GLI1

This gene encodes a member of the Kruppel family of zinc finger proteins. The encoded transcription factor is activated by the sonic hedgehog signal transduction cascade and regulates stem cell proliferation. The activity and nuclear localization of this protein is negatively regulated by p53 in an inhibitory loop. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2009]

GLI1

Acts as a transcriptional activator (PubMed:19706761, PubMed:10806483, PubMed:19878745, PubMed:24076122, PubMed:24311597, PubMed:24217340).

Binds to the DNA consensus sequence 5'-GACCACCCA-3' (PubMed:2105456, PubMed:8378770, PubMed:24217340).

Regulates the transcription of specific genes during normal development (PubMed:19706761).

Plays a role in craniofacial development and digital development, as well as development of the central nervous system and gastrointestinal tract. Mediates SHH signaling (PubMed:19706761, PubMed:28973407).

Plays a role in cell proliferation and differentiation via its role in SHH signaling (PubMed:11238441, PubMed:28973407).

Isoform 2:
Acts as a transcriptional activator, but activates a different set of genes than isoform 1. Activates expression of CD24, unlike isoform 1. Mediates SHH signaling. Promotes cancer cell migration.

Canonical Wnt signaling pathway Source: Ensembl
Cerebellar cortex morphogenesis Source: Ensembl
Digestive tract morphogenesis Source: BHF-UCL
Dorsal/ventral pattern formation Source: Ensembl
Epidermal cell differentiation Source: UniProtKB
Liver regeneration Source: Ensembl
Lung development Source: Ensembl
Negative regulation of canonical Wnt signaling pathway Source: UniProtKB
Notochord regression Source: Ensembl
Osteoblast differentiation Source: UniProtKB
Pituitary gland development Source: Ensembl
Positive regulation of cardiac muscle cell proliferation Source: BHF-UCL
Positive regulation of cell cycle G1/S phase transition Source: BHF-UCL
Positive regulation of cell migration Source: UniProtKB
Positive regulation of cell population proliferation Source: UniProtKB
Positive regulation of DNA replication Source: UniProtKB
Positive regulation of smoothened signaling pathway Source: UniProtKB
Positive regulation of transcription, DNA-templated Source: UniProtKB
Positive regulation of transcription by RNA polymerase II Source: UniProtKB
Prostate gland development Source: Ensembl
Proximal/distal pattern formation Source: Ensembl
Regulation of hepatocyte proliferation Source: Ensembl
Regulation of osteoblast differentiation Source: Ensembl
Regulation of smoothened signaling pathway Source: UniProtKB
Regulation of transcription by RNA polymerase II Source: GO_Central
Response to wounding Source: Ensembl
Smoothened signaling pathway Source: UniProtKB
Smoothened signaling pathway involved in regulation of cerebellar granule cell precursor cell proliferation Source: Ensembl
Spermatogenesis Source: Ensembl
Ventral midline development Source: Ensembl

Nucleus; Cytoplasm. Tethered in the cytoplasm by binding to SUFU (PubMed:10806483). Activation and translocation to the nucleus is promoted by interaction with STK36 (PubMed:10806483). Phosphorylation by ULK3 may promote nuclear localization (PubMed:19878745). Translocation to the nucleus is promoted by interaction with ZIC1 (PubMed:11238441).
Isoform 2: Nucleus; Cytoplasm

Polydactyly, postaxial, A8 (PAPA8):
A form of postaxial polydactyly, a condition characterized by the occurrence of supernumerary digits in the upper and/or lower extremities. In postaxial polydactyly type A, the extra digit is well-formed and articulates with the fifth or a sixth metacarpal/metatarsal. PAPA8 is an autosomal recessive condition characterized by the presence of postaxial extra digits (hexadactyly) on the hands and/or the feet.
Polydactyly, preaxial 1 (PPD1):
A form of polydactyly, a condition defined by the occurrence of supernumerary digits in the upper and/or lower extremities. Preaxial or radial polydactyly refers to the presence of extra digits on the radial side of the hand. PPD1 is an autosomal recessive form characterized by duplication of the distal phalanx of the thumb.

Phosphorylated in vitro by ULK3.
Acetylation at Lys-518 down-regulates transcriptional activity. Deacetylated by HDAC1.
Ubiquitinated by the CRL2(FEM1B) complex, suppressing GLI1 transcriptional activator activity.