Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Vascular endothelial growth factor receptor 3

Gene

Flt4

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: 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. 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' (By similarity).By similarity

Catalytic activityi

ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.PROSITE-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 (By similarity).By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei879ATPPROSITE-ProRule annotation1
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: RGD
  • vascular endothelial growth factor-activated receptor activity Source: RGD

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Kinase, Receptor, Transferase, Tyrosine-protein kinase

Keywords - Biological processi

Angiogenesis

Keywords - Ligandi

ATP-binding, Nucleotide-binding

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:Flt-4, Vegfr3
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi621737. Flt4.

Subcellular locationi

Topology

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

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 24Sequence analysisAdd BLAST24
ChainiPRO_000004528025 – 1363Vascular endothelial growth factor receptor 3Add BLAST1339

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi33N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi51 ↔ 111PROSITE-ProRule annotation
Glycosylationi104N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi158 ↔ 206PROSITE-ProRule annotation
Glycosylationi166N-linked (GlcNAc...)Sequence analysis1
Glycosylationi251N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi252 ↔ 310PROSITE-ProRule annotation
Glycosylationi299N-linked (GlcNAc...)Sequence analysis1
Glycosylationi411N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi445 ↔ 534PROSITE-ProRule annotation
Glycosylationi515N-linked (GlcNAc...)Sequence analysis1
Glycosylationi527N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi578 ↔ 653PROSITE-ProRule annotation
Glycosylationi582N-linked (GlcNAc...)Sequence analysis1
Glycosylationi594N-linked (GlcNAc...)Sequence analysis1
Glycosylationi683N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi699 ↔ 751PROSITE-ProRule annotation
Glycosylationi758N-linked (GlcNAc...)Sequence analysis1
Modified residuei830Phosphotyrosine; by SRCBy similarity1
Modified residuei833Phosphotyrosine; by SRCBy similarity1
Modified residuei1063Phosphotyrosine; by autocatalysis and SRCBy similarity1
Modified residuei1068Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei1230Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei1231Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei1265Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei1333Phosphotyrosine; by autocatalysis and SRCBy similarity1
Modified residuei1337Phosphotyrosine; by autocatalysis and SRCBy similarity1
Modified residuei1363Phosphotyrosine; by autocatalysisBy similarity1

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 (By similarity).By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiQ91ZT1.
PRIDEiQ91ZT1.

PTM databases

iPTMnetiQ91ZT1.
PhosphoSitePlusiQ91ZT1.

Expressioni

Developmental stagei

Increases during pregnancy (2.2-fold at 4 days) and lactation (1.5-fold at 21 days). Decreases in the early phases of involution (33%, 21%, and 45% on days 1, 2, and 3 respectively).1 Publication

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 (By similarity). Identified in a complex with SRC and ITGB1 (By similarity).By similarity

GO - Molecular functioni

  • growth factor binding Source: RGD

Protein-protein interaction databases

IntActiQ91ZT1. 1 interactor.
STRINGi10116.ENSRNOP00000003519.

Structurei

3D structure databases

ProteinModelPortaliQ91ZT1.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini44 – 118Ig-like C2-type 1Add BLAST75
Domaini151 – 213Ig-like C2-type 2Add BLAST63
Domaini230 – 326Ig-like C2-type 3Add BLAST97
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

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi1318 – 1321Poly-Arg4

Domaini

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

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

eggNOGiKOG0200. Eukaryota.
COG0515. LUCA.
HOGENOMiHOG000037949.
HOVERGENiHBG053432.
InParanoidiQ91ZT1.
KOiK05097.
PhylomeDBiQ91ZT1.

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]
PfamiPF07679. I-set. 1 hit.
PF07714. Pkinase_Tyr. 1 hit.
[Graphical view]
PRINTSiPR01835. VEGFRECEPTR3.
SMARTiSM00409. IG. 7 hits.
SM00408. IGc2. 4 hits.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMiSSF48726. SSF48726. 6 hits.
SSF56112. 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 (2)i

Sequence statusi: Complete.

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

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q91ZT1-1) [UniParc]FASTAAdd to basket

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
MQPGAALNRR LWLCLGLLQG LANGYSMTPP TLNITEDSYV IDTGDSLSIS
60 70 80 90 100
CRGQHPLEWT WRGAQEVLTT GGKDSEDTQV VQDCEGTEAR PYCKVLSLAQ
110 120 130 140 150
THANNTGSYY CYYKYIKARI EGTTAASTYV FVRDFEQPFI NKPDTLLVNR
160 170 180 190 200
KDSMWVPCLV SIPGLNITLR SQSSVLHPDG QEVLWDDRRG MRVPTLLLRD
210 220 230 240 250
ALYLQCETTW GDQDFLSNPF LVHITGNELY DIQLYPKKSL ELLVGEKLVL
260 270 280 290 300
NCTVWAEFDS GVTFDWDYPG KQAERAKWVP ERRSQQTHTE LSSILTIHNV
310 320 330 340 350
SQHDLGPYVC EANNGIQQFR ESTEVIVHEK PFISVEWLKG PVLEATAGDE
360 370 380 390 400
MVKLPVKLAA YPPPEFQWYK DRKAVTGRHN PHALVLKEVT EASAGVYTLA
410 420 430 440 450
LWNSAAGLRQ NISLELVVNV PPHIHEKEAS SPSIYSRHSR QTLTCTTYGV
460 470 480 490 500
PQPLSVQWHW RPWTPCKTFA QRSLRRRQPR DGMPQCRDWK EVTTQDAVNP
510 520 530 540 550
IESLDTWTES VEGKNKTVSK LVIQDANVSA MYKCVVFNKV GQDERLIYFY
560 570 580 590 600
VTTIPDGFSI ESEPSEDPLE GQSVRLSCRA DNYTYEHLRW YRLNLSTLHD
610 620 630 640 650
AQGNPLLLDC KNVHLFATPL EANLEEAEPG ARHATLSLNI PRVAPEDEGD
660 670 680 690 700
YVCEVQDRRS QDKHCHKKYL SVQALEAPRL TQNLTDLLVN VRTSLEMRCP
710 720 730 740 750
VAGAHVPSIV WYKDERLLEK ESGIDLADSN QRLSIQRVRE EDAGRYLCSV
760 770 780 790 800
CNAKGCVNSS ASVAVEGSED KGSMEIVILI GTGVIAVFFW VLLLLIFCNM
810 820 830 840 850
KRPAHADIKT GYLSIIMDPG EVPLEEQCEY LSYDVSQWEF PRERLHLGRV
860 870 880 890 900
LGHGAFGKVV EASAFGINKG SSCDTVAVKM LKEGATASEH RALMSELKIL
910 920 930 940 950
IHIGNHLNVV NLLGACTKPN GPLMVIVEFC KYGNLSNFLR VKRETFDPYA
960 970 980 990 1000
EKSPEQRRRF RAMVEGAKAD RRRLGSTDRA LFTRFLMGKG SARRAPFVQE
1010 1020 1030 1040 1050
AEDLWLSPLT MEDLVCYSFQ VARGMEFLAS RKCIHRDLAA RNILLSESDI
1060 1070 1080 1090 1100
VKICDFGLAR DIYKDPDYVR KGSARLPLKW MAPESIFDKV YTTQSDVWSF
1110 1120 1130 1140 1150
GVLLWEIFSL GASPYPGVQI NEEFCQRLKD GTRMRAPELA TPAIRHIMQS
1160 1170 1180 1190 1200
CWSGDPKARP AFSDLVEILG DLLQGGGWQE EEEECMALHS SQSSEEDGFM
1210 1220 1230 1240 1250
QASTTALHIT EADAESSPPS MHCHSLAARY YNCVSFPGRL VRGTKAPGSS
1260 1270 1280 1290 1300
RMKTFEELPM TPTTYKASVD NQTDSGMVLA SEEFEQIESR HRQEGSFSRK
1310 1320 1330 1340 1350
DPGQHMDISR GHPDLQGRRR RPTQGAQGGK VFYNNEYGEV SQPCTEGDCC
1360
PSAGSTFFAD SNY
Length:1,363
Mass (Da):153,317
Last modified:December 1, 2001 - v1
Checksum:i203E79172C614D6C
GO
Isoform 2 (identifier: Q91ZT1-2) [UniParc]FASTAAdd to basket
Also known as: VEGFR3-kt

The sequence of this isoform differs from the canonical sequence as follows:
     1079-1092: KWMAPESIFDKVYT → HTLGYRSMRNSASG
     1093-1363: Missing.

Show »
Length:1,092
Mass (Da):123,178
Checksum:i05D01912DF34F78E
GO

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0167211079 – 1092KWMAP…DKVYT → HTLGYRSMRNSASG in isoform 2. 1 PublicationAdd BLAST14
Alternative sequenceiVSP_0167221093 – 1363Missing in isoform 2. 1 PublicationAdd BLAST271

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF402785 mRNA. Translation: AAL13269.1.
AF402786 mRNA. Translation: AAL13270.1.
AF010131 mRNA. Translation: AAB63249.1.
RefSeqiNP_446104.1. NM_053652.1. [Q91ZT1-1]
UniGeneiRn.81043.

Genome annotation databases

GeneIDi114110.
KEGGirno:114110.
UCSCiRGD:621737. rat. [Q91ZT1-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF402785 mRNA. Translation: AAL13269.1.
AF402786 mRNA. Translation: AAL13270.1.
AF010131 mRNA. Translation: AAB63249.1.
RefSeqiNP_446104.1. NM_053652.1. [Q91ZT1-1]
UniGeneiRn.81043.

3D structure databases

ProteinModelPortaliQ91ZT1.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiQ91ZT1. 1 interactor.
STRINGi10116.ENSRNOP00000003519.

PTM databases

iPTMnetiQ91ZT1.
PhosphoSitePlusiQ91ZT1.

Proteomic databases

PaxDbiQ91ZT1.
PRIDEiQ91ZT1.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi114110.
KEGGirno:114110.
UCSCiRGD:621737. rat. [Q91ZT1-1]

Organism-specific databases

CTDi2324.
RGDi621737. Flt4.

Phylogenomic databases

eggNOGiKOG0200. Eukaryota.
COG0515. LUCA.
HOGENOMiHOG000037949.
HOVERGENiHBG053432.
InParanoidiQ91ZT1.
KOiK05097.
PhylomeDBiQ91ZT1.

Miscellaneous databases

PROiQ91ZT1.

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]
PfamiPF07679. I-set. 1 hit.
PF07714. Pkinase_Tyr. 1 hit.
[Graphical view]
PRINTSiPR01835. VEGFRECEPTR3.
SMARTiSM00409. IG. 7 hits.
SM00408. IGc2. 4 hits.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMiSSF48726. SSF48726. 6 hits.
SSF56112. 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]
ProtoNetiSearch...

Entry informationi

Entry nameiVGFR3_RAT
AccessioniPrimary (citable) accession number: Q91ZT1
Secondary accession number(s): O35755, Q91ZT0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 20, 2005
Last sequence update: December 1, 2001
Last modified: November 2, 2016
This is version 112 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.