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Protein

Vascular endothelial growth factor receptor 3

Gene

flt4

Organism
Danio rerio (Zebrafish) (Brachydanio rerio)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript leveli

Functioni

Tyrosine-protein kinase that acts as a cell-surface receptor for vegf or vegfc. Combinations of multiple VEGF receptors are required for development of different blood vessel types in the embryo. Involved in angiogenesis, specifically in VEGF-induced sprouting of new blood vessels, but not required for proper vasculogenesis or hematopoiesis.1 Publication

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 sitei900ATPPROSITE-ProRule annotation1
Active sitei1045Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi872 – 880ATPPROSITE-ProRule annotation9

GO - Molecular functioni

GO - Biological processi

  • angiogenesis Source: ZFIN
  • lymphangiogenesis Source: ZFIN
  • lymph vessel development Source: ZFIN
  • motor neuron axon guidance Source: ZFIN
  • regulation of vascular endothelial growth factor receptor signaling pathway Source: ZFIN
  • selective angioblast sprouting Source: ZFIN
  • sprouting angiogenesis Source: ZFIN
  • vascular endothelial growth factor receptor signaling pathway Source: ZFIN
  • vasculature development Source: ZFIN
  • venous blood vessel development Source: ZFIN
  • venous endothelial cell migration involved in lymph vessel development Source: ZFIN
Complete GO annotation...

Keywords - Molecular functioni

Developmental protein, Kinase, Receptor, Transferase, Tyrosine-protein kinase

Keywords - Biological processi

Angiogenesis, Differentiation

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
Gene namesi
Name:flt4
Synonyms:flt-4, vegfr3
OrganismiDanio rerio (Zebrafish) (Brachydanio rerio)
Taxonomic identifieri7955 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiActinopterygiiNeopterygiiTeleosteiOstariophysiCypriniformesCyprinidaeDanio
Proteomesi
  • UP000000437 Componenti: Unplaced

Organism-specific databases

ZFINiZDB-GENE-980526-326. flt4.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini25 – 796ExtracellularSequence analysisAdd BLAST772
Transmembranei797 – 817HelicalSequence analysisAdd BLAST21
Topological domaini818 – 1357CytoplasmicSequence analysisAdd BLAST540

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 24Sequence analysisAdd BLAST24
ChainiPRO_000024946425 – 1357Vascular endothelial growth factor receptor 3Add BLAST1333

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi44N-linked (GlcNAc...)Sequence analysis1
Glycosylationi48N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi51 ↔ 121PROSITE-ProRule annotation
Glycosylationi114N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi173 ↔ 225PROSITE-ProRule annotation
Glycosylationi216N-linked (GlcNAc...)Sequence analysis1
Glycosylationi271N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi272 ↔ 331PROSITE-ProRule annotation
Glycosylationi360N-linked (GlcNAc...)Sequence analysis1
Glycosylationi400N-linked (GlcNAc...)Sequence analysis1
Glycosylationi440N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi473 ↔ 562PROSITE-ProRule annotation
Glycosylationi553N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi606 ↔ 674PROSITE-ProRule annotation
Glycosylationi610N-linked (GlcNAc...)Sequence analysis1
Glycosylationi660N-linked (GlcNAc...)Sequence analysis1
Glycosylationi707N-linked (GlcNAc...)Sequence analysis1
Glycosylationi711N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi720 ↔ 772PROSITE-ProRule annotation
Glycosylationi751N-linked (GlcNAc...)Sequence analysis1
Modified residuei1071Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei1076Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei1226Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei1227Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei1334Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei1338Phosphotyrosine; 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 (By similarity).By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiQ5MD89.
PRIDEiQ5MD89.

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 (By similarity).By similarity

Protein-protein interaction databases

STRINGi7955.ENSDARP00000112456.

Structurei

3D structure databases

ProteinModelPortaliQ5MD89.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini25 – 121Ig-like C2-type 1Add BLAST97
Domaini138 – 244Ig-like C2-type 2Add BLAST107
Domaini255 – 343Ig-like C2-type 3Add BLAST89
Domaini352 – 442Ig-like C2-type 4Add BLAST91
Domaini453 – 583Ig-like C2-type 5Add BLAST131
Domaini583 – 690Ig-like C2-type 6Add BLAST108
Domaini699 – 785Ig-like C2-type 7Add BLAST87
Domaini866 – 1181Protein kinasePROSITE-ProRule annotationAdd BLAST316

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.
InParanoidiQ5MD89.
PhylomeDBiQ5MD89.

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. 3 hits.
PfamiPF07679. I-set. 2 hits.
PF07714. Pkinase_Tyr. 1 hit.
[Graphical view]
PRINTSiPR01835. VEGFRECEPTR3.
SMARTiSM00409. IG. 6 hits.
SM00408. IGc2. 6 hits.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMiSSF48726. SSF48726. 7 hits.
SSF56112. SSF56112. 2 hits.
PROSITEiPS50835. IG_LIKE. 5 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]

Sequencei

Sequence statusi: Complete.

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

Q5MD89-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MKRDFTFFCR IWIGIPFFSG LVNGFSMSPP TLDNTKDQLV INANDTLNIT
60 70 80 90 100
CRGQRILDWS WPEESLSKVE FTDRQGQQSP TDTPGYREIR LKECQGVAGK
110 120 130 140 150
PYCKILILTN AQANDSGYYR CFYKDIKAVI DGTTAASIFV FVRDPEHPFI
160 170 180 190 200
KRGDNDMETI FITDSETHIE VPCLVSDPDL KVTLFSLVPY PEPVDGSVVT
210 220 230 240 250
WNNKKGWSIP RHIIQNTSTF IGFYCSISVQ NSQHTSSIYV VQVIGLKFYE
260 270 280 290 300
FKLFPEDSPV ELMQGESLVL NCTALVDFNT GVDFQWDYPG KKENRLASLQ
310 320 330 340 350
PLRNVLDEAT EISSILSIRN IHLDDSGYYT CWANTLEMKR ELTTVVIVHE
360 370 380 390 400
KPFISLDYRN GSVIEAKEGQ KSVRLSVKVS AYPSPEIQWY KNGKLISSKN
410 420 430 440 450
SSRFKVQQHS LQIRDVCKQD AGEYMLVLKN SPAALEKRLN FTLIVNVPPQ
460 470 480 490 500
IHEKEAAPPT NLYGKGTRQI LTCTADGSPP ASISWQWRPW SPCDLERTRR
510 520 530 540 550
ALRRRGGRDQ SPFCHNWMDL DPEHAVNPIE SIDTLTQMVD GKEKTVGRVV
560 570 580 590 600
IQNASVPAMY KCLAENRVGK DERLIYFYVT TIPEGFDIEM EPSEDPLEQD
610 620 630 640 650
LVQLKCNADN FTYENLRWYR LDPQTVPPEL DCKSLHQYAT FLEGQLSFQT
660 670 680 690 700
TSNNWVLQLN ITNIQLQDEG NYVCEVQNRR TGVKHCHRKY IPVKAMEAPR
710 720 730 740 750
YRHNPTNHTV NVSESLQMNC DVEGTPFPQL SWFKDNQPLH QISGILLQDS
760 770 780 790 800
NRTLSIQRVR EEDAGLYTCS ACNQKGCVQS SATVSVIGSD DKTNVEIVIL
810 820 830 840 850
IGTGVIAIFF WVLLLVIFCN VKRVNPADIK TGYLSIIMDP GEVPLEEQCE
860 870 880 890 900
YLPYDSSQWE ISRDRLRLGK VLGHGAFGKV IEASIFGHDK KSSANTVAVK
910 920 930 940 950
MLKEGATASE HKALMSELKI LIHIGNHLNV VNLLGACTKP NGPLMVIVEY
960 970 980 990 1000
CKYGNLSNFL RAKREFFLPY RDRSPKTQSQ VRRMIEAGQA SQSEHQPSTS
1010 1020 1030 1040 1050
STNPPRVTVD DLWKTPLTIE DLICYSFQVA RGMEFLASRK CIHRDLAARN
1060 1070 1080 1090 1100
ILLSENNVVK ICDFGLARDI YKDPDYVRKG NARLPLKWMA PESIFDKVYT
1110 1120 1130 1140 1150
SQSDVWSFGV LLWEIFSLGA SPYPGIQIDE DFCKRLKDGT RMRAPDNASP
1160 1170 1180 1190 1200
EIYGIMLACW QGEPRERPTF PALVEILGDL LQENSLPEIP FNVSQSSEDD
1210 1220 1230 1240 1250
GFSQASSRPP SQEEIRLACN TLPTRYYNCV PFAGCVMVGP SSTCHSRVKT
1260 1270 1280 1290 1300
FEELPMEMTS HKTQHDSQTD SGMVLASDEL ERFEHKHRGA MLTTATTGQS
1310 1320 1330 1340 1350
TDRLISCPSV SSSGSGGGLL RPVFFTQLSG QTFYNNEYGH LSEEGVSDYF

SSSDQAV
Length:1,357
Mass (Da):153,178
Last modified:February 1, 2005 - v1
Checksum:iD68C197828BE278E
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti567R → K in AAS92272 (Ref. 1) Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY524001 mRNA. Translation: AAS92272.1.
AY833404 mRNA. Translation: AAV93318.1.
UniGeneiDr.81298.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY524001 mRNA. Translation: AAS92272.1.
AY833404 mRNA. Translation: AAV93318.1.
UniGeneiDr.81298.

3D structure databases

ProteinModelPortaliQ5MD89.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi7955.ENSDARP00000112456.

Proteomic databases

PaxDbiQ5MD89.
PRIDEiQ5MD89.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Organism-specific databases

ZFINiZDB-GENE-980526-326. flt4.

Phylogenomic databases

eggNOGiKOG0200. Eukaryota.
COG0515. LUCA.
HOGENOMiHOG000037949.
HOVERGENiHBG053432.
InParanoidiQ5MD89.
PhylomeDBiQ5MD89.

Miscellaneous databases

PROiQ5MD89.

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. 3 hits.
PfamiPF07679. I-set. 2 hits.
PF07714. Pkinase_Tyr. 1 hit.
[Graphical view]
PRINTSiPR01835. VEGFRECEPTR3.
SMARTiSM00409. IG. 6 hits.
SM00408. IGc2. 6 hits.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMiSSF48726. SSF48726. 7 hits.
SSF56112. SSF56112. 2 hits.
PROSITEiPS50835. IG_LIKE. 5 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_DANRE
AccessioniPrimary (citable) accession number: Q5MD89
Secondary accession number(s): Q5GIT2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: September 19, 2006
Last sequence update: February 1, 2005
Last modified: November 30, 2016
This is version 97 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, 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.