FGFR1

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0000165 MAPK cascade	TAS PMID:10748122 A novel type I fibroblast growth factor receptor activates m...	MODIFY	Summary: FGFR1 activates ERK/MAPK signalling through FRS2-GRB2-SOS-RAS; the receptor is upstream of, not a component of, the MAP kinase phosphorelay itself. Reason: The receptor does not perform any step of the MAPK three-kinase phosphorelay; it initiates the cascade via FRS2/GRB2/SOS. The cited paper shows ligand-induced MAPK activation through FGFR1 (and a splice variant), which is better captured by positive regulation of MAPK cascade (GO:0043410), a term already carried by FGFR1 via IBA and experimental evidence. Proposed replacements: positive regulation of MAPK cascade Supporting Evidence: PMID:10748122 FGF-1, FGF-2, and FGF-4 enhanced mitogen-activated protein kinase (MAPK) activity, increased steady-state c-fos mRNA levels, and stimulated proliferation through either receptor, whereas KGF was without effect. file:human/FGFR1/FGFR1-uniprot.txt Phosphorylation of FRS2 triggers recruitment of GRB2, GAB1, PIK3R1 and SOS1, and mediates activation of RAS, MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway.
GO:0001501 skeletal system development	TAS PMID:7874169 A common mutation in the fibroblast growth factor receptor 1...	KEEP AS NON CORE	Summary: Gain-of-function FGFR1 P252R causes Pfeiffer syndrome (craniosynostosis, broad thumbs/toes), and FGFR1 variants cause osteoglophonic dysplasia, supporting a role in skeletal development. Reason: Human genetics supports involvement of FGFR1 signalling in skeletal (especially craniofacial) development, but this is a developmental outcome of the core receptor activity rather than a core function per se. Supporting Evidence: PMID:7874169 Here we present evidence that mutations in the fibroblast growth factor receptor-1 (FGFR1) gene, which maps to 8p, cause one form of familial Pfeiffer syndrome. PMID:15863030 A variety of human skeletal dysplasias have been linked to specific point mutations in FGFR1, FGFR2 and FGFR3 leading to severe impairment in cranial, digital and skeletal development.
GO:0001764 neuron migration	TAS PMID:15863030 Cellular signaling by fibroblast growth factor receptors.	KEEP AS NON CORE	Summary: FGFR1 signalling is implicated in migration of neuronal cells, notably GnRH neurons (loss-of-function FGFR1 causes Kallmann syndrome) and anosmin-1-modulated chemotaxis of neuronal cells. Reason: The cited review (PMID:15863030) supports cell migration as an FGFR output generally. Kallmann syndrome genetics (PMID:12627230) and anosmin-1/FGFR1 chemotaxis data (PMID:19696444) support a context-specific role in neuronal migration. This is a downstream developmental role, not a core function. Supporting Evidence: PMID:15863030 A variety of signaling proteins are phosphorylated in response to FGF stimulation including Shc, phospholipase-Cgamma, STAT1, Gab1 and FRS2alpha leading to stimulation of intracellular signaling pathways that control cell proliferation, cell differentiation, cell migration, cell survival and cell shape. PMID:12627230 We establish here that loss-of-function mutations in FGFR1 underlie KAL2 whereas a gain-of-function mutation in FGFR1 has been shown to cause a form of craniosynostosis. PMID:19696444 anosmin-1 was shown to induce opposing effects during chemotaxis of human neuronal cells.
GO:0001837 epithelial to mesenchymal transition	IMP PMID:26451614 MiR-573 inhibits prostate cancer metastasis by regulating ep...	KEEP AS NON CORE	Summary: In prostate cancer cells, FGFR1 knockdown phenocopies miR-573 effects on invasion and TGF-beta1-induced EMT. Reason: Loss-of-function evidence in a cancer cell line model; FGFR1 signalling promotes EMT in this context, but this is a context-dependent cellular outcome of receptor signalling rather than a core function. Supporting Evidence: PMID:26451614 Knockdown of FGFR1 phenocopies the effects of miR-573 expression on PCa cell invasion, whereas overexpression of FGFR1 partially attenuates the functions of miR-573.
GO:0004672 protein kinase activity	IEA GO_REF:0000002	ACCEPT	Summary: InterPro-based mapping of the tyrosine kinase domain to protein kinase activity. Reason: Correct but general; FGFR1 is an experimentally established protein tyrosine kinase (EC 2.7.10.1). Broader IEA terms are acceptable; the more specific transmembrane receptor protein tyrosine kinase / FGFR activity terms are also present. Supporting Evidence: file:human/FGFR1/FGFR1-uniprot.txt Reaction=L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+)
GO:0004713 protein tyrosine kinase activity	EXP PMID:1379697 Point mutation of an FGF receptor abolishes phosphatidylinos...	ACCEPT	Summary: Tyrosine kinase activity of FGFR1: the Y766F receptor still autophosphorylates and phosphorylates cellular proteins. Reason: Direct experimental evidence of FGFR1 catalytic tyrosine kinase activity; core function. Supporting Evidence: PMID:1379697 However, the mutant receptor phosphorylated itself and several other cellular proteins, and it mediated mitogenesis in response to FGF.
GO:0004713 protein tyrosine kinase activity	EXP PMID:15117958 90-kDa ribosomal S6 kinase is a direct target for the nuclea...	ACCEPT	Summary: Nuclear FGFR1 kinase activity is needed to stimulate RSK1; kinase-inactive K514A FGFR1 binds but fails to activate RSK1. Reason: Supports catalytic dependence of FGFR1 function on its tyrosine kinase activity; consistent with the core kinase function. Supporting Evidence: PMID:15117958 Kinase inactive FGFR1 (K514A) bound effectively to nuclear RSK1, but it failed to stimulate RSK1. Thus, active FGFR1 kinase regulates the functions of nuclear RSK1.
GO:0004713 protein tyrosine kinase activity	EXP PMID:18480409 Ubiquitination of fibroblast growth factor receptor 1 is req...	ACCEPT	Summary: Lysine-to-arginine multilysine FGFR1 mutants retain tyrosine kinase activity (receptor autophosphorylation assays). Reason: Experimental assay of FGFR1 tyrosine kinase activity; core function. Supporting Evidence: PMID:18480409 several multilysine FGFR1 mutants, where up to 26 of 29 lysines in the intracellular part of the receptor were mutated, retained tyrosine kinase activity.
GO:0004713 protein tyrosine kinase activity	EXP PMID:19224897 The precise sequence of FGF receptor autophosphorylation is ...	ACCEPT	Summary: Detailed kinetic analysis of FGFR1 kinase domain autophosphorylation and catalytic activation. Reason: Direct biochemical measurement of FGFR1 tyrosine kinase activity; core function. Supporting Evidence: PMID:19224897 First-stage autophosphorylation of an activation loop tyrosine leads to 50- to 100-fold stimulation of kinase activity and is followed by second-stage phosphorylation of three additional tyrosine residues, which are binding sites for signaling molecules.
GO:0004713 protein tyrosine kinase activity	EXP PMID:19665973 The selectivity of receptor tyrosine kinase signaling is con...	ACCEPT	Summary: Structure and biochemistry of activated FGFR1 kinase domain with PLC-gamma; FGFR1 phosphorylates PLC-gamma. Reason: Supports FGFR1 protein tyrosine kinase activity toward its substrate PLC-gamma; core function. Supporting Evidence: PMID:19665973 Here we describe the crystal structure of the activated tyrosine kinase domain of FGFR1 in complex with a phospholipase Cgamma fragment.
GO:0004713 protein tyrosine kinase activity	EXP PMID:20133753 Asymmetric receptor contact is required for tyrosine autopho...	ACCEPT	Summary: Asymmetric kinase-domain dimer required for trans-autophosphorylation of FGFR1 in cells. Reason: Direct evidence for FGFR1 tyrosine kinase catalytic activity (transphosphorylation); core function. Supporting Evidence: PMID:20133753 we present structural and biochemical experiments demonstrating that formation of an asymmetric dimer between activated FGFR1 kinase domains is required for transphosphorylation of FGFR1 in FGF-stimulated cells.
GO:0004713 protein tyrosine kinase activity	IDA PMID:8622701 Identification of six novel autophosphorylation sites on fib...	ACCEPT	Summary: Identification of FGFR1 autophosphorylation sites; Y653/Y654 required for kinase activation. Reason: Direct experimental evidence for FGFR1 protein tyrosine kinase activity; core function. Supporting Evidence: PMID:8622701 We demonstrate that autophosphorylation on tyrosines 653 and 654 is important for activation of tyrosine kinase activity of FGFR1 and is therefore essential for FGFR1-mediated biological responses.
GO:0004713 protein tyrosine kinase activity	IEA GO_REF:0000120	ACCEPT	Summary: Combined automated annotation of protein tyrosine kinase activity. Reason: Consistent with extensive experimental evidence of FGFR1 tyrosine kinase activity. Supporting Evidence: file:human/FGFR1/FGFR1-uniprot.txt Reaction=L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+)
GO:0004714 transmembrane receptor protein tyrosine kinase activity	IEA GO_REF:0000003	ACCEPT	Summary: EC 2.7.10.1 mapping to transmembrane receptor protein tyrosine kinase activity. Reason: FGFR1 is a single-pass transmembrane receptor tyrosine kinase; the EC mapping is correct. The more specific child term fibroblast growth factor receptor activity (GO:0005007) is the preferred core term. Supporting Evidence: file:human/FGFR1/FGFR1-uniprot.txt Tyrosine-protein kinase that acts as a cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of embryonic development, cell proliferation, differentiation and migration.
GO:0005007 fibroblast growth factor receptor activity	IBA GO_REF:0000033	ACCEPT	Summary: PAINT IBA: FGFR activity inherited in the deuterostome FGFR clade (FGFR1-4). Reason: Phylogenetically sound placement; FGFR1 is the prototypic FGF receptor with extensive direct evidence. Core function. Supporting Evidence: file:human/FGFR1/FGFR1-uniprot.txt Tyrosine-protein kinase that acts as a cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of embryonic development, cell proliferation, differentiation and migration.
GO:0005007 fibroblast growth factor receptor activity	IDA PMID:18480409 Ubiquitination of fibroblast growth factor receptor 1 is req...	ACCEPT	Summary: FGF1-stimulated FGFR1 activation, internalization and signalling measured in cells. Reason: Experimental evidence of ligand-activated FGFR1 receptor tyrosine kinase activity; core function. Supporting Evidence: PMID:18480409 The duration of FGFR1 signaling seems to be tightly regulated by receptor ubiquitination and subsequent sorting to the lysosomes for degradation. PMID:18480409 several multilysine FGFR1 mutants, where up to 26 of 29 lysines in the intracellular part of the receptor were mutated, retained tyrosine kinase activity.
GO:0005007 fibroblast growth factor receptor activity	IDA PMID:20133753 Asymmetric receptor contact is required for tyrosine autopho...	ACCEPT	Summary: FGF-stimulated trans-autophosphorylation of FGFR1 in cells. Reason: Ligand-dependent receptor kinase activation is the defining FGFR activity; core function. Supporting Evidence: PMID:20133753 we present structural and biochemical experiments demonstrating that formation of an asymmetric dimer between activated FGFR1 kinase domains is required for transphosphorylation of FGFR1 in FGF-stimulated cells.
GO:0005007 fibroblast growth factor receptor activity	IEA GO_REF:0000120	ACCEPT	Summary: Automated annotation of FGFR activity. Reason: Consistent with experimental evidence; core function. Supporting Evidence: file:human/FGFR1/FGFR1-uniprot.txt Tyrosine-protein kinase that acts as a cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of embryonic development, cell proliferation, differentiation and migration.
GO:0005007 fibroblast growth factor receptor activity	TAS PMID:10748122 A novel type I fibroblast growth factor receptor activates m...	ACCEPT	Summary: FGFR1 (and splice variant FGFR-1L) binds FGF1/FGF2 with high affinity and transduces mitogenic signals. Reason: Supports ligand binding coupled to signalling (receptor activity); core function. Supporting Evidence: PMID:10748122 FGF-1, FGF-2, and FGF-4 enhanced mitogen-activated protein kinase (MAPK) activity, increased steady-state c-fos mRNA levels, and stimulated proliferation through either receptor, whereas KGF was without effect.
GO:0005007 fibroblast growth factor receptor activity	TAS PMID:2167437 Diverse forms of a receptor for acidic and basic fibroblast ...	ACCEPT	Summary: Early cloning paper: two- and three-Ig-domain FGFR1 forms mediate responsiveness to acidic and basic FGF. Reason: Supports FGFR1 as a functional receptor for FGF1/FGF2; core function. Supporting Evidence: PMID:2167437 Both the three- and two-immunoglobulinlike-domain forms mediate biological responsiveness to acidic and basic FGF.
GO:0005515 protein binding	IPI PMID:10490103 Structural basis for FGF receptor dimerization and activatio...	MODIFY	Summary: Crystal structure of FGF2 bound to FGFR1 D2-D3 (IPI with FGF2). Reason: The reported interaction is between the FGFR1 ligand-binding ectodomain (D2-D3) and an FGF ligand; the informative molecular function is fibroblast growth factor binding (GO:0017134), which is part of the core receptor function. Proposed replacements: fibroblast growth factor binding Supporting Evidence: PMID:10490103 Two FGF2:FGFR1 complexes form a 2-fold symmetric dimer. Within each complex, FGF2 interacts extensively with D2 and D3 as well as with the linker between the two domains.
GO:0005515 protein binding	IPI PMID:10830168 Crystal structures of two FGF-FGFR complexes reveal the dete...	MODIFY	Summary: Crystal structures of FGF1-FGFR1 complex defining ligand-receptor specificity (IPI with FGF1). Reason: The reported interaction is between the FGFR1 ligand-binding ectodomain (D2-D3) and an FGF ligand; the informative molecular function is fibroblast growth factor binding (GO:0017134), which is part of the core receptor function. Proposed replacements: fibroblast growth factor binding Supporting Evidence: PMID:10830168 we have determined the crystal structures of FGF1 and FGF2 complexed with the ligand binding domains (immunoglobulin-like domains 2 [D2] and 3 [D3]) of FGF receptor 1 (FGFR1) and FGFR2, respectively.
GO:0005515 protein binding	IPI PMID:11030354 Crystal structure of a ternary FGF-FGFR-heparin complex reve...	MODIFY	Summary: Ternary FGF2-FGFR1-heparin crystal structure (IPI with FGF2). Reason: The reported interaction is between the FGFR1 ligand-binding ectodomain (D2-D3) and an FGF ligand; the informative molecular function is fibroblast growth factor binding (GO:0017134), which is part of the core receptor function. Heparin binding by FGFR1 is separately captured by GO:0008201. Proposed replacements: fibroblast growth factor binding Supporting Evidence: PMID:11030354 Within each 1:1 FGF:FGFR complex, heparin makes numerous contacts with both FGF and FGFR, thereby augmenting FGF-FGFR binding.
GO:0005515 protein binding	IPI PMID:11401320 FGF-1 and FGF-2 modulate the E-cadherin/catenin system in pa...	REMOVE	Summary: Co-immunoprecipitation of FGFR1 with E-cadherin / beta-catenin in pancreatic cancer cell lines after FGF stimulation. Reason: Generic 'protein binding' (GO:0005515) conveys no functional information. Per curation policy this is removed as uninformative; removal does not dispute the reported interaction itself. No specific molecular function of FGFR1 is established by this co-IP. Supporting Evidence: PMID:11401320 FGF stimulation produces phosphorylation of E-cadherin and beta-catenin on tyrosine residues, as well as increased E-cadherin localisation to the cytoplasmic membrane and association with FGFR1 demonstrable by coimmunoprecipitation.
GO:0005515 protein binding	IPI PMID:11401320 FGF-1 and FGF-2 modulate the E-cadherin/catenin system in pa...	REMOVE	Summary: Co-immunoprecipitation of FGFR1 with E-cadherin / beta-catenin in pancreatic cancer cell lines after FGF stimulation. Reason: Generic 'protein binding' (GO:0005515) conveys no functional information. Per curation policy this is removed as uninformative; removal does not dispute the reported interaction itself. No specific molecular function of FGFR1 is established by this co-IP. Supporting Evidence: PMID:11401320 FGF stimulation produces phosphorylation of E-cadherin and beta-catenin on tyrosine residues, as well as increased E-cadherin localisation to the cytoplasmic membrane and association with FGFR1 demonstrable by coimmunoprecipitation.
GO:0005515 protein binding	IPI PMID:14613973 Proline to arginine mutations in FGF receptors 1 and 3 resul...	MODIFY	Summary: SPR/crystallography of wild-type and Pfeiffer P252R FGFR1c binding to FGF1/FGF2 (IPI with FGF1, FGF2). Reason: The reported interaction is between the FGFR1 ligand-binding ectodomain (D2-D3) and an FGF ligand; the informative molecular function is fibroblast growth factor binding (GO:0017134), which is part of the core receptor function. Proposed replacements: fibroblast growth factor binding Supporting Evidence: PMID:14613973 Both Pro252Arg FGFR1c and Pro250Arg FGFR3c exhibit an enhancement in ligand binding in comparison to their respective wild-type receptors.
GO:0005515 protein binding	IPI PMID:14613973 Proline to arginine mutations in FGF receptors 1 and 3 resul...	MODIFY	Summary: SPR/crystallography of wild-type and Pfeiffer P252R FGFR1c binding to FGF1/FGF2 (IPI with FGF1, FGF2). Reason: The reported interaction is between the FGFR1 ligand-binding ectodomain (D2-D3) and an FGF ligand; the informative molecular function is fibroblast growth factor binding (GO:0017134), which is part of the core receptor function. Proposed replacements: fibroblast growth factor binding Supporting Evidence: PMID:14613973 Both Pro252Arg FGFR1c and Pro250Arg FGFR3c exhibit an enhancement in ligand binding in comparison to their respective wild-type receptors.
GO:0005515 protein binding	IPI PMID:1656221 A tyrosine-phosphorylated carboxy-terminal peptide of the fi...	MODIFY	Summary: Phosphorylated Tyr-766 C-terminal peptide of FGFR1 (Flg) binds the SH2 domain of PLC-gamma1. Reason: The partner is PLC-gamma1, recruited to autophosphorylated Tyr-766 (and a secondary kinase-domain site) of FGFR1 and then phosphorylated by it. 'Phospholipase binding' (GO:0043274) is more informative than generic protein binding and accurately records this receptor-effector docking interaction. Proposed replacements: phospholipase binding Supporting Evidence: PMID:1656221 Hence, Tyr-766 and its flanking sequences represent a major binding site in FGFR for PLC-gamma.
GO:0005515 protein binding	IPI PMID:18412956 Myeloproliferative disorder FOP-FGFR1 fusion kinase recruits...	REMOVE	Summary: Interaction of the oncogenic FOP-FGFR1 fusion kinase with p85 (PIK3R1) via Tyr-475 at the centrosome. Reason: Generic 'protein binding' (GO:0005515) conveys no functional information. Per curation policy this is removed as uninformative; removal does not dispute the reported interaction itself. The interaction was shown for a myeloproliferative FOP-FGFR1 fusion protein at the centrosome and does not inform wild-type receptor function. Supporting Evidence: PMID:18412956 We show that p85 interacts with tyrosine 475 of FOP-FGFR1, which is located in a YXXM consensus binding sequence for an SH2 domain of p85.
GO:0005515 protein binding	IPI PMID:18441324 Direct binding of integrin alphavbeta3 to FGF1 plays a role ...	MODIFY	Summary: FGF1 binding to FGFR1 D2D3 (SPR) in a study of integrin alphavbeta3-FGF1 cross-talk. Reason: The reported interaction is between the FGFR1 ligand-binding ectodomain (D2-D3) and an FGF ligand; the informative molecular function is fibroblast growth factor binding (GO:0017134), which is part of the core receptor function. Proposed replacements: fibroblast growth factor binding Supporting Evidence: PMID:18441324 We identified an FGF1 mutant (R50E) that was defective in integrin binding but still bound to heparin and FGFR.
GO:0005515 protein binding	IPI PMID:19665973 The selectivity of receptor tyrosine kinase signaling is con...	MODIFY	Summary: Crystal structure of activated FGFR1 kinase domain in complex with a PLC-gamma fragment (rat PLCG1). Reason: The partner is PLC-gamma1, recruited to autophosphorylated Tyr-766 (and a secondary kinase-domain site) of FGFR1 and then phosphorylated by it. 'Phospholipase binding' (GO:0043274) is more informative than generic protein binding and accurately records this receptor-effector docking interaction. Proposed replacements: phospholipase binding Supporting Evidence: PMID:19665973 Here we describe the crystal structure of the activated tyrosine kinase domain of FGFR1 in complex with a phospholipase Cgamma fragment.
GO:0005515 protein binding	IPI PMID:19696444 Novel mechanisms of fibroblast growth factor receptor 1 regu...	REMOVE	Summary: Anosmin-1 (ANOS1/KAL1) binds FGFR1 D2-D3 with high affinity and modulates FGF2-heparin-FGFR1 complex assembly. Reason: Generic 'protein binding' (GO:0005515) conveys no functional information. Per curation policy this is removed as uninformative; removal does not dispute the reported interaction itself. The interaction is biologically important (Kallmann syndrome genes) but there is no specific GO molecular function term for the receptor's role here; the modulatory relationship is best recorded on anosmin-1. Supporting Evidence: PMID:19696444 Here, we show that anosmin-1 directly binds to FGFR1 with high affinity.
GO:0005515 protein binding	IPI PMID:19966287 Isolated C-terminal tail of FGF23 alleviates hypophosphatemi...	MODIFY	Summary: FGFR1c ectodomain, Klotho and FGF23 form a ternary complex; FGF23 C-terminal tail binds the composite FGFR1c-Klotho interface (IPI with Klotho and FGF23). Reason: The reported interaction is between the FGFR1 ligand-binding ectodomain (D2-D3) and an FGF ligand; the informative molecular function is fibroblast growth factor binding (GO:0017134), which is part of the core receptor function. This paper is key evidence for FGFR1c as the endocrine FGF23 receptor in a Klotho-dependent complex. Proposed replacements: fibroblast growth factor binding Supporting Evidence: PMID:19966287 Here, we show that the soluble ectodomains of FGFR1c and Klotho are sufficient to form a ternary complex with FGF23 in vitro. PMID:19966287 Fibroblast growth factor (FGF) 23 inhibits renal phosphate reabsorption by activating FGF receptor (FGFR) 1c in a Klotho-dependent fashion. file:human/FGFR1/FGFR1-deep-research-falcon.md The FGFR1c isoform is a receptor for the endocrine hormone FGF23, which regulates phosphate homeostasis in the kidney
GO:0005515 protein binding	IPI PMID:19966287 Isolated C-terminal tail of FGF23 alleviates hypophosphatemi...	MODIFY	Summary: FGFR1c ectodomain, Klotho and FGF23 form a ternary complex; FGF23 C-terminal tail binds the composite FGFR1c-Klotho interface (IPI with Klotho and FGF23). Reason: The reported interaction is between the FGFR1 ligand-binding ectodomain (D2-D3) and an FGF ligand; the informative molecular function is fibroblast growth factor binding (GO:0017134), which is part of the core receptor function. This paper is key evidence for FGFR1c as the endocrine FGF23 receptor in a Klotho-dependent complex. Proposed replacements: fibroblast growth factor binding Supporting Evidence: PMID:19966287 Here, we show that the soluble ectodomains of FGFR1c and Klotho are sufficient to form a ternary complex with FGF23 in vitro. PMID:19966287 Fibroblast growth factor (FGF) 23 inhibits renal phosphate reabsorption by activating FGF receptor (FGFR) 1c in a Klotho-dependent fashion. file:human/FGFR1/FGFR1-deep-research-falcon.md The FGFR1c isoform is a receptor for the endocrine hormone FGF23, which regulates phosphate homeostasis in the kidney
GO:0005515 protein binding	IPI PMID:20932831 Grb14 inhibits FGF receptor signaling through the regulation...	REMOVE	Summary: GRB14 is recruited to pY766 of FGFR1 in a trimeric complex with PLC-gamma (BRET, Xenopus oocytes). Reason: Generic 'protein binding' (GO:0005515) conveys no functional information. Per curation policy this is removed as uninformative; removal does not dispute the reported interaction itself. GRB14 and PLC-gamma dock on FGFR1 pY766; the receptor's role is as phosphorylated docking site, already implicit in its kinase/receptor activity. Supporting Evidence: PMID:20932831 We showed that Grb14 was recruited to FGFR1 into a trimeric complex containing also phospholipase C gamma (PLCγ).
GO:0005515 protein binding	IPI PMID:20932831 Grb14 inhibits FGF receptor signaling through the regulation...	REMOVE	Summary: GRB14 is recruited to pY766 of FGFR1 in a trimeric complex with PLC-gamma (BRET, Xenopus oocytes). Reason: Generic 'protein binding' (GO:0005515) conveys no functional information. Per curation policy this is removed as uninformative; removal does not dispute the reported interaction itself. GRB14 and PLC-gamma dock on FGFR1 pY766; the receptor's role is as phosphorylated docking site, already implicit in its kinase/receptor activity. Supporting Evidence: PMID:20932831 We showed that Grb14 was recruited to FGFR1 into a trimeric complex containing also phospholipase C gamma (PLCγ).
GO:0005515 protein binding	IPI PMID:21765395 Nedd4-1 binds and ubiquitylates activated FGFR1 to control i...	REMOVE	Summary: NEDD4-1 binds activated FGFR1 via a non-canonical motif and ubiquitylates it; FRS2 interaction also reported. Reason: Generic 'protein binding' (GO:0005515) conveys no functional information. Per curation policy this is removed as uninformative; removal does not dispute the reported interaction itself. These are regulatory (ubiquitin ligase) and adaptor interactions of the receptor; the NEDD4-1 interaction could alternatively be recorded as ubiquitin protein ligase binding, but this adds little to the functional description of FGFR1. Supporting Evidence: PMID:21765395 Nedd4-1 binds directly to and ubiquitylates activated FGFR1, by interacting primarily via its WW3 domain with a novel non-canonical sequence (non-PY motif) on FGFR1.
GO:0005515 protein binding	IPI PMID:21765395 Nedd4-1 binds and ubiquitylates activated FGFR1 to control i...	REMOVE	Summary: NEDD4-1 binds activated FGFR1 via a non-canonical motif and ubiquitylates it; FRS2 interaction also reported. Reason: Generic 'protein binding' (GO:0005515) conveys no functional information. Per curation policy this is removed as uninformative; removal does not dispute the reported interaction itself. These are regulatory (ubiquitin ligase) and adaptor interactions of the receptor; the NEDD4-1 interaction could alternatively be recorded as ubiquitin protein ligase binding, but this adds little to the functional description of FGFR1. Supporting Evidence: PMID:21765395 Nedd4-1 binds directly to and ubiquitylates activated FGFR1, by interacting primarily via its WW3 domain with a novel non-canonical sequence (non-PY motif) on FGFR1.
GO:0005515 protein binding	IPI PMID:22035699 Fibroblast growth factor receptor 1- 5-hydroxytryptamine 1A ...	REMOVE	Summary: FGFR1-5-HT1A heteroreceptor complexes detected by BRET, co-IP and PLA in hippocampus. Reason: Generic 'protein binding' (GO:0005515) conveys no functional information. Per curation policy this is removed as uninformative; removal does not dispute the reported interaction itself. The heteroreceptor relationship is separately captured by the receptor-receptor interaction annotation (GO:0090722). Supporting Evidence: PMID:22035699 Using bioluminescence resonance energy transfer analysis, fibroblast growth factor receptor 1 (FGFR1)-5-hydroxytryptamine 1A (5-HT1A) receptor complexes have been demonstrated and their specificity and agonist modulation characterized.
GO:0005515 protein binding	IPI PMID:22751148 The F-BAR protein NOSTRIN participates in FGF signal transdu...	REMOVE	Summary: NOSTRIN assembles a signalling complex containing FGFR1, Rac1 and Sos1 in endothelial cells. Reason: Generic 'protein binding' (GO:0005515) conveys no functional information. Per curation policy this is removed as uninformative; removal does not dispute the reported interaction itself. No specific molecular function of FGFR1 is established by this interaction. Supporting Evidence: PMID:22751148 We propose a novel regulatory circuit, in which NOSTRIN assembles a signalling complex containing FGFR1, Rac1 and Sos1 thereby facilitating the activation of Rac1 in endothelial cells during developmental angiogenesis.
GO:0005515 protein binding	IPI PMID:22939624 Quantitative analysis of HSP90-client interactions reveals p...	REMOVE	Summary: Systematic screen of HSP90/CDC37 client kinases (FGFR1 as HSP90 client). Reason: Generic 'protein binding' (GO:0005515) conveys no functional information. Per curation policy this is removed as uninformative; removal does not dispute the reported interaction itself. Chaperone-client association from a high-throughput survey; not a function of FGFR1. Supporting Evidence: PMID:22939624 We systematically and quantitatively surveyed most human kinases, transcription factors, and E3 ligases for interaction with HSP90 and its cochaperone CDC37.
GO:0005515 protein binding	IPI PMID:23063561 Structural and functional integration of the PLCγ interactio...	MODIFY	Summary: PLC-gamma1 nSH2/cSH2 domains mediate binding to and phosphorylation by activated FGFR1. Reason: The partner is PLC-gamma1, recruited to autophosphorylated Tyr-766 (and a secondary kinase-domain site) of FGFR1 and then phosphorylated by it. 'Phospholipase binding' (GO:0043274) is more informative than generic protein binding and accurately records this receptor-effector docking interaction. Proposed replacements: phospholipase binding Supporting Evidence: PMID:23063561 In the context of fibroblast growth-factor receptor signaling, the coordinated involvement of nSH2 and cSH2 domains mediates efficient phosphorylation of PLCγ1 resulting in the interruption of an autoinhibitory interface by direct competition and, independently, dissociation of PLCγ1 from the receptor.
GO:0005515 protein binding	IPI PMID:23597563 Molecular mechanism of SSR128129E, an extracellularly acting...	MODIFY	Summary: FGF2-FGFR1 binding is not competed by the allosteric extracellular inhibitor SSR128129E. Reason: The reported interaction is between the FGFR1 ligand-binding ectodomain (D2-D3) and an FGF ligand; the informative molecular function is fibroblast growth factor binding (GO:0017134), which is part of the core receptor function. Proposed replacements: fibroblast growth factor binding Supporting Evidence: PMID:23597563 SSR does not compete with FGF for binding to FGFR but inhibits FGF-induced signaling linked to FGFR internalization in an allosteric manner
GO:0005515 protein binding	IPI PMID:24157794 Dynamic modulation of FGFR1-5-HT1A heteroreceptor complexes....	REMOVE	Summary: FGFR1-5-HT1A heteroreceptor complexes recruit beta-arrestin2 (BRET). Reason: Generic 'protein binding' (GO:0005515) conveys no functional information. Per curation policy this is removed as uninformative; removal does not dispute the reported interaction itself. No specific FGFR1 molecular function is established by this interaction. Supporting Evidence: PMID:24157794 Taken together, the participation of 5-HT1A and FGFR1 homodimers and recruitment of β-arrestin2 was demonstrated in the FGFR1-5-HT1A heteroreceptor complexes upon agonist treatments.
GO:0005515 protein binding	IPI PMID:25241761 Using an in situ proximity ligation assay to systematically ...	REMOVE	Summary: High-throughput in situ proximity ligation assay of endogenous PPIs in HeLa cells. Reason: Generic 'protein binding' (GO:0005515) conveys no functional information. Per curation policy this is removed as uninformative; removal does not dispute the reported interaction itself. Proximity in a high-throughput PLA screen; no specific molecular function inferred. Supporting Evidence: PMID:25241761 employed a highly sensitive and specific technique, an in situ proximity ligation assay, to investigate 1204 endogenous PPIs in HeLa cells, and 557 PPIs of them tested positive.
GO:0005515 protein binding	IPI PMID:25241761 Using an in situ proximity ligation assay to systematically ...	REMOVE	Summary: High-throughput in situ proximity ligation assay of endogenous PPIs in HeLa cells. Reason: Generic 'protein binding' (GO:0005515) conveys no functional information. Per curation policy this is removed as uninformative; removal does not dispute the reported interaction itself. Proximity in a high-throughput PLA screen; no specific molecular function inferred. Supporting Evidence: PMID:25241761 employed a highly sensitive and specific technique, an in situ proximity ligation assay, to investigate 1204 endogenous PPIs in HeLa cells, and 557 PPIs of them tested positive.
GO:0005515 protein binding	IPI PMID:25241761 Using an in situ proximity ligation assay to systematically ...	REMOVE	Summary: High-throughput in situ proximity ligation assay of endogenous PPIs in HeLa cells. Reason: Generic 'protein binding' (GO:0005515) conveys no functional information. Per curation policy this is removed as uninformative; removal does not dispute the reported interaction itself. Proximity in a high-throughput PLA screen; no specific molecular function inferred. Supporting Evidence: PMID:25241761 employed a highly sensitive and specific technique, an in situ proximity ligation assay, to investigate 1204 endogenous PPIs in HeLa cells, and 557 PPIs of them tested positive.
GO:0005515 protein binding	IPI PMID:25241761 Using an in situ proximity ligation assay to systematically ...	REMOVE	Summary: High-throughput in situ proximity ligation assay of endogenous PPIs in HeLa cells. Reason: Generic 'protein binding' (GO:0005515) conveys no functional information. Per curation policy this is removed as uninformative; removal does not dispute the reported interaction itself. Proximity in a high-throughput PLA screen; no specific molecular function inferred. Supporting Evidence: PMID:25241761 employed a highly sensitive and specific technique, an in situ proximity ligation assay, to investigate 1204 endogenous PPIs in HeLa cells, and 557 PPIs of them tested positive.
GO:0005515 protein binding	IPI PMID:25241761 Using an in situ proximity ligation assay to systematically ...	REMOVE	Summary: High-throughput in situ proximity ligation assay of endogenous PPIs in HeLa cells. Reason: Generic 'protein binding' (GO:0005515) conveys no functional information. Per curation policy this is removed as uninformative; removal does not dispute the reported interaction itself. Proximity in a high-throughput PLA screen; no specific molecular function inferred. Supporting Evidence: PMID:25241761 employed a highly sensitive and specific technique, an in situ proximity ligation assay, to investigate 1204 endogenous PPIs in HeLa cells, and 557 PPIs of them tested positive.
GO:0005515 protein binding	IPI PMID:25485703 Evidence for the existence of FGFR1-5-HT1A heteroreceptor co...	REMOVE	Summary: FGFR1-5-HT1A heteroreceptor complexes in midbrain raphe (PLA, FRET). Reason: Generic 'protein binding' (GO:0005515) conveys no functional information. Per curation policy this is removed as uninformative; removal does not dispute the reported interaction itself. Heteroreceptor relationship is captured by GO:0090722 where retained. Supporting Evidence: PMID:25485703 evidence for the existence of FGFR1-5-HT1A heteroreceptor complexes were obtained in the dorsal and median raphe nuclei of the Sprague-Dawley rat.
GO:0005515 protein binding	IPI PMID:26267536 Long-Pentraxin 3 Derivative as a Small-Molecule FGF Trap for...	MODIFY	Summary: PTX3-derived FGF trap study; FGF2-FGFR1 binding assayed and competed. Reason: The reported interaction is between the FGFR1 ligand-binding ectodomain (D2-D3) and an FGF ligand; the informative molecular function is fibroblast growth factor binding (GO:0017134), which is part of the core receptor function. Proposed replacements: fibroblast growth factor binding Supporting Evidence: PMID:26267536 The soluble pattern recognition receptor long-pentraxin 3 (PTX3) acts as a multi-FGF antagonist.
GO:0005515 protein binding	IPI PMID:31980649 Extensive rewiring of the EGFR network in colorectal cancer ...	REMOVE	Summary: Interaction proteomics of EGFR network in KRAS-mutant colorectal cells (FGFR1-HSP90). Reason: Generic 'protein binding' (GO:0005515) conveys no functional information. Per curation policy this is removed as uninformative; removal does not dispute the reported interaction itself. High-throughput interactome data; chaperone association does not inform FGFR1 function. Supporting Evidence: PMID:31980649 Protein-protein-interaction networks (PPINs) organize fundamental biological
GO:0005515 protein binding	IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling...	REMOVE	Summary: BioPlex 3.0 affinity-purification mass spectrometry interactome (FGFR1 with FGF1, FGFR2). Reason: Generic 'protein binding' (GO:0005515) conveys no functional information. Per curation policy this is removed as uninformative; removal does not dispute the reported interaction itself. High-throughput AP-MS; FGF binding is independently captured with GO:0017134 from low-throughput structural and binding studies. Supporting Evidence: PMID:33961781 Through affinity-purification mass spectrometry, we have created two proteome-scale, cell-line-specific interaction networks.
GO:0005515 protein binding	IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling...	REMOVE	Summary: BioPlex 3.0 affinity-purification mass spectrometry interactome (FGFR1 with FGF1, FGFR2). Reason: Generic 'protein binding' (GO:0005515) conveys no functional information. Per curation policy this is removed as uninformative; removal does not dispute the reported interaction itself. High-throughput AP-MS; FGF binding is independently captured with GO:0017134 from low-throughput structural and binding studies. Supporting Evidence: PMID:33961781 Through affinity-purification mass spectrometry, we have created two proteome-scale, cell-line-specific interaction networks.
GO:0005515 protein binding	IPI PMID:35384245 Physical and functional interactome atlas of human receptor ...	REMOVE	Summary: RTK interactome atlas (AP-MS, BioID and in vitro kinase assays) including FGFR1 partners such as HSP90, FGF2, PLCG1, FGFR2, FGFR3, PIK3R1, CTNNB1, FRS2. Reason: Generic 'protein binding' (GO:0005515) conveys no functional information. Per curation policy this is removed as uninformative; removal does not dispute the reported interaction itself. High-throughput interactome; informative functions (FGF binding, kinase activity toward PLCG1/FRS2) are captured elsewhere by specific terms. Supporting Evidence: PMID:35384245 We use affinity purification coupled to mass spectrometry (AP-MS) to characterize stable binding partners and RTK-protein complexes, proximity-dependent biotin identification (BioID) to identify transient and proximal interactions, and an in vitro kinase assay to identify RTK substrates.
GO:0005515 protein binding	IPI PMID:35384245 Physical and functional interactome atlas of human receptor ...	REMOVE	Summary: RTK interactome atlas (AP-MS, BioID and in vitro kinase assays) including FGFR1 partners such as HSP90, FGF2, PLCG1, FGFR2, FGFR3, PIK3R1, CTNNB1, FRS2. Reason: Generic 'protein binding' (GO:0005515) conveys no functional information. Per curation policy this is removed as uninformative; removal does not dispute the reported interaction itself. High-throughput interactome; informative functions (FGF binding, kinase activity toward PLCG1/FRS2) are captured elsewhere by specific terms. Supporting Evidence: PMID:35384245 We use affinity purification coupled to mass spectrometry (AP-MS) to characterize stable binding partners and RTK-protein complexes, proximity-dependent biotin identification (BioID) to identify transient and proximal interactions, and an in vitro kinase assay to identify RTK substrates.
GO:0005515 protein binding	IPI PMID:35384245 Physical and functional interactome atlas of human receptor ...	REMOVE	Summary: RTK interactome atlas (AP-MS, BioID and in vitro kinase assays) including FGFR1 partners such as HSP90, FGF2, PLCG1, FGFR2, FGFR3, PIK3R1, CTNNB1, FRS2. Reason: Generic 'protein binding' (GO:0005515) conveys no functional information. Per curation policy this is removed as uninformative; removal does not dispute the reported interaction itself. High-throughput interactome; informative functions (FGF binding, kinase activity toward PLCG1/FRS2) are captured elsewhere by specific terms. Supporting Evidence: PMID:35384245 We use affinity purification coupled to mass spectrometry (AP-MS) to characterize stable binding partners and RTK-protein complexes, proximity-dependent biotin identification (BioID) to identify transient and proximal interactions, and an in vitro kinase assay to identify RTK substrates.
GO:0005515 protein binding	IPI PMID:35384245 Physical and functional interactome atlas of human receptor ...	REMOVE	Summary: RTK interactome atlas (AP-MS, BioID and in vitro kinase assays) including FGFR1 partners such as HSP90, FGF2, PLCG1, FGFR2, FGFR3, PIK3R1, CTNNB1, FRS2. Reason: Generic 'protein binding' (GO:0005515) conveys no functional information. Per curation policy this is removed as uninformative; removal does not dispute the reported interaction itself. High-throughput interactome; informative functions (FGF binding, kinase activity toward PLCG1/FRS2) are captured elsewhere by specific terms. Supporting Evidence: PMID:35384245 We use affinity purification coupled to mass spectrometry (AP-MS) to characterize stable binding partners and RTK-protein complexes, proximity-dependent biotin identification (BioID) to identify transient and proximal interactions, and an in vitro kinase assay to identify RTK substrates.
GO:0005515 protein binding	IPI PMID:35384245 Physical and functional interactome atlas of human receptor ...	REMOVE	Summary: RTK interactome atlas (AP-MS, BioID and in vitro kinase assays) including FGFR1 partners such as HSP90, FGF2, PLCG1, FGFR2, FGFR3, PIK3R1, CTNNB1, FRS2. Reason: Generic 'protein binding' (GO:0005515) conveys no functional information. Per curation policy this is removed as uninformative; removal does not dispute the reported interaction itself. High-throughput interactome; informative functions (FGF binding, kinase activity toward PLCG1/FRS2) are captured elsewhere by specific terms. Supporting Evidence: PMID:35384245 We use affinity purification coupled to mass spectrometry (AP-MS) to characterize stable binding partners and RTK-protein complexes, proximity-dependent biotin identification (BioID) to identify transient and proximal interactions, and an in vitro kinase assay to identify RTK substrates.
GO:0005515 protein binding	IPI PMID:35384245 Physical and functional interactome atlas of human receptor ...	REMOVE	Summary: RTK interactome atlas (AP-MS, BioID and in vitro kinase assays) including FGFR1 partners such as HSP90, FGF2, PLCG1, FGFR2, FGFR3, PIK3R1, CTNNB1, FRS2. Reason: Generic 'protein binding' (GO:0005515) conveys no functional information. Per curation policy this is removed as uninformative; removal does not dispute the reported interaction itself. High-throughput interactome; informative functions (FGF binding, kinase activity toward PLCG1/FRS2) are captured elsewhere by specific terms. Supporting Evidence: PMID:35384245 We use affinity purification coupled to mass spectrometry (AP-MS) to characterize stable binding partners and RTK-protein complexes, proximity-dependent biotin identification (BioID) to identify transient and proximal interactions, and an in vitro kinase assay to identify RTK substrates.
GO:0005515 protein binding	IPI PMID:35384245 Physical and functional interactome atlas of human receptor ...	REMOVE	Summary: RTK interactome atlas (AP-MS, BioID and in vitro kinase assays) including FGFR1 partners such as HSP90, FGF2, PLCG1, FGFR2, FGFR3, PIK3R1, CTNNB1, FRS2. Reason: Generic 'protein binding' (GO:0005515) conveys no functional information. Per curation policy this is removed as uninformative; removal does not dispute the reported interaction itself. High-throughput interactome; informative functions (FGF binding, kinase activity toward PLCG1/FRS2) are captured elsewhere by specific terms. Supporting Evidence: PMID:35384245 We use affinity purification coupled to mass spectrometry (AP-MS) to characterize stable binding partners and RTK-protein complexes, proximity-dependent biotin identification (BioID) to identify transient and proximal interactions, and an in vitro kinase assay to identify RTK substrates.
GO:0005515 protein binding	IPI PMID:35384245 Physical and functional interactome atlas of human receptor ...	REMOVE	Summary: RTK interactome atlas (AP-MS, BioID and in vitro kinase assays) including FGFR1 partners such as HSP90, FGF2, PLCG1, FGFR2, FGFR3, PIK3R1, CTNNB1, FRS2. Reason: Generic 'protein binding' (GO:0005515) conveys no functional information. Per curation policy this is removed as uninformative; removal does not dispute the reported interaction itself. High-throughput interactome; informative functions (FGF binding, kinase activity toward PLCG1/FRS2) are captured elsewhere by specific terms. Supporting Evidence: PMID:35384245 We use affinity purification coupled to mass spectrometry (AP-MS) to characterize stable binding partners and RTK-protein complexes, proximity-dependent biotin identification (BioID) to identify transient and proximal interactions, and an in vitro kinase assay to identify RTK substrates.
GO:0005515 protein binding	IPI PMID:8321198 Control of fibroblast growth factor receptor kinase signal t...	MODIFY	Summary: Heterodimers of FGFR1 splice variants: PLC-gamma1 associates with phosphorylated receptor dimers. Reason: The partner is PLC-gamma1, recruited to autophosphorylated Tyr-766 (and a secondary kinase-domain site) of FGFR1 and then phosphorylated by it. 'Phospholipase binding' (GO:0043274) is more informative than generic protein binding and accurately records this receptor-effector docking interaction. Proposed replacements: phospholipase binding Supporting Evidence: PMID:8321198 The SH2 domain substrate, phospholipase C gamma 1 (PLC gamma 1), associated with the phosphorylated type 1-type 2 heterodimers but was phosphorylated only in preparations containing the type 1 kinase homodimer.
GO:0005515 protein binding	IPI PMID:8753773 Association of CD24 with the kinase c-fgr in a small cell lu...	REMOVE	Summary: Paper reports association of CD24 with the Src-family kinases c-fgr (FGR) and lyn; the abstract does not mention FGFR1. Reason: Generic 'protein binding' is uninformative and removed per curation policy. In addition, the cached abstract explicitly describes CD24 association with c-fgr and lyn, not FGFR1, so the attribution to FGFR1 may reflect confusion between FGR and FGFR1; this cannot be confirmed without full text, but removal is justified on the uninformative-term policy alone. Supporting Evidence: PMID:8753773 Western analysis of the precipitates showed an association of c-fgr with CD24 in SW2 cells and lyn in K562 cells.
GO:0005515 protein binding	IPI PMID:9660748 Novel recognition motif on fibroblast growth factor receptor...	REMOVE	Summary: A juxtamembrane segment of FGFR1 binds the PTB domain of FRS2/SNT-1 and SNT-2 directly. Reason: Generic 'protein binding' (GO:0005515) conveys no functional information. Per curation policy this is removed as uninformative; removal does not dispute the reported interaction itself. This constitutive receptor-docking interaction underlies FRS2 phosphorylation, which is captured by FGFR1 kinase activity; no receptor-side MF term adds information. Supporting Evidence: PMID:9660748 A juxtamembrane segment of FGFR-1 and the phosphotyrosine-binding domain of SNTs are both necessary and sufficient for interaction in yeast and in vitro, and FGFR-mediated SNT tyrosine phosphorylation in vivo requires these segments of receptor and SNT.
GO:0005524 ATP binding	IEA GO_REF:0000002	ACCEPT	Summary: InterPro mapping: ATP binding by the kinase domain. Reason: FGFR1 kinase domain binds ATP as phosphate donor; correct supporting MF. Supporting Evidence: file:human/FGFR1/FGFR1-uniprot.txt Reaction=L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+)
GO:0005576 extracellular region	NAS PMID:1652059 The human fibroblast growth factor receptor genes: a common ...	KEEP AS NON CORE	Summary: Alternative exon usage in Ig-domain III generates a putative secreted form of FGFR1. Reason: Secreted/soluble FGFR1 isoforms exist, but the principal functional form is the transmembrane receptor; NAS from gene-structure paper. Supporting Evidence: PMID:1652059 One of these alternatives encodes a sequence that is part of a secreted form of FGFR 1. The other two encode sequences that are likely part of transmembrane forms of FGFR 1.
GO:0005634 nucleus	IEA GO_REF:0000044	KEEP AS NON CORE	Summary: UniProt subcellular location mapping: nucleus. Reason: Nuclear FGFR1 is reported (e.g. interaction with nuclear RSK1, transcriptional regulation), but this is a non-canonical pool; the receptor acts principally at the plasma membrane. Supporting Evidence: file:human/FGFR1/FGFR1-uniprot.txt After ligand binding, both receptor and ligand are rapidly internalized. Can translocate to the nucleus after internalization, or by translocation from the endoplasmic reticulum or Golgi apparatus to the cytosol, and from there to the nucleus. PMID:12141425 FGFR1 isoforms are also present in the nucleus in complex with various fibroblast growth factors where they function to regulate transcription of target genes.
GO:0005829 cytosol	IEA GO_REF:0000044	KEEP AS NON CORE	Summary: UniProt subcellular location mapping: cytosol. Reason: UniProt records cytosolic transit of FGFR1 en route to the nucleus. The cytoplasmic kinase domain faces the cytosol, but a cytosolic pool of the full-length receptor is a minor, non-canonical localization. Supporting Evidence: file:human/FGFR1/FGFR1-uniprot.txt After ligand binding, both receptor and ligand are rapidly internalized. Can translocate to the nucleus after internalization, or by translocation from the endoplasmic reticulum or Golgi apparatus to the cytosol, and from there to the nucleus.
GO:0005886 plasma membrane	IBA GO_REF:0000033	ACCEPT	Summary: PAINT IBA: plasma membrane localization of RTKs. Reason: FGFR1 is a single-pass type I plasma membrane receptor; core location. Supporting Evidence: file:human/FGFR1/FGFR1-uniprot.txt Cell membrane; Single-pass type I membrane protein. Nucleus. Cytoplasm, cytosol. Cytoplasmic vesicle. file:human/FGFR1/FGFR1-deep-research-falcon.md The plasma membrane is the primary functional location of FGFR1, where the receptor binds extracellular FGF ligands and initiates canonical tyrosine kinase signaling
GO:0005886 plasma membrane	IDA PMID:18480409 Ubiquitination of fibroblast growth factor receptor 1 is req...	ACCEPT	Summary: Cell-surface FGFR1 binding, internalization and sorting studied in cells. Reason: Experimental support for plasma membrane localization; core location. Supporting Evidence: PMID:18480409 The duration of FGFR1 signaling seems to be tightly regulated by receptor ubiquitination and subsequent sorting to the lysosomes for degradation.
GO:0005886 plasma membrane	IEA GO_REF:0000044	ACCEPT	Summary: UniProt subcellular location mapping: plasma membrane. Reason: Correct core location. Supporting Evidence: file:human/FGFR1/FGFR1-uniprot.txt Cell membrane; Single-pass type I membrane protein. Nucleus. Cytoplasm, cytosol. Cytoplasmic vesicle.
GO:0005886 plasma membrane	TAS PMID:10918587 Transformation and Stat activation by derivatives of FGFR1, ...	ACCEPT	Summary: Myristylated FGFR1 kinase derivatives targeted to the plasma membrane transform cells and activate STATs. Reason: Consistent with FGFR1 signalling from the plasma membrane; core location. Supporting Evidence: PMID:10918587 We show that the kinase domains of FGFR1, FGFR3, and FGFR4 containing the activation loop mutation, when targeted to the plasma membrane by a myristylation signal, can transform NIH3T3 cells and induce neurite outgrowth in PC12 cells.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-109699	ACCEPT	Summary: Reactome reaction places FGFR1 (wild type, mutant or fusion) at the plasma membrane. Reason: FGFR1 signalling reactions occur at the plasma membrane; consistent with extensive experimental evidence.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-1839094	ACCEPT	Summary: Reactome reaction places FGFR1 (wild type, mutant or fusion) at the plasma membrane. Reason: FGFR1 signalling reactions occur at the plasma membrane; consistent with extensive experimental evidence.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-1839098	ACCEPT	Summary: Reactome reaction places FGFR1 (wild type, mutant or fusion) at the plasma membrane. Reason: FGFR1 signalling reactions occur at the plasma membrane; consistent with extensive experimental evidence.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-1839100	ACCEPT	Summary: Reactome reaction places FGFR1 (wild type, mutant or fusion) at the plasma membrane. Reason: FGFR1 signalling reactions occur at the plasma membrane; consistent with extensive experimental evidence.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-190245	ACCEPT	Summary: Reactome reaction places FGFR1 (wild type, mutant or fusion) at the plasma membrane. Reason: FGFR1 signalling reactions occur at the plasma membrane; consistent with extensive experimental evidence.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-190256	ACCEPT	Summary: Reactome reaction places FGFR1 (wild type, mutant or fusion) at the plasma membrane. Reason: FGFR1 signalling reactions occur at the plasma membrane; consistent with extensive experimental evidence.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-190268	ACCEPT	Summary: Reactome reaction places FGFR1 (wild type, mutant or fusion) at the plasma membrane. Reason: FGFR1 signalling reactions occur at the plasma membrane; consistent with extensive experimental evidence.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-190427	ACCEPT	Summary: Reactome reaction places FGFR1 (wild type, mutant or fusion) at the plasma membrane. Reason: FGFR1 signalling reactions occur at the plasma membrane; consistent with extensive experimental evidence.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-190429	ACCEPT	Summary: Reactome reaction places FGFR1 (wild type, mutant or fusion) at the plasma membrane. Reason: FGFR1 signalling reactions occur at the plasma membrane; consistent with extensive experimental evidence.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-191062	ACCEPT	Summary: Reactome reaction places FGFR1 (wild type, mutant or fusion) at the plasma membrane. Reason: FGFR1 signalling reactions occur at the plasma membrane; consistent with extensive experimental evidence.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-1982065	ACCEPT	Summary: Reactome reaction places FGFR1 (wild type, mutant or fusion) at the plasma membrane. Reason: FGFR1 signalling reactions occur at the plasma membrane; consistent with extensive experimental evidence.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-1982066	ACCEPT	Summary: Reactome reaction places FGFR1 (wild type, mutant or fusion) at the plasma membrane. Reason: FGFR1 signalling reactions occur at the plasma membrane; consistent with extensive experimental evidence.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-2023451	ACCEPT	Summary: Reactome reaction places FGFR1 (wild type, mutant or fusion) at the plasma membrane. Reason: FGFR1 signalling reactions occur at the plasma membrane; consistent with extensive experimental evidence.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-2023455	ACCEPT	Summary: Reactome reaction places FGFR1 (wild type, mutant or fusion) at the plasma membrane. Reason: FGFR1 signalling reactions occur at the plasma membrane; consistent with extensive experimental evidence.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-2023456	ACCEPT	Summary: Reactome reaction places FGFR1 (wild type, mutant or fusion) at the plasma membrane. Reason: FGFR1 signalling reactions occur at the plasma membrane; consistent with extensive experimental evidence.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-2023460	ACCEPT	Summary: Reactome reaction places FGFR1 (wild type, mutant or fusion) at the plasma membrane. Reason: FGFR1 signalling reactions occur at the plasma membrane; consistent with extensive experimental evidence.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-2023462	ACCEPT	Summary: Reactome reaction places FGFR1 (wild type, mutant or fusion) at the plasma membrane. Reason: FGFR1 signalling reactions occur at the plasma membrane; consistent with extensive experimental evidence.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-2316434	ACCEPT	Summary: Reactome reaction places FGFR1 (wild type, mutant or fusion) at the plasma membrane. Reason: FGFR1 signalling reactions occur at the plasma membrane; consistent with extensive experimental evidence.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-2400009	ACCEPT	Summary: Reactome reaction places FGFR1 (wild type, mutant or fusion) at the plasma membrane. Reason: FGFR1 signalling reactions occur at the plasma membrane; consistent with extensive experimental evidence.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-437230	ACCEPT	Summary: Reactome reaction places FGFR1 (wild type, mutant or fusion) at the plasma membrane. Reason: FGFR1 signalling reactions occur at the plasma membrane; consistent with extensive experimental evidence.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-5654149	ACCEPT	Summary: Reactome reaction places FGFR1 (wild type, mutant or fusion) at the plasma membrane. Reason: FGFR1 signalling reactions occur at the plasma membrane; consistent with extensive experimental evidence.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-5654165	ACCEPT	Summary: Reactome reaction places FGFR1 (wild type, mutant or fusion) at the plasma membrane. Reason: FGFR1 signalling reactions occur at the plasma membrane; consistent with extensive experimental evidence.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-5654167	ACCEPT	Summary: Reactome reaction places FGFR1 (wild type, mutant or fusion) at the plasma membrane. Reason: FGFR1 signalling reactions occur at the plasma membrane; consistent with extensive experimental evidence.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-5654392	ACCEPT	Summary: Reactome reaction places FGFR1 (wild type, mutant or fusion) at the plasma membrane. Reason: FGFR1 signalling reactions occur at the plasma membrane; consistent with extensive experimental evidence.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-5654514	ACCEPT	Summary: Reactome reaction places FGFR1 (wild type, mutant or fusion) at the plasma membrane. Reason: FGFR1 signalling reactions occur at the plasma membrane; consistent with extensive experimental evidence.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-5654544	ACCEPT	Summary: Reactome reaction places FGFR1 (wild type, mutant or fusion) at the plasma membrane. Reason: FGFR1 signalling reactions occur at the plasma membrane; consistent with extensive experimental evidence.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-5654545	ACCEPT	Summary: Reactome reaction places FGFR1 (wild type, mutant or fusion) at the plasma membrane. Reason: FGFR1 signalling reactions occur at the plasma membrane; consistent with extensive experimental evidence.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-5654560	ACCEPT	Summary: Reactome reaction places FGFR1 (wild type, mutant or fusion) at the plasma membrane. Reason: FGFR1 signalling reactions occur at the plasma membrane; consistent with extensive experimental evidence.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-5654569	ACCEPT	Summary: Reactome reaction places FGFR1 (wild type, mutant or fusion) at the plasma membrane. Reason: FGFR1 signalling reactions occur at the plasma membrane; consistent with extensive experimental evidence.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-5654571	ACCEPT	Summary: Reactome reaction places FGFR1 (wild type, mutant or fusion) at the plasma membrane. Reason: FGFR1 signalling reactions occur at the plasma membrane; consistent with extensive experimental evidence.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-5654573	ACCEPT	Summary: Reactome reaction places FGFR1 (wild type, mutant or fusion) at the plasma membrane. Reason: FGFR1 signalling reactions occur at the plasma membrane; consistent with extensive experimental evidence.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-5654575	ACCEPT	Summary: Reactome reaction places FGFR1 (wild type, mutant or fusion) at the plasma membrane. Reason: FGFR1 signalling reactions occur at the plasma membrane; consistent with extensive experimental evidence.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-5654578	ACCEPT	Summary: Reactome reaction places FGFR1 (wild type, mutant or fusion) at the plasma membrane. Reason: FGFR1 signalling reactions occur at the plasma membrane; consistent with extensive experimental evidence.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-5654582	ACCEPT	Summary: Reactome reaction places FGFR1 (wild type, mutant or fusion) at the plasma membrane. Reason: FGFR1 signalling reactions occur at the plasma membrane; consistent with extensive experimental evidence.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-5654584	ACCEPT	Summary: Reactome reaction places FGFR1 (wild type, mutant or fusion) at the plasma membrane. Reason: FGFR1 signalling reactions occur at the plasma membrane; consistent with extensive experimental evidence.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-5654586	ACCEPT	Summary: Reactome reaction places FGFR1 (wild type, mutant or fusion) at the plasma membrane. Reason: FGFR1 signalling reactions occur at the plasma membrane; consistent with extensive experimental evidence.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-5654587	ACCEPT	Summary: Reactome reaction places FGFR1 (wild type, mutant or fusion) at the plasma membrane. Reason: FGFR1 signalling reactions occur at the plasma membrane; consistent with extensive experimental evidence.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-5654591	ACCEPT	Summary: Reactome reaction places FGFR1 (wild type, mutant or fusion) at the plasma membrane. Reason: FGFR1 signalling reactions occur at the plasma membrane; consistent with extensive experimental evidence.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-5654592	ACCEPT	Summary: Reactome reaction places FGFR1 (wild type, mutant or fusion) at the plasma membrane. Reason: FGFR1 signalling reactions occur at the plasma membrane; consistent with extensive experimental evidence.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-5654594	ACCEPT	Summary: Reactome reaction places FGFR1 (wild type, mutant or fusion) at the plasma membrane. Reason: FGFR1 signalling reactions occur at the plasma membrane; consistent with extensive experimental evidence.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-5654596	ACCEPT	Summary: Reactome reaction places FGFR1 (wild type, mutant or fusion) at the plasma membrane. Reason: FGFR1 signalling reactions occur at the plasma membrane; consistent with extensive experimental evidence.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-5654597	ACCEPT	Summary: Reactome reaction places FGFR1 (wild type, mutant or fusion) at the plasma membrane. Reason: FGFR1 signalling reactions occur at the plasma membrane; consistent with extensive experimental evidence.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-5654600	ACCEPT	Summary: Reactome reaction places FGFR1 (wild type, mutant or fusion) at the plasma membrane. Reason: FGFR1 signalling reactions occur at the plasma membrane; consistent with extensive experimental evidence.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-5654672	ACCEPT	Summary: Reactome reaction places FGFR1 (wild type, mutant or fusion) at the plasma membrane. Reason: FGFR1 signalling reactions occur at the plasma membrane; consistent with extensive experimental evidence.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-5654673	ACCEPT	Summary: Reactome reaction places FGFR1 (wild type, mutant or fusion) at the plasma membrane. Reason: FGFR1 signalling reactions occur at the plasma membrane; consistent with extensive experimental evidence.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-5654690	ACCEPT	Summary: Reactome reaction places FGFR1 (wild type, mutant or fusion) at the plasma membrane. Reason: FGFR1 signalling reactions occur at the plasma membrane; consistent with extensive experimental evidence.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-5654692	ACCEPT	Summary: Reactome reaction places FGFR1 (wild type, mutant or fusion) at the plasma membrane. Reason: FGFR1 signalling reactions occur at the plasma membrane; consistent with extensive experimental evidence.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-5655240	ACCEPT	Summary: Reactome reaction places FGFR1 (wild type, mutant or fusion) at the plasma membrane. Reason: FGFR1 signalling reactions occur at the plasma membrane; consistent with extensive experimental evidence.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-5655263	ACCEPT	Summary: Reactome reaction places FGFR1 (wild type, mutant or fusion) at the plasma membrane. Reason: FGFR1 signalling reactions occur at the plasma membrane; consistent with extensive experimental evidence.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-5655266	ACCEPT	Summary: Reactome reaction places FGFR1 (wild type, mutant or fusion) at the plasma membrane. Reason: FGFR1 signalling reactions occur at the plasma membrane; consistent with extensive experimental evidence.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-5655269	ACCEPT	Summary: Reactome reaction places FGFR1 (wild type, mutant or fusion) at the plasma membrane. Reason: FGFR1 signalling reactions occur at the plasma membrane; consistent with extensive experimental evidence.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-5655278	ACCEPT	Summary: Reactome reaction places FGFR1 (wild type, mutant or fusion) at the plasma membrane. Reason: FGFR1 signalling reactions occur at the plasma membrane; consistent with extensive experimental evidence.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-5655290	ACCEPT	Summary: Reactome reaction places FGFR1 (wild type, mutant or fusion) at the plasma membrane. Reason: FGFR1 signalling reactions occur at the plasma membrane; consistent with extensive experimental evidence.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-5655326	ACCEPT	Summary: Reactome reaction places FGFR1 (wild type, mutant or fusion) at the plasma membrane. Reason: FGFR1 signalling reactions occur at the plasma membrane; consistent with extensive experimental evidence.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-5656064	ACCEPT	Summary: Reactome reaction places FGFR1 (wild type, mutant or fusion) at the plasma membrane. Reason: FGFR1 signalling reactions occur at the plasma membrane; consistent with extensive experimental evidence.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-5672965	ACCEPT	Summary: Reactome reaction places FGFR1 (wild type, mutant or fusion) at the plasma membrane. Reason: FGFR1 signalling reactions occur at the plasma membrane; consistent with extensive experimental evidence.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-8853322	ACCEPT	Summary: Reactome reaction places FGFR1 (wild type, mutant or fusion) at the plasma membrane. Reason: FGFR1 signalling reactions occur at the plasma membrane; consistent with extensive experimental evidence.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-8853325	ACCEPT	Summary: Reactome reaction places FGFR1 (wild type, mutant or fusion) at the plasma membrane. Reason: FGFR1 signalling reactions occur at the plasma membrane; consistent with extensive experimental evidence.
GO:0006468 protein phosphorylation	NAS PMID:1846977 Fibroblast growth factor receptors from liver vary in three ...	ACCEPT	Summary: Early cDNA paper on FGFR variants; protein phosphorylation inferred from kinase domain. Reason: FGFR1 phosphorylates itself and substrates (FRS2, PLCG1); correct though general. More specific terms (protein autophosphorylation, peptidyl-tyrosine phosphorylation) are also annotated. Supporting Evidence: PMID:1846977 Amino-terminal variants consisted of two transmembrane molecules that contained three and two immunoglobulin-like disulfide loops, as well as a potential intracellular form of the receptor.
GO:0006468 protein phosphorylation	NAS PMID:2159626 Complete sequence of a human receptor for acidic and basic f...	ACCEPT	Summary: Complete sequence of a human FGF receptor; protein phosphorylation inferred from kinase domain. Reason: Correct though general; FGFR1 catalyses protein tyrosine phosphorylation. Supporting Evidence: file:human/FGFR1/FGFR1-uniprot.txt Reaction=L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+)
GO:0008201 heparin binding	IDA PMID:18480409 Ubiquitination of fibroblast growth factor receptor 1 is req...	ACCEPT	Summary: Heparin binding by FGFR1. Reason: FGFR1 D2 contains a basic heparin-binding canyon, and heparin/heparan sulfate is an essential co-receptor forming 2:2:2 FGF:FGFR:heparin complexes. Heparin is used routinely in the cited FGFR1 trafficking assays; binding is well established structurally. Supporting Evidence: PMID:11030354 Within each 1:1 FGF:FGFR complex, heparin makes numerous contacts with both FGF and FGFR, thereby augmenting FGF-FGFR binding. file:human/FGFR1/FGFR1-uniprot.txt The second and third Ig-like domains directly interact with fibroblast growth factors (FGF) and heparan sulfate proteoglycans.
GO:0008284 positive regulation of cell population proliferation	IBA GO_REF:0000033	ACCEPT	Summary: PAINT IBA: positive regulation of cell proliferation inherited in eumetazoan FGFR clade. Reason: FGFR1 is a mitogenic receptor; FGF-induced proliferation through FGFR1 shown in multiple systems. Supporting Evidence: PMID:8663044 we have engineered mitogenically responsive cell lines expressing the major splice variants of all the known FGF receptors. We have assayed the mitogenic activity of the nine known FGF ligands on these cell lines. PMID:10748122 FGF-1, FGF-2, and FGF-4 enhanced mitogen-activated protein kinase (MAPK) activity, increased steady-state c-fos mRNA levels, and stimulated proliferation through either receptor, whereas KGF was without effect.
GO:0008284 positive regulation of cell population proliferation	IDA PMID:8663044 Receptor specificity of the fibroblast growth factor family.	ACCEPT	Summary: FGF ligands stimulate mitogenesis of BaF3 cells expressing FGFR1 splice variants. Reason: Direct evidence of FGFR1-mediated mitogenic response. Supporting Evidence: PMID:8663044 we have engineered mitogenically responsive cell lines expressing the major splice variants of all the known FGF receptors. We have assayed the mitogenic activity of the nine known FGF ligands on these cell lines.
GO:0008284 positive regulation of cell population proliferation	IEA GO_REF:0000120	ACCEPT	Summary: Automated annotation: positive regulation of cell population proliferation. Reason: Consistent with experimental data. Supporting Evidence: PMID:8663044 we have engineered mitogenically responsive cell lines expressing the major splice variants of all the known FGF receptors. We have assayed the mitogenic activity of the nine known FGF ligands on these cell lines.
GO:0008284 positive regulation of cell population proliferation	IGI PMID:8663044 Receptor specificity of the fibroblast growth factor family.	ACCEPT	Summary: IGI with FGF ligands (FGF1, FGF2, FGF3/4/5/6 etc.): ligand-dependent mitogenesis of FGFR1-expressing cells. Reason: Ligand-receptor genetic interaction in mitogenic assays; supports FGFR1 role in promoting proliferation. Supporting Evidence: PMID:8663044 we have engineered mitogenically responsive cell lines expressing the major splice variants of all the known FGF receptors. We have assayed the mitogenic activity of the nine known FGF ligands on these cell lines. PMID:8663044 These studies demonstrate that FGF 1 is the only FGF that can activate all FGF receptor splice variants.
GO:0008284 positive regulation of cell population proliferation	IGI PMID:8663044 Receptor specificity of the fibroblast growth factor family.	ACCEPT	Summary: IGI with FGF ligands (FGF1, FGF2, FGF3/4/5/6 etc.): ligand-dependent mitogenesis of FGFR1-expressing cells. Reason: Ligand-receptor genetic interaction in mitogenic assays; supports FGFR1 role in promoting proliferation. Supporting Evidence: PMID:8663044 we have engineered mitogenically responsive cell lines expressing the major splice variants of all the known FGF receptors. We have assayed the mitogenic activity of the nine known FGF ligands on these cell lines. PMID:8663044 These studies demonstrate that FGF 1 is the only FGF that can activate all FGF receptor splice variants.
GO:0008284 positive regulation of cell population proliferation	IGI PMID:8663044 Receptor specificity of the fibroblast growth factor family.	ACCEPT	Summary: IGI with FGF ligands (FGF1, FGF2, FGF3/4/5/6 etc.): ligand-dependent mitogenesis of FGFR1-expressing cells. Reason: Ligand-receptor genetic interaction in mitogenic assays; supports FGFR1 role in promoting proliferation. Supporting Evidence: PMID:8663044 we have engineered mitogenically responsive cell lines expressing the major splice variants of all the known FGF receptors. We have assayed the mitogenic activity of the nine known FGF ligands on these cell lines. PMID:8663044 These studies demonstrate that FGF 1 is the only FGF that can activate all FGF receptor splice variants.
GO:0008284 positive regulation of cell population proliferation	IGI PMID:8663044 Receptor specificity of the fibroblast growth factor family.	ACCEPT	Summary: IGI with FGF ligands (FGF1, FGF2, FGF3/4/5/6 etc.): ligand-dependent mitogenesis of FGFR1-expressing cells. Reason: Ligand-receptor genetic interaction in mitogenic assays; supports FGFR1 role in promoting proliferation. Supporting Evidence: PMID:8663044 we have engineered mitogenically responsive cell lines expressing the major splice variants of all the known FGF receptors. We have assayed the mitogenic activity of the nine known FGF ligands on these cell lines. PMID:8663044 These studies demonstrate that FGF 1 is the only FGF that can activate all FGF receptor splice variants.
GO:0008284 positive regulation of cell population proliferation	IGI PMID:8663044 Receptor specificity of the fibroblast growth factor family.	ACCEPT	Summary: IGI with FGF ligands (FGF1, FGF2, FGF3/4/5/6 etc.): ligand-dependent mitogenesis of FGFR1-expressing cells. Reason: Ligand-receptor genetic interaction in mitogenic assays; supports FGFR1 role in promoting proliferation. Supporting Evidence: PMID:8663044 we have engineered mitogenically responsive cell lines expressing the major splice variants of all the known FGF receptors. We have assayed the mitogenic activity of the nine known FGF ligands on these cell lines. PMID:8663044 These studies demonstrate that FGF 1 is the only FGF that can activate all FGF receptor splice variants.
GO:0008284 positive regulation of cell population proliferation	IGI PMID:8663044 Receptor specificity of the fibroblast growth factor family.	ACCEPT	Summary: IGI with FGF ligands (FGF1, FGF2, FGF3/4/5/6 etc.): ligand-dependent mitogenesis of FGFR1-expressing cells. Reason: Ligand-receptor genetic interaction in mitogenic assays; supports FGFR1 role in promoting proliferation. Supporting Evidence: PMID:8663044 we have engineered mitogenically responsive cell lines expressing the major splice variants of all the known FGF receptors. We have assayed the mitogenic activity of the nine known FGF ligands on these cell lines. PMID:8663044 These studies demonstrate that FGF 1 is the only FGF that can activate all FGF receptor splice variants.
GO:0008284 positive regulation of cell population proliferation	IMP PMID:8622701 Identification of six novel autophosphorylation sites on fib...	ACCEPT	Summary: Y653/Y654 autophosphorylation mutants abolish FGFR1 mitogenic signalling in L6 cells. Reason: Mutational evidence that FGFR1 kinase activation drives proliferation. Supporting Evidence: PMID:8622701 We demonstrate that autophosphorylation on tyrosines 653 and 654 is important for activation of tyrosine kinase activity of FGFR1 and is therefore essential for FGFR1-mediated biological responses. PMID:8622701 autophosphorylation of the remaining four tyrosines is dispensable for FGFR1-mediated mitogen-activated protein kinase activation and mitogenic signaling in L-6 cells as well as neuronal differentiation of PC12 cells.
GO:0008543 fibroblast growth factor receptor signaling pathway	IBA GO_REF:0000033	ACCEPT	Summary: PAINT IBA: FGF receptor signaling pathway inherited in eumetazoan FGFR clade. Reason: FGFR1 is the receptor that initiates the pathway; core process. Supporting Evidence: file:human/FGFR1/FGFR1-uniprot.txt Tyrosine-protein kinase that acts as a cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of embryonic development, cell proliferation, differentiation and migration.
GO:0008543 fibroblast growth factor receptor signaling pathway	IDA PMID:18480409 Ubiquitination of fibroblast growth factor receptor 1 is req...	ACCEPT	Summary: FGF1-induced FGFR1 signalling and its termination by ubiquitination/lysosomal sorting. Reason: Direct experimental evidence; core process. Supporting Evidence: PMID:18480409 The duration of FGFR1 signaling seems to be tightly regulated by receptor ubiquitination and subsequent sorting to the lysosomes for degradation.
GO:0008543 fibroblast growth factor receptor signaling pathway	IDA PMID:21885851 MicroRNA-16 and microRNA-424 regulate cell-autonomous angiog...	ACCEPT	Summary: miR-16/miR-424 targeting of FGFR1 reduces bFGF signalling in endothelial cells. Reason: FGFR1 mediates bFGF signalling in endothelial cells; core process. Supporting Evidence: PMID:21885851 Reduced expression of VEGFR2 and FGFR1 by miR-16 or miR-424 overexpression regulated VEGF and bFGF signaling through these receptors, thereby affecting the activity of downstream components of the pathways.
GO:0008543 fibroblast growth factor receptor signaling pathway	IDA PMID:8663044 Receptor specificity of the fibroblast growth factor family.	ACCEPT	Summary: Mitogenic responses to FGF ligands via FGFR1 splice variants. Reason: Core process. Supporting Evidence: PMID:8663044 we have engineered mitogenically responsive cell lines expressing the major splice variants of all the known FGF receptors. We have assayed the mitogenic activity of the nine known FGF ligands on these cell lines.
GO:0008543 fibroblast growth factor receptor signaling pathway	IEA GO_REF:0000002	ACCEPT	Summary: InterPro mapping: FGF receptor signaling pathway. Reason: Core process. Supporting Evidence: file:human/FGFR1/FGFR1-uniprot.txt Tyrosine-protein kinase that acts as a cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of embryonic development, cell proliferation, differentiation and migration.
GO:0008543 fibroblast growth factor receptor signaling pathway	IGI PMID:8663044 Receptor specificity of the fibroblast growth factor family.	ACCEPT	Summary: IGI with FGF ligands: ligand-specific activation of FGFR1 splice variants in mitogenic assays. Reason: Ligand-receptor genetic interaction establishing FGFR1 signalling; core process. Supporting Evidence: PMID:8663044 These studies demonstrate that FGF 1 is the only FGF that can activate all FGF receptor splice variants.
GO:0008543 fibroblast growth factor receptor signaling pathway	IGI PMID:8663044 Receptor specificity of the fibroblast growth factor family.	ACCEPT	Summary: IGI with FGF ligands: ligand-specific activation of FGFR1 splice variants in mitogenic assays. Reason: Ligand-receptor genetic interaction establishing FGFR1 signalling; core process. Supporting Evidence: PMID:8663044 These studies demonstrate that FGF 1 is the only FGF that can activate all FGF receptor splice variants.
GO:0008543 fibroblast growth factor receptor signaling pathway	IGI PMID:8663044 Receptor specificity of the fibroblast growth factor family.	ACCEPT	Summary: IGI with FGF ligands: ligand-specific activation of FGFR1 splice variants in mitogenic assays. Reason: Ligand-receptor genetic interaction establishing FGFR1 signalling; core process. Supporting Evidence: PMID:8663044 These studies demonstrate that FGF 1 is the only FGF that can activate all FGF receptor splice variants.
GO:0008543 fibroblast growth factor receptor signaling pathway	IGI PMID:8663044 Receptor specificity of the fibroblast growth factor family.	ACCEPT	Summary: IGI with FGF ligands: ligand-specific activation of FGFR1 splice variants in mitogenic assays. Reason: Ligand-receptor genetic interaction establishing FGFR1 signalling; core process. Supporting Evidence: PMID:8663044 These studies demonstrate that FGF 1 is the only FGF that can activate all FGF receptor splice variants.
GO:0008543 fibroblast growth factor receptor signaling pathway	IGI PMID:8663044 Receptor specificity of the fibroblast growth factor family.	ACCEPT	Summary: IGI with FGF ligands: ligand-specific activation of FGFR1 splice variants in mitogenic assays. Reason: Ligand-receptor genetic interaction establishing FGFR1 signalling; core process. Supporting Evidence: PMID:8663044 These studies demonstrate that FGF 1 is the only FGF that can activate all FGF receptor splice variants.
GO:0008543 fibroblast growth factor receptor signaling pathway	IGI PMID:8663044 Receptor specificity of the fibroblast growth factor family.	ACCEPT	Summary: IGI with FGF ligands: ligand-specific activation of FGFR1 splice variants in mitogenic assays. Reason: Ligand-receptor genetic interaction establishing FGFR1 signalling; core process. Supporting Evidence: PMID:8663044 These studies demonstrate that FGF 1 is the only FGF that can activate all FGF receptor splice variants.
GO:0008543 fibroblast growth factor receptor signaling pathway	IPI PMID:10830168 Crystal structures of two FGF-FGFR complexes reveal the dete...	ACCEPT	Summary: FGF1-FGFR1 crystal structure defines ligand-receptor specificity determinants. Reason: Ligand engagement is the first step of FGFR signalling; accepted as core process. Supporting Evidence: PMID:10830168 we have determined the crystal structures of FGF1 and FGF2 complexed with the ligand binding domains (immunoglobulin-like domains 2 [D2] and 3 [D3]) of FGF receptor 1 (FGFR1) and FGFR2, respectively.
GO:0008543 fibroblast growth factor receptor signaling pathway	TAS PMID:10748122 A novel type I fibroblast growth factor receptor activates m...	ACCEPT	Summary: FGFR1 (and FGFR-1L variant) mediate FGF-induced MAPK activation and mitogenesis. Reason: Core process. Supporting Evidence: PMID:10748122 FGF-1, FGF-2, and FGF-4 enhanced mitogen-activated protein kinase (MAPK) activity, increased steady-state c-fos mRNA levels, and stimulated proliferation through either receptor, whereas KGF was without effect.
GO:0008543 fibroblast growth factor receptor signaling pathway	TAS PMID:22235191 Differentiation of the lateral compartment of the cochlea re...	ACCEPT	Summary: FGF20 signalling via FGFR1 is required for differentiation of lateral cochlear compartment cells (mouse). Reason: Supports FGFR1 as the receptor mediating FGF20 signalling in the developing cochlea; core process. Supporting Evidence: PMID:22235191 These studies suggest that FGF20 might be the ligand for FGFR1 during the early growth and differentiation stages of cochlear development.
GO:0010518 positive regulation of phospholipase activity	TAS PMID:12141425 The structure and function of vertebrate fibroblast growth f...	ACCEPT	Summary: Review: FGFR1 activates PLC-gamma via phosphorylated Tyr-766. Reason: FGFR1 directly recruits and tyrosine-phosphorylates PLC-gamma1, activating its lipase activity; Y766F abolishes PtdIns hydrolysis. Accepted as a direct regulatory effect of the receptor. Supporting Evidence: PMID:1379697 a fibroblast growth factor (FGF) receptor with a single point mutation at residue 766 replacing tyrosine with phenylalanine fails to associate with PLC gamma in response to FGF. This mutant receptor also failed to mediate PtdIns hydrolysis and Ca2+ mobilization after FGF stimulation. PMID:12141425 The restricted expression patterns of FGFR1 isoforms, together with differential expression and binding of specific ligands, leads to activation of common FGFR1 signal transduction pathways, but may result in distinctively different biological responses as a result of differences in cellular context.
GO:0016020 membrane	IEA GO_REF:0000002	ACCEPT	Summary: InterPro mapping: membrane. Reason: Correct but general; plasma membrane is the specific location. Supporting Evidence: file:human/FGFR1/FGFR1-uniprot.txt Cell membrane; Single-pass type I membrane protein. Nucleus. Cytoplasm, cytosol. Cytoplasmic vesicle.
GO:0016020 membrane	NAS PMID:1652059 The human fibroblast growth factor receptor genes: a common ...	ACCEPT	Summary: FGFR1 gene structure: transmembrane forms of FGFR1. Reason: Correct but general. Supporting Evidence: PMID:1652059 One of these alternatives encodes a sequence that is part of a secreted form of FGFR 1. The other two encode sequences that are likely part of transmembrane forms of FGFR 1.
GO:0016020 membrane	NAS PMID:1846977 Fibroblast growth factor receptors from liver vary in three ...	ACCEPT	Summary: Liver FGFR cDNAs encode transmembrane receptors. Reason: Correct but general. Supporting Evidence: PMID:1846977 Amino-terminal variants consisted of two transmembrane molecules that contained three and two immunoglobulin-like disulfide loops, as well as a potential intracellular form of the receptor.
GO:0016020 membrane	NAS PMID:2159626 Complete sequence of a human receptor for acidic and basic f...	ACCEPT	Summary: Complete sequence of human FGFR1; transmembrane receptor. Reason: Correct but general. Supporting Evidence: file:human/FGFR1/FGFR1-uniprot.txt Cell membrane; Single-pass type I membrane protein. Nucleus. Cytoplasm, cytosol. Cytoplasmic vesicle.
GO:0016477 cell migration	TAS PMID:15863030 Cellular signaling by fibroblast growth factor receptors.	KEEP AS NON CORE	Summary: Review: FGFR signalling controls cell migration. Reason: Cell migration is one of several cellular outcomes of FGFR1 signalling rather than a core function. Supporting Evidence: PMID:15863030 A variety of signaling proteins are phosphorylated in response to FGF stimulation including Shc, phospholipase-Cgamma, STAT1, Gab1 and FRS2alpha leading to stimulation of intracellular signaling pathways that control cell proliferation, cell differentiation, cell migration, cell survival and cell shape.
GO:0017134 fibroblast growth factor binding	IBA GO_REF:0000033	ACCEPT	Summary: PAINT IBA: FGF binding inherited in deuterostome FGFR clade. Reason: Core function (ligand binding). Supporting Evidence: file:human/FGFR1/FGFR1-uniprot.txt The second and third Ig-like domains directly interact with fibroblast growth factors (FGF) and heparan sulfate proteoglycans.
GO:0017134 fibroblast growth factor binding	IDA PMID:18480409 Ubiquitination of fibroblast growth factor receptor 1 is req...	ACCEPT	Summary: FGF1 binding to cell-surface FGFR1 in trafficking assays. Reason: Core function. Supporting Evidence: PMID:18480409 The duration of FGFR1 signaling seems to be tightly regulated by receptor ubiquitination and subsequent sorting to the lysosomes for degradation.
GO:0017134 fibroblast growth factor binding	IDA PMID:8663044 Receptor specificity of the fibroblast growth factor family.	ACCEPT	Summary: FGF ligands bind and activate FGFR1 splice variants. Reason: Core function. Supporting Evidence: PMID:8663044 These studies demonstrate that FGF 1 is the only FGF that can activate all FGF receptor splice variants.
GO:0017134 fibroblast growth factor binding	IEA GO_REF:0000117	ACCEPT	Summary: ARBA automated annotation: FGF binding. Reason: Core function. Supporting Evidence: file:human/FGFR1/FGFR1-uniprot.txt The second and third Ig-like domains directly interact with fibroblast growth factors (FGF) and heparan sulfate proteoglycans.
GO:0018108 peptidyl-tyrosine phosphorylation	IDA PMID:8622701 Identification of six novel autophosphorylation sites on fib...	ACCEPT	Summary: FGFR1 autophosphorylates tyrosines and phosphorylates Shc and pp90 (FRS2). Reason: Direct evidence of FGFR1-catalysed tyrosine phosphorylation. Supporting Evidence: PMID:8622701 We demonstrate that autophosphorylation on tyrosines 653 and 654 is important for activation of tyrosine kinase activity of FGFR1 and is therefore essential for FGFR1-mediated biological responses. PMID:8622701 both the wild-type and a mutant FGFR1 (FGFR1-4F) are able to phosphorylate Shc and an unidentified Grb2-associated phosphoprotein of 90 kDa (pp90).
GO:0031410 cytoplasmic vesicle	IEA GO_REF:0000044	KEEP AS NON CORE	Summary: UniProt subcellular location mapping: cytoplasmic vesicle. Reason: Ligand-activated FGFR1 is internalized into endosomal vesicles and sorted to lysosomes or recycling endosomes; a trafficking location rather than the site of core function. Supporting Evidence: file:human/FGFR1/FGFR1-uniprot.txt After ligand binding, both receptor and ligand are rapidly internalized. Can translocate to the nucleus after internalization, or by translocation from the endoplasmic reticulum or Golgi apparatus to the cytosol, and from there to the nucleus. PMID:18480409 The duration of FGFR1 signaling seems to be tightly regulated by receptor ubiquitination and subsequent sorting to the lysosomes for degradation.
GO:0042802 identical protein binding	IPI PMID:19696444 Novel mechanisms of fibroblast growth factor receptor 1 regu...	MODIFY	Summary: Anosmin-1 study reports FGFR1 self-association in the context of FGF2/heparin complexes. Reason: 'Identical protein binding' is uninformative; ligand-induced receptor homodimerization is the relevant activity. Replaced with protein homodimerization activity. Proposed replacements: protein homodimerization activity Supporting Evidence: PMID:19696444 Here, we show that anosmin-1 directly binds to FGFR1 with high affinity.
GO:0042802 identical protein binding	IPI PMID:20133753 Asymmetric receptor contact is required for tyrosine autopho...	MODIFY	Summary: Asymmetric FGFR1 kinase-domain dimers mediate trans-autophosphorylation. Reason: 'Identical protein binding' is uninformative; the experiment demonstrates receptor kinase homodimerization required for transphosphorylation. Proposed replacements: protein homodimerization activity Supporting Evidence: PMID:20133753 we present structural and biochemical experiments demonstrating that formation of an asymmetric dimer between activated FGFR1 kinase domains is required for transphosphorylation of FGFR1 in FGF-stimulated cells.
GO:0042803 protein homodimerization activity	IPI PMID:20133753 Asymmetric receptor contact is required for tyrosine autopho...	KEEP AS NON CORE	Summary: Asymmetric FGFR1 kinase-domain homodimer required for trans-autophosphorylation. Reason: Ligand-induced homodimerization is a mechanistic prerequisite for FGFR1 activation (a sub-step of receptor activity) rather than a separate core function. Supporting Evidence: PMID:20133753 we present structural and biochemical experiments demonstrating that formation of an asymmetric dimer between activated FGFR1 kinase domains is required for transphosphorylation of FGFR1 in FGF-stimulated cells.
GO:0043009 chordate embryonic development	TAS PMID:15863030 Cellular signaling by fibroblast growth factor receptors.	KEEP AS NON CORE	Summary: Review: FGFR signalling in development; FGFR1 required for embryonic development. Reason: FGFR1 is required for gastrulation/mesoderm patterning, but chordate embryonic development is a broad developmental outcome. Supporting Evidence: PMID:15863030 A variety of human skeletal dysplasias have been linked to specific point mutations in FGFR1, FGFR2 and FGFR3 leading to severe impairment in cranial, digital and skeletal development. file:human/FGFR1/FGFR1-uniprot.txt Tyrosine-protein kinase that acts as a cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of embryonic development, cell proliferation, differentiation and migration.
GO:0043235 signaling receptor complex	IBA GO_REF:0000033	ACCEPT	Summary: PAINT IBA: signaling receptor complex (RTK clade). Reason: FGFR1 functions in ligand-induced FGF:FGFR:heparan sulfate (or Klotho) signalling complexes. Supporting Evidence: PMID:11030354 Within each 1:1 FGF:FGFR complex, heparin makes numerous contacts with both FGF and FGFR, thereby augmenting FGF-FGFR binding. PMID:19966287 Here, we show that the soluble ectodomains of FGFR1c and Klotho are sufficient to form a ternary complex with FGF23 in vitro.
GO:0043235 signaling receptor complex	IDA PMID:23382219 Structural basis for endosomal trafficking of diverse transm...	ACCEPT	Summary: PX-FERM (SNX17/SNX27/SNX31) cargo screen including RTKs; curated as FGFR1 part of signaling receptor complex. Reason: The cached text does not explicitly describe FGFR1 complexes, but the full-text screen may. FGFR1 membership in ligand-receptor signalling complexes is well established structurally (PMID:11030354, PMID:19966287); deferring to the curator. Supporting Evidence: PMID:23382219 We further show that the PX-FERM proteins share a promiscuous ability to bind a wide array of putative cargo molecules, including receptor tyrosine kinases
GO:0043406 positive regulation of MAP kinase activity	IDA PMID:8622701 Identification of six novel autophosphorylation sites on fib...	MODIFY	Summary: FGFR1 activation-loop autophosphorylation is required for MAP kinase activation. Reason: FGFR1 does not directly regulate MAP kinase catalytic activity; it initiates the RAS-MAPK cascade via FRS2/GRB2/SOS. Positive regulation of MAPK cascade (GO:0043410) better describes the receptor's role. Proposed replacements: positive regulation of MAPK cascade Supporting Evidence: PMID:8622701 autophosphorylation of the remaining four tyrosines is dispensable for FGFR1-mediated mitogen-activated protein kinase activation and mitogenic signaling in L-6 cells as well as neuronal differentiation of PC12 cells.
GO:0043410 positive regulation of MAPK cascade	IBA GO_REF:0000033	ACCEPT	Summary: PAINT IBA: positive regulation of MAPK cascade in the eumetazoan FGFR clade. Reason: Major FGFR1 output via FRS2-GRB2-SOS-RAS. Supporting Evidence: file:human/FGFR1/FGFR1-uniprot.txt Phosphorylation of FRS2 triggers recruitment of GRB2, GAB1, PIK3R1 and SOS1, and mediates activation of RAS, MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway.
GO:0043410 positive regulation of MAPK cascade	IEA GO_REF:0000117	ACCEPT	Summary: ARBA automated annotation: positive regulation of MAPK cascade. Reason: Consistent with experimental evidence. Supporting Evidence: file:human/FGFR1/FGFR1-uniprot.txt Phosphorylation of FRS2 triggers recruitment of GRB2, GAB1, PIK3R1 and SOS1, and mediates activation of RAS, MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway.
GO:0043410 positive regulation of MAPK cascade	IGI PMID:26451614 MiR-573 inhibits prostate cancer metastasis by regulating ep...	ACCEPT	Summary: miR-573 targets FGFR1 and modulates FGF2-induced downstream signalling in prostate cancer cells. Reason: Consistent with FGFR1-driven ERK activation. Supporting Evidence: PMID:26451614 Consequently, miR-573 modulates the activation of FGFR1-downstream signaling in response to fibroblast growth factor 2 (FGF2).
GO:0043410 positive regulation of MAPK cascade	IMP PMID:8622701 Identification of six novel autophosphorylation sites on fib...	ACCEPT	Summary: Y653/Y654 mutants of FGFR1 fail to activate MAPK. Reason: Direct mutational evidence. Supporting Evidence: PMID:8622701 autophosphorylation of the remaining four tyrosines is dispensable for FGFR1-mediated mitogen-activated protein kinase activation and mitogenic signaling in L-6 cells as well as neuronal differentiation of PC12 cells.
GO:0043536 positive regulation of blood vessel endothelial cell migration	IGI PMID:23263626 An endothelial apelin-FGF link mediated by miR-424 and miR-5...	KEEP AS NON CORE	Summary: APLN-miR-424/503-FGF2/FGFR1 axis in pulmonary artery endothelial cells. Reason: Context-specific endothelial outcome of FGF2/FGFR1 signalling; the evidence is largely via microRNA targeting of FGF2 and FGFR1 together. Supporting Evidence: PMID:23263626 APLN deficiency in these cells led to increased expression of FGF2 and its receptor FGFR1 as a consequence of decreased expression of miR-424 and miR-503, which directly target FGF2 and FGFR1.
GO:0044344 cellular response to fibroblast growth factor stimulus	IDA PMID:21885851 MicroRNA-16 and microRNA-424 regulate cell-autonomous angiog...	ACCEPT	Summary: FGFR1 mediates endothelial responses to bFGF; miR-16/424 reduce FGFR1 and bFGF signalling. Reason: Receptor-mediated cellular response to FGF is intrinsic to FGFR1 function. Supporting Evidence: PMID:21885851 Reduced expression of VEGFR2 and FGFR1 by miR-16 or miR-424 overexpression regulated VEGF and bFGF signaling through these receptors, thereby affecting the activity of downstream components of the pathways.
GO:0045595 regulation of cell differentiation	TAS PMID:12141425 The structure and function of vertebrate fibroblast growth f...	KEEP AS NON CORE	Summary: Review: FGFR1 isoforms and differential biological responses including differentiation. Reason: Broad downstream outcome of FGFR1 signalling. Supporting Evidence: PMID:12141425 The restricted expression patterns of FGFR1 isoforms, together with differential expression and binding of specific ligands, leads to activation of common FGFR1 signal transduction pathways, but may result in distinctively different biological responses as a result of differences in cellular context.
GO:0045597 positive regulation of cell differentiation	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: PAINT IBA: positive regulation of cell differentiation. Reason: FGF signalling promotes differentiation in many contexts (e.g. neuronal, cochlear), but this is a pleiotropic outcome, not a core activity. Supporting Evidence: PMID:8622701 autophosphorylation of the remaining four tyrosines is dispensable for FGFR1-mediated mitogen-activated protein kinase activation and mitogenic signaling in L-6 cells as well as neuronal differentiation of PC12 cells.
GO:0045666 positive regulation of neuron differentiation	IMP PMID:8622701 Identification of six novel autophosphorylation sites on fib...	KEEP AS NON CORE	Summary: FGFR1 activation drives neuronal differentiation of PC12 cells; Y653/Y654 required. Reason: Cell-line differentiation outcome of receptor signalling. Supporting Evidence: PMID:8622701 autophosphorylation of the remaining four tyrosines is dispensable for FGFR1-mediated mitogen-activated protein kinase activation and mitogenic signaling in L-6 cells as well as neuronal differentiation of PC12 cells.
GO:0046777 protein autophosphorylation	IDA PMID:8622701 Identification of six novel autophosphorylation sites on fib...	ACCEPT	Summary: Identification of FGFR1 autophosphorylation sites (Y463, Y583, Y585, Y653, Y654, Y730, Y766). Reason: Core mechanistic step of FGFR1 activation. Supporting Evidence: PMID:8622701 We demonstrate that autophosphorylation on tyrosines 653 and 654 is important for activation of tyrosine kinase activity of FGFR1 and is therefore essential for FGFR1-mediated biological responses. PMID:19224897 First-stage autophosphorylation of an activation loop tyrosine leads to 50- to 100-fold stimulation of kinase activity and is followed by second-stage phosphorylation of three additional tyrosine residues, which are binding sites for signaling molecules.
GO:0048015 phosphatidylinositol-mediated signaling	TAS PMID:12141425 The structure and function of vertebrate fibroblast growth f...	ACCEPT	Summary: Review: FGFR1 activates PLC-gamma-mediated phosphoinositide signalling. Reason: FGFR1 recruits and phosphorylates PLC-gamma1 (via pY766), generating DAG and IP3; one of the canonical FGFR1 signalling branches. Supporting Evidence: PMID:1379697 a fibroblast growth factor (FGF) receptor with a single point mutation at residue 766 replacing tyrosine with phenylalanine fails to associate with PLC gamma in response to FGF. This mutant receptor also failed to mediate PtdIns hydrolysis and Ca2+ mobilization after FGF stimulation. PMID:12141425 The restricted expression patterns of FGFR1 isoforms, together with differential expression and binding of specific ligands, leads to activation of common FGFR1 signal transduction pathways, but may result in distinctively different biological responses as a result of differences in cellular context.
GO:0048699 generation of neurons	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: ARBA automated annotation: generation of neurons. Reason: FGFR1 signalling contributes to neurogenesis, but this is a broad developmental outcome. Supporting Evidence: file:human/FGFR1/FGFR1-uniprot.txt Tyrosine-protein kinase that acts as a cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of embryonic development, cell proliferation, differentiation and migration.
GO:0048705 skeletal system morphogenesis	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: ARBA automated annotation: skeletal system morphogenesis. Reason: Supported by craniosynostosis genetics; developmental outcome. Supporting Evidence: PMID:7874169 Here we present evidence that mutations in the fibroblast growth factor receptor-1 (FGFR1) gene, which maps to 8p, cause one form of familial Pfeiffer syndrome.
GO:0048705 skeletal system morphogenesis	TAS PMID:15863030 Cellular signaling by fibroblast growth factor receptors.	KEEP AS NON CORE	Summary: Review: FGFR mutations impair cranial, digital and skeletal development. Reason: Developmental outcome of FGFR1 signalling. Supporting Evidence: PMID:15863030 A variety of human skeletal dysplasias have been linked to specific point mutations in FGFR1, FGFR2 and FGFR3 leading to severe impairment in cranial, digital and skeletal development.
GO:0051897 positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	IGI PMID:26451614 MiR-573 inhibits prostate cancer metastasis by regulating ep...	ACCEPT	Summary: FGFR1 knockdown/overexpression modulates FGF2-induced downstream (AKT) signalling in prostate cancer cells. Reason: FGFR1 activates PI3K-AKT via FRS2-GRB2-GAB1-p85; consistent canonical output. Supporting Evidence: PMID:26451614 Consequently, miR-573 modulates the activation of FGFR1-downstream signaling in response to fibroblast growth factor 2 (FGF2). file:human/FGFR1/FGFR1-uniprot.txt Phosphorylation of FRS2 triggers recruitment of GRB2, GAB1, PIK3R1 and SOS1, and mediates activation of RAS, MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway.
GO:0051897 positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	TAS PMID:15863030 Cellular signaling by fibroblast growth factor receptors.	ACCEPT	Summary: Review: FRS2 docking proteins mediate FGFR-induced PI3K/Akt signalling. Reason: Canonical FGFR1 output. Supporting Evidence: PMID:15863030 The docking proteins FRS2alpha and FRS2beta are major mediators of the Ras/MAPK and PI-3 kinase/Akt signaling pathways
GO:0090722 receptor-receptor interaction	IDA PMID:24157794 Dynamic modulation of FGFR1-5-HT1A heteroreceptor complexes....	KEEP AS NON CORE	Summary: FGFR1-5-HT1A heteroreceptor complexes in hippocampus/raphe (BRET, PLA). Reason: Evidence comes from one research group using proximity/BRET approaches; physiological significance is uncertain and it is not a core FGFR1 function. Supporting Evidence: PMID:24157794 Taken together, the participation of 5-HT1A and FGFR1 homodimers and recruitment of β-arrestin2 was demonstrated in the FGFR1-5-HT1A heteroreceptor complexes upon agonist treatments. PMID:22035699 Using bioluminescence resonance energy transfer analysis, fibroblast growth factor receptor 1 (FGFR1)-5-hydroxytryptamine 1A (5-HT1A) receptor complexes have been demonstrated and their specificity and agonist modulation characterized.
GO:1905564 positive regulation of vascular endothelial cell proliferation	IGI PMID:23263626 An endothelial apelin-FGF link mediated by miR-424 and miR-5...	KEEP AS NON CORE	Summary: APLN-deficient PAECs show increased FGF2/FGFR1 and proliferation reversed by miR-424/503. Reason: Context-specific endothelial proliferation outcome of FGF2/FGFR1 signalling. Supporting Evidence: PMID:23263626 APLN deficiency in these cells led to increased expression of FGF2 and its receptor FGFR1 as a consequence of decreased expression of miR-424 and miR-503, which directly target FGF2 and FGFR1.
GO:2001028 positive regulation of endothelial cell chemotaxis	IDA PMID:21885851 MicroRNA-16 and microRNA-424 regulate cell-autonomous angiog...	KEEP AS NON CORE	Summary: miR-16/miR-424 targeting VEGFR2 and FGFR1 reduces endothelial migration. Reason: Context-specific endothelial outcome; the microRNA also targets VEGF/VEGFR2, so FGFR1-specific contribution is partial. Supporting Evidence: PMID:21885851 Functionally, miR-16 or miR-424 overexpression reduced proliferation, migration, and cord formation of ECs in vitro

Gene Description

Existing Annotations Review

Core Functions

Ligand-activated receptor tyrosine kinase for FGFs at the plasma membrane: binds FGF (with heparan sulfate or Klotho co-receptors), dimerizes, trans-autophosphorylates and phosphorylates FRS2 and PLC-gamma1 to initiate FGF receptor signalling.

Binding of FGF ligands (paracrine FGF1/FGF2 and others; endocrine FGF23 in a Klotho-dependent ternary complex) via Ig-like domains D2-D3, with isoform-specific (IIIb/IIIc) selectivity.

Heparin/heparan sulfate binding by the D2 domain, stabilizing the 2:2:2 FGF:FGFR:heparin signalling dimer.

Protein tyrosine kinase activity toward downstream substrates (FRS2, PLC-gamma1, SHC1), driving RAS-MAPK, PI3K-AKT and PLC-gamma branches.

References

Suggested Questions for Experts

Suggested Experiments

Deep Research

Falcon

📚 Additional Documentation

Notes

📄 View Raw YAML