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Protein

Fibroblast growth factor receptor 1

Gene

FGFR1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

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 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

GO - Biological processi

Keywordsi

Molecular functionHeparin-binding, Kinase, Receptor, Transferase, Tyrosine-protein kinase
Biological processTranscription, Transcription regulation
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

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

Protein family/group databases

TCDBi8.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
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 8

Organism-specific databases

EuPathDBiHostDB:ENSG00000077782.19
HGNCiHGNC:3688 FGFR1
MIMi136350 gene
neXtProtiNX_P11362

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

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

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
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 dbSNP:rs760884357Ensembl.1
Natural variantiVAR_03096848G → S in HH2; phenotype consistent with normosmic idiopathic hypogonadotropic hypogonadism. 1 PublicationCorresponds to variant dbSNP:rs121909640EnsemblClinVar.1
Natural variantiVAR_07299370G → R in HH2. 1 PublicationCorresponds to variant dbSNP:rs140254426Ensembl.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 dbSNP:rs727505373EnsemblClinVar.1
Natural variantiVAR_030971101C → F in HH2. 1 Publication1
Natural variantiVAR_030972102V → I in HH2. 2 PublicationsCorresponds to variant dbSNP:rs55642501EnsemblClinVar.1
Natural variantiVAR_072994116V → I in HH2. 1 PublicationCorresponds to variant dbSNP:rs747842199Ensembl.1
Natural variantiVAR_069288117N → S in HH2; some patients also carry GNRHR mutations. 2 PublicationsCorresponds to variant dbSNP:rs780765366Ensembl.1
Natural variantiVAR_030973129D → A in HH2. 1 PublicationCorresponds to variant dbSNP:rs765615419EnsemblClinVar.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 dbSNP:rs121909630EnsemblClinVar.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 dbSNP:rs121909635EnsemblClinVar.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 dbSNP:rs121909645EnsemblClinVar.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 PublicationsCorresponds to variant dbSNP:rs1131691929Ensembl.1
Natural variantiVAR_030984274E → G in HH2; also found in a family member with isolated anosmia. Corresponds to variant dbSNP:rs727505369EnsemblClinVar.1
Natural variantiVAR_017888277C → Y in HH2. 1 Publication1
Natural variantiVAR_030985283P → R in HH2. 1 Publication1
Natural variantiVAR_080328324 – 822Missing in HH2. 1 PublicationAdd BLAST499
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 dbSNP:rs121909638EnsemblClinVar.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 PublicationsCorresponds to variant dbSNP:rs886037634EnsemblClinVar.1
Natural variantiVAR_030992366P → L in HH2; with or without anosmia. 1 PublicationCorresponds to variant dbSNP:rs121909641EnsemblClinVar.1
Natural variantiVAR_069292470R → L in HH2; some patients also carry GNRHR mutations. 2 PublicationsCorresponds to variant dbSNP:rs121909637EnsemblClinVar.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 dbSNP:rs397515444EnsemblClinVar.1
Natural variantiVAR_030995520A → T in HH2. 1 PublicationCorresponds to variant dbSNP:rs749758370Ensembl.1
Natural variantiVAR_030996538I → V in HH2. 1 Publication1
Natural variantiVAR_017889607V → M in HH2; with bimanual synkinesis. 1 PublicationCorresponds to variant dbSNP:rs121909629EnsemblClinVar.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_080329622 – 822Missing in HH2. 1 PublicationAdd BLAST201
Natural variantiVAR_030998622R → G in HH2; with severe ear anomalies. 1 PublicationCorresponds to variant dbSNP:rs121909628EnsemblClinVar.1
Natural variantiVAR_030999622R → Q in HH2. 1 Publication1
Natural variantiVAR_080330661 – 822Missing in HH2. 1 PublicationAdd BLAST162
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 dbSNP:rs397515446EnsemblClinVar.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 dbSNP:rs727505376EnsemblClinVar.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 dbSNP:rs397515445EnsemblClinVar.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 dbSNP:rs768957161Ensembl.1
Natural variantiVAR_017891719M → R in HH2. 1 Publication1
Natural variantiVAR_074014719M → V in HH2; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs1085307879Ensembl.1
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 dbSNP:rs267606805EnsemblClinVar.1
Natural variantiVAR_031006722P → S in HH2. 1 PublicationCorresponds to variant dbSNP:rs121909642EnsemblClinVar.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 dbSNP:rs267606806EnsemblClinVar.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 dbSNP:rs121909644EnsemblClinVar.1
Natural variantiVAR_031010795V → 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 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 dbSNP:rs121909632EnsemblClinVar.1
Natural variantiVAR_030993374Y → C in OGD; elevated basal activity and increased FGF2-mediated activity. 1 PublicationCorresponds to variant dbSNP:rs121909631EnsemblClinVar.1
Natural variantiVAR_030994381C → 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 keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_070851165L → S in HRTFDS. 1 PublicationCorresponds to variant dbSNP:rs397515481EnsemblClinVar.1
Natural variantiVAR_070852191L → S in HRTFDS. 1 PublicationCorresponds to variant dbSNP:rs869025669EnsemblClinVar.1
Natural variantiVAR_070853490G → R in HRTFDS. 1 PublicationCorresponds to variant dbSNP:rs869025670EnsemblClinVar.1
Natural variantiVAR_070854623D → Y in HRTFDS. 1 PublicationCorresponds to variant dbSNP:rs398122946EnsemblClinVar.1
Natural variantiVAR_071460627R → T in HRTFDS. 1 PublicationCorresponds to variant dbSNP:rs869025671EnsemblClinVar.1
Natural variantiVAR_070855628N → K in HRTFDS. 1 PublicationCorresponds to variant dbSNP:rs869025672EnsemblClinVar.1
Natural variantiVAR_070856725C → 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 keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_030986300I → 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 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 PublicationsCorresponds to variant dbSNP:rs779707422EnsemblClinVar.1
Natural variantiVAR_075855656K → 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

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
GeneReviewsiFGFR1
MalaCardsiFGFR1
MIMi101600 phenotype
123150 phenotype
147950 phenotype
166250 phenotype
190440 phenotype
613001 phenotype
615465 phenotype
OpenTargetsiENSG00000077782
Orphaneti2396 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
251612 Pilocytic astrocytoma
314950 Primary hypereosinophilic syndrome
220386 Semilobar holoprosencephaly
3157 Septo-optic dysplasia spectrum
PharmGKBiPA28127

Chemistry databases

ChEMBLiCHEMBL3650
DrugBankiDB08577 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
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...) asparagineSequence analysis1
Glycosylationi117N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi178 ↔ 230
Glycosylationi227N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi240N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi264N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi277 ↔ 341
Glycosylationi296N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi317N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi330N-linked (GlcNAc...) asparagineSequence 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
ProteomicsDBi52745
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

CarbonylDBiP11362
GlyConnecti1239
iPTMnetiP11362
PhosphoSitePlusiP11362
SwissPalmiP11362

Miscellaneous databases

PMAP-CutDBiP11362

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 Expressed in 240 organ(s), highest expression level in body of pancreas
CleanExiHS_FGFR1
HS_FLG
ExpressionAtlasiP11362 baseline and differential
GenevisibleiP11362 HS

Organism-specific databases

HPAiCAB033614
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

Protein-protein interaction databases

BioGridi108551, 115 interactors
CORUMiP11362
DIPiDIP-4019N
IntActiP11362, 30 interactors
MINTiP11362
STRINGi9606.ENSP00000393312

Chemistry databases

BindingDBiP11362

Structurei

Secondary structure

1822
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

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

Keywords - Domaini

Immunoglobulin domain, Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

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

Family and domain databases

CDDicd05098 PTKc_FGFR1, 1 hit
Gene3Di2.60.40.10, 3 hits
InterProiView protein in InterPro
IPR028174 FGF_rcpt_1
IPR016248 FGF_rcpt_fam
IPR007110 Ig-like_dom
IPR036179 Ig-like_dom_sf
IPR013783 Ig-like_fold
IPR013098 Ig_I-set
IPR003599 Ig_sub
IPR003598 Ig_sub2
IPR013151 Immunoglobulin
IPR011009 Kinase-like_dom_sf
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
PfamiView protein in Pfam
PF07679 I-set, 2 hits
PF00047 ig, 1 hit
PF07714 Pkinase_Tyr, 1 hit
PIRSFiPIRSF000628 FGFR, 1 hit
PRINTSiPR00109 TYRKINASE
SMARTiView protein in SMART
SM00409 IG, 3 hits
SM00408 IGc2, 3 hits
SM00219 TyrKc, 1 hit
SUPFAMiSSF48726 SSF48726, 3 hits
SSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS50835 IG_LIKE, 3 hits
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00109 PROTEIN_KINASE_TYR, 1 hit

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

This entry has 21 described isoforms and 12 potential isoforms that are computationally mapped.Show allAlign All

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.

Show »
Length:820
Mass (Da):91,580
Checksum:i4644ADCC15A696FD
GO
Isoform 15 (identifier: P11362-14) [UniParc]FASTAAdd to basket
Also known as: I, H3

The sequence of this isoform differs from the canonical sequence as follows:
     31-119: Missing.
     148-149: Missing.

Show »
Length:731
Mass (Da):81,875
Checksum:iBFA81F8DADF4C9F4
GO
Isoform 16 (identifier: P11362-15) [UniParc]FASTAAdd to basket
Also known as: V

The sequence of this isoform differs from the canonical sequence as follows:
     120-150: DALPSSEDDDDDDDSSSEEKETDNTKPNRMP → ACPDLQEAKWCSASFHSITPLPFGLGTRLSD
     151-822: Missing.

Show »
Length:150
Mass (Da):16,487
Checksum:iBA69FDD207CBBDFB
GO
Isoform 17 (identifier: P11362-16) [UniParc]FASTAAdd to basket
Also known as: H4

The sequence of this isoform differs from the canonical sequence as follows:
     31-119: Missing.
     313-391: TAGVNTTDKE...TGAFLISCMV → VIMAPVFVGQ...RAAGMGGAGL
     392-822: Missing.

Show »
Length:302
Mass (Da):33,412
Checksum:iA2FF0FB217358001
GO
Isoform 18 (identifier: P11362-18) [UniParc]FASTAAdd to basket
Also known as: H5

The sequence of this isoform differs from the canonical sequence as follows:
     31-119: Missing.
     148-149: Missing.
     313-391: TAGVNTTDKE...TGAFLISCMV → VIMAPVFVGQ...RAAGMGGAGL
     392-822: Missing.

Show »
Length:300
Mass (Da):33,125
Checksum:i00836E542E75EFA3
GO
Isoform 19 (identifier: P11362-19) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     119-119: S → SVPI
     148-149: Missing.
     313-360: TAGVNTTDKE...HHSAWLTVLE → HSGINSSDAE...QSAWLTVTRP

Show »
Length:822
Mass (Da):91,760
Checksum:i657DE58FE3072EA2
GO
Isoform 20 (identifier: P11362-20) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-30: MWSWKCLLFWAVLVTATLCTARPSPTLPEQ → MAAVTRDFGEMLLHSGRVLPAE
     427-428: Missing.

Show »
Length:812
Mass (Da):90,618
Checksum:i817D54D21F3669F0
GO
Isoform 21 (identifier: P11362-21) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MEARVSLKRRIELTVEYPWRCGALSPTSNCRTGM
     148-149: Missing.

Show »
Length:853
Mass (Da):95,344
Checksum:iADA3C30F9F9DE084
GO

Computationally mapped potential isoform sequencesi

There are 12 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
E7EU09E7EU09_HUMAN
Fibroblast growth factor receptor
FGFR1
733Annotation score:
B5A958B5A958_HUMAN
Fibroblast growth factor receptor 1
FGFR1
228Annotation score:
H0YE20H0YE20_HUMAN
Fibroblast growth factor receptor 1
FGFR1
134Annotation score:
E9PNM3E9PNM3_HUMAN
Fibroblast growth factor receptor 1
FGFR1
298Annotation score:
C9J205C9J205_HUMAN
Fibroblast growth factor receptor 1
FGFR1
106Annotation score:
C1KBH7C1KBH7_HUMAN
Fibroblast growth factor receptor 1...
FGFR1
367Annotation score:
E9PKF2E9PKF2_HUMAN
Fibroblast growth factor receptor 1
FGFR1
145Annotation score:
E9PKV7E9PKV7_HUMAN
Fibroblast growth factor receptor 1
FGFR1
142Annotation score:
C9J1L5C9J1L5_HUMAN
Fibroblast growth factor receptor 1
FGFR1
54Annotation score:
E9PQ40E9PQ40_HUMAN
Fibroblast growth factor receptor 1
FGFR1
85Annotation score:
There are more potential isoformsShow all

Sequence cautioni

The sequence BAD92156 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti24S → C in AAA35958 (PubMed:1846977).Curated1
Sequence conflicti24S → C in AAA35959 (PubMed:1846977).Curated1
Sequence conflicti192K → E in AAA35837 (PubMed:2167437).