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P22182 (FGFR1_XENLA) Reviewed, UniProtKB/Swiss-Prot

Last modified April 3, 2013. Version 113. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
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Names and origin

Protein namesRecommended name:
Fibroblast growth factor receptor 1
Short name=FGFR-1
EC=2.7.10.1
Gene names
Name:fgfr1
Synonyms:fgfra2
OrganismXenopus laevis (African clawed frog)
Taxonomic identifier8355 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Amphibia › Batrachia › Anura › Pipoidea › Pipidae › Xenopodinae › Xenopus › Xenopus

Protein attributes

Sequence length812 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 embryonic development, cell proliferation, differentiation and migration. Required for normal mesoderm patterning and normal skeletogenesis. 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 ubiquitination, internalization and degradation 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 sequential autophosphorylation on tyrosine residues By similarity.

Subunit structure

Monomer. Homodimer after ligand binding By similarity. Interacts with il17rd. Ref.3

Subcellular location

Cell membrane; Single-pass type I membrane protein By similarity. Nucleus By similarity. Cytoplasm › cytosol By similarity. 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.

Domain

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.

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 and proceeds in a highly ordered manner. Phosphotyrosine residues provide docking sites for interacting proteins and so are crucial for FGFR1 function and its regulation By similarity.

Ubiquitinated. FGFR1 is rapidly ubiquitinated after autophosphorylation, leading to internalization and degradation 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.

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.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P22182-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: P22182-2)

The sequence of this isoform differs from the canonical sequence as follows:
     31-118: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2020 By similarity
Chain21 – 812792Fibroblast growth factor receptor 1
PRO_0000016792

Regions

Topological domain21 – 371351Extracellular Potential
Transmembrane372 – 39322Helical; Potential
Topological domain394 – 812419Cytoplasmic Potential
Domain25 – 11894Ig-like C2-type 1
Domain154 – 24289Ig-like C2-type 2
Domain251 – 353103Ig-like C2-type 3
Domain472 – 761290Protein kinase
Nucleotide binding478 – 4847ATP By similarity
Nucleotide binding556 – 5583ATP By similarity

Sites

Active site6171Proton acceptor By similarity
Binding site5081ATP By similarity
Binding site5621ATP By similarity
Binding site6211ATP By similarity
Binding site6351ATP By similarity

Amino acid modifications

Modified residue4571Phosphotyrosine; by autocatalysis By similarity
Modified residue5771Phosphotyrosine; by autocatalysis By similarity
Modified residue5791Phosphotyrosine; by autocatalysis By similarity
Modified residue6471Phosphotyrosine; by autocatalysis By similarity
Modified residue6481Phosphotyrosine; by autocatalysis By similarity
Modified residue7241Phosphotyrosine; by autocatalysis By similarity
Modified residue7601Phosphotyrosine; by autocatalysis By similarity
Glycosylation761N-linked (GlcNAc...) Potential
Glycosylation1161N-linked (GlcNAc...) Potential
Glycosylation1331N-linked (GlcNAc...) Potential
Glycosylation1771N-linked (GlcNAc...) Potential
Glycosylation2231N-linked (GlcNAc...) Potential
Glycosylation2361N-linked (GlcNAc...) Potential
Glycosylation2601N-linked (GlcNAc...) Potential
Glycosylation2921N-linked (GlcNAc...) Potential
Glycosylation3131N-linked (GlcNAc...) Potential
Glycosylation3261N-linked (GlcNAc...) Potential
Disulfide bond54 ↔ 100 By similarity
Disulfide bond174 ↔ 226 By similarity
Disulfide bond273 ↔ 337 By similarity

Natural variations

Alternative sequence31 – 11888Missing in isoform 2.
VSP_011847

Experimental info

Sequence conflict1901N → G in AAA49993. Ref.2
Sequence conflict4191V → L in AAA49993. Ref.2
Sequence conflict6371G → R in AAA49993. Ref.2
Sequence conflict7891M → V in AAA49993. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified August 1, 1991. Version 1.
Checksum: B06333BAFEAC5C9B

FASTA81290,502
        10         20         30         40         50         60 
MFSGMSLLLW GVLLGAALSV ARPPSTLPDE VAPKTKTEVE PYSAQPGDRI TLQCRLREDV 

        70         80         90        100        110        120 
QSINWVKNGV QLSETNRTRI TGEEIQISNA GPEDNGVYAC VTNGPSRTYT VLCSVNVSDA 

       130        140        150        160        170        180 
LPSAEDDDED DDNSSSEEKA AENSKPNRPL WSHPEKMEKK LHAVPAAKTV KFRCPANGTP 

       190        200        210        220        230        240 
TPTLRWLKNN RAFQQDQRIG GYKVRSQTWS LIMDSVVPSD KGNYTCIVEN KYGAINHTYQ 

       250        260        270        280        290        300 
LDVVERSPHR PILQAGLPAN TSVTVGTTAE FSCKVYSDPQ PHIQWLRHIE INGSRVASDG 

       310        320        330        340        350        360 
FPYVEILKTA GVNTSDKDME VLHLRNVTFE DAGQYTCLAA NSIGISHHSA WLTVLKVEDN 

       370        380        390        400        410        420 
KPALLASPLQ LEIIIYCTGA AFVSAMVVTI IIFKMKHPSK KSDFNSQLAV HKLAKSIPVR 

       430        440        450        460        470        480 
RQVTVSGDSS SSMNSGVILV RRLSSSGTPM LSGLSEYELP EDPRWEVARD RLILGKPLGE 

       490        500        510        520        530        540 
GCFGQVVMAE AIGLDKEKPN KVTKVAVKML KSDASEKDLS DLISEMEMMK MIGKHKNIIN 

       550        560        570        580        590        600 
LLGACTQDGP LYVIVEYTSK GNLREYLRAR RPPAMEYCYN PTCVPDQLLS FKDLVSCAYQ 

       610        620        630        640        650        660 
VARGMDYLAS KKCIHRDLAA RNVLVTEDNI MKIADFGLAR DIHHIDYYKK TTNGRLPVKW 

       670        680        690        700        710        720 
MAPEALFDRI YTHQSDVWSF GVLLWEIFTL GGSPYPGVPM EELFKLLKEG HRMDKPTNCT 

       730        740        750        760        770        780 
NELYMMMKDC WHAMPSQRPT FNQLVEDLDR ILALSSNQEY LDLSMPVNQY SPCFPDTRSS 

       790        800        810 
TCSSGEDSMF SHDPLPDEPC LPKYSNGGLK KR

« Hide

Isoform 2 [UniParc].

Checksum: 5856ACBCFE8A5007
Show »

FASTA72480,866

References

[1]"Regulation of the fibroblast growth factor receptor in early Xenopus embryos."
Musci T.J., Amaya E., Kirschner M.W.
Proc. Natl. Acad. Sci. U.S.A. 87:8365-8369(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]"cDNA cloning and developmental expression of fibroblast growth factor receptors from Xenopus laevis."
Friesel R.E., Dawid I.B.
Mol. Cell. Biol. 11:2481-2488(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
[3]"Sef inhibits fibroblast growth factor signaling by inhibiting FGFR1 tyrosine phosphorylation and subsequent ERK activation."
Kovalenko D., Yang X., Nadeau R.J., Harkins L.K., Friesel R.
J. Biol. Chem. 278:14087-14091(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH IL17RD.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ		U24491 mRNA. Translation: AAA86868.1.
M62322 mRNA. Translation: AAA49993.1.
PIRA36477.
RefSeqNP_001081157.1. NM_001087688.1.
NP_001081338.1. NM_001087869.1.
UniGeneXl.34918.
Xl.6480.

3D structure databases

ProteinModelPortalP22182.
SMRP22182. Positions 38-124, 146-355, 458-759.
ModBaseSearch...

Protein-protein interaction databases

MINTMINT-1778523.

Proteomic databases

PRIDEP22182.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID394418.
397782.
KEGGxla:394418.
xla:397782.

Organism-specific databases

CTD394418.
397782.
XenbaseXB-GENE-6254218. fgfr1.

Phylogenomic databases

HOVERGENHBG000345.
KOK04362.

Enzyme and pathway databases

BRENDA2.7.10.1. 6726.

Family and domain databases

Gene3D2.60.40.10. 3 hits.
InterProIPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR013098. Ig_I-set.
IPR003598. Ig_sub2.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_cat_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
IPR008266. Tyr_kinase_AS.
IPR020635. Tyr_kinase_cat_dom.
IPR016248. Tyr_kinase_fibroblast_GF_rcpt.
[Graphical view]
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. Kinase_like. 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 nameFGFR1_XENLA
AccessionPrimary (citable) accession number: P22182
Secondary accession number(s): Q03836
Entry history
Integrated into UniProtKB/Swiss-Prot: August 1, 1991
Last sequence update: August 1, 1991
Last modified: April 3, 2013
This is version 113 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

to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents