Transcription activator GLI2

Function

Transcription factor that acts as a key effector of the smoothened signaling pathway, and which plays a role in skeleton development. Specifically binds to the minimal GLI-consensus sequence 5'-GACCACCCA-3' to activate or repress the expression of target genes (By similarity). Functions both as a transcriptional activator and repressor: the full-length GLI2 form (Transcription activator GLI2) acts as a transcription activator following smoothened activation, while the Transcription repressor GLI2R, which is generated in absence of smoothened, acts as a transcription repressor (By similarity). The transcriptional activator form constitutes the major form of GLI2 (By similarity).

Classification

Family (Pfam)

PF00096 zf-C2H2, PF23561 zf-C2H2_15

InterPro

GLI-like, Znf-C2H2_ZIC1-5/GLI1-3-like, Znf_C2H2_sf, Znf_C2H2_type

Functional cluster

Homeobox & Zinc-Finger Transcription Factors

Gene Ontology · 52

• GO:0005813 centrosome
• GO:0036064 ciliary basal body
• GO:0097546 ciliary base
• GO:0097542 ciliary tip
• GO:0005929 cilium
• GO:0005829 cytosol
• GO:0005730 nucleolus
• GO:0005654 nucleoplasm
• GO:0005634 nucleus
• GO:0003700 DNA-binding transcription factor activity
• GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific
• GO:1990841 promoter-specific chromatin binding
• GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding
• GO:0043565 sequence-specific DNA binding
• GO:1990837 sequence-specific double-stranded DNA binding
• GO:0008270 zinc ion binding
• GO:0007411 axon guidance
• GO:0048754 branching morphogenesis of an epithelial tube
• GO:0098586 cellular response to virus
• GO:0021696 cerebellar cortex morphogenesis
• GO:0048589 developmental growth
• GO:0006351 DNA-templated transcription
• GO:0048566 embryonic digestive tract development
• GO:0009913 epidermal cell differentiation
• GO:0021508 floor plate formation
• GO:0031069 hair follicle morphogenesis
• GO:0007507 heart development
• GO:0030902 hindbrain development
• GO:0007442 hindgut morphogenesis
• GO:0001822 kidney development
• GO:0030324 lung development
• GO:0030879 mammary gland development
• GO:0000122 negative regulation of transcription by RNA polymerase II
• GO:0048666 neuron development
• GO:0042475 odontogenesis of dentin-containing tooth
• GO:0002076 osteoblast development
• GO:0001649 osteoblast differentiation
• GO:0007389 pattern specification process
• GO:0021983 pituitary gland development
• GO:0045740 positive regulation of DNA replication
• GO:0045893 positive regulation of DNA-templated transcription
• GO:0033089 positive regulation of T cell differentiation in thymus
• GO:0045944 positive regulation of transcription by RNA polymerase II
• GO:0009954 proximal/distal pattern formation
• GO:0006357 regulation of transcription by RNA polymerase II
• GO:0001501 skeletal system development
• GO:0007224 smoothened signaling pathway
• GO:0021513 spinal cord dorsal/ventral patterning
• GO:0021965 spinal cord ventral commissure morphogenesis
• GO:0035295 tube development
• GO:0007418 ventral midline development
• GO:0021517 ventral spinal cord development

Disease associations

• holoprosencephaly 9 MONDO:0012563
• postaxial polydactyly-anterior pituitary anomalies-facial dysmorphism syndrome MONDO:0014369

Neighborhood · nearest proteins

Related proteins · sequence + function similarity

• Transcription activator GLI2 0.98
• Zinc finger protein ZIC 5 0.89
• Transcription activator GLI2.S 0.88
• Transcription factor 7-like 1 0.88
• Transcription factor 7-like 1 0.87
• Transcription activator GLI1 0.87
• Zinc finger protein ZIC 5 0.86
• B-cell lymphoma/leukemia 11B 0.86
• Segmentation polarity homeobox protein engrailed 0.85
• Zinc finger protein ZIC 2-B 0.85
• Endothelial transcription factor GATA-2 0.85
• Zinc finger protein ZIC 2-A 0.85

Co-cited proteins · studied together in the literature

• Transcription activator GLI3 6 shared papers
• Transcription activator GLI1 4 shared papers
• Serine/threonine-protein kinase ULK3 2 shared papers
• Suppressor of fused homolog 3 shared papers
• Protein patched homolog 1 1 shared papers
• Dual specificity tyrosine-phosphorylation-regulated kinase 2 2 shared papers
• Zinc finger protein GLI4 1 shared papers
• Zinc finger protein 875 1 shared papers
• Zinc finger and SCAN domain-containing protein 22 1 shared papers
• Transcription activator GLI2 2 shared papers
• Forkhead box protein C1 1 shared papers
• Serine/threonine-protein kinase 36 1 shared papers

Literature · 23 cited papers

• Positive regulation of Hedgehog signaling via phosphorylation of GLI2/GLI3 by DYRK2 kinase. Proc. Natl. Acad. Sci. U.S.A. · 2024
• GLI1 inactivation is associated with developmental phenotypes overlapping with Ellis-van Creveld syndrome. Hum. Mol. Genet. · 2017
• Site-specific mapping of the human SUMO proteome reveals co-modification with phosphorylation. Nat. Struct. Mol. Biol. · 2017
• Analysis of protein-coding genetic variation in 60,706 humans. Nature · 2016
• FOXC1 activates smoothened-independent Hedgehog signaling in basal-like breast cancer. Cell Rep. · 2015
• Structural basis of SUFU-GLI interaction in human Hedgehog signalling regulation. Acta Crystallogr. D · 2013
• Gli2 acetylation at lysine 757 regulates hedgehog-dependent transcriptional output by preventing its promoter occupancy. PLoS ONE · 2013
• Functional characterization of a heterozygous GLI2 missense mutation in patients with multiple pituitary hormone deficiency. J. Clin. Endocrinol. Metab. · 2013
• Novel heterozygous nonsense GLI2 mutations in patients with hypopituitarism and ectopic posterior pituitary lobe without holoprosencephaly. J. Clin. Endocrinol. Metab. · 2010
• Dual function of UNC-51-like kinase 3 (Ulk3) in the Sonic hedgehog signaling pathway. J. Biol. Chem. · 2010
• Kinetics of hedgehog-dependent full-length Gli3 accumulation in primary cilia and subsequent degradation. Mol. Cell. Biol. · 2010
• Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis. Sci. Signal. · 2010
• … and 11 more in the literature graph