PTK2 encodes focal adhesion kinase (FAK), a cytoplasmic non-receptor protein tyrosine kinase with an N-terminal FERM domain, a central kinase domain, proline-rich regions and a C-terminal focal adhesion targeting (FAT) domain. Integrin engagement, and also growth factor and G protein-coupled receptor signalling, triggers autophosphorylation of Tyr397, which creates an SH2 docking site for Src family kinases. Src then phosphorylates the FAK activation loop and further sites that recruit Grb2, PI3K and p120RasGAP, forming a dual FAK-Src kinase complex. FAK is targeted to focal adhesions through FAT domain binding to paxillin and talin. It phosphorylates substrates such as p130Cas/NEDD9 and N-WASP and controls Rho-family GTPase GEFs and GAPs, so it regulates focal adhesion assembly and turnover, cell spreading, directional migration, proliferation and anchorage-dependent survival. A smaller nuclear pool uses the FERM domain as a scaffold that promotes Mdm2-dependent p53 degradation. A kinase-dead C-terminal isoform (FRNK) inhibits FAK signalling. FAK is essential for mouse embryonic development, including vascular, cardiac and neural development. It is part of an integrin adhesome that predates animals: canonical FAK with the full domain set is present in the filasterean Capsaspora owczarzaki, which also uses integrin-based adhesion to a substrate, whereas the choanoflagellates examined lack canonical FAK and have only a FAK-related kinase domain.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0001525 angiogenesis | TAS PMID:20552554 The role of focal adhesion kinase in early development. | KEEP AS NON CORE | Summary: angiogenesis (TAS, review PMID:20552554 on FAK in early development). Reason: The review summarises knockout and conditional-knockout data placing FAK in development of the placenta and of cardiovascular and other organ systems. FAK acts here through its general integrin-signalling, adhesion-turnover and migration functions in the relevant cell types, so angiogenesis is a downstream, animal-specific developmental context rather than a core function. Supporting Evidence: PMID:20552554 Various published data supported the role of the molecule in the development of the placenta, as well as of several organ systems, like the musculoskeletal, nervous, cardiovascular, genitourinary and respiratory organ systems |
| GO:0001725 stress fiber | IDA PMID:24036928 Integrin-Ξ²5 and zyxin mediate formation of ventral stress fi... | KEEP AS NON CORE | Summary: stress fiber (IDA, PMID:24036928): phospho-Tyr861 FAK staining at the ends of TGF-beta-induced ventral stress fibers. Reason: The image shows FAK at the termini of actin fibers, i.e. at the focal adhesions that anchor ventral stress fibers, rather than along the fiber itself. The curator observation is retained, but focal adhesion is the informative location. Supporting Evidence: PMID:24036928 TGF-Ξ²1 increased phospho-Tyr861-FAK staining at the ends of actin fibers in the control cells |
| GO:0001890 placenta development | TAS PMID:20552554 The role of focal adhesion kinase in early development. | KEEP AS NON CORE | Summary: placenta development (TAS, review PMID:20552554 on FAK in early development). Reason: The review summarises knockout and conditional-knockout data placing FAK in development of the placenta and of cardiovascular and other organ systems. FAK acts here through its general integrin-signalling, adhesion-turnover and migration functions in the relevant cell types, so placenta development is a downstream, animal-specific developmental context rather than a core function. Supporting Evidence: PMID:20552554 Various published data supported the role of the molecule in the development of the placenta, as well as of several organ systems, like the musculoskeletal, nervous, cardiovascular, genitourinary and respiratory organ systems |
| GO:0001952 regulation of cell-matrix adhesion | IEA GO_REF:0000117 | ACCEPT | Summary: regulation of cell-matrix adhesion (IEA, ARBA). Reason: FAK controls the strength and turnover of integrin-ECM adhesions; FAK depletion reverses the increased cell-matrix adhesion caused by Coronin 1C loss in intestinal epithelial cells (PMID:19913511). The electronic term is consistent with the experimental picture. Supporting Evidence: PMID:19913511 FAK-mediated signaling is a critical downstream component, which mediates negative effects of Coronin 1C on both cell-matrix adhesion and motility of IECs |
| GO:0003007 heart morphogenesis | TAS PMID:20552554 The role of focal adhesion kinase in early development. | KEEP AS NON CORE | Summary: heart morphogenesis (TAS, review PMID:20552554 on FAK in early development). Reason: The review summarises knockout and conditional-knockout data placing FAK in development of the placenta and of cardiovascular and other organ systems. FAK acts here through its general integrin-signalling, adhesion-turnover and migration functions in the relevant cell types, so heart morphogenesis is a downstream, animal-specific developmental context rather than a core function. Supporting Evidence: PMID:20552554 Various published data supported the role of the molecule in the development of the placenta, as well as of several organ systems, like the musculoskeletal, nervous, cardiovascular, genitourinary and respiratory organ systems |
| GO:0003779 actin binding | IDA PMID:16803572 Role of dystrophins and utrophins in platelet adhesion proce... | UNDECIDED | Summary: actin binding (IDA, PMID:16803572, platelet dystrophin/utrophin study). Reason: Direct F-actin binding by FAK is not an established FAK activity; FAK is linked to actin indirectly through paxillin, talin and vinculin. The cached abstract of PMID:16803572 does not mention FAK at all, and the full text is not available, so the curator evidence cannot be checked. Not removed because it is an experimental annotation whose source we cannot read. |
| GO:0004672 protein kinase activity | IEA GO_REF:0000002 | ACCEPT | Summary: protein kinase activity (IEA, InterPro kinase-domain mapping). Reason: Correct but general; FAK is a tyrosine kinase, captured more precisely by GO:0004715. Supporting Evidence: PMID:9360983 FAK directly phosphorylates Cas proteins primarily at the YDYVHL sequence that is conserved among all Cas proteins |
| GO:0004713 protein tyrosine kinase activity | EXP PMID:10655584 Activation of EphA2 kinase suppresses integrin function and ... | ACCEPT | Summary: protein tyrosine kinase activity (EXP, PMID:10655584): EphA2 study; FAK kinase/autophosphorylation assayed as part of integrin signalling. Reason: FAK is a bona fide non-receptor protein tyrosine kinase that autophosphorylates Tyr397 and phosphorylates substrates such as Cas proteins and N-WASP. Core catalytic activity. Supporting Evidence: PMID:12391143 Autophosphorylation of FAK on Tyr-397 is a critical event, allowing binding of Src family kinases and activation of signal transduction pathways |
| GO:0004713 protein tyrosine kinase activity | EXP PMID:12235133 Phosphorylation of tyrosine 291 enhances the ability of WASp... | ACCEPT | Summary: protein tyrosine kinase activity (EXP, PMID:12235133): WASp Tyr291 phosphorylation study; full text not cached, curator recorded FAK kinase activity. Reason: FAK is a bona fide non-receptor protein tyrosine kinase that autophosphorylates Tyr397 and phosphorylates substrates such as Cas proteins and N-WASP. Core catalytic activity. Supporting Evidence: PMID:9360983 FAK directly phosphorylates Cas proteins primarily at the YDYVHL sequence that is conserved among all Cas proteins |
| GO:0004713 protein tyrosine kinase activity | EXP PMID:12391143 Alternative splicing controls the mechanisms of FAK autophos... | ACCEPT | Summary: protein tyrosine kinase activity (EXP, PMID:12391143): autophosphorylation and kinase activity towards poly(Glu,Tyr) measured for rat FAK splice isoforms; the curator transferred it to the human protein, whose sequence is conserved. Reason: FAK is a bona fide non-receptor protein tyrosine kinase that autophosphorylates Tyr397 and phosphorylates substrates such as Cas proteins and N-WASP. Core catalytic activity. Supporting Evidence: PMID:12391143 Autophosphorylation of FAK on Tyr-397 is a critical event, allowing binding of Src family kinases and activation of signal transduction pathways |
| GO:0004713 protein tyrosine kinase activity | EXP PMID:14676198 Focal adhesion kinase regulation of N-WASP subcellular local... | ACCEPT | Summary: protein tyrosine kinase activity (EXP, PMID:14676198): FAK directly phosphorylates N-WASP Tyr256. Reason: FAK is a bona fide non-receptor protein tyrosine kinase that autophosphorylates Tyr397 and phosphorylates substrates such as Cas proteins and N-WASP. Core catalytic activity. Supporting Evidence: PMID:14676198 N-WASP is phosphorylated by FAK at a conserved tyrosine residue, Tyr(256) |
| GO:0004713 protein tyrosine kinase activity | IEA GO_REF:0000120 | ACCEPT | Summary: protein tyrosine kinase activity (IEA, combined InterPro/RHEA mapping). Reason: Consistent with the experimentally established tyrosine kinase activity (core). Supporting Evidence: PMID:9360983 FAK directly phosphorylates Cas proteins primarily at the YDYVHL sequence that is conserved among all Cas proteins |
| GO:0004713 protein tyrosine kinase activity | TAS Reactome:R-HSA-354073 | ACCEPT | Summary: protein tyrosine kinase activity (TAS, Reactome R-HSA-354073 Autophosphorylation of PTK2 at Y397). Reason: Reactome reactions in which FAK autophosphorylates Tyr397 or phosphorylates a substrate; consistent with the core tyrosine kinase activity. Supporting Evidence: PMID:12391143 Autophosphorylation of FAK on Tyr-397 is a critical event, allowing binding of Src family kinases and activation of signal transduction pathways |
| GO:0004713 protein tyrosine kinase activity | TAS Reactome:R-HSA-8874078 | ACCEPT | Summary: protein tyrosine kinase activity (TAS, Reactome R-HSA-8874078 PTK2 autophosphorylates (downstream of MET)). Reason: Reactome reactions in which FAK autophosphorylates Tyr397 or phosphorylates a substrate; consistent with the core tyrosine kinase activity. Supporting Evidence: PMID:12391143 Autophosphorylation of FAK on Tyr-397 is a critical event, allowing binding of Src family kinases and activation of signal transduction pathways |
| GO:0004713 protein tyrosine kinase activity | TAS Reactome:R-HSA-9625487 | ACCEPT | Summary: protein tyrosine kinase activity (TAS, Reactome R-HSA-9625487 PTK2 autophosphorylates downstream of EGFR). Reason: Reactome reactions in which FAK autophosphorylates Tyr397 or phosphorylates a substrate; consistent with the core tyrosine kinase activity. Supporting Evidence: PMID:12391143 Autophosphorylation of FAK on Tyr-397 is a critical event, allowing binding of Src family kinases and activation of signal transduction pathways |
| GO:0004713 protein tyrosine kinase activity | TAS Reactome:R-HSA-9861469 | ACCEPT | Summary: protein tyrosine kinase activity (TAS, Reactome R-HSA-9861469 p-Y397-PTK2 phosphorylates CHUK). Reason: Reactome reactions in which FAK autophosphorylates Tyr397 or phosphorylates a substrate; consistent with the core tyrosine kinase activity. Supporting Evidence: PMID:12391143 Autophosphorylation of FAK on Tyr-397 is a critical event, allowing binding of Src family kinases and activation of signal transduction pathways |
| GO:0004715 non-membrane spanning protein tyrosine kinase activity | IBA GO_REF:0000033 | ACCEPT | Summary: non-membrane spanning protein tyrosine kinase activity (IBA, PTN002400754, FAK/PYK2 node). Reason: PAINT placed this activity on the FAK/PYK2 (PTK2/PTK2B) ancestral node; human PTK2 appears among the experimentally annotated descendants, which is expected. FAK is a cytoplasmic, non-transmembrane tyrosine kinase, so this is the most precise MF term for the core activity. Supporting Evidence: PMID:9360983 FAK directly phosphorylates Cas proteins primarily at the YDYVHL sequence that is conserved among all Cas proteins PMID:12391143 Autophosphorylation of FAK on Tyr-397 is a critical event, allowing binding of Src family kinases and activation of signal transduction pathways |
| GO:0004715 non-membrane spanning protein tyrosine kinase activity | IDA PMID:10655584 Activation of EphA2 kinase suppresses integrin function and ... | ACCEPT | Summary: non-membrane spanning protein tyrosine kinase activity (IDA, PMID:10655584). Reason: Experimental support for FAK tyrosine kinase activity in the EphA2/integrin study (UniProt cites this paper for FAK catalytic activity). Core. Supporting Evidence: PMID:10655584 this is followed by dephosphorylation of FAK and paxillin, and dissociation of the FAK-EphA2 complex |
| GO:0004715 non-membrane spanning protein tyrosine kinase activity | IDA PMID:11331870 Regulation of the PH-domain-containing tyrosine kinase Etk b... | ACCEPT | Summary: non-membrane spanning protein tyrosine kinase activity (IDA, PMID:11331870). Reason: FAK kinase activity and Tyr397 autophosphorylation were assayed in the Etk/BMX study; FAK regulates Etk through its FERM domain. Core activity. Supporting Evidence: PMID:11331870 The activation of Etk by extracellular matrix proteins is regulated by FAK through an interaction between the PH domain of Etk and the FERM domain of FAK |
| GO:0004715 non-membrane spanning protein tyrosine kinase activity | IEA GO_REF:0000120 | ACCEPT | Summary: non-membrane spanning protein tyrosine kinase activity (IEA, ARBA/EC 2.7.10.2). Reason: Consistent with experimental data (core). Supporting Evidence: PMID:9360983 FAK directly phosphorylates Cas proteins primarily at the YDYVHL sequence that is conserved among all Cas proteins |
| GO:0004725 protein tyrosine phosphatase activity | IMP PMID:9360983 Tyrosine phosphorylation of Crk-associated substrates by foc... | MODIFY | Summary: protein tyrosine phosphatase activity (IMP, PMID:9360983). Reason: PMID:9360983 shows that FAK directly phosphorylates Cas proteins (p130Cas, Cas-L/NEDD9) at the YDYVHL motif, i.e. a kinase activity. FAK has no phosphatase domain, and no study reports phosphatase activity for it, so the phosphatase term contradicts both the paper and the domain architecture. This looks like a term-selection slip; the evidence supports non-membrane spanning protein tyrosine kinase activity. Proposed replacements: non-membrane spanning protein tyrosine kinase activity Supporting Evidence: PMID:9360983 FAK directly phosphorylates Cas proteins primarily at the YDYVHL sequence that is conserved among all Cas proteins |
| GO:0005178 integrin binding | IPI PMID:26763945 Focal Adhesion Kinase Regulates Fibroblast Migration via Int... | ACCEPT | Summary: integrin binding (IPI, PMID:26763945, with ITGB1). Reason: FAK associates with integrin beta1 in fibroblasts on fibronectin, and this association is upstream of FAK activation. Direct binding of the FAK FERM/N-terminus to integrin beta cytoplasmic tails is a long-standing part of the FAK model. Core binding activity at adhesions. Supporting Evidence: PMID:26763945 integrin Ξ²1 binding to FN is necessary for FAK association with integrin Ξ²1 and subsequent FAK activation |
| GO:0005515 protein binding | IPI PMID:10655584 Activation of EphA2 kinase suppresses integrin function and ... | REMOVE | Summary: protein binding (IPI, PMID:10655584) with EPHA2 (P29317). Reason: Generic protein binding (GO:0005515) says nothing about molecular function and is removed under the repository policy. REMOVE does not mean the interaction is false. EphA2 is constitutively associated with FAK in resting cells and dissociates after ephrin-A1 stimulation; the binding mode is not defined. Supporting Evidence: PMID:10655584 EphA2 is constitutively associated with focal-adhesion kinase (FAK) in resting cells |
| GO:0005515 protein binding | IPI PMID:10822899 Protein complexes involving alpha v beta 3 integrins, nonmus... | REMOVE | Summary: protein binding (IPI, PMID:10822899) with MYH9 (P35579). Reason: Generic protein binding (GO:0005515) says nothing about molecular function and is removed under the repository policy. REMOVE does not mean the interaction is false. Co-immunoprecipitation of FAK with nonmuscle myosin heavy chain-A in thrombospondin-treated smooth muscle cells; likely an indirect complex. |
| GO:0005515 protein binding | IPI PMID:11331870 Regulation of the PH-domain-containing tyrosine kinase Etk b... | MODIFY | Summary: protein binding (IPI, PMID:11331870) with BMX/Etk (P51813). Reason: The paper defines the binding mode: the FAK FERM domain binds the Etk PH domain, and this interaction is required for Etk activation by ECM. PH domain binding is a specific, informative replacement. Non-core (Etk is a context-specific partner). Proposed replacements: PH domain binding Supporting Evidence: PMID:11331870 The activation of Etk by extracellular matrix proteins is regulated by FAK through an interaction between the PH domain of Etk and the FERM domain of FAK |
| GO:0005515 protein binding | IPI PMID:14688263 TRIP6 enhances lysophosphatidic acid-induced cell migration ... | REMOVE | Summary: protein binding (IPI, PMID:14688263) with TRIP6 (Q15654). Reason: Generic protein binding (GO:0005515) says nothing about molecular function and is removed under the repository policy. REMOVE does not mean the interaction is false. TRIP6 associates with focal complex components including FAK after LPA stimulation; binding mode not defined. |
| GO:0005515 protein binding | IPI PMID:15657067 Phosphotyrosine signaling networks in epidermal growth facto... | REMOVE | Summary: protein binding (IPI, PMID:15657067) with EGFR (P00533). Reason: Generic protein binding (GO:0005515) says nothing about molecular function and is removed under the repository policy. REMOVE does not mean the interaction is false. Phosphotyrosine proteomics; FAK was in direct or indirect complexes with EGFR. Supporting Evidence: PMID:15657067 EGF receptors in HN5 cells were shown to form direct or indirect physical interactions with additional kinases including ACK1, focal adhesion kinase (FAK), Pyk2, Yes, EphA2, and EphB4 |
| GO:0005515 protein binding | IPI PMID:15855171 Direct interaction of the N-terminal domain of focal adhesio... | MODIFY | Summary: protein binding (IPI, PMID:15855171) with TP53 (P04637). Reason: The FAK N-terminal (FERM) region binds the p53 N-terminal transactivation domain directly; the specific term p53 binding captures this. Non-core: a nuclear scaffolding function of FAK described in animal cells. Proposed replacements: p53 binding Supporting Evidence: PMID:15855171 the N-terminal fragment of FAK directly interacts with the N-terminal transactivation domain of p53 |
| GO:0005515 protein binding | IPI PMID:16291744 Phosphorylated alpha-actinin and protein-tyrosine phosphatas... | MODIFY | Summary: protein binding (IPI, PMID:16291744) with SRC (P12931). Reason: The paper (and the field) define the FAK-Src interaction: autophosphorylated FAK Tyr397 is the docking site for the Src SH2 domain. SH2 domain binding is the informative replacement and is a core part of FAK signalling. Proposed replacements: SH2 domain binding Supporting Evidence: PMID:16291744 Phosphorylation at Tyr-397 activates FAK and creates a binding site for Src family kinases |
| GO:0005515 protein binding | IPI PMID:16354697 Focal adhesion kinase is a substrate and downstream effector... | REMOVE | Summary: protein binding (IPI, PMID:16354697) with PTPN11/SHP2 (Q06124). Reason: Generic protein binding (GO:0005515) says nothing about molecular function and is removed under the repository policy. REMOVE does not mean the interaction is false. FAK is a substrate of SHP2 complexed with H. pylori CagA; an enzyme-substrate contact is not a FAK binding function. Supporting Evidence: PMID:16354697 The decrease in phosphorylated FAK is due to SHP-2-mediated dephosphorylation of FAK at the activating phosphorylation sites |
| GO:0005515 protein binding | IPI PMID:16803572 Role of dystrophins and utrophins in platelet adhesion proce... | REMOVE | Summary: protein binding (IPI, PMID:16803572) with UTRN (P46939). Reason: Generic protein binding (GO:0005515) says nothing about molecular function and is removed under the repository policy. REMOVE does not mean the interaction is false. Platelet dystrophin/utrophin complex study; FAK not mentioned in the cached abstract. |
| GO:0005515 protein binding | IPI PMID:16966330 Phosphorylation of Tyr1214 within VEGFR-2 triggers the recru... | REMOVE | Summary: protein binding (IPI, PMID:16966330) with SRC (P12931). Reason: Generic protein binding (GO:0005515) says nothing about molecular function and is removed under the repository policy. REMOVE does not mean the interaction is false. VEGFR-2 study in which c-Src permits FAK activation; the FAK-Src SH2 docking interaction is captured by the SH2 domain binding replacement on other rows. |
| GO:0005515 protein binding | IPI PMID:17525734 p140Cap protein suppresses tumour cell properties, regulatin... | REMOVE | Summary: protein binding (IPI, PMID:17525734) with SRC (P12931). Reason: Generic protein binding (GO:0005515) says nothing about molecular function and is removed under the repository policy. REMOVE does not mean the interaction is false. p140Cap/Csk study; FAK-Src association is incidental. FAK-Src docking is captured by SH2 domain binding elsewhere. |
| GO:0005515 protein binding | IPI PMID:18256281 A novel Cas family member, HEPL, regulates FAK and cell spre... | REMOVE | Summary: protein binding (IPI, PMID:18256281) with NEDD9 (Q14511). Reason: Generic protein binding (GO:0005515) says nothing about molecular function and is removed under the repository policy. REMOVE does not mean the interaction is false. Cas family proteins bind the FAK proline-rich region through their SH3 domains; the paper is about the Cas family member HEPL and does not itself define the mode in the cached abstract. Supporting Evidence: PMID:18256281 HEPL maintains Cas family function in localization to focal adhesions, as well as regulation of FAK activity, focal adhesion integrity, and cell spreading |
| GO:0005515 protein binding | IPI PMID:18256281 A novel Cas family member, HEPL, regulates FAK and cell spre... | REMOVE | Summary: protein binding (IPI, PMID:18256281) with CASS4/HEPL (Q9NQ75). Reason: Generic protein binding (GO:0005515) says nothing about molecular function and is removed under the repository policy. REMOVE does not mean the interaction is false. HEPL regulates FAK activity at focal adhesions; binding mode not defined in the cached abstract. Supporting Evidence: PMID:18256281 HEPL maintains Cas family function in localization to focal adhesions, as well as regulation of FAK activity, focal adhesion integrity, and cell spreading |
| GO:0005515 protein binding | IPI PMID:18497331 The LIM protein leupaxin is enriched in smooth muscle and fu... | REMOVE | Summary: protein binding (IPI, PMID:18497331) with LPXN (O60711). Reason: Generic protein binding (GO:0005515) says nothing about molecular function and is removed under the repository policy. REMOVE does not mean the interaction is false. Leupaxin was found in a screen for FAK binding partners; paxillin-family LD motifs bind the FAK FAT domain, but GO has no LD-motif binding term. Supporting Evidence: PMID:18497331 we identified leupaxin in a screen for focal adhesion kinase binding partners in aortic smooth muscle |
| GO:0005515 protein binding | IPI PMID:18560762 Mobility of TOAC spin-labelled peptides binding to the Src S... | MODIFY | Summary: protein binding (IPI, PMID:18560762) with mouse Src (P05480). Reason: NMR study of a FAK proline-rich peptide bound to the Src SH3 domain; the binding mode is defined, so SH3 domain binding is the informative replacement. Proposed replacements: SH3 domain binding Supporting Evidence: PMID:18560762 the SH3 domain binds weakly and transiently to proline-rich peptides from FAK |
| GO:0005515 protein binding | IPI PMID:18835089 Inhibition of T24 human bladder carcinoma cell migration by ... | REMOVE | Summary: protein binding (IPI, PMID:18835089) with PTPN23/HD-PTP (Q9H3S7). Reason: Generic protein binding (GO:0005515) says nothing about molecular function and is removed under the repository policy. REMOVE does not mean the interaction is false. HD-PTP binds FAK and is a FAK substrate; binding mode not defined. |
| GO:0005515 protein binding | IPI PMID:19494199 Functional consequences of interactions between FAK and epit... | REMOVE | Summary: protein binding (IPI, PMID:19494199) with EMP2 (P54851). Reason: Generic protein binding (GO:0005515) says nothing about molecular function and is removed under the repository policy. REMOVE does not mean the interaction is false. Co-immunoprecipitation of EMP2 with FAK in ARPE-19 cells; binding mode not defined. |
| GO:0005515 protein binding | IPI PMID:19732724 The Tensin-3 protein, including its SH2 domain, is phosphory... | REMOVE | Summary: protein binding (IPI, PMID:19732724) with TNS3 (Q68CZ2). Reason: Generic protein binding (GO:0005515) says nothing about molecular function and is removed under the repository policy. REMOVE does not mean the interaction is false. Tensin-3 study; FAK interaction is not defined in the cached abstract. |
| GO:0005515 protein binding | IPI PMID:19857493 Role of p53/FAK association and p53Ser46 phosphorylation in ... | MODIFY | Summary: protein binding (IPI, PMID:19857493) with TP53 (P04637). Reason: Nuclear FAK maintains a p53/FAK interaction in oesophageal carcinoma cells; p53 binding is the specific replacement (non-core, animal nuclear scaffold function). Proposed replacements: p53 binding Supporting Evidence: PMID:19857493 both wt and mt HOSCC cells translocate FAK into the nucleus and maintain the p53/FAK interaction post STS treatment |
| GO:0005515 protein binding | IPI PMID:19917054 LIM domain-containing adaptor, leupaxin, localizes in focal ... | REMOVE | Summary: protein binding (IPI, PMID:19917054) with mouse leupaxin (Q99N69). Reason: Generic protein binding (GO:0005515) says nothing about molecular function and is removed under the repository policy. REMOVE does not mean the interaction is false. Leupaxin LD3 motif is required for stable FAK association; no specific GO term for LD-motif binding. Supporting Evidence: PMID:19917054 Leupaxin's LD3 motif, which is critical for stable association with FAK, was dispensable for leupaxin's suppressive ability |
| GO:0005515 protein binding | IPI PMID:20473329 SIRPalpha1 receptors interfere with the EGFRvIII signalosome... | REMOVE | Summary: protein binding (IPI, PMID:20473329) with EGFR (P00533). Reason: Generic protein binding (GO:0005515) says nothing about molecular function and is removed under the repository policy. REMOVE does not mean the interaction is false. FAK recruitment to the EGFRvIII/Grb2/Sos-1/Gab1/SHP-2 signalosome in glioblastoma cells, measured by co-immunoprecipitation; multi-protein complex, binding mode not defined. |
| GO:0005515 protein binding | IPI PMID:20473329 SIRPalpha1 receptors interfere with the EGFRvIII signalosome... | REMOVE | Summary: protein binding (IPI, PMID:20473329) with GRB2 (P62993). Reason: Generic protein binding (GO:0005515) says nothing about molecular function and is removed under the repository policy. REMOVE does not mean the interaction is false. FAK recruitment to the EGFRvIII/Grb2/Sos-1/Gab1/SHP-2 signalosome in glioblastoma cells, measured by co-immunoprecipitation; multi-protein complex, binding mode not defined. |
| GO:0005515 protein binding | IPI PMID:20473329 SIRPalpha1 receptors interfere with the EGFRvIII signalosome... | REMOVE | Summary: protein binding (IPI, PMID:20473329) with PTPN11/SHP2 (Q06124). Reason: Generic protein binding (GO:0005515) says nothing about molecular function and is removed under the repository policy. REMOVE does not mean the interaction is false. FAK recruitment to the EGFRvIII/Grb2/Sos-1/Gab1/SHP-2 signalosome in glioblastoma cells, measured by co-immunoprecipitation; multi-protein complex, binding mode not defined. |
| GO:0005515 protein binding | IPI PMID:20576130 Activated networking of platelet activating factor receptor ... | REMOVE | Summary: protein binding (IPI, PMID:20576130) with PTAFR (P25105). Reason: Generic protein binding (GO:0005515) says nothing about molecular function and is removed under the repository policy. REMOVE does not mean the interaction is false. Co-immunoprecipitation in BRCA1-mutant ovarian epithelial cells; binding mode not defined. |
| GO:0005515 protein binding | IPI PMID:20576130 Activated networking of platelet activating factor receptor ... | REMOVE | Summary: protein binding (IPI, PMID:20576130) with STAT1 (P42224). Reason: Generic protein binding (GO:0005515) says nothing about molecular function and is removed under the repository policy. REMOVE does not mean the interaction is false. Co-immunoprecipitation in BRCA1-mutant ovarian epithelial cells; binding mode not defined. |
| GO:0005515 protein binding | IPI PMID:21034468 Cyanidin-3-glucoside inhibits ethanol-induced invasion of br... | REMOVE | Summary: protein binding (IPI, PMID:21034468) with SRC (P12931). Reason: Generic protein binding (GO:0005515) says nothing about molecular function and is removed under the repository policy. REMOVE does not mean the interaction is false. Co-immunoprecipitation in breast cancer cells treated with ethanol and cyanidin-3-glucoside; binding mode not defined. |
| GO:0005515 protein binding | IPI PMID:21034468 Cyanidin-3-glucoside inhibits ethanol-induced invasion of br... | REMOVE | Summary: protein binding (IPI, PMID:21034468) with PXN (P49023). Reason: Generic protein binding (GO:0005515) says nothing about molecular function and is removed under the repository policy. REMOVE does not mean the interaction is false. Co-immunoprecipitation in breast cancer cells treated with ethanol and cyanidin-3-glucoside; binding mode not defined. |
| GO:0005515 protein binding | IPI PMID:21034468 Cyanidin-3-glucoside inhibits ethanol-induced invasion of br... | REMOVE | Summary: protein binding (IPI, PMID:21034468) with BCAR1 (P56945). Reason: Generic protein binding (GO:0005515) says nothing about molecular function and is removed under the repository policy. REMOVE does not mean the interaction is false. Co-immunoprecipitation in breast cancer cells treated with ethanol and cyanidin-3-glucoside; binding mode not defined. |
| GO:0005515 protein binding | IPI PMID:21266176 Linker length dependent binding of a focal adhesion kinase d... | MODIFY | Summary: protein binding (IPI, PMID:21266176) with mouse Src (P05480). Reason: NMR and calorimetry of a FAK peptide containing both the SH3-binding proline-rich motif and the SH2-binding pTyr397 motif bound to the Src SH3-SH2 domains. Both SH2 domain binding and SH3 domain binding are defined by the paper. Proposed replacements: SH2 domain binding SH3 domain binding Supporting Evidence: PMID:21266176 The interaction between a peptide encompassing the SH3 and SH2 binding motifs of focal adhesion kinase (FAK) and the Src SH3-SH2 domains has been investigated with NMR spectroscopy and calorimetry |
| GO:0005515 protein binding | IPI PMID:21383007 Bit-1 mediates integrin-dependent cell survival through acti... | REMOVE | Summary: protein binding (IPI, PMID:21383007) with PTRH2/Bit-1 (Q9Y3E5). Reason: Generic protein binding (GO:0005515) says nothing about molecular function and is removed under the repository policy. REMOVE does not mean the interaction is false. Bit-1 survival signalling depends on FAK; binding mode not defined. |
| GO:0005515 protein binding | IPI PMID:21741599 Proinvasion metastasis drivers in early-stage melanoma are o... | REMOVE | Summary: protein binding (IPI, PMID:21741599) with PXN (P49023). Reason: Generic protein binding (GO:0005515) says nothing about molecular function and is removed under the repository policy. REMOVE does not mean the interaction is false. Melanoma metastasis-driver study; FAK-paxillin association incidental. The FAK FAT domain-paxillin LD interaction has no specific GO MF term. |
| GO:0005515 protein binding | IPI PMID:21900206 A directed protein interaction network for investigating int... | REMOVE | Summary: protein binding (IPI, PMID:21900206) with TGFB1I1/Hic-5 (O43294). Reason: Generic protein binding (GO:0005515) says nothing about molecular function and is removed under the repository policy. REMOVE does not mean the interaction is false. High-throughput yeast two-hybrid signalling network; binding mode not defined. |
| GO:0005515 protein binding | IPI PMID:21900206 A directed protein interaction network for investigating int... | REMOVE | Summary: protein binding (IPI, PMID:21900206) with LPXN (O60711). Reason: Generic protein binding (GO:0005515) says nothing about molecular function and is removed under the repository policy. REMOVE does not mean the interaction is false. High-throughput yeast two-hybrid signalling network; binding mode not defined. |
| GO:0005515 protein binding | IPI PMID:21900206 A directed protein interaction network for investigating int... | REMOVE | Summary: protein binding (IPI, PMID:21900206) with GRB2 (P62993). Reason: Generic protein binding (GO:0005515) says nothing about molecular function and is removed under the repository policy. REMOVE does not mean the interaction is false. High-throughput yeast two-hybrid signalling network; binding mode not defined. |
| GO:0005515 protein binding | IPI PMID:22270917 FAK promotes recruitment of talin to nascent adhesions to co... | REMOVE | Summary: protein binding (IPI, PMID:22270917) with PXN (P49023). Reason: Generic protein binding (GO:0005515) says nothing about molecular function and is removed under the repository policy. REMOVE does not mean the interaction is false. The paper is about FAK binding talin (captured by the talin binding replacement on row PMID:9786953); the paxillin contact is not characterised. Supporting Evidence: PMID:22270917 The direct binding site for talin on FAK was identified, and a point mutation in FAK (E1015A) prevented talin association and talin localization to nascent adhesions |
| GO:0005515 protein binding | IPI PMID:22402981 Integrin/Fak/Src-mediated regulation of cell survival and an... | REMOVE | Summary: protein binding (IPI, PMID:22402981) with SRC (P12931). Reason: Generic protein binding (GO:0005515) says nothing about molecular function and is removed under the repository policy. REMOVE does not mean the interaction is false. beta1 integrin/Fak/Src/PI3-K complexes in intestinal crypt cells; binding mode not defined. |
| GO:0005515 protein binding | IPI PMID:22402981 Integrin/Fak/Src-mediated regulation of cell survival and an... | REMOVE | Summary: protein binding (IPI, PMID:22402981) with PIK3R3 (Q92569). Reason: Generic protein binding (GO:0005515) says nothing about molecular function and is removed under the repository policy. REMOVE does not mean the interaction is false. beta1 integrin/Fak/Src/PI3-K complexes in intestinal crypt cells; binding mode not defined. |
| GO:0005515 protein binding | IPI PMID:23065768 Activation of rapid oestrogen signalling in aggressive human... | REMOVE | Summary: protein binding (IPI, PMID:23065768) with SRC (P12931). Reason: Generic protein binding (GO:0005515) says nothing about molecular function and is removed under the repository policy. REMOVE does not mean the interaction is false. Proximity ligation assay of ERalpha/Src/PI3K complexes; binding mode not defined. |
| GO:0005515 protein binding | IPI PMID:23574715 The novel actin/focal adhesion-associated protein MISP is in... | REMOVE | Summary: protein binding (IPI, PMID:23574715) with MISP (Q8IVT2). Reason: Generic protein binding (GO:0005515) says nothing about molecular function and is removed under the repository policy. REMOVE does not mean the interaction is false. MISP co-precipitates with FAK; binding mode not defined. |
| GO:0005515 protein binding | IPI PMID:23602568 The protein interaction landscape of the human CMGC kinase g... | REMOVE | Summary: protein binding (IPI, PMID:23602568) with Q96SB4 (SRPK1). Reason: Generic protein binding (GO:0005515) says nothing about molecular function and is removed under the repository policy. REMOVE does not mean the interaction is false. High-throughput AP-MS of CMGC kinase complexes. |
| GO:0005515 protein binding | IPI PMID:24658140 The mammalian-membrane two-hybrid assay (MaMTH) for probing ... | REMOVE | Summary: protein binding (IPI, PMID:24658140) with EGFR (P00533). Reason: Generic protein binding (GO:0005515) says nothing about molecular function and is removed under the repository policy. REMOVE does not mean the interaction is false. MaMTH membrane two-hybrid screen. |
| GO:0005515 protein binding | IPI PMID:25193659 The Chlamydia effector TarP mimics the mammalian leucine-asp... | REMOVE | Summary: protein binding (IPI, PMID:25193659) with Chlamydia caviae TarP (Q824H6). Reason: Generic protein binding (GO:0005515) says nothing about molecular function and is removed under the repository policy. REMOVE does not mean the interaction is false. TarP mimics the paxillin LD2 motif to recruit FAK; host-pathogen interaction, no specific GO term for LD-motif binding. Supporting Evidence: PMID:25193659 FAK recruitment was via binding to a domain within the virulence factor TarP that mimicked the LD2 motif of the FAK binding partner paxillin |
| GO:0005515 protein binding | IPI PMID:25241761 Using an in situ proximity ligation assay to systematically ... | REMOVE | Summary: protein binding (IPI, PMID:25241761) with TP53 (P04637). Reason: Generic protein binding (GO:0005515) says nothing about molecular function and is removed under the repository policy. REMOVE does not mean the interaction is false. Systematic in situ proximity ligation screen; proximity, binding mode not defined. |
| GO:0005515 protein binding | IPI PMID:25241761 Using an in situ proximity ligation assay to systematically ... | REMOVE | Summary: protein binding (IPI, PMID:25241761) with SRC (P12931). Reason: Generic protein binding (GO:0005515) says nothing about molecular function and is removed under the repository policy. REMOVE does not mean the interaction is false. Systematic in situ proximity ligation screen; proximity, binding mode not defined. |
| GO:0005515 protein binding | IPI PMID:25241761 Using an in situ proximity ligation assay to systematically ... | REMOVE | Summary: protein binding (IPI, PMID:25241761) with STAT1 (P42224). Reason: Generic protein binding (GO:0005515) says nothing about molecular function and is removed under the repository policy. REMOVE does not mean the interaction is false. Systematic in situ proximity ligation screen; proximity, binding mode not defined. |
| GO:0005515 protein binding | IPI PMID:25795725 c-Abl mediated tyrosine phosphorylation of paxillin regulate... | REMOVE | Summary: protein binding (IPI, PMID:25795725) with PXN (P49023). Reason: Generic protein binding (GO:0005515) says nothing about molecular function and is removed under the repository policy. REMOVE does not mean the interaction is false. c-Abl/paxillin endothelial study; FAK-paxillin association incidental. |
| GO:0005515 protein binding | IPI PMID:25814554 Phospho-tyrosine dependent protein-protein interaction netwo... | REMOVE | Summary: protein binding (IPI, PMID:25814554) with HCK isoform (P08631-2). Reason: Generic protein binding (GO:0005515) says nothing about molecular function and is removed under the repository policy. REMOVE does not mean the interaction is false. Large-scale phosphotyrosine-dependent yeast two-hybrid screen. The partner has an SH2 domain, but the paper reports that most pY-dependent interactions in the screen are not mediated by canonical motifs, so SH2 domain binding cannot be assigned row by row. Supporting Evidence: PMID:25814554 About one-sixth of the interactions are mediated by known linear sequence binding motifs while the majority of pY-PPIs are mediated by other linear epitopes or governed by alternative recognition modes |
| GO:0005515 protein binding | IPI PMID:25814554 Phospho-tyrosine dependent protein-protein interaction netwo... | REMOVE | Summary: protein binding (IPI, PMID:25814554) with SRC (P12931). Reason: Generic protein binding (GO:0005515) says nothing about molecular function and is removed under the repository policy. REMOVE does not mean the interaction is false. Large-scale phosphotyrosine-dependent yeast two-hybrid screen. The partner has an SH2 domain, but the paper reports that most pY-dependent interactions in the screen are not mediated by canonical motifs, so SH2 domain binding cannot be assigned row by row. Supporting Evidence: PMID:25814554 About one-sixth of the interactions are mediated by known linear sequence binding motifs while the majority of pY-PPIs are mediated by other linear epitopes or governed by alternative recognition modes |
| GO:0005515 protein binding | IPI PMID:25814554 Phospho-tyrosine dependent protein-protein interaction netwo... | REMOVE | Summary: protein binding (IPI, PMID:25814554) with PTPN6 isoform (P29350-3). Reason: Generic protein binding (GO:0005515) says nothing about molecular function and is removed under the repository policy. REMOVE does not mean the interaction is false. Large-scale phosphotyrosine-dependent yeast two-hybrid screen. The partner has an SH2 domain, but the paper reports that most pY-dependent interactions in the screen are not mediated by canonical motifs, so SH2 domain binding cannot be assigned row by row. Supporting Evidence: PMID:25814554 About one-sixth of the interactions are mediated by known linear sequence binding motifs while the majority of pY-PPIs are mediated by other linear epitopes or governed by alternative recognition modes |
| GO:0005515 protein binding | IPI PMID:25814554 Phospho-tyrosine dependent protein-protein interaction netwo... | REMOVE | Summary: protein binding (IPI, PMID:25814554) with CRK (P46108). Reason: Generic protein binding (GO:0005515) says nothing about molecular function and is removed under the repository policy. REMOVE does not mean the interaction is false. Large-scale phosphotyrosine-dependent yeast two-hybrid screen. The partner has an SH2 domain, but the paper reports that most pY-dependent interactions in the screen are not mediated by canonical motifs, so SH2 domain binding cannot be assigned row by row. Supporting Evidence: PMID:25814554 About one-sixth of the interactions are mediated by known linear sequence binding motifs while the majority of pY-PPIs are mediated by other linear epitopes or governed by alternative recognition modes |
| GO:0005515 protein binding | IPI PMID:25814554 Phospho-tyrosine dependent protein-protein interaction netwo... | REMOVE | Summary: protein binding (IPI, PMID:25814554) with GRB7 (Q14451). Reason: Generic protein binding (GO:0005515) says nothing about molecular function and is removed under the repository policy. REMOVE does not mean the interaction is false. Large-scale phosphotyrosine-dependent yeast two-hybrid screen. The partner has an SH2 domain, but the paper reports that most pY-dependent interactions in the screen are not mediated by canonical motifs, so SH2 domain binding cannot be assigned row by row. Supporting Evidence: PMID:25814554 About one-sixth of the interactions are mediated by known linear sequence binding motifs while the majority of pY-PPIs are mediated by other linear epitopes or governed by alternative recognition modes |
| GO:0005515 protein binding | IPI PMID:25814554 Phospho-tyrosine dependent protein-protein interaction netwo... | REMOVE | Summary: protein binding (IPI, PMID:25814554) with PIK3R3 (Q92569). Reason: Generic protein binding (GO:0005515) says nothing about molecular function and is removed under the repository policy. REMOVE does not mean the interaction is false. Large-scale phosphotyrosine-dependent yeast two-hybrid screen. The partner has an SH2 domain, but the paper reports that most pY-dependent interactions in the screen are not mediated by canonical motifs, so SH2 domain binding cannot be assigned row by row. Supporting Evidence: PMID:25814554 About one-sixth of the interactions are mediated by known linear sequence binding motifs while the majority of pY-PPIs are mediated by other linear epitopes or governed by alternative recognition modes |
| GO:0005515 protein binding | IPI PMID:25814554 Phospho-tyrosine dependent protein-protein interaction netwo... | REMOVE | Summary: protein binding (IPI, PMID:25814554) with SH2D2A (Q9NP31). Reason: Generic protein binding (GO:0005515) says nothing about molecular function and is removed under the repository policy. REMOVE does not mean the interaction is false. Large-scale phosphotyrosine-dependent yeast two-hybrid screen. The partner has an SH2 domain, but the paper reports that most pY-dependent interactions in the screen are not mediated by canonical motifs, so SH2 domain binding cannot be assigned row by row. Supporting Evidence: PMID:25814554 About one-sixth of the interactions are mediated by known linear sequence binding motifs while the majority of pY-PPIs are mediated by other linear epitopes or governed by alternative recognition modes |
| GO:0005515 protein binding | IPI PMID:27178753 Activation of focal adhesion kinase through an interaction w... | MODIFY | Summary: protein binding (IPI, PMID:27178753) with ITGB4 (P16144). Reason: Activated beta4 integrin binds FAK and induces Tyr397 phosphorylation; integrin binding is the specific replacement, consistent with the ITGB1 integrin binding row. Proposed replacements: integrin binding Supporting Evidence: PMID:27178753 Activated Ξ²4 integrin interacts with FAK and subsequently induces FAK phosphorylation at Tyr397 |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | REMOVE | Summary: protein binding (IPI, PMID:28514442) with LPXN (O60711). Reason: Generic protein binding (GO:0005515) says nothing about molecular function and is removed under the repository policy. REMOVE does not mean the interaction is false. BioPlex AP-MS interactome. |
| GO:0005515 protein binding | IPI PMID:31413325 HENA, heterogeneous network-based data set for Alzheimer's d... | REMOVE | Summary: protein binding (IPI, PMID:31413325) with FYN (P06241). Reason: Generic protein binding (GO:0005515) says nothing about molecular function and is removed under the repository policy. REMOVE does not mean the interaction is false. HENA Alzheimer network dataset compilation. |
| GO:0005515 protein binding | IPI PMID:31980649 Extensive rewiring of the EGFR network in colorectal cancer ... | REMOVE | Summary: protein binding (IPI, PMID:31980649) with EGFR (P00533). Reason: Generic protein binding (GO:0005515) says nothing about molecular function and is removed under the repository policy. REMOVE does not mean the interaction is false. EGFR-network AP-MS in colorectal cancer cells. |
| GO:0005515 protein binding | IPI PMID:31980649 Extensive rewiring of the EGFR network in colorectal cancer ... | REMOVE | Summary: protein binding (IPI, PMID:31980649) with PXN (P49023). Reason: Generic protein binding (GO:0005515) says nothing about molecular function and is removed under the repository policy. REMOVE does not mean the interaction is false. EGFR-network AP-MS in colorectal cancer cells. |
| GO:0005515 protein binding | IPI PMID:32707033 Kinase Interaction Network Expands Functional and Disease Ro... | REMOVE | Summary: protein binding (IPI, PMID:32707033) with TGFB1I1 (O43294). Reason: Generic protein binding (GO:0005515) says nothing about molecular function and is removed under the repository policy. REMOVE does not mean the interaction is false. Kinase interaction network (high-throughput AP-MS/BioID). |
| GO:0005515 protein binding | IPI PMID:32707033 Kinase Interaction Network Expands Functional and Disease Ro... | REMOVE | Summary: protein binding (IPI, PMID:32707033) with FYN (P06241). Reason: Generic protein binding (GO:0005515) says nothing about molecular function and is removed under the repository policy. REMOVE does not mean the interaction is false. Kinase interaction network (high-throughput AP-MS/BioID). |
| GO:0005515 protein binding | IPI PMID:32707033 Kinase Interaction Network Expands Functional and Disease Ro... | REMOVE | Summary: protein binding (IPI, PMID:32707033) with PXN (P49023). Reason: Generic protein binding (GO:0005515) says nothing about molecular function and is removed under the repository policy. REMOVE does not mean the interaction is false. Kinase interaction network (high-throughput AP-MS/BioID). |
| GO:0005515 protein binding | IPI PMID:32707033 Kinase Interaction Network Expands Functional and Disease Ro... | REMOVE | Summary: protein binding (IPI, PMID:32707033) with Q96SB4 (SRPK1). Reason: Generic protein binding (GO:0005515) says nothing about molecular function and is removed under the repository policy. REMOVE does not mean the interaction is false. Kinase interaction network (high-throughput AP-MS/BioID). |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: protein binding (IPI, PMID:32814053) with SRC (P12931). Reason: Generic protein binding (GO:0005515) says nothing about molecular function and is removed under the repository policy. REMOVE does not mean the interaction is false. Neurodegenerative-disease yeast two-hybrid interactome. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: protein binding (IPI, PMID:33961781) with LPXN (O60711). Reason: Generic protein binding (GO:0005515) says nothing about molecular function and is removed under the repository policy. REMOVE does not mean the interaction is false. Dual proteome-scale BioPlex networks. |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | REMOVE | Summary: protein binding (IPI, PMID:40205054) with LPXN (O60711). Reason: Generic protein binding (GO:0005515) says nothing about molecular function and is removed under the repository policy. REMOVE does not mean the interaction is false. Multimodal cell-map interactome. |
| GO:0005515 protein binding | IPI PMID:7561682 Direct association of pp125FAK with paxillin, the focal adhe... | REMOVE | Summary: protein binding (IPI, PMID:7561682) with CRK (P46108). Reason: Generic protein binding (GO:0005515) says nothing about molecular function and is removed under the repository policy. REMOVE does not mean the interaction is false. The paper concerns paxillin; CRK association not characterised. |
| GO:0005515 protein binding | IPI PMID:7561682 Direct association of pp125FAK with paxillin, the focal adhe... | REMOVE | Summary: protein binding (IPI, PMID:7561682) with PXN (P49023). Reason: Generic protein binding (GO:0005515) says nothing about molecular function and is removed under the repository policy. REMOVE does not mean the interaction is false. The FAK C-terminal (FAT) region binds paxillin directly and this targets FAK to focal adhesions; an important interaction, but GO has no paxillin-binding or LD-motif-binding MF term. The consequence is captured by focal adhesion localisation. Supporting Evidence: PMID:7561682 These findings strongly suggest that pp125FAK is localized to focal adhesions by the direct association with paxillin |
| GO:0005515 protein binding | IPI PMID:7597091 Stimulation of human monocytes with macrophage colony-stimul... | MODIFY | Summary: protein binding (IPI, PMID:7597091) with GRB2 (P62993). Reason: Tyrosine-phosphorylated FAK (pY925, pYENV) binds the GRB2 SH2 domain in M-CSF-stimulated monocytes; SH2 domain binding is the defined mode. Proposed replacements: SH2 domain binding Supporting Evidence: PMID:7597091 tyrosine-phosphorylated pp125FAK directly interacts with the SH2 domain of Grb2 |
| GO:0005515 protein binding | IPI PMID:8649368 Introduction of p130cas signaling complex formation upon int... | REMOVE | Summary: protein binding (IPI, PMID:8649368) with BCAR1 (P56945). Reason: Generic protein binding (GO:0005515) says nothing about molecular function and is removed under the repository policy. REMOVE does not mean the interaction is false. Integrin-induced p130Cas signalling complexes; FAK-Cas association, mode not defined in the cached abstract. |
| GO:0005515 protein binding | IPI PMID:8649368 Introduction of p130cas signaling complex formation upon int... | REMOVE | Summary: protein binding (IPI, PMID:8649368) with BCAR1 (Q6P5Z4). Reason: Generic protein binding (GO:0005515) says nothing about molecular function and is removed under the repository policy. REMOVE does not mean the interaction is false. Integrin-induced p130Cas signalling complexes; FAK-Cas association, mode not defined in the cached abstract. |
| GO:0005515 protein binding | IPI PMID:9285683 Association of PTP-PEST with the SH3 domain of p130cas; a no... | REMOVE | Summary: protein binding (IPI, PMID:9285683) with BCAR1 (P56945). Reason: Generic protein binding (GO:0005515) says nothing about molecular function and is removed under the repository policy. REMOVE does not mean the interaction is false. PTP-PEST/p130Cas SH3 study; FAK-Cas interaction not characterised in the cached abstract. |
| GO:0005515 protein binding | IPI PMID:9756887 Interaction of Hic-5, A senescence-related protein, with foc... | REMOVE | Summary: protein binding (IPI, PMID:9756887) with TGFB1I1/Hic-5 (O43294). Reason: Generic protein binding (GO:0005515) says nothing about molecular function and is removed under the repository policy. REMOVE does not mean the interaction is false. Hic-5 binds FAK through its N-terminal LD-motif region; no specific GO MF term for this paxillin-family interaction. Supporting Evidence: PMID:9756887 Hic-5 binds to focal adhesion kinase (FAK) by its N-terminal domain |
| GO:0005515 protein binding | IPI PMID:9756887 Interaction of Hic-5, A senescence-related protein, with foc... | REMOVE | Summary: protein binding (IPI, PMID:9756887) with PXN (P49023). Reason: Generic protein binding (GO:0005515) says nothing about molecular function and is removed under the repository policy. REMOVE does not mean the interaction is false. Hic-5 binds FAK through its N-terminal LD-motif region; no specific GO MF term for this paxillin-family interaction. Supporting Evidence: PMID:9756887 Hic-5 binds to focal adhesion kinase (FAK) by its N-terminal domain |
| GO:0005515 protein binding | IPI PMID:9756887 Interaction of Hic-5, A senescence-related protein, with foc... | REMOVE | Summary: protein binding (IPI, PMID:9756887) with mouse Hic-5 (Q62219). Reason: Generic protein binding (GO:0005515) says nothing about molecular function and is removed under the repository policy. REMOVE does not mean the interaction is false. Hic-5 binds FAK through its N-terminal LD-motif region; no specific GO MF term for this paxillin-family interaction. Supporting Evidence: PMID:9756887 Hic-5 binds to focal adhesion kinase (FAK) by its N-terminal domain |
| GO:0005515 protein binding | IPI PMID:9786953 Layilin, a novel talin-binding transmembrane protein homolog... | MODIFY | Summary: protein binding (IPI, PMID:9786953) with chicken talin-1 (P54939). Reason: The layilin paper maps a talin N-terminal region that overlaps the FAK binding site on talin. FAK-talin binding is direct (the FAK FAT domain E1015 site, PMID:22270917) and has its own term, talin binding. Non-core in the strict sense but part of the adhesion scaffolding role. Proposed replacements: talin binding Supporting Evidence: PMID:9786953 This region overlaps a binding site for focal adhesion kinase PMID:22270917 The direct binding site for talin on FAK was identified, and a point mutation in FAK (E1015A) prevented talin association and talin localization to nascent adhesions |
| GO:0005524 ATP binding | IEA GO_REF:0000002 | ACCEPT | Summary: ATP binding (IEA, InterPro kinase domain). Reason: Required for the kinase activity; correct. |
| GO:0005634 nucleus | EXP PMID:18206965 Nuclear FAK promotes cell proliferation and survival through... | KEEP AS NON CORE | Summary: nucleus (EXP, PMID:18206965). Reason: FERM-dependent nuclear accumulation of FAK, enhanced by loss of adhesion or staurosporine, where FAK scaffolds Mdm2-dependent p53 degradation. A real but secondary pool. Supporting Evidence: PMID:18206965 Staurosporine or loss of cell adhesion enhanced FERM-dependent FAK nuclear accumulation |
| GO:0005634 nucleus | IDA PMID:15855171 Direct interaction of the N-terminal domain of focal adhesio... | KEEP AS NON CORE | Summary: nucleus (IDA, PMID:15855171). Reason: Co-localization of FAK with p53; nuclear FAK is a minor, stress-induced pool. Supporting Evidence: PMID:15855171 FAK physically and specifically interacts with p53 as demonstrated by pull-down, immunoprecipitation, and co-localization analyses |
| GO:0005634 nucleus | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: nucleus (IEA, UniProt SubCell). Reason: Consistent with experimental nuclear FAK; non-core. |
| GO:0005737 cytoplasm | EXP PMID:15855171 Direct interaction of the N-terminal domain of focal adhesio... | ACCEPT | Summary: cytoplasm (EXP, PMID:15855171). Reason: FAK is a cytoplasmic kinase; the bulk pool is cytosolic and it is recruited to focal adhesions on the cytoplasmic face of the plasma membrane. Supporting Evidence: PMID:15855171 FAK physically and specifically interacts with p53 as demonstrated by pull-down, immunoprecipitation, and co-localization analyses |
| GO:0005737 cytoplasm | EXP PMID:18078954 Structural basis for the interaction between focal adhesion ... | ACCEPT | Summary: cytoplasm (EXP, PMID:18078954). Reason: FAK is a cytoplasmic kinase; the bulk pool is cytosolic and it is recruited to focal adhesions on the cytoplasmic face of the plasma membrane. Supporting Evidence: PMID:18078954 the focal adhesion targeting (FAT) domain of FAK binds specifically to the CD4 endocytosis motif in vitro |
| GO:0005737 cytoplasm | EXP PMID:18206965 Nuclear FAK promotes cell proliferation and survival through... | ACCEPT | Summary: cytoplasm (EXP, PMID:18206965). Reason: FAK is a cytoplasmic kinase; the bulk pool is cytosolic and it is recruited to focal adhesions on the cytoplasmic face of the plasma membrane. Supporting Evidence: PMID:18206965 These studies define a scaffolding role for nuclear FAK in facilitating cell survival through enhanced p53 degradation under conditions of cellular stress |
| GO:0005737 cytoplasm | EXP PMID:18256281 A novel Cas family member, HEPL, regulates FAK and cell spre... | ACCEPT | Summary: cytoplasm (EXP, PMID:18256281). Reason: FAK is a cytoplasmic kinase; the bulk pool is cytosolic and it is recruited to focal adhesions on the cytoplasmic face of the plasma membrane. Supporting Evidence: PMID:18256281 HEPL maintains Cas family function in localization to focal adhesions, as well as regulation of FAK activity, focal adhesion integrity, and cell spreading |
| GO:0005737 cytoplasm | IEA GO_REF:0000120 | ACCEPT | Summary: cytoplasm (IEA, ARBA/SubCell). Reason: Correct. |
| GO:0005813 centrosome | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: centrosome (IEA, UniProt SubCell; by similarity). Reason: UniProt records centrosome localisation by similarity only; FAK at centrosomes is reported in some cell types but is not part of its core adhesion role. |
| GO:0005829 cytosol | IDA GO_REF:0000052 | ACCEPT | Summary: cytosol (IDA, GO_REF:0000052, HPA immunofluorescence). Reason: The unbound FAK pool is cytosolic. |
| GO:0005829 cytosol | IDA PMID:15855171 Direct interaction of the N-terminal domain of focal adhesio... | ACCEPT | Summary: cytosol (IDA, PMID:15855171). Reason: The unbound FAK pool is cytosolic. Supporting Evidence: PMID:15855171 FAK physically and specifically interacts with p53 as demonstrated by pull-down, immunoprecipitation, and co-localization analyses |
| GO:0005829 cytosol | TAS Reactome:R-HSA-201634 | ACCEPT | Summary: cytosol (TAS, Reactome Reactome:R-HSA-201634). Reason: Reactome places FAK (PTK2) in the cytosol for this reaction; FAK is a cytosolic kinase recruited to adhesion sites, so the location is correct. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2197698 | ACCEPT | Summary: cytosol (TAS, Reactome Reactome:R-HSA-2197698). Reason: Reactome places FAK (PTK2) in the cytosol for this reaction; FAK is a cytosolic kinase recruited to adhesion sites, so the location is correct. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-354066 | ACCEPT | Summary: cytosol (TAS, Reactome Reactome:R-HSA-354066). Reason: Reactome places FAK (PTK2) in the cytosol for this reaction; FAK is a cytosolic kinase recruited to adhesion sites, so the location is correct. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-354073 | ACCEPT | Summary: cytosol (TAS, Reactome Reactome:R-HSA-354073). Reason: Reactome places FAK (PTK2) in the cytosol for this reaction; FAK is a cytosolic kinase recruited to adhesion sites, so the location is correct. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-354087 | ACCEPT | Summary: cytosol (TAS, Reactome Reactome:R-HSA-354087). Reason: Reactome places FAK (PTK2) in the cytosol for this reaction; FAK is a cytosolic kinase recruited to adhesion sites, so the location is correct. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-354124 | ACCEPT | Summary: cytosol (TAS, Reactome Reactome:R-HSA-354124). Reason: Reactome places FAK (PTK2) in the cytosol for this reaction; FAK is a cytosolic kinase recruited to adhesion sites, so the location is correct. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-354165 | ACCEPT | Summary: cytosol (TAS, Reactome Reactome:R-HSA-354165). Reason: Reactome places FAK (PTK2) in the cytosol for this reaction; FAK is a cytosolic kinase recruited to adhesion sites, so the location is correct. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-372693 | ACCEPT | Summary: cytosol (TAS, Reactome Reactome:R-HSA-372693). Reason: Reactome places FAK (PTK2) in the cytosol for this reaction; FAK is a cytosolic kinase recruited to adhesion sites, so the location is correct. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-372697 | ACCEPT | Summary: cytosol (TAS, Reactome Reactome:R-HSA-372697). Reason: Reactome places FAK (PTK2) in the cytosol for this reaction; FAK is a cytosolic kinase recruited to adhesion sites, so the location is correct. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-372705 | ACCEPT | Summary: cytosol (TAS, Reactome Reactome:R-HSA-372705). Reason: Reactome places FAK (PTK2) in the cytosol for this reaction; FAK is a cytosolic kinase recruited to adhesion sites, so the location is correct. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-373716 | ACCEPT | Summary: cytosol (TAS, Reactome Reactome:R-HSA-373716). Reason: Reactome places FAK (PTK2) in the cytosol for this reaction; FAK is a cytosolic kinase recruited to adhesion sites, so the location is correct. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-374701 | ACCEPT | Summary: cytosol (TAS, Reactome Reactome:R-HSA-374701). Reason: Reactome places FAK (PTK2) in the cytosol for this reaction; FAK is a cytosolic kinase recruited to adhesion sites, so the location is correct. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-392051 | ACCEPT | Summary: cytosol (TAS, Reactome Reactome:R-HSA-392051). Reason: Reactome places FAK (PTK2) in the cytosol for this reaction; FAK is a cytosolic kinase recruited to adhesion sites, so the location is correct. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-392053 | ACCEPT | Summary: cytosol (TAS, Reactome Reactome:R-HSA-392053). Reason: Reactome places FAK (PTK2) in the cytosol for this reaction; FAK is a cytosolic kinase recruited to adhesion sites, so the location is correct. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-392054 | ACCEPT | Summary: cytosol (TAS, Reactome Reactome:R-HSA-392054). Reason: Reactome places FAK (PTK2) in the cytosol for this reaction; FAK is a cytosolic kinase recruited to adhesion sites, so the location is correct. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-3928592 | ACCEPT | Summary: cytosol (TAS, Reactome Reactome:R-HSA-3928592). Reason: Reactome places FAK (PTK2) in the cytosol for this reaction; FAK is a cytosolic kinase recruited to adhesion sites, so the location is correct. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-3928598 | ACCEPT | Summary: cytosol (TAS, Reactome Reactome:R-HSA-3928598). Reason: Reactome places FAK (PTK2) in the cytosol for this reaction; FAK is a cytosolic kinase recruited to adhesion sites, so the location is correct. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-418850 | ACCEPT | Summary: cytosol (TAS, Reactome Reactome:R-HSA-418850). Reason: Reactome places FAK (PTK2) in the cytosol for this reaction; FAK is a cytosolic kinase recruited to adhesion sites, so the location is correct. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-418856 | ACCEPT | Summary: cytosol (TAS, Reactome Reactome:R-HSA-418856). Reason: Reactome places FAK (PTK2) in the cytosol for this reaction; FAK is a cytosolic kinase recruited to adhesion sites, so the location is correct. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-418858 | ACCEPT | Summary: cytosol (TAS, Reactome Reactome:R-HSA-418858). Reason: Reactome places FAK (PTK2) in the cytosol for this reaction; FAK is a cytosolic kinase recruited to adhesion sites, so the location is correct. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-418868 | ACCEPT | Summary: cytosol (TAS, Reactome Reactome:R-HSA-418868). Reason: Reactome places FAK (PTK2) in the cytosol for this reaction; FAK is a cytosolic kinase recruited to adhesion sites, so the location is correct. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-418874 | ACCEPT | Summary: cytosol (TAS, Reactome Reactome:R-HSA-418874). Reason: Reactome places FAK (PTK2) in the cytosol for this reaction; FAK is a cytosolic kinase recruited to adhesion sites, so the location is correct. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-4420083 | ACCEPT | Summary: cytosol (TAS, Reactome Reactome:R-HSA-4420083). Reason: Reactome places FAK (PTK2) in the cytosol for this reaction; FAK is a cytosolic kinase recruited to adhesion sites, so the location is correct. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5218640 | ACCEPT | Summary: cytosol (TAS, Reactome Reactome:R-HSA-5218640). Reason: Reactome places FAK (PTK2) in the cytosol for this reaction; FAK is a cytosolic kinase recruited to adhesion sites, so the location is correct. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5218642 | ACCEPT | Summary: cytosol (TAS, Reactome Reactome:R-HSA-5218642). Reason: Reactome places FAK (PTK2) in the cytosol for this reaction; FAK is a cytosolic kinase recruited to adhesion sites, so the location is correct. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5218643 | ACCEPT | Summary: cytosol (TAS, Reactome Reactome:R-HSA-5218643). Reason: Reactome places FAK (PTK2) in the cytosol for this reaction; FAK is a cytosolic kinase recruited to adhesion sites, so the location is correct. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5218645 | ACCEPT | Summary: cytosol (TAS, Reactome Reactome:R-HSA-5218645). Reason: Reactome places FAK (PTK2) in the cytosol for this reaction; FAK is a cytosolic kinase recruited to adhesion sites, so the location is correct. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5218809 | ACCEPT | Summary: cytosol (TAS, Reactome Reactome:R-HSA-5218809). Reason: Reactome places FAK (PTK2) in the cytosol for this reaction; FAK is a cytosolic kinase recruited to adhesion sites, so the location is correct. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5218811 | ACCEPT | Summary: cytosol (TAS, Reactome Reactome:R-HSA-5218811). Reason: Reactome places FAK (PTK2) in the cytosol for this reaction; FAK is a cytosolic kinase recruited to adhesion sites, so the location is correct. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5218820 | ACCEPT | Summary: cytosol (TAS, Reactome Reactome:R-HSA-5218820). Reason: Reactome places FAK (PTK2) in the cytosol for this reaction; FAK is a cytosolic kinase recruited to adhesion sites, so the location is correct. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5218822 | ACCEPT | Summary: cytosol (TAS, Reactome Reactome:R-HSA-5218822). Reason: Reactome places FAK (PTK2) in the cytosol for this reaction; FAK is a cytosolic kinase recruited to adhesion sites, so the location is correct. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5218826 | ACCEPT | Summary: cytosol (TAS, Reactome Reactome:R-HSA-5218826). Reason: Reactome places FAK (PTK2) in the cytosol for this reaction; FAK is a cytosolic kinase recruited to adhesion sites, so the location is correct. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5218830 | ACCEPT | Summary: cytosol (TAS, Reactome Reactome:R-HSA-5218830). Reason: Reactome places FAK (PTK2) in the cytosol for this reaction; FAK is a cytosolic kinase recruited to adhesion sites, so the location is correct. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5218838 | ACCEPT | Summary: cytosol (TAS, Reactome Reactome:R-HSA-5218838). Reason: Reactome places FAK (PTK2) in the cytosol for this reaction; FAK is a cytosolic kinase recruited to adhesion sites, so the location is correct. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5218839 | ACCEPT | Summary: cytosol (TAS, Reactome Reactome:R-HSA-5218839). Reason: Reactome places FAK (PTK2) in the cytosol for this reaction; FAK is a cytosolic kinase recruited to adhesion sites, so the location is correct. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5218851 | ACCEPT | Summary: cytosol (TAS, Reactome Reactome:R-HSA-5218851). Reason: Reactome places FAK (PTK2) in the cytosol for this reaction; FAK is a cytosolic kinase recruited to adhesion sites, so the location is correct. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5672965 | ACCEPT | Summary: cytosol (TAS, Reactome Reactome:R-HSA-5672965). Reason: Reactome places FAK (PTK2) in the cytosol for this reaction; FAK is a cytosolic kinase recruited to adhesion sites, so the location is correct. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8874078 | ACCEPT | Summary: cytosol (TAS, Reactome Reactome:R-HSA-8874078). Reason: Reactome places FAK (PTK2) in the cytosol for this reaction; FAK is a cytosolic kinase recruited to adhesion sites, so the location is correct. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8874079 | ACCEPT | Summary: cytosol (TAS, Reactome Reactome:R-HSA-8874079). Reason: Reactome places FAK (PTK2) in the cytosol for this reaction; FAK is a cytosolic kinase recruited to adhesion sites, so the location is correct. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8874080 | ACCEPT | Summary: cytosol (TAS, Reactome Reactome:R-HSA-8874080). Reason: Reactome places FAK (PTK2) in the cytosol for this reaction; FAK is a cytosolic kinase recruited to adhesion sites, so the location is correct. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8874082 | ACCEPT | Summary: cytosol (TAS, Reactome Reactome:R-HSA-8874082). Reason: Reactome places FAK (PTK2) in the cytosol for this reaction; FAK is a cytosolic kinase recruited to adhesion sites, so the location is correct. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8874083 | ACCEPT | Summary: cytosol (TAS, Reactome Reactome:R-HSA-8874083). Reason: Reactome places FAK (PTK2) in the cytosol for this reaction; FAK is a cytosolic kinase recruited to adhesion sites, so the location is correct. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9625482 | ACCEPT | Summary: cytosol (TAS, Reactome Reactome:R-HSA-9625482). Reason: Reactome places FAK (PTK2) in the cytosol for this reaction; FAK is a cytosolic kinase recruited to adhesion sites, so the location is correct. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9625487 | ACCEPT | Summary: cytosol (TAS, Reactome Reactome:R-HSA-9625487). Reason: Reactome places FAK (PTK2) in the cytosol for this reaction; FAK is a cytosolic kinase recruited to adhesion sites, so the location is correct. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9632412 | ACCEPT | Summary: cytosol (TAS, Reactome Reactome:R-HSA-9632412). Reason: Reactome places FAK (PTK2) in the cytosol for this reaction; FAK is a cytosolic kinase recruited to adhesion sites, so the location is correct. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9861469 | ACCEPT | Summary: cytosol (TAS, Reactome Reactome:R-HSA-9861469). Reason: Reactome places FAK (PTK2) in the cytosol for this reaction; FAK is a cytosolic kinase recruited to adhesion sites, so the location is correct. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9861484 | ACCEPT | Summary: cytosol (TAS, Reactome Reactome:R-HSA-9861484). Reason: Reactome places FAK (PTK2) in the cytosol for this reaction; FAK is a cytosolic kinase recruited to adhesion sites, so the location is correct. |
| GO:0005856 cytoskeleton | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: cytoskeleton (IEA, UniProt SubCell). Reason: FAK partitions with the detergent-insoluble cytoskeletal fraction when engaged at adhesions; focal adhesion is the informative term. |
| GO:0005856 cytoskeleton | TAS PMID:10801330 Tyrosine dephosphorylation, but not phosphorylation, of p130... | KEEP AS NON CORE | Summary: cytoskeleton (TAS, PMID:10801330, platelets). Reason: FAK translocates to the cytoskeletal fraction during platelet aggregation; fractionation-based, non-core. Supporting Evidence: PMID:10801330 when FAK translocated to the cytoskeletal fraction |
| GO:0005886 plasma membrane | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: plasma membrane (IBA, PTN002521457, broad tyrosine kinase node). Reason: PAINT placed plasma membrane on a deep node shared by Src, Abl, Tec and FAK families. FAK has no lipid anchor or transmembrane segment; it is a peripheral protein on the cytoplasmic face of the membrane at integrin adhesions (UniProt, by similarity to mouse). The node placement is defensible for the family, but for FAK the informative location is focal adhesion. |
| GO:0005886 plasma membrane | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: plasma membrane (IEA, UniProt SubCell). Reason: Peripheral membrane association at adhesions; non-core relative to focal adhesion. |
| GO:0005886 plasma membrane | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: plasma membrane (ISS from mouse Q00944). Reason: Peripheral membrane association at adhesions; non-core relative to focal adhesion. |
| GO:0005925 focal adhesion | IBA GO_REF:0000033 | ACCEPT | Summary: focal adhesion (IBA, PTN002400754, FAK/PYK2 node). Reason: Focal adhesion targeting via the FAT domain is the defining feature of the family; human PTK2 is among the experimental descendants. Core location. Supporting Evidence: PMID:7561682 These findings strongly suggest that pp125FAK is localized to focal adhesions by the direct association with paxillin |
| GO:0005925 focal adhesion | IDA GO_REF:0000052 | ACCEPT | Summary: focal adhesion (IDA, GO_REF:0000052, HPA immunofluorescence). Reason: Core location. |
| GO:0005925 focal adhesion | IDA PMID:10655584 Activation of EphA2 kinase suppresses integrin function and ... | ACCEPT | Summary: focal adhesion (IDA, PMID:10655584). Reason: FAK localises to focal adhesions (UniProt cites this paper for the location). Core. Supporting Evidence: PMID:10655584 this is followed by dephosphorylation of FAK and paxillin, and dissociation of the FAK-EphA2 complex |
| GO:0005925 focal adhesion | IDA PMID:15855171 Direct interaction of the N-terminal domain of focal adhesio... | ACCEPT | Summary: focal adhesion (IDA, PMID:15855171). Reason: Core location (UniProt cites this paper). |
| GO:0005925 focal adhesion | IDA PMID:23574715 The novel actin/focal adhesion-associated protein MISP is in... | ACCEPT | Summary: focal adhesion (IDA, PMID:23574715). Reason: Autophosphorylated FAK Y397 used as a focal adhesion marker in MISP study. Core. Supporting Evidence: PMID:23574715 Co-immunostaining of MISP with the focal adhesion markers paxillin (middle panel) and autophosphorylated focal adhesion kinase (FAK Y397, lower panel) reveals that fiber-like MISP structures often end in focal adhesions |
| GO:0005925 focal adhesion | IEA GO_REF:0000120 | ACCEPT | Summary: focal adhesion (IEA, combined InterPro FAT domain/ARBA). Reason: Core. |
| GO:0005938 cell cortex | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: cell cortex (IEA, UniProt SubCell). Reason: Correct but less informative than focal adhesion. |
| GO:0007172 signal complex assembly | IEA GO_REF:0000002 | ACCEPT | Summary: signal complex assembly (IEA, InterPro FAT domain). Reason: Autophosphorylated FAK nucleates FAK-Src signalling complexes and recruits adaptors such as Cas, Grb2 and PI3K; assembly of these complexes is a central part of what FAK does. Supporting Evidence: PMID:12391143 Autophosphorylation of FAK on Tyr-397 is a critical event, allowing binding of Src family kinases and activation of signal transduction pathways PMID:16919435 Activated FAK-Src functions to promote cell motility, cell cycle progression and cell survival |
| GO:0007173 epidermal growth factor receptor signaling pathway | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: epidermal growth factor receptor signaling pathway (IBA, PTN001975314). Reason: FAK participates in growth-factor receptor signalling (e.g. EGFR-dependent Y397 autophosphorylation, Reactome R-HSA-9625487), but this is one of many receptor contexts; non-core. |
| GO:0007179 transforming growth factor beta receptor signaling pathway | IDA PMID:24036928 Integrin-Ξ²5 and zyxin mediate formation of ventral stress fi... | KEEP AS NON CORE | Summary: transforming growth factor beta receptor signaling pathway (IDA, PMID:24036928). Reason: FAK phospho-Tyr861 increases with TGF-beta-induced ventral stress fiber formation in an integrin-beta5-dependent manner; FAK acts in the integrin arm of this response, so TGF-beta signalling is context, not core. Supporting Evidence: PMID:24036928 TGF-Ξ²1 increased phospho-Tyr861-FAK staining at the ends of actin fibers in the control cells |
| GO:0007229 integrin-mediated signaling pathway | IDA PMID:24036928 Integrin-Ξ²5 and zyxin mediate formation of ventral stress fi... | ACCEPT | Summary: integrin-mediated signaling pathway (IDA, PMID:24036928). Reason: FAK is a central transducer of integrin outside-in signalling: integrin engagement drives FAK Tyr397 autophosphorylation and FAK-Src complex formation. Core process. Supporting Evidence: PMID:24036928 Accordingly, integrin-Ξ²5-FAK-Src signaling contributes to tumorigenic potential of breast cancer cells |
| GO:0007229 integrin-mediated signaling pathway | IEA GO_REF:0000117 | ACCEPT | Summary: integrin-mediated signaling pathway (IEA, ARBA). Reason: Core process. Supporting Evidence: PMID:9636140 tyrosine phosphorylation of paxillin and FAK elicited by stimulation of muscarinic m3 receptors with the acetylcholine analog carbachol is inhibited by soluble peptides containing the arginine-glycine-aspartate motif |
| GO:0007229 integrin-mediated signaling pathway | IMP PMID:11331870 Regulation of the PH-domain-containing tyrosine kinase Etk b... | ACCEPT | Summary: integrin-mediated signaling pathway (IMP, PMID:11331870). Reason: FAK is a central transducer of integrin outside-in signalling: integrin engagement drives FAK Tyr397 autophosphorylation and FAK-Src complex formation. Core process. Supporting Evidence: PMID:11331870 Disrupting the interaction between Etk and FAK diminished the cell migration promoted by either kinase |
| GO:0007229 integrin-mediated signaling pathway | TAS PMID:15725728 Netrin-integrin signaling in epithelial morphogenesis, axon ... | ACCEPT | Summary: integrin-mediated signaling pathway (TAS, PMID:15725728). Reason: FAK is a central transducer of integrin outside-in signalling: integrin engagement drives FAK Tyr397 autophosphorylation and FAK-Src complex formation. Core process. Supporting Evidence: PMID:15725728 Netrins accomplish these effects, at least in part, through binding to integrins and/or activating integrin-associated kinases such as FAK and Fyn |
| GO:0007229 integrin-mediated signaling pathway | TAS PMID:9636140 Tyrosine phosphorylation of paxillin and focal adhesion kina... | ACCEPT | Summary: integrin-mediated signaling pathway (TAS, PMID:9636140). Reason: FAK is a central transducer of integrin outside-in signalling: integrin engagement drives FAK Tyr397 autophosphorylation and FAK-Src complex formation. Core process. Supporting Evidence: PMID:9636140 tyrosine phosphorylation of paxillin and FAK elicited by stimulation of muscarinic m3 receptors with the acetylcholine analog carbachol is inhibited by soluble peptides containing the arginine-glycine-aspartate motif |
| GO:0007411 axon guidance | TAS PMID:15725728 Netrin-integrin signaling in epithelial morphogenesis, axon ... | KEEP AS NON CORE | Summary: axon guidance (TAS, PMID:15725728). Reason: Netrin-DCC/integrin signalling activates FAK in growth cones; an animal neural context of the general signalling function. Supporting Evidence: PMID:15725728 Netrins accomplish these effects, at least in part, through binding to integrins and/or activating integrin-associated kinases such as FAK and Fyn |
| GO:0008284 positive regulation of cell population proliferation | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: positive regulation of cell population proliferation (IEA, ARBA). Reason: FAK-Src signalling promotes cell-cycle progression in animal cells (PMID:16919435); downstream outcome, non-core. Supporting Evidence: PMID:16919435 Activated FAK-Src functions to promote cell motility, cell cycle progression and cell survival |
| GO:0008284 positive regulation of cell population proliferation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: positive regulation of cell population proliferation (ISS from mouse P34152). Reason: Downstream outcome of FAK signalling; non-core. |
| GO:0008360 regulation of cell shape | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: regulation of cell shape (IEA, ARBA). Reason: FAK affects spreading and shape through Rho GTPase regulation; non-core. |
| GO:0008360 regulation of cell shape | IMP PMID:15166238 Focal adhesion kinase is upstream of phosphatidylinositol 3-... | KEEP AS NON CORE | Summary: regulation of cell shape (IMP, PMID:15166238). Reason: The cached abstract reports a FAK-PI3K/Akt survival pathway in contracting collagen matrices; cell-shape data are presumably in the full text. Retained as non-core. |
| GO:0008432 JUN kinase binding | IDA PMID:10925297 Regulation of neutrophil adhesion by pituitary growth hormon... | UNDECIDED | Summary: JUN kinase binding (IDA, PMID:10925297). Reason: The cached abstract describes a physical association of FAK with Jak2 (Janus kinase 2), and says it is indirect, via STAT3; it does not mention JNK. The term JUN kinase binding (GO:0008432) may have been chosen in error for Janus kinase. The full text is not cached, so the row cannot be resolved here; a curator should check it. Supporting Evidence: PMID:10925297 Immunoprecipitation experiments revealed a physical association of Jak2 with p125FAK via STAT3 in vivo |
| GO:0010594 regulation of endothelial cell migration | TAS PMID:20552554 The role of focal adhesion kinase in early development. | KEEP AS NON CORE | Summary: regulation of endothelial cell migration (TAS, PMID:20552554). Reason: Cell-type-specific case of FAK regulating migration; non-core. Supporting Evidence: PMID:20552554 is responsible, at least in part, for the modulation of cellular proliferation, protection from apoptosis, adhesion, spreading and migration |
| GO:0010632 regulation of epithelial cell migration | IGI PMID:19913511 Coronin 1C negatively regulates cell-matrix adhesion and mot... | KEEP AS NON CORE | Summary: regulation of epithelial cell migration (IGI with CORO1C, PMID:19913511). Reason: FAK signalling mediates Coronin 1C effects on intestinal epithelial motility; cell-type-specific case of the core migration role. Supporting Evidence: PMID:19913511 FAK-mediated signaling is a critical downstream component, which mediates negative effects of Coronin 1C on both cell-matrix adhesion and motility of IECs |
| GO:0010634 positive regulation of epithelial cell migration | IGI PMID:26944318 MicroRNA-379-5p inhibits tumor invasion and metastasis by ta... | KEEP AS NON CORE | Summary: positive regulation of epithelial cell migration (IGI with miR-379, PMID:26944318). Reason: Restoring FAK reverses miR-379-5p suppression of HCC cell migration; cancer-cell context, non-core. Supporting Evidence: PMID:26944318 the tumor suppressive effects of miR-379-5p in HCC cells were reversed by activating AKT signaling or restoring FAK expression |
| GO:0010718 positive regulation of epithelial to mesenchymal transition | IGI PMID:26944318 MicroRNA-379-5p inhibits tumor invasion and metastasis by ta... | KEEP AS NON CORE | Summary: positive regulation of epithelial to mesenchymal transition (IGI with miR-379, PMID:26944318). Reason: FAK/AKT signalling supports EMT in HCC cells; downstream cancer phenotype, non-core. Supporting Evidence: PMID:26944318 the tumor suppressive effects of miR-379-5p in HCC cells were reversed by activating AKT signaling or restoring FAK expression |
| GO:0010759 positive regulation of macrophage chemotaxis | IGI PMID:26754294 miR-28-5p-IL-34-macrophage feedback loop modulates hepatocel... | UNDECIDED | Summary: positive regulation of macrophage chemotaxis (IGI with IL34, PMID:26754294). Reason: The cached abstract describes a miR-28-5p/IL-34/macrophage loop in HCC and does not mention FAK; full text not cached. Cannot verify the FAK-specific evidence. |
| GO:0010763 positive regulation of fibroblast migration | IDA PMID:26763945 Focal Adhesion Kinase Regulates Fibroblast Migration via Int... | KEEP AS NON CORE | Summary: positive regulation of fibroblast migration (IDA, PMID:26763945). Reason: FAK inhibition blocks fibroblast migration on fibronectin; a cell-type-specific case of the core positive regulation of cell migration. Supporting Evidence: PMID:26763945 FAK inhibitor blocks FAK activation and fibroblast migration on FN but has no effect on FAK-integrin Ξ²1 interaction |
| GO:0016477 cell migration | IMP PMID:20305651 Gain of miR-151 on chromosome 8q24.3 facilitates tumour cell... | ACCEPT | Summary: cell migration (IMP, PMID:20305651). Reason: FAK cooperates with miR-151 to enhance HCC cell motility; FAK is directly involved in migration through adhesion turnover and Rho GTPase control. Supporting Evidence: PMID:20305651 miR-151 can function synergistically with FAK to enhance HCC cell motility and spreading |
| GO:0016477 cell migration | IMP PMID:26934001 MicroRNA-92b represses invasion-metastasis cascade of esopha... | ACCEPT | Summary: cell migration (IMP, PMID:26934001). Reason: FAK knockdown represses migration of oesophageal carcinoma cells. Supporting Evidence: PMID:26934001 Knockdown of FAK repressed migration and invasion of 30-D cells in vitro |
| GO:0019901 protein kinase binding | IPI PMID:19118217 EphA1 interacts with integrin-linked kinase and regulates ce... | KEEP AS NON CORE | Summary: protein kinase binding (IPI with EPHA1, PMID:19118217). Reason: UniProt records a kinase-activity-dependent EPHA1-FAK interaction from this paper (not in the cached abstract). Retained as a specific partner-class term, non-core. |
| GO:0019903 protein phosphatase binding | IPI PMID:28759036 Deficiency in VHR/DUSP3, a suppressor of focal adhesion kina... | KEEP AS NON CORE | Summary: protein phosphatase binding (IPI with DUSP3/VHR, PMID:28759036). Reason: VHR binds and dephosphorylates FAK; FAK is the substrate, so the binding describes regulation of FAK, not a FAK function. Retained as non-core. Supporting Evidence: PMID:28759036 We identified focal adhesion kinase (FAK) as a VHR-interacting molecule |
| GO:0022408 negative regulation of cell-cell adhesion | IDA PMID:21703394 Abnormal cell properties and down-regulated FAK-Src complex ... | KEEP AS NON CORE | Summary: negative regulation of cell-cell adhesion (IDA, PMID:21703394). Reason: In autistic B lymphoblasts with low FAK, adhesion to ICAM-1-coated plates was increased and FAK overexpression reversed it. A cell-context observation; non-core. Supporting Evidence: PMID:21703394 the overexpression of FAK could counter the increased adhesion in autistic lymphoblasts |
| GO:0030010 establishment of cell polarity | TAS PMID:19525103 Focal adhesion kinase: switching between GAPs and GEFs in th... | KEEP AS NON CORE | Summary: establishment of cell polarity (TAS, PMID:19525103). Reason: FAK spatially regulates Rho GEFs/GAPs during directional migration; polarity is a facet of that, non-core. Supporting Evidence: PMID:19525103 FAK is in a unique signaling position to modulate RhoGTPase activity in space and time, thereby affecting various steps (integrin activation, leading edge formation, FA turnover, and trailing edge retraction) needed for efficient directional cell migration |
| GO:0030154 cell differentiation | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: cell differentiation (IEA, ARBA). Reason: Too general to be informative; FAK affects differentiation only indirectly through adhesion signalling in specific animal cell types. |
| GO:0030155 regulation of cell adhesion | IBA GO_REF:0000033 | ACCEPT | Summary: regulation of cell adhesion (IBA, PTN001975314). Reason: PAINT node for FAK/PYK2; FAK regulates integrin adhesion strength and turnover. Core-adjacent process. Supporting Evidence: PMID:19913511 FAK-mediated signaling is a critical downstream component, which mediates negative effects of Coronin 1C on both cell-matrix adhesion and motility of IECs |
| GO:0030335 positive regulation of cell migration | IBA GO_REF:0000033 | ACCEPT | Summary: positive regulation of cell migration (IBA, PTN001975314). Reason: FAK promotes directional migration via FAK-Src signalling, Rho GTPase regulation and adhesion turnover; well supported by many descendants including human PTK2. Core process. Supporting Evidence: PMID:16919435 Activated FAK-Src functions to promote cell motility, cell cycle progression and cell survival |
| GO:0030335 positive regulation of cell migration | IDA PMID:11331870 Regulation of the PH-domain-containing tyrosine kinase Etk b... | ACCEPT | Summary: positive regulation of cell migration (IDA, PMID:11331870). Reason: Etk/FAK interaction promotes migration. Supporting Evidence: PMID:11331870 Disrupting the interaction between Etk and FAK diminished the cell migration promoted by either kinase |
| GO:0030335 positive regulation of cell migration | IDA PMID:21703394 Abnormal cell properties and down-regulated FAK-Src complex ... | ACCEPT | Summary: positive regulation of cell migration (IDA, PMID:21703394). Reason: FAK overexpression rescued the migration defect of autistic lymphoblasts. Supporting Evidence: PMID:21703394 overexpression of FAK could rescue the adhesion and migration defects |
| GO:0033629 negative regulation of cell adhesion mediated by integrin | IDA PMID:10655584 Activation of EphA2 kinase suppresses integrin function and ... | MARK AS OVER ANNOTATED | Summary: negative regulation of cell adhesion mediated by integrin (IDA, PMID:10655584). Reason: In this paper EphA2 activation suppresses integrin function, and FAK is the target that is dephosphorylated. The negative regulation is carried out by EphA2 and SHP2; FAK itself promotes integrin adhesion. The GO-CAM model of this pathway (689e7a5d00003515) gives FAK a positive regulatory role, so the negative term on FAK overstates its part. Supporting Evidence: PMID:10655584 this is followed by dephosphorylation of FAK and paxillin, and dissociation of the FAK-EphA2 complex PMID:10655584 activation of endogenous EphA2 kinase induces an inactive conformation of integrins and inhibits cell spreading, migration and integrin-mediated adhesion |
| GO:0033634 positive regulation of cell-cell adhesion mediated by integrin | IDA PMID:10655584 Activation of EphA2 kinase suppresses integrin function and ... | MODIFY | Summary: positive regulation of cell-cell adhesion mediated by integrin (IDA, PMID:10655584). Reason: FAK promotes integrin-mediated adhesion, and the GO-CAM model 689e7a5d00003515 uses this term. But the assays in the paper (cell spreading, migration and integrin-mediated adhesion) measure adhesion to matrix, not to other cells. The parent term, positive regulation of cell adhesion mediated by integrin, fits the evidence without the cell-cell restriction. Proposed replacements: positive regulation of cell adhesion mediated by integrin Supporting Evidence: PMID:10655584 activation of endogenous EphA2 kinase induces an inactive conformation of integrins and inhibits cell spreading, migration and integrin-mediated adhesion |
| GO:0035995 detection of muscle stretch | TAS PMID:30568254 PI3KΞ±-regulated gelsolin activity is a critical determinant ... | KEEP AS NON CORE | Summary: detection of muscle stretch (TAS, PMID:30568254). Reason: The paper treats the integrin/FAK complex as a cardiac mechanosensor and reports FAK phosphorylation under pressure overload. FAK responds to mechanical load, but the stretch detector is the integrin-adhesion assembly. Non-core, animal tissue context. Supporting Evidence: PMID:30568254 The intercellular N-cadherin/Ξ²-catenin complex9,23,24 and the integrin-based/focal adhesion kinase (FAK) complex are important mechanosensors |
| GO:0036064 ciliary basal body | IDA PMID:31630787 De Novo Mutations in FOXJ1 Result in a Motile Ciliopathy wit... | KEEP AS NON CORE | Summary: ciliary basal body (IDA, PMID:31630787). Reason: PTK2 localises near basal bodies in multiciliated respiratory epithelium, where focal-adhesion proteins anchor basal bodies to actin. A specialised animal location. Supporting Evidence: PMID:31630787 PTK2 localizes in the basal body area in respiratory epithelial cells of healthy control subjects |
| GO:0038007 netrin-activated signaling pathway | TAS PMID:15725728 Netrin-integrin signaling in epithelial morphogenesis, axon ... | KEEP AS NON CORE | Summary: netrin-activated signaling pathway (TAS, PMID:15725728). Reason: Netrin receptors activate FAK; one of several receptor inputs. Non-core. Supporting Evidence: PMID:15725728 Netrins accomplish these effects, at least in part, through binding to integrins and/or activating integrin-associated kinases such as FAK and Fyn |
| GO:0038096 Fc-gamma receptor signaling pathway involved in phagocytosis | TAS Reactome:R-HSA-2029480 | KEEP AS NON CORE | Summary: Fc-gamma receptor signaling pathway involved in phagocytosis (TAS, Reactome R-HSA-2029480). Reason: Reactome includes FAK among kinases activated downstream of FCGR clustering in phagocytes; immune-cell context, non-core. |
| GO:0038096 Fc-gamma receptor signaling pathway involved in phagocytosis | TAS Reactome:R-HSA-9664422 | KEEP AS NON CORE | Summary: Fc-gamma receptor signaling pathway involved in phagocytosis (TAS, Reactome R-HSA-9664422). Reason: Reactome includes FAK among kinases activated downstream of FCGR clustering in phagocytes; immune-cell context, non-core. |
| GO:0042127 regulation of cell population proliferation | IMP PMID:18206965 Nuclear FAK promotes cell proliferation and survival through... | KEEP AS NON CORE | Summary: regulation of cell population proliferation (IMP, PMID:18206965). Reason: Nuclear FAK promotes proliferation and survival by enhancing p53 degradation; non-core outcome. Supporting Evidence: PMID:18206965 These studies define a scaffolding role for nuclear FAK in facilitating cell survival through enhanced p53 degradation under conditions of cellular stress |
| GO:0042169 SH2 domain binding | IPI PMID:15077193 Overexpression of FAK promotes Ras activity through the form... | ACCEPT | Summary: SH2 domain binding (IPI with RASA1/p120RasGAP, PMID:15077193). Reason: FAK forms a Tyr397-dependent complex with SH2-containing p120RasGAP. pTyr docking sites for SH2 proteins are the main scaffolding mechanism of FAK. Core. Supporting Evidence: PMID:15077193 the Y397 residue of FAK plays a role in the formation of this complex and in the activation of Ras |
| GO:0043066 negative regulation of apoptotic process | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: negative regulation of apoptotic process (IEA, ARBA). Reason: FAK survival signalling (PI3K/Akt, p53 suppression) is real but downstream; non-core. |
| GO:0043066 negative regulation of apoptotic process | IMP PMID:15166238 Focal adhesion kinase is upstream of phosphatidylinositol 3-... | KEEP AS NON CORE | Summary: negative regulation of apoptotic process (IMP, PMID:15166238). Reason: Dominant-negative FAK increased fibroblast apoptosis during collagen contraction; downstream survival outcome. Supporting Evidence: PMID:15166238 Dominant negative FAK augmented fibroblast apoptosis during collagen contraction |
| GO:0045595 regulation of cell differentiation | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: regulation of cell differentiation (IEA, ARBA). Reason: Too general; differentiation effects are indirect and cell-type specific (e.g. osteoblasts). |
| GO:0045667 regulation of osteoblast differentiation | IMP PMID:16927379 Activation of FAK is necessary for the osteogenic differenti... | KEEP AS NON CORE | Summary: regulation of osteoblast differentiation (IMP, PMID:16927379). Reason: FAK knockdown blocked laminin-5-induced osteogenic differentiation of hMSC via ERK; a downstream, cell-type-specific outcome. Supporting Evidence: PMID:16927379 FAK inhibition blocked osteogenic differentiation of hMSC |
| GO:0048010 vascular endothelial growth factor receptor signaling pathway | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: vascular endothelial growth factor receptor signaling pathway (IEA, ARBA). Reason: FAK acts downstream of VEGFR2 in endothelial migration; one receptor context among many. |
| GO:0048010 vascular endothelial growth factor receptor signaling pathway | TAS Reactome:R-HSA-194138 | KEEP AS NON CORE | Summary: vascular endothelial growth factor receptor signaling pathway (TAS, Reactome R-HSA-194138). Reason: As above; endothelial context. |
| GO:0048013 ephrin receptor signaling pathway | IDA PMID:10655584 Activation of EphA2 kinase suppresses integrin function and ... | KEEP AS NON CORE | Summary: ephrin receptor signaling pathway (IDA, PMID:10655584). Reason: FAK is constitutively associated with EphA2 and is dephosphorylated on ephrin-A1 stimulation; FAK is a target of this pathway. Non-core. Supporting Evidence: PMID:10655584 EphA2 is constitutively associated with focal-adhesion kinase (FAK) in resting cells PMID:10655584 this is followed by dephosphorylation of FAK and paxillin, and dissociation of the FAK-EphA2 complex |
| GO:0048471 perinuclear region of cytoplasm | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: perinuclear region of cytoplasm (IEA, UniProt SubCell). Reason: UniProt records perinuclear FAK (PMID:15855171); minor pool, non-core. |
| GO:0048870 cell motility | TAS PMID:15725728 Netrin-integrin signaling in epithelial morphogenesis, axon ... | ACCEPT | Summary: cell motility (TAS, PMID:15725728). Reason: FAK is directly involved in cell motility; correct though general. Supporting Evidence: PMID:15725728 Netrins accomplish these effects, at least in part, through binding to integrins and/or activating integrin-associated kinases such as FAK and Fyn |
| GO:0051239 regulation of multicellular organismal process | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: regulation of multicellular organismal process (IEA, ARBA). Reason: Uninformative high-level term; FAK acts at the cell level (adhesion, migration signalling). |
| GO:0051493 regulation of cytoskeleton organization | TAS PMID:15725728 Netrin-integrin signaling in epithelial morphogenesis, axon ... | ACCEPT | Summary: regulation of cytoskeleton organization (TAS, PMID:15725728). Reason: FAK regulates actin reorganisation through Rho GEFs/GAPs and N-WASP (PMID:19525103, PMID:14676198). Supporting Evidence: PMID:19525103 FAK is in a unique signaling position to modulate RhoGTPase activity in space and time, thereby affecting various steps (integrin activation, leading edge formation, FA turnover, and trailing edge retraction) needed for efficient directional cell migration |
| GO:0051893 regulation of focal adhesion assembly | IGI PMID:19913511 Coronin 1C negatively regulates cell-matrix adhesion and mot... | ACCEPT | Summary: regulation of focal adhesion assembly (IGI with CORO1C, PMID:19913511). Reason: FAK controls formation and turnover of focal adhesions. Core process. Supporting Evidence: PMID:19913511 FAK-mediated signaling is a critical downstream component, which mediates negative effects of Coronin 1C on both cell-matrix adhesion and motility of IECs |
| GO:0051893 regulation of focal adhesion assembly | TAS PMID:16919435 Integrin-regulated FAK-Src signaling in normal and cancer ce... | ACCEPT | Summary: regulation of focal adhesion assembly (TAS, PMID:16919435). Reason: Core process. Supporting Evidence: PMID:16919435 Activated FAK-Src functions to promote cell motility, cell cycle progression and cell survival |
| GO:0051893 regulation of focal adhesion assembly | TAS PMID:19525103 Focal adhesion kinase: switching between GAPs and GEFs in th... | ACCEPT | Summary: regulation of focal adhesion assembly (TAS, PMID:19525103). Reason: FAK controls FA turnover via GEF/GAP switching. Core. Supporting Evidence: PMID:19525103 FAK is in a unique signaling position to modulate RhoGTPase activity in space and time, thereby affecting various steps (integrin activation, leading edge formation, FA turnover, and trailing edge retraction) needed for efficient directional cell migration |
| GO:0051894 positive regulation of focal adhesion assembly | NAS PMID:39287113 LncRNA FAISL Inhibits Calpain 2-Mediated Proteolysis of FAK ... | KEEP AS NON CORE | Summary: positive regulation of focal adhesion assembly (NAS, PMID:39287113; GO-CAM 682fbcd000002551). Reason: FAK promotes talin recruitment to nascent adhesions (PMID:22270917), but it also drives adhesion disassembly and turnover. The undirected regulation term is the better core term; this row is kept as non-core. Supporting Evidence: PMID:39287113 Proteolysis of FAK by Calpain 2 is an important and specific mechanism for regulating the turnover of focal adhesions PMID:22270917 FAK promotes talin recruitment to nascent adhesions occurring independently of talin binding to Ξ²1 integrins |
| GO:0051897 positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction | IGI PMID:26944318 MicroRNA-379-5p inhibits tumor invasion and metastasis by ta... | KEEP AS NON CORE | Summary: positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (IGI with miR-379, PMID:26944318). Reason: FAK acts upstream of PI3K/Akt; downstream signalling output, non-core. Supporting Evidence: PMID:26944318 the tumor suppressive effects of miR-379-5p in HCC cells were reversed by activating AKT signaling or restoring FAK expression |
| GO:0051897 positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction | IMP PMID:15166238 Focal adhesion kinase is upstream of phosphatidylinositol 3-... | KEEP AS NON CORE | Summary: positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (IMP, PMID:15166238). Reason: Blocking FAK reduced p85 and Akt phosphorylation in fibroblasts; FAK pY397 recruits PI3K. Real but downstream of the core integrin-signalling role. Supporting Evidence: PMID:15166238 Blocking FAK by pharmacologic inhibition or by dominant negative FAK attenuated phosphorylation of p85 subunit of PI3K and Akt |
| GO:0060396 growth hormone receptor signaling pathway | IDA PMID:10925297 Regulation of neutrophil adhesion by pituitary growth hormon... | KEEP AS NON CORE | Summary: growth hormone receptor signaling pathway (IDA, PMID:10925297). Reason: GH induces FAK phosphorylation in neutrophils in association with Jak2/STAT3; FAK is a downstream component in this immune-cell context. Supporting Evidence: PMID:10925297 pituitary GH modulates neutrophil adhesion through tyrosine phosphorylation of Jak2, p125FAK, and paxillin and actin polymerization |
| GO:0090303 positive regulation of wound healing | IDA PMID:26763945 Focal Adhesion Kinase Regulates Fibroblast Migration via Int... | MARK AS OVER ANNOTATED | Summary: positive regulation of wound healing (IDA, PMID:26763945). Reason: The evidence is an in vitro scratch (monolayer wound-closure) migration assay in fibroblasts, which measures cell migration rather than tissue wound healing. Captured by positive regulation of fibroblast/cell migration. Supporting Evidence: PMID:26763945 FAK inhibitor blocks FAK activation and fibroblast migration on FN but has no effect on FAK-integrin Ξ²1 interaction |
| GO:0097706 vascular endothelial cell response to oscillatory fluid shear stress | TAS Reactome:R-HSA-9860927 | KEEP AS NON CORE | Summary: vascular endothelial cell response to oscillatory fluid shear stress (TAS, Reactome R-HSA-9860927). Reason: FAK phosphorylates CHUK downstream of integrins under turbulent flow (R-HSA-9861469); endothelial context, non-core. |
| GO:0120041 positive regulation of macrophage proliferation | IGI PMID:26754294 miR-28-5p-IL-34-macrophage feedback loop modulates hepatocel... | UNDECIDED | Summary: positive regulation of macrophage proliferation (IGI with IL34, PMID:26754294). Reason: The cached abstract does not mention FAK, and the full text is not cached, so the FAK-specific evidence cannot be verified. |
| GO:0140677 molecular function activator activity | EXP PMID:12467573 Structures of the cancer-related Aurora-A, FAK, and EphA2 pr... | UNDECIDED | Summary: molecular function activator activity (EXP, PMID:12467573). Reason: PMID:12467573 reports crystal structures of the FAK kinase domain. The cached abstract does not show FAK activating another protein, and this very general term does not say which activity is activated. Full text not cached; flagged for curator check. |
| GO:1900024 regulation of substrate adhesion-dependent cell spreading | IGI PMID:19913511 Coronin 1C negatively regulates cell-matrix adhesion and mot... | KEEP AS NON CORE | Summary: regulation of substrate adhesion-dependent cell spreading (IGI with CORO1C, PMID:19913511). Reason: FAK signalling mediates Coronin 1C effects on adhesion and spreading; related to the core adhesion-regulation role. Supporting Evidence: PMID:19913511 FAK-mediated signaling is a critical downstream component, which mediates negative effects of Coronin 1C on both cell-matrix adhesion and motility of IECs |
| GO:2000060 positive regulation of ubiquitin-dependent protein catabolic process | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: positive regulation of ubiquitin-dependent protein catabolic process (ISS from mouse P34152). Reason: Nuclear FAK FERM domain scaffolds Mdm2-dependent p53 ubiquitination and degradation (PMID:18206965); non-core. Supporting Evidence: PMID:18206965 These studies define a scaffolding role for nuclear FAK in facilitating cell survival through enhanced p53 degradation under conditions of cellular stress |
| GO:2000811 negative regulation of anoikis | IMP PMID:22402981 Integrin/Fak/Src-mediated regulation of cell survival and an... | KEEP AS NON CORE | Summary: negative regulation of anoikis (IMP, PMID:22402981). Reason: beta1 integrin/Fak/Src/PI3K signalling suppresses anoikis in intestinal crypt cells; a survival outcome of the core integrin signalling. Supporting Evidence: PMID:22402981 signaling originating from Ξ²1 integrins to promote cell survival and anoikis suppression will often implicate focal adhesion kinase (Fak; p125Fak), Src (p60Src) and the phosphatidylinositol-3 kinase (PI3-K)/Akt-1 (PKB; p57Akt-1) pathway |
| GO:0038083 peptidyl-tyrosine autophosphorylation | TAS Reactome:R-HSA-354073 | NEW | Summary: FAK autophosphorylates Tyr397, the switch that creates the Src SH2 docking site. Reason: Autophosphorylation of Tyr397 is the defining activation step of FAK and is represented in Reactome R-HSA-354073 (human) and studied directly with rat FAK splice isoforms in PMID:12391143; the Tyr397 site is conserved in human PTK2. FAK itself catalyses the step, so the participation test is met. No existing row captures the autophosphorylation process. Supporting Evidence: PMID:12391143 Autophosphorylation of FAK on Tyr-397 is a critical event, allowing binding of Src family kinases and activation of signal transduction pathways |
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Download this section (compressed HTML)Q: Does Capsaspora FAK localise to the integrin beta2/vinculin patches in adherent-stage filopodia, and is it activated (Tyr397-equivalent autophosphorylation) on fibronectin-coated substrate? This would show whether FAK acts at adhesions before animals.
Q: Choanoflagellates lack canonical FAK, and M. brevicollis has only a FAK-related kinase domain. Was FAK lost in choanoflagellates together with integrins and the IPP complex, and does the FAK-related kinase domain retain any adhesion-linked role?
Q: Which partner-specific interfaces (FAT-paxillin LD motifs, FAT-talin, FERM-integrin, pTyr397-Src SH2) are conserved in Capsaspora FAK and its adhesome partners? Which arose in animals?
Q: Is the JUN kinase binding annotation from PMID:10925297 a JAK/JNK mix-up? The abstract describes an indirect Jak2-FAK association via STAT3.
Q: GO has no MF term for binding of paxillin-family LD motifs, which is the main focal adhesion targeting mechanism of FAK, Pyk2 and related proteins. Would such a term be useful?
Experiment: Generate a FAK knockout or a kinase-dead knock-in in Capsaspora owczarzaki and measure substrate adhesion, filopodial integrin patch formation and aggregation, to test whether FAK is required for integrin adhesion in a unicellular holozoan.
Experiment: Express recombinant Capsaspora FAK and test Tyr397-equivalent autophosphorylation, binding of Capsaspora Src SH2, and FAT binding to Capsaspora paxillin LD motifs, alongside human FAK.
Experiment: Phosphoproteomics of human FAK-null cells rescued with wild-type, kinase-dead or Y397F FAK, to separate the catalytic and scaffolding contributions to adhesion turnover.
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