P17948 (VGFR1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Vascular endothelial growth factor receptor 1
Short name=VEGFR-1
EC=2.7.10.1

Alternative name(s):
Fms-like tyrosine kinase 1
Short name=FLT-1
Tyrosine-protein kinase FRT
Tyrosine-protein kinase receptor FLT
Short name=FLT
Vascular permeability factor receptor

Gene names

Name:	FLT1
Synonyms:	FLT, FRT, VEGFR1

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	1338 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFB and PGF, and plays an essential role in the development of embryonic vasculature, the regulation of angiogenesis, cell survival, cell migration, macrophage function, chemotaxis, and cancer cell invasion. May play an essential role as a negative regulator of embryonic angiogenesis by inhibiting excessive proliferation of endothelial cells. Can promote endothelial cell proliferation, survival and angiogenesis in adulthood. Its function in promoting cell proliferation seems to be cell-type specific. Promotes PGF-mediated proliferation of endothelial cells, proliferation of some types of cancer cells, but does not promote proliferation of normal fibroblasts (in vitro). Has very high affinity for VEGFA and relatively low protein kinase activity; may function as a negative regulator of VEGFA signaling by limiting the amount of free VEGFA and preventing its binding to KDR. Likewise, isoforms lacking a transmembrane domain, such as isoform 2, isoform 3 and isoform 4, may function as decoy receptors for VEGFA. Modulates KDR signaling by forming heterodimers with KDR. Ligand binding leads to the activation of several signaling cascades. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate and the activation of protein kinase C. Mediates phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase, leading to activation of phosphatidylinositol kinase and the downstream signaling pathway. Mediates activation of MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway. Isoform 1 phosphorylates PLCG1. Promotes phosphorylation of AKT1 at 'Ser-473'. Promotes phosphorylation of PTK2/FAK1; YES1 and CBL. Isoform 7 mediates phosphorylation of SRC at 'Tyr-418' and promotes tumor cell invasion. Ref.2 Ref.4 Ref.5 Ref.6 Ref.15 Ref.16 Ref.17 Ref.19 Ref.21 Ref.22 Ref.23 Ref.24 Ref.26 Ref.27 Ref.30 Ref.31 Ref.32 Ref.34
Catalytic activity	ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate. Ref.14 Ref.15 Ref.17 Ref.22 Ref.24
Enzyme regulation	Present in an inactive conformation in the absence of bound ligand. Binding of VEGFA, VEGFB or PGF leads to dimerization and activation by autophosphorylation on tyrosine residues.
Subunit structure	Interacts with VEGFA, VEGFB and PGF. Monomer in the absence of bound VEGFA, VEGFB or PGF. Homodimer in the presence of bound VEGFA, VEGFB and PGF. Can also form a heterodimer with KDR. Interacts (when tyrosine phosphorylated) with CBL, CRK, GRB2, NCK1, PIK3R1, PLCG1 and PTPN11. Interacts with GNB2L1/RACK1. Identified in a complex with CBL and CD2AP. Ref.2 Ref.3 Ref.14 Ref.15 Ref.17 Ref.18 Ref.20 Ref.22 Ref.24 Ref.25 Ref.33 Ref.43 Ref.45
Subcellular location	Isoform 1: Cell membrane; Single-pass type I membrane protein. Endosome. Note: Autophosphorylation promotes ubiquitination and endocytosis. Ref.2 Ref.4 Ref.5 Ref.20 Ref.25 Isoform 2: Secreted Ref.2 Ref.4 Ref.5 Ref.20 Ref.25. Isoform 3: Secreted Ref.2 Ref.4 Ref.5 Ref.20 Ref.25. Isoform 4: Secreted Ref.2 Ref.4 Ref.5 Ref.20 Ref.25. Isoform 5: Cytoplasm Potential Ref.2 Ref.4 Ref.5 Ref.20 Ref.25. Isoform 6: Cytoplasm Potential Ref.2 Ref.4 Ref.5 Ref.20 Ref.25. Isoform 7: Cytoplasm Potential Ref.2 Ref.4 Ref.5 Ref.20 Ref.25.
Tissue specificity	Detected in normal lung, but also in placenta, liver, kidney, heart and brain tissues. Specifically expressed in most of the vascular endothelial cells, and also expressed in peripheral blood monocytes. Isoform 2 is strongly expressed in placenta. Isoform 3 is expressed in corneal epithelial cells (at protein level). Isoform 3 is expressed in vascular smooth muscle cells (VSMC). Ref.5 Ref.6
Induction	Up-regulated in coculture of VSMC/endothelial cell (EC) or by direct exposure to VEGF of VSMC monoculture. Up-regulated from the second trimester of pregnancy to the term and in the placenta of women with preeclampsia (PE). Up-regulated in monocytes exposed to bacterial lipopolysaccharide (LPS). Ref.5 Ref.16 Ref.23 Ref.34
Domain	The second and third Ig-like C2-type (immunoglobulin-like) domains are sufficient for VEGFA binding. Ref.42 Ref.45
Post-translational modification	N-glycosylated. Ref.3 Ref.20 Ubiquitinated after VEGFA-mediated autophosphorylation, leading to proteolytic degradation. Ref.25 Autophosphorylated on tyrosine residues upon ligand binding. Autophosphorylation occurs in trans, i.e. one subunit of the dimeric receptor phosphorylates tyrosine residues on the other subunit. Phosphorylation at Tyr-1169 is important for interaction with PLCG1. Phosphorylation at Tyr-1213 is important for interaction with PIK3R1, PTPN11, GRB2, and PLCG1. Phosphorylation at Tyr-1333 is important for endocytosis and for interaction with CBL, NCK1 and CRK. Ref.6 Ref.14 Ref.15 Ref.17 Ref.18 Ref.20 Ref.22 Ref.24 Ref.25 Ref.27 Ref.29 Ref.30
Involvement in disease	Note=Can contribute to cancer cell survival, proliferation, migration, and invasion, and tumor angiogenesis and metastasis. May contribute to cancer pathogenesis by promoting inflammatory responses and recruitment of tumor-infiltrating macrophages. Note=Abnormally high expression of soluble isoforms (isoform 2, isoform 3 or isoform 4) may be a cause of preeclampsia.
Sequence similarities	Belongs to the protein kinase superfamily. Tyr protein kinase family. CSF-1/PDGF receptor subfamily. Contains 7 Ig-like C2-type (immunoglobulin-like) domains. Contains 1 protein kinase domain.

Ontologies

Keywords
Biological process	Angiogenesis Chemotaxis Differentiation
Cellular component	Cell membrane Cytoplasm Endosome Membrane Secreted
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Immunoglobulin domain Repeat Signal Transmembrane Transmembrane helix
Ligand	ATP-binding Nucleotide-binding
Molecular function	Developmental protein Kinase Receptor Transferase Tyrosine-protein kinase
PTM	Disulfide bond Glycoprotein Phosphoprotein Ubl conjugation
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological process	cell differentiation Inferred from electronic annotation. Source: UniProtKB-KW embryonic morphogenesis Inferred from sequence or structural similarity. Source: UniProtKB female pregnancy Traceable author statement PubMed 10194760. Source: ProtInc monocyte chemotaxis Inferred from direct assay Ref.30. Source: UniProtKB peptidyl-tyrosine phosphorylation Inferred from direct assay Ref.20Ref.17. Source: UniProtKB positive regulation of MAP kinase activity Inferred from direct assay Ref.17. Source: UniProtKB positive regulation of MAPK cascade Inferred from direct assay Ref.17. Source: UniProtKB positive regulation of angiogenesis Inferred from mutant phenotype Ref.23. Source: UniProtKB positive regulation of cell migration Inferred from direct assay Ref.16. Source: UniProtKB positive regulation of phosphatidylinositol 3-kinase activity Inferred from mutant phenotype Ref.22. Source: UniProtKB positive regulation of phosphatidylinositol 3-kinase cascade Inferred from mutant phenotype Ref.23. Source: UniProtKB positive regulation of phospholipase C activity Inferred from mutant phenotype Ref.22. Source: UniProtKB positive regulation of vascular endothelial growth factor receptor signaling pathway Inferred from direct assay PubMed 1312256. Source: BHF-UCL protein autophosphorylation Inferred from direct assay Ref.20Ref.17. Source: UniProtKB vascular endothelial growth factor receptor signaling pathway Inferred from direct assay Ref.17. Source: UniProtKB
Cellular component	Golgi apparatus Inferred from direct assay PubMed 18029348. Source: HPA endosome Inferred from electronic annotation. Source: UniProtKB-SubCell extracellular space Traceable author statement Ref.2. Source: ProtInc integral to plasma membrane Inferred from direct assay Ref.20. Source: UniProtKB nucleus Inferred from direct assay PubMed 18029348. Source: HPA
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW growth factor binding Inferred from physical interaction PubMed 16109918Ref.20PubMed 12366396Ref.3. Source: UniProtKB vascular endothelial growth factor-activated receptor activity Inferred from direct assay Ref.17. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
VEGFA	P15692	2	EBI-1026718,EBI-1026643

Alternative products

This entry describes 7 isoforms produced by alternative splicing. [Align] [Select]

Note: Additional isoforms seem to exist.

Isoform 1 (identifier: P17948-1)

Also known as: Flt1;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: P17948-2)

Also known as: sFlt1;

The sequence of this isoform differs from the canonical sequence as follows:
     657-687: DQEAPYLLRNLSDHTVAISSSTTLDCHANGV → GEHCNKKAVFSRISKFKSTRNDCTTQSNVKH
     688-1338: Missing.

Isoform 3 (identifier: P17948-3)

Also known as: sFlt1-14;

The sequence of this isoform differs from the canonical sequence as follows:
     706-733: GIILGPGSSTLFIERVTEEDEGVYHCKA → ELYTSTSPSSSSSSPLSSSSSSSSSSSS
     734-1338: Missing.

Isoform 4 (identifier: P17948-4)

The sequence of this isoform differs from the canonical sequence as follows:
     518-541: MASTLVVADSRISGIYICIASNKV → LPPANSSFMLPPTSFSSNYFHFLP
     542-1338: Missing.

Isoform 5 (identifier: P17948-5)

Also known as: i15;

The sequence of this isoform differs from the canonical sequence as follows:
     1-782: Missing.

Isoform 6 (identifier: P17948-6)

Also known as: i18;

The sequence of this isoform differs from the canonical sequence as follows:
     1-875: Missing.

Isoform 7 (identifier: P17948-7)

Also known as: i21;

The sequence of this isoform differs from the canonical sequence as follows:
     1-995: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 26

26

Chain

27 – 1338

1312

Vascular endothelial growth factor receptor 1

PRO_0000016768

Regions

Topological domain

27 – 758

732

Extracellular Potential

Transmembrane

759 – 780

22

Helical; Potential

Topological domain

781 – 1338

558

Cytoplasmic Potential

Domain

32 – 123

92

Ig-like C2-type 1

Domain

151 – 214

64

Ig-like C2-type 2

Domain

230 – 327

98

Ig-like C2-type 3

Domain

335 – 421

87

Ig-like C2-type 4

Domain

428 – 553

126

Ig-like C2-type 5

Domain

556 – 654

99

Ig-like C2-type 6

Domain

661 – 747

87

Ig-like C2-type 7

Domain

827 – 1158

332

Protein kinase

Nucleotide binding

833 – 841

9

ATP By similarity

Sites

Active site

1022

1

Proton acceptor By similarity

Binding site

861

1

ATP By similarity

Amino acid modifications

Modified residue

914

1

Phosphotyrosine; by autocatalysis Probable

Modified residue

1048

1

Phosphotyrosine Ref.29

Modified residue

1053

1

Phosphotyrosine; by autocatalysis By similarity

Modified residue

1169

1

Phosphotyrosine; by autocatalysis Ref.17

Modified residue

1213

1

Phosphotyrosine; by autocatalysis Ref.14 Ref.17 Ref.18 Ref.20 Ref.24

Modified residue

1242

1

Phosphotyrosine; by autocatalysis Ref.14

Modified residue

1309

1

Phosphotyrosine; by autocatalysis Ref.24

Modified residue

1327

1

Phosphotyrosine; by autocatalysis Ref.14 Ref.24

Modified residue

1333

1

Phosphotyrosine; by autocatalysis Ref.14

Glycosylation

100

1

N-linked (GlcNAc...) Potential

Glycosylation

164

1

N-linked (GlcNAc...) Potential

Glycosylation

196

1

N-linked (GlcNAc...) Potential

Glycosylation

251

1

N-linked (GlcNAc...) Potential

Glycosylation

323

1

N-linked (GlcNAc...) Potential

Glycosylation

402

1

N-linked (GlcNAc...) Potential

Glycosylation

417

1

N-linked (GlcNAc...) Potential

Glycosylation

474

1

N-linked (GlcNAc...) Potential

Glycosylation

547

1

N-linked (GlcNAc...) Potential

Glycosylation

597

1

N-linked (GlcNAc...) Potential

Glycosylation

620

1

N-linked (GlcNAc...) Potential

Glycosylation

625

1

N-linked (GlcNAc...) Potential

Glycosylation

666

1

N-linked (GlcNAc...) Potential

Disulfide bond

53 ↔ 107

By similarity

Disulfide bond

158 ↔ 207

Disulfide bond

252 ↔ 311

By similarity

Disulfide bond

454 ↔ 535

By similarity

Disulfide bond

577 ↔ 636

By similarity

Disulfide bond

682 ↔ 731

By similarity

Natural variations

Alternative sequence

1 – 995

995

Missing in isoform 7.

VSP_041983

Alternative sequence

1 – 875

875

Missing in isoform 6.

VSP_041984

Alternative sequence

1 – 782

782

Missing in isoform 5.

VSP_041985

Alternative sequence

518 – 541

24

MASTL…ASNKV → LPPANSSFMLPPTSFSSNYF HFLP in isoform 4.

VSP_041929

Alternative sequence

542 – 1338

797

Missing in isoform 4.

VSP_041930

Alternative sequence

657 – 687

31

DQEAP…HANGV → GEHCNKKAVFSRISKFKSTR NDCTTQSNVKH in isoform 2.

VSP_002955

Alternative sequence

688 – 1338

651

Missing in isoform 2.

VSP_002956

Alternative sequence

706 – 733

28

GIILG…YHCKA → ELYTSTSPSSSSSSPLSSSS SSSSSSSS in isoform 3.

VSP_041927

Alternative sequence

734 – 1338

605

Missing in isoform 3.

VSP_041928

Natural variant

60

1

K → T. Ref.46
Corresponds to variant rs56409818 [ dbSNP | Ensembl ].

VAR_042045

Natural variant

128

1

I → L.
Corresponds to variant rs35073261 [ dbSNP | Ensembl ].

VAR_049719

Natural variant

144

1

E → K. Ref.46
Corresponds to variant rs55974987 [ dbSNP | Ensembl ].

VAR_042046

Natural variant

281

1

R → Q. Ref.46
Corresponds to variant rs55687105 [ dbSNP | Ensembl ].

VAR_042047

Natural variant

422

1

L → I in a lung adenocarcinoma sample; somatic mutation. Ref.46

VAR_042048

Natural variant

781

1

R → Q in a glioma low grade oligodendroglioma sample; somatic mutation. Ref.46

VAR_042049

Natural variant

938

1

M → V. Ref.46
Corresponds to variant rs35549791 [ dbSNP | Ensembl ].

VAR_042050

Natural variant

982

1

E → A. Ref.46
Corresponds to variant rs35832528 [ dbSNP | Ensembl ].

VAR_042051

Natural variant

1061

1

L → V in a bladder transitional cell carcinoma sample; somatic mutation. Ref.46

VAR_042052

Experimental info

Mutagenesis

861

1

K → M: Abolishes enzyme activity. Abolishes interaction with PLCG1. Ref.17

Mutagenesis

914

1

Y → F: Reduces phosphorylation at other tyrosine residues. Ref.14

Mutagenesis

1050

1

N → D: Strongly increases kinase activity. Increases activity in promoting proliferation of endothelial cells. Ref.28

Mutagenesis

1169

1

Y → F: Loss of phosphorylation site. Abolishes interaction with PLCG1. Ref.17

Mutagenesis

1213

1

Y → F: Loss of phosphorylation site. Abolishes interaction with PIK3R1. Ref.14

Mutagenesis

1242

1

Y → F: Loss of phosphorylation site. Ref.14

Mutagenesis

1327

1

Y → F: Loss of phosphorylation site. Ref.14

Mutagenesis

1333

1

Y → F: Loss of phosphorylation site. Abolishes interaction with CBL. Ref.14 Ref.25

Sequence conflict

490

1

F → S in AAC16449. Ref.3

Sequence conflict

779

1

F → L in CAA35946. Ref.1

Sequence conflict

1029

1

L → F in ABI53803. Ref.6

Sequence conflict

1029

1

L → F in ABI53804. Ref.6

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

1338

Helix Strand Turn

Details...

Beta strand

135 – 137

3

Beta strand

144 – 148

5

Beta strand

154 – 156

3

Beta strand

168 – 171

4

Turn

172 – 174

3

Beta strand

175 – 177

3

Beta strand

181 – 187

7

Turn

188 – 190

3

Beta strand

191 – 196

6

Helix

199 – 201

3

Beta strand

203 – 211

9

Beta strand

214 – 224

11

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (Flt1) [UniParc]. Last modified April 3, 2007. Version 2. Checksum: FF3381EEFAF0787C	FASTA	1,338	150,769
	10 20 30 40 50 60 MVSYWDTGVL LCALLSCLLL TGSSSGSKLK DPELSLKGTQ HIMQAGQTLH LQCRGEAAHK 70 80 90 100 110 120 WSLPEMVSKE SERLSITKSA CGRNGKQFCS TLTLNTAQAN HTGFYSCKYL AVPTSKKKET 130 140 150 160 170 180 ESAIYIFISD TGRPFVEMYS EIPEIIHMTE GRELVIPCRV TSPNITVTLK KFPLDTLIPD 190 200 210 220 230 240 GKRIIWDSRK GFIISNATYK EIGLLTCEAT VNGHLYKTNY LTHRQTNTII DVQISTPRPV 250 260 270 280 290 300 KLLRGHTLVL NCTATTPLNT RVQMTWSYPD EKNKRASVRR RIDQSNSHAN IFYSVLTIDK 310 320 330 340 350 360 MQNKDKGLYT CRVRSGPSFK SVNTSVHIYD KAFITVKHRK QQVLETVAGK RSYRLSMKVK 370 380 390 400 410 420 AFPSPEVVWL KDGLPATEKS ARYLTRGYSL IIKDVTEEDA GNYTILLSIK QSNVFKNLTA 430 440 450 460 470 480 TLIVNVKPQI YEKAVSSFPD PALYPLGSRQ ILTCTAYGIP QPTIKWFWHP CNHNHSEARC 490 500 510 520 530 540 DFCSNNEESF ILDADSNMGN RIESITQRMA IIEGKNKMAS TLVVADSRIS GIYICIASNK 550 560 570 580 590 600 VGTVGRNISF YITDVPNGFH VNLEKMPTEG EDLKLSCTVN KFLYRDVTWI LLRTVNNRTM 610 620 630 640 650 660 HYSISKQKMA ITKEHSITLN LTIMNVSLQD SGTYACRARN VYTGEEILQK KEITIRDQEA 670 680 690 700 710 720 PYLLRNLSDH TVAISSSTTL DCHANGVPEP QITWFKNNHK IQQEPGIILG PGSSTLFIER 730 740 750 760 770 780 VTEEDEGVYH CKATNQKGSV ESSAYLTVQG TSDKSNLELI TLTCTCVAAT LFWLLLTLFI 790 800 810 820 830 840 RKMKRSSSEI KTDYLSIIMD PDEVPLDEQC ERLPYDASKW EFARERLKLG KSLGRGAFGK 850 860 870 880 890 900 VVQASAFGIK KSPTCRTVAV KMLKEGATAS EYKALMTELK ILTHIGHHLN VVNLLGACTK 910 920 930 940 950 960 QGGPLMVIVE YCKYGNLSNY LKSKRDLFFL NKDAALHMEP KKEKMEPGLE QGKKPRLDSV 970 980 990 1000 1010 1020 TSSESFASSG FQEDKSLSDV EEEEDSDGFY KEPITMEDLI SYSFQVARGM EFLSSRKCIH 1030 1040 1050 1060 1070 1080 RDLAARNILL SENNVVKICD FGLARDIYKN PDYVRKGDTR LPLKWMAPES IFDKIYSTKS 1090 1100 1110 1120 1130 1140 DVWSYGVLLW EIFSLGGSPY PGVQMDEDFC SRLREGMRMR APEYSTPEIY QIMLDCWHRD 1150 1160 1170 1180 1190 1200 PKERPRFAEL VEKLGDLLQA NVQQDGKDYI PINAILTGNS GFTYSTPAFS EDFFKESISA 1210 1220 1230 1240 1250 1260 PKFNSGSSDD VRYVNAFKFM SLERIKTFEE LLPNATSMFD DYQGDSSTLL ASPMLKRFTW 1270 1280 1290 1300 1310 1320 TDSKPKASLK IDLRVTSKSK ESGLSDVSRP SFCHSSCGHV SEGKRRFTYD HAELERKIAC 1330 CSPPPDYNSV VLYSTPPI
	Isoform 2 (sFlt1) [UniParc]. Checksum: 3F73F4942469DA36	FASTA	687	77,474
	10 20 30 40 50 60 MVSYWDTGVL LCALLSCLLL TGSSSGSKLK DPELSLKGTQ HIMQAGQTLH LQCRGEAAHK 70 80 90 100 110 120 WSLPEMVSKE SERLSITKSA CGRNGKQFCS TLTLNTAQAN HTGFYSCKYL AVPTSKKKET 130 140 150 160 170 180 ESAIYIFISD TGRPFVEMYS EIPEIIHMTE GRELVIPCRV TSPNITVTLK KFPLDTLIPD 190 200 210 220 230 240 GKRIIWDSRK GFIISNATYK EIGLLTCEAT VNGHLYKTNY LTHRQTNTII DVQISTPRPV 250 260 270 280 290 300 KLLRGHTLVL NCTATTPLNT RVQMTWSYPD EKNKRASVRR RIDQSNSHAN IFYSVLTIDK 310 320 330 340 350 360 MQNKDKGLYT CRVRSGPSFK SVNTSVHIYD KAFITVKHRK QQVLETVAGK RSYRLSMKVK 370 380 390 400 410 420 AFPSPEVVWL KDGLPATEKS ARYLTRGYSL IIKDVTEEDA GNYTILLSIK QSNVFKNLTA 430 440 450 460 470 480 TLIVNVKPQI YEKAVSSFPD PALYPLGSRQ ILTCTAYGIP QPTIKWFWHP CNHNHSEARC 490 500 510 520 530 540 DFCSNNEESF ILDADSNMGN RIESITQRMA IIEGKNKMAS TLVVADSRIS GIYICIASNK 550 560 570 580 590 600 VGTVGRNISF YITDVPNGFH VNLEKMPTEG EDLKLSCTVN KFLYRDVTWI LLRTVNNRTM 610 620 630 640 650 660 HYSISKQKMA ITKEHSITLN LTIMNVSLQD SGTYACRARN VYTGEEILQK KEITIRGEHC 670 680 NKKAVFSRIS KFKSTRNDCT TQSNVKH
	Isoform 3 (sFlt1-14) [UniParc]. Checksum: 67B7F8BC1D30CD9E	FASTA	733	82,124
	10 20 30 40 50 60 MVSYWDTGVL LCALLSCLLL TGSSSGSKLK DPELSLKGTQ HIMQAGQTLH LQCRGEAAHK 70 80 90 100 110 120 WSLPEMVSKE SERLSITKSA CGRNGKQFCS TLTLNTAQAN HTGFYSCKYL AVPTSKKKET 130 140 150 160 170 180 ESAIYIFISD TGRPFVEMYS EIPEIIHMTE GRELVIPCRV TSPNITVTLK KFPLDTLIPD 190 200 210 220 230 240 GKRIIWDSRK GFIISNATYK EIGLLTCEAT VNGHLYKTNY LTHRQTNTII DVQISTPRPV 250 260 270 280 290 300 KLLRGHTLVL NCTATTPLNT RVQMTWSYPD EKNKRASVRR RIDQSNSHAN IFYSVLTIDK 310 320 330 340 350 360 MQNKDKGLYT CRVRSGPSFK SVNTSVHIYD KAFITVKHRK QQVLETVAGK RSYRLSMKVK 370 380 390 400 410 420 AFPSPEVVWL KDGLPATEKS ARYLTRGYSL IIKDVTEEDA GNYTILLSIK QSNVFKNLTA 430 440 450 460 470 480 TLIVNVKPQI YEKAVSSFPD PALYPLGSRQ ILTCTAYGIP QPTIKWFWHP CNHNHSEARC 490 500 510 520 530 540 DFCSNNEESF ILDADSNMGN RIESITQRMA IIEGKNKMAS TLVVADSRIS GIYICIASNK 550 560 570 580 590 600 VGTVGRNISF YITDVPNGFH VNLEKMPTEG EDLKLSCTVN KFLYRDVTWI LLRTVNNRTM 610 620 630 640 650 660 HYSISKQKMA ITKEHSITLN LTIMNVSLQD SGTYACRARN VYTGEEILQK KEITIRDQEA 670 680 690 700 710 720 PYLLRNLSDH TVAISSSTTL DCHANGVPEP QITWFKNNHK IQQEPELYTS TSPSSSSSSP 730 LSSSSSSSSS SSS
	Isoform 4 [UniParc]. Checksum: 50BCDAACB69B0EA2	FASTA	541	60,917
	10 20 30 40 50 60 MVSYWDTGVL LCALLSCLLL TGSSSGSKLK DPELSLKGTQ HIMQAGQTLH LQCRGEAAHK 70 80 90 100 110 120 WSLPEMVSKE SERLSITKSA CGRNGKQFCS TLTLNTAQAN HTGFYSCKYL AVPTSKKKET 130 140 150 160 170 180 ESAIYIFISD TGRPFVEMYS EIPEIIHMTE GRELVIPCRV TSPNITVTLK KFPLDTLIPD 190 200 210 220 230 240 GKRIIWDSRK GFIISNATYK EIGLLTCEAT VNGHLYKTNY LTHRQTNTII DVQISTPRPV 250 260 270 280 290 300 KLLRGHTLVL NCTATTPLNT RVQMTWSYPD EKNKRASVRR RIDQSNSHAN IFYSVLTIDK 310 320 330 340 350 360 MQNKDKGLYT CRVRSGPSFK SVNTSVHIYD KAFITVKHRK QQVLETVAGK RSYRLSMKVK 370 380 390 400 410 420 AFPSPEVVWL KDGLPATEKS ARYLTRGYSL IIKDVTEEDA GNYTILLSIK QSNVFKNLTA 430 440 450 460 470 480 TLIVNVKPQI YEKAVSSFPD PALYPLGSRQ ILTCTAYGIP QPTIKWFWHP CNHNHSEARC 490 500 510 520 530 540 DFCSNNEESF ILDADSNMGN RIESITQRMA IIEGKNKLPP ANSSFMLPPT SFSSNYFHFL P
	Isoform 5 (i15) [UniParc]. Checksum: 9150507FBDF43B24	FASTA	556	62,954
	10 20 30 40 50 60 MKRSSSEIKT DYLSIIMDPD EVPLDEQCER LPYDASKWEF ARERLKLGKS LGRGAFGKVV 70 80 90 100 110 120 QASAFGIKKS PTCRTVAVKM LKEGATASEY KALMTELKIL THIGHHLNVV NLLGACTKQG 130 140 150 160 170 180 GPLMVIVEYC KYGNLSNYLK SKRDLFFLNK DAALHMEPKK EKMEPGLEQG KKPRLDSVTS 190 200 210 220 230 240 SESFASSGFQ EDKSLSDVEE EEDSDGFYKE PITMEDLISY SFQVARGMEF LSSRKCIHRD 250 260 270 280 290 300 LAARNILLSE NNVVKICDFG LARDIYKNPD YVRKGDTRLP LKWMAPESIF DKIYSTKSDV 310 320 330 340 350 360 WSYGVLLWEI FSLGGSPYPG VQMDEDFCSR LREGMRMRAP EYSTPEIYQI MLDCWHRDPK 370 380 390 400 410 420 ERPRFAELVE KLGDLLQANV QQDGKDYIPI NAILTGNSGF TYSTPAFSED FFKESISAPK 430 440 450 460 470 480 FNSGSSDDVR YVNAFKFMSL ERIKTFEELL PNATSMFDDY QGDSSTLLAS PMLKRFTWTD 490 500 510 520 530 540 SKPKASLKID LRVTSKSKES GLSDVSRPSF CHSSCGHVSE GKRRFTYDHA ELERKIACCS 550 PPPDYNSVVL YSTPPI
	Isoform 6 (i18) [UniParc]. Checksum: 7D3D572623A1124E	FASTA	463	52,613
	10 20 30 40 50 60 MTELKILTHI GHHLNVVNLL GACTKQGGPL MVIVEYCKYG NLSNYLKSKR DLFFLNKDAA 70 80 90 100 110 120 LHMEPKKEKM EPGLEQGKKP RLDSVTSSES FASSGFQEDK SLSDVEEEED SDGFYKEPIT 130 140 150 160 170 180 MEDLISYSFQ VARGMEFLSS RKCIHRDLAA RNILLSENNV VKICDFGLAR DIYKNPDYVR 190 200 210 220 230 240 KGDTRLPLKW MAPESIFDKI YSTKSDVWSY GVLLWEIFSL GGSPYPGVQM DEDFCSRLRE 250 260 270 280 290 300 GMRMRAPEYS TPEIYQIMLD CWHRDPKERP RFAELVEKLG DLLQANVQQD GKDYIPINAI 310 320 330 340 350 360 LTGNSGFTYS TPAFSEDFFK ESISAPKFNS GSSDDVRYVN AFKFMSLERI KTFEELLPNA 370 380 390 400 410 420 TSMFDDYQGD SSTLLASPML KRFTWTDSKP KASLKIDLRV TSKSKESGLS DVSRPSFCHS 430 440 450 460 SCGHVSEGKR RFTYDHAELE RKIACCSPPP DYNSVVLYST PPI
	Isoform 7 (i21) [UniParc]. Checksum: B7800AF7311BF0D6	FASTA	343	39,148
	10 20 30 40 50 60 MEDLISYSFQ VARGMEFLSS RKCIHRDLAA RNILLSENNV VKICDFGLAR DIYKNPDYVR 70 80 90 100 110 120 KGDTRLPLKW MAPESIFDKI YSTKSDVWSY GVLLWEIFSL GGSPYPGVQM DEDFCSRLRE 130 140 150 160 170 180 GMRMRAPEYS TPEIYQIMLD CWHRDPKERP RFAELVEKLG DLLQANVQQD GKDYIPINAI 190 200 210 220 230 240 LTGNSGFTYS TPAFSEDFFK ESISAPKFNS GSSDDVRYVN AFKFMSLERI KTFEELLPNA 250 260 270 280 290 300 TSMFDDYQGD SSTLLASPML KRFTWTDSKP KASLKIDLRV TSKSKESGLS DVSRPSFCHS 310 320 330 340 SCGHVSEGKR RFTYDHAELE RKIACCSPPP DYNSVVLYST PPI

References

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[1]	"Nucleotide sequence and expression of a novel human receptor-type tyrosine kinase gene (flt) closely related to the fms family." Shibuya M., Yamaguchi S., Yamane A., Ikeda T., Tojo A., Matsushime H., Sato M. Oncogene 5:519-524(1990) [PubMed: 2158038] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Placenta.
[2]	"Inhibition of vascular endothelial cell growth factor activity by an endogenously encoded soluble receptor." Kendall R.L., Thomas K.A. Proc. Natl. Acad. Sci. U.S.A. 90:10705-10709(1993) [PubMed: 8248162] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), PROTEIN SEQUENCE OF N-TERMINUS, SUBCELLULAR LOCATION (ISOFORM 2), INTERACTION WITH VEGFA, FUNCTION. Tissue: Umbilical vein.
[3]	"Characterization of the VEGF binding site on the Flt-1 receptor." Herley M.T., Yu Y., Whitney R.G., Sato J.D. Biochem. Biophys. Res. Commun. 262:731-738(1999) [PubMed: 10471394] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INTERACTION WITH VEGFA, GLYCOSYLATION. Tissue: Umbilical vein.
[4]	"Novel splice variants derived from the receptor tyrosine kinase superfamily are potential therapeutics for rheumatoid arthritis." Jin P., Zhang J., Sumariwalla P.F., Ni I., Jorgensen B., Crawford D., Phillips S., Feldmann M., Shepard H.M., Paleolog E.M. Arthritis Res. Ther. 10:R73-R73(2008) [PubMed: 18593464] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4), FUNCTION IN LIGAND BINDING, SUBCELLULAR LOCATION.
[5]	"A novel human-specific soluble vascular endothelial growth factor receptor 1: cell-type-specific splicing and implications to vascular endothelial growth factor homeostasis and preeclampsia." Sela S., Itin A., Natanson-Yaron S., Greenfield C., Goldman-Wohl D., Yagel S., Keshet E. Circ. Res. 102:1566-1574(2008) [PubMed: 18515749] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, ROLE IN PREECLAMPSIA, INDUCTION.
[6]	"A novel intracellular isoform of VEGFR-1 activates Src and promotes cell invasion in MDA-MB-231 breast cancer cells." Mezquita B., Mezquita J., Pau M., Mezquita C. J. Cell. Biochem. 110:732-742(2010) [PubMed: 20512933] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 5; 6 AND 7), ALTERNATIVE SPLICING, FUNCTION IN PHOSPHORYLATION OF SRC AND CANCER CELL INVASIVENESS, TISSUE SPECIFICITY.
[7]	"A new VEGFR1 receptor transcript coding for the extracellular domains of the protein followed by a C-terminal polyserine tail." Mezquita J., Mezquita B., Pau M., Mezquita C. Submitted (DEC-2007) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
[8]	NHLBI resequencing and genotyping service (RS&G) Submitted (DEC-2007) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[9]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3). Tissue: Placenta and Trachea.
[10]	"The DNA sequence and analysis of human chromosome 13." Dunham A., Matthews L.H., Burton J., Ashurst J.L., Howe K.L., Ashcroft K.J., Beare D.M., Burford D.C., Hunt S.E., Griffiths-Jones S., Jones M.C., Keenan S.J., Oliver K., Scott C.E., Ainscough R., Almeida J.P., Ambrose K.D., Andrews D.T. , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Bannerjee R., Barlow K.F., Bates K., Beasley H., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burrill W., Carder C., Carter N.P., Chapman J.C., Clamp M.E., Clark S.Y., Clarke G., Clee C.M., Clegg S.C., Cobley V., Collins J.E., Corby N., Coville G.J., Deloukas P., Dhami P., Dunham I., Dunn M., Earthrowl M.E., Ellington A.G., Faulkner L., Frankish A.G., Frankland J., French L., Garner P., Garnett J., Gilbert J.G.R., Gilson C.J., Ghori J., Grafham D.V., Gribble S.M., Griffiths C., Hall R.E., Hammond S., Harley J.L., Hart E.A., Heath P.D., Howden P.J., Huckle E.J., Hunt P.J., Hunt A.R., Johnson C., Johnson D., Kay M., Kimberley A.M., King A., Laird G.K., Langford C.J., Lawlor S., Leongamornlert D.A., Lloyd D.M., Lloyd C., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., McLaren S.J., McMurray A., Milne S., Moore M.J.F., Nickerson T., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K.M., Rice C.M., Searle S., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Steward C.A., Sycamore N., Tester J., Thomas D.W., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Wilming L., Wray P.W., Wright M.W., Young L., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Beck S., Bentley D.R., Rogers J., Ross M.T. Nature 428:522-528(2004) [PubMed: 15057823] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[11]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[12]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Ovary.
[13]	"A possible new member of tyrosine kinase family, human frt sequence, is highly conserved in vertebrates and located on human chromosome 13." Matsushime H., Yoshida M.C., Sasaki M., Shibuya M. Jpn. J. Cancer Res. 78:655-661(1987) [PubMed: 3040650] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1018-1058, ALTERNATIVE SPLICING (ISOFORM 1).
[14]	"Identification of vascular endothelial growth factor receptor-1 tyrosine phosphorylation sites and binding of SH2 domain-containing molecules." Ito N., Wernstedt C., Engstrom U., Claesson-Welsh L. J. Biol. Chem. 273:23410-23418(1998) [PubMed: 9722576] [Abstract] Cited for: PARTIAL PROTEIN SEQUENCE, CATALYTIC ACTIVITY, PHOSPHORYLATION AT TYR-914; TYR-1213; TYR-1242; TYR-1327 AND TYR-1333, MUTAGENESIS OF TYR-914; TYR-1213; TYR-1242; TYR-1327 AND TYR-1333, INTERACTION WITH PLCG1; GRB2; CRK; NCK1 AND PTPN11.
[15]	"A unique signal transduction from FLT tyrosine kinase, a receptor for vascular endothelial growth factor VEGF." Seetharam L., Gotoh N., Maru Y., Neufeld G., Yamaguchi S., Shibuya M. Oncogene 10:135-147(1995) [PubMed: 7824266] [Abstract] Cited for: INTERACTION WITH VEGFA, AUTOPHOSPHORYLATION, CATALYTIC ACTIVITY, FUNCTION IN PHOSPHORYLATION OF PLCG1, ABSENCE OF MITOGENIC FUNCTION IN CULTURED FIBROBLASTS.
[16]	"Migration of human monocytes in response to vascular endothelial growth factor (VEGF) is mediated via the VEGF receptor flt-1." Barleon B., Sozzani S., Zhou D., Weich H.A., Mantovani A., Marme D. Blood 87:3336-3343(1996) [PubMed: 8605350] [Abstract] Cited for: FUNCTION IN CELL MIGRATION, FUNCTION IN VEGFA AND PGF SIGNALING, INDUCTION.
[17]	"The phosphorylated 1169-tyrosine containing region of flt-1 kinase (VEGFR-1) is a major binding site for PLCgamma." Sawano A., Takahashi T., Yamaguchi S., Shibuya M. Biochem. Biophys. Res. Commun. 238:487-491(1997) [PubMed: 9299537] [Abstract] Cited for: FUNCTION IN PHOSPHORYLATION OF PLCG1 AND ACTIVATION OF MAP KINASES, INTERACTION WITH PLCG1, CATALYTIC ACTIVITY, MUTAGENESIS OF LYS-861 AND TYR-1169, PHOSPHORYLATION AT TYR-1169 AND TYR-1213.
[18]	"Tyrosine 1213 of Flt-1 is a major binding site of Nck and SHP-2." Igarashi K., Isohara T., Kato T., Shigeta K., Yamano T., Uno I. Biochem. Biophys. Res. Commun. 246:95-99(1998) [PubMed: 9600074] [Abstract] Cited for: INTERACTION WITH PIK3R1; PTPN11 AND NCK1, PHOSPHORYLATION AT TYR-1213.
[19]	"Vascular endothelial growth factor receptor-2-mediated mitogenesis is negatively regulated by vascular endothelial growth factor receptor-1 in tumor epithelial cells." Dunk C., Ahmed A. Am. J. Pathol. 158:265-273(2001) [PubMed: 11141500] [Abstract] Cited for: FUNCTION AS NEGATIVE REGULATOR OF KDR-MEDIATED CELL PROLIFERATION.
[20]	"Direct identification of a major autophosphorylation site on vascular endothelial growth factor receptor Flt-1 that mediates phosphatidylinositol 3'-kinase binding." Yu Y., Hulmes J.D., Herley M.T., Whitney R.G., Crabb J.W., Sato J.D. Biochem. J. 358:465-472(2001) [PubMed: 11513746] [Abstract] Cited for: INTERACTION WITH PIK3R1 AND VEGFA, AUTOPHOSPHORYLATION, PHOSPHORYLATION AT TYR-1213, SUBCELLULAR LOCATION, MASS SPECTROMETRY, GLYCOSYLATION.
[21]	"Effect of placenta growth factor-1 on proliferation and release of nitric oxide, cyclic AMP and cyclic GMP in human epithelial cells expressing the FLT-1 receptor." Angelucci C., Lama G., Iacopino F., Maglione D., Sica G. Growth Factors 19:193-206(2001) [PubMed: 11811792] [Abstract] Cited for: FUNCTION IN PGF-MEDIATED CHORIOCARCINOMA CELL PROLIFERATION.
[22]	"Signaling properties of VEGF receptor-1 and -2 homo- and heterodimers." Huang K., Andersson C., Roomans G.M., Ito N., Claesson-Welsh L. Int. J. Biochem. Cell Biol. 33:315-324(2001) [PubMed: 11312102] [Abstract] Cited for: INTERACTION WITH KDR, CATALYTIC ACTIVITY, AUTOPHOSPHORYLATION, FUNCTION IN VEGFA SIGNALING; PHOSPHORYLATION OF PLCG1 AND ACTIVATION OF PHOSPHATIDYLINOSITOL KINASE AND PHOSPHOLIPASE C.
[23]	"Activation of vascular endothelial growth factor receptor-1 sustains angiogenesis and Bcl-2 expression via the phosphatidylinositol 3-kinase pathway in endothelial cells." Cai J., Ahmad S., Jiang W.G., Huang J., Kontos C.D., Boulton M., Ahmed A. Diabetes 52:2959-2968(2003) [PubMed: 14633857] [Abstract] Cited for: FUNCTION IN SIGNALING VIA ACTIVATION OF THE PHOSPHATIDYLINOSITOL KINASE PATHWAY AND POSITIVE REGULATION OF ANGIOGENESIS IN RESPONSE TO PGF AND VEGFA.
[24]	"Role of PlGF in the intra- and intermolecular cross talk between the VEGF receptors Flt1 and Flk1." Autiero M., Waltenberger J., Communi D., Kranz A., Moons L., Lambrechts D., Kroll J., Plaisance S., De Mol M., Bono F., Kliche S., Fellbrich G., Ballmer-Hofer K., Maglione D., Mayr-Beyrle U., Dewerchin M., Dombrowski S., Stanimirovic D. , Van Hummelen P., Dehio C., Hicklin D.J., Persico G., Herbert J.M., Communi D., Shibuya M., Collen D., Conway E.M., Carmeliet P. Nat. Med. 9:936-943(2003) [PubMed: 12796773] [Abstract] Cited for: INTERACTION WITH PGF AND KDR, FUNCTION IN PHOSPHORYLATION OF KDR; VEGFA AND PGF SIGNALING, CATALYTIC ACTIVITY, MASS SPECTROMETRY, PHOSPHORYLATION AT TYR-1213; TYR-1327 AND TYR-1309.
[25]	"The c-Cbl/CD2AP complex regulates VEGF-induced endocytosis and degradation of Flt-1 (VEGFR-1)." Kobayashi S., Sawano A., Nojima Y., Shibuya M., Maru Y. FASEB J. 18:929-931(2004) [PubMed: 15001553] [Abstract] Cited for: INTERACTION WITH CBL AND CD2AP, UBIQUITINATION, AUTOPHOSPHORYLATION IN RESPONSE TO VEGFA, MUTAGENESIS OF TYR-1333, SUBCELLULAR LOCATION.
[26]	"Expression and function of vascular endothelial growth factor receptor-1 on human colorectal cancer cells." Fan F., Wey J.S., McCarty M.F., Belcheva A., Liu W., Bauer T.W., Somcio R.J., Wu Y., Hooper A., Hicklin D.J., Ellis L.M. Oncogene 24:2647-2653(2005) [PubMed: 15735759] [Abstract] Cited for: FUNCTION IN VEGFA AND VEGFB SIGNALING; CANCER CELL MIGRATION; INVASIVENESS AND ACTIVATION OF MAPK1/ERK2 AND MAPK3/ERK1.
[27]	"Vascular endothelial growth factor receptor-1 mediates migration of human colorectal carcinoma cells by activation of Src family kinases." Lesslie D.P., Summy J.M., Parikh N.U., Fan F., Trevino J.G., Sawyer T.K., Metcalf C.A., Shakespeare W.C., Hicklin D.J., Ellis L.M., Gallick G.E. Br. J. Cancer 94:1710-1717(2006) [PubMed: 16685275] [Abstract] Cited for: FUNCTION IN CELL MIGRATION AND PHOSPHORYLATION OF PTK2/FAK1; YES1 AND SRC.
[28]	"A single amino acid substitution in the activation loop defines the decoy characteristic of VEGFR-1/FLT-1." Meyer R.D., Mohammadi M., Rahimi N. J. Biol. Chem. 281:867-875(2006) [PubMed: 16286478] [Abstract] Cited for: MUTAGENESIS OF ASN-1050.
[29]	"Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer." Rikova K., Guo A., Zeng Q., Possemato A., Yu J., Haack H., Nardone J., Lee K., Reeves C., Li Y., Hu Y., Tan Z., Stokes M., Sullivan L., Mitchell J., Wetzel R., Macneill J., Ren J.M. , Yuan J., Bakalarski C.E., Villen J., Kornhauser J.M., Smith B., Li D., Zhou X., Gygi S.P., Gu T.-L., Polakiewicz R.D., Rush J., Comb M.J. Cell 131:1190-1203(2007) [PubMed: 18083107] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-1048 AND TYR-1053, MASS SPECTROMETRY. Tissue: Lung carcinoma.
[30]	"The molecular basis of VEGFR-1 signal transduction pathways in primary human monocytes." Tchaikovski V., Fellbrich G., Waltenberger J. Arterioscler. Thromb. Vasc. Biol. 28:322-328(2008) [PubMed: 18079407] [Abstract] Cited for: FUNCTION IN PGF AND VEGFA SIGNALING; PHOSPHORYLATION OF AKT1; MAPK3/ERK1 AND MAP KINASES; CHEMOTAXIS AND ACTIVATION OF PHOSPHATIDYLINOSITOL 3-KINASE, AUTOPHOSPHORYLATION IN RESPONSE TO PGF AND VEGFA.
[31]	"Vascular endothelial growth factor receptor-1 regulates postnatal angiogenesis through inhibition of the excessive activation of Akt." Nishi J., Minamino T., Miyauchi H., Nojima A., Tateno K., Okada S., Orimo M., Moriya J., Fong G.H., Sunagawa K., Shibuya M., Komuro I. Circ. Res. 103:261-268(2008) [PubMed: 18583712] [Abstract] Cited for: FUNCTION IN ENDOTHELIAL CELL SURVIVAL AND ANGIOGENESIS.
[32]	"Placental growth factor (PlGF) enhances breast cancer cell motility by mobilising ERK1/2 phosphorylation and cytoskeletal rearrangement." Taylor A.P., Leon E., Goldenberg D.M. Br. J. Cancer 103:82-89(2010) [PubMed: 20551949] [Abstract] Cited for: FUNCTION IN CANCER CELL MIGRATION AND ACTIVATION OF MAPK1/ERK2 AND/OR MAPK3/ERK1.
[33]	"RACK1 regulates VEGF/Flt1-mediated cell migration via activation of a PI3-K/Akt pathway." Wang F., Yamauchi M., Muramatsu M., Osawa T., Tsuchida R., Shibuya M. J. Biol. Chem. 286:9097-9106(2011) [PubMed: 21212275] [Abstract] Cited for: INTERACTION WITH GNB2L1.
[34]	"Autocrine activity of soluble Flt-1 controls endothelial cell function and angiogenesis." Ahmad S., Hewett P.W., Al-Ani B., Sissaoui S., Fujisawa T., Cudmore M.J., Ahmed A. Vasc. Cell 3:15-15(2011) [PubMed: 21752276] [Abstract] Cited for: FUNCTION AS DECOY RECEPTORS; REGULATION OF VEGFA SIGNALING AND REGULATION OF KDR ACTIVITY (ISOFORMS 2/3/4), ROLE IN PREECLAMPSIA.
[35]	"Differential roles of vascular endothelial growth factor receptor-1 and receptor-2 in angiogenesis." Shibuya M. J. Biochem. Mol. Biol. 39:469-478(2006) [PubMed: 17002866] [Abstract] Cited for: REVIEW ON FUNCTION AS NEGATIVE REGULATOR OF ANGIOGENESIS DURING EMBRYONIC DEVELOPMENT; POSITIVE REGULATION OF MACROPHAGE FUNCTION IN ADULTHOOD; ROLE IN CARCINOGENESIS AND INFLAMMATION.
[36]	"VEGF receptor protein-tyrosine kinases: structure and regulation." Roskoski R. Jr. Biochem. Biophys. Res. Commun. 375:287-291(2008) [PubMed: 18680722] [Abstract] Cited for: REVIEW ON STRUCTURE AND FUNCTION.
[37]	"VEGFs and receptors involved in angiogenesis versus lymphangiogenesis." Lohela M., Bry M., Tammela T., Alitalo K. Curr. Opin. Cell Biol. 21:154-165(2009) [PubMed: 19230644] [Abstract] Cited for: REVIEW ON ROLE IN ANGIOGENESIS AND CANCER.
[38]	"Structure-function analysis of VEGF receptor activation and the role of coreceptors in angiogenic signaling." Grunewald F.S., Prota A.E., Giese A., Ballmer-Hofer K. Biochim. Biophys. Acta 1804:567-580(2010) [PubMed: 19761875] [Abstract] Cited for: REVIEW ON LIGAND SPECIFICITY; FUNCTION; STRUCTURE; PHOSPHORYLATION AND SIGNALING.
[39]	"Vascular endothelial growth factor receptor-1 in human cancer: concise review and rationale for development of IMC-18F1 (Human antibody targeting vascular endothelial growth factor receptor-1)." Schwartz J.D., Rowinsky E.K., Youssoufian H., Pytowski B., Wu Y. Cancer 116:1027-1032(2010) [PubMed: 20127948] [Abstract] Cited for: REVIEW ON ROLE IN CANCER.
[40]	"Signal transduction by vascular endothelial growth factor receptors." Koch S., Tugues S., Li X., Gualandi L., Claesson-Welsh L. Biochem. J. 437:169-183(2011) [PubMed: 21711246] [Abstract] Cited for: REVIEW ON LIGAND SPECIFICITY; FUNCTION; STRUCTURE; PHOSPHORYLATION AND SIGNALING.
[41]	"Involvement of Flt-1 (VEGF receptor-1) in cancer and preeclampsia." Shibuya M. Proc. Jpn. Acad., B, Phys. Biol. Sci. 87:167-178(2011) [PubMed: 21558755] [Abstract] Cited for: REVIEW ON ROLE IN CANCER AND PREECLAMPSIA.
[42]	"Crystal structure at 1.7 A resolution of VEGF in complex with domain 2 of the Flt-1 receptor." Wiesmann C., Fuh G., Christinger H.W., Eigenbrot C., Wells J.A., de Vos A.M. Cell 91:695-704(1997) [PubMed: 9393862] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 132-226 IN COMPLEX WITH VEGFA, DOMAIN.
[43]	"Solution structure of the VEGF-binding domain of Flt-1: comparison of its free and bound states." Starovasnik M.A., Christinger H.W., Wiesmann C., Champe M.A., de Vos A.M., Skelton N.J. J. Mol. Biol. 293:531-544(1999) [PubMed: 10543948] [Abstract] Cited for: STRUCTURE BY NMR OF 129-229, X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 129-229 IN COMPLEX WITH VEGFA, SUBUNIT, INTERACTION WITH VEGFA.
[44]	"The crystal structure of placental growth factor in complex with domain 2 of vascular endothelial growth factor receptor-1." Christinger H.W., Fuh G., de Vos A.M., Wiesmann C. J. Biol. Chem. 279:10382-10388(2004) [PubMed: 14684734] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.45 ANGSTROMS) OF 130-229 IN COMPLEX WITH PGF.
[45]	"Structural insights into the binding of vascular endothelial growth factor-B by VEGFR-1(D2): recognition and specificity." Iyer S., Darley P.I., Acharya K.R. J. Biol. Chem. 285:23779-23789(2010) [PubMed: 20501651] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.71 ANGSTROMS) OF 129-226 IN COMPLE WITH VEGFB, INTERACTION WITH VEGFB, SUBUNIT, DOMAIN.
[46]	"Patterns of somatic mutation in human cancer genomes." Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R. Nature 446:153-158(2007) [PubMed: 17344846] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] THR-60; LYS-144; GLN-281; ILE-422; GLN-781; VAL-938; ALA-982 AND VAL-1061.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X51602 mRNA. Translation: CAA35946.1.
U01134 mRNA. Translation: AAC50060.1.
AF063657 mRNA. Translation: AAC16449.2.
EU826561 mRNA. Translation: ACF47597.1.
EU368830 mRNA. Translation: ACA62948.1.
DQ836394 mRNA. Translation: ABI53803.1.
DQ836395 mRNA. Translation: ABI53804.1.
DQ836396 mRNA. Translation: ABI53805.1.
EF491868 mRNA. Translation: ABS32268.1.
EF491869 mRNA. Translation: ABS32269.1.
EU360600 mRNA. Translation: ACB05747.1.
EU332841 Genomic DNA. Translation: ABY87530.1.
AK292936 mRNA. Translation: BAF85625.1.
AK300392 mRNA. Translation: BAG62125.1.
AL138712, AL139005 Genomic DNA. Translation: CAI14846.1.
AL139005, AL138712 Genomic DNA. Translation: CAI17096.1.
CH471075 Genomic DNA. Translation: EAX08431.1.
CH471075 Genomic DNA. Translation: EAX08432.1.
BC039007 mRNA. Translation: AAH39007.1.
D00133 Genomic DNA. Translation: BAA00080.1.

IPI

IPI00018335.
IPI00216043.

PIR

A49636.
S09982.

RefSeq

NP_001153392.1. NM_001159920.1.
NP_001153502.1. NM_001160030.1.
NP_001153503.1. NM_001160031.1.
NP_002010.2. NM_002019.4.

UniGene

Hs.594454.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1FLT	X-ray	1.70	X/Y	132-226	[»]
1QSV	NMR	-	A	129-229	[»]
1QSZ	NMR	-	A	129-229	[»]
1QTY	X-ray	2.70	T/U/X/Y	129-229	[»]
1RV6	X-ray	2.45	X/Y	130-229	[»]
2XAC	X-ray	2.71	C/X	129-226	[»]
3HNG	X-ray	2.70	A	801-1158	[»]

ProteinModelPortal

P17948.

SMR

P17948. Positions 33-471, 522-749, 808-1165.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-643N.

IntAct

P17948. 2 interactions.

MINT

MINT-127610.

STRING

P17948.

PTM databases

PhosphoSite

P17948.

Polymorphism databases

DMDM

143811474.

Proteomic databases

PRIDE

P17948.

Protocols and materials databases

DNASU

2321.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000282397; ENSP00000282397; ENSG00000102755.
ENST00000540678; ENSP00000443311; ENSG00000102755.
ENST00000541932; ENSP00000437631; ENSG00000102755.

GeneID

2321.

KEGG

hsa:2321.

UCSC

uc001usb.3. human.
uc001usc.3. human.

Organism-specific databases

CTD

2321.

GeneCards

GC13M028874.

HGNC

HGNC:3763. FLT1.

HPA

HPA011740.
HPA014290.

MIM

165070. gene.

neXtProt

NX_P17948.

PharmGKB

PA28180.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0515.

GeneTree

ENSGT00650000092881.

HOGENOM

HOG000037949.

HOVERGEN

HBG053432.

InParanoid

P17948.

KO

K05096.

OMA

KPQIYEK.

OrthoDB

EOG47M1X1.

PhylomeDB

P17948.

Enzyme and pathway databases

BRENDA

2.7.10.1. 2681.

Pathway_Interaction_DB

glypican_1pathway. Glypican 1 network.
s1p_s1p3_pathway. S1P3 pathway.
vegfr1_2_pathway. Signaling events mediated by VEGFR1 and VEGFR2.
vegfr1_pathway. VEGFR1 specific signals.

Reactome

REACT_111102. Signal Transduction.

Gene expression databases

ArrayExpress

P17948.

Bgee

B3FR89.

CleanEx

HS_FLT1.

Genevestigator

P17948.

GermOnline

ENSG00000102755. Homo sapiens.

Family and domain databases

Gene3D

G3DSA:2.60.40.10. Ig-like_fold. 8 hits.

InterPro

IPR007110. Ig-like.
IPR013783. Ig-like_fold.
IPR013098. Ig_I-set.
IPR003599. Ig_sub.
IPR003598. Ig_sub2.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_cat_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
IPR008266. Tyr_kinase_AS.
IPR020635. Tyr_kinase_cat_dom.
IPR001824. Tyr_kinase_rcpt_3_CS.
IPR009135. Tyr_kinase_VEGFR1_rcpt_N.
IPR009134. Tyr_kinase_VEGFR_rcpt_N.
[Graphical view]

Pfam

PF07679. I-set. 3 hits.
PF07714. Pkinase_Tyr. 1 hit.
[Graphical view]

PRINTS

PR01832. VEGFRECEPTOR.
PR01833. VEGFRECEPTR1.

SMART

SM00409. IG. 5 hits.
SM00408. IGc2. 2 hits.
SM00219. TyrKc. 1 hit.
[Graphical view]

SUPFAM

SSF56112. Kinase_like. 1 hit.

PROSITE

PS50835. IG_LIKE. 6 hits.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00109. PROTEIN_KINASE_TYR. 1 hit.
PS00240. RECEPTOR_TYR_KIN_III. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

DrugBank

DB01268. Sunitinib.

EvolutionaryTrace

P17948.

NextBio

9421.

SOURCE

Search...

Entry information

Entry name

VGFR1_HUMAN

Accession

Primary (citable) accession number: P17948
Secondary accession number(s): A3E342 , A3E344, A8KA71, B0LPF1, B2BF46, B2BF47, B3FR89, B5A923, F5H5L6, O60722, P16057, Q12954

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1990
Last sequence update:	April 3, 2007
Last modified:	May 16, 2012
This is version 154 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.