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Protein

Vascular endothelial growth factor receptor 1

Gene

Flt1

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript leveli

Functioni

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, and proliferation of some types of cancer cells, but does not promote proliferation of normal fibroblasts. 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. Modulates KDR signaling by forming heterodimers with KDR. Ligand binding leads to the activation of several signaling cascades. Activation of PLCG 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 the 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. Phosphorylates SRC, YES1 and PLCG, and may also phosphorylate CBL. Promotes phosphorylation of AKT1 and PTK2/FAK1 (By similarity).By similarity

Catalytic activityi

ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.PROSITE-ProRule annotation

Enzyme regulationi

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 (By similarity).By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei861ATPPROSITE-ProRule annotation1
Active sitei1022Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi833 – 841ATPPROSITE-ProRule annotation9

GO - Molecular functioni

  • ATP binding Source: RGD
  • growth factor binding Source: RGD
  • receptor signaling protein tyrosine kinase activity Source: RGD
  • transmembrane receptor protein tyrosine kinase activity Source: RGD
  • vascular endothelial growth factor-activated receptor activity Source: RGD

GO - Biological processi

  • activation of MAPKK activity Source: RGD
  • aging Source: RGD
  • angiogenesis Source: UniProtKB-KW
  • blood vessel morphogenesis Source: UniProtKB
  • cell migration Source: UniProtKB
  • cellular response to hypoxia Source: RGD
  • chemotaxis Source: UniProtKB-KW
  • embryonic morphogenesis Source: UniProtKB
  • female pregnancy Source: RGD
  • intracellular receptor signaling pathway Source: RGD
  • liver regeneration Source: RGD
  • negative regulation of sprouting angiogenesis Source: RGD
  • negative regulation of vascular endothelial growth factor production Source: RGD
  • peptidyl-tyrosine phosphorylation Source: UniProtKB
  • positive regulation of cell migration Source: RGD
  • positive regulation of cell proliferation Source: RGD
  • positive regulation of glial cell proliferation Source: RGD
  • positive regulation of smooth muscle cell proliferation Source: RGD
  • protein autophosphorylation Source: UniProtKB
  • protein phosphorylation Source: RGD
  • regulation of smooth muscle contraction Source: RGD
  • response to activity Source: RGD
  • response to estradiol Source: RGD
  • response to ethanol Source: RGD
  • response to hypoxia Source: RGD
  • transmembrane receptor protein tyrosine kinase signaling pathway Source: RGD
  • vascular endothelial growth factor receptor signaling pathway Source: InterPro
Complete GO annotation...

Keywords - Molecular functioni

Developmental protein, Kinase, Receptor, Transferase, Tyrosine-protein kinase

Keywords - Biological processi

Angiogenesis, Chemotaxis, Differentiation

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.10.1. 5301.

Names & Taxonomyi

Protein namesi
Recommended name:
Vascular endothelial growth factor receptor 1 (EC:2.7.10.1)
Short name:
VEGFR-1
Alternative name(s):
Fms-like tyrosine kinase 1
Short name:
FLT-1
Tyrosine-protein kinase receptor FLT
Gene namesi
Name:Flt1
Synonyms:Flt-1, Vegfr1
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi2621. Flt1.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini23 – 758ExtracellularSequence analysisAdd BLAST736
Transmembranei759 – 780HelicalSequence analysisAdd BLAST22
Topological domaini781 – 1336CytoplasmicSequence analysisAdd BLAST556

GO - Cellular componenti

  • endosome Source: UniProtKB-SubCell
  • extracellular space Source: RGD
  • integral component of plasma membrane Source: UniProtKB
  • plasma membrane Source: RGD
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Endosome, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 22Sequence analysisAdd BLAST22
ChainiPRO_000001677023 – 1336Vascular endothelial growth factor receptor 1Add BLAST1314

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi53 ↔ 107PROSITE-ProRule annotation
Glycosylationi100N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi158 ↔ 207PROSITE-ProRule annotation
Glycosylationi164N-linked (GlcNAc...)Sequence analysis1
Glycosylationi196N-linked (GlcNAc...)Sequence analysis1
Glycosylationi251N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi252 ↔ 311PROSITE-ProRule annotation
Glycosylationi323N-linked (GlcNAc...)Sequence analysis1
Glycosylationi417N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi454 ↔ 535PROSITE-ProRule annotation
Glycosylationi474N-linked (GlcNAc...)Sequence analysis1
Glycosylationi516N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi577 ↔ 636PROSITE-ProRule annotation
Glycosylationi597N-linked (GlcNAc...)Sequence analysis1
Glycosylationi625N-linked (GlcNAc...)Sequence analysis1
Glycosylationi666N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi682 ↔ 731PROSITE-ProRule annotation
Glycosylationi713N-linked (GlcNAc...)Sequence analysis1
Modified residuei914Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei1053Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei1169Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei1213Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei1242Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei1325Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei1331Phosphotyrosine; by autocatalysisBy similarity1

Post-translational modificationi

N-glycosylated.By similarity
Ubiquitinated after VEGFA-mediated autophosphorylation, leading to proteolytic degradation.By similarity
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 PLCG. Phosphorylation at Tyr-1213 is important for interaction with PIK3R1, PTPN11, GRB2, and PLCG. Phosphorylation at Tyr-1331 is important for endocytosis and for interaction with CBL, NCK1 and CRK. Is probably dephosphorylated by PTPRB (By similarity).By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei767 – 768Cleavage; by PSEN1By similarity2

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiP53767.
PRIDEiP53767.

PTM databases

iPTMnetiP53767.
PhosphoSitePlusiP53767.

Interactioni

Subunit structurei

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 (tyrosine phosphorylated) with CBL, CRK, GRB2, NCK1, PIK3R1, PLCG, PSEN1 and PTPN11. Probably interacts with PTPRB. Interacts with RACK1. Identified in a complex with CBL and CD2AP (By similarity).By similarity

GO - Molecular functioni

  • growth factor binding Source: RGD

Protein-protein interaction databases

BioGridi248474. 1 interactor.
IntActiP53767. 1 interactor.
MINTiMINT-4593147.
STRINGi10116.ENSRNOP00000001248.

Structurei

3D structure databases

ProteinModelPortaliP53767.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini32 – 121Ig-like C2-type 1Add BLAST90
Domaini151 – 214Ig-like C2-type 2Add BLAST64
Domaini230 – 327Ig-like C2-type 3Add BLAST98
Domaini335 – 421Ig-like C2-type 4Add BLAST87
Domaini429 – 549Ig-like C2-type 5Add BLAST121
Domaini556 – 655Ig-like C2-type 6Add BLAST100
Domaini661 – 747Ig-like C2-type 7Add BLAST87
Domaini827 – 1158Protein kinasePROSITE-ProRule annotationAdd BLAST332

Domaini

The second and third Ig-like C2-type (immunoglobulin-like) domains are sufficient for VEGFA binding.By similarity

Sequence similaritiesi

Belongs to the protein kinase superfamily. Tyr protein kinase family. CSF-1/PDGF receptor subfamily.PROSITE-ProRule annotation
Contains 1 protein kinase domain.PROSITE-ProRule annotation

Keywords - Domaini

Immunoglobulin domain, Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG0200. Eukaryota.
COG0515. LUCA.
HOGENOMiHOG000037949.
HOVERGENiHBG053432.
InParanoidiP53767.
PhylomeDBiP53767.

Family and domain databases

Gene3Di2.60.40.10. 7 hits.
InterProiIPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR013098. Ig_I-set.
IPR003599. Ig_sub.
IPR003598. Ig_sub2.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_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. VEGFR1_rcpt.
[Graphical view]
PfamiPF07679. I-set. 2 hits.
PF07714. Pkinase_Tyr. 1 hit.
[Graphical view]
PRINTSiPR01833. VEGFRECEPTR1.
SMARTiSM00409. IG. 7 hits.
SM00408. IGc2. 5 hits.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMiSSF48726. SSF48726. 8 hits.
SSF56112. SSF56112. 2 hits.
PROSITEiPS50835. 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]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P53767-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MVSCWDTAVL PCALLGCLLL TGYCSGSKLK GPELSLKGTQ HVMQAGQTLF
60 70 80 90 100
LKCRGEAAHS WSLPTTVSQE DKKLSVTRSA CGRNNRQFCS TLTLNMAQAN
110 120 130 140 150
HTGLYSCRYL PKSTSKEKKM ESAIYIFVSD AGSPFIEMHS DIPKLVHMTE
160 170 180 190 200
GRELIIPCRV TSPNITVTLK KFPFDALTPD GQRIAWDSRR GFIIANATYK
210 220 230 240 250
EIGLLTCEAT VNGHLYQTSY LTHRQTNTIL DVQISPPSPV RFLRGQTLVL
260 270 280 290 300
NCTVTTDLNT RVQMSWNYPG KATKRASIRQ RIDQSNPHSN VFHSVLKINN
310 320 330 340 350
VESRDKGLYT CRVKSGSSFR TFNTSVHVYE KGFISVKHRK QQVQETIAGK
360 370 380 390 400
RSHRLSMKVK AFPSPEVVWL KDGVPATEKS ARYSVHGYSL IIKDVTAEDA
410 420 430 440 450
GDYTILLGIK QSKLFRNLTA TLIVNVKPQI YEKSVSSLPS PPLYPLGSRQ
460 470 480 490 500
VLTCTVYGIP QPTIKWLWHP CHYNHSKERN DFCFGSEESF ILDSSSNIGN
510 520 530 540 550
RIEGITQRMM VIEGTNKTVS TLVVADSRTP GSYSCKAFNK IGTVERDIRF
560 570 580 590 600
YVTDVPNGFH VSLEKIPTEG EDLKLSCVVS KFLYRDITWI LLRTVNNRTM
610 620 630 640 650
HHSISKQKMA TTQDYSITLN LVIKNVSLED SGTYACRARN IYTGEEILRK
660 670 680 690 700
TEVLVRDLEA PLLLQNLSDH EVSISGSTTL DCQARGVPAP QITWFKNNHK
710 720 730 740 750
IQQEPGIILG PGNSTLFIER VTEEDEGVYR CRATNQKGVV ESSAYLTVQG
760 770 780 790 800
TSDKSNLELI TLTCTCVAAT LFWLLLTLFI RKLKRSSSEV KTDYLSIIMD
810 820 830 840 850
PDEVPLDEQC ERLPYDASKW EFARERLKLG KSLGRGAFGK VVQASAFGIK
860 870 880 890 900
KSPTCRTVAV KMLKEGATAS EYKALMTELK ILTHIGHHLN VVNLLGACTK
910 920 930 940 950
QGGPLMVIVE YCKYGNLSNY LKSKRDFFCL NKDAALHMEP KKEKLEPDLE
960 970 980 990 1000
QDQKPRLDSV SSSESFTSSG FQEDKSVSDV EGGEDYSEIS KQPLTMEDLI
1010 1020 1030 1040 1050
SYSFQVARGM EFLSSRKCIH RDLAARNILL SENNVVKICD FGLARDIYKN
1060 1070 1080 1090 1100
PDYVRRGDTR LPLKWMAPES IFDKVYSTKS DVWSYGVLLW EIFSLGGSPY
1110 1120 1130 1140 1150
PGVQMDEDFC SRLKEGMRMR TPEYATPEIY QIMLDCWHKD PKERPRFAEL
1160 1170 1180 1190 1200
VEKLGDLLQA NVQQDGKDYI PLNAILTRNS GFTYSVPTFS EDFFKDGFTD
1210 1220 1230 1240 1250
PKFHSGSSDD VRYVNAFKFM SLERIKTFEE LSPNATSMFE DYHLDTSSLL
1260 1270 1280 1290 1300
TSPLLKRFTW TETKPKASMK IDLRITSKSK EAGLSDLPGP SFCFSSCGHI
1310 1320 1330
RPVRQEDEDD PELGKESCCS PPPDYNSVVL YSSPPA
Length:1,336
Mass (Da):150,250
Last modified:October 1, 1996 - v1
Checksum:i0CCCD68C1F3D20CE
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D28498 mRNA. Translation: BAA05857.1.
PIRiI60598.
UniGeneiRn.10239.
Rn.204387.

Genome annotation databases

UCSCiRGD:2621. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D28498 mRNA. Translation: BAA05857.1.
PIRiI60598.
UniGeneiRn.10239.
Rn.204387.

3D structure databases

ProteinModelPortaliP53767.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi248474. 1 interactor.
IntActiP53767. 1 interactor.
MINTiMINT-4593147.
STRINGi10116.ENSRNOP00000001248.

PTM databases

iPTMnetiP53767.
PhosphoSitePlusiP53767.

Proteomic databases

PaxDbiP53767.
PRIDEiP53767.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

UCSCiRGD:2621. rat.

Organism-specific databases

RGDi2621. Flt1.

Phylogenomic databases

eggNOGiKOG0200. Eukaryota.
COG0515. LUCA.
HOGENOMiHOG000037949.
HOVERGENiHBG053432.
InParanoidiP53767.
PhylomeDBiP53767.

Enzyme and pathway databases

BRENDAi2.7.10.1. 5301.

Miscellaneous databases

PROiP53767.

Family and domain databases

Gene3Di2.60.40.10. 7 hits.
InterProiIPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR013098. Ig_I-set.
IPR003599. Ig_sub.
IPR003598. Ig_sub2.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_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. VEGFR1_rcpt.
[Graphical view]
PfamiPF07679. I-set. 2 hits.
PF07714. Pkinase_Tyr. 1 hit.
[Graphical view]
PRINTSiPR01833. VEGFRECEPTR1.
SMARTiSM00409. IG. 7 hits.
SM00408. IGc2. 5 hits.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMiSSF48726. SSF48726. 8 hits.
SSF56112. SSF56112. 2 hits.
PROSITEiPS50835. 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]
ProtoNetiSearch...

Entry informationi

Entry nameiVGFR1_RAT
AccessioniPrimary (citable) accession number: P53767
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: November 2, 2016
This is version 146 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.