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vascular endothelial growth factor receptor 1; VEGFR-1; vascular permeability factor receptor; tyrosine-protein kinase receptor FLT; Flt-1; tyrosine-protein kinase FRT; Fms-like tyrosine kinase 1 (FLT1, FLT, FRT)
Function:
- receptor for VEGF, VEGFB & PGF
- has a tyrosine-protein kinase activity
- the VEGF-kinase ligand/receptor signaling system plays a role in vascular development & regulation of vascular permeability
- isoform SFlt1 may have an inhibitory role in angiogenesis
- interacts in vitro with various phosphotyrosine-binding proteins, including: PLC-gammas, PTPN11, GRB2, CRK & NCK1
- Flt1 & Flk1 bind VEGF with high affinity & are required for embryonic & definitive hematopoiesis
Structure:
- belongs to the protein kinase superfamily, Tyr protein kinase family, CSF-1/PDGF receptor subfamily
- contains 7 Ig-like C2-type domain (immunoglobulin-like)
- contains 1 protein kinase domain
Compartment:
- isoform Flt1: cell membrane
- isoform sFlt1: secreted
Alternative splicing: named isoforms=2
Additional isoforms seem to exist
Expression:
- mostly in normal lung, but also in placenta, liver, kidney, heart & brain
- specifically expressed in most vascular endothelial cells
- also expressed in peripheral blood monocytes
- not expressed in tumor cell lines
- isoform sFlt1 is strongly expressed in placenta
Pathology:
- plasma levels of soluble fms-like tyrosine kinase 1 are increased in women with pre-eclampsia [2]
Laboratory:
- soluble fms-like tyrosine kinase-1 in serum
General
vascular endothelial growth factor [VEGF] receptor
Properties
SIZE: entity length = 1338 aa
MW = 151 kD
COMPARTMENT: cellular membrane
STATE: active state
MOTIF: signal sequence {1-26}
immunoglobulin superfamily domain {32-123}
MOTIF: cysteine residue {C53}
MODIFICATION: cysteine residue {C107}
N-glycosylation site {N100}
cysteine residue {C107}
MODIFICATION: cysteine residue {C53}
immunoglobulin superfamily domain {151-214}
MOTIF: cysteine residue {C158}
MODIFICATION: cysteine residue {C207}
N-glycosylation site {N164}
N-glycosylation site {N196}
cysteine residue {C207}
MODIFICATION: cysteine residue {C158}
immunoglobulin superfamily domain {230-327}
MOTIF: N-glycosylation site {N251}
cysteine residue {C252}
MODIFICATION: cysteine residue {C311}
cysteine residue {C311}
MODIFICATION: cysteine residue {C252}
N-glycosylation site {N323}
immunoglobulin superfamily domain {335-421}
MOTIF: N-glycosylation site {N402}
N-glycosylation site {N417}
immunoglobulin superfamily domain {428-553}
MOTIF: cysteine residue {C454}
MODIFICATION: cysteine residue {C535}
N-glycosylation site {N474}
cysteine residue {C535}
MODIFICATION: cysteine residue {C454}
N-glycosylation site {N547}
immunoglobulin superfamily domain {556-654}
MOTIF: cysteine residue {C577}
MODIFICATION: cysteine residue {C636}
N-glycosylation site {N597}
N-glycosylation site {N620}
N-glycosylation site {N625}
cysteine residue {C636}
MODIFICATION: cysteine residue {C577}
immunoglobulin superfamily domain {661-747}
MOTIF: N-glycosylation site {N666}
cysteine residue {C682}
MODIFICATION: cysteine residue {C731}
cysteine residue {C731}
MODIFICATION: cysteine residue {C682}
transmembrane domain {759-780}
kinase domain
SITE: 827-1158
MOTIF: ATP-binding site
NAME: ATP-binding site
SITE: 833-841
ATP-binding site
NAME: ATP-binding site
SITE: 861-861
aspartate residue {D1022}
Tyr phosphorylation site {Y1048}
Tyr phosphorylation site {Y1053}
Tyr phosphorylation site {Y1169}
Tyr phosphorylation site {Y1213}
Tyr phosphorylation site {Y1242}
Tyr phosphorylation site {Y1327}
Tyr phosphorylation site {Y1333}
Database Correlations
OMIM 165070
UniProt P17948
PFAM correlations
Kegg hsa:2321
ENZYME 2.7.10.1
References
- UniProt :accession P17948
- Zeisler H et al
Predictive Value of the sFlt-1:PlGF Ratio in Women with
Suspected Preeclampsia.
N Engl J Med 2016; 374:13-22. January 7, 2016
PMID: 26735990
http://www.nejm.org/doi/full/10.1056/NEJMoa1414838
- Seely EW, Solomon CG
Improving the Prediction of Preeclampsia
N Engl J Med 2016; 374:83-84. January 7, 2016
PMID: 26735997
http://www.nejm.org/doi/full/10.1056/NEJMe1515223