Biomedical Engineering Reference
In-Depth Information
Figure 10.3 Topological model, structural features, and mutant variants of the Vangl
protein family. The primary sequence and secondary structure of human VANGL1 pro-
tein as established by epitope mapping is presented. The nomenclature adopted in the
figure has been standardized to residues in hVANGL1, which is used as molecular back-
bone. Sequence motifs and individual amino acid residues defining sequence land-
marks are depicted in different colors. This includes Vangl protein variants (both
human hVANGL1 and hVANGL2 and mouse mVangl2) associated with neural tube
defects in mice and humans (orange, pink) and where loss of function has already been
demonstrated (pink) or has yet to be characterized (orange). Residues altered in
mVangl2 (D255E, R259L, S464N) are depicted in black, hVANGL1 (S83L, F153S,
R181Q, L202F, V239I, R274Q, M328T, A404S) are depicted in red, and hVANGL2
(S84F, R135W, R177H, V178I, L242V, T247M, R270H, R353C, F437S, R482H) are depicted
in blue. Also depicted is the ETSV sequence corresponding to a PDZ-binding motif
(green) and two serine phosphorylation sites for which variants have been detected
in human NTD patients (*; S83L in hVANGL1 and S84F in hVANGL2).
frequency. The double heterozygote for
Vangl2
and
Vangl1
mutations
(
Vangl2
Lp/
þ
:
Vangl1
gt/
þ
)(
Torban et al., 2008
) or homozygous for both
Vangl1
and
Vangl2
(
Song et al., 2010
) displays craniorachischisis at high
frequency. These results point at a genetic interaction between
Vangl1
and
Vangl2
and indicate that both proteins play a critical role in NT forma-
tion. Recent studies have also identified a physical interaction between
Vangl1 and Vangl2 proteins (
Yin, Copley, Goodrich, & Deans, 2012
).
