flt4 fms related receptor tyrosine kinase 4 [Danio rerio (zebrafish)] - Gene

Summary

Official Symbol: flt4provided by ZNC
Official Full Name: fms related receptor tyrosine kinase 4provided by ZNC
Primary source: ZFIN:ZDB-GENE-980526-326
See related: Ensembl:ENSDARG00000104453 AllianceGenome:ZFIN:ZDB-GENE-980526-326
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Danio rerio
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes; Danionidae; Danioninae; Danio
Also known as: VEGFR3; cb1059
Summary: Enables identical protein binding activity. Acts upstream of or within several processes, including cardiac muscle tissue regeneration; regulation of signal transduction; and vasculature development. Predicted to be located in cytoplasm; membrane; and nucleus. Predicted to be part of receptor complex. Predicted to be active in plasma membrane. Is expressed in several structures, including angioblastic mesenchymal cell; brain; mesoderm; vascular cord; and vasculature. Human ortholog(s) of this gene implicated in hereditary lymphedema IA. Orthologous to human FLT4 (fms related receptor tyrosine kinase 4). [provided by Alliance of Genome Resources, Jul 2025]
Orthologs: human mouse all
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Genomic context

Location:: chromosome: 14

Exon count:: 31

Annotation release	Status	Assembly	Chr	Location
RS_2025_04	current	GRCz12tu (GCF_049306965.1)	14	NC_133189.1 (18097397..18238581, complement)
RS_2024_08	previous assembly	GRCz11 (GCF_000002035.6)	14	NC_007125.7 (15817054..15956721, complement)

Chromosome 14 - NC_133189.1 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Sequencing the Zebrafish transcriptome from a range of tissues and developmental stages
Description: Sequencing the Zebrafish transcriptome from a range of tissues and developmental stages
BioProject: PRJEB1986
Analysis date: Fri Dec 8 19:48:10 2017

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

FLT4 causes developmental disorders of the cardiovascular and lymphovascular systems via pleiotropic molecular mechanisms.
Title: FLT4 causes developmental disorders of the cardiovascular and lymphovascular systems via pleiotropic molecular mechanisms.
VEGFC/FLT4-induced cell-cycle arrest mediates sprouting and differentiation of venous and lymphatic endothelial cells.
Title: VEGFC/FLT4-induced cell-cycle arrest mediates sprouting and differentiation of venous and lymphatic endothelial cells.
Antagonistic Activities of Vegfr3/Flt4 and Notch1b Fine-tune Mechanosensitive Signaling during Zebrafish Cardiac Valvulogenesis.
Title: Antagonistic Activities of Vegfr3/Flt4 and Notch1b Fine-tune Mechanosensitive Signaling during Zebrafish Cardiac Valvulogenesis.
Overall, the data show that HHEX controls blood vessel and lymphatic vessel formation by regulating the VEGFC/FLT4/PROX1 signaling axis.
Title: HHEX is a transcriptional regulator of the VEGFC/FLT4/PROX1 signaling axis during vascular development.
miR-126a directs lymphatic endothelial cell sprouting and extension by interacting with Cxcl12a-mediated chemokine signaling and Vegfc-Flt4 signal axis.
Title: MicroRNA-126a Directs Lymphangiogenesis Through Interacting With Chemokine and Flt4 Signaling in Zebrafish.
Ca(2+) oscillations depended upon VEGF receptor-2 (Vegfr2) and Vegfr3 in endothelial cells budding from the dorsal aorta (DA) and posterior cardinal vein, respectively.
Title: Endothelial Ca 2+ oscillations reflect VEGFR signaling-regulated angiogenic capacity in vivo.
Experiments in mice and zebrafish demonstrate that changing levels of VEGFR3/Flt4 modulates aortic lumen diameter consistent with flow-dependent remodeling
Title: Vascular remodeling is governed by a VEGFR3-dependent fluid shear stress set point.
In the embryo, phenotypes driven by increased Vegfc are suppressed in the absence of Ccbe1, and Vegfc-driven sprouting is enhanced by local Ccbe1 overexpression. Moreover, Vegfc- and Vegfr3-dependent Erk signaling is impaired in the absence of Ccbe1.
Title: Ccbe1 regulates Vegfc-mediated induction of Vegfr3 signaling during embryonic lymphangiogenesis.
Flt4 plays an essential role in lymphangiogenesis [review]
Title: A fisheye view on lymphangiogenesis.
The parallel growth of motoneuron axons with the dorsal aorta depends on Vegfc/Vegfr3 signaling in zebrafish.
Title: The parallel growth of motoneuron axons with the dorsal aorta depends on Vegfc/Vegfr3 signaling in zebrafish.

Submit: New GeneRIF Correction See all GeneRIFs (12)

General gene information

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Gene Ontology Provided by ZFIN

Function	Evidence Code	Pubs
enables ATP binding	IEA Inferred from Electronic Annotation more info
enables growth factor binding	IBA Inferred from Biological aspect of Ancestor more info
enables identical protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables kinase activity	IEA Inferred from Electronic Annotation more info
enables metal ion binding	IEA Inferred from Electronic Annotation more info
enables nucleotide binding	IEA Inferred from Electronic Annotation more info
enables protein kinase activity	IEA Inferred from Electronic Annotation more info
enables protein tyrosine kinase activity	IEA Inferred from Electronic Annotation more info
enables transferase activity	IEA Inferred from Electronic Annotation more info
enables transmembrane receptor protein tyrosine kinase activity	IEA Inferred from Electronic Annotation more info
enables vascular endothelial growth factor receptor activity	IBA Inferred from Biological aspect of Ancestor more info
enables vascular endothelial growth factor receptor activity	ISS Inferred from Sequence or Structural Similarity more info

Process	Evidence Code	Pubs
acts_upstream_of_or_within angiogenesis	IEA Inferred from Electronic Annotation more info
involved_in angiogenesis	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within angiogenesis	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within angiogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within atrioventricular canal development	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within cardiac muscle tissue regeneration	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within cell differentiation	IEA Inferred from Electronic Annotation more info
involved_in cell migration	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within cell surface receptor protein tyrosine kinase signaling pathway	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within lymph vessel development	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within lymph vessel development	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within lymph vessel morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within lymphangiogenesis	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within lymphangiogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within lymphatic endothelial cell differentiation	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within motor neuron axon guidance	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within phosphorylation	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of MAPK cascade	IBA Inferred from Biological aspect of Ancestor more info
involved_in positive regulation of cell migration	IBA Inferred from Biological aspect of Ancestor more info
involved_in positive regulation of cell population proliferation	IBA Inferred from Biological aspect of Ancestor more info
involved_in protein autophosphorylation	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of_or_within protein phosphorylation	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within regulation of heart looping	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within regulation of vascular endothelial growth factor receptor signaling pathway	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within regulation of vascular endothelial growth factor signaling pathway	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within selective angioblast sprouting	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in sprouting angiogenesis	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within sprouting angiogenesis	IGI Inferred from Genetic Interaction more info	PubMed
involved_in vascular endothelial growth factor receptor signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in vascular endothelial growth factor receptor signaling pathway	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within vascular endothelial growth factor receptor signaling pathway	IGI Inferred from Genetic Interaction more info	PubMed
involved_in vascular endothelial growth factor signaling pathway	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of_or_within vasculature development	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within venous blood vessel development	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within venous endothelial cell migration involved in lymph vessel development	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
located_in cytoplasm	IEA Inferred from Electronic Annotation more info
located_in membrane	IEA Inferred from Electronic Annotation more info
located_in nucleus	IEA Inferred from Electronic Annotation more info
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in plasma membrane	IEA Inferred from Electronic Annotation more info
part_of receptor complex	IBA Inferred from Biological aspect of Ancestor more info

General protein information

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Preferred Names: vascular endothelial growth factor receptor 3

Names: expando; fms-related tyrosine kinase 4; receptor tyrosine kinase Flt4

NP_571020.2

EC 2.7.10.1

XP_009306067.1

EC 2.7.10.1

XP_017214465.1

EC 2.7.10.1

XP_073777241.1

EC 2.7.10.1

XP_073777242.1

EC 2.7.10.1

XP_073777243.1

EC 2.7.10.1

XP_073777244.1

EC 2.7.10.1

XP_073777245.1

EC 2.7.10.1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_130945.2 → NP_571020.2 vascular endothelial growth factor receptor 3 precursor

Status: VALIDATED

Source sequence(s)

JBMGRA010000014

UniProtKB/Swiss-Prot

Q5GIT2, Q5MD89

UniProtKB/TrEMBL

A0A0R4IFS9, A0A8N7UZE5

Related

ENSDARP00000133227.1, ENSDART00000169197.2

Conserved Domains (9) summary

cd00096
Location:602 → 685

Ig; Immunoglobulin domain

cd05862
Location:265 → 350

Ig1_VEGFR; First immunoglobulin (Ig)-like domain of vascular endothelial growth factor (VEGF) receptor(R)

smart00408
Location:714 → 776

IGc2; Immunoglobulin C-2 Type

smart00409
Location:602 → 678

IG; Immunoglobulin

smart00410
Location:362 → 445

IG_like; Immunoglobulin like

pfam07679
Location:705 → 786

I-set; Immunoglobulin I-set domain

pfam07714
Location:866 → 1177

Pkinase_Tyr; Protein tyrosine kinase

cl11960
Location:373 → 445

Ig; Immunoglobulin domain

cl21453
Location:858 → 1184

PKc_like; Protein Kinases, catalytic domain

RefSeqs of Annotated Genomes: GCF_049306965.1-RS_2025_04

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCz12tu Primary Assembly

Genomic

NC_133189.1 Reference GRCz12tu Primary Assembly

Range

18097397..18238581 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_073921140.1 → XP_073777241.1 vascular endothelial growth factor receptor 3 isoform X3

UniProtKB/Swiss-Prot

Q5GIT2, Q5MD89
XM_009307792.5 → XP_009306067.1 vascular endothelial growth factor receptor 3 isoform X1

UniProtKB/Swiss-Prot

Q5GIT2, Q5MD89

UniProtKB/TrEMBL

A0A8M3AZL8

Conserved Domains (9) summary

cd00096
Location:598 → 681

Ig; Immunoglobulin domain

cd04976
Location:373 → 445

Ig2_VEGFR; Second immunoglobulin (Ig)-like domain of vascular endothelial growth factor receptor (VEGFR)

cd05862
Location:265 → 350

Ig1_VEGFR; First immunoglobulin (Ig)-like domain of vascular endothelial growth factor (VEGF) receptor(R)

smart00408
Location:710 → 772

IGc2; Immunoglobulin C-2 Type

smart00409
Location:598 → 674

IG; Immunoglobulin

smart00410
Location:362 → 445

IG_like; Immunoglobulin like

pfam07679
Location:701 → 782

I-set; Immunoglobulin I-set domain

pfam07714
Location:862 → 1173

Pkinase_Tyr; Protein tyrosine kinase

cl21453
Location:854 → 1180

PKc_like; Protein Kinases, catalytic domain
XM_017358976.4 → XP_017214465.1 vascular endothelial growth factor receptor 3 isoform X2

UniProtKB/Swiss-Prot

Q5GIT2, Q5MD89

UniProtKB/TrEMBL

A0A2R8QSE0, A0A8M6Z9D2

Related

ENSDARP00000156181.1
XM_073921142.1 → XP_073777243.1 vascular endothelial growth factor receptor 3 isoform X5
XM_073921143.1 → XP_073777244.1 vascular endothelial growth factor receptor 3 isoform X6
XM_073921141.1 → XP_073777242.1 vascular endothelial growth factor receptor 3 isoform X4
XM_073921144.1 → XP_073777245.1 vascular endothelial growth factor receptor 3 isoform X7