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FLASH GENE
Symbol GLI2 contributors: mct - updated : 06-03-2012
HGNC name GLI family zinc finger 2
HGNC id 4318
Corresponding disease
HPE9 holoprosencephaly 9
Location 2q14.2      Physical location : 121.554.866 - 121.750.228
Synonym name
  • glioma-associated oncogene homolog 2
  • tax helper protein 2
  • zinc finger protein GLI2
  • tax-responsive element-2 holding protein
  • oncogene GLI2
  • GLI-Kruppel family member GLI2
  • glioma-associated oncogene family zinc finger 2
  • Synonym symbol(s) THP2, THP1, THP
    DNA
    TYPE functioning gene
    STRUCTURE 195.36 kb     13 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    motif
    text structure
  • a TGF-beta-responsive region mapped to a 91-bp sequence between nucleotides -119 and -29 of the promoter
  • SMAD and lymphoid enhancer factor/T cell factor binding sites that allow functional cooperation between SMAD3 and beta-catenin, recruited to the promoter in response to TGF-beta to drive GLI2 gene transcription
  • tandem RRRCWWGYYY motifs for TP53, TP63 or TP73, and also four conserved BHLH-binding sites were identified within GLI2 proximal promoter region
  • MAPPING cloned Y linked N status confirmed
    Physical map
    DDX18 2q13 DEAD (Asp-Glu-Ala-Asp) box polypeptide 18 LOC389024 2 LOC389024 LOC343958 2q14.2 similar to 5-HT5B serotonin receptor FLJ10996 2q14.2 hypothetical protein FLJ10996 INSIG2 2q21.2 insulin induced gene 2 LOC389025 2 LOC389025 LOC151154 2q14.2 hypothetical LOC151154 EN1 2q14.2 engrailed homolog 1 MARCO 2q14.2 macrophage receptor with collagenous structure LOC165257 2q14.2 C1q-domain containing protein TSAP6 2q14.2 C1q-domain containing protein LOC389026 2 similar to PRO1546 DBI 2q12-q21 diazepam binding inhibitor (GABA receptor modulator, acyl-Coenzyme A binding protein) PR1 2q14.2 voltage-dependent calcium channel gamma subunit-like protein SCTR 2q14.1 secretin receptor LOC200373 2q14.2 similar to hypothetical protein MGC10993 2q14.2 hypothetical protein MGC10993 PTPN4 2p24.3-p24.1 protein tyrosine phosphatase, non-receptor type 4 (megakaryocyte) EPB41L5 2q21.2 erythrocyte membrane protein band 4.1 like 5 LOC391431 2 similar to NADH dehydrogenase subunit 5 FAM11B 2q21.2 similar to NADH dehydrogenase subunit 5 RALB 2cen-q13 v-ral simian leukemia viral oncogene homolog B (ras related; GTP binding protein) INHBB 2q12-q13 inhibin, beta B (activin AB beta polypeptide) FLJ14816 2q14.2 hypothetical protein FLJ14816 GLI2 2q24 GLI-Kruppel family member GLI2 TFCP2L1 2q14 transcription factor CP2-like 1 CLASP1 2q14-q21 cytoplasmic linker associated protein 1 MKI67IP 2q14.3 MKI67 (FHA domain) interacting nucleolar phosphoprotein TSN 2q21.1 translin LOC389027 2 LOC389027 LOC389028 2 LOC389028 caspr5 2q14.3 caspr5 protein
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    13 - 6780 - 1586 - 2007 18006803
    EXPRESSION
    Type widely
    constitutive of
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestivestomach   highly
    Reproductivemale systemtestis  highly
    Respiratorylung   highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Epithelialbarrier liningepidermis  
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Skin/Tegumentkeratinocyte
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a N-terminal transcriptional repressor domain regulating transcriptional activity
  • a zinc finger domain
  • a DNA binding domain
  • a transactivation domain
  • HOMOLOGY
    interspecies homolog to Drosophila segment polarity gene Cubitus interruptus
    Homologene
    FAMILY
  • GLI C2H2-type zinc-finger protein family
  • CATEGORY transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,nucleus
    basic FUNCTION
  • involved in the formation of lung, trachea and oesophagus
  • playing a role in head development
  • obligatory mediator of SHH signal transduction
  • playing an important role in regulating epidermal proliferation and skin tumorigenesis
  • mediates hedgehog signaling in osteoblasts and is a powerful activator of BMP2 gene expression, which is required in turn for normal osteoblast differentiation
  • plays a critical role in the malignant phenotype of prostate cancer cells
  • key role of GLI2 in activation of the activin/BMP antagonist FST in response to HH signaling
  • functions as a dynamic monitor of SMO activity in the cilium and thereby links Hedgehog pathway activation in the cilium to transcriptional activation in the nucleus
  • GLI2 and GLI3 collectively mediate all major aspects of IHH function during endochondral skeletal development
  • directly involved in driving melanoma invasion and metastasis
  • effector of the cellular function of the Hedgehog pathway, a well established oncogenic pathway in numerous neoplasms
  • intact GLI2 is required for CCL5-induced IL6 expression and functions downstream of the CCR3 signaling cascade
  • GLI2 and MEF2C play important roles in the development of embryonic heart muscle and enhance cardiomyogenesis in stem cells
  • complete range of anterior-posterior positional identities in the limb requires integration of the spatial distribution, timing, and dosage of GLI2 and GLI3 activators and repressors
  • distinct roles of GLI2 and GLI3 in intestine development, suggesting small leucine-rich glycoproteins (SLRPs) as novel regulators of smooth muscle cell differentiation
  • CELLULAR PROCESS nucleotide, transcription
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • CCL5-GLI2-IL6 axis in the stromal microenvironment regulating Ig secretion by malignant cells
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • binds the GLI-binding consensus sequence in the GLI1 promoter (GLI2 directly activates GLI1)
  • interacting with SUFU and SPOP (SUFU regulates GLI protein levels by antagonizing the activity of SPOP, a conserved GLI-degrading factor)
  • PIAS1-dependent SUMOylation influences GLI1, GLI2, GLI3 protein activity and thereby identifies SUMOylation as a post-translational mechanism that regulates the hedgehog signaling pathway
  • CCL5-GLI2-IL6 interaction in B cell malignancies regulates immunoglobulin secretion
  • potentially, upon Hedgehog input, GLI1 functions collectively with GLI2 and GLI3 in osteogenesis
  • TMEM107 acts in combination with GLI2 and GLI3 to pattern ventral and intermediate neuronal cell types
  • KIF7 is required to establish high intracellular GLI activity by antagonizing the SUFU-inhibition of GLI2
  • cell & other
    REGULATION
    activated by GLI1 (GLI1-GLI2 feedback loop in Hh-mediated epidermal cell proliferation)
    CCL5 (activates GLI2 via PI3K/AKT signaling)
    Other
  • inhibition of microtubule assembly inhibes proteasomal processing of GLI2 and increases intracellular GLI2 concentration, leading to enhancement of BMP2 gene transcription and subsequent bone formation
  • regulated by a regulatory loop between GLI2, MEOX1, and PAX3 that is essential for specification of mesodermal cells into the muscle lineage
    SUMO modification inhibits GLI2 transcriptional activity by recruiting HDAC5
    ASSOCIATED DISORDERS
    corresponding disease(s) HPE9
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional germinal mutation      
    loss of function mutations in pituitary anomalies and holoprosencephaly-like features
    tumoral     --over  
    overexpression of MAP3K10 resulted in upregulation of GLI1 and GLI2 in pancreatic ductal adenocarcinoma (PDAC) cells
    tumoral     --other  
    dysregulation of HH/GLI1 signaling disrupts tissue homeostasis and causes basal cell carcinoma (BCC)
    Susceptibility for cleft lip/palate
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerreproductiveprostate
    may potentially become an attractive therapeutic target for the treatment of prostate cancer
    ANIMAL & CELL MODELS