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    GLS2 glutaminase 2 [ Homo sapiens (human) ]

    Gene ID: 27165, updated on 10-Dec-2024

    Summary

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    Official Symbol
    GLS2provided by HGNC
    Official Full Name
    glutaminase 2provided by HGNC
    Primary source
    HGNC:HGNC:29570
    See related
    Ensembl:ENSG00000135423 MIM:606365; AllianceGenome:HGNC:29570
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    GA; GLS; LGA; hLGA
    Summary
    The protein encoded by this gene is a mitochondrial phosphate-activated glutaminase that catalyzes the hydrolysis of glutamine to stoichiometric amounts of glutamate and ammonia. Originally thought to be liver-specific, this protein has been found in other tissues as well. Alternative splicing results in multiple transcript variants that encode different isoforms. [provided by RefSeq, Jul 2013]
    Expression
    Biased expression in liver (RPKM 39.1), brain (RPKM 4.2) and 2 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See GLS2 in Genome Data Viewer
    Location:
    12q13.3
    Exon count:
    19
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 12 NC_000012.12 (56470952..56488161, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 12 NC_060936.1 (56438665..56455831, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 12 NC_000012.11 (56864736..56881945, complement)

    Chromosome 12 - NC_000012.12Genomic Context describing neighboring genes Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr12:56817170-56818369 Neighboring gene timeless circadian regulator Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr12:56837017-56837650 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:56842091-56842611 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6496 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6497 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6498 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6499 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6500 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6501 Neighboring gene major intrinsic protein of lens fiber Neighboring gene SPRY domain containing 4 Neighboring gene uncharacterized LOC124902944 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6502 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4559 Neighboring gene small nucleolar RNA, H/ACA box 105C Neighboring gene H3K27ac hESC enhancer GRCh37_chr12:56916039-56916782 Neighboring gene heat shock protein family D (Hsp60) member 1 pseudogene 4 Neighboring gene RNA binding motif single stranded interacting protein 2 Neighboring gene H3K27ac hESC enhancer GRCh37_chr12:56959127-56959665 Neighboring gene H3K27ac hESC enhancer GRCh37_chr12:56959666-56960203 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6503 Neighboring gene RNA, U6 small nuclear 343, pseudogene

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. Transfection of a human glioblastoma cell line with liver-type glutaminase (LGA) down-regulates the expression of DNA-repair gene MGMT and sensitizes the cells to alkylating agents. Szeliga M, et al. J Neurochem, 2012 Nov. PMID 22888977
    2. CFIm25 regulates glutaminase alternative terminal exon definition to modulate miR-23 function. Masamha CP, et al. RNA, 2016 Jun. PMID 27095025, Free PMC Article
    3. Silencing of GLS and overexpression of GLS2 genes cooperate in decreasing the proliferation and viability of glioblastoma cells. Szeliga M, et al. Tumour Biol, 2014 Mar. PMID 24096582, Free PMC Article
    4. Knock-down of glutaminase 2 expression decreases glutathione, NADH, and sensitizes cervical cancer to ionizing radiation. Xiang L, et al. Biochim Biophys Acta, 2013 Dec. PMID 23954443
    5. Human genetic variation in GLS2 is associated with development of complicated Staphylococcus aureus bacteremia. Scott WK, et al. PLoS Genet, 2018 Oct. PMID 30289878, Free PMC Article

    See all (64) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. GLS2 Is a Tumor Suppressor and a Regulator of Ferroptosis in Hepatocellular Carcinoma.
      Title: GLS2 Is a Tumor Suppressor and a Regulator of Ferroptosis in Hepatocellular Carcinoma.
    2. Upregulation of glutaminase 2 and neutrophil cytosolic factor 2 is associated with the poor prognosis of glioblastoma.
      Title: Upregulation of glutaminase 2 and neutrophil cytosolic factor 2 is associated with the poor prognosis of glioblastoma.
    3. Glutaminase isoforms expression switches microRNA levels and oxidative status in glioblastoma cells.
      Title: Glutaminase isoforms expression switches microRNA levels and oxidative status in glioblastoma cells.
    4. Structure and activation mechanism of the human liver-type glutaminase GLS2.
      Title: Structure and activation mechanism of the human liver-type glutaminase GLS2.
    5. Nuclear Translocation of Glutaminase GLS2 in Human Cancer Cells Associates with Proliferation Arrest and Differentiation.
      Title: Nuclear Translocation of Glutaminase GLS2 in Human Cancer Cells Associates with Proliferation Arrest and Differentiation.
    6. Liver-Type Glutaminase GLS2 Is a Druggable Metabolic Node in Luminal-Subtype Breast Cancer.
      Title: Liver-Type Glutaminase GLS2 Is a Druggable Metabolic Node in Luminal-Subtype Breast Cancer.
    7. Study verified that several breast cancer cell lines express endogenous GLS2 and GLS2 expression is linked to enhanced in vitro cell migration and invasion, mesenchymal markers and in vivo lung metastasis. GLS2 amplification or overexpression is linked to worse survival prognosis in breast cancer. Data establish an unforeseen role of GLS2 in sustaining tumor proliferation and underlying metastasis in breast cancer.
      Title: GLS2 is protumorigenic in breast cancers.
    8. Gene-based analysis of the 342 genes in the replication sample using SKAT-O identified one gene, GLS2, significantly associated with complicated Staphylococcus aureus bacteremia(p = 1.2 x 10-4) after Bonferroni correction. The strongest association across all 10,931 variants in the replication sample was with rs2657878 in GLS2 (p = 5 x 10-4). This variant is strongly correlated with a missense variant (rs2657879)
      Title: Human genetic variation in GLS2 is associated with development of complicated Staphylococcus aureus bacteremia.
    9. This study assessed the relation of GLS2 downregulation in glioblastoma cells to its methylation and TP53 status. Aberrant methylation of CpG islands, appear to contribute to silencing of GLS2 in glioblastoma cells by a mechanism bypassing TP53 mutations.
      Title: Downregulation of GLS2 in glioblastoma cells is related to DNA hypermethylation but not to the p53 status.
    10. Non-glutaminolysis function of GLS2 inhibits migration and invasion of hepatocellular carcinoma cells by repressing the epithelial-mesenchymal transition via the Dicer-miR-34a-Snail axis.
      Title: Glutaminase 2 stabilizes Dicer to repress Snail and metastasis in hepatocellular carcinoma cells.
    Submit: New GeneRIF Correction See all GeneRIFs (36)

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    EBI GWAS Catalog

    Description
    An atlas of genetic influences on human blood metabolites.
    EBI GWAS Catalog
    Genome-wide association study identifies multiple loci influencing human serum metabolite levels.
    EBI GWAS Catalog
    Human metabolic individuality in biomedical and pharmaceutical research.
    EBI GWAS Catalog
    Nine loci for ocular axial length identified through genome-wide association studies, including shared loci with refractive error.
    EBI GWAS Catalog
    Novel Loci for metabolic networks and multi-tissue expression studies reveal genes for atherosclerosis.
    EBI GWAS Catalog

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • MGC71567

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables glutaminase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in amino acid metabolic process TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in glutamate biosynthetic process IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in glutamine catabolic process IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    acts_upstream_of_or_within reactive oxygen species metabolic process IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    acts_upstream_of_or_within regulation of apoptotic process IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    Component Evidence Code Pubs
    located_in mitochondrial matrix TAS
    Traceable Author Statement
    more info
    		  
    located_in mitochondrion HTP PubMed 
    located_in mitochondrion IDA
    Inferred from Direct Assay
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    glutaminase liver isoform, mitochondrial
    Names
    L-glutamine amidohydrolase
    breast cell glutaminase
    glutaminase 2 (liver, mitochondrial)
    glutaminase I
    phosphate-activated glutaminase
    phosphate-dependent glutaminase
    NP_001267725.1
    NP_001267726.1
    NP_001267727.1
    NP_037399.2
    XP_005268854.1
    XP_054227725.1

    NCBI Reference Sequences (RefSeq)

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    NEW Try the new Transcript table

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    mRNA and Protein(s)

    1. NM_001280796.2 → NP_001267725.1  glutaminase liver isoform, mitochondrial isoform 3

      See identical proteins and their annotated locations for NP_001267725.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) differs in the 5' UTR and 5' coding region, uses an alternate start codon, and uses an alternate in-frame splice site in the 5' coding region compared to variant 1. It encodes isoform 3 which has a distinct and shorter N-terminus compared to isoform 1.
      Source sequence(s)
      AI241400, BC048344
      Conserved Domains (4) summary
      cd00204
      Location:214 → 299
      ANK; ankyrin repeats; ankyrin repeats mediate protein-protein interactions in very diverse families of proteins. The number of ANK repeats in a protein can range from 2 to over 20 (ankyrins, for example). ANK repeats may occur in combinations with other ...
      pfam13637
      Location:244 → 296
      Ank_4; Ankyrin repeats (many copies)
      sd00045
      Location:214 → 240
      ANK; ANK repeat [structural motif]
      cl00907
      Location:35 → 187
      Glutaminase; Glutaminase

    2. NM_001280797.2 → NP_001267726.1  glutaminase liver isoform, mitochondrial isoform 4

      See identical proteins and their annotated locations for NP_001267726.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) differs in the 5' UTR and 5' coding region and uses a downstream start codon compared to variant 1. It encodes isoform 4 which has a shorter N-terminus compared to isoform 1. Both variants 4 and 5 encode the same isoform (4).
      Source sequence(s)
      BC025661, DA180204
      Consensus CDS
      CCDS73482.1
      UniProtKB/TrEMBL
      A0A087X004
      Related
      ENSP00000485315.1, ENST00000623608.3
      Conserved Domains (4) summary
      cd00204
      Location:225 → 310
      ANK; ankyrin repeats; ankyrin repeats mediate protein-protein interactions in very diverse families of proteins. The number of ANK repeats in a protein can range from 2 to over 20 (ankyrins, for example). ANK repeats may occur in combinations with other ...
      pfam04960
      Location:1 → 198
      Glutaminase; Glutaminase
      pfam13637
      Location:255 → 307
      Ank_4; Ankyrin repeats (many copies)
      sd00045
      Location:225 → 251
      ANK; ANK repeat [structural motif]

    3. NM_001280798.2 → NP_001267727.1  glutaminase liver isoform, mitochondrial isoform 4

      See identical proteins and their annotated locations for NP_001267727.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (5) differs in the 5' UTR and 5' coding region and uses a downstream start codon compared to variant 1. It encodes isoform 4 which has a shorter N-terminus compared to isoform 1. Both variants 4 and 5 encode the same isoform (4).
      Source sequence(s)
      AF110331, DA060302, DA180204
      Consensus CDS
      CCDS73482.1
      UniProtKB/TrEMBL
      A0A087X004
      Related
      ENSP00000483010.1, ENST00000610413.4
      Conserved Domains (4) summary
      cd00204
      Location:225 → 310
      ANK; ankyrin repeats; ankyrin repeats mediate protein-protein interactions in very diverse families of proteins. The number of ANK repeats in a protein can range from 2 to over 20 (ankyrins, for example). ANK repeats may occur in combinations with other ...
      pfam04960
      Location:1 → 198
      Glutaminase; Glutaminase
      pfam13637
      Location:255 → 307
      Ank_4; Ankyrin repeats (many copies)
      sd00045
      Location:225 → 251
      ANK; ANK repeat [structural motif]

    4. NM_013267.4 → NP_037399.2  glutaminase liver isoform, mitochondrial isoform 1 precursor

      See identical proteins and their annotated locations for NP_037399.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) encodes the longest isoform (1).
      Source sequence(s)
      AF110331, AF223944
      Consensus CDS
      CCDS8921.1
      UniProtKB/Swiss-Prot
      B7Z8Q9, Q8IX91, Q9NYY2, Q9UI31, Q9UI32
      UniProtKB/TrEMBL
      E5G743
      Related
      ENSP00000310447.4, ENST00000311966.9
      Conserved Domains (4) summary
      cd00204
      Location:490 → 575
      ANK; ankyrin repeats; ankyrin repeats mediate protein-protein interactions in very diverse families of proteins. The number of ANK repeats in a protein can range from 2 to over 20 (ankyrins, for example). ANK repeats may occur in combinations with other ...
      pfam04960
      Location:177 → 463
      Glutaminase; Glutaminase
      pfam13637
      Location:520 → 572
      Ank_4; Ankyrin repeats (many copies)
      sd00045
      Location:490 → 516
      ANK; ANK repeat [structural motif]

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000012.12 Reference GRCh38.p14 Primary Assembly

      Range
      56470952..56488161 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_005268797.1 → XP_005268854.1  glutaminase liver isoform, mitochondrial isoform X1

      UniProtKB/TrEMBL
      E5G743
      Conserved Domains (4) summary
      cd00204
      Location:454 → 539
      ANK; ankyrin repeats; ankyrin repeats mediate protein-protein interactions in very diverse families of proteins. The number of ANK repeats in a protein can range from 2 to over 20 (ankyrins, for example). ANK repeats may occur in combinations with other ...
      pfam04960
      Location:141 → 427
      Glutaminase; Glutaminase
      pfam13637
      Location:484 → 536
      Ank_4; Ankyrin repeats (many copies)
      sd00045
      Location:454 → 480
      ANK; ANK repeat [structural motif]

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060936.1 Alternate T2T-CHM13v2.0

      Range
      56438665..56455831 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054371750.1 → XP_054227725.1  glutaminase liver isoform, mitochondrial isoform X2

      UniProtKB/TrEMBL
      E5G743

    Suppressed Reference Sequence(s)

    The following Reference Sequences have been suppressed. Explain

    1. NM_138566.1: Suppressed sequence

      Description
      NM_138566.1: This RefSeq was permanently suppressed because it is a nonsense-mediated mRNA decay (NMD) candidate.
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q9UI32.2 GenPept UniProtKB/Swiss-Prot:Q9UI32

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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