GLUD2 glutamate dehydrogenase 2 [Homo sapiens (human)] - Gene

Summary

Official Symbol: GLUD2provided by HGNC
Official Full Name: glutamate dehydrogenase 2provided by HGNC
Primary source: HGNC:HGNC:4336
See related: Ensembl:ENSG00000182890 MIM:300144; AllianceGenome:HGNC:4336
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: GDH2; GLUDP1
Summary: The protein encoded by this gene is localized to the mitochondrion and acts as a homohexamer to recycle glutamate during neurotransmission. The encoded enzyme catalyzes the reversible oxidative deamination of glutamate to alpha-ketoglutarate. This gene is intronless.[provided by RefSeq, Jan 2010]
Orthologs: all
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Genomic context

Location:: Xq24

Exon count:: 1

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	X	NC_000023.11 (121047610..121050094)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	X	NC_060947.1 (119347469..119349953)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	X	NC_000023.10 (120181464..120183948)

Chromosome X - NC_000023.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Ammonia inhibits energy metabolism in astrocytes in a rapid and glutamate dehydrogenase 2-dependent manner.
Title: Ammonia inhibits energy metabolism in astrocytes in a rapid and glutamate dehydrogenase 2-dependent manner.
Crystal structure of glutamate dehydrogenase 2, a positively selected novel human enzyme involved in brain biology and cancer pathophysiology.
Title: Crystal structure of glutamate dehydrogenase 2, a positively selected novel human enzyme involved in brain biology and cancer pathophysiology.
Functional validation of a human GLUD2 variant in a murine model of Parkinson's disease.
Title: Functional validation of a human GLUD2 variant in a murine model of Parkinson's disease.
present data, showing that GLUD2 expression in Tg mice improves in vivo glucose homeostasis by boosting fasting serum insulin levels, suggest that evolutionary adaptation of hGDH2 has enabled humans to achieve narrow-range euglycemia by regulating glutamate-mediated basal insulin secretion
Title: Transgenic expression of the positive selected human GLUD2 gene improves in vivo glucose homeostasis by regulating basic insulin secretion.
The autoantibodies to GluD2 are common in patients with OMAS, bind to surface determinants, and are potentially pathogenic.
Title: Glutamate receptor δ2 serum antibodies in pediatric opsoclonus myoclonus ataxia syndrome.
In HEK293 cell lines GDH2 and GDH1 were over-expressed and found to be co-localized in subcellular fractions.
Title: Localization of Human Glutamate Dehydrogenases Provides Insights into Their Metabolic Role and Their Involvement in Disease Processes.
GLUD2 overexpression inhibited Glioblastoma (GBM) cell growth suggesting a novel potential drug target for control of GBM progression. The possibility to enhance GLUD2 activity in GBM could result in a blocked/reduced proliferation of GBM cells without affecting the survival of the surrounding neurons.
Title: Mitochondrial enzyme GLUD2 plays a critical role in glioblastoma progression.
hGDH2 evolution bestowed large human neurons with enhanced glutamate metabolizing capacity, thus strengthening cortical excitatory transmission.
Title: Evolution of GLUD2 Glutamate Dehydrogenase Allows Expression in Human Cortical Neurons.
This study demonstrated that hGDH2 expression increases capacity for uptake and oxidative metabolism of glutamate, particularly during increased workload and hypoglycemia.
Title: Expression of the human isoform of glutamate dehydrogenase, hGDH2, augments TCA cycle capacity and oxidative metabolism of glutamate during glucose deprivation in astrocytes.
This proliferation requires glutamate dehydrogenase 2, which synthesizes glutamate from ammonia and alpha-ketoglutarate and is expressed in MCF7 and T47D cells. Our findings provide insight into how cancer cells survive under glutamine deprivation conditions and thus contribute to elucidating the mechanisms of tumor growth.
Title: Glutamate production from ammonia via glutamate dehydrogenase 2 activity supports cancer cell proliferation under glutamine depletion.

Submit: New GeneRIF Correction See all GeneRIFs (33)

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

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Vpr	vpr	A stable-isotope labeling by amino acids in cell culture coupled with mass spectrometry-based proteomics identifies downregulation of glutamate dehydrogenase 2 (GLUD2) expression by HIV-1 Vpr in Vpr transduced macrophages	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

GLUD1-1 (e-PCR)
- UniSTS:511772

DXS7028E (e-PCR)
- UniSTS:99109

GLUD1_1725 (e-PCR)
- UniSTS:277286

D10S2137 (e-PCR)
- UniSTS:79931

RH80866 (e-PCR)
- UniSTS:85863

L47793 (e-PCR)
- UniSTS:77672

G44300 (e-PCR)
- UniSTS:95094

GDB:193864 (e-PCR)
- UniSTS:155772

RH65005 (e-PCR)
- UniSTS:76935

RH79929 (e-PCR)
- UniSTS:88720

L77323 (e-PCR)
- UniSTS:24257

GDB:277890 (e-PCR)
- UniSTS:156370

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables ADP binding	IDA Inferred from Direct Assay more info	PubMed
enables GTP binding	IDA Inferred from Direct Assay more info	PubMed
enables L-leucine binding	IDA Inferred from Direct Assay more info	PubMed
enables glutamate dehydrogenase (NAD+) activity	IBA Inferred from Biological aspect of Ancestor more info
enables glutamate dehydrogenase (NAD+) activity	IDA Inferred from Direct Assay more info	PubMed
enables glutamate dehydrogenase (NADP+) activity	IEA Inferred from Electronic Annotation more info
enables glutamate dehydrogenase [NAD(P)+] activity	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in glutamate biosynthetic process	IDA Inferred from Direct Assay more info	PubMed
involved_in glutamate catabolic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in glutamate catabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in glutamate metabolic process	IDA Inferred from Direct Assay more info	PubMed

Component	Evidence Code	Pubs
NOT located_in cytosol	IDA Inferred from Direct Assay more info	PubMed
located_in mitochondrial matrix	IEA Inferred from Electronic Annotation more info
is_active_in mitochondrion	IBA Inferred from Biological aspect of Ancestor more info
located_in mitochondrion	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: glutamate dehydrogenase 2, mitochondrial

Names: GDH 2; glutamate dehydrogenase pseudogene 1; testicular secretory protein Li 14

NP_036216.2

EC 1.4.1.3

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.

Genomic

NG_016456.1 RefSeqGene

Range

5003..7487

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_012084.4 → NP_036216.2 glutamate dehydrogenase 2, mitochondrial precursor

See identical proteins and their annotated locations for NP_036216.2

Status: REVIEWED

Source sequence(s)

AC006144, BC050732

Consensus CDS

CCDS14603.1

UniProtKB/Swiss-Prot

B2R8G0, P49448, Q9UDQ4

UniProtKB/TrEMBL

A0A140VK14, Q53GW3

Related

ENSP00000327589.1, ENST00000328078.3

Conserved Domains (3) summary

cd01076
Location:263 → 548

NAD_bind_1_Glu_DH; NAD(P) binding domain of glutamate dehydrogenase, subgroup 1

COG0334
Location:104 → 555

GdhA; Glutamate dehydrogenase/leucine dehydrogenase [Amino acid transport and metabolism]

pfam02812
Location:113 → 240

ELFV_dehydrog_N; Glu/Leu/Phe/Val dehydrogenase, dimerization domain