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Protein

Fibroblast growth factor receptor 1

Gene

Fgfr1

Organism
Rattus norvegicus (Rat)
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 similarity).By similarity

Catalytic activityi

ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.PROSITE-ProRule annotationBy similarity

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 (By similarity).By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei514ATPPROSITE-ProRule annotation1
Binding sitei568ATPPROSITE-ProRule annotation1
Active sitei623Proton acceptorPROSITE-ProRule annotation1
Binding sitei627ATPPROSITE-ProRule annotation1
Binding sitei641ATPPROSITE-ProRule annotation1
Sitei766Mediates interaction with PLCG1 and SHBBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi484 – 490ATPPROSITE-ProRule annotation7
Nucleotide bindingi562 – 564ATPPROSITE-ProRule annotation3

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionHeparin-binding, Kinase, Receptor, Transferase, Tyrosine-protein kinase
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.10.1 5301

Names & Taxonomyi

Protein namesi
Recommended name:
Fibroblast growth factor receptor 1 (EC:2.7.10.1By similarity)
Short name:
FGFR-1
Short name:
bFGF-R-1
Alternative name(s):
Basic fibroblast growth factor receptor 1
MFR
Proto-oncogene c-Fgr
CD_antigen: CD331
Gene namesi
Name:Fgfr1
Synonyms:Flg
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi620713 Fgfr1

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

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 21Sequence analysisAdd BLAST21
ChainiPRO_000001678222 – 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 ↔ 230PROSITE-ProRule annotation
Glycosylationi227N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi240N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi264N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi277 ↔ 341PROSITE-ProRule annotation
Glycosylationi296N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi317N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi330N-linked (GlcNAc...) asparagineSequence analysis1
Modified residuei463Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei583Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei585Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei653Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei654Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei730Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei766Phosphotyrosine; by autocatalysisBy similarity1

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 (By similarity).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).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).By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiQ04589
PRIDEiQ04589

PTM databases

iPTMnetiQ04589

Expressioni

Tissue specificityi

Expressed in the parathyroid.1 Publication

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). 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 RPS6KA1 (PubMed:15117958). Interacts with KL (By similarity). Interacts with SHB (via SH2 domain) and GRB10. Interacts with ANOS1; this interaction does not interfere with FGF2-binding to FGFR1, but prevents binding of heparin-bound FGF2. Interacts with SOX2 and SOX3 (By similarity). Interacts with FLRT1, FLRT2 and FLRT3. Found in a ternary complex with FGF1 and ITGAV:ITGB3 (By similarity).By similarity1 Publication

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi249399, 3 interactors
CORUMiQ04589
IntActiQ04589, 3 interactors
MINTiQ04589
STRINGi10116.ENSRNOP00000036885

Structurei

3D structure databases

ProteinModelPortaliQ04589
SMRiQ04589
ModBaseiSearch...
MobiDBiSearch...

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 (By similarity).By similarity

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
HOGENOMiHOG000263410
HOVERGENiHBG000345
InParanoidiQ04589
KOiK04362
PhylomeDBiQ04589

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

Sequence (1+)i

Sequence statusi: Complete.

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

This entry has 1 described isoform and 2 potential isoforms that are computationally mapped.Show allAlign All

Q04589-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MWGWRGLLFW AVLVTATLCT ARPAPTLPEQ AQPWGVPVEV ESLLVHPGDL
60 70 80 90 100
LQLRCRLRDD VQSINWLRDG VQLAESNRTR ITGEEVEVRD SIPADSGLYA
110 120 130 140 150
CVTNSPSGSD TTYFSVNVSD ALPSSEDDDD DDDSSSEEKE TDNTKPNRRP
160 170 180 190 200
VAPYWTSPEK MEKKLHAVPA AKTVKFKCPS SGTPSPTLRW 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
GPDNLPYDQI LKTAGVNTTD KEMEVLHLRN VSFEDAGEYT CLAGNSIGLS
360 370 380 390 400
HHSAWLTVLE ALEERPAVMT SPLYLEIIIY CTGAFLISCM VGSVIIYKMK
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
NPGVPVEELF KLLKEGHRMD KPSNCTNELY MMMRDCWNAV PSQRPTFKQL
760 770 780 790 800
VEDLDRIVAL TSNQEYLDLS MPLDQDSPSF PDTRSSTCSS GEDSVFSHEP
810 820
FPEEPCLPRH PTQLANGGLN RR
Length:822
Mass (Da):91,825
Last modified:June 1, 1994 - v1
Checksum:iE59D924D0A1DE5C5
GO

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
Q63827Q63827_RAT
Fibroblast growth factor receptor
Fgfr1
729Annotation score:
F1LM54F1LM54_RAT
Fibroblast growth factor receptor
Fgfr1
727Annotation score:

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D12498 mRNA Translation: BAA02059.1
PIRiS29840
RefSeqiNP_077060.1, NM_024146.1
UniGeneiRn.207203
Rn.9797

Genome annotation databases

GeneIDi79114
KEGGirno:79114
UCSCiRGD:620713 rat

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D12498 mRNA Translation: BAA02059.1
PIRiS29840
RefSeqiNP_077060.1, NM_024146.1
UniGeneiRn.207203
Rn.9797

3D structure databases

ProteinModelPortaliQ04589
SMRiQ04589
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi249399, 3 interactors
CORUMiQ04589
IntActiQ04589, 3 interactors
MINTiQ04589
STRINGi10116.ENSRNOP00000036885

PTM databases

iPTMnetiQ04589

Proteomic databases

PaxDbiQ04589
PRIDEiQ04589

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi79114
KEGGirno:79114
UCSCiRGD:620713 rat

Organism-specific databases

CTDi2260
RGDi620713 Fgfr1

Phylogenomic databases

eggNOGiKOG0200 Eukaryota
COG0515 LUCA
HOGENOMiHOG000263410
HOVERGENiHBG000345
InParanoidiQ04589
KOiK04362
PhylomeDBiQ04589

Enzyme and pathway databases

BRENDAi2.7.10.1 5301

Miscellaneous databases

PROiPR:Q04589

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
ProtoNetiSearch...

Entry informationi

Entry nameiFGFR1_RAT
AccessioniPrimary (citable) accession number: Q04589
Entry historyiIntegrated into UniProtKB/Swiss-Prot: June 1, 1994
Last sequence update: June 1, 1994
Last modified: November 7, 2018
This is version 165 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
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Main funding by: National Institutes of Health

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