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Fibroblast growth factor receptor: Difference between revisions

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<StructureSection load='1evt' size='350' side='right' scene='' caption='Human fibroblast growth factor receptor 1 ligand-binding domain modules D2 and D3 (pink and yellow) complex with fibroblast growth factor 1 (grey and green) and sulfate (PDB code [[1evt]]) '>
<StructureSection load='1evt' size='350' side='right' scene='54/544712/Cv/1' caption='Human fibroblast growth factor receptor 1 ligand-binding domain modules D2 and D3 (pink and yellow) complex with fibroblast growth factor 1 (cyan and green) and sulfate (PDB code [[1evt]]) '>


== Function ==
== Function ==


'''Fibroblast growth factor receptors''' (FGFR) are receptors which bind fibroblast growth factors (FGF).    Each FGFR can activate several FGFs.  Five FGFRs have been identified so far.  FGFRs differ in their ligand specificity and tissue distribution.  The binding of FGF to FGFR starts a cascade of signaling which influences mitogenesis and differentiation<ref>PMID:8713482</ref>.
'''Fibroblast growth factor receptors''' (FGFR) are receptors which bind [[fibroblast growth factors]] (FGF).    Each FGFR can activate several FGFs.  Five FGFRs have been identified so far.  FGFRs differ in their ligand specificity and tissue distribution.  The binding of FGF to FGFR starts a cascade of signaling which influences mitogenesis and differentiation<ref>PMID:8713482</ref>. See also [[Receptor tyrosine kinases]] and [[Kinase-linked, enzyme-linked and related receptors]].
*'''FGFR2''' is essential for limb induction<ref>PMID:9435295</ref>. 
*'''FGFR3''' is involved in skeletal dysplasia<ref>PMID:22045636</ref>.


== Disease ==
== Disease ==


Mutation in FGFR3 causes achondroplasia and is involved in myeloma.  Mutations in FGFR2 causes Crouzon syndrome.
Mutation in FGFR3 causes achondroplasia<ref>PMID:9718331</ref> and is involved in myeloma<ref>PMID:11529856</ref>.  Mutations in FGFR2 cause Crouzon syndrome<ref>PMID:7493034</ref>.


== Structural insights ==
== Structural insights ==


FGFR consist of an extracellular ligand-binding domain (LBD), transmembrane helix domain and cytoplasmic tyrosine kinase activity domain (TKD) with phosphorylated tyrosine designated PTR. FGFR LBD contains 3 immunoglobulin-like domains D1, D2 and D3.
FGFR consist of an extracellular ligand-binding domain (LBD), transmembrane helix domain and cytoplasmic tyrosine kinase activity domain (TKD) with phosphorylated tyrosine designated PTR. FGFR LBD contains 3 immunoglobulin-like domains D1, D2 and D3.
</StructureSection>
==3D structures of fibroblast growth factor receptor==


Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
<scene name='54/544712/Cv/2'>Human fibroblast growth factor receptor 1 ligand-binding domain modules D2 and D3 with 2 molecules of fibroblast growth factor 1</scene> (PDB code [[1evt]]).
{{#tree:id=OrganizedByTopic|openlevels=0|


*FGFR1
==3D structures of fibroblast growth factor receptor==
[[Fibroblast growth factor receptor 3D receptor]]


*''FGFR1 tyrosine kinase domain''
</StructureSection>
 
**[[1fgk]], [[3kxx]], [[3ky2]] – hFGFR1 TKD (mutant) - human <br />
**[[4uwy]] – hFGFR1 TKD <br />
**[[4wun]], [[5am6]] – hFGFR1 TKD + inhibitor <br />
**[[1agw]], [[1fgi]], [[2fgi]], [[3c4f]], [[3js2]], [[3rhx]], [[4f63]], [[4f64]], [[4f65]], [[3tt0]], [[4nk9]], [[4nka]], [[4nks]], [[3wj6]], [[5am7]]  – hFGFR1 TKD (mutant) + inhibitor <br />
**[[3krj]] – hFGFR1 TKD residues 538-678, 753-922 (mutant) + inhibitor <br />
**[[1xr0]] – hFGFR1 residues 409-430 + FGFR signaling adaptor N terminal - NMR<br />
**[[3gqi]] – hFGFR1 TKD (mutant) with PTR + ACP <br />
**[[3gql]] – hFGFR1 TKD (mutant) + substrate <br />
 
*''FGFR1 ligand-binding domain''
 
**[[2cr3]] – hFGFR1 LBD D1 - NMR<br />
**[[2ckn]] – FGFR1 LBD D1 – mouse - NMR<br />
 
*''FGFR1 complex with FGF''
 
**[[3ojv]] – hFGFR1 LBD D2,D3 (mutant) + hFGF1 - human <br />
**[[1cvs]] – hFGFR1 LBD D2,D3 (mutant)  + hFGF2 (mutant)  <br />
**[[1evt]] – hFGFR1 LBD D2,D3 + hFGF1  <br />
**[[1fq9]] – hFGFR1 (mutant) LBD D2,D3 + hFGF2 (mutant) + HS<br />
 
*FGFR2
 
*''FGFR2 tyrosine kinase domain''
 
**[[1gjo]], [[1oec]], [[2psq]] – hFGFR2 TKD  <br />
**[[2pvy]], [[2pwl]], [[2py3]], [[2pz5]], [[2pzp]], [[2pzr]], [[2q0b]], [[4j95]], [[4j96]], [[4j97]], [[4j98]], [[4j99]] – hFGFR2 TKD  (mutant) + ACP<br />
**[[3b2t]] – hFGFR2 TKD  (mutant) + adenosine derivative<br />
**[[2pvf]] – hFGFR2 TKD  with PTR + ACP + substrate peptide<br />
**[[3cly]] – hFGFR2 TKD  (mutant) with PTR + ACP <br />
**[[3ri1]] – hFGFR2 TKD  + inhibitor<br />
 
*''FGFR2 ligand-binding domain''
 
**[[3dar]], [[3caf]], [[3euu]] – hFGFR2 LBD D2 <br />
**[[1wvz]] – hFGFR2 LBD D2 - NMR<br />
**[[4hwu]] – hFGFR2 LBD D1 <br />
 
*''FGFR2 complex with FGF''
 
**[[1e0o]] – hFGFR2 (mutant) LBD D2,D3 + hFGF1 (mutant) + HS<br />
**[[3oj2]], [[3ojm]] – hFGFR2 (mutant) LBD D2,D3 + hFGF1 <br />
**[[1djs]] – hFGFR2 LBD D2,D3 (mutant) + hFGF1 <br />
**[[1ev2]], [[1ii4]], [[1iil]] – hFGFR2 LBD D2,D3 + hFGF2 (mutant) <br />
**[[4j23]] – hFGFR2 LBD D2,D3 (mutant) + hFGF2 (mutant) + inhibitor <br />
**[[3cu1]] – hFGFR2 LBD D2 + hFGF1 <br />
**[[2fdb]] – hFGFR2 LBD D2,D3 + hFGF8b  <br />
**[[1nun]] – hFGFR2 LBD D2,D3 + hFGF10  <br />
 
*FGFR3
 
**[[3grw]] – hFGFR3 LBD D2,D3 + antibody<br />
**[[2lzl]] – hFGFR3 residues 357-399 – NMR<br />
**[[4k33]] – hFGFR3 kinase domain (mutant)<br />
 
*''FGFR3 complex with FGF''
 
**[[1ry7]] – hFGFR3 LBD + hFGF1<br />
 
*FGFR4
 
*''FGFR4 tyrosine kinase domain''
 
**[[4tye]], [[4tyg]], [[4tyi]], [[4tyj]] – hFGFR4 TKD <br />
**[[4qqj]] – hFGFR4 TKD (mutant) <br />
**[[4qrc]], [[4r6v]], [[4qqc]], [[4qq5]], [[4uxq]], [[4xcu]] – hFGFR4 TKD (mutant) + irreversible inhibitor<br />


}}
== References ==
<references/>
[[Category:Topic Page]]
[[Category:Topic Page]]

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

Michal Harel, Alexander Berchansky
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