DB code: M00127

RLCP classification 3.103.130000.1162 : Transfer
CATH domain 2.60.40.10 : Immunoglobulin-like
2.60.40.10 : Immunoglobulin-like
2.60.40.10 : Immunoglobulin-like
3.30.200.20 : Phosphorylase Kinase; domain 1
1.10.510.10 : Transferase(Phosphotransferase); domain 1 Catalytic domain
E.C. 2.7.10.1
CSA
M-CSA
MACiE

CATH domain Related DB codes (homologues)
1.10.510.10 : Transferase(Phosphotransferase); domain 1 M00125 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-like M00131 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 1 M00125 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

Uniprot Enzyme Name
UniprotKB Protein name Synonyms RefSeq Pfam MEROPS
P11362 Fibroblast 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;
None NP_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)
PF07679 (I-set)
PF07714 (Pkinase_Tyr)
[Graphical View]
P21802 Fibroblast growth factor receptor 2 (FGFR-2) (EC 2.7.10.1) (K-sam) (KGFR) (Keratinocyte growth factor receptor)AltName: CD_antigen=CD332;
None 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)
PF07679 (I-set)
PF07714 (Pkinase_Tyr)
[Graphical View] 		I43.001 ()

KEGG enzyme name
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

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P11362 FGFR1_HUMAN ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate. Interacts with SHB. Interacts with KLB (By similarity). Membrane, Single-pass type I membrane protein.
P21802 FGFR2_HUMAN ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate. Cell membrane, Single-pass type I membrane protein. Isoform 14: Secreted. Isoform 19: Secreted.

KEGG Pathways
Map code Pathways E.C.

Compound table
Cofactors Substrates Products Intermediates
KEGG-id C00305 C00002 C00585 C00008 C01167
E.C.
Compound Magnesium ATP [Protein]-L-tyrosine ADP [Protein]-L-tyrosine phosphate
Type divalent metal (Ca2+, Mg2+) amine group,nucleotide aromatic ring (only carbon atom),peptide/protein amine group,nucleotide aromatic ring (only carbon atom),peptide/protein,phosphate group/phosphate ion
ChEBI 18420
 18420
 		15422
 15422
 		16761
 16761
PubChem 888
 888
 		5957
 5957
 		6022
 6022
1djsA01 Unbound Unbound Unbound Unbound Unbound
1e0oB01 Unbound Unbound Unbound Unbound Unbound
1e0oD01 Unbound Unbound Unbound Unbound Unbound
1ev2E01 Unbound Unbound Unbound Unbound Unbound
1ev2F01 Unbound Unbound Unbound Unbound Unbound
1ev2G01 Unbound Unbound Unbound Unbound Unbound
1ev2H01 Unbound Unbound Unbound Unbound Unbound
1ii4E01 Unbound Unbound Unbound Unbound Unbound
1ii4F01 Unbound Unbound Unbound Unbound Unbound
1ii4G01 Unbound Unbound Unbound Unbound Unbound
1ii4H01 Unbound Unbound Unbound Unbound Unbound
1iilE01 Unbound Unbound Unbound Unbound Unbound
1iilF01 Unbound Unbound Unbound Unbound Unbound
1iilG01 Unbound Unbound Unbound Unbound Unbound
1iilH01 Unbound Unbound Unbound Unbound Unbound
1nunB01 Unbound Unbound Unbound Unbound Unbound
1djsA02 Unbound Unbound Unbound Unbound Unbound
1e0oB02 Unbound Unbound Unbound Unbound Unbound
1e0oD02 Unbound Unbound Unbound Unbound Unbound
1ev2E02 Unbound Unbound Unbound Unbound Unbound
1ev2F02 Unbound Unbound Unbound Unbound Unbound
1ev2G02 Unbound Unbound Unbound Unbound Unbound
1ev2H02 Unbound Unbound Unbound Unbound Unbound
1ii4E02 Unbound Unbound Unbound Unbound Unbound
1ii4F02 Unbound Unbound Unbound Unbound Unbound
1ii4G02 Unbound Unbound Unbound Unbound Unbound
1ii4H02 Unbound Unbound Unbound Unbound Unbound
1iilE02 Unbound Unbound Unbound Unbound Unbound
1iilF02 Unbound Unbound Unbound Unbound Unbound
1iilG02 Unbound Unbound Unbound Unbound Unbound
1iilH02 Unbound Unbound Unbound Unbound Unbound
1nunB02 Unbound Unbound Unbound Unbound Unbound
1gjoA01 Unbound Unbound Unbound Unbound Unbound
1agwA01 Unbound Unbound Unbound Unbound Unbound
1agwB01 Unbound Unbound Unbound Unbound Unbound
1fgiA01 Unbound Unbound Unbound Unbound Unbound
1fgiB01 Unbound Unbound Unbound Unbound Unbound
1fgkA01 Unbound Unbound Unbound Unbound Unbound
1fgkB01 Unbound Unbound Unbound Unbound Unbound
2fgiA01 Unbound Unbound Unbound Unbound Unbound
2fgiB01 Unbound Unbound Unbound Unbound Unbound
1gjoA02 Unbound Unbound Unbound Unbound Unbound
1agwA02 Unbound Unbound Unbound Unbound Unbound
1agwB02 Unbound Unbound Unbound Unbound Unbound
1fgiA02 Unbound Unbound Unbound Unbound Unbound
1fgiB02 Unbound Unbound Unbound Unbound Unbound
1fgkA02 Unbound Unbound Unbound Unbound Unbound
1fgkB02 Unbound Unbound Unbound Unbound Unbound
2fgiA02 Unbound Unbound Unbound Unbound Unbound
2fgiB02 Unbound Unbound Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.
Swiss-prot & similarity with M00129

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
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
1gjoA02 ASP 626;ARG 630 ASN 631;ASP 644(Magnesium binding) TYR 657(auto-phosphorylation)
1agwA02 ASP 623;ARG 627 ASN 628;ASP 641(Magnesium binding) TYR 654(auto-Phosphorylation) mutant(invisible) C584S
1agwB02 ASP 623;ARG 627 ASN 628;ASP 641(Magnesium binding) TYR 654(auto-Phosphorylation) mutant(invisible) C584S
1fgiA02 ASP 623;ARG 627 ASN 628;ASP 641(Magnesium binding) TYR 654(auto-Phosphorylation) mutant(invisible) C584S
1fgiB02 ASP 623;ARG 627 ASN 628;ASP 641(Magnesium binding) TYR 654(auto-Phosphorylation) mutant(invisible) C584S
1fgkA02 ASP 623;ARG 627 ASN 628;ASP 641(Magnesium binding) TYR 654(auto-Phosphorylation) mutant(invisible) C584S
1fgkB02 ASP 623;ARG 627 ASN 628;ASP 641(Magnesium binding) TYR 654(auto-Phosphorylation) mutant(invisible) C584S
2fgiA02 ASP 623;ARG 627 ASN 628;ASP 641(Magnesium binding) TYR 654(auto-Phosphorylation) mutant(invisible) C584S
2fgiB02 ASP 623;ARG 627 ASN 628;ASP 641(Magnesium binding) TYR 654(auto-Phosphorylation) mutant(invisible) C584S

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[1]

References
[1]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 464-762.
Medline ID 96361355
PubMed ID 8752212
Journal Cell
Year 1996
Volume 86
Pages 577-87
Authors Mohammadi M, Schlessinger J, Hubbard SR
Title Structure of the FGF receptor tyrosine kinase domain reveals a novel autoinhibitory mechanism.
Related PDB 1fgk
Related UniProtKB P11362
[2]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 464-762.
Medline ID 97284786
PubMed ID 9139660
Journal Science
Year 1997
Volume 276
Pages 955-60
Authors Mohammadi M, McMahon G, Sun L, Tang C, Hirth P, Yeh BK, Hubbard SR, Schlessinger J
Title Structures of the tyrosine kinase domain of fibroblast growth factor receptor in complex with inhibitors.
Related PDB 1agw 1fgi
Related UniProtKB P11362
[3]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 9774334
Journal EMBO J
Year 1998
Volume 17
Pages 5896-904
Authors Mohammadi M, Froum S, Hamby JM, Schroeder MC, Panek RL, Lu GH, Eliseenkova AV, Green D, Schlessinger J, Hubbard SR
Title Crystal structure of an angiogenesis inhibitor bound to the FGF receptor tyrosine kinase domain.
Related PDB 2fgi
Related UniProtKB
[4]
Resource
Comments
Medline ID
PubMed ID 9521581
Journal Hum Genet
Year 1998
Volume 102
Pages 145-50
Authors Steinberger D, Vriend G, Mulliken JB, Muller U
Title The mutations in FGFR2-associated craniosynostoses are clustered in five structural elements of immunoglobulin-like domain III of the receptor.
Related PDB
Related UniProtKB
[5]
Resource
Comments
Medline ID
PubMed ID 10490614
Journal Mol Cell Biol
Year 1999
Volume 19
Pages 6754-64
Authors Sakaguchi K, Lorenzi MV, Bottaro DP, Miki T
Title The acidic domain and first immunoglobulin-like loop of fibroblast growth factor receptor 2 modulate downstream signaling through glycosaminoglycan modification.
Related PDB
Related UniProtKB
[6]
Resource
Comments
Medline ID
PubMed ID 10490103
Journal Cell
Year 1999
Volume 98
Pages 641-50
Authors Plotnikov AN, Schlessinger J, Hubbard SR, Mohammadi M
Title Structural basis for FGF receptor dimerization and activation.
Related PDB
Related UniProtKB
[7]
Resource
Comments
Medline ID
PubMed ID 9890894
Journal Biochemistry
Year 1999
Volume 38
Pages 160-71
Authors Wang F, Lu W, McKeehan K, Mohamedali K, Gabriel JL, Kan M, McKeehan WL
Title Common and specific determinants for fibroblast growth factors in the ectodomain of the receptor kinase complex.
Related PDB
Related UniProtKB
[8]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 10618369
Journal Proc Natl Acad Sci U S A
Year 2000
Volume 97
Pages 49-54
Authors Stauber DJ, DiGabriele AD, Hendrickson WA
Title Structural interactions of fibroblast growth factor receptor with its ligands.
Related PDB 1djs
Related UniProtKB
[9]
Resource
Comments
Medline ID
PubMed ID 11069186
Journal Nature
Year 2000
Volume 407
Pages 1029-34
Authors Pellegrini L, Burke DF, von Delft F, Mulloy B, Blundell TL
Title Crystal structure of fibroblast growth factor receptor ectodomain bound to ligand and heparin.
Related PDB 1e0o
Related UniProtKB
[10]
Resource
Comments
Medline ID
PubMed ID 10860838
Journal Biochem Biophys Res Commun
Year 2000
Volume 272
Pages 830-6
Authors Uematsu F, Kan M, Wang F, Jang JH, Luo Y, McKeehan WL
Title Ligand binding properties of binary complexes of heparin and immunoglobulin-like modules of FGF receptor 2.
Related PDB
Related UniProtKB
[11]
Resource
Comments
Medline ID
PubMed ID 10830168
Journal Cell
Year 2000
Volume 101
Pages 413-24
Authors Plotnikov AN, Hubbard SR, Schlessinger J, Mohammadi M
Title Crystal structures of two FGF-FGFR complexes reveal the determinants of ligand-receptor specificity.
Related PDB 1ev2
Related UniProtKB
[12]
Resource
Comments
Medline ID
PubMed ID 11390973
Journal Proc Natl Acad Sci U S A
Year 2001
Volume 98
Pages 7182-7
Authors Ibrahimi OA, Eliseenkova AV, Plotnikov AN, Yu K, Ornitz DM, Mohammadi M
Title Structural basis for fibroblast growth factor receptor 2 activation in Apert syndrome.
Related PDB 1ii4 1iil
Related UniProtKB
[13]
Resource
Comments
Medline ID
PubMed ID 11785766
Journal Curr Opin Struct Biol
Year 2001
Volume 11
Pages 629-34
Authors Pellegrini L
Title Role of heparan sulfate in fibroblast growth factor signalling: a structural view.
Related PDB
Related UniProtKB
[14]
Resource
Comments
Medline ID
PubMed ID 12242295
Journal Mol Cell Biol
Year 2002
Volume 22
Pages 7184-92
Authors Yeh BK, Eliseenkova AV, Plotnikov AN, Green D, Pinnell J, Polat T, Gritli-Linde A, Linhardt RJ, Mohammadi M
Title Structural basis for activation of fibroblast growth factor signaling by sucrose octasulfate.
Related PDB
Related UniProtKB
[15]
Resource
Comments
Medline ID
PubMed ID 11714710
Journal J Biol Chem
Year 2002
Volume 277
Pages 2444-53
Authors Ostrovsky O, Berman B, Gallagher J, Mulloy B, Fernig DG, Delehedde M, Ron D
Title Differential effects of heparin saccharides on the formation of specific fibroblast growth factor (FGF) and FGF receptor complexes.
Related PDB
Related UniProtKB
[16]
Resource
Comments
Medline ID
PubMed ID 12034712
Journal J Biol Chem
Year 2002
Volume 277
Pages 28554-63
Authors Powell AK, Fernig DG, Turnbull JE
Title Fibroblast growth factor receptors 1 and 2 interact differently with heparin/heparan sulfate. Implications for dynamic assembly of a ternary signaling complex.
Related PDB
Related UniProtKB
[17]
Resource
Comments
Medline ID
PubMed ID 12591959
Journal Proc Natl Acad Sci U S A
Year 2003
Volume 100
Pages 2266-71
Authors Yeh BK, Igarashi M, Eliseenkova AV, Plotnikov AN, Sher I, Ron D, Aaronson SA, Mohammadi M
Title Structural basis by which alternative splicing confers specificity in fibroblast growth factor receptors.
Related PDB 1nun
Related UniProtKB

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.

Created Updated
2003-07-22 2009-02-26