DB code: M00131

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
2.60.40.10 : Immunoglobulin-like
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 T00224 M00127 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 T00257 T00005 M00113 M00127 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 T00224 M00127 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
P17948 Vascular endothelial growth factor receptor 1
VEGFR-1
EC 2.7.10.1
Vascular permeability factor receptor
Tyrosine-protein kinase receptor FLT
Flt-1
Tyrosine-protein kinase FRT
Fms-like tyrosine kinase 1
NP_001153392.1 (Protein)
NM_001159920.1 (DNA/RNA sequence)
NP_001153502.1 (Protein)
NM_001160030.1 (DNA/RNA sequence)
NP_001153503.1 (Protein)
NM_001160031.1 (DNA/RNA sequence)
NP_002010.2 (Protein)
NM_002019.4 (DNA/RNA sequence)
PF07679 (I-set)
PF07714 (Pkinase_Tyr)
[Graphical View]
P35968 Vascular endothelial growth factor receptor 2 (VEGFR-2) (EC 2.7.10.1) (Kinase insert domain receptor) (Protein-tyrosine kinase receptor Flk-1)AltName: CD_antigen=CD309;
None NP_002244.1 (Protein)
NM_002253.2 (DNA/RNA sequence)
PF07679 (I-set)
PF07714 (Pkinase_Tyr)
PF07686 (V-set)
[Graphical View]

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
P17948 VGFR1_HUMAN ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate. Interacts in vitro with various phosphotyrosine-binding proteins, including PLC-gammas, PTPN11, GRB2, CRK and NCK1. Isoform Flt1: Cell membrane, Single-pass type I membrane protein. Isoform sFlt1: Secreted.
P35968 VGFR2_HUMAN ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate. Interacts with SHB upon VEGF activation. Interacts with HIV-1 Tat. Membrane, Single-pass type I membrane protein.

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
15422
16761
PubChem 888
5957
6022
1fltX Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1fltY Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1qsvA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1qszA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1qtyX Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1qtyY Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1qtyT Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1qtyU Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1vr2A01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1vr2A02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.
Swiss-prot, literature [5] & similarity with M00129

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1fltX Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1fltY Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1qsvA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1qszA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1qtyX Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1qtyY Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1qtyT Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1qtyU Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1vr2A01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1vr2A02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 1028;ARG 1032 ASN 1033;ASP 1046(Magnesium binding) deletion 940-997

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[5]
p.323-325

References
[1]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 9393862
Journal Cell
Year 1997
Volume 91
Pages 695-704
Authors Wiesmann C, Fuh G, Christinger HW, Eigenbrot C, Wells JA, de Vos AM
Title Crystal structure at 1.7 A resolution of VEGF in complex with domain 2 of the Flt-1 receptor.
Related PDB 1flt
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID 9790910
Journal Biochem Biophys Res Commun
Year 1998
Volume 251
Pages 77-82
Authors Igarashi K, Shigeta K, Isohara T, Yamano T, Uno I
Title Sck interacts with KDR and Flt-1 via its SH2 domain.
Related PDB
Related UniProtKB
[3]
Resource
Comments PARTIAL SEQUENCE, PHOSPHORYLATION SITES, AND MUTAGENESIS OF TYR-914; TYR-1213; TYR-1242; TYR-1327 AND TYR-1333
Medline ID 98389777
PubMed ID 9722576
Journal J Biol Chem
Year 1998
Volume 273
Pages 23410-8
Authors Ito N, Wernstedt C, Engstrom U, Claesson-Welsh L
Title Identification of vascular endothelial growth factor receptor-1 tyrosine phosphorylation sites and binding of SH2 domain-containing molecules.
Related PDB
Related UniProtKB P17948
[4]
Resource
Comments STRUCTURE BY NMR OF 129-229
Medline ID 20013066
PubMed ID 10543948
Journal J Mol Biol
Year 1999
Volume 293
Pages 531-44
Authors Starovasnik MA, Christinger HW, Wiesmann C, Champe MA, de Vos AM, Skelton NJ
Title Solution structure of the VEGF-binding domain of Flt-1: comparison of its free and bound states.
Related PDB 1qsv 1qsz 1qty
Related UniProtKB P17948
[5]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 10368301
Journal Structure Fold Des
Year 1999
Volume 7
Pages 319-30
Authors McTigue MA, Wickersham JA, Pinko C, Showalter RE, Parast CV, Tempczyk-Russell A, Gehring MR, Mroczkowski B, Kan CC, Villafranca JE, Appelt K
Title Crystal structure of the kinase domain of human vascular endothelial growth factor receptor 2: a key enzyme in angiogenesis.
Related PDB 1vr2
Related UniProtKB
[6]
Resource
Comments
Medline ID
PubMed ID 11866530
Journal J Mol Biol
Year 2002
Volume 316
Pages 769-87
Authors Pan B, Li B, Russell SJ, Tom JY, Cochran AG, Fairbrother WJ
Title Solution structure of a phage-derived peptide antagonist in complex with vascular endothelial growth factor.
Related PDB
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 seven Ig-like C2-type domains, whilst the cytoplasmic region contains protein kinase domain, which is homologous to other tyrosine protein kinase domains. This receptor belongs to the CSF-1/PDGF receptor superfamily.
PDB structures, 1flt, 1qsv, 1qsz, & 1qty, correspond to the second Ig-like C2-type domain, whilst the remainder structure, 1vr2, corresponds to protein kinase domain.
According to the literature [5], kinase activation loop, autophosphorylated at Tyr1059, seems to occupies a position inhibitory to substrate binding, which will regulate the kinase activity.
The literature [5] also reported that Asp1028 and Arg1032 are catalytic, although it did not mention the detailed mechanism. However, since this protein kinase domain is homologous to other kinase domains, with complete conservation of active site residues, the mechanism may be similar to others (see M00129).

Created Updated
2002-12-20 2009-02-26