NeuropilingeneorganizationandproteinstructureTheNRP1.ppt

Neuropilin gene organization and protein structure The NRP1 gene comprises 17 exons black rectangles , encoding a full-length protein of 923 amino acids aa consisting of an extracellular region with two tandem CUB a1 and a2 domains pink rectangles , t... Caroline Pellet-Many et al. Biochem. J. 2008;411:211-226 ?2008 by Portland Press Ltd Neuropilin gene organization and protein structure The NRP1 gene comprises 17 exons black rectangles , encoding a full-length protein of 923 amino acids aa consisting of an extracellular region with two tandem CUB a1 and a2 domains pink rectangles , two tandem Factor V/VIII homology b1 and b2 domains green ellipses , a linker region and one MAM c domain yellow rectangle ; a single transmembrane domain TM ; and a 44-amino-acid cytoplasmic Cyt domain containing a C-terminal PDZ-binding domain motif blue oval , with the sequence, SEA. Locations of binding sites for semaphorins and VEGF, and the putative oligomerization domain are indicated. Red arrowheads indicate: the positions of Ser612 in NRP1, the major site of O-linked CS-GAG modification; insertion at residue 808 in NRP2 of five amino acids GEDFL; and addition of nine amino acids VGCSWRLPL following truncation of the b2 domain at residue 548 in soluble NRP2 sNRP2 . Soluble NRP1 sNRP1 is truncated at the linker region between the second Factor V/VIII and the MAM domain and ends with the three amino acids GIK. Note that not all sNRP1 isoforms contain Ser612, and are not all modifiable by CS-GAG addition. The percentage amino acid homologies between the domains of full length NRP1 and NRP2a isoforms a1/a2, b1/b2, MAM, and intracellular domains respectively; left to right and between the NRP2a and NRP2b isoforms extracellular region and transmembrane domain plus intracellular domain respectively are indicated.