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FLASH GENE
Symbol GLS contributors: mct - updated : 09-07-2015
HGNC name glutaminase
HGNC id 4331
DNA
TYPE functioning gene
STRUCTURE 84.73 kb     18 Exon(s)
10 Kb 5' upstream gene genomic sequence study
MAPPING cloned Y linked N status confirmed
Physical map
TFPI 2q31-q32.1 tissue factor pathway inhibitor (lipoprotein-associated coagulation inhibitor) LOC344328 2q32.2 similar to heat shock 70kD protein binding protein; progesterone receptor-associated p48 protein; putative tumor suppressor ST13; Hsp70-interacting protein CED-6 2q32.3-q33 similar to heat shock 70kD protein binding protein; progesterone receptor-associated p48 protein; putative tumor suppressor ST13; Hsp70-interacting protein DIRC1 2q33 disrupted in renal carcinoma 1 COL3A1 2q32.2 collagen, type III, alpha 1 (Ehlers-Danlos syndrome type IV, autosomal dominant) COL5A2 2q24.3-q31 collagen, type V, alpha 2 LOC339781 2q32.3 similar to Keratin, type I cytoskeletal 18 (Cytokeratin 18) (K18) (CK 18) FLJ12519 2q32.3 hypothetical protein FLJ12519 SLC40A1 2q32 solute carrier family 40 (iron-regulated transporter), member 1 NS3TP1 2p24.3-q21.3 HCV NS3-transactivated protein 1 FLJ25415 2q32.3 hypothetical protein FLJ25415 OSGEPL1 2q32 O-sialoglycoprotein endopeptidase-like 1 LOC51240 2q32.3 hypothetical protein LOC51240 PMS1 2q31.1 PMS1 postmeiotic segregation increased 1 (S. cerevisiae) LOC285011 2q32.3 similar to HNRPC protein GDF8 2q32.2 growth differentiation factor 8 MGC13057 2q32.3 hypothetical protein MGC13057 HIBCH 2q32.3 3-hydroxyisobutyryl-Coenzyme A hydrolase INPP1 2q32 inositol polyphosphate-1-phosphatase FLJ20160 2q32.3 FLJ20160 protein LOC391468 2 similar to Hypothetical protein KIAA0286 (HA6800) NAB1 2q32.3-q33 NGFI-A binding protein 1 (EGR1 binding protein 1) GLS 2q32-q34 glutaminase STAT1 2q32.2-q32.3 signal transducer and activator of transcription 1, 91kDa STAT4 2q32.2-q32.3 signal transducer and activator of transcription 4 MYO1B 2q12-q34 myosin IB FLJ22833 2q32.3 hypothetical protein FLJ22833 SDPR 2q32-q33 serum deprivation response (phosphatidylserine binding protein) HSP40 2q32.3 HSP40 pseudogene TMEFF2 2q32.3-q33 transmembrane protein with EGF-like and two follistatin-like domains 2 LOC391469 2 similar to hypothetical protein FLJ10634 LOC389067 2 LOC389067 LOC343981 2q33.1 similar to Glutamine synthetase (Glutamate--ammonia ligase)
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
18 splicing 4850 - 669 expressed predominantly in brain and kidney but not in liver 1999 11015561
KGA
- splicing - - - is expressed solely in cardiac and skeletal muscle 1999 11015561
15 splicing 4509 - 598 is expressed principally in cardiac muscle and pancreas but not in liver or brain 1999 11015561
  • GAC
  • contains an open reading frame that matches KGA except for a unique COOH-terminal amino acid sequence
  • EXPRESSION
    Type
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Nervousbrain     Homo sapiens
    Urinarykidney     Homo sapiens
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Muscularstriatumskeletal   Homo sapiens
    Muscularstriatumcardiac   Homo sapiens
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Nervousastrocyte Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    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