Skip Header

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

Q04589

- FGFR1_RAT

UniProt

Q04589 - FGFR1_RAT

(max 400 entries)x

Your basket is currently empty.

Select item(s) and click on "Add to basket" to create your own collection here
(400 entries max)

Protein

Fibroblast growth factor receptor 1

Gene

Fgfr1

Organism
Rattus norvegicus (Rat)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

Functioni

Tyrosine-protein kinase that acts as cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of embryonic development, cell proliferation, differentiation and migration. Required for normal mesoderm patterning and correct axial organization during embryonic development, normal skeletogenesis and normal development of the gonadotropin-releasing hormone (GnRH) neuronal system. Phosphorylates PLCG1, FRS2, GAB1 and SHB. Ligand binding leads to the activation of several signaling cascades. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate. Phosphorylation of FRS2 triggers recruitment of GRB2, GAB1, PIK3R1 and SOS1, and mediates activation of RAS, MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway. Promotes phosphorylation of SHC1, STAT1 and PTPN11/SHP2. In the nucleus, enhances RPS6KA1 and CREB1 activity and contributes to the regulation of transcription. FGFR1 signaling is down-regulated by IL17RD/SEF, and by FGFR1 ubiquitination, internalization and degradation (By similarity).By similarity

Catalytic activityi

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

Enzyme regulationi

Present in an inactive conformation in the absence of bound ligand. Ligand binding leads to dimerization and activation by sequential autophosphorylation on tyrosine residues (By similarity).By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei514 – 5141ATPPROSITE-ProRule annotation
Binding sitei568 – 5681ATPPROSITE-ProRule annotation
Active sitei623 – 6231Proton acceptorPROSITE-ProRule annotation
Binding sitei627 – 6271ATPPROSITE-ProRule annotation
Binding sitei641 – 6411ATPPROSITE-ProRule annotation
Sitei766 – 7661Mediates interaction with PLCG1 and SHBBy similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi484 – 4907ATPPROSITE-ProRule annotation
Nucleotide bindingi562 – 5643ATPPROSITE-ProRule annotation

GO - Molecular functioni

  1. ATP binding Source: UniProtKB-KW
  2. cell adhesion molecule binding Source: RGD
  3. fibroblast growth factor-activated receptor activity Source: UniProtKB
  4. fibroblast growth factor binding Source: UniProtKB
  5. glycoprotein binding Source: RGD
  6. heparin binding Source: UniProtKB
  7. protein complex binding Source: RGD

GO - Biological processi

  1. central nervous system neuron development Source: RGD
  2. fibroblast growth factor receptor signaling pathway Source: UniProtKB
  3. motogenic signaling involved in postnatal olfactory bulb interneuron migration Source: RGD
  4. negative regulation of osteoblast differentiation Source: RGD
  5. neuron projection development Source: RGD
  6. peptidyl-tyrosine phosphorylation Source: UniProtKB
  7. positive regulation of cell proliferation Source: UniProtKB
  8. positive regulation of MAP kinase activity Source: UniProtKB
  9. positive regulation of mesenchymal cell proliferation Source: RGD
  10. positive regulation of neuron differentiation Source: UniProtKB
  11. positive regulation of neuron projection development Source: RGD
  12. positive regulation of phospholipase C activity Source: UniProtKB
  13. positive regulation of transcription from RNA polymerase II promoter Source: BHF-UCL
  14. protein autophosphorylation Source: UniProtKB
  15. regulation of cell proliferation Source: RGD
  16. regulation of sensory perception of pain Source: RGD
  17. regulation of stem cell proliferation Source: RGD
  18. stem cell maintenance Source: RGD
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Receptor, Transferase, Tyrosine-protein kinase

Keywords - Ligandi

ATP-binding, Heparin-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.10.1. 5301.

Names & Taxonomyi

Protein namesi
Recommended name:
Fibroblast growth factor receptor 1 (EC:2.7.10.1)
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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
ProteomesiUP000002494: Unplaced

Organism-specific databases

RGDi620713. Fgfr1.

Subcellular locationi

Cell membrane 1 Publication; Single-pass type I membrane protein 1 Publication. Nucleus 1 Publication. Cytoplasmcytosol 1 Publication. 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).By similarity

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini22 – 376355ExtracellularSequence AnalysisAdd
BLAST
Transmembranei377 – 39721HelicalSequence AnalysisAdd
BLAST
Topological domaini398 – 822425CytoplasmicSequence AnalysisAdd
BLAST

GO - Cellular componenti

  1. cytoplasmic vesicle Source: UniProtKB-KW
  2. integral component of membrane Source: UniProtKB-KW
  3. nucleus Source: UniProtKB-KW
  4. plasma membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Cytoplasmic vesicle, Membrane, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2121Sequence AnalysisAdd
BLAST
Chaini22 – 822801Fibroblast growth factor receptor 1PRO_0000016782Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi55 ↔ 101PROSITE-ProRule annotation
Glycosylationi77 – 771N-linked (GlcNAc...)Sequence Analysis
Glycosylationi117 – 1171N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi178 ↔ 230PROSITE-ProRule annotation
Glycosylationi227 – 2271N-linked (GlcNAc...)Sequence Analysis
Glycosylationi240 – 2401N-linked (GlcNAc...)Sequence Analysis
Glycosylationi264 – 2641N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi277 ↔ 341PROSITE-ProRule annotation
Glycosylationi296 – 2961N-linked (GlcNAc...)Sequence Analysis
Glycosylationi317 – 3171N-linked (GlcNAc...)Sequence Analysis
Glycosylationi330 – 3301N-linked (GlcNAc...)Sequence Analysis
Modified residuei463 – 4631Phosphotyrosine; by autocatalysisBy similarity
Modified residuei583 – 5831Phosphotyrosine; by autocatalysisBy similarity
Modified residuei585 – 5851Phosphotyrosine; by autocatalysisBy similarity
Modified residuei653 – 6531Phosphotyrosine; by autocatalysisBy similarity
Modified residuei654 – 6541Phosphotyrosine; by autocatalysisBy similarity
Modified residuei730 – 7301Phosphotyrosine; by autocatalysisBy similarity
Modified residuei766 – 7661Phosphotyrosine; by autocatalysisBy similarity

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.

Expressioni

Tissue specificityi

Expressed in the parathyroid.1 Publication

Gene expression databases

GenevestigatoriQ04589.

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 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).By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
Htr1aP193276EBI-2480918,EBI-6570156
Plcg1P106862EBI-2480918,EBI-520788

Protein-protein interaction databases

BioGridi249399. 1 interaction.
IntActiQ04589. 3 interactions.
MINTiMINT-1520059.

Structurei

3D structure databases

ProteinModelPortaliQ04589.
SMRiQ04589. Positions 25-119, 150-359, 464-765.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini25 – 11995Ig-like C2-type 1Add
BLAST
Domaini158 – 24689Ig-like C2-type 2Add
BLAST
Domaini255 – 357103Ig-like C2-type 3Add
BLAST
Domaini478 – 767290Protein kinasePROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni160 – 17718Heparin-bindingAdd
BLAST

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
Contains 1 protein kinase domain.PROSITE-ProRule annotation

Keywords - Domaini

Immunoglobulin domain, Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiCOG0515.
HOGENOMiHOG000263410.
HOVERGENiHBG000345.
InParanoidiQ04589.
KOiK04362.
PhylomeDBiQ04589.

Family and domain databases

Gene3Di2.60.40.10. 3 hits.
InterProiIPR028174. FGF_rcpt_1/4.
IPR016248. FGF_rcpt_fam.
IPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR013098. Ig_I-set.
IPR003598. Ig_sub2.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
IPR008266. Tyr_kinase_AS.
IPR020635. Tyr_kinase_cat_dom.
[Graphical view]
PANTHERiPTHR24416:SF131. PTHR24416:SF131. 1 hit.
PfamiPF07679. I-set. 3 hits.
PF07714. Pkinase_Tyr. 1 hit.
[Graphical view]
PIRSFiPIRSF000628. FGFR. 1 hit.
PRINTSiPR00109. TYRKINASE.
SMARTiSM00408. IGc2. 3 hits.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS50835. IG_LIKE. 3 hits.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00109. PROTEIN_KINASE_TYR. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

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

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

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.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D12498 mRNA. Translation: BAA02059.1 .
PIRi S29840.
RefSeqi NP_077060.1. NM_024146.1.
UniGenei Rn.207203.
Rn.9797.

3D structure databases

ProteinModelPortali Q04589.
SMRi Q04589. Positions 25-119, 150-359, 464-765.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 249399. 1 interaction.
IntActi Q04589. 3 interactions.
MINTi MINT-1520059.

Proteomic databases

PaxDbi Q04589.
PRIDEi Q04589.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

GeneIDi 79114.
KEGGi rno:79114.
UCSCi RGD:620713. rat.

Organism-specific databases

CTDi 2260.
RGDi 620713. Fgfr1.

Phylogenomic databases

eggNOGi COG0515.
HOGENOMi HOG000263410.
HOVERGENi HBG000345.
InParanoidi Q04589.
KOi K04362.
PhylomeDBi Q04589.

Enzyme and pathway databases

BRENDAi 2.7.10.1. 5301.

Miscellaneous databases

NextBioi 614518.

Gene expression databases

Genevestigatori Q04589.

Family and domain databases

Gene3Di 2.60.40.10. 3 hits.
InterProi IPR028174. FGF_rcpt_1/4.
IPR016248. FGF_rcpt_fam.
IPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR013098. Ig_I-set.
IPR003598. Ig_sub2.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
IPR008266. Tyr_kinase_AS.
IPR020635. Tyr_kinase_cat_dom.
[Graphical view ]
PANTHERi PTHR24416:SF131. PTHR24416:SF131. 1 hit.
Pfami PF07679. I-set. 3 hits.
PF07714. Pkinase_Tyr. 1 hit.
[Graphical view ]
PIRSFi PIRSF000628. FGFR. 1 hit.
PRINTSi PR00109. TYRKINASE.
SMARTi SM00408. IGc2. 3 hits.
SM00219. TyrKc. 1 hit.
[Graphical view ]
SUPFAMi SSF56112. SSF56112. 1 hit.
PROSITEi 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 ]
ProtoNeti Search...

Publicationsi

  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. Cited for: TISSUE SPECIFICITY.

Entry informationi

Entry nameiFGFR1_RAT
AccessioniPrimary (citable) accession number: Q04589
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 1, 1994
Last sequence update: June 1, 1994
Last modified: October 29, 2014
This is version 136 of the entry and version 1 of the sequence. [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

External Data

Dasty 3