4bld

Structural highlights

Disease

[GLI3_HUMAN] Postaxial polydactyly type B, unilateral;Postaxial polydactyly type A, unilateral;Pallister-Hall syndrome;Postaxial polydactyly type A, bilateral;Polysyndactyly, bilateral;Polysyndactyly, unilateral;Greig cephalopolysyndactyly syndrome;Acrocallosal syndrome;Postaxial polydactyly type B, bilateral. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry.

Function

[MALE_ECOLI] Involved in the high-affinity maltose membrane transport system MalEFGK. Initial receptor for the active transport of and chemotaxis toward maltooligosaccharides. [GLI3_HUMAN] Has a dual function as a transcriptional activator and a repressor of the sonic hedgehog (Shh) pathway, and plays a role in limb development. The full-length GLI3 form (GLI3FL) after phosphorylation and nuclear translocation, acts as an activator (GLI3A) while GLI3R, its C-terminally truncated form, acts as a repressor. A proper balance between the GLI3 activator and the repressor GLI3R, rather than the repressor gradient itself or the activator/repressor ratio gradient, specifies limb digit number and identity. In concert with TRPS1, plays a role in regulating the size of the zone of distal chondrocytes, in restricting the zone of PTHLH expression in distal cells and in activating chondrocyte proliferation. Binds to the minimal GLI-consensus sequence 5'-GGGTGGTC-3'.^{[1] [2] [3]}

References

1. ↑ Wang B, Fallon JF, Beachy PA. Hedgehog-regulated processing of Gli3 produces an anterior/posterior repressor gradient in the developing vertebrate limb. Cell. 2000 Feb 18;100(4):423-34. PMID:10693759
2. ↑ Koyabu Y, Nakata K, Mizugishi K, Aruga J, Mikoshiba K. Physical and functional interactions between Zic and Gli proteins. J Biol Chem. 2001 Mar 9;276(10):6889-92. Epub 2001 Jan 12. PMID:11238441 doi:http://dx.doi.org/10.1074/jbc.C000773200
3. ↑ Zhu L, Zhou G, Poole S, Belmont JW. Characterization of the interactions of human ZIC3 mutants with GLI3. Hum Mutat. 2008 Jan;29(1):99-105. PMID:17764085 doi:10.1002/humu.20606
4. ↑ Cherry AL, Finta C, Karlstrom M, Jin Q, Schwend T, Astorga-Wells J, Zubarev RA, Del Campo M, Criswell AR, de Sanctis D, Jovine L, Toftgard R. Structural basis of SUFU-GLI interaction in human Hedgehog signalling regulation. Acta Crystallogr D Biol Crystallogr. 2013 Dec;69(Pt 12):2563-79. doi:, 10.1107/S0907444913028473. Epub 2013 Nov 19. PMID:24311597 doi:http://dx.doi.org/10.1107/S0907444913028473