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GLS2 glutaminase 2 [ Homo sapiens (human) ]

Gene ID: 27165, updated on 3-Apr-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
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Genomic context

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Location:
12q13.3
Exon count:
19
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 12 NC_000012.12 (56470952..56488161, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 12 NC_060936.1 (56438665..56455831, complement)
105.20220307 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. Structure and activation mechanism of the human liver-type glutaminase GLS2. Ferreira IM, et al. Biochimie, 2021 Jun. PMID 33746066, Free PMC Article
  2. Nuclear Translocation of Glutaminase GLS2 in Human Cancer Cells Associates with Proliferation Arrest and Differentiation. López de la Oliva AR, et al. Sci Rep, 2020 Feb 10. PMID 32042057, Free PMC Article
  3. Liver-Type Glutaminase GLS2 Is a Druggable Metabolic Node in Luminal-Subtype Breast Cancer. Lukey MJ, et al. Cell Rep, 2019 Oct 1. PMID 31577957, Free PMC Article
  4. GLS2 is protumorigenic in breast cancers. Dias MM, et al. Oncogene, 2020 Jan. PMID 31541193
  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 (62) 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)

Genotypes

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 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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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_2023_10

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

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

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