| Post Translational Modifications | Phosphorylated on multiple sites by protein kinase A (PKA) and phosphorylation by PKA primes further phosphorylation by CK1 and GSK3. Phosphorylated by DYRK2 (in vitro). Phosphorylation is essential for its proteolytic processing. Transcriptional repressor GLI3R, a C-terminally truncated form, is generated from the full-length GLI3 protein (GLI3FL/GLI3-190) through proteolytic processing. This process requires PKA-primed phosphorylation of GLI3, ubiquitination of GLI3 and the presence of BTRC. GLI3FL is complexed with SUFU in the cytoplasm and is maintained in a neutral state. Without the Hh signal, the SUFU-GLI3 complex is recruited to cilia, leading to the efficient processing of GLI3FL into GLI3R. GLI3R formation leads to its dissociation from SUFU, allowing it to translocate into the nucleus, and repress Hh target genes. When Hh signaling is initiated, SUFU dissociates from GLI3FL and this has two consequences. First, GLI3R production is halted. Second, free GLI3FL translocates to the nucleus, where it is phosphorylated, destabilized, and converted to a transcriptional activator (GLI3A). Phosphorylated in vitro by ULK3. |
| Function | 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'. |
| Protein Name | Transcriptional Activator Gli3Gli3 Form Of 190 KdaGli3-190Gli3 Full-Length ProteinGli3fl Cleaved Into - Transcriptional Repressor Gli3rGli3 C-Terminally Truncated FormGli3 Form Of 83 KdaGli3-83 |
| Database Links | Reactome: R-HSA-5610785Reactome: R-HSA-5610787Reactome: R-HSA-5632684Reactome: R-HSA-5635851Reactome: R-HSA-8940973 |
| Cellular Localisation | NucleusCytoplasmCell ProjectionCiliumGli3fl Is Localized Predominantly In The Cytoplasm While Gli3r Resides Mainly In The NucleusCiliary Accumulation Requires The Presence Of Kif7 And SmoTranslocation To The Nucleus Is Promoted By Interaction With Zic1 |
| Alternative Protein Names | Transcriptional Activator Gli3 proteinGli3 Form Of 190 Kda proteinGli3-190 proteinGli3 Full-Length Protein proteinGli3fl Cleaved Into - Transcriptional Repressor Gli3r proteinGli3 C-Terminally Truncated Form proteinGli3 Form Of 83 Kda proteinGli3-83 proteinGLI3 protein |
Information sourced from Uniprot.org
