Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Fibroblast growth factor receptor 1

Gene

FGFR1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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 + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.PROSITE-ProRule annotation7 Publications

Enzyme 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 keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei514ATP1
Binding sitei568ATP1
Active sitei623Proton acceptorPROSITE-ProRule annotation1 Publication1
Binding sitei627ATP1
Binding sitei641ATP1
Sitei766Mediates interaction with PLCG1 and SHB1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi484 – 490ATP7
Nucleotide bindingi562 – 564ATP3

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

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Kinase, Receptor, Transferase, Tyrosine-protein kinase

Keywords - Biological processi

Transcription, Transcription regulation

Keywords - Ligandi

ATP-binding, Heparin-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciZFISH:HS01257-MONOMER.
BRENDAi2.7.10.1. 2681.
ReactomeiR-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.
SignaLinkiP11362.
SIGNORiP11362.

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
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 8

Organism-specific databases

HGNCiHGNC:3688. FGFR1.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini22 – 376ExtracellularSequence analysisAdd BLAST355
Transmembranei377 – 397HelicalSequence analysisAdd BLAST21
Topological domaini398 – 822CytoplasmicSequence analysisAdd BLAST425

GO - Cellular componenti

  • cytoplasmic, membrane-bounded vesicle Source: UniProtKB-SubCell
  • cytosol Source: UniProtKB-SubCell
  • extracellular region Source: UniProtKB
  • integral component of membrane Source: UniProtKB
  • integral component of plasma membrane Source: ProtInc
  • nucleus Source: UniProtKB-SubCell
  • plasma membrane Source: UniProtKB
  • receptor complex Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Cytoplasmic vesicle, Membrane, Nucleus

Pathology & 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 keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_004111252P → R in PS and JWS. 2 PublicationsCorresponds to variant rs121909627dbSNPEnsembl.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 keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0740124W → C in HH2; unknown pathological significance. 1 PublicationCorresponds to variant rs760884357dbSNPEnsembl.1
Natural variantiVAR_03096848G → S in HH2; phenotype consistent with normosmic idiopathic hypogonadotropic hypogonadism. 1 PublicationCorresponds to variant rs121909640dbSNPEnsembl.1
Natural variantiVAR_07299370G → R in HH2. 1 PublicationCorresponds to variant rs140254426dbSNPEnsembl.1
Natural variantiVAR_03097078R → C in HH2. 1 Publication1
Natural variantiVAR_07401396S → C in HH2; unknown pathological significance. 1 Publication1
Natural variantiVAR_01788597G → D in HH2. 1 Publication1
Natural variantiVAR_01788699Y → C in HH2; impairs the tertiary folding resulting in incomplete glycosylation and reduced cell surface expression. 2 PublicationsCorresponds to variant rs727505373dbSNPEnsembl.1
Natural variantiVAR_030971101C → F in HH2. 1 Publication1
Natural variantiVAR_030972102V → I in HH2. 2 PublicationsCorresponds to variant rs55642501dbSNPEnsembl.1
Natural variantiVAR_072994116V → I in HH2. 1 PublicationCorresponds to variant rs747842199dbSNPEnsembl.1
Natural variantiVAR_069288117N → S in HH2; some patients also carry GNRHR mutations. 2 PublicationsCorresponds to variant rs780765366dbSNPEnsembl.1
Natural variantiVAR_030973129D → A in HH2. 1 PublicationCorresponds to variant rs765615419dbSNPEnsembl.1
Natural variantiVAR_017887167A → S in HH2; with cleft palate, corpus callosum agenesis, unilateral deafness and fusion of fourth and fifth metacarpal bones. 1 PublicationCorresponds to variant rs121909630dbSNPEnsembl.1
Natural variantiVAR_072995174V → A in HH2. 1 Publication1
Natural variantiVAR_030974178C → S in HH2; with severe ear anomalies. 1 Publication1
Natural variantiVAR_030976224D → H in HH2. 1 Publication1
Natural variantiVAR_069289228Y → D in HH2; some patients also carry KISS1R mutations; impairs the tertiary folding resulting in incomplete glycosylation and reduced cell surface expression. 2 Publications1
Natural variantiVAR_030977237G → D in HH2. 1 Publication1
Natural variantiVAR_030978237G → S in HH2; with or without anosmia; also found in a family member with isolated anosmia; may impair proper folding. 1 PublicationCorresponds to variant rs121909635dbSNPEnsembl.1
Natural variantiVAR_069290239I → 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 Publications1
Natural variantiVAR_030979245L → P in HH2. 1 Publication1
Natural variantiVAR_069291250R → 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 rs121909645dbSNPEnsembl.1
Natural variantiVAR_030980250R → W in HH2. 2 Publications1
Natural variantiVAR_030981254R → Q in HH2. 1 Publication1
Natural variantiVAR_030982270G → D in HH2. 1 Publication1
Natural variantiVAR_030983273V → M in HH2. 2 Publications1
Natural variantiVAR_030984274E → G in HH2; also found in a family member with isolated anosmia. Corresponds to variant rs727505369dbSNPEnsembl.1
Natural variantiVAR_017888277C → Y in HH2. 1 Publication1
Natural variantiVAR_030985283P → R in HH2. 1 Publication1
Natural variantiVAR_030988332S → C in HH2. 1 Publication1
Natural variantiVAR_030989339Y → C in HH2. 1 Publication1
Natural variantiVAR_069954342L → S in HH2; phenotype consistent with Kallmann syndrome; the patient also carries a splice site mutation in NSMF. 1 PublicationCorresponds to variant rs121909638dbSNPEnsembl.1
Natural variantiVAR_030990343A → V in HH2. 1 Publication1
Natural variantiVAR_030991346S → C in HH2; also found in a family member with isolated anosmia. 1 Publication1
Natural variantiVAR_069955348G → R in HH2; phenotype consistent with Kallmann syndrome; the patient also carries a mutation in IL17RD. 2 Publications1
Natural variantiVAR_030992366P → L in HH2; with or without anosmia. 1 PublicationCorresponds to variant rs121909641dbSNPEnsembl.1
Natural variantiVAR_069292470R → L in HH2; some patients also carry GNRHR mutations. 2 PublicationsCorresponds to variant rs121909637dbSNPEnsembl.1
Natural variantiVAR_069956483P → T in HH2; phenotype consistent with Kallmann syndrome; the patient also carries a rare variant in SPRY4. 1 PublicationCorresponds to variant rs397515444dbSNPEnsembl.1
Natural variantiVAR_030995520A → T in HH2. 1 PublicationCorresponds to variant rs749758370dbSNPEnsembl.1
Natural variantiVAR_030996538I → V in HH2. 1 Publication1
Natural variantiVAR_017889607V → M in HH2; with bimanual synkinesis. 1 PublicationCorresponds to variant rs121909629dbSNPEnsembl.1
Natural variantiVAR_069293618K → N in HH2; some patients also carry GNRHR mutations; impairs tyrosine kinase activity. 2 Publications1
Natural variantiVAR_030997621H → R in HH2. 1 Publication1
Natural variantiVAR_030998622R → G in HH2; with severe ear anomalies. 1 Publication1
Natural variantiVAR_030999622R → Q in HH2. 1 Publication1
Natural variantiVAR_017890666W → R in HH2; with cleft palate. 1 Publication1
Natural variantiVAR_069957670E → K in HH2; phenotype consistent with Kallmann syndrome; the patient also carries a rare variant in FLRT3. 1 PublicationCorresponds to variant rs397515446dbSNPEnsembl.1
Natural variantiVAR_069294671A → P in HH2. 1 Publication1
Natural variantiVAR_031000685S → F in HH2. 1 Publication1
Natural variantiVAR_031001687G → R in HH2. 2 PublicationsCorresponds to variant rs727505376dbSNPEnsembl.1
Natural variantiVAR_069958692E → G in HH2; phenotype consistent with Kallmann syndrome; the patient also carries a rare variant in DUSP6. 1 PublicationCorresponds to variant rs397515445dbSNPEnsembl.1
Natural variantiVAR_031002693I → F in HH2. 1 Publication1
Natural variantiVAR_031003703G → R in HH2. 1 Publication1
Natural variantiVAR_031004703G → S in HH2. 1 PublicationCorresponds to variant rs768957161dbSNPEnsembl.1
Natural variantiVAR_017891719M → R in HH2. 1 Publication1
Natural variantiVAR_074014719M → V in HH2; unknown pathological significance. 1 Publication1
Natural variantiVAR_031005722P → H in HH2; associated with K-724; also found in a family member with isolated anosmia; reduced tyrosine kinase activity. 2 PublicationsCorresponds to variant rs267606805dbSNPEnsembl.1
Natural variantiVAR_031006722P → S in HH2. 1 PublicationCorresponds to variant rs121909642dbSNPEnsembl.1
Natural variantiVAR_031007724N → K in HH2; associated with H-722; also found in a family member with isolated anosmia; reduced tyrosine kinase activity. 2 PublicationsCorresponds to variant rs267606806dbSNPEnsembl.1
Natural variantiVAR_031008745P → S in HH2. 2 Publications1
Natural variantiVAR_069959768D → Y in HH2; the patient also carries a rare variant in FGF8. 1 PublicationCorresponds to variant rs121909644dbSNPEnsembl.1
Natural variantiVAR_017892772P → S in HH2; with cleft palate, unilateral absence of nasal cartilage, iris coloboma. 2 PublicationsCorresponds to variant rs56234888dbSNPEnsembl.1
Natural variantiVAR_031010795V → I in HH2; also found in a family member with isolated anosmia. 1 PublicationCorresponds to variant rs781328162dbSNPEnsembl.1
Isoform 19 (identifier: P11362-19)
Natural varianti353A → T in HH2, unknown pathological significance. 1 Publication1
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 keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_030987330N → I in OGD. 2 PublicationsCorresponds to variant rs121909632dbSNPEnsembl.1
Natural variantiVAR_030993374Y → C in OGD; elevated basal activity and increased FGF2-mediated activity. 1 PublicationCorresponds to variant rs121909631dbSNPEnsembl.1
Natural variantiVAR_030994381C → R in OGD. 2 PublicationsCorresponds to variant rs121909634dbSNPEnsembl.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 keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_070851165L → S in HRTFDS. 1 PublicationCorresponds to variant rs397515481dbSNPEnsembl.1
Natural variantiVAR_070852191L → S in HRTFDS. 1 Publication1
Natural variantiVAR_070853490G → R in HRTFDS. 1 Publication1
Natural variantiVAR_070854623D → Y in HRTFDS. 1 PublicationCorresponds to variant rs398122946dbSNPEnsembl.1
Natural variantiVAR_071460627R → T in HRTFDS. 1 Publication1
Natural variantiVAR_070855628N → K in HRTFDS. 1 Publication1
Natural variantiVAR_070856725C → Y in HRTFDS. 1 PublicationCorresponds to variant rs398122945dbSNPEnsembl.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 keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_030986300I → T in TRIGNO1. 1 PublicationCorresponds to variant rs121909633dbSNPEnsembl.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.

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.

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)1 Publication
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 keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_075853546N → K in ECCL; somatic mutation; activating mutation; strongly increased speed of the first autophosphorylation and loss of the normal sequential order of autophosphorylation. 2 Publications1
Natural variantiVAR_075855656K → E in ECCL; somatic mutation. 1 Publication1
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 keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_004111252P → R in PS and JWS. 2 PublicationsCorresponds to variant rs121909627dbSNPEnsembl.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi514K → A: Loss of kinase activity. 1 Publication1
Mutagenesisi577R → E: Strongly reduced autophosphorylation in response to FGF signaling. No effect on in vitro kinase activity. 1 Publication1
Mutagenesisi609R → V: Abolishes interaction with PLCG1. 1
Mutagenesisi623D → A: Loss of kinase activity. 1 Publication1
Mutagenesisi653Y → F: No effect on kinase activity. Loss of autophosphorylation and kinase activity; when associated with F-654. 1 Publication1
Mutagenesisi654Y → F: Reduced kinase activity. Loss of autophosphorylation and kinase activity; when associated with F-653. 1 Publication1
Mutagenesisi755D → V: Abolishes interaction with PLCG1. 1
Mutagenesisi766Y → F: Abolishes interaction with PLCG1 and SHB. Decreases phosphorylation of FRS2, activation of RAS and MAP kinase signaling and stimulation of cell proliferation. 4 Publications1

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei428 – 429Breakpoint for translocation to form CNTRL-FGFR1 OR FGFR1-CNTRL fusion proteins1 Publication2
Sitei428 – 429Breakpoint for translocation to form FGFR1OP-FGFR1 or FGFR1-FGFR1OP fusion proteins1 Publication2
Sitei428 – 429Breakpoint for translocation to form FGFR1OP2-FGFR13 Publications2

Keywords - Diseasei

Craniosynostosis, Disease mutation, Dwarfism, Holoprosencephaly, Hypogonadotropic hypogonadism, Kallmann syndrome, Mental retardation

Organism-specific databases

DisGeNETi2260.
MalaCardsiFGFR1.
MIMi101600. phenotype.
123150. phenotype.
147950. phenotype.
166250. phenotype.
190440. phenotype.
613001. phenotype.
615465. phenotype.
OpenTargetsiENSG00000077782.
Orphaneti251579. Giant cell glioblastoma.
251576. Gliosarcoma.
2117. Hartsfield-Bixler-Demyer syndrome.
2227. Hypodontia.
3366. Isolated trigonocephaly.
478. Kallmann syndrome.
168953. Myeloid neoplasm associated with FGFR1 rearrangement.
432. Normosmic congenital hypogonadotropic hypogonadism.
99798. Oligodontia.
2645. Osteoglophonic dwarfism.
93258. Pfeiffer syndrome type 1.
251612. Pilocytic astrocytoma.
314950. Primary hypereosinophilic syndrome.
3157. Septo-optic dysplasia.
PharmGKBiPA28127.

Chemistry databases

ChEMBLiCHEMBL3650.
DrugBankiDB09078. Lenvatinib.
DB09079. Nintedanib.
DB00039. Palifermin.
DB08901. Ponatinib.
DB08896. Regorafenib.
DB00398. Sorafenib.
GuidetoPHARMACOLOGYi1808.

Polymorphism and mutation databases

BioMutaiFGFR1.
DMDMi120046.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 21Add BLAST21
ChainiPRO_000001678022 – 822Fibroblast growth factor receptor 1Add BLAST801

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi55 ↔ 101PROSITE-ProRule annotation
Glycosylationi77N-linked (GlcNAc...)Sequence analysis1
Glycosylationi117N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi178 ↔ 230
Glycosylationi227N-linked (GlcNAc...)Sequence analysis1
Glycosylationi240N-linked (GlcNAc...)Sequence analysis1
Glycosylationi264N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi277 ↔ 341
Glycosylationi296N-linked (GlcNAc...)1 Publication1
Glycosylationi317N-linked (GlcNAc...)Sequence analysis1
Glycosylationi330N-linked (GlcNAc...)Sequence analysis1
Modified residuei463Phosphotyrosine; by autocatalysis3 Publications1
Modified residuei583Phosphotyrosine; by autocatalysis3 Publications1
Modified residuei585Phosphotyrosine; by autocatalysis3 Publications1
Modified residuei653Phosphotyrosine; by autocatalysis4 Publications1
Modified residuei654Phosphotyrosine; by autocatalysis4 Publications1
Modified residuei730Phosphotyrosine; by autocatalysis2 Publications1
Modified residuei766Phosphotyrosine; by autocatalysis1 Publication1

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 conjugation

Proteomic databases

EPDiP11362.
MaxQBiP11362.
PaxDbiP11362.
PeptideAtlasiP11362.
PRIDEiP11362.

PTM databases

iPTMnetiP11362.
PhosphoSitePlusiP11362.
SwissPalmiP11362.

Miscellaneous databases

PMAP-CutDBP11362.

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

BgeeiENSG00000077782.
CleanExiHS_FGFR1.
HS_FLG.
ExpressionAtlasiP11362. baseline and differential.
GenevisibleiP11362. HS.

Organism-specific databases

HPAiCAB033614.
HPA056402.

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

WithEntry#Exp.IntActNotes
itself3EBI-1028277,EBI-1028277
ANOS1P233527EBI-1028277,EBI-5272188
CDH1P128303EBI-1028277,EBI-727477
CRKP461082EBI-1028277,EBI-886
CTNNB1P352222EBI-1028277,EBI-491549
FGF1P052303EBI-1028277,EBI-698068
FGF2P090385EBI-1028277,EBI-977447
Grb14O889003EBI-1028277,EBI-7639197From a different organism.
HTR1AP0890811EBI-1028277,EBI-6570214
NEDD4P4693426EBI-1028277,EBI-726944
NOSTRINQ8IVI95EBI-1028277,EBI-1391643
PIK3R1P279865EBI-1028277,EBI-79464
PLCG1P191745EBI-1028277,EBI-79387
Plcg1P106864EBI-1028277,EBI-520788From a different organism.

GO - Molecular functioni

  • fibroblast growth factor binding Source: UniProtKB
  • identical protein binding Source: IntAct
  • protein homodimerization activity Source: UniProtKB

Protein-protein interaction databases

BioGridi108551. 70 interactors.
DIPiDIP-4019N.
IntActiP11362. 26 interactors.
MINTiMINT-1499363.
STRINGi9606.ENSP00000393312.

Chemistry databases

BindingDBiP11362.

Structurei

Secondary structure

1822
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi40 – 42Combined sources3
Beta strandi51 – 54Combined sources4
Beta strandi63 – 72Combined sources10
Beta strandi77 – 81Combined sources5
Beta strandi83 – 88Combined sources6
Turni93 – 95Combined sources3
Beta strandi97 – 105Combined sources9
Beta strandi108 – 116Combined sources9
Beta strandi151 – 156Combined sources6
Helixi158 – 161Combined sources4
Helixi165 – 183Combined sources19
Beta strandi187 – 192Combined sources6
Helixi199 – 201Combined sources3
Beta strandi207 – 209Combined sources3
Turni210 – 213Combined sources4
Beta strandi214 – 219Combined sources6
Helixi222 – 224Combined sources3
Beta strandi226 – 234Combined sources9
Beta strandi237 – 248Combined sources12
Beta strandi265 – 267Combined sources3
Beta strandi273 – 276Combined sources4
Beta strandi286 – 293Combined sources8
Beta strandi295 – 297Combined sources3
Beta strandi306 – 313Combined sources8
Helixi320 – 323Combined sources4
Beta strandi325 – 328Combined sources4
Helixi333 – 335Combined sources3
Beta strandi337 – 344Combined sources8
Beta strandi349 – 358Combined sources10
Helixi460 – 462Combined sources3
Turni469 – 471Combined sources3
Helixi475 – 477Combined sources3
Beta strandi478 – 486Combined sources9
Beta strandi488 – 499Combined sources12
Beta strandi501 – 503Combined sources3
Beta strandi508 – 516Combined sources9
Helixi522 – 538Combined sources17
Beta strandi547 – 551Combined sources5
Beta strandi553 – 555Combined sources3
Beta strandi558 – 562Combined sources5
Helixi569 – 574Combined sources6
Beta strandi579 – 583Combined sources5
Beta strandi584 – 586Combined sources3
Helixi591 – 593Combined sources3
Helixi597 – 616Combined sources20
Helixi626 – 628Combined sources3
Beta strandi629 – 631Combined sources3
Beta strandi637 – 639Combined sources3
Beta strandi641 – 643Combined sources3
Helixi648 – 650Combined sources3
Beta strandi653 – 655Combined sources3
Beta strandi658 – 660Combined sources3
Helixi663 – 666Combined sources4
Helixi669 – 674Combined sources6
Beta strandi676 – 678Combined sources3
Helixi679 – 694Combined sources16
Helixi706 – 714Combined sources9
Beta strandi722 – 724Combined sources3
Helixi727 – 736Combined sources10
Helixi741 – 743Combined sources3
Helixi747 – 760Combined sources14

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1AGWX-ray2.40A/B456-765[»]
1CVSX-ray2.80C/D141-365[»]
1EVTX-ray2.80C/D141-365[»]
1FGIX-ray2.50A/B456-765[»]
1FGKX-ray2.00A/B456-765[»]
1FQ9X-ray3.00C/D141-365[»]
1XR0NMR-A409-430[»]
2CR3NMR-A38-123[»]
2FGIX-ray2.50A/B456-765[»]
3C4FX-ray2.07A/B464-765[»]
3DPKX-ray1.95A577-615[»]
3GQIX-ray2.50A458-774[»]
3GQLX-ray2.80A/B/C458-774[»]
3JS2X-ray2.20A/B458-765[»]
3KRJX-ray2.10A577-597[»]
3KRLX-ray2.40A577-597[»]
3KXXX-ray3.20A/B/C/D458-765[»]
3KY2X-ray2.70A/B458-765[»]
3OJVX-ray2.60C/D142-365[»]
3RHXX-ray2.01A/B461-765[»]
3TT0X-ray2.80A/B456-765[»]
4F63X-ray2.55A/B458-765[»]
4F64X-ray2.05A/B458-765[»]
4F65X-ray2.26A/B458-765[»]
4NK9X-ray2.57A/B458-765[»]
4NKAX-ray2.19A/B458-765[»]
4NKSX-ray2.50A/B458-765[»]
4RWIX-ray2.29A/B458-765[»]
4RWJX-ray2.49A/B458-765[»]
4RWKX-ray2.98A/B458-765[»]
4RWLX-ray2.19A/B458-765[»]
4UWBX-ray2.31A/B458-765[»]
4UWCX-ray1.96A/B458-765[»]
4UWYX-ray2.31A/B458-765[»]
4V01X-ray2.33A/B458-765[»]
4V04X-ray2.12A/B458-765[»]
4V05X-ray2.57A/B458-765[»]
4WUNX-ray1.65A/B459-765[»]
4ZSAX-ray2.00A/B458-765[»]
5A46X-ray2.63A/B437-822[»]
5A4CX-ray2.09A/B461-765[»]
5AM6X-ray1.96A/B458-765[»]
5AM7X-ray1.96A/B458-765[»]
5B7VX-ray2.15A/B456-765[»]
5EW8X-ray1.63A/B458-765[»]
5FLFX-ray2.58A/B/C/D/E458-765[»]
ProteinModelPortaliP11362.
SMRiP11362.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP11362.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini25 – 119Ig-like C2-type 1Add BLAST95
Domaini158 – 246Ig-like C2-type 2Add BLAST89
Domaini255 – 357Ig-like C2-type 3Add BLAST103
Domaini478 – 767Protein kinasePROSITE-ProRule annotationAdd BLAST290

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni160 – 177Heparin-bindingAdd BLAST18

Domaini

The second and third Ig-like domains directly interact with fibroblast growth factors (FGF) and heparan sulfate proteoglycans. Isoforms lacking the first Ig-like domain have higher affinity for fibroblast growth factors (FGF) and heparan sulfate proteoglycans than isoforms with all three Ig-like domains.

Sequence similaritiesi

Belongs to the protein kinase superfamily. Tyr protein kinase family. Fibroblast growth factor receptor subfamily.PROSITE-ProRule annotation
Contains 1 protein kinase domain.PROSITE-ProRule annotation

Keywords - Domaini

Immunoglobulin domain, Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG0200. Eukaryota.
COG0515. LUCA.
GeneTreeiENSGT00760000118923.
HOGENOMiHOG000263410.
HOVERGENiHBG000345.
InParanoidiP11362.
KOiK04362.
OMAiKVRDHMW.
OrthoDBiEOG091G0CQZ.
PhylomeDBiP11362.
TreeFamiTF316307.

Family and domain databases

Gene3Di2.60.40.10. 3 hits.
InterProiIPR028174. FGF_rcpt_1.
IPR016248. FGF_rcpt_fam.
IPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR013098. Ig_I-set.
IPR003599. Ig_sub.
IPR003598. Ig_sub2.
IPR013151. Immunoglobulin.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
IPR008266. Tyr_kinase_AS.
IPR020635. Tyr_kinase_cat_dom.
[Graphical view]
PANTHERiPTHR24416:SF131. PTHR24416:SF131. 1 hit.
PfamiPF07679. I-set. 2 hits.
PF00047. ig. 1 hit.
PF07714. Pkinase_Tyr. 1 hit.
[Graphical view]
PIRSFiPIRSF000628. FGFR. 1 hit.
PRINTSiPR00109. TYRKINASE.
SMARTiSM00409. IG. 3 hits.
SM00408. IGc2. 3 hits.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMiSSF48726. SSF48726. 3 hits.
SSF56112. SSF56112. 1 hit.
PROSITEiPS50835. IG_LIKE. 3 hits.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00109. PROTEIN_KINASE_TYR. 1 hit.
[Graphical view]

Sequences (21)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 21 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P11362-1) [UniParc]FASTAAdd to basket
Also known as: Alpha A1, IV

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MWSWKCLLFW AVLVTATLCT ARPSPTLPEQ AQPWGAPVEV ESFLVHPGDL
60 70 80 90 100
LQLRCRLRDD VQSINWLRDG VQLAESNRTR ITGEEVEVQD SVPADSGLYA
110 120 130 140 150
CVTSSPSGSD TTYFSVNVSD ALPSSEDDDD DDDSSSEEKE TDNTKPNRMP
160 170 180 190 200
VAPYWTSPEK MEKKLHAVPA AKTVKFKCPS SGTPNPTLRW LKNGKEFKPD
210 220 230 240 250
HRIGGYKVRY ATWSIIMDSV VPSDKGNYTC IVENEYGSIN HTYQLDVVER
260 270 280 290 300
SPHRPILQAG LPANKTVALG SNVEFMCKVY SDPQPHIQWL KHIEVNGSKI
310 320 330 340 350
GPDNLPYVQI LKTAGVNTTD KEMEVLHLRN VSFEDAGEYT CLAGNSIGLS
360 370 380 390 400
HHSAWLTVLE ALEERPAVMT SPLYLEIIIY CTGAFLISCM VGSVIVYKMK
410 420 430 440 450
SGTKKSDFHS QMAVHKLAKS IPLRRQVTVS ADSSASMNSG VLLVRPSRLS
460 470 480 490 500
SSGTPMLAGV SEYELPEDPR WELPRDRLVL GKPLGEGCFG QVVLAEAIGL
510 520 530 540 550
DKDKPNRVTK VAVKMLKSDA TEKDLSDLIS EMEMMKMIGK HKNIINLLGA
560 570 580 590 600
CTQDGPLYVI VEYASKGNLR EYLQARRPPG LEYCYNPSHN PEEQLSSKDL
610 620 630 640 650
VSCAYQVARG MEYLASKKCI HRDLAARNVL VTEDNVMKIA DFGLARDIHH
660 670 680 690 700
IDYYKKTTNG RLPVKWMAPE ALFDRIYTHQ SDVWSFGVLL WEIFTLGGSP
710 720 730 740 750
YPGVPVEELF KLLKEGHRMD KPSNCTNELY MMMRDCWHAV PSQRPTFKQL
760 770 780 790 800
VEDLDRIVAL TSNQEYLDLS MPLDQYSPSF PDTRSSTCSS GEDSVFSHEP
810 820
LPEEPCLPRH PAQLANGGLK RR
Length:822
Mass (Da):91,868
Last modified:May 1, 1991 - v3
Checksum:i93A01B5D78C3E72C
GO
Isoform 2 (identifier: P11362-8) [UniParc]FASTAAdd to basket
Also known as: Alpha A2

The sequence of this isoform differs from the canonical sequence as follows:
     619-662: CIHRDLAARN...YYKKTTNGRL → VWNLKAPLVH...RTGHSPHRLL
     663-822: Missing.

Show »
Length:662
Mass (Da):73,475
Checksum:iE9419E4DCB3D8A15
GO
Isoform 3 (identifier: P11362-17) [UniParc]FASTAAdd to basket
Also known as: Alpha A3

The sequence of this isoform differs from the canonical sequence as follows:
     32-61: QPWGAPVEVESFLVHPGDLLQLRCRLRDDV → CPDLQEAKSCSASFHSITPLPFGLGTRLSD
     62-822: Missing.

Show »
Length:61
Mass (Da):6,682
Checksum:i13F5DEE578AF5D86
GO
Isoform 4 (identifier: P11362-2) [UniParc]FASTAAdd to basket
Also known as: Alpha B1

The sequence of this isoform differs from the canonical sequence as follows:
     428-429: Missing.

Show »
Length:820
Mass (Da):91,668
Checksum:i16B07518ECFC98F5
GO
Isoform 5 (identifier: P11362-9) [UniParc]FASTAAdd to basket
Also known as: Alpha B2

The sequence of this isoform differs from the canonical sequence as follows:
     428-429: Missing.
     619-662: CIHRDLAARN...YYKKTTNGRL → VWNLKAPLVH...RTGHSPHRLL
     663-822: Missing.

Show »
Length:660
Mass (Da):73,274
Checksum:i2D2E9EEAC7BDDE3F
GO
Isoform 6 (identifier: P11362-3) [UniParc]FASTAAdd to basket
Also known as: Beta A1, II, H2

The sequence of this isoform differs from the canonical sequence as follows:
     31-119: Missing.

Show »
Length:733
Mass (Da):82,162
Checksum:iED3CD2B1CA825F7E
GO
Isoform 7 (identifier: P11362-10) [UniParc]FASTAAdd to basket
Also known as: Beta A2

The sequence of this isoform differs from the canonical sequence as follows:
     31-119: Missing.
     619-662: CIHRDLAARN...YYKKTTNGRL → VWNLKAPLVH...RTGHSPHRLL
     663-822: Missing.

Show »
Length:573
Mass (Da):63,769
Checksum:iBA9898B9E682D31C
GO
Isoform 8 (identifier: P11362-4) [UniParc]FASTAAdd to basket
Also known as: Beta B1

The sequence of this isoform differs from the canonical sequence as follows:
     31-119: Missing.
     428-429: Missing.

Show »
Length:731
Mass (Da):81,962
Checksum:iEF5CC75954AEC7FC
GO
Isoform 9 (identifier: P11362-11) [UniParc]FASTAAdd to basket
Also known as: Beta B2

The sequence of this isoform differs from the canonical sequence as follows:
     31-119: Missing.
     428-429: Missing.
     619-662: CIHRDLAARN...YYKKTTNGRL → VWNLKAPLVH...RTGHSPHRLL
     663-822: Missing.

Show »
Length:571
Mass (Da):63,569
Checksum:i0BDAB3559EB4B141
GO
Isoform 10 (identifier: P11362-5) [UniParc]FASTAAdd to basket
Also known as: Gamma A1

The sequence of this isoform differs from the canonical sequence as follows:
     1-160: Missing.

Show »
Length:662
Mass (Da):74,133
Checksum:iF51EB57977705DE1
GO
Isoform 11 (identifier: P11362-12) [UniParc]FASTAAdd to basket
Also known as: Gamma A2

The sequence of this isoform differs from the canonical sequence as follows:
     1-160: Missing.
     619-662: CIHRDLAARN...YYKKTTNGRL → VWNLKAPLVH...RTGHSPHRLL
     663-822: Missing.

Show »
Length:502
Mass (Da):55,740
Checksum:i3D3E866B4D4CEBEF
GO
Isoform 12 (identifier: P11362-6) [UniParc]FASTAAdd to basket
Also known as: Gamma B1

The sequence of this isoform differs from the canonical sequence as follows:
     1-160: Missing.
     428-429: Missing.

Show »
Length:660
Mass (Da):73,933
Checksum:iE8947AAB5631D58E
GO
Isoform 13 (identifier: P11362-13) [UniParc]FASTAAdd to basket
Also known as: Gamma B2

The sequence of this isoform differs from the canonical sequence as follows:
     1-160: Missing.
     428-429: Missing.
     619-662: CIHRDLAARN...YYKKTTNGRL → VWNLKAPLVH...RTGHSPHRLL
     663-822: Missing.

Show »
Length:500
Mass (Da):55,540
Checksum:iD508189BA6475745
GO
Isoform 14 (identifier: P11362-7) [UniParc]FASTAAdd to basket
Also known as: A, III

The sequence of this isoform differs from the canonical sequence as follows:
     148-149: Missing.