Tclin FLT4 Vascular endothelial growth factor receptor 3

Protein Classes

DTO Classes

Protein / Kinase / Protein Kinase / Tk Group / Vegfr Family / Vascular Endothelial Growth Factor Receptor 3

Protein Summary

Description

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'. 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]

Uniprot Accession IDs

• P35916
• A8K6L4
• B5A926
• Q16067
• Q86W07
• Q86W08
• VEGFR-3

Gene Name

• FLT4

Ensembl ID

• ENST00000261937
• ENSP00000261937
• ENSG00000037280
• ENST00000393347
• ENSP00000377016

Symbol

• VEGFR3
• PCL
• FLT-4
• FLT41
• LMPH1A
• LMPHM1
• VEGFR3
• VEGFR-3

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
protein domain	1
molecular function	0.99
biological process	0.87
PubMedID	0.77
biological term	0.72

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ARCHS4

ARCHS4 provides access to gene-function predictions based on RNA-seq co-expression, and gene expression levels across cell and tissues.

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IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 716.47   (req: < 5)

Gene RIFs: 183   (req: <= 3)

Antibodies: 968   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 716.47   (req: >= 5)

Gene RIFs: 183   (req: > 3)

Antibodies: 968   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 34

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 139

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drugs: 7

Approved Drugs (7)

Explore Approved Drugs

1 – 7 of 7

sunitinib

FLT4Tclin Kinase

INHIBITOR Ki : 7.77

nintedanib

FLT4Tclin Kinase

INHIBITOR IC50 : 8.30103016

sorafenib

FLT4Tclin Kinase

INHIBITOR Kd : 7.8

pazopanib

FLT4Tclin Kinase

INHIBITOR Kd : 7.57

axitinib

FLT4Tclin Kinase

INHIBITOR Kd : 6.77

lenvatinib

FLT4Tclin Kinase

INHIBITOR IC50 : 8.28399658

tivozanib

FLT4Tclin Kinase

INHIBITOR IC50 : 9.619789

Active Ligands (139)

Explore Active Ligands

1 – 10 of 139

CHEMBL388978

FLT4Tclin Kinase

Kd : 7.55

CHEMBL603469

FLT4Tclin Kinase

Kd : 7.77

CHEMBL1230609

FLT4Tclin Kinase

Kd : 8.82

CHEMBL475251

FLT4Tclin Kinase

Kd : 8.04

CHEMBL495727

FLT4Tclin Kinase

IC50 : 9

CHEMBL522892

FLT4Tclin Kinase

IC50 : 8.6

CHEMBL1784637

FLT4Tclin Kinase

IC50 : 8.59

CHEMBL1980297

FLT4Tclin Kinase

IC50 : 7.36999989

CHEMBL491473

FLT4Tclin Kinase

Kd : 8.37

CHEMBL223360

FLT4Tclin Kinase

Kd : 7.8

Orthologs (13)

1 – 5 of 13

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	fms related tyrosine kinase 4	VGNC:6876	462339
Macaque	fms related tyrosine kinase 4		716412
Mouse	FMS-like tyrosine kinase 4	MGI:95561	14257
Rat	fms-related tyrosine kinase 4	RGD:621737	114110
Dog	fms related tyrosine kinase 4	VGNC:40910	481464

Species	Name	OMA	EggNOG	Inparanoid
Chimp	fms related tyrosine kinase 4
Macaque	fms related tyrosine kinase 4
Mouse	FMS-like tyrosine kinase 4
Rat	fms-related tyrosine kinase 4
Dog	fms related tyrosine kinase 4

Protein Structure (2 Structures, 1 AlphaFold Model)

Representation

  axes   backbone   ball+stick   cartoon   rocket   rope   spacefill

Color Scheme

  target   atomindex   bfactor   chainname   electrostatic   element   hydrophobicity   resname   sstruc

Click on a row in the table to change the structure displayed.
More information can be found at RCSB PDB

AF-P35916-F1-model_v1

AlphaFold Structures Developed by DeepMind and EMBL-EBI

1 – 2 of 2

PDB Structure Id	Ligand	Method	Resolution (Å)	Residues	Fraction of Total Protein	Pub Year	Title

PDB Structure Id	Fraction of Total Protein	Resolution	Pub Year

Pathways (166)

Reactome (8)

KEGG (7)

PathwayCommons (7)

WikiPathways (144)

NOTCH4 Intracellular Domain Regulates Transcription (R-HSA-9013695)

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Find Similar Targets

Items per page:

5

1 – 5 of 8

Data Source	Name	Explore in Pharos	Explore in Source
Reactome	NOTCH4 Intracellular Domain Regulates Transcription	20 targets	R-HSA-9013695
Reactome	Signal Transduction	2704 targets	R-HSA-162582
Reactome	Signaling by NOTCH	205 targets	R-HSA-157118
Reactome	Signaling by NOTCH4	83 targets	R-HSA-9013694
Reactome	Signaling by Receptor Tyrosine Kinases	455 targets	R-HSA-9006934

Name	Explore in Pharos	Explore in Source
NOTCH4 Intracellular Domain Regulates Transcription	20 targets	R-HSA-9013695
Signal Transduction	2704 targets	R-HSA-162582
Signaling by NOTCH	205 targets	R-HSA-157118
Signaling by NOTCH4	83 targets	R-HSA-9013694
Signaling by Receptor Tyrosine Kinases	455 targets	R-HSA-9006934

Gene Ontology Terms (40)

Functions (8)

Components (6)

Processes (26)

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Items per page:

10

1 – 8 of 8

GO Term	Evidence	Assigned by
protein homodimerization activity	Inferred from Direct Assay (IDA)	UniProtKB
vascular endothelial growth factor-activated receptor activity	Inferred from Direct Assay (IDA)	MGI
VEGF-C-activated receptor activity	Inferred from Direct Assay (IDA)	UniProtKB
growth factor binding	Inferred from Physical Interaction (IPI)	UniProtKB
protein phosphatase binding	Inferred from Physical Interaction (IPI)	UniProtKB
transmembrane receptor protein tyrosine kinase activity	Inferred from Mutant Phenotype (IMP)	UniProtKB
transmembrane signaling receptor activity	Inferred from Biological aspect of Ancestor (IBA)	GO_Central
ATP binding	Inferred from Electronic Annotation (IEA)	UniProtKB-KW

Protein-Protein Interactions (203)

Explore Interacting Targets

1 – 10 of 203

• See Interactions on String-DB

CLEC4A

Tbio

Novelty: 0.01821643

p_int: 0.999517955

p_ni: 0.000482043

p_wrong: 2e-9

Score: 0.263

Data Source: BioPlex,STRINGDB

LGALS8

Tchem

Novelty: 0.00623836

p_int: 0.997814357

p_ni: 0.002185643

Score: 0.236

Data Source: BioPlex,STRINGDB

PTGER3

Tclin

Family: GPCR

Novelty: 0.0012681

p_int: 0.982596757

p_ni: 0.017403239

p_wrong: 3e-9

Score: 0.192

Data Source: BioPlex,STRINGDB

MAS1

Tchem

Family: GPCR

Novelty: 0.0089712

p_int: 0.944953846

p_ni: 0.055046154

Data Source: BioPlex

PCDHGB1

Tdark

Novelty: 0.60440805

p_int: 0.944579863

p_ni: 0.055420137

Data Source: BioPlex

NPY2R

Tchem

Family: GPCR

Novelty: 0.01177255

p_int: 0.925277448

p_ni: 0.074722552

Data Source: BioPlex

TMEM52B

Tdark

Novelty: 1.55824039

p_int: 0.896526996

p_ni: 0.103473004

Data Source: BioPlex

LPCAT2

Tbio

Family: Enzyme

Novelty: 0.02794035

p_int: 0.823472772

p_ni: 0.176517704

p_wrong: 0.000009524

Data Source: BioPlex

ACVR2B

Tchem

Family: Kinase

Novelty: 0.00555742

p_int: 0.820444269

p_ni: 0.179417569

p_wrong: 0.000138161

Data Source: BioPlex

LGALS3

Tchem

Novelty: 0.00032754

p_int: 0.77906112

p_ni: 0.22093888

Score: 0.231

Data Source: BioPlex,STRINGDB

Publication Statistics

PubMed Score  716.47

PubMed score by year

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PubTator Score  699.69

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Amino Acid Sequence

Residue Counts

Protein Sequence

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Ortholog Sequence Conservation

WebLogo Color Code

PolarG S T Y C

NeutralQ N

BasicK R H

AcidicD E

HydrophobicA V L I P W F M

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Structural Annotations

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3D-structure
Alternative splicing
Angiogenesis
ATP-binding
Cell membrane
Complete proteome
Cytoplasm
Direct protein sequencing
Disease mutation
Disulfide bond

MGI Phenotype Find Similar Targets

adipose tissue phenotype
cardiovascular system phenotype
digestive/alimentary phenotype
embryo phenotype
growth/size/body region phenotype
homeostasis/metabolism phenotype
immune system phenotype
integument phenotype
liver/biliary system phenotype
mortality/aging