Vascular endothelial growth factor receptor 3

Details

Name
Vascular endothelial growth factor receptor 3
Synonyms
  • 2.7.10.1
  • FLT-4
  • Fms-like tyrosine kinase 4
  • Tyrosine-protein kinase receptor FLT4
  • VEGFR-3
  • VEGFR3
Gene Name
FLT4
Organism
Humans
Amino acid sequence
>lcl|BSEQ0036936|Vascular endothelial growth factor receptor 3
MQRGAALCLRLWLCLGLLDGLVSGYSMTPPTLNITEESHVIDTGDSLSISCRGQHPLEWA
WPGAQEAPATGDKDSEDTGVVRDCEGTDARPYCKVLLLHEVHANDTGSYVCYYKYIKARI
EGTTAASSYVFVRDFEQPFINKPDTLLVNRKDAMWVPCLVSIPGLNVTLRSQSSVLWPDG
QEVVWDDRRGMLVSTPLLHDALYLQCETTWGDQDFLSNPFLVHITGNELYDIQLLPRKSL
ELLVGEKLVLNCTVWAEFNSGVTFDWDYPGKQAERGKWVPERRSQQTHTELSSILTIHNV
SQHDLGSYVCKANNGIQRFRESTEVIVHENPFISVEWLKGPILEATAGDELVKLPVKLAA
YPPPEFQWYKDGKALSGRHSPHALVLKEVTEASTGTYTLALWNSAAGLRRNISLELVVNV
PPQIHEKEASSPSIYSRHSRQALTCTAYGVPLPLSIQWHWRPWTPCKMFAQRSLRRRQQQ
DLMPQCRDWRAVTTQDAVNPIESLDTWTEFVEGKNKTVSKLVIQNANVSAMYKCVVSNKV
GQDERLIYFYVTTIPDGFTIESKPSEELLEGQPVLLSCQADSYKYEHLRWYRLNLSTLHD
AHGNPLLLDCKNVHLFATPLAASLEEVAPGARHATLSLSIPRVAPEHEGHYVCEVQDRRS
HDKHCHKKYLSVQALEAPRLTQNLTDLLVNVSDSLEMQCLVAGAHAPSIVWYKDERLLEE
KSGVDLADSNQKLSIQRVREEDAGRYLCSVCNAKGCVNSSASVAVEGSEDKGSMEIVILV
GTGVIAVFFWVLLLLIFCNMRRPAHADIKTGYLSIIMDPGEVPLEEQCEYLSYDASQWEF
PRERLHLGRVLGYGAFGKVVEASAFGIHKGSSCDTVAVKMLKEGATASEHRALMSELKIL
IHIGNHLNVVNLLGACTKPQGPLMVIVEFCKYGNLSNFLRAKRDAFSPCAEKSPEQRGRF
RAMVELARLDRRRPGSSDRVLFARFSKTEGGARRASPDQEAEDLWLSPLTMEDLVCYSFQ
VARGMEFLASRKCIHRDLAARNILLSESDVVKICDFGLARDIYKDPDYVRKGSARLPLKW
MAPESIFDKVYTTQSDVWSFGVLLWEIFSLGASPYPGVQINEEFCQRLRDGTRMRAPELA
TPAIRRIMLNCWSGDPKARPAFSELVEILGDLLQGRGLQEEEEVCMAPRSSQSSEEGSFS
QVSTMALHIAQADAEDSPPSLQRHSLAARYYNWVSFPGCLARGAETRGSSRMKTFEEFPM
TPTTYKGSVDNQTDSGMVLASEEFEQIESRHRQESGFSCKGPGQNVAVTRAHPDSQGRRR
RPERGARGGQVFYNSEYGELSEPSEEDHCSPSARVTFFTDNSY
Number of residues
1363
Molecular Weight
152755.94
Theoretical pI
6.24
GO Classification
Functions
ATP binding / growth factor binding / protein phosphatase binding / transmembrane receptor protein tyrosine kinase activity / vascular endothelial growth factor-activated receptor activity
Processes
blood vessel morphogenesis / cellular response to vascular endothelial growth factor stimulus / lymph vessel development / lymphangiogenesis / negative regulation of apoptotic process / peptidyl-tyrosine phosphorylation / positive regulation of cell proliferation / positive regulation of endothelial cell migration / positive regulation of endothelial cell proliferation / positive regulation of ERK1 and ERK2 cascade / positive regulation of JNK cascade / positive regulation of MAPK cascade / positive regulation of protein kinase C signaling / positive regulation of protein phosphorylation / positive regulation of vascular endothelial growth factor production / protein autophosphorylation / regulation of blood vessel remodeling / sprouting angiogenesis / transmembrane receptor protein tyrosine kinase signaling pathway / vascular endothelial growth factor receptor signaling pathway / vascular endothelial growth factor signaling pathway / vasculature development
Components
cytoplasm / extracellular region / integral component of plasma membrane / nucleus / plasma membrane / receptor complex
General Function
Vascular endothelial growth factor-activated receptor activity
Specific 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'.
Pfam Domain Function
Transmembrane Regions
776-796
Cellular Location
Cell membrane
Gene sequence
>lcl|BSEQ0010134|Vascular endothelial growth factor receptor 3 (FLT4)
ATGCAGCGGGGCGCCGCGCTGTGCCTGCGACTGTGGCTCTGCCTGGGACTCCTGGACGGC
CTGGTGAGTGGCTACTCCATGACCCCCCCGACCTTGAACATCACGGAGGAGTCACACGTC
ATCGACACCGGTGACAGCCTGTCCATCTCCTGCAGGGGACAGCACCCCCTCGAGTGGGCT
TGGCCAGGAGCTCAGGAGGCGCCAGCCACCGGAGACAAGGACAGCGAGGACACGGGGGTG
GTGCGAGACTGCGAGGGCACAGACGCCAGGCCCTACTGCAAGGTGTTGCTGCTGCACGAG
GTACATGCCAACGACACAGGCAGCTACGTCTGCTACTACAAGTACATCAAGGCACGCATC
GAGGGCACCACGGCCGCCAGCTCCTACGTGTTCGTGAGAGACTTTGAGCAGCCATTCATC
AACAAGCCTGACACGCTCTTGGTCAACAGGAAGGACGCCATGTGGGTGCCCTGTCTGGTG
TCCATCCCCGGCCTCAATGTCACGCTGCGCTCGCAAAGCTCGGTGCTGTGGCCAGACGGG
CAGGAGGTGGTGTGGGATGACCGGCGGGGCATGCTCGTGTCCACGCCACTGCTGCACGAT
GCCCTGTACCTGCAGTGCGAGACCACCTGGGGAGACCAGGACTTCCTTTCCAACCCCTTC
CTGGTGCACATCACAGGCAACGAGCTCTATGACATCCAGCTGTTGCCCAGGAAGTCGCTG
GAGCTGCTGGTAGGGGAGAAGCTGGTCCTGAACTGCACCGTGTGGGCTGAGTTTAACTCA
GGTGTCACCTTTGACTGGGACTACCCAGGGAAGCAGGCAGAGCGGGGTAAGTGGGTGCCC
GAGCGACGCTCCCAGCAGACCCACACAGAACTCTCCAGCATCCTGACCATCCACAACGTC
AGCCAGCACGACCTGGGCTCGTATGTGTGCAAGGCCAACAACGGCATCCAGCGATTTCGG
GAGAGCACCGAGGTCATTGTGCATGAAAATCCCTTCATCAGCGTCGAGTGGCTCAAAGGA
CCCATCCTGGAGGCCACGGCAGGAGACGAGCTGGTGAAGCTGCCCGTGAAGCTGGCAGCG
TACCCCCCGCCCGAGTTCCAGTGGTACAAGGATGGAAAGGCACTGTCCGGGCGCCACAGT
CCACATGCCCTGGTGCTCAAGGAGGTGACAGAGGCCAGCACAGGCACCTACACCCTCGCC
CTGTGGAACTCCGCTGCTGGCCTGAGGCGCAACATCAGCCTGGAGCTGGTGGTGAATGTG
CCCCCCCAGATACATGAGAAGGAGGCCTCCTCCCCCAGCATCTACTCGCGTCACAGCCGC
CAGGCCCTCACCTGCACGGCCTACGGGGTGCCCCTGCCTCTCAGCATCCAGTGGCACTGG
CGGCCCTGGACACCCTGCAAGATGTTTGCCCAGCGTAGTCTCCGGCGGCGGCAGCAGCAA
GACCTCATGCCACAGTGCCGTGACTGGAGGGCGGTGACCACGCAGGATGCCGTGAACCCC
ATCGAGAGCCTGGACACCTGGACCGAGTTTGTGGAGGGAAAGAATAAGACTGTGAGCAAG
CTGGTGATCCAGAATGCCAACGTGTCTGCCATGTACAAGTGTGTGGTCTCCAACAAGGTG
GGCCAGGATGAGCGGCTCATCTACTTCTATGTGACCACCATCCCCGACGGCTTCACCATC
GAATCCAAGCCATCCGAGGAGCTACTAGAGGGCCAGCCGGTGCTCCTGAGCTGCCAAGCC
GACAGCTACAAGTACGAGCATCTGCGCTGGTACCGCCTCAACCTGTCCACGCTGCACGAT
GCGCACGGGAACCCGCTTCTGCTCGACTGCAAGAACGTGCATCTGTTCGCCACCCCTCTG
GCCGCCAGCCTGGAGGAGGTGGCACCTGGGGCGCGCCACGCCACGCTCAGCCTGAGTATC
CCCCGCGTCGCGCCCGAGCACGAGGGCCACTATGTGTGCGAAGTGCAAGACCGGCGCAGC
CATGACAAGCACTGCCACAAGAAGTACCTGTCGGTGCAGGCCCTGGAAGCCCCTCGGCTC
ACGCAGAACTTGACCGACCTCCTGGTGAACGTGAGCGACTCGCTGGAGATGCAGTGCTTG
GTGGCCGGAGCGCACGCGCCCAGCATCGTGTGGTACAAAGACGAGAGGCTGCTGGAGGAA
AAGTCTGGAGTCGACTTGGCGGACTCCAACCAGAAGCTGAGCATCCAGCGCGTGCGCGAG
GAGGATGCGGGACGCTATCTGTGCAGCGTGTGCAACGCCAAGGGCTGCGTCAACTCCTCC
GCCAGCGTGGCCGTGGAAGGCTCCGAGGATAAGGGCAGCATGGAGATCGTGATCCTTGTC
GGTACCGGCGTCATCGCTGTCTTCTTCTGGGTCCTCCTCCTCCTCATCTTCTGTAACATG
AGGAGGCCGGCCCACGCAGACATCAAGACGGGCTACCTGTCCATCATCATGGACCCCGGG
GAGGTGCCTCTGGAGGAGCAATGCGAATACCTGTCCTACGATGCCAGCCAGTGGGAATTC
CCCCGAGAGCGGCTGCACCTGGGGAGAGTGCTCGGCTACGGCGCCTTCGGGAAGGTGGTG
GAAGCCTCCGCTTTCGGCATCCACAAGGGCAGCAGCTGTGACACCGTGGCCGTGAAAATG
CTGAAAGAGGGCGCCACGGCCAGCGAGCACCGCGCGCTGATGTCGGAGCTCAAGATCCTC
ATTCACATCGGCAACCACCTCAACGTGGTCAACCTCCTCGGGGCGTGCACCAAGCCGCAG
GGCCCCCTCATGGTGATCGTGGAGTTCTGCAAGTACGGCAACCTCTCCAACTTCCTGCGC
GCCAAGCGGGACGCCTTCAGCCCCTGCGCGGAGAAGTCTCCCGAGCAGCGCGGACGCTTC
CGCGCCATGGTGGAGCTCGCCAGGCTGGATCGGAGGCGGCCGGGGAGCAGCGACAGGGTC
CTCTTCGCGCGGTTCTCGAAGACCGAGGGCGGAGCGAGGCGGGCTTCTCCAGACCAAGAA
GCTGAGGACCTGTGGCTGAGCCCGCTGACCATGGAAGATCTTGTCTGCTACAGCTTCCAG
GTGGCCAGAGGGATGGAGTTCCTGGCTTCCCGAAAGTGCATCCACAGAGACCTGGCTGCT
CGGAACATTCTGCTGTCGGAAAGCGACGTGGTGAAGATCTGTGACTTTGGCCTTGCCCGG
GACATCTACAAAGACCCCGACTACGTCCGCAAGGGCAGTGCCCGGCTGCCCCTGAAGTGG
ATGGCCCCTGAAAGCATCTTCGACAAGGTGTACACCACGCAGAGTGACGTGTGGTCCTTT
GGGGTGCTTCTCTGGGAGATCTTCTCTCTGGGGGCCTCCCCGTACCCTGGGGTGCAGATC
AATGAGGAGTTCTGCCAGCGGCTGAGAGACGGCACAAGGATGAGGGCCCCGGAGCTGGCC
ACTCCCGCCATACGCCGCATCATGCTGAACTGCTGGTCCGGAGACCCCAAGGCGAGACCT
GCATTCTCGGAGCTGGTGGAGATCCTGGGGGACCTGCTCCAGGGCAGGGGCCTGCAAGAG
GAAGAGGAGGTCTGCATGGCCCCGCGCAGCTCTCAGAGCTCAGAAGAGGGCAGCTTCTCG
CAGGTGTCCACCATGGCCCTACACATCGCCCAGGCTGACGCTGAGGACAGCCCGCCAAGC
CTGCAGCGCCACAGCCTGGCCGCCAGGTATTACAACTGGGTGTCCTTTCCCGGGTGCCTG
GCCAGAGGGGCTGAGACCCGTGGTTCCTCCAGGATGAAGACATTTGAGGAATTCCCCATG
ACCCCAACGACCTACAAAGGCTCTGTGGACAACCAGACAGACAGTGGGATGGTGCTGGCC
TCGGAGGAGTTTGAGCAGATAGAGAGCAGGCATAGACAAGAAAGCGGCTTCAGGTAG
Chromosome Location
5
Locus
5q35.3
External Identifiers
ResourceLink
UniProtKB IDP35916
UniProtKB Entry NameVGFR3_HUMAN
GenBank Protein ID297050
GenBank Gene IDX69878
GenAtlas IDFLT4
HGNC IDHGNC:3767
General References
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Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB00398Sorafenibapproved, investigationalyesantagonistDetails
DB01268Sunitinibapproved, investigationalyesinhibitorDetails
DB04879VatalanibinvestigationalunknownDetails
DB05075TG-100801investigationalunknownDetails
DB06080LinifanibinvestigationalunknownDetails
DB06101IMC-1C11investigationalunknownDetails
DB05932DenibulininvestigationalunknownDetails
DB06589PazopanibapprovedyesDetails
DB06626Axitinibapproved, investigationalyesinhibitorDetails
DB08896RegorafenibapprovedyesinhibitorDetails
DB09078Lenvatinibapproved, investigationalyesinhibitorDetails
DB09079NintedanibapprovedyesinhibitorDetails
DB12010Fostamatinibapproved, investigationalunknowninhibitorDetails
DB15685Selpercatinibapproved, investigationalunknowninhibitorDetails
DB11800Tivozanibapproved, investigationalyesinhibitorDetails