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Q5MD89

- VGFR3_DANRE

UniProt

Q5MD89 - VGFR3_DANRE

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Protein
Vascular endothelial growth factor receptor 3
Gene
flt4, flt-4, vegfr3
Organism
Danio rerio (Zebrafish) (Brachydanio rerio)
Status
Reviewed - Annotation score: 4 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.

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.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei900 – 9001ATP By similarity
Active sitei1045 – 10451Proton acceptor By similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi872 – 8809ATP By similarity

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; 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 – 796772Extracellular Reviewed prediction
Add
BLAST
Transmembranei797 – 81721Helical; Reviewed prediction
Add
BLAST
Topological domaini818 – 1357540Cytoplasmic Reviewed prediction
Add
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 – 2424 Reviewed prediction
Add
BLAST
Chaini25 – 13571333Vascular endothelial growth factor receptor 3
PRO_0000249464Add
BLAST

Amino acid modifications

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

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.

Protein-protein interaction databases

STRINGi7955.ENSDARP00000005480.

Structurei

3D structure databases

ProteinModelPortaliQ5MD89.
SMRiQ5MD89. Positions 848-1185.

Family & Domainsi

Domains and Repeats

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

Sequence similaritiesi

Keywords - Domaini

Immunoglobulin domain, Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiCOG0515.
HOGENOMiHOG000037949.
HOVERGENiHBG053432.
InParanoidiQ5GIT2.
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

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MKRDFTFFCR IWIGIPFFSG LVNGFSMSPP TLDNTKDQLV INANDTLNIT     50
CRGQRILDWS WPEESLSKVE FTDRQGQQSP TDTPGYREIR LKECQGVAGK 100
PYCKILILTN AQANDSGYYR CFYKDIKAVI DGTTAASIFV FVRDPEHPFI 150
KRGDNDMETI FITDSETHIE VPCLVSDPDL KVTLFSLVPY PEPVDGSVVT 200
WNNKKGWSIP RHIIQNTSTF IGFYCSISVQ NSQHTSSIYV VQVIGLKFYE 250
FKLFPEDSPV ELMQGESLVL NCTALVDFNT GVDFQWDYPG KKENRLASLQ 300
PLRNVLDEAT EISSILSIRN IHLDDSGYYT CWANTLEMKR ELTTVVIVHE 350
KPFISLDYRN GSVIEAKEGQ KSVRLSVKVS AYPSPEIQWY KNGKLISSKN 400
SSRFKVQQHS LQIRDVCKQD AGEYMLVLKN SPAALEKRLN FTLIVNVPPQ 450
IHEKEAAPPT NLYGKGTRQI LTCTADGSPP ASISWQWRPW SPCDLERTRR 500
ALRRRGGRDQ SPFCHNWMDL DPEHAVNPIE SIDTLTQMVD GKEKTVGRVV 550
IQNASVPAMY KCLAENRVGK DERLIYFYVT TIPEGFDIEM EPSEDPLEQD 600
LVQLKCNADN FTYENLRWYR LDPQTVPPEL DCKSLHQYAT FLEGQLSFQT 650
TSNNWVLQLN ITNIQLQDEG NYVCEVQNRR TGVKHCHRKY IPVKAMEAPR 700
YRHNPTNHTV NVSESLQMNC DVEGTPFPQL SWFKDNQPLH QISGILLQDS 750
NRTLSIQRVR EEDAGLYTCS ACNQKGCVQS SATVSVIGSD DKTNVEIVIL 800
IGTGVIAIFF WVLLLVIFCN VKRVNPADIK TGYLSIIMDP GEVPLEEQCE 850
YLPYDSSQWE ISRDRLRLGK VLGHGAFGKV IEASIFGHDK KSSANTVAVK 900
MLKEGATASE HKALMSELKI LIHIGNHLNV VNLLGACTKP NGPLMVIVEY 950
CKYGNLSNFL RAKREFFLPY RDRSPKTQSQ VRRMIEAGQA SQSEHQPSTS 1000
STNPPRVTVD DLWKTPLTIE DLICYSFQVA RGMEFLASRK CIHRDLAARN 1050
ILLSENNVVK ICDFGLARDI YKDPDYVRKG NARLPLKWMA PESIFDKVYT 1100
SQSDVWSFGV LLWEIFSLGA SPYPGIQIDE DFCKRLKDGT RMRAPDNASP 1150
EIYGIMLACW QGEPRERPTF PALVEILGDL LQENSLPEIP FNVSQSSEDD 1200
GFSQASSRPP SQEEIRLACN TLPTRYYNCV PFAGCVMVGP SSTCHSRVKT 1250
FEELPMEMTS HKTQHDSQTD SGMVLASDEL ERFEHKHRGA MLTTATTGQS 1300
TDRLISCPSV SSSGSGGGLL RPVFFTQLSG QTFYNNEYGH LSEEGVSDYF 1350
SSSDQAV 1357
Length:1,357
Mass (Da):153,178
Last modified:February 1, 2005 - v1
Checksum:iD68C197828BE278E
GO

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti567 – 5671R → K in AAS92272. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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:
EMBL
GenBank
DDBJ
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 Q5GIT2.
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: April 16, 2014
This is version 83 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

Similar proteinsi