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Category Symbol Source: HGNC EntrezGene Ensembl GeneCards RNA genes CroW21

GIFtS
-

FLT4 Gene

protein-coding GIFtS: 77
GCID: GC05M180028

fms-related tyrosine kinase 4

Explore 101 diseases affiliated with
FLT4 via

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(According to ¹HGNC, ²Entrez Gene,
³UniProtKB/Swiss-Prot, ⁴UniProtKB/TrEMBL, ⁵OMIM, ⁶GeneLoc, ⁷Ensembl, ⁸DME, ⁹miRBase, and/or ¹⁰fRNAdb)
About This Section

Aliases
Fms-Related Tyrosine Kinase 4¹ ²		LMPH1A² ⁵
VEGFR3¹ ² ³ ⁵		FLT41²
PCL¹ ² ⁵		Soluble VEGFR3 Variant 1²
Fms-Like Tyrosine Kinase 4² ³		Soluble VEGFR3 Variant 2²
Tyrosine-Protein Kinase Receptor FLT4² ³		Soluble VEGFR3 Variant 3²
FLT-4² ³		Vascular Endothelial Growth Factor Receptor 3²
VEGFR-3² ³		EC 2.7.10⁸
EC 2.7.10.1³ ⁸

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

(According to Entrez Gene, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
About This Section

Entrez Gene summary for FLT4:

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)

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:

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

(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 69), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section

RefSeq DNA sequence:

NC_000005.9 NC_018916.1 NT_023133.13

Regulatory elements:

SABiosciences 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 SABiosciences Chromatin IP Primers for FLT4

Epigenetics:

QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays 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

(According to ¹UniProtKB, HORDE, neXtProt, Ensembl, and/or Reactome, Modification sites according to ²PhosphoSitePlus, Specific Peptides from DME, Protein expression images according to data from SPIRE MOPED and PaxDb, 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 Uscn,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Uscn, Ontologies according to Gene Ontology Consortium 01 Mar 2013 and Entrez Gene, Antibodies by EMD Millipore, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, and/or Uscn)
About This Section

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

Subcellular location: Cell membrane; Single-pass type I membrane protein. Cytoplasm. Nucleus. Note=Ligand-mediated

autophosphorylation leads to rapid internalization

Subcellular location: Isoform 1: Cell membrane; Single-pass type I membrane protein. Note=Ligand-mediated

autophosphorylation leads to rapid internalization

Subcellular location: Isoform 2: Cell membrane; Single-pass type I membrane protein

Subcellular location: Isoform 3: Secreted. Cytoplasm

Sequence caution: Sequence=CAA48290.1; Type=Erroneous initiation; Note=Translation N-terminally shortened;

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

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

View modification sites using PhosphoSitePlus²

View neXtProt modification sites for NX_P35916

4/37 DME Specific Peptides for FLT4 (P35916) (see all 37)

GTRMRAP

QVARGME

KHCHKKY

RDLAARN

FLT4 Protein expression data from MOPED and PaxDb: About this image

REFSEQ proteins (2 alternative transcripts):

NP_002011.2 NP_891555.2

ENSEMBL proteins:

ENSP00000261937 ENSP00000377016 ENSP00000426057 ENSP00000421535

Reactome Protein details: P35916
Human Recombinant Protein Products for FLT4:

	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: FLT4 OriGene Custom Protein Services for FLT4
	GenScript Purified and Recombinant Proteins for FLT4
	Novus Biologicals FLT4 Proteins Novus Biologicals FLT4 Lysate
	Sino Biological Recombinant Protein for FLT4
	ProSpec Recombinant Protein for FLT4
	Uscn Proteins for FLT4

Gene Ontology (GO): 5 cellular component terms (GO ID links to tree view): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0005576	extracellular region	IEA	--
GO:0005634	nucleus	IEA	--
GO:0005737	cytoplasm	IEA	--
GO:0005886	plasma membrane	TAS	--
GO:0005887	integral to plasma membrane	IEA	--

FLT4 for ontologies About GeneDecksing

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 (VEGFR-3)
	Browse OriGene Antibodies OriGene Custom Antibody Services for FLT4
	GenScript Custom Superior Antibodies Services for FLT4
	Novus Biologicals FLT4 Antibodies
	Abcam antibodies for FLT4
	Uscn Antibodies for FLT4
	ThermoFisher Antibodies for FLT4

Assay Products for FLT4:

	Browse Kits and Assays available from EMD Millipore
	OriGene Custom Immunoassay Development Browse OriGene Fluorogenic Cell Assay Kits
	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
	Uscn ELISAs and CLIAs for FLT4

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

FLT4 for domains About GeneDecksing

5/14 InterPro domains/families (see all 14):

IPR003598 Ig_sub2

IPR017441 Protein_kinase_ATP_BS

IPR013098 Ig_I-set

IPR011009 Kinase-like_dom

IPR009137 Tyr_kinase_VEGFR3_rcpt_N

Graphical View of Domain Structure for InterPro Entry P35916

ProtoNet protein and cluster: P35916

5 Blocks protein families:

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

(According to ¹UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or ²DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory,
bound targets from SABiosciences, miRNA Gene Targets from miRTarBase, shRNA from OriGene, Sirion Biotech, RNAi from EMD Millipore, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, Gene Editing from DNA2.0, Sirion Biotech, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, LifeMap BioReagents, Sirion Biotech, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene.)
About This Section

Molecular Function:

UniProtKB/Swiss-Prot Summary: VGFR3_HUMAN, P35916