EzCatDB: M00131
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DB codeM00131
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 42.60.40.10 : Immunoglobulin-like
Domain 52.60.40.10 : Immunoglobulin-like
Domain 62.60.40.10 : Immunoglobulin-like
Domain 72.60.40.10 : Immunoglobulin-like
Domain 83.30.200.20 : Phosphorylase Kinase; domain 1
Domain 91.10.510.10 : Transferase(Phosphotransferase); domain 1Catalytic domain
Domain 10-.-.-.-
E.C.2.7.10.1

CATH domainRelated DB codes (homologues)
1.10.510.10 : Transferase(Phosphotransferase); domain 1M00125,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-likeT00257,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 1M00125,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

Enzyme Name
UniProtKBKEGG

P17948P35968
Protein nameVascular endothelial growth factor receptor 1Vascular 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;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
SynonymsVEGFR-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
None
RefSeqNP_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)
NP_002244.1 (Protein)
NM_002253.2 (DNA/RNA sequence)
PfamPF07679 (I-set)
PF07714 (Pkinase_Tyr)
[Graphical view]
PF07679 (I-set)
PF07714 (Pkinase_Tyr)
PF07686 (V-set)
[Graphical view]


UniProtKB:Accession NumberP17948P35968
Entry nameVGFR1_HUMANVGFR2_HUMAN
ActivityATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.
SubunitInteracts in vitro with various phosphotyrosine-binding proteins, including PLC-gammas, PTPN11, GRB2, CRK and NCK1.Interacts with SHB upon VEGF activation. Interacts with HIV-1 Tat.
Subcellular locationIsoform Flt1: Cell membrane, Single-pass type I membrane protein.,Isoform sFlt1: Secreted.Membrane, Single-pass type I membrane protein.
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

             
1fltXUnboundUnboundUnboundUnboundUnbound
1fltYUnboundUnboundUnboundUnboundUnbound
1qsvAUnboundUnboundUnboundUnboundUnbound
1qszAUnboundUnboundUnboundUnboundUnbound
1qtyXUnboundUnboundUnboundUnboundUnbound
1qtyYUnboundUnboundUnboundUnboundUnbound
1qtyTUnboundUnboundUnboundUnboundUnbound
1qtyUUnboundUnboundUnboundUnboundUnbound
1vr2A01UnboundUnboundUnboundUnboundUnbound
1vr2A02UnboundUnboundUnboundUnboundUnbound

Active-site residues
resource
Swiss-prot, literature [5] & similarity with M00129
pdbCatalytic residuesCofactor-binding residuescomment
           
1fltX 
 
 
1fltY 
 
 
1qsvA 
 
 
1qszA 
 
 
1qtyX 
 
 
1qtyY 
 
 
1qtyT 
 
 
1qtyU 
 
 
1vr2A01 
 
 
1vr2A02ASP 1028;ARG 1032
ASN 1033;ASP 1046(Magnesium binding)
deletion 940-997

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[5]p.323-325

references
[1]
CommentsX-ray crystallography
PubMed ID9393862
JournalCell
Year1997
Volume91
Pages695-704
AuthorsWiesmann C, Fuh G, Christinger HW, Eigenbrot C, Wells JA, de Vos AM
TitleCrystal structure at 1.7 A resolution of VEGF in complex with domain 2 of the Flt-1 receptor.
Related PDB1flt
[2]
PubMed ID9790910
JournalBiochem Biophys Res Commun
Year1998
Volume251
Pages77-82
AuthorsIgarashi K, Shigeta K, Isohara T, Yamano T, Uno I
TitleSck interacts with KDR and Flt-1 via its SH2 domain.
[3]
CommentsPARTIAL SEQUENCE, PHOSPHORYLATION SITES, AND MUTAGENESIS OF TYR-914; TYR-1213; TYR-1242; TYR-1327 AND TYR-1333
Medline ID98389777
PubMed ID9722576
JournalJ Biol Chem
Year1998
Volume273
Pages23410-8
AuthorsIto N, Wernstedt C, Engstrom U, Claesson-Welsh L
TitleIdentification of vascular endothelial growth factor receptor-1 tyrosine phosphorylation sites and binding of SH2 domain-containing molecules.
Related UniProtKBP17948
[4]
CommentsSTRUCTURE BY NMR OF 129-229
Medline ID20013066
PubMed ID10543948
JournalJ Mol Biol
Year1999
Volume293
Pages531-44
AuthorsStarovasnik MA, Christinger HW, Wiesmann C, Champe MA, de Vos AM, Skelton NJ
TitleSolution structure of the VEGF-binding domain of Flt-1: comparison of its free and bound states.
Related PDB1qsv,1qsz,1qty
Related UniProtKBP17948
[5]
CommentsX-ray crystallography
PubMed ID10368301
JournalStructure Fold Des
Year1999
Volume7
Pages319-30
AuthorsMcTigue MA, Wickersham JA, Pinko C, Showalter RE, Parast CV, Tempczyk-Russell A, Gehring MR, Mroczkowski B, Kan CC, Villafranca JE, Appelt K
TitleCrystal structure of the kinase domain of human vascular endothelial growth factor receptor 2: a key enzyme in angiogenesis.
Related PDB1vr2
[6]
PubMed ID11866530
JournalJ Mol Biol
Year2002
Volume316
Pages769-87
AuthorsPan B, Li B, Russell SJ, Tom JY, Cochran AG, Fairbrother WJ
TitleSolution structure of a phage-derived peptide antagonist in complex with vascular endothelial growth factor.

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).

createdupdated
2002-12-202009-02-26


Copyright: Nozomi Nagano, JST & CBRC-AIST
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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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