Skip Header

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

Fibroblast growth factor receptor 2

Gene

FGFR2

Organism
Gallus gallus (Chicken)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript leveli

Functioni

Tyrosine-protein kinase that acts as cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of cell proliferation, differentiation, migration and apoptosis, and in the regulation of embryonic development. Required for normal embryonic patterning, limb bud development, lung morphogenesis, osteogenesis and skin development. Plays an essential role in the regulation of osteoblast differentiation, proliferation and apoptosis, and is required for normal skeleton development. Promotes cell proliferation in keratinocytes and immature osteoblasts, but promotes apoptosis in differentiated osteoblasts. Phosphorylates PLCG1, FRS2 and PAK4. 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. FGFR2 signaling is down-regulated by ubiquitination, internalization and degradation. Mutations that lead to constitutive kinase activation or impair normal FGFR2 maturation, internalization and degradation lead to aberrant signaling. Over-expressed FGFR2 promotes activation of STAT1 (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 autophosphorylation on tyrosine residues (By similarity).By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei519ATPPROSITE-ProRule annotation1
Binding sitei573ATPPROSITE-ProRule annotation1
Active sitei628Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi489 – 497ATPPROSITE-ProRule annotation9
Nucleotide bindingi567 – 569ATPPROSITE-ProRule annotation3

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionKinase, Receptor, Transferase, Tyrosine-protein kinase
Biological processApoptosis
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.10.1. 1306.
ReactomeiR-GGA-109704. PI3K Cascade.
R-GGA-1257604. PIP3 activates AKT signaling.
R-GGA-190375. FGFR2c ligand binding and activation.
R-GGA-190377. FGFR2b ligand binding and activation.
R-GGA-5654221. Phospholipase C-mediated cascade, FGFR2.
R-GGA-5654693. FRS-mediated FGFR1 signaling.
R-GGA-5654695. PI-3K cascade:FGFR2.
R-GGA-5654699. SHC-mediated cascade:FGFR2.
R-GGA-5654700. FRS-mediated FGFR2 signaling.
R-GGA-5654706. FRS-mediated FGFR3 signaling.
R-GGA-5654712. FRS-mediated FGFR4 signaling.
R-GGA-5654727. Negative regulation of FGFR2 signaling.
R-GGA-5673001. RAF/MAP kinase cascade.
R-GGA-6811558. PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.

Names & Taxonomyi

Protein namesi
Recommended name:
Fibroblast growth factor receptor 2 (EC:2.7.10.1)
Short name:
FGFR-2
Alternative name(s):
Tyrosine kinase receptor CEK3
Gene namesi
Name:FGFR2
Synonyms:CEK3
OrganismiGallus gallus (Chicken)
Taxonomic identifieri9031 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiArchelosauriaArchosauriaDinosauriaSaurischiaTheropodaCoelurosauriaAvesNeognathaeGalloanseraeGalliformesPhasianidaePhasianinaeGallus
Proteomesi
  • UP000000539 Componenti: Chromosome 6

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 domaini24 – 379ExtracellularSequence analysisAdd BLAST356
Transmembranei380 – 400HelicalSequence analysisAdd BLAST21
Topological domaini401 – 823CytoplasmicSequence analysisAdd BLAST423

Keywords - Cellular componenti

Cell membrane, Cytoplasmic vesicle, Golgi apparatus, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 23Sequence analysisAdd BLAST23
ChainiPRO_000001679124 – 823Fibroblast growth factor receptor 2Add BLAST800

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi65 ↔ 110PROSITE-ProRule annotation
Glycosylationi86N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi126N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi148N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi181 ↔ 233PROSITE-ProRule annotation
Glycosylationi230N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi243N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi267N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi280 ↔ 344PROSITE-ProRule annotation
Glycosylationi299N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi320N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi333N-linked (GlcNAc...) asparagineSequence analysis1
Modified residuei468Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei588Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei658Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei659Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei771Phosphotyrosine; 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 (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
Ubiquitinated. FGFR2 is rapidly ubiquitinated after autophosphorylation, leading to internalization and degradation. Subject to degradation both in lysosomes and by the proteasome (By similarity).By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiP18461.
PRIDEiP18461.

Expressioni

Gene expression databases

BgeeiENSGALG00000009495.
ExpressionAtlasiP18461. baseline and differential.

Interactioni

Subunit structurei

Monomer. Homodimer after ligand binding (By similarity).By similarity

Protein-protein interaction databases

STRINGi9031.ENSGALP00000037940.

Structurei

3D structure databases

ProteinModelPortaliP18461.
SMRiP18461.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini27 – 128Ig-like C2-type 1Add BLAST102
Domaini156 – 249Ig-like C2-type 2Add BLAST94
Domaini258 – 360Ig-like C2-type 3Add BLAST103
Domaini483 – 772Protein kinasePROSITE-ProRule annotationAdd BLAST290

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni163 – 180Heparin-bindingBy similarityAdd BLAST18

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi135 – 145Asp/Glu-rich (highly acidic)Add BLAST11

Domaini

The second and third Ig-like domains directly interact with fibroblast growth factors (FGF) and heparan sulfate proteoglycans.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.
GeneTreeiENSGT00760000118923.
HOGENOMiHOG000263410.
HOVERGENiHBG000345.
InParanoidiP18461.
KOiK05093.
OrthoDBiEOG091G0CQZ.

Family and domain databases

Gene3Di2.60.40.10. 3 hits.
InterProiView protein in InterPro
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.
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. 3 hits.
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.

Sequencei

Sequence statusi: Complete.

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

P18461-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MVSWDSGCLI CLVVVTMAGL SLARPSFNLV VEDATLEPEE PPTKYQISQP
60 70 80 90 100
DVHSALPGEP LELRCQLKDA VMISWTKDGV PLGPDNRTVI IGEYLQIKDA
110 120 130 140 150
SPRDSGLYAC TAIRTLDSDT LYFIVNVTDA LSSGDDEDDN DGSEDFVNDS
160 170 180 190 200
NQMRAPYWTH TDKMEKRLHA VPAANTVKFR CPAMGNPTPT MRWLKNGKEF
210 220 230 240 250
KQEHRIGGYK VRNQHWSLIM ESVVPSDKGN YTCIVENQYG SINHTYHLDV
260 270 280 290 300
VERSPHRPIL QAGLPANASA VVGGDVEFVC KVYSDAQPHI QWIKHVERNG
310 320 330 340 350
SKYGPDGLPY LQVLKAAGVN TTDKEIEVLY IRNVTFEDAG EYTCLAGNSI
360 370 380 390 400
GISFHTAWLT VLPAPEKEKE FPTSPDYLEI AIYCIGVFLI ACMVLTVILC
410 420 430 440 450
RMKNTTKKPD FSSQPAVHKL TKRIPLRRQV TVSADSSSSM NSNTPLVRIT
460 470 480 490 500
TRLSSTADAP MLAGVSEYEL PEDPKWEFPR DKLTLGKPLG EGCFGQVVMA
510 520 530 540 550
EAVGIDKDRP KEAVTVAVKM LKDDATEKDL SDLVSEMEMM KMIGKHKNII
560 570 580 590 600
NLLGACTQDG PLYVIVEYAS KGNLREYLRA RRPPGMEYSF DINRVPEEQM
610 620 630 640 650
TFKDLVSCTY QLARGMEYLA SQKCIHRDLA ARNVLVTENN VMKIADFGLA
660 670 680 690 700
RDINNIDYYK KTTNGRLPVK WMAPEALFDR VYTHQSDVWS FGVLMWEIFT
710 720 730 740 750
LGGSPYPGIP VEELFKLLKE GHRMDKPANC TNELYMMMRD CWQAVPSQRP
760 770 780 790 800
TFKQLVEDLD RILTLTTNEE YLDLSGPLEQ YSPSYPDTRS SCSSGDDSVF
810 820
SPDPMPYEPC LPKYQHMNGS VKT
Length:823
Mass (Da):92,299
Last modified:November 1, 1990 - v1
Checksum:i42BF3CC4EA02FD43
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M35196 mRNA. Translation: AAA48665.1.
PIRiB35963.
RefSeqiNP_990650.1. NM_205319.2.
UniGeneiGga.1680.

Genome annotation databases

EnsembliENSGALT00000038732; ENSGALP00000037940; ENSGALG00000009495.
GeneIDi396259.
KEGGigga:396259.

Similar proteinsi

Entry informationi

Entry nameiFGFR2_CHICK
AccessioniPrimary (citable) accession number: P18461
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1990
Last sequence update: November 1, 1990
Last modified: November 22, 2017
This is version 153 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