UniProtKB - P35916 (VGFR3_HUMAN)
Vascular endothelial growth factor receptor 3
FLT4
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 PublicationsCatalytic activityi
- ATP + L-tyrosyl-[protein] = ADP + H+ + O-phospho-L-tyrosyl-[protein]PROSITE-ProRule annotation2 PublicationsEC:2.7.10.1PROSITE-ProRule annotation2 Publications
Activity regulationi
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 879 | ATPCurated | 1 | |
Active sitei | 1037 | Proton acceptorPROSITE-ProRule annotation | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 851 – 859 | ATPPROSITE-ProRule annotation | 9 |
GO - Molecular functioni
- ATP binding Source: UniProtKB-KW
- growth factor binding Source: UniProtKB
- protein homodimerization activity Source: UniProtKB
- protein phosphatase binding Source: UniProtKB
- protein serine/threonine/tyrosine kinase activity Source: RHEA
- transmembrane receptor protein tyrosine kinase activity Source: UniProtKB
- vascular endothelial growth factor-activated receptor activity Source: UniProtKB
GO - Biological processi
- blood vessel morphogenesis Source: UniProtKB
- cellular response to vascular endothelial growth factor stimulus Source: UniProtKB
- hematopoietic progenitor cell differentiation Source: GO_Central
- lung alveolus development Source: Ensembl
- lymphangiogenesis Source: UniProtKB
- lymph vessel development Source: BHF-UCL
- negative regulation of apoptotic process Source: UniProtKB
- peptidyl-tyrosine phosphorylation Source: UniProtKB
- positive regulation of cell population proliferation Source: UniProtKB
- positive regulation of endothelial cell migration Source: UniProtKB
- positive regulation of endothelial cell proliferation Source: UniProtKB
- positive regulation of ERK1 and ERK2 cascade Source: UniProtKB
- positive regulation of JNK cascade Source: UniProtKB
- positive regulation of kinase activity Source: GO_Central
- positive regulation of MAPK cascade Source: UniProtKB
- positive regulation of protein kinase C signaling Source: UniProtKB
- positive regulation of protein phosphorylation Source: UniProtKB
- positive regulation of vascular endothelial growth factor production Source: UniProtKB
- protein autophosphorylation Source: UniProtKB
- regulation of blood vessel remodeling Source: UniProtKB
- respiratory system process Source: Ensembl
- sprouting angiogenesis Source: UniProtKB
- transmembrane receptor protein tyrosine kinase signaling pathway Source: GO_Central
- vascular endothelial growth factor receptor signaling pathway Source: MGI
- vascular endothelial growth factor signaling pathway Source: UniProtKB
- vasculature development Source: UniProtKB
Keywordsi
Molecular function | Kinase, Receptor, Transferase, Tyrosine-protein kinase |
Biological process | Angiogenesis |
Ligand | ATP-binding, Nucleotide-binding |
Enzyme and pathway databases
BRENDAi | 2.7.10.1, 2681 |
PathwayCommonsi | P35916 |
Reactomei | R-HSA-195399, VEGF binds to VEGFR leading to receptor dimerization R-HSA-9013695, NOTCH4 Intracellular Domain Regulates Transcription |
SignaLinki | P35916 |
SIGNORi | P35916 |
Names & Taxonomyi
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 |
Gene namesi | Name:FLT4 Synonyms:VEGFR3 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:3767, FLT4 |
MIMi | 136352, gene |
neXtProti | NX_P35916 |
VEuPathDBi | HostDB:ENSG00000037280 |
Subcellular locationi
Plasma membrane
- Cell membrane 2 Publications; Single-pass type I membrane protein
Cytoplasm and Cytosol
- Cytoplasm 2 Publications
Nucleus
- Nucleus 1 Publication
Note: Ligand-mediated autophosphorylation leads to rapid internalization.1 Publication
Plasma membrane
Note: Ligand-mediated autophosphorylation leads to rapid internalization.
Plasma membrane
Cytosol
- cytosol Source: HPA
Extracellular region or secreted
- extracellular region Source: UniProtKB-SubCell
Nucleus
- nucleoplasm Source: HPA
Plasma Membrane
- integral component of plasma membrane Source: GO_Central
- plasma membrane Source: UniProtKB
Other locations
- receptor complex Source: MGI
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 25 – 775 | ExtracellularSequence analysisAdd BLAST | 751 | |
Transmembranei | 776 – 796 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 797 – 1363 | CytoplasmicSequence analysisAdd BLAST | 567 |
Keywords - Cellular componenti
Cell membrane, Cytoplasm, Membrane, Nucleus, SecretedPathology & Biotechi
Involvement in diseasei
Lymphatic malformation 1 (LMPHM1)10 Publications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_074044 | 855 | A → 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_018409 | 857 | G → R in LMPHM1; loss of kinase activity. 2 PublicationsCorresponds to variant dbSNP:rs267606818EnsemblClinVar. | 1 | |
Natural variantiVAR_074045 | 878 | V → M in LMPHM1. 1 PublicationCorresponds to variant dbSNP:rs121909654EnsemblClinVar. | 1 | |
Natural variantiVAR_074046 | 1020 | Q → L in LMPHM1. 1 Publication | 1 | |
Natural variantiVAR_018412 | 1035 | H → R in LMPHM1; loss of kinase activity. 1 PublicationCorresponds to variant dbSNP:rs121909653EnsemblClinVar. | 1 | |
Natural variantiVAR_018413 | 1041 | R → P in LMPHM1; loss of kinase activity. 2 PublicationsCorresponds to variant dbSNP:rs121909650EnsemblClinVar. | 1 | |
Natural variantiVAR_018414 | 1044 | L → P in LMPHM1; loss of kinase activity. 1 PublicationCorresponds to variant dbSNP:rs121909651EnsemblClinVar. | 1 | |
Natural variantiVAR_074048 | 1086 | I → T in LMPHM1. 1 PublicationCorresponds to variant dbSNP:rs121909655EnsemblClinVar. | 1 | |
Natural variantiVAR_074049 | 1106 | E → K in LMPHM1. 1 PublicationCorresponds to variant dbSNP:rs121909656EnsemblClinVar. | 1 | |
Natural variantiVAR_074050 | 1108 | Missing in LMPHM1. 1 Publication | 1 | |
Natural variantiVAR_018415 | 1114 | P → L in LMPHM1; loss of kinase activity. 2 PublicationsCorresponds to variant dbSNP:rs121909652EnsemblClinVar. | 1 | |
Natural variantiVAR_074051 | 1235 | S → C in LMPHM1; recessive form. 1 Publication | 1 |
Hemangioma, capillary infantile (HCI)1 Publication
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_018411 | 954 | P → S in HCI. 1 PublicationCorresponds to variant dbSNP:rs34255532EnsemblClinVar. | 1 | |
Natural variantiVAR_018416 | 1137 | P → S in HCI. 1 Publication | 1 |
Congenital heart defects, multiple types, 7 (CHTD7)2 Publications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_083806 | 82 – 1363 | Missing in CHTD7. 1 PublicationAdd BLAST | 1282 | |
Natural variantiVAR_083807 | 361 – 1363 | Missing in CHTD7. 1 PublicationAdd BLAST | 1003 | |
Natural variantiVAR_083808 | 736 – 1363 | Missing in CHTD7. 1 PublicationAdd BLAST | 628 | |
Natural variantiVAR_083809 | 741 | Missing in CHTD7; unknown pathological significance. 1 Publication | 1 | |
Natural variantiVAR_083810 | 833 – 1363 | Missing in CHTD7. 1 PublicationAdd BLAST | 531 | |
Natural variantiVAR_083811 | 999 – 1363 | Missing in CHTD7. 1 PublicationAdd BLAST | 365 | |
Natural variantiVAR_083812 | 1173 | L → V in CHTD7; unknown pathological significance. 1 Publication | 1 | |
Natural variantiVAR_083813 | 1192 – 1363 | Missing in CHTD7. 1 PublicationAdd BLAST | 172 |
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 446 | T → 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 Publication | 1 | |
Mutagenesisi | 516 | K → 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 Publication | 1 | |
Mutagenesisi | 737 | R → 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 Publication | 1 | |
Mutagenesisi | 879 | K → G: Abolishes enzyme activity. 1 Publication | 1 | |
Mutagenesisi | 1063 | Y → F: Loss of phosphorylation site. No effect on stimulation of cell proliferation and cell migration. 2 Publications | 1 | |
Mutagenesisi | 1068 | Y → F: Global loss of autophosphorylation. Abolishes stimulation of cell proliferation and cell migration. 2 Publications | 1 | |
Mutagenesisi | 1230 | Y → F: Loss of phosphorylation site. Strongly reduces stimulation of cell proliferation and cell migration. 2 Publications | 1 | |
Mutagenesisi | 1231 | Y → F: Loss of phosphorylation site. Strongly reduces stimulation of cell proliferation and cell migration. 2 Publications | 1 | |
Mutagenesisi | 1265 | Y → F: Loss of phosphorylation site. No effect on stimulation of cell proliferation and cell migration. 1 Publication | 1 | |
Mutagenesisi | 1333 | Y → F: Loss of phosphorylation site. Reduced autophosphorylation. 2 Publications | 1 | |
Mutagenesisi | 1337 | Y → F: Reduced autophosphorylation. Strongly reduces stimulation of cell proliferation and cell migration. 3 Publications | 1 | |
Mutagenesisi | 1363 | Y → F: Loss of phosphorylation site. Slightly reduced autophosphorylation. 2 Publications | 1 |
Keywords - Diseasei
Disease variantOrganism-specific databases
DisGeNETi | 2324 |
GeneReviewsi | FLT4 |
MalaCardsi | FLT4 |
MIMi | 153100, phenotype 602089, phenotype 618780, phenotype |
OpenTargetsi | ENSG00000037280 |
Orphaneti | 79452, Milroy disease 464293, NON RARE IN EUROPE: Infantile capillary hemangioma 3303, Tetralogy of Fallot |
PharmGKBi | PA28183 |
Miscellaneous databases
Pharosi | P35916, Tclin |
Chemistry databases
ChEMBLi | CHEMBL1955 |
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 |
DrugCentrali | P35916 |
GuidetoPHARMACOLOGYi | 1814 |
Genetic variation databases
BioMutai | FLT4 |
DMDMi | 357529070 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 24 | 1 PublicationAdd BLAST | 24 | |
ChainiPRO_0000016776 | 25 – 1363 | Vascular endothelial growth factor receptor 3Add BLAST | 1339 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Glycosylationi | 33 | N-linked (GlcNAc...) asparagineCombined sources1 Publication | 1 | |
Disulfide bondi | 51 ↔ 111 | PROSITE-ProRule annotation1 Publication | ||
Glycosylationi | 104 | N-linked (GlcNAc...) asparagineCombined sources1 Publication | 1 | |
Disulfide bondi | 158 ↔ 206 | PROSITE-ProRule annotation1 Publication | ||
Glycosylationi | 166 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 251 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Disulfide bondi | 252 ↔ 310 | PROSITE-ProRule annotation | ||
Glycosylationi | 299 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 411 | N-linked (GlcNAc...) asparagineCombined sources1 Publication | 1 | |
Disulfide bondi | 445 ↔ 534 | PROSITE-ProRule annotation1 Publication | ||
Disulfide bondi | 466 ↔ 486 | 1 Publication | ||
Glycosylationi | 515 | N-linked (GlcNAc...) asparagineCombined sources1 Publication | 1 | |
Glycosylationi | 527 | N-linked (GlcNAc...) asparagine1 Publication | 1 | |
Disulfide bondi | 578 ↔ 653 | PROSITE-ProRule annotation | ||
Glycosylationi | 594 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 683 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 690 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Disulfide bondi | 699 ↔ 751 | PROSITE-ProRule annotation | ||
Glycosylationi | 758 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Modified residuei | 830 | Phosphotyrosine; by SRC1 Publication | 1 | |
Modified residuei | 833 | Phosphotyrosine; by SRC1 Publication | 1 | |
Modified residuei | 853 | Phosphotyrosine; by SRC1 Publication | 1 | |
Modified residuei | 1063 | Phosphotyrosine; by autocatalysis and SRC2 Publications | 1 | |
Modified residuei | 1068 | Phosphotyrosine; by autocatalysis2 Publications | 1 | |
Modified residuei | 1230 | Phosphotyrosine; by autocatalysis2 Publications | 1 | |
Modified residuei | 1231 | Phosphotyrosine; by autocatalysis2 Publications | 1 | |
Modified residuei | 1265 | Phosphotyrosine; by autocatalysis1 Publication | 1 | |
Modified residuei | 1333 | Phosphotyrosine; by autocatalysis and SRC2 Publications | 1 | |
Modified residuei | 1337 | Phosphotyrosine; by autocatalysis and SRC3 Publications | 1 | |
Modified residuei | 1363 | Phosphotyrosine; by autocatalysis1 Publication | 1 |
Post-translational modificationi
Keywords - PTMi
Disulfide bond, Glycoprotein, PhosphoproteinProteomic databases
jPOSTi | P35916 |
MassIVEi | P35916 |
PaxDbi | P35916 |
PeptideAtlasi | P35916 |
PRIDEi | P35916 |
ProteomicsDBi | 55166 [P35916-2] 55167 [P35916-1] 55168 [P35916-3] |
PTM databases
GlyGeni | P35916, 12 sites |
iPTMneti | P35916 |
PhosphoSitePlusi | P35916 |
Expressioni
Tissue specificityi
Gene expression databases
Bgeei | ENSG00000037280, Expressed in left lobe of thyroid gland and 141 other tissues |
ExpressionAtlasi | P35916, baseline and differential |
Genevisiblei | P35916, HS |
Organism-specific databases
HPAi | ENSG00000037280, Low tissue specificity |
Interactioni
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 PublicationsBinary interactionsi
P35916
With | #Exp. | IntAct |
---|---|---|
HSP90AB1 [P08238] | 2 | EBI-1005467,EBI-352572 |
KDR [P35968] | 5 | EBI-1005467,EBI-1005487 |
VEGFC [P49767] | 2 | EBI-1005467,EBI-3405539 |
GO - Molecular functioni
- growth factor binding Source: UniProtKB
- protein homodimerization activity Source: UniProtKB
- protein phosphatase binding Source: UniProtKB
Protein-protein interaction databases
BioGRIDi | 108612, 35 interactors |
CORUMi | P35916 |
DIPi | DIP-5739N |
IntActi | P35916, 18 interactors |
MINTi | P35916 |
STRINGi | 9606.ENSP00000261937 |
Chemistry databases
BindingDBi | P35916 |
Miscellaneous databases
RNActi | P35916, protein |
Structurei
Secondary structure
3D structure databases
SMRi | P35916 |
ModBasei | Search... |
PDBe-KBi | Search... |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 30 – 127 | Ig-like C2-type 1Add BLAST | 98 | |
Domaini | 151 – 213 | Ig-like C2-type 2Add BLAST | 63 | |
Domaini | 219 – 326 | Ig-like C2-type 3Add BLAST | 108 | |
Domaini | 331 – 415 | Ig-like C2-type 4Add BLAST | 85 | |
Domaini | 422 – 552 | Ig-like C2-type 5Add BLAST | 131 | |
Domaini | 555 – 671 | Ig-like C2-type 6Add BLAST | 117 | |
Domaini | 678 – 764 | Ig-like C2-type 7Add BLAST | 87 | |
Domaini | 845 – 1173 | Protein kinasePROSITE-ProRule annotationAdd BLAST | 329 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 1291 – 1331 | DisorderedSequence analysisAdd BLAST | 41 |
Domaini
Sequence similaritiesi
Keywords - Domaini
Immunoglobulin domain, Repeat, Signal, Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | KOG0200, Eukaryota |
GeneTreei | ENSGT00940000159358 |
HOGENOMi | CLU_000288_49_4_1 |
InParanoidi | P35916 |
OMAi | RPYCKRL |
OrthoDBi | 236292at2759 |
PhylomeDBi | P35916 |
TreeFami | TF325768 |
Family and domain databases
DisProti | DP02600 |
Gene3Di | 2.60.40.10, 7 hits |
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 |
PANTHERi | PTHR24416:SF562, PTHR24416:SF562, 1 hit |
Pfami | View protein in Pfam PF07679, I-set, 1 hit PF07714, PK_Tyr_Ser-Thr, 1 hit PF17988, VEGFR-2_TMD, 1 hit |
SMARTi | View protein in SMART SM00409, IG, 6 hits SM00408, IGc2, 4 hits SM00219, TyrKc, 1 hit |
SUPFAMi | SSF48726, SSF48726, 6 hits SSF56112, SSF56112, 1 hit |
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 |
s (3+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry describes 3 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 3 described isoforms and 3 potential isoforms that are computationally mapped.Show allAlign All
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
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
Computationally mapped potential isoform sequencesi
There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketE9PD35 | E9PD35_HUMAN | Vascular endothelial growth factor ... | FLT4 | 1,306 | Annotation score: | ||
B5A927 | B5A927_HUMAN | Soluble VEGFR3 variant 2 | FLT4 VEGFR3 | 295 | Annotation score: | ||
D6RFF2 | D6RFF2_HUMAN | Vascular endothelial growth factor ... | FLT4 | 142 | Annotation score: |
Sequence cautioni
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 24 | G → D in CAA49505 (PubMed:1319394).Curated | 1 | |
Sequence conflicti | 24 | G → D in AAO89504 (Ref. 7) Curated | 1 | |
Sequence conflicti | 24 | G → D in AAO89505 (Ref. 7) Curated | 1 | |
Sequence conflicti | 538 | N → D in BAF84368 (PubMed:14702039).Curated | 1 | |
Sequence conflicti | 745 | R → P in CAA49505 (PubMed:1319394).Curated | 1 | |
Sequence conflicti | 745 | R → P in AAO89504 (Ref. 7) Curated | 1 | |
Sequence conflicti | 745 | R → P in AAO89505 (Ref. 7) Curated | 1 | |
Sequence conflicti | 752 – 753 | NA → RP in CAA49505 (PubMed:1319394).Curated | 2 | |
Sequence conflicti | 752 – 753 | NA → RP in AAO89504 (Ref. 7) Curated | 2 | |
Sequence conflicti | 752 – 753 | NA → RP in AAO89505 (Ref. 7) Curated | 2 | |
Sequence conflicti | 1128 | L → V in CAA49505 (PubMed:1319394).Curated | 1 | |
Sequence conflicti | 1128 | L → V in AAO89504 (Ref. 7) Curated | 1 | |
Sequence conflicti | 1128 | L → V in AAO89505 (Ref. 7) Curated | 1 | |
Sequence conflicti | 1164 | E → D in CAA49505 (PubMed:1319394).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_083806 | 82 – 1363 | Missing in CHTD7. 1 PublicationAdd BLAST | 1282 | |
Natural variantiVAR_042062 | 149 | N → D1 PublicationCorresponds to variant dbSNP:rs34221241EnsemblClinVar. | 1 | |
Natural variantiVAR_083807 | 361 – 1363 | Missing in CHTD7. 1 PublicationAdd BLAST | 1003 | |
Natural variantiVAR_042063 | 378 | R → C in a renal clear cell carcinoma sample; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs372947534Ensembl. | 1 | |
Natural variantiVAR_018407 | 494 | T → A2 PublicationsCorresponds to variant dbSNP:rs307826EnsemblClinVar. | 1 | |
Natural variantiVAR_034379 | 527 | N → S1 PublicationCorresponds to variant dbSNP:rs35874891EnsemblClinVar. | 1 | |
Natural variantiVAR_018408 | 641 | P → S2 PublicationsCorresponds to variant dbSNP:rs55667289EnsemblClinVar. | 1 | |
Natural variantiVAR_083808 | 736 – 1363 | Missing in CHTD7. 1 PublicationAdd BLAST | 628 | |
Natural variantiVAR_083809 | 741 | Missing in CHTD7; unknown pathological significance. 1 Publication | 1 | |
Natural variantiVAR_083810 | 833 – 1363 | Missing in CHTD7. 1 PublicationAdd BLAST | 531 | |
Natural variantiVAR_074044 | 855 | A → 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_018409 | 857 | G → R in LMPHM1; loss of kinase activity. 2 PublicationsCorresponds to variant dbSNP:rs267606818EnsemblClinVar. | 1 | |
Natural variantiVAR_042064 | 868 | H → Y1 PublicationCorresponds to variant dbSNP:rs35171798EnsemblClinVar. | 1 | |
Natural variantiVAR_074045 | 878 | V → M in LMPHM1. 1 PublicationCorresponds to variant dbSNP:rs121909654EnsemblClinVar. | 1 | |
Natural variantiVAR_018410 | 890 | H → Q4 PublicationsCorresponds to variant dbSNP:rs448012EnsemblClinVar. | 1 | |
Natural variantiVAR_018411 | 954 | P → S in HCI. 1 PublicationCorresponds to variant dbSNP:rs34255532EnsemblClinVar. | 1 | |
Natural variantiVAR_083811 | 999 – 1363 | Missing in CHTD7. 1 PublicationAdd BLAST | 365 | |
Natural variantiVAR_042065 | 1010 | T → I in a metastatic melanoma sample; somatic mutation. 1 Publication | 1 | |
Natural variantiVAR_074046 | 1020 | Q → L in LMPHM1. 1 Publication | 1 | |
Natural variantiVAR_042066 | 1031 | R → Q1 PublicationCorresponds to variant dbSNP:rs56082504Ensembl. | 1 | |
Natural variantiVAR_074047 | 1035 | H → Q Probable disease-associated variant found in sporadic congenital lymphedema; de novo mutation. 1 Publication | 1 | |
Natural variantiVAR_018412 | 1035 | H → R in LMPHM1; loss of kinase activity. 1 PublicationCorresponds to variant dbSNP:rs121909653EnsemblClinVar. | 1 | |
Natural variantiVAR_018413 | 1041 | R → P in LMPHM1; loss of kinase activity. 2 PublicationsCorresponds to variant dbSNP:rs121909650EnsemblClinVar. | 1 | |
Natural variantiVAR_018414 | 1044 | L → P in LMPHM1; loss of kinase activity. 1 PublicationCorresponds to variant dbSNP:rs121909651EnsemblClinVar. | 1 | |
Natural variantiVAR_042067 | 1049 | D → N1 PublicationCorresponds to variant dbSNP:rs56310180Ensembl. | 1 | |
Natural variantiVAR_042068 | 1075 | R → Q1 PublicationCorresponds to variant dbSNP:rs1400220848Ensembl. | 1 | |
Natural variantiVAR_074048 | 1086 | I → T in LMPHM1. 1 PublicationCorresponds to variant dbSNP:rs121909655EnsemblClinVar. | 1 | |
Natural variantiVAR_074049 | 1106 | E → K in LMPHM1. 1 PublicationCorresponds to variant dbSNP:rs121909656EnsemblClinVar. | 1 | |
Natural variantiVAR_074050 | 1108 | Missing in LMPHM1. 1 Publication | 1 | |
Natural variantiVAR_018415 | 1114 | P → L in LMPHM1; loss of kinase activity. 2 PublicationsCorresponds to variant dbSNP:rs121909652EnsemblClinVar. | 1 | |
Natural variantiVAR_018416 | 1137 | P → S in HCI. 1 Publication | 1 | |
Natural variantiVAR_018417 | 1146 | R → H4 PublicationsCorresponds to variant dbSNP:rs1130379EnsemblClinVar. | 1 | |
Natural variantiVAR_083812 | 1173 | L → V in CHTD7; unknown pathological significance. 1 Publication | 1 | |
Natural variantiVAR_083813 | 1192 – 1363 | Missing in CHTD7. 1 PublicationAdd BLAST | 172 | |
Natural variantiVAR_074051 | 1235 | S → C in LMPHM1; recessive form. 1 Publication | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_041993 | 724 – 765 | VDLAD…ASVAV → REGGPGEGQVRRPARPTIPN PGGPAPPPHPLQESTWRTPT RS in isoform 3. 1 PublicationAdd BLAST | 42 | |
Alternative sequenceiVSP_041994 | 766 – 1298 | Missing in isoform 3. 1 PublicationAdd BLAST | 533 | |
Alternative sequenceiVSP_041995 | 1298 – 1363 | SCKGP…TDNSY → R in isoform 2. 6 PublicationsAdd BLAST | 66 |
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 |
CCDSi | CCDS43412.1 [P35916-1] CCDS4457.1 [P35916-2] |
PIRi | A48999 |
RefSeqi | NP_002011.2, NM_002020.4 [P35916-1] NP_891555.2, NM_182925.4 [P35916-2] |
Genome annotation databases
Ensembli | ENST00000261937; ENSP00000261937; ENSG00000037280 ENST00000393347; ENSP00000377016; ENSG00000037280 [P35916-1] |
GeneIDi | 2324 |
KEGGi | hsa:2324 |
MANE-Selecti | ENST00000261937.11; ENSP00000261937.6; NM_182925.5; NP_891555.2 |
UCSCi | uc003mlz.4, human [P35916-2] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
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 |
CCDSi | CCDS43412.1 [P35916-1] CCDS4457.1 [P35916-2] |
PIRi | A48999 |
RefSeqi | NP_002011.2, NM_002020.4 [P35916-1] NP_891555.2, NM_182925.4 [P35916-2] |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
4BSJ | X-ray | 2.50 | A | 330-553 | [»] | |
4BSK | X-ray | 4.20 | A | 23-229 | [»] | |
SMRi | P35916 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 108612, 35 interactors |
CORUMi | P35916 |
DIPi | DIP-5739N |
IntActi | P35916, 18 interactors |
MINTi | P35916 |
STRINGi | 9606.ENSP00000261937 |
Chemistry databases
BindingDBi | P35916 |
ChEMBLi | CHEMBL1955 |
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 |
DrugCentrali | P35916 |
GuidetoPHARMACOLOGYi | 1814 |
PTM databases
GlyGeni | P35916, 12 sites |
iPTMneti | P35916 |
PhosphoSitePlusi | P35916 |
Genetic variation databases
BioMutai | FLT4 |
DMDMi | 357529070 |
Proteomic databases
jPOSTi | P35916 |
MassIVEi | P35916 |
PaxDbi | P35916 |
PeptideAtlasi | P35916 |
PRIDEi | P35916 |
ProteomicsDBi | 55166 [P35916-2] 55167 [P35916-1] 55168 [P35916-3] |
Protocols and materials databases
Antibodypediai | 3429, 1065 antibodies from 45 providers |
DNASUi | 2324 |
Genome annotation databases
Ensembli | ENST00000261937; ENSP00000261937; ENSG00000037280 ENST00000393347; ENSP00000377016; ENSG00000037280 [P35916-1] |
GeneIDi | 2324 |
KEGGi | hsa:2324 |
MANE-Selecti | ENST00000261937.11; ENSP00000261937.6; NM_182925.5; NP_891555.2 |
UCSCi | uc003mlz.4, human [P35916-2] |
Organism-specific databases
CTDi | 2324 |
DisGeNETi | 2324 |
GeneCardsi | FLT4 |
GeneReviewsi | FLT4 |
HGNCi | HGNC:3767, FLT4 |
HPAi | ENSG00000037280, Low tissue specificity |
MalaCardsi | FLT4 |
MIMi | 136352, gene 153100, phenotype 602089, phenotype 618780, phenotype |
neXtProti | NX_P35916 |
OpenTargetsi | ENSG00000037280 |
Orphaneti | 79452, Milroy disease 464293, NON RARE IN EUROPE: Infantile capillary hemangioma 3303, Tetralogy of Fallot |
PharmGKBi | PA28183 |
VEuPathDBi | HostDB:ENSG00000037280 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG0200, Eukaryota |
GeneTreei | ENSGT00940000159358 |
HOGENOMi | CLU_000288_49_4_1 |
InParanoidi | P35916 |
OMAi | RPYCKRL |
OrthoDBi | 236292at2759 |
PhylomeDBi | P35916 |
TreeFami | TF325768 |
Enzyme and pathway databases
BRENDAi | 2.7.10.1, 2681 |
PathwayCommonsi | P35916 |
Reactomei | R-HSA-195399, VEGF binds to VEGFR leading to receptor dimerization R-HSA-9013695, NOTCH4 Intracellular Domain Regulates Transcription |
SignaLinki | P35916 |
SIGNORi | P35916 |
Miscellaneous databases
BioGRID-ORCSi | 2324, 6 hits in 1069 CRISPR screens |
ChiTaRSi | FLT4, human |
GeneWikii | FLT4 |
GenomeRNAii | 2324 |
Pharosi | P35916, Tclin |
PROi | PR:P35916 |
RNActi | P35916, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000037280, Expressed in left lobe of thyroid gland and 141 other tissues |
ExpressionAtlasi | P35916, baseline and differential |
Genevisiblei | P35916, HS |
Family and domain databases
DisProti | DP02600 |
Gene3Di | 2.60.40.10, 7 hits |
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 |
PANTHERi | PTHR24416:SF562, PTHR24416:SF562, 1 hit |
Pfami | View protein in Pfam PF07679, I-set, 1 hit PF07714, PK_Tyr_Ser-Thr, 1 hit PF17988, VEGFR-2_TMD, 1 hit |
SMARTi | View protein in SMART SM00409, IG, 6 hits SM00408, IGc2, 4 hits SM00219, TyrKc, 1 hit |
SUPFAMi | SSF48726, SSF48726, 6 hits SSF56112, SSF56112, 1 hit |
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 |
MobiDBi | Search... |
Entry informationi
Entry namei | VGFR3_HUMAN | |
Accessioni | P35916Primary (citable) accession number: P35916 Secondary accession number(s): A8K6L4 Q86W08 | |
Entry historyi | Integrated 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. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any 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. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Direct protein sequencing, Reference proteomeDocuments
- Human and mouse protein kinases
Human and mouse protein kinases: classification and index - Human chromosome 5
Human chromosome 5: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families