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P35916

- VGFR3_HUMAN

UniProt

P35916 - VGFR3_HUMAN

Protein

Vascular endothelial growth factor receptor 3

Gene

FLT4

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 168 (01 Oct 2014)
      Sequence version 3 (16 Nov 2011)
      Previous versions | rss
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    Functioni

    Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFC and VEGFD, and plays an essential role in adult lymphangiogenesis and in the development of the vascular network and the cardiovascular system during embryonic development. Promotes proliferation, survival and migration of endothelial cells, and regulates angiogenic sprouting. Signaling by activated FLT4 leads to enhanced production of VEGFC, and to a lesser degree VEGFA, thereby creating a positive feedback loop that enhances FLT4 signaling. Modulates KDR signaling by forming heterodimers. The secreted isoform 3 may function as a decoy receptor for VEGFC and/or VEGFD and play an important role as a negative regulator of VEGFC-mediated lymphangiogenesis and angiogenesis. Binding of vascular growth factors to isoform 1 or isoform 2 leads to the activation of several signaling cascades; isoform 2 seems to be less efficient in signal transduction, because it has a truncated C-terminus and therefore lacks several phosphorylation sites. Mediates activation of the MAPK1/ERK2, MAPK3/ERK1 signaling pathway, of MAPK8 and the JUN signaling pathway, and of the AKT1 signaling pathway. Phosphorylates SHC1. Mediates phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase. Promotes phosphorylation of MAPK8 at 'Thr-183' and 'Tyr-185', and of AKT1 at 'Ser-473'.15 Publications

    Catalytic activityi

    ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.2 PublicationsPROSITE-ProRule annotation

    Enzyme regulationi

    Present in an inactive conformation in the absence of bound ligand. Binding of VEGFC or VEGFD leads to dimerization and activation by autophosphorylation on tyrosine residues. Inhibited by MAZ51.3 Publications

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei879 – 8791ATPCurated
    Active sitei1037 – 10371Proton acceptorPROSITE-ProRule annotation

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi851 – 8599ATPPROSITE-ProRule annotation

    GO - Molecular functioni

    1. ATP binding Source: UniProtKB-KW
    2. growth factor binding Source: UniProtKB
    3. protein binding Source: IntAct
    4. protein phosphatase binding Source: UniProtKB
    5. transmembrane receptor protein tyrosine kinase activity Source: UniProtKB
    6. vascular endothelial growth factor-activated receptor activity Source: UniProtKB

    GO - Biological processi

    1. blood vessel morphogenesis Source: UniProtKB
    2. cellular response to vascular endothelial growth factor stimulus Source: UniProtKB
    3. lymphangiogenesis Source: UniProtKB
    4. lymph vessel development Source: BHF-UCL
    5. negative regulation of apoptotic process Source: UniProtKB
    6. peptidyl-tyrosine phosphorylation Source: UniProtKB
    7. positive regulation of cell proliferation Source: UniProtKB
    8. positive regulation of endothelial cell migration Source: UniProtKB
    9. positive regulation of endothelial cell proliferation Source: UniProtKB
    10. positive regulation of ERK1 and ERK2 cascade Source: UniProtKB
    11. positive regulation of JNK cascade Source: UniProtKB
    12. positive regulation of MAPK cascade Source: UniProtKB
    13. positive regulation of protein kinase C signaling Source: UniProtKB
    14. positive regulation of protein phosphorylation Source: UniProtKB
    15. positive regulation vascular endothelial growth factor production Source: UniProtKB
    16. protein autophosphorylation Source: UniProtKB
    17. regulation of blood vessel remodeling Source: UniProtKB
    18. sprouting angiogenesis Source: UniProtKB
    19. transmembrane receptor protein tyrosine kinase signaling pathway Source: ProtInc
    20. vascular endothelial growth factor receptor signaling pathway Source: UniProtKB
    21. vasculature development Source: UniProtKB

    Keywords - Molecular functioni

    Kinase, Receptor, Transferase, Tyrosine-protein kinase

    Keywords - Biological processi

    Angiogenesis

    Keywords - Ligandi

    ATP-binding, Nucleotide-binding

    Enzyme and pathway databases

    BRENDAi2.7.10.1. 2681.
    ReactomeiREACT_12583. VEGF binds to VEGFR leading to receptor dimerization.
    SignaLinkiP35916.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Vascular endothelial growth factor receptor 3 (EC:2.7.10.1)
    Short name:
    VEGFR-3
    Alternative name(s):
    Fms-like tyrosine kinase 4
    Short name:
    FLT-4
    Tyrosine-protein kinase receptor FLT4
    Gene namesi
    Name:FLT4
    Synonyms:VEGFR3
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 5

    Organism-specific databases

    HGNCiHGNC:3767. FLT4.

    Subcellular locationi

    Cell membrane; Single-pass type I membrane protein. Cytoplasm. Nucleus
    Note: Ligand-mediated autophosphorylation leads to rapid internalization.
    Isoform 1 : Cell membrane; Single-pass type I membrane protein
    Note: Ligand-mediated autophosphorylation leads to rapid internalization.

    GO - Cellular componenti

    1. cytoplasm Source: UniProtKB-SubCell
    2. extracellular region Source: UniProtKB-SubCell
    3. integral component of plasma membrane Source: ProtInc
    4. nucleus Source: UniProtKB-SubCell
    5. plasma membrane Source: UniProtKB
    6. receptor complex Source: MGI

    Keywords - Cellular componenti

    Cell membrane, Cytoplasm, Membrane, Nucleus, Secreted

    Pathology & Biotechi

    Involvement in diseasei

    Lymphedema, hereditary, 1A (LMPH1A) [MIM:153100]: A chronic disabling condition which results in swelling of the extremities due to altered lymphatic flow. Patients with lymphedema suffer from recurrent local infections and physical impairment.3 Publications
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti857 – 8571G → R in LMPH1A; loss of kinase activity. 1 Publication
    VAR_018409
    Natural varianti1035 – 10351H → R in LMPH1A; loss of kinase activity.
    VAR_018412
    Natural varianti1041 – 10411R → P in LMPH1A; loss of kinase activity. 1 Publication
    VAR_018413
    Natural varianti1044 – 10441L → P in LMPH1A; loss of kinase activity. 1 Publication
    VAR_018414
    Natural varianti1114 – 11141P → L in LMPH1A; loss of kinase activity. 2 Publications
    VAR_018415
    Hemangioma, capillary infantile (HCI) [MIM:602089]: A condition characterized by dull red, firm, dome-shaped hemangiomas, sharply demarcated from surrounding skin, usually presenting at birth or occurring within the first two or three months of life. They result from highly proliferative, localized growth of capillary endothelium and generally undergo regression and involution without scarring.1 Publication
    Note: Disease susceptibility is associated with variations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti954 – 9541P → S in HCI. 1 Publication
    Corresponds to variant rs34255532 [ dbSNP | Ensembl ].
    VAR_018411
    Natural varianti1137 – 11371P → S in HCI. 1 Publication
    VAR_018416
    Plays an important role in tumor lymphangiogenesis, in cancer cell survival, migration, and formation of metastases.

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi879 – 8791K → G: Abolishes enzyme activity. 1 Publication
    Mutagenesisi1063 – 10631Y → F: Loss of phosphorylation site. No effect on stimulation of cell proliferation and cell migration. 2 Publications
    Mutagenesisi1068 – 10681Y → F: Global loss of autophosphorylation. Abolishes stimulation of cell proliferation and cell migration. 2 Publications
    Mutagenesisi1230 – 12301Y → F: Loss of phosphorylation site. Strongly reduces stimulation of cell proliferation and cell migration. 2 Publications
    Mutagenesisi1231 – 12311Y → F: Loss of phosphorylation site. Strongly reduces stimulation of cell proliferation and cell migration. 2 Publications
    Mutagenesisi1265 – 12651Y → F: Loss of phosphorylation site. No effect on stimulation of cell proliferation and cell migration. 1 Publication
    Mutagenesisi1333 – 13331Y → F: Loss of phosphorylation site. Reduced autophosphorylation. 2 Publications
    Mutagenesisi1337 – 13371Y → F: Reduced autophosphorylation. Strongly reduces stimulation of cell proliferation and cell migration. 3 Publications
    Mutagenesisi1363 – 13631Y → F: Loss of phosphorylation site. Slighly reduced autophosphorylation. 2 Publications

    Keywords - Diseasei

    Disease mutation

    Organism-specific databases

    MIMi153100. phenotype.
    602089. phenotype.
    Orphaneti79452. Milroy disease.
    PharmGKBiPA28183.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 24241 PublicationAdd
    BLAST
    Chaini25 – 13631339Vascular endothelial growth factor receptor 3PRO_0000016776Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Glycosylationi33 – 331N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi51 ↔ 111PROSITE-ProRule annotation
    Glycosylationi104 – 1041N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi158 ↔ 206PROSITE-ProRule annotation
    Glycosylationi166 – 1661N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi251 – 2511N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi252 ↔ 310PROSITE-ProRule annotation
    Glycosylationi299 – 2991N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi411 – 4111N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi445 ↔ 534PROSITE-ProRule annotation
    Glycosylationi515 – 5151N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi527 – 5271N-linked (GlcNAc...)2 Publications
    Disulfide bondi578 ↔ 653PROSITE-ProRule annotation
    Glycosylationi594 – 5941N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi683 – 6831N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi690 – 6901N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi699 ↔ 751PROSITE-ProRule annotation
    Glycosylationi758 – 7581N-linked (GlcNAc...)Sequence Analysis
    Modified residuei830 – 8301Phosphotyrosine; by SRC1 Publication
    Modified residuei833 – 8331Phosphotyrosine; by SRC1 Publication
    Modified residuei853 – 8531Phosphotyrosine; by SRC1 Publication
    Modified residuei1063 – 10631Phosphotyrosine; by autocatalysis and SRC2 Publications
    Modified residuei1068 – 10681Phosphotyrosine; by autocatalysis2 Publications
    Modified residuei1230 – 12301Phosphotyrosine; by autocatalysis2 Publications
    Modified residuei1231 – 12311Phosphotyrosine; by autocatalysis2 Publications
    Modified residuei1265 – 12651Phosphotyrosine; by autocatalysis1 Publication
    Modified residuei1333 – 13331Phosphotyrosine; by autocatalysis and SRC2 Publications
    Modified residuei1337 – 13371Phosphotyrosine; by autocatalysis and SRC3 Publications
    Modified residuei1363 – 13631Phosphotyrosine; by autocatalysis1 Publication

    Post-translational modificationi

    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 in response to H2O2 is mediated by a process that requires SRC and PRKCD activity. Phosphorylation at Tyr-1068 is required for autophosphorylation at additional tyrosine residues. Phosphorylation at Tyr-1063 and Tyr-1337 is important for interaction with CRK and subsequent activation of MAPK8. Phosphorylation at Tyr-1230, Tyr-1231 and Tyr-1337 is important for interaction with GRB2 and subsequent activation of the AKT1 and MAPK1/ERK2 and/or MAPK3/ERK1 signaling pathways. In response to endothelial cell adhesion onto collagen, can also be phosphorylated in the absence of FLT4 kinase activity by SRC at Tyr-830, Tyr-833, Tyr-853, Tyr-1063, Tyr-1333, and Tyr-1337.6 Publications

    Keywords - PTMi

    Disulfide bond, Glycoprotein, Phosphoprotein

    Proteomic databases

    PaxDbiP35916.
    PRIDEiP35916.

    PTM databases

    PhosphoSiteiP35916.

    Expressioni

    Tissue specificityi

    Detected in endothelial cells (at protein level). Widely expressed. Detected in fetal spleen, lung and brain. Detected in adult liver, muscle, thymus, placenta, lung, testis, ovary, prostate, heart, and kidney.3 Publications

    Gene expression databases

    ArrayExpressiP35916.
    BgeeiP35916.
    CleanExiHS_FLT4.
    GenevestigatoriP35916.

    Organism-specific databases

    HPAiCAB000099.

    Interactioni

    Subunit structurei

    Interacts with VEGFC and VEGFD. Monomer in the absence of bound VEGFC or VEGFD. Homodimer in the presence of bound VEGFC or VEGFD. Can also form a heterodimer with KDR. Interacts with PTPN14; the interaction is enhanced by stimulation with VEGFC. Interacts with CRK, GRB2, PTK2/FAK1, SHC1, PIK3R1 and PTPN11/SHP-2. Identified in a complex with SRC and ITGB1.13 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    HSP90AB1P082382EBI-1005467,EBI-352572
    KDRP359685EBI-1005467,EBI-1005487
    VEGFCP497672EBI-1005467,EBI-3405539

    Protein-protein interaction databases

    BioGridi108612. 9 interactions.
    DIPiDIP-5739N.
    IntActiP35916. 7 interactions.
    MINTiMINT-1182429.
    STRINGi9606.ENSP00000261937.

    Structurei

    Secondary structure

    1
    1363
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi332 – 3398
    Beta strandi341 – 3466
    Beta strandi350 – 36213
    Beta strandi365 – 3706
    Beta strandi381 – 3888
    Helixi391 – 3933
    Beta strandi395 – 4039
    Turni404 – 4074
    Beta strandi408 – 42417
    Helixi425 – 4284
    Beta strandi441 – 45111
    Beta strandi457 – 4648
    Beta strandi501 – 51111
    Beta strandi514 – 52411
    Beta strandi530 – 5389
    Beta strandi541 – 5499

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    4BSJX-ray2.50A330-553[»]
    4BSKX-ray4.20A23-229[»]
    ProteinModelPortaliP35916.
    SMRiP35916. Positions 28-553, 632-765, 823-1180.
    ModBaseiSearch...
    MobiDBiSearch...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini25 – 775751ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini797 – 1363567CytoplasmicSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei776 – 79621HelicalSequence AnalysisAdd
    BLAST

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini30 – 12798Ig-like C2-type 1Add
    BLAST
    Domaini151 – 21363Ig-like C2-type 2Add
    BLAST
    Domaini219 – 326108Ig-like C2-type 3Add
    BLAST
    Domaini331 – 41585Ig-like C2-type 4Add
    BLAST
    Domaini422 – 552131Ig-like C2-type 5Add
    BLAST
    Domaini555 – 671117Ig-like C2-type 6Add
    BLAST
    Domaini678 – 76487Ig-like C2-type 7Add
    BLAST
    Domaini845 – 1173329Protein kinasePROSITE-ProRule annotationAdd
    BLAST

    Domaini

    The first and second Ig-like C2-type (immunoglobulin-like) domains are sufficient for VEGFC binding.

    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.
    KOiK05097.
    OMAiPAHADIK.
    OrthoDBiEOG75F4CC.
    PhylomeDBiP35916.
    TreeFamiTF325768.

    Family and domain databases

    Gene3Di2.60.40.10. 9 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.
    IPR009137. VEGFR3_rcpt.
    [Graphical view]
    PANTHERiPTHR24416:SF49. PTHR24416:SF49. 1 hit.
    PfamiPF07679. I-set. 2 hits.
    PF07714. Pkinase_Tyr. 1 hit.
    [Graphical view]
    PRINTSiPR01835. VEGFRECEPTR3.
    SMARTiSM00409. IG. 4 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 (3)i

    Sequence statusi: Complete.

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

    This entry describes 3 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: P35916-2) [UniParc]FASTAAdd to Basket

    Also known as: Long

    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

    MQRGAALCLR LWLCLGLLDG LVSGYSMTPP TLNITEESHV IDTGDSLSIS     50
    CRGQHPLEWA WPGAQEAPAT GDKDSEDTGV VRDCEGTDAR PYCKVLLLHE 100
    VHANDTGSYV CYYKYIKARI EGTTAASSYV FVRDFEQPFI NKPDTLLVNR 150
    KDAMWVPCLV SIPGLNVTLR SQSSVLWPDG QEVVWDDRRG MLVSTPLLHD 200
    ALYLQCETTW GDQDFLSNPF LVHITGNELY DIQLLPRKSL ELLVGEKLVL 250
    NCTVWAEFNS GVTFDWDYPG KQAERGKWVP ERRSQQTHTE LSSILTIHNV 300
    SQHDLGSYVC KANNGIQRFR ESTEVIVHEN PFISVEWLKG PILEATAGDE 350
    LVKLPVKLAA YPPPEFQWYK DGKALSGRHS PHALVLKEVT EASTGTYTLA 400
    LWNSAAGLRR NISLELVVNV PPQIHEKEAS SPSIYSRHSR QALTCTAYGV 450
    PLPLSIQWHW RPWTPCKMFA QRSLRRRQQQ DLMPQCRDWR AVTTQDAVNP 500
    IESLDTWTEF VEGKNKTVSK LVIQNANVSA MYKCVVSNKV GQDERLIYFY 550
    VTTIPDGFTI ESKPSEELLE GQPVLLSCQA DSYKYEHLRW YRLNLSTLHD 600
    AHGNPLLLDC KNVHLFATPL AASLEEVAPG ARHATLSLSI PRVAPEHEGH 650
    YVCEVQDRRS HDKHCHKKYL SVQALEAPRL TQNLTDLLVN VSDSLEMQCL 700
    VAGAHAPSIV WYKDERLLEE KSGVDLADSN QKLSIQRVRE EDAGRYLCSV 750
    CNAKGCVNSS ASVAVEGSED KGSMEIVILV GTGVIAVFFW VLLLLIFCNM 800
    RRPAHADIKT GYLSIIMDPG EVPLEEQCEY LSYDASQWEF PRERLHLGRV 850
    LGYGAFGKVV EASAFGIHKG SSCDTVAVKM LKEGATASEH RALMSELKIL 900
    IHIGNHLNVV NLLGACTKPQ GPLMVIVEFC KYGNLSNFLR AKRDAFSPCA 950
    EKSPEQRGRF RAMVELARLD RRRPGSSDRV LFARFSKTEG GARRASPDQE 1000
    AEDLWLSPLT MEDLVCYSFQ VARGMEFLAS RKCIHRDLAA RNILLSESDV 1050
    VKICDFGLAR DIYKDPDYVR KGSARLPLKW MAPESIFDKV YTTQSDVWSF 1100
    GVLLWEIFSL GASPYPGVQI NEEFCQRLRD GTRMRAPELA TPAIRRIMLN 1150
    CWSGDPKARP AFSELVEILG DLLQGRGLQE EEEVCMAPRS SQSSEEGSFS 1200
    QVSTMALHIA QADAEDSPPS LQRHSLAARY YNWVSFPGCL ARGAETRGSS 1250
    RMKTFEEFPM TPTTYKGSVD NQTDSGMVLA SEEFEQIESR HRQESGFSCK 1300
    GPGQNVAVTR AHPDSQGRRR RPERGARGGQ VFYNSEYGEL SEPSEEDHCS 1350
    PSARVTFFTD NSY 1363
    Length:1,363
    Mass (Da):152,757
    Last modified:November 16, 2011 - v3
    Checksum:iB1473AAAC95E7E93
    GO
    Isoform 2 (identifier: P35916-1) [UniParc]FASTAAdd to Basket

    Also known as: Short

    The sequence of this isoform differs from the canonical sequence as follows:
         1298-1363: SCKGPGQNVAVTRAHPDSQGRRRRPERGARGGQVFYNSEYGELSEPSEEDHCSPSARVTFFTDNSY → R

    Show »
    Length:1,298
    Mass (Da):145,599
    Checksum:i3DC469ED3CB8B3B1
    GO
    Isoform 3 (identifier: P35916-3) [UniParc]FASTAAdd to Basket

    Also known as: sVegfr3

    The sequence of this isoform differs from the canonical sequence as follows:
         724-765: VDLADSNQKL...CVNSSASVAV → REGGPGEGQV...ESTWRTPTRS
         766-1298: Missing.

    Show »
    Length:830
    Mass (Da):93,174
    Checksum:i873CB1459C93C49A
    GO

    Sequence cautioni

    The sequence CAA48290.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti24 – 241G → D in CAA49505. (PubMed:1319394)Curated
    Sequence conflicti24 – 241G → D in AAO89504. 1 PublicationCurated
    Sequence conflicti24 – 241G → D in AAO89505. 1 PublicationCurated
    Sequence conflicti538 – 5381N → D in BAF84368. (PubMed:14702039)Curated
    Sequence conflicti745 – 7451R → P in CAA49505. (PubMed:1319394)Curated
    Sequence conflicti745 – 7451R → P in AAO89504. 1 PublicationCurated
    Sequence conflicti745 – 7451R → P in AAO89505. 1 PublicationCurated
    Sequence conflicti752 – 7532NA → RP in CAA49505. (PubMed:1319394)Curated
    Sequence conflicti752 – 7532NA → RP in AAO89504. 1 PublicationCurated
    Sequence conflicti752 – 7532NA → RP in AAO89505. 1 PublicationCurated
    Sequence conflicti1128 – 11281L → V in CAA49505. (PubMed:1319394)Curated
    Sequence conflicti1128 – 11281L → V in AAO89504. 1 PublicationCurated
    Sequence conflicti1128 – 11281L → V in AAO89505. 1 PublicationCurated
    Sequence conflicti1164 – 11641E → D in CAA49505. (PubMed:1319394)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti149 – 1491N → D.1 Publication
    Corresponds to variant rs34221241 [ dbSNP | Ensembl ].
    VAR_042062
    Natural varianti378 – 3781R → C in a renal clear cell carcinoma sample; somatic mutation. 1 Publication
    VAR_042063
    Natural varianti494 – 4941T → A.2 Publications
    Corresponds to variant rs307826 [ dbSNP | Ensembl ].
    VAR_018407
    Natural varianti527 – 5271N → S.1 Publication
    Corresponds to variant rs35874891 [ dbSNP | Ensembl ].
    VAR_034379
    Natural varianti641 – 6411P → S.2 Publications
    Corresponds to variant rs55667289 [ dbSNP | Ensembl ].
    VAR_018408
    Natural varianti857 – 8571G → R in LMPH1A; loss of kinase activity. 1 Publication
    VAR_018409
    Natural varianti868 – 8681H → Y.1 Publication
    Corresponds to variant rs35171798 [ dbSNP | Ensembl ].
    VAR_042064
    Natural varianti890 – 8901H → Q.4 Publications
    Corresponds to variant rs448012 [ dbSNP | Ensembl ].
    VAR_018410
    Natural varianti954 – 9541P → S in HCI. 1 Publication
    Corresponds to variant rs34255532 [ dbSNP | Ensembl ].
    VAR_018411
    Natural varianti1010 – 10101T → I in a metastatic melanoma sample; somatic mutation. 1 Publication
    VAR_042065
    Natural varianti1031 – 10311R → Q.1 Publication
    Corresponds to variant rs56082504 [ dbSNP | Ensembl ].
    VAR_042066
    Natural varianti1035 – 10351H → R in LMPH1A; loss of kinase activity.
    VAR_018412
    Natural varianti1041 – 10411R → P in LMPH1A; loss of kinase activity. 1 Publication
    VAR_018413
    Natural varianti1044 – 10441L → P in LMPH1A; loss of kinase activity. 1 Publication
    VAR_018414
    Natural varianti1049 – 10491D → N.1 Publication
    Corresponds to variant rs56310180 [ dbSNP | Ensembl ].
    VAR_042067
    Natural varianti1075 – 10751R → Q.1 Publication
    VAR_042068
    Natural varianti1114 – 11141P → L in LMPH1A; loss of kinase activity. 2 Publications
    VAR_018415
    Natural varianti1137 – 11371P → S in HCI. 1 Publication
    VAR_018416
    Natural varianti1146 – 11461R → H.4 Publications
    Corresponds to variant rs1130379 [ dbSNP | Ensembl ].
    VAR_018417

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei724 – 76542VDLAD…ASVAV → REGGPGEGQVRRPARPTIPN PGGPAPPPHPLQESTWRTPT RS in isoform 3. 1 PublicationVSP_041993Add
    BLAST
    Alternative sequencei766 – 1298533Missing in isoform 3. 1 PublicationVSP_041994Add
    BLAST
    Alternative sequencei1298 – 136366SCKGP…TDNSY → R in isoform 2. 6 PublicationsVSP_041995Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X69878 mRNA. Translation: CAA49505.1.
    U43143 mRNA. Translation: AAA85215.1.
    EU826564 mRNA. Translation: ACF47600.1.
    AY233382 mRNA. Translation: AAO89504.1.
    AY233383 mRNA. Translation: AAO89505.1.
    AK291679 mRNA. Translation: BAF84368.1.
    AC122714 Genomic DNA. No translation available.
    X68203 mRNA. Translation: CAA48290.1. Different initiation.
    S66407 mRNA. Translation: AAB28539.1.
    CCDSiCCDS43412.1. [P35916-1]
    CCDS4457.1. [P35916-2]
    PIRiA48999.
    RefSeqiNP_002011.2. NM_002020.4. [P35916-1]
    NP_891555.2. NM_182925.4. [P35916-2]
    UniGeneiHs.646917.

    Genome annotation databases

    EnsembliENST00000261937; ENSP00000261937; ENSG00000037280. [P35916-2]
    ENST00000393347; ENSP00000377016; ENSG00000037280. [P35916-1]
    GeneIDi2324.
    KEGGihsa:2324.
    UCSCiuc003mlz.4. human. [P35916-2]
    uc003mma.4. human. [P35916-1]
    uc011dgy.2. human. [P35916-3]

    Polymorphism databases

    DMDMi357529070.

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Web resourcesi

    Wikipedia

    FLT4 entry

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X69878 mRNA. Translation: CAA49505.1 .
    U43143 mRNA. Translation: AAA85215.1 .
    EU826564 mRNA. Translation: ACF47600.1 .
    AY233382 mRNA. Translation: AAO89504.1 .
    AY233383 mRNA. Translation: AAO89505.1 .
    AK291679 mRNA. Translation: BAF84368.1 .
    AC122714 Genomic DNA. No translation available.
    X68203 mRNA. Translation: CAA48290.1 . Different initiation.
    S66407 mRNA. Translation: AAB28539.1 .
    CCDSi CCDS43412.1. [P35916-1 ]
    CCDS4457.1. [P35916-2 ]
    PIRi A48999.
    RefSeqi NP_002011.2. NM_002020.4. [P35916-1 ]
    NP_891555.2. NM_182925.4. [P35916-2 ]
    UniGenei Hs.646917.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    4BSJ X-ray 2.50 A 330-553 [» ]
    4BSK X-ray 4.20 A 23-229 [» ]
    ProteinModelPortali P35916.
    SMRi P35916. Positions 28-553, 632-765, 823-1180.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 108612. 9 interactions.
    DIPi DIP-5739N.
    IntActi P35916. 7 interactions.
    MINTi MINT-1182429.
    STRINGi 9606.ENSP00000261937.

    Chemistry

    BindingDBi P35916.
    ChEMBLi CHEMBL1955.
    DrugBanki DB00398. Sorafenib.
    DB01268. Sunitinib.
    GuidetoPHARMACOLOGYi 1814.

    PTM databases

    PhosphoSitei P35916.

    Polymorphism databases

    DMDMi 357529070.

    Proteomic databases

    PaxDbi P35916.
    PRIDEi P35916.

    Protocols and materials databases

    DNASUi 2324.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000261937 ; ENSP00000261937 ; ENSG00000037280 . [P35916-2 ]
    ENST00000393347 ; ENSP00000377016 ; ENSG00000037280 . [P35916-1 ]
    GeneIDi 2324.
    KEGGi hsa:2324.
    UCSCi uc003mlz.4. human. [P35916-2 ]
    uc003mma.4. human. [P35916-1 ]
    uc011dgy.2. human. [P35916-3 ]

    Organism-specific databases

    CTDi 2324.
    GeneCardsi GC05M180028.
    GeneReviewsi FLT4.
    HGNCi HGNC:3767. FLT4.
    HPAi CAB000099.
    MIMi 136352. gene.
    153100. phenotype.
    602089. phenotype.
    neXtProti NX_P35916.
    Orphaneti 79452. Milroy disease.
    PharmGKBi PA28183.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG0515.
    HOGENOMi HOG000037949.
    HOVERGENi HBG053432.
    KOi K05097.
    OMAi PAHADIK.
    OrthoDBi EOG75F4CC.
    PhylomeDBi P35916.
    TreeFami TF325768.

    Enzyme and pathway databases

    BRENDAi 2.7.10.1. 2681.
    Reactomei REACT_12583. VEGF binds to VEGFR leading to receptor dimerization.
    SignaLinki P35916.

    Miscellaneous databases

    ChiTaRSi FLT4. human.
    GeneWikii FLT4.
    GenomeRNAii 2324.
    NextBioi 9433.
    PROi P35916.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P35916.
    Bgeei P35916.
    CleanExi HS_FLT4.
    Genevestigatori P35916.

    Family and domain databases

    Gene3Di 2.60.40.10. 9 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.
    IPR009137. VEGFR3_rcpt.
    [Graphical view ]
    PANTHERi PTHR24416:SF49. PTHR24416:SF49. 1 hit.
    Pfami PF07679. I-set. 2 hits.
    PF07714. Pkinase_Tyr. 1 hit.
    [Graphical view ]
    PRINTSi PR01835. VEGFRECEPTR3.
    SMARTi SM00409. IG. 4 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. "FLT4 receptor tyrosine kinase contains seven immunoglobulin-like loops and is expressed in multiple human tissues and cell lines."
      Pajusola K., Aprelikova O., Korhonen J., Kaipainen A., Pertovaara L., Alitalo R., Alitalo K.
      Cancer Res. 52:5738-5743(1992) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), TISSUE SPECIFICITY.
    2. "Chromosomal localization of FLT4, a novel receptor-type tyrosine kinase gene."
      Galland F., Karamysheva A., Mattei M.-G., Rosnet O., Marchetto S., Birnbaum D.
      Genomics 13:475-478(1992) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
    3. "The FLT4 gene encodes a transmembrane tyrosine kinase related to the vascular endothelial growth factor receptor."
      Galland F., Karamysheva A., Pebusque M.-J., Borg J.-P., Rottapel R., Dubreuil P., Rosnet O., Birnbaum D.
      Oncogene 8:1233-1240(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), VARIANTS GLN-890 AND HIS-1146.
      Tissue: Placenta.
    4. "Vascular endothelial growth factor-related protein: a ligand and specific activator of the tyrosine kinase receptor Flt4."
      Lee J., Gray A., Yuan J., Luoh S.-M., Avraham H., Wood W.I.
      Proc. Natl. Acad. Sci. U.S.A. 93:1988-1992(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), INTERACTION WITH VEGFC, PHOSPHORYLATION, FUNCTION IN CELL PROLIFERATION.
    5. "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 3), INTERACTION WITH VEGFD, SUBCELLULAR LOCATION.
    6. Lian Z., Feitelson M.
      Submitted (FEB-2003) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), VARIANTS GLN-890 AND HIS-1146.
    7. "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] (ISOFORM 2), VARIANT GLN-890.
      Tissue: Placenta.
    8. "The DNA sequence and comparative analysis of human chromosome 5."
      Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S., Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M., She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S.
      , Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R., Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.
      Nature 431:268-274(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    9. "FLT4, a novel class III receptor tyrosine kinase in chromosome 5q33-qter."
      Aprelikova O., Pajusola K., Partanen J., Armstrong E., Alitalo R., Bailey S.K., McMahon J., Wasmuth J., Huebner K., Alitalo K.
      Cancer Res. 52:746-748(1992) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 761-1190.
    10. "Two human FLT4 receptor tyrosine kinase isoforms with distinct carboxy terminal tails are produced by alternative processing of primary transcripts."
      Pajusola K., Aprelikova O., Armstrong E., Morris S., Alitalo K.
      Oncogene 8:2931-2937(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1293-1363 (ISOFORM 1), ALTERNATIVE SPLICING.
    11. "Signal peptide prediction based on analysis of experimentally verified cleavage sites."
      Zhang Z., Henzel W.J.
      Protein Sci. 13:2819-2824(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEIN SEQUENCE OF 25-39.
    12. "Biochemical characterization of two isoforms of FLT4, a VEGF receptor-related tyrosine kinase."
      Borg J.P., deLapeyriere O., Noguchi T., Rottapel R., Dubreuil P., Birnbaum D.
      Oncogene 10:973-984(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: CATALYTIC ACTIVITY, GLYCOSYLATION, SUBCELLULAR LOCATION.
    13. "Mutation at tyrosine residue 1337 abrogates ligand-dependent transforming capacity of the FLT4 receptor."
      Fournier E., Dubreuil P., Birnbaum D., Borg J.P.
      Oncogene 11:921-931(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN CELL PROLIFERATION AND PHOSPHORYLATION OF SHC1, CHARACTERIZATION OF ISOFORM 1 AND ISOFORM 2, INTERACTION WITH SHC1 AND GRB2, AUTOPHOSPHORYLATION, MUTAGENESIS OF TYR-1333; TYR-1337 AND TYR-1363, TISSUE SPECIFICITY.
    14. "Vascular endothelial growth factor D (VEGF-D) is a ligand for the tyrosine kinases VEGF receptor 2 (Flk1) and VEGF receptor 3 (Flt4)."
      Achen M.G., Jeltsch M., Kukk E., Maekinen T., Vitali A., Wilks A.F., Alitalo K., Stacker S.A.
      Proc. Natl. Acad. Sci. U.S.A. 95:548-553(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH VEGFD, FUNCTION AS VEGFD RECEPTOR, AUTOPHOSPHORYLATION.
    15. "Isolated lymphatic endothelial cells transduce growth, survival and migratory signals via the VEGF-C/D receptor VEGFR-3."
      Makinen T., Veikkola T., Mustjoki S., Karpanen T., Catimel B., Nice E.C., Wise L., Mercer A., Kowalski H., Kerjaschki D., Stacker S.A., Achen M.G., Alitalo K.
      EMBO J. 20:4762-4773(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION AS RECEPTOR FOR VEGFC AND VEGFD IN CELL SURVIVAL; PROLIFERATION AND MIGRATION, FUNCTION IN ACTIVATION OF PROTEIN KINASE C; AKT1; PIK3R1; MAPK1/ERK2 AND MAPK3/ERK1.
    16. "Ligand-induced vascular endothelial growth factor receptor-3 (VEGFR-3) heterodimerization with VEGFR-2 in primary lymphatic endothelial cells regulates tyrosine phosphorylation sites."
      Dixelius J., Makinen T., Wirzenius M., Karkkainen M.J., Wernstedt C., Alitalo K., Claesson-Welsh L.
      J. Biol. Chem. 278:40973-40979(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH KDR, CATALYTIC ACTIVITY, AUTOPHOSPHORYLATION, CHARACTERIZATION OF VARIANT LMPH1A PRO-1041, MUTAGENESIS OF LYS-879; TYR-1230; TYR-1231; TYR-1265; TYR-1333; TYR-1337 AND TYR-1363, PHOSPHORYLATION AT TYR-1230; TYR-1231; TYR-1265; TYR-1333; TYR-1337 AND TYR-1363.
    17. "Heterodimerization with vascular endothelial growth factor receptor-2 (VEGFR-2) is necessary for VEGFR-3 activity."
      Alam A., Herault J.P., Barron P., Favier B., Fons P., Delesque-Touchard N., Senegas I., Laboudie P., Bonnin J., Cassan C., Savi P., Ruggeri B., Carmeliet P., Bono F., Herbert J.M.
      Biochem. Biophys. Res. Commun. 324:909-915(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN KDR SIGNALING AND IN ANGIOGENESIS, INTERACTION WITH KDR, PHOSPHORYLATION.
    18. "Activation of vascular endothelial growth factor receptor-3 and its downstream signaling promote cell survival under oxidative stress."
      Wang J.F., Zhang X., Groopman J.E.
      J. Biol. Chem. 279:27088-27097(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN CELL SURVIVAL, PHOSPHORYLATION IN RESPONSE TO OXIDATIVE STRESS, INTERACTION WITH PIK3R1; SHC1; GRB2; PTPN11 AND PLCG1, ENZYME REGULATION BY MAZ51, CHARACTERIZATION OF VARIANT LMPH1A ARG-857.
    19. "Direct recruitment of CRK and GRB2 to VEGFR-3 induces proliferation, migration, and survival of endothelial cells through the activation of ERK, AKT, and JNK pathways."
      Salameh A., Galvagni F., Bardelli M., Bussolino F., Oliviero S.
      Blood 106:3423-3431(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN ACTIVATION OF AKT1; MAPK1/ERK2; MAPK3/ERK1 AND MAPK8, FUNCTION IN PROMOTING CELL SURVIVAL; PROLIFERATION AND MIGRATION, CHARACTERIZATION OF ISOFORM 1 AND ISOFORM 2, INTERACTION WITH CRK AND GRB2, PHOSPHORYLATION AT TYR-1063; TYR-1068; TYR-1230; TYR-1231 AND TYR-1337, MUTAGENESIS OF TYR-1063; TYR-1068; TYR-1230 AND TYR-1231.
    20. "Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry."
      Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J., Smith R.D.
      J. Proteome Res. 4:2070-2080(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-527.
      Tissue: Plasma.
    21. "Vascular endothelial growth factor receptor-3 and focal adhesion kinase bind and suppress apoptosis in breast cancer cells."
      Garces C.A., Kurenova E.V., Golubovskaya V.M., Cance W.G.
      Cancer Res. 66:1446-1454(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN PROMOTING CELL SURVIVAL, INTERACTION WITH PTK2/FAK1, SUBCELLULAR LOCATION.
    22. "Cooperative and redundant roles of VEGFR-2 and VEGFR-3 signaling in adult lymphangiogenesis."
      Goldman J., Rutkowski J.M., Shields J.D., Pasquier M.C., Cui Y., Schmokel H.G., Willey S., Hicklin D.J., Pytowski B., Swartz M.A.
      FASEB J. 21:1003-1012(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN LYMPHANGIOGENESIS.
    23. "Autocrine loop between vascular endothelial growth factor (VEGF)-C and VEGF receptor-3 positively regulates tumor-associated lymphangiogenesis in oral squamoid cancer cells."
      Matsuura M., Onimaru M., Yonemitsu Y., Suzuki H., Nakano T., Ishibashi H., Shirasuna K., Sueishi K.
      Am. J. Pathol. 175:1709-1721(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: ROLE IN CANCER, FUNCTION AS VEGFC RECEPTOR IN TUMOR LYMPHANGIOGENESIS; CELL PROLIFERATION; CELL SURVIVAL; IN ACTIVATION OF PIK3R1; AKT1 AND MAP KINASES AND IN UP-REGULATION OF VEGFA AND VEGFC EXPRESSION, ENZYME REGULATION, AUTOPHOSPHORYLATION.
    24. "Small molecule chloropyramine hydrochloride (C4) targets the binding site of focal adhesion kinase and vascular endothelial growth factor receptor 3 and suppresses breast cancer growth in vivo."
      Kurenova E.V., Hunt D.L., He D., Magis A.T., Ostrov D.A., Cance W.G.
      J. Med. Chem. 52:4716-4724(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: ROLE IN CANCER, INTERACTION WITH PTK2/FAK1.
    25. "Protein tyrosine phosphatase PTPN14 is a regulator of lymphatic function and choanal development in humans."
      Au A.C., Hernandez P.A., Lieber E., Nadroo A.M., Shen Y.M., Kelley K.A., Gelb B.D., Diaz G.A.
      Am. J. Hum. Genet. 87:436-444(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH PTPN14.
    26. "Endothelial cell adhesion to the extracellular matrix induces c-Src-dependent VEGFR-3 phosphorylation without the activation of the receptor intrinsic kinase activity."
      Galvagni F., Pennacchini S., Salameh A., Rocchigiani M., Neri F., Orlandini M., Petraglia F., Gotta S., Sardone G.L., Matteucci G., Terstappen G.C., Oliviero S.
      Circ. Res. 106:1839-1848(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION AT TYR-830; TYR-833; TYR-853; TYR-1063; TYR-1068; TYR-1333 AND TYR-1337, IDENTIFICATION IN A COMPLEX WITH SRC AND ITGB1, MUTAGENESIS OF TYR-1063; TYR-1068 AND TYR-1337, ENZYME REGULATION BY MAZ51, INTERACTION WITH ITGB1; CRK AND SHC1, FUNCTION IN ACTIVATION OF MAPK8 AND IN REGULATION OF ANGIOGENIC SPROUTING, IDENTIFICATION BY MASS SPECTROMETRY.
    27. Cited for: INTERACTION WITH KDR, FUNCTION IN MODULATING KDR SIGNALING AND IN ANGIOGENESIS, TISSUE SPECIFICITY.
    28. Cited for: FUNCTION IN ACTIVATION OF SIGNALING PATHWAYS, SUBCELLULAR LOCATION.
    29. "Combined blockade of VEGFR-2 and VEGFR-3 inhibits inflammatory lymphangiogenesis in early and middle stages."
      Yuen D., Pytowski B., Chen L.
      Invest. Ophthalmol. Vis. Sci. 52:2593-2597(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN LYMPHANGIOGENESIS.
    30. "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.
    31. "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 LYMPHANGIOGENESIS AND CANCER.
    32. "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.
    33. "Lymphangiogenesis and cancer metastasis."
      Al-Rawi M.A., Jiang W.G.
      Front. Biosci. 16:723-739(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW ON FUNCTION IN LYMPHANGIOGENESIS AND ROLE IN CANCER.
    34. Cited for: VARIANT LMPH1A LEU-1114.
    35. "Congenital hereditary lymphedema caused by a mutation that inactivates VEGFR3 tyrosine kinase."
      Irrthum A., Karkkainen M.J., Devriendt K., Alitalo K., Vikkula M.
      Am. J. Hum. Genet. 67:295-301(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: INVOLVEMENT IN LMPH1A, CHARACTERIZATION OF VARIANT LMPH1A ARG-1035.
    36. "Missense mutations interfere with VEGFR-3 signalling in primary lymphoedema."
      Karkkainen M.J., Ferrell R.E., Lawrence E.C., Kimak M.A., Levinson K.L., McTigue M.A., Alitalo K., Finegold D.N.
      Nat. Genet. 25:153-159(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS LMPH1A ARG-857; PRO-1041; PRO-1044 AND LEU-1114, VARIANT SER-641, CHARACTERIZATION OF VARIANTS.
    37. "Somatic mutation of vascular endothelial growth factor receptors in juvenile hemangioma."
      Walter J.W., North P.E., Waner M., Mizeracki A., Blei F., Walker J.W.T., Reinisch J.F., Marchuk D.A.
      Genes Chromosomes Cancer 33:295-303(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS HCI SER-954 AND SER-1137, VARIANTS ALA-494; GLN-890 AND HIS-1146.
    38. "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] ASP-149; CYS-378; ALA-494; SER-527; SER-641; TYR-868; ILE-1010; GLN-1031; ASN-1049; GLN-1075 AND HIS-1146.

    Entry informationi

    Entry nameiVGFR3_HUMAN
    AccessioniPrimary (citable) accession number: P35916
    Secondary accession number(s): A8K6L4
    , B5A926, Q16067, Q86W07, Q86W08
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: June 1, 1994
    Last sequence update: November 16, 2011
    Last modified: October 1, 2014
    This is version 168 of the entry and version 3 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 5
      Human chromosome 5: 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