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FLASH GENE
Symbol GLI2 contributors: mct - updated : 06-03-2017
HGNC name GLI family zinc finger 2
HGNC id 4318
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
  • GLI2, the major transcriptional activator of HH signaling, is essential for hair follicle development and its overexpression in epidermis induces basal cell carcinoma (BCC) formation and maintains tumor growth
  • 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
  • IFT122 leads to accumulation of GLI2 and GLI3 at cilia tips while blocking the ciliary localization of the antagonist TULP3
  • CCL5-GLI2-IL6 interaction in B cell malignancies regulates immunoglobulin secretion
  • potentially, upon Hedgehog input, GLI1 functions collectively with GLI2 and GLI3 in osteogenesis
  • GLI2, is a direct transcriptional target of the TGFB1/SMAD pathway and contributes to melanoma progression, exerting antagonistic activities against M-MITF to control melanoma cell invasiveness
  • SUMO modification inhibits GLI2 transcriptional activity by recruiting HDAC5
  • 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
  • GLI1 and GLI2 activated the expression of a basic helix-loop-helix type suppressor BHLHE41 through a GLI-binding site in the promoter
  • PKD1L1-PKD2L1 acts as a ciliary calcium channel controlling ciliary calcium concentration and thereby modifying SMO-activated GLI2 translocation and GLI1 expression
  • GLI1, GLI2, GLI3 interacts synergistically with KIFAP3 and KIF3A
  • TAF9 interacts with the oncogenic GLI family members GLI1 and GLI2 but not GLI3
  • SPOP targets GLI2 and GLI3 for degradation and negatively regulates Hedgehog (Hh) signaling
  • GLI1 and GLI2 directly bind to the promoter regions of NEK2 gene and induced its transcription
  • OTUB2 is a regulator of GLI2 protein degradation
  • 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)
    tumoral somatic mutation      
    in hypothalamic hamartoma with gelastic epilepsy
    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