Transcription activator GLI3

Function

Transcription factor that acts as a key effector of the smoothened signaling pathway, and which plays a role in the development and patterning of various body structures, including the brain and limbs. Specifically binds to the minimal GLI-consensus sequence 5'-GACCACCCA-3' to activate or repress the expression of target genes. Functions both as a transcriptional activator and repressor: the full-length GLI3 form (Transcription activator GLI3) acts as a transcription activator following smoothened activation, while the Transcription repressor GLI3R, which is generated in absence of smoothened, acts as a transcription repressor. The repressor form (GLI3R) constitutes the major form of GLI3.

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

RNA-Polymerase II Transcription Factors

Experimental structures · PDB · 1

• 4BLD X-ray 2.80A

A predicted model is available from AlphaFold.

Gene Ontology · 40

• GO:0005930 axoneme
• GO:0097546 ciliary base
• GO:0097542 ciliary tip
• GO:0005929 cilium
• GO:0005737 cytoplasm
• GO:0005829 cytosol
• GO:0016607 nuclear speck
• GO:0005654 nucleoplasm
• GO:0005634 nucleus
• GO:0017053 transcription repressor complex
• GO:0008013 beta-catenin binding
• GO:0003682 chromatin binding
• GO:0003700 DNA-binding transcription factor activity
• GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific
• GO:0035035 histone acetyltransferase binding
• GO:0042826 histone deacetylase binding
• GO:0036033 mediator complex binding
• GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding
• GO:0000977 RNA polymerase II transcription regulatory region sequence-specific DNA binding
• GO:1990837 sequence-specific double-stranded DNA binding
• GO:0008270 zinc ion binding
• GO:0006351 DNA-templated transcription
• GO:0048566 embryonic digestive tract development
• GO:0042733 embryonic digit morphogenesis
• GO:0035108 limb morphogenesis
• GO:0046639 negative regulation of alpha-beta T cell differentiation
• GO:0090090 negative regulation of canonical Wnt signaling pathway
• GO:0045892 negative regulation of DNA-templated transcription
• GO:0045879 negative regulation of smoothened signaling pathway
• GO:0000122 negative regulation of transcription by RNA polymerase II
• GO:0045060 negative thymic T cell selection
• GO:0043585 nose morphogenesis
• GO:0046638 positive regulation of alpha-beta T cell differentiation
• GO:0045893 positive regulation of DNA-templated transcription
• GO:0045944 positive regulation of transcription by RNA polymerase II
• GO:0006355 regulation of DNA-templated transcription
• GO:0006357 regulation of transcription by RNA polymerase II
• GO:0007224 smoothened signaling pathway
• GO:0033077 T cell differentiation in thymus
• GO:0070242 thymocyte apoptotic process

Disease associations

• Pallister-Hall syndrome MONDO:0007804
• polydactyly, postaxial, type A1 MONDO:0008266
• polysyndactyly 4 MONDO:0008272
• Greig cephalopolysyndactyly syndrome MONDO:0008287

Neighborhood · nearest proteins

Related proteins · sequence + function similarity

• Transcription activator GLI3 0.99
• Transcription activator GLI3 0.98
• Transcription activator GLI3 0.96
• Transcription activator GLI2.L 0.93
• Transcription activator GLI2.S 0.90
• Zinc finger protein GLI4 0.89
• DNA-binding protein creA 0.88
• Probable DNA-binding protein creA 0.88
• DNA-binding protein creA 0.88
• Probable DNA-binding protein creA 0.87
• DNA-binding protein creA 0.87
• DNA-binding protein creA 0.87

Co-cited proteins · studied together in the literature

• Transcription activator GLI1 6 shared papers
• Transcription activator GLI2 6 shared papers
• Transcription activator GLI1.S 1 shared papers
• Transcription activator GLI2.S 1 shared papers
• Transcription activator GLI3 1 shared papers
• Zinc finger protein ZIC 3 1 shared papers
• Transcription activator GLI3 5 shared papers
• Histone-lysine N-methyltransferase SETD7 1 shared papers
• Transcription activator GLI2 2 shared papers
• Dual specificity tyrosine-phosphorylation-regulated kinase 2 2 shared papers
• Zinc finger transcription factor Trps1 1 shared papers
• Suppressor of fused homolog 2 shared papers

Literature · 35 cited papers

• Positive regulation of Hedgehog signaling via phosphorylation of GLI2/GLI3 by DYRK2 kinase. Proc. Natl. Acad. Sci. U.S.A. · 2024
• WDR11-mediated Hedgehog signalling defects underlie a new ciliopathy related to Kallmann syndrome. EMBO Rep. · 2018
• Hypomorphic Recessive Variants in SUFU Impair the Sonic Hedgehog Pathway and Cause Joubert Syndrome with Cranio-facial and Skeletal Defects. Am. J. Hum. Genet. · 2017
• Site-specific mapping of the human SUMO proteome reveals co-modification with phosphorylation. Nat. Struct. Mol. Biol. · 2017
• Set7 mediated Gli3 methylation plays a positive role in the activation of Sonic Hedgehog pathway in mammals. Elife · 2016
• Structural basis of SUFU-GLI interaction in human Hedgehog signalling regulation. Acta Crystallogr. D · 2013
• Centrosomal protein DZIP1 regulates Hedgehog signaling by promoting cytoplasmic retention of transcription factor GLI3 and affecting ciliogenesis. J. Biol. Chem. · 2013
• Toward a comprehensive characterization of a human cancer cell phosphoproteome. J. Proteome Res. · 2013
• A three-part signal governs differential processing of Gli1 and Gli3 proteins by the proteasome. J. Biol. Chem. · 2011
• System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation. Sci. Signal. · 2011
• Kinetics of hedgehog-dependent full-length Gli3 accumulation in primary cilia and subsequent degradation. Mol. Cell. Biol. · 2010
• Identification of a novel serine/threonine kinase ULK3 as a positive regulator of Hedgehog pathway. Exp. Cell Res. · 2010
• … and 23 more in the literature graph