GLI2
Domain
The N-terminal domain confers transcriptional repressor activity, while the C-terminal domain mediates transcriptional activation.
Function
Functions as a transcription regulator in the hedgehog (Hh) pathway (PubMed:18455992, PubMed:26565916). Functions as a transcriptional activator (PubMed:19878745, PubMed:24311597, PubMed:9557682). 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
Involved in the smoothened (SHH) signaling pathway.
Isoform 2
Involved in the smoothened (SHH) signaling pathway.
Isoform 3
Involved in the smoothened (SHH) signaling pathway.
Isoform 4
Involved in the smoothened (SHH) signaling pathway.
Isoform 1
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 2
(Microbial infection) Acts as a transcriptional activators 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 3
(Microbial infection) Acts as a transcriptional activators 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 4
(Microbial infection) Acts as a transcriptional activators 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.
Involvement in disease
Holoprosencephaly 9
HPE9
A form of holoprosencephaly, a structural anomaly of the brain in which the developing forebrain fails to correctly separate into right and left hemispheres. It is a genetically and clinically heterogeneous disorder with a wide spectrum of severity, ranging from alobar holoprosencephaly with severe facial abnormalities, such as cyclopia and proboscis, to mild forms that include lobar or microform holoprosencephaly, without cerebral malformations and with mild craniofacial defects. HPE9 is characterized by defective anterior pituitary formation and pan-hypopituitarism, with or without overt forebrain cleavage abnormalities, and holoprosencephaly-like midfacial hypoplasia. HPE9 inheritance is autosomal dominant.
None
The disease is caused by variants affecting the gene represented in this entry.
Culler-Jones syndrome
CJS
An autosomal dominant disorder with incomplete penetrance and variable expressivity, characterized by pituitary abnormalities including ectopic or non-visible posterior pituitary lobe, growth hormone deficiency, combined pituitary hormone deficiency, and, in some patients, additional features such as postaxial polydactyly, midline facial defects, and developmental delay.
None
The disease is caused by variants affecting the gene represented in this entry.
Post-translational modifications
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.
Sequence Similarities
Belongs to the GLI C2H2-type zinc-finger protein family.
Tissue Specificity
Expressed in breast cancers (at protein level) (PubMed:26565916). Isoform 1 and isoform 4 are expressed in HTLV-1-infected T-cell lines (at protein level) (PubMed:9557682). Isoform 1 and isoform 2 are strongly expressed in HTLV-1-infected T-cell lines (PubMed:9557682). Isoform 3 and isoform 4 are weakly expressed in HTLV-1-infected T-cell lines (PubMed:9557682).
Cellular localization
- Nucleus
- Cytoplasm
- Cell projection
- Cilium
- STK36 promotes translocation to the nucleus (PubMed:10806483). In keratinocytes, it is sequestered in the cytoplasm by SUFU. In the absence of SUFU, it translocates to the nucleus (By similarity). TMEM216 promotes its nuclear localization (By similarity).
- Isoform 1
- Nucleus
- Isoform 2
- Nucleus
Alternative names
THP, GLI2, Zinc finger protein GLI2, GLI family zinc finger protein 2, Tax helper protein