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FLASH GENE
Symbol GLS contributors: mct - updated : 09-07-2015
HGNC name glutaminase
HGNC id 4331
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • one ankyrin repeat domain
  • two domains with the active site located at the interface
    • secondary structure
  • domain I comprises (Ile221-Pro281 and Cys424 -Leu533) of a five-stranded anti-parallel beta-sheet surrounded by six alpha-helices and several loops
  • domain II (Phe282-Thr423) mainly consists of seven alpha-helices
    • HOMOLOGY
    interspecies homolog to murine Gls
    Homologene
    FAMILY glutaminase family
    CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,mitochondria,matrix
    intracellular,cytoplasm,cytosolic
    basic FUNCTION
  • catalyzing the first reaction in the primary pathway for the renal catabolism of glutamine
  • activity of GLS is directly regulated by RAF-MEK-ERK downstream of EGF receptor
  • neuronal glutaminase is a potential component of neurotoxicity during inflammation and modulation of glutaminase may provide therapeutic avenues for neurodegenerative diseases
  • metabolic enzyme responsible for glutaminolysis, a process harnessed by cancer cells to feed their accelerated growth and proliferation
  • mitochondrial enzyme that converts glutamine to glutamate
  • kidney-type isoform is associated with cell proliferation
  • GLS, NCALD and INSR are involved in nutrient signaling pathways and energy homeostasis suggesting a role in celiac disease pathogenesis
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism aminoacid
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • through binding to GLS, ATCAY could regulate glutamate synthesis at synapses during neurotransmission
  • its activity in cells is stimulated by EGF, and GLS associates with all three kinase components of the RAF1/MEK2/ERK signaling module
    • cell & other
    REGULATION
    activated by MYC and RHO and is subjected to ubiquitination
    Other regulated by oncogene MYC
    is regulated by phosphorylation
    ASSOCIATED DISORDERS
    corresponding disease(s) EIEE71 , CASGID
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral        
    GLS silencing reduced proliferation of glioblastoma T98G cells and strengthen the antiproliferative effect evoked by previous GLS2 overexpression
    tumoral     --over  
    in colorectal cancer
    tumoral     --low  
    kills cells that overexpress MYC and catabolize glutamine
    tumoral     --over  
    in hepatocellular carcinoma
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker GLS expression is a sensitive and specific biomarker for pathological diagnosis and prognosis of hepatocellular carcinoma
    Therapy target
    SystemTypeDisorderPubmed
    cancerdigestivecolon
    may serve as a target for colorectal cancer therapy
    ANIMAL & CELL MODELS