1FGI,3GQI,3TT0


Conserved Protein Domain Family
PTKc_FGFR1

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cd05098: PTKc_FGFR1 
Click on image for an interactive view with Cn3D
Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 1
PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Alternative splicing of FGFR1 transcripts produces a variety of isoforms, which are differentially expressed in cells. FGFR1 binds the ligands, FGF1 and FGF2, with high affinity and has also been reported to bind FGF4, FGF6, and FGF9. FGFR1 signaling is critical in the control of cell migration during embryo development. It promotes cell proliferation in fibroblasts. Nuclear FGFR1 plays a role in the regulation of transcription. Mutations, insertions or deletions of FGFR1 have been identified in patients with Kallman's syndrome (KS), an inherited disorder characterized by hypogonadotropic hypogonadism and loss of olfaction. Aberrant FGFR1 expression has been found in some human cancers including 8P11 myeloproliferative syndrome (EMS), breast cancer, and pancreatic adenocarcinoma. FGFR1 is part of the FGFR subfamily, which are receptor PTKs (RTKs) containing an extracellular ligand-binding region with three immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding of FGFRs to their ligands, the FGFs, results in receptor dimerization and activation, and intracellular signaling. The binding of FGFs to FGFRs is promiscuous, in that a receptor may be activated by several ligands and a ligand may bind to more that one type of receptor. The FGFR1 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.
Statistics
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PSSM-Id: 270678
Aligned: 6 rows
Threshold Bit Score: 647.84
Created: 10-Jul-2007
Updated: 2-Oct-2020
Structure
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Program:
Drawing:
Aligned Rows:
 
Conserved site includes 17 residues -Click on image for an interactive view with Cn3D
Feature 1:ATP binding site [chemical binding site]
Evidence:
  • Structure:3GQI; Human FGFR1 try kinase binds MgAMP-PCP; contacts at 4A.
  • Structure:1FGI; Human FGFR1 tyr kinase binds Su5402 inhibitor; defined at 4A contacts.
  • Citation:PMID 9139660
  • Structure:3TT0: Human FGFR1 binds a pyrimidine inhibitor; contacts at 4A.

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
Feature 1                         ## # #  #                   # #                             
1FGI_A      9 ELPEDPRWELPRDRLVLGKPLGEGAFGQVVLAEAIGLDKDKPNRVTKVAVKMLKSDATEKDLSDLISEMEMMKMIGKHKN 88  human
P21804    462 ELPEDPRWELPRDRLILGKPLGEGCFGQVVLAEAIGLDKDKPNRVTKVAVKMLKSDATEKDLSDLISEMEMMKMIGKHKN 541 chicken
P22182    458 ELPEDPRWEVARDRLILGKPLGEGCFGQVVMAEAIGLDKEKPNKVTKVAVKMLKSDASEKDLSDLISEMEMMKMIGKHKN 537 African clawed frog
CAM13573  450 ELPQDPRWEVQRDRLVLGKPLGEGCFGQVMMAEAMGMDKEKPNRITKVAVKMLKSDATEKDLSDLISEMEMMKIIGKHKN 529 zebrafish
3GQI_A     16 ELPEDPRWELPRDRLVLGKPLGEGAFGQVVLAEAIGLDKDKPNRVTKVAVKMLKSDATEKDLSDLISEMEMMKMIGKHKN 95  human
3TT0_A     57 ELPEDPRWELPRDRLVLGKPLGEGAFGQVVLAEAIGLDKDKPNRVTKVAVKMLKSDATEKDLSDLISEMEMMKMIGKHKN 136 human
Feature 1      #               ####   #                                                       
1FGI_A     89 IINLLGACTQDGPLYVIVEYASKGNLREYLQARRPPGLEYSYNPSHNPEEQLSSKDLVSCAYQVARGMEYLASKKCIHRD 168 human
P21804    542 IINLLGACTQDGPLYVIVEYASKGNLREYLQARRPPGMEYCYNPTRIPEEQLSFKDLVSCAYQVARGMEYLASKKCIHRD 621 chicken
P22182    538 IINLLGACTQDGPLYVIVEYTSKGNLREYLRARRPPAMEYCYNPTCVPDQLLSFKDLVSCAYQVARGMDYLASKKCIHRD 617 African clawed frog
CAM13573  530 IINLLGACTQDGPLYVIVEFAAKGNLREYLRVRRPPGMEYCYNPDQVPVENMSIKDLVSCAYQVARGMEYLASKKCIHRD 609 zebrafish
3GQI_A     96 IINLLGACTQDGPLYVIVEYASKGNLREYLQARRPPGLEFSFNPSHNPEEQLSSKDLVSCAYQVARGMEYLASKKCIHRD 175 human
3TT0_A    137 IINLLGACTQDGPLYVIVEYASKGNLREYLQARRPPGLEYSYNPSHNPEEQLSSKDLVSCAYQVARGMEYLASKKCIHRD 216 human
Feature 1        ## #          #                                                              
1FGI_A    169 LAARNVLVTEdNVMKIADFGLARDIHHIDYYKKTTNGRLPVKWMAPEALFDRIYTHQSDVWSFGVLLWEIFTLGGSPYPG 248 human
P21804    622 LAARNVLVTEdNVMKIADFGLARDIHHIDYYKKTTNGRLPVKWMAPEALFDRIYTHQSDVWSFGVLLWEIFTLGGSPYPG 701 chicken
P22182    618 LAARNVLVTEdNIMKIADFGLARDIHHIDYYKKTTNGRLPVKWMAPEALFDRIYTHQSDVWSFGVLLWEIFTLGGSPYPG 697 African clawed frog
CAM13573  610 LAARNVLVTEdNVMKIADFGLARDIHHIDYYKKTTNGRLPVKWMAPEALFDRIYTHQSDVWSFGVLLWEIFTLGGSPYPG 689 zebrafish
3GQI_A    176 LAARNVLVTEdNVMKIADFGLARDIHHIDXXKKTTNGRLPVKWMAPEALFDRIYTHQSDVWSFGVLLWEIFTLGGSPYPG 255 human
3TT0_A    217 LAARNVLVTEdNVMKIADFGLARDIHHIDYYKKTTNGRLPVKWMAPEALFDRIYTHQSDVWSFGVLLWEIFTLGGSPYPG 296 human
Feature 1                                                                   
1FGI_A    249 VPVEELFKLLKEGHRMDKPSNCTNELYMMMRDCWHAvPSQRPTFKQLVEDLDRIVALTSNQE 310 human
P21804    702 VPVEELFKLLKEGHRMDKPSNCTNELYMMMRDCWHAvPSQRPTFKQLVEDLDRIVAMTSNQE 763 chicken
P22182    698 VPMEELFKLLKEGHRMDKPTNCTNELYMMMKDCWHAmPSQRPTFNQLVEDLDRILALSSNQE 759 African clawed frog
CAM13573  690 VPVEELFKLLKEGHRMDRPSTCTHELYMMMRDCWHAvPSQRPTFKQLVEDLDRTLSMTSNQE 751 zebrafish
3GQI_A    256 VPVEELFKLLKEGHRMDKPSNCTNELYMMMRDCWHAvPSQRPTFKQLVEDLDRIVALTSNQE 317 human
3TT0_A    297 VPVEELFKLLKEGHRMDKPSNCTNELYMMMRDCWHAvPSQRPTFKQLVEDLDRIVALTSNQE 358 human

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