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FLT4 fms related tyrosine kinase 4 [ Homo sapiens (human) ]

Gene ID: 2324, updated on 9-Sep-2018

Summary

Official Symbol
FLT4provided by HGNC
Official Full Name
fms related tyrosine kinase 4provided by HGNC
Primary source
HGNC:HGNC:3767
See related
Ensembl:ENSG00000037280 MIM:136352; Vega:OTTHUMG00000130931
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
PCL; FLT-4; FLT41; LMPH1A; VEGFR3; VEGFR-3
Summary
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]
Expression
Broad expression in spleen (RPKM 7.7), lung (RPKM 6.7) and 21 other tissues See more
Orthologs

Genomic context

See FLT4 in Genome Data Viewer
Location:
5q35.3
Exon count:
35
Annotation release Status Assembly Chr Location
109 current GRCh38.p12 (GCF_000001405.38) 5 NC_000005.10 (180601506..180650298, complement)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 5 NC_000005.9 (180028506..180076624, complement)

Chromosome 5 - NC_000005.10Genomic Context describing neighboring genes Neighboring gene CCR4-NOT transcription complex subunit 6 Neighboring gene proteolipid protein 2 (colonic epithelium-enriched) pseudogene Neighboring gene secretoglobin family 3A member 1 Neighboring gene coiled-coil domain containing 86 pseudogene Neighboring gene long intergenic non-protein coding RNA 2222

Genomic regions, transcripts, and products

Expression

  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Jun 15 11:32:44 2016

Bibliography

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

Pathways from BioSystems

  • Breast cancer, organism-specific biosystem (from KEGG)
    Breast cancer, organism-specific biosystemBreast cancer is the leading cause of cancer death among women worldwide. The vast majority of breast cancers are carcinomas that originate from cells lining the milk-forming ducts of the mammary gla...
  • Breast cancer, conserved biosystem (from KEGG)
    Breast cancer, conserved biosystemBreast cancer is the leading cause of cancer death among women worldwide. The vast majority of breast cancers are carcinomas that originate from cells lining the milk-forming ducts of the mammary gla...
  • Cytokine-cytokine receptor interaction, organism-specific biosystem (from KEGG)
    Cytokine-cytokine receptor interaction, organism-specific biosystemCytokines are soluble extracellular proteins or glycoproteins that are crucial intercellular regulators and mobilizers of cells engaged in innate as well as adaptive inflammatory host defenses, cell ...
  • Cytokine-cytokine receptor interaction, conserved biosystem (from KEGG)
    Cytokine-cytokine receptor interaction, conserved biosystemCytokines are soluble extracellular proteins or glycoproteins that are crucial intercellular regulators and mobilizers of cells engaged in innate as well as adaptive inflammatory host defenses, cell ...
  • Focal adhesion, organism-specific biosystem (from KEGG)
    Focal adhesion, organism-specific biosystemCell-matrix adhesions play essential roles in important biological processes including cell motility, cell proliferation, cell differentiation, regulation of gene expression and cell survival. At the...
  • Focal adhesion, conserved biosystem (from KEGG)
    Focal adhesion, conserved biosystemCell-matrix adhesions play essential roles in important biological processes including cell motility, cell proliferation, cell differentiation, regulation of gene expression and cell survival. At the...
  • PI3K-Akt signaling pathway, organism-specific biosystem (from KEGG)
    PI3K-Akt signaling pathway, organism-specific biosystemThe phosphatidylinositol 3' -kinase(PI3K)-Akt signaling pathway is activated by many types of cellular stimuli or toxic insults and regulates fundamental cellular functions such as transcription, tra...
  • PI3K-Akt signaling pathway, conserved biosystem (from KEGG)
    PI3K-Akt signaling pathway, conserved biosystemThe phosphatidylinositol 3' -kinase(PI3K)-Akt signaling pathway is activated by many types of cellular stimuli or toxic insults and regulates fundamental cellular functions such as transcription, tra...
  • Rap1 signaling pathway, organism-specific biosystem (from KEGG)
    Rap1 signaling pathway, organism-specific biosystemRap1 is a small GTPase that controls diverse processes, such as cell adhesion, cell-cell junction formation and cell polarity. Like all G proteins, Rap1 cycles between an inactive GDP-bound and an ac...
  • Rap1 signaling pathway, conserved biosystem (from KEGG)
    Rap1 signaling pathway, conserved biosystemRap1 is a small GTPase that controls diverse processes, such as cell adhesion, cell-cell junction formation and cell polarity. Like all G proteins, Rap1 cycles between an inactive GDP-bound and an ac...
  • Ras signaling pathway, organism-specific biosystem (from KEGG)
    Ras signaling pathway, organism-specific biosystemThe Ras proteins are GTPases that function as molecular switches for signaling pathways regulating cell proliferation, survival, growth, migration, differentiation or cytoskeletal dynamism. Ras prote...
  • Signal Transduction, organism-specific biosystem (from REACTOME)
    Signal Transduction, organism-specific biosystemSignal transduction is a process in which extracellular signals elicit changes in cell state and activity. Transmembrane receptors sense changes in the cellular environment by binding ligands, such a...
  • Signaling by VEGF, organism-specific biosystem (from REACTOME)
    Signaling by VEGF, organism-specific biosystemIn normal development vascular endothelial growth factors (VEGFs) are crucial regulators of vascular development during embryogenesis (vasculogenesis) and blood-vessel formation in the adult (angioge...
  • Signaling events mediated by VEGFR1 and VEGFR2, organism-specific biosystem (from Pathway Interaction Database)
    Signaling events mediated by VEGFR1 and VEGFR2, organism-specific biosystem
    Signaling events mediated by VEGFR1 and VEGFR2
  • VEGF binds to VEGFR leading to receptor dimerization, organism-specific biosystem (from REACTOME)
    VEGF binds to VEGFR leading to receptor dimerization, organism-specific biosystemThe binding of VEGF ligands to VEGFR receptors in the cell membrane induces dimerization and activation of the latter, initiating intracellular signaling cascades that result in proliferation, surviv...
  • VEGF ligand-receptor interactions, organism-specific biosystem (from REACTOME)
    VEGF ligand-receptor interactions, organism-specific biosystemThe VEGF family is encoded by seven genes (VEGF-A, B, C, D, E: PLGF (Placenta Growth Factor)-1, 2). Six isoforms of VEGF-A protein, containing 121, 145, 165, 183, 189, and 206 amino acid residues, an...
  • VEGFR3 signaling in lymphatic endothelium, organism-specific biosystem (from Pathway Interaction Database)
    VEGFR3 signaling in lymphatic endothelium, organism-specific biosystem
    VEGFR3 signaling in lymphatic endothelium

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
ATP binding IEA
Inferred from Electronic Annotation
more info
 
VEGF-C-activated receptor activity IDA
Inferred from Direct Assay
more info
PubMed 
growth factor binding IPI
Inferred from Physical Interaction
more info
PubMed 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
protein homodimerization activity IDA
Inferred from Direct Assay
more info
PubMed 
protein phosphatase binding IPI
Inferred from Physical Interaction
more info
PubMed 
transmembrane receptor protein tyrosine kinase activity IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
transmembrane receptor protein tyrosine kinase activity IMP
Inferred from Mutant Phenotype
more info
PubMed 
transmembrane signaling receptor activity IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
vascular endothelial growth factor-activated receptor activity IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
vascular endothelial growth factor-activated receptor activity IDA
Inferred from Direct Assay
more info
PubMed 
vascular endothelial growth factor-activated receptor activity IMP
Inferred from Mutant Phenotype
more info
PubMed 
Process Evidence Code Pubs
blood vessel morphogenesis ISS
Inferred from Sequence or Structural Similarity
more info
 
cell differentiation IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
cellular response to vascular endothelial growth factor stimulus IDA
Inferred from Direct Assay
more info
PubMed 
cellular response to vascular endothelial growth factor stimulus IMP
Inferred from Mutant Phenotype
more info
PubMed 
lung alveolus development IEA
Inferred from Electronic Annotation
more info
 
lymph vessel development ISS
Inferred from Sequence or Structural Similarity
more info
 
lymphangiogenesis IMP
Inferred from Mutant Phenotype
more info
PubMed 
lymphangiogenesis ISS
Inferred from Sequence or Structural Similarity
more info
 
negative regulation of apoptotic process IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
negative regulation of apoptotic process IMP
Inferred from Mutant Phenotype
more info
PubMed 
negative regulation of signal transduction IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
peptidyl-tyrosine phosphorylation IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of ERK1 and ERK2 cascade IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
positive regulation of ERK1 and ERK2 cascade IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of JNK cascade IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of MAPK cascade IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of cell proliferation IGI
Inferred from Genetic Interaction
more info
PubMed 
positive regulation of cell proliferation IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of endothelial cell migration IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of endothelial cell proliferation IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of protein kinase C signaling IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of protein phosphorylation IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of vascular endothelial growth factor production IMP
Inferred from Mutant Phenotype
more info
PubMed 
protein autophosphorylation IDA
Inferred from Direct Assay
more info
PubMed 
regulation of blood vessel remodeling ISS
Inferred from Sequence or Structural Similarity
more info
 
respiratory system process IEA
Inferred from Electronic Annotation
more info
 
sprouting angiogenesis IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
sprouting angiogenesis ISS
Inferred from Sequence or Structural Similarity
more info
 
transmembrane receptor protein tyrosine kinase signaling pathway TAS
Traceable Author Statement
more info
PubMed 
vascular endothelial growth factor receptor signaling pathway IDA
Inferred from Direct Assay
more info
PubMed 
vascular endothelial growth factor receptor signaling pathway IGI
Inferred from Genetic Interaction
more info
PubMed 
vascular endothelial growth factor receptor signaling pathway IMP
Inferred from Mutant Phenotype
more info
PubMed 
vascular endothelial growth factor receptor signaling pathway TAS
Traceable Author Statement
more info
 
vascular endothelial growth factor signaling pathway IDA
Inferred from Direct Assay
more info
PubMed 
vasculature development ISS
Inferred from Sequence or Structural Similarity
more info
 
Component Evidence Code Pubs
cytoplasm IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
cytoplasm IEA
Inferred from Electronic Annotation
more info
 
extracellular region IEA
Inferred from Electronic Annotation
more info
 
integral component of plasma membrane IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
integral component of plasma membrane IEA
Inferred from Electronic Annotation
more info
 
nucleoplasm IDA
Inferred from Direct Assay
more info
 
plasma membrane IDA
Inferred from Direct Assay
more info
PubMed 
plasma membrane TAS
Traceable Author Statement
more info
 
receptor complex IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
receptor complex IDA
Inferred from Direct Assay
more info
PubMed 

General protein information

Preferred Names
vascular endothelial growth factor receptor 3
Names
fms-like tyrosine kinase 4
tyrosine-protein kinase receptor FLT4
NP_001341918.1
NP_002011.2
NP_891555.2
XP_011532780.1
XP_011532786.1
XP_016864752.1
XP_016864753.1
XP_016864754.1
XP_016864755.1
XP_016864756.1
XP_016864757.1

NCBI Reference Sequences (RefSeq)

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.

Genomic

  1. NG_011536.1 RefSeqGene

    Range
    5001..53119
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001354989.1NP_001341918.1  vascular endothelial growth factor receptor 3 isoform 3 precursor

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) contains an alternate 3' terminal exon compared to variant 1. This results in an isoform (3) with a shorter C-terminus compared to isoform 1.
    Source sequence(s)
    AC122714
    Consensus CDS
    CCDS87360.1
    Related
    ENSP00000426057.1, ENST00000502649.5
    Conserved Domains (6) summary
    cd05862
    Location:245329
    Ig_VEGFR; Immunoglobulin (Ig)-like domain of vascular endothelial growth factor (VEGF) receptor(R)
    cd05863
    Location:352418
    Ig_VEGFR-3; Immunoglobulin (Ig)-like domain of vascular endothelial growth factor receptor 3 (VEGFR-3)
    smart00408
    Location:693755
    IGc2; Immunoglobulin C-2 Type
    smart00410
    Location:564657
    IG_like; Immunoglobulin like
    cd05102
    Location:8371176
    PTKc_VEGFR3; Catalytic domain of the Protein Tyrosine Kinase, Vascular Endothelial Growth Factor Receptor 3
    pfam13895
    Location:137224
    Ig_2; Immunoglobulin domain
  2. NM_002020.4NP_002011.2  vascular endothelial growth factor receptor 3 isoform 2 precursor

    See identical proteins and their annotated locations for NP_002011.2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) contains an alternate 3' terminal exon compared to variant 1. This results in an isoform (2) with a shorter C-terminus compared to isoform 1.
    Source sequence(s)
    AC122714, AY233382, DB455035, X68203
    Consensus CDS
    CCDS43412.1
    UniProtKB/Swiss-Prot
    P35916
    Related
    ENSP00000377016.3, OTTHUMP00000223511, ENST00000393347.7, OTTHUMT00000372538
    Conserved Domains (10) summary
    cd05862
    Location:245329
    Ig1_VEGFR; First immunoglobulin (Ig)-like domain of vascular endothelial growth factor (VEGF) receptor(R)
    cd05863
    Location:352418
    Ig2_VEGFR-3; Second immunoglobulin (Ig)-like domain of vascular endothelial growth factor receptor 3 (VEGFR-3)
    smart00408
    Location:693755
    IGc2; Immunoglobulin C-2 Type
    smart00409
    Location:564657
    IG; Immunoglobulin
    smart00410
    Location:238327
    IG_like; Immunoglobulin like
    pfam07679
    Location:678765
    I-set; Immunoglobulin I-set domain
    cd05102
    Location:8371176
    PTKc_VEGFR3; Catalytic domain of the Protein Tyrosine Kinase, Vascular Endothelial Growth Factor Receptor 3
    pfam07714
    Location:8451169
    Pkinase_Tyr; Protein tyrosine kinase
    pfam13895
    Location:138224
    Ig_2; Immunoglobulin domain
    cl11960
    Location:570658
    Ig; Immunoglobulin domain
  3. NM_182925.4NP_891555.2  vascular endothelial growth factor receptor 3 isoform 1 precursor

    See identical proteins and their annotated locations for NP_891555.2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) encodes the longest isoform (1).
    Source sequence(s)
    AC122714, AY233383, DB455035, X68203
    Consensus CDS
    CCDS4457.1
    UniProtKB/Swiss-Prot
    P35916
    Related
    ENSP00000261937.6, OTTHUMP00000161539, ENST00000261937.10, OTTHUMT00000253527
    Conserved Domains (10) summary
    cd05862
    Location:245329
    Ig1_VEGFR; First immunoglobulin (Ig)-like domain of vascular endothelial growth factor (VEGF) receptor(R)
    cd05863
    Location:352418
    Ig2_VEGFR-3; Second immunoglobulin (Ig)-like domain of vascular endothelial growth factor receptor 3 (VEGFR-3)
    smart00408
    Location:693755
    IGc2; Immunoglobulin C-2 Type
    smart00409
    Location:564657
    IG; Immunoglobulin
    smart00410
    Location:238327
    IG_like; Immunoglobulin like
    pfam07679
    Location:678765
    I-set; Immunoglobulin I-set domain
    cd05102
    Location:8371176
    PTKc_VEGFR3; Catalytic domain of the Protein Tyrosine Kinase, Vascular Endothelial Growth Factor Receptor 3
    pfam07714
    Location:8451169
    Pkinase_Tyr; Protein tyrosine kinase
    pfam13895
    Location:138224
    Ig_2; Immunoglobulin domain
    cl11960
    Location:570658
    Ig; Immunoglobulin domain

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109 details...Open this link in a new tab

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

Reference GRCh38.p12 Primary Assembly

Genomic

  1. NC_000005.10 Reference GRCh38.p12 Primary Assembly

    Range
    180601506..180650298 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_017009268.1XP_016864757.1  vascular endothelial growth factor receptor 3 isoform X5

  2. XM_017009263.1XP_016864752.1  vascular endothelial growth factor receptor 3 isoform X2

  3. XM_011534478.3XP_011532780.1  vascular endothelial growth factor receptor 3 isoform X1

    Conserved Domains (10) summary
    cd05862
    Location:322406
    Ig1_VEGFR; First immunoglobulin (Ig)-like domain of vascular endothelial growth factor (VEGF) receptor(R)
    cd05863
    Location:429495
    Ig2_VEGFR-3; Second immunoglobulin (Ig)-like domain of vascular endothelial growth factor receptor 3 (VEGFR-3)
    smart00408
    Location:770832
    IGc2; Immunoglobulin C-2 Type
    smart00409
    Location:641734
    IG; Immunoglobulin
    smart00410
    Location:315404
    IG_like; Immunoglobulin like
    pfam07679
    Location:755842
    I-set; Immunoglobulin I-set domain
    cd05102
    Location:9141253
    PTKc_VEGFR3; Catalytic domain of the Protein Tyrosine Kinase, Vascular Endothelial Growth Factor Receptor 3
    pfam07714
    Location:9221246
    Pkinase_Tyr; Protein tyrosine kinase
    pfam13895
    Location:215301
    Ig_2; Immunoglobulin domain
    cl11960
    Location:647735
    Ig; Immunoglobulin domain
  4. XM_011534484.2XP_011532786.1  vascular endothelial growth factor receptor 3 isoform X6

    Conserved Domains (10) summary
    cd05862
    Location:92176
    Ig1_VEGFR; First immunoglobulin (Ig)-like domain of vascular endothelial growth factor (VEGF) receptor(R)
    cd05863
    Location:199265
    Ig2_VEGFR-3; Second immunoglobulin (Ig)-like domain of vascular endothelial growth factor receptor 3 (VEGFR-3)
    smart00408
    Location:540602
    IGc2; Immunoglobulin C-2 Type
    smart00409
    Location:411504
    IG; Immunoglobulin
    smart00410
    Location:85174
    IG_like; Immunoglobulin like
    pfam07679
    Location:525612
    I-set; Immunoglobulin I-set domain
    cd05102
    Location:6841023
    PTKc_VEGFR3; Catalytic domain of the Protein Tyrosine Kinase, Vascular Endothelial Growth Factor Receptor 3
    pfam07714
    Location:6921016
    Pkinase_Tyr; Protein tyrosine kinase
    pfam13895
    Location:171
    Ig_2; Immunoglobulin domain
    cl11960
    Location:417505
    Ig; Immunoglobulin domain
  5. XM_017009266.1XP_016864755.1  vascular endothelial growth factor receptor 3 isoform X3

  6. XM_017009264.2XP_016864753.1  vascular endothelial growth factor receptor 3 isoform X2

  7. XM_017009265.1XP_016864754.1  vascular endothelial growth factor receptor 3 isoform X2

  8. XM_017009267.2XP_016864756.1  vascular endothelial growth factor receptor 3 isoform X4

RNA

  1. XR_001742050.2 RNA Sequence

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