Details of Protein

General Information of Protein (ID: PRT01210)
Name L-glutamine amidohydrolase (GLS)
Synonyms   Click to Show/Hide Synonyms of This Protein
GLS; K-glutaminase; Glutaminase kidney isoform, mitochondriale; GLS; GLS1; KIAA0838
Gene Name GLS Gene ID
2744
UniProt ID
O94925
Family Hydrolases (EC 3)
EC Number   EC: 3.5.1.2  (Click to Show/Hide the Complete EC Tree)
Hydrolases
Carbon-nitrogen hydrolase
Linear amide hydrolase
EC: 3.5.1.2
  Click to Show/Hide the Molecular/Functional Data (Sequence/Structure/Function) of This Protein
Sequence
MMRLRGSGMLRDLLLRSPAGVSATLRRAQPLVTLCRRPRGGGRPAAGPAAAARLHPWWGG
GGWPAEPLARGLSSSPSEILQELGKGSTHPQPGVSPPAAPAAPGPKDGPGETDAFGNSEG
KELVASGENKIKQGLLPSLEDLLFYTIAEGQEKIPVHKFITALKSTGLRTSDPRLKECMD
MLRLTLQTTSDGVMLDKDLFKKCVQSNIVLLTQAFRRKFVIPDFMSFTSHIDELYESAKK
QSGGKVADYIPQLAKFSPDLWGVSVCTVDGQRHSTGDTKVPFCLQSCVKPLKYAIAVNDL
GTEYVHRYVGKEPSGLRFNKLFLNEDDKPHNPMVNAGAIVVTSLIKQGVNNAEKFDYVMQ
FLNKMAGNEYVGFSNATFQSERESGDRNFAIGYYLKEKKCFPEGTDMVGILDFYFQLCSI
EVTCESASVMAATLANGGFCPITGERVLSPEAVRNTLSLMHSCGMYDFSGQFAFHVGLPA
KSGVAGGILLVVPNVMGMMCWSPPLDKMGNSVKGIHFCHDLVSLCNFHNYDNLRHFAKKL
DPRREGGDQRVKSVINLLFAAYTGDVSALRRFALSAMDMEQRDYDSRTALHVAAAEGHVE
VVKFLLEACKVNPFPKDRWNNTPMDEALHFGHHDVFKILQEYQVQYTPQGDSDNGKENQT
VHKNLDGLL
Structure
3CZD ; 3UNW ; 3UO9 ; 3VOY ; 3VOZ ; 3VP0 ; 3VP1 ; 3VP2 ; 3VP3 ; 3VP4 ; 4O7D ; 5D3O ; 5FI2 ; 5FI6 ; 5FI7 ; 5HL1 ; 5I94 ; 5JYO ; 5JYP ; 5U0I ; 5U0J ; 5UQE ; 5WJ6 ; 6LOX ; 6UJG ; 6UJM ; 6UK6 ; 6UKB ; 6UL9 ; 6ULA ; 6ULJ ; 6UMC ; 6UMD ; 6UME ; 6UMF
Function Catalyzes the first reaction in the primary pathway for the renal catabolism of glutamine. Plays a role in maintaining acid-base homeostasis. Regulates the levels of the neurotransmitter glutamate, the main excitatory neurotransmitter in the brain.; [Isoform 2]: Lacks catalytic activity.
Regulatory Network
Full List of Metabolite(s) Regulated by This Protein
      Organic acids and derivatives
            Glutamine Click to Show/Hide the Full List of Regulating Pair(s):   2 Pair(s)
               Detailed Information Metabo  Info click to show the details of this metabolite
               Regulating Pair (1) Experim Info click to show the details of experiment for validating this pair [1]
                      Introduced Variation Overexpression of GLS1
                      Induced Change Glutamine concentration: increase
                      Summary Introduced Variation         Induced Change 
                      Disease Status Prostate cancer [ICD-11: 2C82]
                      Details It is reported that overexpression of GLS1 leads to the increase of glutamine levels compared with control group.
               Regulating Pair (2) Experim Info click to show the details of experiment for validating this pair [2]
                      Introduced Variation Inhibition (968) of GLS1
                      Induced Change Glutamine concentration: decrease
                      Summary Introduced Variation         Induced Change 
                      Disease Status Lung cancer [ICD-11: 2C25]
                      Details It is reported that inhibition of GLS1 leads to the decrease of glutamine levels compared with control group.
Full List of Metabolite(s) Regulating This Protein
      Organic acids and derivatives
            Glutamine Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Metabo  Info click to show the details of this metabolite
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [3]
                      Introduced Variation Glutamine decrease (48 hours)
                      Induced Change GLS protein expression levels: decrease
                      Summary Introduced Variation         Induced Change 
                      Disease Status Hepatocellular carcinoma [ICD-11: 2C12]
                      Details It is reported that glutamine decrease causes the decrease of GLS protein expression compared with control group.
            Lactic acid Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Metabo  Info click to show the details of this metabolite
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [4]
                      Introduced Variation Lactic acid addition (6 hours)
                      Induced Change GLS protein expression levels: increase (FC = 1.6)
                      Summary Introduced Variation         Induced Change 
                      Disease Status Cervical Cancer [ICD-11: 2C77]
                      Details It is reported that lactic acid addition causes the increase of GLS protein expression compared with control group.
      Organic oxygen compounds
            Glucose Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Metabo  Info click to show the details of this metabolite
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [3]
                      Introduced Variation Glucose decrease (48 hours)
                      Induced Change GLS protein expression levels: increase
                      Summary Introduced Variation         Induced Change 
                      Disease Status Hepatocellular carcinoma [ICD-11: 2C12]
                      Details It is reported that glucose decrease causes the increase of GLS protein expression compared with control group.
References
1 c-Myc suppression of miR-23a/b enhances mitochondrial glutaminase expression and glutamine metabolism. Nature. 2009 Apr 9;458(7239):762-5.
2 Phosphorylation of glutaminase by PKC is essential for its enzymatic activity and critically contributes to tumorigenesis. Cell Res. 2018 Jun;28(6):655-669.
3 cMyc-mediated activation of serine biosynthesis pathway is critical for cancer progression under nutrient deprivation conditions. Cell Res. 2015 Apr;25(4):429-44.
4 Lactate promotes glutamine uptake and metabolism in oxidative cancer cells. Cell Cycle. 2016;15(1):72-83.

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