KinaseNET

Nomenclature

Short Name:

FLT1

Full Name:

Vascular endothelial growth factor receptor 1

Alias:

EC 2.7.1.112
FRT
Tyrosine-protein kinase FRT
Tyrosine-protein kinase receptor FLT
VGFR1
EC 2.7.10.1
FLT
Flt-1
Fms-like tyrosine kinase 1
Fms-related tyrosine kinase 1

Classification

Type:

Protein-tyrosine kinase

Group:

Family:

VEGFR

SubFamily:

Specific Links

Entrez-Gene Entry:	2321
Entrez-Protein Entry:	NP_002010
GeneCards Entry:	FLT
KinBASE Entry:	FLT1
OMIM Entry:	165070
Pfam Entry:	P17948
PhosphoNET Entry:	P17948
Phosphosite Plus Entry:	1140
Protein Data Bank Entry:	1FLT
ScanSite Entry:	P17948
Source Entry:	FLT1
UCSD-Nature Entry:	A000948
UniProt Entry:	P17948
Kinexus Products:	FLT1 Vascular endothelial growth factor receptor 1 pan-specific antibody AB-NK226-1 Vascular endothelial growth factor receptor 1 pan-specific antibody AB-NK226-2 Vascular endothelial growth factor receptor 1 pan-specific antibody AB-NK226-2P Vascular endothelial growth factor receptor 1 Y1048 phosphosite-specific antibody AB-PK850 Vascular endothelial growth factor receptor 1 Y1053 phosphosite-specific antibody AB-PK851 Vascular endothelial growth factor receptor 1 (S318-A332, human) peptide - Powder PE-01BGC86 Vascular endothelial growth factor receptor 1 (R1045-P1051, human) pY1048 phosphopeptide - Powder PE-04AFM99 Vascular endothelial growth factor receptor 1 (N1050-K1056, human) pY1053 phosphopeptide - Powder PE-04AGP99 Vascular endothelial growth factor receptor 1 (N1050-K1056, human) pY1053 phosphopeptide - Powder PE-04BBK00 Vascular endothelial growth factor receptor 1 (R1045-P1051, human) pY1048 phosphopeptide - Powder PE-04BBL00

General Links

Structure

Mol. Mass (Da):

150769

# Amino Acids:

1338

# mRNA Isoforms:

mRNA Isoforms:

150,769 Da (1338 AA; P17948); 82,124 Da (733 AA; P17948-3); 77,474 Da (687 AA; P17948-2); 62,954 Da (556 AA; P17948-5); 60,917 Da (541 AA; P17948-4); 52,613 Da (463 AA; P17948-6); 41,175 Da (361 AA; P17948-8); 39,148 Da (343 AA; P17948-7)

4D Structure:

Interacts in vitro with various phosphotyrosine-binding proteins, including PLC-gammas, PTPN11, GRB2, CRK and NCK1.

1D Structure:

Retrieve Gene Sequence
Retrieve Full Protein Sequence
Retrieve Catalytic Domain Sequence

3D Image (rendered using PV Viewer):

PDB ID

3HNG

Subfamily Alignment

Domain Distribution:

Start	End	Domain
1	26	signal_peptide
32	123	IG
151	214	IGc2
230	327	IGc2
335	421	IGc2
428	553	IG
556	654	IGc2
661	747	IGc2
759	779	TMD
827	1156	Pkinase

Kinexus Products

Click on entries below for direct links to relevant products from Kinexus for this protein kinase.

hiddentext

○	Vascular endothelial growth factor receptor 1 pan-specific antibody AB-NK226-1
○	Vascular endothelial growth factor receptor 1 pan-specific antibody AB-NK226-2
○	Vascular endothelial growth factor receptor 1 pan-specific antibody AB-NK226-2P
○	Vascular endothelial growth factor receptor 1 Y1048 phosphosite-specific antibody AB-PK850
○	Vascular endothelial growth factor receptor 1 Y1053 phosphosite-specific antibody AB-PK851
○	Vascular endothelial growth factor receptor 1 (S318-A332, human) peptide - Powder PE-01BGC86
○	Vascular endothelial growth factor receptor 1 (R1045-P1051, human) pY1048 phosphopeptide - Powder PE-04AFM99
○	Vascular endothelial growth factor receptor 1 (N1050-K1056, human) pY1053 phosphopeptide - Powder PE-04AGP99
○	Vascular endothelial growth factor receptor 1 (N1050-K1056, human) pY1053 phosphopeptide - Powder PE-04BBK00
○	Vascular endothelial growth factor receptor 1 (R1045-P1051, human) pY1048 phosphopeptide - Powder PE-04BBL00

Post-translation Modifications

For detailed information on phosphorylation of this kinase go to PhosphoNET

Methylated:

K306, K831, K932, K1153.

N-GlcNAcylated:

N100, N164, N196, N251, N323, N402, N417, N474, N547, N597, N620, N625, N666.

Serine phosphorylated:

S267, S631, S739, S742, S743, S1197, S1199, S1205, S1207.

Threonine phosphorylated:

T218, T222, T255, T265, T404, T588, T599, T618, T633.

Tyrosine phosphorylated:

Y383, Y388, Y745, Y794, Y815, Y911, Y920, Y1048+, Y1053+, Y1169+, Y1213+, Y1242, Y1327, Y1333+.

Ubiquitinated:

K410.

Distribution

Based on gene microarray analysis from the NCBI

Human Tissue Distribution

% Max Expression:

Mean Expression:

Number of Samples:

Standard Deviation:

100

1227

63

1269
4

43

31

37
26

321

32

1305
28

340

256

1409
64

791

59

559
6

69

158

164
27

328

93

540
48

592

108

1476
26

313

24

238
14

168

277

251
4

49

80

55
36

440

400

543
5

59

65

79
3

32

26

20
10

117

74

403
3

35

42

27
13

154

798

1680
26

319

51

1833
7

91

231

249
52

637

246

636
15

184

71

957
10

122

73

280
12

153

51

323
5

66

53

195
17

205

71

1426
64

788

170

1124
13

159

68

843
13

165

53

847
19

229

52

524
7

85

84

78
22

274

30

338
34

412

60

397
4

44

115

165
58

711

166

660
13

163

87

197

Evolution

Species Conservation

PhosphoNET % Identity:
PhosphoNET % Similarity:
Homologene %
Identity:

100

100

100
99.3

99.9

99
88.3

89.3

98
-

-

84
-

-

95
89.9

95.4

90
-

-

-
81.7

90.4

82
82.4

90.7

82
-

-

-
71.9

83.9

-
69

80.4

71
25.6

41.7

49
44.2

61.4

54
28.7

45.1

-
-

-

-
-

-

-
-

-

23
-

-

-
-

-

-
-

-

-
-

-

-
-

-

-
-

-

-
-

-

-

For a wider analysis go to PhosphoNET Evolution in PhosphoNET

Regulation

Activation:

Activated by binding vascular endothelial growth factor (VEGF), which induces dimerization and autophosphorylation. Autophosphorylation of Tyr-1169 induces interaction with PLCg1. Autophosphorylation of Tyr-1213 increases phosphotransferase activity and induces interaction with Grb2, PLCg1 and SHP2. Autophosphorylation of Tyr-1333 induces interaction with Cbl, Crk, Nck1 and PLCg1.

Inhibition:

Synthesis:

Degradation:

Kinections Map

Click here to download a PPT of the image below

Known Upstream Kinases

For further details on these substrates click on the Substrate Short Name or UniProt ID. Phosphosite Location is hyperlinked to PhosphoNET predictions.

Based on in vitro and/or in vivo phosphorylation data

Kinase Short Name	UniProt ID (Human)	Phosphosite Location	Phosphosite Sequence	Effect of Phosphorylation

FLT1	P17948	Y1169	VQQDGKDYIPINAIL	+
FLT1	P17948	Y1213	GSSDDVRYVNAFKFM	+
FLT1	P17948	Y1242	ATSMFDDYQGDSSTL	?
FLT1	P17948	Y1327	CCSPPPDYNSVVLYS
FLT1	P17948	Y1333	DYNSVVLYSTPPI__	+

Known Downstream Substrates

For further details on these substrates click on the Substrate Short Name or UniProt ID. Phosphosite Location is hyperlinked to PhosphoNET predictions.

Based on in vitro and/or in vivo phosphorylation data

Substrate Short Name	UniProt ID (Human)	Phosphosite Location	Phosphosite Sequence	Effect of Phosphorylation

FLT1 (VEGFR1)	P17948	Y1053	DIYKNPDYVRKGDTR
FLT1 (VEGFR1)	P17948	Y1169	VQQDGKDYIPINAIL	+
FLT1 (VEGFR1)	P17948	Y1213	GSSDDVRYVNAFKFM	+
FLT1 (VEGFR1)	P17948	Y1242	ATSMFDDYQGDSSTL	?
FLT1 (VEGFR1)	P17948	Y1309	EGKRRFTYDHAELER
FLT1 (VEGFR1)	P17948	Y1327	CCSPPPDYNSVVLYS
FLT1 (VEGFR1)	P17948	Y1333	DYNSVVLYSTPPI__	+
FLT1 (VEGFR1)	P17948	Y914	VIVEYCKYGNLSNYL

Protein Kinase Specificity

Matrix of observed frequency (%) of amino acids in aligned protein substrate phosphosites

Matrix Type:

Predicted from the application of the Kinexus Kinase Substrate Predictor Version 2.0 algorithm, which was trained with over 10,000 kinase-protein substrate pairs and 8,000 kinase-peptide substrate pairs.

Domain #:

Inhibitors

For further details on these inhibitors click on the Compound Name and enter it into DrugKiNET or click on the ID's

Based on in vitro and/or in vivo phosphorylation data

Compound Name	KD, Ki or IC50 (nM)	PubChem ID	ChEMBL ID	PubMed ID

Sunitinib	Kd = 200 pM	5329102	535	18077425
Tivozanib	IC50 = 210 pM	9911830		16982756
Axitinib	IC50 = 250 pM	6450551	1289926	20869793
Cediranib	Kd = 740 pM	9933475	491473	22037378
Ki8751	IC50 = 900 pM	11317348	178455	15743179
KRN633	IC50 = 1 nM		406381	18077363
2ofv	IC50 = 2 nM	15991573		16970394
DCC2036	IC50 = 2 nM	25066467
CHEMBL1784637	IC50 = 2.3 nM	46864270	1784637	21561767
Lestaurtinib	Kd = 2.3 nM	126565		18183025
CHEMBL201511	IC50 = 2.5 nM	11530963	201511	16480264
Dovitinib	IC50 = 3 nM	57336746		19113866
Linifanib	IC50 = 3 nM	11485656	223360	17343372
Motesanib	IC50 = 3 nM	11667893	572881	20869793
Staurosporine	IC50 = 3.5 nM	5279		19397322
Ponatinib	IC50 = 3.7 nM	24826799		20513156
Foretinib	Kd = 3.8 nM	42642645	1230609	22037378
BML-275	IC50 = 4 nM	11524144	478629	20932747
TTT-3002	IC50 < 4 nM
SU14813	Kd = 4.7 nM	10138259	1721885	18183025
Nintedanib	IC50 = 5 nM	9809715	502835	19522465
CHEMBL504075	Kd = 5.7 nM	25218459	504075	19128971
OSI-930	IC50 = 8 nM	53396311		16424037
Pazopanib	IC50 = 8 nM	10113978	477772	18620382
Semaxinib	IC50 = 8 nM	5329098	276711	10882357
Vandetanib	IC50 = 9 nM	3081361	24828	15743202
CHEMBL1684800	IC50 = 9.42 nM	52938983	1684800	21353571
Vatalanib	Kd = 9.6 nM	151194	101253	18183025
Brivanib	Kd = 10 nM	11234052	377300	22037378
BX517	IC50 = 10 nM	11161844	228654
MK2461	IC50 = 10 nM	44137946		21608528
PF-03814735	IC50 = 10 nM	49830590		20354118
Cabozantinib	IC50 = 12 nM	25102847		21926191
CHEMBL223147	IC50 = 12 nM	24894130	223147	18630890
PP121	IC50 = 12 nM	24905142		18849971
Regorafenib	IC50 = 13 nM	11167602		21170960
VEGFR Kinase Inhibitor II	Ki = 15 nM	9797919	101683	17869515
CHEMBL281820	IC50 = 17 nM	44275237	281820	12477352
VEGFR2 Kinase Inhibitor IV	IC50 = 19 nM	5329468	92461	12217372
2hiw	EC50 = 22 nM	10062694		18077425
Lenvatinib	IC50 = 22 nM	9823820		17943726
PDK1/Akt/Flt Dual Pathway Inhibitor	IC50 < 25 nM	5113385	599894	22037377
MGCD-265	IC50 = 26 nM	24901704		18434145
Sorafenib	IC50 = 27 nM	216239	1336	18849971
SU11652	IC50 = 27 nM	24906267	13485	12646019
Kinome_714	IC50 = 29 nM	46886323		20346655
AT9283	IC50 < 30 nM	24905142		19143567
Cdk1/2 Inhibitor III	IC50 = 32 nM	5330812	261720	15974571
ENMD 2076	IC50 = 36 nM	16041424		19320489
(5Z)-7-Oxozeaenol	IC50 < 40 nM		1077979
Amgen TBK 1 inhibitor (Compound II)	IC50 < 40 nM
Hypothemycin	IC50 < 40 nM	5477775	471474
R406	IC50 < 40 nM	11984591
Staurosporine aglycone	IC50 < 40 nM	3035817	281948
SureCN3470757	IC50 < 40 nM	11588244	375236
Quizartinib	Kd = 41 nM	24889392	576982	19654408
GSK1070916	IC50 = 42 nM	46885626		20420387
Novonex	IC50 = 42 nM	23696523		15766665
K-252a; Nocardiopsis sp.	IC50 = 43 nM	3813	281948	12270156
CHEMBL482967	Ki = 44 nM	6420138	482967	20462263
AC1NS4N8	Kd < 50 nM	23649240		19035792
BMS-690514	IC50 = 50 nM	11349170		21531814
CHEMBL1092754	IC50 = 50 nM	44541014	1092754	20188552
Hesperadin	Kd < 50 nM	10142586	514409	19035792
SB218078	IC50 > 50 nM	447446	289422	22037377
Toceranib	IC50 = 50 nM	5329106	13608	12646019
TWS119	IC50 > 50 nM	9549289	405759	22037377
A-83-01	IC50 < 60 nM	16218924	1170377
GSK-3 Inhibitor IX	IC50 < 60 nM	5287844	409450
MK5108	IC50 > 61 nM	24748204		20053775
VEGFR2 Kinase Inhibitor I	IC50 = 70 nM	6419834	86943	18077363
VEGFR2 Kinase Inhibitor II	IC50 = 70 nM	5329155	88606	10893303
KW2449	Kd = 73 nM	11427553	1908397	22037378
BX795	IC50 < 80 nM	10077147	577784
Ibrutinib	IC50 < 80 nM	24821094	1873475
AST-487	Kd = 86 nM	11409972	574738	18183025
AC1NS90N	IC50 = 94 nM	5330391	371169	16033269
BI-D1870	IC50 = 100 nM	25023738	573107
JNKIN7	IC50 = 100 nM	57340685
LDN193189	IC50 = 100 nM	25195294	513147
PP242	IC50 = 100 nM	25243800
Princeton's TrkA inhibitor compound 20h	IC50 = 100 nM
Ro-31-8220	IC50 < 100 nM	5083	6291
Syk Inhibitor	IC50 = 100 nM	6419747	104279
Tozasertib	Kd = 100 nM	5494449	572878	18183025
Wyeth PDK1 Inhibitor Compound 1	IC50 = 100 nM
CHEMBL398606	IC50 = 103 nM	11248502	398606	17887663
Barasertib	Kd = 110 nM	16007391	215152	18183025
PD173074	IC50 = 120 nM	1401	189584	16000000
JNJ-7706621	IC50 = 130 nM	5330790	191003	15974571
Ki-20227	Kd = 130 nM	9869779	1908396	22037378
SU9516	IC50 = 130 nM	5289419	258805	12749903
Gö6983	IC50 > 150 nM	3499	261491	22037377
SureCN7018367	Kd < 150 nM	18792927	450519	19035792
CHEMBL1258913	IC50 = 162 nM	11847343	1258913	20817473
Pyrrolo-pyrimidone; 17	IC50 = 190 nM	16119021	461140	18945615
PHA-665752	IC50 = 200 nM	10461815	450786	18077425
Syk Inhibitor IV	IC50 = 200 nM	10200390
Doramapimod	IC50 = 250 nM	156422	103667	22014550
JAK3 Inhibitor VI	IC50 > 250 nM	16760524		22037377
PKR Inhibitor	IC50 > 250 nM	6490494	235641	22037377
CHEMBL1288582	IC50 = 310 nM	49839480	1288582	20965724
GW 843682X	IC50 = 360 nM	9826308	514499	19097784
Brivanib alaninate	IC50 = 380 nM	11154925		18829493
CHEMBL377734	IC50 = 400 nM	11632737	377734	16789733
CZC-25146	IC50 < 400 nM
GW441756 hydrochloride	IC50 < 400 nM	16219400
HG-9-91-01	IC50 < 400 nM
IKK-3 inhibitor IX	IC50 < 400 nM	11626927	373751
K00596a	IC50 < 400 nM	9549298	200027
PP1	IC50 < 400 nM	1400	306380
Danusertib	IC50 = 432 nM	21874004	402548	17125279
CHEMBL248757	Ki > 440 nM	44444843	248757	17935989
JNK Inhibitor VIII	Ki > 440 nM	11624601	210618	16759099
Kinome_3024	Ki > 440 nM	11539329	210963	16759099
Kinome_3027	Ki > 440 nM	11640926	378627	16759099
Kinome_3028	Ki > 440 nM	11590363	210928	16759099
CP673451	IC50 = 450 nM	10158940		15705896
N-Benzoylstaurosporine	Kd = 450 nM	56603681	608533	18183025
CHIR-124	IC50 = 464 nM	11502647		17255282
Bisindolylmaleimide IV	IC50 = 500 nM	2399	266487	22037377
Bosutinib	IC50 = 500 nM	5328940	288441	22037377
IDR E804	IC50 = 500 nM	6419764	1802727	22037377
CHEMBL363607	IC50 = 510 nM	44398371	363607	15974571
ZINC00016978	IC50 = 510 nM	5329009	301018	19211246
NVP-TAE684	Kd = 550 nM	16038120	509032	22037378
SureCN4139760	IC50 = 591 nM	25065806		18691885
IKK-2 Inhibitor IV	IC50 < 600 nM	9903786	257167
KIN 112	IC50 < 600 nM
LY364947	IC50 < 600 nM	447966	261454
Quercetagetin	IC50 < 600 nM	5281680	413552
Ruboxistaurin	IC50 < 600 nM	153999	91829
Orantinib	IC50 = 680 nM	5329099	274654	19110422
AMG458	IC50 = 690 nM	16086104	386661	18553959
ZD4190	IC50 = 700 nM	5329032	281872	11881999
AG1478	IC50 < 800 nM	2051	7917
BI-78D3	IC50 < 800 nM	2747117	508280
GW 843682X	IC50 < 800 nM	9826308	514499
PP2	IC50 < 800 nM	4878	406845
RAF265	Kd = 800 nM	11656518	558752	18183025
CUDC-101	IC50 = 849 nM	24756910	598797	20143778
Neratinib	IC50 = 858.2 nM	9915743	180022	17416531
AG-E-60384	IC50 > 1 µM	6419741	413188	22037377
ALX-270-403-M001	IC50 > 1 µM			22037377
AX20017	IC50 = 1 µM
Baricitinib	IC50 > 1 µM	44205240		20363976
Chelerythrine	IC50 = 1 µM	72311
CHEMBL201307	IC50 = 1 µM	9916282	201307	16451062
Curcumin	IC50 = 1 µM	5281767	116438
Gö6976	IC50 > 1 µM	3501	302449	22037377
Icotinib	IC50 > 1 µM	22024915		22112293
JNKIN8	IC50 = 1 µM	57340686
MLN8054	Kd = 1 µM	11712649	259084	18183025
PLX4720	IC50 = 1 µM	24180719	1230020
Purvalanol B	IC50 = 1 µM	448991	23254
Silmitasertib	IC50 > 1 µM	24748573		21174434
SNS314	IC50 > 1 µM	16047143	514582	18678489
SureCN3774124	IC50 = 1 µM	10209082	368895	15771419
Tofacitinib	IC50 = 1 µM	9926791	221959
Vemurafenib	IC50 = 1 µM	42611257	1229517
WZ3146	Kd > 1 µM	44607360		20033049
WZ4002	Kd > 1 µM	44607530		20033049
CHEMBL249097	Kd < 1.25 µM	25138012	249097	19035792
BCP9000906	IC50 = 1.4 µM	5494425	21156	11934592
CHEMBL103055	IC50 = 1.41 µM	10207821	103055	12941331
Compound 56	IC50 = 1.489 µM	2857	29197	17416531
Gefitinib	IC50 = 1.9 µM	123631	939	18849971
Momelotinib	IC50 > 2 µM	25062766		19295546
Tandutinib	IC50 = 2.07 µM	3038522	124660
SureCN4875304	IC50 = 2.1 µM	46871765		20472445
A674563	Ki = 2.2 µM	11314340	379218	16678413
Crizotinib	Kd = 2.3 µM	11626560	601719	22037378
1PU	IC50 = 2.8 µM	445840	141247	11741480
IRAK-1-4 Inhibitor I	IC50 < 3 µM	11983295	379787
IRAK-4 kinase inhibitor b	IC50 > 3 µM
Purvalanol A	IC50 > 3 µM	456214	23327
TG101209	IC50 > 3 µM	16722832		17541402
JNJ-10198409	IC50 = 3.1 µM	9797370	120077	16366598
Pelitinib	IC50 = 3.131 µM	6445562	607707	17416531
CHEMBL191336	IC50 = 3.5 µM	9863538	191336	15999992
Sotrastaurin	IC50 = 3.9 µM	10296883	565612	19827831
EGCG (Epigallocatechin Gallate)	IC50 < 4 µM	65064	297453
GSK650394A	IC50 < 4 µM	25022668	558642
H-89	IC50 < 4 µM	449241	104264
JNJ-28871063	IC50 > 4 µM	17747413		17975007
Sodium salicylate (Aspirin)	IC50 < 4 µM	16760658	447868
SU6656	IC50 < 4 µM	5353978	605003
CHEMBL489083	IC50 = 4.1 µM	25178539	489083	19053831
TG101348	Kd = 4.3 µM	16722836	1287853	22037378
Erlotinib	Kd = 4.4 µM	176870	553	18183025
Akt Inhibitor VIII	IC50 > 4.5 µM	10196499	258844
AZD8055	IC50 > 4.5 µM	25262965	1801204
MRT67307	IC50 > 4.5 µM	44464263
Ruxolitinib	IC50 > 4.5 µM	25126798	1789941

Disease Linkage

General Disease Association:

Cancer, reproductive disorders

Specific Diseases (Non-cancerous):

Pre-eclampsia; Eclampsia; Placental insufficiency; Acute mountain sickness; Lipodermatosclerosis

Comments:

Pre-eclampsia is a pregancy complication characterized by the maternal development of high blood pressure (hypertension) and high levels of protein in the urine. This complication usually occurs in the last few months of the pregnancy and commonly results in the premature delivery of the infant. Placental insufficiency is a pregnancy complication characterized by insufficient blood flow to the placenta, which can results in fetal distress and a range of other pregnancy complications, including fetal death. Mutations in FLT1 are associated with these disorders. In women with pre-eclampsia, increased expression of FLT1 correlated with decreased levels of circulating VEGF and PGF, which is predicted to cause defects in the endothelial cells of the blood vessels. In animal studies, administration of the FLT1 protein to pregnant rats resulted in the development of hypertension, proteinuria (protein in the urine), and glomerula endothliosis, which closely resembled the pre-eclampsia phenotype in humans. Therefore, increased activity and/or expression of the FLT1 protein has been implicated in the pathogenesis of pre-eclampsia and placental insufficiently.

Specific Cancer Types:

Breast cancer; Meningioma; Astrocytoma; Epithelioid hemangioendothelioma; Cancer-associated retinopathy; Microcystic meningioma

Comments:

FLT1 appears to be an oncoprotein (OP). Cancer-related mutations in human tumours point to a gain of function of the protein kinase. Gain-of-function mutations in the FLT1 gene are associated with cancer development. FLT1 expression has been shown to contribute to cancer cell survival, proliferation, migration, tissue invasion, tumour angiogenesis, and metastasis. In addition, FLT1 may promote cancer pathogenesis by enhancing inflammatory responses and recruiting tumor-infiltrating macrophages.

Gene Expression in Cancers:

TranscriptoNET (www.transcriptonet.ca) analysis with mRNA expression data retrieved from the National Center for Biotechnology Information's Gene Expression Omnibus (GEO) database, which was normalized against 60 abundantly and commonly found proteins, indicated altered expression for this protein kinase as shown here as the percent change from normal tissue controls (%CFC) as supported with the Student T-test in the following types of human cancers: Clear cell renal cell carcinomas (cRCC) (%CFC= +288, p<0.0006); Clear cell renal cell carcinomas (cRCC) (%CFC= +130, p<0.075); Clear cell renal cell carcinomas (cRCC) stage I (%CFC= +311, p<0.009); Malignant pleural mesotheliomas (MPM) tumours (%CFC= -51, p<0.02); Ovary adenocarcinomas (%CFC= +139, p<0.0001); Skin melanomas (%CFC= -46, p<0.1); and Skin melanomas - malignant (%CFC= -52, p<0.045). The COSMIC website notes an up-regulated expression score for FLT1 in diverse human cancers of 347, which is 0.8-fold of the average score of 462 for the human protein kinases. The down-regulated expression score of 0 for this protein kinase in human cancers was 100% lower than the average score of 60 for the human protein kinases.

Mutagenesis Experiments:

Insertional mutagenesis studies in mice have not yet revealed a role for this protein kinase in mouse cancer oncogenesis.

Mutation Rate in All Cancers:

Percent mutation rates per 100 amino acids length in human cancers: 0.12 % in 25596 diverse cancer specimens. This rate is a modest 1.54-fold higher than the average rate of 0.075 % calculated for human protein kinases in general.

Mutation Rate in Specific Cancers:

Highest percent mutation rates per 100 amino acids length in human cancers: 0.7 % in 856 skin cancers tested; 0.57 % in 1128 large intestine cancers tested; 0.34 % in 590 stomach cancers tested; 0.21 % in 1949 lung cancers tested; 0.19 % in 602 endometrium cancers tested; 0.12 % in 605 oesophagus cancers tested; 0.07 % in 1270 liver cancers tested; 0.07 % in 1226 kidney cancers tested; 0.05 % in 1963 central nervous system cancers tested.

Frequency of Mutated Sites:

Most frequent mutations with the number of reports indicated in brackets: R781Q (9).

Comments:

Only 7 deletion, 2 insertions and no complex mutations are noted on the COSMIC website.

COSMIC Entry:

FLT1

OMIM Entry:

165070

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