VGFR3_DANRE
ID VGFR3_DANRE Reviewed; 1357 AA.
AC Q5MD89; Q5GIT2;
DT 19-SEP-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-2005, sequence version 1.
DT 03-AUG-2022, entry version 123.
DE RecName: Full=Vascular endothelial growth factor receptor 3;
DE Short=VEGFR-3;
DE EC=2.7.10.1;
DE Flags: Precursor;
GN Name=flt4; Synonyms=flt-4, vegfr3;
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Habeck H., Langhoff J., Vogel A.M., Trowe T., Koblizek T.I.,
RA Schulte-Merker S.;
RT "Synergistic signaling of vegf receptors is required for vasculogenesis in
RT zebrafish.";
RL Submitted (JAN-2004) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND FUNCTION.
RX PubMed=16617120; DOI=10.1073/pnas.0506886103;
RA Covassin L.D., Villefranc J.A., Kacergis M.C., Weinstein B.M., Lawson N.D.;
RT "Distinct genetic interactions between multiple Vegf receptors are required
RT for development of different blood vessel types in zebrafish.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:6554-6559(2006).
CC -!- FUNCTION: Tyrosine-protein kinase that acts as a cell-surface receptor
CC for vegf or vegfc. Combinations of multiple VEGF receptors are required
CC for development of different blood vessel types in the embryo. Involved
CC in angiogenesis, specifically in VEGF-induced sprouting of new blood
CC vessels, but not required for proper vasculogenesis or hematopoiesis.
CC {ECO:0000269|PubMed:16617120}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl-
CC [protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA-
CC COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858,
CC ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=2.7.10.1;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU10028};
CC -!- ACTIVITY REGULATION: Present in an inactive conformation in the absence
CC of bound ligand. Binding of vegfc or vegfd leads to dimerization and
CC activation by autophosphorylation on tyrosine residues (By similarity).
CC {ECO:0000250|UniProtKB:P35916}.
CC -!- SUBUNIT: Interacts with vegfc and vegfd. Monomer in the absence of
CC bound vegfc or vegfd. Homodimer in the presence of bound vegfc or vegfd
CC (By similarity). {ECO:0000250|UniProtKB:P35916}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P35917};
CC Single-pass type I membrane protein {ECO:0000250|UniProtKB:P35917}.
CC Cytoplasm {ECO:0000250|UniProtKB:P35917}. Nucleus
CC {ECO:0000250|UniProtKB:P35916}. Note=Ligand-mediated
CC autophosphorylation leads to rapid internalization.
CC {ECO:0000250|UniProtKB:P35917}.
CC -!- DOMAIN: The first and second Ig-like C2-type (immunoglobulin-like)
CC domains are sufficient for VEGFC binding. The fourth and fifth Ig-like
CC C2-type (immunoglobulin-like) domains are sufficient for
CC homodimerization. The fifth and seventh Ig-like C2-type
CC (immunoglobulin-like) domains are required for autophosphorylation and
CC further activation. {ECO:0000250|UniProtKB:P35916}.
CC -!- PTM: Autophosphorylated on tyrosine residues upon ligand binding.
CC Autophosphorylation occurs in trans, i.e. one subunit of the dimeric
CC receptor phosphorylates tyrosine residues on the other subunit (By
CC similarity). {ECO:0000250|UniProtKB:P35916}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein
CC kinase family. CSF-1/PDGF receptor subfamily. {ECO:0000255|PROSITE-
CC ProRule:PRU00159}.
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DR EMBL; AY524001; AAS92272.1; -; mRNA.
DR EMBL; AY833404; AAV93318.1; -; mRNA.
DR AlphaFoldDB; Q5MD89; -.
DR SMR; Q5MD89; -.
DR STRING; 7955.ENSDARP00000112456; -.
DR PaxDb; Q5MD89; -.
DR ZFIN; ZDB-GENE-980526-326; flt4.
DR eggNOG; KOG0200; Eukaryota.
DR InParanoid; Q5MD89; -.
DR PhylomeDB; Q5MD89; -.
DR Reactome; R-DRE-195399; VEGF binds to VEGFR leading to receptor dimerization.
DR PRO; PR:Q5MD89; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Unplaced.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0043235; C:receptor complex; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0042802; F:identical protein binding; IPI:ZFIN.
DR GO; GO:0004714; F:transmembrane receptor protein tyrosine kinase activity; IBA:GO_Central.
DR GO; GO:0005021; F:vascular endothelial growth factor receptor activity; ISS:UniProtKB.
DR GO; GO:0001525; P:angiogenesis; IMP:ZFIN.
DR GO; GO:0002244; P:hematopoietic progenitor cell differentiation; IBA:GO_Central.
DR GO; GO:0001945; P:lymph vessel development; IMP:ZFIN.
DR GO; GO:0036303; P:lymph vessel morphogenesis; IMP:ZFIN.
DR GO; GO:0001946; P:lymphangiogenesis; IMP:ZFIN.
DR GO; GO:0060836; P:lymphatic endothelial cell differentiation; IMP:ZFIN.
DR GO; GO:0008045; P:motor neuron axon guidance; IMP:ZFIN.
DR GO; GO:0033674; P:positive regulation of kinase activity; IBA:GO_Central.
DR GO; GO:0046777; P:protein autophosphorylation; ISS:UniProtKB.
DR GO; GO:0030947; P:regulation of vascular endothelial growth factor receptor signaling pathway; IGI:ZFIN.
DR GO; GO:1900746; P:regulation of vascular endothelial growth factor signaling pathway; IGI:ZFIN.
DR GO; GO:0035474; P:selective angioblast sprouting; IMP:ZFIN.
DR GO; GO:0002040; P:sprouting angiogenesis; IGI:ZFIN.
DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central.
DR GO; GO:0048010; P:vascular endothelial growth factor receptor signaling pathway; IGI:ZFIN.
DR GO; GO:0038084; P:vascular endothelial growth factor signaling pathway; ISS:UniProtKB.
DR GO; GO:0001944; P:vasculature development; IMP:ZFIN.
DR GO; GO:0060841; P:venous blood vessel development; IMP:ZFIN.
DR GO; GO:0060855; P:venous endothelial cell migration involved in lymph vessel development; IMP:ZFIN.
DR Gene3D; 2.60.40.10; -; 7.
DR InterPro; IPR007110; Ig-like_dom.
DR InterPro; IPR036179; Ig-like_dom_sf.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR013098; Ig_I-set.
DR InterPro; IPR003599; Ig_sub.
DR InterPro; IPR003598; Ig_sub2.
DR InterPro; IPR013151; Immunoglobulin.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
DR InterPro; IPR008266; Tyr_kinase_AS.
DR InterPro; IPR020635; Tyr_kinase_cat_dom.
DR InterPro; IPR001824; Tyr_kinase_rcpt_3_CS.
DR InterPro; IPR041348; VEGFR-2_TMD.
DR InterPro; IPR009137; VEGFR3_rcpt.
DR PANTHER; PTHR24416:SF562; PTHR24416:SF562; 1.
DR Pfam; PF07679; I-set; 2.
DR Pfam; PF00047; ig; 1.
DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1.
DR Pfam; PF17988; VEGFR-2_TMD; 1.
DR SMART; SM00409; IG; 6.
DR SMART; SM00408; IGc2; 6.
DR SMART; SM00219; TyrKc; 1.
DR SUPFAM; SSF48726; SSF48726; 6.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS50835; IG_LIKE; 5.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00109; PROTEIN_KINASE_TYR; 1.
DR PROSITE; PS00240; RECEPTOR_TYR_KIN_III; 1.
PE 2: Evidence at transcript level;
KW Angiogenesis; ATP-binding; Cell membrane; Cytoplasm; Developmental protein;
KW Differentiation; Disulfide bond; Glycoprotein; Immunoglobulin domain;
KW Kinase; Membrane; Nucleotide-binding; Nucleus; Phosphoprotein; Receptor;
KW Reference proteome; Repeat; Signal; Transferase; Transmembrane;
KW Transmembrane helix; Tyrosine-protein kinase.
FT SIGNAL 1..24
FT /evidence="ECO:0000255"
FT CHAIN 25..1357
FT /note="Vascular endothelial growth factor receptor 3"
FT /id="PRO_0000249464"
FT TOPO_DOM 25..796
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 797..817
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 818..1357
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 25..121
FT /note="Ig-like C2-type 1"
FT DOMAIN 138..244
FT /note="Ig-like C2-type 2"
FT DOMAIN 255..343
FT /note="Ig-like C2-type 3"
FT DOMAIN 352..442
FT /note="Ig-like C2-type 4"
FT DOMAIN 453..583
FT /note="Ig-like C2-type 5"
FT DOMAIN 583..690
FT /note="Ig-like C2-type 6"
FT DOMAIN 699..785
FT /note="Ig-like C2-type 7"
FT DOMAIN 866..1181
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 978..1007
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1190..1212
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 980..1007
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 1045
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10028"
FT BINDING 872..880
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 900
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 1071
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 1076
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 1226
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 1227
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 1334
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 1338
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT CARBOHYD 44
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 48
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 114
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 216
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 271
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 360
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 400
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 440
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 553
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 610
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 660
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 707
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 711
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 751
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 51..121
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 173..225
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 272..331
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 473..562
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 493..514
FT /evidence="ECO:0000250|UniProtKB:P35916"
FT DISULFID 606..674
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 720..772
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT CONFLICT 567
FT /note="R -> K (in Ref. 1; AAS92272)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1357 AA; 153178 MW; D68C197828BE278E CRC64;
MKRDFTFFCR IWIGIPFFSG LVNGFSMSPP TLDNTKDQLV INANDTLNIT CRGQRILDWS
WPEESLSKVE FTDRQGQQSP TDTPGYREIR LKECQGVAGK PYCKILILTN AQANDSGYYR
CFYKDIKAVI DGTTAASIFV FVRDPEHPFI KRGDNDMETI FITDSETHIE VPCLVSDPDL
KVTLFSLVPY PEPVDGSVVT WNNKKGWSIP RHIIQNTSTF IGFYCSISVQ NSQHTSSIYV
VQVIGLKFYE FKLFPEDSPV ELMQGESLVL NCTALVDFNT GVDFQWDYPG KKENRLASLQ
PLRNVLDEAT EISSILSIRN IHLDDSGYYT CWANTLEMKR ELTTVVIVHE KPFISLDYRN
GSVIEAKEGQ KSVRLSVKVS AYPSPEIQWY KNGKLISSKN SSRFKVQQHS LQIRDVCKQD
AGEYMLVLKN SPAALEKRLN FTLIVNVPPQ IHEKEAAPPT NLYGKGTRQI LTCTADGSPP
ASISWQWRPW SPCDLERTRR ALRRRGGRDQ SPFCHNWMDL DPEHAVNPIE SIDTLTQMVD
GKEKTVGRVV IQNASVPAMY KCLAENRVGK DERLIYFYVT TIPEGFDIEM EPSEDPLEQD
LVQLKCNADN FTYENLRWYR LDPQTVPPEL DCKSLHQYAT FLEGQLSFQT TSNNWVLQLN
ITNIQLQDEG NYVCEVQNRR TGVKHCHRKY IPVKAMEAPR YRHNPTNHTV NVSESLQMNC
DVEGTPFPQL SWFKDNQPLH QISGILLQDS NRTLSIQRVR EEDAGLYTCS ACNQKGCVQS
SATVSVIGSD DKTNVEIVIL IGTGVIAIFF WVLLLVIFCN VKRVNPADIK TGYLSIIMDP
GEVPLEEQCE YLPYDSSQWE ISRDRLRLGK VLGHGAFGKV IEASIFGHDK KSSANTVAVK
MLKEGATASE HKALMSELKI LIHIGNHLNV VNLLGACTKP NGPLMVIVEY CKYGNLSNFL
RAKREFFLPY RDRSPKTQSQ VRRMIEAGQA SQSEHQPSTS STNPPRVTVD DLWKTPLTIE
DLICYSFQVA RGMEFLASRK CIHRDLAARN ILLSENNVVK ICDFGLARDI YKDPDYVRKG
NARLPLKWMA PESIFDKVYT SQSDVWSFGV LLWEIFSLGA SPYPGIQIDE DFCKRLKDGT
RMRAPDNASP EIYGIMLACW QGEPRERPTF PALVEILGDL LQENSLPEIP FNVSQSSEDD
GFSQASSRPP SQEEIRLACN TLPTRYYNCV PFAGCVMVGP SSTCHSRVKT FEELPMEMTS
HKTQHDSQTD SGMVLASDEL ERFEHKHRGA MLTTATTGQS TDRLISCPSV SSSGSGGGLL
RPVFFTQLSG QTFYNNEYGH LSEEGVSDYF SSSDQAV
