RAF1 (CRAF, c-Raf, Raf-1) is a ubiquitously expressed RAF-family serine/threonine protein kinase (EC 2.7.11.1) that acts as a mitogen-activated protein kinase kinase kinase (MAP3K) linking membrane-bound RAS GTPases to the MEK-ERK cascade. Its N-terminal regulatory region contains a RAS-binding domain (RBD) and a cysteine-rich C1-like domain (CRD), followed by the Ser259 14-3-3 docking site and a C-terminal kinase domain with a second (Ser621) 14-3-3 site. In resting cells RAF1 is a cytosolic, autoinhibited monomer held by a 14-3-3 dimer and stabilised by the HSP90-CDC37 chaperone system. GTP-loaded RAS recruits RAF1 to the plasma membrane; SHOC2-MRAS-PP1C and PP2A dephosphorylate Ser259, activating phosphorylation (Ser338/Tyr341 and activation loop) follows, and RAF1 forms side-to-side homodimers or heterodimers with BRAF that phosphorylate the activation-loop serines of MEK1 and MEK2, which in turn activate ERK1/2. ERK feedback phosphorylation, RKIP/PEBP1 binding and Golgi sequestration by PAQR3 restrain its activity. Beyond MEK activation, RAF1 has kinase-independent scaffold functions: it binds and inhibits the pro-apoptotic kinases ASK1 (MAP3K5) and MST2 (STK3) and the Rho effector ROCK2, and a mitochondrial pool phosphorylates BAD, together suppressing apoptosis and regulating migration and differentiation. Germline gain-of-function RAF1 variants cause Noonan syndrome 5 and LEOPARD syndrome with hypertrophic cardiomyopathy, and RAF1 is required for RAS-driven signalling and for paradoxical ERK activation by BRAF inhibitors in cancer.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000165 MAPK cascade | IBA GO_REF:0000033 | ACCEPT | Summary: IBA (PAINT node PTN001147804, the RAF kinase clade) for MAPK cascade. RAF1 is the MAP3K tier of the RAS-RAF-MEK-ERK cascade. Reason: The RAF clade node is the correct place for this function; RAF1 phosphorylates MEK1/2 as the first kinase of the ERK cascade. Consistent with IDA evidence (PMID:8576262) and the BRAF review. Supporting Evidence: file:human/RAF1/RAF1-uniprot.txt activation initiates a mitogen-activated protein kinase (MAPK) cascade file:human/RAF1/RAF1-deep-research-falcon.md RAF1βs best-established catalytic function is to phosphorylate the activation loops of **MEK1/MAP2K1 and MEK2/MAP2K2** |
| GO:0000165 MAPK cascade | IDA PMID:8576262 Interleukin-8 regulation of the Ras/Raf/mitogen-activated pr... | ACCEPT | Summary: IDA: IL-8 stimulates Ras GTP loading and activates Raf-1, B-Raf and MAPK in human neutrophils. Reason: Direct measurement of Raf-1 activation within the MAPK cascade; core process. Supporting Evidence: PMID:8576262 IL-8 stimulation of its receptor on neutrophils activates Ras GTP loading and the mitogen-activated protein kinase (MAPK) pathway including Raf-1 and B-Raf |
| GO:0000165 MAPK cascade | IEA GO_REF:0000107 | ACCEPT | Summary: Ensembl Compara projection from mouse Raf1 for MAPK cascade. Reason: Correct core process, identical to the IBA/IDA rows. Supporting Evidence: file:human/RAF1/RAF1-uniprot.txt activation initiates a mitogen-activated protein kinase (MAPK) cascade |
| GO:0004672 protein kinase activity | EXP PMID:9446616 Interferon gamma activation of Raf-1 is Jak1-dependent and p... | ACCEPT | Summary: Reactome EXP: IFN-gamma activates Raf-1 kinase activity in a JAK1-dependent manner. Reason: Raf-1 kinase activity was assayed directly; correct though general (GO:0004709 is the precise MF). Supporting Evidence: PMID:9446616 Treatment of HeLa cells with IFNgamma resulted in the rapid and transient activation of Raf-1 and MAPK. |
| GO:0004672 protein kinase activity | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro2GO (protein kinase domain / Ser-Thr kinase active site) for protein kinase activity. Reason: Correct but general; RAF1 has a catalytically active kinase domain. The more specific GO:0004709 / GO:0004674 are also annotated. Supporting Evidence: file:human/RAF1/RAF1-uniprot.txt Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + |
| GO:0004672 protein kinase activity | TAS PMID:8063729 Signaling through transforming G protein-coupled receptors i... | ACCEPT | Summary: TAS (PINC) from a study showing carbachol-stimulated m1 receptors activate c-Raf kinase measured with MEK as substrate. Reason: Correct though general; MAP3K activity (GO:0004709) is the precise term. Supporting Evidence: PMID:8063729 Carbachol potently induced c-Raf activity as judged by its in vitro phosphorylating activity using MEK as a substrate. |
| GO:0004672 protein kinase activity | TAS PMID:8929532 Bcl-2 targets the protein kinase Raf-1 to mitochondria. | ACCEPT | Summary: TAS (PINC) from Wang et al. 1996: mitochondria-targeted Raf-1 kinase phosphorylates BAD. Reason: Correct; kinase activity is required for the anti-apoptotic effect. Supporting Evidence: PMID:8929532 allowing this kinase to phosphorylate BAD or possibly other protein substrates involved in apoptosis regulation |
| GO:0004674 protein serine/threonine kinase activity | IDA PMID:19667065 Identification of novel in vivo phosphorylation sites of the... | ACCEPT | Summary: UniProt IDA: RAF kinases phosphorylate human BAD at Ser75/Ser99/Ser118 in vivo, blocked by sorafenib but not MEK inhibitors. Reason: Direct evidence of RAF Ser/Thr kinase activity on a non-MEK substrate. Supporting Evidence: PMID:19667065 Our results indicate that RAF kinases represent, besides protein kinase A, PAK, and Akt/protein kinase B, in vivo BAD-phosphorylating kinases. |
| GO:0004674 protein serine/threonine kinase activity | IDA PMID:8576262 Interleukin-8 regulation of the Ras/Raf/mitogen-activated pr... | ACCEPT | Summary: IDA: Raf-1 kinase activity measured after IL-8/C5a stimulation of neutrophils. Reason: Kinase assays of immunoprecipitated Raf-1 support Ser/Thr kinase activity. Supporting Evidence: PMID:8576262 Raf-1 activation is rapid but transient, returning to near basal levels by 10 min. |
| GO:0004674 protein serine/threonine kinase activity | IEA GO_REF:0000120 | ACCEPT | Summary: IEA (UniProt EC 2.7.11.1 mapping / mouse ortholog) for protein serine/threonine kinase activity. Reason: Correct: RAF1 is EC 2.7.11.1 with experimentally supported Ser and Thr phosphorylation (PMID:17603483 in UniProt). Supporting Evidence: file:human/RAF1/RAF1-uniprot.txt Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + |
| GO:0004709 MAP kinase kinase kinase activity | IBA GO_REF:0000033 | ACCEPT | Summary: IBA (PAINT node PTN001147804, RAF clade) for MAP kinase kinase kinase activity, the defining RAF1 molecular function. Reason: RAF1 phosphorylates the activation-loop serines of MAP2K1/MAP2K2; this is its core catalytic function and the node placement (RAF clade, with Drosophila pole hole, C. elegans lin-45 and vertebrate RAFs) is sound. Supporting Evidence: file:human/RAF1/RAF1-deep-research-falcon.md RAF1βs best-established catalytic function is to phosphorylate the activation loops of **MEK1/MAP2K1 and MEK2/MAP2K2** Reactome:R-HSA-5672978 Although all three RAF kinases can phosphorylate MAP2K1 and MAP2K2 |
| GO:0004709 MAP kinase kinase kinase activity | IEA GO_REF:0000107 | ACCEPT | Summary: Ensembl Compara projection from mouse Raf1 for MAP kinase kinase kinase activity. Reason: Correct core MF, identical to the IBA row. Supporting Evidence: file:human/RAF1/RAF1-deep-research-falcon.md RAF1βs best-established catalytic function is to phosphorylate the activation loops of **MEK1/MAP2K1 and MEK2/MAP2K2** |
| GO:0005515 protein binding | IPI PMID:10433554 14-3-3Gamma interacts with and is phosphorylated by multiple... | MODIFY | Summary: IPI (study of 14-3-3gamma in PDGF-stimulated vascular smooth muscle cells) for RAF1 binding YWHAG. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is YWHAG. RAF1 is a canonical phospho-dependent 14-3-3 client: a 14-3-3 dimer engaging pSer259 and pSer621 holds the autoinhibited monomer, and the pSer621 site also stabilises the active dimer. 14-3-3 protein binding captures this regulatory interaction (same term as the BRAF review). Proposed replacements: 14-3-3 protein binding Supporting Evidence: PMID:10433554 We found that 14-3-3gamma interacted with the signal transduction protein Raf-1 file:human/RAF1/RAF1-uniprot.txt P04049; P61981: YWHAG; NbExp=24; IntAct=EBI-365996, EBI-359832; |
| GO:0005515 protein binding | IPI PMID:10523642 JSAP1, a novel jun N-terminal protein kinase (JNK)-binding p... | MODIFY | Summary: IPI (study identifying the mouse JNK scaffold JSAP1 (Mapk8ip3), which also coprecipitated Raf-1) for RAF1 binding mouse Mapk8ip3/JSAP1 (MAPK scaffold). Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is mouse Mapk8ip3/JSAP1 (MAPK scaffold). The partner is a MAPK-pathway scaffold that assembles RAF with RAS/MEK or phosphatase; scaffold protein binding is the informative term (same choice as the BRAF review for KSR/IQGAP1/RGS12). Proposed replacements: scaffold protein binding Supporting Evidence: PMID:10523642 Although JSAP1 coprecipitated with MEK1 MAPKK and Raf-1 MAPKKK |
| GO:0005515 protein binding | IPI PMID:10523642 JSAP1, a novel jun N-terminal protein kinase (JNK)-binding p... | MODIFY | Summary: IPI (study identifying the mouse JNK scaffold JSAP1 (Mapk8ip3), which also coprecipitated Raf-1) for RAF1 binding mouse Mapk8ip3/JSAP1 isoform 2 (MAPK scaffold). Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is mouse Mapk8ip3/JSAP1 isoform 2 (MAPK scaffold). The partner is a MAPK-pathway scaffold that assembles RAF with RAS/MEK or phosphatase; scaffold protein binding is the informative term (same choice as the BRAF review for KSR/IQGAP1/RGS12). Proposed replacements: scaffold protein binding Supporting Evidence: PMID:10523642 Although JSAP1 coprecipitated with MEK1 MAPKK and Raf-1 MAPKKK file:human/RAF1/RAF1-uniprot.txt P04049; Q9ESN9-2: Mapk8ip3; Xeno; NbExp=2; IntAct=EBI-365996, EBI-9549291; |
| GO:0005515 protein binding | IPI PMID:11697890 Functional conservation of 14-3-3 isoforms in inhibiting bad... | MODIFY | Summary: IPI (study of functional conservation of 14-3-3 isoforms binding Bad, Raf-1 and Cbl) for RAF1 binding YWHAQ. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is YWHAQ. RAF1 is a canonical phospho-dependent 14-3-3 client: a 14-3-3 dimer engaging pSer259 and pSer621 holds the autoinhibited monomer, and the pSer621 site also stabilises the active dimer. 14-3-3 protein binding captures this regulatory interaction (same term as the BRAF review). Proposed replacements: 14-3-3 protein binding Supporting Evidence: PMID:11697890 isoforms of 14-3-3 proteins were capable of binding to several ligands, Bad, Raf-1, and Cbl file:human/RAF1/RAF1-uniprot.txt P04049; P27348: YWHAQ; NbExp=24; IntAct=EBI-365996, EBI-359854; |
| GO:0005515 protein binding | IPI PMID:11697890 Functional conservation of 14-3-3 isoforms in inhibiting bad... | MODIFY | Summary: IPI (study of functional conservation of 14-3-3 isoforms binding Bad, Raf-1 and Cbl) for RAF1 binding YWHAB. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is YWHAB. RAF1 is a canonical phospho-dependent 14-3-3 client: a 14-3-3 dimer engaging pSer259 and pSer621 holds the autoinhibited monomer, and the pSer621 site also stabilises the active dimer. 14-3-3 protein binding captures this regulatory interaction (same term as the BRAF review). Proposed replacements: 14-3-3 protein binding Supporting Evidence: PMID:11697890 isoforms of 14-3-3 proteins were capable of binding to several ligands, Bad, Raf-1, and Cbl file:human/RAF1/RAF1-uniprot.txt P04049; P31946: YWHAB; NbExp=39; IntAct=EBI-365996, EBI-359815; |
| GO:0005515 protein binding | IPI PMID:11697890 Functional conservation of 14-3-3 isoforms in inhibiting bad... | MODIFY | Summary: IPI (study of functional conservation of 14-3-3 isoforms binding Bad, Raf-1 and Cbl) for RAF1 binding SFN (14-3-3 sigma). Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is SFN (14-3-3 sigma). RAF1 is a canonical phospho-dependent 14-3-3 client: a 14-3-3 dimer engaging pSer259 and pSer621 holds the autoinhibited monomer, and the pSer621 site also stabilises the active dimer. 14-3-3 protein binding captures this regulatory interaction (same term as the BRAF review). Proposed replacements: 14-3-3 protein binding Supporting Evidence: PMID:11697890 isoforms of 14-3-3 proteins were capable of binding to several ligands, Bad, Raf-1, and Cbl file:human/RAF1/RAF1-uniprot.txt P04049; P31947: SFN; NbExp=9; IntAct=EBI-365996, EBI-476295; |
| GO:0005515 protein binding | IPI PMID:11697890 Functional conservation of 14-3-3 isoforms in inhibiting bad... | MODIFY | Summary: IPI (study of functional conservation of 14-3-3 isoforms binding Bad, Raf-1 and Cbl) for RAF1 binding YWHAG. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is YWHAG. RAF1 is a canonical phospho-dependent 14-3-3 client: a 14-3-3 dimer engaging pSer259 and pSer621 holds the autoinhibited monomer, and the pSer621 site also stabilises the active dimer. 14-3-3 protein binding captures this regulatory interaction (same term as the BRAF review). Proposed replacements: 14-3-3 protein binding Supporting Evidence: PMID:11697890 isoforms of 14-3-3 proteins were capable of binding to several ligands, Bad, Raf-1, and Cbl file:human/RAF1/RAF1-uniprot.txt P04049; P61981: YWHAG; NbExp=24; IntAct=EBI-365996, EBI-359832; |
| GO:0005515 protein binding | IPI PMID:11697890 Functional conservation of 14-3-3 isoforms in inhibiting bad... | MODIFY | Summary: IPI (study of functional conservation of 14-3-3 isoforms binding Bad, Raf-1 and Cbl) for RAF1 binding YWHAE. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is YWHAE. RAF1 is a canonical phospho-dependent 14-3-3 client: a 14-3-3 dimer engaging pSer259 and pSer621 holds the autoinhibited monomer, and the pSer621 site also stabilises the active dimer. 14-3-3 protein binding captures this regulatory interaction (same term as the BRAF review). Proposed replacements: 14-3-3 protein binding Supporting Evidence: PMID:11697890 isoforms of 14-3-3 proteins were capable of binding to several ligands, Bad, Raf-1, and Cbl file:human/RAF1/RAF1-uniprot.txt P04049; P62258: YWHAE; NbExp=25; IntAct=EBI-365996, EBI-356498; |
| GO:0005515 protein binding | IPI PMID:11697890 Functional conservation of 14-3-3 isoforms in inhibiting bad... | MODIFY | Summary: IPI (study of functional conservation of 14-3-3 isoforms binding Bad, Raf-1 and Cbl) for RAF1 binding YWHAZ. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is YWHAZ. RAF1 is a canonical phospho-dependent 14-3-3 client: a 14-3-3 dimer engaging pSer259 and pSer621 holds the autoinhibited monomer, and the pSer621 site also stabilises the active dimer. 14-3-3 protein binding captures this regulatory interaction (same term as the BRAF review). Proposed replacements: 14-3-3 protein binding Supporting Evidence: PMID:11697890 isoforms of 14-3-3 proteins were capable of binding to several ligands, Bad, Raf-1, and Cbl file:human/RAF1/RAF1-uniprot.txt P04049; P63104: YWHAZ; NbExp=32; IntAct=EBI-365996, EBI-347088; |
| GO:0005515 protein binding | IPI PMID:11697890 Functional conservation of 14-3-3 isoforms in inhibiting bad... | MODIFY | Summary: IPI (study of functional conservation of 14-3-3 isoforms binding Bad, Raf-1 and Cbl) for RAF1 binding YWHAH. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is YWHAH. RAF1 is a canonical phospho-dependent 14-3-3 client: a 14-3-3 dimer engaging pSer259 and pSer621 holds the autoinhibited monomer, and the pSer621 site also stabilises the active dimer. 14-3-3 protein binding captures this regulatory interaction (same term as the BRAF review). Proposed replacements: 14-3-3 protein binding Supporting Evidence: PMID:11697890 isoforms of 14-3-3 proteins were capable of binding to several ligands, Bad, Raf-1, and Cbl file:human/RAF1/RAF1-uniprot.txt P04049; Q04917: YWHAH; NbExp=27; IntAct=EBI-365996, EBI-306940; |
| GO:0005515 protein binding | IPI PMID:11909642 Identification of interaction between MEK2 and A-Raf-1. | MODIFY | Summary: IPI (MEK2-bait yeast two-hybrid screen that recovered c-Raf, KSR and A-Raf) for RAF1 binding MAP2K2/MEK2. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is MAP2K2/MEK2. MEK1/MEK2 are the physiological substrates of RAF1 and form RAF-MEK complexes; MAPKK binding is the informative term (same term as the BRAF review). Proposed replacements: mitogen-activated protein kinase kinase binding Supporting Evidence: PMID:11909642 besides c-Raf and KSR, A-Raf was identified as a novel partner that interacts with MEK2 file:human/RAF1/RAF1-uniprot.txt P04049; P36507: MAP2K2; NbExp=7; IntAct=EBI-365996, EBI-1056930; |
| GO:0005515 protein binding | IPI PMID:12620389 Novel raf kinase protein-protein interactions found by an ex... | REMOVE | Summary: IPI (exhaustive yeast two-hybrid screen using the A-Raf/C-Raf N-terminal regulatory domain as bait) for RAF1 binding OIP5. Reason: GO:0005515 protein binding is uninformative. Yeast two-hybrid hit with the RAF N-terminal/CRD bait, not independently validated. Removal does not mean the reported interaction is false; it means no informative RAF1 molecular-function term can be justified from it. Supporting Evidence: PMID:12620389 A total of 20 different human proteins were found to interact with Raf isoforms file:human/RAF1/RAF1-uniprot.txt P04049; O43482: OIP5; NbExp=4; IntAct=EBI-365996, EBI-536879; |
| GO:0005515 protein binding | IPI PMID:12620389 Novel raf kinase protein-protein interactions found by an ex... | MODIFY | Summary: IPI (exhaustive yeast two-hybrid screen using the A-Raf/C-Raf N-terminal regulatory domain as bait) for RAF1 binding HRAS. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is HRAS. RAF1 is a direct RAS effector: its RAS-binding domain (RBD) and CRD bind GTP-loaded RAS family GTPases, recruiting RAF1 to the plasma membrane; this is the entry step of RAF activation. small GTPase binding is the informative term (same term as the BRAF review). Proposed replacements: small GTPase binding Supporting Evidence: PMID:12620389 A total of 20 different human proteins were found to interact with Raf isoforms file:human/RAF1/RAF1-uniprot.txt P04049; P01112: HRAS; NbExp=30; IntAct=EBI-365996, EBI-350145; |
| GO:0005515 protein binding | IPI PMID:12620389 Novel raf kinase protein-protein interactions found by an ex... | REMOVE | Summary: IPI (exhaustive yeast two-hybrid screen using the A-Raf/C-Raf N-terminal regulatory domain as bait) for RAF1 binding PKM. Reason: GO:0005515 protein binding is uninformative. Yeast two-hybrid hit with the RAF N-terminal/CRD bait, not independently validated. Removal does not mean the reported interaction is false; it means no informative RAF1 molecular-function term can be justified from it. Supporting Evidence: PMID:12620389 A total of 20 different human proteins were found to interact with Raf isoforms file:human/RAF1/RAF1-uniprot.txt P04049; P14618: PKM; NbExp=3; IntAct=EBI-365996, EBI-353408; |
| GO:0005515 protein binding | IPI PMID:12620389 Novel raf kinase protein-protein interactions found by an ex... | REMOVE | Summary: IPI (exhaustive yeast two-hybrid screen using the A-Raf/C-Raf N-terminal regulatory domain as bait) for RAF1 binding CPS1. Reason: GO:0005515 protein binding is uninformative. Yeast two-hybrid / AP-MS hit (mitochondrial urea-cycle enzyme), not functionally related to RAF1. Removal does not mean the reported interaction is false; it means no informative RAF1 molecular-function term can be justified from it. Supporting Evidence: PMID:12620389 A total of 20 different human proteins were found to interact with Raf isoforms file:human/RAF1/RAF1-uniprot.txt P04049; P31327: CPS1; NbExp=4; IntAct=EBI-365996, EBI-536811; |
| GO:0005515 protein binding | IPI PMID:12620389 Novel raf kinase protein-protein interactions found by an ex... | MODIFY | Summary: IPI (exhaustive yeast two-hybrid screen using the A-Raf/C-Raf N-terminal regulatory domain as bait) for RAF1 binding YWHAB. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is YWHAB. RAF1 is a canonical phospho-dependent 14-3-3 client: a 14-3-3 dimer engaging pSer259 and pSer621 holds the autoinhibited monomer, and the pSer621 site also stabilises the active dimer. 14-3-3 protein binding captures this regulatory interaction (same term as the BRAF review). Proposed replacements: 14-3-3 protein binding Supporting Evidence: PMID:12620389 A total of 20 different human proteins were found to interact with Raf isoforms file:human/RAF1/RAF1-uniprot.txt P04049; P31946: YWHAB; NbExp=39; IntAct=EBI-365996, EBI-359815; |
| GO:0005515 protein binding | IPI PMID:12620389 Novel raf kinase protein-protein interactions found by an ex... | MODIFY | Summary: IPI (exhaustive yeast two-hybrid screen using the A-Raf/C-Raf N-terminal regulatory domain as bait) for RAF1 binding CCT3 (TRiC chaperonin subunit). Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is CCT3 (TRiC chaperonin subunit). The partner is a protein-folding chaperone or co-chaperone, and RAF1 is a chaperone client (HSP90-CDC37 dependence is well established); protein-folding chaperone binding describes the interaction from the RAF1 side. Proposed replacements: protein-folding chaperone binding Supporting Evidence: PMID:12620389 A total of 20 different human proteins were found to interact with Raf isoforms file:human/RAF1/RAF1-uniprot.txt P04049; P49368: CCT3; NbExp=8; IntAct=EBI-365996, EBI-356673; |
| GO:0005515 protein binding | IPI PMID:12620389 Novel raf kinase protein-protein interactions found by an ex... | REMOVE | Summary: IPI (exhaustive yeast two-hybrid screen using the A-Raf/C-Raf N-terminal regulatory domain as bait) for RAF1 binding TIMM50. Reason: GO:0005515 protein binding is uninformative. Yeast two-hybrid / AP-MS hit (mitochondrial import component), no functional characterisation for RAF1. Removal does not mean the reported interaction is false; it means no informative RAF1 molecular-function term can be justified from it. Supporting Evidence: PMID:12620389 A total of 20 different human proteins were found to interact with Raf isoforms file:human/RAF1/RAF1-uniprot.txt P04049; Q3ZCQ8: TIMM50; NbExp=7; IntAct=EBI-365996, EBI-355175; |
| GO:0005515 protein binding | IPI PMID:14688280 Dynamic changes in C-Raf phosphorylation and 14-3-3 protein ... | MODIFY | Summary: IPI (biochemical study of C-Raf pS259/pS621 14-3-3 binding sites) for RAF1 binding YWHAZ. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is YWHAZ. RAF1 is a canonical phospho-dependent 14-3-3 client: a 14-3-3 dimer engaging pSer259 and pSer621 holds the autoinhibited monomer, and the pSer621 site also stabilises the active dimer. 14-3-3 protein binding captures this regulatory interaction (same term as the BRAF review). Proposed replacements: 14-3-3 protein binding Supporting Evidence: PMID:14688280 Direct C-Raf.14-3-3 binding studies with purified proteins combined with competition assays revealed file:human/RAF1/RAF1-uniprot.txt P04049; P63104: YWHAZ; NbExp=32; IntAct=EBI-365996, EBI-347088; |
| GO:0005515 protein binding | IPI PMID:15778465 Targeted proteomic analysis of 14-3-3 sigma, a p53 effector ... | MODIFY | Summary: IPI (TAP/MudPIT proteomics of 14-3-3 sigma partners) for RAF1 binding SFN (14-3-3 sigma). Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is SFN (14-3-3 sigma). RAF1 is a canonical phospho-dependent 14-3-3 client: a 14-3-3 dimer engaging pSer259 and pSer621 holds the autoinhibited monomer, and the pSer621 site also stabilises the active dimer. 14-3-3 protein binding captures this regulatory interaction (same term as the BRAF review). Proposed replacements: 14-3-3 protein binding Supporting Evidence: PMID:15778465 proteins previously implicated in oncogenic signaling (APC, A-RAF, B-RAF, and c-RAF) file:human/RAF1/RAF1-uniprot.txt P04049; P31947: SFN; NbExp=9; IntAct=EBI-365996, EBI-476295; |
| GO:0005515 protein binding | IPI PMID:15935327 Raf-1 is a binding partner of DSCR1. | REMOVE | Summary: IPI (DSCR1 (RCAN1) pull-down identifying Raf-1 as a binding partner) for RAF1 binding RCAN1/DSCR1 isoform. Reason: GO:0005515 protein binding is uninformative. RCAN1 binding is a single-paper pull-down/co-IP observation of unknown functional consequence for RAF1. Removal does not mean the reported interaction is false; it means no informative RAF1 molecular-function term can be justified from it. Supporting Evidence: PMID:15935327 We performed pull-down analysis using DSCR1 as a bait and identified Raf-1 as a binding partner file:human/RAF1/RAF1-uniprot.txt P04049; P53805-2: RCAN1; NbExp=4; IntAct=EBI-365996, EBI-1541912; |
| GO:0005515 protein binding | IPI PMID:16239230 Positive regulation of Raf1-MEK1/2-ERK1/2 signaling by prote... | MODIFY | Summary: IPI (study of PP2A B-alpha/B-delta holoenzymes positively regulating Raf1-MEK-ERK) for RAF1 binding PPP2CA (PP2A catalytic subunit). Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is PPP2CA (PP2A catalytic subunit). The partner is (a subunit of) a protein phosphatase that dephosphorylates RAF1 (PP2A, PP1C on pSer259) or, for CDC25A, a phosphatase that RAF1 binds and activates; phosphatase binding is the informative term. Proposed replacements: phosphatase binding Supporting Evidence: PMID:16239230 Furthermore both PP2A holoenzymes were found to associate with Raf1 file:human/RAF1/RAF1-uniprot.txt P04049; P67775: PPP2CA; NbExp=2; IntAct=EBI-365996, EBI-712311; |
| GO:0005515 protein binding | IPI PMID:16239230 Positive regulation of Raf1-MEK1/2-ERK1/2 signaling by prote... | MODIFY | Summary: IPI (study of PP2A B-alpha/B-delta holoenzymes positively regulating Raf1-MEK-ERK) for RAF1 binding PPP2R5C (PP2A B56-gamma subunit). Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is PPP2R5C (PP2A B56-gamma subunit). The partner is (a subunit of) a protein phosphatase that dephosphorylates RAF1 (PP2A, PP1C on pSer259) or, for CDC25A, a phosphatase that RAF1 binds and activates; phosphatase binding is the informative term. Proposed replacements: phosphatase binding Supporting Evidence: PMID:16239230 Furthermore both PP2A holoenzymes were found to associate with Raf1 file:human/RAF1/RAF1-uniprot.txt P04049; Q13362: PPP2R5C; NbExp=2; IntAct=EBI-365996, EBI-1266156; |
| GO:0005515 protein binding | IPI PMID:16306228 14-3-3 cooperates with LKB1 to regulate the activity and loc... | MODIFY | Summary: IPI (14-3-3/LKB1 study of QSK and SIK; RAF1 is not mentioned in the cached abstract (possibly a control 14-3-3 client)) for RAF1 binding YWHAZ. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is YWHAZ. RAF1 is a canonical phospho-dependent 14-3-3 client: a 14-3-3 dimer engaging pSer259 and pSer621 holds the autoinhibited monomer, and the pSer621 site also stabilises the active dimer. 14-3-3 protein binding captures this regulatory interaction (same term as the BRAF review). The cached text of this reference does not describe the RAF1 interaction, so the IntAct/BioGRID curation (made from the full text or supplementary data) is deferred to; the partner-type mapping is supported by independent RAF1 evidence cited here. Proposed replacements: 14-3-3 protein binding Supporting Evidence: file:human/RAF1/RAF1-uniprot.txt the binding of a 14-3-3 protein that contacts two phosphorylation file:human/RAF1/RAF1-uniprot.txt P04049; P63104: YWHAZ; NbExp=32; IntAct=EBI-365996, EBI-347088; |
| GO:0005515 protein binding | IPI PMID:16330544 Chaperoning checkpoint kinase 1 (Chk1), an Hsp90 client, wit... | MODIFY | Summary: IPI (in vitro chaperoning study of the Hsp90 client Chk1; RAF1 is not mentioned in the cached abstract (possibly a control Hsp90 client)) for RAF1 binding HSP90AB1. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is HSP90AB1. RAF1 is a strongly HSP90-dependent client kinase whose folding and stability require HSP90-CDC37; Hsp90 protein binding is the informative term (same term as the BRAF review). The cached text of this reference does not describe the RAF1 interaction, so the IntAct/BioGRID curation (made from the full text or supplementary data) is deferred to; the partner-type mapping is supported by independent RAF1 evidence cited here. Proposed replacements: Hsp90 protein binding Supporting Evidence: file:human/RAF1/RAF1-uniprot.txt complex composed of chaperones HSP90 and HSP70, co-chaperones CDC37, file:human/RAF1/RAF1-uniprot.txt P04049; P08238: HSP90AB1; NbExp=17; IntAct=EBI-365996, EBI-352572; |
| GO:0005515 protein binding | IPI PMID:16405965 Raf-1 kinase associates with Hepatitis C virus NS5A and regu... | REMOVE | Summary: IPI (study identifying Raf-1 as a binding partner of HCV NS5A) for RAF1 binding hepatitis C virus NS5A. Reason: GO:0005515 protein binding is uninformative. Host-virus interaction (NS5A recruits RAF1 to the HCV replication complex); not a normal molecular function of RAF1, and viral-protein binding is better expressed from the viral side. Removal does not mean the reported interaction is false; it means no informative RAF1 molecular-function term can be justified from it. Supporting Evidence: PMID:16405965 the kinase Raf-1 was identified as a novel cellular binding partner of NS5A file:human/RAF1/RAF1-uniprot.txt P04049; O39474: NS5A; Xeno; NbExp=4; IntAct=EBI-365996, EBI-7016711; |
| GO:0005515 protein binding | IPI PMID:16837009 A dimeric kinase assembly underlying autophosphorylation in ... | MODIFY | Summary: IPI (structural study of PAK2/PAK1 kinase-domain dimers; RAF1 is not mentioned in the cached abstract) for RAF1 binding PAK2. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is PAK2. The partner is a protein kinase that either regulates RAF1 by phosphorylation (PAK S338, AKT S259), is inhibited by RAF1 binding (MST2), or is an upstream receptor tyrosine kinase; protein kinase binding is the informative term. The cached text of this reference does not describe the RAF1 interaction, so the IntAct/BioGRID curation (made from the full text or supplementary data) is deferred to; the partner-type mapping is supported by independent RAF1 evidence cited here. Proposed replacements: protein kinase binding Supporting Evidence: file:human/RAF1/RAF1-uniprot.txt P04049; Q13177: PAK2; NbExp=2; IntAct=EBI-365996, EBI-1045887; |
| GO:0005515 protein binding | IPI PMID:17097642 Regulation of RKIP binding to the N-region of the Raf-1 kina... | REMOVE | Summary: IPI (study mapping the RKIP-binding N-region of Raf-1, which is also the PAK/SRC-phosphorylated region) for RAF1 binding PEBP1/RKIP. Reason: GO:0005515 protein binding is uninformative. RKIP is a genuine negative regulator that binds the RAF1 N-region and displaces MEK, but no GO MF term describes being bound by a kinase inhibitor protein; the regulatory relationship belongs on PEBP1 (protein kinase inhibitor activity). Removal does not mean the reported interaction is false; it means no informative RAF1 molecular-function term can be justified from it. Supporting Evidence: PMID:17097642 The Raf kinase inhibitory protein (RKIP) binds to Raf-1 interfering with binding of the MEK substrate file:human/RAF1/RAF1-uniprot.txt P04049; P30086: PEBP1; NbExp=10; IntAct=EBI-365996, EBI-716384; |
| GO:0005515 protein binding | IPI PMID:17097642 Regulation of RKIP binding to the N-region of the Raf-1 kina... | MODIFY | Summary: IPI (study mapping the RKIP-binding N-region of Raf-1, which is also the PAK/SRC-phosphorylated region) for RAF1 binding PAK1. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is PAK1. The partner is a protein kinase that either regulates RAF1 by phosphorylation (PAK S338, AKT S259), is inhibited by RAF1 binding (MST2), or is an upstream receptor tyrosine kinase; protein kinase binding is the informative term. Proposed replacements: protein kinase binding Supporting Evidence: PMID:17097642 PAK1 and 2 have been shown to phosphorylate Ser 338 file:human/RAF1/RAF1-uniprot.txt P04049; Q13153: PAK1; NbExp=2; IntAct=EBI-365996, EBI-1307; |
| GO:0005515 protein binding | IPI PMID:17229891 DYRK1A autophosphorylation on serine residue 520 modulates i... | MODIFY | Summary: IPI (DYRK1A/14-3-3 study; RAF1 and Kras are not mentioned in the cached abstract (likely a RAS-GTP/RBD assay in the full text)) for RAF1 binding mouse Kras. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is mouse Kras. RAF1 is a direct RAS effector: its RAS-binding domain (RBD) and CRD bind GTP-loaded RAS family GTPases, recruiting RAF1 to the plasma membrane; this is the entry step of RAF activation. small GTPase binding is the informative term (same term as the BRAF review). The cached text of this reference does not describe the RAF1 interaction, so the IntAct/BioGRID curation (made from the full text or supplementary data) is deferred to; the partner-type mapping is supported by independent RAF1 evidence cited here. Proposed replacements: small GTPase binding Supporting Evidence: file:human/RAF1/RAF1-uniprot.txt Ras-GTP recruits RAF1 to the file:human/RAF1/RAF1-uniprot.txt P04049; P32883: Kras; Xeno; NbExp=2; IntAct=EBI-365996, EBI-644267; |
| GO:0005515 protein binding | IPI PMID:17724343 Spatial regulation of Raf kinase signaling by RKTG. | MODIFY | Summary: IPI (study of RKTG (PAQR3) trapping Raf-1 at the Golgi) for RAF1 binding MAP2K1/MEK1. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is MAP2K1/MEK1. MEK1/MEK2 are the physiological substrates of RAF1 and form RAF-MEK complexes; MAPKK binding is the informative term (same term as the BRAF review). Proposed replacements: mitogen-activated protein kinase kinase binding Supporting Evidence: PMID:17724343 reduces the interaction of Raf-1 with Ras and MEK1 file:human/RAF1/RAF1-uniprot.txt P04049; Q02750: MAP2K1; NbExp=39; IntAct=EBI-365996, EBI-492564; |
| GO:0005515 protein binding | IPI PMID:17724343 Spatial regulation of Raf kinase signaling by RKTG. | REMOVE | Summary: IPI (study of RKTG (PAQR3) trapping Raf-1 at the Golgi) for RAF1 binding PAQR3/RKTG. Reason: GO:0005515 protein binding is uninformative. RKTG sequesters RAF1 at the Golgi and inhibits ERK signalling; the relationship is captured on PAQR3 and by the RAF1 Golgi CC row; no informative RAF1-side MF exists. Removal does not mean the reported interaction is false; it means no informative RAF1 molecular-function term can be justified from it. Supporting Evidence: PMID:17724343 reduces the interaction of Raf-1 with Ras and MEK1 file:human/RAF1/RAF1-uniprot.txt P04049; Q6TCH7: PAQR3; NbExp=3; IntAct=EBI-365996, EBI-15654365; |
| GO:0005515 protein binding | IPI PMID:17979178 A novel tandem affinity purification strategy for the effici... | MODIFY | Summary: IPI (SF-TAP purification of native Raf-associated complexes from HEK293 cells) for RAF1 binding HSP90AB1. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is HSP90AB1. RAF1 is a strongly HSP90-dependent client kinase whose folding and stability require HSP90-CDC37; Hsp90 protein binding is the informative term (same term as the BRAF review). Proposed replacements: Hsp90 protein binding Supporting Evidence: PMID:17979178 purification of Raf associated protein complexes from HEK293 cells file:human/RAF1/RAF1-uniprot.txt P04049; P08238: HSP90AB1; NbExp=17; IntAct=EBI-365996, EBI-352572; |
| GO:0005515 protein binding | IPI PMID:17979178 A novel tandem affinity purification strategy for the effici... | MODIFY | Summary: IPI (SF-TAP purification of native Raf-associated complexes from HEK293 cells) for RAF1 binding YWHAZ. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is YWHAZ. RAF1 is a canonical phospho-dependent 14-3-3 client: a 14-3-3 dimer engaging pSer259 and pSer621 holds the autoinhibited monomer, and the pSer621 site also stabilises the active dimer. 14-3-3 protein binding captures this regulatory interaction (same term as the BRAF review). Proposed replacements: 14-3-3 protein binding Supporting Evidence: PMID:17979178 purification of Raf associated protein complexes from HEK293 cells file:human/RAF1/RAF1-uniprot.txt P04049; P63104: YWHAZ; NbExp=32; IntAct=EBI-365996, EBI-347088; |
| GO:0005515 protein binding | IPI PMID:17979178 A novel tandem affinity purification strategy for the effici... | MODIFY | Summary: IPI (SF-TAP purification of native Raf-associated complexes from HEK293 cells) for RAF1 binding MAP2K1/MEK1. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is MAP2K1/MEK1. MEK1/MEK2 are the physiological substrates of RAF1 and form RAF-MEK complexes; MAPKK binding is the informative term (same term as the BRAF review). Proposed replacements: mitogen-activated protein kinase kinase binding Supporting Evidence: PMID:17979178 purification of Raf associated protein complexes from HEK293 cells file:human/RAF1/RAF1-uniprot.txt P04049; Q02750: MAP2K1; NbExp=39; IntAct=EBI-365996, EBI-492564; |
| GO:0005515 protein binding | IPI PMID:17979178 A novel tandem affinity purification strategy for the effici... | MODIFY | Summary: IPI (SF-TAP purification of native Raf-associated complexes from HEK293 cells) for RAF1 binding YWHAH. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is YWHAH. RAF1 is a canonical phospho-dependent 14-3-3 client: a 14-3-3 dimer engaging pSer259 and pSer621 holds the autoinhibited monomer, and the pSer621 site also stabilises the active dimer. 14-3-3 protein binding captures this regulatory interaction (same term as the BRAF review). Proposed replacements: 14-3-3 protein binding Supporting Evidence: PMID:17979178 purification of Raf associated protein complexes from HEK293 cells file:human/RAF1/RAF1-uniprot.txt P04049; Q04917: YWHAH; NbExp=27; IntAct=EBI-365996, EBI-306940; |
| GO:0005515 protein binding | IPI PMID:17979178 A novel tandem affinity purification strategy for the effici... | MODIFY | Summary: IPI (SF-TAP purification of native Raf-associated complexes from HEK293 cells) for RAF1 binding CDC37 (HSP90 kinase co-chaperone). Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is CDC37 (HSP90 kinase co-chaperone). The partner is a protein-folding chaperone or co-chaperone, and RAF1 is a chaperone client (HSP90-CDC37 dependence is well established); protein-folding chaperone binding describes the interaction from the RAF1 side. Proposed replacements: protein-folding chaperone binding Supporting Evidence: PMID:17979178 purification of Raf associated protein complexes from HEK293 cells file:human/RAF1/RAF1-uniprot.txt P04049; Q16543: CDC37; NbExp=20; IntAct=EBI-365996, EBI-295634; |
| GO:0005515 protein binding | IPI PMID:18064632 GRP78 and Raf-1 cooperatively confer resistance to endoplasm... | MODIFY | Summary: IPI (study of GRP78 and Raf-1 cooperating at mitochondria against ER stress-induced apoptosis) for RAF1 binding HSPA5/GRP78. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is HSPA5/GRP78. The partner is a protein-folding chaperone or co-chaperone, and RAF1 is a chaperone client (HSP90-CDC37 dependence is well established); protein-folding chaperone binding describes the interaction from the RAF1 side. Proposed replacements: protein-folding chaperone binding Supporting Evidence: PMID:18064632 GRP78 associated and colocalized with Raf-1 on the outer membrane of mitochondria file:human/RAF1/RAF1-uniprot.txt P04049; P11021: HSPA5; NbExp=5; IntAct=EBI-365996, EBI-354921; |
| GO:0005515 protein binding | IPI PMID:18073111 Transformation efficiency of RasQ61 mutants linked to struct... | MODIFY | Summary: IPI (structural study of RasQ61 mutants in the presence of Raf) for RAF1 binding HRAS. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is HRAS. RAF1 is a direct RAS effector: its RAS-binding domain (RBD) and CRD bind GTP-loaded RAS family GTPases, recruiting RAF1 to the plasma membrane; this is the entry step of RAF activation. small GTPase binding is the informative term (same term as the BRAF review). Proposed replacements: small GTPase binding Supporting Evidence: PMID:18073111 We show that Raf impairs the GTPase activity of RasQ61L file:human/RAF1/RAF1-uniprot.txt P04049; P01112: HRAS; NbExp=30; IntAct=EBI-365996, EBI-350145; |
| GO:0005515 protein binding | IPI PMID:18273062 A novel switch region regulates H-ras membrane orientation a... | MODIFY | Summary: IPI (FRET study of H-ras membrane orientation; RAF1 is not mentioned in the cached abstract (the C-Raf RBD is commonly used as the effector readout)) for RAF1 binding HRAS. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is HRAS. RAF1 is a direct RAS effector: its RAS-binding domain (RBD) and CRD bind GTP-loaded RAS family GTPases, recruiting RAF1 to the plasma membrane; this is the entry step of RAF activation. small GTPase binding is the informative term (same term as the BRAF review). The cached text of this reference does not describe the RAF1 interaction, so the IntAct/BioGRID curation (made from the full text or supplementary data) is deferred to; the partner-type mapping is supported by independent RAF1 evidence cited here. Proposed replacements: small GTPase binding Supporting Evidence: file:human/RAF1/RAF1-uniprot.txt Ras-GTP recruits RAF1 to the file:human/RAF1/RAF1-uniprot.txt P04049; P01112: HRAS; NbExp=30; IntAct=EBI-365996, EBI-350145; |
| GO:0005515 protein binding | IPI PMID:18641128 Endothelial nitric oxide synthase regulates N-Ras activation... | MODIFY | Summary: IPI (study of N-Ras activation on the Golgi using the Raf-1 RBD as an active-Ras reporter) for RAF1 binding NRAS. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is NRAS. RAF1 is a direct RAS effector: its RAS-binding domain (RBD) and CRD bind GTP-loaded RAS family GTPases, recruiting RAF1 to the plasma membrane; this is the entry step of RAF activation. small GTPase binding is the informative term (same term as the BRAF review). Proposed replacements: small GTPase binding Supporting Evidence: PMID:18641128 as indicated by the redistribution of RBD-Raf-1 toward this organelle file:human/RAF1/RAF1-uniprot.txt P04049; P01111: NRAS; NbExp=15; IntAct=EBI-365996, EBI-721993; |
| GO:0005515 protein binding | IPI PMID:19049963 Regulation of RAF activity by 14-3-3 proteins: RAF kinases a... | MODIFY | Summary: IPI (SPR/MS study of RAF isoform association with 14-3-3 isoforms) for RAF1 binding YWHAZ. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is YWHAZ. RAF1 is a canonical phospho-dependent 14-3-3 client: a 14-3-3 dimer engaging pSer259 and pSer621 holds the autoinhibited monomer, and the pSer621 site also stabilises the active dimer. 14-3-3 protein binding captures this regulatory interaction (same term as the BRAF review). Proposed replacements: 14-3-3 protein binding Supporting Evidence: PMID:19049963 While B- and C-RAF exhibited binding to all seven 14-3-3 isoforms file:human/RAF1/RAF1-uniprot.txt P04049; P63104: YWHAZ; NbExp=32; IntAct=EBI-365996, EBI-347088; |
| GO:0005515 protein binding | IPI PMID:19063885 Regulation of growth and survival of activated T cells by ce... | MODIFY | Summary: IPI (study of cell-transducing Ras inhibitors in T cells; RAF1 is not mentioned in the cached abstract (the inhibitors are plausibly RBD-derived)) for RAF1 binding HRAS. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is HRAS. RAF1 is a direct RAS effector: its RAS-binding domain (RBD) and CRD bind GTP-loaded RAS family GTPases, recruiting RAF1 to the plasma membrane; this is the entry step of RAF activation. small GTPase binding is the informative term (same term as the BRAF review). The cached text of this reference does not describe the RAF1 interaction, so the IntAct/BioGRID curation (made from the full text or supplementary data) is deferred to; the partner-type mapping is supported by independent RAF1 evidence cited here. Proposed replacements: small GTPase binding Supporting Evidence: file:human/RAF1/RAF1-uniprot.txt Ras-GTP recruits RAF1 to the file:human/RAF1/RAF1-uniprot.txt P04049; P01112: HRAS; NbExp=30; IntAct=EBI-365996, EBI-350145; |
| GO:0005515 protein binding | IPI PMID:19164755 Identification of small-molecule inducers of pancreatic beta... | MODIFY | Summary: IPI (small-molecule screen for beta-cell expansion; neither RAF1 nor Kras is mentioned in the cached abstract) for RAF1 binding mouse Kras. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is mouse Kras. RAF1 is a direct RAS effector: its RAS-binding domain (RBD) and CRD bind GTP-loaded RAS family GTPases, recruiting RAF1 to the plasma membrane; this is the entry step of RAF activation. small GTPase binding is the informative term (same term as the BRAF review). The cached text of this reference does not describe the RAF1 interaction, so the IntAct/BioGRID curation (made from the full text or supplementary data) is deferred to; the partner-type mapping is supported by independent RAF1 evidence cited here. Proposed replacements: small GTPase binding Supporting Evidence: file:human/RAF1/RAF1-uniprot.txt Ras-GTP recruits RAF1 to the file:human/RAF1/RAF1-uniprot.txt P04049; P32883: Kras; Xeno; NbExp=2; IntAct=EBI-365996, EBI-644267; |
| GO:0005515 protein binding | IPI PMID:19197339 Regulation of human myoblast differentiation by PEBP4. | MODIFY | Summary: IPI (study showing PEBP4 scaffolds RAF1-MEK ternary complexes in myoblasts) for RAF1 binding AKT1. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is AKT1. The partner is a protein kinase that either regulates RAF1 by phosphorylation (PAK S338, AKT S259), is inhibited by RAF1 binding (MST2), or is an upstream receptor tyrosine kinase; protein kinase binding is the informative term. Proposed replacements: protein kinase binding Supporting Evidence: PMID:19197339 PEBP4 forms ternary complexes with RAF1 and MEK file:human/RAF1/RAF1-uniprot.txt P04049; P31749: AKT1; NbExp=3; IntAct=EBI-365996, EBI-296087; |
| GO:0005515 protein binding | IPI PMID:19197339 Regulation of human myoblast differentiation by PEBP4. | MODIFY | Summary: IPI (study showing PEBP4 scaffolds RAF1-MEK ternary complexes in myoblasts) for RAF1 binding MAP2K1/MEK1. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is MAP2K1/MEK1. MEK1/MEK2 are the physiological substrates of RAF1 and form RAF-MEK complexes; MAPKK binding is the informative term (same term as the BRAF review). Proposed replacements: mitogen-activated protein kinase kinase binding Supporting Evidence: PMID:19197339 PEBP4 forms ternary complexes with RAF1 and MEK file:human/RAF1/RAF1-uniprot.txt P04049; Q02750: MAP2K1; NbExp=39; IntAct=EBI-365996, EBI-492564; |
| GO:0005515 protein binding | IPI PMID:19197339 Regulation of human myoblast differentiation by PEBP4. | MODIFY | Summary: IPI (study showing PEBP4 scaffolds RAF1-MEK ternary complexes in myoblasts) for RAF1 binding PEBP4 (RAF1-MEK scaffold). Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is PEBP4 (RAF1-MEK scaffold). The partner is a MAPK-pathway scaffold that assembles RAF with RAS/MEK or phosphatase; scaffold protein binding is the informative term (same choice as the BRAF review for KSR/IQGAP1/RGS12). Proposed replacements: scaffold protein binding Supporting Evidence: PMID:19197339 PEBP4 forms ternary complexes with RAF1 and MEK file:human/RAF1/RAF1-uniprot.txt P04049; Q96S96: PEBP4; NbExp=4; IntAct=EBI-365996, EBI-8563667; |
| GO:0005515 protein binding | IPI PMID:19222999 Reassessment of the role of FKBP38 in the Rheb/mTORC1 pathwa... | MODIFY | Summary: IPI (Rheb/FKBP38 reassessment; RAF1 is not mentioned in the cached abstract (Raf-RBD binding of Ras is a standard control)) for RAF1 binding HRAS. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is HRAS. RAF1 is a direct RAS effector: its RAS-binding domain (RBD) and CRD bind GTP-loaded RAS family GTPases, recruiting RAF1 to the plasma membrane; this is the entry step of RAF activation. small GTPase binding is the informative term (same term as the BRAF review). The cached text of this reference does not describe the RAF1 interaction, so the IntAct/BioGRID curation (made from the full text or supplementary data) is deferred to; the partner-type mapping is supported by independent RAF1 evidence cited here. Proposed replacements: small GTPase binding Supporting Evidence: file:human/RAF1/RAF1-uniprot.txt Ras-GTP recruits RAF1 to the file:human/RAF1/RAF1-uniprot.txt P04049; P01112: HRAS; NbExp=30; IntAct=EBI-365996, EBI-350145; |
| GO:0005515 protein binding | IPI PMID:19595761 The C-terminus of Raf-1 acts as a 14-3-3-dependent activatio... | MODIFY | Summary: IPI (study of the C-terminal pS621 14-3-3 site as an activation switch of Raf-1) for RAF1 binding YWHAB. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is YWHAB. RAF1 is a canonical phospho-dependent 14-3-3 client: a 14-3-3 dimer engaging pSer259 and pSer621 holds the autoinhibited monomer, and the pSer621 site also stabilises the active dimer. 14-3-3 protein binding captures this regulatory interaction (same term as the BRAF review). Proposed replacements: 14-3-3 protein binding Supporting Evidence: PMID:19595761 Mutations that prevent the binding of 14-3-3 proteins to S621 render Raf-1 inactive file:human/RAF1/RAF1-uniprot.txt P04049; P31946: YWHAB; NbExp=39; IntAct=EBI-365996, EBI-359815; |
| GO:0005515 protein binding | IPI PMID:19696784 Nucleocytoplasmic transport of Alp7/TACC organizes spatiotem... | MODIFY | Summary: IPI (fission yeast Alp7/TACC nucleocytoplasmic transport paper; neither RAF1 nor HRAS is mentioned in the cached abstract, so the curated RAF1-HRAS interaction cannot be located in this reference) for RAF1 binding HRAS. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is HRAS. RAF1 is a direct RAS effector: its RAS-binding domain (RBD) and CRD bind GTP-loaded RAS family GTPases, recruiting RAF1 to the plasma membrane; this is the entry step of RAF activation. small GTPase binding is the informative term (same term as the BRAF review). The cached text of this reference does not describe the RAF1 interaction, so the IntAct/BioGRID curation (made from the full text or supplementary data) is deferred to; the partner-type mapping is supported by independent RAF1 evidence cited here. Proposed replacements: small GTPase binding Supporting Evidence: file:human/RAF1/RAF1-uniprot.txt Ras-GTP recruits RAF1 to the file:human/RAF1/RAF1-uniprot.txt P04049; P01112: HRAS; NbExp=30; IntAct=EBI-365996, EBI-350145; |
| GO:0005515 protein binding | IPI PMID:20052757 Molecular and clinical analysis of RAF1 in Noonan syndrome a... | MODIFY | Summary: IPI (study of RAF1 Noonan syndrome mutations and Ser259 dephosphorylation) for RAF1 binding YWHAZ. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is YWHAZ. RAF1 is a canonical phospho-dependent 14-3-3 client: a 14-3-3 dimer engaging pSer259 and pSer621 holds the autoinhibited monomer, and the pSer621 site also stabilises the active dimer. 14-3-3 protein binding captures this regulatory interaction (same term as the BRAF review). Proposed replacements: 14-3-3 protein binding Supporting Evidence: PMID:20052757 dephosphorylation of serine 259 as the essential mechanism for mutant activation file:human/RAF1/RAF1-uniprot.txt P04049; P63104: YWHAZ; NbExp=32; IntAct=EBI-365996, EBI-347088; |
| GO:0005515 protein binding | IPI PMID:20080631 Ras membrane orientation and nanodomain localization generat... | MODIFY | Summary: IPI (study of Ras G-domain orientation recognised by the C-Raf RBD) for RAF1 binding NRAS. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is NRAS. RAF1 is a direct RAS effector: its RAS-binding domain (RBD) and CRD bind GTP-loaded RAS family GTPases, recruiting RAF1 to the plasma membrane; this is the entry step of RAF activation. small GTPase binding is the informative term (same term as the BRAF review). Proposed replacements: small GTPase binding Supporting Evidence: PMID:20080631 is recognized by the Ras binding domain of C-Raf file:human/RAF1/RAF1-uniprot.txt P04049; P01111: NRAS; NbExp=15; IntAct=EBI-365996, EBI-721993; |
| GO:0005515 protein binding | IPI PMID:20080631 Ras membrane orientation and nanodomain localization generat... | MODIFY | Summary: IPI (study of Ras G-domain orientation recognised by the C-Raf RBD) for RAF1 binding HRAS. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is HRAS. RAF1 is a direct RAS effector: its RAS-binding domain (RBD) and CRD bind GTP-loaded RAS family GTPases, recruiting RAF1 to the plasma membrane; this is the entry step of RAF activation. small GTPase binding is the informative term (same term as the BRAF review). Proposed replacements: small GTPase binding Supporting Evidence: PMID:20080631 is recognized by the Ras binding domain of C-Raf file:human/RAF1/RAF1-uniprot.txt P04049; P01112: HRAS; NbExp=30; IntAct=EBI-365996, EBI-350145; |
| GO:0005515 protein binding | IPI PMID:20080631 Ras membrane orientation and nanodomain localization generat... | MODIFY | Summary: IPI (study of Ras G-domain orientation recognised by the C-Raf RBD) for RAF1 binding KRAS isoform 2B (KRAS4B). Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is KRAS isoform 2B (KRAS4B). RAF1 is a direct RAS effector: its RAS-binding domain (RBD) and CRD bind GTP-loaded RAS family GTPases, recruiting RAF1 to the plasma membrane; this is the entry step of RAF activation. small GTPase binding is the informative term (same term as the BRAF review). Proposed replacements: small GTPase binding Supporting Evidence: PMID:20080631 is recognized by the Ras binding domain of C-Raf file:human/RAF1/RAF1-uniprot.txt P04049; P01116-2: KRAS; NbExp=6; IntAct=EBI-365996, EBI-367427; |
| GO:0005515 protein binding | IPI PMID:20130576 RAF inhibitors prime wild-type RAF to activate the MAPK path... | MODIFY | Summary: IPI (study showing RAF inhibitors prime wild-type RAF dimers to activate MAPK signalling) for RAF1 binding BRAF. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is BRAF. RAF1 forms side-to-side kinase-domain heterodimers with BRAF, the most active RAF species and the basis of paradoxical activation by RAF inhibitors; protein heterodimerization activity is the informative term (same term as the BRAF review). The cached text of this reference does not describe the RAF1 interaction, so the IntAct/BioGRID curation (made from the full text or supplementary data) is deferred to; the partner-type mapping is supported by independent RAF1 evidence cited here. Proposed replacements: protein heterodimerization activity Supporting Evidence: file:human/RAF1/RAF1-uniprot.txt Heterodimerizes with BRAF and this file:human/RAF1/RAF1-uniprot.txt P04049; P15056: BRAF; NbExp=73; IntAct=EBI-365996, EBI-365980; |
| GO:0005515 protein binding | IPI PMID:20133694 Allosteric gating of Son of sevenless activity by the histon... | MODIFY | Summary: IPI (study of SOS histone-domain autoinhibition; RAF1 is not mentioned in the cached abstract (RBD pull-down is the standard Ras-GTP assay)) for RAF1 binding HRAS. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is HRAS. RAF1 is a direct RAS effector: its RAS-binding domain (RBD) and CRD bind GTP-loaded RAS family GTPases, recruiting RAF1 to the plasma membrane; this is the entry step of RAF activation. small GTPase binding is the informative term (same term as the BRAF review). The cached text of this reference does not describe the RAF1 interaction, so the IntAct/BioGRID curation (made from the full text or supplementary data) is deferred to; the partner-type mapping is supported by independent RAF1 evidence cited here. Proposed replacements: small GTPase binding Supporting Evidence: file:human/RAF1/RAF1-uniprot.txt Ras-GTP recruits RAF1 to the file:human/RAF1/RAF1-uniprot.txt P04049; P01112: HRAS; NbExp=30; IntAct=EBI-365996, EBI-350145; |
| GO:0005515 protein binding | IPI PMID:20141835 Kinase-dead BRAF and oncogenic RAS cooperate to drive tumor ... | MODIFY | Summary: IPI (study showing kinase-dead BRAF and oncogenic RAS signal through CRAF) for RAF1 binding BRAF. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is BRAF. RAF1 forms side-to-side kinase-domain heterodimers with BRAF, the most active RAF species and the basis of paradoxical activation by RAF inhibitors; protein heterodimerization activity is the informative term (same term as the BRAF review). Proposed replacements: protein heterodimerization activity Supporting Evidence: PMID:20141835 Kinase-dead BRAF and oncogenic RAS cooperate to drive tumor progression through CRAF file:human/RAF1/RAF1-uniprot.txt P04049; P15056: BRAF; NbExp=73; IntAct=EBI-365996, EBI-365980; |
| GO:0005515 protein binding | IPI PMID:20178605 Genetic and functional characterization of putative Ras/Raf ... | MODIFY | Summary: IPI (study of putative Ras/Raf interaction inhibitors (MCP compounds)) for RAF1 binding HRAS. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is HRAS. RAF1 is a direct RAS effector: its RAS-binding domain (RBD) and CRD bind GTP-loaded RAS family GTPases, recruiting RAF1 to the plasma membrane; this is the entry step of RAF activation. small GTPase binding is the informative term (same term as the BRAF review). Proposed replacements: small GTPase binding Supporting Evidence: PMID:20178605 determine whether MCP treatment results in impaired interaction between Ras and its effector Raf file:human/RAF1/RAF1-uniprot.txt P04049; P01112: HRAS; NbExp=30; IntAct=EBI-365996, EBI-350145; |
| GO:0005515 protein binding | IPI PMID:20179103 Active Mek2 as a regulatory scaffold that promotes Pin1 bind... | REMOVE | Summary: IPI (study of active Mek2 bridging Pin1 and BPGAP1; RAF1 is not mentioned in the cached abstract) for RAF1 binding PIN1. Reason: GO:0005515 protein binding is uninformative. PIN1 isomerises ERK-phosphorylated RAF1 (UniProt), but the cited paper(s) concern PIN1 with MEK1/MEK2; there is no informative RAF1-side MF for being an isomerase substrate. Removal does not mean the reported interaction is false; it means no informative RAF1 molecular-function term can be justified from it. Supporting Evidence: file:human/RAF1/RAF1-uniprot.txt P04049; Q13526: PIN1; NbExp=2; IntAct=EBI-365996, EBI-714158; |
| GO:0005515 protein binding | IPI PMID:20179161 The prolyl isomerase Pin1 enhances HER-2 expression and cell... | REMOVE | Summary: IPI (study of Pin1 interaction with MEK1 inducing HER-2; RAF1 is not mentioned in the cached abstract) for RAF1 binding PIN1. Reason: GO:0005515 protein binding is uninformative. PIN1 isomerises ERK-phosphorylated RAF1 (UniProt), but the cited paper(s) concern PIN1 with MEK1/MEK2; there is no informative RAF1-side MF for being an isomerase substrate. Removal does not mean the reported interaction is false; it means no informative RAF1 molecular-function term can be justified from it. Supporting Evidence: file:human/RAF1/RAF1-uniprot.txt P04049; Q13526: PIN1; NbExp=2; IntAct=EBI-365996, EBI-714158; |
| GO:0005515 protein binding | IPI PMID:20679480 Impaired binding of 14-3-3 to C-RAF in Noonan syndrome sugge... | MODIFY | Summary: IPI (crystal structure/biophysics of 14-3-3 bound to C-RAF pS259 and Noonan mutants) for RAF1 binding YWHAZ. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is YWHAZ. RAF1 is a canonical phospho-dependent 14-3-3 client: a 14-3-3 dimer engaging pSer259 and pSer621 holds the autoinhibited monomer, and the pSer621 site also stabilises the active dimer. 14-3-3 protein binding captures this regulatory interaction (same term as the BRAF review). Proposed replacements: 14-3-3 protein binding Supporting Evidence: PMID:20679480 We show that these mutations impair binding of 14-3-3 proteins to C-RAF file:human/RAF1/RAF1-uniprot.txt P04049; P63104: YWHAZ; NbExp=32; IntAct=EBI-365996, EBI-347088; |
| GO:0005515 protein binding | IPI PMID:20802526 K-Ras4B phosphorylation at Ser181 is inhibited by calmodulin... | MODIFY | Summary: IPI (study of K-Ras4B Ser181 phosphorylation; RAF1 is not mentioned in the cached abstract (RBD pull-down is the standard activity assay)) for RAF1 binding KRAS isoform 2B (KRAS4B). Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is KRAS isoform 2B (KRAS4B). RAF1 is a direct RAS effector: its RAS-binding domain (RBD) and CRD bind GTP-loaded RAS family GTPases, recruiting RAF1 to the plasma membrane; this is the entry step of RAF activation. small GTPase binding is the informative term (same term as the BRAF review). The cached text of this reference does not describe the RAF1 interaction, so the IntAct/BioGRID curation (made from the full text or supplementary data) is deferred to; the partner-type mapping is supported by independent RAF1 evidence cited here. Proposed replacements: small GTPase binding Supporting Evidence: file:human/RAF1/RAF1-uniprot.txt Ras-GTP recruits RAF1 to the file:human/RAF1/RAF1-uniprot.txt P04049; P01116-2: KRAS; NbExp=6; IntAct=EBI-365996, EBI-367427; |
| GO:0005515 protein binding | IPI PMID:21139044 Rb-Raf-1 interaction disruptor RRD-251 induces apoptosis in ... | REMOVE | Summary: IPI (study of the Rb-Raf-1 interaction disruptor RRD-251) for RAF1 binding RB1. Reason: GO:0005515 protein binding is uninformative. RAF1 binds and phosphorylates RB early in G1 (a proposed non-MEK substrate); RB1 as a substrate is better captured by kinase activity, not a binding MF. Removal does not mean the reported interaction is false; it means no informative RAF1 molecular-function term can be justified from it. Supporting Evidence: PMID:21139044 the signaling kinase Raf-1 can physically bind and phosphorylate Rb file:human/RAF1/RAF1-uniprot.txt P04049; P06400: RB1; NbExp=3; IntAct=EBI-365996, EBI-491274; |
| GO:0005515 protein binding | IPI PMID:21457714 The membrane localization of Ras2p and the association betwe... | MODIFY | Summary: IPI (yeast Ras2p localization study; RAF1 is not mentioned in the cached abstract (Raf-RBD pull-down of Ras2-GTP is plausible)) for RAF1 binding S. cerevisiae RAS2. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is S. cerevisiae RAS2. RAF1 is a direct RAS effector: its RAS-binding domain (RBD) and CRD bind GTP-loaded RAS family GTPases, recruiting RAF1 to the plasma membrane; this is the entry step of RAF activation. small GTPase binding is the informative term (same term as the BRAF review). The cached text of this reference does not describe the RAF1 interaction, so the IntAct/BioGRID curation (made from the full text or supplementary data) is deferred to; the partner-type mapping is supported by independent RAF1 evidence cited here. Proposed replacements: small GTPase binding Supporting Evidence: file:human/RAF1/RAF1-uniprot.txt Ras-GTP recruits RAF1 to the file:human/RAF1/RAF1-uniprot.txt P04049; P01120: RAS2; Xeno; NbExp=2; IntAct=EBI-365996, EBI-14838; |
| GO:0005515 protein binding | IPI PMID:21478863 ERK and PDE4 cooperate to induce RAF isoform switching in me... | MODIFY | Summary: IPI (study of ERK/PDE4-driven RAF isoform switching in NRAS-mutant melanoma) for RAF1 binding NRAS. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is NRAS. RAF1 is a direct RAS effector: its RAS-binding domain (RBD) and CRD bind GTP-loaded RAS family GTPases, recruiting RAF1 to the plasma membrane; this is the entry step of RAF activation. small GTPase binding is the informative term (same term as the BRAF review). Proposed replacements: small GTPase binding Supporting Evidence: PMID:21478863 melanomas harboring Ras mutations use CRAF to activate the MAPK pathway file:human/RAF1/RAF1-uniprot.txt P04049; P01111: NRAS; NbExp=15; IntAct=EBI-365996, EBI-721993; |
| GO:0005515 protein binding | IPI PMID:21536655 The Ras signaling inhibitor LOX-PP interacts with Hsp70 and ... | REMOVE | Summary: IPI (study showing LOX-PP interacts with Hsp70 and c-Raf) for RAF1 binding mouse Lox (LOX propeptide). Reason: GO:0005515 protein binding is uninformative. LOX-PP (lysyl oxidase propeptide) binds c-Raf and reduces ERK activation; the partner is a propeptide fragment of an enzyme, and no informative MF describes the RAF1 side. Removal does not mean the reported interaction is false; it means no informative RAF1 molecular-function term can be justified from it. Supporting Evidence: PMID:21536655 LOX-PP interacted with the Hsp70 chaperoned protein c-Raf. file:human/RAF1/RAF1-uniprot.txt P04049; P28301: Lox; Xeno; NbExp=2; IntAct=EBI-365996, EBI-642911; |
| GO:0005515 protein binding | IPI PMID:21831839 15-Lipoxygenase 1 interacts with phosphatidylethanolamine-bi... | REMOVE | Summary: IPI (study of 15-lipoxygenase-1 displacing PEBP1 from Raf-1) for RAF1 binding PEBP1/RKIP. Reason: GO:0005515 protein binding is uninformative. RKIP is a genuine negative regulator that binds the RAF1 N-region and displaces MEK, but no GO MF term describes being bound by a kinase inhibitor protein; the regulatory relationship belongs on PEBP1 (protein kinase inhibitor activity). Removal does not mean the reported interaction is false; it means no informative RAF1 molecular-function term can be justified from it. Supporting Evidence: PMID:21831839 causing PEBP1 to dissociate from Raf-1 and activate ERK file:human/RAF1/RAF1-uniprot.txt P04049; P30086: PEBP1; NbExp=10; IntAct=EBI-365996, EBI-716384; |
| GO:0005515 protein binding | IPI PMID:21988832 Toward an understanding of the protein interaction network o... | MODIFY | Summary: IPI (large-scale human liver protein interaction network (yeast two-hybrid)) for RAF1 binding MAP2K2/MEK2. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is MAP2K2/MEK2. MEK1/MEK2 are the physiological substrates of RAF1 and form RAF-MEK complexes; MAPKK binding is the informative term (same term as the BRAF review). The cached text of this reference does not describe the RAF1 interaction, so the IntAct/BioGRID curation (made from the full text or supplementary data) is deferred to; the partner-type mapping is supported by independent RAF1 evidence cited here. Proposed replacements: mitogen-activated protein kinase kinase binding Supporting Evidence: file:human/RAF1/RAF1-uniprot.txt Interacts with MAP2K1/MEK1 and file:human/RAF1/RAF1-uniprot.txt P04049; P36507: MAP2K2; NbExp=7; IntAct=EBI-365996, EBI-1056930; |
| GO:0005515 protein binding | IPI PMID:22169110 Nilotinib and MEK inhibitors induce synthetic lethality thro... | MODIFY | Summary: IPI (study of nilotinib/MEK inhibitor synthetic lethality via paradoxical BRAF-CRAF activation) for RAF1 binding HRAS. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is HRAS. RAF1 is a direct RAS effector: its RAS-binding domain (RBD) and CRD bind GTP-loaded RAS family GTPases, recruiting RAF1 to the plasma membrane; this is the entry step of RAF activation. small GTPase binding is the informative term (same term as the BRAF review). Proposed replacements: small GTPase binding Supporting Evidence: PMID:22169110 hyper-activated BRAF, CRAF, MEK and ERK in cells expressing oncogenic RAS file:human/RAF1/RAF1-uniprot.txt P04049; P01112: HRAS; NbExp=30; IntAct=EBI-365996, EBI-350145; |
| GO:0005515 protein binding | IPI PMID:22169110 Nilotinib and MEK inhibitors induce synthetic lethality thro... | MODIFY | Summary: IPI (study of nilotinib/MEK inhibitor synthetic lethality via paradoxical BRAF-CRAF activation) for RAF1 binding BRAF. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is BRAF. RAF1 forms side-to-side kinase-domain heterodimers with BRAF, the most active RAF species and the basis of paradoxical activation by RAF inhibitors; protein heterodimerization activity is the informative term (same term as the BRAF review). Proposed replacements: protein heterodimerization activity Supporting Evidence: PMID:22169110 BRAF inhibition drives BRAF binding to CRAF file:human/RAF1/RAF1-uniprot.txt P04049; P15056: BRAF; NbExp=73; IntAct=EBI-365996, EBI-365980; |
| GO:0005515 protein binding | IPI PMID:22510884 Distinct requirement for an intact dimer interface in wild-t... | MODIFY | Summary: IPI (study of the RAF dimer interface requirements) for RAF1 binding BRAF. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is BRAF. RAF1 forms side-to-side kinase-domain heterodimers with BRAF, the most active RAF species and the basis of paradoxical activation by RAF inhibitors; protein heterodimerization activity is the informative term (same term as the BRAF review). Proposed replacements: protein heterodimerization activity Supporting Evidence: PMID:22510884 the B-Raf DIF is not required for dimerisation between Raf-1 and B-Raf file:human/RAF1/RAF1-uniprot.txt P04049; P15056: BRAF; NbExp=73; IntAct=EBI-365996, EBI-365980; |
| GO:0005515 protein binding | IPI PMID:22886302 FAM83B mediates EGFR- and RAS-driven oncogenic transformatio... | REMOVE | Summary: IPI (study of FAM83B in EGFR/RAS-driven transformation) for RAF1 binding FAM83B. Reason: GO:0005515 protein binding is uninformative. FAM83B binds CRAF, displaces 14-3-3 and increases CRAF membrane localisation, but its defined molecular role is as a CK1-anchoring scaffold; no RAF1-side MF term can be assigned without over-interpreting the interaction. Removal does not mean the reported interaction is false; it means no informative RAF1 molecular-function term can be justified from it. Supporting Evidence: PMID:22886302 We found that FAM83B coprecipitated with a downstream effector of RAS, CRAF. |
| GO:0005515 protein binding | IPI PMID:22886303 FAM83A confers EGFR-TKI resistance in breast cancer cells an... | REMOVE | Summary: IPI (study of FAM83A in EGFR-TKI resistance) for RAF1 binding FAM83A. Reason: GO:0005515 protein binding is uninformative. FAM83 proteins (SACK1 family) bind CRAF and promote MAPK activation, but their defined molecular role is as CK1-anchoring scaffolds; no RAF1-side MF term can be assigned without over-interpreting the interaction. Removal does not mean the reported interaction is false; it means no informative RAF1 molecular-function term can be justified from it. Supporting Evidence: PMID:22886303 FAM83A interacts with c-RAF and PI3K upstream of MEK1/2 activation. |
| GO:0005515 protein binding | IPI PMID:22939624 Quantitative analysis of HSP90-client interactions reveals p... | MODIFY | Summary: IPI (quantitative LUMIER analysis of HSP90-client interactions across the kinome) for RAF1 binding HSP90AB1. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is HSP90AB1. RAF1 is a strongly HSP90-dependent client kinase whose folding and stability require HSP90-CDC37; Hsp90 protein binding is the informative term (same term as the BRAF review). The cached text of this reference does not describe the RAF1 interaction, so the IntAct/BioGRID curation (made from the full text or supplementary data) is deferred to; the partner-type mapping is supported by independent RAF1 evidence cited here. Proposed replacements: Hsp90 protein binding Supporting Evidence: file:human/RAF1/RAF1-uniprot.txt complex composed of chaperones HSP90 and HSP70, co-chaperones CDC37, file:human/RAF1/RAF1-uniprot.txt P04049; P08238: HSP90AB1; NbExp=17; IntAct=EBI-365996, EBI-352572; |
| GO:0005515 protein binding | IPI PMID:23327923 MASL1 induces erythroid differentiation in human erythropoie... | REMOVE | Summary: IPI (study of MASL1 (MFHAS1) in erythroid differentiation) for RAF1 binding MFHAS1/MASL1. Reason: GO:0005515 protein binding is uninformative. MASL1 binding to RAF1 is reported in erythroid differentiation; no informative MF term for the RAF1 side. Removal does not mean the reported interaction is false; it means no informative RAF1 molecular-function term can be justified from it. Supporting Evidence: PMID:23327923 MASL1 interacts physically with Raf1 |
| GO:0005515 protein binding | IPI PMID:23680146 RAF inhibitors activate the MAPK pathway by relieving inhibi... | MODIFY | Summary: IPI (study of RAF inhibitors relieving inhibitory autophosphorylation of wild-type RAF) for RAF1 binding BRAF. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is BRAF. RAF1 forms side-to-side kinase-domain heterodimers with BRAF, the most active RAF species and the basis of paradoxical activation by RAF inhibitors; protein heterodimerization activity is the informative term (same term as the BRAF review). The cached text of this reference does not describe the RAF1 interaction, so the IntAct/BioGRID curation (made from the full text or supplementary data) is deferred to; the partner-type mapping is supported by independent RAF1 evidence cited here. Proposed replacements: protein heterodimerization activity Supporting Evidence: file:human/RAF1/RAF1-uniprot.txt Heterodimerizes with BRAF and this file:human/RAF1/RAF1-uniprot.txt P04049; P15056: BRAF; NbExp=73; IntAct=EBI-365996, EBI-365980; |
| GO:0005515 protein binding | IPI PMID:23934108 Mechanism of MEK inhibition determines efficacy in mutant KR... | MODIFY | Summary: IPI (structural/functional study of MEK inhibitors in KRAS- vs BRAF-driven cancers) for RAF1 binding BRAF. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is BRAF. RAF1 forms side-to-side kinase-domain heterodimers with BRAF, the most active RAF species and the basis of paradoxical activation by RAF inhibitors; protein heterodimerization activity is the informative term (same term as the BRAF review). The cached text of this reference does not describe the RAF1 interaction, so the IntAct/BioGRID curation (made from the full text or supplementary data) is deferred to; the partner-type mapping is supported by independent RAF1 evidence cited here. Proposed replacements: protein heterodimerization activity Supporting Evidence: file:human/RAF1/RAF1-uniprot.txt Heterodimerizes with BRAF and this file:human/RAF1/RAF1-uniprot.txt P04049; P15056: BRAF; NbExp=73; IntAct=EBI-365996, EBI-365980; |
| GO:0005515 protein binding | IPI PMID:23934108 Mechanism of MEK inhibition determines efficacy in mutant KR... | MODIFY | Summary: IPI (structural/functional study of MEK inhibitors in KRAS- vs BRAF-driven cancers) for RAF1 binding MAP2K1/MEK1. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is MAP2K1/MEK1. MEK1/MEK2 are the physiological substrates of RAF1 and form RAF-MEK complexes; MAPKK binding is the informative term (same term as the BRAF review). The cached text of this reference does not describe the RAF1 interaction, so the IntAct/BioGRID curation (made from the full text or supplementary data) is deferred to; the partner-type mapping is supported by independent RAF1 evidence cited here. Proposed replacements: mitogen-activated protein kinase kinase binding Supporting Evidence: file:human/RAF1/RAF1-uniprot.txt Interacts with MAP2K1/MEK1 and file:human/RAF1/RAF1-uniprot.txt P04049; Q02750: MAP2K1; NbExp=39; IntAct=EBI-365996, EBI-492564; |
| GO:0005515 protein binding | IPI PMID:24008843 Structure homology and interaction redundancy for discoverin... | REMOVE | Summary: IPI (structure-homology virus-host interaction prediction and validation) for RAF1 binding influenza A virus NS1. Reason: GO:0005515 protein binding is uninformative. Host-virus interaction predicted/validated in a structure-homology virus-host screen; not a normal molecular function of RAF1. Removal does not mean the reported interaction is false; it means no informative RAF1 molecular-function term can be justified from it. Supporting Evidence: file:human/RAF1/RAF1-uniprot.txt P04049; P03495: NS; Xeno; NbExp=2; IntAct=EBI-365996, EBI-2548993; |
| GO:0005515 protein binding | IPI PMID:24189400 Perturbation of the mutated EGFR interactome identifies vuln... | MODIFY | Summary: IPI (interactome of mutant EGFR in lung cancer cells) for RAF1 binding CDC37 (HSP90 kinase co-chaperone). Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is CDC37 (HSP90 kinase co-chaperone). The partner is a protein-folding chaperone or co-chaperone, and RAF1 is a chaperone client (HSP90-CDC37 dependence is well established); protein-folding chaperone binding describes the interaction from the RAF1 side. The cached text of this reference does not describe the RAF1 interaction, so the IntAct/BioGRID curation (made from the full text or supplementary data) is deferred to; the partner-type mapping is supported by independent RAF1 evidence cited here. Proposed replacements: protein-folding chaperone binding Supporting Evidence: file:human/RAF1/RAF1-uniprot.txt complex composed of chaperones HSP90 and HSP70, co-chaperones CDC37, file:human/RAF1/RAF1-uniprot.txt P04049; Q16543: CDC37; NbExp=20; IntAct=EBI-365996, EBI-295634; |
| GO:0005515 protein binding | IPI PMID:24255178 Protein interaction network of the mammalian Hippo pathway r... | MODIFY | Summary: IPI (AP-MS interaction network of the mammalian Hippo pathway) for RAF1 binding YWHAB. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is YWHAB. RAF1 is a canonical phospho-dependent 14-3-3 client: a 14-3-3 dimer engaging pSer259 and pSer621 holds the autoinhibited monomer, and the pSer621 site also stabilises the active dimer. 14-3-3 protein binding captures this regulatory interaction (same term as the BRAF review). The cached text of this reference does not describe the RAF1 interaction, so the IntAct/BioGRID curation (made from the full text or supplementary data) is deferred to; the partner-type mapping is supported by independent RAF1 evidence cited here. Proposed replacements: 14-3-3 protein binding Supporting Evidence: file:human/RAF1/RAF1-uniprot.txt the binding of a 14-3-3 protein that contacts two phosphorylation file:human/RAF1/RAF1-uniprot.txt P04049; P31946: YWHAB; NbExp=39; IntAct=EBI-365996, EBI-359815; |
| GO:0005515 protein binding | IPI PMID:24330068 Nuclear Raf-1 kinase regulates the CXCR5 promoter by associa... | MODIFY | Summary: IPI (study of nuclear Raf-1 associating with NFATc3 at the CXCR5 promoter) for RAF1 binding NFATC3. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is NFATC3. The partner is a DNA-binding transcription factor bound by a nuclear RAF1 pool; DNA-binding transcription factor binding is the informative term. Proposed replacements: DNA-binding transcription factor binding Supporting Evidence: PMID:24330068 Nuclear Raf-1 kinase regulates the CXCR5 promoter by associating with NFATc3 file:human/RAF1/RAF1-uniprot.txt P04049; Q12968: NFATC3; NbExp=2; IntAct=EBI-365996, EBI-5278441; |
| GO:0005515 protein binding | IPI PMID:24658140 The mammalian-membrane two-hybrid assay (MaMTH) for probing ... | MODIFY | Summary: IPI (mammalian-membrane two-hybrid (MaMTH) assay of membrane-protein interactions) for RAF1 binding EGFR. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is EGFR. The partner is a protein kinase that either regulates RAF1 by phosphorylation (PAK S338, AKT S259), is inhibited by RAF1 binding (MST2), or is an upstream receptor tyrosine kinase; protein kinase binding is the informative term. The cached text of this reference does not describe the RAF1 interaction, so the IntAct/BioGRID curation (made from the full text or supplementary data) is deferred to; the partner-type mapping is supported by independent RAF1 evidence cited here. Proposed replacements: protein kinase binding Supporting Evidence: file:human/RAF1/RAF1-uniprot.txt P04049; P00533: EGFR; NbExp=3; IntAct=EBI-365996, EBI-297353; |
| GO:0005515 protein binding | IPI PMID:24736947 Conserved oncogenic behavior of the FAM83 family regulates M... | REMOVE | Summary: IPI (study of FAM83 family members regulating MAPK signalling via CRAF) for RAF1 binding FAM83E. Reason: GO:0005515 protein binding is uninformative. FAM83E was tested alongside other FAM83 members for CRAF binding; no RAF1-side MF term can be assigned without over-interpreting the interaction. Removal does not mean the reported interaction is false; it means no informative RAF1 molecular-function term can be justified from it. Supporting Evidence: PMID:24736947 Importantly, FAM83A also interacts with CRAF to promote MAPK activation. |
| GO:0005515 protein binding | IPI PMID:24736947 Conserved oncogenic behavior of the FAM83 family regulates M... | REMOVE | Summary: IPI (study of FAM83 family members regulating MAPK signalling via CRAF) for RAF1 binding FAM83A. Reason: GO:0005515 protein binding is uninformative. FAM83 proteins (SACK1 family) bind CRAF and promote MAPK activation, but their defined molecular role is as CK1-anchoring scaffolds; no RAF1-side MF term can be assigned without over-interpreting the interaction. Removal does not mean the reported interaction is false; it means no informative RAF1 molecular-function term can be justified from it. Supporting Evidence: PMID:24736947 Importantly, FAM83A also interacts with CRAF to promote MAPK activation. |
| GO:0005515 protein binding | IPI PMID:24736947 Conserved oncogenic behavior of the FAM83 family regulates M... | REMOVE | Summary: IPI (study of FAM83 family members regulating MAPK signalling via CRAF) for RAF1 binding FAM83C. Reason: GO:0005515 protein binding is uninformative. FAM83C was tested alongside other FAM83 members for CRAF binding; no RAF1-side MF term can be assigned without over-interpreting the interaction. Removal does not mean the reported interaction is false; it means no informative RAF1 molecular-function term can be justified from it. Supporting Evidence: PMID:24736947 Importantly, FAM83A also interacts with CRAF to promote MAPK activation. |
| GO:0005515 protein binding | IPI PMID:24736947 Conserved oncogenic behavior of the FAM83 family regulates M... | REMOVE | Summary: IPI (study of FAM83 family members regulating MAPK signalling via CRAF) for RAF1 binding FAM83D. Reason: GO:0005515 protein binding is uninformative. FAM83D was tested alongside other FAM83 members for CRAF binding; no RAF1-side MF term can be assigned without over-interpreting the interaction. Removal does not mean the reported interaction is false; it means no informative RAF1 molecular-function term can be justified from it. Supporting Evidence: PMID:24736947 Importantly, FAM83A also interacts with CRAF to promote MAPK activation. |
| GO:0005515 protein binding | IPI PMID:24746704 Disruption of CRAF-mediated MEK activation is required for e... | MODIFY | Summary: IPI (study of CRAF-mediated MEK activation in KRAS-mutant tumours) for RAF1 binding MAP2K2/MEK2. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is MAP2K2/MEK2. MEK1/MEK2 are the physiological substrates of RAF1 and form RAF-MEK complexes; MAPKK binding is the informative term (same term as the BRAF review). Proposed replacements: mitogen-activated protein kinase kinase binding Supporting Evidence: PMID:24746704 Disruption of CRAF-mediated MEK activation is required for effective MEK inhibition in KRAS mutant tumors. file:human/RAF1/RAF1-uniprot.txt P04049; P36507: MAP2K2; NbExp=7; IntAct=EBI-365996, EBI-1056930; |
| GO:0005515 protein binding | IPI PMID:24746704 Disruption of CRAF-mediated MEK activation is required for e... | MODIFY | Summary: IPI (study of CRAF-mediated MEK activation in KRAS-mutant tumours) for RAF1 binding MAP2K1/MEK1. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is MAP2K1/MEK1. MEK1/MEK2 are the physiological substrates of RAF1 and form RAF-MEK complexes; MAPKK binding is the informative term (same term as the BRAF review). Proposed replacements: mitogen-activated protein kinase kinase binding Supporting Evidence: PMID:24746704 Disruption of CRAF-mediated MEK activation is required for effective MEK inhibition in KRAS mutant tumors. file:human/RAF1/RAF1-uniprot.txt P04049; Q02750: MAP2K1; NbExp=39; IntAct=EBI-365996, EBI-492564; |
| GO:0005515 protein binding | IPI PMID:24929361 Protein interaction switches coordinate Raf-1 and MST2/Hippo... | MODIFY | Summary: IPI (study of protein-interaction switches coordinating Raf-1 and MST2/Hippo signalling) for RAF1 binding HRAS. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is HRAS. RAF1 is a direct RAS effector: its RAS-binding domain (RBD) and CRD bind GTP-loaded RAS family GTPases, recruiting RAF1 to the plasma membrane; this is the entry step of RAF activation. small GTPase binding is the informative term (same term as the BRAF review). Proposed replacements: small GTPase binding Supporting Evidence: PMID:24929361 Raf-1 regulates the MST-LATS and MEK-ERK pathways file:human/RAF1/RAF1-uniprot.txt P04049; P01112: HRAS; NbExp=30; IntAct=EBI-365996, EBI-350145; |
| GO:0005515 protein binding | IPI PMID:24929361 Protein interaction switches coordinate Raf-1 and MST2/Hippo... | MODIFY | Summary: IPI (study of protein-interaction switches coordinating Raf-1 and MST2/Hippo signalling) for RAF1 binding STK3/MST2. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is STK3/MST2. The partner is a protein kinase that either regulates RAF1 by phosphorylation (PAK S338, AKT S259), is inhibited by RAF1 binding (MST2), or is an upstream receptor tyrosine kinase; protein kinase binding is the informative term. Proposed replacements: protein kinase binding Supporting Evidence: PMID:24929361 Raf-1 regulates the MST-LATS and MEK-ERK pathways file:human/RAF1/RAF1-uniprot.txt P04049; Q13188: STK3; NbExp=6; IntAct=EBI-365996, EBI-992580; |
| GO:0005515 protein binding | IPI PMID:24929361 Protein interaction switches coordinate Raf-1 and MST2/Hippo... | MODIFY | Summary: IPI (study of protein-interaction switches coordinating Raf-1 and MST2/Hippo signalling) for RAF1 binding KSR1 (RAF-MEK scaffold). Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is KSR1 (RAF-MEK scaffold). The partner is a MAPK-pathway scaffold that assembles RAF with RAS/MEK or phosphatase; scaffold protein binding is the informative term (same choice as the BRAF review for KSR/IQGAP1/RGS12). Proposed replacements: scaffold protein binding Supporting Evidence: PMID:24929361 Raf-1 regulates the MST-LATS and MEK-ERK pathways file:human/RAF1/RAF1-uniprot.txt P04049; Q8IVT5: KSR1; NbExp=5; IntAct=EBI-365996, EBI-486984; |
| GO:0005515 protein binding | IPI PMID:25036637 A quantitative chaperone interaction network reveals the arc... | MODIFY | Summary: IPI (quantitative chaperone/co-chaperone interaction network (LUMIER)) for RAF1 binding BAG2 (HSP70 co-chaperone). Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is BAG2 (HSP70 co-chaperone). The partner is a protein-folding chaperone or co-chaperone, and RAF1 is a chaperone client (HSP90-CDC37 dependence is well established); protein-folding chaperone binding describes the interaction from the RAF1 side. The cached text of this reference does not describe the RAF1 interaction, so the IntAct/BioGRID curation (made from the full text or supplementary data) is deferred to; the partner-type mapping is supported by independent RAF1 evidence cited here. Proposed replacements: protein-folding chaperone binding Supporting Evidence: file:human/RAF1/RAF1-uniprot.txt complex composed of chaperones HSP90 and HSP70, co-chaperones CDC37, file:human/RAF1/RAF1-uniprot.txt P04049; O95816: BAG2; NbExp=12; IntAct=EBI-365996, EBI-355275; |
| GO:0005515 protein binding | IPI PMID:25036637 A quantitative chaperone interaction network reveals the arc... | MODIFY | Summary: IPI (quantitative chaperone/co-chaperone interaction network (LUMIER)) for RAF1 binding HSP90AA1. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is HSP90AA1. RAF1 is a strongly HSP90-dependent client kinase whose folding and stability require HSP90-CDC37; Hsp90 protein binding is the informative term (same term as the BRAF review). The cached text of this reference does not describe the RAF1 interaction, so the IntAct/BioGRID curation (made from the full text or supplementary data) is deferred to; the partner-type mapping is supported by independent RAF1 evidence cited here. Proposed replacements: Hsp90 protein binding Supporting Evidence: file:human/RAF1/RAF1-uniprot.txt complex composed of chaperones HSP90 and HSP70, co-chaperones CDC37, file:human/RAF1/RAF1-uniprot.txt P04049; P07900: HSP90AA1; NbExp=15; IntAct=EBI-365996, EBI-296047; |
| GO:0005515 protein binding | IPI PMID:25036637 A quantitative chaperone interaction network reveals the arc... | REMOVE | Summary: IPI (quantitative chaperone/co-chaperone interaction network (LUMIER)) for RAF1 binding MLF2. Reason: GO:0005515 protein binding is uninformative. Chaperone-network / AP-MS co-purifying protein without functional characterisation for RAF1. Removal does not mean the reported interaction is false; it means no informative RAF1 molecular-function term can be justified from it. Supporting Evidence: file:human/RAF1/RAF1-uniprot.txt P04049; Q15773: MLF2; NbExp=4; IntAct=EBI-365996, EBI-1051875; |
| GO:0005515 protein binding | IPI PMID:25036637 A quantitative chaperone interaction network reveals the arc... | MODIFY | Summary: IPI (quantitative chaperone/co-chaperone interaction network (LUMIER)) for RAF1 binding CDC37 (HSP90 kinase co-chaperone). Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is CDC37 (HSP90 kinase co-chaperone). The partner is a protein-folding chaperone or co-chaperone, and RAF1 is a chaperone client (HSP90-CDC37 dependence is well established); protein-folding chaperone binding describes the interaction from the RAF1 side. The cached text of this reference does not describe the RAF1 interaction, so the IntAct/BioGRID curation (made from the full text or supplementary data) is deferred to; the partner-type mapping is supported by independent RAF1 evidence cited here. Proposed replacements: protein-folding chaperone binding Supporting Evidence: file:human/RAF1/RAF1-uniprot.txt complex composed of chaperones HSP90 and HSP70, co-chaperones CDC37, file:human/RAF1/RAF1-uniprot.txt P04049; Q16543: CDC37; NbExp=20; IntAct=EBI-365996, EBI-295634; |
| GO:0005515 protein binding | IPI PMID:25036637 A quantitative chaperone interaction network reveals the arc... | MODIFY | Summary: IPI (quantitative chaperone/co-chaperone interaction network (LUMIER)) for RAF1 binding STUB1/CHIP (E3 ubiquitin ligase). Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is STUB1/CHIP (E3 ubiquitin ligase). The partner is an E3 ubiquitin ligase acting on RAF1 as a substrate/client; ubiquitin protein ligase binding is the informative term (same choice as the BRAF review for HERC2). The cached text of this reference does not describe the RAF1 interaction, so the IntAct/BioGRID curation (made from the full text or supplementary data) is deferred to; the partner-type mapping is supported by independent RAF1 evidence cited here. Proposed replacements: ubiquitin protein ligase binding Supporting Evidence: file:human/RAF1/RAF1-uniprot.txt P04049; Q9UNE7: STUB1; NbExp=8; IntAct=EBI-365996, EBI-357085; |
| GO:0005515 protein binding | IPI PMID:25137548 A Novel SHOC2 Variant in Rasopathy. | MODIFY | Summary: IPI (report of a SHOC2 RASopathy variant; SHOC2 tethers RAS, RAF-1 and PP1c) for RAF1 binding SHOC2 (RAS-RAF-PP1C scaffold). Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is SHOC2 (RAS-RAF-PP1C scaffold). The partner is a MAPK-pathway scaffold that assembles RAF with RAS/MEK or phosphatase; scaffold protein binding is the informative term (same choice as the BRAF review for KSR/IQGAP1/RGS12). Proposed replacements: scaffold protein binding Supporting Evidence: PMID:25137548 which tethers RAS, RAF-1 and the catalytic subunit of protein phosphatase 1c (PP1c) |
| GO:0005515 protein binding | IPI PMID:25155755 Structure of the BRAF-MEK complex reveals a kinase activity ... | MODIFY | Summary: IPI (structural study of BRAF-MEK complexes) for RAF1 binding BRAF. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is BRAF. RAF1 forms side-to-side kinase-domain heterodimers with BRAF, the most active RAF species and the basis of paradoxical activation by RAF inhibitors; protein heterodimerization activity is the informative term (same term as the BRAF review). The cached text of this reference does not describe the RAF1 interaction, so the IntAct/BioGRID curation (made from the full text or supplementary data) is deferred to; the partner-type mapping is supported by independent RAF1 evidence cited here. Proposed replacements: protein heterodimerization activity Supporting Evidence: file:human/RAF1/RAF1-uniprot.txt Heterodimerizes with BRAF and this file:human/RAF1/RAF1-uniprot.txt P04049; P15056: BRAF; NbExp=73; IntAct=EBI-365996, EBI-365980; |
| GO:0005515 protein binding | IPI PMID:25155755 Structure of the BRAF-MEK complex reveals a kinase activity ... | MODIFY | Summary: IPI (structural study of BRAF-MEK complexes) for RAF1 binding MAP2K1/MEK1. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is MAP2K1/MEK1. MEK1/MEK2 are the physiological substrates of RAF1 and form RAF-MEK complexes; MAPKK binding is the informative term (same term as the BRAF review). The cached text of this reference does not describe the RAF1 interaction, so the IntAct/BioGRID curation (made from the full text or supplementary data) is deferred to; the partner-type mapping is supported by independent RAF1 evidence cited here. Proposed replacements: mitogen-activated protein kinase kinase binding Supporting Evidence: file:human/RAF1/RAF1-uniprot.txt Interacts with MAP2K1/MEK1 and file:human/RAF1/RAF1-uniprot.txt P04049; Q02750: MAP2K1; NbExp=39; IntAct=EBI-365996, EBI-492564; |
| GO:0005515 protein binding | IPI PMID:25241761 Using an in situ proximity ligation assay to systematically ... | MODIFY | Summary: IPI (in situ proximity ligation assay survey of endogenous PPIs in HeLa cells) for RAF1 binding AKT1. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is AKT1. The partner is a protein kinase that either regulates RAF1 by phosphorylation (PAK S338, AKT S259), is inhibited by RAF1 binding (MST2), or is an upstream receptor tyrosine kinase; protein kinase binding is the informative term. The cached text of this reference does not describe the RAF1 interaction, so the IntAct/BioGRID curation (made from the full text or supplementary data) is deferred to; the partner-type mapping is supported by independent RAF1 evidence cited here. Proposed replacements: protein kinase binding Supporting Evidence: file:human/RAF1/RAF1-uniprot.txt P04049; P31749: AKT1; NbExp=3; IntAct=EBI-365996, EBI-296087; |
| GO:0005515 protein binding | IPI PMID:25684575 Allosteric effects of the oncogenic RasQ61L mutant on Raf-RB... | MODIFY | Summary: IPI (NMR/structural study of RasQ61L effects on Raf-RBD) for RAF1 binding HRAS. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is HRAS. RAF1 is a direct RAS effector: its RAS-binding domain (RBD) and CRD bind GTP-loaded RAS family GTPases, recruiting RAF1 to the plasma membrane; this is the entry step of RAF activation. small GTPase binding is the informative term (same term as the BRAF review). Proposed replacements: small GTPase binding Supporting Evidence: PMID:25684575 The binding of C-Raf-CRD to Ras is enhanced by farnesylation of Ras file:human/RAF1/RAF1-uniprot.txt P04049; P01112: HRAS; NbExp=30; IntAct=EBI-365996, EBI-350145; |
| GO:0005515 protein binding | IPI PMID:25852190 Integrative analysis of kinase networks in TRAIL-induced apo... | MODIFY | Summary: IPI (integrative kinase interaction network (LUMIER/AP-MS) in TRAIL-induced apoptosis) for RAF1 binding KRAS. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is KRAS. RAF1 is a direct RAS effector: its RAS-binding domain (RBD) and CRD bind GTP-loaded RAS family GTPases, recruiting RAF1 to the plasma membrane; this is the entry step of RAF activation. small GTPase binding is the informative term (same term as the BRAF review). The cached text of this reference does not describe the RAF1 interaction, so the IntAct/BioGRID curation (made from the full text or supplementary data) is deferred to; the partner-type mapping is supported by independent RAF1 evidence cited here. Proposed replacements: small GTPase binding Supporting Evidence: file:human/RAF1/RAF1-uniprot.txt Ras-GTP recruits RAF1 to the file:human/RAF1/RAF1-uniprot.txt P04049; P01116: KRAS; NbExp=6; IntAct=EBI-365996, EBI-367415; |
| GO:0005515 protein binding | IPI PMID:25852190 Integrative analysis of kinase networks in TRAIL-induced apo... | MODIFY | Summary: IPI (integrative kinase interaction network (LUMIER/AP-MS) in TRAIL-induced apoptosis) for RAF1 binding YWHAQ. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is YWHAQ. RAF1 is a canonical phospho-dependent 14-3-3 client: a 14-3-3 dimer engaging pSer259 and pSer621 holds the autoinhibited monomer, and the pSer621 site also stabilises the active dimer. 14-3-3 protein binding captures this regulatory interaction (same term as the BRAF review). The cached text of this reference does not describe the RAF1 interaction, so the IntAct/BioGRID curation (made from the full text or supplementary data) is deferred to; the partner-type mapping is supported by independent RAF1 evidence cited here. Proposed replacements: 14-3-3 protein binding Supporting Evidence: file:human/RAF1/RAF1-uniprot.txt the binding of a 14-3-3 protein that contacts two phosphorylation file:human/RAF1/RAF1-uniprot.txt P04049; P27348: YWHAQ; NbExp=24; IntAct=EBI-365996, EBI-359854; |
| GO:0005515 protein binding | IPI PMID:25852190 Integrative analysis of kinase networks in TRAIL-induced apo... | MODIFY | Summary: IPI (integrative kinase interaction network (LUMIER/AP-MS) in TRAIL-induced apoptosis) for RAF1 binding YWHAB. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is YWHAB. RAF1 is a canonical phospho-dependent 14-3-3 client: a 14-3-3 dimer engaging pSer259 and pSer621 holds the autoinhibited monomer, and the pSer621 site also stabilises the active dimer. 14-3-3 protein binding captures this regulatory interaction (same term as the BRAF review). The cached text of this reference does not describe the RAF1 interaction, so the IntAct/BioGRID curation (made from the full text or supplementary data) is deferred to; the partner-type mapping is supported by independent RAF1 evidence cited here. Proposed replacements: 14-3-3 protein binding Supporting Evidence: file:human/RAF1/RAF1-uniprot.txt the binding of a 14-3-3 protein that contacts two phosphorylation file:human/RAF1/RAF1-uniprot.txt P04049; P31946: YWHAB; NbExp=39; IntAct=EBI-365996, EBI-359815; |
| GO:0005515 protein binding | IPI PMID:25852190 Integrative analysis of kinase networks in TRAIL-induced apo... | MODIFY | Summary: IPI (integrative kinase interaction network (LUMIER/AP-MS) in TRAIL-induced apoptosis) for RAF1 binding SFN (14-3-3 sigma). Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is SFN (14-3-3 sigma). RAF1 is a canonical phospho-dependent 14-3-3 client: a 14-3-3 dimer engaging pSer259 and pSer621 holds the autoinhibited monomer, and the pSer621 site also stabilises the active dimer. 14-3-3 protein binding captures this regulatory interaction (same term as the BRAF review). The cached text of this reference does not describe the RAF1 interaction, so the IntAct/BioGRID curation (made from the full text or supplementary data) is deferred to; the partner-type mapping is supported by independent RAF1 evidence cited here. Proposed replacements: 14-3-3 protein binding Supporting Evidence: file:human/RAF1/RAF1-uniprot.txt the binding of a 14-3-3 protein that contacts two phosphorylation file:human/RAF1/RAF1-uniprot.txt P04049; P31947: SFN; NbExp=9; IntAct=EBI-365996, EBI-476295; |
| GO:0005515 protein binding | IPI PMID:25852190 Integrative analysis of kinase networks in TRAIL-induced apo... | MODIFY | Summary: IPI (integrative kinase interaction network (LUMIER/AP-MS) in TRAIL-induced apoptosis) for RAF1 binding YWHAG. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is YWHAG. RAF1 is a canonical phospho-dependent 14-3-3 client: a 14-3-3 dimer engaging pSer259 and pSer621 holds the autoinhibited monomer, and the pSer621 site also stabilises the active dimer. 14-3-3 protein binding captures this regulatory interaction (same term as the BRAF review). The cached text of this reference does not describe the RAF1 interaction, so the IntAct/BioGRID curation (made from the full text or supplementary data) is deferred to; the partner-type mapping is supported by independent RAF1 evidence cited here. Proposed replacements: 14-3-3 protein binding Supporting Evidence: file:human/RAF1/RAF1-uniprot.txt the binding of a 14-3-3 protein that contacts two phosphorylation file:human/RAF1/RAF1-uniprot.txt P04049; P61981: YWHAG; NbExp=24; IntAct=EBI-365996, EBI-359832; |
| GO:0005515 protein binding | IPI PMID:25852190 Integrative analysis of kinase networks in TRAIL-induced apo... | MODIFY | Summary: IPI (integrative kinase interaction network (LUMIER/AP-MS) in TRAIL-induced apoptosis) for RAF1 binding YWHAE. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is YWHAE. RAF1 is a canonical phospho-dependent 14-3-3 client: a 14-3-3 dimer engaging pSer259 and pSer621 holds the autoinhibited monomer, and the pSer621 site also stabilises the active dimer. 14-3-3 protein binding captures this regulatory interaction (same term as the BRAF review). The cached text of this reference does not describe the RAF1 interaction, so the IntAct/BioGRID curation (made from the full text or supplementary data) is deferred to; the partner-type mapping is supported by independent RAF1 evidence cited here. Proposed replacements: 14-3-3 protein binding Supporting Evidence: file:human/RAF1/RAF1-uniprot.txt the binding of a 14-3-3 protein that contacts two phosphorylation file:human/RAF1/RAF1-uniprot.txt P04049; P62258: YWHAE; NbExp=25; IntAct=EBI-365996, EBI-356498; |
| GO:0005515 protein binding | IPI PMID:25852190 Integrative analysis of kinase networks in TRAIL-induced apo... | MODIFY | Summary: IPI (integrative kinase interaction network (LUMIER/AP-MS) in TRAIL-induced apoptosis) for RAF1 binding YWHAZ. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is YWHAZ. RAF1 is a canonical phospho-dependent 14-3-3 client: a 14-3-3 dimer engaging pSer259 and pSer621 holds the autoinhibited monomer, and the pSer621 site also stabilises the active dimer. 14-3-3 protein binding captures this regulatory interaction (same term as the BRAF review). The cached text of this reference does not describe the RAF1 interaction, so the IntAct/BioGRID curation (made from the full text or supplementary data) is deferred to; the partner-type mapping is supported by independent RAF1 evidence cited here. Proposed replacements: 14-3-3 protein binding Supporting Evidence: file:human/RAF1/RAF1-uniprot.txt the binding of a 14-3-3 protein that contacts two phosphorylation file:human/RAF1/RAF1-uniprot.txt P04049; P63104: YWHAZ; NbExp=32; IntAct=EBI-365996, EBI-347088; |
| GO:0005515 protein binding | IPI PMID:25852190 Integrative analysis of kinase networks in TRAIL-induced apo... | MODIFY | Summary: IPI (integrative kinase interaction network (LUMIER/AP-MS) in TRAIL-induced apoptosis) for RAF1 binding YWHAH. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is YWHAH. RAF1 is a canonical phospho-dependent 14-3-3 client: a 14-3-3 dimer engaging pSer259 and pSer621 holds the autoinhibited monomer, and the pSer621 site also stabilises the active dimer. 14-3-3 protein binding captures this regulatory interaction (same term as the BRAF review). The cached text of this reference does not describe the RAF1 interaction, so the IntAct/BioGRID curation (made from the full text or supplementary data) is deferred to; the partner-type mapping is supported by independent RAF1 evidence cited here. Proposed replacements: 14-3-3 protein binding Supporting Evidence: file:human/RAF1/RAF1-uniprot.txt the binding of a 14-3-3 protein that contacts two phosphorylation file:human/RAF1/RAF1-uniprot.txt P04049; Q04917: YWHAH; NbExp=27; IntAct=EBI-365996, EBI-306940; |
| GO:0005515 protein binding | IPI PMID:25852190 Integrative analysis of kinase networks in TRAIL-induced apo... | REMOVE | Summary: IPI (integrative kinase interaction network (LUMIER/AP-MS) in TRAIL-induced apoptosis) for RAF1 binding TIMM50. Reason: GO:0005515 protein binding is uninformative. Yeast two-hybrid / AP-MS hit (mitochondrial import component), no functional characterisation for RAF1. Removal does not mean the reported interaction is false; it means no informative RAF1 molecular-function term can be justified from it. Supporting Evidence: file:human/RAF1/RAF1-uniprot.txt P04049; Q3ZCQ8: TIMM50; NbExp=7; IntAct=EBI-365996, EBI-355175; |
| GO:0005515 protein binding | IPI PMID:26466569 RAF inhibitors that evade paradoxical MAPK pathway activatio... | MODIFY | Summary: IPI (study of paradox-breaker RAF inhibitors) for RAF1 binding BRAF. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is BRAF. RAF1 forms side-to-side kinase-domain heterodimers with BRAF, the most active RAF species and the basis of paradoxical activation by RAF inhibitors; protein heterodimerization activity is the informative term (same term as the BRAF review). The cached text of this reference does not describe the RAF1 interaction, so the IntAct/BioGRID curation (made from the full text or supplementary data) is deferred to; the partner-type mapping is supported by independent RAF1 evidence cited here. Proposed replacements: protein heterodimerization activity Supporting Evidence: file:human/RAF1/RAF1-uniprot.txt Heterodimerizes with BRAF and this file:human/RAF1/RAF1-uniprot.txt P04049; P15056: BRAF; NbExp=73; IntAct=EBI-365996, EBI-365980; |
| GO:0005515 protein binding | IPI PMID:26496610 A human interactome in three quantitative dimensions organiz... | MODIFY | Summary: IPI (quantitative HeLa interactome (Hein et al.)) for RAF1 binding MAP2K1/MEK1. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is MAP2K1/MEK1. MEK1/MEK2 are the physiological substrates of RAF1 and form RAF-MEK complexes; MAPKK binding is the informative term (same term as the BRAF review). The cached text of this reference does not describe the RAF1 interaction, so the IntAct/BioGRID curation (made from the full text or supplementary data) is deferred to; the partner-type mapping is supported by independent RAF1 evidence cited here. Proposed replacements: mitogen-activated protein kinase kinase binding Supporting Evidence: file:human/RAF1/RAF1-uniprot.txt Interacts with MAP2K1/MEK1 and file:human/RAF1/RAF1-uniprot.txt P04049; Q02750: MAP2K1; NbExp=39; IntAct=EBI-365996, EBI-492564; |
| GO:0005515 protein binding | IPI PMID:26496610 A human interactome in three quantitative dimensions organiz... | MODIFY | Summary: IPI (quantitative HeLa interactome (Hein et al.)) for RAF1 binding YWHAH. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is YWHAH. RAF1 is a canonical phospho-dependent 14-3-3 client: a 14-3-3 dimer engaging pSer259 and pSer621 holds the autoinhibited monomer, and the pSer621 site also stabilises the active dimer. 14-3-3 protein binding captures this regulatory interaction (same term as the BRAF review). The cached text of this reference does not describe the RAF1 interaction, so the IntAct/BioGRID curation (made from the full text or supplementary data) is deferred to; the partner-type mapping is supported by independent RAF1 evidence cited here. Proposed replacements: 14-3-3 protein binding Supporting Evidence: file:human/RAF1/RAF1-uniprot.txt the binding of a 14-3-3 protein that contacts two phosphorylation file:human/RAF1/RAF1-uniprot.txt P04049; Q04917: YWHAH; NbExp=27; IntAct=EBI-365996, EBI-306940; |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | MODIFY | Summary: IPI (BioPlex 2.0 AP-MS human interactome) for RAF1 binding YWHAQ. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is YWHAQ. RAF1 is a canonical phospho-dependent 14-3-3 client: a 14-3-3 dimer engaging pSer259 and pSer621 holds the autoinhibited monomer, and the pSer621 site also stabilises the active dimer. 14-3-3 protein binding captures this regulatory interaction (same term as the BRAF review). The cached text of this reference does not describe the RAF1 interaction, so the IntAct/BioGRID curation (made from the full text or supplementary data) is deferred to; the partner-type mapping is supported by independent RAF1 evidence cited here. Proposed replacements: 14-3-3 protein binding Supporting Evidence: file:human/RAF1/RAF1-uniprot.txt the binding of a 14-3-3 protein that contacts two phosphorylation file:human/RAF1/RAF1-uniprot.txt P04049; P27348: YWHAQ; NbExp=24; IntAct=EBI-365996, EBI-359854; |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | MODIFY | Summary: IPI (BioPlex 2.0 AP-MS human interactome) for RAF1 binding YWHAG. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is YWHAG. RAF1 is a canonical phospho-dependent 14-3-3 client: a 14-3-3 dimer engaging pSer259 and pSer621 holds the autoinhibited monomer, and the pSer621 site also stabilises the active dimer. 14-3-3 protein binding captures this regulatory interaction (same term as the BRAF review). The cached text of this reference does not describe the RAF1 interaction, so the IntAct/BioGRID curation (made from the full text or supplementary data) is deferred to; the partner-type mapping is supported by independent RAF1 evidence cited here. Proposed replacements: 14-3-3 protein binding Supporting Evidence: file:human/RAF1/RAF1-uniprot.txt the binding of a 14-3-3 protein that contacts two phosphorylation file:human/RAF1/RAF1-uniprot.txt P04049; P61981: YWHAG; NbExp=24; IntAct=EBI-365996, EBI-359832; |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | MODIFY | Summary: IPI (BioPlex 2.0 AP-MS human interactome) for RAF1 binding YWHAH. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is YWHAH. RAF1 is a canonical phospho-dependent 14-3-3 client: a 14-3-3 dimer engaging pSer259 and pSer621 holds the autoinhibited monomer, and the pSer621 site also stabilises the active dimer. 14-3-3 protein binding captures this regulatory interaction (same term as the BRAF review). The cached text of this reference does not describe the RAF1 interaction, so the IntAct/BioGRID curation (made from the full text or supplementary data) is deferred to; the partner-type mapping is supported by independent RAF1 evidence cited here. Proposed replacements: 14-3-3 protein binding Supporting Evidence: file:human/RAF1/RAF1-uniprot.txt the binding of a 14-3-3 protein that contacts two phosphorylation file:human/RAF1/RAF1-uniprot.txt P04049; Q04917: YWHAH; NbExp=27; IntAct=EBI-365996, EBI-306940; |
| GO:0005515 protein binding | IPI PMID:30194290 Interrogating the protein interactomes of RAS isoforms ident... | MODIFY | Summary: IPI (BioID proximity interactomes of RAS isoforms) for RAF1 binding NRAS. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is NRAS. RAF1 is a direct RAS effector: its RAS-binding domain (RBD) and CRD bind GTP-loaded RAS family GTPases, recruiting RAF1 to the plasma membrane; this is the entry step of RAF activation. small GTPase binding is the informative term (same term as the BRAF review). Proposed replacements: small GTPase binding Supporting Evidence: PMID:30194290 Among these were the well-described RAS effectors ARAF, BRAF, and RAF1 (CRAF), which directly bind to activated RAS through a Ras-binding domain file:human/RAF1/RAF1-uniprot.txt P04049; P01111: NRAS; NbExp=15; IntAct=EBI-365996, EBI-721993; |
| GO:0005515 protein binding | IPI PMID:30194290 Interrogating the protein interactomes of RAS isoforms ident... | MODIFY | Summary: IPI (BioID proximity interactomes of RAS isoforms) for RAF1 binding HRAS. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is HRAS. RAF1 is a direct RAS effector: its RAS-binding domain (RBD) and CRD bind GTP-loaded RAS family GTPases, recruiting RAF1 to the plasma membrane; this is the entry step of RAF activation. small GTPase binding is the informative term (same term as the BRAF review). Proposed replacements: small GTPase binding Supporting Evidence: PMID:30194290 Among these were the well-described RAS effectors ARAF, BRAF, and RAF1 (CRAF), which directly bind to activated RAS through a Ras-binding domain file:human/RAF1/RAF1-uniprot.txt P04049; P01112: HRAS; NbExp=30; IntAct=EBI-365996, EBI-350145; |
| GO:0005515 protein binding | IPI PMID:30194290 Interrogating the protein interactomes of RAS isoforms ident... | MODIFY | Summary: IPI (BioID proximity interactomes of RAS isoforms) for RAF1 binding KRAS. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is KRAS. RAF1 is a direct RAS effector: its RAS-binding domain (RBD) and CRD bind GTP-loaded RAS family GTPases, recruiting RAF1 to the plasma membrane; this is the entry step of RAF activation. small GTPase binding is the informative term (same term as the BRAF review). Proposed replacements: small GTPase binding Supporting Evidence: PMID:30194290 Among these were the well-described RAS effectors ARAF, BRAF, and RAF1 (CRAF), which directly bind to activated RAS through a Ras-binding domain file:human/RAF1/RAF1-uniprot.txt P04049; P01116: KRAS; NbExp=6; IntAct=EBI-365996, EBI-367415; |
| GO:0005515 protein binding | IPI PMID:31024343 A YWHAZ Variant Associated With Cardiofaciocutaneous Syndrom... | MODIFY | Summary: IPI (study of a YWHAZ variant in cardiofaciocutaneous syndrome that enhances RAF1 binding) for RAF1 binding YWHAZ. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is YWHAZ. RAF1 is a canonical phospho-dependent 14-3-3 client: a 14-3-3 dimer engaging pSer259 and pSer621 holds the autoinhibited monomer, and the pSer621 site also stabilises the active dimer. 14-3-3 protein binding captures this regulatory interaction (same term as the BRAF review). Proposed replacements: 14-3-3 protein binding Supporting Evidence: PMID:31024343 strongly enhanced GFP-Erk2 phosphorylation when co-expressed with craf file:human/RAF1/RAF1-uniprot.txt P04049; P63104: YWHAZ; NbExp=32; IntAct=EBI-365996, EBI-347088; |
| GO:0005515 protein binding | IPI PMID:31980649 Extensive rewiring of the EGFR network in colorectal cancer ... | MODIFY | Summary: IPI (AP-MS rewiring of the EGFR network in mutant-KRAS colorectal cancer cells) for RAF1 binding BAG2 (HSP70 co-chaperone). Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is BAG2 (HSP70 co-chaperone). The partner is a protein-folding chaperone or co-chaperone, and RAF1 is a chaperone client (HSP90-CDC37 dependence is well established); protein-folding chaperone binding describes the interaction from the RAF1 side. Proposed replacements: protein-folding chaperone binding Supporting Evidence: PMID:31980649 many of the major hubs (highly connected nodes) in EGFRNetmtKRAS-Hi are also hubs in EGFRNetmtKRAS-Lo including GRB2, RAB5A, RAF1, and SH2D3C file:human/RAF1/RAF1-uniprot.txt P04049; O95816: BAG2; NbExp=12; IntAct=EBI-365996, EBI-355275; |
| GO:0005515 protein binding | IPI PMID:31980649 Extensive rewiring of the EGFR network in colorectal cancer ... | MODIFY | Summary: IPI (AP-MS rewiring of the EGFR network in mutant-KRAS colorectal cancer cells) for RAF1 binding EGFR. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is EGFR. The partner is a protein kinase that either regulates RAF1 by phosphorylation (PAK S338, AKT S259), is inhibited by RAF1 binding (MST2), or is an upstream receptor tyrosine kinase; protein kinase binding is the informative term. Proposed replacements: protein kinase binding Supporting Evidence: PMID:31980649 many of the major hubs (highly connected nodes) in EGFRNetmtKRAS-Hi are also hubs in EGFRNetmtKRAS-Lo including GRB2, RAB5A, RAF1, and SH2D3C file:human/RAF1/RAF1-uniprot.txt P04049; P00533: EGFR; NbExp=3; IntAct=EBI-365996, EBI-297353; |
| GO:0005515 protein binding | IPI PMID:31980649 Extensive rewiring of the EGFR network in colorectal cancer ... | MODIFY | Summary: IPI (AP-MS rewiring of the EGFR network in mutant-KRAS colorectal cancer cells) for RAF1 binding NRAS. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is NRAS. RAF1 is a direct RAS effector: its RAS-binding domain (RBD) and CRD bind GTP-loaded RAS family GTPases, recruiting RAF1 to the plasma membrane; this is the entry step of RAF activation. small GTPase binding is the informative term (same term as the BRAF review). Proposed replacements: small GTPase binding Supporting Evidence: PMID:31980649 many of the major hubs (highly connected nodes) in EGFRNetmtKRAS-Hi are also hubs in EGFRNetmtKRAS-Lo including GRB2, RAB5A, RAF1, and SH2D3C file:human/RAF1/RAF1-uniprot.txt P04049; P01111: NRAS; NbExp=15; IntAct=EBI-365996, EBI-721993; |
| GO:0005515 protein binding | IPI PMID:31980649 Extensive rewiring of the EGFR network in colorectal cancer ... | MODIFY | Summary: IPI (AP-MS rewiring of the EGFR network in mutant-KRAS colorectal cancer cells) for RAF1 binding KRAS. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is KRAS. RAF1 is a direct RAS effector: its RAS-binding domain (RBD) and CRD bind GTP-loaded RAS family GTPases, recruiting RAF1 to the plasma membrane; this is the entry step of RAF activation. small GTPase binding is the informative term (same term as the BRAF review). Proposed replacements: small GTPase binding Supporting Evidence: PMID:31980649 many of the major hubs (highly connected nodes) in EGFRNetmtKRAS-Hi are also hubs in EGFRNetmtKRAS-Lo including GRB2, RAB5A, RAF1, and SH2D3C file:human/RAF1/RAF1-uniprot.txt P04049; P01116: KRAS; NbExp=6; IntAct=EBI-365996, EBI-367415; |
| GO:0005515 protein binding | IPI PMID:31980649 Extensive rewiring of the EGFR network in colorectal cancer ... | MODIFY | Summary: IPI (AP-MS rewiring of the EGFR network in mutant-KRAS colorectal cancer cells) for RAF1 binding HSP90AA1. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is HSP90AA1. RAF1 is a strongly HSP90-dependent client kinase whose folding and stability require HSP90-CDC37; Hsp90 protein binding is the informative term (same term as the BRAF review). Proposed replacements: Hsp90 protein binding Supporting Evidence: PMID:31980649 many of the major hubs (highly connected nodes) in EGFRNetmtKRAS-Hi are also hubs in EGFRNetmtKRAS-Lo including GRB2, RAB5A, RAF1, and SH2D3C file:human/RAF1/RAF1-uniprot.txt P04049; P07900: HSP90AA1; NbExp=15; IntAct=EBI-365996, EBI-296047; |
| GO:0005515 protein binding | IPI PMID:31980649 Extensive rewiring of the EGFR network in colorectal cancer ... | MODIFY | Summary: IPI (AP-MS rewiring of the EGFR network in mutant-KRAS colorectal cancer cells) for RAF1 binding HSP90AB1. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is HSP90AB1. RAF1 is a strongly HSP90-dependent client kinase whose folding and stability require HSP90-CDC37; Hsp90 protein binding is the informative term (same term as the BRAF review). Proposed replacements: Hsp90 protein binding Supporting Evidence: PMID:31980649 many of the major hubs (highly connected nodes) in EGFRNetmtKRAS-Hi are also hubs in EGFRNetmtKRAS-Lo including GRB2, RAB5A, RAF1, and SH2D3C file:human/RAF1/RAF1-uniprot.txt P04049; P08238: HSP90AB1; NbExp=17; IntAct=EBI-365996, EBI-352572; |
| GO:0005515 protein binding | IPI PMID:31980649 Extensive rewiring of the EGFR network in colorectal cancer ... | MODIFY | Summary: IPI (AP-MS rewiring of the EGFR network in mutant-KRAS colorectal cancer cells) for RAF1 binding BRAF. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is BRAF. RAF1 forms side-to-side kinase-domain heterodimers with BRAF, the most active RAF species and the basis of paradoxical activation by RAF inhibitors; protein heterodimerization activity is the informative term (same term as the BRAF review). Proposed replacements: protein heterodimerization activity Supporting Evidence: PMID:31980649 many of the major hubs (highly connected nodes) in EGFRNetmtKRAS-Hi are also hubs in EGFRNetmtKRAS-Lo including GRB2, RAB5A, RAF1, and SH2D3C file:human/RAF1/RAF1-uniprot.txt P04049; P15056: BRAF; NbExp=73; IntAct=EBI-365996, EBI-365980; |
| GO:0005515 protein binding | IPI PMID:31980649 Extensive rewiring of the EGFR network in colorectal cancer ... | MODIFY | Summary: IPI (AP-MS rewiring of the EGFR network in mutant-KRAS colorectal cancer cells) for RAF1 binding YWHAQ. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is YWHAQ. RAF1 is a canonical phospho-dependent 14-3-3 client: a 14-3-3 dimer engaging pSer259 and pSer621 holds the autoinhibited monomer, and the pSer621 site also stabilises the active dimer. 14-3-3 protein binding captures this regulatory interaction (same term as the BRAF review). Proposed replacements: 14-3-3 protein binding Supporting Evidence: PMID:31980649 many of the major hubs (highly connected nodes) in EGFRNetmtKRAS-Hi are also hubs in EGFRNetmtKRAS-Lo including GRB2, RAB5A, RAF1, and SH2D3C file:human/RAF1/RAF1-uniprot.txt P04049; P27348: YWHAQ; NbExp=24; IntAct=EBI-365996, EBI-359854; |
| GO:0005515 protein binding | IPI PMID:31980649 Extensive rewiring of the EGFR network in colorectal cancer ... | MODIFY | Summary: IPI (AP-MS rewiring of the EGFR network in mutant-KRAS colorectal cancer cells) for RAF1 binding YWHAB. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is YWHAB. RAF1 is a canonical phospho-dependent 14-3-3 client: a 14-3-3 dimer engaging pSer259 and pSer621 holds the autoinhibited monomer, and the pSer621 site also stabilises the active dimer. 14-3-3 protein binding captures this regulatory interaction (same term as the BRAF review). Proposed replacements: 14-3-3 protein binding Supporting Evidence: PMID:31980649 many of the major hubs (highly connected nodes) in EGFRNetmtKRAS-Hi are also hubs in EGFRNetmtKRAS-Lo including GRB2, RAB5A, RAF1, and SH2D3C file:human/RAF1/RAF1-uniprot.txt P04049; P31946: YWHAB; NbExp=39; IntAct=EBI-365996, EBI-359815; |
| GO:0005515 protein binding | IPI PMID:31980649 Extensive rewiring of the EGFR network in colorectal cancer ... | MODIFY | Summary: IPI (AP-MS rewiring of the EGFR network in mutant-KRAS colorectal cancer cells) for RAF1 binding SFN (14-3-3 sigma). Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is SFN (14-3-3 sigma). RAF1 is a canonical phospho-dependent 14-3-3 client: a 14-3-3 dimer engaging pSer259 and pSer621 holds the autoinhibited monomer, and the pSer621 site also stabilises the active dimer. 14-3-3 protein binding captures this regulatory interaction (same term as the BRAF review). Proposed replacements: 14-3-3 protein binding Supporting Evidence: PMID:31980649 many of the major hubs (highly connected nodes) in EGFRNetmtKRAS-Hi are also hubs in EGFRNetmtKRAS-Lo including GRB2, RAB5A, RAF1, and SH2D3C file:human/RAF1/RAF1-uniprot.txt P04049; P31947: SFN; NbExp=9; IntAct=EBI-365996, EBI-476295; |
| GO:0005515 protein binding | IPI PMID:31980649 Extensive rewiring of the EGFR network in colorectal cancer ... | MODIFY | Summary: IPI (AP-MS rewiring of the EGFR network in mutant-KRAS colorectal cancer cells) for RAF1 binding MAP2K2/MEK2. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is MAP2K2/MEK2. MEK1/MEK2 are the physiological substrates of RAF1 and form RAF-MEK complexes; MAPKK binding is the informative term (same term as the BRAF review). Proposed replacements: mitogen-activated protein kinase kinase binding Supporting Evidence: PMID:31980649 many of the major hubs (highly connected nodes) in EGFRNetmtKRAS-Hi are also hubs in EGFRNetmtKRAS-Lo including GRB2, RAB5A, RAF1, and SH2D3C file:human/RAF1/RAF1-uniprot.txt P04049; P36507: MAP2K2; NbExp=7; IntAct=EBI-365996, EBI-1056930; |
| GO:0005515 protein binding | IPI PMID:31980649 Extensive rewiring of the EGFR network in colorectal cancer ... | MODIFY | Summary: IPI (AP-MS rewiring of the EGFR network in mutant-KRAS colorectal cancer cells) for RAF1 binding CCT3 (TRiC chaperonin subunit). Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is CCT3 (TRiC chaperonin subunit). The partner is a protein-folding chaperone or co-chaperone, and RAF1 is a chaperone client (HSP90-CDC37 dependence is well established); protein-folding chaperone binding describes the interaction from the RAF1 side. Proposed replacements: protein-folding chaperone binding Supporting Evidence: PMID:31980649 many of the major hubs (highly connected nodes) in EGFRNetmtKRAS-Hi are also hubs in EGFRNetmtKRAS-Lo including GRB2, RAB5A, RAF1, and SH2D3C file:human/RAF1/RAF1-uniprot.txt P04049; P49368: CCT3; NbExp=8; IntAct=EBI-365996, EBI-356673; |
| GO:0005515 protein binding | IPI PMID:31980649 Extensive rewiring of the EGFR network in colorectal cancer ... | MODIFY | Summary: IPI (AP-MS rewiring of the EGFR network in mutant-KRAS colorectal cancer cells) for RAF1 binding YWHAG. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is YWHAG. RAF1 is a canonical phospho-dependent 14-3-3 client: a 14-3-3 dimer engaging pSer259 and pSer621 holds the autoinhibited monomer, and the pSer621 site also stabilises the active dimer. 14-3-3 protein binding captures this regulatory interaction (same term as the BRAF review). Proposed replacements: 14-3-3 protein binding Supporting Evidence: PMID:31980649 many of the major hubs (highly connected nodes) in EGFRNetmtKRAS-Hi are also hubs in EGFRNetmtKRAS-Lo including GRB2, RAB5A, RAF1, and SH2D3C file:human/RAF1/RAF1-uniprot.txt P04049; P61981: YWHAG; NbExp=24; IntAct=EBI-365996, EBI-359832; |
| GO:0005515 protein binding | IPI PMID:31980649 Extensive rewiring of the EGFR network in colorectal cancer ... | MODIFY | Summary: IPI (AP-MS rewiring of the EGFR network in mutant-KRAS colorectal cancer cells) for RAF1 binding YWHAE. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is YWHAE. RAF1 is a canonical phospho-dependent 14-3-3 client: a 14-3-3 dimer engaging pSer259 and pSer621 holds the autoinhibited monomer, and the pSer621 site also stabilises the active dimer. 14-3-3 protein binding captures this regulatory interaction (same term as the BRAF review). Proposed replacements: 14-3-3 protein binding Supporting Evidence: PMID:31980649 many of the major hubs (highly connected nodes) in EGFRNetmtKRAS-Hi are also hubs in EGFRNetmtKRAS-Lo including GRB2, RAB5A, RAF1, and SH2D3C file:human/RAF1/RAF1-uniprot.txt P04049; P62258: YWHAE; NbExp=25; IntAct=EBI-365996, EBI-356498; |
| GO:0005515 protein binding | IPI PMID:31980649 Extensive rewiring of the EGFR network in colorectal cancer ... | MODIFY | Summary: IPI (AP-MS rewiring of the EGFR network in mutant-KRAS colorectal cancer cells) for RAF1 binding YWHAZ. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is YWHAZ. RAF1 is a canonical phospho-dependent 14-3-3 client: a 14-3-3 dimer engaging pSer259 and pSer621 holds the autoinhibited monomer, and the pSer621 site also stabilises the active dimer. 14-3-3 protein binding captures this regulatory interaction (same term as the BRAF review). Proposed replacements: 14-3-3 protein binding Supporting Evidence: PMID:31980649 many of the major hubs (highly connected nodes) in EGFRNetmtKRAS-Hi are also hubs in EGFRNetmtKRAS-Lo including GRB2, RAB5A, RAF1, and SH2D3C file:human/RAF1/RAF1-uniprot.txt P04049; P63104: YWHAZ; NbExp=32; IntAct=EBI-365996, EBI-347088; |
| GO:0005515 protein binding | IPI PMID:31980649 Extensive rewiring of the EGFR network in colorectal cancer ... | MODIFY | Summary: IPI (AP-MS rewiring of the EGFR network in mutant-KRAS colorectal cancer cells) for RAF1 binding MAP2K1/MEK1. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is MAP2K1/MEK1. MEK1/MEK2 are the physiological substrates of RAF1 and form RAF-MEK complexes; MAPKK binding is the informative term (same term as the BRAF review). Proposed replacements: mitogen-activated protein kinase kinase binding Supporting Evidence: PMID:31980649 many of the major hubs (highly connected nodes) in EGFRNetmtKRAS-Hi are also hubs in EGFRNetmtKRAS-Lo including GRB2, RAB5A, RAF1, and SH2D3C file:human/RAF1/RAF1-uniprot.txt P04049; Q02750: MAP2K1; NbExp=39; IntAct=EBI-365996, EBI-492564; |
| GO:0005515 protein binding | IPI PMID:31980649 Extensive rewiring of the EGFR network in colorectal cancer ... | MODIFY | Summary: IPI (AP-MS rewiring of the EGFR network in mutant-KRAS colorectal cancer cells) for RAF1 binding YWHAH. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is YWHAH. RAF1 is a canonical phospho-dependent 14-3-3 client: a 14-3-3 dimer engaging pSer259 and pSer621 holds the autoinhibited monomer, and the pSer621 site also stabilises the active dimer. 14-3-3 protein binding captures this regulatory interaction (same term as the BRAF review). Proposed replacements: 14-3-3 protein binding Supporting Evidence: PMID:31980649 many of the major hubs (highly connected nodes) in EGFRNetmtKRAS-Hi are also hubs in EGFRNetmtKRAS-Lo including GRB2, RAB5A, RAF1, and SH2D3C file:human/RAF1/RAF1-uniprot.txt P04049; Q04917: YWHAH; NbExp=27; IntAct=EBI-365996, EBI-306940; |
| GO:0005515 protein binding | IPI PMID:31980649 Extensive rewiring of the EGFR network in colorectal cancer ... | MODIFY | Summary: IPI (AP-MS rewiring of the EGFR network in mutant-KRAS colorectal cancer cells) for RAF1 binding CDC37 (HSP90 kinase co-chaperone). Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is CDC37 (HSP90 kinase co-chaperone). The partner is a protein-folding chaperone or co-chaperone, and RAF1 is a chaperone client (HSP90-CDC37 dependence is well established); protein-folding chaperone binding describes the interaction from the RAF1 side. Proposed replacements: protein-folding chaperone binding Supporting Evidence: PMID:31980649 many of the major hubs (highly connected nodes) in EGFRNetmtKRAS-Hi are also hubs in EGFRNetmtKRAS-Lo including GRB2, RAB5A, RAF1, and SH2D3C file:human/RAF1/RAF1-uniprot.txt P04049; Q16543: CDC37; NbExp=20; IntAct=EBI-365996, EBI-295634; |
| GO:0005515 protein binding | IPI PMID:31980649 Extensive rewiring of the EGFR network in colorectal cancer ... | REMOVE | Summary: IPI (AP-MS rewiring of the EGFR network in mutant-KRAS colorectal cancer cells) for RAF1 binding TIMM50. Reason: GO:0005515 protein binding is uninformative. Yeast two-hybrid / AP-MS hit (mitochondrial import component), no functional characterisation for RAF1. Removal does not mean the reported interaction is false; it means no informative RAF1 molecular-function term can be justified from it. Supporting Evidence: PMID:31980649 many of the major hubs (highly connected nodes) in EGFRNetmtKRAS-Hi are also hubs in EGFRNetmtKRAS-Lo including GRB2, RAB5A, RAF1, and SH2D3C file:human/RAF1/RAF1-uniprot.txt P04049; Q3ZCQ8: TIMM50; NbExp=7; IntAct=EBI-365996, EBI-355175; |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | MODIFY | Summary: IPI (HuRI reference binary (yeast two-hybrid) human interactome) for RAF1 binding NRAS. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is NRAS. RAF1 is a direct RAS effector: its RAS-binding domain (RBD) and CRD bind GTP-loaded RAS family GTPases, recruiting RAF1 to the plasma membrane; this is the entry step of RAF activation. small GTPase binding is the informative term (same term as the BRAF review). The cached text of this reference does not describe the RAF1 interaction, so the IntAct/BioGRID curation (made from the full text or supplementary data) is deferred to; the partner-type mapping is supported by independent RAF1 evidence cited here. Proposed replacements: small GTPase binding Supporting Evidence: file:human/RAF1/RAF1-uniprot.txt Ras-GTP recruits RAF1 to the file:human/RAF1/RAF1-uniprot.txt P04049; P01111: NRAS; NbExp=15; IntAct=EBI-365996, EBI-721993; |
| GO:0005515 protein binding | IPI PMID:32707033 Kinase Interaction Network Expands Functional and Disease Ro... | MODIFY | Summary: IPI (kinase interaction network (Buljan et al.) AP-MS of human kinases) for RAF1 binding HSP90AA1. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is HSP90AA1. RAF1 is a strongly HSP90-dependent client kinase whose folding and stability require HSP90-CDC37; Hsp90 protein binding is the informative term (same term as the BRAF review). The cached text of this reference does not describe the RAF1 interaction, so the IntAct/BioGRID curation (made from the full text or supplementary data) is deferred to; the partner-type mapping is supported by independent RAF1 evidence cited here. Proposed replacements: Hsp90 protein binding Supporting Evidence: file:human/RAF1/RAF1-uniprot.txt complex composed of chaperones HSP90 and HSP70, co-chaperones CDC37, file:human/RAF1/RAF1-uniprot.txt P04049; P07900: HSP90AA1; NbExp=15; IntAct=EBI-365996, EBI-296047; |
| GO:0005515 protein binding | IPI PMID:32707033 Kinase Interaction Network Expands Functional and Disease Ro... | MODIFY | Summary: IPI (kinase interaction network (Buljan et al.) AP-MS of human kinases) for RAF1 binding HSP90AB1. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is HSP90AB1. RAF1 is a strongly HSP90-dependent client kinase whose folding and stability require HSP90-CDC37; Hsp90 protein binding is the informative term (same term as the BRAF review). The cached text of this reference does not describe the RAF1 interaction, so the IntAct/BioGRID curation (made from the full text or supplementary data) is deferred to; the partner-type mapping is supported by independent RAF1 evidence cited here. Proposed replacements: Hsp90 protein binding Supporting Evidence: file:human/RAF1/RAF1-uniprot.txt complex composed of chaperones HSP90 and HSP70, co-chaperones CDC37, file:human/RAF1/RAF1-uniprot.txt P04049; P08238: HSP90AB1; NbExp=17; IntAct=EBI-365996, EBI-352572; |
| GO:0005515 protein binding | IPI PMID:32707033 Kinase Interaction Network Expands Functional and Disease Ro... | MODIFY | Summary: IPI (kinase interaction network (Buljan et al.) AP-MS of human kinases) for RAF1 binding YWHAQ. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is YWHAQ. RAF1 is a canonical phospho-dependent 14-3-3 client: a 14-3-3 dimer engaging pSer259 and pSer621 holds the autoinhibited monomer, and the pSer621 site also stabilises the active dimer. 14-3-3 protein binding captures this regulatory interaction (same term as the BRAF review). The cached text of this reference does not describe the RAF1 interaction, so the IntAct/BioGRID curation (made from the full text or supplementary data) is deferred to; the partner-type mapping is supported by independent RAF1 evidence cited here. Proposed replacements: 14-3-3 protein binding Supporting Evidence: file:human/RAF1/RAF1-uniprot.txt the binding of a 14-3-3 protein that contacts two phosphorylation file:human/RAF1/RAF1-uniprot.txt P04049; P27348: YWHAQ; NbExp=24; IntAct=EBI-365996, EBI-359854; |
| GO:0005515 protein binding | IPI PMID:32707033 Kinase Interaction Network Expands Functional and Disease Ro... | MODIFY | Summary: IPI (kinase interaction network (Buljan et al.) AP-MS of human kinases) for RAF1 binding YWHAB. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is YWHAB. RAF1 is a canonical phospho-dependent 14-3-3 client: a 14-3-3 dimer engaging pSer259 and pSer621 holds the autoinhibited monomer, and the pSer621 site also stabilises the active dimer. 14-3-3 protein binding captures this regulatory interaction (same term as the BRAF review). The cached text of this reference does not describe the RAF1 interaction, so the IntAct/BioGRID curation (made from the full text or supplementary data) is deferred to; the partner-type mapping is supported by independent RAF1 evidence cited here. Proposed replacements: 14-3-3 protein binding Supporting Evidence: file:human/RAF1/RAF1-uniprot.txt the binding of a 14-3-3 protein that contacts two phosphorylation file:human/RAF1/RAF1-uniprot.txt P04049; P31946: YWHAB; NbExp=39; IntAct=EBI-365996, EBI-359815; |
| GO:0005515 protein binding | IPI PMID:32707033 Kinase Interaction Network Expands Functional and Disease Ro... | MODIFY | Summary: IPI (kinase interaction network (Buljan et al.) AP-MS of human kinases) for RAF1 binding MAP2K2/MEK2. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is MAP2K2/MEK2. MEK1/MEK2 are the physiological substrates of RAF1 and form RAF-MEK complexes; MAPKK binding is the informative term (same term as the BRAF review). The cached text of this reference does not describe the RAF1 interaction, so the IntAct/BioGRID curation (made from the full text or supplementary data) is deferred to; the partner-type mapping is supported by independent RAF1 evidence cited here. Proposed replacements: mitogen-activated protein kinase kinase binding Supporting Evidence: file:human/RAF1/RAF1-uniprot.txt Interacts with MAP2K1/MEK1 and file:human/RAF1/RAF1-uniprot.txt P04049; P36507: MAP2K2; NbExp=7; IntAct=EBI-365996, EBI-1056930; |
| GO:0005515 protein binding | IPI PMID:32707033 Kinase Interaction Network Expands Functional and Disease Ro... | MODIFY | Summary: IPI (kinase interaction network (Buljan et al.) AP-MS of human kinases) for RAF1 binding YWHAG. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is YWHAG. RAF1 is a canonical phospho-dependent 14-3-3 client: a 14-3-3 dimer engaging pSer259 and pSer621 holds the autoinhibited monomer, and the pSer621 site also stabilises the active dimer. 14-3-3 protein binding captures this regulatory interaction (same term as the BRAF review). The cached text of this reference does not describe the RAF1 interaction, so the IntAct/BioGRID curation (made from the full text or supplementary data) is deferred to; the partner-type mapping is supported by independent RAF1 evidence cited here. Proposed replacements: 14-3-3 protein binding Supporting Evidence: file:human/RAF1/RAF1-uniprot.txt the binding of a 14-3-3 protein that contacts two phosphorylation file:human/RAF1/RAF1-uniprot.txt P04049; P61981: YWHAG; NbExp=24; IntAct=EBI-365996, EBI-359832; |
| GO:0005515 protein binding | IPI PMID:32707033 Kinase Interaction Network Expands Functional and Disease Ro... | MODIFY | Summary: IPI (kinase interaction network (Buljan et al.) AP-MS of human kinases) for RAF1 binding YWHAE. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is YWHAE. RAF1 is a canonical phospho-dependent 14-3-3 client: a 14-3-3 dimer engaging pSer259 and pSer621 holds the autoinhibited monomer, and the pSer621 site also stabilises the active dimer. 14-3-3 protein binding captures this regulatory interaction (same term as the BRAF review). The cached text of this reference does not describe the RAF1 interaction, so the IntAct/BioGRID curation (made from the full text or supplementary data) is deferred to; the partner-type mapping is supported by independent RAF1 evidence cited here. Proposed replacements: 14-3-3 protein binding Supporting Evidence: file:human/RAF1/RAF1-uniprot.txt the binding of a 14-3-3 protein that contacts two phosphorylation file:human/RAF1/RAF1-uniprot.txt P04049; P62258: YWHAE; NbExp=25; IntAct=EBI-365996, EBI-356498; |
| GO:0005515 protein binding | IPI PMID:32707033 Kinase Interaction Network Expands Functional and Disease Ro... | MODIFY | Summary: IPI (kinase interaction network (Buljan et al.) AP-MS of human kinases) for RAF1 binding YWHAZ. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is YWHAZ. RAF1 is a canonical phospho-dependent 14-3-3 client: a 14-3-3 dimer engaging pSer259 and pSer621 holds the autoinhibited monomer, and the pSer621 site also stabilises the active dimer. 14-3-3 protein binding captures this regulatory interaction (same term as the BRAF review). The cached text of this reference does not describe the RAF1 interaction, so the IntAct/BioGRID curation (made from the full text or supplementary data) is deferred to; the partner-type mapping is supported by independent RAF1 evidence cited here. Proposed replacements: 14-3-3 protein binding Supporting Evidence: file:human/RAF1/RAF1-uniprot.txt the binding of a 14-3-3 protein that contacts two phosphorylation file:human/RAF1/RAF1-uniprot.txt P04049; P63104: YWHAZ; NbExp=32; IntAct=EBI-365996, EBI-347088; |
| GO:0005515 protein binding | IPI PMID:32707033 Kinase Interaction Network Expands Functional and Disease Ro... | MODIFY | Summary: IPI (kinase interaction network (Buljan et al.) AP-MS of human kinases) for RAF1 binding MAP2K1/MEK1. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is MAP2K1/MEK1. MEK1/MEK2 are the physiological substrates of RAF1 and form RAF-MEK complexes; MAPKK binding is the informative term (same term as the BRAF review). The cached text of this reference does not describe the RAF1 interaction, so the IntAct/BioGRID curation (made from the full text or supplementary data) is deferred to; the partner-type mapping is supported by independent RAF1 evidence cited here. Proposed replacements: mitogen-activated protein kinase kinase binding Supporting Evidence: file:human/RAF1/RAF1-uniprot.txt Interacts with MAP2K1/MEK1 and file:human/RAF1/RAF1-uniprot.txt P04049; Q02750: MAP2K1; NbExp=39; IntAct=EBI-365996, EBI-492564; |
| GO:0005515 protein binding | IPI PMID:32707033 Kinase Interaction Network Expands Functional and Disease Ro... | MODIFY | Summary: IPI (kinase interaction network (Buljan et al.) AP-MS of human kinases) for RAF1 binding YWHAH. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is YWHAH. RAF1 is a canonical phospho-dependent 14-3-3 client: a 14-3-3 dimer engaging pSer259 and pSer621 holds the autoinhibited monomer, and the pSer621 site also stabilises the active dimer. 14-3-3 protein binding captures this regulatory interaction (same term as the BRAF review). The cached text of this reference does not describe the RAF1 interaction, so the IntAct/BioGRID curation (made from the full text or supplementary data) is deferred to; the partner-type mapping is supported by independent RAF1 evidence cited here. Proposed replacements: 14-3-3 protein binding Supporting Evidence: file:human/RAF1/RAF1-uniprot.txt the binding of a 14-3-3 protein that contacts two phosphorylation file:human/RAF1/RAF1-uniprot.txt P04049; Q04917: YWHAH; NbExp=27; IntAct=EBI-365996, EBI-306940; |
| GO:0005515 protein binding | IPI PMID:32707033 Kinase Interaction Network Expands Functional and Disease Ro... | MODIFY | Summary: IPI (kinase interaction network (Buljan et al.) AP-MS of human kinases) for RAF1 binding CDC37 (HSP90 kinase co-chaperone). Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is CDC37 (HSP90 kinase co-chaperone). The partner is a protein-folding chaperone or co-chaperone, and RAF1 is a chaperone client (HSP90-CDC37 dependence is well established); protein-folding chaperone binding describes the interaction from the RAF1 side. The cached text of this reference does not describe the RAF1 interaction, so the IntAct/BioGRID curation (made from the full text or supplementary data) is deferred to; the partner-type mapping is supported by independent RAF1 evidence cited here. Proposed replacements: protein-folding chaperone binding Supporting Evidence: file:human/RAF1/RAF1-uniprot.txt complex composed of chaperones HSP90 and HSP70, co-chaperones CDC37, file:human/RAF1/RAF1-uniprot.txt P04049; Q16543: CDC37; NbExp=20; IntAct=EBI-365996, EBI-295634; |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: IPI (neurodegenerative-disease protein interactome (yeast two-hybrid)) for RAF1 binding APP. Reason: GO:0005515 protein binding is uninformative. Large-scale neurodegeneration-protein interactome hit without functional characterisation for RAF1. Removal does not mean the reported interaction is false; it means no informative RAF1 molecular-function term can be justified from it. Supporting Evidence: file:human/RAF1/RAF1-uniprot.txt P04049; P05067: APP; NbExp=3; IntAct=EBI-365996, EBI-77613; |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: IPI (neurodegenerative-disease protein interactome (yeast two-hybrid)) for RAF1 binding CASP8. Reason: GO:0005515 protein binding is uninformative. Large-scale neurodegeneration-protein interactome hit without functional characterisation for RAF1. Removal does not mean the reported interaction is false; it means no informative RAF1 molecular-function term can be justified from it. Supporting Evidence: file:human/RAF1/RAF1-uniprot.txt P04049; Q14790: CASP8; NbExp=3; IntAct=EBI-365996, EBI-78060; |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MODIFY | Summary: IPI (BioPlex 3.0 dual-cell-line AP-MS interactome) for RAF1 binding BRAF. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is BRAF. RAF1 forms side-to-side kinase-domain heterodimers with BRAF, the most active RAF species and the basis of paradoxical activation by RAF inhibitors; protein heterodimerization activity is the informative term (same term as the BRAF review). The cached text of this reference does not describe the RAF1 interaction, so the IntAct/BioGRID curation (made from the full text or supplementary data) is deferred to; the partner-type mapping is supported by independent RAF1 evidence cited here. Proposed replacements: protein heterodimerization activity Supporting Evidence: file:human/RAF1/RAF1-uniprot.txt Heterodimerizes with BRAF and this file:human/RAF1/RAF1-uniprot.txt P04049; P15056: BRAF; NbExp=73; IntAct=EBI-365996, EBI-365980; |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MODIFY | Summary: IPI (BioPlex 3.0 dual-cell-line AP-MS interactome) for RAF1 binding YWHAQ. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is YWHAQ. RAF1 is a canonical phospho-dependent 14-3-3 client: a 14-3-3 dimer engaging pSer259 and pSer621 holds the autoinhibited monomer, and the pSer621 site also stabilises the active dimer. 14-3-3 protein binding captures this regulatory interaction (same term as the BRAF review). The cached text of this reference does not describe the RAF1 interaction, so the IntAct/BioGRID curation (made from the full text or supplementary data) is deferred to; the partner-type mapping is supported by independent RAF1 evidence cited here. Proposed replacements: 14-3-3 protein binding Supporting Evidence: file:human/RAF1/RAF1-uniprot.txt the binding of a 14-3-3 protein that contacts two phosphorylation file:human/RAF1/RAF1-uniprot.txt P04049; P27348: YWHAQ; NbExp=24; IntAct=EBI-365996, EBI-359854; |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MODIFY | Summary: IPI (BioPlex 3.0 dual-cell-line AP-MS interactome) for RAF1 binding YWHAB. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is YWHAB. RAF1 is a canonical phospho-dependent 14-3-3 client: a 14-3-3 dimer engaging pSer259 and pSer621 holds the autoinhibited monomer, and the pSer621 site also stabilises the active dimer. 14-3-3 protein binding captures this regulatory interaction (same term as the BRAF review). The cached text of this reference does not describe the RAF1 interaction, so the IntAct/BioGRID curation (made from the full text or supplementary data) is deferred to; the partner-type mapping is supported by independent RAF1 evidence cited here. Proposed replacements: 14-3-3 protein binding Supporting Evidence: file:human/RAF1/RAF1-uniprot.txt the binding of a 14-3-3 protein that contacts two phosphorylation file:human/RAF1/RAF1-uniprot.txt P04049; P31946: YWHAB; NbExp=39; IntAct=EBI-365996, EBI-359815; |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MODIFY | Summary: IPI (BioPlex 3.0 dual-cell-line AP-MS interactome) for RAF1 binding YWHAG. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is YWHAG. RAF1 is a canonical phospho-dependent 14-3-3 client: a 14-3-3 dimer engaging pSer259 and pSer621 holds the autoinhibited monomer, and the pSer621 site also stabilises the active dimer. 14-3-3 protein binding captures this regulatory interaction (same term as the BRAF review). The cached text of this reference does not describe the RAF1 interaction, so the IntAct/BioGRID curation (made from the full text or supplementary data) is deferred to; the partner-type mapping is supported by independent RAF1 evidence cited here. Proposed replacements: 14-3-3 protein binding Supporting Evidence: file:human/RAF1/RAF1-uniprot.txt the binding of a 14-3-3 protein that contacts two phosphorylation file:human/RAF1/RAF1-uniprot.txt P04049; P61981: YWHAG; NbExp=24; IntAct=EBI-365996, EBI-359832; |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MODIFY | Summary: IPI (BioPlex 3.0 dual-cell-line AP-MS interactome) for RAF1 binding YWHAH. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is YWHAH. RAF1 is a canonical phospho-dependent 14-3-3 client: a 14-3-3 dimer engaging pSer259 and pSer621 holds the autoinhibited monomer, and the pSer621 site also stabilises the active dimer. 14-3-3 protein binding captures this regulatory interaction (same term as the BRAF review). The cached text of this reference does not describe the RAF1 interaction, so the IntAct/BioGRID curation (made from the full text or supplementary data) is deferred to; the partner-type mapping is supported by independent RAF1 evidence cited here. Proposed replacements: 14-3-3 protein binding Supporting Evidence: file:human/RAF1/RAF1-uniprot.txt the binding of a 14-3-3 protein that contacts two phosphorylation file:human/RAF1/RAF1-uniprot.txt P04049; Q04917: YWHAH; NbExp=27; IntAct=EBI-365996, EBI-306940; |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MODIFY | Summary: IPI (BioPlex 3.0 dual-cell-line AP-MS interactome) for RAF1 binding CDC37 (HSP90 kinase co-chaperone). Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is CDC37 (HSP90 kinase co-chaperone). The partner is a protein-folding chaperone or co-chaperone, and RAF1 is a chaperone client (HSP90-CDC37 dependence is well established); protein-folding chaperone binding describes the interaction from the RAF1 side. The cached text of this reference does not describe the RAF1 interaction, so the IntAct/BioGRID curation (made from the full text or supplementary data) is deferred to; the partner-type mapping is supported by independent RAF1 evidence cited here. Proposed replacements: protein-folding chaperone binding Supporting Evidence: file:human/RAF1/RAF1-uniprot.txt complex composed of chaperones HSP90 and HSP70, co-chaperones CDC37, file:human/RAF1/RAF1-uniprot.txt P04049; Q16543: CDC37; NbExp=20; IntAct=EBI-365996, EBI-295634; |
| GO:0005515 protein binding | IPI PMID:34591612 A protein interaction landscape of breast cancer. | MODIFY | Summary: IPI (breast cancer protein interaction landscape (AP-MS)) for RAF1 binding HRAS. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is HRAS. RAF1 is a direct RAS effector: its RAS-binding domain (RBD) and CRD bind GTP-loaded RAS family GTPases, recruiting RAF1 to the plasma membrane; this is the entry step of RAF activation. small GTPase binding is the informative term (same term as the BRAF review). The cached text of this reference does not describe the RAF1 interaction, so the IntAct/BioGRID curation (made from the full text or supplementary data) is deferred to; the partner-type mapping is supported by independent RAF1 evidence cited here. Proposed replacements: small GTPase binding Supporting Evidence: file:human/RAF1/RAF1-uniprot.txt Ras-GTP recruits RAF1 to the file:human/RAF1/RAF1-uniprot.txt P04049; P01112: HRAS; NbExp=30; IntAct=EBI-365996, EBI-350145; |
| GO:0005515 protein binding | IPI PMID:34591642 A protein network map of head and neck cancer reveals PIK3CA... | MODIFY | Summary: IPI (head and neck cancer protein network map (AP-MS)) for RAF1 binding NRAS. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is NRAS. RAF1 is a direct RAS effector: its RAS-binding domain (RBD) and CRD bind GTP-loaded RAS family GTPases, recruiting RAF1 to the plasma membrane; this is the entry step of RAF activation. small GTPase binding is the informative term (same term as the BRAF review). The cached text of this reference does not describe the RAF1 interaction, so the IntAct/BioGRID curation (made from the full text or supplementary data) is deferred to; the partner-type mapping is supported by independent RAF1 evidence cited here. Proposed replacements: small GTPase binding Supporting Evidence: file:human/RAF1/RAF1-uniprot.txt Ras-GTP recruits RAF1 to the file:human/RAF1/RAF1-uniprot.txt P04049; P01111: NRAS; NbExp=15; IntAct=EBI-365996, EBI-721993; |
| GO:0005515 protein binding | IPI PMID:34591642 A protein network map of head and neck cancer reveals PIK3CA... | MODIFY | Summary: IPI (head and neck cancer protein network map (AP-MS)) for RAF1 binding HRAS. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is HRAS. RAF1 is a direct RAS effector: its RAS-binding domain (RBD) and CRD bind GTP-loaded RAS family GTPases, recruiting RAF1 to the plasma membrane; this is the entry step of RAF activation. small GTPase binding is the informative term (same term as the BRAF review). The cached text of this reference does not describe the RAF1 interaction, so the IntAct/BioGRID curation (made from the full text or supplementary data) is deferred to; the partner-type mapping is supported by independent RAF1 evidence cited here. Proposed replacements: small GTPase binding Supporting Evidence: file:human/RAF1/RAF1-uniprot.txt Ras-GTP recruits RAF1 to the file:human/RAF1/RAF1-uniprot.txt P04049; P01112: HRAS; NbExp=30; IntAct=EBI-365996, EBI-350145; |
| GO:0005515 protein binding | IPI PMID:35044719 Proteome-scale mapping of binding sites in the unstructured ... | MODIFY | Summary: IPI (proteome-scale phage-display mapping of SLiM binding sites) for RAF1 binding SFN (14-3-3 sigma). Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is SFN (14-3-3 sigma). RAF1 is a canonical phospho-dependent 14-3-3 client: a 14-3-3 dimer engaging pSer259 and pSer621 holds the autoinhibited monomer, and the pSer621 site also stabilises the active dimer. 14-3-3 protein binding captures this regulatory interaction (same term as the BRAF review). The cached text of this reference does not describe the RAF1 interaction, so the IntAct/BioGRID curation (made from the full text or supplementary data) is deferred to; the partner-type mapping is supported by independent RAF1 evidence cited here. Proposed replacements: 14-3-3 protein binding Supporting Evidence: file:human/RAF1/RAF1-uniprot.txt the binding of a 14-3-3 protein that contacts two phosphorylation file:human/RAF1/RAF1-uniprot.txt P04049; P31947: SFN; NbExp=9; IntAct=EBI-365996, EBI-476295; |
| GO:0005515 protein binding | IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce... | MODIFY | Summary: IPI (OpenCell endogenous-tagging interactome) for RAF1 binding YWHAQ. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is YWHAQ. RAF1 is a canonical phospho-dependent 14-3-3 client: a 14-3-3 dimer engaging pSer259 and pSer621 holds the autoinhibited monomer, and the pSer621 site also stabilises the active dimer. 14-3-3 protein binding captures this regulatory interaction (same term as the BRAF review). The cached text of this reference does not describe the RAF1 interaction, so the IntAct/BioGRID curation (made from the full text or supplementary data) is deferred to; the partner-type mapping is supported by independent RAF1 evidence cited here. Proposed replacements: 14-3-3 protein binding Supporting Evidence: file:human/RAF1/RAF1-uniprot.txt the binding of a 14-3-3 protein that contacts two phosphorylation file:human/RAF1/RAF1-uniprot.txt P04049; P27348: YWHAQ; NbExp=24; IntAct=EBI-365996, EBI-359854; |
| GO:0005515 protein binding | IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce... | MODIFY | Summary: IPI (OpenCell endogenous-tagging interactome) for RAF1 binding YWHAB. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is YWHAB. RAF1 is a canonical phospho-dependent 14-3-3 client: a 14-3-3 dimer engaging pSer259 and pSer621 holds the autoinhibited monomer, and the pSer621 site also stabilises the active dimer. 14-3-3 protein binding captures this regulatory interaction (same term as the BRAF review). The cached text of this reference does not describe the RAF1 interaction, so the IntAct/BioGRID curation (made from the full text or supplementary data) is deferred to; the partner-type mapping is supported by independent RAF1 evidence cited here. Proposed replacements: 14-3-3 protein binding Supporting Evidence: file:human/RAF1/RAF1-uniprot.txt the binding of a 14-3-3 protein that contacts two phosphorylation file:human/RAF1/RAF1-uniprot.txt P04049; P31946: YWHAB; NbExp=39; IntAct=EBI-365996, EBI-359815; |
| GO:0005515 protein binding | IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce... | MODIFY | Summary: IPI (OpenCell endogenous-tagging interactome) for RAF1 binding MAP2K2/MEK2. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is MAP2K2/MEK2. MEK1/MEK2 are the physiological substrates of RAF1 and form RAF-MEK complexes; MAPKK binding is the informative term (same term as the BRAF review). The cached text of this reference does not describe the RAF1 interaction, so the IntAct/BioGRID curation (made from the full text or supplementary data) is deferred to; the partner-type mapping is supported by independent RAF1 evidence cited here. Proposed replacements: mitogen-activated protein kinase kinase binding Supporting Evidence: file:human/RAF1/RAF1-uniprot.txt Interacts with MAP2K1/MEK1 and file:human/RAF1/RAF1-uniprot.txt P04049; P36507: MAP2K2; NbExp=7; IntAct=EBI-365996, EBI-1056930; |
| GO:0005515 protein binding | IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce... | MODIFY | Summary: IPI (OpenCell endogenous-tagging interactome) for RAF1 binding YWHAG. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is YWHAG. RAF1 is a canonical phospho-dependent 14-3-3 client: a 14-3-3 dimer engaging pSer259 and pSer621 holds the autoinhibited monomer, and the pSer621 site also stabilises the active dimer. 14-3-3 protein binding captures this regulatory interaction (same term as the BRAF review). The cached text of this reference does not describe the RAF1 interaction, so the IntAct/BioGRID curation (made from the full text or supplementary data) is deferred to; the partner-type mapping is supported by independent RAF1 evidence cited here. Proposed replacements: 14-3-3 protein binding Supporting Evidence: file:human/RAF1/RAF1-uniprot.txt the binding of a 14-3-3 protein that contacts two phosphorylation file:human/RAF1/RAF1-uniprot.txt P04049; P61981: YWHAG; NbExp=24; IntAct=EBI-365996, EBI-359832; |
| GO:0005515 protein binding | IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce... | MODIFY | Summary: IPI (OpenCell endogenous-tagging interactome) for RAF1 binding YWHAE. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is YWHAE. RAF1 is a canonical phospho-dependent 14-3-3 client: a 14-3-3 dimer engaging pSer259 and pSer621 holds the autoinhibited monomer, and the pSer621 site also stabilises the active dimer. 14-3-3 protein binding captures this regulatory interaction (same term as the BRAF review). The cached text of this reference does not describe the RAF1 interaction, so the IntAct/BioGRID curation (made from the full text or supplementary data) is deferred to; the partner-type mapping is supported by independent RAF1 evidence cited here. Proposed replacements: 14-3-3 protein binding Supporting Evidence: file:human/RAF1/RAF1-uniprot.txt the binding of a 14-3-3 protein that contacts two phosphorylation file:human/RAF1/RAF1-uniprot.txt P04049; P62258: YWHAE; NbExp=25; IntAct=EBI-365996, EBI-356498; |
| GO:0005515 protein binding | IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce... | MODIFY | Summary: IPI (OpenCell endogenous-tagging interactome) for RAF1 binding YWHAZ. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is YWHAZ. RAF1 is a canonical phospho-dependent 14-3-3 client: a 14-3-3 dimer engaging pSer259 and pSer621 holds the autoinhibited monomer, and the pSer621 site also stabilises the active dimer. 14-3-3 protein binding captures this regulatory interaction (same term as the BRAF review). The cached text of this reference does not describe the RAF1 interaction, so the IntAct/BioGRID curation (made from the full text or supplementary data) is deferred to; the partner-type mapping is supported by independent RAF1 evidence cited here. Proposed replacements: 14-3-3 protein binding Supporting Evidence: file:human/RAF1/RAF1-uniprot.txt the binding of a 14-3-3 protein that contacts two phosphorylation file:human/RAF1/RAF1-uniprot.txt P04049; P63104: YWHAZ; NbExp=32; IntAct=EBI-365996, EBI-347088; |
| GO:0005515 protein binding | IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce... | MODIFY | Summary: IPI (OpenCell endogenous-tagging interactome) for RAF1 binding MAP2K1/MEK1. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is MAP2K1/MEK1. MEK1/MEK2 are the physiological substrates of RAF1 and form RAF-MEK complexes; MAPKK binding is the informative term (same term as the BRAF review). The cached text of this reference does not describe the RAF1 interaction, so the IntAct/BioGRID curation (made from the full text or supplementary data) is deferred to; the partner-type mapping is supported by independent RAF1 evidence cited here. Proposed replacements: mitogen-activated protein kinase kinase binding Supporting Evidence: file:human/RAF1/RAF1-uniprot.txt Interacts with MAP2K1/MEK1 and file:human/RAF1/RAF1-uniprot.txt P04049; Q02750: MAP2K1; NbExp=39; IntAct=EBI-365996, EBI-492564; |
| GO:0005515 protein binding | IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce... | MODIFY | Summary: IPI (OpenCell endogenous-tagging interactome) for RAF1 binding YWHAH. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is YWHAH. RAF1 is a canonical phospho-dependent 14-3-3 client: a 14-3-3 dimer engaging pSer259 and pSer621 holds the autoinhibited monomer, and the pSer621 site also stabilises the active dimer. 14-3-3 protein binding captures this regulatory interaction (same term as the BRAF review). The cached text of this reference does not describe the RAF1 interaction, so the IntAct/BioGRID curation (made from the full text or supplementary data) is deferred to; the partner-type mapping is supported by independent RAF1 evidence cited here. Proposed replacements: 14-3-3 protein binding Supporting Evidence: file:human/RAF1/RAF1-uniprot.txt the binding of a 14-3-3 protein that contacts two phosphorylation file:human/RAF1/RAF1-uniprot.txt P04049; Q04917: YWHAH; NbExp=27; IntAct=EBI-365996, EBI-306940; |
| GO:0005515 protein binding | IPI PMID:35512704 Systematic discovery of mutation-directed neo-protein-protei... | MODIFY | Summary: IPI (systematic discovery of mutation-directed neo-protein-protein interactions) for RAF1 binding EGFR. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is EGFR. The partner is a protein kinase that either regulates RAF1 by phosphorylation (PAK S338, AKT S259), is inhibited by RAF1 binding (MST2), or is an upstream receptor tyrosine kinase; protein kinase binding is the informative term. The cached text of this reference does not describe the RAF1 interaction, so the IntAct/BioGRID curation (made from the full text or supplementary data) is deferred to; the partner-type mapping is supported by independent RAF1 evidence cited here. Proposed replacements: protein kinase binding Supporting Evidence: file:human/RAF1/RAF1-uniprot.txt P04049; P00533: EGFR; NbExp=3; IntAct=EBI-365996, EBI-297353; |
| GO:0005515 protein binding | IPI PMID:35512704 Systematic discovery of mutation-directed neo-protein-protei... | MODIFY | Summary: IPI (systematic discovery of mutation-directed neo-protein-protein interactions) for RAF1 binding BRAF. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is BRAF. RAF1 forms side-to-side kinase-domain heterodimers with BRAF, the most active RAF species and the basis of paradoxical activation by RAF inhibitors; protein heterodimerization activity is the informative term (same term as the BRAF review). The cached text of this reference does not describe the RAF1 interaction, so the IntAct/BioGRID curation (made from the full text or supplementary data) is deferred to; the partner-type mapping is supported by independent RAF1 evidence cited here. Proposed replacements: protein heterodimerization activity Supporting Evidence: file:human/RAF1/RAF1-uniprot.txt Heterodimerizes with BRAF and this file:human/RAF1/RAF1-uniprot.txt P04049; P15056: BRAF; NbExp=73; IntAct=EBI-365996, EBI-365980; |
| GO:0005515 protein binding | IPI PMID:35512704 Systematic discovery of mutation-directed neo-protein-protei... | MODIFY | Summary: IPI (systematic discovery of mutation-directed neo-protein-protein interactions) for RAF1 binding AKT1. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is AKT1. The partner is a protein kinase that either regulates RAF1 by phosphorylation (PAK S338, AKT S259), is inhibited by RAF1 binding (MST2), or is an upstream receptor tyrosine kinase; protein kinase binding is the informative term. The cached text of this reference does not describe the RAF1 interaction, so the IntAct/BioGRID curation (made from the full text or supplementary data) is deferred to; the partner-type mapping is supported by independent RAF1 evidence cited here. Proposed replacements: protein kinase binding Supporting Evidence: file:human/RAF1/RAF1-uniprot.txt P04049; P31749: AKT1; NbExp=3; IntAct=EBI-365996, EBI-296087; |
| GO:0005515 protein binding | IPI PMID:35512704 Systematic discovery of mutation-directed neo-protein-protei... | REMOVE | Summary: IPI (systematic discovery of mutation-directed neo-protein-protein interactions) for RAF1 binding SMAD4. Reason: GO:0005515 protein binding is uninformative. Neo-PPI screen hit (mutation-directed interactions) without functional characterisation for RAF1. Removal does not mean the reported interaction is false; it means no informative RAF1 molecular-function term can be justified from it. Supporting Evidence: file:human/RAF1/RAF1-uniprot.txt P04049; Q13485: SMAD4; NbExp=6; IntAct=EBI-365996, EBI-347263; |
| GO:0005515 protein binding | IPI PMID:35839996 A Proteomic Approach Identifies Isoform-Specific and Nucleot... | MODIFY | Summary: IPI (proteomic study of isoform- and nucleotide-dependent RAS interactors) for RAF1 binding NRAS. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is NRAS. RAF1 is a direct RAS effector: its RAS-binding domain (RBD) and CRD bind GTP-loaded RAS family GTPases, recruiting RAF1 to the plasma membrane; this is the entry step of RAF activation. small GTPase binding is the informative term (same term as the BRAF review). Proposed replacements: small GTPase binding Supporting Evidence: PMID:35839996 RAF1 interacted with WT and G12D forms of KRAS4A similarly file:human/RAF1/RAF1-uniprot.txt P04049; P01111: NRAS; NbExp=15; IntAct=EBI-365996, EBI-721993; |
| GO:0005515 protein binding | IPI PMID:35839996 A Proteomic Approach Identifies Isoform-Specific and Nucleot... | MODIFY | Summary: IPI (proteomic study of isoform- and nucleotide-dependent RAS interactors) for RAF1 binding HRAS. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is HRAS. RAF1 is a direct RAS effector: its RAS-binding domain (RBD) and CRD bind GTP-loaded RAS family GTPases, recruiting RAF1 to the plasma membrane; this is the entry step of RAF activation. small GTPase binding is the informative term (same term as the BRAF review). Proposed replacements: small GTPase binding Supporting Evidence: PMID:35839996 RAF1 interacted with WT and G12D forms of KRAS4A similarly file:human/RAF1/RAF1-uniprot.txt P04049; P01112: HRAS; NbExp=30; IntAct=EBI-365996, EBI-350145; |
| GO:0005515 protein binding | IPI PMID:35839996 A Proteomic Approach Identifies Isoform-Specific and Nucleot... | MODIFY | Summary: IPI (proteomic study of isoform- and nucleotide-dependent RAS interactors) for RAF1 binding KRAS isoform 2B (KRAS4B). Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is KRAS isoform 2B (KRAS4B). RAF1 is a direct RAS effector: its RAS-binding domain (RBD) and CRD bind GTP-loaded RAS family GTPases, recruiting RAF1 to the plasma membrane; this is the entry step of RAF activation. small GTPase binding is the informative term (same term as the BRAF review). Proposed replacements: small GTPase binding Supporting Evidence: PMID:35839996 RAF1 interacted with WT and G12D forms of KRAS4A similarly file:human/RAF1/RAF1-uniprot.txt P04049; P01116-2: KRAS; NbExp=6; IntAct=EBI-365996, EBI-367427; |
| GO:0005515 protein binding | IPI PMID:36175670 Structure of the SHOC2-MRAS-PP1C complex provides insights i... | MODIFY | Summary: IPI (cryo-EM/biochemistry of the SHOC2-MRAS-PP1C complex acting on RAF) for RAF1 binding PPP1CA (PP1 catalytic subunit). Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is PPP1CA (PP1 catalytic subunit). The partner is (a subunit of) a protein phosphatase that dephosphorylates RAF1 (PP2A, PP1C on pSer259) or, for CDC25A, a phosphatase that RAF1 binds and activates; phosphatase binding is the informative term. Proposed replacements: phosphatase binding Supporting Evidence: PMID:36175670 Dephosphorylation activity of PP1C towards RAF substrates is enhanced upon complex formation with SHOC2 and MRAS. file:human/RAF1/RAF1-uniprot.txt P04049; P62136: PPP1CA; NbExp=2; IntAct=EBI-365996, EBI-357253; |
| GO:0005515 protein binding | IPI PMID:36241744 HERC2 deficiency activates C-RAF/MKK3/p38 signalling pathway... | MODIFY | Summary: IPI (study showing HERC2 regulates C-RAF ubiquitylation) for RAF1 binding HERC2 (HECT E3 ubiquitin ligase). Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is HERC2 (HECT E3 ubiquitin ligase). The partner is an E3 ubiquitin ligase acting on RAF1 as a substrate/client; ubiquitin protein ligase binding is the informative term (same choice as the BRAF review for HERC2). Proposed replacements: ubiquitin protein ligase binding Supporting Evidence: PMID:36241744 HERC2 regulates C-RAF ubiquitylation file:human/RAF1/RAF1-uniprot.txt P04049; O95714: HERC2; NbExp=6; IntAct=EBI-365996, EBI-1058922; |
| GO:0005515 protein binding | IPI PMID:36931259 A central chaperone-like role for 14-3-3 proteins in human c... | MODIFY | Summary: IPI (proteome-wide study of 14-3-3 chaperone-like clients) for RAF1 binding YWHAQ. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is YWHAQ. RAF1 is a canonical phospho-dependent 14-3-3 client: a 14-3-3 dimer engaging pSer259 and pSer621 holds the autoinhibited monomer, and the pSer621 site also stabilises the active dimer. 14-3-3 protein binding captures this regulatory interaction (same term as the BRAF review). The cached text of this reference does not describe the RAF1 interaction, so the IntAct/BioGRID curation (made from the full text or supplementary data) is deferred to; the partner-type mapping is supported by independent RAF1 evidence cited here. Proposed replacements: 14-3-3 protein binding Supporting Evidence: file:human/RAF1/RAF1-uniprot.txt the binding of a 14-3-3 protein that contacts two phosphorylation file:human/RAF1/RAF1-uniprot.txt P04049; P27348: YWHAQ; NbExp=24; IntAct=EBI-365996, EBI-359854; |
| GO:0005515 protein binding | IPI PMID:36931259 A central chaperone-like role for 14-3-3 proteins in human c... | MODIFY | Summary: IPI (proteome-wide study of 14-3-3 chaperone-like clients) for RAF1 binding YWHAB. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is YWHAB. RAF1 is a canonical phospho-dependent 14-3-3 client: a 14-3-3 dimer engaging pSer259 and pSer621 holds the autoinhibited monomer, and the pSer621 site also stabilises the active dimer. 14-3-3 protein binding captures this regulatory interaction (same term as the BRAF review). The cached text of this reference does not describe the RAF1 interaction, so the IntAct/BioGRID curation (made from the full text or supplementary data) is deferred to; the partner-type mapping is supported by independent RAF1 evidence cited here. Proposed replacements: 14-3-3 protein binding Supporting Evidence: file:human/RAF1/RAF1-uniprot.txt the binding of a 14-3-3 protein that contacts two phosphorylation file:human/RAF1/RAF1-uniprot.txt P04049; P31946: YWHAB; NbExp=39; IntAct=EBI-365996, EBI-359815; |
| GO:0005515 protein binding | IPI PMID:36931259 A central chaperone-like role for 14-3-3 proteins in human c... | MODIFY | Summary: IPI (proteome-wide study of 14-3-3 chaperone-like clients) for RAF1 binding SFN (14-3-3 sigma). Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is SFN (14-3-3 sigma). RAF1 is a canonical phospho-dependent 14-3-3 client: a 14-3-3 dimer engaging pSer259 and pSer621 holds the autoinhibited monomer, and the pSer621 site also stabilises the active dimer. 14-3-3 protein binding captures this regulatory interaction (same term as the BRAF review). The cached text of this reference does not describe the RAF1 interaction, so the IntAct/BioGRID curation (made from the full text or supplementary data) is deferred to; the partner-type mapping is supported by independent RAF1 evidence cited here. Proposed replacements: 14-3-3 protein binding Supporting Evidence: file:human/RAF1/RAF1-uniprot.txt the binding of a 14-3-3 protein that contacts two phosphorylation file:human/RAF1/RAF1-uniprot.txt P04049; P31947: SFN; NbExp=9; IntAct=EBI-365996, EBI-476295; |
| GO:0005515 protein binding | IPI PMID:36931259 A central chaperone-like role for 14-3-3 proteins in human c... | MODIFY | Summary: IPI (proteome-wide study of 14-3-3 chaperone-like clients) for RAF1 binding YWHAG. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is YWHAG. RAF1 is a canonical phospho-dependent 14-3-3 client: a 14-3-3 dimer engaging pSer259 and pSer621 holds the autoinhibited monomer, and the pSer621 site also stabilises the active dimer. 14-3-3 protein binding captures this regulatory interaction (same term as the BRAF review). The cached text of this reference does not describe the RAF1 interaction, so the IntAct/BioGRID curation (made from the full text or supplementary data) is deferred to; the partner-type mapping is supported by independent RAF1 evidence cited here. Proposed replacements: 14-3-3 protein binding Supporting Evidence: file:human/RAF1/RAF1-uniprot.txt the binding of a 14-3-3 protein that contacts two phosphorylation file:human/RAF1/RAF1-uniprot.txt P04049; P61981: YWHAG; NbExp=24; IntAct=EBI-365996, EBI-359832; |
| GO:0005515 protein binding | IPI PMID:36931259 A central chaperone-like role for 14-3-3 proteins in human c... | MODIFY | Summary: IPI (proteome-wide study of 14-3-3 chaperone-like clients) for RAF1 binding YWHAE. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is YWHAE. RAF1 is a canonical phospho-dependent 14-3-3 client: a 14-3-3 dimer engaging pSer259 and pSer621 holds the autoinhibited monomer, and the pSer621 site also stabilises the active dimer. 14-3-3 protein binding captures this regulatory interaction (same term as the BRAF review). The cached text of this reference does not describe the RAF1 interaction, so the IntAct/BioGRID curation (made from the full text or supplementary data) is deferred to; the partner-type mapping is supported by independent RAF1 evidence cited here. Proposed replacements: 14-3-3 protein binding Supporting Evidence: file:human/RAF1/RAF1-uniprot.txt the binding of a 14-3-3 protein that contacts two phosphorylation file:human/RAF1/RAF1-uniprot.txt P04049; P62258: YWHAE; NbExp=25; IntAct=EBI-365996, EBI-356498; |
| GO:0005515 protein binding | IPI PMID:36931259 A central chaperone-like role for 14-3-3 proteins in human c... | MODIFY | Summary: IPI (proteome-wide study of 14-3-3 chaperone-like clients) for RAF1 binding YWHAZ. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is YWHAZ. RAF1 is a canonical phospho-dependent 14-3-3 client: a 14-3-3 dimer engaging pSer259 and pSer621 holds the autoinhibited monomer, and the pSer621 site also stabilises the active dimer. 14-3-3 protein binding captures this regulatory interaction (same term as the BRAF review). The cached text of this reference does not describe the RAF1 interaction, so the IntAct/BioGRID curation (made from the full text or supplementary data) is deferred to; the partner-type mapping is supported by independent RAF1 evidence cited here. Proposed replacements: 14-3-3 protein binding Supporting Evidence: file:human/RAF1/RAF1-uniprot.txt the binding of a 14-3-3 protein that contacts two phosphorylation file:human/RAF1/RAF1-uniprot.txt P04049; P63104: YWHAZ; NbExp=32; IntAct=EBI-365996, EBI-347088; |
| GO:0005515 protein binding | IPI PMID:36931259 A central chaperone-like role for 14-3-3 proteins in human c... | MODIFY | Summary: IPI (proteome-wide study of 14-3-3 chaperone-like clients) for RAF1 binding YWHAH. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is YWHAH. RAF1 is a canonical phospho-dependent 14-3-3 client: a 14-3-3 dimer engaging pSer259 and pSer621 holds the autoinhibited monomer, and the pSer621 site also stabilises the active dimer. 14-3-3 protein binding captures this regulatory interaction (same term as the BRAF review). The cached text of this reference does not describe the RAF1 interaction, so the IntAct/BioGRID curation (made from the full text or supplementary data) is deferred to; the partner-type mapping is supported by independent RAF1 evidence cited here. Proposed replacements: 14-3-3 protein binding Supporting Evidence: file:human/RAF1/RAF1-uniprot.txt the binding of a 14-3-3 protein that contacts two phosphorylation file:human/RAF1/RAF1-uniprot.txt P04049; Q04917: YWHAH; NbExp=27; IntAct=EBI-365996, EBI-306940; |
| GO:0005515 protein binding | IPI PMID:37045861 Interactome dynamics of RAF1-BRAF kinase monomers and dimers... | MODIFY | Summary: IPI (quantitative interactomes of RAF1 monomers and RAF1-BRAF dimers) for RAF1 binding BAG2 (HSP70 co-chaperone). Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is BAG2 (HSP70 co-chaperone). The partner is a protein-folding chaperone or co-chaperone, and RAF1 is a chaperone client (HSP90-CDC37 dependence is well established); protein-folding chaperone binding describes the interaction from the RAF1 side. Proposed replacements: protein-folding chaperone binding Supporting Evidence: PMID:37045861 using quantitative proteomics we mapped the interactomes of RAF1 monomers, RAF1-BRAF and RAF1-BRAFV600E dimers file:human/RAF1/RAF1-uniprot.txt P04049; O95816: BAG2; NbExp=12; IntAct=EBI-365996, EBI-355275; |
| GO:0005515 protein binding | IPI PMID:37045861 Interactome dynamics of RAF1-BRAF kinase monomers and dimers... | MODIFY | Summary: IPI (quantitative interactomes of RAF1 monomers and RAF1-BRAF dimers) for RAF1 binding HSP90AA1. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is HSP90AA1. RAF1 is a strongly HSP90-dependent client kinase whose folding and stability require HSP90-CDC37; Hsp90 protein binding is the informative term (same term as the BRAF review). Proposed replacements: Hsp90 protein binding Supporting Evidence: PMID:37045861 using quantitative proteomics we mapped the interactomes of RAF1 monomers, RAF1-BRAF and RAF1-BRAFV600E dimers file:human/RAF1/RAF1-uniprot.txt P04049; P07900: HSP90AA1; NbExp=15; IntAct=EBI-365996, EBI-296047; |
| GO:0005515 protein binding | IPI PMID:37045861 Interactome dynamics of RAF1-BRAF kinase monomers and dimers... | MODIFY | Summary: IPI (quantitative interactomes of RAF1 monomers and RAF1-BRAF dimers) for RAF1 binding HSP90AB1. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is HSP90AB1. RAF1 is a strongly HSP90-dependent client kinase whose folding and stability require HSP90-CDC37; Hsp90 protein binding is the informative term (same term as the BRAF review). Proposed replacements: Hsp90 protein binding Supporting Evidence: PMID:37045861 using quantitative proteomics we mapped the interactomes of RAF1 monomers, RAF1-BRAF and RAF1-BRAFV600E dimers file:human/RAF1/RAF1-uniprot.txt P04049; P08238: HSP90AB1; NbExp=17; IntAct=EBI-365996, EBI-352572; |
| GO:0005515 protein binding | IPI PMID:37045861 Interactome dynamics of RAF1-BRAF kinase monomers and dimers... | MODIFY | Summary: IPI (quantitative interactomes of RAF1 monomers and RAF1-BRAF dimers) for RAF1 binding BRAF. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is BRAF. RAF1 forms side-to-side kinase-domain heterodimers with BRAF, the most active RAF species and the basis of paradoxical activation by RAF inhibitors; protein heterodimerization activity is the informative term (same term as the BRAF review). Proposed replacements: protein heterodimerization activity Supporting Evidence: PMID:37045861 using quantitative proteomics we mapped the interactomes of RAF1 monomers, RAF1-BRAF and RAF1-BRAFV600E dimers file:human/RAF1/RAF1-uniprot.txt P04049; P15056: BRAF; NbExp=73; IntAct=EBI-365996, EBI-365980; |
| GO:0005515 protein binding | IPI PMID:37045861 Interactome dynamics of RAF1-BRAF kinase monomers and dimers... | MODIFY | Summary: IPI (quantitative interactomes of RAF1 monomers and RAF1-BRAF dimers) for RAF1 binding YWHAQ. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is YWHAQ. RAF1 is a canonical phospho-dependent 14-3-3 client: a 14-3-3 dimer engaging pSer259 and pSer621 holds the autoinhibited monomer, and the pSer621 site also stabilises the active dimer. 14-3-3 protein binding captures this regulatory interaction (same term as the BRAF review). Proposed replacements: 14-3-3 protein binding Supporting Evidence: PMID:37045861 using quantitative proteomics we mapped the interactomes of RAF1 monomers, RAF1-BRAF and RAF1-BRAFV600E dimers file:human/RAF1/RAF1-uniprot.txt P04049; P27348: YWHAQ; NbExp=24; IntAct=EBI-365996, EBI-359854; |
| GO:0005515 protein binding | IPI PMID:37045861 Interactome dynamics of RAF1-BRAF kinase monomers and dimers... | MODIFY | Summary: IPI (quantitative interactomes of RAF1 monomers and RAF1-BRAF dimers) for RAF1 binding YWHAB. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is YWHAB. RAF1 is a canonical phospho-dependent 14-3-3 client: a 14-3-3 dimer engaging pSer259 and pSer621 holds the autoinhibited monomer, and the pSer621 site also stabilises the active dimer. 14-3-3 protein binding captures this regulatory interaction (same term as the BRAF review). Proposed replacements: 14-3-3 protein binding Supporting Evidence: PMID:37045861 using quantitative proteomics we mapped the interactomes of RAF1 monomers, RAF1-BRAF and RAF1-BRAFV600E dimers file:human/RAF1/RAF1-uniprot.txt P04049; P31946: YWHAB; NbExp=39; IntAct=EBI-365996, EBI-359815; |
| GO:0005515 protein binding | IPI PMID:37045861 Interactome dynamics of RAF1-BRAF kinase monomers and dimers... | MODIFY | Summary: IPI (quantitative interactomes of RAF1 monomers and RAF1-BRAF dimers) for RAF1 binding CCT3 (TRiC chaperonin subunit). Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is CCT3 (TRiC chaperonin subunit). The partner is a protein-folding chaperone or co-chaperone, and RAF1 is a chaperone client (HSP90-CDC37 dependence is well established); protein-folding chaperone binding describes the interaction from the RAF1 side. Proposed replacements: protein-folding chaperone binding Supporting Evidence: PMID:37045861 using quantitative proteomics we mapped the interactomes of RAF1 monomers, RAF1-BRAF and RAF1-BRAFV600E dimers file:human/RAF1/RAF1-uniprot.txt P04049; P49368: CCT3; NbExp=8; IntAct=EBI-365996, EBI-356673; |
| GO:0005515 protein binding | IPI PMID:37045861 Interactome dynamics of RAF1-BRAF kinase monomers and dimers... | MODIFY | Summary: IPI (quantitative interactomes of RAF1 monomers and RAF1-BRAF dimers) for RAF1 binding YWHAG. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is YWHAG. RAF1 is a canonical phospho-dependent 14-3-3 client: a 14-3-3 dimer engaging pSer259 and pSer621 holds the autoinhibited monomer, and the pSer621 site also stabilises the active dimer. 14-3-3 protein binding captures this regulatory interaction (same term as the BRAF review). Proposed replacements: 14-3-3 protein binding Supporting Evidence: PMID:37045861 using quantitative proteomics we mapped the interactomes of RAF1 monomers, RAF1-BRAF and RAF1-BRAFV600E dimers file:human/RAF1/RAF1-uniprot.txt P04049; P61981: YWHAG; NbExp=24; IntAct=EBI-365996, EBI-359832; |
| GO:0005515 protein binding | IPI PMID:37045861 Interactome dynamics of RAF1-BRAF kinase monomers and dimers... | MODIFY | Summary: IPI (quantitative interactomes of RAF1 monomers and RAF1-BRAF dimers) for RAF1 binding YWHAE. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is YWHAE. RAF1 is a canonical phospho-dependent 14-3-3 client: a 14-3-3 dimer engaging pSer259 and pSer621 holds the autoinhibited monomer, and the pSer621 site also stabilises the active dimer. 14-3-3 protein binding captures this regulatory interaction (same term as the BRAF review). Proposed replacements: 14-3-3 protein binding Supporting Evidence: PMID:37045861 using quantitative proteomics we mapped the interactomes of RAF1 monomers, RAF1-BRAF and RAF1-BRAFV600E dimers file:human/RAF1/RAF1-uniprot.txt P04049; P62258: YWHAE; NbExp=25; IntAct=EBI-365996, EBI-356498; |
| GO:0005515 protein binding | IPI PMID:37045861 Interactome dynamics of RAF1-BRAF kinase monomers and dimers... | MODIFY | Summary: IPI (quantitative interactomes of RAF1 monomers and RAF1-BRAF dimers) for RAF1 binding YWHAZ. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is YWHAZ. RAF1 is a canonical phospho-dependent 14-3-3 client: a 14-3-3 dimer engaging pSer259 and pSer621 holds the autoinhibited monomer, and the pSer621 site also stabilises the active dimer. 14-3-3 protein binding captures this regulatory interaction (same term as the BRAF review). Proposed replacements: 14-3-3 protein binding Supporting Evidence: PMID:37045861 using quantitative proteomics we mapped the interactomes of RAF1 monomers, RAF1-BRAF and RAF1-BRAFV600E dimers file:human/RAF1/RAF1-uniprot.txt P04049; P63104: YWHAZ; NbExp=32; IntAct=EBI-365996, EBI-347088; |
| GO:0005515 protein binding | IPI PMID:37045861 Interactome dynamics of RAF1-BRAF kinase monomers and dimers... | MODIFY | Summary: IPI (quantitative interactomes of RAF1 monomers and RAF1-BRAF dimers) for RAF1 binding YWHAH. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is YWHAH. RAF1 is a canonical phospho-dependent 14-3-3 client: a 14-3-3 dimer engaging pSer259 and pSer621 holds the autoinhibited monomer, and the pSer621 site also stabilises the active dimer. 14-3-3 protein binding captures this regulatory interaction (same term as the BRAF review). Proposed replacements: 14-3-3 protein binding Supporting Evidence: PMID:37045861 using quantitative proteomics we mapped the interactomes of RAF1 monomers, RAF1-BRAF and RAF1-BRAFV600E dimers file:human/RAF1/RAF1-uniprot.txt P04049; Q04917: YWHAH; NbExp=27; IntAct=EBI-365996, EBI-306940; |
| GO:0005515 protein binding | IPI PMID:37045861 Interactome dynamics of RAF1-BRAF kinase monomers and dimers... | REMOVE | Summary: IPI (quantitative interactomes of RAF1 monomers and RAF1-BRAF dimers) for RAF1 binding MLF2. Reason: GO:0005515 protein binding is uninformative. Chaperone-network / AP-MS co-purifying protein without functional characterisation for RAF1. Removal does not mean the reported interaction is false; it means no informative RAF1 molecular-function term can be justified from it. Supporting Evidence: PMID:37045861 using quantitative proteomics we mapped the interactomes of RAF1 monomers, RAF1-BRAF and RAF1-BRAFV600E dimers file:human/RAF1/RAF1-uniprot.txt P04049; Q15773: MLF2; NbExp=4; IntAct=EBI-365996, EBI-1051875; |
| GO:0005515 protein binding | IPI PMID:37045861 Interactome dynamics of RAF1-BRAF kinase monomers and dimers... | MODIFY | Summary: IPI (quantitative interactomes of RAF1 monomers and RAF1-BRAF dimers) for RAF1 binding CDC37 (HSP90 kinase co-chaperone). Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is CDC37 (HSP90 kinase co-chaperone). The partner is a protein-folding chaperone or co-chaperone, and RAF1 is a chaperone client (HSP90-CDC37 dependence is well established); protein-folding chaperone binding describes the interaction from the RAF1 side. Proposed replacements: protein-folding chaperone binding Supporting Evidence: PMID:37045861 using quantitative proteomics we mapped the interactomes of RAF1 monomers, RAF1-BRAF and RAF1-BRAFV600E dimers file:human/RAF1/RAF1-uniprot.txt P04049; Q16543: CDC37; NbExp=20; IntAct=EBI-365996, EBI-295634; |
| GO:0005515 protein binding | IPI PMID:37045861 Interactome dynamics of RAF1-BRAF kinase monomers and dimers... | REMOVE | Summary: IPI (quantitative interactomes of RAF1 monomers and RAF1-BRAF dimers) for RAF1 binding TIMM50. Reason: GO:0005515 protein binding is uninformative. Yeast two-hybrid / AP-MS hit (mitochondrial import component), no functional characterisation for RAF1. Removal does not mean the reported interaction is false; it means no informative RAF1 molecular-function term can be justified from it. Supporting Evidence: PMID:37045861 using quantitative proteomics we mapped the interactomes of RAF1 monomers, RAF1-BRAF and RAF1-BRAFV600E dimers file:human/RAF1/RAF1-uniprot.txt P04049; Q3ZCQ8: TIMM50; NbExp=7; IntAct=EBI-365996, EBI-355175; |
| GO:0005515 protein binding | IPI PMID:37045861 Interactome dynamics of RAF1-BRAF kinase monomers and dimers... | MODIFY | Summary: IPI (quantitative interactomes of RAF1 monomers and RAF1-BRAF dimers) for RAF1 binding KSR1 (RAF-MEK scaffold). Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is KSR1 (RAF-MEK scaffold). The partner is a MAPK-pathway scaffold that assembles RAF with RAS/MEK or phosphatase; scaffold protein binding is the informative term (same choice as the BRAF review for KSR/IQGAP1/RGS12). Proposed replacements: scaffold protein binding Supporting Evidence: PMID:37045861 using quantitative proteomics we mapped the interactomes of RAF1 monomers, RAF1-BRAF and RAF1-BRAFV600E dimers file:human/RAF1/RAF1-uniprot.txt P04049; Q8IVT5: KSR1; NbExp=5; IntAct=EBI-365996, EBI-486984; |
| GO:0005515 protein binding | IPI PMID:37045861 Interactome dynamics of RAF1-BRAF kinase monomers and dimers... | MODIFY | Summary: IPI (quantitative interactomes of RAF1 monomers and RAF1-BRAF dimers) for RAF1 binding STUB1/CHIP (E3 ubiquitin ligase). Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is STUB1/CHIP (E3 ubiquitin ligase). The partner is an E3 ubiquitin ligase acting on RAF1 as a substrate/client; ubiquitin protein ligase binding is the informative term (same choice as the BRAF review for HERC2). Proposed replacements: ubiquitin protein ligase binding Supporting Evidence: PMID:37045861 using quantitative proteomics we mapped the interactomes of RAF1 monomers, RAF1-BRAF and RAF1-BRAFV600E dimers file:human/RAF1/RAF1-uniprot.txt P04049; Q9UNE7: STUB1; NbExp=8; IntAct=EBI-365996, EBI-357085; |
| GO:0005515 protein binding | IPI PMID:39251607 Systematic identification of post-transcriptional regulatory... | MODIFY | Summary: IPI (large-scale identification of post-transcriptional regulatory modules (interactome component)) for RAF1 binding YWHAG. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is YWHAG. RAF1 is a canonical phospho-dependent 14-3-3 client: a 14-3-3 dimer engaging pSer259 and pSer621 holds the autoinhibited monomer, and the pSer621 site also stabilises the active dimer. 14-3-3 protein binding captures this regulatory interaction (same term as the BRAF review). The cached text of this reference does not describe the RAF1 interaction, so the IntAct/BioGRID curation (made from the full text or supplementary data) is deferred to; the partner-type mapping is supported by independent RAF1 evidence cited here. Proposed replacements: 14-3-3 protein binding Supporting Evidence: file:human/RAF1/RAF1-uniprot.txt the binding of a 14-3-3 protein that contacts two phosphorylation file:human/RAF1/RAF1-uniprot.txt P04049; P61981: YWHAG; NbExp=24; IntAct=EBI-365996, EBI-359832; |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | MODIFY | Summary: IPI (multimodal cell maps (AP-MS + imaging) of human cell organisation) for RAF1 binding YWHAQ. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is YWHAQ. RAF1 is a canonical phospho-dependent 14-3-3 client: a 14-3-3 dimer engaging pSer259 and pSer621 holds the autoinhibited monomer, and the pSer621 site also stabilises the active dimer. 14-3-3 protein binding captures this regulatory interaction (same term as the BRAF review). The cached text of this reference does not describe the RAF1 interaction, so the IntAct/BioGRID curation (made from the full text or supplementary data) is deferred to; the partner-type mapping is supported by independent RAF1 evidence cited here. Proposed replacements: 14-3-3 protein binding Supporting Evidence: file:human/RAF1/RAF1-uniprot.txt the binding of a 14-3-3 protein that contacts two phosphorylation file:human/RAF1/RAF1-uniprot.txt P04049; P27348: YWHAQ; NbExp=24; IntAct=EBI-365996, EBI-359854; |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | MODIFY | Summary: IPI (multimodal cell maps (AP-MS + imaging) of human cell organisation) for RAF1 binding YWHAB. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is YWHAB. RAF1 is a canonical phospho-dependent 14-3-3 client: a 14-3-3 dimer engaging pSer259 and pSer621 holds the autoinhibited monomer, and the pSer621 site also stabilises the active dimer. 14-3-3 protein binding captures this regulatory interaction (same term as the BRAF review). The cached text of this reference does not describe the RAF1 interaction, so the IntAct/BioGRID curation (made from the full text or supplementary data) is deferred to; the partner-type mapping is supported by independent RAF1 evidence cited here. Proposed replacements: 14-3-3 protein binding Supporting Evidence: file:human/RAF1/RAF1-uniprot.txt the binding of a 14-3-3 protein that contacts two phosphorylation file:human/RAF1/RAF1-uniprot.txt P04049; P31946: YWHAB; NbExp=39; IntAct=EBI-365996, EBI-359815; |
| GO:0005515 protein binding | IPI PMID:7644510 14-3-3 proteins associate with cdc25 phosphatases. | MODIFY | Summary: IPI (study of 14-3-3 association with cdc25 phosphatases, noting Raf-1 binds and activates cdc25A) for RAF1 binding CDC25A phosphatase. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is CDC25A phosphatase. The partner is (a subunit of) a protein phosphatase that dephosphorylates RAF1 (PP2A, PP1C on pSer259) or, for CDC25A, a phosphatase that RAF1 binds and activates; phosphatase binding is the informative term. Proposed replacements: phosphatase binding Supporting Evidence: PMID:7644510 Raf-1, which is known to bind 14-3-3 proteins, has recently been shown to associate with cdc25A and to stimulate its phosphatase activity. file:human/RAF1/RAF1-uniprot.txt P04049; P30304: CDC25A; NbExp=4; IntAct=EBI-365996, EBI-747671; |
| GO:0005515 protein binding | IPI PMID:7644510 14-3-3 proteins associate with cdc25 phosphatases. | MODIFY | Summary: IPI (study of 14-3-3 association with cdc25 phosphatases, noting Raf-1 binds and activates cdc25A) for RAF1 binding YWHAB. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is YWHAB. RAF1 is a canonical phospho-dependent 14-3-3 client: a 14-3-3 dimer engaging pSer259 and pSer621 holds the autoinhibited monomer, and the pSer621 site also stabilises the active dimer. 14-3-3 protein binding captures this regulatory interaction (same term as the BRAF review). Proposed replacements: 14-3-3 protein binding Supporting Evidence: PMID:7644510 Raf-1, which is known to bind 14-3-3 proteins, has recently been shown to associate with cdc25A and to stimulate its phosphatase activity. file:human/RAF1/RAF1-uniprot.txt P04049; P31946: YWHAB; NbExp=39; IntAct=EBI-365996, EBI-359815; |
| GO:0005515 protein binding | IPI PMID:7644510 14-3-3 proteins associate with cdc25 phosphatases. | MODIFY | Summary: IPI (study of 14-3-3 association with cdc25 phosphatases, noting Raf-1 binds and activates cdc25A) for RAF1 binding YWHAE. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is YWHAE. RAF1 is a canonical phospho-dependent 14-3-3 client: a 14-3-3 dimer engaging pSer259 and pSer621 holds the autoinhibited monomer, and the pSer621 site also stabilises the active dimer. 14-3-3 protein binding captures this regulatory interaction (same term as the BRAF review). Proposed replacements: 14-3-3 protein binding Supporting Evidence: PMID:7644510 Raf-1, which is known to bind 14-3-3 proteins, has recently been shown to associate with cdc25A and to stimulate its phosphatase activity. file:human/RAF1/RAF1-uniprot.txt P04049; P62258: YWHAE; NbExp=25; IntAct=EBI-365996, EBI-356498; |
| GO:0005515 protein binding | IPI PMID:7760835 14-3-3 is not essential for Raf-1 function: identification o... | MODIFY | Summary: IPI (study of Raf-1 residues required for 14-3-3 binding) for RAF1 binding YWHAQ. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is YWHAQ. RAF1 is a canonical phospho-dependent 14-3-3 client: a 14-3-3 dimer engaging pSer259 and pSer621 holds the autoinhibited monomer, and the pSer621 site also stabilises the active dimer. 14-3-3 protein binding captures this regulatory interaction (same term as the BRAF review). Proposed replacements: 14-3-3 protein binding Supporting Evidence: PMID:7760835 Mutation of either Cys-165 and Cys-168 or Ser-259 prevented the stable interaction of Raf-1 with 14-3-3 in vivo. file:human/RAF1/RAF1-uniprot.txt P04049; P27348: YWHAQ; NbExp=24; IntAct=EBI-365996, EBI-359854; |
| GO:0005515 protein binding | IPI PMID:7791872 The 2.2 A crystal structure of the Ras-binding domain of the... | MODIFY | Summary: IPI (crystal structure of the c-Raf1 RBD bound to Rap1A-GppNHp) for RAF1 binding RAP1A. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is RAP1A. RAF1 is a direct RAS effector: its RAS-binding domain (RBD) and CRD bind GTP-loaded RAS family GTPases, recruiting RAF1 to the plasma membrane; this is the entry step of RAF activation. small GTPase binding is the informative term (same term as the BRAF review). Proposed replacements: small GTPase binding Supporting Evidence: PMID:7791872 The interaction between the two proteins is mediated by an apparent central antiparallel beta-sheet file:human/RAF1/RAF1-uniprot.txt P04049; P62834: RAP1A; NbExp=2; IntAct=EBI-365996, EBI-491414; |
| GO:0005515 protein binding | IPI PMID:7882972 Regulation of Raf-1 kinase activity by the 14-3-3 family of ... | MODIFY | Summary: IPI (study of 14-3-3 as a latent co-activator of Raf-1) for RAF1 binding YWHAB. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is YWHAB. RAF1 is a canonical phospho-dependent 14-3-3 client: a 14-3-3 dimer engaging pSer259 and pSer621 holds the autoinhibited monomer, and the pSer621 site also stabilises the active dimer. 14-3-3 protein binding captures this regulatory interaction (same term as the BRAF review). Proposed replacements: 14-3-3 protein binding Supporting Evidence: PMID:7882972 Purified bovine brain 14-3-3 interacted specifically with both c-Raf-1 and the isolated Raf-1 kinase domain. file:human/RAF1/RAF1-uniprot.txt P04049; P31946: YWHAB; NbExp=39; IntAct=EBI-365996, EBI-359815; |
| GO:0005515 protein binding | IPI PMID:7935795 Activation of Raf-1 by 14-3-3 proteins. | MODIFY | Summary: IPI (yeast two-hybrid identification of 14-3-3 zeta/beta as Raf-1 N-terminal partners) for RAF1 binding YWHAB. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is YWHAB. RAF1 is a canonical phospho-dependent 14-3-3 client: a 14-3-3 dimer engaging pSer259 and pSer621 holds the autoinhibited monomer, and the pSer621 site also stabilises the active dimer. 14-3-3 protein binding captures this regulatory interaction (same term as the BRAF review). Proposed replacements: 14-3-3 protein binding Supporting Evidence: PMID:7935795 we identified two structurally related proteins that interact with the aminoterminal region of Raf-1 file:human/RAF1/RAF1-uniprot.txt P04049; P31946: YWHAB; NbExp=39; IntAct=EBI-365996, EBI-359815; |
| GO:0005515 protein binding | IPI PMID:7935795 Activation of Raf-1 by 14-3-3 proteins. | MODIFY | Summary: IPI (yeast two-hybrid identification of 14-3-3 zeta/beta as Raf-1 N-terminal partners) for RAF1 binding YWHAZ. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is YWHAZ. RAF1 is a canonical phospho-dependent 14-3-3 client: a 14-3-3 dimer engaging pSer259 and pSer621 holds the autoinhibited monomer, and the pSer621 site also stabilises the active dimer. 14-3-3 protein binding captures this regulatory interaction (same term as the BRAF review). Proposed replacements: 14-3-3 protein binding Supporting Evidence: PMID:7935795 we identified two structurally related proteins that interact with the aminoterminal region of Raf-1 file:human/RAF1/RAF1-uniprot.txt P04049; P63104: YWHAZ; NbExp=32; IntAct=EBI-365996, EBI-347088; |
| GO:0005515 protein binding | IPI PMID:7939632 Interaction of the protein kinase Raf-1 with 14-3-3 proteins... | MODIFY | Summary: IPI (study of Raf-1 association with 14-3-3 proteins) for RAF1 binding YWHAZ. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is YWHAZ. RAF1 is a canonical phospho-dependent 14-3-3 client: a 14-3-3 dimer engaging pSer259 and pSer621 holds the autoinhibited monomer, and the pSer621 site also stabilises the active dimer. 14-3-3 protein binding captures this regulatory interaction (same term as the BRAF review). Proposed replacements: 14-3-3 protein binding Supporting Evidence: PMID:7939632 were found by several experimental approaches to associate with Raf-1 file:human/RAF1/RAF1-uniprot.txt P04049; P63104: YWHAZ; NbExp=32; IntAct=EBI-365996, EBI-347088; |
| GO:0005515 protein binding | IPI PMID:8085158 Binding of 14-3-3 proteins to the protein kinase Raf and eff... | MODIFY | Summary: IPI (two-hybrid and mammalian-cell study of 14-3-3 binding to Raf) for RAF1 binding YWHAB. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is YWHAB. RAF1 is a canonical phospho-dependent 14-3-3 client: a 14-3-3 dimer engaging pSer259 and pSer621 holds the autoinhibited monomer, and the pSer621 site also stabilises the active dimer. 14-3-3 protein binding captures this regulatory interaction (same term as the BRAF review). Proposed replacements: 14-3-3 protein binding Supporting Evidence: PMID:8085158 14-3-3 proteins associated with Raf in mammalian cells and accompanied Raf to the membrane in the presence of activated Ras. file:human/RAF1/RAF1-uniprot.txt P04049; P31946: YWHAB; NbExp=39; IntAct=EBI-365996, EBI-359815; |
| GO:0005515 protein binding | IPI PMID:8085158 Binding of 14-3-3 proteins to the protein kinase Raf and eff... | MODIFY | Summary: IPI (two-hybrid and mammalian-cell study of 14-3-3 binding to Raf) for RAF1 binding YWHAZ. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is YWHAZ. RAF1 is a canonical phospho-dependent 14-3-3 client: a 14-3-3 dimer engaging pSer259 and pSer621 holds the autoinhibited monomer, and the pSer621 site also stabilises the active dimer. 14-3-3 protein binding captures this regulatory interaction (same term as the BRAF review). Proposed replacements: 14-3-3 protein binding Supporting Evidence: PMID:8085158 14-3-3 proteins associated with Raf in mammalian cells and accompanied Raf to the membrane in the presence of activated Ras. file:human/RAF1/RAF1-uniprot.txt P04049; P63104: YWHAZ; NbExp=32; IntAct=EBI-365996, EBI-347088; |
| GO:0005515 protein binding | IPI PMID:8332187 Normal and oncogenic p21ras proteins bind to the amino-termi... | MODIFY | Summary: IPI (study showing p21ras binds the Raf-1 N-terminal regulatory domain) for RAF1 binding HRAS. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is HRAS. RAF1 is a direct RAS effector: its RAS-binding domain (RBD) and CRD bind GTP-loaded RAS family GTPases, recruiting RAF1 to the plasma membrane; this is the entry step of RAF activation. small GTPase binding is the informative term (same term as the BRAF review). Proposed replacements: small GTPase binding Supporting Evidence: PMID:8332187 Raf-1 (1-257) binds GTP-Ras in preference to GDP-Ras file:human/RAF1/RAF1-uniprot.txt P04049; P01112: HRAS; NbExp=30; IntAct=EBI-365996, EBI-350145; |
| GO:0005515 protein binding | IPI PMID:8601312 Interaction of 14-3-3 with signaling proteins is mediated by... | MODIFY | Summary: IPI (study defining the phosphoserine 14-3-3 binding motif using Raf-1 peptides) for RAF1 binding YWHAZ. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is YWHAZ. RAF1 is a canonical phospho-dependent 14-3-3 client: a 14-3-3 dimer engaging pSer259 and pSer621 holds the autoinhibited monomer, and the pSer621 site also stabilises the active dimer. 14-3-3 protein binding captures this regulatory interaction (same term as the BRAF review). Proposed replacements: 14-3-3 protein binding Supporting Evidence: PMID:8601312 Using a panel of phosphorylated peptides based on Raf-1, we have defined the 14-3-3 binding motif file:human/RAF1/RAF1-uniprot.txt P04049; P63104: YWHAZ; NbExp=32; IntAct=EBI-365996, EBI-347088; |
| GO:0005515 protein binding | IPI PMID:8670882 Identification of a novel Rac1-interacting protein involved ... | MODIFY | Summary: IPI (identification of the Rac1 effector POR1; RAF1 is not mentioned in the cached abstract (Raf binding of Ras is a standard comparator)) for RAF1 binding HRAS. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is HRAS. RAF1 is a direct RAS effector: its RAS-binding domain (RBD) and CRD bind GTP-loaded RAS family GTPases, recruiting RAF1 to the plasma membrane; this is the entry step of RAF activation. small GTPase binding is the informative term (same term as the BRAF review). The cached text of this reference does not describe the RAF1 interaction, so the IntAct/BioGRID curation (made from the full text or supplementary data) is deferred to; the partner-type mapping is supported by independent RAF1 evidence cited here. Proposed replacements: small GTPase binding Supporting Evidence: file:human/RAF1/RAF1-uniprot.txt Ras-GTP recruits RAF1 to the file:human/RAF1/RAF1-uniprot.txt P04049; P01112: HRAS; NbExp=30; IntAct=EBI-365996, EBI-350145; |
| GO:0005515 protein binding | IPI PMID:8756332 Ras/Rap effector specificity determined by charge reversal. | MODIFY | Summary: IPI (structural study of Ras/Rap effector specificity towards c-Raf) for RAF1 binding RAP1A. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is RAP1A. RAF1 is a direct RAS effector: its RAS-binding domain (RBD) and CRD bind GTP-loaded RAS family GTPases, recruiting RAF1 to the plasma membrane; this is the entry step of RAF activation. small GTPase binding is the informative term (same term as the BRAF review). Proposed replacements: small GTPase binding Supporting Evidence: PMID:8756332 such as the protein kinase c-Raf and the Ral-specific guanine nucleotide exchange factor file:human/RAF1/RAF1-uniprot.txt P04049; P62834: RAP1A; NbExp=2; IntAct=EBI-365996, EBI-491414; |
| GO:0005515 protein binding | IPI PMID:9111084 14-3-3 (epsilon) interacts with the insulin-like growth fact... | MODIFY | Summary: IPI (study of 14-3-3 epsilon binding IGF-IR and IRS-1; RAF1 is not mentioned in the cached abstract (a known 14-3-3 client used as comparator)) for RAF1 binding YWHAE. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is YWHAE. RAF1 is a canonical phospho-dependent 14-3-3 client: a 14-3-3 dimer engaging pSer259 and pSer621 holds the autoinhibited monomer, and the pSer621 site also stabilises the active dimer. 14-3-3 protein binding captures this regulatory interaction (same term as the BRAF review). The cached text of this reference does not describe the RAF1 interaction, so the IntAct/BioGRID curation (made from the full text or supplementary data) is deferred to; the partner-type mapping is supported by independent RAF1 evidence cited here. Proposed replacements: 14-3-3 protein binding Supporting Evidence: file:human/RAF1/RAF1-uniprot.txt the binding of a 14-3-3 protein that contacts two phosphorylation file:human/RAF1/RAF1-uniprot.txt P04049; P62258: YWHAE; NbExp=25; IntAct=EBI-365996, EBI-356498; |
| GO:0005515 protein binding | IPI PMID:9144171 Protein binding and signaling properties of RIN1 suggest a u... | MODIFY | Summary: IPI (study of RIN1 as a RAS effector compared with RAF1) for RAF1 binding HRAS. Reason: GO:0005515 protein binding is uninformative; the WITH/FROM partner is HRAS. RAF1 is a direct RAS effector: its RAS-binding domain (RBD) and CRD bind GTP-loaded RAS family GTPases, recruiting RAF1 to the plasma membrane; this is the entry step of RAF activation. small GTPase binding is the informative term (same term as the BRAF review). Proposed replacements: small GTPase binding Supporting Evidence: PMID:9144171 others that are distinct from, those required for the binding of RAF1, a known RAS effector file:human/RAF1/RAF1-uniprot.txt P04049; P01112: HRAS; NbExp=30; IntAct=EBI-365996, EBI-350145; |
| GO:0005515 protein binding | IPI PMID:9624170 Binding of c-Raf1 kinase to a conserved acidic sequence with... | REMOVE | Summary: IPI (study mapping c-Raf1 binding to an acidic motif in HIV-1 Nef) for RAF1 binding HIV-1 Nef. Reason: GO:0005515 protein binding is uninformative. Host-virus interaction (Nef acidic motif binds c-Raf1); not a normal molecular function of RAF1. Removal does not mean the reported interaction is false; it means no informative RAF1 molecular-function term can be justified from it. Supporting Evidence: PMID:9624170 map the specific interaction between the HIV-1LAI Nef and c-Raf1 |
| GO:0005524 ATP binding | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro2GO (protein kinase ATP-binding region) for ATP binding. Reason: Correct: RAF1 is an ATP-dependent kinase; the pS621/14-3-3 site is even required for its ATP binding (PMID:19595761). Supporting Evidence: PMID:19595761 render Raf-1 inactive by specifically disrupting its capacity to bind to ATP |
| GO:0005634 nucleus | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: UniProt subcellular-location mapping (SL-0191) for nucleus. UniProt notes that retinoic-acid-induced pSer621 RAF1 is predominantly nuclear. Reason: A nuclear RAF1 pool is reported in retinoic-acid-induced myeloid differentiation (PMID:24330068) but is not a general or canonical location. Supporting Evidence: file:human/RAF1/RAF1-uniprot.txt Retinoic acid-induced Ser-621 PMID:24330068 Nuclear Raf-1 kinase regulates the CXCR5 promoter by associating with NFATc3 |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: IBA (PAINT node PTN002892787, broad kinase clade including RAF1 and BRAF) for cytoplasmic activity. Inactive RAF1 resides in the cytosol bound to 14-3-3 and HSP90-CDC37, and signals from the cytoplasmic face of the plasma membrane. Reason: Correct and well supported; RAF1 itself is among the experimental descendants of the node, which is expected, not circular. Cytoplasm is broader than the cytosol term also carried, but not wrong. Supporting Evidence: file:human/RAF1/RAF1-deep-research-falcon.md RAF1 is predominantly an inactive **cytosolic** complex at baseline and is recruited transiently to the cytoplasmic face of the **plasma membrane** by RAS-GTP file:human/RAF1/RAF1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm. Cell membrane. Mitochondrion. Nucleus. |
| GO:0005737 cytoplasm | IDA PMID:17724343 Spatial regulation of Raf kinase signaling by RKTG. | ACCEPT | Summary: MGI IDA for cytoplasm: Raf-1 is cytoplasmic in the absence of RKTG. Reason: Correct resting localisation. Supporting Evidence: PMID:17724343 RKTG changes the localization of Raf-1 from cytoplasm to the Golgi apparatus |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt subcellular-location mapping (SL-0086) for cytoplasm. Reason: Correct; inactive RAF1 is cytoplasmic/cytosolic. Supporting Evidence: file:human/RAF1/RAF1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm. Cell membrane. Mitochondrion. Nucleus. |
| GO:0005737 cytoplasm | ISS GO_REF:0000024 | ACCEPT | Summary: UniProt ISS from rat Raf1 (P11345) for cytoplasm. Reason: Correct; consistent with human experimental data. Supporting Evidence: file:human/RAF1/RAF1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm. Cell membrane. Mitochondrion. Nucleus. |
| GO:0005739 mitochondrion | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: IBA (PAINT node PTN000584576) for mitochondrial activity, seeded by mouse Raf1/Braf. A PAK-phosphorylated or Bcl-2-targeted RAF1 pool acts at the mitochondrial outer membrane to suppress apoptosis. Reason: The mitochondrial pool of RAF1 is real (PMID:8929532, PMID:18064632) but context-dependent and not the site of canonical MEK activation; keep as non-core. Supporting Evidence: file:human/RAF1/RAF1-deep-research-falcon.md A context-specific RAF1 pool translocates to the **mitochondrial surface** PMID:8929532 Bcl-2 can therefore target Raf-1 to mitochondrial membranes |
| GO:0005739 mitochondrion | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: UniProt subcellular-location mapping (SL-0173) for mitochondrion. Reason: Context-specific mitochondrial pool (Bcl-2 targeting, PAK S338/S339 phosphorylation); not the canonical signalling location. Supporting Evidence: file:human/RAF1/RAF1-uniprot.txt Phosphorylation at Ser-338 and Ser-339 by PAK1 is required for its file:human/RAF1/RAF1-deep-research-falcon.md A context-specific RAF1 pool translocates to the **mitochondrial surface** |
| GO:0005741 mitochondrial outer membrane | TAS PMID:8929532 Bcl-2 targets the protein kinase Raf-1 to mitochondria. | ACCEPT | Summary: TAS (PINC) for mitochondrial outer membrane: Bcl-2 targets Raf-1 to mitochondrial membranes. Reason: The mitochondrial outer membrane pool (also GRP78 co-localisation, PMID:18064632) is the site of the anti-apoptotic RAF1 function captured as a core function; it is context-dependent and secondary to the plasma-membrane signalling site, but the specific location is correct. Supporting Evidence: PMID:8929532 Bcl-2 can therefore target Raf-1 to mitochondrial membranes PMID:18064632 GRP78 associated and colocalized with Raf-1 on the outer membrane of mitochondria |
| GO:0005794 Golgi apparatus | IPI PMID:17724343 Spatial regulation of Raf kinase signaling by RKTG. | KEEP AS NON CORE | Summary: MGI IPI (with PAQR3/RKTG) for Golgi apparatus: RKTG, a Golgi seven-transmembrane protein, sequesters Raf-1 at the Golgi. Reason: Golgi localisation is induced by RKTG binding and represents an inhibitory sequestration, not a general RAF1 signalling location. Supporting Evidence: PMID:17724343 RKTG changes the localization of Raf-1 from cytoplasm to the Golgi apparatus |
| GO:0005829 cytosol | IBA GO_REF:0000033 | ACCEPT | Summary: IBA (PAINT node PTN000584576) for cytosol activity. The autoinhibited RAF1-14-3-3 complex is cytosolic. Reason: Correct; RAF1 and BRAF experimental cytosol annotations seed this node (target-in-WITH is expected). Supporting Evidence: file:human/RAF1/RAF1-deep-research-falcon.md RAF1 is predominantly an inactive **cytosolic** complex at baseline and is recruited transiently to the cytoplasmic face of the **plasma membrane** by RAS-GTP |
| GO:0005829 cytosol | IDA GO_REF:0000052 | ACCEPT | Summary: HPA immunofluorescence for cytosol. Reason: Consistent with the known cytosolic resting pool of RAF1. Supporting Evidence: file:human/RAF1/RAF1-deep-research-falcon.md RAF1 is predominantly an inactive **cytosolic** complex at baseline and is recruited transiently to the cytoplasmic face of the **plasma membrane** by RAS-GTP |
| GO:0005829 cytosol | IDA PMID:16009725 CAPRI and RASAL impose different modes of information proces... | ACCEPT | Summary: UniProt IDA for cytosol from a study of CAPRI/RASAL that used GFP-tagged Raf-1 RBD (residues 51-131) as an active-Ras reporter; the reporter is cytosolic in resting cells. Reason: The observation is on a RAF1 fragment used as a biosensor, but cytosolic localisation of resting RAF1 is independently well established. Supporting Evidence: PMID:16009725 We therefore used the Ras-binding domain from Raf-1 tagged to GFP (GFP-RBD) as a reporter of active Ras on cell membranes |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2682349 | ACCEPT | Summary: Reactome TAS for cytosol from the event "RAF1:SGK:TSC22D3:WPP ubiquitinates SCNN channels". RAF1:SGK:TSC22D3:WPP complex ubiquitinates SCNN (ENaC) channels; RAF1 as a cytosolic complex member. Reason: Cytosolic localisation of RAF1 is well supported (resting 14-3-3/HSP90-bound pool, and the cytoplasmic face of membranes where signalling complexes form); Reactome places this RAF1-containing entity in the cytosol for this event. Accept. Supporting Evidence: Reactome:R-HSA-2682349 RAF1:SGK:TSC22D3:WPP ubiquitinates SCNN channels file:human/RAF1/RAF1-deep-research-falcon.md RAF1 is predominantly an inactive **cytosolic** complex at baseline and is recruited transiently to the cytoplasmic face of the **plasma membrane** by RAS-GTP |
| GO:0005829 cytosol | TAS Reactome:R-HSA-392835 | ACCEPT | Summary: Reactome TAS for cytosol from the event "Rap1 sequesters Raf1 to inhibit ERK cascade". Rap1 sequesters Raf1 to inhibit the ERK cascade. Reason: Cytosolic localisation of RAF1 is well supported (resting 14-3-3/HSP90-bound pool, and the cytoplasmic face of membranes where signalling complexes form); Reactome places this RAF1-containing entity in the cytosol for this event. Accept. Supporting Evidence: Reactome:R-HSA-392835 Rap1 sequesters Raf1 to inhibit ERK cascade file:human/RAF1/RAF1-deep-research-falcon.md RAF1 is predominantly an inactive **cytosolic** complex at baseline and is recruited transiently to the cytoplasmic face of the **plasma membrane** by RAS-GTP |
| GO:0005829 cytosol | TAS Reactome:R-HSA-443439 | ACCEPT | Summary: Reactome TAS for cytosol from the event "c-Src binds Raf1". c-Src binds Raf1. Reason: Cytosolic localisation of RAF1 is well supported (resting 14-3-3/HSP90-bound pool, and the cytoplasmic face of membranes where signalling complexes form); Reactome places this RAF1-containing entity in the cytosol for this event. Accept. Supporting Evidence: Reactome:R-HSA-443439 c-Src binds Raf1 file:human/RAF1/RAF1-deep-research-falcon.md RAF1 is predominantly an inactive **cytosolic** complex at baseline and is recruited transiently to the cytoplasmic face of the **plasma membrane** by RAS-GTP |
| GO:0005829 cytosol | TAS Reactome:R-HSA-443831 | ACCEPT | Summary: Reactome TAS for cytosol from the event "14-3-3-zeta binds Raf1". 14-3-3-zeta binds Raf1. Reason: Cytosolic localisation of RAF1 is well supported (resting 14-3-3/HSP90-bound pool, and the cytoplasmic face of membranes where signalling complexes form); Reactome places this RAF1-containing entity in the cytosol for this event. Accept. Supporting Evidence: Reactome:R-HSA-443831 14-3-3-zeta binds Raf1 file:human/RAF1/RAF1-deep-research-falcon.md RAF1 is predominantly an inactive **cytosolic** complex at baseline and is recruited transiently to the cytoplasmic face of the **plasma membrane** by RAS-GTP |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5624486 | ACCEPT | Summary: Reactome TAS for cytosol from the event "SFKs phosphorylates RAF1 on Y340,Y341". SRC-family kinases phosphorylate RAF1 Y340/Y341. Reason: Cytosolic localisation of RAF1 is well supported (resting 14-3-3/HSP90-bound pool, and the cytoplasmic face of membranes where signalling complexes form); Reactome places this RAF1-containing entity in the cytosol for this event. Accept. Supporting Evidence: Reactome:R-HSA-5624486 SFKs phosphorylates RAF1 on Y340,Y341 file:human/RAF1/RAF1-deep-research-falcon.md RAF1 is predominantly an inactive **cytosolic** complex at baseline and is recruited transiently to the cytoplasmic face of the **plasma membrane** by RAS-GTP |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5624492 | ACCEPT | Summary: Reactome TAS for cytosol from the event "PAK phosphorylates p21 RAF1 on S338". PAK phosphorylates RAF1 S338. Reason: Cytosolic localisation of RAF1 is well supported (resting 14-3-3/HSP90-bound pool, and the cytoplasmic face of membranes where signalling complexes form); Reactome places this RAF1-containing entity in the cytosol for this event. Accept. Supporting Evidence: Reactome:R-HSA-5624492 PAK phosphorylates p21 RAF1 on S338 file:human/RAF1/RAF1-deep-research-falcon.md RAF1 is predominantly an inactive **cytosolic** complex at baseline and is recruited transiently to the cytoplasmic face of the **plasma membrane** by RAS-GTP |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5624494 | ACCEPT | Summary: Reactome TAS for cytosol from the event "RAF1 binds p21 RAS:GTP". RAF1 binds p21 RAS:GTP. Reason: Cytosolic localisation of RAF1 is well supported (resting 14-3-3/HSP90-bound pool, and the cytoplasmic face of membranes where signalling complexes form); Reactome places this RAF1-containing entity in the cytosol for this event. Accept. Supporting Evidence: Reactome:R-HSA-5624494 RAF1 binds p21 RAS:GTP file:human/RAF1/RAF1-deep-research-falcon.md RAF1 is predominantly an inactive **cytosolic** complex at baseline and is recruited transiently to the cytoplasmic face of the **plasma membrane** by RAS-GTP |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5672951 | ACCEPT | Summary: Reactome TAS for cytosol from the event "Inactive RAFs bind YWHAB". Inactive RAFs bind YWHAB (14-3-3) in the cytosol. Reason: Cytosolic localisation of RAF1 is well supported (resting 14-3-3/HSP90-bound pool, and the cytoplasmic face of membranes where signalling complexes form); Reactome places this RAF1-containing entity in the cytosol for this event. Accept. Supporting Evidence: Reactome:R-HSA-5672951 Inactive RAFs bind YWHAB file:human/RAF1/RAF1-deep-research-falcon.md RAF1 is predominantly an inactive **cytosolic** complex at baseline and is recruited transiently to the cytoplasmic face of the **plasma membrane** by RAS-GTP |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5672960 | ACCEPT | Summary: Reactome TAS for cytosol from the event "YWHAB dimer dissociates from dephosphorylated RAF". YWHAB dimer dissociates from dephosphorylated RAF. Reason: Cytosolic localisation of RAF1 is well supported (resting 14-3-3/HSP90-bound pool, and the cytoplasmic face of membranes where signalling complexes form); Reactome places this RAF1-containing entity in the cytosol for this event. Accept. Supporting Evidence: Reactome:R-HSA-5672960 YWHAB dimer dissociates from dephosphorylated RAF file:human/RAF1/RAF1-deep-research-falcon.md RAF1 is predominantly an inactive **cytosolic** complex at baseline and is recruited transiently to the cytoplasmic face of the **plasma membrane** by RAS-GTP |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5672961 | ACCEPT | Summary: Reactome TAS for cytosol from the event "PP2A dephosphorylates inactive RAFs". PP2A dephosphorylates inactive RAFs. Reason: Cytosolic localisation of RAF1 is well supported (resting 14-3-3/HSP90-bound pool, and the cytoplasmic face of membranes where signalling complexes form); Reactome places this RAF1-containing entity in the cytosol for this event. Accept. Supporting Evidence: Reactome:R-HSA-5672961 PP2A dephosphorylates inactive RAFs file:human/RAF1/RAF1-deep-research-falcon.md RAF1 is predominantly an inactive **cytosolic** complex at baseline and is recruited transiently to the cytoplasmic face of the **plasma membrane** by RAS-GTP |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5672966 | ACCEPT | Summary: Reactome TAS for cytosol from the event "RAS:GTP:'activator' RAF homo/heterodimerizes with other RAF monomers". RAS:GTP-bound RAF homo/heterodimerizes with other RAF monomers. Reason: Cytosolic localisation of RAF1 is well supported (resting 14-3-3/HSP90-bound pool, and the cytoplasmic face of membranes where signalling complexes form); Reactome places this RAF1-containing entity in the cytosol for this event. Accept. Supporting Evidence: Reactome:R-HSA-5672966 RAS:GTP:'activator' RAF homo/heterodimerizes with other RAF monomers file:human/RAF1/RAF1-deep-research-falcon.md RAF1 is predominantly an inactive **cytosolic** complex at baseline and is recruited transiently to the cytoplasmic face of the **plasma membrane** by RAS-GTP |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5672969 | ACCEPT | Summary: Reactome TAS for cytosol from the event "Phosphorylation of RAF". Phosphorylation of RAF in the RAS:RAF complex. Reason: Cytosolic localisation of RAF1 is well supported (resting 14-3-3/HSP90-bound pool, and the cytoplasmic face of membranes where signalling complexes form); Reactome places this RAF1-containing entity in the cytosol for this event. Accept. Supporting Evidence: Reactome:R-HSA-5672969 Phosphorylation of RAF file:human/RAF1/RAF1-deep-research-falcon.md RAF1 is predominantly an inactive **cytosolic** complex at baseline and is recruited transiently to the cytoplasmic face of the **plasma membrane** by RAS-GTP |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5674130 | ACCEPT | Summary: Reactome TAS for cytosol from the event "MAP2Ks and MAPKs are phosphorylated at the endosome membrane". MAP2K/MAPK phosphorylation at the endosome membrane; RAF1 listed in the cytosolic compartment. Reason: Cytosolic localisation of RAF1 is well supported (resting 14-3-3/HSP90-bound pool, and the cytoplasmic face of membranes where signalling complexes form); Reactome places this RAF1-containing entity in the cytosol for this event. Accept. Supporting Evidence: Reactome:R-HSA-5674130 MAP2Ks and MAPKs are phosphorylated at the endosome membrane file:human/RAF1/RAF1-deep-research-falcon.md RAF1 is predominantly an inactive **cytosolic** complex at baseline and is recruited transiently to the cytoplasmic face of the **plasma membrane** by RAS-GTP |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5674132 | ACCEPT | Summary: Reactome TAS for cytosol from the event "WDR83:LAMTOR2:LAMTOR3 binds MAPK components". WDR83:LAMTOR2:LAMTOR3 scaffold binding of MAPK components; RAF1 in the cytosolic compartment. Reason: Cytosolic localisation of RAF1 is well supported (resting 14-3-3/HSP90-bound pool, and the cytoplasmic face of membranes where signalling complexes form); Reactome places this RAF1-containing entity in the cytosol for this event. Accept. Supporting Evidence: Reactome:R-HSA-5674132 WDR83:LAMTOR2:LAMTOR3 binds MAPK components file:human/RAF1/RAF1-deep-research-falcon.md RAF1 is predominantly an inactive **cytosolic** complex at baseline and is recruited transiently to the cytoplasmic face of the **plasma membrane** by RAS-GTP |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5674140 | ACCEPT | Summary: Reactome TAS for cytosol from the event "PAQR3 binds inactive RAFs". PAQR3 binds inactive RAFs. Reason: Cytosolic localisation of RAF1 is well supported (resting 14-3-3/HSP90-bound pool, and the cytoplasmic face of membranes where signalling complexes form); Reactome places this RAF1-containing entity in the cytosol for this event. Accept. Supporting Evidence: Reactome:R-HSA-5674140 PAQR3 binds inactive RAFs file:human/RAF1/RAF1-deep-research-falcon.md RAF1 is predominantly an inactive **cytosolic** complex at baseline and is recruited transiently to the cytoplasmic face of the **plasma membrane** by RAS-GTP |
| GO:0005829 cytosol | TAS Reactome:R-HSA-6802916 | ACCEPT | Summary: Reactome TAS for cytosol from the event "RAF is phosphorylated downstream of moderate kinase activity BRAF mutants". RAF phosphorylated downstream of moderate-activity BRAF mutants. Reason: Cytosolic localisation of RAF1 is well supported (resting 14-3-3/HSP90-bound pool, and the cytoplasmic face of membranes where signalling complexes form); Reactome places this RAF1-containing entity in the cytosol for this event. Accept. Supporting Evidence: Reactome:R-HSA-6802916 RAF is phosphorylated downstream of moderate kinase activity BRAF mutants file:human/RAF1/RAF1-deep-research-falcon.md RAF1 is predominantly an inactive **cytosolic** complex at baseline and is recruited transiently to the cytoplasmic face of the **plasma membrane** by RAS-GTP |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8936676 | ACCEPT | Summary: Reactome TAS for cytosol from the event "Moderate kinase activity BRAF mutants:RAS:GTP homo/heterodimerize". Moderate-activity BRAF mutants:RAS:GTP homo/heterodimerize (with RAF1). Reason: Cytosolic localisation of RAF1 is well supported (resting 14-3-3/HSP90-bound pool, and the cytoplasmic face of membranes where signalling complexes form); Reactome places this RAF1-containing entity in the cytosol for this event. Accept. Supporting Evidence: Reactome:R-HSA-8936676 Moderate kinase activity BRAF mutants:RAS:GTP homo/heterodimerize file:human/RAF1/RAF1-deep-research-falcon.md RAF1 is predominantly an inactive **cytosolic** complex at baseline and is recruited transiently to the cytoplasmic face of the **plasma membrane** by RAS-GTP |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8936731 | ACCEPT | Summary: Reactome TAS for cytosol from the event "Inactive BRAF mutants:mutant RAS:GTP bind RAF1". Inactive BRAF mutants:mutant RAS:GTP bind RAF1. Reason: Cytosolic localisation of RAF1 is well supported (resting 14-3-3/HSP90-bound pool, and the cytoplasmic face of membranes where signalling complexes form); Reactome places this RAF1-containing entity in the cytosol for this event. Accept. Supporting Evidence: Reactome:R-HSA-8936731 Inactive BRAF mutants:mutant RAS:GTP bind RAF1 file:human/RAF1/RAF1-deep-research-falcon.md RAF1 is predominantly an inactive **cytosolic** complex at baseline and is recruited transiently to the cytoplasmic face of the **plasma membrane** by RAS-GTP |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9653108 | ACCEPT | Summary: Reactome TAS for cytosol from the event "Raf dimer inhibitors bind RAF heterodimers". RAF-dimer inhibitors bind RAF heterodimers. Reason: Cytosolic localisation of RAF1 is well supported (resting 14-3-3/HSP90-bound pool, and the cytoplasmic face of membranes where signalling complexes form); Reactome places this RAF1-containing entity in the cytosol for this event. Accept. Supporting Evidence: Reactome:R-HSA-9653108 Raf dimer inhibitors bind RAF heterodimers file:human/RAF1/RAF1-deep-research-falcon.md RAF1 is predominantly an inactive **cytosolic** complex at baseline and is recruited transiently to the cytoplasmic face of the **plasma membrane** by RAS-GTP |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9656207 | ACCEPT | Summary: Reactome TAS for cytosol from the event "CR2 RAF1 mutants don't bind YWHAB". CR2 (S259-region) RAF1 mutants fail to bind YWHAB; cytosolic mutant RAF1 context. Reason: Cytosolic localisation of RAF1 is well supported (resting 14-3-3/HSP90-bound pool, and the cytoplasmic face of membranes where signalling complexes form); Reactome places this RAF1-containing entity in the cytosol for this event. Accept. Supporting Evidence: Reactome:R-HSA-9656207 CR2 RAF1 mutants don't bind YWHAB file:human/RAF1/RAF1-deep-research-falcon.md RAF1 is predominantly an inactive **cytosolic** complex at baseline and is recruited transiently to the cytoplasmic face of the **plasma membrane** by RAS-GTP |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9656209 | ACCEPT | Summary: Reactome TAS for cytosol from the event "Dissociation of RAS:RAF1 mutant complex". Dissociation of RAS from mutant RAF1 complexes. Reason: Cytosolic localisation of RAF1 is well supported (resting 14-3-3/HSP90-bound pool, and the cytoplasmic face of membranes where signalling complexes form); Reactome places this RAF1-containing entity in the cytosol for this event. Accept. Supporting Evidence: Reactome:R-HSA-9656209 Dissociation of RAS:RAF1 mutant complex file:human/RAF1/RAF1-deep-research-falcon.md RAF1 is predominantly an inactive **cytosolic** complex at baseline and is recruited transiently to the cytoplasmic face of the **plasma membrane** by RAS-GTP |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9656211 | ACCEPT | Summary: Reactome TAS for cytosol from the event "MAP2Ks and MAPKs bind to the activated mutant RAF1 complex". MAP2Ks and MAPKs bind activated mutant RAF1 complexes. Reason: Cytosolic localisation of RAF1 is well supported (resting 14-3-3/HSP90-bound pool, and the cytoplasmic face of membranes where signalling complexes form); Reactome places this RAF1-containing entity in the cytosol for this event. Accept. Supporting Evidence: Reactome:R-HSA-9656211 MAP2Ks and MAPKs bind to the activated mutant RAF1 complex file:human/RAF1/RAF1-deep-research-falcon.md RAF1 is predominantly an inactive **cytosolic** complex at baseline and is recruited transiently to the cytoplasmic face of the **plasma membrane** by RAS-GTP |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9656212 | ACCEPT | Summary: Reactome TAS for cytosol from the event "Phosphorylation of RAF1 mutants". Phosphorylation of RAF1 mutants. Reason: Cytosolic localisation of RAF1 is well supported (resting 14-3-3/HSP90-bound pool, and the cytoplasmic face of membranes where signalling complexes form); Reactome places this RAF1-containing entity in the cytosol for this event. Accept. Supporting Evidence: Reactome:R-HSA-9656212 Phosphorylation of RAF1 mutants file:human/RAF1/RAF1-deep-research-falcon.md RAF1 is predominantly an inactive **cytosolic** complex at baseline and is recruited transiently to the cytoplasmic face of the **plasma membrane** by RAS-GTP |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9656213 | ACCEPT | Summary: Reactome TAS for cytosol from the event "RAF1 mutants show enhanced heterodimerization with BRAF". RAF1 mutants show enhanced heterodimerization with BRAF. Reason: Cytosolic localisation of RAF1 is well supported (resting 14-3-3/HSP90-bound pool, and the cytoplasmic face of membranes where signalling complexes form); Reactome places this RAF1-containing entity in the cytosol for this event. Accept. Supporting Evidence: Reactome:R-HSA-9656213 RAF1 mutants show enhanced heterodimerization with BRAF file:human/RAF1/RAF1-deep-research-falcon.md RAF1 is predominantly an inactive **cytosolic** complex at baseline and is recruited transiently to the cytoplasmic face of the **plasma membrane** by RAS-GTP |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9656214 | ACCEPT | Summary: Reactome TAS for cytosol from the event "MAP2Ks phosphorylate MAPKs downstream of RAF1 mutants". MAP2Ks phosphorylate MAPKs downstream of RAF1 mutants. Reason: Cytosolic localisation of RAF1 is well supported (resting 14-3-3/HSP90-bound pool, and the cytoplasmic face of membranes where signalling complexes form); Reactome places this RAF1-containing entity in the cytosol for this event. Accept. Supporting Evidence: Reactome:R-HSA-9656214 MAP2Ks phosphorylate MAPKs downstream of RAF1 mutants file:human/RAF1/RAF1-deep-research-falcon.md RAF1 is predominantly an inactive **cytosolic** complex at baseline and is recruited transiently to the cytoplasmic face of the **plasma membrane** by RAS-GTP |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9656215 | ACCEPT | Summary: Reactome TAS for cytosol from the event "RAF1 mutant complexes phosphorylate MAP2K dimer". RAF1 mutant complexes phosphorylate the MAP2K dimer. Reason: Cytosolic localisation of RAF1 is well supported (resting 14-3-3/HSP90-bound pool, and the cytoplasmic face of membranes where signalling complexes form); Reactome places this RAF1-containing entity in the cytosol for this event. Accept. Supporting Evidence: Reactome:R-HSA-9656215 RAF1 mutant complexes phosphorylate MAP2K dimer file:human/RAF1/RAF1-deep-research-falcon.md RAF1 is predominantly an inactive **cytosolic** complex at baseline and is recruited transiently to the cytoplasmic face of the **plasma membrane** by RAS-GTP |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9658445 | ACCEPT | Summary: Reactome TAS for cytosol from the event "MRAS:SHOC2:PPP1CC dephosphorylates inactive RAFs". MRAS:SHOC2:PPP1CC dephosphorylates inactive RAFs (pS259). Reason: Cytosolic localisation of RAF1 is well supported (resting 14-3-3/HSP90-bound pool, and the cytoplasmic face of membranes where signalling complexes form); Reactome places this RAF1-containing entity in the cytosol for this event. Accept. Supporting Evidence: Reactome:R-HSA-9658445 MRAS:SHOC2:PPP1CC dephosphorylates inactive RAFs file:human/RAF1/RAF1-deep-research-falcon.md RAF1 is predominantly an inactive **cytosolic** complex at baseline and is recruited transiently to the cytoplasmic face of the **plasma membrane** by RAS-GTP |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9660536 | ACCEPT | Summary: Reactome TAS for cytosol from the event "SHOC2 M173I disrupts the SHOC2:MRAS:PP1 complex". SHOC2 M173I disrupts the SHOC2:MRAS:PP1 complex (RASopathy variant context). Reason: Cytosolic localisation of RAF1 is well supported (resting 14-3-3/HSP90-bound pool, and the cytoplasmic face of membranes where signalling complexes form); Reactome places this RAF1-containing entity in the cytosol for this event. Accept. Supporting Evidence: Reactome:R-HSA-9660536 SHOC2 M173I disrupts the SHOC2:MRAS:PP1 complex file:human/RAF1/RAF1-deep-research-falcon.md RAF1 is predominantly an inactive **cytosolic** complex at baseline and is recruited transiently to the cytoplasmic face of the **plasma membrane** by RAS-GTP |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9660538 | ACCEPT | Summary: Reactome TAS for cytosol from the event "Mutant MRAS:SHOC2:PPP1CC complexes dephosphorylate inactive RAFs". Mutant MRAS:SHOC2:PPP1CC complexes dephosphorylate inactive RAFs. Reason: Cytosolic localisation of RAF1 is well supported (resting 14-3-3/HSP90-bound pool, and the cytoplasmic face of membranes where signalling complexes form); Reactome places this RAF1-containing entity in the cytosol for this event. Accept. Supporting Evidence: Reactome:R-HSA-9660538 Mutant MRAS:SHOC2:PPP1CC complexes dephosphorylate inactive RAFs file:human/RAF1/RAF1-deep-research-falcon.md RAF1 is predominantly an inactive **cytosolic** complex at baseline and is recruited transiently to the cytoplasmic face of the **plasma membrane** by RAS-GTP |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9732729 | ACCEPT | Summary: Reactome TAS for cytosol from the event "Activated JAK1 binds RAF1". Activated JAK1 binds RAF1. Reason: Cytosolic localisation of RAF1 is well supported (resting 14-3-3/HSP90-bound pool, and the cytoplasmic face of membranes where signalling complexes form); Reactome places this RAF1-containing entity in the cytosol for this event. Accept. Supporting Evidence: Reactome:R-HSA-9732729 Activated JAK1 binds RAF1 file:human/RAF1/RAF1-deep-research-falcon.md RAF1 is predominantly an inactive **cytosolic** complex at baseline and is recruited transiently to the cytoplasmic face of the **plasma membrane** by RAS-GTP |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9732738 | ACCEPT | Summary: Reactome TAS for cytosol from the event "JAK1-mediated phosphorylation of RAF1". JAK1 phosphorylates RAF1 downstream of IFN-gamma; RAF1 is cytosolic in this step. Reason: Cytosolic localisation of RAF1 is well supported (resting 14-3-3/HSP90-bound pool, and the cytoplasmic face of membranes where signalling complexes form); Reactome places this RAF1-containing entity in the cytosol for this event. Accept. Supporting Evidence: Reactome:R-HSA-9732738 JAK1-mediated phosphorylation of RAF1 file:human/RAF1/RAF1-deep-research-falcon.md RAF1 is predominantly an inactive **cytosolic** complex at baseline and is recruited transiently to the cytoplasmic face of the **plasma membrane** by RAS-GTP |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9732753 | ACCEPT | Summary: Reactome TAS for cytosol from the event "JAK1-activated RAF1 phosphorylates MAPKs". JAK1-activated RAF1 phosphorylates downstream MAPK-pathway kinases. Reason: Cytosolic localisation of RAF1 is well supported (resting 14-3-3/HSP90-bound pool, and the cytoplasmic face of membranes where signalling complexes form); Reactome places this RAF1-containing entity in the cytosol for this event. Accept. Supporting Evidence: Reactome:R-HSA-9732753 JAK1-activated RAF1 phosphorylates MAPKs file:human/RAF1/RAF1-deep-research-falcon.md RAF1 is predominantly an inactive **cytosolic** complex at baseline and is recruited transiently to the cytoplasmic face of the **plasma membrane** by RAS-GTP |
| GO:0005886 plasma membrane | IDA GO_REF:0000052 | ACCEPT | Summary: HPA immunofluorescence for plasma membrane. Reason: Consistent with RAS-GTP-dependent recruitment of RAF1 to the plasma membrane. Supporting Evidence: file:human/RAF1/RAF1-uniprot.txt Recruited to the cell membrane by the active Ras protein. |
| GO:0005886 plasma membrane | IDA PMID:16009725 CAPRI and RASAL impose different modes of information proces... | ACCEPT | Summary: UniProt IDA colocalizes_with plasma membrane: the Raf-1 RBD reporter translocates to the plasma membrane with active Ras. Reason: Colocalization of the RAF1 RBD with RAS-GTP at the plasma membrane reflects the RAS-binding function that recruits full-length RAF1; the colocalizes_with qualifier appropriately reflects the reporter nature. Supporting Evidence: PMID:16009725 We therefore used the Ras-binding domain from Raf-1 tagged to GFP (GFP-RBD) as a reporter of active Ras on cell membranes |
| GO:0005886 plasma membrane | IDA PMID:17724343 Spatial regulation of Raf kinase signaling by RKTG. | ACCEPT | Summary: MGI IDA for plasma membrane: EGF stimulates Raf-1 membrane translocation, which RKTG blocks. Reason: Correct; canonical RAS-dependent membrane recruitment. Supporting Evidence: PMID:17724343 blocks EGF-stimulated Raf-1 membrane translocation |
| GO:0005886 plasma membrane | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt subcellular-location mapping (SL-0039) for plasma membrane (cell membrane). Reason: Correct; RAS-GTP recruits RAF1 to the inner leaflet of the plasma membrane where dimerization and MEK phosphorylation occur. Supporting Evidence: file:human/RAF1/RAF1-uniprot.txt Recruited to the cell membrane by the active Ras protein. file:human/RAF1/RAF1-deep-research-falcon.md RAF1 is predominantly an inactive **cytosolic** complex at baseline and is recruited transiently to the cytoplasmic face of the **plasma membrane** by RAS-GTP |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-5672969 | ACCEPT | Summary: Reactome TAS for plasma membrane from the event "Phosphorylation of RAF". Phosphorylation of RAF in the RAS:RAF complex. Reason: RAF1 in RAS:GTP-bound (and downstream RAF:MAP2K:MAPK) complexes is membrane-associated at the inner leaflet of the plasma membrane; Reactome places this RAF1-containing entity at the plasma membrane for this event. Accept. Supporting Evidence: Reactome:R-HSA-5672969 Phosphorylation of RAF file:human/RAF1/RAF1-uniprot.txt Recruited to the cell membrane by the active Ras protein. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-5672972 | ACCEPT | Summary: Reactome TAS for plasma membrane from the event "MAP2Ks and MAPKs bind to the activated RAF complex". MAP2Ks and MAPKs bind the activated RAF complex. Reason: RAF1 in RAS:GTP-bound (and downstream RAF:MAP2K:MAPK) complexes is membrane-associated at the inner leaflet of the plasma membrane; Reactome places this RAF1-containing entity at the plasma membrane for this event. Accept. Supporting Evidence: Reactome:R-HSA-5672972 MAP2Ks and MAPKs bind to the activated RAF complex file:human/RAF1/RAF1-uniprot.txt Recruited to the cell membrane by the active Ras protein. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-5672973 | ACCEPT | Summary: Reactome TAS for plasma membrane from the event "MAP2Ks phosphorylate MAPKs". MAP2Ks phosphorylate MAPKs within the RAS:RAF:MAP2K complex. Reason: RAF1 in RAS:GTP-bound (and downstream RAF:MAP2K:MAPK) complexes is membrane-associated at the inner leaflet of the plasma membrane; Reactome places this RAF1-containing entity at the plasma membrane for this event. Accept. Supporting Evidence: Reactome:R-HSA-5672973 MAP2Ks phosphorylate MAPKs file:human/RAF1/RAF1-uniprot.txt Recruited to the cell membrane by the active Ras protein. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-5672978 | ACCEPT | Summary: Reactome TAS for plasma membrane from the event "RAF phosphorylates MAP2K dimer". RAF phosphorylates the MAP2K dimer (the core RAF1 catalytic step). Reason: RAF1 in RAS:GTP-bound (and downstream RAF:MAP2K:MAPK) complexes is membrane-associated at the inner leaflet of the plasma membrane; Reactome places this RAF1-containing entity at the plasma membrane for this event. Accept. Supporting Evidence: Reactome:R-HSA-5672978 RAF phosphorylates MAP2K dimer file:human/RAF1/RAF1-uniprot.txt Recruited to the cell membrane by the active Ras protein. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-5672980 | ACCEPT | Summary: Reactome TAS for plasma membrane from the event "Dissociation of RAS:RAF complex". Dissociation of the RAS:RAF complex. Reason: RAF1 in RAS:GTP-bound (and downstream RAF:MAP2K:MAPK) complexes is membrane-associated at the inner leaflet of the plasma membrane; Reactome places this RAF1-containing entity at the plasma membrane for this event. Accept. Supporting Evidence: Reactome:R-HSA-5672980 Dissociation of RAS:RAF complex file:human/RAF1/RAF1-uniprot.txt Recruited to the cell membrane by the active Ras protein. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-5675194 | ACCEPT | Summary: Reactome TAS for plasma membrane from the event "Activated MAPK phosphorylates RAF1". Activated MAPK feedback-phosphorylates RAF1. Reason: RAF1 in RAS:GTP-bound (and downstream RAF:MAP2K:MAPK) complexes is membrane-associated at the inner leaflet of the plasma membrane; Reactome places this RAF1-containing entity at the plasma membrane for this event. Accept. Supporting Evidence: Reactome:R-HSA-5675194 Activated MAPK phosphorylates RAF1 file:human/RAF1/RAF1-uniprot.txt Recruited to the cell membrane by the active Ras protein. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-5675417 | ACCEPT | Summary: Reactome TAS for plasma membrane from the event "PEBP1 binds activated RAF1". PEBP1 binds activated RAF1. Reason: RAF1 in RAS:GTP-bound (and downstream RAF:MAP2K:MAPK) complexes is membrane-associated at the inner leaflet of the plasma membrane; Reactome places this RAF1-containing entity at the plasma membrane for this event. Accept. Supporting Evidence: Reactome:R-HSA-5675417 PEBP1 binds activated RAF1 file:human/RAF1/RAF1-uniprot.txt Recruited to the cell membrane by the active Ras protein. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-5675431 | ACCEPT | Summary: Reactome TAS for plasma membrane from the event "PP2A dephosphorylates RAF1". PP2A dephosphorylates RAF1 (membrane-associated activated complex). Reason: RAF1 in RAS:GTP-bound (and downstream RAF:MAP2K:MAPK) complexes is membrane-associated at the inner leaflet of the plasma membrane; Reactome places this RAF1-containing entity at the plasma membrane for this event. Accept. Supporting Evidence: Reactome:R-HSA-5675431 PP2A dephosphorylates RAF1 file:human/RAF1/RAF1-uniprot.txt Recruited to the cell membrane by the active Ras protein. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-5675433 | ACCEPT | Summary: Reactome TAS for plasma membrane from the event "PP5 dephosphorylates RAF1 S338". PP5 dephosphorylates RAF1 S338. Reason: RAF1 in RAS:GTP-bound (and downstream RAF:MAP2K:MAPK) complexes is membrane-associated at the inner leaflet of the plasma membrane; Reactome places this RAF1-containing entity at the plasma membrane for this event. Accept. Supporting Evidence: Reactome:R-HSA-5675433 PP5 dephosphorylates RAF1 S338 file:human/RAF1/RAF1-uniprot.txt Recruited to the cell membrane by the active Ras protein. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-6802908 | ACCEPT | Summary: Reactome TAS for plasma membrane from the event "RAS mutants bind inactive RAF". RAS mutants bind inactive RAF. Reason: RAF1 in RAS:GTP-bound (and downstream RAF:MAP2K:MAPK) complexes is membrane-associated at the inner leaflet of the plasma membrane; Reactome places this RAF1-containing entity at the plasma membrane for this event. Accept. Supporting Evidence: Reactome:R-HSA-6802908 RAS mutants bind inactive RAF file:human/RAF1/RAF1-uniprot.txt Recruited to the cell membrane by the active Ras protein. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-6802914 | ACCEPT | Summary: Reactome TAS for plasma membrane from the event "RAS:GTP:moderate kinase activity p-RAF complexes bind MAP2Ks and MAPKs". RAS:GTP:moderate-activity BRAF-mutant:RAF complexes bind MAP2Ks and MAPKs. Reason: RAF1 in RAS:GTP-bound (and downstream RAF:MAP2K:MAPK) complexes is membrane-associated at the inner leaflet of the plasma membrane; Reactome places this RAF1-containing entity at the plasma membrane for this event. Accept. Supporting Evidence: Reactome:R-HSA-6802914 RAS:GTP:moderate kinase activity p-RAF complexes bind MAP2Ks and MAPKs file:human/RAF1/RAF1-uniprot.txt Recruited to the cell membrane by the active Ras protein. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-6802916 | ACCEPT | Summary: Reactome TAS for plasma membrane from the event "RAF is phosphorylated downstream of moderate kinase activity BRAF mutants". RAF phosphorylated downstream of moderate-activity BRAF mutants. Reason: RAF1 in RAS:GTP-bound (and downstream RAF:MAP2K:MAPK) complexes is membrane-associated at the inner leaflet of the plasma membrane; Reactome places this RAF1-containing entity at the plasma membrane for this event. Accept. Supporting Evidence: Reactome:R-HSA-6802916 RAF is phosphorylated downstream of moderate kinase activity BRAF mutants file:human/RAF1/RAF1-uniprot.txt Recruited to the cell membrane by the active Ras protein. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-6802918 | ACCEPT | Summary: Reactome TAS for plasma membrane from the event "Activated MAP2Ks phosphorylate MAPKs downstream of inactive BRAF mutants". MAP2Ks phosphorylate MAPKs downstream of inactive BRAF mutants (RAF1-mediated). Reason: RAF1 in RAS:GTP-bound (and downstream RAF:MAP2K:MAPK) complexes is membrane-associated at the inner leaflet of the plasma membrane; Reactome places this RAF1-containing entity at the plasma membrane for this event. Accept. Supporting Evidence: Reactome:R-HSA-6802918 Activated MAP2Ks phosphorylate MAPKs downstream of inactive BRAF mutants file:human/RAF1/RAF1-uniprot.txt Recruited to the cell membrane by the active Ras protein. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-6802919 | ACCEPT | Summary: Reactome TAS for plasma membrane from the event "RAS:GTP:moderate kinase activity p-RAF complexes phosphorylate MAP2Ks". RAS:GTP:moderate-activity p-RAF complexes phosphorylate MAP2Ks. Reason: RAF1 in RAS:GTP-bound (and downstream RAF:MAP2K:MAPK) complexes is membrane-associated at the inner leaflet of the plasma membrane; Reactome places this RAF1-containing entity at the plasma membrane for this event. Accept. Supporting Evidence: Reactome:R-HSA-6802919 RAS:GTP:moderate kinase activity p-RAF complexes phosphorylate MAP2Ks file:human/RAF1/RAF1-uniprot.txt Recruited to the cell membrane by the active Ras protein. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-6802921 | ACCEPT | Summary: Reactome TAS for plasma membrane from the event "Activated MAP2Ks phosphorylate MAPKs downstream of moderate kinase activity BRAF mutants". MAP2Ks phosphorylate MAPKs downstream of moderate-activity BRAF mutants. Reason: RAF1 in RAS:GTP-bound (and downstream RAF:MAP2K:MAPK) complexes is membrane-associated at the inner leaflet of the plasma membrane; Reactome places this RAF1-containing entity at the plasma membrane for this event. Accept. Supporting Evidence: Reactome:R-HSA-6802921 Activated MAP2Ks phosphorylate MAPKs downstream of moderate kinase activity BRAF mutants file:human/RAF1/RAF1-uniprot.txt Recruited to the cell membrane by the active Ras protein. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-6802922 | ACCEPT | Summary: Reactome TAS for plasma membrane from the event "Activated MAP2Ks phosphorylate MAPKs downstream of oncogenic RAS". MAP2Ks phosphorylate MAPKs downstream of oncogenic RAS. Reason: RAF1 in RAS:GTP-bound (and downstream RAF:MAP2K:MAPK) complexes is membrane-associated at the inner leaflet of the plasma membrane; Reactome places this RAF1-containing entity at the plasma membrane for this event. Accept. Supporting Evidence: Reactome:R-HSA-6802922 Activated MAP2Ks phosphorylate MAPKs downstream of oncogenic RAS file:human/RAF1/RAF1-uniprot.txt Recruited to the cell membrane by the active Ras protein. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-6802924 | ACCEPT | Summary: Reactome TAS for plasma membrane from the event "RAF is phosphorylated downstream of oncogenic RAS". RAF phosphorylated downstream of oncogenic RAS. Reason: RAF1 in RAS:GTP-bound (and downstream RAF:MAP2K:MAPK) complexes is membrane-associated at the inner leaflet of the plasma membrane; Reactome places this RAF1-containing entity at the plasma membrane for this event. Accept. Supporting Evidence: Reactome:R-HSA-6802924 RAF is phosphorylated downstream of oncogenic RAS file:human/RAF1/RAF1-uniprot.txt Recruited to the cell membrane by the active Ras protein. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-6802925 | ACCEPT | Summary: Reactome TAS for plasma membrane from the event "Mutant RAS:p-RAF complexes bind MAP2Ks and MAPKs". Mutant RAS:p-RAF complexes bind MAP2Ks and MAPKs. Reason: RAF1 in RAS:GTP-bound (and downstream RAF:MAP2K:MAPK) complexes is membrane-associated at the inner leaflet of the plasma membrane; Reactome places this RAF1-containing entity at the plasma membrane for this event. Accept. Supporting Evidence: Reactome:R-HSA-6802925 Mutant RAS:p-RAF complexes bind MAP2Ks and MAPKs file:human/RAF1/RAF1-uniprot.txt Recruited to the cell membrane by the active Ras protein. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-6802926 | ACCEPT | Summary: Reactome TAS for plasma membrane from the event "Mutant RAS:p-RAF complexes phosphorylate MAP2Ks". Mutant RAS:p-RAF complexes phosphorylate MAP2Ks. Reason: RAF1 in RAS:GTP-bound (and downstream RAF:MAP2K:MAPK) complexes is membrane-associated at the inner leaflet of the plasma membrane; Reactome places this RAF1-containing entity at the plasma membrane for this event. Accept. Supporting Evidence: Reactome:R-HSA-6802926 Mutant RAS:p-RAF complexes phosphorylate MAP2Ks file:human/RAF1/RAF1-uniprot.txt Recruited to the cell membrane by the active Ras protein. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-6802941 | ACCEPT | Summary: Reactome TAS for plasma membrane from the event "RAF is paradoxically phosphorylated downstream of kinase-inactive RAF". RAF paradoxically phosphorylated downstream of kinase-inactive RAF. Reason: RAF1 in RAS:GTP-bound (and downstream RAF:MAP2K:MAPK) complexes is membrane-associated at the inner leaflet of the plasma membrane; Reactome places this RAF1-containing entity at the plasma membrane for this event. Accept. Supporting Evidence: Reactome:R-HSA-6802941 RAF is paradoxically phosphorylated downstream of kinase-inactive RAF file:human/RAF1/RAF1-uniprot.txt Recruited to the cell membrane by the active Ras protein. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-6802942 | ACCEPT | Summary: Reactome TAS for plasma membrane from the event "RAS:GTP:p-RAF complexes paradoxically bind MAP2Ks and MAPKs". Paradoxically activated RAS:GTP:p-RAF complexes bind MAP2Ks and MAPKs. Reason: RAF1 in RAS:GTP-bound (and downstream RAF:MAP2K:MAPK) complexes is membrane-associated at the inner leaflet of the plasma membrane; Reactome places this RAF1-containing entity at the plasma membrane for this event. Accept. Supporting Evidence: Reactome:R-HSA-6802942 RAS:GTP:p-RAF complexes paradoxically bind MAP2Ks and MAPKs file:human/RAF1/RAF1-uniprot.txt Recruited to the cell membrane by the active Ras protein. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-6802943 | ACCEPT | Summary: Reactome TAS for plasma membrane from the event "RAS:GTP:inactive p-RAF complexes phosphorylate MAP2Ks". RAS:GTP:inactive p-RAF complexes phosphorylate MAP2Ks. Reason: RAF1 in RAS:GTP-bound (and downstream RAF:MAP2K:MAPK) complexes is membrane-associated at the inner leaflet of the plasma membrane; Reactome places this RAF1-containing entity at the plasma membrane for this event. Accept. Supporting Evidence: Reactome:R-HSA-6802943 RAS:GTP:inactive p-RAF complexes phosphorylate MAP2Ks file:human/RAF1/RAF1-uniprot.txt Recruited to the cell membrane by the active Ras protein. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-6803230 | ACCEPT | Summary: Reactome TAS for plasma membrane from the event "Dissociation of moderate activity BRAF complexes". Dissociation of moderate-activity BRAF complexes. Reason: RAF1 in RAS:GTP-bound (and downstream RAF:MAP2K:MAPK) complexes is membrane-associated at the inner leaflet of the plasma membrane; Reactome places this RAF1-containing entity at the plasma membrane for this event. Accept. Supporting Evidence: Reactome:R-HSA-6803230 Dissociation of moderate activity BRAF complexes file:human/RAF1/RAF1-uniprot.txt Recruited to the cell membrane by the active Ras protein. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-6803233 | ACCEPT | Summary: Reactome TAS for plasma membrane from the event "Dissociation of oncogenic RAS:RAF complex". Dissociation of oncogenic RAS:RAF complex. Reason: RAF1 in RAS:GTP-bound (and downstream RAF:MAP2K:MAPK) complexes is membrane-associated at the inner leaflet of the plasma membrane; Reactome places this RAF1-containing entity at the plasma membrane for this event. Accept. Supporting Evidence: Reactome:R-HSA-6803233 Dissociation of oncogenic RAS:RAF complex file:human/RAF1/RAF1-uniprot.txt Recruited to the cell membrane by the active Ras protein. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-6803234 | ACCEPT | Summary: Reactome TAS for plasma membrane from the event "Dissociation of paradoxically activated RAS:BRAF complexes". Dissociation of paradoxically activated RAS:BRAF complexes. Reason: RAF1 in RAS:GTP-bound (and downstream RAF:MAP2K:MAPK) complexes is membrane-associated at the inner leaflet of the plasma membrane; Reactome places this RAF1-containing entity at the plasma membrane for this event. Accept. Supporting Evidence: Reactome:R-HSA-6803234 Dissociation of paradoxically activated RAS:BRAF complexes file:human/RAF1/RAF1-uniprot.txt Recruited to the cell membrane by the active Ras protein. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-6803240 | ACCEPT | Summary: Reactome TAS for plasma membrane from the event "Homo- or heterodimerization of RAF downstream of mutant RAS". Homo- or heterodimerization of RAF downstream of mutant RAS. Reason: RAF1 in RAS:GTP-bound (and downstream RAF:MAP2K:MAPK) complexes is membrane-associated at the inner leaflet of the plasma membrane; Reactome places this RAF1-containing entity at the plasma membrane for this event. Accept. Supporting Evidence: Reactome:R-HSA-6803240 Homo- or heterodimerization of RAF downstream of mutant RAS file:human/RAF1/RAF1-uniprot.txt Recruited to the cell membrane by the active Ras protein. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8936731 | ACCEPT | Summary: Reactome TAS for plasma membrane from the event "Inactive BRAF mutants:mutant RAS:GTP bind RAF1". Inactive BRAF mutants:mutant RAS:GTP bind RAF1. Reason: RAF1 in RAS:GTP-bound (and downstream RAF:MAP2K:MAPK) complexes is membrane-associated at the inner leaflet of the plasma membrane; Reactome places this RAF1-containing entity at the plasma membrane for this event. Accept. Supporting Evidence: Reactome:R-HSA-8936731 Inactive BRAF mutants:mutant RAS:GTP bind RAF1 file:human/RAF1/RAF1-uniprot.txt Recruited to the cell membrane by the active Ras protein. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9657599 | ACCEPT | Summary: Reactome TAS for plasma membrane from the event "Dual mechanism MAP2K inhibitors bind MAP2Ks". Dual-mechanism MAP2K inhibitors bind MAP2Ks in RAS:RAF:MAP2K complexes. Reason: RAF1 in RAS:GTP-bound (and downstream RAF:MAP2K:MAPK) complexes is membrane-associated at the inner leaflet of the plasma membrane; Reactome places this RAF1-containing entity at the plasma membrane for this event. Accept. Supporting Evidence: Reactome:R-HSA-9657599 Dual mechanism MAP2K inhibitors bind MAP2Ks file:human/RAF1/RAF1-uniprot.txt Recruited to the cell membrane by the active Ras protein. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9657603 | ACCEPT | Summary: Reactome TAS for plasma membrane from the event "Dual mechanism MAPK inhibitors bind MAPKs". Dual-mechanism MAPK inhibitors bind MAPKs in RAS:RAF complexes. Reason: RAF1 in RAS:GTP-bound (and downstream RAF:MAP2K:MAPK) complexes is membrane-associated at the inner leaflet of the plasma membrane; Reactome places this RAF1-containing entity at the plasma membrane for this event. Accept. Supporting Evidence: Reactome:R-HSA-9657603 Dual mechanism MAPK inhibitors bind MAPKs file:human/RAF1/RAF1-uniprot.txt Recruited to the cell membrane by the active Ras protein. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9657606 | ACCEPT | Summary: Reactome TAS for plasma membrane from the event "Single mechanism MAP2K inhibitors bind phosphorylated MAP2Ks". Single-mechanism MAP2K inhibitors bind phosphorylated MAP2Ks. Reason: RAF1 in RAS:GTP-bound (and downstream RAF:MAP2K:MAPK) complexes is membrane-associated at the inner leaflet of the plasma membrane; Reactome places this RAF1-containing entity at the plasma membrane for this event. Accept. Supporting Evidence: Reactome:R-HSA-9657606 Single mechanism MAP2K inhibitors bind phosphorylated MAP2Ks file:human/RAF1/RAF1-uniprot.txt Recruited to the cell membrane by the active Ras protein. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9657608 | ACCEPT | Summary: Reactome TAS for plasma membrane from the event "Single mechanism MAPK inhibitors bind phosphorylated MAPK". Single-mechanism MAPK inhibitors bind phosphorylated MAPK. Reason: RAF1 in RAS:GTP-bound (and downstream RAF:MAP2K:MAPK) complexes is membrane-associated at the inner leaflet of the plasma membrane; Reactome places this RAF1-containing entity at the plasma membrane for this event. Accept. Supporting Evidence: Reactome:R-HSA-9657608 Single mechanism MAPK inhibitors bind phosphorylated MAPK file:human/RAF1/RAF1-uniprot.txt Recruited to the cell membrane by the active Ras protein. |
| GO:0006468 protein phosphorylation | TAS PMID:8063729 Signaling through transforming G protein-coupled receptors i... | ACCEPT | Summary: TAS (PINC) for protein phosphorylation. Reason: Correct; RAF1 phosphorylates MEK (and BAD). Supporting Evidence: PMID:8063729 Carbachol potently induced c-Raf activity as judged by its in vitro phosphorylating activity using MEK as a substrate. |
| GO:0006915 apoptotic process | TAS PMID:8929532 Bcl-2 targets the protein kinase Raf-1 to mitochondria. | MODIFY | Summary: GO_Central TAS "acts upstream of or within, positive effect" apoptotic process, citing Wang et al. 1996 (Bcl-2 targets Raf-1 to mitochondria). Reason: The paper shows the opposite sign: mitochondria-targeted active Raf-1 protects cells from apoptosis and phosphorylates BAD, and kinase-inactive Raf-1 abrogates Bcl-2-mediated survival. The correct representation is negative regulation of apoptotic process. Proposed replacements: negative regulation of apoptotic process Supporting Evidence: PMID:8929532 Untargeted active Raf-1 improved Bcl-2-mediated resistance to apoptosis, whereas a kinase-inactive Raf-1 mutant abrogated apoptosis suppression by Bcl-2. |
| GO:0007165 signal transduction | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro2GO (Raf-like Ras-binding domain, IPR003116) for signal transduction. Reason: Correct but very general; RAF1 relays RAS signals to MEK. The specific process (MAPK cascade) is also annotated. Broad IEA terms are acceptable. Supporting Evidence: file:human/RAF1/RAF1-uniprot.txt Serine/threonine-protein kinase that acts as a regulatory |
| GO:0007165 signal transduction | TAS PMID:8063729 Signaling through transforming G protein-coupled receptors i... | ACCEPT | Summary: TAS (PINC) for signal transduction: Raf-1 mediates transforming GPCR (m1 muscarinic) signalling. Reason: Correct but general; MAPK cascade is the precise process. Supporting Evidence: PMID:8063729 our findings implicate Raf-1 activation in transformation by G protein-coupled receptors |
| GO:0007528 neuromuscular junction development | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ensembl Compara projection from mouse Raf1 for neuromuscular junction development. Reason: Derived from mouse genetic data (ERK pathway requirement in NMJ/Schwann cell development). RAF1 contributes as the MAP3K of the ERK cascade used in this tissue context; a pleiotropic downstream outcome rather than a core function. Supporting Evidence: file:human/RAF1/RAF1-uniprot.txt Serine/threonine-protein kinase that acts as a regulatory |
| GO:0008285 negative regulation of cell population proliferation | IDA PMID:9765203 Premature senescence involving p53 and p16 is activated in r... | UNDECIDED | Summary: BHF-UCL IDA for negative regulation of cell population proliferation from Lin et al. 1998 (premature senescence in response to constitutive MEK/MAPK signalling). Reason: The cached publication contains no abstract or text, and the PubMed abstract describes constitutively active MEK inducing p53/p16-dependent senescence without mentioning RAF1. The RAF1 experiment (probably an activated Raf construct) is presumably in the full text, which is not available here. Even if confirmed, oncogene-induced senescence from supraphysiological signalling would be non-core for RAF1, whose normal role is pro-proliferative. Supporting Evidence: file:human/RAF1/RAF1-uniprot.txt determining cell fate decisions including proliferation, |
| GO:0008286 insulin receptor signaling pathway | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ensembl Compara projection from mouse Raf1 for insulin receptor signaling pathway. Reason: RAF1 is the MAP3K in the RAS-ERK arm downstream of the insulin receptor; plausible participation, but one of many receptor pathways feeding the same cascade. Supporting Evidence: file:human/RAF1/RAF1-uniprot.txt Serine/threonine-protein kinase that acts as a regulatory |
| GO:0010856 adenylate cyclase activator activity | IDA PMID:15385642 Raf kinase activation of adenylyl cyclases: isoform-selectiv... | KEEP AS NON CORE | Summary: BHF-UCL IDA for adenylate cyclase activator activity: c-Raf phosphorylates adenylyl cyclase VI (and II, V), sensitizing/activating it. Reason: The mechanism is RAF1 kinase-mediated phosphorylation of AC; an activator-activity MF is a defensible representation of the effect but this is a non-canonical, isoform-selective target, not a core RAF1 function. Supporting Evidence: PMID:15385642 we now demonstrate that in reconstitution studies, c-Raf kinase can mediate phosphorylation of AC VI |
| GO:0014044 Schwann cell development | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ensembl Compara projection from mouse Raf1 for Schwann cell development. Reason: Mouse-derived developmental phenotype mediated by ERK signalling; pleiotropic downstream outcome, not a core RAF1 function. Supporting Evidence: file:human/RAF1/RAF1-uniprot.txt Serine/threonine-protein kinase that acts as a regulatory |
| GO:0019899 enzyme binding | IPI PMID:23509299 Phosphodiesterase-8A binds to and regulates Raf-1 kinase. | KEEP AS NON CORE | Summary: IPI (UniProt) with PDE8A: PDE8A binds Raf-1 with picomolar affinity and regulates it (PKA-dependent S259 phosphorylation). Reason: Enzyme binding is generic but not wrong; the interaction is a regulatory input onto RAF1 rather than a RAF1 activity. Keep as non-core. Supporting Evidence: PMID:23509299 PDE8A binds to Raf-1 with high (picomolar) affinity. |
| GO:0031143 pseudopodium | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ensembl Compara projection from mouse Raf1 for pseudopodium. Reason: A pool of RAF1 may localize to pseudopodia in migrating cells (RAF1 regulates motility via Rok-alpha), but this is a context-specific location. Supporting Evidence: PMID:21779496 the regulation of cell motility and differentiation by controlling the activity of Rok-Ξ± |
| GO:0031267 small GTPase binding | IPI NOT PMID:12194967 Di-Ras, a distinct subgroup of ras family GTPases with uniqu... | REMOVE | Summary: UniProt NOT enables small GTPase binding, with Di-Ras (DIRAS1/2) as WITH/FROM: Di-Ras fails to bind the Raf RBD. Reason: The experimental observation is correct for Di-Ras, but a NOT annotation on the general term small GTPase binding asserts that RAF1 does not bind any small GTPase, which is contradicted by the defining RAF1 function as a direct RAS/RAP effector (PMID:8332187, PMID:7791872, PMID:33608534). The Di-Ras-specific negative result cannot be expressed by negating the general term; the negation should be removed. Supporting Evidence: PMID:12194967 Di-Ras fails to interact with the Ras-binding domain of Raf PMID:8332187 Raf-1 (1-257) binds GTP-Ras in preference to GDP-Ras |
| GO:0031333 negative regulation of protein-containing complex assembly | IDA PMID:19667065 Identification of novel in vivo phosphorylation sites of the... | KEEP AS NON CORE | Summary: UniProt IDA for negative regulation of protein-containing complex assembly: RAF phosphorylation of BAD alters BAD association with Bcl-2/Bcl-XL and 14-3-3. Reason: This describes a downstream consequence of BAD phosphorylation by RAF (reduced BAD-Bcl-2/Bcl-XL complex) rather than a direct RAF1 activity; non-core and fairly indirect. Supporting Evidence: PMID:19667065 we analyzed the direct consequences of BAD phosphorylation by RAF with respect to association with 14-3-3 and Bcl-2/Bcl-X(L) proteins |
| GO:0033138 positive regulation of peptidyl-serine phosphorylation | IDA PMID:19667065 Identification of novel in vivo phosphorylation sites of the... | KEEP AS NON CORE | Summary: UniProt IDA for positive regulation of peptidyl-serine phosphorylation (of BAD). Reason: RAF-dependent BAD phosphorylation is largely direct and already captured by the kinase MF; as a process annotation it is acceptable but describes a context-specific output, non-core. Supporting Evidence: PMID:19667065 RAF-induced phosphorylation of BAD was reduced to control levels using the RAF inhibitor BAY 43-9006. |
| GO:0035023 regulation of Rho protein signal transduction | TAS PMID:16649144 Back to the roots: the remarkable RAF oncogene story. | KEEP AS NON CORE | Summary: UniProt TAS (review) for regulation of Rho protein signal transduction: RAF1 binds and inhibits Rok-alpha (ROCK2). Reason: A kinase-independent function established by Raf-1 knockout studies (keratinocyte/fibroblast migration); genuine but non-core. The cited review abstract is general; the mechanism is summarised in PMID:21779496. Supporting Evidence: PMID:21779496 the regulation of cell motility and differentiation by controlling the activity of Rok-Ξ± PMID:16649144 the last 20 years have seen the dissection of the signaling pathways in which RAF kinases function |
| GO:0038112 interleukin-8-mediated signaling pathway | IDA PMID:8576262 Interleukin-8 regulation of the Ras/Raf/mitogen-activated pr... | KEEP AS NON CORE | Summary: IDA: Raf-1 is activated downstream of the IL-8 receptor in neutrophils. Reason: RAF1 participates in IL-8-induced MAPK signalling, but this is one of many receptor contexts feeding the core cascade. Supporting Evidence: PMID:8576262 IL-8 activation of MAPK follows a time course suggesting an involvement of both Raf-1 and B-Raf. |
| GO:0038127 ERBB signaling pathway | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ensembl Compara projection from mouse Raf1 for ERBB signaling pathway. Reason: RAF1 relays EGFR/ERBB-RAS signals to MEK; genuine participation but a specific upstream receptor context of the core cascade. Supporting Evidence: PMID:22886303 FAM83A interacts with c-RAF and PI3K upstream of MEK1/2 activation. |
| GO:0038133 ERBB2-ERBB3 signaling pathway | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ensembl Compara projection from mouse Raf1 for ERBB2-ERBB3 signaling pathway. Reason: Mouse-derived (Schwann-cell neuregulin/ERBB2-ERBB3 signalling to ERK); a specific receptor context, non-core. Supporting Evidence: file:human/RAF1/RAF1-uniprot.txt Serine/threonine-protein kinase that acts as a regulatory |
| GO:0042060 wound healing | TAS PMID:15943972 Second nature: biological functions of the Raf-1 "kinase". | KEEP AS NON CORE | Summary: UniProt TAS (review of kinase-independent Raf-1 functions) for wound healing. Reason: Raf-1 is required for normal keratinocyte migration and wound healing via Rok-alpha restraint (mouse genetics); a tissue-level outcome, non-core. Supporting Evidence: PMID:15943972 This review focuses on the regulation and biology of the best-studied Raf isoform, Raf-1, in the context of its kinase-independent functions. file:human/RAF1/RAF1-uniprot.txt migration, and is required for normal wound healing |
| GO:0042552 myelination | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ensembl Compara projection from mouse Raf1 for myelination. Reason: Mouse-derived developmental outcome of ERK signalling in Schwann cells; pleiotropic and non-core. Supporting Evidence: file:human/RAF1/RAF1-uniprot.txt Serine/threonine-protein kinase that acts as a regulatory |
| GO:0042802 identical protein binding | IPI PMID:17979178 A novel tandem affinity purification strategy for the effici... | ACCEPT | Summary: IPI (IntAct, self-interaction) from a SF-TAP purification of native Raf complexes for RAF1 homo-oligomerization. Reason: RAF1 homodimerization via the side-to-side kinase-domain interface is part of normal and drug-induced (paradoxical) RAF activation; identical protein binding is informative here and matches the BRAF review, which accepted the same term. The cached abstract does not itself state the self-interaction; deferring to the curator who read the full text. Supporting Evidence: PMID:17979178 purification of Raf associated protein complexes from HEK293 cells file:human/RAF1/RAF1-uniprot.txt SUBUNIT: Monomer. Homodimer. Heterodimerizes with BRAF and this |
| GO:0042802 identical protein binding | IPI PMID:20130576 RAF inhibitors prime wild-type RAF to activate the MAPK path... | ACCEPT | Summary: IPI (IntAct, self-interaction) from a RAF inhibitor-induced dimerization of wild-type RAF for RAF1 homo-oligomerization. Reason: RAF1 homodimerization via the side-to-side kinase-domain interface is part of normal and drug-induced (paradoxical) RAF activation; identical protein binding is informative here and matches the BRAF review, which accepted the same term. The cached abstract does not itself state the self-interaction; deferring to the curator who read the full text. Supporting Evidence: file:human/RAF1/RAF1-uniprot.txt SUBUNIT: Monomer. Homodimer. Heterodimerizes with BRAF and this |
| GO:0042802 identical protein binding | IPI PMID:22169110 Nilotinib and MEK inhibitors induce synthetic lethality thro... | ACCEPT | Summary: IPI (IntAct, self-interaction) from a paradoxical RAF activation by nilotinib, including CRAF homodimers for RAF1 homo-oligomerization. Reason: RAF1 homodimerization via the side-to-side kinase-domain interface is part of normal and drug-induced (paradoxical) RAF activation; identical protein binding is informative here and matches the BRAF review, which accepted the same term. Supporting Evidence: PMID:22169110 Paradoxical activation of the pathway can also be achieved by CRAF inhibition, which drives CRAF homodimerization file:human/RAF1/RAF1-uniprot.txt SUBUNIT: Monomer. Homodimer. Heterodimerizes with BRAF and this |
| GO:0042802 identical protein binding | IPI PMID:22510884 Distinct requirement for an intact dimer interface in wild-t... | ACCEPT | Summary: IPI (IntAct, self-interaction) from a dissection of the RAF dimer interface for RAF1 homo-oligomerization. Reason: RAF1 homodimerization via the side-to-side kinase-domain interface is part of normal and drug-induced (paradoxical) RAF activation; identical protein binding is informative here and matches the BRAF review, which accepted the same term. Supporting Evidence: PMID:22510884 as well as the paradoxical activation of Raf-1 by kinase-inactivated B-Raf require an intact DIF file:human/RAF1/RAF1-uniprot.txt SUBUNIT: Monomer. Homodimer. Heterodimerizes with BRAF and this |
| GO:0042981 regulation of apoptotic process | TAS PMID:21779496 Raf family kinases: old dogs have learned new tricks. | MODIFY | Summary: UniProt TAS (review) for regulation of apoptotic process. Reason: Correct in essence, but the direction is known: RAF1 suppresses apoptosis (inhibition of ASK1 and MST2, BAD phosphorylation, restriction of caspase activation). Replace with the more precise negative regulation term. Proposed replacements: negative regulation of apoptotic process Supporting Evidence: PMID:21779496 These include the regulation of apoptosis by suppressing the activity of the proapoptotic kinases, ASK1 and MST2 PMID:21779496 a main function of Raf-1 was to restrict caspase activation in response to selected stimuli |
| GO:0043066 negative regulation of apoptotic process | IDA PMID:19667065 Identification of novel in vivo phosphorylation sites of the... | ACCEPT | Summary: UniProt IDA: constitutively active RAF suppresses BAD-induced apoptosis. Reason: Well-supported anti-apoptotic RAF1 function (also via ASK1/MST2 inhibition); consistent with BRAF review accepting the same row. Supporting Evidence: PMID:19667065 expression of constitutively active RAF suppressed apoptosis induced by BAD |
| GO:0043066 negative regulation of apoptotic process | IEA GO_REF:0000117 | ACCEPT | Summary: ARBA rule for negative regulation of apoptotic process. Reason: Correct; RAF1 suppresses apoptosis through kinase-independent inhibition of ASK1 and MST2 and through mitochondrial BAD phosphorylation. Consistent with IDA evidence (PMID:19667065) and the BRAF review. Supporting Evidence: PMID:21779496 These include the regulation of apoptosis by suppressing the activity of the proapoptotic kinases, ASK1 and MST2 file:human/RAF1/RAF1-uniprot.txt Can protect cells from apoptosis also by |
| GO:0043410 positive regulation of MAPK cascade | IDA PMID:10644344 Hepatitis C virus core protein interacts with 14-3-3 protein... | ACCEPT | Summary: IDA (GO_Central) from a study showing HCV core protein binds 14-3-3 and activates Raf-1. Reason: Raf-1 activation drives MEK-ERK activation; positive regulation of MAPK cascade is acceptable for the RAF tier (consistent with the ComplexPortal row and the BRAF review). The viral context does not change the RAF1 role. Supporting Evidence: PMID:10644344 Hepatitis C virus core protein interacts with 14-3-3 protein and activates the kinase Raf-1. |
| GO:0043410 positive regulation of MAPK cascade | NAS PMID:33608534 KRAS interaction with RAF1 RAS-binding domain and cysteine-r... | ACCEPT | Summary: ComplexPortal NAS for positive regulation of MAPK cascade, attached to the KRAS-RAF1 complex (RBD-CRD structure paper). Reason: The KRAS-RAF1 complex initiates ERK cascade activation; positive regulation of MAPK cascade is an acceptable complex-level process (BRAF review accepted the analogous ERK-cascade regulation term). Supporting Evidence: PMID:33608534 The interaction of membrane-bound active RAS with RAF is the first step in the activation of this pathway |
| GO:0045595 regulation of cell differentiation | TAS PMID:21779496 Raf family kinases: old dogs have learned new tricks. | KEEP AS NON CORE | Summary: UniProt TAS (review) for regulation of cell differentiation. Reason: RAF1 influences differentiation (Rok-alpha control, erythroid and myeloid differentiation), but the term is broad and the effects are context-specific; non-core. Supporting Evidence: PMID:21779496 the regulation of cell motility and differentiation by controlling the activity of Rok-Ξ± |
| GO:0048009 insulin-like growth factor receptor signaling pathway | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ensembl Compara projection from mouse Raf1 for insulin-like growth factor receptor signaling pathway. Reason: RAF1 is the MAP3K in the RAS-ERK arm downstream of IGF1R; specific receptor context, non-core. Supporting Evidence: file:human/RAF1/RAF1-uniprot.txt Serine/threonine-protein kinase that acts as a regulatory |
| GO:0060333 type II interferon-mediated signaling pathway | TAS Reactome:R-HSA-877300 | KEEP AS NON CORE | Summary: Reactome pathway "Interferon gamma signaling" includes JAK1-mediated RAF1 activation. Reason: IFN-gamma activates Raf-1 in a JAK1-dependent, RAS-independent manner (PMID:9446616); RAF1 participates in a branch of this pathway, but it is not a core RAF1 process. Supporting Evidence: PMID:9446616 These observations suggest that a kinase-active Jak1 is required for IFNgamma activation of Raf-1 that is p21(ras)-independent. Reactome:R-HSA-877300 Interferon gamma signaling |
| GO:0106310 protein serine kinase activity | EXP PMID:17603483 Gain-of-function RAF1 mutations cause Noonan and LEOPARD syn... | ACCEPT | Summary: UniProt EXP (catalytic activity evidence) from the Noonan/LEOPARD RAF1 mutation study, which measured RAF1 kinase activity of wild-type and mutant proteins. Reason: RAF1 kinase activity (MEK/ERK activation) was measured directly; supports protein serine kinase activity. Supporting Evidence: PMID:17603483 Ectopically expressed RAF1 mutants from the two HCM hotspots had increased kinase activity and enhanced ERK activation |
| GO:0106310 protein serine kinase activity | IEA GO_REF:0000116 | ACCEPT | Summary: Rhea mapping (RHEA:17989, protein L-serine phosphorylation) for protein serine kinase activity. Reason: Correct; RAF1 phosphorylates serines (MEK1 S218/S222, MEK2 S222/S226, BAD S75). Supporting Evidence: file:human/RAF1/RAF1-uniprot.txt Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + |
| GO:1902554 serine/threonine protein kinase complex | IPI PMID:33608534 KRAS interaction with RAF1 RAS-binding domain and cysteine-r... | ACCEPT | Summary: ComplexPortal IPI placing RAF1 in a serine/threonine protein kinase complex (KRAS-RAF1 RBD-CRD complex). Reason: RAF1 bound to RAS-GTP is a Ser/Thr kinase-containing complex; the structure paper directly characterises the KRAS-RAF1 RBD-CRD interaction. Supporting Evidence: PMID:33608534 KRAS interaction with RAF1 RAS-binding domain and cysteine-rich domain provides insights into RAS-mediated RAF activation. |
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Download this section (compressed HTML)Q: Should the UniProt NOT small GTPase binding annotation (Di-Ras, PMID:12194967) be withdrawn or re-expressed as a partner-specific negative interaction, given that the general term is contradicted by RAF1 being a canonical RAS/RAP effector?
Q: Several IntAct RAF1-RAS IPI records cite papers whose abstracts do not mention RAF1 (e.g. PMID:19696784 on fission-yeast Alp7/TACC); are these RBD pull-down controls, and should the fission-yeast citation be corrected?
Q: What fraction of RAF1-dependent signalling in KRAS-mutant tissues is catalytic (MEK phosphorylation) versus scaffold (BRAF heterodimer allosteric activation, MST2/ASK1 inhibition), and does this differ between RAF1-dependent tumours and Noonan-syndrome cardiomyocytes?
Q: Are BAD, adenylyl cyclases, RB1 and PPP1R12A direct physiological RAF1 substrates in vivo, comparable to MEK1/2, or context-specific in vitro targets?
Experiment: Knock-in of a kinase-dead (e.g. K375M) versus an RBD-dead (R89L) RAF1 allele in human cardiomyocyte and KRAS-mutant cancer cell models, combined with phosphoproteomics and apoptosis readouts.
Hypothesis: Anti-apoptotic and tumour-maintenance functions of RAF1 require RAS binding and dimerization but not catalytic activity, whereas MEK activation in cells lacking BRAF requires RAF1 catalysis.
Type: genetic
Experiment: Quantitative substrate profiling (analogue-sensitive RAF1 with thiophosphate labelling) in cells with mitochondria-targeted versus membrane-targeted RAF1.
Hypothesis: Membrane RAF1 phosphorylates essentially only MEK1/2, while the mitochondrial pool phosphorylates BAD and a small set of additional apoptosis regulators.
Type: biochemical
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