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FLT4 Gene

protein-coding   GIFtS: 77
GCID: GC05M180028

Fms-Related Tyrosine Kinase 4
  See related diseases
at
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Aliases
for FLT4 gene

(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, 10fRNAdb, 12H-InvDB, 13NCBI, 14NONCODE, and/or 15RNAdb)
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Aliases
Fms-Related Tyrosine Kinase 41 2     PCL2 5
VEGFR32 3 5     FLT412
Fms-Like Tyrosine Kinase 42 3     Soluble VEGFR3 Variant 12
Tyrosine-Protein Kinase Receptor FLT42 3     Soluble VEGFR3 Variant 22
FLT-42 3     Soluble VEGFR3 Variant 32
VEGFR-32 3     Vascular Endothelial Growth Factor Receptor 32
EC 2.7.10.13 8     EC 2.7.108
LMPH1A2 5     

External Ids:    HGNC: 37671   Entrez Gene: 23242   Ensembl: ENSG000000372807   OMIM: 1363525   UniProtKB: P359163   

Export aliases for FLT4 gene to outside databases

Previous GC identifers: GC05M180162 GC05M181012 GC05M180139 GC05M180132 GC05M179962 GC05M174752


Summaries
for FLT4 gene

(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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Entrez Gene summary for FLT4 Gene:
This gene encodes a tyrosine kinase receptor for vascular endothelial growth factors C and D. The protein is
thought to be involved in lymphangiogenesis and maintenance of the lymphatic endothelium. Mutations in this gene
cause hereditary lymphedema type IA. (provided by RefSeq, Jul 2008)

GeneCards Summary for FLT4 Gene:
FLT4 (fms-related tyrosine kinase 4) is a protein-coding gene. Diseases associated with FLT4 include hereditary lymphedema, and lymphangiosarcoma. GO annotations related to this gene include protein phosphatase binding and growth factor binding. An important paralog of this gene is FGFR4.

UniProtKB/Swiss-Prot: VGFR3_HUMAN, P35916
Function: 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'

summary for FLT4 Gene:
Vascular endothelial growth factor is a signaling protein involved in the regulation of angiogenesis and
vasculogenesis. VEGF binds to and activates a receptor tyrosine kinase, VEGFR. Three VEGFR isoforms have
been identified in humans; VEGFR-1 (Flt-1), VEGFR-2 (KDR/Flk-1) and VEGFR-3 (Flt-4). VEGFR-2 mediates the
majority of cellular responses to VEGF. VEGFR-1 is thought to modulate VEGFR-2 signaling or to act as a
dummy/decoy receptor to sequester VEGF away from VEGFR-2.

Gene Wiki entry for FLT4 Gene


Genomic Views
for FLT4 gene

(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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RefSeq DNA sequence:
NC_000005.10  NC_018916.2  NT_023133.14  
Regulatory elements:
   Regulatory transcription factor binding sites in the FLT4 gene promoter:
         GR   AP-1   ATF-2   c-Jun   GR-alpha   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmid: FLT4 promoter sequence
   Search Chromatin IP Primers for FLT4

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat FLT4


Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 5q35.3   Ensembl cytogenetic band:  5q35.3   HGNC cytogenetic band: 5q34-q35

FLT4 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
FLT4 gene location

GeneLoc information about chromosome 5         GeneLoc Exon Structure

GeneLoc location for GC05M180028:  view genomic region     (about GC identifiers)

Start:
 180,028,506 bp from pter      End:
 180,076,624 bp from pter
Size:
 48,119 bases      Orientation:
 minus strand

Proteins
for FLT4 gene

(According to 1UniProtKB, HORDE, 2neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Cloud-Clone Corp.,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Cloud-Clone Corp., Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, and/or Cloud-Clone Corp.)
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UniProtKB/Swiss-Prot: VGFR3_HUMAN, P35916 (See protein sequence)
Recommended Name: Vascular endothelial growth factor receptor 3 precursor  
Size: 1363 amino acids; 152757 Da
Subunit: 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
Sequence caution: Sequence=CAA48290.1; Type=Erroneous initiation; Note=Translation N-terminally shortened;
2 PDB 3D structures from and Proteopedia for FLT4:
4BSJ (3D)        4BSK (3D)    
Secondary accessions: A8K6L4 B5A926 Q16067 Q86W07 Q86W08
Alternative splicing: 3 isoforms:  P35916-2   P35916-1   P35916-3   

Explore the universe of human proteins at neXtProt for FLT4: NX_P35916

Explore proteomics data for FLT4 at MOPED

Post-translational modifications: 

  • 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
    H(2)O(2) 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-13371
  • Ubiquitination2 at Lys1253
  • Glycosylation2 at Asn33, Asn104, Asn166, Asn251, Asn299, Asn411, Asn515, Asn527, Asn594, Asn683,
                                 Asn690, Asn758
  • Modification sites at PhosphoSitePlus
    • Selected DME Specific Peptides for FLT4 (P35916) (see all 37)
     GTRMRAP  QVARGME  KHCHKKY  RDLAARN 


    See FLT4 Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

    REFSEQ proteins (2 alternative transcripts): 
    NP_002011.2  NP_891555.2  

    ENSEMBL proteins: 
     ENSP00000261937   ENSP00000377016   ENSP00000426057   ENSP00000421535  
    Reactome Protein details: P35916

    FLT4 Human Recombinant Protein Products:

    EMD Millipore Purified and/or Recombinant FLT4 Protein
    R&D Systems Recombinant & Natural Proteins for FLT4 (VEGF R3/Flt-4)
    Browse recombinant and purified proteins available from Enzo Life Sciences
    Browse OriGene full length recombinant human proteins expressed in human HEK293 cells
    OriGene Protein Over-expression Lysate for FLT4
    OriGene Custom MassSpec
    OriGene Custom Protein Services for FLT4
    GenScript Custom Purified and Recombinant Proteins Services for FLT4
    Novus Biologicals FLT4 Proteins
    Novus Biologicals FLT4 Lysate
    Sino Biological Recombinant Protein for FLT4
    Sino Biological Cell Lysate for FLT4
    ProSpec Recombinant Protein for FLT4
    Browse Proteins at Cloud-Clone Corp.

    FLT4 Antibody Products:

    EMD Millipore Mono- and Polyclonal Antibodies for the study of FLT4
    R&D Systems Antibodies for FLT4 (VEGF R3/Flt-4)
    Cell Signaling Technology (CST) Antibodies for FLT4  (VEGFR3)
    OriGene Antibodies for FLT4
    OriGene Custom Antibody Services for FLT4
    Novus Biologicals FLT4 Antibodies
    Abcam antibodies for FLT4
    Browse Antibodies at Cloud-Clone Corp.
    ThermoFisher Antibody for FLT4
    LSBio Antibodies in human, mouse, rat for FLT4

    FLT4 Assay Products:

    Browse Kits and Assays available from EMD Millipore
    OriGene Custom Assay Services for FLT4
    R&D Systems ELISAs for FLT4 (VEGF R3/Flt-4)         (see all)
    GenScript Custom Assay Services for FLT4
    Browse Enzo Life Sciences for kits & assays
    Browse ELISAs at Cloud-Clone Corp.
    Browse CLIAs at Cloud-Clone Corp.

    Domains /
    Families
    for FLT4 gene

    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
    About This Section

    TryGeneCards Plus    		 HGNC Gene Families:
    ISET: Immunoglobulin superfamily / I-set domain containing
    IGD: Immunoglobulin superfamily / Immunoglobulin-like domain containing

    IUPHAR Guide to PHARMACOLOGY protein family classification: fms-related tyrosine kinase 4
    VEGF (vascular endothelial growth factor) receptor family
    VEGF (vascular endothelial growth factor) receptor family

    Selected InterPro protein domains (see all 13):
     IPR003598 Ig_sub2
     IPR017441 Protein_kinase_ATP_BS
     IPR013098 Ig_I-set
     IPR011009 Kinase-like_dom
     IPR009137 VEGFR3_rcpt

    Graphical View of Domain Structure for InterPro Entry P35916

    ProtoNet protein and cluster: P35916

    5 Blocks protein domains:
    IPB001824 Receptor tyrosine kinase
    IPB003598 Immunoglobulin C-2 type
    IPB008266 Tyrosine protein kinase
    IPB009134 Vascular endothelial growth factor receptor signature
    IPB013098 Immunoglobulin I-set


    UniProtKB/Swiss-Prot: VGFR3_HUMAN, P35916
    Domain: The first and second Ig-like C2-type (immunoglobulin-like) domains are sufficient for VEGFC binding
    Similarity: Belongs to the protein kinase superfamily. Tyr protein kinase family. CSF-1/PDGF receptor subfamily
    Similarity: Contains 7 Ig-like C2-type (immunoglobulin-like) domains
    Similarity: Contains 1 protein kinase domain


    FLT4 for domains           About GeneDecksing


    Function
    for FLT4 gene

    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory, genOway,
    transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
    About This Section

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    Molecular Function:

         UniProtKB/Swiss-Prot Summary: VGFR3_HUMAN, P35916
    Function: 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'
    Catalytic activity: ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate
    Enzyme regulation: 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

         Genatlas biochemistry entry for FLT4:
    fms-related receptor t tyrosine kinase 4,expressed on the surface on endothelial cells

         Enzyme Numbers (IUBMB): EC 2.7.10.11 2 EC 2.7.102

         Gene Ontology (GO): Selected molecular function terms (see all 9):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0004672protein kinase activity ----
    GO:0004713protein tyrosine kinase activity ----
    GO:0004714transmembrane receptor protein tyrosine kinase activity IMP7898938
    GO:0005021vascular endothelial growth factor-activated receptor activity IMP11532940
    GO:0005515protein binding IPI16530705
         
    FLT4 for ontologies           About GeneDecksing


    Phenotypes:
         3 GenomeRNAi human phenotypes for FLT4:
     Decreased substrate adherent c  Increased cilium length after   Increased mitotic index 

         14 MGI mutant phenotypes (inferred from 8 alleles) (MGI details for Flt4):
     adipose tissue  cardiovascular system  digestive/alimentary  embryogenesis  growth/size/body 
     homeostasis/metabolism  immune system  integument  liver/biliary system  mortality/aging 
     muscle  no phenotypic analysis  normal  reproductive system 

    FLT4 for phenotypes           About GeneDecksing

    Animal Models:
       inGenious Targeting Laboratory: Let us create your new Knockout/Knockin mouse model for FLT4
       inGenious Targeting Laboratory: Contact us about creating complex and humanized mouse models for FLT4

       genOway customized KO model: permanent, tissue-specific or time-controlled inactivation for FLT4
       genOway customized Knockin model: humanization, point mutation, expression monitoring, etc. for FLT4

    miRNA
    Products:            		miRTarBase miRNAs that target FLT4:
    hsa-mir-331-3p (MIRT043539)

    Block miRNA regulation of human, mouse, rat FLT4 using miScript Target Protectors
    3 qRT-PCR Assays for microRNAs that regulate FLT4:
    hsa-miR-214* hsa-miR-2276 hsa-miR-1236
    SwitchGear 3'UTR luciferase reporter plasmid: FLT4 3' UTR sequence
    Inhib. RNA
    Products:            		OriGene RNAi products in human, mouse, rat for FLT4
    Predesigned siRNA for gene silencing in human, mouse, rat FLT4

    Gene Editing
    Products:    		DNA2.0 Custom Protein Engineering Service for FLT4

    Clone
    Products:             		 OriGene clones in human, mouse for FLT4 (see all 16)
    OriGene ORF clones in mouse, rat for FLT4
    OriGene custom cloning services - gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
    GenScript: all cDNA clones in your preferred vector (see all 2): FLT4 (NM_002020)
    Sino Biological Human cDNA Clone for FLT4
    DNA2.0 Custom Codon Optimized Gene Synthesis Service for FLT4
    Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat FLT4

    Cell Line
    Products:             		GenScript Custom overexpressing Cell Line Services for FLT4
    Browse ESI BIO Cell Lines and PureStem Progenitors for FLT4 
    In Situ Assay
    Products:       
         		Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for FLT4


    Localization
    for FLT4 gene

    (According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
    About This Section

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    Subcellular locations from UniProtKB/Swiss-Prot
    VGFR3_HUMAN, P35916: Cell membrane; Single-pass type I membrane protein. Cytoplasm. Nucleus. Note=Ligand-mediated
    autophosphorylation leads to rapid internalization
    VGFR3_HUMAN, P35916: Isoform 1: Cell membrane; Single-pass type I membrane protein. Note=Ligand-mediated
    autophosphorylation leads to rapid internalization
    VGFR3_HUMAN, P35916: Isoform 2: Cell membrane; Single-pass type I membrane protein
    VGFR3_HUMAN, P35916: Isoform 3: Secreted. Cytoplasm
    Subcellular locations from COMPARTMENTS: 

    CompartmentConfidence
    extracellular5
    nucleus5
    plasma membrane5
    cytoskeleton1
    endoplasmic reticulum1

    Gene Ontology (GO): Selected cellular component terms (see all 6):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005576extracellular region IEA--
    GO:0005634nucleus IEA--
    GO:0005737cytoplasm IEA--
    GO:0005886plasma membrane TAS--
    GO:0005887integral component of plasma membrane IEA--

    FLT4 for ontologies           About GeneDecksing


    Pathways & Interactions
    for FLT4 gene

    (SuperPaths according to PathCards, Pathways according to R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to QIAGEN, and/or STRING, Interactions according to 1UniProtKB, 2MINT, 3I2D, and/or 4STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene).
    About This Section

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    SuperPaths for FLT4 About   (see all 29)                                                                                              See pathways by source

    SuperPathSelected contained pathways About (see all per SuperPath)
    1Sorafenib Pharmacodynamics
    		Sorafenib Pharmacodynamics0.37
    		VEGF Pathway0.36
    		Vemurafenib Pathway, Pharmacodynamics0.37
    2PEDF Induced Signaling
    		Endothelin-1 Signaling Pathway0.46
    		Cytokine-cytokine receptor interaction0.43
    3VEGF Pathway
    		VEGF Family Ligands and Receptor Interactions0.66
    		Development VEGF family signaling0.36
    4Apoptotic Pathways in Synovial Fibroblasts
    		Mitochondrial Apoptosis0.85
    		PPAR Pathway0.66
    		Cellular Apoptosis Pathway0.85
    		Rac1 Pathway0.65
    		Apoptotic Pathways in Synovial Fibroblasts0.84
    		Actin-Based Motility by Rho Family GTPases0.62
    		p53 Mediated Apoptosis0.84
    		ERK5 Signaling0.61
    5GPCR Pathway
    		Ras Pathway0.73
    		Breast Cancer Regulation by Stathmin10.58
    		Paxillin Interactions0.73
    		NFAT in Immune Response0.58
    		GPCR Pathway0.62
    		Estrogen Pathway0.55
    		Pancreatic Adenocarcinoma0.59
    		P2Y Receptor Signaling0.38

    Pathways by source                                                                                                                                                                 See SuperPaths
    Show all pathways

    1 R&D Systems Pathway for FLT4
        Akt Signaling Pathway

    Selected Downloadable PowerPoint Slides of GeneGlobe Pathway Central Maps for FLT4 (see all 56)
        Nuclear Receptor Activation by Vitamin-A
    Paxillin Interactions
    Telomerase Components in Cell Signaling
    Mitochondrial Apoptosis
    Molecular Mechanisms of Cancer

    2 Cell Signaling Technology (CST) Pathways for FLT4
        Angiogenesis
    Tyrosine Kinases / Adaptors

    4 Tocris Bioscience Pathways for FLT4
        Akt Pathway
    Apoptosis Pathway
    NF-kappaB Pathway
    VEGF Pathway

    1 GeneGo (Thomson Reuters) Pathway for FLT4
        Development VEGF-family signaling

    2 BioSystems Pathways for FLT4
        Signaling events mediated by VEGFR1 and VEGFR2
    VEGFR3 signaling in lymphatic endothelium

    1 Sino Biological Pathway for FLT4
        VEGF Signaling

    1 Reactome Pathway for FLT4
        VEGF binds to VEGFR leading to receptor dimerization

    2 PharmGKB Pathways for FLT4
        Sorafenib Pharmacodynamics
    Vemurafenib Pathway, Pharmacodynamics

    5 Kegg Pathways  (Kegg details for FLT4):
        Ras signaling pathway
    Rap1 signaling pathway
    Cytokine-cytokine receptor interaction
    PI3K-Akt signaling pathway
    Focal adhesion


    FLT4 for pathways           About GeneDecksing

        Pathway & Disease-focused RT2 Profiler PCR Arrays including FLT4: 
              Cancer Drug Targets in human mouse rat
              VEGF Signaling in human mouse rat
              Tumor Metastasis in human mouse rat

    Interactions:

        GeneGlobe Interaction Network for FLT4

    STRING Interaction Network Preview (showing 5 interactants - click image to see 25)

    Selected Interacting proteins for FLT4 (P359161, 2, 3 ENSP000002619374) via UniProtKB, MINT, STRING, and/or I2D (see all 77)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    VEGFCP497671, 3, ENSP000002801934EBI-1005467,EBI-3405539 I2D: score=3 STRING: ENSP00000280193
    KDRP359681, 2, 3, ENSP000002639234EBI-1005467,EBI-1005487 MINT-7938244 MINT-7938235 I2D: score=4 STRING: ENSP00000263923
    FIGFO439153, ENSP000002979044I2D: score=2 STRING: ENSP00000297904
    SHC1P293533, ENSP000004013034I2D: score=2 STRING: ENSP00000401303
    PTPN11Q061243, ENSP000003409444I2D: score=1 STRING: ENSP00000340944
    About this table

    Gene Ontology (GO): Selected biological process terms (see all 23):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0001934positive regulation of protein phosphorylation IMP11532940
    GO:0001938positive regulation of endothelial cell proliferation IMP11532940
    GO:0001944vasculature development ISS--
    GO:0001945lymph vessel development ISS--
    GO:0001946lymphangiogenesis ISS--

    FLT4 for ontologies           About GeneDecksing



    Drugs & Compounds
    for FLT4 gene

    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
    About This Section

    TryGeneCards Plus
    Browse Small Molecules at EMD Millipore
       Enzo Life Sciences drugs & compounds for FLT4
      Browse compounds at ApexBio 

    Compounds for FLT4 available from Tocris Bioscience    About this table
    CompoundAction CAS #
    Ki 8751 Potent, selective VEGFR-2 inhibitor [228559-41-9]
    ZM 323881 hydrochloride Potent, selective inhibitor of VEGFR-2 [324077-30-7]
    Axitinib Potent VEGFR-1, -2 and -3 inhibitor [319460-85-0]
    DMH4Selective VEGFR-2 inhibitor[515880-75-8]
    ZM 306416 hydrochlorideInhibitor of VEGF receptor tyrosine kinase[690206-97-4]

    2 HMDB Compounds for FLT4    About this table
    CompoundSynonyms CAS #PubMed Ids
    ADPadenosindiphosphorsaeure (see all 8)58-64-0--
    Adenosine triphosphate5'-(tetrahydrogen triphosphate) Adenosine (see all 24)56-65-5--

    5 DrugBank Compounds for FLT4    About this table
    CompoundSynonyms CAS #TypeActionsPubMed Ids
    Sorafenib-- 284461-73-0targetantagonist16133532 16729906 16757355 17296815 16474853
    SunitinibSU011248 (see all 2)557795-19-4targetantagonist16685460 17367763 17296815 17605814 15688612
    Axitinib-- 319460-85-0targetinhibitor18541897
    PazopanibGW-786034 (see all 2)444731-52-6target--17288876
    Regorafenib-- 755037-03-7targetinhibitor--

    3 IUPHAR Ligands for FLT4 (fms-related tyrosine kinase 4)    About this table
    LigandTypeActionAffinityPubmed IDs
    VEGFC
    		NoneNone--
    VEGFE
    		NoneNone--
    VEGFD
    		NoneNone--

    Selected Novoseek inferred chemical compound relationships for FLT4 gene (see all 16)    About this table
    Compound   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    vegf 87.8 252 18225391 (8), 15364128 (4), 10831352 (4), 14507895 (4) (see all 99)
    azd 2171 78.4 2 17671138 (1), 17671152 (1)
    tyrosine 66.8 120 11553610 (5), 12881528 (3), 18680722 (2), 16452200 (2) (see all 81)
    zd6474 64.2 1 18177496 (1)
    sorafenib 50.5 6 19089671 (1), 16133532 (1), 17935273 (1), 16757355 (1) (see all 6)
    sunitinib 49.9 2 17605814 (1), 17935273 (1)
    su5416 39.7 1 17169805 (1)
    matrigel 31.1 1 19825968 (1)
    paraffin 20.9 2 17970053 (1), 17327058 (1)
    oxygen 4.43 1 8630024 (1)



    FLT4 for compounds           About GeneDecksing



    Transcripts
    for FLT4 gene

    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
    RefSeq according to Entrez Gene,
    DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
    Conferences by KenesGroup, exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
    Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, Primers from OriGene, and/or QIAGEN )
    About This Section

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    REFSEQ mRNAs for FLT4 gene (2 alternative transcripts): 
    NM_002020.4  NM_182925.4  

    Unigene Cluster for FLT4:

    Fms-related tyrosine kinase 4
    Hs.646917  [show with all ESTs]
    Unigene Representative Sequence: NM_182925
    11 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000261937(uc003mlz.4) ENST00000502603 ENST00000507059(uc003mmb.1)
    ENST00000393347(uc003mma.4 uc011dgz.1 uc011dha.1) ENST00000502649
    ENST00000510000 ENST00000514810 ENST00000512795 ENST00000424276(uc011dgy.2)
    ENST00000502293 ENST00000513527
    miRNA
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    3 qRT-PCR Assays for microRNAs that regulate FLT4:
    hsa-miR-214* hsa-miR-2276 hsa-miR-1236
    SwitchGear 3'UTR luciferase reporter plasmid: FLT4 3' UTR sequence
    Inhib. RNA
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    GenScript: all cDNA clones in your preferred vector (see all 2): FLT4 (NM_002020)
    DNA2.0 Custom Codon Optimized Gene Synthesis Service for FLT4
    Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat FLT4
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      QuantiFast Probe-based Assays in human, mouse, rat FLT4

    Additional mRNA sequence: 

    AK291679.1 AK309910.1 AY233382.1 AY233383.1 BC027302.1 EU826564.1 EU826565.1 EU826566.1 
    S66407.1 U43143.1 X68203.1 X69878.1 

    6 DOTS entries:

    DT.209171  DT.91824963  DT.99969842  DT.120877112  DT.120877154  DT.75122823 

    Selected AceView cDNA sequences (see all 96):

    AW950567 AA368926 X68203 BC027302 N30566 S66407 AY233382 NM_182925 
    AA894453 AA242766 CB045179 BF594265 AA262959 AY233383 AA193259 U43143 
    BU621870 NM_002020 CA438330 BE247382 BF525742 BE245688 BM993496 X69878 

    GeneLoc Exon Structure


    Expression
    for FLT4 gene

    (RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
    About This Section

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    FLT4 expression in normal human tissues (normalized intensities)      FLT4 embryonic expression: see
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: TTCTGAGAAA
    FLT4 Expression
    About this image


    FLT4 expression in embryonic tissues and stem cells    About this table
    Data from LifeMap, the Embryonic Development and Stem Cells Database
     selected tissues (see all 7) fully expand
     
     Endothelium (Cardiovascular System)    fully expand to see all 4 entries
             Endothelial Tip Cells Arteries
             Endothelial-like cells
     
     Heart (Cardiovascular System)
             Venous Endothelial Cells Cardinal Veins
     
     Lymph (Hematopoietic System)
             Lymphatic Endothelial Cells Lymphatic Vessels
     
     Skeletal Muscle (Muscoskeletal System)    fully expand to see all 2 entries
             Myoblasts Mandibular Arch Muscles
     
     Fibroblasts
             Dermal Fibroblasts Dorsal Dermis
    FLT4 Protein expression data from MOPED1, PaxDb2 and MaxQB3:     About this image

    FLT4 Protein Expression

    SOURCE GeneReport for Unigene cluster: Hs.646917

    UniProtKB/Swiss-Prot: VGFR3_HUMAN, P35916
    Tissue specificity: 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

        Pathway & Disease-focused RT2 Profiler PCR Arrays including FLT4: 
              Cancer Drug Targets in human mouse rat
              VEGF Signaling in human mouse rat
              Tumor Metastasis in human mouse rat

    Primer
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    In Situ
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         		Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for FLT4

    Orthologs
    for FLT4 gene

    (Orthologs according to 1,2HomoloGene (2older version, for species not in 1newer version), 3euGenes, 4SGD , 5MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or 6Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
    About This Section

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    This gene was present in the common ancestor of animals.

    Orthologs for FLT4 gene from Selected species (see all 13)    About this table
    Organism Taxonomic
    classification    		 Gene Description Human
    Similarity    		 Orthology
    Type    		 Details
    mouse
    (Mus musculus)    		 Mammalia Flt41 , 5 FMS-like tyrosine kinase 41, 5 85.3(n)1
    87.45(a)1    		   11 (29.69 cM)5
    142571  NM_008029.31  NP_032055.11 
     496092635 
    chicken
    (Gallus gallus)    		 Aves FLT41 fms-related tyrosine kinase 4 72.13(n)
    70.92(a)    		   395742  XM_414600.4  XP_414600.3 
    lizard
    (Anolis carolinensis)    		 Reptilia FLT46
    		 fms-related tyrosine kinase 4
    		 67(a)
    		 1 ↔ 1
    		 2(139845484-139958547)
    tropical clawed frog
    (Xenopus tropicalis)    		 Amphibia LOC1004938011 vascular endothelial growth factor receptor 3-like 63.74(n)
    64.64(a)    		   100493801  XM_002932304.2  XP_002932350.2 
    zebrafish
    (Danio rerio)    		 Actinopterygii flt41 fms-related tyrosine kinase 4 60.63(n)
    56.82(a)    		   30121  NM_130945.1  NP_571020.1 
    fruit fly
    (Drosophila melanogaster)    		 Insecta tor3 eggshell pattern formation
    transmembrane receptor more    		 50(a)   43E12   --


    ENSEMBL Gene Tree for FLT4 (if available)
    TreeFam Gene Tree for FLT4 (if available)

    Paralogs
    for FLT4 gene

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
    About This Section

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    Paralogs for FLT4 gene
    FGFR42  PDGFRB2  CSF1R2  KIT2  FGFR32  PDGFRA2  RET2  KDR2  
    FGFR12  FGFR22  FLT32  FLT12  
    Selected SIMAP similar genes for FLT4 using alignment to 7 protein entries:     VGFR3_HUMAN (see all proteins) (see all similar genes):
    VEGFR3    FLT-1    RET    CSF1R    KIT    CCDC6-RETa
    CCDC6-RETc    R11    R12    EGFR    TYRO3    JAK2
    ABL1    AXL    PTK2    MET    MST1R    EZR-ROS1

    FLT4 for paralogs           About GeneDecksing



    Genomic Variants
    for FLT4 gene

    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, 4UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
    About This Section

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    Selected SNPs for FLT4 (see all 1890)    About this table    
    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance    		Chr 5 posSequence#AA
    Chg    		TypeMore#Allele
    freq    		PopTotal
    sample    		More
    ----------
    rs342555321,2,,4
    		C,FHemangioma, capillary infantile (HCI)4 other1180045911(-) AGTCTC/TCCGAG 4 P S mis12Minor allele frequency- T:0.01NA EU 177
    VAR_0184124
    		Lymphedema, hereditary, 1A (LMPH1A)4--see VAR_0184122 H R mis40--------
    VAR_0184144
    		Lymphedema, hereditary, 1A (LMPH1A)4--see VAR_0184142 L P mis40--------
    VAR_0184154
    		Lymphedema, hereditary, 1A (LMPH1A)4--see VAR_0184152 P L mis40--------
    VAR_0184094
    		Lymphedema, hereditary, 1A (LMPH1A)4--see VAR_0184092 G R mis40--------
    VAR_0420634
    		A renal clear cell carcinoma sample4--see VAR_0420632 R C mis40--------
    VAR_0184134
    		Lymphedema, hereditary, 1A (LMPH1A)4--see VAR_0184132 R P mis40--------
    VAR_0420654
    		A metastatic melanoma sample4--see VAR_0420652 T I mis40--------
    VAR_0184164
    		Hemangioma, capillary infantile (HCI)4--see VAR_0184162 P S mis40--------
    rs1219096571,2
    		Cpathogenic1180046749(-) ACGGCA/GCCTTC 4 T A mis10--------

    HapMap Linkage Disequilibrium report for FLT4 (180028506 - 180076624 bp)

    Structural Variations
         Database of Genomic Variants (DGV) Selected variations for FLT4 (see all 26):    About this table    
    Variant IDTypeSubtypePubMed ID
    nsv820663CNV Deletion20802225
    esv2387627CNV Deletion18987734
    esv4093CNV Deletion18987735
    esv2731345CNV Deletion23290073
    esv2665740CNV Deletion23128226
    esv2731348CNV Deletion23290073
    esv1049221CNV Deletion17803354
    esv2731346CNV Deletion23290073
    esv2731347CNV Deletion23290073
    nsv509111CNV Insertion20534489

    Human Gene Mutation Database (HGMD): FLT4
    Site Specific Mutation Identification with PCR Assays
    SeqTarget long-range PCR primers for resequencing FLT4
    DNA2.0 Custom Variant and Variant Library Synthesis for FLT4

    Disorders / Diseases
    for FLT4 gene

    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Conferences by KenesGroup, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
    About This Section

    TryGeneCards Plus    		 OMIM gene information: 136352   
    OMIM disorders: 153100  602089  
    UniProtKB/Swiss-Prot: VGFR3_HUMAN, P35916
  • 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. Note=The disease is caused by mutations affecting the gene represented in this entry
  • 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. Note=Disease
    susceptibility is associated with variations affecting the gene represented in this entry
  • Note=Plays an important role in tumor lymphangiogenesis, in cancer cell survival, migration, and
    formation of metastases

    • Selected diseases for FLT4 (see all 101):    About MalaCards
    hereditary lymphedema    lymphangiosarcoma    hemangioma, capillary infantile, somatic    lymphedema
    lymphatic malformation    hydrocele    hemifacial spasm    orbital lymphangioma
    lymphangioma    kaposiform hemangioendothelioma    tufted angioma    intracranial arteriovenous malformation
    hemangioma    cellulitis    hemangioendothelioma    ovarian carcinosarcoma
    intestinal lymphangiectasia    hemangioma, capillary infantile    arteriovenous malformation    capillary hemangioma

    2 diseases from the University of Copenhagen DISEASES database for FLT4:
    Lymphedema     Lymphangioma

    FLT4 for disorders           About GeneDecksing

    Selected Novoseek inferred disease relationships for FLT4 gene (see all 79)    About this table

    Disease   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    congenital lymphedema 89.3 42 16965327 (5), 19002718 (4), 17458866 (3), 15904433 (3) (see all 15)
    lymphatic metastasis 85.5 19 19589137 (3), 16159440 (2), 16219148 (2), 19744460 (1) (see all 10)
    lymphedema primary 79.9 5 12900893 (1), 15693535 (1), 18564920 (1)
    lymphedema 76.4 26 19289394 (5), 10835628 (3), 19002718 (3), 12386934 (1) (see all 12)
    metastasis 68.1 98 16044920 (4), 19787226 (4), 19628565 (3), 16510584 (3) (see all 54)
    tumors 60.3 199 17234768 (6), 19956902 (5), 10590384 (5), 19556880 (4) (see all 94)
    lymphangioma 59.8 26 19151999 (4), 11742043 (2), 17584927 (2), 12060670 (1) (see all 7)
    hemangioendothelioma 58.7 6 10697276 (2), 19262246 (1), 15920541 (1)
    vascular neoplasms 57.5 1 10590384 (1)
    neovascularization 52.6 12 20008149 (2), 10590384 (2), 15032727 (1), 18694556 (1) (see all 8)

    GeneTests: FLT4
    GeneReviews: FLT4
    Genetic Association Database (GAD): FLT4
    Human Genome Epidemiology (HuGE) Navigator: FLT4 (14 documents)

    Export disorders for FLT4 gene to outside databases

    Publications
    for FLT4 gene

    (in PubMed. Associations of this gene to articles via 1Entrez Gene, 2UniProtKB/Swiss-Prot, 3HGNC, 4GAD, 5PharmGKB, 6HMDB, 7DrugBank, 8UniProtKB/TrEMBL, 9 Novoseek, and/or 10fRNAdb)
    About This Section

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    PubMed articles for FLT4 gene, integrated from 10 sources (see all 559):
    (articles sorted by number of sources associating them with FLT4)    		    Utopia: connect your pdf to the dynamic
    world of online information

    1. Chromosomal localization of FLT4, a novel receptor-type tyrosine kinase gene. (PubMed id 1319394)1, 2, 3, 9 Galland F....Birnbaum D. (Genomics 1992)
    2. Activation of vascular endothelial growth factor receptor-3 and its downstream signaling promote cell survival under oxidative stress. (PubMed id 15102829)1, 2, 9 Wang J.F.... Groopman J.E. (J. Biol. Chem. 2004)
    3. Analysis of the coding regions of VEGFR3 and VEGFC in Milroy disease and other primary lymphoedemas. (PubMed id 19002718)1, 4, 9 Connell F.C....Jeffery S. (Hum. Genet. 2009)
    4. Vascular endothelial growth factor receptor-3 and focal adhesion kinase bind and suppress apoptosis in breast cancer cells. (PubMed id 16452200)1, 2, 9 Garces C.A.... Cance W.G. (Cancer Res. 2006)
    5. Ligand-induced vascular endothelial growth factor receptor-3 (VEGFR- 3) heterodimerization with VEGFR-2 in primary lymphatic endothelial cells regulates tyrosine phosphorylation sites. (PubMed id 12881528)1, 2, 9 Dixelius J.... Claesson-Welsh L. (J. Biol. Chem. 2003)
    6. FLT4 receptor tyrosine kinase contains seven immunoglobulin-like loops and is expressed in multiple human tissues and cell lines. (PubMed id 1327515)1, 2, 9 Pajusola K.... Alitalo K. (Cancer Res. 1992)
    7. Heterodimerization with vascular endothelial growth factor receptor-2 (VEGFR-2) is necessary for VEGFR-3 activity. (PubMed id 15474514)1, 2, 9 Alam A.... Herbert J.M. (Biochem. Biophys. Res. Commun. 2004)
    8. 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. (PubMed id 16076871)1, 2, 9 Salameh A.... Oliviero S. (Blood 2005)
    9. Autocrine loop between vascular endothelial growth factor (VEGF)-C and VEGF receptor-3 positively regulates tumor-associated lymphangiogenesis in oral squamoid cancer cells. (PubMed id 19779139)1, 2, 9 Matsuura M.... Sueishi K. (Am. J. Pathol. 2009)
    10. Missense mutations interfere with VEGFR-3 signalling in primary lymphoedema. (PubMed id 10835628)1, 2, 9 Karkkainen M.J.... Finegold D.N. (Nat. Genet. 2000)

    External Searches for FLT4 gene

    (in PubMed, OMIM, and NCBI Bookshelf)
    About This Section

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     ANDOR
    Aliases
    Disorders
    Free Text  
      Query String
    		PubMed
    OMIM
    NCBI Bookshelf
      (Note: In FireFox, select the above section and copy using Ctrl-C)

    Genome Databases showing FLT4 gene

    (According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
    About This Section

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    Entrez Gene: 2324 HGNC: 3767 AceView: FLT4 Ensembl:ENSG00000037280 euGenes: HUgn2324
    ECgene: FLT4 Kegg: 2324 H-InvDB: FLT4

    Other Databases showing FLT4 gene

    (According to HUGE)
    About This Section

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    Specialized Databases showing FLT4 gene

    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
    About This Section

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    NameDescription
    PharmGKB entry for FLT4 Pharmacogenomics, SNPs, Pathways
    ATLAS Chromosomes in Cancer entry for FLT4 Genetics and Cytogenetics in Oncology and Haematology
    GeneReviewshttp://www.ncbi.nlm.nih.gov/books/NBK1116/?term=FLT4[genesymbol]
    Wikipedia http://en.wikipedia.org/wiki/FLT4

    Intellectual Property
    for FLT4 gene

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
    About This Section

    TryGeneCards Plus    		Patent Information for FLT4 gene:
    Search GeneIP for patents involving FLT4

    Licensable Technologies for FLT4 gene:
    Weizmann Institute:Porphyrin and Corrole -like analogs as potent inhibitors of Growth Factor Receptor Binding and Activation
    GeneCards and IP:
    Japan Patent Office Licenses GeneCards     European Patent Office Licenses GeneCards     Improving the IP Search



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