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UniProtKB - P35916 (VGFR3_HUMAN)

Entry version 223 (23 Feb 2022)
Sequence version 3 (16 Nov 2011)
Previous versions | rss
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Protein

Vascular endothelial growth factor receptor 3

Gene

FLT4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score:

Annotation score:5 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>-Experimental evidence at protein leveli <p>This indicates the type of evidence that supports the existence of the protein. Note that the 'protein existence' evidence does not give information on the accuracy or correctness of the sequence(s) displayed.<p><a href='/help/protein_existence' target='_top'>More...</a></p>

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

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'.

15 Publications

<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section describes the catalytic activity of an enzyme, i.e. a chemical reaction that the enzyme catalyzes.<p><a href='/help/catalytic_activity' target='_top'>More...</a></p>Catalytic activityi

<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section describes regulatory mechanisms for enzymes, transporters or microbial transcription factors, and reports the components which regulate (by activation or inhibition) the reaction.<p><a href='/help/activity_regulation' target='_top'>More...</a></p>Activity regulationi

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 MAZ51.3 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section describes the interaction between a single amino acid and another chemical entity. Priority is given to the annotation of physiological ligands.<p><a href='/help/binding' target='_top'>More...</a></p>Binding sitei879ATPCurated1
<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section is used for enzymes and indicates the residues directly involved in catalysis.<p><a href='/help/act_site' target='_top'>More...</a></p>Active sitei1037Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section describes a region in the protein which binds nucleotide phosphates. It always involves more than one amino acid and includes all residues involved in nucleotide-binding.<p><a href='/help/np_bind' target='_top'>More...</a></p>Nucleotide bindingi851 – 859ATPPROSITE-ProRule annotation9

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

Complete GO annotation on QuickGO ...

GO - Biological processi

Complete GO annotation on QuickGO ...

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsi

Molecular functionKinase, Receptor, Transferase, Tyrosine-protein kinase
Biological processAngiogenesis
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDA Comprehensive Enzyme Information System

More...BRENDAi		2.7.10.1, 2681

Pathway Commons web resource for biological pathway data

More...PathwayCommonsi		P35916

Reactome - a knowledgebase of biological pathways and processes

More...Reactomei		R-HSA-195399, VEGF binds to VEGFR leading to receptor dimerization
R-HSA-9013695, NOTCH4 Intracellular Domain Regulates Transcription

SignaLink: a signaling pathway resource with multi-layered regulatory networks

More...SignaLinki		P35916

SIGNOR Signaling Network Open Resource

More...SIGNORi		P35916

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>Protein namesi
Recommended name:
Vascular endothelial growth factor receptor 3 (EC:2.7.10.1)
Short name:
VEGFR-3
Alternative name(s):
Fms-like tyrosine kinase 4
Short name:
FLT-4
Tyrosine-protein kinase receptor FLT4
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. Four distinct tokens exist: 'Name', 'Synonyms', 'Ordered locus names' and 'ORF names'.<p><a href='/help/gene_name' target='_top'>More...</a></p>Gene namesi
Name:FLT4
Synonyms:VEGFR3
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>OrganismiHomo sapiens (Human)
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the 'taxonomic identifier' or 'taxid'.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri9606 [NCBI]
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section is present for entries that are part of a <a href="http://www.uniprot.org/proteomes">proteome</a>, i.e. of a set of proteins thought to be expressed by organisms whose genomes have been completely sequenced.<p><a href='/help/proteomes_manual' target='_top'>More...</a></p>Proteomesi
  • UP000005640 <p>A UniProt <a href="http://www.uniprot.org/manual/proteomes%5Fmanual">proteome</a> can consist of several components.<br></br>The component name refers to the genomic component encoding a set of proteins.<p><a href='/help/proteome_component' target='_top'>More...</a></p> Componenti: Chromosome 5

Organism-specific databases

Human Gene Nomenclature Database

More...HGNCi		HGNC:3767, FLT4

Online Mendelian Inheritance in Man (OMIM)

More...MIMi		136352, gene

neXtProt; the human protein knowledge platform

More...neXtProti		NX_P35916

Eukaryotic Pathogen, Vector and Host Database Resources

More...VEuPathDBi		HostDB:ENSG00000037280

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/subcellular%5Flocation%5Fsection">'Subcellular location'</a> section describes the subcellular compartment where each non-membrane region of a membrane-spanning protein is found.<p><a href='/help/topo_dom' target='_top'>More...</a></p>Topological domaini25 – 775ExtracellularSequence analysisAdd BLAST751
<p>This subsection of the <a href="http://www.uniprot.org/help/subcellular%5Flocation%5Fsection">'Subcellular location'</a> section describes the extent of a membrane-spanning region of the protein. It denotes the presence of both alpha-helical transmembrane regions and the membrane spanning regions of beta-barrel transmembrane proteins.<p><a href='/help/transmem' target='_top'>More...</a></p>Transmembranei776 – 796HelicalSequence analysisAdd BLAST21
Topological domaini797 – 1363CytoplasmicSequence analysisAdd BLAST567

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane, Nucleus, Secreted

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

<p>This subsection of the 'Pathology and Biotech' section provides information on the disease(s) associated with genetic variations in a given protein. The information is extracted from the scientific literature and diseases that are also described in the <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?db=omim">OMIM</a> database are represented with a <a href="http://www.uniprot.org/diseases">controlled vocabulary</a> in the following way:<p><a href='/help/involvement_in_disease' target='_top'>More...</a></p>Involvement in diseasei

Lymphatic malformation 1 (LMPHM1)10 Publications
The disease is caused by variants affecting the gene represented in this entry.
Disease descriptionA form of primary lymphedema, a disease characterized by swelling of body parts due to developmental anomalies and functional defects of the lymphatic system. Patients with lymphedema may suffer from recurrent local infections. LMPHM1 is an autosomal dominant form with variable expression and severity. Onset is usually at birth or in early childhood but can occur later. Affected individuals manifest lymphedema, predominantly in the lower limbs, and hypoplasia of lymphatic vessels. Additional features are hemangioma and nail dysplasia or papillomatosis.
Related information in OMIM
Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Sequence' section describes natural variant(s) of the protein sequence.<p><a href='/help/variant' target='_top'>More...</a></p>Natural variantiVAR_074044855A → T in LMPHM1; recessive form; results in reduced autophosphorylation; results in impaired ligand-induced receptor internalization and downstream signaling. 1 PublicationCorresponds to variant dbSNP:rs121909657EnsemblClinVar.1
Natural variantiVAR_018409857G → R in LMPHM1; loss of kinase activity. 2 PublicationsCorresponds to variant dbSNP:rs267606818EnsemblClinVar.1
Natural variantiVAR_074045878V → M in LMPHM1. 1 PublicationCorresponds to variant dbSNP:rs121909654EnsemblClinVar.1
Natural variantiVAR_0740461020Q → L in LMPHM1. 1 Publication1
Natural variantiVAR_0184121035H → R in LMPHM1; loss of kinase activity. 1 PublicationCorresponds to variant dbSNP:rs121909653EnsemblClinVar.1
Natural variantiVAR_0184131041R → P in LMPHM1; loss of kinase activity. 2 PublicationsCorresponds to variant dbSNP:rs121909650EnsemblClinVar.1
Natural variantiVAR_0184141044L → P in LMPHM1; loss of kinase activity. 1 PublicationCorresponds to variant dbSNP:rs121909651EnsemblClinVar.1
Natural variantiVAR_0740481086I → T in LMPHM1. 1 PublicationCorresponds to variant dbSNP:rs121909655EnsemblClinVar.1
Natural variantiVAR_0740491106E → K in LMPHM1. 1 PublicationCorresponds to variant dbSNP:rs121909656EnsemblClinVar.1
Natural variantiVAR_0740501108Missing in LMPHM1. 1 Publication1
Natural variantiVAR_0184151114P → L in LMPHM1; loss of kinase activity. 2 PublicationsCorresponds to variant dbSNP:rs121909652EnsemblClinVar.1
Natural variantiVAR_0740511235S → C in LMPHM1; recessive form. 1 Publication1
Hemangioma, capillary infantile (HCI)1 Publication
Disease susceptibility is associated with variants affecting the gene represented in this entry.
Disease descriptionA 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.
Related information in OMIM
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_018411954P → S in HCI. 1 PublicationCorresponds to variant dbSNP:rs34255532EnsemblClinVar.1
Natural variantiVAR_0184161137P → S in HCI. 1 Publication1
Plays an important role in tumor lymphangiogenesis, in cancer cell survival, migration, and formation of metastases.
Congenital heart defects, multiple types, 7 (CHTD7)2 Publications
The disease is caused by variants affecting the gene represented in this entry.
Disease descriptionAn autosomal dominant disorder with incomplete penetrance characterized by congenital developmental abnormalities involving structures of the heart. Common defects include tetralogy of Fallot, pulmonary stenosis or atresia, absent pulmonary valve, right aortic arch, double aortic arch, and major aortopulmonary collateral arteries.
Related information in OMIM
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_08380682 – 1363Missing in CHTD7. 1 PublicationAdd BLAST1282
Natural variantiVAR_083807361 – 1363Missing in CHTD7. 1 PublicationAdd BLAST1003
Natural variantiVAR_083808736 – 1363Missing in CHTD7. 1 PublicationAdd BLAST628
Natural variantiVAR_083809741Missing in CHTD7; unknown pathological significance. 1 Publication1
Natural variantiVAR_083810833 – 1363Missing in CHTD7. 1 PublicationAdd BLAST531
Natural variantiVAR_083811999 – 1363Missing in CHTD7. 1 PublicationAdd BLAST365
Natural variantiVAR_0838121173L → V in CHTD7; unknown pathological significance. 1 Publication1
Natural variantiVAR_0838131192 – 1363Missing in CHTD7. 1 PublicationAdd BLAST172

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/manual/pathology%5Fand%5Fbiotech%5Fsection">'Pathology and Biotech'</a> section describes the effect of the experimental mutation of one or more amino acid(s) on the biological properties of the protein.<p><a href='/help/mutagen' target='_top'>More...</a></p>Mutagenesisi446T → E: Decreases autophosphorylation on tyrosine residues upon ligand binding; when associated with A-516. Abolishes autophosphorylation on tyrosine residues upon ligand binding; when associated with A-516 and A-737. 1 Publication1
Mutagenesisi516K → A: Decreases autophosphorylation on tyrosine residues upon ligand binding; when associated with E-446. Abolishes autophosphorylation on tyrosine residues upon ligand binding; when associated with E-446 and A-737. 1 Publication1
Mutagenesisi737R → A: Decreases autophosphorylation on tyrosine residues upon ligand binding. Abolishes autophosphorylation on tyrosine residues upon ligand binding; when associated with E-446 and A-516. 1 Publication1
Mutagenesisi879K → G: Abolishes enzyme activity. 1 Publication1
Mutagenesisi1063Y → F: Loss of phosphorylation site. No effect on stimulation of cell proliferation and cell migration. 2 Publications1
Mutagenesisi1068Y → F: Global loss of autophosphorylation. Abolishes stimulation of cell proliferation and cell migration. 2 Publications1
Mutagenesisi1230Y → F: Loss of phosphorylation site. Strongly reduces stimulation of cell proliferation and cell migration. 2 Publications1
Mutagenesisi1231Y → F: Loss of phosphorylation site. Strongly reduces stimulation of cell proliferation and cell migration. 2 Publications1
Mutagenesisi1265Y → F: Loss of phosphorylation site. No effect on stimulation of cell proliferation and cell migration. 1 Publication1
Mutagenesisi1333Y → F: Loss of phosphorylation site. Reduced autophosphorylation. 2 Publications1
Mutagenesisi1337Y → F: Reduced autophosphorylation. Strongly reduces stimulation of cell proliferation and cell migration. 3 Publications1
Mutagenesisi1363Y → F: Loss of phosphorylation site. Slightly reduced autophosphorylation. 2 Publications1

Keywords - Diseasei

Disease variant

Organism-specific databases

DisGeNET

More...DisGeNETi		2324

GeneReviews a resource of expert-authored, peer-reviewed disease descriptions.

More...GeneReviewsi		FLT4

MalaCards human disease database

More...MalaCardsi		FLT4
MIMi153100, phenotype
602089, phenotype
618780, phenotype

Open Targets

More...OpenTargetsi		ENSG00000037280

Orphanet; a database dedicated to information on rare diseases and orphan drugs

More...Orphaneti		79452, Milroy disease
464293, NON RARE IN EUROPE: Infantile capillary hemangioma
3303, Tetralogy of Fallot

The Pharmacogenetics and Pharmacogenomics Knowledge Base

More...PharmGKBi		PA28183

Miscellaneous databases

Pharos NIH Druggable Genome Knowledgebase

More...Pharosi		P35916, Tclin

Chemistry databases

ChEMBL database of bioactive drug-like small molecules

More...ChEMBLi		CHEMBL1955

Drug and drug target database

More...DrugBanki		DB06080, ABT-869
DB06626, Axitinib
DB05932, Denibulin
DB12010, Fostamatinib
DB06101, IMC-1C11
DB09078, Lenvatinib
DB09079, Nintedanib
DB06589, Pazopanib
DB08896, Regorafenib
DB15685, Selpercatinib
DB00398, Sorafenib
DB01268, Sunitinib
DB05075, TG-100801
DB04879, Vatalanib

DrugCentral

More...DrugCentrali		P35916

IUPHAR/BPS Guide to PHARMACOLOGY

More...GuidetoPHARMACOLOGYi		1814

Genetic variation databases

BioMuta curated single-nucleotide variation and disease association database

More...BioMutai		FLT4

Domain mapping of disease mutations (DMDM)

More...DMDMi		357529070

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'PTM / Processing' section denotes the presence of an N-terminal signal peptide.<p><a href='/help/signal' target='_top'>More...</a></p>Signal peptidei1 – 241 PublicationAdd BLAST24
<p>This subsection of the 'PTM / Processing' section describes the extent of a polypeptide chain in the mature protein following processing or proteolytic cleavage.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_000001677625 – 1363Vascular endothelial growth factor receptor 3Add BLAST1339

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/ptm%5Fprocessing%5Fsection">PTM / Processing</a> section specifies the position and type of each covalently attached glycan group (mono-, di-, or polysaccharide).<p><a href='/help/carbohyd' target='_top'>More...</a></p>Glycosylationi33N-linked (GlcNAc...) asparagineCombined sources1 Publication1
<p>This subsection of the PTM / Processing":/help/ptm_processing_section section describes the positions of cysteine residues participating in disulfide bonds.<p><a href='/help/disulfid' target='_top'>More...</a></p>Disulfide bondi51 ↔ 111PROSITE-ProRule annotation1 Publication
Glycosylationi104N-linked (GlcNAc...) asparagineCombined sources1 Publication1
Disulfide bondi158 ↔ 206PROSITE-ProRule annotation1 Publication
Glycosylationi166N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi251N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi252 ↔ 310PROSITE-ProRule annotation
Glycosylationi299N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi411N-linked (GlcNAc...) asparagineCombined sources1 Publication1
Disulfide bondi445 ↔ 534PROSITE-ProRule annotation1 Publication
Disulfide bondi466 ↔ 4861 Publication
Glycosylationi515N-linked (GlcNAc...) asparagineCombined sources1 Publication1
Glycosylationi527N-linked (GlcNAc...) asparagine1 Publication1
Disulfide bondi578 ↔ 653PROSITE-ProRule annotation
Glycosylationi594N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi683N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi690N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi699 ↔ 751PROSITE-ProRule annotation
Glycosylationi758N-linked (GlcNAc...) asparagineSequence analysis1
<p>This subsection of the 'PTM / Processing' section specifies the position and type of each modified residue excluding <a href="http://www.uniprot.org/manual/lipid">lipids</a>, <a href="http://www.uniprot.org/manual/carbohyd">glycans</a> and <a href="http://www.uniprot.org/manual/crosslnk">protein cross-links</a>.<p><a href='/help/mod_res' target='_top'>More...</a></p>Modified residuei830Phosphotyrosine; by SRC1 Publication1
Modified residuei833Phosphotyrosine; by SRC1 Publication1
Modified residuei853Phosphotyrosine; by SRC1 Publication1
Modified residuei1063Phosphotyrosine; by autocatalysis and SRC2 Publications1
Modified residuei1068Phosphotyrosine; by autocatalysis2 Publications1
Modified residuei1230Phosphotyrosine; by autocatalysis2 Publications1
Modified residuei1231Phosphotyrosine; by autocatalysis2 Publications1
Modified residuei1265Phosphotyrosine; by autocatalysis1 Publication1
Modified residuei1333Phosphotyrosine; by autocatalysis and SRC2 Publications1
Modified residuei1337Phosphotyrosine; by autocatalysis and SRC3 Publications1
Modified residuei1363Phosphotyrosine; by autocatalysis1 Publication1

<p>This subsection of the <a href="http://www.uniprot.org/help/ptm%5Fprocessing%5Fsection">PTM/processing</a> section describes post-translational modifications (PTMs). This subsection <strong>complements</strong> the information provided at the sequence level or describes modifications for which <strong>position-specific data is not yet available</strong>.<p><a href='/help/post-translational_modification' target='_top'>More...</a></p>Post-translational modificationi

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 H2O2 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-1337.7 Publications

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

jPOST - Japan Proteome Standard Repository/Database

More...jPOSTi		P35916

MassIVE - Mass Spectrometry Interactive Virtual Environment

More...MassIVEi		P35916

PaxDb, a database of protein abundance averages across all three domains of life

More...PaxDbi		P35916

PeptideAtlas

More...PeptideAtlasi		P35916

PRoteomics IDEntifications database

More...PRIDEi		P35916

ProteomicsDB: a multi-organism proteome resource

More...ProteomicsDBi		55166 [P35916-2]
55167 [P35916-1]
55168 [P35916-3]

PTM databases

GlyGen: Computational and Informatics Resources for Glycoscience

More...GlyGeni		P35916, 12 sites

iPTMnet integrated resource for PTMs in systems biology context

More...iPTMneti		P35916

Comprehensive resource for the study of protein post-translational modifications (PTMs) in human, mouse and rat.

More...PhosphoSitePlusi		P35916

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

<p>This subsection of the 'Expression' section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms. By default, the information is derived from experiments at the mRNA level, unless specified 'at protein level'.<br></br>Examples: <a href="http://www.uniprot.org/uniprot/P92958#expression">P92958</a>, <a href="http://www.uniprot.org/uniprot/Q8TDN4#expression">Q8TDN4</a>, <a href="http://www.uniprot.org/uniprot/O14734#expression">O14734</a><p><a href='/help/tissue_specificity' target='_top'>More...</a></p>Tissue specificityi

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.3 Publications

Gene expression databases

Bgee dataBase for Gene Expression Evolution

More...Bgeei		ENSG00000037280, Expressed in left lobe of thyroid gland and 141 other tissues

ExpressionAtlas, Differential and Baseline Expression

More...ExpressionAtlasi		P35916, baseline and differential

Genevisible search portal to normalized and curated expression data from Genevestigator

More...Genevisiblei		P35916, HS

Organism-specific databases

Human Protein Atlas

More...HPAi		ENSG00000037280, Low tissue specificity

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

<p>This subsection of the <a href="http://www.uniprot.org/help/interaction%5Fsection">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function%5Fsection">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structurei

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.

14 Publications

<p>This subsection of the '<a href="http://www.uniprot.org/help/interaction%5Fsection">Interaction</a>' section provides information about binary protein-protein interactions. The data presented in this section are a quality-filtered subset of binary interactions automatically derived from the <a href="https://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated at every <a href="http://www.uniprot.org/help/synchronization">UniProt release</a>.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsi

Hide details

GO - Molecular functioni

Complete GO annotation on QuickGO ...

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGRID)

More...BioGRIDi		108612, 35 interactors

CORUM comprehensive resource of mammalian protein complexes

More...CORUMi		P35916

Database of interacting proteins

More...DIPi		DIP-5739N

Protein interaction database and analysis system

More...IntActi		P35916, 18 interactors

Molecular INTeraction database

More...MINTi		P35916

STRING: functional protein association networks

More...STRINGi		9606.ENSP00000261937

Chemistry databases

BindingDB database of measured binding affinities

More...BindingDBi		P35916

Miscellaneous databases

RNAct, Protein-RNA interaction predictions for model organisms.

More...RNActi		P35916, protein

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

Secondary structure

11363
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

SWISS-MODEL Repository - a database of annotated 3D protein structure models

More...SMRi		P35916

Database of comparative protein structure models

More...ModBasei		Search...

Protein Data Bank in Europe - Knowledge Base

More...PDBe-KBi		Search...

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/family%5Fand%5Fdomains%5Fsection">Family and Domains</a> section describes the position and type of a domain, which is defined as a specific combination of secondary structures organized into a characteristic three-dimensional structure or fold.<p><a href='/help/domain' target='_top'>More...</a></p>Domaini30 – 127Ig-like C2-type 1Add BLAST98
Domaini151 – 213Ig-like C2-type 2Add BLAST63
Domaini219 – 326Ig-like C2-type 3Add BLAST108
Domaini331 – 415Ig-like C2-type 4Add BLAST85
Domaini422 – 552Ig-like C2-type 5Add BLAST131
Domaini555 – 671Ig-like C2-type 6Add BLAST117
Domaini678 – 764Ig-like C2-type 7Add BLAST87
Domaini845 – 1173Protein kinasePROSITE-ProRule annotationAdd BLAST329

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Family and Domains' section describes a region of interest that cannot be described in other subsections.<p><a href='/help/region' target='_top'>More...</a></p>Regioni1291 – 1331DisorderedSequence analysisAdd BLAST41

<p>This subsection of the 'Family and domains' section provides general information on the biological role of a domain. The term 'domain' is intended here in its wide acceptation, it may be a structural domain, a transmembrane region or a functional domain. Several domains are described in this subsection.<p><a href='/help/domain_cc' target='_top'>More...</a></p>Domaini

The first and second Ig-like C2-type (immunoglobulin-like) domains are sufficient for VEGFC binding (PubMed:23878260). The fourth and fifth Ig-like C2-type domains are sufficient for homodimerization (PubMed:23878260). The fifth and seventh Ig-like C2-type domains are required for autophosphorylation and further activation (PubMed:23878260).1 Publication

<p>This subsection of the 'Family and domains' section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Belongs to the protein kinase superfamily. Tyr protein kinase family. CSF-1/PDGF receptor subfamily.PROSITE-ProRule annotation

Keywords - Domaini

Immunoglobulin domain, Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

evolutionary genealogy of genes: Non-supervised Orthologous Groups

More...eggNOGi		KOG0200, Eukaryota

Ensembl GeneTree

More...GeneTreei		ENSGT00940000159358

The HOGENOM Database of Homologous Genes from Fully Sequenced Organisms

More...HOGENOMi		CLU_000288_49_4_1

InParanoid: Eukaryotic Ortholog Groups

More...InParanoidi		P35916

Identification of Orthologs from Complete Genome Data

More...OMAi		RPYCKRL

Database of Orthologous Groups

More...OrthoDBi		236292at2759

Database for complete collections of gene phylogenies

More...PhylomeDBi		P35916

TreeFam database of animal gene trees

More...TreeFami		TF325768

Family and domain databases

Database of protein disorder

More...DisProti		DP02600

Gene3D Structural and Functional Annotation of Protein Families

More...Gene3Di		2.60.40.10, 7 hits

Integrated resource of protein families, domains and functional sites

More...InterProi		View protein in InterPro
IPR007110, Ig-like_dom
IPR036179, Ig-like_dom_sf
IPR013783, Ig-like_fold
IPR013098, Ig_I-set
IPR003599, Ig_sub
IPR003598, Ig_sub2
IPR011009, Kinase-like_dom_sf
IPR000719, Prot_kinase_dom
IPR017441, Protein_kinase_ATP_BS
IPR001245, Ser-Thr/Tyr_kinase_cat_dom
IPR008266, Tyr_kinase_AS
IPR020635, Tyr_kinase_cat_dom
IPR001824, Tyr_kinase_rcpt_3_CS
IPR041348, VEGFR-2_TMD
IPR009137, VEGFR3_rcpt

The PANTHER Classification System

More...PANTHERi		PTHR24416:SF562, PTHR24416:SF562, 1 hit

Pfam protein domain database

More...Pfami		View protein in Pfam
PF07679, I-set, 1 hit
PF07714, PK_Tyr_Ser-Thr, 1 hit
PF17988, VEGFR-2_TMD, 1 hit

Simple Modular Architecture Research Tool; a protein domain database

More...SMARTi		View protein in SMART
SM00409, IG, 6 hits
SM00408, IGc2, 4 hits
SM00219, TyrKc, 1 hit

Superfamily database of structural and functional annotation

More...SUPFAMi		SSF48726, SSF48726, 6 hits
SSF56112, SSF56112, 1 hit

PROSITE; a protein domain and family database

More...PROSITEi		View protein in PROSITE
PS50835, IG_LIKE, 6 hits
PS00107, PROTEIN_KINASE_ATP, 1 hit
PS50011, PROTEIN_KINASE_DOM, 1 hit
PS00109, PROTEIN_KINASE_TYR, 1 hit
PS00240, RECEPTOR_TYR_KIN_III, 1 hit

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence%5Flength">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>. The information is filed in different subsections. The current subsections and their content are listed below:<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequences (3+)i

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences%5Fsection">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusi: Complete.

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences%5Fsection">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> displayed by default in the entry is in its mature form or if it represents the precursor.<p><a href='/help/sequence_processing' target='_top'>More...</a></p>Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 3 <p>This subsection of the 'Sequence' section lists the alternative protein sequences (isoforms) that can be generated from the same gene by a single or by the combination of up to four biological events (alternative promoter usage, alternative splicing, alternative initiation and ribosomal frameshifting). Additionally, this section gives relevant information on each alternative protein isoform.<p><a href='/help/alternative_products' target='_top'>More...</a></p> isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 3 described isoforms and 3 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: P35916-2) [UniParc]FASTAAdd to basket
Also known as: Long

This isoform has been chosen as the <p><strong>What is the canonical sequence?</strong><p><a href='/help/canonical_and_isoforms' target='_top'>More...</a></p>canonicali sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MQRGAALCLR LWLCLGLLDG LVSGYSMTPP TLNITEESHV IDTGDSLSIS 
        60         70         80         90        100
CRGQHPLEWA WPGAQEAPAT GDKDSEDTGV VRDCEGTDAR PYCKVLLLHE 
       110        120        130        140        150
VHANDTGSYV CYYKYIKARI EGTTAASSYV FVRDFEQPFI NKPDTLLVNR 
       160        170        180        190        200
KDAMWVPCLV SIPGLNVTLR SQSSVLWPDG QEVVWDDRRG MLVSTPLLHD 
       210        220        230        240        250
ALYLQCETTW GDQDFLSNPF LVHITGNELY DIQLLPRKSL ELLVGEKLVL 
       260        270        280        290        300
NCTVWAEFNS GVTFDWDYPG KQAERGKWVP ERRSQQTHTE LSSILTIHNV 
       310        320        330        340        350
SQHDLGSYVC KANNGIQRFR ESTEVIVHEN PFISVEWLKG PILEATAGDE 
       360        370        380        390        400
LVKLPVKLAA YPPPEFQWYK DGKALSGRHS PHALVLKEVT EASTGTYTLA 
       410        420        430        440        450
LWNSAAGLRR NISLELVVNV PPQIHEKEAS SPSIYSRHSR QALTCTAYGV 
       460        470        480        490        500
PLPLSIQWHW RPWTPCKMFA QRSLRRRQQQ DLMPQCRDWR AVTTQDAVNP 
       510        520        530        540        550
IESLDTWTEF VEGKNKTVSK LVIQNANVSA MYKCVVSNKV GQDERLIYFY 
       560        570        580        590        600
VTTIPDGFTI ESKPSEELLE GQPVLLSCQA DSYKYEHLRW YRLNLSTLHD 
       610        620        630        640        650
AHGNPLLLDC KNVHLFATPL AASLEEVAPG ARHATLSLSI PRVAPEHEGH 
       660        670        680        690        700
YVCEVQDRRS HDKHCHKKYL SVQALEAPRL TQNLTDLLVN VSDSLEMQCL 
       710        720        730        740        750
VAGAHAPSIV WYKDERLLEE KSGVDLADSN QKLSIQRVRE EDAGRYLCSV 
       760        770        780        790        800
CNAKGCVNSS ASVAVEGSED KGSMEIVILV GTGVIAVFFW VLLLLIFCNM 
       810        820        830        840        850
RRPAHADIKT GYLSIIMDPG EVPLEEQCEY LSYDASQWEF PRERLHLGRV 
       860        870        880        890        900
LGYGAFGKVV EASAFGIHKG SSCDTVAVKM LKEGATASEH RALMSELKIL 
       910        920        930        940        950
IHIGNHLNVV NLLGACTKPQ GPLMVIVEFC KYGNLSNFLR AKRDAFSPCA 
       960        970        980        990       1000
EKSPEQRGRF RAMVELARLD RRRPGSSDRV LFARFSKTEG GARRASPDQE 
      1010       1020       1030       1040       1050
AEDLWLSPLT MEDLVCYSFQ VARGMEFLAS RKCIHRDLAA RNILLSESDV 
      1060       1070       1080       1090       1100
VKICDFGLAR DIYKDPDYVR KGSARLPLKW MAPESIFDKV YTTQSDVWSF 
      1110       1120       1130       1140       1150
GVLLWEIFSL GASPYPGVQI NEEFCQRLRD GTRMRAPELA TPAIRRIMLN 
      1160       1170       1180       1190       1200
CWSGDPKARP AFSELVEILG DLLQGRGLQE EEEVCMAPRS SQSSEEGSFS 
      1210       1220       1230       1240       1250
QVSTMALHIA QADAEDSPPS LQRHSLAARY YNWVSFPGCL ARGAETRGSS 
      1260       1270       1280       1290       1300
RMKTFEEFPM TPTTYKGSVD NQTDSGMVLA SEEFEQIESR HRQESGFSCK 
      1310       1320       1330       1340       1350
GPGQNVAVTR AHPDSQGRRR RPERGARGGQ VFYNSEYGEL SEPSEEDHCS 
      1360 
PSARVTFFTD NSY
Length:1,363
Mass (Da):152,757
Last modified:November 16, 2011 - v3
<p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.</p> <p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.</p> <p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).</p> <p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x<sup>64</sup> + x<sup>4</sup> + x<sup>3</sup> + x + 1. The algorithm is described in the ISO 3309 standard. </p> <p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.<br /> <strong>Cyclic redundancy and other checksums</strong><br /> <a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993)</a>)</p> Checksum:iB1473AAAC95E7E93
GO
Isoform 2 (identifier: P35916-1) [UniParc]FASTAAdd to basket
Also known as: Short

The sequence of this isoform differs from the canonical sequence as follows:
     1298-1363: SCKGPGQNVAVTRAHPDSQGRRRRPERGARGGQVFYNSEYGELSEPSEEDHCSPSARVTFFTDNSY → R

Show »
Length:1,298
Mass (Da):145,599
Checksum:i3DC469ED3CB8B3B1
GO
Isoform 3 (identifier: P35916-3) [UniParc]FASTAAdd to basket
Also known as: sVegfr3

The sequence of this isoform differs from the canonical sequence as follows:
     724-765: VDLADSNQKL...CVNSSASVAV → REGGPGEGQV...ESTWRTPTRS
     766-1298: Missing.

Show »
Length:830
Mass (Da):93,174
Checksum:i873CB1459C93C49A
GO

<p>In eukaryotic reference proteomes, unreviewed entries that are likely to belong to the same gene are computationally mapped, based on gene identifiers from Ensembl, EnsemblGenomes and model organism databases.<p><a href='/help/gene_centric_isoform_mapping' target='_top'>More...</a></p>Computationally mapped potential isoform sequencesi

There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
E9PD35E9PD35_HUMAN
Vascular endothelial growth factor ...
FLT4
1,306Annotation score:

Annotation score:4 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
B5A927B5A927_HUMAN
Soluble VEGFR3 variant 2
FLT4 VEGFR3
295Annotation score:

Annotation score:2 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
D6RFF2D6RFF2_HUMAN
Vascular endothelial growth factor ...
FLT4
142Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>

<p>This subsection of the 'Sequence' section reports difference(s) between the protein sequence shown in the UniProtKB entry and other available protein sequences derived from the same gene.<p><a href='/help/sequence_caution' target='_top'>More...</a></p>Sequence cautioni

The sequence CAA48290 differs from that shown. Reason: Erroneous initiation. Extended N-terminus.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Sequence' section reports difference(s) between the canonical sequence (displayed by default in the entry) and the different sequence submissions merged in the entry. These various submissions may originate from different sequencing projects, different types of experiments, or different biological samples. Sequence conflicts are usually of unknown origin.<p><a href='/help/conflict' target='_top'>More...</a></p>Sequence conflicti24G → D in CAA49505 (PubMed:1319394).Curated1
Sequence conflicti24G → D in AAO89504 (Ref. 7) Curated1
Sequence conflicti24G → D in AAO89505 (Ref. 7) Curated1
Sequence conflicti538N → D in BAF84368 (PubMed:14702039).Curated1
Sequence conflicti745R → P in CAA49505 (PubMed:1319394).Curated1
Sequence conflicti745R → P in AAO89504 (Ref. 7) Curated1
Sequence conflicti745R → P in AAO89505 (Ref. 7) Curated1
Sequence conflicti752 – 753NA → RP in CAA49505 (PubMed:1319394).Curated2
Sequence conflicti752 – 753NA → RP in AAO89504 (Ref. 7) Curated2
Sequence conflicti752 – 753NA → RP in AAO89505 (Ref. 7) Curated2
Sequence conflicti1128L → V in CAA49505 (PubMed:1319394).Curated1
Sequence conflicti1128L → V in AAO89504 (Ref. 7) Curated1
Sequence conflicti1128L → V in AAO89505 (Ref. 7) Curated1
Sequence conflicti1164E → D in CAA49505 (PubMed:1319394).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_08380682 – 1363Missing in CHTD7. 1 PublicationAdd BLAST1282
Natural variantiVAR_042062149N → D1 PublicationCorresponds to variant dbSNP:rs34221241EnsemblClinVar.1
Natural variantiVAR_083807361 – 1363Missing in CHTD7. 1 PublicationAdd BLAST1003
Natural variantiVAR_042063378R → C in a renal clear cell carcinoma sample; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs372947534Ensembl.1
Natural variantiVAR_018407494T → A2 PublicationsCorresponds to variant dbSNP:rs307826EnsemblClinVar.1
Natural variantiVAR_034379527N → S1 PublicationCorresponds to variant dbSNP:rs35874891EnsemblClinVar.1
Natural variantiVAR_018408641P → S2 PublicationsCorresponds to variant dbSNP:rs55667289EnsemblClinVar.1
Natural variantiVAR_083808736 – 1363Missing in CHTD7. 1 PublicationAdd BLAST628
Natural variantiVAR_083809741Missing in CHTD7; unknown pathological significance. 1 Publication1
Natural variantiVAR_083810833 – 1363Missing in CHTD7. 1 PublicationAdd BLAST531
Natural variantiVAR_074044855A → T in LMPHM1; recessive form; results in reduced autophosphorylation; results in impaired ligand-induced receptor internalization and downstream signaling. 1 PublicationCorresponds to variant dbSNP:rs121909657EnsemblClinVar.1
Natural variantiVAR_018409857G → R in LMPHM1; loss of kinase activity. 2 PublicationsCorresponds to variant dbSNP:rs267606818EnsemblClinVar.1
Natural variantiVAR_042064868H → Y1 PublicationCorresponds to variant dbSNP:rs35171798EnsemblClinVar.1
Natural variantiVAR_074045878V → M in LMPHM1. 1 PublicationCorresponds to variant dbSNP:rs121909654EnsemblClinVar.1
Natural variantiVAR_018410890H → Q4 PublicationsCorresponds to variant dbSNP:rs448012EnsemblClinVar.1
Natural variantiVAR_018411954P → S in HCI. 1 PublicationCorresponds to variant dbSNP:rs34255532EnsemblClinVar.1
Natural variantiVAR_083811999 – 1363Missing in CHTD7. 1 PublicationAdd BLAST365
Natural variantiVAR_0420651010T → I in a metastatic melanoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_0740461020Q → L in LMPHM1. 1 Publication1
Natural variantiVAR_0420661031R → Q1 PublicationCorresponds to variant dbSNP:rs56082504Ensembl.1
Natural variantiVAR_0740471035H → Q Probable disease-associated variant found in sporadic congenital lymphedema; de novo mutation. 1 Publication1
Natural variantiVAR_0184121035H → R in LMPHM1; loss of kinase activity. 1 PublicationCorresponds to variant dbSNP:rs121909653EnsemblClinVar.1
Natural variantiVAR_0184131041R → P in LMPHM1; loss of kinase activity. 2 PublicationsCorresponds to variant dbSNP:rs121909650EnsemblClinVar.1
Natural variantiVAR_0184141044L → P in LMPHM1; loss of kinase activity. 1 PublicationCorresponds to variant dbSNP:rs121909651EnsemblClinVar.1
Natural variantiVAR_0420671049D → N1 PublicationCorresponds to variant dbSNP:rs56310180Ensembl.1
Natural variantiVAR_0420681075R → Q1 PublicationCorresponds to variant dbSNP:rs1400220848Ensembl.1
Natural variantiVAR_0740481086I → T in LMPHM1. 1 PublicationCorresponds to variant dbSNP:rs121909655EnsemblClinVar.1
Natural variantiVAR_0740491106E → K in LMPHM1. 1 PublicationCorresponds to variant dbSNP:rs121909656EnsemblClinVar.1
Natural variantiVAR_0740501108Missing in LMPHM1. 1 Publication1
Natural variantiVAR_0184151114P → L in LMPHM1; loss of kinase activity. 2 PublicationsCorresponds to variant dbSNP:rs121909652EnsemblClinVar.1
Natural variantiVAR_0184161137P → S in HCI. 1 Publication1
Natural variantiVAR_0184171146R → H4 PublicationsCorresponds to variant dbSNP:rs1130379EnsemblClinVar.1
Natural variantiVAR_0838121173L → V in CHTD7; unknown pathological significance. 1 Publication1
Natural variantiVAR_0838131192 – 1363Missing in CHTD7. 1 PublicationAdd BLAST172
Natural variantiVAR_0740511235S → C in LMPHM1; recessive form. 1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Sequence' section describes the sequence of naturally occurring alternative protein isoform(s). The changes in the amino acid sequence may be due to alternative splicing, alternative promoter usage, alternative initiation, or ribosomal frameshifting.<p><a href='/help/var_seq' target='_top'>More...</a></p>Alternative sequenceiVSP_041993724 – 765VDLAD…ASVAV → REGGPGEGQVRRPARPTIPN PGGPAPPPHPLQESTWRTPT RS in isoform 3. 1 PublicationAdd BLAST42
Alternative sequenceiVSP_041994766 – 1298Missing in isoform 3. 1 PublicationAdd BLAST533
Alternative sequenceiVSP_0419951298 – 1363SCKGP…TDNSY → R in isoform 2. 6 PublicationsAdd BLAST66

Sequence databases

Select the link destinations:

EMBL nucleotide sequence database

More...EMBLi

GenBank nucleotide sequence database

More...GenBanki

DNA Data Bank of Japan; a nucleotide sequence database

More...DDBJi
Links Updated
X69878 mRNA Translation: CAA49505.1
U43143 mRNA Translation: AAA85215.1
EU826564 mRNA Translation: ACF47600.1
AY233382 mRNA Translation: AAO89504.1
AY233383 mRNA Translation: AAO89505.1
AK291679 mRNA Translation: BAF84368.1
AC122714 Genomic DNA No translation available.
X68203 mRNA Translation: CAA48290.1 Different initiation.
S66407 mRNA Translation: AAB28539.1

The Consensus CDS (CCDS) project

More...CCDSi		CCDS43412.1 [P35916-1]
CCDS4457.1 [P35916-2]

Protein sequence database of the Protein Information Resource

More...PIRi		A48999

NCBI Reference Sequences

More...RefSeqi		NP_002011.2, NM_002020.4 [P35916-1]
NP_891555.2, NM_182925.4 [P35916-2]

Genome annotation databases

Ensembl eukaryotic genome annotation project

More...Ensembli		ENST00000261937; ENSP00000261937; ENSG00000037280
ENST00000393347; ENSP00000377016; ENSG00000037280 [P35916-1]

Database of genes from NCBI RefSeq genomes

More...GeneIDi		2324

KEGG: Kyoto Encyclopedia of Genes and Genomes

More...KEGGi		hsa:2324

Matched Annotation from NCBI and EMBL-EBI (MANE) - Phase one

More...MANE-Selecti		ENST00000261937.11; ENSP00000261937.6; NM_182925.5; NP_891555.2

UCSC genome browser

More...UCSCi		uc003mlz.4, human [P35916-2]

Keywords - Coding sequence diversityi

Alternative splicing

<p>This section provides links to proteins that are similar to the protein sequence(s) described in this entry at different levels of sequence identity thresholds (100%, 90% and 50%) based on their membership in UniProt Reference Clusters (<a href="http://www.uniprot.org/help/uniref">UniRef</a>).<p><a href='/help/similar_proteins_section' target='_top'>More...</a></p>Similar proteinsi

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

<p>This subsection of the <a href="http://www.uniprot.org/manual/cross%5Freferences%5Fsection">Cross-references</a> section provides links to various web resources that are relevant for a specific protein.<p><a href='/help/web_resource' target='_top'>More...</a></p>Web resourcesi

Wikipedia

FLT4 entry

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X69878 mRNA Translation: CAA49505.1
U43143 mRNA Translation: AAA85215.1
EU826564 mRNA Translation: ACF47600.1
AY233382 mRNA Translation: AAO89504.1
AY233383 mRNA Translation: AAO89505.1
AK291679 mRNA Translation: BAF84368.1
AC122714 Genomic DNA No translation available.
X68203 mRNA Translation: CAA48290.1 Different initiation.
S66407 mRNA Translation: AAB28539.1
CCDSiCCDS43412.1 [P35916-1]
CCDS4457.1 [P35916-2]
PIRiA48999
RefSeqiNP_002011.2, NM_002020.4 [P35916-1]
NP_891555.2, NM_182925.4 [P35916-2]

3D structure databases

Select the link destinations:

Protein Data Bank Europe

More...PDBei

Protein Data Bank RCSB

More...RCSB PDBi

Protein Data Bank Japan

More...PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4BSJX-ray2.50A330-553[»]
4BSKX-ray4.20A23-229[»]
SMRiP35916
ModBaseiSearch...
PDBe-KBiSearch...

Protein-protein interaction databases

BioGRIDi108612, 35 interactors
CORUMiP35916
DIPiDIP-5739N
IntActiP35916, 18 interactors
MINTiP35916
STRINGi9606.ENSP00000261937

Chemistry databases

BindingDBiP35916
ChEMBLiCHEMBL1955
DrugBankiDB06080, ABT-869
DB06626, Axitinib
DB05932, Denibulin
DB12010, Fostamatinib
DB06101, IMC-1C11
DB09078, Lenvatinib
DB09079, Nintedanib
DB06589, Pazopanib
DB08896, Regorafenib
DB15685, Selpercatinib
DB00398, Sorafenib
DB01268, Sunitinib
DB05075, TG-100801
DB04879, Vatalanib
DrugCentraliP35916
GuidetoPHARMACOLOGYi1814

PTM databases

GlyGeniP35916, 12 sites
iPTMnetiP35916
PhosphoSitePlusiP35916

Genetic variation databases

BioMutaiFLT4
DMDMi357529070

Proteomic databases

jPOSTiP35916
MassIVEiP35916
PaxDbiP35916
PeptideAtlasiP35916
PRIDEiP35916
ProteomicsDBi55166 [P35916-2]
55167 [P35916-1]
55168 [P35916-3]

Protocols and materials databases

Antibodypedia a portal for validated antibodies

More...Antibodypediai		3429, 1065 antibodies from 45 providers

The DNASU plasmid repository

More...DNASUi		2324

Genome annotation databases

EnsembliENST00000261937; ENSP00000261937; ENSG00000037280
ENST00000393347; ENSP00000377016; ENSG00000037280 [P35916-1]
GeneIDi2324
KEGGihsa:2324
MANE-SelectiENST00000261937.11; ENSP00000261937.6; NM_182925.5; NP_891555.2
UCSCiuc003mlz.4, human [P35916-2]

Organism-specific databases

Comparative Toxicogenomics Database

More...CTDi		2324
DisGeNETi2324

GeneCards: human genes, protein and diseases

More...GeneCardsi		FLT4
GeneReviewsiFLT4
HGNCiHGNC:3767, FLT4
HPAiENSG00000037280, Low tissue specificity
MalaCardsiFLT4
MIMi136352, gene
153100, phenotype
602089, phenotype
618780, phenotype
neXtProtiNX_P35916
OpenTargetsiENSG00000037280
Orphaneti79452, Milroy disease
464293, NON RARE IN EUROPE: Infantile capillary hemangioma
3303, Tetralogy of Fallot
PharmGKBiPA28183
VEuPathDBiHostDB:ENSG00000037280

GenAtlas: human gene database

More...GenAtlasi		Search...

Phylogenomic databases

eggNOGiKOG0200, Eukaryota
GeneTreeiENSGT00940000159358
HOGENOMiCLU_000288_49_4_1
InParanoidiP35916
OMAiRPYCKRL
OrthoDBi236292at2759
PhylomeDBiP35916
TreeFamiTF325768

Enzyme and pathway databases

BRENDAi2.7.10.1, 2681
PathwayCommonsiP35916
ReactomeiR-HSA-195399, VEGF binds to VEGFR leading to receptor dimerization
R-HSA-9013695, NOTCH4 Intracellular Domain Regulates Transcription
SignaLinkiP35916
SIGNORiP35916

Miscellaneous databases

BioGRID ORCS database of CRISPR phenotype screens

More...BioGRID-ORCSi		2324, 6 hits in 1069 CRISPR screens

ChiTaRS: a database of human, mouse and fruit fly chimeric transcripts and RNA-sequencing data

More...ChiTaRSi		FLT4, human

The Gene Wiki collection of pages on human genes and proteins

More...GeneWikii		FLT4

Database of phenotypes from RNA interference screens in Drosophila and Homo sapiens

More...GenomeRNAii		2324
PharosiP35916, Tclin

Protein Ontology

More...PROi		PR:P35916
RNActiP35916, protein

The Stanford Online Universal Resource for Clones and ESTs

More...SOURCEi		Search...

Gene expression databases

BgeeiENSG00000037280, Expressed in left lobe of thyroid gland and 141 other tissues
ExpressionAtlasiP35916, baseline and differential
GenevisibleiP35916, HS

Family and domain databases

DisProtiDP02600
Gene3Di2.60.40.10, 7 hits
InterProiView protein in InterPro
IPR007110, Ig-like_dom
IPR036179, Ig-like_dom_sf
IPR013783, Ig-like_fold
IPR013098, Ig_I-set
IPR003599, Ig_sub
IPR003598, Ig_sub2
IPR011009, Kinase-like_dom_sf
IPR000719, Prot_kinase_dom
IPR017441, Protein_kinase_ATP_BS
IPR001245, Ser-Thr/Tyr_kinase_cat_dom
IPR008266, Tyr_kinase_AS
IPR020635, Tyr_kinase_cat_dom
IPR001824, Tyr_kinase_rcpt_3_CS
IPR041348, VEGFR-2_TMD
IPR009137, VEGFR3_rcpt
PANTHERiPTHR24416:SF562, PTHR24416:SF562, 1 hit
PfamiView protein in Pfam
PF07679, I-set, 1 hit
PF07714, PK_Tyr_Ser-Thr, 1 hit
PF17988, VEGFR-2_TMD, 1 hit
SMARTiView protein in SMART
SM00409, IG, 6 hits
SM00408, IGc2, 4 hits
SM00219, TyrKc, 1 hit
SUPFAMiSSF48726, SSF48726, 6 hits
SSF56112, SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS50835, IG_LIKE, 6 hits
PS00107, PROTEIN_KINASE_ATP, 1 hit
PS50011, PROTEIN_KINASE_DOM, 1 hit
PS00109, PROTEIN_KINASE_TYR, 1 hit
PS00240, RECEPTOR_TYR_KIN_III, 1 hit

MobiDB: a database of protein disorder and mobility annotations

More...MobiDBi		Search...

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This subsection of the 'Entry information' section provides a mnemonic identifier for a UniProtKB entry, but it is not a stable identifier. Each reviewed entry is assigned a unique entry name upon integration into UniProtKB/Swiss-Prot.<p><a href='/help/entry_name' target='_top'>More...</a></p>Entry nameiVGFR3_HUMAN
<p>This subsection of the 'Entry information' section provides one or more accession number(s). These are stable identifiers and should be used to cite UniProtKB entries. Upon integration into UniProtKB, each entry is assigned a unique accession number, which is called 'Primary (citable) accession number'.<p><a href='/help/accession_numbers' target='_top'>More...</a></p>AccessioniPrimary (citable) accession number: P35916
Secondary accession number(s): A8K6L4
, B5A926, Q16067, Q86W07, Q86W08
<p>This subsection of the 'Entry information' section shows the date of integration of the entry into UniProtKB, the date of the last sequence update and the date of the last annotation modification ('Last modified'). The version number for both the entry and the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> are also displayed.<p><a href='/help/entry_history' target='_top'>More...</a></p>Entry historyiIntegrated into UniProtKB/Swiss-Prot: June 1, 1994
Last sequence update: November 16, 2011
Last modified: February 23, 2022
This is version 223 of the entry and version 3 of the sequence. See complete history.
<p>This subsection of the 'Entry information' section indicates whether the entry has been manually annotated and reviewed by UniProtKB curators or not, in other words, if the entry belongs to the Swiss-Prot section of UniProtKB (<strong>reviewed</strong>) or to the computer-annotated TrEMBL section (<strong>unreviewed</strong>).<p><a href='/help/entry_status' target='_top'>More...</a></p>Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

<p>This section contains any relevant information that doesn't fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Keywords - Technical termi

3D-structure, Direct protein sequencing, Reference proteome

Documents

  1. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  2. Human chromosome 5
    Human chromosome 5: entries, gene names and cross-references to MIM
  3. Human entries with genetic variants
    List of human entries with genetic variants
  4. Human variants curated from literature reports
    Index of human variants curated from literature reports
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. SIMILARITY comments
    Index of protein domains and families
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