Protein detail
VGFR3
Vascular endothelial growth factor receptor 3 (VEGFR-3) (EC 2.7.10.1) (Fms-like tyrosine kinase 4) (FLT-4) (Tyrosine-protein kinase receptor FLT4)
Protein symbol VGFR3 | UniProt ID | EVMP score 0.38 |
Frequency 1 | Transmembrane count 1 | Protein classification Cancer-related genesDisease related genesEnzymesFDA approved drug targetsHuman disease related genesPlasma proteinsPredicted intracellular proteinsPredicted membrane proteinsPredicted secreted proteinsRAS pathway related proteinsTransporters |
EVMP score: annotation confidence score.
Extremely high >= 0.85High >= 0.70Medium >= 0.55Low >= 0.40
Basic Information
Protein Names
Vascular endothelial growth factor receptor 3 (VEGFR-3) (EC 2.7.10.1) (Fms-like tyrosine kinase 4) (FLT-4) (Tyrosine-protein kinase receptor FLT4)
Protein Class
Cancer-related genesDisease related genesEnzymesFDA approved drug targetsHuman disease related genesPlasma proteinsPredicted intracellular proteinsPredicted membrane proteinsPredicted secreted proteinsRAS pathway related proteinsTransporters
Protein Function
- Human disease related genes:Cardiovascular diseases:Vascular diseases
- Predicted intracellular proteins
- ENZYME proteins:Transferases
- RAS pathway related proteins
- Human disease related genes:Congenital malformations:Congenital malformations of the circulatory system
- Enzymes
- Cancer-related genes:Candidate cancer biomarkers
- Human disease related genes:Congenital malformations:Congenital malformations of skin
- Predicted secreted proteins
- Transporters:Accessory Factors Involved in Transport
- Kinases:Tyr protein kinases
- Disease related genes
- FDA approved drug targets:Small molecule drugs
Transmembrane
776..796; Helical
Transmembrane Count
1
Ensembl
Entrez Gene Symbol
Gene Synonym
PCLVEGFR-3VEGFR3
Gene Description
Fms related receptor tyrosine kinase 4
Chromosome
5
Position
180601506-180649624
Frequency
1
EVMP Score
0.38
Fluorescence & Localization
Tissue SpecificintestineCell SpecificB-cellsSingle-Nuclei Brain SpecificleukocyteBlood Cell Specificnaive CD4 T-cellBlood Lineage SpecificT-cells
Function & Pathway
Protein Function
- Human disease related genes:Cardiovascular diseases:Vascular diseases
- Predicted intracellular proteins
- ENZYME proteins:Transferases
- RAS pathway related proteins
- Human disease related genes:Congenital malformations:Congenital malformations of the circulatory system
- Enzymes
- Cancer-related genes:Candidate cancer biomarkers
- Human disease related genes:Congenital malformations:Congenital malformations of skin
- Predicted secreted proteins
- Transporters:Accessory Factors Involved in Transport
- Kinases:Tyr protein kinases
- Disease related genes
- FDA approved drug targets:Small molecule drugs
Cellular Component
Molecular Function
Biological Process
KEGG
- hsa04010 MAPK signaling pathway
- KEGG:hsa04014 Ras signaling pathway
- KEGG:hsa04015 Rap1 signaling pathway
- KEGG:hsa04020 Calcium signaling pathway
- KEGG:hsa04151 PI3K-Akt signaling pathway
- KEGG:hsa04510 Focal adhesion
- KEGG:hsa04518 Integrin signaling
- KEGG:hsa04519 Cadherin signaling
- KEGG:hsa05200 Pathways in cancer
- KEGG:hsa05224 Breast cancer
Reactome
- R-hsa-9855142 cellular responses to mechanical stimuli
- R-hsa-8953897 cellular responses to stimuli
- R-hsa-9856530 high laminar flow shear stress activates signaling by piezo1 and pecam1 cdh5 kdr in endothelial cells
- R-hsa-9013695 notch4 intracellular domain regulates transcription
- R-hsa-157118 signaling by notch
- R-hsa-9013694 signaling by notch4
- R-hsa-9006934 signaling by receptor tyrosine kinases
- R-hsa-194138 signaling by vegf
- R-hsa-194313 vegf ligand receptor interactions
Mediation Categories
Clinical-translation mediationImmune mediationReceptor-signaling mediation
Relations & Evidence
Enzyme-Mediated Modification
7 records.
| Substrate Gene Symbol | Enzyme Gene Symbol | Enzyme UniProt ID | Residue Type | Residue Offset | Modification | Database | References |
|---|---|---|---|---|---|---|---|
| FLT4 | SRC | P12931 | Y | 830 | phosphorylation | PhosphoSite_MIMPMIMPSIGNORProtMapperdbPTMSIGNOR_ProtMapperPhosphoSitePhosphoSite_ProtMapper | ProtMapper:20431062SIGNOR:20431062dbPTM:20431062 |
| FLT4 | SRC | P12931 | Y | 833 | phosphorylation | PhosphoSite_MIMPMIMPSIGNORProtMapperRLIMS-P_ProtMapperdbPTMSIGNOR_ProtMapperPhosphoSitePhosphoSite_ProtMapper | ProtMapper:20431062SIGNOR:20431062dbPTM:20431062 |
| FLT4 | SRC | P12931 | Y | 853 | phosphorylation | PhosphoSite_MIMPMIMPSIGNORProtMapperdbPTMSIGNOR_ProtMapperPhosphoSitePhosphoSite_ProtMapper | ProtMapper:20431062SIGNOR:20431062dbPTM:20431062 |
| FLT4 | SRC | P12931 | Y | 1,063 | phosphorylation | phosphoELM_MIMPPhosphoSite_MIMPMIMPSIGNORProtMapperdbPTMSIGNOR_ProtMapperPhosphoSitePhosphoSite_ProtMapper | ProtMapper:20431062SIGNOR:20431062dbPTM:18083107dbPTM:20431062dbPTM:16076871 |
| FLT4 | KDR | P35968 | Y | 1,230 | phosphorylation | MIMPHPRD_MIMPphosphoELM_MIMPPhosphoSite_MIMP | |
| FLT4 | KDR | P35968 | Y | 1,231 | phosphorylation | MIMPHPRD_MIMPphosphoELM_MIMPPhosphoSite_MIMP | |
| FLT4 | KDR | P35968 | Y | 1,265 | phosphorylation | MIMPHPRD_MIMPphosphoELM_MIMP |
Ligand-Receptor Signaling
69 records.
| Category | Parent | Database | Transmitter | Receiver | Secreted | Plasma Membrane (Transmembrane) | Plasma Membrane (Peripheral) |
|---|---|---|---|---|---|---|---|
| receptor | receptor | Baccin2019 | No | Yes | Yes | Yes | No |
| receptor | receptor | SignaLink_function | No | Yes | Yes | Yes | No |
| kinase | receptor | Almen2009 | No | Yes | Yes | Yes | No |
| growth_factor | receptor | Baccin2019 | No | Yes | Yes | Yes | No |
| receptor_tyrosine_kinases_rtk | receptor | HPMR | No | Yes | Yes | Yes | No |
| vegf_pdgf | receptor | HPMR | No | Yes | Yes | Yes | No |
| kinase | receptor | Surfaceome | No | Yes | Yes | Yes | No |
| growth_factor | receptor | ICELLNET | No | Yes | Yes | Yes | No |
| growth_factor_vegf_family | receptor | ICELLNET | No | Yes | Yes | Yes | No |
| receptor | receptor | OmniPath | No | Yes | Yes | Yes | No |
Regulatory Interaction Network
6 records.
| Source Protein Symbol | Source UniProt ID | Target Protein Symbol | Target UniProt ID | Is Directed | Is Stimulation | Is Inhibition | Database | References |
|---|---|---|---|---|---|---|---|---|
| VGFR3 | P35916 | SHC1 | P29353 | Yes | Yes | No | WangphosphoELM_MIMPPhosphoSite_MIMPMIMPHPRD_MIMPiPTMnetPhosphoPointSIGNORProtMapperHPRDHINTPhosphoSite_KEAKEASignaLink3phosphoELM_KEAphosphoELMLi2012SIGNOR_ProtMapper | KEA:10896916SignaLink3:9927207KEA:9927207phosphoELM:9927207KEA:9685404KEA:9096689KEA:9446569ProtMapper:9927207KEA:9710204KEA:10764799KEA:10891441KEA:10921922KEA:11075717HPRD:7675451KEA:10816433SIGNOR:9927207HPRD:8662748HINT:7970715KEA:9741627HPRD:9927207KEA:9388490HINT:8662748KEA:15592455SignaLink3:23331499KEA:11687594KEA:9121430KEA:12522270KEA:8702728KEA:8610109KEA:12237775KEA:10482988 |
| VGFR3 | P35916 | KS6A3 | P51812 | Yes | No | Yes | SIGNOR_ProtMapperiPTMnetSIGNORProtMapper | ProtMapper:12601080SIGNOR:12601080 |
| VEGFC | P49767 | VGFR3 | P35916 | Yes | Yes | No | iTALKKirouac2010Guide2Pharma_LRdbICELLNETProtMapperSIGNORHINTUniProt_LRdbDIPHPMR_talklrHPMRCellChatDBHPRD_LRdbDLRP_CellinkertalklrscConnectHPRDRamilowski2015_Baccin2019DLRP_talklrGuide2Pharma_CellinkerWangRamilowski2015HPMR_LRdbCellPhoneDBGuide2Pharma_talklrHPRD_talklrBaccin2019CellinkerSTRING_talklrEMBRACECellCallGuide2PharmaCellTalkDBFantom5_LRdbSparser_ProtMapperHPMR_CellinkerconnectomeDB2020LRdb | HINT:23878260connectomeDB2020:12881528connectomeDB2020:16530705Cellinker:16530705Baccin2019:16530705HPRD:8700872HPRD:16530705LRdb:8700872ICELLNET:11532940Cellinker:8700872Baccin2019:8700872HINT:12810700ICELLNET:16336962SIGNOR:9435229CellChatDB:16633338connectomeDB2020:8700872DIP:8700872LRdb:12881528ProtMapper:24798152Baccin2019:12881528LRdb:16530705CellTalkDB:12881528HINT:8700872HPMR:12881528Cellinker:12881528 |
| SRC | P12931 | VGFR3 | P35916 | Yes | Yes | No | phosphoELM_MIMPPhosphoSite_MIMPMIMPHPRD_MIMPPhosphoSite_norefSIGNORiPTMnetProtMapperRLIMS-P_ProtMapperdbPTMSIGNOR_ProtMapperPhosphoSitePhosphoSite_ProtMapper | PhosphoSite:20431062dbPTM:12881528ProtMapper:20431062SIGNOR:20431062dbPTM:18083107dbPTM:20431062dbPTM:16076871 |
| VGFR3 | P35916 | LGUL | Q04760 | Yes | Yes | No | SIGNOR | SIGNOR:34838714 |
| VEGFD | O43915 | VGFR3 | P35916 | Yes | Yes | No | iTALKGuide2Pharma_LRdbICELLNETSIGNORHINTUniProt_LRdbHPMR_talklrCellChatDBHPRD_LRdbtalklrscConnectHPRDDLRP_talklrWangRamilowski2015HPMR_LRdbCellPhoneDBGuide2Pharma_talklrHPRD_talklrBioGRIDCellinkerSTRING_talklrCellCallGuide2PharmaCellTalkDBFantom5_LRdbconnectomeDB2020LRdb | HPRD:9435229CellTalkDB:9435229HINT:11279005ICELLNET:16336962CellChatDB:16633338SIGNOR:9435229Cellinker:9435229connectomeDB2020:9435229ICELLNET:11532940connectomeDB2020:21148085HINT:18593464HINT:9435229BioGRID:11279005 |
Protein Complex Composition
Sequence, Structure & Domains
Sequences
Length
1,363
Mass
152,757
Sequence
MQRGAALCLRLWLCLGLLDGLVSGYSMTPPTLNITEESHVIDTGDSLSISCRGQHPLEWAWPGAQEAPATGDKDSEDTGVVRDCEGTDARPYCKVLLLHEVHANDTGSYVCYYKYIKARIEGTTAASSYVFVRDFEQPFINKPDTLLVNRKDAMWVPCLVSIPGLNVTLRSQSSVLWPDGQEVVWDDRRGMLVSTPLLHDALYLQCETTWGDQDFLSNPFLVHITGNELYDIQLLPRKSLELLVGEKLVLNCTVWAEFNSGVTFDWDYPGKQAERGKWVPERRSQQTHTELSSILTIHNVSQHDLGSYVCKANNGIQRFRESTEVIVHENPFISVEWLKGPILEATAGDELVKLPVKLAAYPPPEFQWYKDGKALSGRHSPHALVLKEVTEASTGTYTLALWNSAAGLRRNISLELVVNVPPQIHEKEASSPSIYSRHSRQALTCTAYGVPLPLSIQWHWRPWTPCKMFAQRSLRRRQQQDLMPQCRDWRAVTTQDAVNPIESLDTWTEFVEGKNKTVSKLVIQNANVSAMYKCVVSNKVGQDERLIYFYVTTIPDGFTIESKPSEELLEGQPVLLSCQADSYKYEHLRWYRLNLSTLHDAHGNPLLLDCKNVHLFATPLAASLEEVAPGARHATLSLSIPRVAPEHEGHYVCEVQDRRSHDKHCHKKYLSVQALEAPRLTQNLTDLLVNVSDSLEMQCLVAGAHAPSIVWYKDERLLEEKSGVDLADSNQKLSIQRVREEDAGRYLCSVCNAKGCVNSSASVAVEGSEDKGSMEIVILVGTGVIAVFFWVLLLLIFCNMRRPAHADIKTGYLSIIMDPGEVPLEEQCEYLSYDASQWEFPRERLHLGRVLGYGAFGKVVEASAFGIHKGSSCDTVAVKMLKEGATASEHRALMSELKILIHIGNHLNVVNLLGACTKPQGPLMVIVEFCKYGNLSNFLRAKRDAFSPCAEKSPEQRGRFRAMVELARLDRRRPGSSDRVLFARFSKTEGGARRASPDQEAEDLWLSPLTMEDLVCYSFQVARGMEFLASRKCIHRDLAARNILLSESDVVKICDFGLARDIYKDPDYVRKGSARLPLKWMAPESIFDKVYTTQSDVWSFGVLLWEIFSLGASPYPGVQINEEFCQRLRDGTRMRAPELATPAIRRIMLNCWSGDPKARPAFSELVEILGDLLQGRGLQEEEEVCMAPRSSQSSEEGSFSQVSTMALHIAQADAEDSPPSLQRHSLAARYYNWVSFPGCLARGAETRGSSRMKTFEEFPMTPTTYKGSVDNQTDSGMVLASEEFEQIESRHRQESGFSCKGPGQNVAVTRAHPDSQGRRRRPERGARGGQVFYNSEYGELSEPSEEDHCSPSARVTFFTDNSY
Alternative Products
Event=Alternative splicing; Named isoforms=3; Name=1; Synonyms=Long; IsoId=P35916-2; Sequence=Displayed; Name=2; Synonyms=Short; IsoId=P35916-1; Sequence=VSP_041995; Name=3; Synonyms=sVegfr3; IsoId=P35916-3; Sequence=VSP_041993, VSP_041994
Alternative Sequence
724..765; VDLADSNQKLSIQRVREEDAGRYLCSVCNAKGCVNSSASVAV -> REGGPGEGQVRRPARPTIPNPGGPAPPPHPLQESTWRTPTRS (in isoform 3); 766..1298; Missing (in isoform 3); 1298..1363; SCKGPGQNVAVTRAHPDSQGRRRRPERGARGGQVFYNSEYGELSEPSEEDHCSPSARVTFFTDNSY -> R (in isoform 2)
3D Structural Models
Turn
404..407
Helix
391..393; 425..428
Beta Strand
332..339; 341..346; 350..362; 365..370; 381..388; 395..403; 408..424; 441..451; 457..464; 501..511; 514..524; 530..538; 541..549
3D Structure
X-ray crystallography (2)
Domain & Motif Annotations
Domain (CC)
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).
Domain (FT)
30..127; Ig-like C2-type 1; 151..213; Ig-like C2-type 2; 219..326; Ig-like C2-type 3; 331..415; Ig-like C2-type 4; 422..552; Ig-like C2-type 5; 555..671; Ig-like C2-type 6; 678..764; Ig-like C2-type 7; 845..1173; Protein kinase
Region
1291..1331; Disordered
Protein Families
- Protein kinase superfamily
- Tyr protein kinase family
- CSF-1/PDGF receptor subfamily
Sequence Similarities
Belongs to the protein kinase superfamily. Tyr protein kinase family. CSF-1/PDGF receptor subfamily.
Clinical Relevance
Disease Involvement
Cancer-related genesDisease variantFDA approved drug targets
Drug Targets
FDA approved drug targets
Drugs
CEDIRANIBGW441756XGLESATINIBPAZOPANIBX-82SUNITINIBNULLIMC-3C5CEP-7055GW843682XAXITINIBXL820XL999NINTEDANIB ESYLATERG-1530BRIVANIBGO-6976TANDUTINIBSORAFENIBREGORAFENIB1-AZAKENPAULLONEENMD-2076SULFATINIBBARASERTIB-HQPATABERMINOGENE VADENOVECMOTESANIBTIVOZANIBFRUQUINTINIBPTC299MK-2461CHLORPYRAMIN HYDROCHLORIDEVATALANIBSB203580MUPARFOSTATCP-459632VEGF RECEPTOR TYROSINE KINASE INHIBITOR IIIOSI-930DOVITINIBSP-600125LINIFANIBFAMITINIBMLN-8054TELATINIBVANDETANIBILORASERTIBCENISERTIBLUCITANIBSU-014813CEP-5214XL-8204SC-203NVP-TAE684SOTRASTAURINALSTERPAULLONEVARGATEFCP-547632IBCASERTIBGSK-269962ARABEPRAZOLETESEVATINIBSB220025L-21649JNJ-26483327KENPAULLONEPEGPLERANIB SODIUMSEMAXANIBERLOTINIBLENVATINIBAG-13958TAK-715DORAMAPIMODCEP-11981BMS-690514ENTRECTINIBFORETINIBTOZASERTIBANLOTINIBGEFITINIBTIVOZANIB HYDROCHLORIDEXL-999TAK-593BRIVANIB ALANINATEPF-562271LENVATINIB MESYLATEORANTINIB