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P35916

- VGFR3_HUMAN

UniProt

P35916 - VGFR3_HUMAN

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Protein

Vascular endothelial growth factor receptor 3

Gene

FLT4

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- 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.2 PublicationsPROSITE-ProRule annotation

Enzyme 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)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei879 – 8791ATPCurated
Active sitei1037 – 10371Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi851 – 8599ATPPROSITE-ProRule annotation

GO - Molecular functioni

  1. ATP binding Source: UniProtKB-KW
  2. growth factor binding Source: UniProtKB
  3. protein phosphatase binding Source: UniProtKB
  4. transmembrane receptor protein tyrosine kinase activity Source: UniProtKB
  5. vascular endothelial growth factor-activated receptor activity Source: UniProtKB

GO - Biological processi

  1. blood vessel morphogenesis Source: UniProtKB
  2. cellular response to vascular endothelial growth factor stimulus Source: UniProtKB
  3. lymphangiogenesis Source: UniProtKB
  4. lymph vessel development Source: BHF-UCL
  5. negative regulation of apoptotic process Source: UniProtKB
  6. peptidyl-tyrosine phosphorylation Source: UniProtKB
  7. positive regulation of cell proliferation Source: UniProtKB
  8. positive regulation of endothelial cell migration Source: UniProtKB
  9. positive regulation of endothelial cell proliferation Source: UniProtKB
  10. positive regulation of ERK1 and ERK2 cascade Source: UniProtKB
  11. positive regulation of JNK cascade Source: UniProtKB
  12. positive regulation of MAPK cascade Source: UniProtKB
  13. positive regulation of protein kinase C signaling Source: UniProtKB
  14. positive regulation of protein phosphorylation Source: UniProtKB
  15. positive regulation vascular endothelial growth factor production Source: UniProtKB
  16. protein autophosphorylation Source: UniProtKB
  17. regulation of blood vessel remodeling Source: UniProtKB
  18. sprouting angiogenesis Source: UniProtKB
  19. transmembrane receptor protein tyrosine kinase signaling pathway Source: ProtInc
  20. vascular endothelial growth factor receptor signaling pathway Source: UniProtKB
  21. vascular endothelial growth factor signaling pathway Source: GOC
  22. vasculature development Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Receptor, Transferase, Tyrosine-protein kinase

Keywords - Biological processi

Angiogenesis

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.10.1. 2681.
ReactomeiREACT_12583. VEGF binds to VEGFR leading to receptor dimerization.
SignaLinkiP35916.

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
ProteomesiUP000005640: Chromosome 5

Organism-specific databases

HGNCiHGNC:3767. FLT4.

Subcellular locationi

Cell membrane; Single-pass type I membrane protein. Cytoplasm. Nucleus
Note: Ligand-mediated autophosphorylation leads to rapid internalization.
Isoform 1 : Cell membrane; Single-pass type I membrane protein
Note: Ligand-mediated autophosphorylation leads to rapid internalization.

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini25 – 775751ExtracellularSequence AnalysisAdd
BLAST
Transmembranei776 – 79621HelicalSequence AnalysisAdd
BLAST
Topological domaini797 – 1363567CytoplasmicSequence AnalysisAdd
BLAST

GO - Cellular componenti

  1. cytoplasm Source: UniProtKB-KW
  2. extracellular region Source: UniProtKB-KW
  3. integral component of plasma membrane Source: ProtInc
  4. nucleus Source: UniProtKB-KW
  5. plasma membrane Source: UniProtKB
  6. receptor complex Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane, Nucleus, Secreted

Pathology & Biotechi

Involvement in diseasei

Lymphedema, hereditary, 1A (LMPH1A) [MIM:153100]: A 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.3 Publications
Note: The disease is caused by mutations affecting the gene represented in this entry.
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti857 – 8571G → R in LMPH1A; loss of kinase activity. 1 Publication
VAR_018409
Natural varianti1035 – 10351H → R in LMPH1A; loss of kinase activity.
VAR_018412
Natural varianti1041 – 10411R → P in LMPH1A; loss of kinase activity. 1 Publication
VAR_018413
Natural varianti1044 – 10441L → P in LMPH1A; loss of kinase activity. 1 Publication
VAR_018414
Natural varianti1114 – 11141P → L in LMPH1A; loss of kinase activity. 2 Publications
VAR_018415
Hemangioma, capillary infantile (HCI) [MIM:602089]: A 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.1 Publication
Note: Disease susceptibility is associated with variations affecting the gene represented in this entry.
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti954 – 9541P → S in HCI. 1 Publication
Corresponds to variant rs34255532 [ dbSNP | Ensembl ].
VAR_018411
Natural varianti1137 – 11371P → S in HCI. 1 Publication
VAR_018416
Plays an important role in tumor lymphangiogenesis, in cancer cell survival, migration, and formation of metastases.

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi879 – 8791K → G: Abolishes enzyme activity. 1 Publication
Mutagenesisi1063 – 10631Y → F: Loss of phosphorylation site. No effect on stimulation of cell proliferation and cell migration. 2 Publications
Mutagenesisi1068 – 10681Y → F: Global loss of autophosphorylation. Abolishes stimulation of cell proliferation and cell migration. 2 Publications
Mutagenesisi1230 – 12301Y → F: Loss of phosphorylation site. Strongly reduces stimulation of cell proliferation and cell migration. 2 Publications
Mutagenesisi1231 – 12311Y → F: Loss of phosphorylation site. Strongly reduces stimulation of cell proliferation and cell migration. 2 Publications
Mutagenesisi1265 – 12651Y → F: Loss of phosphorylation site. No effect on stimulation of cell proliferation and cell migration. 1 Publication
Mutagenesisi1333 – 13331Y → F: Loss of phosphorylation site. Reduced autophosphorylation. 2 Publications
Mutagenesisi1337 – 13371Y → F: Reduced autophosphorylation. Strongly reduces stimulation of cell proliferation and cell migration. 3 Publications
Mutagenesisi1363 – 13631Y → F: Loss of phosphorylation site. Slighly reduced autophosphorylation. 2 Publications

Keywords - Diseasei

Disease mutation

Organism-specific databases

MIMi153100. phenotype.
602089. phenotype.
Orphaneti79452. Milroy disease.
PharmGKBiPA28183.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 24241 PublicationAdd
BLAST
Chaini25 – 13631339Vascular endothelial growth factor receptor 3PRO_0000016776Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi33 – 331N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi51 ↔ 111PROSITE-ProRule annotation
Glycosylationi104 – 1041N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi158 ↔ 206PROSITE-ProRule annotation
Glycosylationi166 – 1661N-linked (GlcNAc...)Sequence Analysis
Glycosylationi251 – 2511N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi252 ↔ 310PROSITE-ProRule annotation
Glycosylationi299 – 2991N-linked (GlcNAc...)Sequence Analysis
Glycosylationi411 – 4111N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi445 ↔ 534PROSITE-ProRule annotation
Glycosylationi515 – 5151N-linked (GlcNAc...)Sequence Analysis
Glycosylationi527 – 5271N-linked (GlcNAc...)1 Publication
Disulfide bondi578 ↔ 653PROSITE-ProRule annotation
Glycosylationi594 – 5941N-linked (GlcNAc...)Sequence Analysis
Glycosylationi683 – 6831N-linked (GlcNAc...)Sequence Analysis
Glycosylationi690 – 6901N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi699 ↔ 751PROSITE-ProRule annotation
Glycosylationi758 – 7581N-linked (GlcNAc...)Sequence Analysis
Modified residuei830 – 8301Phosphotyrosine; by SRC1 Publication
Modified residuei833 – 8331Phosphotyrosine; by SRC1 Publication
Modified residuei853 – 8531Phosphotyrosine; by SRC1 Publication
Modified residuei1063 – 10631Phosphotyrosine; by autocatalysis and SRC2 Publications
Modified residuei1068 – 10681Phosphotyrosine; by autocatalysis2 Publications
Modified residuei1230 – 12301Phosphotyrosine; by autocatalysis2 Publications
Modified residuei1231 – 12311Phosphotyrosine; by autocatalysis2 Publications
Modified residuei1265 – 12651Phosphotyrosine; by autocatalysis1 Publication
Modified residuei1333 – 13331Phosphotyrosine; by autocatalysis and SRC2 Publications
Modified residuei1337 – 13371Phosphotyrosine; by autocatalysis and SRC3 Publications
Modified residuei1363 – 13631Phosphotyrosine; by autocatalysis1 Publication

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-1337.6 Publications

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiP35916.
PRIDEiP35916.

PTM databases

PhosphoSiteiP35916.

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

BgeeiP35916.
CleanExiHS_FLT4.
ExpressionAtlasiP35916. baseline and differential.
GenevestigatoriP35916.

Organism-specific databases

HPAiCAB000099.

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 ITGB1.13 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
HSP90AB1P082382EBI-1005467,EBI-352572
KDRP359685EBI-1005467,EBI-1005487
VEGFCP497672EBI-1005467,EBI-3405539

Protein-protein interaction databases

BioGridi108612. 17 interactions.
DIPiDIP-5739N.
IntActiP35916. 7 interactions.
MINTiMINT-1182429.
STRINGi9606.ENSP00000261937.

Structurei

Secondary structure

1
1363
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi332 – 3398Combined sources
Beta strandi341 – 3466Combined sources
Beta strandi350 – 36213Combined sources
Beta strandi365 – 3706Combined sources
Beta strandi381 – 3888Combined sources
Helixi391 – 3933Combined sources
Beta strandi395 – 4039Combined sources
Turni404 – 4074Combined sources
Beta strandi408 – 42417Combined sources
Helixi425 – 4284Combined sources
Beta strandi441 – 45111Combined sources
Beta strandi457 – 4648Combined sources
Beta strandi501 – 51111Combined sources
Beta strandi514 – 52411Combined sources
Beta strandi530 – 5389Combined sources
Beta strandi541 – 5499Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
4BSJX-ray2.50A330-553[»]
4BSKX-ray4.20A23-229[»]
ProteinModelPortaliP35916.
SMRiP35916. Positions 28-553, 566-592, 632-765, 823-1180.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini30 – 12798Ig-like C2-type 1Add
BLAST
Domaini151 – 21363Ig-like C2-type 2Add
BLAST
Domaini219 – 326108Ig-like C2-type 3Add
BLAST
Domaini331 – 41585Ig-like C2-type 4Add
BLAST
Domaini422 – 552131Ig-like C2-type 5Add
BLAST
Domaini555 – 671117Ig-like C2-type 6Add
BLAST
Domaini678 – 76487Ig-like C2-type 7Add
BLAST
Domaini845 – 1173329Protein kinasePROSITE-ProRule annotationAdd
BLAST

Domaini

The first and second Ig-like C2-type (immunoglobulin-like) domains are sufficient for VEGFC binding.

Sequence similaritiesi

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

Keywords - Domaini

Immunoglobulin domain, Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiCOG0515.
GeneTreeiENSGT00760000118923.
HOGENOMiHOG000037949.
HOVERGENiHBG053432.
InParanoidiP35916.
KOiK05097.
OMAiPAHADIK.
OrthoDBiEOG75F4CC.
PhylomeDBiP35916.
TreeFamiTF325768.

Family and domain databases

Gene3Di2.60.40.10. 9 hits.
InterProiIPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR013098. Ig_I-set.
IPR003599. Ig_sub.
IPR003598. Ig_sub2.
IPR011009. Kinase-like_dom.
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.
[Graphical view]
PANTHERiPTHR24416:SF49. PTHR24416:SF49. 1 hit.
PfamiPF07679. I-set. 2 hits.
PF07714. Pkinase_Tyr. 1 hit.
[Graphical view]
PRINTSiPR01835. VEGFRECEPTR3.
SMARTiSM00409. IG. 4 hits.
SM00408. IGc2. 2 hits.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 2 hits.
PROSITEiPS50835. 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.
[Graphical view]

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. Align

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

Sequence cautioni

The sequence CAA48290.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti24 – 241G → D in CAA49505. (PubMed:1319394)Curated
Sequence conflicti24 – 241G → D in AAO89504. 1 PublicationCurated
Sequence conflicti24 – 241G → D in AAO89505. 1 PublicationCurated
Sequence conflicti538 – 5381N → D in BAF84368. (PubMed:14702039)Curated
Sequence conflicti745 – 7451R → P in CAA49505. (PubMed:1319394)Curated
Sequence conflicti745 – 7451R → P in AAO89504. 1 PublicationCurated
Sequence conflicti745 – 7451R → P in AAO89505. 1 PublicationCurated
Sequence conflicti752 – 7532NA → RP in CAA49505. (PubMed:1319394)Curated
Sequence conflicti752 – 7532NA → RP in AAO89504. 1 PublicationCurated
Sequence conflicti752 – 7532NA → RP in AAO89505. 1 PublicationCurated
Sequence conflicti1128 – 11281L → V in CAA49505. (PubMed:1319394)Curated
Sequence conflicti1128 – 11281L → V in AAO89504. 1 PublicationCurated
Sequence conflicti1128 – 11281L → V in AAO89505. 1 PublicationCurated
Sequence conflicti1164 – 11641E → D in CAA49505. (PubMed:1319394)Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti149 – 1491N → D.1 Publication
Corresponds to variant rs34221241 [ dbSNP | Ensembl ].
VAR_042062
Natural varianti378 – 3781R → C in a renal clear cell carcinoma sample; somatic mutation. 1 Publication
VAR_042063
Natural varianti494 – 4941T → A.2 Publications
Corresponds to variant rs307826 [ dbSNP | Ensembl ].
VAR_018407
Natural varianti527 – 5271N → S.1 Publication
Corresponds to variant rs35874891 [ dbSNP | Ensembl ].
VAR_034379
Natural varianti641 – 6411P → S.2 Publications
Corresponds to variant rs55667289 [ dbSNP | Ensembl ].
VAR_018408
Natural varianti857 – 8571G → R in LMPH1A; loss of kinase activity. 1 Publication
VAR_018409
Natural varianti868 – 8681H → Y.1 Publication
Corresponds to variant rs35171798 [ dbSNP | Ensembl ].
VAR_042064
Natural varianti890 – 8901H → Q.4 Publications
Corresponds to variant rs448012 [ dbSNP | Ensembl ].
VAR_018410
Natural varianti954 – 9541P → S in HCI. 1 Publication
Corresponds to variant rs34255532 [ dbSNP | Ensembl ].
VAR_018411
Natural varianti1010 – 10101T → I in a metastatic melanoma sample; somatic mutation. 1 Publication
VAR_042065
Natural varianti1031 – 10311R → Q.1 Publication
Corresponds to variant rs56082504 [ dbSNP | Ensembl ].
VAR_042066
Natural varianti1035 – 10351H → R in LMPH1A; loss of kinase activity.
VAR_018412
Natural varianti1041 – 10411R → P in LMPH1A; loss of kinase activity. 1 Publication
VAR_018413
Natural varianti1044 – 10441L → P in LMPH1A; loss of kinase activity. 1 Publication
VAR_018414
Natural varianti1049 – 10491D → N.1 Publication
Corresponds to variant rs56310180 [ dbSNP | Ensembl ].
VAR_042067
Natural varianti1075 – 10751R → Q.1 Publication
VAR_042068
Natural varianti1114 – 11141P → L in LMPH1A; loss of kinase activity. 2 Publications
VAR_018415
Natural varianti1137 – 11371P → S in HCI. 1 Publication
VAR_018416
Natural varianti1146 – 11461R → H.4 Publications
Corresponds to variant rs1130379 [ dbSNP | Ensembl ].
VAR_018417

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei724 – 76542VDLAD…ASVAV → REGGPGEGQVRRPARPTIPN PGGPAPPPHPLQESTWRTPT RS in isoform 3. 1 PublicationVSP_041993Add
BLAST
Alternative sequencei766 – 1298533Missing in isoform 3. 1 PublicationVSP_041994Add
BLAST
Alternative sequencei1298 – 136366SCKGP…TDNSY → R in isoform 2. 6 PublicationsVSP_041995Add
BLAST

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]
uc003mma.4. human. [P35916-1]
uc011dgy.2. human. [P35916-3]

Polymorphism databases

DMDMi357529070.

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

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 ]
UniGenei Hs.646917.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
4BSJ X-ray 2.50 A 330-553 [» ]
4BSK X-ray 4.20 A 23-229 [» ]
ProteinModelPortali P35916.
SMRi P35916. Positions 28-553, 566-592, 632-765, 823-1180.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 108612. 17 interactions.
DIPi DIP-5739N.
IntActi P35916. 7 interactions.
MINTi MINT-1182429.
STRINGi 9606.ENSP00000261937.

Chemistry

BindingDBi P35916.
ChEMBLi CHEMBL2111409.
DrugBanki DB06626. Axitinib.
DB06589. Pazopanib.
DB08896. Regorafenib.
DB00398. Sorafenib.
DB01268. Sunitinib.
GuidetoPHARMACOLOGYi 1814.

PTM databases

PhosphoSitei P35916.

Polymorphism databases

DMDMi 357529070.

Proteomic databases

PaxDbi P35916.
PRIDEi P35916.

Protocols and materials databases

DNASUi 2324.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000261937 ; ENSP00000261937 ; ENSG00000037280 . [P35916-2 ]
ENST00000393347 ; ENSP00000377016 ; ENSG00000037280 . [P35916-1 ]
GeneIDi 2324.
KEGGi hsa:2324.
UCSCi uc003mlz.4. human. [P35916-2 ]
uc003mma.4. human. [P35916-1 ]
uc011dgy.2. human. [P35916-3 ]

Organism-specific databases

CTDi 2324.
GeneCardsi GC05M180028.
GeneReviewsi FLT4.
HGNCi HGNC:3767. FLT4.
HPAi CAB000099.
MIMi 136352. gene.
153100. phenotype.
602089. phenotype.
neXtProti NX_P35916.
Orphaneti 79452. Milroy disease.
PharmGKBi PA28183.
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG0515.
GeneTreei ENSGT00760000118923.
HOGENOMi HOG000037949.
HOVERGENi HBG053432.
InParanoidi P35916.
KOi K05097.
OMAi PAHADIK.
OrthoDBi EOG75F4CC.
PhylomeDBi P35916.
TreeFami TF325768.

Enzyme and pathway databases

BRENDAi 2.7.10.1. 2681.
Reactomei REACT_12583. VEGF binds to VEGFR leading to receptor dimerization.
SignaLinki P35916.

Miscellaneous databases

ChiTaRSi FLT4. human.
GeneWikii FLT4.
GenomeRNAii 2324.
NextBioi 9433.
PROi P35916.
SOURCEi Search...

Gene expression databases

Bgeei P35916.
CleanExi HS_FLT4.
ExpressionAtlasi P35916. baseline and differential.
Genevestigatori P35916.

Family and domain databases

Gene3Di 2.60.40.10. 9 hits.
InterProi IPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR013098. Ig_I-set.
IPR003599. Ig_sub.
IPR003598. Ig_sub2.
IPR011009. Kinase-like_dom.
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.
[Graphical view ]
PANTHERi PTHR24416:SF49. PTHR24416:SF49. 1 hit.
Pfami PF07679. I-set. 2 hits.
PF07714. Pkinase_Tyr. 1 hit.
[Graphical view ]
PRINTSi PR01835. VEGFRECEPTR3.
SMARTi SM00409. IG. 4 hits.
SM00408. IGc2. 2 hits.
SM00219. TyrKc. 1 hit.
[Graphical view ]
SUPFAMi SSF56112. SSF56112. 2 hits.
PROSITEi 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.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. "FLT4 receptor tyrosine kinase contains seven immunoglobulin-like loops and is expressed in multiple human tissues and cell lines."
    Pajusola K., Aprelikova O., Korhonen J., Kaipainen A., Pertovaara L., Alitalo R., Alitalo K.
    Cancer Res. 52:5738-5743(1992) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), TISSUE SPECIFICITY.
  2. "Chromosomal localization of FLT4, a novel receptor-type tyrosine kinase gene."
    Galland F., Karamysheva A., Mattei M.-G., Rosnet O., Marchetto S., Birnbaum D.
    Genomics 13:475-478(1992) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
  3. "The FLT4 gene encodes a transmembrane tyrosine kinase related to the vascular endothelial growth factor receptor."
    Galland F., Karamysheva A., Pebusque M.-J., Borg J.-P., Rottapel R., Dubreuil P., Rosnet O., Birnbaum D.
    Oncogene 8:1233-1240(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), VARIANTS GLN-890 AND HIS-1146.
    Tissue: Placenta.
  4. "Vascular endothelial growth factor-related protein: a ligand and specific activator of the tyrosine kinase receptor Flt4."
    Lee J., Gray A., Yuan J., Luoh S.-M., Avraham H., Wood W.I.
    Proc. Natl. Acad. Sci. U.S.A. 93:1988-1992(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), INTERACTION WITH VEGFC, PHOSPHORYLATION, FUNCTION IN CELL PROLIFERATION.
  5. "Novel splice variants derived from the receptor tyrosine kinase superfamily are potential therapeutics for rheumatoid arthritis."
    Jin P., Zhang J., Sumariwalla P.F., Ni I., Jorgensen B., Crawford D., Phillips S., Feldmann M., Shepard H.M., Paleolog E.M.
    Arthritis Res. Ther. 10:R73-R73(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), INTERACTION WITH VEGFD, SUBCELLULAR LOCATION.
  6. Lian Z., Feitelson M.
    Submitted (FEB-2003) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), VARIANTS GLN-890 AND HIS-1146.
  7. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
    Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
    , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
    Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), VARIANT GLN-890.
    Tissue: Placenta.
  8. "The DNA sequence and comparative analysis of human chromosome 5."
    Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S., Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M., She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S.
    , Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R., Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.
    Nature 431:268-274(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  9. "FLT4, a novel class III receptor tyrosine kinase in chromosome 5q33-qter."
    Aprelikova O., Pajusola K., Partanen J., Armstrong E., Alitalo R., Bailey S.K., McMahon J., Wasmuth J., Huebner K., Alitalo K.
    Cancer Res. 52:746-748(1992) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 761-1190.
  10. "Two human FLT4 receptor tyrosine kinase isoforms with distinct carboxy terminal tails are produced by alternative processing of primary transcripts."
    Pajusola K., Aprelikova O., Armstrong E., Morris S., Alitalo K.
    Oncogene 8:2931-2937(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1293-1363 (ISOFORM 1), ALTERNATIVE SPLICING.
  11. "Signal peptide prediction based on analysis of experimentally verified cleavage sites."
    Zhang Z., Henzel W.J.
    Protein Sci. 13:2819-2824(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 25-39.
  12. "Biochemical characterization of two isoforms of FLT4, a VEGF receptor-related tyrosine kinase."
    Borg J.P., deLapeyriere O., Noguchi T., Rottapel R., Dubreuil P., Birnbaum D.
    Oncogene 10:973-984(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: CATALYTIC ACTIVITY, GLYCOSYLATION, SUBCELLULAR LOCATION.
  13. "Mutation at tyrosine residue 1337 abrogates ligand-dependent transforming capacity of the FLT4 receptor."
    Fournier E., Dubreuil P., Birnbaum D., Borg J.P.
    Oncogene 11:921-931(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN CELL PROLIFERATION AND PHOSPHORYLATION OF SHC1, CHARACTERIZATION OF ISOFORM 1 AND ISOFORM 2, INTERACTION WITH SHC1 AND GRB2, AUTOPHOSPHORYLATION, MUTAGENESIS OF TYR-1333; TYR-1337 AND TYR-1363, TISSUE SPECIFICITY.
  14. "Vascular endothelial growth factor D (VEGF-D) is a ligand for the tyrosine kinases VEGF receptor 2 (Flk1) and VEGF receptor 3 (Flt4)."
    Achen M.G., Jeltsch M., Kukk E., Maekinen T., Vitali A., Wilks A.F., Alitalo K., Stacker S.A.
    Proc. Natl. Acad. Sci. U.S.A. 95:548-553(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH VEGFD, FUNCTION AS VEGFD RECEPTOR, AUTOPHOSPHORYLATION.
  15. "Isolated lymphatic endothelial cells transduce growth, survival and migratory signals via the VEGF-C/D receptor VEGFR-3."
    Makinen T., Veikkola T., Mustjoki S., Karpanen T., Catimel B., Nice E.C., Wise L., Mercer A., Kowalski H., Kerjaschki D., Stacker S.A., Achen M.G., Alitalo K.
    EMBO J. 20:4762-4773(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION AS RECEPTOR FOR VEGFC AND VEGFD IN CELL SURVIVAL; PROLIFERATION AND MIGRATION, FUNCTION IN ACTIVATION OF PROTEIN KINASE C; AKT1; PIK3R1; MAPK1/ERK2 AND MAPK3/ERK1.
  16. "Ligand-induced vascular endothelial growth factor receptor-3 (VEGFR-3) heterodimerization with VEGFR-2 in primary lymphatic endothelial cells regulates tyrosine phosphorylation sites."
    Dixelius J., Makinen T., Wirzenius M., Karkkainen M.J., Wernstedt C., Alitalo K., Claesson-Welsh L.
    J. Biol. Chem. 278:40973-40979(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH KDR, CATALYTIC ACTIVITY, AUTOPHOSPHORYLATION, CHARACTERIZATION OF VARIANT LMPH1A PRO-1041, MUTAGENESIS OF LYS-879; TYR-1230; TYR-1231; TYR-1265; TYR-1333; TYR-1337 AND TYR-1363, PHOSPHORYLATION AT TYR-1230; TYR-1231; TYR-1265; TYR-1333; TYR-1337 AND TYR-1363.
  17. "Heterodimerization with vascular endothelial growth factor receptor-2 (VEGFR-2) is necessary for VEGFR-3 activity."
    Alam A., Herault J.P., Barron P., Favier B., Fons P., Delesque-Touchard N., Senegas I., Laboudie P., Bonnin J., Cassan C., Savi P., Ruggeri B., Carmeliet P., Bono F., Herbert J.M.
    Biochem. Biophys. Res. Commun. 324:909-915(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN KDR SIGNALING AND IN ANGIOGENESIS, INTERACTION WITH KDR, PHOSPHORYLATION.
  18. "Activation of vascular endothelial growth factor receptor-3 and its downstream signaling promote cell survival under oxidative stress."
    Wang J.F., Zhang X., Groopman J.E.
    J. Biol. Chem. 279:27088-27097(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN CELL SURVIVAL, PHOSPHORYLATION IN RESPONSE TO OXIDATIVE STRESS, INTERACTION WITH PIK3R1; SHC1; GRB2; PTPN11 AND PLCG1, ENZYME REGULATION BY MAZ51, CHARACTERIZATION OF VARIANT LMPH1A ARG-857.
  19. "Direct recruitment of CRK and GRB2 to VEGFR-3 induces proliferation, migration, and survival of endothelial cells through the activation of ERK, AKT, and JNK pathways."
    Salameh A., Galvagni F., Bardelli M., Bussolino F., Oliviero S.
    Blood 106:3423-3431(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN ACTIVATION OF AKT1; MAPK1/ERK2; MAPK3/ERK1 AND MAPK8, FUNCTION IN PROMOTING CELL SURVIVAL; PROLIFERATION AND MIGRATION, CHARACTERIZATION OF ISOFORM 1 AND ISOFORM 2, INTERACTION WITH CRK AND GRB2, PHOSPHORYLATION AT TYR-1063; TYR-1068; TYR-1230; TYR-1231 AND TYR-1337, MUTAGENESIS OF TYR-1063; TYR-1068; TYR-1230 AND TYR-1231.
  20. "Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry."
    Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J., Smith R.D.
    J. Proteome Res. 4:2070-2080(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-527.
    Tissue: Plasma.
  21. "Vascular endothelial growth factor receptor-3 and focal adhesion kinase bind and suppress apoptosis in breast cancer cells."
    Garces C.A., Kurenova E.V., Golubovskaya V.M., Cance W.G.
    Cancer Res. 66:1446-1454(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN PROMOTING CELL SURVIVAL, INTERACTION WITH PTK2/FAK1, SUBCELLULAR LOCATION.
  22. "Cooperative and redundant roles of VEGFR-2 and VEGFR-3 signaling in adult lymphangiogenesis."
    Goldman J., Rutkowski J.M., Shields J.D., Pasquier M.C., Cui Y., Schmokel H.G., Willey S., Hicklin D.J., Pytowski B., Swartz M.A.
    FASEB J. 21:1003-1012(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN LYMPHANGIOGENESIS.
  23. "Autocrine loop between vascular endothelial growth factor (VEGF)-C and VEGF receptor-3 positively regulates tumor-associated lymphangiogenesis in oral squamoid cancer cells."
    Matsuura M., Onimaru M., Yonemitsu Y., Suzuki H., Nakano T., Ishibashi H., Shirasuna K., Sueishi K.
    Am. J. Pathol. 175:1709-1721(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: ROLE IN CANCER, FUNCTION AS VEGFC RECEPTOR IN TUMOR LYMPHANGIOGENESIS; CELL PROLIFERATION; CELL SURVIVAL; IN ACTIVATION OF PIK3R1; AKT1 AND MAP KINASES AND IN UP-REGULATION OF VEGFA AND VEGFC EXPRESSION, ENZYME REGULATION, AUTOPHOSPHORYLATION.
  24. "Small molecule chloropyramine hydrochloride (C4) targets the binding site of focal adhesion kinase and vascular endothelial growth factor receptor 3 and suppresses breast cancer growth in vivo."
    Kurenova E.V., Hunt D.L., He D., Magis A.T., Ostrov D.A., Cance W.G.
    J. Med. Chem. 52:4716-4724(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: ROLE IN CANCER, INTERACTION WITH PTK2/FAK1.
  25. "Protein tyrosine phosphatase PTPN14 is a regulator of lymphatic function and choanal development in humans."
    Au A.C., Hernandez P.A., Lieber E., Nadroo A.M., Shen Y.M., Kelley K.A., Gelb B.D., Diaz G.A.
    Am. J. Hum. Genet. 87:436-444(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH PTPN14.
  26. "Endothelial cell adhesion to the extracellular matrix induces c-Src-dependent VEGFR-3 phosphorylation without the activation of the receptor intrinsic kinase activity."
    Galvagni F., Pennacchini S., Salameh A., Rocchigiani M., Neri F., Orlandini M., Petraglia F., Gotta S., Sardone G.L., Matteucci G., Terstappen G.C., Oliviero S.
    Circ. Res. 106:1839-1848(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION AT TYR-830; TYR-833; TYR-853; TYR-1063; TYR-1068; TYR-1333 AND TYR-1337, IDENTIFICATION IN A COMPLEX WITH SRC AND ITGB1, MUTAGENESIS OF TYR-1063; TYR-1068 AND TYR-1337, ENZYME REGULATION BY MAZ51, INTERACTION WITH ITGB1; CRK AND SHC1, FUNCTION IN ACTIVATION OF MAPK8 AND IN REGULATION OF ANGIOGENIC SPROUTING, IDENTIFICATION BY MASS SPECTROMETRY.
  27. Cited for: INTERACTION WITH KDR, FUNCTION IN MODULATING KDR SIGNALING AND IN ANGIOGENESIS, TISSUE SPECIFICITY.
  28. Cited for: FUNCTION IN ACTIVATION OF SIGNALING PATHWAYS, SUBCELLULAR LOCATION.
  29. "Combined blockade of VEGFR-2 and VEGFR-3 inhibits inflammatory lymphangiogenesis in early and middle stages."
    Yuen D., Pytowski B., Chen L.
    Invest. Ophthalmol. Vis. Sci. 52:2593-2597(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN LYMPHANGIOGENESIS.
  30. "VEGF receptor protein-tyrosine kinases: structure and regulation."
    Roskoski R. Jr.
    Biochem. Biophys. Res. Commun. 375:287-291(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW ON STRUCTURE AND FUNCTION.
  31. "VEGFs and receptors involved in angiogenesis versus lymphangiogenesis."
    Lohela M., Bry M., Tammela T., Alitalo K.
    Curr. Opin. Cell Biol. 21:154-165(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW ON ROLE IN LYMPHANGIOGENESIS AND CANCER.
  32. "Signal transduction by vascular endothelial growth factor receptors."
    Koch S., Tugues S., Li X., Gualandi L., Claesson-Welsh L.
    Biochem. J. 437:169-183(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW ON LIGAND SPECIFICITY; FUNCTION; STRUCTURE; PHOSPHORYLATION AND SIGNALING.
  33. "Lymphangiogenesis and cancer metastasis."
    Al-Rawi M.A., Jiang W.G.
    Front. Biosci. 16:723-739(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW ON FUNCTION IN LYMPHANGIOGENESIS AND ROLE IN CANCER.
  34. Cited for: VARIANT LMPH1A LEU-1114.
  35. "Congenital hereditary lymphedema caused by a mutation that inactivates VEGFR3 tyrosine kinase."
    Irrthum A., Karkkainen M.J., Devriendt K., Alitalo K., Vikkula M.
    Am. J. Hum. Genet. 67:295-301(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: INVOLVEMENT IN LMPH1A, CHARACTERIZATION OF VARIANT LMPH1A ARG-1035.
  36. "Missense mutations interfere with VEGFR-3 signalling in primary lymphoedema."
    Karkkainen M.J., Ferrell R.E., Lawrence E.C., Kimak M.A., Levinson K.L., McTigue M.A., Alitalo K., Finegold D.N.
    Nat. Genet. 25:153-159(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANTS LMPH1A ARG-857; PRO-1041; PRO-1044 AND LEU-1114, VARIANT SER-641, CHARACTERIZATION OF VARIANTS.
  37. "Somatic mutation of vascular endothelial growth factor receptors in juvenile hemangioma."
    Walter J.W., North P.E., Waner M., Mizeracki A., Blei F., Walker J.W.T., Reinisch J.F., Marchuk D.A.
    Genes Chromosomes Cancer 33:295-303(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANTS HCI SER-954 AND SER-1137, VARIANTS ALA-494; GLN-890 AND HIS-1146.
  38. "Patterns of somatic mutation in human cancer genomes."
    Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.
    , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.
    Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANTS [LARGE SCALE ANALYSIS] ASP-149; CYS-378; ALA-494; SER-527; SER-641; TYR-868; ILE-1010; GLN-1031; ASN-1049; GLN-1075 AND HIS-1146.

Entry informationi

Entry nameiVGFR3_HUMAN
AccessioniPrimary (citable) accession number: P35916
Secondary accession number(s): A8K6L4
, B5A926, Q16067, Q86W07, Q86W08
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 1, 1994
Last sequence update: November 16, 2011
Last modified: November 26, 2014
This is version 170 of the entry and version 3 of the sequence. [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. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  7. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3