VGFR3_COTCO
ID VGFR3_COTCO Reviewed; 1379 AA.
AC P79701;
DT 19-SEP-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1997, sequence version 1.
DT 03-AUG-2022, entry version 119.
DE RecName: Full=Vascular endothelial growth factor receptor 3;
DE Short=VEGFR-3;
DE EC=2.7.10.1;
DE AltName: Full=Endothelial kinase receptor EK2;
DE AltName: Full=Quek 2;
DE Short=Quek2;
DE Flags: Precursor;
GN Name=FLT4; Synonyms=K2, VEGFR3;
OS Coturnix coturnix (Common quail) (Tetrao coturnix).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Archelosauria; Archosauria; Dinosauria; Saurischia; Theropoda;
OC Coelurosauria; Aves; Neognathae; Galloanserae; Galliformes; Phasianidae;
OC Perdicinae; Coturnix.
OX NCBI_TaxID=9091;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Embryo;
RX PubMed=8863722; DOI=10.1016/0378-1119(96)00159-x;
RA Eichmann A., Marcelle C., Breant C., Le Douarin N.M.;
RT "Molecular cloning of Quek 1 and 2, two quail vascular endothelial growth
RT factor (VEGF) receptor-like molecules.";
RL Gene 174:3-8(1996).
CC -!- FUNCTION: Tyrosine-protein kinase that acts as a cell-surface receptor
CC for VEGFC and VEGFD, and plays an essential role in lymphangiogenesis
CC and in the development of the vascular network and the cardiovascular
CC system during embryonic development. Promotes proliferation, survival
CC and migration of endothelial cells, and regulates angiogenic sprouting.
CC Mediates activation of the MAPK1/ERK2, MAPK3/ERK1 signaling pathway, of
CC MAPK8 and the JUN signaling pathway, and of the AKT1 signaling pathway
CC (By similarity). {ECO:0000250|UniProtKB:P35916,
CC ECO:0000250|UniProtKB:P35917}.
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; X83287; CAA58267.1; -; mRNA.
DR AlphaFoldDB; P79701; -.
DR SMR; P79701; -.
DR PRIDE; P79701; -.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005887; C:integral component of plasma membrane; IEA:InterPro.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR GO; GO:0005021; F:vascular endothelial growth factor receptor activity; ISS:UniProtKB.
DR GO; GO:0001525; P:angiogenesis; IEA:UniProtKB-KW.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0046777; P:protein autophosphorylation; ISS:UniProtKB.
DR GO; GO:0048010; P:vascular endothelial growth factor receptor signaling pathway; IEA:InterPro.
DR GO; GO:0038084; P:vascular endothelial growth factor signaling pathway; ISS:UniProtKB.
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; 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; 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; 4.
DR SMART; SM00219; TyrKc; 1.
DR SUPFAM; SSF48726; SSF48726; 7.
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; Differentiation;
KW Disulfide bond; Glycoprotein; Immunoglobulin domain; Kinase; Membrane;
KW Nucleotide-binding; Nucleus; Phosphoprotein; Receptor; Repeat; Signal;
KW Transferase; Transmembrane; Transmembrane helix; Tyrosine-protein kinase.
FT SIGNAL 1..19
FT /evidence="ECO:0000255"
FT CHAIN 20..1379
FT /note="Vascular endothelial growth factor receptor 3"
FT /id="PRO_0000249463"
FT TOPO_DOM 20..788
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 789..809
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 810..1379
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 30..136
FT /note="Ig-like C2-type 1"
FT DOMAIN 160..222
FT /note="Ig-like C2-type 2"
FT DOMAIN 240..335
FT /note="Ig-like C2-type 3"
FT DOMAIN 340..421
FT /note="Ig-like C2-type 4"
FT DOMAIN 430..566
FT /note="Ig-like C2-type 5"
FT DOMAIN 569..684
FT /note="Ig-like C2-type 6"
FT DOMAIN 691..777
FT /note="Ig-like C2-type 7"
FT DOMAIN 858..1185
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 73..93
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1196..1224
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1299..1379
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1196..1221
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1333..1347
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 1049
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10028"
FT BINDING 864..872
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 892
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 1075
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 1080
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 1239
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 1240
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 1274
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 1342
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 1346
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT CARBOHYD 113
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 175
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 260
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 308
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 529
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 541
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 596
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 608
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 655
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 696
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 703
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 771
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 51..120
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 167..215
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 261..319
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 453..548
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 474..500
FT /evidence="ECO:0000250|UniProtKB:P35916"
FT DISULFID 592..666
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 712..761
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
SQ SEQUENCE 1379 AA; 156963 MW; 8411621AEF565520 CRC64;
MKRVCTLPLW LWLGIVSEAD LVSSYSMTPP TLSITEEEHI INAKDTLTIT CRGQHPLEWS
WPGARWTPVE GRRRWNSQPQ QRPVGAGNPE EDCEGTGTKP YCKVLVLTES QANDTGYYHC
YYKYIDAKIE GTTAVSAYIF VRDFEQPFIN KPETLLISKK ENTWVPCLVS IPDLNVTLIS
QNSLIHPDRK TIFWDNKKGM QVPTQLIRDS LFVQCETVID NKVFKSNFFI IHIAGIELYD
IQLYPKKAME LLVGEKLVLN CTVWAEFNSG VRFQWTYPGK QMQRAVIESE RRSLQTHTEL
SSILTLHNVS QQDLGRYTCT ATNGAQMLEE STDVIVHEKP FINVEWRKGP VIEATAGDEA
VKLPVKVVAY PQPDFQWYKA GKLIPKQSQS SMQIKDVAEH HAGTYTLVLR NRLVGLEKRI
SLQLIVNVPP RIHEKETSSP SIYSRRSPQA LTCTVYGIPA PEVIQWQWRP WMPCRMFSRR
SLNSRHRAAR RHQRDRMPEC KDWKDVSRQD AVNPIESIDT WVEFVEGRNK TVSKLAIQEA
NVSAMYKCIA SNKVGRDERL IYFYVTTIPD GFEIESQPSE EPIEGQDLQL SCNADNYTYE
NLQWYRLNLS KLHDEEGNPL VLDCKNVHHY ATKMQGELRF QPDSNDATLL LTIPNISLGE
EGDYVCEVQN RKTREKHCHK KYISVQALEI PRLKQNLTDI WVNVSDSIEM RCKVDGNHVP
DISWYKDEKL VEEVSGIDLA DFNQRLSIQR VREEDAGLYL CSVCNAKGCV NSSASVSVEG
SDDKTNVEIV ILIGTGVIAV FFWILLIIIF CNIKRPAHAD IKTGYLSIIM DPGEVPLEEQ
CAYLPYDSSK WEFPRDRLRL GKVLGHGAFG KVVEASAFGI NKSNSCETVA AKMLKEGATA
SEQKALMSEL KILIHIGNHL NVVNLLGACT KPNGPLMVIV EFCKYGNLSN YLRTKREGFS
PYREKSPRLR IQVQSIVEAV RADRRSRSGT SDSAIFNRFL MHKSQTVQPI QEVDDLWQSP
LTMEDLICYS FQVARGMEFL ASRKCIHRDL AARNILLSEN NVVKICDFGL ARDIYKDPDY
VRKGSARLPL KWMAPESIFD KVYTTQSDVW SFGVLLWEIF SLGASPYPGV QINEEFCQRF
KDGTRMRAPE YTTAEIYRIM LSCWHGDPKE RPTFSDLVEI LGNLLQENVQ QEGKDYIPLN
DSHSSEDDGF SQVPSSAQQN SDEEDFDMRI RCHSLAARYY NCVSFPGCLT GGNQIRCSSR
IKTFEEFPMT HTMYKAHPDN QTDSGMVLAS EEFERIENRH RKEGGFSSKG PNRTAELSAE
QSDLRGRCRP SYGSQVGGQT FYNSEYGELS EHSEDRSCTP PAEGASPPAL HASFFSEQY
