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vascular endothelial growth factor receptor 2; VEGFR-2; kinase insert domain receptor; protein-tyrosine kinase receptor Flk-1; CD309 (KDR, FLK1)
Function:
- receptor for VEGF or VEGFC
- has a tyrosine-protein kinase activity
- the VEGF-kinase ligand/receptor signaling system plays a role in vascular development & regulation of vascular permeability
- interacts with SHB upon VEGF activation
- Flk1 & Flt1 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: membrane
Expression:
- expressed in developing blood islands of primitive streak stage embryos
- expressed in posterior splanchnopleure & fetal liver hematopoietic precursors
Pathology:
- interacts with HIV-1 Tat
- in case of HIV-1 infection, the interaction with extracellular viral Tat protein seems to enhance angiogenesis in Kaposi's sarcoma lesions
Pharmacology:
- ramucirumab used for treatment of advanced gastric cancer,
- gastroesophageal junction adenocarcinoma & metastatic colorectal cancer inhibits VEGFR2 via its ligand-binding site
General
cluster-of-differentiation antigen; cluster designation antigen; CD antigen
vascular endothelial growth factor [VEGF] receptor
Properties
SIZE: entity length = 1356 aa
MW = 152 kD
COMPARTMENT: cellular membrane
STATE: active state
MOTIF: signal sequence {1-19}
immunoglobulin superfamily domain {46-110}
MOTIF: N-glycosylation site {N46}
N-glycosylation site {N66}
N-glycosylation site {N96}
immunoglobulin superfamily domain {141-207}
MOTIF: N-glycosylation site {N143}
N-glycosylation site {N158}
immunoglobulin superfamily domain {224-320}
MOTIF: N-glycosylation site {N245}
N-glycosylation site {N318}
immunoglobulin superfamily domain {328-414}
MOTIF: N-glycosylation site {N374}
N-glycosylation site {N395}
immunoglobulin superfamily domain {421-548}
MOTIF: N-glycosylation site {N511}
N-glycosylation site {N523}
immunoglobulin superfamily domain {551-660}
MOTIF: N-glycosylation site {N580}
N-glycosylation site {N613}
N-glycosylation site {N619}
N-glycosylation site {N631}
immunoglobulin superfamily domain {667-753}
MOTIF: N-glycosylation site {N675}
N-glycosylation site {N704}
N-glycosylation site {N721}
transmembrane domain {765-789}
kinase domain
SITE: 834-1162
MOTIF: ATP-binding site
NAME: ATP-binding site
SITE: 840-848
ATP-binding site
NAME: ATP-binding site
SITE: 868-868
aspartate residue {D1028}
Tyr phosphorylation site {Y1054}
Tyr phosphorylation site {Y1059}
tyrosine residue {1175}
Database Correlations
OMIM 191306
MORBIDMAP 191306
UniProt P35968
PFAM correlations
Kegg hsa:3791
ENZYME 2.7.10.1
References
- UniProt :accession P35968
- Shalaby F et al
A requirement for Flk1 in primitive and definitive hematopoiesis
and vasculogenesis.
Cell 89:981-990, 1997
PMID: 9200616