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

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 18420	15422 15422		16761 16761
PubChem	888 888	5957 5957		6022 6022

1fltX	Unbound	Unbound	Unbound	Unbound	Unbound
1fltY	Unbound	Unbound	Unbound	Unbound	Unbound
1qsvA	Unbound	Unbound	Unbound	Unbound	Unbound
1qszA	Unbound	Unbound	Unbound	Unbound	Unbound
1qtyX	Unbound	Unbound	Unbound	Unbound	Unbound
1qtyY	Unbound	Unbound	Unbound	Unbound	Unbound
1qtyT	Unbound	Unbound	Unbound	Unbound	Unbound
1qtyU	Unbound	Unbound	Unbound	Unbound	Unbound
1vr2A01	Unbound	Unbound	Unbound	Unbound	Unbound
1vr2A02	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
1fltY
1qsvA
1qszA
1qtyX
1qtyY
1qtyT
1qtyU
1vr2A01
1vr2A02	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).

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