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Q8JG38 (FGFR2_DANRE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 90. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Fibroblast growth factor receptor 2

Short name=FGFR-2
EC=2.7.10.1
Gene names
Name:fgfr2
OrganismDanio rerio (Zebrafish) (Brachydanio rerio) [Reference proteome]
Taxonomic identifier7955 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiActinopterygiiNeopterygiiTeleosteiOstariophysiCypriniformesCyprinidaeDanio

Protein attributes

Sequence length817 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence 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 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.

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 autophosphorylation on tyrosine residues By similarity.

Subunit structure

Monomer. Homodimer after ligand binding By similarity.

Subcellular location

Cell membrane; Single-pass type I membrane protein. Golgi apparatus By similarity. Cytoplasmic vesicle By similarity. Note: Detected on osteoblast plasma membrane lipid rafts. After ligand binding, the activated receptor is rapidly internalized and degraded By similarity.

Domain

The second and third Ig-like domains directly interact with fibroblast growth factors (FGF) and heparan sulfate proteoglycans 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 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.

Ubiquitinated. FGFR2 is rapidly ubiquitinated after autophosphorylation, leading to internalization and degradation. Subject to degradation both in lysosomes and by the proteasome 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.

Binary interactions

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2222 Potential
Chain23 – 817795Fibroblast growth factor receptor 2
PRO_0000249203

Regions

Topological domain23 – 377355Extracellular Potential
Transmembrane378 – 39821Helical; Potential
Topological domain399 – 817419Cytoplasmic Potential
Domain26 – 126101Ig-like C2-type 1
Domain159 – 24789Ig-like C2-type 2
Domain256 – 358103Ig-like C2-type 3
Domain477 – 766290Protein kinase
Nucleotide binding483 – 4919ATP By similarity
Nucleotide binding561 – 5633ATP By similarity
Region161 – 17818Heparin-binding By similarity
Compositional bias431 – 44111Poly-Ser

Sites

Active site6221Proton acceptor By similarity
Binding site5131ATP By similarity
Binding site5671ATP By similarity

Amino acid modifications

Modified residue4621Phosphotyrosine; by autocatalysis By similarity
Modified residue5821Phosphotyrosine; by autocatalysis By similarity
Modified residue6521Phosphotyrosine; by autocatalysis By similarity
Modified residue6531Phosphotyrosine; by autocatalysis By similarity
Modified residue7651Phosphotyrosine; by autocatalysis By similarity
Glycosylation321N-linked (GlcNAc...) Potential
Glycosylation841N-linked (GlcNAc...) Potential
Glycosylation1241N-linked (GlcNAc...) Potential
Glycosylation2281N-linked (GlcNAc...) Potential
Glycosylation2651N-linked (GlcNAc...) Potential
Glycosylation2971N-linked (GlcNAc...) Potential
Glycosylation3181N-linked (GlcNAc...) Potential
Glycosylation3311N-linked (GlcNAc...) Potential
Disulfide bond63 ↔ 108 By similarity
Disulfide bond179 ↔ 231 By similarity
Disulfide bond278 ↔ 342 By similarity

Sequences

Sequence LengthMass (Da)Tools
Q8JG38 [UniParc].

Last modified October 1, 2002. Version 1.
Checksum: 0A6D9F5412B27D69

FASTA81791,388
        10         20         30         40         50         60 
MFARGWLLGA LLLMTLATVS VARPSLKIDL VNTSAPEEPP TKNQNCVPVL FSVHPGELLK 

        70         80         90        100        110        120 
LKCPLSGADD VVWTKDSSSL RPDNRTLVAR DWLQISDATP KDSGLYSCSA TGLRDCDVFS 

       130        140        150        160        170        180 
FIVNVTDAIS SGDDEDDTER SDDVGADGEQ MRLPYWTFPE KMEKKLHAVP AANTVKFRCA 

       190        200        210        220        230        240 
AAGNPKPKMR WLKNAKPFRQ EDRMGGYKVR LQHWTLIMES VVPSDKGNYT CLVENQYGSI 

       250        260        270        280        290        300 
DHTYTLDVVE RSPHRPILQA GLPANVTVQV GQDAKFVCKV YSDAQPHIQW LQHYTKNGSC 

       310        320        330        340        350        360 
CGPDGLPYVR VLKTAGVNTT DKEIEVLYLP NVTFEDAGEY TCLAGNSIGI SYHTAWLTVH 

       370        380        390        400        410        420 
PAETNPIETD YPPDYVEIAI YCIGVFLIAC MVVIVVVCRM RTSAKKPDFS SQPAVHKLTK 

       430        440        450        460        470        480 
QIPLRRQVTV SSDSSSSMSS STPLVRITTR RSSAHDDPIP EYDLPEDPRW EFSRDKLTLG 

       490        500        510        520        530        540 
KPLGEGCFGQ VVMAEALGID KDKPKEAVTV AVKMLKDDAT EKDLSDLVSE MEMMKMIGRH 

       550        560        570        580        590        600 
KNIINLLGAC TQDGPLYVIV EYASKGNLRE YLRARRPPGM EYSYDIARVS DEPLTFKDLV 

       610        620        630        640        650        660 
SCTYQVARGM EYLASQKCIH RDLAARNVLV TESNVMKIAD FGLARDVHNI DYYKKTTNGR 

       670        680        690        700        710        720 
LPVKWMAPEA LFDRVYTHQS DVWSFGVLMW EIFTLGGSPY PGIPVEELFK LLKEGHRMDK 

       730        740        750        760        770        780 
PANCTNELYM MMKDCWHAIS SHRPTFKQLV EDLDRILTLA TNEEYLDLCA PVEQYSPSFP 

       790        800        810 
DTRSSCPSGD DSVFSHDPLA DEPCLPKYQH INGGIKT 

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References

[1]"Cloning and characterization of zebrafish fibroblast growth factor receptor 2 (Z-FGFR2): role of FGFR2-signaling in bone development."
Kaps C., Schlombs K., Kraus B., Odenthal J., Langheinrich U., Trowe T.
Submitted (APR-2001) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AJ309303 mRNA. Translation: CAC84705.1.
UniGeneDr.116399.
Dr.31427.

3D structure databases

ProteinModelPortalQ8JG38.
SMRQ8JG38. Positions 152-362, 463-761.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActQ8JG38. 3 interactions.

Proteomic databases

PRIDEQ8JG38.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Organism-specific databases

ZFINZDB-GENE-030323-1. fgfr2.

Phylogenomic databases

eggNOGNOG242770.
HOGENOMHOG000263410.
HOVERGENHBG000345.
PhylomeDBQ8JG38.

Family and domain databases

Gene3D2.60.40.10. 3 hits.
InterProIPR028175. FGF_rcpt_2.
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]
PANTHERPTHR24416:SF130. PTHR24416:SF130. 1 hit.
PfamPF07679. I-set. 3 hits.
PF07714. Pkinase_Tyr. 1 hit.
[Graphical view]
PIRSFPIRSF000628. FGFR. 1 hit.
PRINTSPR00109. TYRKINASE.
SMARTSM00408. IGc2. 3 hits.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMSSF56112. SSF56112. 1 hit.
PROSITEPS50835. IG_LIKE. 3 hits.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00109. PROTEIN_KINASE_TYR. 1 hit.
[Graphical view]
ProtoNetSearch...

Entry information

Entry nameFGFR2_DANRE
AccessionPrimary (citable) accession number: Q8JG38
Entry history
Integrated into UniProtKB/Swiss-Prot: September 5, 2006
Last sequence update: October 1, 2002
Last modified: April 16, 2014
This is version 90 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families