FLT4
entrez
2324
canonical
uniprot
P35916
canonical
ensembl
ENSG00000037280
resolver
ensp
ENSP00000261937
resolver
ensp
ENSP00000377016
resolver
ensp
ENSP00000426057
resolver
enst
ENST00000502649
resolver
genesymbol
FLT4
resolver
genesymbol_syn
VEGFR3
resolver
hgnc
HGNC:3767
resolver
uniprot
A8K6L4
resolver
uniprot
B5A926
resolver
uniprot
E9PD35
resolver
uniprot
Q16067
resolver
uniprot
Q86W07
resolver
uniprot
Q86W08
resolver
uniprot_entry
E9PD35_HUMAN
resolver
uniprot_entry
VGFR3_HUMAN
resolver
uniprot_sec
A8K6L4
resolver
uniprot_sec
B5A926
resolver
uniprot_sec
Q16067
resolver
uniprot_sec
Q86W07
resolver
uniprot_sec
Q86W08
resolver
activity_regulation
ACTIVITY REGULATION: 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. Inhibited by MAZ51. {ECO:0000269|PubMed:15102829, ECO:0000269|PubMed:19779139, ECO:0000269|PubMed:20431062}.
uniprot
proteins
amino_acid_sequence
MQRGAALCLRLWLCLGLLDGLVSGYSMTPPTLNITEESHVIDTGDSLSISCRGQHPLEWAWPGAQEAPATGDKDSEDTGVVRDCEGTDARPYCKVLLLHEVHANDTGSYVCYYKYIKARIEGTTAASSYVFVRDFEQPFINKPDTLLVNRKDAMWVPCLVSIPGLNVTLRSQSSVLWPDGQEVVWDDRRGMLVSTPLLHDALYLQCETTWGDQDFLSNPFLVHITGNELYDIQLLPRKSLELLVGEKLVLNCTVWAEFNSGVTFDWDYPGKQAERGKWVPERRSQQTHTELSSILTIHNVSQHDLGSYVCKANNGIQRFRESTEVIVHENPFISVEWLKGPILEATAGDELVKLPVKLAAYPPPEFQWYKDGKALSGRHSPHALVLKEVTEASTGTYTLALWNSAAGLRRNISLELVVNVPPQIHEKEASSPSIYSRHSRQALTCTAYGVPLPLSIQWHWRPWTPCKMFAQRSLRRRQQQDLMPQCRDWRAVTTQDAVNPIESLDTWTEFVEGKNKTVSKLVIQNANVSAMYKCVVSNKVGQDERLIYFYVTTIPDGFTIESKPSEELLEGQPVLLSCQADSYKYEHLRWYRLNLSTLHDAHGNPLLLDCKNVHLFATPLAASLEEVAPGARHATLSLSIPRVAPEHEGHYVCEVQDRRSHDKHCHKKYLSVQALEAPRLTQNLTDLLVNVSDSLEMQCLVAGAHAPSIVWYKDERLLEEKSGVDLADSNQKLSIQRVREEDAGRYLCSVCNAKGCVNSSASVAVEGSEDKGSMEIVILVGTGVIAVFFWVLLLLIFCNMRRPAHADIKTGYLSIIMDPGEVPLEEQCEYLSYDASQWEFPRERLHLGRVLGYGAFGKVVEASAFGIHKGSSCDTVAVKMLKEGATASEHRALMSELKILIHIGNHLNVVNLLGACTKPQGPLMVIVEFCKYGNLSNFLRAKRDAFSPCAEKSPEQRGRFRAMVELARLDRRRPGSSDRVLFARFSKTEGGARRASPDQEAEDLWLSPLTMEDLVCYSFQVARGMEFLASRKCIHRDLAARNILLSESDVVKICDFGLARDIYKDPDYVRKGSARLPLKWMAPESIFDKVYTTQSDVWSFGVLLWEIFSLGASPYPGVQINEEFCQRLRDGTRMRAPELATPAIRRIMLNCWSGDPKARPAFSELVEILGDLLQGRGLQEEEEVCMAPRSSQSSEEGSFSQVSTMALHIAQADAEDSPPSLQRHSLAARYYNWVSFPGCLARGAETRGSSRMKTFEEFPMTPTTYKGSVDNQTDSGMVLASEEFEQIESRHRQESGFSCKGPGQNVAVTRAHPDSQGRRRRPERGARGGQVFYNSEYGELSEPSEEDHCSPSARVTFFTDNSY
uniprot
proteins
disease_involvement
DISEASE: Lymphatic malformation 1 (LMPHM1) [MIM:153100]: A form of primary lymphedema, a disease characterized by swelling of body parts due to developmental anomalies and functional defects of the lymphatic system. Patients with lymphedema may suffer from recurrent local infections. LMPHM1 is an autosomal dominant form with variable expression and severity. Onset is usually at birth or in early childhood but can occur later. Affected individuals manifest lymphedema, predominantly in the lower limbs, and hypoplasia of lymphatic vessels. Additional features are hemangioma and nail dysplasia or papillomatosis. {ECO:0000269|PubMed:10835628, ECO:0000269|PubMed:10856194, ECO:0000269|PubMed:12881528, ECO:0000269|PubMed:15102829, ECO:0000269|PubMed:16924388, ECO:0000269|PubMed:16965327, ECO:0000269|PubMed:17458866, ECO:0000269|PubMed:19289394, ECO:0000269|PubMed:26091405, ECO:0000269|PubMed:9817924}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Hemangioma, capillary infantile (HCI) [MIM:602089]: A condition characterized by dull red, firm, dome-shaped hemangiomas, sharply demarcated from surrounding skin, usually presenting at birth or occurring within the first two or three months of life. They result from highly proliferative, localized growth of capillary endothelium and generally undergo regression and involution without scarring. {ECO:0000269|PubMed:11807987}. Note=Disease susceptibility is associated with variants affecting the gene represented in this entry.; DISEASE: Note=Plays an important role in tumor lymphangiogenesis, in cancer cell survival, migration, and formation of metastases.; DISEASE: Congenital heart defects, multiple types, 7 (CHTD7) [MIM:618780]: An autosomal dominant disorder with incomplete penetrance characterized by congenital developmental abnormalities involving structures of the heart. Common defects include tetralogy of Fallot, pulmonary stenosis or atresia, absent pulmonary valve, right aortic arch, double aortic arch, and major aortopulmonary collateral arteries. {ECO:0000269|PubMed:28991257, ECO:0000269|PubMed:30232381}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
ec_number
2.7.10.1
uniprot
proteins
function
FUNCTION: 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'. {ECO:0000269|PubMed:11532940, ECO:0000269|PubMed:15102829, ECO:0000269|PubMed:15474514, ECO:0000269|PubMed:16076871, ECO:0000269|PubMed:16452200, ECO:0000269|PubMed:17210781, ECO:0000269|PubMed:19610651, ECO:0000269|PubMed:19779139, ECO:0000269|PubMed:20224550, ECO:0000269|PubMed:20431062, ECO:0000269|PubMed:20445537, ECO:0000269|PubMed:21273538, ECO:0000269|PubMed:7675451, ECO:0000269|PubMed:8700872, ECO:0000269|PubMed:9435229}.
uniprot
proteins
mass_dalton
152757
uniprot
proteins
mutagenesis
MUTAGEN 446; /note="T->E: Decreases autophosphorylation on tyrosine residues upon ligand binding; when associated with A-516. Abolishes autophosphorylation on tyrosine residues upon ligand binding; when associated with A-516 and A-737."; /evidence="ECO:0000269|PubMed:23878260"; MUTAGEN 516; /note="K->A: Decreases autophosphorylation on tyrosine residues upon ligand binding; when associated with E-446. Abolishes autophosphorylation on tyrosine residues upon ligand binding; when associated with E-446 and A-737."; /evidence="ECO:0000269|PubMed:23878260"; MUTAGEN 737; /note="R->A: Decreases autophosphorylation on tyrosine residues upon ligand binding. Abolishes autophosphorylation on tyrosine residues upon ligand binding; when associated with E-446 and A-516."; /evidence="ECO:0000269|PubMed:23878260"; MUTAGEN 879; /note="K->G: Abolishes enzyme activity."; /evidence="ECO:0000269|PubMed:12881528"; MUTAGEN 1063; /note="Y->F: Loss of phosphorylation site. No effect on stimulation of cell proliferation and cell migration."; /evidence="ECO:0000269|PubMed:16076871, ECO:0000269|PubMed:20431062"; MUTAGEN 1068; /note="Y->F: Global loss of autophosphorylation. Abolishes stimulation of cell proliferation and cell migration."; /evidence="ECO:0000269|PubMed:16076871, ECO:0000269|PubMed:20431062"; MUTAGEN 1230; /note="Y->F: Loss of phosphorylation site. Strongly reduces stimulation of cell proliferation and cell migration."; /evidence="ECO:0000269|PubMed:12881528, ECO:0000269|PubMed:16076871"; MUTAGEN 1231; /note="Y->F: Loss of phosphorylation site. Strongly reduces stimulation of cell proliferation and cell migration."; /evidence="ECO:0000269|PubMed:12881528, ECO:0000269|PubMed:16076871"; MUTAGEN 1265; /note="Y->F: Loss of phosphorylation site. No effect on stimulation of cell proliferation and cell migration."; /evidence="ECO:0000269|PubMed:12881528"; MUTAGEN 1333; /note="Y->F: Loss of phosphorylation site. Reduced autophosphorylation."; /evidence="ECO:0000269|PubMed:12881528, ECO:0000269|PubMed:7675451"; MUTAGEN 1337; /note="Y->F: Reduced autophosphorylation. Strongly reduces stimulation of cell proliferation and cell migration."; /evidence="ECO:0000269|PubMed:12881528, ECO:0000269|PubMed:20431062, ECO:0000269|PubMed:7675451"; MUTAGEN 1363; /note="Y->F: Loss of phosphorylation site. Slightly reduced autophosphorylation."; /evidence="ECO:0000269|PubMed:12881528, ECO:0000269|PubMed:7675451
uniprot
proteins
post_translational_modification
PTM: 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. Phosphorylation in response to H(2)O(2) is mediated by a process that requires SRC and PRKCD activity. Phosphorylation at Tyr-1068 is required for autophosphorylation at additional tyrosine residues. Phosphorylation at Tyr-1063 and Tyr-1337 is important for interaction with CRK and subsequent activation of MAPK8. Phosphorylation at Tyr-1230, Tyr-1231 and Tyr-1337 is important for interaction with GRB2 and subsequent activation of the AKT1 and MAPK1/ERK2 and/or MAPK3/ERK1 signaling pathways. In response to endothelial cell adhesion onto collagen, can also be phosphorylated in the absence of FLT4 kinase activity by SRC at Tyr-830, Tyr-833, Tyr-853, Tyr-1063, Tyr-1333, and Tyr-1337. {ECO:0000269|PubMed:12881528, ECO:0000269|PubMed:15102829, ECO:0000269|PubMed:15474514, ECO:0000269|PubMed:16076871, ECO:0000269|PubMed:20431062, ECO:0000269|PubMed:23878260, ECO:0000269|PubMed:8700872}.
uniprot
proteins
protein_family
CSF-1/PDGF receptor subfamily
uniprot
proteins
protein_family
Protein kinase superfamily
uniprot
proteins
protein_family
Tyr protein kinase family
uniprot
proteins
pubmed
10835628
uniprot
proteins
pubmed
10856194
uniprot
proteins
pubmed
11532940
uniprot
proteins
pubmed
11807987
uniprot
proteins
pubmed
12881528
uniprot
proteins
pubmed
1310071
uniprot
proteins
pubmed
1319394
uniprot
proteins
pubmed
1327515
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15102829
uniprot
proteins
pubmed
15340161
uniprot
proteins
pubmed
15372022
uniprot
proteins
pubmed
15474514
uniprot
proteins
pubmed
16076871
uniprot
proteins
pubmed
16335952
uniprot
proteins
pubmed
16452200
uniprot
proteins
pubmed
16924388
uniprot
proteins
pubmed
16965327
uniprot
proteins
pubmed
17210781
uniprot
proteins
pubmed
17344846
uniprot
proteins
pubmed
17458866
uniprot
proteins
pubmed
18593464
uniprot
proteins
pubmed
18680722
uniprot
proteins
pubmed
19230644
uniprot
proteins
pubmed
19289394
uniprot
proteins
pubmed
19610651
uniprot
proteins
pubmed
19779139
uniprot
proteins
pubmed
20224550
uniprot
proteins
pubmed
20431062
uniprot
proteins
pubmed
20445537
uniprot
proteins
pubmed
20826270
uniprot
proteins
pubmed
21196198
uniprot
proteins
pubmed
21273538
uniprot
proteins
pubmed
21711246
uniprot
proteins
pubmed
23878260
uniprot
proteins
pubmed
26091405
uniprot
proteins
pubmed
28991257
uniprot
proteins
pubmed
30232381
uniprot
proteins
pubmed
7675451
uniprot
proteins
pubmed
7692369
uniprot
proteins
pubmed
7898938
uniprot
proteins
pubmed
8386825
uniprot
proteins
pubmed
8700872
uniprot
proteins
pubmed
9435229
uniprot
proteins
pubmed
9817924
uniprot
proteins
sequence_length
1363
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:20445537, ECO:0000269|PubMed:7898938}; Single-pass type I membrane protein. Cytoplasm {ECO:0000269|PubMed:16452200, ECO:0000269|PubMed:20445537}. Nucleus {ECO:0000269|PubMed:16452200}. Note=Ligand-mediated autophosphorylation leads to rapid internalization. {ECO:0000269|PubMed:20445537}.; SUBCELLULAR LOCATION: [Isoform 1]: Cell membrane; Single-pass type I membrane protein. Note=Ligand-mediated autophosphorylation leads to rapid internalization.; SUBCELLULAR LOCATION: [Isoform 2]: Cell membrane; Single-pass type I membrane protein.; SUBCELLULAR LOCATION: [Isoform 3]: Secreted. Cytoplasm.
uniprot
proteins
transmembrane_region
TRANSMEM 776..796; /note="Helical"; /evidence="ECO:0000255
uniprot
proteins