IPR041348
VEGFR-2, transmembrane domain
InterPro entry
Short name | VEGFR-2_TMD |
Description
This is a transmembrane domain (TMD) of vascular endothelial growth factor receptor 2 which regulates blood vessel homeostasis. Transmembrane signalling by receptor tyrosine kinases (RTKs) requires specific orientation of the intracellular kinase domains in active receptor dimers. Two mutants in VEGFR-2 TMD showed constitutive kinase activity, suggesting that precise TMD orientation is mandatory for kinase activation. Scanning mutagenesis and structural analysis indicated that introducing two polar amino acids in distinct positions of the TMD (G770E/F777E and I771E/L778E mutations) reorients transmembrane helices and leads to stable dimer formation. Therefore, it has been suggested that the transition between the inactive and the active dimeric state of VEGFR-2 implicates alternative dimeric TMD conformations
[1].
Proteins containing this domain also include VEGFR-1 and VEGFR-3 from animals and VEGFR-4 (also known as kdrl) from zebrafish
[2].
References
1.Structural and functional characterization of alternative transmembrane domain conformations in VEGF receptor 2 activation. Manni S, Mineev KS, Usmanova D, Lyukmanova EN, Shulepko MA, Kirpichnikov MP, Winter J, Matkovic M, Deupi X, Arseniev AS, Ballmer-Hofer K. Structure 22, 1077-1089, (2014). View articlePMID: 24980797
2.Zebrafish VEGF receptors: a guideline to nomenclature. Bussmann J, Lawson N, Zon L, Schulte-Merker S; Zebrafish Nomenclature Committee. PLoS Genet. 4, e1000064, (2008). View articlePMID: 18516225
Cross References
ENZYME
Contributing Member Database Entry
- Pfam:PF17988