UniProtKB - P11362 (FGFR1_HUMAN)
Protein
Fibroblast growth factor receptor 1
Gene
FGFR1
Organism
Homo sapiens (Human)
Status
Functioni
Tyrosine-protein kinase that acts as cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of embryonic development, cell proliferation, differentiation and migration. Required for normal mesoderm patterning and correct axial organization during embryonic development, normal skeletogenesis and normal development of the gonadotropin-releasing hormone (GnRH) neuronal system. Phosphorylates PLCG1, FRS2, GAB1 and SHB. Ligand binding leads to the activation of several signaling cascades. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate. 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. Promotes phosphorylation of SHC1, STAT1 and PTPN11/SHP2. In the nucleus, enhances RPS6KA1 and CREB1 activity and contributes to the regulation of transcription. FGFR1 signaling is down-regulated by IL17RD/SEF, and by FGFR1 ubiquitination, internalization and degradation.By similarity18 Publications
Catalytic activityi
- ATP + L-tyrosyl-[protein] = ADP + H+ + O-phospho-L-tyrosyl-[protein]PROSITE-ProRule annotation7 PublicationsEC:2.7.10.1PROSITE-ProRule annotation7 Publications
Activity regulationi
Present in an inactive conformation in the absence of bound ligand. Ligand binding leads to dimerization and activation by sequential autophosphorylation on tyrosine residues. Inhibited by ARQ 069; this compound maintains the kinase in an inactive conformation and inhibits autophosphorylation. Inhibited by PD173074.4 Publications
Sites
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Binding sitei | 514 | ATP | 1 | |
| Binding sitei | 568 | ATP | 1 | |
| Active sitei | 623 | Proton acceptorPROSITE-ProRule annotation1 Publication | 1 | |
| Binding sitei | 627 | ATP | 1 | |
| Binding sitei | 641 | ATP | 1 | |
| Sitei | 766 | Mediates interaction with PLCG1 and SHB | 1 |
Regions
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Nucleotide bindingi | 484 – 490 | ATP | 7 | |
| Nucleotide bindingi | 562 – 564 | ATP | 3 |
GO - Molecular functioni
- 1-phosphatidylinositol-3-kinase activity Source: Reactome
- ATP binding Source: UniProtKB-KW
- fibroblast growth factor-activated receptor activity Source: UniProtKB
- fibroblast growth factor binding Source: UniProtKB
- heparin binding Source: UniProtKB
- identical protein binding Source: IntAct
- phosphatidylinositol-4,5-bisphosphate 3-kinase activity Source: Reactome
- protein homodimerization activity Source: UniProtKB
- protein tyrosine kinase activity Source: UniProtKB
- Ras guanyl-nucleotide exchange factor activity Source: Reactome
- receptor-receptor interaction Source: ParkinsonsUK-UCL
- SH2 domain binding Source: Ensembl
- transmembrane receptor protein tyrosine kinase activity Source: GO_Central
GO - Biological processi
- angiogenesis Source: Ensembl
- auditory receptor cell development Source: Ensembl
- branching involved in salivary gland morphogenesis Source: Ensembl
- cell maturation Source: Ensembl
- cell migration Source: UniProtKB
- chondrocyte differentiation Source: Ensembl
- chordate embryonic development Source: UniProtKB
- embryonic limb morphogenesis Source: Ensembl
- fibroblast growth factor receptor signaling pathway Source: UniProtKB
- fibroblast growth factor receptor signaling pathway involved in orbitofrontal cortex development Source: Ensembl
- inner ear morphogenesis Source: Ensembl
- in utero embryonic development Source: Ensembl
- lung-associated mesenchyme development Source: Ensembl
- MAPK cascade Source: Reactome
- mesenchymal cell differentiation Source: Ensembl
- midbrain development Source: Ensembl
- middle ear morphogenesis Source: Ensembl
- negative regulation of fibroblast growth factor production Source: Ensembl
- negative regulation of transcription by RNA polymerase II Source: Ensembl
- nervous system development Source: GO_Central
- neuron migration Source: UniProtKB
- organ induction Source: Ensembl
- outer ear morphogenesis Source: Ensembl
- paraxial mesoderm development Source: Ensembl
- peptidyl-tyrosine phosphorylation Source: UniProtKB
- phosphatidylinositol-mediated signaling Source: UniProtKB
- positive regulation of blood vessel endothelial cell migration Source: BHF-UCL
- positive regulation of cardiac muscle cell proliferation Source: Ensembl
- positive regulation of cell differentiation Source: GO_Central
- positive regulation of cell population proliferation Source: UniProtKB
- positive regulation of endothelial cell chemotaxis to fibroblast growth factor Source: BHF-UCL
- positive regulation of MAPK cascade Source: UniProtKB
- positive regulation of MAP kinase activity Source: UniProtKB
- positive regulation of MAPKKK cascade by fibroblast growth factor receptor signaling pathway Source: Ensembl
- positive regulation of mesenchymal cell proliferation Source: Ensembl
- positive regulation of mitotic cell cycle DNA replication Source: Ensembl
- positive regulation of neuron differentiation Source: UniProtKB
- positive regulation of neuron projection development Source: Ensembl
- positive regulation of parathyroid hormone secretion Source: Ensembl
- positive regulation of phosphatidylinositol 3-kinase signaling Source: UniProtKB
- positive regulation of phospholipase activity Source: UniProtKB
- positive regulation of phospholipase C activity Source: UniProtKB
- positive regulation of protein kinase B signaling Source: Reactome
- positive regulation of vascular endothelial cell proliferation Source: BHF-UCL
- protein autophosphorylation Source: UniProtKB
- protein phosphorylation Source: UniProtKB
- regulation of branching involved in salivary gland morphogenesis by mesenchymal-epithelial signaling Source: Ensembl
- regulation of cell differentiation Source: UniProtKB
- regulation of extrinsic apoptotic signaling pathway in absence of ligand Source: Ensembl
- regulation of lateral mesodermal cell fate specification Source: Ensembl
- regulation of phosphate transport Source: Ensembl
- sensory perception of sound Source: Ensembl
- skeletal system development Source: ProtInc
- skeletal system morphogenesis Source: UniProtKB
- transmembrane receptor protein tyrosine kinase signaling pathway Source: GO_Central
- ureteric bud development Source: Ensembl
- ventricular zone neuroblast division Source: Ensembl
- vitamin D3 metabolic process Source: Ensembl
Keywordsi
| Molecular function | Heparin-binding, Kinase, Receptor, Transferase, Tyrosine-protein kinase |
| Biological process | Transcription, Transcription regulation |
| Ligand | ATP-binding, Nucleotide-binding |
Enzyme and pathway databases
| BRENDAi | 2.7.10.1 2681 |
| Reactomei | R-HSA-109704 PI3K Cascade R-HSA-1257604 PIP3 activates AKT signaling R-HSA-1839120 Signaling by FGFR1 amplification mutants R-HSA-1839122 Signaling by activated point mutants of FGFR1 R-HSA-190370 FGFR1b ligand binding and activation R-HSA-190373 FGFR1c ligand binding and activation R-HSA-190374 FGFR1c and Klotho ligand binding and activation R-HSA-2219530 Constitutive Signaling by Aberrant PI3K in Cancer R-HSA-375165 NCAM signaling for neurite out-growth R-HSA-445144 Signal transduction by L1 R-HSA-5654219 Phospholipase C-mediated cascade: FGFR1 R-HSA-5654687 Downstream signaling of activated FGFR1 R-HSA-5654688 SHC-mediated cascade:FGFR1 R-HSA-5654689 PI-3K cascade:FGFR1 R-HSA-5654693 FRS-mediated FGFR1 signaling R-HSA-5654726 Negative regulation of FGFR1 signaling R-HSA-5655302 Signaling by FGFR1 in disease R-HSA-5673001 RAF/MAP kinase cascade R-HSA-6811558 PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling R-HSA-8853336 Signaling by plasma membrane FGFR1 fusions |
| SignaLinki | P11362 |
| SIGNORi | P11362 |
Protein family/group databases
| TCDBi | 8.A.23.1.7 the basigin (basigin) family |
Names & Taxonomyi
| Protein namesi | Recommended name: Fibroblast growth factor receptor 1 (EC:2.7.10.17 Publications)Short name: FGFR-1 Alternative name(s): Basic fibroblast growth factor receptor 1 Short name: BFGFR Short name: bFGF-R-1 Fms-like tyrosine kinase 2 Short name: FLT-2 N-sam Proto-oncogene c-Fgr CD_antigen: CD331 |
| Gene namesi | Name:FGFR1 Synonyms:BFGFR, CEK, FGFBR, FLG, FLT2, HBGFR |
| Organismi | Homo sapiens (Human) |
| Taxonomic identifieri | 9606 [NCBI] |
| Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
| Proteomesi |
|
Organism-specific databases
| EuPathDBi | HostDB:ENSG00000077782.19 |
| HGNCi | HGNC:3688 FGFR1 |
| MIMi | 136350 gene |
| neXtProti | NX_P11362 |
Subcellular locationi
Plasma membrane
Nucleus
Cytosol
Other locations
Note: 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.
Cytosol
- cytosol Source: UniProtKB-SubCell
Extracellular region or secreted
- extracellular region Source: UniProtKB
Nucleus
- nucleolus Source: HPA
Plasma Membrane
- integral component of plasma membrane Source: GO_Central
- plasma membrane Source: UniProtKB
Other locations
- cytoplasmic vesicle Source: UniProtKB-KW
- integral component of membrane Source: UniProtKB
- receptor complex Source: MGI
Topology
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Topological domaini | 22 – 376 | ExtracellularSequence analysisAdd BLAST | 355 | |
| Transmembranei | 377 – 397 | HelicalSequence analysisAdd BLAST | 21 | |
| Topological domaini | 398 – 822 | CytoplasmicSequence analysisAdd BLAST | 425 |
Keywords - Cellular componenti
Cell membrane, Cytoplasm, Cytoplasmic vesicle, Membrane, NucleusPathology & Biotechi
Involvement in diseasei
Pfeiffer syndrome (PS)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA syndrome characterized by the association of craniosynostosis, broad and deviated thumbs and big toes, and partial syndactyly of the fingers and toes. Three subtypes are known: mild autosomal dominant form (type 1); cloverleaf skull, elbow ankylosis, early death, sporadic (type 2); craniosynostosis, early demise, sporadic (type 3).
See also OMIM:101600| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Natural variantiVAR_004111 | 252 | P → R in PS and JWS. 2 PublicationsCorresponds to variant dbSNP:rs121909627EnsemblClinVar. | 1 |
Hypogonadotropic hypogonadism 2 with or without anosmia (HH2)15 Publications
The disease is caused by mutations affecting distinct genetic loci, including the gene represented in this entry. Some patients carrying mutations in FGFR1 also have a mutation other HH-associated genes including DUSP6, FGF8, FGF17, FLRT3, GNRH1, GNRHR, HS6ST1, IL17RD, ANOS1, KISS1R, NSMF, PROKR2, SPRY4 and TACR3 (PubMed:23643382).1 Publication
Disease descriptionA disorder characterized by absent or incomplete sexual maturation by the age of 18 years, in conjunction with low levels of circulating gonadotropins and testosterone and no other abnormalities of the hypothalamic-pituitary axis. In some cases, it is associated with non-reproductive phenotypes, such as anosmia, cleft palate, and sensorineural hearing loss. Anosmia or hyposmia is related to the absence or hypoplasia of the olfactory bulbs and tracts. Hypogonadism is due to deficiency in gonadotropin-releasing hormone and probably results from a failure of embryonic migration of gonadotropin-releasing hormone-synthesizing neurons. In the presence of anosmia, idiopathic hypogonadotropic hypogonadism is referred to as Kallmann syndrome, whereas in the presence of a normal sense of smell, it has been termed normosmic idiopathic hypogonadotropic hypogonadism (nIHH).
See also OMIM:147950| Feature key | Position(s) | DescriptionActions | Graphical view | Length | |
|---|---|---|---|---|---|
| Natural variantiVAR_074012 | 4 | W → C in HH2; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs760884357Ensembl. | 1 | ||
| Natural variantiVAR_030968 | 48 | G → S in HH2; phenotype consistent with normosmic idiopathic hypogonadotropic hypogonadism. 1 PublicationCorresponds to variant dbSNP:rs121909640EnsemblClinVar. | 1 | ||
| Natural variantiVAR_072993 | 70 | G → R in HH2. 1 PublicationCorresponds to variant dbSNP:rs140254426Ensembl. | 1 | ||
| Natural variantiVAR_030970 | 78 | R → C in HH2. 1 Publication | 1 | ||
| Natural variantiVAR_074013 | 96 | S → C in HH2; unknown pathological significance. 1 Publication | 1 | ||
| Natural variantiVAR_017885 | 97 | G → D in HH2. 1 Publication | 1 | ||
| Natural variantiVAR_017886 | 99 | Y → C in HH2; impairs the tertiary folding resulting in incomplete glycosylation and reduced cell surface expression. 2 PublicationsCorresponds to variant dbSNP:rs727505373EnsemblClinVar. | 1 | ||
| Natural variantiVAR_030971 | 101 | C → F in HH2. 1 Publication | 1 | ||
| Natural variantiVAR_030972 | 102 | V → I in HH2. 2 PublicationsCorresponds to variant dbSNP:rs55642501EnsemblClinVar. | 1 | ||
| Natural variantiVAR_072994 | 116 | V → I in HH2. 1 PublicationCorresponds to variant dbSNP:rs747842199Ensembl. | 1 | ||
| Natural variantiVAR_069288 | 117 | N → S in HH2; some patients also carry GNRHR mutations. 2 PublicationsCorresponds to variant dbSNP:rs780765366Ensembl. | 1 | ||
| Natural variantiVAR_030973 | 129 | D → A in HH2. 1 PublicationCorresponds to variant dbSNP:rs765615419EnsemblClinVar. | 1 | ||
| Natural variantiVAR_017887 | 167 | A → S in HH2; with cleft palate, corpus callosum agenesis, unilateral deafness and fusion of fourth and fifth metacarpal bones. 1 PublicationCorresponds to variant dbSNP:rs121909630EnsemblClinVar. | 1 | ||
| Natural variantiVAR_072995 | 174 | V → A in HH2. 1 Publication | 1 | ||
| Natural variantiVAR_030974 | 178 | C → S in HH2; with severe ear anomalies. 1 Publication | 1 | ||
| Natural variantiVAR_030976 | 224 | D → H in HH2. 1 Publication | 1 | ||
| Natural variantiVAR_069289 | 228 | Y → D in HH2; some patients also carry KISS1R mutations; impairs the tertiary folding resulting in incomplete glycosylation and reduced cell surface expression. 2 Publications | 1 | ||
| Natural variantiVAR_030977 | 237 | G → D in HH2. 1 Publication | 1 | ||
| Natural variantiVAR_030978 | 237 | G → S in HH2; with or without anosmia; also found in a family member with isolated anosmia; may impair proper folding. 1 PublicationCorresponds to variant dbSNP:rs121909635EnsemblClinVar. | 1 | ||
| Natural variantiVAR_069290 | 239 | I → T in HH2; some patients also carry PROKR2 and GNRH1 mutations; impairs the tertiary folding resulting in incomplete glycosylation and reduced cell surface expression. 2 Publications | 1 | ||
| Natural variantiVAR_030979 | 245 | L → P in HH2. 1 Publication | 1 | ||
| Natural variantiVAR_069291 | 250 | R → Q in HH2; with or without anosmia; results in Kallmann syndrome in the presence of HS6ST1 mutation TRP-306; reduces receptor affinity for fibroblast growth factor. 4 PublicationsCorresponds to variant dbSNP:rs121909645EnsemblClinVar. | 1 | ||
| Natural variantiVAR_030980 | 250 | R → W in HH2. 2 Publications | 1 | ||
| Natural variantiVAR_030981 | 254 | R → Q in HH2. 1 Publication | 1 | ||
| Natural variantiVAR_030982 | 270 | G → D in HH2. 1 Publication | 1 | ||
| Natural variantiVAR_030983 | 273 | V → M in HH2. 2 PublicationsCorresponds to variant dbSNP:rs1131691929EnsemblClinVar. | 1 | ||
| Natural variantiVAR_030984 | 274 | E → G in HH2; also found in a family member with isolated anosmia. Corresponds to variant dbSNP:rs727505369EnsemblClinVar. | 1 | ||
| Natural variantiVAR_017888 | 277 | C → Y in HH2. 1 Publication | 1 | ||
| Natural variantiVAR_030985 | 283 | P → R in HH2. 1 Publication | 1 | ||
| Natural variantiVAR_080328 | 324 – 822 | Missing in HH2. 1 PublicationAdd BLAST | 499 | ||
| Natural variantiVAR_030988 | 332 | S → C in HH2. 1 Publication | 1 | ||
| Natural variantiVAR_030989 | 339 | Y → C in HH2. 1 Publication | 1 | ||
| Natural variantiVAR_069954 | 342 | L → S in HH2; phenotype consistent with Kallmann syndrome; the patient also carries a splice site mutation in NSMF. 1 PublicationCorresponds to variant dbSNP:rs121909638EnsemblClinVar. | 1 | ||
| Natural variantiVAR_030990 | 343 | A → V in HH2. 1 Publication | 1 | ||
| Natural variantiVAR_030991 | 346 | S → C in HH2; also found in a family member with isolated anosmia. 1 Publication | 1 | ||
| Natural variantiVAR_069955 | 348 | G → R in HH2; phenotype consistent with Kallmann syndrome; the patient also carries a mutation in IL17RD. 2 PublicationsCorresponds to variant dbSNP:rs886037634EnsemblClinVar. | 1 | ||
| Natural variantiVAR_030992 | 366 | P → L in HH2; with or without anosmia. 1 PublicationCorresponds to variant dbSNP:rs121909641EnsemblClinVar. | 1 | ||
| Natural variantiVAR_069292 | 470 | R → L in HH2; some patients also carry GNRHR mutations. 2 PublicationsCorresponds to variant dbSNP:rs121909637EnsemblClinVar. | 1 | ||
| Natural variantiVAR_069956 | 483 | P → T in HH2; phenotype consistent with Kallmann syndrome; the patient also carries a rare variant in SPRY4. 1 PublicationCorresponds to variant dbSNP:rs397515444EnsemblClinVar. | 1 | ||
| Natural variantiVAR_030995 | 520 | A → T in HH2. 1 PublicationCorresponds to variant dbSNP:rs749758370Ensembl. | 1 | ||
| Natural variantiVAR_030996 | 538 | I → V in HH2. 1 Publication | 1 | ||
| Natural variantiVAR_017889 | 607 | V → M in HH2; with bimanual synkinesis. 1 PublicationCorresponds to variant dbSNP:rs121909629EnsemblClinVar. | 1 | ||
| Natural variantiVAR_069293 | 618 | K → N in HH2; some patients also carry GNRHR mutations; impairs tyrosine kinase activity. 2 Publications | 1 | ||
| Natural variantiVAR_030997 | 621 | H → R in HH2. 1 Publication | 1 | ||
| Natural variantiVAR_080329 | 622 – 822 | Missing in HH2. 1 PublicationAdd BLAST | 201 | ||
| Natural variantiVAR_030998 | 622 | R → G in HH2; with severe ear anomalies. 1 PublicationCorresponds to variant dbSNP:rs121909628EnsemblClinVar. | 1 | ||
| Natural variantiVAR_030999 | 622 | R → Q in HH2. 1 Publication | 1 | ||
| Natural variantiVAR_080330 | 661 – 822 | Missing in HH2. 1 PublicationAdd BLAST | 162 | ||
| Natural variantiVAR_017890 | 666 | W → R in HH2; with cleft palate. 1 Publication | 1 | ||
| Natural variantiVAR_069957 | 670 | E → K in HH2; phenotype consistent with Kallmann syndrome; the patient also carries a rare variant in FLRT3. 1 PublicationCorresponds to variant dbSNP:rs397515446EnsemblClinVar. | 1 | ||
| Natural variantiVAR_069294 | 671 | A → P in HH2. 1 Publication | 1 | ||
| Natural variantiVAR_031000 | 685 | S → F in HH2. 1 Publication | 1 | ||
| Natural variantiVAR_031001 | 687 | G → R in HH2. 2 PublicationsCorresponds to variant dbSNP:rs727505376EnsemblClinVar. | 1 | ||
| Natural variantiVAR_069958 | 692 | E → G in HH2; phenotype consistent with Kallmann syndrome; the patient also carries a rare variant in DUSP6. 1 PublicationCorresponds to variant dbSNP:rs397515445EnsemblClinVar. | 1 | ||
| Natural variantiVAR_031002 | 693 | I → F in HH2. 1 Publication | 1 | ||
| Natural variantiVAR_031003 | 703 | G → R in HH2. 1 Publication | 1 | ||
| Natural variantiVAR_031004 | 703 | G → S in HH2. 1 PublicationCorresponds to variant dbSNP:rs768957161Ensembl. | 1 | ||
| Natural variantiVAR_017891 | 719 | M → R in HH2. 1 Publication | 1 | ||
| Natural variantiVAR_074014 | 719 | M → V in HH2; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs1085307879EnsemblClinVar. | 1 | ||
| Natural variantiVAR_031005 | 722 | P → H in HH2; associated with K-724; also found in a family member with isolated anosmia; reduced tyrosine kinase activity. 2 PublicationsCorresponds to variant dbSNP:rs267606805EnsemblClinVar. | 1 | ||
| Natural variantiVAR_031006 | 722 | P → S in HH2. 1 PublicationCorresponds to variant dbSNP:rs121909642EnsemblClinVar. | 1 | ||
| Natural variantiVAR_031007 | 724 | N → K in HH2; associated with H-722; also found in a family member with isolated anosmia; reduced tyrosine kinase activity. 2 PublicationsCorresponds to variant dbSNP:rs267606806EnsemblClinVar. | 1 | ||
| Natural variantiVAR_031008 | 745 | P → S in HH2. 2 Publications | 1 | ||
| Natural variantiVAR_069959 | 768 | D → Y in HH2; the patient also carries a rare variant in FGF8. 1 PublicationCorresponds to variant dbSNP:rs121909644EnsemblClinVar. | 1 | ||
| Natural variantiVAR_031010 | 795 | V → I in HH2; also found in a family member with isolated anosmia. 1 PublicationCorresponds to variant dbSNP:rs781328162Ensembl. | 1 | ||
| Isoform 19 (identifier: P11362-19) | |||||
| Natural varianti | 353 | A → T in HH2, unknown pathological significance. 1 Publication | 1 | ||
Osteoglophonic dysplasia (OGD)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionCharacterized by craniosynostosis, prominent supraorbital ridge, and depressed nasal bridge, as well as by rhizomelic dwarfism and nonossifying bone lesions. Inheritance is autosomal dominant.
See also OMIM:166250| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Natural variantiVAR_030987 | 330 | N → I in OGD. 2 PublicationsCorresponds to variant dbSNP:rs121909632EnsemblClinVar. | 1 | |
| Natural variantiVAR_030993 | 374 | Y → C in OGD; elevated basal activity and increased FGF2-mediated activity. 1 PublicationCorresponds to variant dbSNP:rs121909631EnsemblClinVar. | 1 | |
| Natural variantiVAR_030994 | 381 | C → R in OGD. 2 PublicationsCorresponds to variant dbSNP:rs121909634EnsemblClinVar. | 1 |
Hartsfield syndrome (HRTFDS)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA syndrome characterized by the triad of holoprosencephaly, ectrodactyly, and cleft/lip palate. Profound mental retardation is also present. Multiple other congenital anomalies usually occur.
See also OMIM:615465| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Natural variantiVAR_070851 | 165 | L → S in HRTFDS. 1 PublicationCorresponds to variant dbSNP:rs397515481EnsemblClinVar. | 1 | |
| Natural variantiVAR_070852 | 191 | L → S in HRTFDS. 1 PublicationCorresponds to variant dbSNP:rs869025669EnsemblClinVar. | 1 | |
| Natural variantiVAR_070853 | 490 | G → R in HRTFDS. 1 PublicationCorresponds to variant dbSNP:rs869025670EnsemblClinVar. | 1 | |
| Natural variantiVAR_070854 | 623 | D → Y in HRTFDS. 1 PublicationCorresponds to variant dbSNP:rs398122946EnsemblClinVar. | 1 | |
| Natural variantiVAR_071460 | 627 | R → T in HRTFDS. 1 PublicationCorresponds to variant dbSNP:rs869025671EnsemblClinVar. | 1 | |
| Natural variantiVAR_070855 | 628 | N → K in HRTFDS. 1 PublicationCorresponds to variant dbSNP:rs869025672EnsemblClinVar. | 1 | |
| Natural variantiVAR_070856 | 725 | C → Y in HRTFDS. 1 PublicationCorresponds to variant dbSNP:rs398122945EnsemblClinVar. | 1 |
Trigonocephaly 1 (TRIGNO1)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA keel-shaped deformation of the forehead, caused by premature fusion of the metopic sutures. It results in a triangular shape of the head.
See also OMIM:190440| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Natural variantiVAR_030986 | 300 | I → T in TRIGNO1. 1 PublicationCorresponds to variant dbSNP:rs121909633EnsemblClinVar. | 1 |
A chromosomal aberration involving FGFR1 may be a cause of stem cell leukemia lymphoma syndrome (SCLL). Translocation t(8;13)(p11;q12) with ZMYM2. SCLL usually presents as lymphoblastic lymphoma in association with a myeloproliferative disorder, often accompanied by pronounced peripheral eosinophilia and/or prominent eosinophilic infiltrates in the affected bone marrow.1 Publication
A chromosomal aberration involving FGFR1 may be a cause of stem cell myeloproliferative disorder (MPD). Translocation t(6;8)(q27;p11) with FGFR1OP. Insertion ins(12;8)(p11;p11p22) with FGFR1OP2. MPD is characterized by myeloid hyperplasia, eosinophilia and T-cell or B-cell lymphoblastic lymphoma. In general it progresses to acute myeloid leukemia. The fusion proteins FGFR1OP2-FGFR1, FGFR1OP-FGFR1 or FGFR1-FGFR1OP may exhibit constitutive kinase activity and be responsible for the transforming activity.5 Publications
A chromosomal aberration involving FGFR1 may be a cause of stem cell myeloproliferative disorder (MPD). Translocation t(8;9)(p12;q33) with CNTRL. MPD is characterized by myeloid hyperplasia, eosinophilia and T-cell or B-cell lymphoblastic lymphoma. In general it progresses to acute myeloid leukemia. The fusion protein CNTRL-FGFR1 is found in the cytoplasm, exhibits constitutive kinase activity and may be responsible for the transforming activity.
Encephalocraniocutaneous lipomatosis (ECCL)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA sporadically occurring, neurocutaneous disorder characterized by ocular anomalies, skin lesions, and central nervous system anomalies. Clinical features include a well-demarcated hairless fatty nevus on the scalp, benign ocular tumors, intracranial and intraspinal lipomas, and congenital abnormalities of the meninges. Seizures, spasticity, and intellectual disability can be present.
See also OMIM:613001| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Natural variantiVAR_075853 | 546 | N → K in ECCL; somatic mutation; activating mutation; strongly increased speed of the first autophosphorylation and loss of the normal sequential order of autophosphorylation. 2 PublicationsCorresponds to variant dbSNP:rs779707422EnsemblClinVar. | 1 | |
| Natural variantiVAR_075855 | 656 | K → E in ECCL; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs869320694EnsemblClinVar. | 1 |
Jackson-Weiss syndrome (JWS)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn autosomal dominant craniosynostosis syndrome characterized by craniofacial abnormalities and abnormality of the feet: broad great toes with medial deviation and tarsal-metatarsal coalescence.
See also OMIM:123150| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Natural variantiVAR_004111 | 252 | P → R in PS and JWS. 2 PublicationsCorresponds to variant dbSNP:rs121909627EnsemblClinVar. | 1 |
Mutagenesis
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Mutagenesisi | 514 | K → A: Loss of kinase activity. 1 Publication | 1 | |
| Mutagenesisi | 577 | R → E: Strongly reduced autophosphorylation in response to FGF signaling. No effect on in vitro kinase activity. 1 Publication | 1 | |
| Mutagenesisi | 609 | R → V: Abolishes interaction with PLCG1. | 1 | |
| Mutagenesisi | 623 | D → A: Loss of kinase activity. 1 Publication | 1 | |
| Mutagenesisi | 653 | Y → F: No effect on kinase activity. Loss of autophosphorylation and kinase activity; when associated with F-654. 1 Publication | 1 | |
| Mutagenesisi | 654 | Y → F: Reduced kinase activity. Loss of autophosphorylation and kinase activity; when associated with F-653. 1 Publication | 1 | |
| Mutagenesisi | 755 | D → V: Abolishes interaction with PLCG1. | 1 | |
| Mutagenesisi | 766 | Y → F: Abolishes interaction with PLCG1 and SHB. Decreases phosphorylation of FRS2, activation of RAS and MAP kinase signaling and stimulation of cell proliferation. 4 Publications | 1 |
Sites
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Sitei | 428 – 429 | Breakpoint for translocation to form CNTRL-FGFR1 OR FGFR1-CNTRL fusion proteins1 Publication | 2 | |
| Sitei | 428 – 429 | Breakpoint for translocation to form FGFR1OP-FGFR1 or FGFR1-FGFR1OP fusion proteins1 Publication | 2 | |
| Sitei | 428 – 429 | Breakpoint for translocation to form FGFR1OP2-FGFR13 Publications | 2 |
Keywords - Diseasei
Craniosynostosis, Disease mutation, Dwarfism, Holoprosencephaly, Hypogonadotropic hypogonadism, Kallmann syndrome, Mental retardationOrganism-specific databases
| DisGeNETi | 2260 |
| GeneReviewsi | FGFR1 |
| MalaCardsi | FGFR1 |
| MIMi | 101600 phenotype 123150 phenotype 147950 phenotype 166250 phenotype 190440 phenotype 613001 phenotype 615465 phenotype |
| OpenTargetsi | ENSG00000077782 |
| Orphaneti | 2396 Encephalocraniocutaneous lipomatosis 251579 Giant cell glioblastoma 251576 Gliosarcoma 2117 Hartsfield syndrome 3366 Isolated trigonocephaly 478 Kallmann syndrome 93924 Lobar holoprosencephaly 280200 Microform holoprosencephaly 168953 Myeloid/lymphoid neoplasm associated with FGFR1 rearrangement 2227 NON RARE IN EUROPE: Hypodontia 432 Normosmic congenital hypogonadotropic hypogonadism 99798 Oligodontia 2645 Osteoglosphonic dysplasia 93258 Pfeiffer syndrome type 1 251615 Pilomyxoid astrocytoma 314950 Primary hypereosinophilic syndrome 220386 Semilobar holoprosencephaly 3157 Septo-optic dysplasia spectrum |
| PharmGKBi | PA28127 |
Chemistry databases
| ChEMBLi | CHEMBL3650 |
| DrugBanki | DB08577 3-[(3-(2-CARBOXYETHYL)-4-METHYLPYRROL-2-YL)METHYLENE]-2-INDOLINONE DB09078 Lenvatinib DB09079 Nintedanib DB00039 Palifermin DB08901 Ponatinib DB08896 Regorafenib DB00398 Sorafenib DB02058 SU4984 DB05014 XL999 |
| GuidetoPHARMACOLOGYi | 1808 |
Polymorphism and mutation databases
| BioMutai | FGFR1 |
| DMDMi | 120046 |
PTM / Processingi
Molecule processing
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Signal peptidei | 1 – 21 | Add BLAST | 21 | |
| ChainiPRO_0000016780 | 22 – 822 | Fibroblast growth factor receptor 1Add BLAST | 801 |
Amino acid modifications
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Disulfide bondi | 55 ↔ 101 | PROSITE-ProRule annotation | ||
| Glycosylationi | 77 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
| Glycosylationi | 117 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
| Disulfide bondi | 178 ↔ 230 | |||
| Glycosylationi | 227 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
| Glycosylationi | 240 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
| Glycosylationi | 264 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
| Disulfide bondi | 277 ↔ 341 | |||
| Glycosylationi | 296 | N-linked (GlcNAc...) asparagine1 Publication | 1 | |
| Glycosylationi | 317 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
| Glycosylationi | 330 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
| Modified residuei | 463 | Phosphotyrosine; by autocatalysis3 Publications | 1 | |
| Modified residuei | 583 | Phosphotyrosine; by autocatalysis3 Publications | 1 | |
| Modified residuei | 585 | Phosphotyrosine; by autocatalysis3 Publications | 1 | |
| Modified residuei | 653 | Phosphotyrosine; by autocatalysis4 Publications | 1 | |
| Modified residuei | 654 | Phosphotyrosine; by autocatalysis4 Publications | 1 | |
| Modified residuei | 730 | Phosphotyrosine; by autocatalysis2 Publications | 1 | |
| Modified residuei | 766 | Phosphotyrosine; by autocatalysis1 Publication | 1 |
Post-translational modificationi
Autophosphorylated. Binding of FGF family members together with heparan sulfate proteoglycan or heparin promotes receptor dimerization and autophosphorylation on tyrosine residues. Autophosphorylation occurs in trans between the two FGFR molecules present in the dimer and proceeds in a highly ordered manner. Initial autophosphorylation at Tyr-653 increases the kinase activity by a factor of 50 to 100. After this, Tyr-583 becomes phosphorylated, followed by phosphorylation of Tyr-463, Tyr-766, Tyr-583 and Tyr-585. In a third stage, Tyr-654 is autophosphorylated, resulting in a further tenfold increase of kinase activity. Phosphotyrosine residues provide docking sites for interacting proteins and so are crucial for FGFR1 function and its regulation.4 Publications
Ubiquitinated. FGFR1 is rapidly ubiquitinated by NEDD4 after autophosphorylation, leading to internalization and lysosomal degradation. CBL is recruited to activated FGFR1 via FRS2 and GRB2, and mediates ubiquitination and subsequent degradation of FGFR1.2 Publications
N-glycosylated in the endoplasmic reticulum. The N-glycan chains undergo further maturation to an Endo H-resistant form in the Golgi apparatus.3 Publications
Keywords - PTMi
Disulfide bond, Glycoprotein, Phosphoprotein, Ubl conjugationProteomic databases
| EPDi | P11362 |
| jPOSTi | P11362 |
| MaxQBi | P11362 |
| PaxDbi | P11362 |
| PeptideAtlasi | P11362 |
| PRIDEi | P11362 |
| ProteomicsDBi | 52745 52746 [P11362-10] 52747 [P11362-11] 52748 [P11362-12] 52749 [P11362-13] 52750 [P11362-14] 52751 [P11362-15] 52752 [P11362-16] 52753 [P11362-17] 52754 [P11362-18] 52755 [P11362-19] 52756 [P11362-2] 52757 [P11362-20] 52758 [P11362-21] 52759 [P11362-3] 52760 [P11362-4] 52761 [P11362-5] 52762 [P11362-6] 52763 [P11362-7] 52764 [P11362-8] 52765 [P11362-9] |
PTM databases
| CarbonylDBi | P11362 |
| GlyConnecti | 1239 |
| iPTMneti | P11362 |
| PhosphoSitePlusi | P11362 |
| SwissPalmi | P11362 |
Miscellaneous databases
| PMAP-CutDBi | P11362 |
Expressioni
Tissue specificityi
Detected in astrocytoma, neuroblastoma and adrenal cortex cell lines. Some isoforms are detected in foreskin fibroblast cell lines, however isoform 17, isoform 18 and isoform 19 are not detected in these cells.1 Publication
Gene expression databases
| Bgeei | ENSG00000077782 Expressed in 240 organ(s), highest expression level in body of pancreas |
| ExpressionAtlasi | P11362 baseline and differential |
| Genevisiblei | P11362 HS |
Organism-specific databases
| HPAi | CAB033614 HPA056402 HPA076274 |
Interactioni
Subunit structurei
Monomer. Homodimer after ligand binding. Interacts predominantly with FGF1 and FGF2, but can also interact with FGF3, FGF4, FGF5, FGF6, FGF8, FGF10, FGF19, FGF21, FGF22 and FGF23 (in vitro) (PubMed:1697263, PubMed:1722683, PubMed:8663044, PubMed:9655399, PubMed:12181353, PubMed:16597617, PubMed:17623664). Ligand specificity is determined by tissue-specific expression of isoforms, and differences in the third Ig-like domain are crucial for ligand specificity. Affinity for fibroblast growth factors (FGFs) is increased by heparan sulfate glycosaminoglycans that function as coreceptors. Likewise, KLB increases the affinity for FGF19, FGF21 and FGF23 (PubMed:19966287). Interacts (phosphorylated on Tyr-766) with PLCG1 (via SH2 domains) (PubMed:1656221, PubMed:1379697, PubMed:21765395). Interacts with FRS2 (PubMed:21765395). Interacts with RPS6KA1 (PubMed:15117958). Interacts (via C-terminus) with NEDD4 (via WW3 domain) (PubMed:21765395). Interacts with KL (By similarity). Interacts with SHB (via SH2 domain) (PubMed:12181353). Interacts with GRB10 (PubMed:10454568). Interacts with ANOS1; this interaction does not interfere with FGF2-binding to FGFR1, but prevents binding of heparin-bound FGF2 (PubMed:19696444). Interacts with SOX2 and SOX3. Interacts with FLRT1, FLRT2 and FLRT3 (By similarity). Found in a ternary complex with FGF1 and ITGAV:ITGB3 (PubMed:20422052, PubMed:18441324).By similarity16 Publications
Binary interactionsi
GO - Molecular functioni
- fibroblast growth factor binding Source: UniProtKB
- identical protein binding Source: IntAct
- protein homodimerization activity Source: UniProtKB
- Ras guanyl-nucleotide exchange factor activity Source: Reactome
- receptor-receptor interaction Source: ParkinsonsUK-UCL
- SH2 domain binding Source: Ensembl
Protein-protein interaction databases
| BioGridi | 108551, 180 interactors |
| CORUMi | P11362 |
| DIPi | DIP-4019N |
| IntActi | P11362, 31 interactors |
| MINTi | P11362 |
| STRINGi | 9606.ENSP00000393312 |
Chemistry databases
| BindingDBi | P11362 |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
| Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
| 1AGW | X-ray | 2.40 | A/B | 456-765 | [»] | |
| 1CVS | X-ray | 2.80 | C/D | 141-365 | [»] | |
| 1EVT | X-ray | 2.80 | C/D | 141-365 | [»] | |
| 1FGI | X-ray | 2.50 | A/B |