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
Search proteins in UniProtKB for this molecule.
Search chemical reactions in Rhea for this molecule.
See the description of this molecule in ChEBI.
+
L-tyrosyl-[protein]
Search proteins in UniProtKB for this molecule.
Search chemical reactions in Rhea for this molecule.
=
ADP
Search proteins in UniProtKB for this molecule.
Search chemical reactions in Rhea for this molecule.
See the description of this molecule in ChEBI.
+
H⁺
Search proteins in UniProtKB for this molecule.
Search chemical reactions in Rhea for this molecule.
See the description of this molecule in ChEBI.
+
O-phospho-L-tyrosyl-[protein]
Search proteins in UniProtKB for this molecule.
Search chemical reactions in Rhea for this molecule.
PROSITE-ProRule annotation
Manual assertion according to rulesⁱ
- PROSITE-ProRule:PRU10028
7 Publications
Manual assertion based on experiment inⁱ
- Ref.22
  "Point mutation of an FGF receptor abolishes phosphatidylinositol turnover and Ca2+ flux but not mitogenesis."
  Peters K.G., Marie J., Wilson E., Ives H.E., Escobedo J., del Rosario M., Mirda D., Williams L.T.
  Nature 358:678-681(1992) [PubMed] [Europe PMC] [Abstract]
  Cited for: MUTAGENESIS OF TYR-766, FUNCTION, CATALYTIC ACTIVITY, AUTOPHOSPHORYLATION, INTERACTION WITH PLCG1.
- Ref.25
  "Identification of six novel autophosphorylation sites on fibroblast growth factor receptor 1 and elucidation of their importance in receptor activation and signal transduction."
  Mohammadi M., Dikic I., Sorokin A., Burgess W.H., Jaye M., Schlessinger J.
  Mol. Cell. Biol. 16:977-989(1996) [PubMed] [Europe PMC] [Abstract]
  Cited for: PHOSPHORYLATION AT TYR-463; TYR-583; TYR-585; TYR-653; TYR-654 AND TYR-730, CATALYTIC ACTIVITY, ACTIVITY REGULATION, FUNCTION IN PHOSPHORYLATION OF PLCG1 AND SHC1; ACTIVATION OF MAP KINASES AND REGULATION OF CELL PROLIFERATION AND DIFFERENTIATION, MUTAGENESIS OF TYR-653 AND TYR-654.
- Ref.36
  "90-kDa ribosomal S6 kinase is a direct target for the nuclear fibroblast growth factor receptor 1 (FGFR1): role in FGFR1 signaling."
  Hu Y., Fang X., Dunham S.M., Prada C., Stachowiak E.K., Stachowiak M.K.
  J. Biol. Chem. 279:29325-29335(2004) [PubMed] [Europe PMC] [Abstract]
  Cited for: FUNCTION IN ACTIVATION OF RPS6KA1 AND CREB1, CATALYTIC ACTIVITY, INTERACTION WITH RPS6KA1, MUTAGENESIS OF LYS-514, SUBCELLULAR LOCATION.
- Ref.46
  "Ubiquitination of fibroblast growth factor receptor 1 is required for its intracellular sorting but not for its endocytosis."
  Haugsten E.M., Malecki J., Bjorklund S.M., Olsnes S., Wesche J.
  Mol. Biol. Cell 19:3390-3403(2008) [PubMed] [Europe PMC] [Abstract]
  Cited for: UBIQUITINATION, CATALYTIC ACTIVITY, FUNCTION AS FGF1 RECEPTOR AND IN ACTIVATION OF PLCG1; FRS2; MAPK1/ERK2 AND MAPK3/ERK1, ACTIVITY REGULATION, SUBCELLULAR LOCATION.
- Ref.49
  "The precise sequence of FGF receptor autophosphorylation is kinetically driven and is disrupted by oncogenic mutations."
  Lew E.D., Furdui C.M., Anderson K.S., Schlessinger J.
  Sci. Signal. 2:RA6-RA6(2009) [PubMed] [Europe PMC] [Abstract]
  Cited for: FUNCTION AS PROTO-ONCOGENE, ACTIVE SITE, MUTAGENESIS OF ASP-623, CATALYTIC ACTIVITY, PHOSPHORYLATION AT TYR-463; TYR-653; TYR-654; TYR-583; TYR-585 AND TYR-730, CHARACTERIZATION OF VARIANT ECCL LYS-546, IDENTIFICATION BY MASS SPECTROMETRY, ACTIVITY REGULATION.
- Ref.63
  "The selectivity of receptor tyrosine kinase signaling is controlled by a secondary SH2 domain binding site."
  Bae J.H., Lew E.D., Yuzawa S., Tome F., Lax I., Schlessinger J.
  Cell 138:514-524(2009) [PubMed] [Europe PMC] [Abstract]
  Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 458-774 IN COMPLEX WITH PLCG1 AND ATP ANALOG, FUNCTION, CATALYTIC ACTIVITY, SUBUNIT, AUTOPHOSPHORYLATION, PHOSPHORYLATION AT TYR-653; TYR-654 AND TYR-766.
- Ref.64
  "Asymmetric receptor contact is required for tyrosine autophosphorylation of fibroblast growth factor receptor in living cells."
  Bae J.H., Boggon T.J., Tome F., Mandiyan V., Lax I., Schlessinger J.
  Proc. Natl. Acad. Sci. U.S.A. 107:2866-2871(2010) [PubMed] [Europe PMC] [Abstract]
  Cited for: X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 458-765 OF MUTANT GLU-577, FUNCTION, CATALYTIC ACTIVITY, SUBUNIT, MUTAGENESIS OF ARG-577.
EC:
2.7.10.1
- Search proteins in UniProtKB for this EC number.
- See the description of this EC number in ENZYME.
- Search reactions for this EC number in Rhea.
PROSITE-ProRule annotation
Manual assertion according to rulesⁱ
- PROSITE-ProRule:PRU10028
7 Publications
Manual assertion based on experiment inⁱ
- Ref.22
  "Point mutation of an FGF receptor abolishes phosphatidylinositol turnover and Ca2+ flux but not mitogenesis."
  Peters K.G., Marie J., Wilson E., Ives H.E., Escobedo J., del Rosario M., Mirda D., Williams L.T.
  Nature 358:678-681(1992) [PubMed] [Europe PMC] [Abstract]
  Cited for: MUTAGENESIS OF TYR-766, FUNCTION, CATALYTIC ACTIVITY, AUTOPHOSPHORYLATION, INTERACTION WITH PLCG1.
- Ref.25
  "Identification of six novel autophosphorylation sites on fibroblast growth factor receptor 1 and elucidation of their importance in receptor activation and signal transduction."
  Mohammadi M., Dikic I., Sorokin A., Burgess W.H., Jaye M., Schlessinger J.
  Mol. Cell. Biol. 16:977-989(1996) [PubMed] [Europe PMC] [Abstract]
  Cited for: PHOSPHORYLATION AT TYR-463; TYR-583; TYR-585; TYR-653; TYR-654 AND TYR-730, CATALYTIC ACTIVITY, ACTIVITY REGULATION, FUNCTION IN PHOSPHORYLATION OF PLCG1 AND SHC1; ACTIVATION OF MAP KINASES AND REGULATION OF CELL PROLIFERATION AND DIFFERENTIATION, MUTAGENESIS OF TYR-653 AND TYR-654.
- Ref.36
  "90-kDa ribosomal S6 kinase is a direct target for the nuclear fibroblast growth factor receptor 1 (FGFR1): role in FGFR1 signaling."
  Hu Y., Fang X., Dunham S.M., Prada C., Stachowiak E.K., Stachowiak M.K.
  J. Biol. Chem. 279:29325-29335(2004) [PubMed] [Europe PMC] [Abstract]
  Cited for: FUNCTION IN ACTIVATION OF RPS6KA1 AND CREB1, CATALYTIC ACTIVITY, INTERACTION WITH RPS6KA1, MUTAGENESIS OF LYS-514, SUBCELLULAR LOCATION.
- Ref.46
  "Ubiquitination of fibroblast growth factor receptor 1 is required for its intracellular sorting but not for its endocytosis."
  Haugsten E.M., Malecki J., Bjorklund S.M., Olsnes S., Wesche J.
  Mol. Biol. Cell 19:3390-3403(2008) [PubMed] [Europe PMC] [Abstract]
  Cited for: UBIQUITINATION, CATALYTIC ACTIVITY, FUNCTION AS FGF1 RECEPTOR AND IN ACTIVATION OF PLCG1; FRS2; MAPK1/ERK2 AND MAPK3/ERK1, ACTIVITY REGULATION, SUBCELLULAR LOCATION.
- Ref.49
  "The precise sequence of FGF receptor autophosphorylation is kinetically driven and is disrupted by oncogenic mutations."
  Lew E.D., Furdui C.M., Anderson K.S., Schlessinger J.
  Sci. Signal. 2:RA6-RA6(2009) [PubMed] [Europe PMC] [Abstract]
  Cited for: FUNCTION AS PROTO-ONCOGENE, ACTIVE SITE, MUTAGENESIS OF ASP-623, CATALYTIC ACTIVITY, PHOSPHORYLATION AT TYR-463; TYR-653; TYR-654; TYR-583; TYR-585 AND TYR-730, CHARACTERIZATION OF VARIANT ECCL LYS-546, IDENTIFICATION BY MASS SPECTROMETRY, ACTIVITY REGULATION.
- Ref.63
  "The selectivity of receptor tyrosine kinase signaling is controlled by a secondary SH2 domain binding site."
  Bae J.H., Lew E.D., Yuzawa S., Tome F., Lax I., Schlessinger J.
  Cell 138:514-524(2009) [PubMed] [Europe PMC] [Abstract]
  Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 458-774 IN COMPLEX WITH PLCG1 AND ATP ANALOG, FUNCTION, CATALYTIC ACTIVITY, SUBUNIT, AUTOPHOSPHORYLATION, PHOSPHORYLATION AT TYR-653; TYR-654 AND TYR-766.
- Ref.64
  "Asymmetric receptor contact is required for tyrosine autophosphorylation of fibroblast growth factor receptor in living cells."
  Bae J.H., Boggon T.J., Tome F., Mandiyan V., Lax I., Schlessinger J.
  Proc. Natl. Acad. Sci. U.S.A. 107:2866-2871(2010) [PubMed] [Europe PMC] [Abstract]
  Cited for: X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 458-765 OF MUTANT GLU-577, FUNCTION, CATALYTIC ACTIVITY, SUBUNIT, MUTAGENESIS OF ARG-577.
Source:
Rhea
Search for this reaction in UniProtKB.
See the description of this reaction in Rhea.
. Show »« Hide
ATP
+
L-tyrosyl-[protein]
L-tyrosine residue
zoom
=
ADP
+
H⁺
+
O-phospho-L-tyrosyl-[protein]
L-tyrosine-phosphate residue
zoom

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

Manual assertion based on experiment inⁱ

Ref.25
"Identification of six novel autophosphorylation sites on fibroblast growth factor receptor 1 and elucidation of their importance in receptor activation and signal transduction."
Mohammadi M., Dikic I., Sorokin A., Burgess W.H., Jaye M., Schlessinger J.
Mol. Cell. Biol. 16:977-989(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT TYR-463; TYR-583; TYR-585; TYR-653; TYR-654 AND TYR-730, CATALYTIC ACTIVITY, ACTIVITY REGULATION, FUNCTION IN PHOSPHORYLATION OF PLCG1 AND SHC1; ACTIVATION OF MAP KINASES AND REGULATION OF CELL PROLIFERATION AND DIFFERENTIATION, MUTAGENESIS OF TYR-653 AND TYR-654.
Ref.46
"Ubiquitination of fibroblast growth factor receptor 1 is required for its intracellular sorting but not for its endocytosis."
Haugsten E.M., Malecki J., Bjorklund S.M., Olsnes S., Wesche J.
Mol. Biol. Cell 19:3390-3403(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: UBIQUITINATION, CATALYTIC ACTIVITY, FUNCTION AS FGF1 RECEPTOR AND IN ACTIVATION OF PLCG1; FRS2; MAPK1/ERK2 AND MAPK3/ERK1, ACTIVITY REGULATION, SUBCELLULAR LOCATION.
Ref.49
"The precise sequence of FGF receptor autophosphorylation is kinetically driven and is disrupted by oncogenic mutations."
Lew E.D., Furdui C.M., Anderson K.S., Schlessinger J.
Sci. Signal. 2:RA6-RA6(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION AS PROTO-ONCOGENE, ACTIVE SITE, MUTAGENESIS OF ASP-623, CATALYTIC ACTIVITY, PHOSPHORYLATION AT TYR-463; TYR-653; TYR-654; TYR-583; TYR-585 AND TYR-730, CHARACTERIZATION OF VARIANT ECCL LYS-546, IDENTIFICATION BY MASS SPECTROMETRY, ACTIVITY REGULATION.
Ref.65
"A novel mode of protein kinase inhibition exploiting hydrophobic motifs of autoinhibited kinases: discovery of ATP-independent inhibitors of fibroblast growth factor receptor."
Eathiraj S., Palma R., Hirschi M., Volckova E., Nakuci E., Castro J., Chen C.R., Chan T.C., France D.S., Ashwell M.A.
J. Biol. Chem. 286:20677-20687(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.01 ANGSTROMS) OF 461-765 IN COMPLEX WITH ARQ 069, ACTIVITY REGULATION.

Sites

Feature key	Position(s)	DescriptionActions	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

Complete GO annotation on QuickGO ...

GO - Biological processⁱ

Complete GO annotation on QuickGO ...

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
PathwayCommonsⁱ	P11362
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 [P11362-19] R-HSA-190373, FGFR1c ligand binding and activation [P11362-1] R-HSA-190374, FGFR1c and Klotho ligand binding and activation [P11362-1] R-HSA-2219530, Constitutive Signaling by Aberrant PI3K in Cancer R-HSA-375165, NCAM signaling for neurite out-growth [P11362-1] R-HSA-445144, Signal transduction by L1 [P11362-1] 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

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	cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Boreoeutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo
Proteomesⁱ	UP000005640 Componentⁱ: Chromosome 8

Organism-specific databases

Human Gene Nomenclature Database More...HGNCⁱ	HGNC:3688, FGFR1
MIMⁱ	136350, gene
neXtProtⁱ	NX_P11362
VEuPathDBⁱ	HostDB:ENSG00000077782

Topology

Feature key	Position(s)	DescriptionActions	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, Nucleus

Pathology & Biotechⁱ

Involvement in diseaseⁱ

Pfeiffer syndrome (PS)1 Publication

The disease is caused by variants 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).

Related information in OMIM

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Natural variantⁱVAR_004111	252	P → R in PS and JWS. 2 PublicationsCorresponds to variant dbSNP:rs121909627Ensembl.		1

Hypogonadotropic hypogonadism 2 with or without anosmia (HH2)15 Publications

The disease is caused by variants 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).

Related information in OMIM

Feature key	Position(s)	DescriptionActions	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:rs121909640Ensembl.	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 PublicationCorresponds to variant dbSNP:rs1554570706EnsemblClinVar.	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:rs121909630Ensembl.	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:rs121909635Ensembl.	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:rs121909645Ensembl.	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:rs121909638Ensembl.	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:rs121909637Ensembl.	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:rs397515444Ensembl.	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:rs121909629Ensembl.	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 PublicationCorresponds to variant dbSNP:rs1563433902EnsemblClinVar.	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:rs397515446Ensembl.	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:rs397515445Ensembl.	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:rs267606805Ensembl.	1
Natural variantⁱVAR_031006	722	P → S in HH2. 1 PublicationCorresponds to variant dbSNP:rs121909642Ensembl.	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:rs267606806Ensembl.	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:rs121909644Ensembl.	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 variantⁱVAR_082843	353	A → T in HH2; unknown pathological significance. 1 Publication	1

Osteoglophonic dysplasia (OGD)2 Publications

The disease is caused by variants 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.

Related information in OMIM

Feature key	Position(s)	DescriptionActions	Length
Natural variantⁱVAR_030987	330	N → I in OGD. 2 PublicationsCorresponds to variant dbSNP:rs121909632Ensembl.	1
Natural variantⁱVAR_030993	374	Y → C in OGD; elevated basal activity and increased FGF2-mediated activity. 1 PublicationCorresponds to variant dbSNP:rs121909631Ensembl.	1
Natural variantⁱVAR_030994	381	C → R in OGD. 2 PublicationsCorresponds to variant dbSNP:rs121909634Ensembl.	1

Hartsfield syndrome (HRTFDS)2 Publications

The disease is caused by variants 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.

Related information in OMIM

Feature key	Position(s)	DescriptionActions	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 variants 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.

Related information in OMIM

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Natural variantⁱVAR_030986	300	I → T in TRIGNO1. 1 PublicationCorresponds to variant dbSNP:rs121909633EnsemblClinVar.		1

Chromosomal aberrations involving FGFR1 are a cause of chromosome 8p11 myeloproliferative syndrome. Translocation t(8;13)(p11;q12) with ZMYM2. Translocation t(6;8)(q27;p11) with CEP43. Insertion ins(12;8)(p11;p11p22) with FGFR1OP2. Translocation t(8;9)(p12;q33) with CNTRL. Translocation t(2;8)(q12;p11) with RANBP2. Chromosome 8p11 myeloproliferative syndrome 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, CEP43-FGFR1 or FGFR1-CEP43 may exhibit constitutive kinase activity and be responsible for the transforming activity. The fusion protein CNTRL-FGFR1 is found in the cytoplasm, exhibits constitutive kinase activity and may be responsible for the transforming activity.7 Publications

Encephalocraniocutaneous lipomatosis (ECCL)2 Publications

The disease is caused by variants 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.

Related information in OMIM

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 variants 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.

Related information in OMIM

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Natural variantⁱVAR_004111	252	P → R in PS and JWS. 2 PublicationsCorresponds to variant dbSNP:rs121909627Ensembl.		1

Mutagenesis

Feature key	Position(s)	DescriptionActions	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	Length
Siteⁱ	428 – 429	Breakpoint for translocation to form CEP43-FGFR1 or FGFR1-CEP43 fusion proteins1 Publication	2
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 FGFR1OP2-FGFR13 Publications	2

Keywords - Diseaseⁱ

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

Organism-specific databases

DisGeNET More...DisGeNETⁱ	2260
GeneReviewsⁱ	FGFR1
MalaCards human disease database More...MalaCardsⁱ	FGFR1
MIMⁱ	101600, phenotype 123150, phenotype 147950, phenotype 166250, phenotype 190440, phenotype 613001, phenotype 615465, phenotype
Open Targets More...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

Miscellaneous databases

Pharosⁱ	P11362, Tclin

Pharosⁱ

P11362, Tclin

Chemistry databases

ChEMBLⁱ	CHEMBL3650
Drug and drug target database More...DrugBankⁱ	DB07840, (E)-[4-(3,5-Difluorophenyl)-3H-pyrrolo[2,3-b]pyridin-3-ylidene](3-methoxyphenyl)methanol DB07525, 3-(3-methoxybenzyl)-1H-pyrrolo[2,3-b]pyridine DB08577, 3-[(3-(2-CARBOXYETHYL)-4-METHYLPYRROL-2-YL)METHYLENE]-2-INDOLINONE DB02058, 3-[4-(1-formylpiperazin-4-yl)-benzylidenyl]-2-indolinone DB12147, Erdafitinib DB12010, Fostamatinib DB01109, Heparin DB09078, Lenvatinib DB09079, Nintedanib DB00039, Palifermin DB15102, Pemigatinib DB08901, Ponatinib DB15822, Pralsetinib DB08896, Regorafenib DB15685, Selpercatinib DB00398, Sorafenib DB05014, XL999
DrugCentral More...DrugCentralⁱ	P11362
IUPHAR/BPS Guide to PHARMACOLOGY More...GuidetoPHARMACOLOGYⁱ	1808

Genetic variation 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	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 conjugation

Proteomic databases

The CPTAC Assay portal More...CPTACⁱ	CPTAC-1773 CPTAC-1780
EPDⁱ	P11362
jPOSTⁱ	P11362
MassIVEⁱ	P11362
MaxQB - The MaxQuant DataBase More...MaxQBⁱ	P11362
PaxDbⁱ	P11362
PeptideAtlas More...PeptideAtlasⁱ	P11362
PRIDEⁱ	P11362
ProteomicsDBⁱ	52745 [P11362-1] 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, 8 N-Linked glycans (4 sites)
GlyGenⁱ	P11362, 11 sites, 11 N-linked glycans (5 sites)
iPTMnetⁱ	P11362
PhosphoSitePlusⁱ	P11362
SwissPalmⁱ	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 body of pancreas and 251 other tissues
ExpressionAtlasⁱ	P11362, baseline and differential
Genevisibleⁱ	P11362, HS

Organism-specific databases

Human Protein Atlas More...HPAⁱ	ENSG00000077782, Low tissue specificity

HPAⁱ

ENSG00000077782, Low tissue specificity

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

Hide details

P11362

With	#Exp.	IntAct
ANOS1 [P23352]	7	EBI-1028277,EBI-5272188
CDH1 [P12830]	3	EBI-1028277,EBI-727477
FGF1 [P05230]	4	EBI-1028277,EBI-698068
FGF2 [P09038]	7	EBI-1028277,EBI-977447
FGF23 [Q9GZV9]	2	EBI-1028277,EBI-6594125
itself	4	EBI-1028277,EBI-1028277
HSP90AB1 [P08238]	2	EBI-1028277,EBI-352572
HTR1A [P08908]	9	EBI-1028277,EBI-6570214
NEDD4 [P46934]	26	EBI-1028277,EBI-726944
NOSTRIN [Q8IVI9]	5	EBI-1028277,EBI-1391643
PIK3R1 [P27986]	5	EBI-1028277,EBI-79464
PLCG1 [P19174]	9	EBI-1028277,EBI-79387
Grb14 [O88900] from Rattus norvegicus.	3	EBI-1028277,EBI-7639197
Kl [O35082] from Mus musculus.	2	EBI-1028277,EBI-1570828
Plcg1 [P10686] from Rattus norvegicus.	4	EBI-1028277,EBI-520788

Isoform 4 [P11362-2]

With	#Exp.	IntAct
ID2 [Q02363]	3	EBI-25852941,EBI-713450
PELO [Q9BRX2]	3	EBI-25852941,EBI-1043580

Isoform 14 [P11362-7]

With	#Exp.	IntAct
FGF2 [P09038]	2	EBI-15609945,EBI-977447
Kl [O35082] from Mus musculus.	3	EBI-15609945,EBI-1570828

Isoform 15 [P11362-14]

With	#Exp.	IntAct
FGF2 [P09038]	2	EBI-6622185,EBI-977447

GO - Molecular functionⁱ

Complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGRIDⁱ	108551, 241 interactors
CORUMⁱ	P11362
Database of interacting proteins More...DIPⁱ	DIP-4019N
IntActⁱ	P11362, 165 interactors
Molecular INTeraction database More...MINTⁱ	P11362
STRINGⁱ	9606.ENSP00000393312

Chemistry databases

BindingDBⁱ	P11362

BindingDBⁱ

P11362

Miscellaneous databases

RNActⁱ	P11362, protein

RNActⁱ

P11362, protein

Structureⁱ

Secondary structure

Legend: HelixTurnBeta strandPDB Structure known for this area

Feature key	Position(s)	DescriptionActions	Length
Beta strandⁱ	40 – 42	Combined sources	3
Beta strandⁱ	51 – 54	Combined sources	4
Beta strandⁱ	63 – 72	Combined sources	10
Beta strandⁱ	77 – 81	Combined sources	5
Beta strandⁱ	83 – 88	Combined sources	6
Turnⁱ	93 – 95	Combined sources	3
Beta strandⁱ	97 – 105	Combined sources	9
Beta strandⁱ	108 – 116	Combined sources	9
Beta strandⁱ	151 – 156	Combined sources	6
Helixⁱ	159 – 161	Combined sources	3
Beta strandⁱ	165 – 169	Combined sources	5
Beta strandⁱ	174 – 177	Combined sources	4
Beta strandⁱ	180 – 184	Combined sources	5
Beta strandⁱ	187 – 192	Combined sources	6
Helixⁱ	199 – 201	Combined sources	3
Beta strandⁱ	207 – 209	Combined sources	3
Turnⁱ	210 – 213	Combined sources	4
Beta strandⁱ	214 – 217	Combined sources	4
Helixⁱ	222 – 224	Combined sources	3
Beta strandⁱ	226 – 234	Combined sources	9
Beta strandⁱ	237 – 248	Combined sources	12
Beta strandⁱ	265 – 268	Combined sources	4
Beta strandⁱ	269 – 271	Combined sources	3
Beta strandⁱ	273 – 276	Combined sources	4
Beta strandⁱ	286 – 293	Combined sources	8
Beta strandⁱ	295 – 297	Combined sources	3
Beta strandⁱ	307 – 313	Combined sources	7
Helixⁱ	320 – 323	Combined sources	4
Beta strandⁱ	325 – 328	Combined sources	4
Helixⁱ	333 – 335	Combined sources	3
Beta strandⁱ	337 – 345	Combined sources	9
Beta strandⁱ	348 – 359	Combined sources	12
Turnⁱ	461 – 463	Combined sources	3
Turnⁱ	469 – 471	Combined sources	3
Helixⁱ	475 – 477	Combined sources	3
Beta strandⁱ	478 – 486	Combined sources	9
Beta strandⁱ	488 – 499	Combined sources	12
Beta strandⁱ	501 – 503	Combined sources	3
Beta strandⁱ	508 – 516	Combined sources	9
Helixⁱ	522 – 538	Combined sources	17
Beta strandⁱ	547 – 551	Combined sources	5
Beta strandⁱ	553 – 555	Combined sources	3
Beta strandⁱ	558 – 562	Combined sources	5
Helixⁱ	569 – 574	Combined sources	6
Beta strandⁱ	582 – 584	Combined sources	3
Beta strandⁱ	585 – 588	Combined sources	4
Helixⁱ	591 – 593	Combined sources	3
Helixⁱ	597 – 616	Combined sources	20
Helixⁱ	626 – 628	Combined sources	3
Beta strandⁱ	629 – 631	Combined sources	3
Beta strandⁱ	637 – 639	Combined sources	3
Beta strandⁱ	641 – 643	Combined sources	3
Helixⁱ	648 – 650	Combined sources	3
Beta strandⁱ	653 – 655	Combined sources	3
Beta strandⁱ	658 – 660	Combined sources	3
Helixⁱ	663 – 666	Combined sources	4
Helixⁱ	669 – 674	Combined sources	6
Beta strandⁱ	676 – 678	Combined sources	3
Helixⁱ	679 – 694	Combined sources	16
Helixⁱ	706 – 714	Combined sources	9
Beta strandⁱ	722 – 724	Combined sources	3
Helixⁱ	727 – 736	Combined sources	10
Helixⁱ	741 – 743	Combined sources	3
Helixⁱ	747 – 760	Combined sources	14

Show more details

3D structure databases

BMRBⁱ	P11362
SMRⁱ	P11362
ModBaseⁱ	Search...
PDBe-KBⁱ	Search...

Miscellaneous databases

EvolutionaryTraceⁱ	P11362

EvolutionaryTraceⁱ

P11362

Family & Domainsⁱ

Domains and Repeats

Feature key	Position(s)	DescriptionActions	Length
Domainⁱ	25 – 119	Ig-like C2-type 1Add BLAST	95
Domainⁱ	158 – 246	Ig-like C2-type 2Add BLAST	89
Domainⁱ	255 – 357	Ig-like C2-type 3Add BLAST	103
Domainⁱ	478 – 767	Protein kinasePROSITE-ProRule annotationAdd BLAST	290

Region

Feature key	Position(s)	DescriptionActions	Length
Regionⁱ	120 – 154	DisorderedSequence analysisAdd BLAST	35
Regionⁱ	160 – 177	Heparin-bindingAdd BLAST	18
Regionⁱ	778 – 822	DisorderedSequence analysisAdd BLAST	45

Compositional bias

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Compositional biasⁱ	123 – 137	Acidic residuesSequence analysisAdd BLAST		15
Compositional biasⁱ	778 – 794	Polar residuesSequence analysisAdd BLAST		17

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

eggNOGⁱ	KOG0200, Eukaryota
Ensembl GeneTree More...GeneTreeⁱ	ENSGT00940000155860
HOGENOMⁱ	CLU_000288_74_3_1
InParanoidⁱ	P11362
OMAⁱ	RCLILWA
Database of Orthologous Groups More...OrthoDBⁱ	220433at2759
PhylomeDBⁱ	P11362
TreeFamⁱ	TF316307

Family and domain databases

Conserved Domains Database More...CDDⁱ	cd05098, PTKc_FGFR1, 1 hit
Gene3Dⁱ	2.60.40.10, 3 hits
IDEALⁱ	IID00650
InterProⁱ	View protein in InterPro IPR028174, FGF_rcpt_1 IPR016248, FGF_rcpt_fam IPR041159, FGFR_TM 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
Pfam protein domain database More...Pfamⁱ	View protein in Pfam PF18123, FGFR3_TM, 1 hit PF07679, I-set, 2 hits PF00047, ig, 1 hit PF07714, PK_Tyr_Ser-Thr, 1 hit
PIRSFⁱ	PIRSF000628, FGFR, 1 hit
PRINTSⁱ	PR00109, TYRKINASE
SMARTⁱ	View protein in SMART SM00409, IG, 3 hits SM00408, IGc2, 3 hits SM00219, TyrKc, 1 hit
SUPFAMⁱ	SSF48726, SSF48726, 3 hits SSF56112, SSF56112, 1 hit
PROSITEⁱ	View 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. Align Add to basket

This entry has 21 described isoforms and 17 potential isoforms that are computationally mapped.Show all Align All

Isoform 1 (identifier: P11362-1) [UniParc]FASTA Add to basket

Also known as: Alpha A1, IV

This isoform has been chosen as the canonicalⁱ 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

Isoform 2 (identifier: P11362-8) [UniParc]FASTA Add 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.

« 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 MEYLASKKVW NLKAPLVHTP RPGSQECPGD RGQCDEDSRL 
       660 
WPRTGHSPHR LL

Show »

Length:662

Mass (Da):73,475

Checksum:ⁱE9419E4DCB3D8A15

Isoform 3 (identifier: P11362-17) [UniParc]FASTA Add 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.

« Hide

        10         20         30         40         50
MWSWKCLLFW AVLVTATLCT ARPSPTLPEQ ACPDLQEAKS CSASFHSITP 
        60 
LPFGLGTRLS D

Show »

Annotation systems

Supporting data

UniProtKB - P11362 (FGFR1_HUMAN)

Your basket is currently empty. i <p>When browsing through different UniProt proteins, you can use the 'basket' to save them, so that you can back to find or analyse them later.<p><a href='/help/basket' target='_top'>More...</a></p>

Fibroblast growth factor receptor 1

FGFR1

Select a section on the left to see content.

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">Function</a> section describes the catalytic activity of an enzyme, i.e. a chemical reaction that the enzyme catalyzes.<p><a href='/help/catalytic_activity' target='_top'>More...</a></p>Catalytic activityi

Sites

Regions

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

GO - Biological processi

Enzyme and pathway databases

Protein family/group databases

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

Organism-specific databases

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Plasma membrane

Cytoplasm and Cytosol

Nucleus

Other locations

Cytosol

Extracellular region or secreted

Nucleus

Plasma Membrane

Other locations

Topology

Keywords - Cellular componenti

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

Mutagenesis

Sites

Keywords - Diseasei

Organism-specific databases

Miscellaneous databases

Chemistry databases

Genetic variation databases

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Amino acid modifications

Keywords - PTMi

Proteomic databases

PTM databases

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

Gene expression databases

Organism-specific databases

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

GO - Molecular functioni

Protein-protein interaction databases

Chemistry databases

Miscellaneous databases

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

Secondary structure

3D structure databases

Miscellaneous databases

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Domains and Repeats

Region

Compositional bias

<p>This subsection of the 'Family and domains' section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Keywords - Domaini

Phylogenomic databases

Family and domain databases

Your basket is currently empty. ⁱ

Functionⁱ

Catalytic activityⁱ

GO - Molecular functionⁱ

GO - Biological processⁱ

Names & Taxonomyⁱ

Subcellular locationⁱ

Keywords - Cellular componentⁱ

Pathology & Biotechⁱ

Keywords - Diseaseⁱ

PTM / Processingⁱ

Keywords - PTMⁱ

Expressionⁱ

Interactionⁱ

GO - Molecular functionⁱ

Structureⁱ

Family & Domainsⁱ

Sequence similaritiesⁱ

Keywords - Domainⁱ