GLI2

This gene encodes a protein which belongs to the C2H2-type zinc finger protein subclass of the Gli family. Members of this subclass are characterized as transcription factors which bind DNA through zinc finger motifs. These motifs contain conserved H-C links. Gli family zinc finger proteins are mediators of Sonic hedgehog (Shh) signaling and they are implicated as potent oncogenes in the embryonal carcinoma cell. The protein encoded by this gene localizes to the cytoplasm and activates patched Drosophila homolog (PTCH) gene expression. It is also thought to play a role during embryogenesis. The encoded protein is associated with several phenotypes- Greig cephalopolysyndactyly syndrome, Pallister-Hall syndrome, preaxial polydactyly type IV, postaxial polydactyly types A1 and B.

Gli Family Zinc Finger 2

Functions as transcription regulator in the hedgehog (Hh) pathway (PubMed:18455992, PubMed:26565916).

Functions as transcriptional activator (PubMed:9557682, PubMed:19878745, PubMed:24311597).

May also function as transcriptional repressor (By similarity).

Requires STK36 for full transcriptional activator activity. Required for normal embryonic development (PubMed:15994174, PubMed:20685856).

Isoform 1&2&3&4:
Involved in the smoothened (SHH) signaling pathway.

Isoform 1&2&3&4:
Acts as a transcriptional activator in T-cell leukemia virus type 1 (HTLV-1)-infected cells in a Tax-dependent manner. Binds to the DNA sequence 5'-GAACCACCCA-3' which is part of the Tax-responsive element (TRE-2S) regulatory element that augments the Tax-dependent enhancer of HTLV-1 (PubMed:9557682).

Isoform 5:
Acts as a transcriptional repressor.

Anterior/posterior pattern specification Source: Ensembl
Axon guidance Source: UniProtKB
Branching morphogenesis of an epithelial tube Source: UniProtKB
Cellular response to organic cyclic compound Source: Ensembl
Cellular response to virus Source: UniProtKB
Cerebellar cortex morphogenesis Source: UniProtKB
Chondrocyte differentiation Source: Ensembl
Cochlea morphogenesis Source: Ensembl
Developmental growth Source: UniProtKB
Embryonic digestive tract development Source: UniProtKB
Embryonic digit morphogenesis Source: Ensembl
Epidermal cell differentiation Source: UniProtKB
Floor plate formation Source: UniProtKB
Hair follicle morphogenesis Source: UniProtKB
Heart development Source: UniProtKB
Hindbrain development Source: UniProtKB
Hindgut morphogenesis Source: UniProtKB
In utero embryonic development Source: Ensembl
Kidney development Source: UniProtKB
Lung development Source: UniProtKB
Mammary gland development Source: UniProtKB
Mammary gland duct morphogenesis Source: Ensembl
Negative regulation of apoptotic process Source: Ensembl
Negative regulation of chondrocyte differentiation Source: Ensembl
Negative regulation of smoothened signaling pathway Source: Ensembl
Negative regulation of transcription by RNA polymerase II Source: UniProtKB
Neuron development Source: UniProtKB
Notochord regression Source: Ensembl
Odontogenesis of dentin-containing tooth Source: UniProtKB
Osteoblast development Source: UniProtKB
Osteoblast differentiation Source: UniProtKB
Pattern specification process Source: UniProtKB
Pituitary gland development Source: UniProtKB
Positive regulation of DNA replication Source: UniProtKB
Positive regulation of neuron differentiation Source: Ensembl
Positive regulation of T cell differentiation in thymus Source: BHF-UCL
Positive regulation of transcription, DNA-templated Source: UniProtKB
Positive regulation of transcription by RNA polymerase II Source: UniProtKB
Prostatic bud formation Source: Ensembl
Proximal/distal pattern formation Source: UniProtKB
Regulation of smoothened signaling pathway involved in dorsal/ventral neural tube patterning Source: Ensembl
Regulation of transcription by RNA polymerase II Source: GO_Central
Skeletal system development Source: UniProtKB
Smoothened signaling pathway Source: UniProtKB
Smoothened signaling pathway involved in dorsal/ventral neural tube patterning Source: Ensembl
Smoothened signaling pathway involved in regulation of cerebellar granule cell precursor cell proliferation Source: Ensembl
Smoothened signaling pathway involved in spinal cord motor neuron cell fate specification Source: Ensembl
Smoothened signaling pathway involved in ventral spinal cord interneuron specification Source: UniProtKB
Spinal cord dorsal/ventral patterning Source: UniProtKB
Spinal cord ventral commissure morphogenesis Source: UniProtKB
Tube development Source: UniProtKB
Ventral midline development Source: UniProtKB
Ventral spinal cord development Source: UniProtKB

Nucleus; Cytoplasm; Cilium. STK36 promotes translocation to the nucleus. In keratinocytes, it is sequestered in the cytoplasm by SUFU. In the absence of SUFU, it translocates to the nucleus.
Isoform 1&2: Nucleus

Holoprosencephaly 9 (HPE9):
A structural anomaly of the brain, in which the developing forebrain fails to correctly separate into right and left hemispheres. Holoprosencephaly is genetically heterogeneous and associated with several distinct facies and phenotypic variability. Holoprosencephaly type 9 is characterized by defective anterior pituitary formation and pan-hypopituitarism, with or without overt forebrain cleavage abnormalities, and holoprosencephaly-like midfacial hypoplasia.
Culler-Jones syndrome (CJS):
An autosomal dominant disorder characterized by a wide range of clinical manifestations. Clinical features include hypothalamic hamartoma, pituitary dysfunction, central or postaxial polydactyly, and syndactyly. Malformations are frequent in the viscera, e.g. anal atresia, bifid uvula, congenital heart malformations, pulmonary or renal dysplasia.

Phosphorylated in vitro by ULK3. Phosphorylated by DYRK2; this inhibits GLI2 transcription factor activity and promotes proteasomal degradation of GLI2.
Acetylation at Lys-757 inhibits Hh target gene expression, probably by impeding entry into chromatin thus preventing promoter occupancy.