Q04589 (FGFR1_RAT) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Fibroblast growth factor receptor 1
Short name=FGFR-1
Short name=bFGF-R-1
EC=2.7.10.1

Alternative name(s):
Basic fibroblast growth factor receptor 1
MFR
Proto-oncogene c-Fgr
CD_antigen=CD331

Gene names

Name:	Fgfr1
Synonyms:	Flg

Organism

Rattus norvegicus (Rat) [Reference proteome]

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	822 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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 similarity.
Catalytic activity	ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.
Enzyme regulation	Present in an inactive conformation in the absence of bound ligand. Ligand binding leads to dimerization and activation by sequential autophosphorylation on tyrosine residues By similarity.
Subunit structure	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). 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. Interacts (phosphorylated on Tyr-766) with PLCG1 (via SH2 domains). Interacts with FRS2. Interacts (via C-terminus) with NEDD4 (via WW3 domain). Interacts with KL By similarity. Interacts with SHB (via SH2 domain) and GRB10. Interacts with KAL1; this interaction does not interfere with FGF2-binding to FGFR1, but prevents binding of heparin-bound FGF2. Interacts with SOX2 and SOX3 By similarity. Ref.2
Subcellular location	Cell membrane; Single-pass type I membrane protein. Nucleus. Cytoplasm › cytosol. Cytoplasmic vesicle By similarity. Note: After ligand binding, both receptor and ligand are rapidly internalized. Can translocate to the nucleus after internalization, or by translocation from the endoplasmic reticulum or Golgi apparatus to the cytosol, and from there to the nucleus By similarity. Ref.2
Tissue specificity	Expressed in the parathyroid. Ref.3
Domain	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 By similarity.
Post-translational modification	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 By similarity. 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 By similarity. N-glycosylated in the endoplasmic reticulum. The N-glycan chains undergo further maturation to an Endo H-resistant form in the Golgi apparatus By similarity.
Sequence similarities	Belongs to the protein kinase superfamily. Tyr protein kinase family. Fibroblast growth factor receptor subfamily. Contains 3 Ig-like C2-type (immunoglobulin-like) domains. Contains 1 protein kinase domain.

Ontologies

Keywords
Cellular component	Cell membrane Cytoplasm Cytoplasmic vesicle Membrane Nucleus
Domain	Immunoglobulin domain Repeat Signal Transmembrane Transmembrane helix
Ligand	ATP-binding Heparin-binding Nucleotide-binding
Molecular function	Kinase Receptor Transferase Tyrosine-protein kinase
PTM	Disulfide bond Glycoprotein Phosphoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	central nervous system neuron development Inferred from mutant phenotype PubMed 17314281. Source: RGD motogenic signaling involved in postnatal olfactory bulb interneuron migration Inferred from mutant phenotype PubMed 20083104. Source: RGD negative regulation of osteoblast differentiation Inferred from mutant phenotype PubMed 18690792. Source: RGD neuron projection development Inferred from direct assay PubMed 12791257. Source: RGD peptidyl-tyrosine phosphorylation Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of MAP kinase activity Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of mesenchymal cell proliferation Inferred from mutant phenotype PubMed 18690792. Source: RGD positive regulation of neuron differentiation Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of neuron projection development Inferred from direct assay PubMed 19952283. Source: RGD positive regulation of phospholipase C activity Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of transcription from RNA polymerase II promoter Inferred from mutant phenotype PubMed 19229075. Source: BHF-UCL protein autophosphorylation Inferred from sequence or structural similarity. Source: UniProtKB regulation of sensory perception of pain Inferred from mutant phenotype PubMed 17905520. Source: RGD regulation of stem cell proliferation Inferred from mutant phenotype PubMed 18690792. Source: RGD stem cell maintenance Inferred from mutant phenotype PubMed 19505325. Source: RGD
Cellular_component	cytoplasmic membrane-bounded vesicle Inferred from electronic annotation. Source: UniProtKB-SubCell cytosol Inferred from electronic annotation. Source: UniProtKB-SubCell integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell plasma membrane Inferred from sequence or structural similarity. Source: UniProtKB
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW fibroblast growth factor binding Inferred from sequence or structural similarity. Source: UniProtKB fibroblast growth factor-activated receptor activity Inferred from sequence or structural similarity. Source: UniProtKB glycoprotein binding Inferred from direct assay PubMed 19952283. Source: RGD heparin binding Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Plcg1	P10686	2	EBI-2480918,EBI-520788

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 21	21	Potential
	Chain	22 – 822	801	Fibroblast growth factor receptor 1		PRO_0000016782
Regions
	Topological domain	22 – 376	355	Extracellular Potential
	Transmembrane	377 – 397	21	Helical; Potential
	Topological domain	398 – 822	425	Cytoplasmic Potential
	Domain	25 – 119	95	Ig-like C2-type 1
	Domain	158 – 246	89	Ig-like C2-type 2
	Domain	255 – 357	103	Ig-like C2-type 3
	Domain	478 – 767	290	Protein kinase
	Nucleotide binding	484 – 490	7	ATP By similarity
	Nucleotide binding	562 – 564	3	ATP By similarity
	Region	160 – 177	18	Heparin-binding
Sites
	Active site	623	1	Proton acceptor By similarity
	Binding site	514	1	ATP By similarity
	Binding site	568	1	ATP By similarity
	Binding site	627	1	ATP By similarity
	Binding site	641	1	ATP By similarity
	Site	766	1	Mediates interaction with PLCG1 and SHB By similarity
Amino acid modifications
	Modified residue	463	1	Phosphotyrosine; by autocatalysis By similarity
	Modified residue	583	1	Phosphotyrosine; by autocatalysis By similarity
	Modified residue	585	1	Phosphotyrosine; by autocatalysis By similarity
	Modified residue	653	1	Phosphotyrosine; by autocatalysis By similarity
	Modified residue	654	1	Phosphotyrosine; by autocatalysis By similarity
	Modified residue	730	1	Phosphotyrosine; by autocatalysis By similarity
	Modified residue	766	1	Phosphotyrosine; by autocatalysis By similarity
	Glycosylation	77	1	N-linked (GlcNAc...) Potential
	Glycosylation	117	1	N-linked (GlcNAc...) Potential
	Glycosylation	227	1	N-linked (GlcNAc...) Potential
	Glycosylation	240	1	N-linked (GlcNAc...) Potential
	Glycosylation	264	1	N-linked (GlcNAc...) Potential
	Glycosylation	296	1	N-linked (GlcNAc...) Potential
	Glycosylation	317	1	N-linked (GlcNAc...) Potential
	Glycosylation	330	1	N-linked (GlcNAc...) Potential
	Disulfide bond	55 ↔ 101		By similarity
	Disulfide bond	178 ↔ 230		By similarity
	Disulfide bond	277 ↔ 341		By similarity

Sequences

	Sequence		Length	Mass (Da)
	Q04589 [UniParc]. Last modified June 1, 1994. Version 1. Checksum: E59D924D0A1DE5C5	FASTA	822	91,825
	10 20 30 40 50 60 MWGWRGLLFW AVLVTATLCT ARPAPTLPEQ AQPWGVPVEV ESLLVHPGDL LQLRCRLRDD 70 80 90 100 110 120 VQSINWLRDG VQLAESNRTR ITGEEVEVRD SIPADSGLYA CVTNSPSGSD TTYFSVNVSD 130 140 150 160 170 180 ALPSSEDDDD DDDSSSEEKE TDNTKPNRRP VAPYWTSPEK MEKKLHAVPA AKTVKFKCPS 190 200 210 220 230 240 SGTPSPTLRW LKNGKEFKPD HRIGGYKVRY ATWSIIMDSV VPSDKGNYTC IVENEYGSIN 250 260 270 280 290 300 HTYQLDVVER SPHRPILQAG LPANKTVALG SNVEFMCKVY SDPQPHIQWL KHIEVNGSKI 310 320 330 340 350 360 GPDNLPYDQI LKTAGVNTTD KEMEVLHLRN VSFEDAGEYT CLAGNSIGLS HHSAWLTVLE 370 380 390 400 410 420 ALEERPAVMT SPLYLEIIIY CTGAFLISCM VGSVIIYKMK SGTKKSDFHS QMAVHKLAKS 430 440 450 460 470 480 IPLRRQVTVS ADSSASMNSG VLLVRPSRLS SSGTPMLAGV SEYELPEDPR WELPRDRLVL 490 500 510 520 530 540 GKPLGEGCFG QVVLAEAIGL DKDKPNRVTK VAVKMLKSDA TEKDLSDLIS EMEMMKMIGK 550 560 570 580 590 600 HKNIINLLGA CTQDGPLYVI VEYASKGNLR EYLQARRPPG LEYCYNPSHN PEEQLSSKDL 610 620 630 640 650 660 VSCAYQVARG MEYLASKKCI HRDLAARNVL VTEDNVMKIA DFGLARDIHH IDYYKKTTNG 670 680 690 700 710 720 RLPVKWMAPE ALFDRIYTHQ SDVWSFGVLL WEIFTLGGSP NPGVPVEELF KLLKEGHRMD 730 740 750 760 770 780 KPSNCTNELY MMMRDCWNAV PSQRPTFKQL VEDLDRIVAL TSNQEYLDLS MPLDQDSPSF 790 800 810 820 PDTRSSTCSS GEDSVFSHEP FPEEPCLPRH PTQLANGGLN RR

References

[1]	"The structure and expression of the FGF receptor-1 mRNA isoforms in rat tissues." Yazaki N., Hiroko F., Mitsuhiro O., Toshisuke K., Nobuyuki I. Biochim. Biophys. Acta 1172:37-42(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"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: INTERACTION WITH RPS6KA1, SUBCELLULAR LOCATION.
[3]	"The parathyroid is a target organ for FGF23 in rats." Ben-Dov I.Z., Galitzer H., Lavi-Moshayoff V., Goetz R., Kuro-o M., Mohammadi M., Sirkis R., Naveh-Many T., Silver J. J. Clin. Invest. 117:4003-4008(2007) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	D12498 mRNA. Translation: BAA02059.1.
IPI	IPI00215356.
PIR	S29840.
RefSeq	NP_077060.1. NM_024146.1.
UniGene	Rn.207203. Rn.9797.
3D structure databases
ProteinModelPortal	Q04589.
SMR	Q04589. Positions 25-119, 150-359, 464-765.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q04589. 1 interaction.
Proteomic databases
PaxDb	Q04589.
PRIDE	Q04589.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
GeneID	79114.
KEGG	rno:79114.
UCSC	RGD:620713. rat.
Organism-specific databases
CTD	2260.
RGD	620713. Fgfr1.
Phylogenomic databases
eggNOG	COG0515.
HOGENOM	HOG000263410.
HOVERGEN	HBG000345.
KO	K04362.
OrthoDB	EOG4BCDMC.
Enzyme and pathway databases
BRENDA	2.7.10.1. 5301.
Gene expression databases
ArrayExpress	Q04589.
Genevestigator	Q04589.
GermOnline	ENSRNOG00000016050. Rattus norvegicus.
Family and domain databases
Gene3D	2.60.40.10. 3 hits.
InterPro	IPR007110. Ig-like_dom. IPR013783. Ig-like_fold. IPR013098. Ig_I-set. IPR003598. Ig_sub2. IPR011009. Kinase-like_dom. IPR000719. Prot_kinase_cat_dom. IPR017441. Protein_kinase_ATP_BS. IPR001245. Ser-Thr/Tyr_kinase_cat_dom. IPR008266. Tyr_kinase_AS. IPR020635. Tyr_kinase_cat_dom. IPR016248. Tyr_kinase_fibroblast_GF_rcpt. [Graphical view]
Pfam	PF07679. I-set. 3 hits. PF07714. Pkinase_Tyr. 1 hit. [Graphical view]
PIRSF	PIRSF000628. FGFR. 1 hit.
PRINTS	PR00109. TYRKINASE.
SMART	SM00408. IGc2. 3 hits. SM00219. TyrKc. 1 hit. [Graphical view]
SUPFAM	SSF56112. Kinase_like. 1 hit.
PROSITE	PS50835. IG_LIKE. 3 hits. PS00107. PROTEIN_KINASE_ATP. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00109. PROTEIN_KINASE_TYR. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	614518.

Entry information

Entry name

FGFR1_RAT

Accession

Primary (citable) accession number: Q04589

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 1, 1994
Last sequence update:	June 1, 1994
Last modified:	April 3, 2013
This is version 122 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program