EzCatDB: M00127
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DB codeM00127
RLCP classification3.103.130000.1162 : Transfer
CATH domainDomain 12.60.40.10 : Immunoglobulin-like
Domain 22.60.40.10 : Immunoglobulin-like
Domain 32.60.40.10 : Immunoglobulin-like
Domain 43.30.200.20 : Phosphorylase Kinase; domain 1
Domain 51.10.510.10 : Transferase(Phosphotransferase); domain 1Catalytic domain
E.C.2.7.10.1

CATH domainRelated DB codes (homologues)
1.10.510.10 : Transferase(Phosphotransferase); domain 1M00125,M00124,M00131,T00224,M00129,M00130,M00132,M00136,M00196,M00197,M00198,M00304,M00323,M00325,M00326,M00327,M00328,M00329,M00330,M00331,M00332,M00333,M00335,M00339,M00344
2.60.40.10 : Immunoglobulin-likeM00131,T00257,T00005,M00113,M00132,M00323,M00325,M00327,M00329,M00330,M00331,M00332,T00307,D00166,D00500,M00112,M00193,T00063,T00065,T00067,T00245
3.30.200.20 : Phosphorylase Kinase; domain 1M00125,M00124,M00131,T00224,M00129,M00130,M00132,M00136,M00196,M00197,M00198,M00304,M00323,M00325,M00326,M00327,M00328,M00329,M00330,M00331,M00332,M00333,M00335,M00339,M00344,D00298

Enzyme Name
UniProtKBKEGG

P11362P21802
Protein nameFibroblast growth factor receptor 1 (FGFR-1) (EC 2.7.10.1) (Basic fibroblast growth factor receptor 1) (BFGFR) (bFGF-R-1) (Fms-like tyrosine kinase 2) (FLT-2) (N-sam) (Proto-oncogene c-Fgr)AltName: CD_antigen=CD331;Fibroblast growth factor receptor 2 (FGFR-2) (EC 2.7.10.1) (K-sam) (KGFR) (Keratinocyte growth factor receptor)AltName: CD_antigen=CD332;receptor protein-tyrosine kinase
AATK
AATYK
AATYK2
AATYK3
ACH
ALK
anaplastic lymphoma kinase
ARK
ATP:protein-tyrosine O-phosphotransferase (ambiguous)
AXL
Bek
Bfgfr
BRT
Bsk
C-FMS
CAK
CCK4
CD115
CD135
CDw135
Cek1
Cek10
Cek11
Cek2
Cek3
Cek5
Cek6
Cek7
CFD1
CKIT
CSF1R
DAlk
DDR1
DDR2
Dek
DKFZp434C1418
Drosophila Eph kinase
DRT
DTK
Ebk
ECK
EDDR1
Eek
EGFR
Ehk2
Ehk3
Elk
EPH
EPHA1
EPHA2
EPHA6
EPHA7
EPHA8
EPHB1
EPHB2
EPHB3
EPHB4
EphB5
ephrin-B3 receptor tyrosine kinase
EPHT
EPHT2
EPHT3
EPHX
ERBB
ERBB1
ERBB2
ERBB3
ERBB4
ERK
Eyk
FGFR1
FGFR2
FGFR3
FGFR4
FLG
FLK1
FLK2
FLT1
FLT2
FLT3
FLT4
FMS
Fv2
HBGFR
HEK11
HEK2
HEK3
HEK5
HEK6
HEP
HER2
HER3
HER4
HGFR
HSCR1
HTK
IGF1R
INSR
INSRR
insulin receptor protein-tyrosine kinase
IR
IRR
JTK12
JTK13
JTK14
JWS
K-SAM
KDR
KGFR
KIA0641
KIAA1079
KIAA1459
Kil
Kin15
Kin16
KIT
KLG
LTK
MCF3
Mdk1
Mdk2
Mdk5
MEhk1
MEN2A/B
Mep
MER
MERTK
MET
Mlk1
Mlk2
Mrk
MST1R
MTC1
MUSK
Myk1
N-SAM
NEP
NET
Neu
neurite outgrowth regulating kinase
NGL
NOK
nork
novel oncogene with kinase-domain
Nsk2
NTRK1
NTRK2
NTRK3
NTRK4
NTRKR1
NTRKR2
NTRKR3
Nuk
NYK
PCL
PDGFR
PDGFRA
PDGFRB
PHB6
protein-tyrosine kinase (ambiguous)
protein tyrosine kinase (ambiguous)
PTK
PTK3
PTK7
receptor protein tyrosine kinase
RET
RON
ROR1
ROR2
ROS1
RSE
RTK
RYK
SEA
Sek2
Sek3
Sek4
Sfr
SKY
STK
STK1
TEK
TIE
TIE1
TIE2
TIF
TKT
TRK
TRKA
TRKB
TRKC
TRKE
TYK1
TYRO10
Tyro11
TYRO3
Tyro5
Tyro6
TYRO7
UFO
VEGFR1
VEGFR2
VEGFR3
Vik
YK1
Yrk
SynonymsNoneNone
RefSeqNP_001167534.1 (Protein)
NM_001174063.1 (DNA/RNA sequence)
NP_001167535.1 (Protein)
NM_001174064.1 (DNA/RNA sequence)
NP_001167536.1 (Protein)
NM_001174065.1 (DNA/RNA sequence)
NP_001167537.1 (Protein)
NM_001174066.1 (DNA/RNA sequence)
NP_001167538.1 (Protein)
NM_001174067.1 (DNA/RNA sequence)
NP_056934.2 (Protein)
NM_015850.3 (DNA/RNA sequence)
NP_075593.1 (Protein)
NM_023105.2 (DNA/RNA sequence)
NP_075594.1 (Protein)
NM_023106.2 (DNA/RNA sequence)
NP_075598.2 (Protein)
NM_023110.2 (DNA/RNA sequence)
NP_000132.3 (Protein)
NM_000141.4 (DNA/RNA sequence)
NP_001138385.1 (Protein)
NM_001144913.1 (DNA/RNA sequence)
NP_001138386.1 (Protein)
NM_001144914.1 (DNA/RNA sequence)
NP_001138387.1 (Protein)
NM_001144915.1 (DNA/RNA sequence)
NP_001138388.1 (Protein)
NM_001144916.1 (DNA/RNA sequence)
NP_001138389.1 (Protein)
NM_001144917.1 (DNA/RNA sequence)
NP_001138390.1 (Protein)
NM_001144918.1 (DNA/RNA sequence)
NP_001138391.1 (Protein)
NM_001144919.1 (DNA/RNA sequence)
NP_075259.4 (Protein)
NM_022970.3 (DNA/RNA sequence)
NP_075418.1 (Protein)
NM_023029.2 (DNA/RNA sequence)
PfamPF07679 (I-set)
PF07714 (Pkinase_Tyr)
[Graphical view]
PF07679 (I-set)
PF07714 (Pkinase_Tyr)
[Graphical view]


UniProtKB:Accession NumberP11362P21802
Entry nameFGFR1_HUMANFGFR2_HUMAN
ActivityATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.
SubunitInteracts with SHB. Interacts with KLB (By similarity).
Subcellular locationMembrane, Single-pass type I membrane protein.Cell membrane, Single-pass type I membrane protein.,Isoform 14: Secreted.,Isoform 19: Secreted.
Cofactor


Compound table: links to PDB-related databases & PoSSuM

CofactorsSubstratesProducts
KEGG-idC00305C00002C00585C00008C01167
CompoundMagnesiumATP[Protein]-L-tyrosineADP[Protein]-L-tyrosine phosphate
Typedivalent metal (Ca2+, Mg2+)amine group,nucleotidearomatic ring (only carbon atom),peptide/proteinamine group,nucleotidearomatic ring (only carbon atom),peptide/protein,phosphate group/phosphate ion
ChEBI18420
15422

16761

PubChem888
5957

6022

             
1djsA01UnboundUnboundUnboundUnboundUnbound
1e0oB01UnboundUnboundUnboundUnboundUnbound
1e0oD01UnboundUnboundUnboundUnboundUnbound
1ev2E01UnboundUnboundUnboundUnboundUnbound
1ev2F01UnboundUnboundUnboundUnboundUnbound
1ev2G01UnboundUnboundUnboundUnboundUnbound
1ev2H01UnboundUnboundUnboundUnboundUnbound
1ii4E01UnboundUnboundUnboundUnboundUnbound
1ii4F01UnboundUnboundUnboundUnboundUnbound
1ii4G01UnboundUnboundUnboundUnboundUnbound
1ii4H01UnboundUnboundUnboundUnboundUnbound
1iilE01UnboundUnboundUnboundUnboundUnbound
1iilF01UnboundUnboundUnboundUnboundUnbound
1iilG01UnboundUnboundUnboundUnboundUnbound
1iilH01UnboundUnboundUnboundUnboundUnbound
1nunB01UnboundUnboundUnboundUnboundUnbound
1djsA02UnboundUnboundUnboundUnboundUnbound
1e0oB02UnboundUnboundUnboundUnboundUnbound
1e0oD02UnboundUnboundUnboundUnboundUnbound
1ev2E02UnboundUnboundUnboundUnboundUnbound
1ev2F02UnboundUnboundUnboundUnboundUnbound
1ev2G02UnboundUnboundUnboundUnboundUnbound
1ev2H02UnboundUnboundUnboundUnboundUnbound
1ii4E02UnboundUnboundUnboundUnboundUnbound
1ii4F02UnboundUnboundUnboundUnboundUnbound
1ii4G02UnboundUnboundUnboundUnboundUnbound
1ii4H02UnboundUnboundUnboundUnboundUnbound
1iilE02UnboundUnboundUnboundUnboundUnbound
1iilF02UnboundUnboundUnboundUnboundUnbound
1iilG02UnboundUnboundUnboundUnboundUnbound
1iilH02UnboundUnboundUnboundUnboundUnbound
1nunB02UnboundUnboundUnboundUnboundUnbound
1gjoA01UnboundUnboundUnboundUnboundUnbound
1agwA01UnboundUnboundUnboundUnboundUnbound
1agwB01UnboundUnboundUnboundUnboundUnbound
1fgiA01UnboundUnboundUnboundUnboundUnbound
1fgiB01UnboundUnboundUnboundUnboundUnbound
1fgkA01UnboundUnboundUnboundUnboundUnbound
1fgkB01UnboundUnboundUnboundUnboundUnbound
2fgiA01UnboundUnboundUnboundUnboundUnbound
2fgiB01UnboundUnboundUnboundUnboundUnbound
1gjoA02UnboundUnboundUnboundUnboundUnbound
1agwA02UnboundUnboundUnboundUnboundUnbound
1agwB02UnboundUnboundUnboundUnboundUnbound
1fgiA02UnboundUnboundUnboundUnboundUnbound
1fgiB02UnboundUnboundUnboundUnboundUnbound
1fgkA02UnboundUnboundUnboundUnboundUnbound
1fgkB02UnboundUnboundUnboundUnboundUnbound
2fgiA02UnboundUnboundUnboundUnboundUnbound
2fgiB02UnboundUnboundUnboundUnboundUnbound

Active-site residues
resource
Swiss-prot & similarity with M00129
pdbCatalytic residuesCofactor-binding residuesModified residuescomment
            
1djsA01 
 
 
 
1e0oB01 
 
 
 
1e0oD01 
 
 
 
1ev2E01 
 
 
 
1ev2F01 
 
 
 
1ev2G01 
 
 
 
1ev2H01 
 
 
 
1ii4E01 
 
 
 
1ii4F01 
 
 
 
1ii4G01 
 
 
 
1ii4H01 
 
 
 
1iilE01 
 
 
 
1iilF01 
 
 
 
1iilG01 
 
 
 
1iilH01 
 
 
 
1nunB01 
 
 
 
1djsA02 
 
 
 
1e0oB02 
 
 
 
1e0oD02 
 
 
 
1ev2E02 
 
 
 
1ev2F02 
 
 
 
1ev2G02 
 
 
 
1ev2H02 
 
 
 
1ii4E02 
 
 
 
1ii4F02 
 
 
 
1ii4G02 
 
 
 
1ii4H02 
 
 
 
1iilE02 
 
 
 
1iilF02 
 
 
 
1iilG02 
 
 
 
1iilH02 
 
 
 
1nunB02 
 
 
 
1gjoA01 
 
 
 
1agwA01 
 
 
mutant(invisible) I457V & C488A
1agwB01 
 
 
mutant(invisible) I457V, mutant I457V
1fgiA01 
 
 
mutant(invisible) I457V, mutant I457V
1fgiB01 
 
 
mutant(invisible) I457V, mutant I457V
1fgkA01 
 
 
mutant(invisible) I457V & C488A
1fgkB01 
 
 
mutant(invisible) I457V, mutant I457V
2fgiA01 
 
 
mutant(invisible) I457V & C488A
2fgiB01 
 
 
mutant(invisible) I457V, mutant I457V
1gjoA02ASP 626;ARG 630
ASN 631;ASP 644(Magnesium binding)
TYR 657(auto-phosphorylation)
 
1agwA02ASP 623;ARG 627
ASN 628;ASP 641(Magnesium binding)
TYR 654(auto-Phosphorylation)
mutant(invisible) C584S
1agwB02ASP 623;ARG 627
ASN 628;ASP 641(Magnesium binding)
TYR 654(auto-Phosphorylation)
mutant(invisible) C584S
1fgiA02ASP 623;ARG 627
ASN 628;ASP 641(Magnesium binding)
TYR 654(auto-Phosphorylation)
mutant(invisible) C584S
1fgiB02ASP 623;ARG 627
ASN 628;ASP 641(Magnesium binding)
TYR 654(auto-Phosphorylation)
mutant(invisible) C584S
1fgkA02ASP 623;ARG 627
ASN 628;ASP 641(Magnesium binding)
TYR 654(auto-Phosphorylation)
mutant(invisible) C584S
1fgkB02ASP 623;ARG 627
ASN 628;ASP 641(Magnesium binding)
TYR 654(auto-Phosphorylation)
mutant(invisible) C584S
2fgiA02ASP 623;ARG 627
ASN 628;ASP 641(Magnesium binding)
TYR 654(auto-Phosphorylation)
mutant(invisible) C584S
2fgiB02ASP 623;ARG 627
ASN 628;ASP 641(Magnesium binding)
TYR 654(auto-Phosphorylation)
mutant(invisible) C584S

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[1]


references
[1]
CommentsX-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 464-762.
Medline ID96361355
PubMed ID8752212
JournalCell
Year1996
Volume86
Pages577-87
AuthorsMohammadi M, Schlessinger J, Hubbard SR
TitleStructure of the FGF receptor tyrosine kinase domain reveals a novel autoinhibitory mechanism.
Related PDB1fgk
Related UniProtKBP11362
[2]
CommentsX-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 464-762.
Medline ID97284786
PubMed ID9139660
JournalScience
Year1997
Volume276
Pages955-60
AuthorsMohammadi M, McMahon G, Sun L, Tang C, Hirth P, Yeh BK, Hubbard SR, Schlessinger J
TitleStructures of the tyrosine kinase domain of fibroblast growth factor receptor in complex with inhibitors.
Related PDB1agw,1fgi
Related UniProtKBP11362
[3]
CommentsX-ray crystallography
PubMed ID9774334
JournalEMBO J
Year1998
Volume17
Pages5896-904
AuthorsMohammadi M, Froum S, Hamby JM, Schroeder MC, Panek RL, Lu GH, Eliseenkova AV, Green D, Schlessinger J, Hubbard SR
TitleCrystal structure of an angiogenesis inhibitor bound to the FGF receptor tyrosine kinase domain.
Related PDB2fgi
[4]
PubMed ID9521581
JournalHum Genet
Year1998
Volume102
Pages145-50
AuthorsSteinberger D, Vriend G, Mulliken JB, Muller U
TitleThe mutations in FGFR2-associated craniosynostoses are clustered in five structural elements of immunoglobulin-like domain III of the receptor.
[5]
PubMed ID10490614
JournalMol Cell Biol
Year1999
Volume19
Pages6754-64
AuthorsSakaguchi K, Lorenzi MV, Bottaro DP, Miki T
TitleThe acidic domain and first immunoglobulin-like loop of fibroblast growth factor receptor 2 modulate downstream signaling through glycosaminoglycan modification.
[6]
PubMed ID10490103
JournalCell
Year1999
Volume98
Pages641-50
AuthorsPlotnikov AN, Schlessinger J, Hubbard SR, Mohammadi M
TitleStructural basis for FGF receptor dimerization and activation.
[7]
PubMed ID9890894
JournalBiochemistry
Year1999
Volume38
Pages160-71
AuthorsWang F, Lu W, McKeehan K, Mohamedali K, Gabriel JL, Kan M, McKeehan WL
TitleCommon and specific determinants for fibroblast growth factors in the ectodomain of the receptor kinase complex.
[8]
CommentsX-ray crystallography
PubMed ID10618369
JournalProc Natl Acad Sci U S A
Year2000
Volume97
Pages49-54
AuthorsStauber DJ, DiGabriele AD, Hendrickson WA
TitleStructural interactions of fibroblast growth factor receptor with its ligands.
Related PDB1djs
[9]
PubMed ID11069186
JournalNature
Year2000
Volume407
Pages1029-34
AuthorsPellegrini L, Burke DF, von Delft F, Mulloy B, Blundell TL
TitleCrystal structure of fibroblast growth factor receptor ectodomain bound to ligand and heparin.
Related PDB1e0o
[10]
PubMed ID10860838
JournalBiochem Biophys Res Commun
Year2000
Volume272
Pages830-6
AuthorsUematsu F, Kan M, Wang F, Jang JH, Luo Y, McKeehan WL
TitleLigand binding properties of binary complexes of heparin and immunoglobulin-like modules of FGF receptor 2.
[11]
PubMed ID10830168
JournalCell
Year2000
Volume101
Pages413-24
AuthorsPlotnikov AN, Hubbard SR, Schlessinger J, Mohammadi M
TitleCrystal structures of two FGF-FGFR complexes reveal the determinants of ligand-receptor specificity.
Related PDB1ev2
[12]
PubMed ID11390973
JournalProc Natl Acad Sci U S A
Year2001
Volume98
Pages7182-7
AuthorsIbrahimi OA, Eliseenkova AV, Plotnikov AN, Yu K, Ornitz DM, Mohammadi M
TitleStructural basis for fibroblast growth factor receptor 2 activation in Apert syndrome.
Related PDB1ii4,1iil
[13]
PubMed ID11785766
JournalCurr Opin Struct Biol
Year2001
Volume11
Pages629-34
AuthorsPellegrini L
TitleRole of heparan sulfate in fibroblast growth factor signalling: a structural view.
[14]
PubMed ID12242295
JournalMol Cell Biol
Year2002
Volume22
Pages7184-92
AuthorsYeh BK, Eliseenkova AV, Plotnikov AN, Green D, Pinnell J, Polat T, Gritli-Linde A, Linhardt RJ, Mohammadi M
TitleStructural basis for activation of fibroblast growth factor signaling by sucrose octasulfate.
[15]
PubMed ID11714710
JournalJ Biol Chem
Year2002
Volume277
Pages2444-53
AuthorsOstrovsky O, Berman B, Gallagher J, Mulloy B, Fernig DG, Delehedde M, Ron D
TitleDifferential effects of heparin saccharides on the formation of specific fibroblast growth factor (FGF) and FGF receptor complexes.
[16]
PubMed ID12034712
JournalJ Biol Chem
Year2002
Volume277
Pages28554-63
AuthorsPowell AK, Fernig DG, Turnbull JE
TitleFibroblast growth factor receptors 1 and 2 interact differently with heparin/heparan sulfate. Implications for dynamic assembly of a ternary signaling complex.
[17]
PubMed ID12591959
JournalProc Natl Acad Sci U S A
Year2003
Volume100
Pages2266-71
AuthorsYeh BK, Igarashi M, Eliseenkova AV, Plotnikov AN, Sher I, Ron D, Aaronson SA, Mohammadi M
TitleStructural basis by which alternative splicing confers specificity in fibroblast growth factor receptors.
Related PDB1nun

comments
The E.C. was transferred from 2.7.1.112 to 2.7.10.1.
The receptor enzymes have N-terminal extracellular region, transmembrane region, and C-terminal cytoplasmic region. The extracellular region is composed of three Ig-like C2-type domains, whilst the cytoplasmic region contains protein kinase domain, which is homologous to other tyrosine protein kinase domains.
The PDB structures, 1gjo, 1agw, 1fgi, 1fgk & 2fig, correspond to the kinase domain composed of the fourth and fifth domains, whilst the other structures (1djs, 1e0o, 1ev2, 1ii4, 1iil & 1nun) correspond to the second and third domains of IG-like C2-type domains.
Although the literature [1] suggested that Asp623 acts as a general base, its detailed mechanism has not been indicated. However, the protein kinase seems to have a similar catalytic mechanism to other protein kinases of receptor proteins (see M00129), as the active site is completely the same as the conterpart enzyme.

createdupdated
2003-07-222009-02-26


Copyright: Nozomi Nagano, JST & CBRC-AIST
Funded by PRESTO/Japan Science and Technology Corporation (JST) (December 2001 - November 2004)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2006)
Funded by Grant-in-Aid for Scientific Research (B)/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (September 2005 - September 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (October 2007 - September 2010)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2011 - March 2012)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2012 - March 2013)
Supported by the commission for the Development of Artificial Gene Synthesis Technology for Creating Innovative Biomaterial from the Ministry of Economy, Trade and Industry (METI) (October 2012 - )
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