Flt4 FMS-like tyrosine kinase 4 [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Flt4provided by MGI
Official Full Name: FMS-like tyrosine kinase 4provided by MGI
Primary source: MGI:MGI:95561
See related: Ensembl:ENSMUSG00000020357 AllianceGenome:MGI:95561
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: Chy; Flt-4; VEGFR3; VEGFR-3
Summary: Enables vascular endothelial growth factor receptor activity. Involved in lymphangiogenesis; regulation of blood vessel remodeling; and sprouting angiogenesis. Acts upstream of or within lung alveolus development; positive regulation of cell population proliferation; and respiratory system process. Predicted to be located in cytosol and nucleoplasm. Predicted to be part of receptor complex. Predicted to be active in plasma membrane. Is expressed in several structures, including alimentary system; cardiovascular system; central nervous system; extraembryonic component; and genitourinary system. Used to study hereditary lymphedema. 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, Oct 2024]
Expression: Broad expression in lung adult (RPKM 14.6), ovary adult (RPKM 10.5) and 23 other tissues See more
Orthologs: human all
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Genomic context

Location:: 11 B1.2; 11 29.69 cM

Exon count:: 30

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	11	NC_000077.7 (49500506..49543566)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	11	NC_000077.6 (49609679..49652739)

Chromosome 11 - NC_000077.7 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: Mouse ENCODE transcriptome data Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Profibrotic VEGFR3-Dependent Lymphatic Vessel Growth in Autoimmune Valvular Carditis.
Title: Profibrotic VEGFR3-Dependent Lymphatic Vessel Growth in Autoimmune Valvular Carditis.
The pathological roles and potential mechanisms of vascular endothelial growth factor receptor-3 in gastric cancer.
Title: The pathological roles and potential mechanisms of vascular endothelial growth factor receptor-3 in gastric cancer.
Heterozygous Mutation of Vegfr3 Reduces Renal Lymphatics without Renal Dysfunction.
Title: Heterozygous Mutation of Vegfr3 Reduces Renal Lymphatics without Renal Dysfunction.
Formation of the glomerular microvasculature is regulated by VEGFR-3.
Title: Formation of the glomerular microvasculature is regulated by VEGFR-3.
ADSCs stimulated by VEGF-C alleviate intestinal inflammation via dual mechanisms of enhancing lymphatic drainage by a VEGF-C/VEGFR-3-dependent mechanism and inhibiting the NF-kappaB pathway by the secretome.
Title: ADSCs stimulated by VEGF-C alleviate intestinal inflammation via dual mechanisms of enhancing lymphatic drainage by a VEGF-C/VEGFR-3-dependent mechanism and inhibiting the NF-κB pathway by the secretome.
Pro-lymphangiogenic VEGFR-3 signaling modulates memory T cell responses in allergic airway inflammation.
Title: Pro-lymphangiogenic VEGFR-3 signaling modulates memory T cell responses in allergic airway inflammation.
VEGF-C/VEGFR3 signaling activates lymphatic endothelium in cervical lymph nodes after ischemic stroke.
Title: Brain-to-cervical lymph node signaling after stroke.
results demonstrate a novel role for ARRB1 in VEGFR regulation and suggest a mechanism for cross talk between G protein-coupled receptors and VEGFRs in pulmonary arterial hypertension.
Title: Vascular Endothelial Growth Factor Receptor 3 Regulates Endothelial Function Through β-Arrestin 1.
ROS produced in diabetes induced c-Src-dependent but VEGF-C-independent VEGFR3 phosphorylation, and upregulated epsins through the activation of transcription factor AP-1. Augmented epsins bound to and promoted degradation of newly synthesized VEGFR3 in the Golgi, resulting in reduced availability of VEGFR3 at the cell surface.
Title: Epsin deficiency promotes lymphangiogenesis through regulation of VEGFR3 degradation in diabetes.
The data suggested that VEGFC/VEGFR3 signaling promotes the proliferation of spermatogonial cells via the AKT /MAPK and cyclin D1 pathway.
Title: VEGFC/VEGFR3 Signaling Regulates Mouse Spermatogonial Cell Proliferation via the Activation of AKT/MAPK and Cyclin D1 Pathway and Mediates the Apoptosis by affecting Caspase 3/9 and Bcl-2.

Submit: New GeneRIF Correction See all GeneRIFs (77)

Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Chemically induced (ENU) (1)
Endonuclease-mediated (5)
Targeted (11) 1 citation

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

Flt4 (e-PCR), detects polymorphism
- UniSTS:143122

L07296 (e-PCR)
- UniSTS:160091

39.MMHAP15FRE12.seq (e-PCR)
- UniSTS:124310

ha2078 (e-PCR)
- UniSTS:515482

Flt4 (e-PCR), detects polymorphism
- UniSTS:496830

AI323512 (e-PCR)
- UniSTS:180182

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables ATP binding	IEA Inferred from Electronic Annotation more info
enables growth factor binding	IEA Inferred from Electronic Annotation more info
enables growth factor binding	ISO Inferred from Sequence Orthology more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein homodimerization activity	ISO Inferred from Sequence Orthology more info
enables protein homodimerization activity	ISS Inferred from Sequence or Structural Similarity more info
enables protein phosphatase binding	IEA Inferred from Electronic Annotation more info
enables protein phosphatase binding	ISO Inferred from Sequence Orthology more info
enables transmembrane receptor protein tyrosine kinase activity	ISO Inferred from Sequence Orthology 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	IGI Inferred from Genetic Interaction more info	PubMed
enables vascular endothelial growth factor receptor activity	ISO Inferred from Sequence Orthology more info
enables vascular endothelial growth factor receptor activity	ISS Inferred from Sequence or Structural Similarity more info

Process	Evidence Code	Pubs
involved_in blood vessel morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cellular response to vascular endothelial growth factor stimulus	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within lung alveolus development	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within lymph vessel development	IGI Inferred from Genetic Interaction more info	PubMed
involved_in lymph vessel development	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in lymphangiogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in lymphangiogenesis	ISO Inferred from Sequence Orthology more info
involved_in multicellular organism development	IBA Inferred from Biological aspect of Ancestor more info
involved_in negative regulation of apoptotic process	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of apoptotic process	ISO Inferred from Sequence Orthology more info
involved_in peptidyl-tyrosine phosphorylation	IEA Inferred from Electronic Annotation more info
involved_in peptidyl-tyrosine phosphorylation	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of ERK1 and ERK2 cascade	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of ERK1 and ERK2 cascade	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of JNK cascade	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of JNK cascade	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of MAPK cascade	IBA Inferred from Biological aspect of Ancestor more info
involved_in positive regulation of MAPK cascade	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of cell growth	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of cell migration	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within positive regulation of cell population proliferation	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within positive regulation of cell population proliferation	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of cell population proliferation	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of endothelial cell migration	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of endothelial cell migration	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of endothelial cell proliferation	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of endothelial cell proliferation	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of protein kinase C signaling	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of protein phosphorylation	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of protein phosphorylation	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of vascular endothelial growth factor production	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of vascular endothelial growth factor production	ISO Inferred from Sequence Orthology more info
involved_in protein autophosphorylation	ISO Inferred from Sequence Orthology more info
involved_in protein autophosphorylation	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of blood vessel remodeling	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within respiratory gaseous exchange by respiratory system	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within respiratory system process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in sprouting angiogenesis	IBA Inferred from Biological aspect of Ancestor more info
involved_in sprouting angiogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in vascular endothelial growth factor receptor signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within vascular endothelial growth factor receptor signaling pathway	ISO Inferred from Sequence Orthology more info
involved_in vascular endothelial growth factor receptor signaling pathway	ISO Inferred from Sequence Orthology more info
involved_in vascular endothelial growth factor signaling pathway	ISO Inferred from Sequence Orthology more info
involved_in vascular endothelial growth factor signaling pathway	ISS Inferred from Sequence or Structural Similarity more info
involved_in vasculature development	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
located_in cytosol	IEA Inferred from Electronic Annotation more info
located_in cytosol	ISO Inferred from Sequence Orthology more info
located_in nucleoplasm	IEA Inferred from Electronic Annotation more info
located_in nucleoplasm	ISO Inferred from Sequence Orthology 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
located_in plasma membrane	ISO Inferred from Sequence Orthology more info
part_of receptor complex	IBA Inferred from Biological aspect of Ancestor more info
part_of receptor complex	ISO Inferred from Sequence Orthology more info	PubMed

General protein information

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Preferred Names: vascular endothelial growth factor receptor 3

Names: chylous ascites; receptor protein tyrosine kinase; tyrosine-protein kinase receptor FLT4

NP_032055.1

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_008029.3 → NP_032055.1 vascular endothelial growth factor receptor 3 precursor

See identical proteins and their annotated locations for NP_032055.1

Status: VALIDATED

Source sequence(s)

AL646088, BC138346, BU757635, BY311090

Consensus CDS

CCDS24618.1

UniProtKB/Swiss-Prot

P35917

UniProtKB/TrEMBL

Q5SU94

Related

ENSMUSP00000020617.3, ENSMUST00000020617.3

Conserved Domains (8) summary

cd05862
Location:245 → 329

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

smart00408
Location:693 → 755

IGc2; Immunoglobulin C-2 Type

smart00409
Location:570 → 663

IG; Immunoglobulin

smart00410
Location:238 → 327

IG_like; Immunoglobulin like

pfam07679
Location:678 → 765

I-set; Immunoglobulin I-set domain

pfam07714
Location:845 → 1169

Pkinase_Tyr; Protein tyrosine kinase

cl11960
Location:352 → 418

Ig; Immunoglobulin domain

cl21453
Location:837 → 1175

PKc_like; Protein Kinases, catalytic domain