GLI2 GLI family zinc finger 2 [Homo sapiens] - Gene

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Summary

Official Symbol: GLI2provided by HGNC
Official Full Name: GLI family zinc finger 2provided by HGNC
Primary source: HGNC:4318
See related: Ensembl:ENSG00000074047; HPRD:01312; MIM:165230; Vega:OTTHUMG00000153741
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: HPE9; THP1; THP2
Summary: 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. [provided by RefSeq, Jul 2008]

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Genomic context

Location :: 2q14

Sequence :: Chromosome: 2; NC_000002.11 (121554867..121750229)

See GLI2 in Epigenomics, MapViewer

Chromosome 2 - NC_000002.11 Genomic Context describing neighboring genes

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Genomic regions, transcripts, and products

Genomic Sequence

Go to nucleotideGraphics FASTA GenBank

Go to reference sequence details

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Bibliography

GeneRIFs: Gene References Into Functions What's a GeneRIF?

Novel sequence variants were found in the GLI2 gene in patients with marked involvement of the temporomandibular joint, a new clinical finding observed with mutations of this gene.
Title: Clinical findings in patients with GLI2 mutations--phenotypic variability.
data suggest that Gli2 plays a predominant role in the proliferation and apoptosis resistance of HCC cells, and that knockdown of Gli2 may be a novel anticancer strategy for the treatment of HCC
Title: shRNA-mediated silencing of Gli2 gene inhibits proliferation and sensitizes human hepatocellular carcinoma cells towards TRAIL-induced apoptosis.
This short review summarizes recent knowledge about GLI2 function and mechanisms of action downstream of TGF-beta in cancer.[Review]
Title: TGF-β/SMAD/GLI2 signaling axis in cancer progression and metastasis.
CCL5 signaling induces GLI2 through a PI3K-AKT-IkappaBalpha-p65 pathway and requires GLI2 transcriptional activity to modulate IL-6 expression and Ig secretion in vitro and in vivo
Title: GLI2 transcription factor mediates cytokine cross-talk in the tumor microenvironment.
our findings support a possible contribution of GLI2 to tardive dyskinesia susceptibility.
Title: Evidence for association of the GLI2 gene with tardive dyskinesia in patients with chronic schizophrenia.
Constitutive expression of the human hGli2 Delta N in porcine keratinocytes causes cutaneous changes not seen in the murine model. A multiple species animal model approach is needed to understand the role of Gli2 in mammalian skin.
Title: Varying phenotypes in swine versus murine transgenic models constitutively expressing the same human Sonic hedgehog transcriptional activator, K5-HGLI2 Delta N.
A fragment of the Hh-responsive GLI2 transcription factor directly binds and inhibits the p16 promoter and senescence is associated with the loss of nuclear GLI2.
Title: Primary cilium-dependent and -independent Hedgehog signaling inhibits p16(INK4A).
In human hepatocellular, the hedgehog signaling pathway is involved in the differentiation and proliferation of tumor cells, in part through inducing nuclear accumulation of Gli2 protein and subsequent upregulation of FoxM1 protein.
Title: Nuclear accumulation of glioma-associated oncogene 2 protein and enhanced expression of forkhead-box transcription factor M1 protein in human hepatocellular carcinoma.
These phenotypes support partial penetrance, variable polydactyly, midline facial defects, and pituitary hormone deficiencies, including diabetes insipidus, conferred by heterozygous frameshift or nonsense GLI2 mutations.
Title: Novel heterozygous nonsense GLI2 mutations in patients with hypopituitarism and ectopic posterior pituitary lobe without holoprosencephaly.
In human melanoma cells, GLI2 expression was heterogeneous, associated with loss of E-cadherin and increased in the most aggressive tumors. In this preclinical study, GLI2 was directly involved in driving melanoma invasion and metastasis.
Title: GLI2-mediated melanoma invasion and metastasis.

Submit: New GeneRIF Correction See all (33)

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Phenotypes

Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Genome-wide association study to identify single nucleotide polymorphisms (SNPs) associated with the development of erectile dysfunction in African-American men after radiotherapy for prostate cancer.

Pituitary anomalies with holoprosencephaly-like features

MIM: 165230

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HIV-1 protein interactions

Protein	Gene	Interaction	Pubs
Tat	tat	GLI-2 physically interacts with HIV-1 Tat (demonstrated in GST pull-down experiments) and strongly synergizes with Tat during transactivation of the HIV-1 LTR promoter	PubMed

Go to the HIV-1, Human Protein Interaction Database

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Products	Interactant	Other Gene	Source	Pubs	Description
P10070	P16220	CREB1	HPRD	PubMed
P10070	Q9UKB1	FBXW11	HPRD	PubMed
P10070	P12755	SKI	HPRD	PubMed
P10070	Q9NRP7	STK36	HPRD	PubMed
P10070	Q9UMX1	SUFU	HPRD	PubMed
P10070	Q15915	ZIC1	HPRD	PubMed
P10070	O95409	ZIC2	HPRD	PubMed
BioGRID:108998	BioGRID:107775	CREB1	BioGRID	PubMed	Reconstituted Complex
BioGRID:108998	BioGRID:109315	HDAC1	BioGRID	PubMed	Affinity Capture-Western
BioGRID:108998	BioGRID:112388	SKI	BioGRID	PubMed	Reconstituted Complex; Two-hybrid
BioGRID:108998	BioGRID:118032	STK36	BioGRID	PubMed	Affinity Capture-Western
BioGRID:108998	BioGRID:119676	SUFU	BioGRID	PubMed	Reconstituted Complex
	NP_003185.1	TBP	BIND	PubMed	TBP interacts with GLI-2. This interaction was modeled on a demonstrated interaction between TBP from an unspecified species and human GLI-2.
BioGRID:108998	BioGRID:113377	ZIC1	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex
BioGRID:108998	BioGRID:113378	ZIC2	BioGRID	PubMed	Affinity Capture-Western

Function	Evidence Code	Pubs
chromatin binding	IEA Inferred from Electronic Annotation more info
metal ion binding	IEA Inferred from Electronic Annotation more info
protein binding	IPI Inferred from Physical Interaction more info	PubMed
sequence-specific DNA binding	IDA Inferred from Direct Assay more info	PubMed
sequence-specific DNA binding	IEA Inferred from Electronic Annotation more info
sequence-specific DNA binding transcription factor activity	IDA Inferred from Direct Assay more info	PubMed
sequence-specific DNA binding transcription factor activity	IEA Inferred from Electronic Annotation more info
transcription regulatory region DNA binding	IEA Inferred from Electronic Annotation more info
zinc ion binding	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
apoptotic process	IEA Inferred from Electronic Annotation more info
axon guidance	IEA Inferred from Electronic Annotation more info
axon guidance	ISS Inferred from Sequence or Structural Similarity more info
branching morphogenesis of a tube	IEA Inferred from Electronic Annotation more info
branching morphogenesis of a tube	ISS Inferred from Sequence or Structural Similarity more info
cell differentiation	IEA Inferred from Electronic Annotation more info
cell proliferation	IDA Inferred from Direct Assay more info	PubMed
cellular response to organic cyclic compound	IEA Inferred from Electronic Annotation more info
cerebellar cortex morphogenesis	IEA Inferred from Electronic Annotation more info
cerebellar cortex morphogenesis	ISS Inferred from Sequence or Structural Similarity more info
cochlea morphogenesis	IEA Inferred from Electronic Annotation more info
developmental growth	IEA Inferred from Electronic Annotation more info
developmental growth	ISS Inferred from Sequence or Structural Similarity more info
embryonic digestive tract development	IEA Inferred from Electronic Annotation more info
embryonic digestive tract development	ISS Inferred from Sequence or Structural Similarity more info
embryonic digit morphogenesis	IEA Inferred from Electronic Annotation more info
epidermal cell differentiation	IDA Inferred from Direct Assay more info	PubMed
floor plate formation	IEA Inferred from Electronic Annotation more info
floor plate formation	ISS Inferred from Sequence or Structural Similarity more info
head development	IEA Inferred from Electronic Annotation more info
heart development	IEA Inferred from Electronic Annotation more info
heart development	ISS Inferred from Sequence or Structural Similarity more info
hindbrain development	IEA Inferred from Electronic Annotation more info
hindbrain development	ISS Inferred from Sequence or Structural Similarity more info
hindgut morphogenesis	IEA Inferred from Electronic Annotation more info
hindgut morphogenesis	ISS Inferred from Sequence or Structural Similarity more info
in utero embryonic development	IEA Inferred from Electronic Annotation more info
kidney development	IEA Inferred from Electronic Annotation more info
kidney development	ISS Inferred from Sequence or Structural Similarity more info
lung development	IEA Inferred from Electronic Annotation more info
lung development	ISS Inferred from Sequence or Structural Similarity more info
mammary gland development	IEA Inferred from Electronic Annotation more info
mammary gland development	ISS Inferred from Sequence or Structural Similarity more info
mammary gland duct morphogenesis	IEA Inferred from Electronic Annotation more info
morphogenesis of an epithelium	IEA Inferred from Electronic Annotation more info
negative regulation of chondrocyte differentiation	IEA Inferred from Electronic Annotation more info
negative regulation of transcription from RNA polymerase II promoter	IEA Inferred from Electronic Annotation more info
negative regulation of transcription from RNA polymerase II promoter	IMP Inferred from Mutant Phenotype more info	PubMed
neural tube development	IEA Inferred from Electronic Annotation more info
neuron development	IEA Inferred from Electronic Annotation more info
neuron development	ISS Inferred from Sequence or Structural Similarity more info
notochord regression	IEA Inferred from Electronic Annotation more info
odontogenesis of dentin-containing tooth	IEA Inferred from Electronic Annotation more info
odontogenesis of dentin-containing tooth	ISS Inferred from Sequence or Structural Similarity more info
osteoblast development	IEA Inferred from Electronic Annotation more info
osteoblast development	ISS Inferred from Sequence or Structural Similarity more info
osteoblast differentiation	IDA Inferred from Direct Assay more info	PubMed
pattern specification process	IEA Inferred from Electronic Annotation more info
pattern specification process	ISS Inferred from Sequence or Structural Similarity more info
pituitary gland development	IEA Inferred from Electronic Annotation more info
pituitary gland development	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of DNA replication	IDA Inferred from Direct Assay more info	PubMed
positive regulation of T cell differentiation in thymus	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of cell proliferation	IEA Inferred from Electronic Annotation more info
positive regulation of neuron differentiation	IEA Inferred from Electronic Annotation more info
positive regulation of transcription from RNA polymerase II promoter	IDA Inferred from Direct Assay more info	PubMed
positive regulation of transcription from RNA polymerase II promoter	IEA Inferred from Electronic Annotation more info
positive regulation of transcription, DNA-dependent	IDA Inferred from Direct Assay more info	PubMed
prostatic bud formation	IEA Inferred from Electronic Annotation more info
proximal/distal pattern formation	IEA Inferred from Electronic Annotation more info
proximal/distal pattern formation	ISS Inferred from Sequence or Structural Similarity more info
regulation of smoothened signaling pathway	IEA Inferred from Electronic Annotation more info
regulation of transcription, DNA-dependent	IDA Inferred from Direct Assay more info	PubMed
skeletal system development	IEA Inferred from Electronic Annotation more info
skeletal system development	ISS Inferred from Sequence or Structural Similarity more info
smoothened signaling pathway	IDA Inferred from Direct Assay more info	PubMed
smoothened signaling pathway involved in dorsal/ventral neural tube patterning	IEA Inferred from Electronic Annotation more info
smoothened signaling pathway involved in regulation of cerebellar granule cell precursor cell proliferation	IEA Inferred from Electronic Annotation more info
smoothened signaling pathway involved in spinal cord motor neuron cell fate specification	IEA Inferred from Electronic Annotation more info
smoothened signaling pathway involved in ventral spinal cord interneuron specification	IEA Inferred from Electronic Annotation more info
smoothened signaling pathway involved in ventral spinal cord interneuron specification	ISS Inferred from Sequence or Structural Similarity more info
specification of segmental identity, maxillary segment	IEA Inferred from Electronic Annotation more info
spinal cord dorsal/ventral patterning	IEA Inferred from Electronic Annotation more info
spinal cord dorsal/ventral patterning	ISS Inferred from Sequence or Structural Similarity more info
spinal cord ventral commissure morphogenesis	IEA Inferred from Electronic Annotation more info
spinal cord ventral commissure morphogenesis	ISS Inferred from Sequence or Structural Similarity more info
tube development	IEA Inferred from Electronic Annotation more info
tube development	ISS Inferred from Sequence or Structural Similarity more info
ventral midline development	ISS Inferred from Sequence or Structural Similarity more info
ventral spinal cord development	IEA Inferred from Electronic Annotation more info
ventral spinal cord development	ISS Inferred from Sequence or Structural Similarity more info

Component	Evidence Code	Pubs
cilium	IEA Inferred from Electronic Annotation more info
cytoplasm	IEA Inferred from Electronic Annotation more info
intracellular	IEA Inferred from Electronic Annotation more info
membrane fraction	IEA Inferred from Electronic Annotation more info
motile primary cilium	IEA Inferred from Electronic Annotation more info
nucleus	IDA Inferred from Direct Assay more info	PubMed
nucleus	IEA Inferred from Electronic Annotation more info

General protein information

Preferred Names: zinc finger protein GLI2

Names: zinc finger protein GLI2; oncogene GLI2; tax helper protein 1; tax helper protein 2; GLI-Kruppel family member GLI2; tax-responsive element-2 holding protein; glioma-associated oncogene family zinc finger 2; tax-responsive element-25-bp sequence binding protein

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NCBI Reference Sequences (RefSeq)

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_009030.1 RefSeqGene

Range

5001..200363

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_005270.4 → NP_005261.2 zinc finger protein GLI2

Status: REVIEWED

Source sequence(s)

AB209354, AJ707583, DQ004398, DQ086814

Consensus CDS

CCDS33283.1

UniProtKB/Swiss-Prot

P10070

UniProtKB/TrEMBL

Q1PSW9

UniProtKB/TrEMBL

Q59FV5

Related

ENSP00000354586, ENST00000361492

Conserved Domains (2) summary

pfam09770
Location:1160 – 1348
Blast Score: 108

PAT1; Topoisomerase II-associated protein PAT1

pfam13465
Location:489 – 516
Blast Score: 102

zf-H2C2_2; Zinc-finger double domain

RefSeqs of Annotated Genomes: Build 37.3

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh37.p5 Primary Assembly

Genomic

NC_000002.11 Reference GRCh37.p5 Primary Assembly

Range

121554867..121750229

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000134.1 Alternate HuRef

Range

113876969..114072693

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

NM_030379.1: Suppressed sequence

Description

NM_030379.1: This RefSeq was permanently suppressed because it is a nonsense-mediated mRNA decay (NMD) candidate.
NM_030380.1: Suppressed sequence

Description

NM_030380.1: This RefSeq was permanently suppressed because it is a nonsense-mediated mRNA decay (NMD) candidate.
NM_030381.1: Suppressed sequence

Description

NM_030381.1: This RefSeq was permanently suppressed because it is a nonsense-mediated mRNA decay (NMD) candidate.

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Related Sequences

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	AC016764.8	None
genomic	AC017033.5 (60663..181886)	None
genomic	M20672.1	None
genomic	M20673.1	AAA35898.1
mRNA	AB007295.1	BAA25665.1
mRNA	AB007296.1	BAA25666.1
mRNA	AB007297.1	BAA25667.1
mRNA	AB007298.1	BAA25668.1
mRNA	AB209354.1	BAD92591.1
mRNA	AJ707583.1	None
mRNA	AK300071.1	BAG61875.1
mRNA	AY493737.1	AAS72889.1
mRNA	AY493738.1	AAS72890.1
mRNA	AY493739.1	AAS72891.1
mRNA	BC111410.1	AAI11411.1
mRNA	D14827.1	BAA03568.1
mRNA	D14828.1	BAA03569.1
mRNA	DQ004396.1	AAY58315.1
mRNA	DQ004397.1	AAY58316.1
mRNA	DQ004398.1	AAY58317.1
mRNA	DQ086814.1	AAY87165.1
other-genetic	BC172434.1	AAI72434.1

Protein Accession	Links
Protein Accession	GenPept Link	UniProtKB Link
P10070.4	GenPept	UniProtKB/Swiss-Prot:P10070
Q0VGA0	GenPept	UniProtKB/TrEMBL:Q0VGA0
Q1PSW9	GenPept	UniProtKB/TrEMBL:Q1PSW9
Q1PSX1	GenPept	UniProtKB/TrEMBL:Q1PSX1
Q59FV5	GenPept	UniProtKB/TrEMBL:Q59FV5
Q6RSW0	GenPept	UniProtKB/TrEMBL:Q6RSW0
Q6RSW1	GenPept	UniProtKB/TrEMBL:Q6RSW1
Q6RSW2	GenPept	UniProtKB/TrEMBL:Q6RSW2