Affinage

GPT2

Alanine aminotransferase 2 · UniProt Q8TD30

Length
523 aa
Mass
57.9 kDa
Annotated
2026-04-28
53 papers in source corpus 23 papers cited in narrative 23 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

GPT2 is a mitochondrial pyridoxal phosphate-dependent transaminase that catalyzes the reversible transamination of glutamate and pyruvate to alanine and α-ketoglutarate, thereby sustaining TCA cycle anaplerosis, alanine biosynthesis, and glutamate homeostasis across multiple tissues (PMID:27601654, PMID:25758935). In the nervous system, GPT2 is essential for postnatal brain growth, motor neuron survival, synaptic glutamate release, and locus coeruleus noradrenergic neuron maintenance; loss-of-function mutations cause a human syndrome of postnatal microcephaly and intellectual disability (PMID:27601654, PMID:34519342, PMID:39604975, PMID:35908744). In cancer, GPT2-generated α-ketoglutarate modulates HIF1α stability and Hedgehog signaling, while GPT2-derived GABA activates GABAA receptor–Ca²⁺–PKC–CREB metastatic cascades; GPT2 loss impairs mTORC1 activity and induces autophagy, and GPT2 is transcriptionally induced by ATF4 upon glutaminase inhibition, by HIF-2 under hypoxia, and by thyroid hormones in skeletal muscle (PMID:28839461, PMID:36923530, PMID:33368291, PMID:30765862, PMID:36010673, PMID:35196498). GPT2, together with the mitochondrial transporter SLC25A11, supplies nuclear α-ketoglutarate pools that regulate chromatin demethylation during brain development (PMID:27601654).

Mechanistic history

Synthesis pass · year-by-year structured walk · 10 steps
  1. 2015 High

    The first direct demonstration that a specific GPT2 missense variant (p.Ser153Arg) abolishes transaminase activity established that GPT2 enzymatic function is required for normal neurodevelopment.

    Evidence In vitro enzymatic activity assay of recombinant wild-type vs. mutant ALT2 protein

    PMID:25758935

    Open questions at the time
    • Only a single mutation tested
    • No animal model to confirm in vivo relevance
    • Tissue-specific requirements of GPT2 not addressed
  2. 2016 High

    Comprehensive biochemical, metabolomic, and genetic studies defined GPT2 as a mitochondrial transaminase whose loss abolishes alanine synthesis and TCA cycle anaplerosis, causing postnatal microcephaly in humans and reduced brain growth in mice — establishing the core enzymatic and disease mechanism.

    Evidence Recombinant mutant protein assays; subcellular fractionation; metabolomics and 13C-isotope tracing in Gpt2-null mice; human genetic data

    PMID:27601654

    Open questions at the time
    • Cell-type-specific contributions (neuronal vs. glial) not resolved
    • Whether alanine deficiency or α-KG depletion is the primary driver of neuropathology unclear
  3. 2017 High

    The discovery that GPT2 modulates intracellular α-KG levels to regulate PHD2–HIF1α stability and Sonic Hedgehog signaling revealed a non-canonical oncogenic function linking transaminase activity to cancer stemness.

    Evidence GPT2 overexpression/knockdown in breast cancer cells and xenograft models; measurement of α-KG and PHD2 activity

    PMID:28839461

    Open questions at the time
    • Whether GPT2 generates or consumes α-KG depends on reaction direction — directionality in tumor microenvironment not fully defined
    • Contribution of GPT1 (cytosolic isoform) not addressed
  4. 2019 High

    Identification of ATF4 as a stress-responsive transcriptional inducer of GPT2 upon glutaminase inhibition revealed how cancer cells adaptively upregulate anaplerosis, establishing GPT2 as a resistance mechanism and combination therapy target.

    Evidence Genetic knockdown of GPT2 combined with GLS inhibition; ROS measurement; ATF4-GPT2 transcriptional regulation in cancer cells

    PMID:30765862

    Open questions at the time
    • ATF4 binding site on GPT2 promoter not mapped
    • Whether this axis operates in non-cancer tissues unknown
  5. 2021 High

    GPT2 loss in triple-negative breast cancer was shown to impair mTORC1 signaling and induce autophagy, linking transaminase-derived metabolites to nutrient-sensing pathways and tumor growth control.

    Evidence GPT2 knockout in TNBC cells; TCA metabolite, mTORC1, and autophagy marker analysis; xenograft models

    PMID:33368291

    Open questions at the time
    • Whether mTORC1 suppression is directly via α-KG or via general amino acid depletion not distinguished
    • Autophagy-tumor growth relationship is correlative in vivo
  6. 2022 High

    A series of studies defined tissue-specific GPT2 functions: neuron-specific deletion proved that neuronal GPT2 is essential for motor neuron survival and brain anaplerosis; synaptosome analyses showed GPT2 maintains presynaptic glutamate pools for excitatory transmission; locus coeruleus noradrenergic neurons degenerate early in Gpt2-null mice with mTOR/autophagy dysregulation; thyroid hormones transcriptionally regulate muscle GPT2 to support glutamine anaplerosis and prevent atrophy; and HIF-2 directly drives GPT2 transcription in glioblastoma.

    Evidence Neuron-specific conditional KO mice; electrophysiology and synaptosome biochemistry; LC histology and neurochemistry; isotope tracing in skeletal muscle; HIF-2 ChIP on GPT2 HRE

    PMID:34519342 PMID:35196498 PMID:35908744 PMID:36010673 PMID:39604975

    Open questions at the time
    • Glial contributions remain unresolved
    • Whether TH regulation of GPT2 is direct (TH response element) or indirect not confirmed
    • Mechanism by which GPT2 loss triggers selective neuronal vulnerability (LC vs. other populations) unclear
  7. 2022 Medium

    Transcriptional and post-transcriptional regulators of GPT2 were identified: the lncRNA UCA1 recruits hnRNP I/L to the GPT2 promoter in bladder cancer, and SPTBN1 regulates GPT2 mRNA stability in renal carcinoma.

    Evidence RNA immunoprecipitation and promoter binding assay; actinomycin D mRNA stability assay; knockdown/overexpression with metabolic readouts

    PMID:35021150 PMID:36527113

    Open questions at the time
    • UCA1-hnRNP binding to GPT2 promoter shown in single lab only
    • SPTBN1-GPT2 mRNA interaction site not mapped
    • Physiological (non-cancer) relevance of these regulatory mechanisms unknown
  8. 2023 High

    A non-metabolic signaling role for GPT2 was defined: GPT2 increases GABA production from glutamate, activating GABAA receptor (GABRD subunit)–Ca²⁺–PKC–CREB signaling to drive breast cancer metastasis; separately, exosomal GPT2 was found to interact with BTRC to promote IκBα degradation.

    Evidence GABA measurement, Ca²⁺ imaging, PKC-CREB pathway analysis, GABRD knockdown, conditional tumor models; exosome Co-IP with BTRC

    PMID:36923530 PMID:37287397

    Open questions at the time
    • Whether GPT2 directly synthesizes GABA or acts indirectly through glutamate decarboxylase not resolved
    • Exosomal GPT2–BTRC interaction lacks reciprocal validation and structural basis
    • GABA signaling role in non-breast cancer contexts untested
  9. 2024 Medium

    The Ku70–SIX1 nuclear complex was identified as a transcriptional activator of GPT2 in prostate cancer, adding another direct upstream regulator and linking DNA repair machinery to metabolic gene control.

    Evidence Co-immunoprecipitation; ChIP-seq of SIX1 at GPT2 promoter; domain mapping; proliferation/migration assays upon Ku70/SIX1 depletion

    PMID:39488663

    Open questions at the time
    • Ku70–SIX1 binding interface modeled by simulation, not crystallography
    • Whether Ku70 enhances SIX1 binding or transcriptional activation not mechanistically distinguished
    • Single study in one cancer type
  10. 2025 Medium

    An inter-organelle metabolic circuit was proposed: GPT2 cooperates with mitochondrial transporter SLC25A11 to supply nuclear α-KG, which regulates chromatin demethylation during brain development — connecting mitochondrial metabolism to epigenetic regulation.

    Evidence α-KG biosensor; genetic screen; Gpt2-deficient mouse model with chromatin methylation analysis (preprint)

    PMID:bio_10.1101_2025.04.06.647450

    Open questions at the time
    • Preprint, not yet peer-reviewed
    • SLC25A11 contribution inferred from screen; direct biochemical reconstitution of the GPT2–SLC25A11–nuclear α-KG axis not shown
    • Chromatin targets affected by α-KG depletion not identified genome-wide

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: the structural basis of GPT2 substrate specificity and druggability; the relative contributions of alanine deficiency versus α-KG depletion to neuronal pathology; whether GPT2 enzymatic activity or a non-catalytic scaffolding function underlies its exosomal and signaling roles; and the physiological contexts in which GPT2 operates in the forward versus reverse transamination direction.
  • No crystal structure of human GPT2 available
  • Forward vs. reverse reaction directionality not systematically assessed across tissues
  • Catalytic vs. non-catalytic functions not genetically separated

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016740 transferase activity 7 GO:0140096 catalytic activity, acting on a protein 2
Localization
GO:0005739 mitochondrion 6 GO:0005634 nucleus 1
Pathway
R-HSA-1430728 Metabolism 6 R-HSA-1643685 Disease 5 R-HSA-1266738 Developmental Biology 3 R-HSA-162582 Signal Transduction 3 R-HSA-112316 Neuronal System 2 R-HSA-9612973 Autophagy 2 R-HSA-4839726 Chromatin organization 1
Partners
ATF4BTRCHNRNPIHNRNPLSIX1SLC25A11SPTBN1XRCC6

Evidence

Reading pass · 23 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2016 GPT2 encodes a mitochondrial glutamate pyruvate transaminase that catalyzes the reversible transfer of an amino group from glutamate to pyruvate, generating alanine and alpha-ketoglutarate; loss-of-function mutations (p.Arg404* nonsense and p.Pro272Leu missense) abolish enzymatic activity, cause defects in alanine synthesis, TCA cycle anaplerosis, and are associated with postnatal microcephaly and intellectual disability in humans; Gpt2-null mice recapitulate reduced brain growth. Biochemical loss-of-function assay of recombinant mutant proteins; metabolomics and isotope tracing in Gpt2-null mice; subcellular fractionation confirming mitochondrial localization Proceedings of the National Academy of Sciences of the United States of America High 27601654
2015 A homozygous missense variant p.Ser153Arg in GPT2 causes severe loss of enzymatic transaminase activity as demonstrated by functional assays of recombinant wild-type vs. mutant ALT2 proteins, establishing GPT2 loss-of-function as a cause of developmental encephalopathy. In vitro enzymatic activity assay of recombinant wild-type and p.Ser153Arg mutant GPT2 protein Journal of inherited metabolic disease High 25758935
2019 Mitochondrial GPT2 sustains TCA cycle anaplerosis after glutaminase (GLS) inhibition; elevated reactive oxygen species upon GLS inhibition induce GPT2 expression via activating transcription factor 4 (ATF4); GPT2 inhibition combined with GLS suppression synergistically reduces cancer cell proliferation and increases cell death. Genetic knockdown/inhibition experiments in cancer cells; measurement of TCA cycle intermediates; identification of ATF4 as transcriptional inducer of GPT2 under ROS stress Oncogene High 30765862
2017 GPT2 reduces intracellular alpha-ketoglutarate (α-KG) levels, thereby inhibiting prolyl hydroxylase 2 (PHD2) activity, leading to HIF1α stabilization and constitutive activation of Sonic Hedgehog (Shh) signaling to promote breast cancer stemness and tumorigenesis. GPT2 overexpression/knockdown in breast cancer cells and xenograft mouse models; measurement of α-KG, PHD2 activity, HIF1α levels; stem cell subpopulation analysis Theranostics High 28839461
2022 GPT2 governs neuronal alanine synthesis and TCA cycle anaplerosis during postnatal brain development; neuron-specific deletion of GPT2 in mice causes motor abnormalities and death pre-weaning identical to germline Gpt2-null; exogenous alanine rescues Gpt2-null neuronal survival in vitro but not motor function in vivo; selective loss of lower motor neurons is observed with age in Gpt2-null mice. Neuron-specific conditional knockout mouse model; metabolomics across postnatal development; in vitro neuronal survival assays with alanine supplementation; in vivo motor neuron histology Human molecular genetics High 34519342
2022 GPT2 is enriched in mitochondria of synaptosomes; loss of Gpt2 leads to decreased excitatory post-synaptic currents (mEPSCs) in hippocampal CA1 pyramidal neurons without changes in inhibitory currents; glutamate release from Gpt2-null synaptosomes is reduced and rescued by alpha-ketoglutarate supplementation; Gpt2-null synaptosomes show decreased TCA cycle intermediates and increased glutamate dehydrogenase activity. Synaptosome fractionation; whole-cell patch-clamp electrophysiology in hippocampal slices; biochemical glutamate release assay from synaptosomes; alpha-ketoglutarate supplementation rescue Molecular brain High 39604975
2022 GPT2 is a direct transcriptional target of HIF-2 (but not HIF-1) in glioblastoma; hypoxia upregulates GPT2 mRNA and protein in a HIF-2-dependent manner via a hypoxia response element in the GPT2 gene; GPT2 localizes to both nucleus and mitochondria in GBM cells and reduces α-KG levels; GPT2 knockout inhibits GBM tumor growth in mice. HIF-2 ChIP/binding to GPT2 hypoxia response element; genetic KO of GPT2 in mouse xenograft; measurement of α-KG levels; HIF-1 vs. HIF-2 selective knockdown Cells High 36010673
2022 Thyroid hormones (THs) transcriptionally upregulate GPT2 in skeletal muscle, thereby regulating glutamine metabolism and anaplerotic fluxes; the TH/GPT2 axis regulates muscle fiber diameter and muscle weight, and protects from muscle atrophy during denervation. Molecular biology, biochemical assays, isotope-tracing with mass spectrometry, denervation experiments in mouse skeletal muscle Cell reports High 35196498
2022 Loss of mitochondrial GPT2 causes early degeneration of locus coeruleus (LC) noradrenergic neurons in mice, with reduced TH+ neuron numbers, selective microgliosis and astrogliosis in LC, decreased norepinephrine in hippocampus and spinal cord, abnormal action potentials, early decreases in phospho-S6 (suggesting impaired protein synthesis/mTOR), and subsequent p62 aggregation and autophagy dysregulation. Gpt2-null mouse model; immunohistochemistry (TH, Fluoro-Jade C, LC3B, p62, p-S6); whole-cell patch-clamp electrophysiology; norepinephrine measurement by HPLC Neurobiology of disease High 35908744
2021 Abrogation of GPT2 in triple-negative breast cancer decreases TCA cycle intermediates, impairs mTORC1 activity, and induces autophagy; in vivo xenograft studies show that autophagy induction correlates with decreased tumor growth upon GPT2 loss. GPT2 knockout in TNBC cell lines; measurement of TCA cycle intermediates; mTORC1 activity assay; autophagy marker analysis; in vivo xenograft experiment International journal of cancer High 33368291
2023 GPT2 promotes breast cancer metastasis by increasing GABA production from glutamate; GABA activates GABAA receptors (specifically requiring the delta subunit GABRD), increasing Ca2+ influx through associated calcium channels, triggering PKC-CREB pathway activation, and upregulating metastasis-related genes (PODXL, MMP3, MMP9). In vitro migration/invasion assays; GABA measurement; Ca2+ influx assay; PKC-CREB pathway analysis; tail vein and mammary gland conditional Gpt2 spontaneous tumor mouse models; GABRD knockdown Theranostics High 36923530
2022 Long noncoding RNA UCA1 interacts with hnRNP I and hnRNP L (RNA-binding proteins) and facilitates their binding to the GPT2 promoter, upregulating GPT2 expression and enhancing glutamine-derived carbon flux into the TCA cycle in bladder cancer cells. RNA immunoprecipitation (RIP); promoter binding assay; GPT2 knockdown/rescue; metabolic flux analysis Translational oncology Medium 35021150
2024 Ku70 interacts with SIX1 in the nucleus of prostate cancer cells (requiring the HD domain of SIX1 and DBD domain of Ku70), and this complex is recruited to the GPT2 promoter; Ku70 enhances SIX1-mediated transcriptional activation of GPT2, promoting α-KG generation and GPT2-dependent cell proliferation and migration. Co-immunoprecipitation; molecular dynamics simulation of Ku70-SIX1 complex; ChIP-seq showing SIX1 binding to GPT2 promoter; Ku70/SIX1 depletion with proliferation/migration assays Oncogene Medium 39488663
2021 PIK3CA mutation in colorectal cancer renders cells more dependent on glutamine by upregulating GPT2 expression through both MEK and PDK1 signaling pathways (PI3K-MEK/PDK1-GPT2 axis); MEK inhibition reduces GPT2 expression and inhibits CRC proliferation. MEK and PDK1 inhibitor treatment; GPT2 expression analysis; in vitro proliferation assays; in vivo tumor models Oncology reports Medium 34751411
2023 Exosomal GPT2 derived from triple-negative breast cancer cells binds to BTRC (beta-transducin repeat containing E3 ubiquitin protein ligase) via co-immunoprecipitation, leading to degradation of phospho-IκBα and promoting breast cancer cell metastasis. Exosome isolation by ultracentrifugation; Co-immunoprecipitation of GPT2 and BTRC; in vitro migration/invasion assays; in vivo tail vein metastasis model Thoracic cancer Medium 37287397
2025 GPT2 acts as a sequential mitochondrial transaminase that, together with the SLC25A11 transporter, supplies nuclear alpha-ketoglutarate (αKG); loss of GPT2 in a mouse model of GPT2 deficiency impairs chromatin demethylation in the developing brain, revealing an inter-organelle pathway linking mitochondrial transaminase activity to nuclear αKG signaling and chromatin regulation. αKG-responsive biosensor system; genetic screen; mouse GPT2 deficiency model; chromatin methylation analysis bioRxivpreprint Medium bio_10.1101_2025.04.06.647450
2025 In Paneth cells, GPT2-mediated alanine catabolism is upregulated during dietary restriction (DR), converting alanine to pyruvate and then to lactate via gluconeogenesis; alanine-derived lactate is shuttled from Paneth cells to neighboring intestinal stem cells to promote TCA cycle activity and enhance ISC function under DR; conditional Gpt2 knockout in vivo abolishes the DR-induced Paneth cell support of ISC function. U-13C alanine isotope tracing; FACS-sorted Paneth cell/ISC co-culture organoid assay; pharmacological and conditional genetic KO of Gpt2; metabolomics bioRxivpreprint Medium bio_10.1101_2025.08.28.672976
2025 GPT2 is the predominant alanine-catabolizing enzyme in MYC-driven liver tumors; GPT2-dependent alanine catabolism feeds the TCA cycle, nucleotide production, and amino acid synthesis; genetic ablation of GPT2 limits MYC-driven liver tumorigenesis; pharmacological inhibition with L-cycloserine (a GPT2 inhibitor) diminishes tumor frequency and attenuates growth of established human liver tumors in transgenic mouse models. In vivo isotope tracing; genetic GPT2 ablation in transgenic MYC-driven liver tumor mice; pharmacological inhibition with L-cycloserine; xenograft human liver tumor models bioRxivpreprint Medium bio_10.1101_2025.07.29.667471
2025 TGF-β activates GPT2 in lung fibroblasts via a glutamine-glutamate-α-ketoglutarate axis to synthesize alanine; GPT2-derived alanine is required for myofibroblast differentiation (α-SMA and COL1A1 expression); GPT2 inhibition depletes alanine and suppresses TGF-β-induced fibrogenic responses, reversible by alanine supplementation; alanine provides carbon/nitrogen for glutamate and proline biosynthesis supporting myofibroblast differentiation. GPT2 inhibition and alanine supplementation rescue; metabolomics; TGF-β-induced differentiation assay; human precision-cut lung slice model bioRxivpreprint Medium bio_10.1101_2025.07.23.666333
2025 β-cell specific Gpt2 deficiency enhances the incretin response (GLP-1 and GIP-mediated insulin secretion) in mice; GPT2 silencing in human β-cells enhances incretin sensitivity, improves β-cell survival, and reverses incretin unresponsiveness in type 2 diabetes islets; GPT2 is markedly induced in human islets from T2D donors and under glucolipotoxicity, positioning GPT2 as a stress-inducible suppressor of incretin signaling. β-cell specific Gpt2 conditional KO mouse model; oral glucose tolerance and insulin secretion assays; GPT2 siRNA silencing in human islets; diet-induced obesity T2D model Research squarepreprint Medium 40630539
2026 Under cardiac pressure overload stress, fibroblasts increase GPT2-mediated conversion of glutamate to α-ketoglutarate, boosting mitochondrial ATP production, leading to fibroblast activation and excess collagen deposition; microRNA-30c-5p delivered via mesenchymal stem cell-derived extracellular vesicles inhibits GPT2, reducing fibrosis in mice and human cardiac cells. GPT2 inhibition by miR-30c-5p delivered via MSC-derived EVs; mouse pressure overload model; human cardiac fibroblast experiments; metabolic assays JACC. Basic to translational science Medium 41880732
2027 GPT2 knockout in platinum-resistant ovarian cancer cells restores metabolic phenotype to that of platinum-sensitive cells by reducing glutaminolysis and TCA-related metabolites and OXPHOS dependency, reversing drug resistance; GPT2 is identified as a critical link between glutaminolysis, TCA cycle, and oxidative phosphorylation in chemoresistance. GPT2 knockout in chemoresistant ovarian cancer cell lines; metabolic profiling; drug sensitivity assays Scientific reports Medium 40835655
2022 SPTBN1, acting as an RNA-binding protein, regulates the mRNA stability of GPT2 in renal clear cell carcinoma; knockdown of SPTBN1 increases GPT2 expression and activates GPT2-dependent glycolysis, promoting ccRCC progression. RNA immunoprecipitation (RIP); actinomycin D mRNA stability assay; SPTBN1 knockdown/overexpression with GPT2 expression and glycolysis readouts; in vivo xenograft Journal of translational medicine Medium 36527113

Source papers

Stage 0 corpus · 53 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2015 Aluminum-Dependent Terminal Differentiation of the Arabidopsis Root Tip Is Mediated through an ATR-, ALT2-, and SOG1-Regulated Transcriptional Response. The Plant cell 88 26320227
2019 Mitochondrial GPT2 plays a pivotal role in metabolic adaptation to the perturbation of mitochondrial glutamine metabolism. Oncogene 69 30765862
2015 Acclimation of metabolism to light in Arabidopsis thaliana: the glucose 6-phosphate/phosphate translocator GPT2 directs metabolic acclimation. Plant, cell & environment 64 25474495
2017 Glutamic Pyruvate Transaminase GPT2 Promotes Tumorigenesis of Breast Cancer Cells by Activating Sonic Hedgehog Signaling. Theranostics 63 28839461
2004 The larval specific lymphatic filarial ALT-2: induction of protection using protein or DNA vaccination. Microbiology and immunology 61 15611611
2012 The Arabidopsis cell cycle checkpoint regulators TANMEI/ALT2 and ATR mediate the active process of aluminum-dependent root growth inhibition. The Plant cell 59 22345493
2016 Mutations in mitochondrial enzyme GPT2 cause metabolic dysfunction and neurological disease with developmental and progressive features. Proceedings of the National Academy of Sciences of the United States of America 54 27601654
2008 Comparison of immunogenicity, protective efficacy of single and cocktail DNA vaccine of Brugia malayi abundant larval transcript (ALT-2) and thioredoxin peroxidase (TPX) in mice. Acta tropica 48 18547532
2000 p24/ING1-ALT1 and p47/ING1-ALT2, distinct alternative transcripts of p33/ING1. Journal of human genetics 48 10807544
2024 Post-translational modification prediction via prompt-based fine-tuning of a GPT-2 model. Nature communications 34 39107330
2015 Loss of function mutation in glutamic pyruvate transaminase 2 (GPT2) causes developmental encephalopathy. Journal of inherited metabolic disease 27 25758935
2021 Abrogating GPT2 in triple-negative breast cancer inhibits tumor growth and promotes autophagy. International journal of cancer 26 33368291
2014 GPT2: a glucose 6-phosphate/phosphate translocator with a novel role in the regulation of sugar signalling during seedling development. Annals of botany 26 24489010
2023 The delta subunit of the GABAA receptor is necessary for the GPT2-promoted breast cancer metastasis. Theranostics 25 36923530
2022 Thyroid hormone regulates glutamine metabolism and anaplerotic fluxes by inducing mitochondrial glutamate aminotransferase GPT2. Cell reports 23 35196498
2020 Enhanced glutamine utilization mediated by SLC1A5 and GPT2 is an essential metabolic feature of colorectal signet ring cell carcinoma with therapeutic potential. Annals of translational medicine 21 32355746
2012 Paralogous ALT1 and ALT2 retention and diversification have generated catalytically active and inactive aminotransferases in Saccharomyces cerevisiae. PloS one 21 23049841
2022 Long noncoding RNA UCA1 promotes glutamine-driven anaplerosis of bladder cancer by interacting with hnRNP I/L to upregulate GPT2 expression. Translational oncology 20 35021150
1992 Adult T-cell leukaemia-derived factor/thioredoxin expression on the HTLV-I transformed T-cell lines: heterogeneous expression in ALT-2 cells. Immunology 17 1398748
2022 GPT2 Is Induced by Hypoxia-Inducible Factor (HIF)-2 and Promotes Glioblastoma Growth. Cells 15 36010673
2019 Phosphorylation of the lipid droplet localized glycerol‑3‑phosphate acyltransferase Gpt2 prevents a futile triacylglycerol cycle in yeast. Biochimica et biophysica acta. Molecular and cell biology of lipids 15 31421179
2021 PIK3CA mutation affects the proliferation of colorectal cancer cells through the PI3K-MEK/PDK1-GPT2 pathway. Oncology reports 14 34751411
2011 The adjuvant-free immunoprotection of recombinant filarial protein Abundant Larval Transcript-2 (ALT-2) in Mastomys coucha and the immunoprophylactic importance of its putative signal sequence. Experimental parasitology 13 21864531
2010 Production and single-step purification of Brugia malayi abundant larval transcript (ALT-2) using hydrophobic interaction chromatography. Journal of industrial microbiology & biotechnology 13 20593300
2018 GPT2 mutations cause developmental encephalopathy with microcephaly and features of complicated hereditary spastic paraplegia. Clinical genetics 12 29882329
2022 Mitochondrial enzyme GPT2 regulates metabolic mechanisms required for neuron growth and motor function in vivo. Human molecular genetics 11 34519342
2022 SPTBN1 abrogates renal clear cell carcinoma progression via glycolysis reprogramming in a GPT2-dependent manner. Journal of translational medicine 11 36527113
2022 Loss of mitochondrial enzyme GPT2 causes early neurodegeneration in locus coeruleus. Neurobiology of disease 10 35908744
2017 Novel compound heterozygous mutations in GPT2 linked to microcephaly, and intellectual developmental disability with or without spastic paraplegia. American journal of medical genetics. Part A 10 29226631
2023 System analysis based on glutamine catabolic-related enzymes identifies GPT2 as a novel immunotherapy target for lung adenocarcinoma. Computers in biology and medicine 7 37657356
2020 A novel missense variant in GPT2 causes non-syndromic autosomal recessive intellectual disability in a consanguineous Iranian family. European journal of medical genetics 7 31978613
2019 GPT2 mutations in autosomal recessive developmental disability: extending the clinical phenotype and population prevalence estimates. Human genetics 7 31471722
2016 Epitope mapping of Brugia malayi ALT-2 and the development of a multi-epitope vaccine for lymphatic filariasis. Journal of helminthology 7 26892175
2025 Targeting HVEM-GPT2 axis: a novel approach to T cell activation and metabolic reprogramming in non-small cell lung cancer therapy. Cancer immunology, immunotherapy : CII 6 39904774
2017 A Homozygous Mutation in GPT2 Associated with Nonsyndromic Intellectual Disability in a Consanguineous Family from Costa Rica. JIMD reports 6 28130718
2016 Filarial Abundant Larval Transcript Protein ALT-2: An Immunomodulatory Therapeutic Agent for Type 1 Diabetes. Indian journal of clinical biochemistry : IJCB 6 28149012
2023 Exosomal GPT2 derived from triple-negative breast cancer cells promotes metastasis by activating BTRC. Thoracic cancer 5 37287397
2024 The Ku70-SIX1-GPT2 axis regulates alpha-ketoglutarate metabolism to drive progression of prostate cancer. Oncogene 4 39488663
2022 Comment on 'Long noncoding RNA UCA1 promotes glutamine-driven anaplerosis of bladder cancer by interacting with hnRNP I/L to upregulate GPT2 expression' by Chen et al.'". Translational oncology 3 35182956
2025 A Role for the Plastidial GPT2 Translocator in the Modulation of Lignin Biosynthesis. Plant, cell & environment 2 40377235
2025 GPT2 mediates glutamine metabolism-driven metabolic alterations in platinum-resistant ovarian cancer cells. Scientific reports 2 40835655
2024 Loss of mitochondrial enzyme GPT2 leads to reprogramming of synaptic glutamate metabolism. Molecular brain 2 39604975
2024 Oncogenic Functions of Alternatively Spliced MDM2-ALT2 Isoform in Retroperitoneal Liposarcoma. International journal of molecular sciences 2 39769278
2022 Paternal uniparental disomy of chromosome 16 resulting in homozygosity of a GPT2 mutation causes intellectual and developmental disability. European journal of medical genetics 2 35793769
2014 Immunomodulation of ALT-2 and TLR may collude in antigen specific T cell hyporesponsiveness: proposed mechanism for elevated IL-10 levels in Balb/C mice. Acta parasitologica 2 24570047
2025 GPT2 mediates metabolic alterations in platinum-resistant ovarian cancer cells. Research square 1 40386427
2024 Loss of mitochondrial enzyme GPT2 leads to reprogramming of synaptic glutamate metabolism. bioRxiv : the preprint server for biology 1 39574728
2026 GPT2-mediated Glutamate to α-Ketoglutaric Acid Conversion in Cardiac Fibroblast Promotes Fibrosis. JACC. Basic to translational science 0 41880732
2025 The pancreatic β-cell incretin response is modulated by mitochondrial transaminase GPT2. Research square 0 40630539
2025 GPT2-ICC: A data-driven approach for accurate ion channel identification using pre-trained large language models. Journal of pharmaceutical analysis 0 40919588
2025 A Deep Learning Pipeline for Epilepsy Genomic Analysis Using GPT-2 XL and NVIDIA H100. ArXiv 0 41256893
2014 Functional analysis of a highly conserved abundant larval transcript-2 (alt-2) intron 2 repeat region of lymphatic filarial parasites. Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases 0 24681262
2010 [Expression of recombinant human alanine aminotransferase (ALT) isoenzyme 2 and preparation of anti-ALT2 monoclonal antibody]. Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology 0 21138690