Transcription activator GLI1

Function

Transcription activator that acts as a key effector of the smoothened signaling pathway, and which plays a role in craniofacial development and digital development, as well as development of the central nervous system and gastrointestinal tract. Binds to the DNA consensus sequence 5'-GACCACCCA-3'. Activated in response to smoothened signaling: in presence of hedgehog (DHH, IHH or SHH) and subsequent activation of smoothened, GLI1 translocates to the nucleus and promotes expression of target genes. In contrast to GLI2 and GLI3, does not contain a repressor domain and only acts as a transcription activator.

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

Experimental structures · PDB · 5

• 2GLI X-ray 2.60A
• 4BLB X-ray 2.80A
• 4KMD X-ray 1.70A
• 5OM0 X-ray 3.20A
• 7T91 X-ray 2.05A

A predicted model is available from AlphaFold.

Gene Ontology · 39

• GO:0005930 axoneme
• GO:0036064 ciliary basal body
• GO:0097546 ciliary base
• GO:0097542 ciliary tip
• GO:0005737 cytoplasm
• GO:0005829 cytosol
• GO:0005654 nucleoplasm
• GO:0005634 nucleus
• GO:0003682 chromatin binding
• GO:0003677 DNA binding
• GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific
• GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific
• GO:0008017 microtubule 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:0043565 sequence-specific DNA binding
• GO:0000976 transcription cis-regulatory region binding
• GO:0008270 zinc ion binding
• GO:0048546 digestive tract morphogenesis
• GO:0006351 DNA-templated transcription
• GO:0009913 epidermal cell differentiation
• GO:0097421 liver regeneration
• GO:0090090 negative regulation of canonical Wnt signaling pathway
• GO:0001649 osteoblast differentiation
• GO:0060045 positive regulation of cardiac muscle cell proliferation
• GO:1902808 positive regulation of cell cycle G1/S phase transition
• GO:0030335 positive regulation of cell migration
• GO:0008284 positive regulation of cell population proliferation
• GO:0045740 positive regulation of DNA replication
• GO:0045893 positive regulation of DNA-templated transcription
• GO:0045880 positive regulation of smoothened signaling pathway
• GO:0045944 positive regulation of transcription by RNA polymerase II
• GO:0030850 prostate gland development
• GO:0006355 regulation of DNA-templated transcription
• GO:0045667 regulation of osteoblast differentiation
• GO:0008589 regulation of smoothened signaling pathway
• GO:0006357 regulation of transcription by RNA polymerase II
• GO:0007224 smoothened signaling pathway
• GO:0007286 spermatid development

Disease associations

• polydactyly of a biphalangeal thumb MONDO:0008269
• polydactyly, postaxial, type A8 MONDO:0029130

Neighborhood · nearest proteins

Related proteins · sequence + function similarity

• Transcription activator GLI1 0.98
• Zinc finger protein GLIS1 0.89
• Zinc finger protein GLIS1 0.89
• Zinc finger protein GLIS3 0.89
• Krueppel-like factor 4 0.88
• E3 SUMO-protein ligase EGR2 0.85
• Transcription factor SOX-7 0.85
• E3 SUMO-protein ligase EGR2 0.85
• Krueppel-like factor 4 0.84
• Transcription factor SOX-7 0.84
• Homeobox protein Hox-B1 0.82
• Wilms tumor protein homolog 0.82

Co-cited proteins · studied together in the literature

• Suppressor of fused homolog 6 shared papers
• Transcription activator GLI3 6 shared papers
• Transcription activator GLI2 4 shared papers
• Protein fem-1 homolog B 1 shared papers
• BTB/POZ domain-containing protein KCTD11 1 shared papers
• Serine/threonine-protein kinase ULK3 1 shared papers
• Cadherin-related family member 1 1 shared papers
• Serine/threonine-protein kinase 36 1 shared papers
• Serine/threonine-protein kinase 36 1 shared papers
• Transcription activator GLI2 2 shared papers
• Zinc finger protein ZIC 1 1 shared papers
• Zinc finger protein ZIC 3 1 shared papers

Literature · 23 cited papers

• ERK2 MAP kinase regulates SUFU binding by multisite phosphorylation of GLI1. Life. Sci Alliance · 2022
• A novel homozygous sequence variant in GLI1 underlies first case of autosomal recessive pre-axial polydactyly. Clin. Genet. · 2019
• GLI1 inactivation is associated with developmental phenotypes overlapping with Ellis-van Creveld syndrome. Hum. Mol. Genet. · 2017
• 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
• Structural basis of SUFU-GLI interaction in human Hedgehog signalling regulation. Acta Crystallogr. D · 2013
• Structural insight into the mutual recognition and regulation between Suppressor of Fused and Gli/Ci. Nat. Commun. · 2013
• Fem1b promotes ubiquitylation and suppresses transcriptional activity of Gli1. Biochem. Biophys. Res. Commun. · 2013
• A three-part signal governs differential processing of Gli1 and Gli3 proteins by the proteasome. J. Biol. Chem. · 2011
• Histone deacetylase and Cullin3-REN(KCTD11) ubiquitin ligase interplay regulates Hedgehog signalling through Gli acetylation. Nat. Cell Biol. · 2010
• Identification of a novel serine/threonine kinase ULK3 as a positive regulator of Hedgehog pathway. Exp. Cell Res. · 2010
• A novel splice variant of GLI1 that promotes glioblastoma cell migration and invasion. Cancer Res. · 2009
• … and 11 more in the literature graph