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P17948

- VGFR1_HUMAN

UniProt

P17948 - VGFR1_HUMAN

Protein

Vascular endothelial growth factor receptor 1

Gene

FLT1

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 181 (01 Oct 2014)
      Sequence version 2 (03 Apr 2007)
      Previous versions | rss
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    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, 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 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 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 and YES1, and may also phosphorylate CBL. Isoform 1 phosphorylates PLCG. Promotes phosphorylation of AKT1 at 'Ser-473'. Promotes phosphorylation of PTK2/FAK1. Isoform 7 has a truncated kinase domain; it increases phosphorylation of SRC at 'Tyr-418' by unknown means and promotes tumor cell invasion.18 Publications

    Catalytic activityi

    ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.5 PublicationsPROSITE-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.

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sitei767 – 7682Cleavage; by PSEN1Curated
    Binding sitei861 – 8611ATPPROSITE-ProRule annotation
    Active sitei1022 – 10221Proton acceptorPROSITE-ProRule annotation

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi833 – 8419ATPPROSITE-ProRule annotation

    GO - Molecular functioni

    1. ATP binding Source: UniProtKB-KW
    2. growth factor binding Source: UniProtKB
    3. placental growth factor-activated receptor activity Source: UniProtKB
    4. protein binding Source: IntAct
    5. transmembrane receptor protein tyrosine kinase activity Source: ProtInc
    6. vascular endothelial growth factor-activated receptor activity Source: UniProtKB
    7. VEGF-A-activated receptor activity Source: UniProtKB
    8. VEGF-B-activated receptor activity Source: UniProtKB

    GO - Biological processi

    1. blood vessel morphogenesis Source: UniProtKB
    2. cell differentiation Source: UniProtKB-KW
    3. cell migration Source: UniProtKB
    4. cellular response to vascular endothelial growth factor stimulus Source: UniProtKB
    5. embryonic morphogenesis Source: UniProtKB
    6. monocyte chemotaxis Source: UniProtKB
    7. patterning of blood vessels Source: Ensembl
    8. peptidyl-tyrosine phosphorylation Source: UniProtKB
    9. positive regulation of angiogenesis Source: UniProtKB
    10. positive regulation of cell migration Source: UniProtKB
    11. positive regulation of cell proliferation Source: ProtInc
    12. positive regulation of MAPK cascade Source: UniProtKB
    13. positive regulation of MAP kinase activity Source: UniProtKB
    14. positive regulation of phosphatidylinositol 3-kinase activity Source: UniProtKB
    15. positive regulation of phosphatidylinositol 3-kinase signaling Source: UniProtKB
    16. positive regulation of phospholipase C activity Source: UniProtKB
    17. positive regulation of vascular endothelial growth factor receptor signaling pathway Source: BHF-UCL
    18. protein autophosphorylation Source: UniProtKB
    19. sprouting angiogenesis Source: Ensembl
    20. transmembrane receptor protein tyrosine kinase signaling pathway Source: ProtInc
    21. vascular endothelial growth factor receptor-1 signaling pathway Source: UniProtKB
    22. vascular endothelial growth factor receptor signaling pathway Source: UniProtKB

    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. 2681.
    ReactomeiREACT_12473. Neurophilin interactions with VEGF and VEGFR.
    REACT_12583. VEGF binds to VEGFR leading to receptor dimerization.
    SignaLinkiP17948.

    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 FRT
    Tyrosine-protein kinase receptor FLT
    Short name:
    FLT
    Vascular permeability factor receptor
    Gene namesi
    Name:FLT1
    Synonyms:FLT, FRT, VEGFR1
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 13

    Organism-specific databases

    HGNCiHGNC:3763. FLT1.

    Subcellular locationi

    Isoform 1 : Cell membrane; Single-pass type I membrane protein. Endosome
    Note: Autophosphorylation promotes ubiquitination and endocytosis.
    Isoform 2 : Secreted 1 Publication

    GO - Cellular componenti

    1. endosome Source: UniProtKB-SubCell
    2. extracellular space Source: ProtInc
    3. integral component of plasma membrane Source: UniProtKB
    4. plasma membrane Source: Reactome
    5. receptor complex Source: MGI

    Keywords - Cellular componenti

    Cell membrane, Cytoplasm, Endosome, Membrane, Secreted

    Pathology & Biotechi

    Involvement in diseasei

    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.
    Abnormally high expression of soluble isoforms (isoform 2, isoform 3 or isoform 4) may be a cause of preeclampsia.

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi767 – 7671V → A: Abolishes proteolytic cleavage by PSEN1. 1 Publication
    Mutagenesisi861 – 8611K → M: Abolishes enzyme activity. Abolishes interaction with PLCG. 1 Publication
    Mutagenesisi914 – 9141Y → F: Reduces phosphorylation at other tyrosine residues. 1 Publication
    Mutagenesisi1050 – 10501N → D: Strongly increases kinase activity. Increases activity in promoting proliferation of endothelial cells. 1 Publication
    Mutagenesisi1169 – 11691Y → F: Loss of phosphorylation site. Abolishes interaction with PLCG. 1 Publication
    Mutagenesisi1213 – 12131Y → F: Loss of phosphorylation site. Abolishes interaction with PIK3R1. 1 Publication
    Mutagenesisi1242 – 12421Y → F: Loss of phosphorylation site. 1 Publication
    Mutagenesisi1327 – 13271Y → F: Loss of phosphorylation site. 1 Publication
    Mutagenesisi1333 – 13331Y → F: Loss of phosphorylation site. Abolishes interaction with CBL. 2 Publications

    Organism-specific databases

    PharmGKBiPA28180.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 26261 PublicationAdd
    BLAST
    Chaini27 – 13381312Vascular endothelial growth factor receptor 1PRO_0000016768Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Disulfide bondi53 ↔ 107PROSITE-ProRule annotation
    Glycosylationi100 – 1001N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi158 ↔ 207
    Glycosylationi164 – 1641N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi196 – 1961N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi251 – 2511N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi252 ↔ 311PROSITE-ProRule annotation
    Glycosylationi323 – 3231N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi402 – 4021N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi417 – 4171N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi454 ↔ 535PROSITE-ProRule annotation
    Glycosylationi474 – 4741N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi547 – 5471N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi577 ↔ 636PROSITE-ProRule annotation
    Glycosylationi597 – 5971N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi620 – 6201N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi625 – 6251N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi666 – 6661N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi682 ↔ 731PROSITE-ProRule annotation
    Modified residuei914 – 9141Phosphotyrosine; by autocatalysis1 Publication
    Modified residuei1053 – 10531Phosphotyrosine; by autocatalysisBy similarity
    Modified residuei1169 – 11691Phosphotyrosine; by autocatalysis1 Publication
    Modified residuei1213 – 12131Phosphotyrosine; by autocatalysis5 Publications
    Modified residuei1242 – 12421Phosphotyrosine; by autocatalysis1 Publication
    Modified residuei1309 – 13091Phosphotyrosine; by autocatalysis1 Publication
    Modified residuei1327 – 13271Phosphotyrosine; by autocatalysis2 Publications
    Modified residuei1333 – 13331Phosphotyrosine; by autocatalysis1 Publication

    Post-translational modificationi

    N-glycosylated.2 Publications
    Ubiquitinated after VEGFA-mediated autophosphorylation, leading to proteolytic degradation.1 Publication
    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-1333 is important for endocytosis and for interaction with CBL, NCK1 and CRK. Is probably dephosphorylated by PTPRB.5 Publications

    Keywords - PTMi

    Disulfide bond, Glycoprotein, Phosphoprotein, Ubl conjugation

    Proteomic databases

    PaxDbiP17948.
    PRIDEiP17948.

    PTM databases

    PhosphoSiteiP17948.

    Expressioni

    Tissue specificityi

    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).2 Publications

    Inductioni

    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).2 Publications

    Gene expression databases

    ArrayExpressiP17948.
    BgeeiP17948.
    CleanExiHS_FLT1.
    GenevestigatoriP17948.

    Organism-specific databases

    HPAiHPA011740.
    HPA014290.

    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 (when tyrosine phosphorylated) with CBL, CRK, GRB2, NCK1, PIK3R1, PLCG, PSEN1 and PTPN11. Probably interacts also with PTPRB. Interacts with GNB2L1/RACK1. Identified in a complex with CBL and CD2AP.16 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    CBLP226812EBI-1026718,EBI-518228
    CRKLP461099EBI-1026718,EBI-910
    CTNNB1P352222EBI-1026718,EBI-491549
    HCKP086312EBI-1026718,EBI-346340
    PGFP497632EBI-1026718,EBI-1037633
    PIK3R1P279862EBI-1026718,EBI-79464
    PLCG1P191742EBI-1026718,EBI-79387
    PTK2Q053972EBI-1026718,EBI-702142
    PTPN11Q061242EBI-1026718,EBI-297779
    PTPRJQ129132EBI-1026718,EBI-2264500
    VEGFAP156924EBI-1026718,EBI-1026643
    VEGFAP15692-43EBI-1026718,EBI-1026691

    Protein-protein interaction databases

    BioGridi108609. 11 interactions.
    DIPiDIP-643N.
    IntActiP17948. 27 interactions.
    MINTiMINT-127610.
    STRINGi9606.ENSP00000282397.

    Structurei

    Secondary structure

    1
    1338
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Turni130 – 1323
    Beta strandi135 – 1373
    Beta strandi140 – 1423
    Beta strandi144 – 1485
    Beta strandi150 – 1523
    Beta strandi154 – 1563
    Beta strandi160 – 1623
    Helixi163 – 1653
    Beta strandi168 – 1714
    Turni172 – 1743
    Beta strandi175 – 1773
    Beta strandi181 – 1877
    Turni188 – 1903
    Beta strandi191 – 1966
    Helixi199 – 2013
    Beta strandi203 – 2119
    Beta strandi214 – 22411
    Helixi806 – 8094
    Helixi817 – 8204
    Helixi824 – 8263
    Beta strandi827 – 8359
    Beta strandi837 – 84812
    Helixi849 – 8513
    Beta strandi854 – 86310
    Helixi869 – 88315
    Beta strandi894 – 8985
    Beta strandi906 – 9105
    Helixi917 – 9226
    Helixi996 – 101419
    Turni1015 – 10173
    Helixi1025 – 10273
    Beta strandi1028 – 10303
    Helixi1032 – 10343
    Beta strandi1036 – 10383
    Helixi1042 – 10443
    Turni1047 – 10493
    Beta strandi1053 – 10553
    Helixi1063 – 10653
    Helixi1068 – 10736
    Helixi1078 – 109316
    Helixi1107 – 11137
    Turni1114 – 11163
    Helixi1127 – 113610
    Helixi1141 – 11433
    Helixi1147 – 115711

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1FLTX-ray1.70X/Y132-226[»]
    1QSVNMR-A129-229[»]
    1QSZNMR-A129-229[»]
    1QTYX-ray2.70T/U/X/Y129-229[»]
    1RV6X-ray2.45X/Y130-229[»]
    2XACX-ray2.71C/X129-226[»]
    3HNGX-ray2.70A801-1158[»]
    ProteinModelPortaliP17948.
    SMRiP17948. Positions 32-750, 787-1196.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP17948.

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini27 – 758732ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini781 – 1338558CytoplasmicSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei759 – 78022HelicalSequence AnalysisAdd
    BLAST

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini32 – 12392Ig-like C2-type 1Add
    BLAST
    Domaini151 – 21464Ig-like C2-type 2Add
    BLAST
    Domaini230 – 32798Ig-like C2-type 3Add
    BLAST
    Domaini335 – 42187Ig-like C2-type 4Add
    BLAST
    Domaini428 – 553126Ig-like C2-type 5Add
    BLAST
    Domaini556 – 65499Ig-like C2-type 6Add
    BLAST
    Domaini661 – 74787Ig-like C2-type 7Add
    BLAST
    Domaini827 – 1158332Protein kinasePROSITE-ProRule annotationAdd
    BLAST

    Domaini

    The second and third Ig-like C2-type (immunoglobulin-like) domains are sufficient for VEGFA binding.2 Publications

    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

    eggNOGiCOG0515.
    HOGENOMiHOG000037949.
    HOVERGENiHBG053432.
    InParanoidiP17948.
    KOiK05096.
    OMAiKWEFARE.
    OrthoDBiEOG75F4CC.
    PhylomeDBiP17948.
    TreeFamiTF325768.

    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]
    PANTHERiPTHR24416:SF126. PTHR24416:SF126. 1 hit.
    PfamiPF07679. I-set. 3 hits.
    PF07714. Pkinase_Tyr. 1 hit.
    [Graphical view]
    PRINTSiPR01833. VEGFRECEPTR1.
    SMARTiSM00409. IG. 5 hits.
    SM00408. IGc2. 2 hits.
    SM00219. TyrKc. 1 hit.
    [Graphical view]
    SUPFAMiSSF56112. 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]

    Sequences (8)i

    Sequence statusi: Complete.

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

    This entry describes 8 isoformsi produced by alternative splicing. Align

    Note: Additional isoforms seem to exist.

    Isoform 1 (identifier: P17948-1) [UniParc]FASTAAdd to Basket

    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.

    « Hide

    MVSYWDTGVL LCALLSCLLL TGSSSGSKLK DPELSLKGTQ HIMQAGQTLH     50
    LQCRGEAAHK WSLPEMVSKE SERLSITKSA CGRNGKQFCS TLTLNTAQAN 100
    HTGFYSCKYL AVPTSKKKET ESAIYIFISD TGRPFVEMYS EIPEIIHMTE 150
    GRELVIPCRV TSPNITVTLK KFPLDTLIPD GKRIIWDSRK GFIISNATYK 200
    EIGLLTCEAT VNGHLYKTNY LTHRQTNTII DVQISTPRPV KLLRGHTLVL 250
    NCTATTPLNT RVQMTWSYPD EKNKRASVRR RIDQSNSHAN IFYSVLTIDK 300
    MQNKDKGLYT CRVRSGPSFK SVNTSVHIYD KAFITVKHRK QQVLETVAGK 350
    RSYRLSMKVK AFPSPEVVWL KDGLPATEKS ARYLTRGYSL IIKDVTEEDA 400
    GNYTILLSIK QSNVFKNLTA TLIVNVKPQI YEKAVSSFPD PALYPLGSRQ 450
    ILTCTAYGIP QPTIKWFWHP CNHNHSEARC DFCSNNEESF ILDADSNMGN 500
    RIESITQRMA IIEGKNKMAS TLVVADSRIS GIYICIASNK VGTVGRNISF 550
    YITDVPNGFH VNLEKMPTEG EDLKLSCTVN KFLYRDVTWI LLRTVNNRTM 600
    HYSISKQKMA ITKEHSITLN LTIMNVSLQD SGTYACRARN VYTGEEILQK 650
    KEITIRDQEA PYLLRNLSDH TVAISSSTTL DCHANGVPEP QITWFKNNHK 700
    IQQEPGIILG PGSSTLFIER VTEEDEGVYH CKATNQKGSV ESSAYLTVQG 750
    TSDKSNLELI TLTCTCVAAT LFWLLLTLFI RKMKRSSSEI KTDYLSIIMD 800
    PDEVPLDEQC ERLPYDASKW EFARERLKLG KSLGRGAFGK VVQASAFGIK 850
    KSPTCRTVAV KMLKEGATAS EYKALMTELK ILTHIGHHLN VVNLLGACTK 900
    QGGPLMVIVE YCKYGNLSNY LKSKRDLFFL NKDAALHMEP KKEKMEPGLE 950
    QGKKPRLDSV TSSESFASSG FQEDKSLSDV EEEEDSDGFY KEPITMEDLI 1000
    SYSFQVARGM EFLSSRKCIH RDLAARNILL SENNVVKICD FGLARDIYKN 1050
    PDYVRKGDTR LPLKWMAPES IFDKIYSTKS DVWSYGVLLW EIFSLGGSPY 1100
    PGVQMDEDFC SRLREGMRMR APEYSTPEIY QIMLDCWHRD PKERPRFAEL 1150
    VEKLGDLLQA NVQQDGKDYI PINAILTGNS GFTYSTPAFS EDFFKESISA 1200
    PKFNSGSSDD VRYVNAFKFM SLERIKTFEE LLPNATSMFD DYQGDSSTLL 1250
    ASPMLKRFTW TDSKPKASLK IDLRVTSKSK ESGLSDVSRP SFCHSSCGHV 1300
    SEGKRRFTYD HAELERKIAC CSPPPDYNSV VLYSTPPI 1338
    Length:1,338
    Mass (Da):150,769
    Last modified:April 3, 2007 - v2
    Checksum:iFF3381EEFAF0787C
    GO
    Isoform 2 (identifier: P17948-2) [UniParc]FASTAAdd to Basket

    Also known as: sFlt1

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

    Show »
    Length:687
    Mass (Da):77,474
    Checksum:i3F73F4942469DA36
    GO
    Isoform 3 (identifier: P17948-3) [UniParc]FASTAAdd to Basket

    Also known as: sFlt1-14

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

    Show »
    Length:733
    Mass (Da):82,124
    Checksum:i67B7F8BC1D30CD9E
    GO
    Isoform 4 (identifier: P17948-4) [UniParc]FASTAAdd to Basket

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

    Show »
    Length:541
    Mass (Da):60,917
    Checksum:i50BCDAACB69B0EA2
    GO
    Isoform 5 (identifier: P17948-5) [UniParc]FASTAAdd to Basket

    Also known as: i15

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

    Show »
    Length:556
    Mass (Da):62,954
    Checksum:i9150507FBDF43B24
    GO
    Isoform 6 (identifier: P17948-6) [UniParc]FASTAAdd to Basket

    Also known as: i18

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

    Show »
    Length:463
    Mass (Da):52,613
    Checksum:i7D3D572623A1124E
    GO
    Isoform 7 (identifier: P17948-7) [UniParc]FASTAAdd to Basket

    Also known as: i21

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

    Show »
    Length:343
    Mass (Da):39,148
    Checksum:iB7800AF7311BF0D6
    GO
    Isoform 8 (identifier: P17948-8) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-7: MVSYWDT → MNSDLLV
         8-984: Missing.

    Show »
    Length:361
    Mass (Da):41,175
    Checksum:i34E2B38DE128BA53
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti490 – 4901F → S in AAC16449. (PubMed:10471394)Curated
    Sequence conflicti779 – 7791F → L in CAA35946. (PubMed:2158038)Curated
    Sequence conflicti1029 – 10291L → F in ABI53803. (PubMed:20512933)Curated
    Sequence conflicti1029 – 10291L → F in ABI53804. (PubMed:20512933)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti60 – 601K → T.1 Publication
    Corresponds to variant rs56409818 [ dbSNP | Ensembl ].
    VAR_042045
    Natural varianti128 – 1281I → L.
    Corresponds to variant rs35073261 [ dbSNP | Ensembl ].
    VAR_049719
    Natural varianti144 – 1441E → K.1 Publication
    Corresponds to variant rs55974987 [ dbSNP | Ensembl ].
    VAR_042046
    Natural varianti281 – 2811R → Q.1 Publication
    Corresponds to variant rs55687105 [ dbSNP | Ensembl ].
    VAR_042047
    Natural varianti422 – 4221L → I in a lung adenocarcinoma sample; somatic mutation. 1 Publication
    VAR_042048
    Natural varianti781 – 7811R → Q in a glioma low grade oligodendroglioma sample; somatic mutation. 1 Publication
    VAR_042049
    Natural varianti938 – 9381M → V.1 Publication
    Corresponds to variant rs35549791 [ dbSNP | Ensembl ].
    VAR_042050
    Natural varianti982 – 9821E → A.1 Publication
    Corresponds to variant rs35832528 [ dbSNP | Ensembl ].
    VAR_042051
    Natural varianti1061 – 10611L → V in a bladder transitional cell carcinoma sample; somatic mutation. 1 Publication
    VAR_042052

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 995995Missing in isoform 7. 1 PublicationVSP_041983Add
    BLAST
    Alternative sequencei1 – 875875Missing in isoform 6. 1 PublicationVSP_041984Add
    BLAST
    Alternative sequencei1 – 782782Missing in isoform 5. 1 PublicationVSP_041985Add
    BLAST
    Alternative sequencei1 – 77MVSYWDT → MNSDLLV in isoform 8. 1 PublicationVSP_047759
    Alternative sequencei8 – 984977Missing in isoform 8. 1 PublicationVSP_047760Add
    BLAST
    Alternative sequencei518 – 54124MASTL…ASNKV → LPPANSSFMLPPTSFSSNYF HFLP in isoform 4. 1 PublicationVSP_041929Add
    BLAST
    Alternative sequencei542 – 1338797Missing in isoform 4. 1 PublicationVSP_041930Add
    BLAST
    Alternative sequencei657 – 68731DQEAP…HANGV → GEHCNKKAVFSRISKFKSTR NDCTTQSNVKH in isoform 2. 3 PublicationsVSP_002955Add
    BLAST
    Alternative sequencei688 – 1338651Missing in isoform 2. 3 PublicationsVSP_002956Add
    BLAST
    Alternative sequencei706 – 73328GIILG…YHCKA → ELYTSTSPSSSSSSPLSSSS SSSSSSSS in isoform 3. 3 PublicationsVSP_041927Add
    BLAST
    Alternative sequencei734 – 1338605Missing in isoform 3. 3 PublicationsVSP_041928Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    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.
    EF491870 mRNA. Translation: ABS32270.1.
    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.
    CCDSiCCDS53860.1. [P17948-3]
    CCDS53861.1. [P17948-4]
    CCDS9330.1. [P17948-1]
    PIRiA49636.
    S09982.
    RefSeqiNP_001153392.1. NM_001159920.1. [P17948-2]
    NP_001153502.1. NM_001160030.1. [P17948-3]
    NP_001153503.1. NM_001160031.1. [P17948-4]
    NP_002010.2. NM_002019.4. [P17948-1]
    UniGeneiHs.594454.

    Genome annotation databases

    EnsembliENST00000282397; ENSP00000282397; ENSG00000102755. [P17948-1]
    ENST00000539099; ENSP00000442630; ENSG00000102755. [P17948-4]
    ENST00000540678; ENSP00000443311; ENSG00000102755. [P17948-5]
    ENST00000541932; ENSP00000437631; ENSG00000102755. [P17948-3]
    ENST00000543394; ENSP00000437841; ENSG00000102755. [P17948-8]
    GeneIDi2321.
    KEGGihsa:2321.
    UCSCiuc001usa.3. human. [P17948-5]
    uc001usb.3. human. [P17948-1]
    uc001usc.3. human. [P17948-2]
    uc010aap.2. human. [P17948-7]
    uc010aaq.2. human. [P17948-6]
    uc010aar.1. human. [P17948-3]
    uc010tdp.1. human. [P17948-4]

    Polymorphism databases

    DMDMi143811474.

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    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 .
    EF491870 mRNA. Translation: ABS32270.1 .
    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 .
    CCDSi CCDS53860.1. [P17948-3 ]
    CCDS53861.1. [P17948-4 ]
    CCDS9330.1. [P17948-1 ]
    PIRi A49636.
    S09982.
    RefSeqi NP_001153392.1. NM_001159920.1. [P17948-2 ]
    NP_001153502.1. NM_001160030.1. [P17948-3 ]
    NP_001153503.1. NM_001160031.1. [P17948-4 ]
    NP_002010.2. NM_002019.4. [P17948-1 ]
    UniGenei Hs.594454.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    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 [» ]
    ProteinModelPortali P17948.
    SMRi P17948. Positions 32-750, 787-1196.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 108609. 11 interactions.
    DIPi DIP-643N.
    IntActi P17948. 27 interactions.
    MINTi MINT-127610.
    STRINGi 9606.ENSP00000282397.

    Chemistry

    BindingDBi P17948.
    ChEMBLi CHEMBL1868.
    DrugBanki DB01268. Sunitinib.
    GuidetoPHARMACOLOGYi 1812.

    PTM databases

    PhosphoSitei P17948.

    Polymorphism databases

    DMDMi 143811474.

    Proteomic databases

    PaxDbi P17948.
    PRIDEi P17948.

    Protocols and materials databases

    DNASUi 2321.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000282397 ; ENSP00000282397 ; ENSG00000102755 . [P17948-1 ]
    ENST00000539099 ; ENSP00000442630 ; ENSG00000102755 . [P17948-4 ]
    ENST00000540678 ; ENSP00000443311 ; ENSG00000102755 . [P17948-5 ]
    ENST00000541932 ; ENSP00000437631 ; ENSG00000102755 . [P17948-3 ]
    ENST00000543394 ; ENSP00000437841 ; ENSG00000102755 . [P17948-8 ]
    GeneIDi 2321.
    KEGGi hsa:2321.
    UCSCi uc001usa.3. human. [P17948-5 ]
    uc001usb.3. human. [P17948-1 ]
    uc001usc.3. human. [P17948-2 ]
    uc010aap.2. human. [P17948-7 ]
    uc010aaq.2. human. [P17948-6 ]
    uc010aar.1. human. [P17948-3 ]
    uc010tdp.1. human. [P17948-4 ]

    Organism-specific databases

    CTDi 2321.
    GeneCardsi GC13M028874.
    H-InvDB HIX0130593.
    HGNCi HGNC:3763. FLT1.
    HPAi HPA011740.
    HPA014290.
    MIMi 165070. gene.
    neXtProti NX_P17948.
    PharmGKBi PA28180.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG0515.
    HOGENOMi HOG000037949.
    HOVERGENi HBG053432.
    InParanoidi P17948.
    KOi K05096.
    OMAi KWEFARE.
    OrthoDBi EOG75F4CC.
    PhylomeDBi P17948.
    TreeFami TF325768.

    Enzyme and pathway databases

    BRENDAi 2.7.10.1. 2681.
    Reactomei REACT_12473. Neurophilin interactions with VEGF and VEGFR.
    REACT_12583. VEGF binds to VEGFR leading to receptor dimerization.
    SignaLinki P17948.

    Miscellaneous databases

    EvolutionaryTracei P17948.
    GeneWikii FLT1.
    GenomeRNAii 2321.
    NextBioi 35467213.
    PROi P17948.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P17948.
    Bgeei P17948.
    CleanExi HS_FLT1.
    Genevestigatori P17948.

    Family and domain databases

    Gene3Di 2.60.40.10. 7 hits.
    InterProi IPR007110. 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 ]
    PANTHERi PTHR24416:SF126. PTHR24416:SF126. 1 hit.
    Pfami PF07679. I-set. 3 hits.
    PF07714. Pkinase_Tyr. 1 hit.
    [Graphical view ]
    PRINTSi PR01833. VEGFRECEPTR1.
    SMARTi SM00409. IG. 5 hits.
    SM00408. IGc2. 2 hits.
    SM00219. TyrKc. 1 hit.
    [Graphical view ]
    SUPFAMi SSF56112. SSF56112. 2 hits.
    PROSITEi 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 ]
    ProtoNeti Search...

    Publicationsi

    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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 5; 6; 7 AND 8), 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] [Europe PMC] [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] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    11. 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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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 PLCG; 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] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH VEGFA, AUTOPHOSPHORYLATION, CATALYTIC ACTIVITY, FUNCTION IN PHOSPHORYLATION OF PLCG, 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] [Europe PMC] [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] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN PHOSPHORYLATION OF PLCG AND ACTIVATION OF MAP KINASES, INTERACTION WITH PLCG, 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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH PIK3R1 AND VEGFA, AUTOPHOSPHORYLATION, PHOSPHORYLATION AT TYR-1213, SUBCELLULAR LOCATION, IDENTIFICATION BY 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] [Europe PMC] [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] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH KDR, CATALYTIC ACTIVITY, AUTOPHOSPHORYLATION, FUNCTION IN VEGFA SIGNALING; PHOSPHORYLATION OF PLCG 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] [Europe PMC] [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. Cited for: INTERACTION WITH PGF AND KDR, FUNCTION IN PHOSPHORYLATION OF KDR; VEGFA AND PGF SIGNALING, CATALYTIC ACTIVITY, IDENTIFICATION BY 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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract]
      Cited for: MUTAGENESIS OF ASN-1050.
    29. "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] [Europe PMC] [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.
    30. "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] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN ENDOTHELIAL CELL SURVIVAL AND ANGIOGENESIS.
    31. "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] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN CANCER CELL MIGRATION AND ACTIVATION OF MAPK1/ERK2 AND/OR MAPK3/ERK1.
    32. "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] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH GNB2L1.
    33. "gamma-Secretase and presenilin mediate cleavage and phosphorylation of vascular endothelial growth factor receptor-1."
      Cai J., Chen Z., Ruan Q., Han S., Liu L., Qi X., Boye S.L., Hauswirth W.W., Grant M.B., Boulton M.E.
      J. Biol. Chem. 286:42514-42523(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH PSEN1 AND PTPRB, DEPHOSPHORYLATION BY PTPRB, MUTAGENESIS OF VAL-767, PROTEOLYTIC CLEAVAGE BY PSEN1 AT VAL-767.
    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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.71 ANGSTROMS) OF 129-226 IN COMPLEX 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] [Europe PMC] [Abstract]
      Cited for: VARIANTS [LARGE SCALE ANALYSIS] THR-60; LYS-144; GLN-281; ILE-422; GLN-781; VAL-938; ALA-982 AND VAL-1061.

    Entry informationi

    Entry nameiVGFR1_HUMAN
    AccessioniPrimary (citable) accession number: P17948
    Secondary accession number(s): A3E342
    , A3E344, A8KA71, B0LPF1, B2BF46, B2BF47, B2BF48, B3FR89, B5A923, F5H5L6, O60722, P16057, Q12954
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: November 1, 1990
    Last sequence update: April 3, 2007
    Last modified: October 1, 2014
    This is version 181 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny 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.

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. Human chromosome 13
      Human chromosome 13: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    6. Human and mouse protein kinases
      Human and mouse protein kinases: classification and index
    7. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3