions (protein serine/threonine kinase activity, signaling adaptor/scaffold activity in TNFR1 complex I, death domain binding, RHIM-mediated binding to RIPK3) are captured by other annotations in this review. |
| GO:0005515 protein binding | IPI PMID:23104095 Immunodeficiency, autoinflammation and amylopectinosis in hu... | REMOVE | Summary: IPI-based protein binding annotation from PMID:23104095; the reported partner(s) in this context: LUBAC components (HOIL-1/HOIP). Reason: Generic protein binding is uninformative and does not describe RIPK1's molecular activity; removal does not dispute the interaction. RIPK1's informative functions (protein serine/threonine kinase activity, signaling adaptor/scaffold activity in TNFR1 complex I, death domain binding, RHIM-mediated binding to RIPK3) are captured by other annotations in this review. |
| GO:0005515 protein binding | IPI PMID:23313255 Ubiquitin-specific protease 4 promotes TNF-Ξ±-induced apoptos... | REMOVE | Summary: IPI-based protein binding annotation from PMID:23313255; the reported partner(s) in this context: USP4 (deubiquitinase of RIP1). Reason: Generic protein binding is uninformative and does not describe RIPK1's molecular activity; removal does not dispute the interaction. RIPK1's informative functions (protein serine/threonine kinase activity, signaling adaptor/scaffold activity in TNFR1 complex I, death domain binding, RHIM-mediated binding to RIPK3) are captured by other annotations in this review. |
| GO:0005515 protein binding | IPI PMID:23955153 Pathogen blocks host death receptor signalling by arginine G... | REMOVE | Summary: IPI-based protein binding annotation from PMID:23955153; the reported partner(s) in this context: EPEC effector NleB (bacterial GlcNAc transferase). Reason: Generic protein binding is uninformative and does not describe RIPK1's molecular activity; removal does not dispute the interaction. RIPK1's informative functions (protein serine/threonine kinase activity, signaling adaptor/scaffold activity in TNFR1 complex I, death domain binding, RHIM-mediated binding to RIPK3) are captured by other annotations in this review. |
| GO:0005515 protein binding | IPI PMID:24025841 A type III effector antagonizes death receptor signalling du... | REMOVE | Summary: IPI-based protein binding annotation from PMID:24025841; the reported partner(s) in this context: EPEC effector NleB (bacterial). Reason: Generic protein binding is uninformative and does not describe RIPK1's molecular activity; removal does not dispute the interaction. RIPK1's informative functions (protein serine/threonine kinase activity, signaling adaptor/scaffold activity in TNFR1 complex I, death domain binding, RHIM-mediated binding to RIPK3) are captured by other annotations in this review. |
| GO:0005515 protein binding | IPI PMID:24130170 SH3RF2 functions as an oncogene by mediating PAK4 protein st... | REMOVE | Summary: IPI-based protein binding annotation from PMID:24130170; the reported partner(s) in this context: SH3RF2/TNFR1 complex components. Reason: Generic protein binding is uninformative and does not describe RIPK1's molecular activity; removal does not dispute the interaction. RIPK1's informative functions (protein serine/threonine kinase activity, signaling adaptor/scaffold activity in TNFR1 complex I, death domain binding, RHIM-mediated binding to RIPK3) are captured by other annotations in this review. |
| GO:0005515 protein binding | IPI PMID:25402006 In silico prediction of physical protein interactions and ch... | REMOVE | Summary: IPI-based protein binding annotation from PMID:25402006; the reported partner(s) in this context: in silico predicted partners. Reason: Generic protein binding is uninformative and does not describe RIPK1's molecular activity; removal does not dispute the interaction. RIPK1's informative functions (protein serine/threonine kinase activity, signaling adaptor/scaffold activity in TNFR1 complex I, death domain binding, RHIM-mediated binding to RIPK3) are captured by other annotations in this review. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: IPI-based protein binding annotation from PMID:25416956; the reported partner(s) in this context: yeast two-hybrid partners (proteome-scale screen). Reason: Generic protein binding is uninformative and does not describe RIPK1's molecular activity; removal does not dispute the interaction. RIPK1's informative functions (protein serine/threonine kinase activity, signaling adaptor/scaffold activity in TNFR1 complex I, death domain binding, RHIM-mediated binding to RIPK3) are captured by other annotations in this review. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: IPI-based protein binding annotation from PMID:25416956; the reported partner(s) in this context: yeast two-hybrid partners (proteome-scale screen). Reason: Generic protein binding is uninformative and does not describe RIPK1's molecular activity; removal does not dispute the interaction. RIPK1's informative functions (protein serine/threonine kinase activity, signaling adaptor/scaffold activity in TNFR1 complex I, death domain binding, RHIM-mediated binding to RIPK3) are captured by other annotations in this review. |
| GO:0005515 protein binding | IPI PMID:25736436 WDFY1 mediates TLR3/4 signaling by recruiting TRIF. | REMOVE | Summary: IPI-based protein binding annotation from PMID:25736436; the reported partner(s) in this context: TICAM1/TRIF (with WDFY1). Reason: Generic protein binding is uninformative and does not describe RIPK1's molecular activity; removal does not dispute the interaction. RIPK1's informative functions (protein serine/threonine kinase activity, signaling adaptor/scaffold activity in TNFR1 complex I, death domain binding, RHIM-mediated binding to RIPK3) are captured by other annotations in this review. |
| GO:0005515 protein binding | IPI PMID:25911380 The seventh zinc finger motif of A20 is required for the sup... | REMOVE | Summary: IPI-based protein binding annotation from PMID:25911380; the reported partner(s) in this context: A20 (TNFAIP3). Reason: Generic protein binding is uninformative and does not describe RIPK1's molecular activity; removal does not dispute the interaction. RIPK1's informative functions (protein serine/threonine kinase activity, signaling adaptor/scaffold activity in TNFR1 complex I, death domain binding, RHIM-mediated binding to RIPK3) are captured by other annotations in this review. |
| GO:0005515 protein binding | IPI PMID:26559832 Herpes Simplex Virus 1 (HSV-1) and HSV-2 Mediate Species-Spe... | REMOVE | Summary: IPI-based protein binding annotation from PMID:26559832; the reported partner(s) in this context: HSV-1/HSV-2 ICP6/ICP10 (RHIM-containing viral proteins). Reason: Generic protein binding is uninformative and does not describe RIPK1's molecular activity; removal does not dispute the interaction. RIPK1's informative functions (protein serine/threonine kinase activity, signaling adaptor/scaffold activity in TNFR1 complex I, death domain binding, RHIM-mediated binding to RIPK3) are captured by other annotations in this review. |
| GO:0005515 protein binding | IPI PMID:26559832 Herpes Simplex Virus 1 (HSV-1) and HSV-2 Mediate Species-Spe... | REMOVE | Summary: IPI-based protein binding annotation from PMID:26559832; the reported partner(s) in this context: HSV-1/HSV-2 ICP6/ICP10 (RHIM-containing viral proteins). Reason: Generic protein binding is uninformative and does not describe RIPK1's molecular activity; removal does not dispute the interaction. RIPK1's informative functions (protein serine/threonine kinase activity, signaling adaptor/scaffold activity in TNFR1 complex I, death domain binding, RHIM-mediated binding to RIPK3) are captured by other annotations in this review. |
| GO:0005515 protein binding | IPI PMID:29883609 PELI1 Selectively Targets Kinase-Active RIP3 for Ubiquitylat... | REMOVE | Summary: IPI-based protein binding annotation from PMID:29883609; the reported partner(s) in this context: PELI1 / RIPK3. Reason: Generic protein binding is uninformative and does not describe RIPK1's molecular activity; removal does not dispute the interaction. RIPK1's informative functions (protein serine/threonine kinase activity, signaling adaptor/scaffold activity in TNFR1 complex I, death domain binding, RHIM-mediated binding to RIPK3) are captured by other annotations in this review. |
| GO:0005515 protein binding | IPI PMID:29883609 PELI1 Selectively Targets Kinase-Active RIP3 for Ubiquitylat... | REMOVE | Summary: IPI-based protein binding annotation from PMID:29883609; the reported partner(s) in this context: PELI1 / RIPK3. Reason: Generic protein binding is uninformative and does not describe RIPK1's molecular activity; removal does not dispute the interaction. RIPK1's informative functions (protein serine/threonine kinase activity, signaling adaptor/scaffold activity in TNFR1 complex I, death domain binding, RHIM-mediated binding to RIPK3) are captured by other annotations in this review. |
| GO:0005515 protein binding | IPI PMID:30561431 A protein-protein interaction map of the TNF-induced NF-ΞΊB s... | REMOVE | Summary: IPI-based protein binding annotation from PMID:30561431; the reported partner(s) in this context: TNF/NF-kB pathway components (systematic interaction map). Reason: Generic protein binding is uninformative and does not describe RIPK1's molecular activity; removal does not dispute the interaction. RIPK1's informative functions (protein serine/threonine kinase activity, signaling adaptor/scaffold activity in TNFR1 complex I, death domain binding, RHIM-mediated binding to RIPK3) are captured by other annotations in this review. |
| GO:0005515 protein binding | IPI PMID:30561431 A protein-protein interaction map of the TNF-induced NF-ΞΊB s... | REMOVE | Summary: IPI-based protein binding annotation from PMID:30561431; the reported partner(s) in this context: TNF/NF-kB pathway components (systematic interaction map). Reason: Generic protein binding is uninformative and does not describe RIPK1's molecular activity; removal does not dispute the interaction. RIPK1's informative functions (protein serine/threonine kinase activity, signaling adaptor/scaffold activity in TNFR1 complex I, death domain binding, RHIM-mediated binding to RIPK3) are captured by other annotations in this review. |
| GO:0005515 protein binding | IPI PMID:30561431 A protein-protein interaction map of the TNF-induced NF-ΞΊB s... | REMOVE | Summary: IPI-based protein binding annotation from PMID:30561431; the reported partner(s) in this context: TNF/NF-kB pathway components (systematic interaction map). Reason: Generic protein binding is uninformative and does not describe RIPK1's molecular activity; removal does not dispute the interaction. RIPK1's informative functions (protein serine/threonine kinase activity, signaling adaptor/scaffold activity in TNFR1 complex I, death domain binding, RHIM-mediated binding to RIPK3) are captured by other annotations in this review. |
| GO:0005515 protein binding | IPI PMID:30561431 A protein-protein interaction map of the TNF-induced NF-ΞΊB s... | REMOVE | Summary: IPI-based protein binding annotation from PMID:30561431; the reported partner(s) in this context: TNF/NF-kB pathway components (systematic interaction map). Reason: Generic protein binding is uninformative and does not describe RIPK1's molecular activity; removal does not dispute the interaction. RIPK1's informative functions (protein serine/threonine kinase activity, signaling adaptor/scaffold activity in TNFR1 complex I, death domain binding, RHIM-mediated binding to RIPK3) are captured by other annotations in this review. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: IPI-based protein binding annotation from PMID:32296183; the reported partner(s) in this context: binary Y2H partners (HuRI). Reason: Generic protein binding is uninformative and does not describe RIPK1's molecular activity; removal does not dispute the interaction. RIPK1's informative functions (protein serine/threonine kinase activity, signaling adaptor/scaffold activity in TNFR1 complex I, death domain binding, RHIM-mediated binding to RIPK3) are captured by other annotations in this review. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: IPI-based protein binding annotation from PMID:32296183; the reported partner(s) in this context: binary Y2H partners (HuRI). Reason: Generic protein binding is uninformative and does not describe RIPK1's molecular activity; removal does not dispute the interaction. RIPK1's informative functions (protein serine/threonine kinase activity, signaling adaptor/scaffold activity in TNFR1 complex I, death domain binding, RHIM-mediated binding to RIPK3) are captured by other annotations in this review. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: IPI-based protein binding annotation from PMID:32296183; the reported partner(s) in this context: binary Y2H partners (HuRI). Reason: Generic protein binding is uninformative and does not describe RIPK1's molecular activity; removal does not dispute the interaction. RIPK1's informative functions (protein serine/threonine kinase activity, signaling adaptor/scaffold activity in TNFR1 complex I, death domain binding, RHIM-mediated binding to RIPK3) are captured by other annotations in this review. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: IPI-based protein binding annotation from PMID:32296183; the reported partner(s) in this context: binary Y2H partners (HuRI). Reason: Generic protein binding is uninformative and does not describe RIPK1's molecular activity; removal does not dispute the interaction. RIPK1's informative functions (protein serine/threonine kinase activity, signaling adaptor/scaffold activity in TNFR1 complex I, death domain binding, RHIM-mediated binding to RIPK3) are captured by other annotations in this review. |
| GO:0005515 protein binding | IPI PMID:32353859 A SARS-CoV-2 protein interaction map reveals targets for dru... | REMOVE | Summary: IPI-based protein binding annotation from PMID:32353859; the reported partner(s) in this context: SARS-CoV-2 proteins (AP-MS). Reason: Generic protein binding is uninformative and does not describe RIPK1's molecular activity; removal does not dispute the interaction. RIPK1's informative functions (protein serine/threonine kinase activity, signaling adaptor/scaffold activity in TNFR1 complex I, death domain binding, RHIM-mediated binding to RIPK3) are captured by other annotations in this review. |
| GO:0005515 protein binding | IPI PMID:32707033 Kinase Interaction Network Expands Functional and Disease Ro... | REMOVE | Summary: IPI-based protein binding annotation from PMID:32707033; the reported partner(s) in this context: kinase interactors (systematic AP-MS). Reason: Generic protein binding is uninformative and does not describe RIPK1's molecular activity; removal does not dispute the interaction. RIPK1's informative functions (protein serine/threonine kinase activity, signaling adaptor/scaffold activity in TNFR1 complex I, death domain binding, RHIM-mediated binding to RIPK3) are captured by other annotations in this review. |
| GO:0005515 protein binding | IPI PMID:32707033 Kinase Interaction Network Expands Functional and Disease Ro... | REMOVE | Summary: IPI-based protein binding annotation from PMID:32707033; the reported partner(s) in this context: kinase interactors (systematic AP-MS). Reason: Generic protein binding is uninformative and does not describe RIPK1's molecular activity; removal does not dispute the interaction. RIPK1's informative functions (protein serine/threonine kinase activity, signaling adaptor/scaffold activity in TNFR1 complex I, death domain binding, RHIM-mediated binding to RIPK3) are captured by other annotations in this review. |
| GO:0005515 protein binding | IPI PMID:33060197 Comparative host-coronavirus protein interaction networks re... | REMOVE | Summary: IPI-based protein binding annotation from PMID:33060197; the reported partner(s) in this context: coronavirus proteins (AP-MS). Reason: Generic protein binding is uninformative and does not describe RIPK1's molecular activity; removal does not dispute the interaction. RIPK1's informative functions (protein serine/threonine kinase activity, signaling adaptor/scaffold activity in TNFR1 complex I, death domain binding, RHIM-mediated binding to RIPK3) are captured by other annotations in this review. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: IPI-based protein binding annotation from PMID:33961781; the reported partner(s) in this context: binary partners (proteome-scale networks). Reason: Generic protein binding is uninformative and does not describe RIPK1's molecular activity; removal does not dispute the interaction. RIPK1's informative functions (protein serine/threonine kinase activity, signaling adaptor/scaffold activity in TNFR1 complex I, death domain binding, RHIM-mediated binding to RIPK3) are captured by other annotations in this review. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: IPI-based protein binding annotation from PMID:33961781; the reported partner(s) in this context: binary partners (proteome-scale networks). Reason: Generic protein binding is uninformative and does not describe RIPK1's molecular activity; removal does not dispute the interaction. RIPK1's informative functions (protein serine/threonine kinase activity, signaling adaptor/scaffold activity in TNFR1 complex I, death domain binding, RHIM-mediated binding to RIPK3) are captured by other annotations in this review. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: IPI-based protein binding annotation from PMID:33961781; the reported partner(s) in this context: binary partners (proteome-scale networks). Reason: Generic protein binding is uninformative and does not describe RIPK1's molecular activity; removal does not dispute the interaction. RIPK1's informative functions (protein serine/threonine kinase activity, signaling adaptor/scaffold activity in TNFR1 complex I, death domain binding, RHIM-mediated binding to RIPK3) are captured by other annotations in this review. |
| GO:0005515 protein binding | IPI PMID:34663909 SARS-CoV-2 promotes RIPK1 activation to facilitate viral pro... | REMOVE | Summary: IPI-based protein binding annotation from PMID:34663909; the reported partner(s) in this context: SARS-CoV-2 NSP12. Reason: Generic protein binding is uninformative and does not describe RIPK1's molecular activity; removal does not dispute the interaction. RIPK1's informative functions (protein serine/threonine kinase activity, signaling adaptor/scaffold activity in TNFR1 complex I, death domain binding, RHIM-mediated binding to RIPK3) are captured by other annotations in this review. |
| GO:0005515 protein binding | IPI PMID:36179048 Novel biochemical, structural, and systems insights into inf... | REMOVE | Summary: IPI-based protein binding annotation from PMID:36179048; the reported partner(s) in this context: TNF-RSC components. Reason: Generic protein binding is uninformative and does not describe RIPK1's molecular activity; removal does not dispute the interaction. RIPK1's informative functions (protein serine/threonine kinase activity, signaling adaptor/scaffold activity in TNFR1 complex I, death domain binding, RHIM-mediated binding to RIPK3) are captured by other annotations in this review. |
| GO:0005515 protein binding | IPI PMID:36217030 A comprehensive SARS-CoV-2-human protein-protein interactome... | REMOVE | Summary: IPI-based protein binding annotation from PMID:36217030; the reported partner(s) in this context: SARS-CoV-2 proteins. Reason: Generic protein binding is uninformative and does not describe RIPK1's molecular activity; removal does not dispute the interaction. RIPK1's informative functions (protein serine/threonine kinase activity, signaling adaptor/scaffold activity in TNFR1 complex I, death domain binding, RHIM-mediated binding to RIPK3) are captured by other annotations in this review. |
| GO:0005515 protein binding | IPI PMID:37089942 Curcumin alleviates experimental colitis in mice by suppress... | REMOVE | Summary: IPI-based protein binding annotation from PMID:37089942; the reported partner(s) in this context: RIPK3. Reason: Generic protein binding is uninformative and does not describe RIPK1's molecular activity; removal does not dispute the interaction. RIPK1's informative functions (protein serine/threonine kinase activity, signaling adaptor/scaffold activity in TNFR1 complex I, death domain binding, RHIM-mediated binding to RIPK3) are captured by other annotations in this review. |
| GO:0005524 ATP binding | IEA GO_REF:0000002 | ACCEPT | Summary: IEA ATP binding from InterPro kinase domain. Reason: RIPK1 has a catalytically active kinase domain that binds ATP; ATP-pocket-adjacent inhibitors (necrostatins) were co-crystallized with the kinase domain. Supporting Evidence: PMID:23473668 Here, we report the crystal structures of the RIP1 kinase domain individually bound to necrostatin-1 analog, necrostatin-3 analog, and necrostatin-4 |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: Cytoplasm (IBA). Reason: RIPK1 is a cytoplasmic signaling protein acting at receptor complexes and in cytosolic death complexes. Supporting Evidence: file:human/RIPK1/RIPK1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0005737 cytoplasm | IEA GO_REF:0000120 | ACCEPT | Summary: Cytoplasm (IEA). Reason: RIPK1 is a cytoplasmic signaling protein acting at receptor complexes and in cytosolic death complexes. Supporting Evidence: file:human/RIPK1/RIPK1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0005737 cytoplasm | ISS GO_REF:0000024 | ACCEPT | Summary: Cytoplasm (ISS). Reason: RIPK1 is a cytoplasmic signaling protein acting at receptor complexes and in cytosolic death complexes. Supporting Evidence: file:human/RIPK1/RIPK1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0005739 mitochondrion | IDA PMID:16507998 Inhibition of ADP/ATP exchange in receptor-interacting prote... | KEEP AS NON CORE | Summary: Mitochondrion (IDA) from a study of RIP-mediated inhibition of mitochondrial ADP/ATP exchange. Reason: The abstract describes RIP-dependent inhibition of ANT function rather than RIPK1 residence in mitochondria; the curator may have seen fractionation data in the full text (not cached). Mitochondrial association is at most a minor/conditional pool, so retain as non-core. Supporting Evidence: PMID:16507998 tumor necrosis factor alpha induced RIP-dependent inhibition of adenine nucleotide translocase (ANT)-conducted transport of ADP into mitochondria, which resulted in reduced ATP and necrotic cell death |
| GO:0005829 cytosol | TAS Reactome:R-HSA-139952 | ACCEPT | Summary: Cytosol (TAS, Reactome:R-HSA-139952). Reason: Reactome places RIPK1-containing complexes (complex II, ripoptosome, necrosome) in the cytosol; consistent with RIPK1 as a cytoplasmic signaling protein. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-140978 | ACCEPT | Summary: Cytosol (TAS, Reactome:R-HSA-140978). Reason: Reactome places RIPK1-containing complexes (complex II, ripoptosome, necrosome) in the cytosol; consistent with RIPK1 as a cytoplasmic signaling protein. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-141159 | ACCEPT | Summary: Cytosol (TAS, Reactome:R-HSA-141159). Reason: Reactome places RIPK1-containing complexes (complex II, ripoptosome, necrosome) in the cytosol; consistent with RIPK1 as a cytoplasmic signaling protein. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-168915 | ACCEPT | Summary: Cytosol (TAS, Reactome:R-HSA-168915). Reason: Reactome places RIPK1-containing complexes (complex II, ripoptosome, necrosome) in the cytosol; consistent with RIPK1 as a cytoplasmic signaling protein. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-168921 | ACCEPT | Summary: Cytosol (TAS, Reactome:R-HSA-168921). Reason: Reactome places RIPK1-containing complexes (complex II, ripoptosome, necrosome) in the cytosol; consistent with RIPK1 as a cytoplasmic signaling protein. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-168930 | ACCEPT | Summary: Cytosol (TAS, Reactome:R-HSA-168930). Reason: Reactome places RIPK1-containing complexes (complex II, ripoptosome, necrosome) in the cytosol; consistent with RIPK1 as a cytoplasmic signaling protein. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-168934 | ACCEPT | Summary: Cytosol (TAS, Reactome:R-HSA-168934). Reason: Reactome places RIPK1-containing complexes (complex II, ripoptosome, necrosome) in the cytosol; consistent with RIPK1 as a cytoplasmic signaling protein. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1810457 | ACCEPT | Summary: Cytosol (TAS, Reactome:R-HSA-1810457). Reason: Reactome places RIPK1-containing complexes (complex II, ripoptosome, necrosome) in the cytosol; consistent with RIPK1 as a cytoplasmic signaling protein. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2562541 | ACCEPT | Summary: Cytosol (TAS, Reactome:R-HSA-2562541). Reason: Reactome places RIPK1-containing complexes (complex II, ripoptosome, necrosome) in the cytosol; consistent with RIPK1 as a cytoplasmic signaling protein. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2562564 | ACCEPT | Summary: Cytosol (TAS, Reactome:R-HSA-2562564). Reason: Reactome places RIPK1-containing complexes (complex II, ripoptosome, necrosome) in the cytosol; consistent with RIPK1 as a cytoplasmic signaling protein. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-3371360 | ACCEPT | Summary: Cytosol (TAS, Reactome:R-HSA-3371360). Reason: Reactome places RIPK1-containing complexes (complex II, ripoptosome, necrosome) in the cytosol; consistent with RIPK1 as a cytoplasmic signaling protein. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-3465429 | ACCEPT | Summary: Cytosol (TAS, Reactome:R-HSA-3465429). Reason: Reactome places RIPK1-containing complexes (complex II, ripoptosome, necrosome) in the cytosol; consistent with RIPK1 as a cytoplasmic signaling protein. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-3465448 | ACCEPT | Summary: Cytosol (TAS, Reactome:R-HSA-3465448). Reason: Reactome places RIPK1-containing complexes (complex II, ripoptosome, necrosome) in the cytosol; consistent with RIPK1 as a cytoplasmic signaling protein. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5213462 | ACCEPT | Summary: Cytosol (TAS, Reactome:R-HSA-5213462). Reason: Reactome places RIPK1-containing complexes (complex II, ripoptosome, necrosome) in the cytosol; consistent with RIPK1 as a cytoplasmic signaling protein. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5213464 | ACCEPT | Summary: Cytosol (TAS, Reactome:R-HSA-5213464). Reason: Reactome places RIPK1-containing complexes (complex II, ripoptosome, necrosome) in the cytosol; consistent with RIPK1 as a cytoplasmic signaling protein. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5213466 | ACCEPT | Summary: Cytosol (TAS, Reactome:R-HSA-5213466). Reason: Reactome places RIPK1-containing complexes (complex II, ripoptosome, necrosome) in the cytosol; consistent with RIPK1 as a cytoplasmic signaling protein. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5218891 | ACCEPT | Summary: Cytosol (TAS, Reactome:R-HSA-5218891). Reason: Reactome places RIPK1-containing complexes (complex II, ripoptosome, necrosome) in the cytosol; consistent with RIPK1 as a cytoplasmic signaling protein. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5218905 | ACCEPT | Summary: Cytosol (TAS, Reactome:R-HSA-5218905). Reason: Reactome places RIPK1-containing complexes (complex II, ripoptosome, necrosome) in the cytosol; consistent with RIPK1 as a cytoplasmic signaling protein. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5218906 | ACCEPT | Summary: Cytosol (TAS, Reactome:R-HSA-5218906). Reason: Reactome places RIPK1-containing complexes (complex II, ripoptosome, necrosome) in the cytosol; consistent with RIPK1 as a cytoplasmic signaling protein. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5357757 | ACCEPT | Summary: Cytosol (TAS, Reactome:R-HSA-5357757). Reason: Reactome places RIPK1-containing complexes (complex II, ripoptosome, necrosome) in the cytosol; consistent with RIPK1 as a cytoplasmic signaling protein. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5357776 | ACCEPT | Summary: Cytosol (TAS, Reactome:R-HSA-5357776). Reason: Reactome places RIPK1-containing complexes (complex II, ripoptosome, necrosome) in the cytosol; consistent with RIPK1 as a cytoplasmic signaling protein. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5357780 | ACCEPT | Summary: Cytosol (TAS, Reactome:R-HSA-5357780). Reason: Reactome places RIPK1-containing complexes (complex II, ripoptosome, necrosome) in the cytosol; consistent with RIPK1 as a cytoplasmic signaling protein. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5357828 | ACCEPT | Summary: Cytosol (TAS, Reactome:R-HSA-5357828). Reason: Reactome places RIPK1-containing complexes (complex II, ripoptosome, necrosome) in the cytosol; consistent with RIPK1 as a cytoplasmic signaling protein. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5357845 | ACCEPT | Summary: Cytosol (TAS, Reactome:R-HSA-5357845). Reason: Reactome places RIPK1-containing complexes (complex II, ripoptosome, necrosome) in the cytosol; consistent with RIPK1 as a cytoplasmic signaling protein. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5357860 | ACCEPT | Summary: Cytosol (TAS, Reactome:R-HSA-5357860). Reason: Reactome places RIPK1-containing complexes (complex II, ripoptosome, necrosome) in the cytosol; consistent with RIPK1 as a cytoplasmic signaling protein. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5357904 | ACCEPT | Summary: Cytosol (TAS, Reactome:R-HSA-5357904). Reason: Reactome places RIPK1-containing complexes (complex II, ripoptosome, necrosome) in the cytosol; consistent with RIPK1 as a cytoplasmic signaling protein. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5357927 | ACCEPT | Summary: Cytosol (TAS, Reactome:R-HSA-5357927). Reason: Reactome places RIPK1-containing complexes (complex II, ripoptosome, necrosome) in the cytosol; consistent with RIPK1 as a cytoplasmic signaling protein. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5357928 | ACCEPT | Summary: Cytosol (TAS, Reactome:R-HSA-5357928). Reason: Reactome places RIPK1-containing complexes (complex II, ripoptosome, necrosome) in the cytosol; consistent with RIPK1 as a cytoplasmic signaling protein. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5620975 | ACCEPT | Summary: Cytosol (TAS, Reactome:R-HSA-5620975). Reason: Reactome places RIPK1-containing complexes (complex II, ripoptosome, necrosome) in the cytosol; consistent with RIPK1 as a cytoplasmic signaling protein. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5634221 | ACCEPT | Summary: Cytosol (TAS, Reactome:R-HSA-5634221). Reason: Reactome places RIPK1-containing complexes (complex II, ripoptosome, necrosome) in the cytosol; consistent with RIPK1 as a cytoplasmic signaling protein. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5675456 | ACCEPT | Summary: Cytosol (TAS, Reactome:R-HSA-5675456). Reason: Reactome places RIPK1-containing complexes (complex II, ripoptosome, necrosome) in the cytosol; consistent with RIPK1 as a cytoplasmic signaling protein. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5690159 | ACCEPT | Summary: Cytosol (TAS, Reactome:R-HSA-5690159). Reason: Reactome places RIPK1-containing complexes (complex II, ripoptosome, necrosome) in the cytosol; consistent with RIPK1 as a cytoplasmic signaling protein. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5690827 | ACCEPT | Summary: Cytosol (TAS, Reactome:R-HSA-5690827). Reason: Reactome places RIPK1-containing complexes (complex II, ripoptosome, necrosome) in the cytosol; consistent with RIPK1 as a cytoplasmic signaling protein. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5690856 | ACCEPT | Summary: Cytosol (TAS, Reactome:R-HSA-5690856). Reason: Reactome places RIPK1-containing complexes (complex II, ripoptosome, necrosome) in the cytosol; consistent with RIPK1 as a cytoplasmic signaling protein. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5693055 | ACCEPT | Summary: Cytosol (TAS, Reactome:R-HSA-5693055). Reason: Reactome places RIPK1-containing complexes (complex II, ripoptosome, necrosome) in the cytosol; consistent with RIPK1 as a cytoplasmic signaling protein. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5693108 | ACCEPT | Summary: Cytosol (TAS, Reactome:R-HSA-5693108). Reason: Reactome places RIPK1-containing complexes (complex II, ripoptosome, necrosome) in the cytosol; consistent with RIPK1 as a cytoplasmic signaling protein. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5696627 | ACCEPT | Summary: Cytosol (TAS, Reactome:R-HSA-5696627). Reason: Reactome places RIPK1-containing complexes (complex II, ripoptosome, necrosome) in the cytosol; consistent with RIPK1 as a cytoplasmic signaling protein. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-75240 | ACCEPT | Summary: Cytosol (TAS, Reactome:R-HSA-75240). Reason: Reactome places RIPK1-containing complexes (complex II, ripoptosome, necrosome) in the cytosol; consistent with RIPK1 as a cytoplasmic signaling protein. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-83582 | ACCEPT | Summary: Cytosol (TAS, Reactome:R-HSA-83582). Reason: Reactome places RIPK1-containing complexes (complex II, ripoptosome, necrosome) in the cytosol; consistent with RIPK1 as a cytoplasmic signaling protein. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-83656 | ACCEPT | Summary: Cytosol (TAS, Reactome:R-HSA-83656). Reason: Reactome places RIPK1-containing complexes (complex II, ripoptosome, necrosome) in the cytosol; consistent with RIPK1 as a cytoplasmic signaling protein. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9013889 | ACCEPT | Summary: Cytosol (TAS, Reactome:R-HSA-9013889). Reason: Reactome places RIPK1-containing complexes (complex II, ripoptosome, necrosome) in the cytosol; consistent with RIPK1 as a cytoplasmic signaling protein. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9013895 | ACCEPT | Summary: Cytosol (TAS, Reactome:R-HSA-9013895). Reason: Reactome places RIPK1-containing complexes (complex II, ripoptosome, necrosome) in the cytosol; consistent with RIPK1 as a cytoplasmic signaling protein. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9014342 | ACCEPT | Summary: Cytosol (TAS, Reactome:R-HSA-9014342). Reason: Reactome places RIPK1-containing complexes (complex II, ripoptosome, necrosome) in the cytosol; consistent with RIPK1 as a cytoplasmic signaling protein. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9014343 | ACCEPT | Summary: Cytosol (TAS, Reactome:R-HSA-9014343). Reason: Reactome places RIPK1-containing complexes (complex II, ripoptosome, necrosome) in the cytosol; consistent with RIPK1 as a cytoplasmic signaling protein. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-933523 | ACCEPT | Summary: Cytosol (TAS, Reactome:R-HSA-933523). Reason: Reactome places RIPK1-containing complexes (complex II, ripoptosome, necrosome) in the cytosol; consistent with RIPK1 as a cytoplasmic signaling protein. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-933526 | ACCEPT | Summary: Cytosol (TAS, Reactome:R-HSA-933526). Reason: Reactome places RIPK1-containing complexes (complex II, ripoptosome, necrosome) in the cytosol; consistent with RIPK1 as a cytoplasmic signaling protein. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-933532 | ACCEPT | Summary: Cytosol (TAS, Reactome:R-HSA-933532). Reason: Reactome places RIPK1-containing complexes (complex II, ripoptosome, necrosome) in the cytosol; consistent with RIPK1 as a cytoplasmic signaling protein. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-933539 | ACCEPT | Summary: Cytosol (TAS, Reactome:R-HSA-933539). Reason: Reactome places RIPK1-containing complexes (complex II, ripoptosome, necrosome) in the cytosol; consistent with RIPK1 as a cytoplasmic signaling protein. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-937029 | ACCEPT | Summary: Cytosol (TAS, Reactome:R-HSA-937029). Reason: Reactome places RIPK1-containing complexes (complex II, ripoptosome, necrosome) in the cytosol; consistent with RIPK1 as a cytoplasmic signaling protein. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9686336 | ACCEPT | Summary: Cytosol (TAS, Reactome:R-HSA-9686336). Reason: Reactome places RIPK1-containing complexes (complex II, ripoptosome, necrosome) in the cytosol; consistent with RIPK1 as a cytoplasmic signaling protein. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9686338 | ACCEPT | Summary: Cytosol (TAS, Reactome:R-HSA-9686338). Reason: Reactome places RIPK1-containing complexes (complex II, ripoptosome, necrosome) in the cytosol; consistent with RIPK1 as a cytoplasmic signaling protein. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9686345 | ACCEPT | Summary: Cytosol (TAS, Reactome:R-HSA-9686345). Reason: Reactome places RIPK1-containing complexes (complex II, ripoptosome, necrosome) in the cytosol; consistent with RIPK1 as a cytoplasmic signaling protein. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9686920 | ACCEPT | Summary: Cytosol (TAS, Reactome:R-HSA-9686920). Reason: Reactome places RIPK1-containing complexes (complex II, ripoptosome, necrosome) in the cytosol; consistent with RIPK1 as a cytoplasmic signaling protein. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9686922 | ACCEPT | Summary: Cytosol (TAS, Reactome:R-HSA-9686922). Reason: Reactome places RIPK1-containing complexes (complex II, ripoptosome, necrosome) in the cytosol; consistent with RIPK1 as a cytoplasmic signaling protein. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9687465 | ACCEPT | Summary: Cytosol (TAS, Reactome:R-HSA-9687465). Reason: Reactome places RIPK1-containing complexes (complex II, ripoptosome, necrosome) in the cytosol; consistent with RIPK1 as a cytoplasmic signaling protein. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9687625 | ACCEPT | Summary: Cytosol (TAS, Reactome:R-HSA-9687625). Reason: Reactome places RIPK1-containing complexes (complex II, ripoptosome, necrosome) in the cytosol; consistent with RIPK1 as a cytoplasmic signaling protein. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9687638 | ACCEPT | Summary: Cytosol (TAS, Reactome:R-HSA-9687638). Reason: Reactome places RIPK1-containing complexes (complex II, ripoptosome, necrosome) in the cytosol; consistent with RIPK1 as a cytoplasmic signaling protein. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9688456 | ACCEPT | Summary: Cytosol (TAS, Reactome:R-HSA-9688456). Reason: Reactome places RIPK1-containing complexes (complex II, ripoptosome, necrosome) in the cytosol; consistent with RIPK1 as a cytoplasmic signaling protein. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9688832 | ACCEPT | Summary: Cytosol (TAS, Reactome:R-HSA-9688832). Reason: Reactome places RIPK1-containing complexes (complex II, ripoptosome, necrosome) in the cytosol; consistent with RIPK1 as a cytoplasmic signaling protein. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9693929 | ACCEPT | Summary: Cytosol (TAS, Reactome:R-HSA-9693929). Reason: Reactome places RIPK1-containing complexes (complex II, ripoptosome, necrosome) in the cytosol; consistent with RIPK1 as a cytoplasmic signaling protein. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9693978 | ACCEPT | Summary: Cytosol (TAS, Reactome:R-HSA-9693978). Reason: Reactome places RIPK1-containing complexes (complex II, ripoptosome, necrosome) in the cytosol; consistent with RIPK1 as a cytoplasmic signaling protein. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9697747 | ACCEPT | Summary: Cytosol (TAS, Reactome:R-HSA-9697747). Reason: Reactome places RIPK1-containing complexes (complex II, ripoptosome, necrosome) in the cytosol; consistent with RIPK1 as a cytoplasmic signaling protein. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9697750 | ACCEPT | Summary: Cytosol (TAS, Reactome:R-HSA-9697750). Reason: Reactome places RIPK1-containing complexes (complex II, ripoptosome, necrosome) in the cytosol; consistent with RIPK1 as a cytoplasmic signaling protein. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9793444 | ACCEPT | Summary: Cytosol (TAS, Reactome:R-HSA-9793444). Reason: Reactome places RIPK1-containing complexes (complex II, ripoptosome, necrosome) in the cytosol; consistent with RIPK1 as a cytoplasmic signaling protein. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9793451 | ACCEPT | Summary: Cytosol (TAS, Reactome:R-HSA-9793451). Reason: Reactome places RIPK1-containing complexes (complex II, ripoptosome, necrosome) in the cytosol; consistent with RIPK1 as a cytoplasmic signaling protein. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9793679 | ACCEPT | Summary: Cytosol (TAS, Reactome:R-HSA-9793679). Reason: Reactome places RIPK1-containing complexes (complex II, ripoptosome, necrosome) in the cytosol; consistent with RIPK1 as a cytoplasmic signaling protein. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9793680 | ACCEPT | Summary: Cytosol (TAS, Reactome:R-HSA-9793680). Reason: Reactome places RIPK1-containing complexes (complex II, ripoptosome, necrosome) in the cytosol; consistent with RIPK1 as a cytoplasmic signaling protein. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9796342 | ACCEPT | Summary: Cytosol (TAS, Reactome:R-HSA-9796342). Reason: Reactome places RIPK1-containing complexes (complex II, ripoptosome, necrosome) in the cytosol; consistent with RIPK1 as a cytoplasmic signaling protein. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9796346 | ACCEPT | Summary: Cytosol (TAS, Reactome:R-HSA-9796346). Reason: Reactome places RIPK1-containing complexes (complex II, ripoptosome, necrosome) in the cytosol; consistent with RIPK1 as a cytoplasmic signaling protein. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9796368 | ACCEPT | Summary: Cytosol (TAS, Reactome:R-HSA-9796368). Reason: Reactome places RIPK1-containing complexes (complex II, ripoptosome, necrosome) in the cytosol; consistent with RIPK1 as a cytoplasmic signaling protein. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9796379 | ACCEPT | Summary: Cytosol (TAS, Reactome:R-HSA-9796379). Reason: Reactome places RIPK1-containing complexes (complex II, ripoptosome, necrosome) in the cytosol; consistent with RIPK1 as a cytoplasmic signaling protein. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9796387 | ACCEPT | Summary: Cytosol (TAS, Reactome:R-HSA-9796387). Reason: Reactome places RIPK1-containing complexes (complex II, ripoptosome, necrosome) in the cytosol; consistent with RIPK1 as a cytoplasmic signaling protein. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9815501 | ACCEPT | Summary: Cytosol (TAS, Reactome:R-HSA-9815501). Reason: Reactome places RIPK1-containing complexes (complex II, ripoptosome, necrosome) in the cytosol; consistent with RIPK1 as a cytoplasmic signaling protein. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9817362 | ACCEPT | Summary: Cytosol (TAS, Reactome:R-HSA-9817362). Reason: Reactome places RIPK1-containing complexes (complex II, ripoptosome, necrosome) in the cytosol; consistent with RIPK1 as a cytoplasmic signaling protein. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9817397 | ACCEPT | Summary: Cytosol (TAS, Reactome:R-HSA-9817397). Reason: Reactome places RIPK1-containing complexes (complex II, ripoptosome, necrosome) in the cytosol; consistent with RIPK1 as a cytoplasmic signaling protein. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9817400 | ACCEPT | Summary: Cytosol (TAS, Reactome:R-HSA-9817400). Reason: Reactome places RIPK1-containing complexes (complex II, ripoptosome, necrosome) in the cytosol; consistent with RIPK1 as a cytoplasmic signaling protein. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9817411 | ACCEPT | Summary: Cytosol (TAS, Reactome:R-HSA-9817411). Reason: Reactome places RIPK1-containing complexes (complex II, ripoptosome, necrosome) in the cytosol; consistent with RIPK1 as a cytoplasmic signaling protein. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9818789 | ACCEPT | Summary: Cytosol (TAS, Reactome:R-HSA-9818789). Reason: Reactome places RIPK1-containing complexes (complex II, ripoptosome, necrosome) in the cytosol; consistent with RIPK1 as a cytoplasmic signaling protein. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9818975 | ACCEPT | Summary: Cytosol (TAS, Reactome:R-HSA-9818975). Reason: Reactome places RIPK1-containing complexes (complex II, ripoptosome, necrosome) in the cytosol; consistent with RIPK1 as a cytoplasmic signaling protein. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9819106 | ACCEPT | Summary: Cytosol (TAS, Reactome:R-HSA-9819106). Reason: Reactome places RIPK1-containing complexes (complex II, ripoptosome, necrosome) in the cytosol; consistent with RIPK1 as a cytoplasmic signaling protein. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9824874 | ACCEPT | Summary: Cytosol (TAS, Reactome:R-HSA-9824874). Reason: Reactome places RIPK1-containing complexes (complex II, ripoptosome, necrosome) in the cytosol; consistent with RIPK1 as a cytoplasmic signaling protein. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9921857 | ACCEPT | Summary: Cytosol (TAS, Reactome:R-HSA-9921857). Reason: Reactome places RIPK1-containing complexes (complex II, ripoptosome, necrosome) in the cytosol; consistent with RIPK1 as a cytoplasmic signaling protein. |
| GO:0005886 plasma membrane | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Plasma membrane (IEA, GO_REF:0000044). Reason: RIPK1 is a cytoplasmic protein that is recruited to ligand-bound TNFR1 at the plasma membrane as part of complex I; it is peripheral, not an integral membrane protein. Acceptable as non-core location (the TNFR superfamily complex term is more informative). Supporting Evidence: PMID:12887920 The initial plasma membrane bound complex (complex I) consists of TNFR1, the adaptor TRADD, the kinase RIP1, and TRAF2 and rapidly signals activation of NF-kappa B |
| GO:0005886 plasma membrane | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Plasma membrane (ISS, GO_REF:0000024). Reason: RIPK1 is a cytoplasmic protein that is recruited to ligand-bound TNFR1 at the plasma membrane as part of complex I; it is peripheral, not an integral membrane protein. Acceptable as non-core location (the TNFR superfamily complex term is more informative). Supporting Evidence: PMID:12887920 The initial plasma membrane bound complex (complex I) consists of TNFR1, the adaptor TRADD, the kinase RIP1, and TRAF2 and rapidly signals activation of NF-kappa B |
| GO:0005886 plasma membrane | NAS PMID:33495445 A conformation-selective monoclonal antibody against a small... | KEEP AS NON CORE | Summary: Plasma membrane (NAS, PMID:33495445). Reason: RIPK1 is a cytoplasmic protein that is recruited to ligand-bound TNFR1 at the plasma membrane as part of complex I; it is peripheral, not an integral membrane protein. Acceptable as non-core location (the TNFR superfamily complex term is more informative). Supporting Evidence: PMID:12887920 The initial plasma membrane bound complex (complex I) consists of TNFR1, the adaptor TRADD, the kinase RIP1, and TRAF2 and rapidly signals activation of NF-kappa B |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9679839 | KEEP AS NON CORE | Summary: Plasma membrane (TAS, Reactome:R-HSA-9679839). Reason: RIPK1 is a cytoplasmic protein that is recruited to ligand-bound TNFR1 at the plasma membrane as part of complex I; it is peripheral, not an integral membrane protein. Acceptable as non-core location (the TNFR superfamily complex term is more informative). Supporting Evidence: Reactome:R-HSA-9679839 TNF-alpha signaling leads to the assembly of a large receptor-bound signaling complex, which includes multiple adaptors (TRADD, TRAF2, and RIPK1) |
| GO:0006915 apoptotic process | IEA GO_REF:0000107 | ACCEPT | Summary: Apoptotic process (IEA, GO_REF:0000107). Reason: RIPK1 kinase activity drives caspase-8 activation in complex IIa/ripoptosome (RIPK1-dependent apoptosis), so RIPK1 participates in apoptotic signaling; the more specific extrinsic apoptotic signaling pathway term is also annotated. Supporting Evidence: PMID:30988283 As a scaffold, RIPK1 inhibits caspase-8-dependent apoptosis and RIPK3/MLKL-dependent necroptosis. As a kinase, RIPK1 paradoxically induces these cell death modalities |
| GO:0006915 apoptotic process | IMP PMID:21737330 cIAPs block Ripoptosome formation, a RIP1/caspase-8 containi... | ACCEPT | Summary: Apoptotic process (IMP, PMID:21737330). Reason: RIPK1 kinase activity drives caspase-8 activation in complex IIa/ripoptosome (RIPK1-dependent apoptosis), so RIPK1 participates in apoptotic signaling; the more specific extrinsic apoptotic signaling pathway term is also annotated. Supporting Evidence: PMID:21737330 loss of cIAPs promotes the spontaneous formation of an intracellular platform that activates either apoptosis or necroptosis |
| GO:0006915 apoptotic process | IMP PMID:22891283 Vesicles released by activated T cells induce both Fas-media... | ACCEPT | Summary: Apoptotic process (IMP, PMID:22891283). Reason: RIPK1 kinase activity drives caspase-8 activation in complex IIa/ripoptosome (RIPK1-dependent apoptosis), so RIPK1 participates in apoptotic signaling; the more specific extrinsic apoptotic signaling pathway term is also annotated. Supporting Evidence: PMID:22891283 It could be partially inhibited by blocking cathepsin D enzyme activity and required the presence of RIP |
| GO:0006915 apoptotic process | IMP PMID:29440439 Death-domain dimerization-mediated activation of RIPK1 contr... | ACCEPT | Summary: Apoptotic process (IMP, PMID:29440439). Reason: RIPK1 kinase activity drives caspase-8 activation in complex IIa/ripoptosome (RIPK1-dependent apoptosis), so RIPK1 participates in apoptotic signaling; the more specific extrinsic apoptotic signaling pathway term is also annotated. Supporting Evidence: PMID:29440439 Ripk1K584R/K584R knockin mutant cells are resistant to RIPK1 kinase-dependent apoptosis and necroptosis |
| GO:0006954 inflammatory response | NAS PMID:33800290 The Role of Tumor Necrosis Factor Alpha (TNF-Ξ±) in Autoimmun... | KEEP AS NON CORE | Summary: Inflammatory response (NAS) from a review of TNF in autoimmune disease. Reason: RIPK1 drives TNF-induced inflammatory gene expression and inflammatory cell death; supported experimentally by RIPK1 non-cleavable variants causing autoinflammation. Retain as non-core. Supporting Evidence: PMID:33800290 Complex IIc (known as necrosome) is known to be formed by RIPK1 and RIPK3, which bind to form the complex when they remain uncleaved PMID:31827280 The patients showed strong RIPK1-dependent activation of inflammatory signalling pathways and overproduction of inflammatory cytokines and chemokines |
| GO:0006979 response to oxidative stress | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: response to oxidative stress (IEA). Reason: RIPK1 kinase activity contributes to oxidative-stress (H2O2)-induced necrotic death in some cell types (blocked by necrostatin-1 or RIPK1 knockdown); this reflects RIPK1's role in necroptosis rather than a dedicated oxidative-stress response function. |
| GO:0006979 response to oxidative stress | IMP PMID:20550618 MicroRNA-155 prevents necrotic cell death in human cardiomyo... | KEEP AS NON CORE | Summary: response to oxidative stress (IMP). Reason: RIPK1 kinase activity contributes to oxidative-stress (H2O2)-induced necrotic death in some cell types (blocked by necrostatin-1 or RIPK1 knockdown); this reflects RIPK1's role in necroptosis rather than a dedicated oxidative-stress response function. Supporting Evidence: PMID:20550618 inhibiting RIP1, either by pre-incubating the cells with a RIP1 specific inhibitor, Necrostatin-1 or siRNA mediated knockdown, reduced necrosis |
| GO:0007165 signal transduction | IEA GO_REF:0000002 | ACCEPT | Summary: IEA signal transduction from InterPro. Reason: Correct but very general; RIPK1 is a signal transducer downstream of TNFR1, FAS, TLR3/4 and ZBP1. Supporting Evidence: PMID:8612133 RIP is a serine-threonine kinase that is recruited by TRADD to TNFR1 in a TNF-dependent process |
| GO:0007249 canonical NF-kappaB signal transduction | IMP PMID:8612133 TNF-dependent recruitment of the protein kinase RIP to the T... | ACCEPT | Summary: Canonical NF-kappaB signal transduction (IMP, 8612133). Reason: Core kinase-independent scaffold function: RIPK1 overexpression activates NF-kB and its isolated death domain is dominant-negative for TNF-induced NF-kB activation. Supporting Evidence: PMID:8612133 Overexpression of the intact RIP protein induces both NF-kappa B activation and apoptosis PMID:10521396 We demonstrated that the cleavage of RIP resulted in the blockage of TNF-induced NF-kappaB activation |
| GO:0008625 extrinsic apoptotic signaling pathway via death domain receptors | NAS PMID:36380021 Death by TNF: a road to inflammation. | ACCEPT | Summary: Extrinsic apoptotic signaling pathway via death domain receptors (NAS, review). Reason: RIPK1 participates in TNFR1/FAS-initiated apoptosis through complex IIa (RIPK1-FADD-caspase-8). Supporting Evidence: PMID:36380021 Accordingly, inactivation of caspase 8 switches the TNF response to RIPK1 kinase activity-dependent necroptosis, which additionally requires recruitment of the kinase RIPK3 and of the potential pore-forming pseudo-kinase mixed lineage kinase domain-like protein (MLKL) to complex II PMID:21525013 Knockdown of RIP1 by siRNA prevented TWEAK-induced association of FADD with caspase-8 but not formation of the FN14-TRAF2-cIAP1 complex and inhibited apoptosis activation |
| GO:0008630 intrinsic apoptotic signaling pathway in response to DNA damage | NAS PMID:21458669 NEMO and RIP1 control cell fate in response to extensive DNA... | MARK AS OVER ANNOTATED | Summary: Intrinsic apoptotic signaling pathway in response to DNA damage (NAS, 21458669). Reason: In the cited work, extensive DNA damage triggers ATM/NEMO-dependent autocrine TNF-alpha-TNFR1 signaling; RIPK1 kinase then drives FADD-mediated caspase-8 activation, i.e. an extrinsic-type death-receptor mechanism. RIPK1 is not a component of the intrinsic (mitochondrial) DNA-damage pathway per se. Supporting Evidence: PMID:21458669 In turn, RIP1 kinase triggered JNK3/MAPK10-dependent interleukin-8 secretion and FADD-mediated proapoptotic caspase-8 activation |
| GO:0010008 endosome membrane | TAS Reactome:R-HSA-168930 | KEEP AS NON CORE | Summary: Endosome membrane (TAS, Reactome:R-HSA-168930) for TLR3/TRIF-associated RIPK1. Reason: RIPK1 is recruited via its RHIM to TRIF at endosomal TLR3 complexes, and internalized TNFR complexes on endocytic vesicles contain ubiquitinated RIP; a peripheral, context-dependent location. Supporting Evidence: Reactome:R-HSA-168930 RIP1 is recruited to the activated TLR receptor by binding to TICAM1(TRIF) PMID:18450452 CARP-2 localized to endocytic vesicles, where it interacted with internalized TNF-receptor complex, resulting in RIP ubiquitination and degradation |
| GO:0010008 endosome membrane | TAS Reactome:R-HSA-9013889 | KEEP AS NON CORE | Summary: Endosome membrane (TAS, Reactome:R-HSA-9013889) for TLR3/TRIF-associated RIPK1. Reason: RIPK1 is recruited via its RHIM to TRIF at endosomal TLR3 complexes, and internalized TNFR complexes on endocytic vesicles contain ubiquitinated RIP; a peripheral, context-dependent location. Supporting Evidence: Reactome:R-HSA-168930 RIP1 is recruited to the activated TLR receptor by binding to TICAM1(TRIF) PMID:18450452 CARP-2 localized to endocytic vesicles, where it interacted with internalized TNF-receptor complex, resulting in RIP ubiquitination and degradation |
| GO:0010008 endosome membrane | TAS Reactome:R-HSA-9014342 | KEEP AS NON CORE | Summary: Endosome membrane (TAS, Reactome:R-HSA-9014342) for TLR3/TRIF-associated RIPK1. Reason: RIPK1 is recruited via its RHIM to TRIF at endosomal TLR3 complexes, and internalized TNFR complexes on endocytic vesicles contain ubiquitinated RIP; a peripheral, context-dependent location. Supporting Evidence: Reactome:R-HSA-168930 RIP1 is recruited to the activated TLR receptor by binding to TICAM1(TRIF) PMID:18450452 CARP-2 localized to endocytic vesicles, where it interacted with internalized TNF-receptor complex, resulting in RIP ubiquitination and degradation |
| GO:0010628 positive regulation of gene expression | IDA PMID:26020802 MicroRNA analysis suggests an additional level of feedback r... | KEEP AS NON CORE | Summary: Positive regulation of gene expression (IDA, 26020802). Reason: RIPK1 overexpression drives NF-kB-dependent gene (miRNA) expression; this is an indirect downstream consequence of its NF-kB scaffold function. Supporting Evidence: PMID:26020802 we observed that overexpression of both full-length and short forms of RIPK1 mimic many aspects of TNFΞ± treatment and sustains constitutive activation of NF-ΞΊB |
| GO:0031264 death-inducing signaling complex | IDA PMID:11101870 Fas triggers an alternative, caspase-8-independent cell deat... | ACCEPT | Summary: Death-inducing signaling complex (IDA, 11101870). Reason: RIPK1 is recruited to FAS signaling complexes together with FADD and is required for FasL-induced caspase-independent death, consistent with its DD-mediated association with FAS. Supporting Evidence: PMID:11101870 This Fas ligand-induced caspase-independent death is absent in T cells that are deficient in either Fas-associated death domain (FADD) or receptor-interacting protein (RIP) PMID:7538908 we have identified two gene products that associate with the intracellular domain of Fas: Fas itself, and a novel 74 kDa protein we have named RIP |
| GO:0031625 ubiquitin protein ligase binding | IPI PMID:18450452 CARP-2 is an endosome-associated ubiquitin ligase for RIP an... | KEEP AS NON CORE | Summary: Ubiquitin protein ligase binding (IPI, CARP-2/RFFL). Reason: RIPK1 binds several E3 ligases (cIAP1/2, LUBAC, CARP-2, TRAF2) as their substrate; ubiquitination is central to its regulation, but binding E3s is a feature of being a substrate rather than an executed function. Supporting Evidence: PMID:18450452 CARP-2 localized to endocytic vesicles, where it interacted with internalized TNF-receptor complex, resulting in RIP ubiquitination and degradation |
| GO:0032147 activation of protein kinase activity | IMP PMID:22817896 The RIP1/RIP3 necrosome forms a functional amyloid signaling... | KEEP AS NON CORE | Summary: Activation of protein kinase activity (IMP, 22817896). Reason: RHIM-mediated RIPK1-RIPK3 assembly is required for kinase activation in the necrosome; RIPK1 promotes RIPK3 activation. Reasonable but less informative than necroptotic signaling terms. Supporting Evidence: PMID:22817896 Mutations in the RHIMs of RIP1 and RIP3 that are defective in the interaction compromise cluster formation, kinase activation, and programmed necrosis in vivo |
| GO:0032757 positive regulation of interleukin-8 production | IDA PMID:16127453 IPS-1, an adaptor triggering RIG-I- and Mda5-mediated type I... | KEEP AS NON CORE | Summary: positive regulation of interleukin-8 production (IDA, 16127453). Reason: RIPK1 promotes pro-inflammatory cytokine production (IL-8, TNF, IL-6), well supported by RIPK1-dependent cytokine overproduction in patients with non-cleavable RIPK1 and by RIP1-kinase-driven IL-8 secretion after DNA damage. The cited IPS-1 paper (abstract only) does not discuss RIPK1 in its abstract, so the specific evidence could not be checked, but the biology is sound. Supporting Evidence: PMID:31827280 The patients showed strong RIPK1-dependent activation of inflammatory signalling pathways and overproduction of inflammatory cytokines and chemokines PMID:21458669 In turn, RIP1 kinase triggered JNK3/MAPK10-dependent interleukin-8 secretion and FADD-mediated proapoptotic caspase-8 activation |
| GO:0032760 positive regulation of tumor necrosis factor production | IDA PMID:16127453 IPS-1, an adaptor triggering RIG-I- and Mda5-mediated type I... | KEEP AS NON CORE | Summary: positive regulation of tumor necrosis factor production (IDA, 16127453). Reason: RIPK1 promotes pro-inflammatory cytokine production (IL-8, TNF, IL-6), well supported by RIPK1-dependent cytokine overproduction in patients with non-cleavable RIPK1 and by RIP1-kinase-driven IL-8 secretion after DNA damage. The cited IPS-1 paper (abstract only) does not discuss RIPK1 in its abstract, so the specific evidence could not be checked, but the biology is sound. Supporting Evidence: PMID:31827280 The patients showed strong RIPK1-dependent activation of inflammatory signalling pathways and overproduction of inflammatory cytokines and chemokines PMID:21458669 In turn, RIP1 kinase triggered JNK3/MAPK10-dependent interleukin-8 secretion and FADD-mediated proapoptotic caspase-8 activation |
| GO:0032991 protein-containing complex | IDA PMID:22817896 The RIP1/RIP3 necrosome forms a functional amyloid signaling... | ACCEPT | Summary: Protein-containing complex (IDA). Reason: RIPK1 functions in multiple complexes (complex I, complex IIa, ripoptosome, RIPK1-RIPK3 necrosome amyloid). Generic but correct; more specific complex terms are also annotated. Supporting Evidence: PMID:22817896 the RIP homotypic interaction motifs (RHIMs) of RIP1 and RIP3 mediate the assembly of heterodimeric filamentous structures |
| GO:0032991 protein-containing complex | IEA GO_REF:0000107 | ACCEPT | Summary: Protein-containing complex (IEA). Reason: RIPK1 functions in multiple complexes (complex I, complex IIa, ripoptosome, RIPK1-RIPK3 necrosome amyloid). Generic but correct; more specific complex terms are also annotated. |
| GO:0033209 tumor necrosis factor-mediated signaling pathway | IC PMID:8612133 TNF-dependent recruitment of the protein kinase RIP to the T... | ACCEPT | Summary: TNF-mediated signaling pathway (IC). Reason: Core process: RIPK1 is recruited to TNFR1 and transduces both NF-kB survival signals and death signals. Supporting Evidence: PMID:8612133 RIP is a serine-threonine kinase that is recruited by TRADD to TNFR1 in a TNF-dependent process PMID:12887920 The initial plasma membrane bound complex (complex I) consists of TNFR1, the adaptor TRADD, the kinase RIP1, and TRAF2 and rapidly signals activation of NF-kappa B |
| GO:0033209 tumor necrosis factor-mediated signaling pathway | NAS PMID:33495441 Structural insights into the disruption of TNF-TNFR1 signall... | ACCEPT | Summary: TNF-mediated signaling pathway (NAS). Reason: Core process: RIPK1 is recruited to TNFR1 and transduces both NF-kB survival signals and death signals. Supporting Evidence: PMID:8612133 RIP is a serine-threonine kinase that is recruited by TRADD to TNFR1 in a TNF-dependent process PMID:12887920 The initial plasma membrane bound complex (complex I) consists of TNFR1, the adaptor TRADD, the kinase RIP1, and TRAF2 and rapidly signals activation of NF-kappa B |
| GO:0034612 response to tumor necrosis factor | IMP PMID:10521396 Cleavage of the death domain kinase RIP by caspase-8 prompts... | ACCEPT | Summary: response to tumor necrosis factor (IMP). Reason: RIPK1 is a central transducer of TNF signaling; consistent with core function, though TNF-mediated signaling pathway is the more informative term. Supporting Evidence: PMID:10521396 We demonstrated that the cleavage of RIP resulted in the blockage of TNF-induced NF-kappaB activation |
| GO:0035556 intracellular signal transduction | IDA PMID:26020802 MicroRNA analysis suggests an additional level of feedback r... | ACCEPT | Summary: Intracellular signal transduction (IDA, PMID:26020802). Reason: General but correct: RIPK1 is an intracellular signal transducer downstream of death receptors and pattern recognition receptors. Supporting Evidence: PMID:26020802 we observed that overexpression of both full-length and short forms of RIPK1 mimic many aspects of TNFΞ± treatment and sustains constitutive activation of NF-ΞΊB |
| GO:0035556 intracellular signal transduction | IMP PMID:21931591 cIAP1/2 are direct E3 ligases conjugating diverse types of u... | ACCEPT | Summary: Intracellular signal transduction (IMP, PMID:21931591). Reason: General but correct: RIPK1 is an intracellular signal transducer downstream of death receptors and pattern recognition receptors. Supporting Evidence: PMID:21931591 we show that repressing cIAP1/2 levels affects the activation of NF-ΞΊB that is dependent on RIP1, -2, -3 and -4 |
| GO:0035591 signaling adaptor activity | IEA GO_REF:0000107 | ACCEPT | Summary: Signaling adaptor activity (IEA, Ensembl Compara). Reason: Captures RIPK1's kinase-independent scaffold role: in complex I ubiquitinated RIPK1 recruits NEMO/IKK and TAK1 to activate NF-kB, and its DD/RHIM recruit FADD and RIPK3 into death complexes. Supporting Evidence: PMID:30988283 As a scaffold, RIPK1 inhibits caspase-8-dependent apoptosis and RIPK3/MLKL-dependent necroptosis. As a kinase, RIPK1 paradoxically induces these cell death modalities PMID:14653779 a portion of RIP, which is similar to this 50-residue domain of ABIN-2, is also essential for RIP interaction with IKKgamma file:human/RIPK1/RIPK1-uniprot.txt Has kinase-independent scaffold functions: upon binding of TNF to TNFR1, RIPK1 is recruited to the TNF-R1 signaling complex |
| GO:0042327 positive regulation of phosphorylation | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Positive regulation of phosphorylation (IEA). Reason: RIPK1 promotes phosphorylation (autophosphorylation, RIPK3 activation, DAB2IP); vague process term, non-core. Supporting Evidence: PMID:17389591 RIP1 (the Ser/Thr protein kinase receptor-interacting protein) associates with the GAP domain of AIP1 and mediates TNF-induced AIP1 phosphorylation at Ser-604 and JNK/p38 activation |
| GO:0042802 identical protein binding | EXP PMID:22817896 The RIP1/RIP3 necrosome forms a functional amyloid signaling... | KEEP AS NON CORE | Summary: Identical protein binding (EXP, PMID:22817896). Reason: RIPK1 self-associates through its death domain (homodimerization activating its kinase) and its RHIM; self-interaction is mechanistically relevant, but protein homodimerization activity (also annotated) captures it better. Supporting Evidence: PMID:22817896 The fibrils exhibit classical characteristics of |
| GO:0042802 identical protein binding | IPI PMID:22817896 The RIP1/RIP3 necrosome forms a functional amyloid signaling... | KEEP AS NON CORE | Summary: Identical protein binding (IPI, PMID:22817896). Reason: RIPK1 self-associates through its death domain (homodimerization activating its kinase) and its RHIM; self-interaction is mechanistically relevant, but protein homodimerization activity (also annotated) captures it better. Supporting Evidence: PMID:22817896 The fibrils exhibit classical characteristics of |
| GO:0042802 identical protein binding | IPI PMID:23473668 Structural basis of RIP1 inhibition by necrostatins. | KEEP AS NON CORE | Summary: Identical protein binding (IPI, PMID:23473668). Reason: RIPK1 self-associates through its death domain (homodimerization activating its kinase) and its RHIM; self-interaction is mechanistically relevant, but protein homodimerization activity (also annotated) captures it better. Supporting Evidence: PMID:23473668 Here, we report the crystal structures of the RIP1 kinase domain individually bound to necrostatin-1 analog, necrostatin-3 analog, and necrostatin-4 |
| GO:0042802 identical protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | KEEP AS NON CORE | Summary: Identical protein binding (IPI, PMID:25416956). Reason: RIPK1 self-associates through its death domain (homodimerization activating its kinase) and its RHIM; self-interaction is mechanistically relevant, but protein homodimerization activity (also annotated) captures it better. Supporting Evidence: PMID:29440439 Our study demonstrates the role of RIPK1-DD in mediating RIPK1 dimerization and activation of its kinase activity during necroptosis and RIPK1-dependent apoptosis |
| GO:0042802 identical protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: Identical protein binding (IPI, PMID:32296183). Reason: RIPK1 self-associates through its death domain (homodimerization activating its kinase) and its RHIM; self-interaction is mechanistically relevant, but protein homodimerization activity (also annotated) captures it better. Supporting Evidence: PMID:29440439 Our study demonstrates the role of RIPK1-DD in mediating RIPK1 dimerization and activation of its kinase activity during necroptosis and RIPK1-dependent apoptosis |
| GO:0042803 protein homodimerization activity | IDA PMID:29440439 Death-domain dimerization-mediated activation of RIPK1 contr... | ACCEPT | Summary: Protein homodimerization activity (IDA). Reason: Death-domain-mediated RIPK1 homodimerization activates its kinase in necroptosis and RIPK1-dependent apoptosis. Supporting Evidence: PMID:29440439 Our study demonstrates the role of RIPK1-DD in mediating RIPK1 dimerization and activation of its kinase activity during necroptosis and RIPK1-dependent apoptosis file:human/RIPK1/RIPK1-uniprot.txt SUBUNIT: Homodimer |
| GO:0042803 protein homodimerization activity | IEA GO_REF:0000120 | ACCEPT | Summary: Protein homodimerization activity (IEA). Reason: Death-domain-mediated RIPK1 homodimerization activates its kinase in necroptosis and RIPK1-dependent apoptosis. Supporting Evidence: PMID:29440439 Our study demonstrates the role of RIPK1-DD in mediating RIPK1 dimerization and activation of its kinase activity during necroptosis and RIPK1-dependent apoptosis file:human/RIPK1/RIPK1-uniprot.txt SUBUNIT: Homodimer |
| GO:0043065 positive regulation of apoptotic process | IDA PMID:17389591 RIP1-mediated AIP1 phosphorylation at a 14-3-3-binding site ... | ACCEPT | Summary: Positive regulation of apoptotic process (IDA, PMID:17389591). Reason: Kinase-dependent pro-apoptotic function of RIPK1 (RIPK1-dependent apoptosis via complex IIa). Supporting Evidence: PMID:17389591 RIP1 synergizes with AIP1 (but not AIP1-S604A) in inducing both JNK/p38 activation and EC apoptosis |
| GO:0043065 positive regulation of apoptotic process | IDA PMID:8612133 TNF-dependent recruitment of the protein kinase RIP to the T... | ACCEPT | Summary: Positive regulation of apoptotic process (IDA, PMID:8612133). Reason: Kinase-dependent pro-apoptotic function of RIPK1 (RIPK1-dependent apoptosis via complex IIa). Supporting Evidence: PMID:8612133 Overexpression of the intact RIP protein induces both NF-kappa B activation and apoptosis |
| GO:0043065 positive regulation of apoptotic process | IMP PMID:22173242 RIP1 is required for IAP inhibitor-mediated sensitization of... | ACCEPT | Summary: Positive regulation of apoptotic process (IMP, PMID:22173242). Reason: Kinase-dependent pro-apoptotic function of RIPK1 (RIPK1-dependent apoptosis via complex IIa). Supporting Evidence: PMID:22173242 Knockdown of RIP1 abolishes formation of this complex and subsequent activation of caspase-8 and -3, mitochondrial perturbations and apoptosis |
| GO:0043066 negative regulation of apoptotic process | IEA GO_REF:0000107 | ACCEPT | Summary: Negative regulation of apoptotic process (IEA). Reason: Kinase-independent scaffold function: RIPK1 limits caspase-8-dependent apoptosis (via NF-kB-dependent survival genes and by restraining TRADD-FADD association); its loss causes perinatal lethality from excess apoptosis/necroptosis in mice. Supporting Evidence: PMID:30988283 As a scaffold, RIPK1 inhibits caspase-8-dependent apoptosis and RIPK3/MLKL-dependent necroptosis. As a kinase, RIPK1 paradoxically induces these cell death modalities file:human/RIPK1/RIPK1-uniprot.txt RIPK1 is required to limit CASP8-dependent TNFR1-induced apoptosis file:human/RIPK1/RIPK1-uniprot.txt Required to inhibit apoptosis and necroptosis during embryonic development |
| GO:0043066 negative regulation of apoptotic process | ISS GO_REF:0000024 | ACCEPT | Summary: Negative regulation of apoptotic process (ISS). Reason: Kinase-independent scaffold function: RIPK1 limits caspase-8-dependent apoptosis (via NF-kB-dependent survival genes and by restraining TRADD-FADD association); its loss causes perinatal lethality from excess apoptosis/necroptosis in mice. Supporting Evidence: PMID:30988283 As a scaffold, RIPK1 inhibits caspase-8-dependent apoptosis and RIPK3/MLKL-dependent necroptosis. As a kinase, RIPK1 paradoxically induces these cell death modalities file:human/RIPK1/RIPK1-uniprot.txt RIPK1 is required to limit CASP8-dependent TNFR1-induced apoptosis file:human/RIPK1/RIPK1-uniprot.txt Required to inhibit apoptosis and necroptosis during embryonic development |
| GO:0043068 positive regulation of programmed cell death | IMP PMID:16611992 Competitive control of independent programs of tumor necrosi... | ACCEPT | Summary: Positive regulation of programmed cell death (IMP, 16611992). Reason: RIPK1 is required for TNFR1-induced necrotic death in the cited study, consistent with kinase-dependent death signaling. Supporting Evidence: PMID:16611992 necrotic cell death, which depends on receptor-interacting protein kinase 1 (RIP1) |
| GO:0043123 positive regulation of canonical NF-kappaB signal transduction | IDA PMID:17389591 RIP1-mediated AIP1 phosphorylation at a 14-3-3-binding site ... | ACCEPT | Summary: Positive regulation of canonical NF-kappaB signal transduction (IDA, PMID:17389591). Reason: Core kinase-independent scaffold function of RIPK1 in TNFR1 complex I. Supporting Evidence: PMID:8612133 Overexpression of the intact RIP protein induces both NF-kappa B activation and apoptosis |
| GO:0043123 positive regulation of canonical NF-kappaB signal transduction | IEA GO_REF:0000117 | ACCEPT | Summary: Positive regulation of canonical NF-kappaB signal transduction (IEA, GO_REF:0000117). Reason: Core kinase-independent scaffold function of RIPK1 in TNFR1 complex I. Supporting Evidence: PMID:8612133 Overexpression of the intact RIP protein induces both NF-kappa B activation and apoptosis |
| GO:0043123 positive regulation of canonical NF-kappaB signal transduction | IEP PMID:12761501 Large-scale identification and characterization of human gen... | ACCEPT | Summary: Positive regulation of canonical NF-kappaB signal transduction (IEP, PMID:12761501). Reason: Core kinase-independent scaffold function of RIPK1 in TNFR1 complex I. Supporting Evidence: PMID:12761501 For analysis of the NF-kappaB signaling pathway, we introduced each of the cDNAs into human embryonic kidney 293 cells |
| GO:0043123 positive regulation of canonical NF-kappaB signal transduction | IMP PMID:10521396 Cleavage of the death domain kinase RIP by caspase-8 prompts... | ACCEPT | Summary: Positive regulation of canonical NF-kappaB signal transduction (IMP, PMID:10521396). Reason: Core kinase-independent scaffold function of RIPK1 in TNFR1 complex I. Supporting Evidence: PMID:10521396 We demonstrated that the cleavage of RIP resulted in the blockage of TNF-induced NF-kappaB activation |
| GO:0043124 negative regulation of canonical NF-kappaB signal transduction | IMP PMID:17047155 Caspase-8 prevents sustained activation of NF-kappaB in mono... | UNDECIDED | Summary: Negative regulation of canonical NF-kappaB signal transduction (IMP, 17047155). Reason: In the cited study caspase-8 cleaves RIP1 in differentiating monocytes, preventing sustained NF-kB activation; the negative regulator is caspase-8 (and possibly the RIP1 cleavage fragment), whereas intact RIPK1 promotes NF-kB. The full text (not cached) may show a RIP1-fragment effect, so this cannot be adjudicated from the abstract. Supporting Evidence: PMID:17047155 Active caspase-8 cleaves RIP1, which prevents sustained NF-kappaB activation, and activates downstream caspases |
| GO:0043235 signaling receptor complex | IDA PMID:8612133 TNF-dependent recruitment of the protein kinase RIP to the T... | ACCEPT | Summary: Signaling receptor complex (IDA, 8612133). Reason: RIPK1 is recruited by TRADD into the TNF-dependent TNFR1 signaling complex; the TNFR superfamily complex term is more specific. Supporting Evidence: PMID:8612133 RIP is a serine-threonine kinase that is recruited by TRADD to TNFR1 in a TNF-dependent process |
| GO:0043525 positive regulation of neuron apoptotic process | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Positive regulation of neuron apoptotic process (IEA, Ensembl Compara). Reason: RIPK1 kinase-dependent death has been implicated in neuronal and glial cell death in rodent models; a cell-type-specific instance of its general pro-death function. |
| GO:0044877 protein-containing complex binding | IDA PMID:22265414 The mitochondrial phosphatase PGAM5 functions at the converg... | KEEP AS NON CORE | Summary: Protein-containing complex binding (IDA). Reason: RIPK1 associates with multiprotein complexes (TNFR1 complex, RIPK3/MLKL/PGAM5 necrosis complexes); uninformative MF, non-core. Supporting Evidence: PMID:22265414 We report the identification of RIP1- and RIP3-containing protein complexes that form specifically in response to necrosis induction |
| GO:0044877 protein-containing complex binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Protein-containing complex binding (IEA). Reason: RIPK1 associates with multiprotein complexes (TNFR1 complex, RIPK3/MLKL/PGAM5 necrosis complexes); uninformative MF, non-core. |
| GO:0045651 positive regulation of macrophage differentiation | IMP PMID:17047155 Caspase-8 prevents sustained activation of NF-kappaB in mono... | UNDECIDED | Summary: Positive regulation of macrophage differentiation (IMP, 17047155). Reason: The cited abstract establishes that caspase-8 activity and RIP1 cleavage accompany M-CSF-driven monocyte-to-macrophage differentiation; a positive role for RIPK1 itself in differentiation is not evident from the abstract and full text is not cached. Supporting Evidence: PMID:17047155 Active caspase-8 cleaves RIP1, which prevents sustained NF-kappaB activation, and activates downstream caspases |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IDA PMID:16127453 IPS-1, an adaptor triggering RIG-I- and Mda5-mediated type I... | KEEP AS NON CORE | Summary: Positive regulation of transcription by RNA polymerase II (IDA, PMID:16127453). Reason: Reporter-assay readouts of RIPK1-driven NF-kB/AP-1 activity; an indirect consequence of signaling rather than a transcriptional function of RIPK1. Supporting Evidence: PMID:8612133 Overexpression of the intact RIP protein induces both NF-kappa B activation and apoptosis |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IDA PMID:17389591 RIP1-mediated AIP1 phosphorylation at a 14-3-3-binding site ... | KEEP AS NON CORE | Summary: Positive regulation of transcription by RNA polymerase II (IDA, PMID:17389591). Reason: Reporter-assay readouts of RIPK1-driven NF-kB/AP-1 activity; an indirect consequence of signaling rather than a transcriptional function of RIPK1. Supporting Evidence: PMID:8612133 Overexpression of the intact RIP protein induces both NF-kappa B activation and apoptosis |
| GO:0046330 positive regulation of JNK cascade | IDA PMID:17389591 RIP1-mediated AIP1 phosphorylation at a 14-3-3-binding site ... | KEEP AS NON CORE | Summary: Positive regulation of JNK cascade (IDA, 17389591). Reason: RIPK1 mediates TNF-induced DAB2IP phosphorylation and ASK1-JNK/p38 activation in endothelial cells; real but peripheral to core functions. Supporting Evidence: PMID:17389591 RIP1 (the Ser/Thr protein kinase receptor-interacting protein) associates with the GAP domain of AIP1 and mediates TNF-induced AIP1 phosphorylation at Ser-604 and JNK/p38 activation |
| GO:0050729 positive regulation of inflammatory response | IEA GO_REF:0000120 | ACCEPT | Summary: Positive regulation of inflammatory response (IEA). Reason: RIPK1 kinase activation promotes inflammatory cytokine production and inflammatory cell death; non-cleavable RIPK1 variants cause autoinflammatory disease. Supporting Evidence: PMID:31827280 The patients showed strong RIPK1-dependent activation of inflammatory signalling pathways and overproduction of inflammatory cytokines and chemokines |
| GO:0050729 positive regulation of inflammatory response | IMP PMID:31827280 A dominant autoinflammatory disease caused by non-cleavable ... | ACCEPT | Summary: Positive regulation of inflammatory response (IMP). Reason: RIPK1 kinase activation promotes inflammatory cytokine production and inflammatory cell death; non-cleavable RIPK1 variants cause autoinflammatory disease. Supporting Evidence: PMID:31827280 The patients showed strong RIPK1-dependent activation of inflammatory signalling pathways and overproduction of inflammatory cytokines and chemokines |
| GO:0060544 regulation of necroptotic process | IEA GO_REF:0000117 | ACCEPT | Summary: regulation of necroptotic process (IEA, GO_REF:0000117). Reason: Kinase-dependent pro-necroptotic function: RIPK1 kinase activation recruits RIPK3 via RHIM to form the necrosome, leading to MLKL phosphorylation by RIPK3. Supporting Evidence: PMID:11101870 In contrast to its role in nuclear factor kappa B activation, RIP requires its own kinase activity for death signaling |
| GO:0060545 positive regulation of necroptotic process | IEA GO_REF:0000107 | ACCEPT | Summary: positive regulation of necroptotic process (IEA, GO_REF:0000107). Reason: Kinase-dependent pro-necroptotic function: RIPK1 kinase activation recruits RIPK3 via RHIM to form the necrosome, leading to MLKL phosphorylation by RIPK3. Supporting Evidence: PMID:11101870 In contrast to its role in nuclear factor kappa B activation, RIP requires its own kinase activity for death signaling |
| GO:0060545 positive regulation of necroptotic process | IMP PMID:22028622 Smac mimetic bypasses apoptosis resistance in FADD- or caspa... | ACCEPT | Summary: positive regulation of necroptotic process (IMP, PMID:22028622). Reason: Kinase-dependent pro-necroptotic function: RIPK1 kinase activation recruits RIPK3 via RHIM to form the necrosome, leading to MLKL phosphorylation by RIPK3. Supporting Evidence: PMID:22028622 necrostatin-1, an RIP1 kinase inhibitor, abolishes Smac mimetic- and TNFΞ±-induced cell death in FADD- or caspase-8-deficient |
| GO:0060545 positive regulation of necroptotic process | IMP PMID:22274400 Pick your poison: the Ripoptosome, a cell death platform reg... | ACCEPT | Summary: positive regulation of necroptotic process (IMP, PMID:22274400). Reason: Kinase-dependent pro-necroptotic function: RIPK1 kinase activation recruits RIPK3 via RHIM to form the necrosome, leading to MLKL phosphorylation by RIPK3. Supporting Evidence: PMID:22274400 The Ripoptosome is a signaling platform that can switch modes between apoptotic and necroptotic cell death |
| GO:0060545 positive regulation of necroptotic process | IMP PMID:22817896 The RIP1/RIP3 necrosome forms a functional amyloid signaling... | ACCEPT | Summary: positive regulation of necroptotic process (IMP, PMID:22817896). Reason: Kinase-dependent pro-necroptotic function: RIPK1 kinase activation recruits RIPK3 via RHIM to form the necrosome, leading to MLKL phosphorylation by RIPK3. Supporting Evidence: PMID:22817896 Mutations in the RHIMs of RIP1 and RIP3 that are defective in the interaction compromise cluster formation, kinase activation, and programmed necrosis in vivo |
| GO:0060546 negative regulation of necroptotic process | IEA GO_REF:0000107 | ACCEPT | Summary: Negative regulation of necroptotic process (IEA). Reason: Kinase-independent scaffold function: RIPK1 restrains RIPK3/MLKL necroptosis (e.g. ZBP1-driven) and recruits FADD/caspase-8 that cleaves RIPK1 and RIPK3. Supporting Evidence: PMID:30988283 As a scaffold, RIPK1 inhibits caspase-8-dependent apoptosis and RIPK3/MLKL-dependent necroptosis. As a kinase, RIPK1 paradoxically induces these cell death modalities PMID:36380021 these results identify RIPK1 scaffold function as an inhibitor of RIPK3βMLKL-dependent necroptosis in keratinocytes file:human/RIPK1/RIPK1-uniprot.txt In normal conditions, RIPK1 acts as an inhibitor of RIPK3-dependent necroptosis |
| GO:0060546 negative regulation of necroptotic process | ISS GO_REF:0000024 | ACCEPT | Summary: Negative regulation of necroptotic process (ISS). Reason: Kinase-independent scaffold function: RIPK1 restrains RIPK3/MLKL necroptosis (e.g. ZBP1-driven) and recruits FADD/caspase-8 that cleaves RIPK1 and RIPK3. Supporting Evidence: PMID:30988283 As a scaffold, RIPK1 inhibits caspase-8-dependent apoptosis and RIPK3/MLKL-dependent necroptosis. As a kinase, RIPK1 paradoxically induces these cell death modalities PMID:36380021 these results identify RIPK1 scaffold function as an inhibitor of RIPK3βMLKL-dependent necroptosis in keratinocytes file:human/RIPK1/RIPK1-uniprot.txt In normal conditions, RIPK1 acts as an inhibitor of RIPK3-dependent necroptosis |
| GO:0062100 positive regulation of programmed necrotic cell death | IMP PMID:20550618 MicroRNA-155 prevents necrotic cell death in human cardiomyo... | ACCEPT | Summary: positive regulation of programmed necrotic cell death (IMP, PMID:20550618). Reason: Kinase-dependent pro-necroptotic function: RIPK1 kinase activation recruits RIPK3 via RHIM to form the necrosome, leading to MLKL phosphorylation by RIPK3. Supporting Evidence: PMID:20550618 inhibiting RIP1, either by pre-incubating the cells with a RIP1 specific inhibitor, Necrostatin-1 or siRNA mediated knockdown, reduced necrosis |
| GO:0070105 positive regulation of interleukin-6-mediated signaling pathway | IEA GO_REF:0000120 | MODIFY | Summary: Positive regulation of interleukin-6-mediated signaling pathway (IEA). Reason: The supporting evidence shows RIPK1 activation promotes production of IL-6 (and TNF), not signaling downstream of the IL-6 receptor. The correct term is positive regulation of interleukin-6 production. Proposed replacements: positive regulation of interleukin-6 production Supporting Evidence: PMID:31827280 but also induction of pro-inflammatory cytokines such as IL-6 and TNF |
| GO:0070105 positive regulation of interleukin-6-mediated signaling pathway | IMP PMID:31827280 A dominant autoinflammatory disease caused by non-cleavable ... | MODIFY | Summary: Positive regulation of interleukin-6-mediated signaling pathway (IMP). Reason: The supporting evidence shows RIPK1 activation promotes production of IL-6 (and TNF), not signaling downstream of the IL-6 receptor. The correct term is positive regulation of interleukin-6 production. Proposed replacements: positive regulation of interleukin-6 production Supporting Evidence: PMID:31827280 but also induction of pro-inflammatory cytokines such as IL-6 and TNF |
| GO:0070231 T cell apoptotic process | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: T cell apoptotic process (IEA). Reason: Transferred from rodent data on RIPK1 in T cell death/survival; a cell-type-specific instance of RIPK1's general role in death-receptor signaling. RIPK1 is required for Fas-induced caspase-independent death of activated T cells. Supporting Evidence: PMID:11101870 This Fas ligand-induced caspase-independent death is absent in T cells that are deficient in either Fas-associated death domain (FADD) or receptor-interacting protein (RIP) |
| GO:0070231 T cell apoptotic process | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: T cell apoptotic process (ISS). Reason: Transferred from rodent data on RIPK1 in T cell death/survival; a cell-type-specific instance of RIPK1's general role in death-receptor signaling. RIPK1 is required for Fas-induced caspase-independent death of activated T cells. Supporting Evidence: PMID:11101870 This Fas ligand-induced caspase-independent death is absent in T cells that are deficient in either Fas-associated death domain (FADD) or receptor-interacting protein (RIP) |
| GO:0070266 necroptotic process | IEA GO_REF:0000107 | ACCEPT | Summary: necroptotic process (IEA, GO_REF:0000107). Reason: Core process: RIPK1 kinase activity and its RHIM are required to assemble the RIPK1-RIPK3 necrosome, in which RIPK3 phosphorylates MLKL to execute necroptosis. Supporting Evidence: PMID:36380021 Accordingly, inactivation of caspase 8 switches the TNF response to RIPK1 kinase activity-dependent necroptosis, which additionally requires recruitment of the kinase RIPK3 and of the potential pore-forming pseudo-kinase mixed lineage kinase domain-like protein (MLKL) to complex II |
| GO:0070266 necroptotic process | IMP PMID:21737330 cIAPs block Ripoptosome formation, a RIP1/caspase-8 containi... | ACCEPT | Summary: necroptotic process (IMP, PMID:21737330). Reason: Core process: RIPK1 kinase activity and its RHIM are required to assemble the RIPK1-RIPK3 necrosome, in which RIPK3 phosphorylates MLKL to execute necroptosis. Supporting Evidence: PMID:21737330 loss of cIAPs promotes the spontaneous formation of an intracellular platform that activates either apoptosis or necroptosis |
| GO:0070266 necroptotic process | IMP PMID:22265414 The mitochondrial phosphatase PGAM5 functions at the converg... | ACCEPT | Summary: necroptotic process (IMP, PMID:22265414). Reason: Core process: RIPK1 kinase activity and its RHIM are required to assemble the RIPK1-RIPK3 necrosome, in which RIPK3 phosphorylates MLKL to execute necroptosis. Supporting Evidence: PMID:22265414 The programmed necrosis induced by TNF-Ξ± requires the activities of the receptor-interacting serine-threonine kinases RIP1 and RIP3 |
| GO:0070266 necroptotic process | IMP PMID:22817896 The RIP1/RIP3 necrosome forms a functional amyloid signaling... | ACCEPT | Summary: necroptotic process (IMP, PMID:22817896). Reason: Core process: RIPK1 kinase activity and its RHIM are required to assemble the RIPK1-RIPK3 necrosome, in which RIPK3 phosphorylates MLKL to execute necroptosis. Supporting Evidence: PMID:22817896 Mutations in the RHIMs of RIP1 and RIP3 that are defective in the interaction compromise cluster formation, kinase activation, and programmed necrosis in vivo |
| GO:0070266 necroptotic process | IMP PMID:29440439 Death-domain dimerization-mediated activation of RIPK1 contr... | ACCEPT | Summary: necroptotic process (IMP, PMID:29440439). Reason: Core process: RIPK1 kinase activity and its RHIM are required to assemble the RIPK1-RIPK3 necrosome, in which RIPK3 phosphorylates MLKL to execute necroptosis. Supporting Evidence: PMID:29440439 Ripk1K584R/K584R knockin mutant cells are resistant to RIPK1 kinase-dependent apoptosis and necroptosis |
| GO:0070266 necroptotic process | IMP PMID:30988283 Serine 25 phosphorylation inhibits RIPK1 kinase-dependent ce... | ACCEPT | Summary: necroptotic process (IMP, PMID:30988283). Reason: Core process: RIPK1 kinase activity and its RHIM are required to assemble the RIPK1-RIPK3 necrosome, in which RIPK3 phosphorylates MLKL to execute necroptosis. Supporting Evidence: PMID:30988283 As a scaffold, RIPK1 inhibits caspase-8-dependent apoptosis and RIPK3/MLKL-dependent necroptosis. As a kinase, RIPK1 paradoxically induces these cell death modalities |
| GO:0070266 necroptotic process | ISS GO_REF:0000024 | ACCEPT | Summary: necroptotic process (ISS, GO_REF:0000024). Reason: Core process: RIPK1 kinase activity and its RHIM are required to assemble the RIPK1-RIPK3 necrosome, in which RIPK3 phosphorylates MLKL to execute necroptosis. Supporting Evidence: PMID:36380021 Accordingly, inactivation of caspase 8 switches the TNF response to RIPK1 kinase activity-dependent necroptosis, which additionally requires recruitment of the kinase RIPK3 and of the potential pore-forming pseudo-kinase mixed lineage kinase domain-like protein (MLKL) to complex II |
| GO:0070266 necroptotic process | TAS Reactome:R-HSA-5213460 | ACCEPT | Summary: necroptotic process (TAS, Reactome:R-HSA-5213460). Reason: Core process: RIPK1 kinase activity and its RHIM are required to assemble the RIPK1-RIPK3 necrosome, in which RIPK3 phosphorylates MLKL to execute necroptosis. Supporting Evidence: Reactome:R-HSA-5213460 The kinase activities of |
| GO:0070301 cellular response to hydrogen peroxide | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: cellular response to hydrogen peroxide (IEA). Reason: RIPK1 kinase activity contributes to oxidative-stress (H2O2)-induced necrotic death in some cell types (blocked by necrostatin-1 or RIPK1 knockdown); this reflects RIPK1's role in necroptosis rather than a dedicated oxidative-stress response function. |
| GO:0070301 cellular response to hydrogen peroxide | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: cellular response to hydrogen peroxide (ISS). Reason: RIPK1 kinase activity contributes to oxidative-stress (H2O2)-induced necrotic death in some cell types (blocked by necrostatin-1 or RIPK1 knockdown); this reflects RIPK1's role in necroptosis rather than a dedicated oxidative-stress response function. |
| GO:0070513 death domain binding | IPI PMID:8612133 TNF-dependent recruitment of the protein kinase RIP to the T... | ACCEPT | Summary: Death domain binding (IPI, PMID:8612133). Reason: RIPK1's C-terminal death domain binds the death domains of TRADD, FAS, FADD and CRADD; this DD-binding activity underlies its recruitment to receptor and death complexes. Supporting Evidence: PMID:8612133 TRADD interacts strongly with RIP |
| GO:0070513 death domain binding | IPI PMID:9044836 CRADD, a novel human apoptotic adaptor molecule for caspase-... | ACCEPT | Summary: Death domain binding (IPI, PMID:9044836). Reason: RIPK1's C-terminal death domain binds the death domains of TRADD, FAS, FADD and CRADD; this DD-binding activity underlies its recruitment to receptor and death complexes. Supporting Evidence: PMID:9044836 It has an NH2-terminal caspase homology domain that interacts with caspase-2 and a COOH-terminal DD that interacts with RIP |
| GO:0071356 cellular response to tumor necrosis factor | IDA PMID:17389591 RIP1-mediated AIP1 phosphorylation at a 14-3-3-binding site ... | ACCEPT | Summary: cellular response to tumor necrosis factor (IDA). Reason: RIPK1 is a central transducer of TNF signaling; consistent with core function, though TNF-mediated signaling pathway is the more informative term. Supporting Evidence: PMID:17389591 RIP1 (the Ser/Thr protein kinase receptor-interacting protein) associates with the GAP domain of AIP1 and mediates TNF-induced AIP1 phosphorylation at Ser-604 and JNK/p38 activation |
| GO:0071356 cellular response to tumor necrosis factor | IEA GO_REF:0000117 | ACCEPT | Summary: cellular response to tumor necrosis factor (IEA). Reason: RIPK1 is a central transducer of TNF signaling; consistent with core function, though TNF-mediated signaling pathway is the more informative term. |
| GO:0071363 cellular response to growth factor stimulus | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Cellular response to growth factor stimulus (IEA, Ensembl Compara). Reason: No specific human evidence; RIPK1 associates with M-CSF-induced caspase-8 complexes and interacts with EGFR, but a growth-factor response role is peripheral at best. |
| GO:0097191 extrinsic apoptotic signaling pathway | IDA PMID:7538908 RIP: a novel protein containing a death domain that interact... | ACCEPT | Summary: Extrinsic apoptotic signaling pathway (IDA, PMID:7538908). Reason: RIPK1 participates in death-receptor-initiated apoptosis: recruited to FAS/TNFR1, it nucleates complex IIa (RIPK1-FADD-caspase-8) and its kinase activity drives RIPK1-dependent apoptosis. Supporting Evidence: PMID:7538908 Transient overexpression of RIP causes transfected cells to undergo the morphological changes characteristic of apoptosis |
| GO:0097191 extrinsic apoptotic signaling pathway | IEA GO_REF:0000117 | ACCEPT | Summary: Extrinsic apoptotic signaling pathway (IEA, GO_REF:0000117). Reason: RIPK1 participates in death-receptor-initiated apoptosis: recruited to FAS/TNFR1, it nucleates complex IIa (RIPK1-FADD-caspase-8) and its kinase activity drives RIPK1-dependent apoptosis. Supporting Evidence: PMID:21525013 Knockdown of RIP1 by siRNA prevented TWEAK-induced association of FADD with caspase-8 but not formation of the FN14-TRAF2-cIAP1 complex and inhibited apoptosis activation |
| GO:0097191 extrinsic apoptotic signaling pathway | IMP PMID:10521396 Cleavage of the death domain kinase RIP by caspase-8 prompts... | ACCEPT | Summary: Extrinsic apoptotic signaling pathway (IMP, PMID:10521396). Reason: RIPK1 participates in death-receptor-initiated apoptosis: recruited to FAS/TNFR1, it nucleates complex IIa (RIPK1-FADD-caspase-8) and its kinase activity drives RIPK1-dependent apoptosis. Supporting Evidence: PMID:10521396 Most importantly, the Caspase-8 resistant RIP mutants protected cells against TNF-induced apopotosis |
| GO:0097191 extrinsic apoptotic signaling pathway | IMP PMID:8612133 TNF-dependent recruitment of the protein kinase RIP to the T... | ACCEPT | Summary: Extrinsic apoptotic signaling pathway (IMP, PMID:8612133). Reason: RIPK1 participates in death-receptor-initiated apoptosis: recruited to FAS/TNFR1, it nucleates complex IIa (RIPK1-FADD-caspase-8) and its kinase activity drives RIPK1-dependent apoptosis. Supporting Evidence: PMID:8612133 Overexpression of the intact RIP protein induces both NF-kappa B activation and apoptosis |
| GO:0097300 programmed necrotic cell death | IEA GO_REF:0000107 | MODIFY | Summary: Programmed necrotic cell death (IEA). Reason: GO advises this term for necrotic death where RIPK1/RIPK3 involvement is not shown; for RIPK1 itself, the specific necroptotic process term applies. Proposed replacements: necroptotic process Supporting Evidence: PMID:11101870 In contrast to its role in nuclear factor kappa B activation, RIP requires its own kinase activity for death signaling |
| GO:0097300 programmed necrotic cell death | ISS GO_REF:0000024 | MODIFY | Summary: Programmed necrotic cell death (ISS). Reason: GO advises this term for necrotic death where RIPK1/RIPK3 involvement is not shown; for RIPK1 itself, the specific necroptotic process term applies. Proposed replacements: necroptotic process Supporting Evidence: PMID:11101870 In contrast to its role in nuclear factor kappa B activation, RIP requires its own kinase activity for death signaling |
| GO:0097342 ripoptosome | IDA PMID:21737330 cIAPs block Ripoptosome formation, a RIP1/caspase-8 containi... | ACCEPT | Summary: Ripoptosome (IDA, 21737330). Reason: RIPK1 is the core component of the ripoptosome (RIPK1-FADD-caspase-8/10-cFLIP). Supporting Evidence: PMID:21737330 RIP1 is the core component of the complex PMID:21737330 It contains RIP1, FADD, caspase-8, caspase-10, and caspase inhibitor cFLIP isoforms |
| GO:0097343 ripoptosome assembly | IMP PMID:21737330 cIAPs block Ripoptosome formation, a RIP1/caspase-8 containi... | ACCEPT | Summary: ripoptosome assembly (IMP). Reason: RIPK1 is required for and nucleates assembly of the ripoptosome/necrosome death platforms. Supporting Evidence: PMID:21737330 RIP1 is the core component of the complex |
| GO:0097527 necroptotic signaling pathway | IBA GO_REF:0000033 | ACCEPT | Summary: necroptotic signaling pathway (IBA, GO_REF:0000033). Reason: Core process: RIPK1 kinase activity and its RHIM are required to assemble the RIPK1-RIPK3 necrosome, in which RIPK3 phosphorylates MLKL to execute necroptosis. Supporting Evidence: PMID:36380021 Accordingly, inactivation of caspase 8 switches the TNF response to RIPK1 kinase activity-dependent necroptosis, which additionally requires recruitment of the kinase RIPK3 and of the potential pore-forming pseudo-kinase mixed lineage kinase domain-like protein (MLKL) to complex II |
| GO:0097527 necroptotic signaling pathway | IEA GO_REF:0000120 | ACCEPT | Summary: necroptotic signaling pathway (IEA, GO_REF:0000120). Reason: Core process: RIPK1 kinase activity and its RHIM are required to assemble the RIPK1-RIPK3 necrosome, in which RIPK3 phosphorylates MLKL to execute necroptosis. Supporting Evidence: PMID:36380021 Accordingly, inactivation of caspase 8 switches the TNF response to RIPK1 kinase activity-dependent necroptosis, which additionally requires recruitment of the kinase RIPK3 and of the potential pore-forming pseudo-kinase mixed lineage kinase domain-like protein (MLKL) to complex II |
| GO:0097527 necroptotic signaling pathway | IMP PMID:11101870 Fas triggers an alternative, caspase-8-independent cell deat... | ACCEPT | Summary: necroptotic signaling pathway (IMP, PMID:11101870). Reason: Core process: RIPK1 kinase activity and its RHIM are required to assemble the RIPK1-RIPK3 necrosome, in which RIPK3 phosphorylates MLKL to execute necroptosis. Supporting Evidence: PMID:11101870 In contrast to its role in nuclear factor kappa B activation, RIP requires its own kinase activity for death signaling |
| GO:0097527 necroptotic signaling pathway | IMP PMID:16507998 Inhibition of ADP/ATP exchange in receptor-interacting prote... | ACCEPT | Summary: necroptotic signaling pathway (IMP, PMID:16507998). Reason: Core process: RIPK1 kinase activity and its RHIM are required to assemble the RIPK1-RIPK3 necrosome, in which RIPK3 phosphorylates MLKL to execute necroptosis. Supporting Evidence: PMID:16507998 tumor necrosis factor alpha induced RIP-dependent inhibition of adenine nucleotide translocase (ANT)-conducted transport of ADP into mitochondria, which resulted in reduced ATP and necrotic cell death |
| GO:0097527 necroptotic signaling pathway | IMP PMID:22265413 Mixed lineage kinase domain-like protein mediates necrosis s... | ACCEPT | Summary: necroptotic signaling pathway (IMP, PMID:22265413). Reason: Core process: RIPK1 kinase activity and its RHIM are required to assemble the RIPK1-RIPK3 necrosome, in which RIPK3 phosphorylates MLKL to execute necroptosis. Supporting Evidence: PMID:22265413 MLKL was phosphorylated by RIP3 at the threonine 357 and serine 358 residues |
| GO:0097527 necroptotic signaling pathway | IMP PMID:22817896 The RIP1/RIP3 necrosome forms a functional amyloid signaling... | ACCEPT | Summary: necroptotic signaling pathway (IMP, PMID:22817896). Reason: Core process: RIPK1 kinase activity and its RHIM are required to assemble the RIPK1-RIPK3 necrosome, in which RIPK3 phosphorylates MLKL to execute necroptosis. Supporting Evidence: PMID:22817896 Mutations in the RHIMs of RIP1 and RIP3 that are defective in the interaction compromise cluster formation, kinase activation, and programmed necrosis in vivo |
| GO:0097527 necroptotic signaling pathway | IMP PMID:31827280 A dominant autoinflammatory disease caused by non-cleavable ... | ACCEPT | Summary: necroptotic signaling pathway (IMP, PMID:31827280). Reason: Core process: RIPK1 kinase activity and its RHIM are required to assemble the RIPK1-RIPK3 necrosome, in which RIPK3 phosphorylates MLKL to execute necroptosis. Supporting Evidence: PMID:31827280 Impaired cleavage of RIPK1 D324 variants by caspase-8 sensitized patients' peripheral blood mononuclear cells to RIPK1 activation, apoptosis and necroptosis induced by TNF |
| GO:0097527 necroptotic signaling pathway | ISS GO_REF:0000024 | ACCEPT | Summary: necroptotic signaling pathway (ISS, GO_REF:0000024). Reason: Core process: RIPK1 kinase activity and its RHIM are required to assemble the RIPK1-RIPK3 necrosome, in which RIPK3 phosphorylates MLKL to execute necroptosis. Supporting Evidence: PMID:36380021 Accordingly, inactivation of caspase 8 switches the TNF response to RIPK1 kinase activity-dependent necroptosis, which additionally requires recruitment of the kinase RIPK3 and of the potential pore-forming pseudo-kinase mixed lineage kinase domain-like protein (MLKL) to complex II |
| GO:0106310 protein serine kinase activity | EXP PMID:23473668 Structural basis of RIP1 inhibition by necrostatins. | ACCEPT | Summary: Protein serine kinase activity (EXP, PMID:23473668). Reason: Core molecular function. RIPK1 autophosphorylates (S14/15, S20, S161, S166) and phosphorylates RIPK3 and DAB2IP; kinase activity is required for RIPK1-dependent apoptosis and necroptosis but dispensable for its scaffold/NF-kB function. Supporting Evidence: PMID:8612133 RIP is a serine-threonine kinase that is recruited by TRADD to TNFR1 in a TNF-dependent process PMID:23473668 Necrostatins, a series of small-molecule inhibitors, suppress necroptosis by specifically inhibiting RIP1 kinase activity |
| GO:0106310 protein serine kinase activity | EXP PMID:30988283 Serine 25 phosphorylation inhibits RIPK1 kinase-dependent ce... | ACCEPT | Summary: Protein serine kinase activity (EXP, PMID:30988283). Reason: Core molecular function. RIPK1 autophosphorylates (S14/15, S20, S161, S166) and phosphorylates RIPK3 and DAB2IP; kinase activity is required for RIPK1-dependent apoptosis and necroptosis but dispensable for its scaffold/NF-kB function. Supporting Evidence: PMID:30988283 We identify phosphorylation of RIPK1 on Ser25 by IKKs as a key mechanism directly inhibiting RIPK1 kinase activity |
| GO:0106310 protein serine kinase activity | EXP PMID:31827280 A dominant autoinflammatory disease caused by non-cleavable ... | ACCEPT | Summary: Protein serine kinase activity (EXP, PMID:31827280). Reason: Core molecular function. RIPK1 autophosphorylates (S14/15, S20, S161, S166) and phosphorylates RIPK3 and DAB2IP; kinase activity is required for RIPK1-dependent apoptosis and necroptosis but dispensable for its scaffold/NF-kB function. Supporting Evidence: PMID:31827280 Impaired cleavage of RIPK1 D324 variants by caspase-8 sensitized patients' peripheral blood mononuclear cells to RIPK1 activation, apoptosis and necroptosis induced by TNF |
| GO:0106310 protein serine kinase activity | EXP PMID:8612133 TNF-dependent recruitment of the protein kinase RIP to the T... | ACCEPT | Summary: Protein serine kinase activity (EXP, PMID:8612133). Reason: Core molecular function. RIPK1 autophosphorylates (S14/15, S20, S161, S166) and phosphorylates RIPK3 and DAB2IP; kinase activity is required for RIPK1-dependent apoptosis and necroptosis but dispensable for its scaffold/NF-kB function. Supporting Evidence: PMID:8612133 RIP is a serine-threonine kinase that is recruited by TRADD to TNFR1 in a TNF-dependent process PMID:23473668 Necrostatins, a series of small-molecule inhibitors, suppress necroptosis by specifically inhibiting RIP1 kinase activity |
| GO:0106310 protein serine kinase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Protein serine kinase activity (IEA, GO_REF:0000120). Reason: Core molecular function. RIPK1 autophosphorylates (S14/15, S20, S161, S166) and phosphorylates RIPK3 and DAB2IP; kinase activity is required for RIPK1-dependent apoptosis and necroptosis but dispensable for its scaffold/NF-kB function. Supporting Evidence: PMID:8612133 RIP is a serine-threonine kinase that is recruited by TRADD to TNFR1 in a TNF-dependent process PMID:23473668 Necrostatins, a series of small-molecule inhibitors, suppress necroptosis by specifically inhibiting RIP1 kinase activity |
| GO:0120283 protein serine/threonine kinase binding | EXP PMID:22817896 The RIP1/RIP3 necrosome forms a functional amyloid signaling... | ACCEPT | Summary: Protein serine/threonine kinase binding (EXP, 22817896). Reason: RIPK1 binds RIPK3 via RHIM-RHIM hetero-amyloid assembly, the key interaction forming the necrosome. Supporting Evidence: PMID:22817896 the RIP homotypic interaction motifs (RHIMs) of RIP1 and RIP3 mediate the assembly of heterodimeric filamentous structures PMID:19524512 Upon induction of necrosis, RIP3 is recruited to RIPK1 to form a necrosis-inducing complex |
| GO:0120283 protein serine/threonine kinase binding | IPI PMID:22817896 The RIP1/RIP3 necrosome forms a functional amyloid signaling... | ACCEPT | Summary: Protein serine/threonine kinase binding (IPI, 22817896). Reason: RIPK1 binds RIPK3 via RHIM-RHIM hetero-amyloid assembly, the key interaction forming the necrosome. Supporting Evidence: PMID:22817896 the RIP homotypic interaction motifs (RHIMs) of RIP1 and RIP3 mediate the assembly of heterodimeric filamentous structures PMID:19524512 Upon induction of necrosis, RIP3 is recruited to RIPK1 to form a necrosis-inducing complex |
| GO:1900119 positive regulation of execution phase of apoptosis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Positive regulation of execution phase of apoptosis (IEA). Reason: RIPK1 kinase promotes caspase-8 activation upstream of execution caspases; the regulation of execution phase per se is indirect. |
| GO:1901026 ripoptosome assembly involved in necroptotic process | IEA GO_REF:0000117 | ACCEPT | Summary: ripoptosome assembly involved in necroptotic process (IEA). Reason: RIPK1 is required for and nucleates assembly of the ripoptosome/necrosome death platforms. |
| GO:1901026 ripoptosome assembly involved in necroptotic process | IMP PMID:22817896 The RIP1/RIP3 necrosome forms a functional amyloid signaling... | ACCEPT | Summary: ripoptosome assembly involved in necroptotic process (IMP). Reason: RIPK1 is required for and nucleates assembly of the ripoptosome/necrosome death platforms. Supporting Evidence: PMID:22817896 the RIP homotypic interaction motifs (RHIMs) of RIP1 and RIP3 mediate the assembly of heterodimeric filamentous structures |
| GO:1901224 positive regulation of non-canonical NF-kappaB signal transduction | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Positive regulation of non-canonical NF-kappaB signal transduction (IEA). Reason: RIPK1's established NF-kB role is in the canonical pathway; any non-canonical contribution is limited/contextual. |
| GO:1903265 positive regulation of tumor necrosis factor-mediated signaling pathway | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Positive regulation of TNF-mediated signaling pathway (IEA). Reason: RIPK1 is a component of the TNF signaling pathway rather than a regulator of it; TNF-mediated signaling pathway (also annotated) is the better description. |
| GO:1903800 positive regulation of miRNA processing | IDA PMID:26020802 MicroRNA analysis suggests an additional level of feedback r... | MARK AS OVER ANNOTATED | Summary: Positive regulation of miRNA processing (IDA, 26020802). Reason: The study (full text available) shows that RIPK1 overexpression induces NF-kB-dependent expression of miR-146a, miR-215 and miR-497; it does not examine miRNA processing. The effect is transcriptional and indirect. Supporting Evidence: PMID:26020802 In the current study, we identify miRNAs that are up-regulated following up-regulation of short RIPK1, and we document that these miRNAs are induced by other NF-ΞΊB-stimulating events in an NF-ΞΊB-dependent manner |
| GO:1990000 amyloid fibril formation | EXP PMID:22817896 The RIP1/RIP3 necrosome forms a functional amyloid signaling... | KEEP AS NON CORE | Summary: Amyloid fibril formation (EXP, 22817896). Reason: The RHIMs of RIPK1 and RIPK3 form functional hetero-amyloid fibrils that constitute the necrosome core; RIPK1 genuinely participates in this assembly, but it is a mechanism of necroptotic signaling rather than an independent process. Supporting Evidence: PMID:22817896 the RIP homotypic interaction motifs (RHIMs) of RIP1 and RIP3 mediate the assembly of heterodimeric filamentous structures PMID:22817896 The fibrils exhibit classical characteristics of |
| GO:1990000 amyloid fibril formation | IDA PMID:22817896 The RIP1/RIP3 necrosome forms a functional amyloid signaling... | KEEP AS NON CORE | Summary: Amyloid fibril formation (IDA, 22817896). Reason: The RHIMs of RIPK1 and RIPK3 form functional hetero-amyloid fibrils that constitute the necrosome core; RIPK1 genuinely participates in this assembly, but it is a mechanism of necroptotic signaling rather than an independent process. Supporting Evidence: PMID:22817896 the RIP homotypic interaction motifs (RHIMs) of RIP1 and RIP3 mediate the assembly of heterodimeric filamentous structures PMID:22817896 The fibrils exhibit classical characteristics of |
| GO:1990000 amyloid fibril formation | IMP PMID:22817896 The RIP1/RIP3 necrosome forms a functional amyloid signaling... | KEEP AS NON CORE | Summary: Amyloid fibril formation (IMP, 22817896). Reason: The RHIMs of RIPK1 and RIPK3 form functional hetero-amyloid fibrils that constitute the necrosome core; RIPK1 genuinely participates in this assembly, but it is a mechanism of necroptotic signaling rather than an independent process. Supporting Evidence: PMID:22817896 the RIP homotypic interaction motifs (RHIMs) of RIP1 and RIP3 mediate the assembly of heterodimeric filamentous structures PMID:22817896 The fibrils exhibit classical characteristics of |
| GO:2000377 regulation of reactive oxygen species metabolic process | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: regulation of reactive oxygen species metabolic process (IEA). Reason: RIPK1/RIPK3 necrosome activation triggers ROS production and RIPK1 also controls antioxidant gene expression via NF-kB; context-dependent, non-core. Supporting Evidence: PMID:19524513 The phosphorylation of RIP1 and RIP3 stabilizes their association within the pronecrotic complex, activates the pronecrotic kinase activity, and triggers downstream reactive oxygen species production |
| GO:2000379 positive regulation of reactive oxygen species metabolic process | TAS PMID:17979836 From death receptor to reactive oxygen species and c-Jun N-t... | KEEP AS NON CORE | Summary: positive regulation of reactive oxygen species metabolic process (TAS). Reason: RIPK1/RIPK3 necrosome activation triggers ROS production and RIPK1 also controls antioxidant gene expression via NF-kB; context-dependent, non-core. Supporting Evidence: PMID:17979836 may link DR-associated signaling complexes to ROS production by mitochondria |
| GO:2001237 negative regulation of extrinsic apoptotic signaling pathway | IEA GO_REF:0000117 | ACCEPT | Summary: Negative regulation of extrinsic apoptotic signaling pathway (IEA). Reason: Kinase-independent scaffold function of RIPK1 restrains caspase-8-dependent apoptosis downstream of TNFR1. (For the IMP row from 21525013, whose abstract emphasises the pro-apoptotic role, the specific supporting data are in the full text, which is not cached; the function is nonetheless well established.) Supporting Evidence: PMID:30988283 As a scaffold, RIPK1 inhibits caspase-8-dependent apoptosis and RIPK3/MLKL-dependent necroptosis. As a kinase, RIPK1 paradoxically induces these cell death modalities file:human/RIPK1/RIPK1-uniprot.txt RIPK1 is required to limit CASP8-dependent TNFR1-induced apoptosis |
| GO:2001237 negative regulation of extrinsic apoptotic signaling pathway | IMP PMID:21525013 TWEAK induces apoptosis through a death-signaling complex co... | ACCEPT | Summary: Negative regulation of extrinsic apoptotic signaling pathway (IMP). Reason: Kinase-independent scaffold function of RIPK1 restrains caspase-8-dependent apoptosis downstream of TNFR1. (For the IMP row from 21525013, whose abstract emphasises the pro-apoptotic role, the specific supporting data are in the full text, which is not cached; the function is nonetheless well established.) Supporting Evidence: PMID:30988283 As a scaffold, RIPK1 inhibits caspase-8-dependent apoptosis and RIPK3/MLKL-dependent necroptosis. As a kinase, RIPK1 paradoxically induces these cell death modalities file:human/RIPK1/RIPK1-uniprot.txt RIPK1 is required to limit CASP8-dependent TNFR1-induced apoptosis |
| GO:2001238 positive regulation of extrinsic apoptotic signaling pathway | IEA GO_REF:0000117 | ACCEPT | Summary: Positive regulation of extrinsic apoptotic signaling pathway (IEA, GO_REF:0000117). Reason: Kinase-dependent RIPK1 function promoting complex IIa formation and caspase-8 activation. Supporting Evidence: PMID:29440439 Ripk1K584R/K584R knockin mutant cells are resistant to RIPK1 kinase-dependent apoptosis and necroptosis |
| GO:2001238 positive regulation of extrinsic apoptotic signaling pathway | IMP PMID:21525013 TWEAK induces apoptosis through a death-signaling complex co... | ACCEPT | Summary: Positive regulation of extrinsic apoptotic signaling pathway (IMP, PMID:21525013). Reason: Kinase-dependent RIPK1 function promoting complex IIa formation and caspase-8 activation. Supporting Evidence: PMID:21525013 Knockdown of RIP1 by siRNA prevented TWEAK-induced association of FADD with caspase-8 but not formation of the FN14-TRAF2-cIAP1 complex and inhibited apoptosis activation |
| GO:2001238 positive regulation of extrinsic apoptotic signaling pathway | IMP PMID:22274400 Pick your poison: the Ripoptosome, a cell death platform reg... | ACCEPT | Summary: Positive regulation of extrinsic apoptotic signaling pathway (IMP, PMID:22274400). Reason: Kinase-dependent RIPK1 function promoting complex IIa formation and caspase-8 activation. Supporting Evidence: PMID:22274400 The Ripoptosome is a signaling platform that can switch modes between apoptotic and necroptotic cell death |
| GO:2001240 negative regulation of extrinsic apoptotic signaling pathway in absence of ligand | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Negative regulation of extrinsic apoptotic signaling pathway in absence of ligand (IEA). Reason: Electronic transfer from rodent data; RIPK1's anti-apoptotic scaffold role is mainly ligand (TNF)-dependent, so this specific framing is weakly supported. |
Loading supporting contentβ¦
Download this section (compressed HTML)Q: Which proteins are bona fide physiological substrates of RIPK1 kinase activity beyond RIPK1 itself and RIPK3 (e.g. DAB2IP), and is any substrate other than autophosphorylation required for RIPK1-dependent apoptosis?
Suggested experts: RIPK1/necroptosis biologists, kinase biochemists
Q: How should GO represent the opposing kinase-independent (anti-death, pro-NF-kB) and kinase-dependent (pro-death) roles of RIPK1 so that both positive and negative regulation annotations are retained without appearing contradictory?
Suggested experts: GO cell death curators
Q: GO:0097342 ripoptosome is defined with RIPK1 and RIPK3 as core components, carries necrosome only as a related synonym, and its comment describes the caspase-8/FADD/cFLIP-containing platform. Should the caspase-8-activating complex IIa and the RIPK1-RIPK3 necrosome (complex IIb) be separate child terms?
Suggested experts: GO ontology editors
Experiment: Compare kinase-dead (D138N/K45A) and wild-type RIPK1 knock-in human iPSC-derived neurons and microglia under TNF, TNF+SMAC mimetic and TNF+SMAC+zVAD conditions, measuring complex I composition, NF-kB targets, caspase-8 activity and pMLKL.
Hypothesis: In human neural cell types RIPK1 scaffold function is sufficient for NF-kB signaling and survival, whereas necroptotic and apoptotic death require RIPK1 kinase activity.
Type: genetic knock-in and pharmacological (necrostatin) perturbation
Experiment: Unbiased phosphoproteomics after acute activation of RIPK1 in RIPK3-null and caspase-8-null backgrounds, with analog-sensitive RIPK1 to label direct substrates.
Hypothesis: RIPK1 has a limited set of direct substrates beyond autophosphorylation and RIPK3.
Type: chemical-genetic kinase substrate identification
Loading supporting contentβ¦
Download this section (compressed HTML)Loading supporting contentβ¦
Download this section (compressed HTML)