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Protein

Fibroblast growth factor receptor 2

Gene

fgfr2

Organism
Danio rerio (Zebrafish) (Brachydanio rerio)
Status
Reviewed-Annotation score: 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 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)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei513 – 5131ATPPROSITE-ProRule annotation
Binding sitei567 – 5671ATPPROSITE-ProRule annotation
Active sitei622 – 6221Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi483 – 4919ATPPROSITE-ProRule annotation
Nucleotide bindingi561 – 5633ATPPROSITE-ProRule annotation

GO - Molecular functioni

GO - Biological processi

  • apoptotic process Source: UniProtKB-KW
  • cell proliferation in midbrain Source: ZFIN
  • cilium assembly Source: ZFIN
  • determination of heart left/right asymmetry Source: ZFIN
  • determination of left/right asymmetry in lateral mesoderm Source: ZFIN
  • determination of liver left/right asymmetry Source: ZFIN
  • determination of pancreatic left/right asymmetry Source: ZFIN
  • digestive tract development Source: ZFIN
  • midbrain development Source: ZFIN
  • positive regulation of cell proliferation Source: InterPro
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Receptor, Transferase, Tyrosine-protein kinase

Keywords - Biological processi

Apoptosis

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Fibroblast growth factor receptor 2 (EC:2.7.10.1)
Short name:
FGFR-2
Gene namesi
Name:fgfr2
OrganismiDanio rerio (Zebrafish) (Brachydanio rerio)
Taxonomic identifieri7955 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiActinopterygiiNeopterygiiTeleosteiOstariophysiCypriniformesCyprinidaeDanio
Proteomesi
  • UP000000437 Componenti: Unplaced

Organism-specific databases

ZFINiZDB-GENE-030323-1. fgfr2.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini23 – 377355ExtracellularSequence analysisAdd
BLAST
Transmembranei378 – 39821HelicalSequence analysisAdd
BLAST
Topological domaini399 – 817419CytoplasmicSequence analysisAdd
BLAST

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasmic vesicle, Golgi apparatus, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2222Sequence analysisAdd
BLAST
Chaini23 – 817795Fibroblast growth factor receptor 2PRO_0000249203Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi32 – 321N-linked (GlcNAc...)Sequence analysis
Disulfide bondi63 ↔ 108PROSITE-ProRule annotation
Glycosylationi84 – 841N-linked (GlcNAc...)Sequence analysis
Glycosylationi124 – 1241N-linked (GlcNAc...)Sequence analysis
Disulfide bondi179 ↔ 231PROSITE-ProRule annotation
Glycosylationi228 – 2281N-linked (GlcNAc...)Sequence analysis
Glycosylationi265 – 2651N-linked (GlcNAc...)Sequence analysis
Disulfide bondi278 ↔ 342PROSITE-ProRule annotation
Glycosylationi297 – 2971N-linked (GlcNAc...)Sequence analysis
Glycosylationi318 – 3181N-linked (GlcNAc...)Sequence analysis
Glycosylationi331 – 3311N-linked (GlcNAc...)Sequence analysis
Modified residuei462 – 4621Phosphotyrosine; by autocatalysisBy similarity
Modified residuei582 – 5821Phosphotyrosine; by autocatalysisBy similarity
Modified residuei652 – 6521Phosphotyrosine; by autocatalysisBy similarity
Modified residuei653 – 6531Phosphotyrosine; by autocatalysisBy similarity
Modified residuei765 – 7651Phosphotyrosine; 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 (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

PaxDbiQ8JG38.
PRIDEiQ8JG38.

Interactioni

Subunit structurei

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

Binary interactionsi

WithEntry#Exp.IntActNotes
fgfrl1bB3DGS12EBI-2268234,EBI-2268218
lrrtm4l1A8BB402EBI-2268234,EBI-2263384
vstm4bA4JYE72EBI-2268234,EBI-2268137

GO - Molecular functioni

  • fibroblast growth factor binding Source: ZFIN

Protein-protein interaction databases

IntActiQ8JG38. 3 interactions.
STRINGi7955.ENSDARP00000124761.

Structurei

3D structure databases

ProteinModelPortaliQ8JG38.
SMRiQ8JG38. Positions 152-362, 463-761.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini26 – 126101Ig-like C2-type 1Add
BLAST
Domaini159 – 24789Ig-like C2-type 2Add
BLAST
Domaini256 – 358103Ig-like C2-type 3Add
BLAST
Domaini477 – 766290Protein kinasePROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni161 – 17818Heparin-bindingBy similarityAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi431 – 44111Poly-SerAdd
BLAST

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
Contains 1 protein kinase domain.PROSITE-ProRule annotation

Keywords - Domaini

Immunoglobulin domain, Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG0200. Eukaryota.
COG0515. LUCA.
HOGENOMiHOG000263410.
HOVERGENiHBG000345.
InParanoidiQ8JG38.
PhylomeDBiQ8JG38.

Family and domain databases

Gene3Di2.60.40.10. 3 hits.
InterProiIPR016248. FGF_rcpt_fam.
IPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR013098. Ig_I-set.
IPR003599. Ig_sub.
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]
PfamiPF07679. I-set. 3 hits.
PF07714. Pkinase_Tyr. 1 hit.
[Graphical view]
PIRSFiPIRSF000628. FGFR. 1 hit.
PRINTSiPR00109. TYRKINASE.
SMARTiSM00409. IG. 3 hits.
SM00408. IGc2. 3 hits.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMiSSF48726. SSF48726. 3 hits.
SSF56112. 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.

Q8JG38-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MFARGWLLGA LLLMTLATVS VARPSLKIDL VNTSAPEEPP TKNQNCVPVL
60 70 80 90 100
FSVHPGELLK LKCPLSGADD VVWTKDSSSL RPDNRTLVAR DWLQISDATP
110 120 130 140 150
KDSGLYSCSA TGLRDCDVFS FIVNVTDAIS SGDDEDDTER SDDVGADGEQ
160 170 180 190 200
MRLPYWTFPE KMEKKLHAVP AANTVKFRCA AAGNPKPKMR WLKNAKPFRQ
210 220 230 240 250
EDRMGGYKVR LQHWTLIMES VVPSDKGNYT CLVENQYGSI DHTYTLDVVE
260 270 280 290 300
RSPHRPILQA GLPANVTVQV GQDAKFVCKV YSDAQPHIQW LQHYTKNGSC
310 320 330 340 350
CGPDGLPYVR VLKTAGVNTT DKEIEVLYLP NVTFEDAGEY TCLAGNSIGI
360 370 380 390 400
SYHTAWLTVH PAETNPIETD YPPDYVEIAI YCIGVFLIAC MVVIVVVCRM
410 420 430 440 450
RTSAKKPDFS SQPAVHKLTK QIPLRRQVTV SSDSSSSMSS STPLVRITTR
460 470 480 490 500
RSSAHDDPIP EYDLPEDPRW EFSRDKLTLG KPLGEGCFGQ VVMAEALGID
510 520 530 540 550
KDKPKEAVTV AVKMLKDDAT EKDLSDLVSE MEMMKMIGRH KNIINLLGAC
560 570 580 590 600
TQDGPLYVIV EYASKGNLRE YLRARRPPGM EYSYDIARVS DEPLTFKDLV
610 620 630 640 650
SCTYQVARGM EYLASQKCIH RDLAARNVLV TESNVMKIAD FGLARDVHNI
660 670 680 690 700
DYYKKTTNGR LPVKWMAPEA LFDRVYTHQS DVWSFGVLMW EIFTLGGSPY
710 720 730 740 750
PGIPVEELFK LLKEGHRMDK PANCTNELYM MMKDCWHAIS SHRPTFKQLV
760 770 780 790 800
EDLDRILTLA TNEEYLDLCA PVEQYSPSFP DTRSSCPSGD DSVFSHDPLA
810
DEPCLPKYQH INGGIKT
Length:817
Mass (Da):91,388
Last modified:October 1, 2002 - v1
Checksum:i0A6D9F5412B27D69
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ309303 mRNA. Translation: CAC84705.1.
UniGeneiDr.116399.
Dr.31427.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ309303 mRNA. Translation: CAC84705.1.
UniGeneiDr.116399.
Dr.31427.

3D structure databases

ProteinModelPortaliQ8JG38.
SMRiQ8JG38. Positions 152-362, 463-761.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiQ8JG38. 3 interactions.
STRINGi7955.ENSDARP00000124761.

Proteomic databases

PaxDbiQ8JG38.
PRIDEiQ8JG38.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Organism-specific databases

ZFINiZDB-GENE-030323-1. fgfr2.

Phylogenomic databases

eggNOGiKOG0200. Eukaryota.
COG0515. LUCA.
HOGENOMiHOG000263410.
HOVERGENiHBG000345.
InParanoidiQ8JG38.
PhylomeDBiQ8JG38.

Miscellaneous databases

PROiQ8JG38.

Family and domain databases

Gene3Di2.60.40.10. 3 hits.
InterProiIPR016248. FGF_rcpt_fam.
IPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR013098. Ig_I-set.
IPR003599. Ig_sub.
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]
PfamiPF07679. I-set. 3 hits.
PF07714. Pkinase_Tyr. 1 hit.
[Graphical view]
PIRSFiPIRSF000628. FGFR. 1 hit.
PRINTSiPR00109. TYRKINASE.
SMARTiSM00409. IG. 3 hits.
SM00408. IGc2. 3 hits.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMiSSF48726. SSF48726. 3 hits.
SSF56112. 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]
ProtoNetiSearch...

Entry informationi

Entry nameiFGFR2_DANRE
AccessioniPrimary (citable) accession number: Q8JG38
Entry historyi
Integrated into UniProtKB/Swiss-Prot: September 5, 2006
Last sequence update: October 1, 2002
Last modified: May 11, 2016
This is version 103 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.