UniProt Accession

 VGFR3_HUMAN; P35916; A8K6L4; B5A926; Q16067; Q86W07; Q86W08 

Genbank Protein ID

 X69878; U43143; EU826564; AY233382; AY233383; AK291679; AC122714; X68203; S66407 

Genbank Nucleotide ID

 CAA49505.1; AAA85215.1; ACF47600.1; AAO89504.1; AAO89505.1; BAF84368.1; CAA48290.1; AAB28539.1 

Protein Name

 Vascular endothelial growth factor receptor 3 

Protein Synonyms/Alias

 VEGFR-3; Fms-like tyrosine kinase 4; FLT-4; Tyrosine-protein kinase receptor FLT4 

Gene Name

 FLT4 

Gene Synonyms/Alias

 VEGFR3 

Created Date

 July 27, 2013 

Organism

 Homo sapiens (Human) 

NCBI Taxa ID

 9606 

Lysine Modification

Position	Peptide	Type	References
1064	GLARDIYKDPDYVRK	ubiquitination	[1, 2]
1079	GSARLPLKWMAPESI	ubiquitination	[1, 2]
1253	TRGSSRMKTFEEFPM	ubiquitination	[1, 2]
1266	PMTPTTYKGSVDNQT	ubiquitination	[1]
1300	QESGFSCKGPGQNVA	ubiquitination	[2]

Reference

 [1] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
 [2] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961] 

Functional Description

 Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFC and VEGFD, and plays an essential role in adult lymphangiogenesis and in the development of the vascular network and the cardiovascular system during embryonic development. Promotes proliferation, survival and migration of endothelial cells, and regulates angiogenic sprouting. Signaling by activated FLT4 leads to enhanced production of VEGFC, and to a lesser degree VEGFA, thereby creating a positive feedback loop that enhances FLT4 signaling. Modulates KDR signaling by forming heterodimers. The secreted isoform 3 may function as a decoy receptor for VEGFC and/or VEGFD and play an important role as a negative regulator of VEGFC-mediated lymphangiogenesis and angiogenesis. Binding of vascular growth factors to isoform 1 or isoform 2 leads to the activation of several signaling cascades; isoform 2 seems to be less efficient in signal transduction, because it has a truncated C-terminus and therefore lacks several phosphorylation sites. Mediates activation of the MAPK1/ERK2, MAPK3/ERK1 signaling pathway, of MAPK8 and the JUN signaling pathway, and of the AKT1 signaling pathway. Phosphorylates SHC1. Mediates phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3- kinase. Promotes phosphorylation of MAPK8 at 'Thr-183' and 'Tyr- 185', and of AKT1 at 'Ser-473'. 

Sequence Annotation

 DOMAIN 30 127 Ig-like C2-type 1.
 DOMAIN 151 213 Ig-like C2-type 2.
 DOMAIN 219 326 Ig-like C2-type 3.
 DOMAIN 331 415 Ig-like C2-type 4.
 DOMAIN 422 552 Ig-like C2-type 5.
 DOMAIN 555 671 Ig-like C2-type 6.
 DOMAIN 678 764 Ig-like C2-type 7.
 DOMAIN 845 1173 Protein kinase.
 NP_BIND 851 859 ATP (By similarity).
 ACT_SITE 1037 1037 Proton acceptor (By similarity).
 BINDING 879 879 ATP (Probable).
 MOD_RES 830 830 Phosphotyrosine; by SRC.
 MOD_RES 833 833 Phosphotyrosine; by SRC.
 MOD_RES 853 853 Phosphotyrosine; by SRC.
 MOD_RES 1063 1063 Phosphotyrosine; by autocatalysis and
 MOD_RES 1068 1068 Phosphotyrosine; by autocatalysis.
 MOD_RES 1230 1230 Phosphotyrosine; by autocatalysis.
 MOD_RES 1231 1231 Phosphotyrosine; by autocatalysis.
 MOD_RES 1265 1265 Phosphotyrosine; by autocatalysis.
 MOD_RES 1333 1333 Phosphotyrosine; by autocatalysis and
 MOD_RES 1337 1337 Phosphotyrosine; by autocatalysis and
 MOD_RES 1363 1363 Phosphotyrosine; by autocatalysis.
 CARBOHYD 33 33 N-linked (GlcNAc...) (Potential).
 CARBOHYD 104 104 N-linked (GlcNAc...) (Potential).
 CARBOHYD 166 166 N-linked (GlcNAc...) (Potential).
 CARBOHYD 251 251 N-linked (GlcNAc...) (Potential).
 CARBOHYD 299 299 N-linked (GlcNAc...) (Potential).
 CARBOHYD 411 411 N-linked (GlcNAc...) (Potential).
 CARBOHYD 515 515 N-linked (GlcNAc...) (Potential).
 CARBOHYD 527 527 N-linked (GlcNAc...).
 CARBOHYD 594 594 N-linked (GlcNAc...) (Potential).
 CARBOHYD 683 683 N-linked (GlcNAc...) (Potential).
 CARBOHYD 690 690 N-linked (GlcNAc...) (Potential).
 CARBOHYD 758 758 N-linked (GlcNAc...) (Potential).
 DISULFID 51 111 By similarity.
 DISULFID 158 206 By similarity.
 DISULFID 252 310 By similarity.
 DISULFID 445 534 By similarity.
 DISULFID 578 653 By similarity.
 DISULFID 699 751 By similarity.  

Keyword

 Alternative splicing; Angiogenesis; ATP-binding; Cell membrane; Complete proteome; Cytoplasm; Direct protein sequencing; Disease mutation; Disulfide bond; Glycoprotein; Immunoglobulin domain; Kinase; Membrane; Nucleotide-binding; Nucleus; Phosphoprotein; Polymorphism; Receptor; Reference proteome; Repeat; Secreted; Signal; Transferase; Transmembrane; Transmembrane helix; Tyrosine-protein kinase. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 1363 AA 

Protein Sequence

Gene Ontology

 GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
 GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
 GO:0005887; C:integral to plasma membrane; TAS:ProtInc.
 GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
 GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
 GO:0005021; F:vascular endothelial growth factor-activated receptor activity; IMP:UniProtKB.
 GO:0001946; P:lymphangiogenesis; IMP:UniProtKB.
 GO:0043066; P:negative regulation of apoptotic process; IMP:UniProtKB.
 GO:0018108; P:peptidyl-tyrosine phosphorylation; IDA:UniProtKB.
 GO:0010595; P:positive regulation of endothelial cell migration; IMP:UniProtKB.
 GO:0001938; P:positive regulation of endothelial cell proliferation; IMP:UniProtKB.
 GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IMP:UniProtKB.
 GO:0046330; P:positive regulation of JNK cascade; IMP:UniProtKB.
 GO:0090037; P:positive regulation of protein kinase C signaling cascade; IMP:UniProtKB.
 GO:0001934; P:positive regulation of protein phosphorylation; IMP:UniProtKB.
 GO:0010575; P:positive regulation vascular endothelial growth factor production; IMP:UniProtKB.
 GO:0046777; P:protein autophosphorylation; IDA:UniProtKB.
 GO:0060312; P:regulation of blood vessel remodeling; ISS:UniProtKB.
 GO:0002040; P:sprouting angiogenesis; ISS:UniProtKB.
 GO:0048010; P:vascular endothelial growth factor receptor signaling pathway; IMP:UniProtKB. 

Interpro

 IPR007110; Ig-like_dom.
 IPR013783; Ig-like_fold.
 IPR013098; Ig_I-set.
 IPR003599; Ig_sub.
 IPR003598; Ig_sub2.
 IPR011009; Kinase-like_dom.
 IPR000719; Prot_kinase_cat_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; Tyr_kinase_VEGFR3_rcpt_N.
 IPR009134; Tyr_kinase_VEGFR_rcpt_N. 

Pfam

 PF07679; I-set
 PF07714; Pkinase_Tyr 

SMART

 SM00409; IG
 SM00408; IGc2
 SM00219; TyrKc 

PROSITE

 PS50835; IG_LIKE
 PS00107; PROTEIN_KINASE_ATP
 PS50011; PROTEIN_KINASE_DOM
 PS00109; PROTEIN_KINASE_TYR
 PS00240; RECEPTOR_TYR_KIN_III 

PRINTS

 PR01832; VEGFRECEPTOR.
 PR01835; VEGFRECEPTR3.