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FLASH GENE

Symbol

GLS

contributors: mct - updated : 09-07-2015

HGNC name	glutaminase
HGNC id	4331

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

EXPRESSION

Type

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Nervous brain         Homo sapiens Urinary kidney         Homo sapiens

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Muscular striatum skeletal     Homo sapiens Muscular striatum cardiac     Homo sapiens

cells

System Cell Pubmed Species Stage Rna symbol Nervous astrocyte 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)

Type Gene Modification Chromosome rearrangement Protein expression Protein 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
	System Type Disorder Pubmed cancer digestive colon may serve as a target for colorectal cancer therapy

ANIMAL & CELL MODELS