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Q5MD89

- VGFR3_DANRE

UniProt

Q5MD89 - VGFR3_DANRE

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Protein

Vascular endothelial growth factor receptor 3

Gene

flt4

Organism
Danio rerio (Zebrafish) (Brachydanio rerio)
Status
Reviewed - 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)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei900 – 9001ATPPROSITE-ProRule annotation
Active sitei1045 – 10451Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi872 – 8809ATPPROSITE-ProRule annotation

GO - Molecular functioni

  1. ATP binding Source: UniProtKB-KW
  2. vascular endothelial growth factor-activated receptor activity Source: InterPro

GO - Biological processi

  1. angiogenesis Source: UniProtKB-KW
  2. cell differentiation Source: UniProtKB-KW
  3. vascular endothelial growth factor receptor signaling pathway Source: InterPro
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
ProteomesiUP000000437: Unplaced

Organism-specific databases

ZFINiZDB-GENE-980526-326. flt4.

Subcellular locationi

Cell membrane By similarity; Single-pass type I membrane protein By similarity
Note: Ligand-mediated autophosphorylation leads to rapid internalization.By similarity

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini25 – 796772ExtracellularSequence AnalysisAdd
BLAST
Transmembranei797 – 81721HelicalSequence AnalysisAdd
BLAST
Topological domaini818 – 1357540CytoplasmicSequence AnalysisAdd
BLAST

GO - Cellular componenti

  1. integral component of plasma membrane Source: InterPro
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2424Sequence AnalysisAdd
BLAST
Chaini25 – 13571333Vascular endothelial growth factor receptor 3PRO_0000249464Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi44 – 441N-linked (GlcNAc...)Sequence Analysis
Glycosylationi48 – 481N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi51 ↔ 121PROSITE-ProRule annotation
Glycosylationi114 – 1141N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi173 ↔ 225PROSITE-ProRule annotation
Glycosylationi216 – 2161N-linked (GlcNAc...)Sequence Analysis
Glycosylationi271 – 2711N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi272 ↔ 331PROSITE-ProRule annotation
Glycosylationi360 – 3601N-linked (GlcNAc...)Sequence Analysis
Glycosylationi400 – 4001N-linked (GlcNAc...)Sequence Analysis
Glycosylationi440 – 4401N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi473 ↔ 562PROSITE-ProRule annotation
Glycosylationi553 – 5531N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi606 ↔ 674PROSITE-ProRule annotation
Glycosylationi610 – 6101N-linked (GlcNAc...)Sequence Analysis
Glycosylationi660 – 6601N-linked (GlcNAc...)Sequence Analysis
Glycosylationi707 – 7071N-linked (GlcNAc...)Sequence Analysis
Glycosylationi711 – 7111N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi720 ↔ 772PROSITE-ProRule annotation
Glycosylationi751 – 7511N-linked (GlcNAc...)Sequence Analysis
Modified residuei1071 – 10711Phosphotyrosine; by autocatalysisBy similarity
Modified residuei1076 – 10761Phosphotyrosine; by autocatalysisBy similarity
Modified residuei1226 – 12261Phosphotyrosine; by autocatalysisBy similarity
Modified residuei1227 – 12271Phosphotyrosine; by autocatalysisBy similarity
Modified residuei1334 – 13341Phosphotyrosine; by autocatalysisBy similarity
Modified residuei1338 – 13381Phosphotyrosine; by autocatalysisBy similarity

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

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.ENSDARP00000005480.

Structurei

3D structure databases

ProteinModelPortaliQ5MD89.
SMRiQ5MD89. Positions 848-1185.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini25 – 12197Ig-like C2-type 1Add
BLAST
Domaini138 – 244107Ig-like C2-type 2Add
BLAST
Domaini255 – 34389Ig-like C2-type 3Add
BLAST
Domaini352 – 44291Ig-like C2-type 4Add
BLAST
Domaini453 – 583131Ig-like C2-type 5Add
BLAST
Domaini583 – 690108Ig-like C2-type 6Add
BLAST
Domaini699 – 78587Ig-like C2-type 7Add
BLAST
Domaini866 – 1181316Protein kinasePROSITE-ProRule annotationAdd
BLAST

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.
HOGENOMiHOG000037949.
HOVERGENiHBG053432.
InParanoidiQ5MD89.
KOiK05097.
PhylomeDBiQ5MD89.

Family and domain databases

Gene3Di2.60.40.10. 7 hits.
InterProiIPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR013098. Ig_I-set.
IPR003599. Ig_sub.
IPR003598. Ig_sub2.
IPR013106. Ig_V-set.
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.
PF07686. V-set. 1 hit.
[Graphical view]
PRINTSiPR01835. VEGFRECEPTR3.
SMARTiSM00409. IG. 3 hits.
SM00408. IGc2. 2 hits.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. 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)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti567 – 5671R → K in AAS92272. 1 PublicationCurated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY524001 mRNA. Translation: AAS92272.1.
AY833404 mRNA. Translation: AAV93318.1.
RefSeqiNP_571020.1. NM_130945.1.
UniGeneiDr.81298.

Genome annotation databases

GeneIDi30121.
KEGGidre:30121.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY524001 mRNA. Translation: AAS92272.1 .
AY833404 mRNA. Translation: AAV93318.1 .
RefSeqi NP_571020.1. NM_130945.1.
UniGenei Dr.81298.

3D structure databases

ProteinModelPortali Q5MD89.
SMRi Q5MD89. Positions 848-1185.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

STRINGi 7955.ENSDARP00000005480.

Proteomic databases

PRIDEi Q5MD89.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

GeneIDi 30121.
KEGGi dre:30121.

Organism-specific databases

CTDi 2324.
ZFINi ZDB-GENE-980526-326. flt4.

Phylogenomic databases

eggNOGi COG0515.
HOGENOMi HOG000037949.
HOVERGENi HBG053432.
InParanoidi Q5MD89.
KOi K05097.
PhylomeDBi Q5MD89.

Miscellaneous databases

NextBioi 20806600.
PROi Q5MD89.

Family and domain databases

Gene3Di 2.60.40.10. 7 hits.
InterProi IPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR013098. Ig_I-set.
IPR003599. Ig_sub.
IPR003598. Ig_sub2.
IPR013106. Ig_V-set.
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.
PF07686. V-set. 1 hit.
[Graphical view ]
PRINTSi PR01835. VEGFRECEPTR3.
SMARTi SM00409. IG. 3 hits.
SM00408. IGc2. 2 hits.
SM00219. TyrKc. 1 hit.
[Graphical view ]
SUPFAMi SSF56112. SSF56112. 2 hits.
PROSITEi PS50835. 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 ]
ProtoNeti Search...

Publicationsi

  1. "Synergistic signaling of vegf receptors is required for vasculogenesis in zebrafish."
    Habeck H., Langhoff J., Vogel A.M., Trowe T., Koblizek T.I., Schulte-Merker S.
    Submitted (JAN-2004) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  2. "Distinct genetic interactions between multiple Vegf receptors are required for development of different blood vessel types in zebrafish."
    Covassin L.D., Villefranc J.A., Kacergis M.C., Weinstein B.M., Lawson N.D.
    Proc. Natl. Acad. Sci. U.S.A. 103:6554-6559(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION.

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: October 29, 2014
This is version 85 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

External Data

Dasty 3