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Protein

Vascular endothelial growth factor receptor 3

Gene

FLT4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

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

Catalytic activityi

ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.PROSITE-ProRule annotation2 Publications

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
Binding sitei879ATPCurated1
Active sitei1037Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi851 – 859ATPPROSITE-ProRule annotation9

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • growth factor binding Source: UniProtKB
  • protein homodimerization activity Source: UniProtKB
  • protein phosphatase binding Source: UniProtKB
  • transmembrane receptor protein tyrosine kinase activity Source: UniProtKB
  • vascular endothelial growth factor-activated receptor activity Source: MGI
  • VEGF-C-activated receptor activity Source: UniProtKB

GO - Biological processi

Keywordsi

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

Enzyme and pathway databases

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

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
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 5

Organism-specific databases

EuPathDBiHostDB:ENSG00000037280.15
HGNCiHGNC:3767 FLT4
MIMi136352 gene
neXtProtiNX_P35916

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini25 – 775ExtracellularSequence analysisAdd BLAST751
Transmembranei776 – 796HelicalSequence analysisAdd BLAST21
Topological domaini797 – 1363CytoplasmicSequence analysisAdd BLAST567

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane, Nucleus, Secreted

Pathology & Biotechi

Involvement in diseasei

Lymphedema, hereditary, 1A (LMPH1A)10 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA chronic disabling condition which results in swelling of the extremities due to altered lymphatic flow. Patients with lymphedema suffer from recurrent local infections and physical impairment.
See also OMIM:153100
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_074044855A → T in LMPH1A; recessive form; results in reduced autophosphorylation; results in impaired ligand-induced receptor internalisation and downstream signaling. 1 PublicationCorresponds to variant dbSNP:rs121909657EnsemblClinVar.1
Natural variantiVAR_018409857G → R in LMPH1A; loss of kinase activity. 2 PublicationsCorresponds to variant dbSNP:rs267606818EnsemblClinVar.1
Natural variantiVAR_074045878V → M in LMPH1A. 1 PublicationCorresponds to variant dbSNP:rs121909654EnsemblClinVar.1
Natural variantiVAR_0740461020Q → L in LMPH1A. 1 Publication1
Natural variantiVAR_0184121035H → R in LMPH1A; loss of kinase activity. 1 PublicationCorresponds to variant dbSNP:rs121909653EnsemblClinVar.1
Natural variantiVAR_0184131041R → P in LMPH1A; loss of kinase activity. 2 PublicationsCorresponds to variant dbSNP:rs121909650EnsemblClinVar.1
Natural variantiVAR_0184141044L → P in LMPH1A; loss of kinase activity. 1 PublicationCorresponds to variant dbSNP:rs121909651EnsemblClinVar.1
Natural variantiVAR_0740481086I → T in LMPH1A. 1 PublicationCorresponds to variant dbSNP:rs121909655EnsemblClinVar.1
Natural variantiVAR_0740491106E → K in LMPH1A. 1 PublicationCorresponds to variant dbSNP:rs121909656EnsemblClinVar.1
Natural variantiVAR_0740501108Missing in LMPH1A. 1 Publication1
Natural variantiVAR_0184151114P → L in LMPH1A; loss of kinase activity. 2 PublicationsCorresponds to variant dbSNP:rs121909652EnsemblClinVar.1
Natural variantiVAR_0740511235S → C in LMPH1A; recessive form. 1 Publication1
Hemangioma, capillary infantile (HCI)1 Publication
Disease susceptibility is associated with variations 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.
See also OMIM:602089
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.

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
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. Slighly reduced autophosphorylation. 2 Publications1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi2324
GeneReviewsiFLT4
MalaCardsiFLT4
MIMi153100 phenotype
602089 phenotype
OpenTargetsiENSG00000037280
Orphaneti79452 Milroy disease
PharmGKBiPA28183

Chemistry databases

ChEMBLiCHEMBL1955
DrugBankiDB06080 ABT-869
DB06626 Axitinib
DB06101 IMC-1C11
DB09078 Lenvatinib
DB09079 Nintedanib
DB06589 Pazopanib
DB08896 Regorafenib
DB00398 Sorafenib
DB01268 Sunitinib
DB05075 TG100801
DB04879 Vatalanib
GuidetoPHARMACOLOGYi1814

Polymorphism and mutation databases

BioMutaiFLT4
DMDMi357529070

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 241 PublicationAdd BLAST24
ChainiPRO_000001677625 – 1363Vascular endothelial growth factor receptor 3Add BLAST1339

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi33N-linked (GlcNAc...) asparagineCombined sources1 Publication1
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
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

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

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

PTM databases

iPTMnetiP35916
PhosphoSitePlusiP35916

Expressioni

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

BgeeiENSG00000037280 Expressed in 121 organ(s), highest expression level in left lobe of thyroid gland
CleanExiHS_FLT4
ExpressionAtlasiP35916 baseline and differential
GenevisibleiP35916 HS

Organism-specific databases

HPAiCAB000099
HPA046519
HPA067906

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 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi108612, 28 interactors
CORUMiP35916
DIPiDIP-5739N
IntActiP35916, 8 interactors
MINTiP35916
STRINGi9606.ENSP00000261937

Chemistry databases

BindingDBiP35916

Structurei

Secondary structure

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

3D structure databases

ProteinModelPortaliP35916
SMRiP35916
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
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

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

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

eggNOGiKOG0200 Eukaryota
COG0515 LUCA
GeneTreeiENSGT00760000118923
HOGENOMiHOG000037949
HOVERGENiHBG053432
InParanoidiP35916
KOiK05097
OMAiPLEEQCE
OrthoDBiEOG091G01TL
PhylomeDBiP35916
TreeFamiTF325768

Family and domain databases

Gene3Di2.60.40.10, 6 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
IPR009137 VEGFR3_rcpt
PANTHERiPTHR24416:SF49 PTHR24416:SF49, 1 hit
PfamiView protein in Pfam
PF07679 I-set, 1 hit
PF07714 Pkinase_Tyr, 1 hit
SMARTiView protein in SMART
SM00409 IG, 6 hits
SM00408 IGc2, 4 hits
SM00219 TyrKc, 1 hit
SUPFAMiSSF48726 SSF48726, 6 hits
SSF56112 SSF56112, 2 hits
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

Sequences (3+)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 3 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 'canonical' 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
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

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:
B5A927B5A927_HUMAN
Soluble VEGFR3 variant 2
FLT4 VEGFR3
295Annotation score:
D6RFF2D6RFF2_HUMAN
Vascular endothelial growth factor ...
FLT4
142Annotation score:

Sequence cautioni

The sequence CAA48290 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti24G → D in CAA49505 (PubMed:1319394).Curated1
Sequence conflicti24G → D in AAO89504 (Ref. 6) Curated1
Sequence conflicti24G → D in AAO89505 (Ref. 6) Curated1
Sequence conflicti538N → D in BAF84368 (PubMed:14702039).Curated1
Sequence conflicti745R → P in CAA49505 (PubMed:1319394).Curated1
Sequence conflicti745R → P in AAO89504 (Ref. 6) Curated1
Sequence conflicti745R → P in AAO89505 (Ref. 6) Curated1
Sequence conflicti752 – 753NA → RP in CAA49505 (PubMed:1319394).Curated2
Sequence conflicti752 – 753NA → RP in AAO89504 (Ref. 6) Curated2
Sequence conflicti752 – 753NA → RP in AAO89505 (Ref. 6) Curated2
Sequence conflicti1128L → V in CAA49505 (PubMed:1319394).Curated1
Sequence conflicti1128L → V in AAO89504 (Ref. 6) Curated1
Sequence conflicti1128L → V in AAO89505 (Ref. 6) Curated1
Sequence conflicti1164E → D in CAA49505 (PubMed:1319394).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_042062149N → D1 PublicationCorresponds to variant dbSNP:rs34221241EnsemblClinVar.1
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_074044855A → T in LMPH1A; recessive form; results in reduced autophosphorylation; results in impaired ligand-induced receptor internalisation and downstream signaling. 1 PublicationCorresponds to variant dbSNP:rs121909657EnsemblClinVar.1
Natural variantiVAR_018409857G → R in LMPH1A; loss of kinase activity. 2 PublicationsCorresponds to variant dbSNP:rs267606818EnsemblClinVar.1
Natural variantiVAR_042064868H → Y1 PublicationCorresponds to variant dbSNP:rs35171798Ensembl.1
Natural variantiVAR_074045878V → M in LMPH1A. 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_0420651010T → I in a metastatic melanoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_0740461020Q → L in LMPH1A. 1 Publication1
Natural variantiVAR_0420661031R → Q1 PublicationCorresponds to variant dbSNP:rs56082504Ensembl.1
Natural variantiVAR_0740471035H → Q Probable disease-associated mutation found in sporadic congenital lymphedema; de novo mutation. 1 Publication1
Natural variantiVAR_0184121035H → R in LMPH1A; loss of kinase activity. 1 PublicationCorresponds to variant dbSNP:rs121909653EnsemblClinVar.1
Natural variantiVAR_0184131041R → P in LMPH1A; loss of kinase activity. 2 PublicationsCorresponds to variant dbSNP:rs121909650EnsemblClinVar.1
Natural variantiVAR_0184141044L → P in LMPH1A; 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 Publication1
Natural variantiVAR_0740481086I → T in LMPH1A. 1 PublicationCorresponds to variant dbSNP:rs121909655EnsemblClinVar.1
Natural variantiVAR_0740491106E → K in LMPH1A. 1 PublicationCorresponds to variant dbSNP:rs121909656EnsemblClinVar.1
Natural variantiVAR_0740501108Missing in LMPH1A. 1 Publication1
Natural variantiVAR_0184151114P → L in LMPH1A; 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_0740511235S → C in LMPH1A; recessive form. 1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
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:
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]
UniGeneiHs.646917

Genome annotation databases

EnsembliENST00000261937; ENSP00000261937; ENSG00000037280 [P35916-2]
ENST00000393347; ENSP00000377016; ENSG00000037280 [P35916-1]
GeneIDi2324
KEGGihsa:2324
UCSCiuc003mlz.4 human [P35916-2]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar 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
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]
UniGeneiHs.646917

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4BSJX-ray2.50A330-553[»]
4BSKX-ray4.20A23-229[»]
ProteinModelPortaliP35916
SMRiP35916
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi108612, 28 interactors
CORUMiP35916
DIPiDIP-5739N
IntActiP35916, 8 interactors
MINTiP35916
STRINGi9606.ENSP00000261937

Chemistry databases

BindingDBiP35916
ChEMBLiCHEMBL1955
DrugBankiDB06080 ABT-869
DB06626 Axitinib
DB06101 IMC-1C11
DB09078 Lenvatinib
DB09079 Nintedanib
DB06589 Pazopanib
DB08896 Regorafenib
DB00398 Sorafenib
DB01268 Sunitinib
DB05075 TG100801
DB04879 Vatalanib
GuidetoPHARMACOLOGYi1814

PTM databases

iPTMnetiP35916
PhosphoSitePlusiP35916

Polymorphism and mutation databases

BioMutaiFLT4
DMDMi357529070

Proteomic databases

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

Protocols and materials databases

DNASUi2324
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000261937; ENSP00000261937; ENSG00000037280 [P35916-2]
ENST00000393347; ENSP00000377016; ENSG00000037280 [P35916-1]
GeneIDi2324
KEGGihsa:2324
UCSCiuc003mlz.4 human [P35916-2]

Organism-specific databases

CTDi2324
DisGeNETi2324
EuPathDBiHostDB:ENSG00000037280.15
GeneCardsiFLT4
GeneReviewsiFLT4
HGNCiHGNC:3767 FLT4
HPAiCAB000099
HPA046519
HPA067906
MalaCardsiFLT4
MIMi136352 gene
153100 phenotype
602089 phenotype
neXtProtiNX_P35916
OpenTargetsiENSG00000037280
Orphaneti79452 Milroy disease
PharmGKBiPA28183
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0200 Eukaryota
COG0515 LUCA
GeneTreeiENSGT00760000118923
HOGENOMiHOG000037949
HOVERGENiHBG053432
InParanoidiP35916
KOiK05097
OMAiPLEEQCE
OrthoDBiEOG091G01TL
PhylomeDBiP35916
TreeFamiTF325768

Enzyme and pathway databases

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

Miscellaneous databases

ChiTaRSiFLT4 human
GeneWikiiFLT4
GenomeRNAii2324
PROiPR:P35916
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000037280 Expressed in 121 organ(s), highest expression level in left lobe of thyroid gland
CleanExiHS_FLT4
ExpressionAtlasiP35916 baseline and differential
GenevisibleiP35916 HS

Family and domain databases

Gene3Di2.60.40.10, 6 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
IPR009137 VEGFR3_rcpt
PANTHERiPTHR24416:SF49 PTHR24416:SF49, 1 hit
PfamiView protein in Pfam
PF07679 I-set, 1 hit
PF07714 Pkinase_Tyr, 1 hit
SMARTiView protein in SMART
SM00409 IG, 6 hits
SM00408 IGc2, 4 hits
SM00219 TyrKc, 1 hit
SUPFAMiSSF48726 SSF48726, 6 hits
SSF56112 SSF56112, 2 hits
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
ProtoNetiSearch...

Entry informationi

Entry nameiVGFR3_HUMAN
AccessioniPrimary (citable) accession number: P35916
Secondary accession number(s): A8K6L4
, B5A926, Q16067, Q86W07, Q86W08
Entry historyiIntegrated into UniProtKB/Swiss-Prot: June 1, 1994
Last sequence update: November 16, 2011
Last modified: September 12, 2018
This is version 202 of the entry and version 3 of the sequence. See complete history.
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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

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