Affinage

GAN

Gigaxonin · UniProt Q9H2C0

Round 2 corrected
Length
597 aa
Mass
67.6 kDa
Annotated
2026-04-28
130 papers in source corpus 10 papers cited in narrative 10 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

Gigaxonin is a BTB-Kelch substrate adaptor for the Cul3-based E3 ubiquitin ligase complex that targets cytoskeletal and intermediate filament proteins for proteasomal degradation. Its N-terminal BTB domain binds ubiquitin-activating enzyme E1 and mediates Cul3 interaction, while its C-terminal kelch-repeat β-propeller engages substrates including MAP1B light chain, tubulin folding cofactor B (TBCB), vimentin, peripherin, GFAP, and neurofilament proteins, promoting their ubiquitin-dependent turnover (PMID:16227972, PMID:16303566, PMID:23585478). Loss-of-function mutations in GAN cause giant axonal neuropathy, a severe autosomal recessive sensorimotor neuropathy characterized by pathological accumulation of intermediate filaments and cytoskeletal proteins in neurons, astrocytes, and fibroblasts (PMID:11062483, PMID:37672338). Patient-derived iPSC models demonstrate that vimentin is an early effector of gigaxonin deficiency, with perinuclear vimentin aggregates driving secondary GFAP accumulation and abnormal nuclear morphology in astrocytes (PMID:37672338).

Mechanistic history

Synthesis pass · year-by-year structured walk · 5 steps
  1. 2000 High

    Positional cloning identified GAN as the causative gene for giant axonal neuropathy, revealing a novel BTB-kelch domain protein whose loss-of-function mutations cause generalized intermediate filament disorganization — establishing that a single E3-adaptor-like protein governs IF homeostasis.

    Evidence Positional cloning and mutation screening in GAN patient families

    PMID:11062483

    Open questions at the time
    • No biochemical substrates or binding partners identified at this stage
    • Mechanism of IF accumulation unknown
  2. 2002 High

    Discovery that gigaxonin directly binds MAP1B light chain via its kelch repeats identified the first substrate interaction and linked gigaxonin to microtubule stability and axonal transport, with disease mutations abolishing this binding.

    Evidence Yeast two-hybrid, reciprocal co-IP, co-localization in neurons, disease-mutation disruption

    PMID:12147674

    Open questions at the time
    • Whether gigaxonin promotes MAP1B-LC degradation or merely sequesters it was unclear
    • Other substrates not yet tested
  3. 2005 High

    Three convergent studies established gigaxonin as a ubiquitin-proteasome pathway adaptor: it drives proteasomal degradation of MAP1B-LC and TBCB, binds E1 via its BTB domain, and is itself ubiquitinated by a Cul3-dependent complex — placing it firmly in the BTB-Kelch/Cul3 E3 ligase system and demonstrating that substrate accumulation upon gigaxonin loss is directly neurotoxic.

    Evidence GAN-null mouse neurons with rescue and survival assays (MAP1B-LC); co-IP with proteasome inhibitor block (TBCB); in vivo Cul3-dependent ubiquitination assays

    PMID:15983046 PMID:16227972 PMID:16303566

    Open questions at the time
    • Whether gigaxonin directly ubiquitinates substrates or recruits Cul3 to do so was not resolved biochemically
    • Intermediate filament proteins not yet tested as substrates
    • Structural basis of kelch–substrate interaction unknown
  4. 2013 High

    Extension of gigaxonin's substrate repertoire to intermediate filament proteins — vimentin in fibroblasts and peripherin/neurofilaments in neurons — demonstrated that gigaxonin is a master regulator of IF turnover, not only of MAPs, providing the molecular explanation for the hallmark IF aggregates in GAN.

    Evidence GAN patient fibroblasts, Gan−/− mouse neurons, gigaxonin overexpression/MG-132 proteasome inhibition, immunoblot and immunofluorescence

    PMID:23585478

    Open questions at the time
    • Whether gigaxonin targets all IF classes or only neuronal and type III IFs is unclear
    • Precise ubiquitination sites on IF substrates not mapped
    • No reconstituted in vitro ubiquitination assay with purified components
  5. 2023 High

    Patient iPSC-derived astrocytes and brain organoids revealed that vimentin is the earliest effector of gigaxonin loss, with vimentin aggregates secondarily promoting GFAP accumulation and trapping KLHL16 mRNA — establishing a feed-forward aggregation mechanism in astrocytes.

    Evidence GAN patient iPSC-derived NPCs, astrocytes, and brain organoids with CRISPR isogenic controls; overexpression assays; RNA FISH

    PMID:37672338

    Open questions at the time
    • Whether mRNA trapping by vimentin aggregates reduces gigaxonin protein and worsens pathology in vivo is untested
    • Contribution of astrocyte dysfunction vs. neuronal pathology to disease progression not delineated
    • No therapeutic rescue demonstrated in organoid model

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key open questions include the structural basis of kelch-domain substrate recognition, whether gigaxonin directly assembles a Cul3-RING catalytic complex for substrate ubiquitination (vs. indirect degradation routes), and the relative contribution of individual substrate accumulation to neurodegeneration in vivo.
  • No crystal or cryo-EM structure of gigaxonin–substrate complex
  • No reconstituted Cul3–gigaxonin ubiquitination assay with defined substrates
  • Relative pathogenic contribution of MAP1B-LC, TBCB, and IF accumulation not resolved in animal models

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008092 cytoskeletal protein binding 4 GO:0060090 molecular adaptor activity 4
Localization
GO:0005856 cytoskeleton 3 GO:0005829 cytosol 2
Pathway
R-HSA-112316 Neuronal System 4 R-HSA-392499 Metabolism of proteins 4 R-HSA-1643685 Disease 3
Partners
CUL3GFAPMAP1BPRPHTBCBVIM
Complex memberships
Cul3-BTB-Kelch E3 ubiquitin ligase complex

Evidence

Reading pass · 10 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 Identification of the GAN gene encoding gigaxonin, a novel ubiquitously expressed protein with an N-terminal BTB domain followed by six kelch repeats predicted to form a beta-propeller. Loss-of-function mutations (frameshift, nonsense, and missense) in GAN cause giant axonal neuropathy, a severe autosomal recessive sensorimotor neuropathy characterized by neurofilament accumulation and generalized intermediate filament disorganization (vimentin in fibroblasts/Schwann cells/endothelial cells, GFAP in astrocytes). Positional cloning, mutation screening (sequencing of GAN patients), domain analysis Nature genetics High 11062483
2002 Gigaxonin directly binds to the light chain (LC) of microtubule-associated protein 1B (MAP1B-LC) through its C-terminal kelch repeat domain. This interaction was demonstrated by yeast two-hybrid screening, co-transfection, and co-immunoprecipitation. Gigaxonin and MAP1B-LC co-localize in neurons, and their interaction enhances microtubule stability required for axonal transport. At least two GAN patient mutations abolish the gigaxonin-MAP1B-LC interaction. Yeast two-hybrid screening, co-immunoprecipitation, double immunofluorescence microscopy, ultrastructural analysis, co-transfection The Journal of cell biology High 12147674
2005 Gigaxonin controls proteasome-dependent degradation of MAP1B-LC by binding to ubiquitin-activating enzyme E1 through its N-terminal BTB domain while engaging MAP1B-LC via its kelch repeats. Overexpression of gigaxonin enhances MAP1B-LC degradation, which is blocked by proteasome inhibitors. Ablation of gigaxonin in GAN-null neurons causes substantial MAP1B-LC accumulation. Overexpression of MAP1B in wild-type neurons causes neuronal death similar to GAN-null neurons, while reducing MAP1B improves survival of null neurons, establishing MAP1B-LC accumulation as a causal mechanism of neurodegeneration. Co-immunoprecipitation, overexpression/knockdown in cortical neurons, proteasome inhibitor treatment, GAN-null mouse neurons, neuronal survival assays Nature High 16227972
2005 Gigaxonin controls ubiquitin-proteasome-dependent degradation of tubulin folding cofactor B (TBCB). GAN patient mutations impair this function, leading to TBCB protein accumulation. Gigaxonin interacts with TBCB, and this interaction is disrupted by disease-associated GAN mutations, providing a mechanism for the microtubule deficiency (few microtubules) observed in GAN cytoskeletal pathology. Co-immunoprecipitation, overexpression studies, proteasome inhibition, patient mutation analysis Current biology High 16303566
2005 Gigaxonin (GAN1) is ubiquitinated by a Cul3-dependent E3 ubiquitin ligase complex, establishing gigaxonin as both a substrate adaptor for Cul3 and itself a substrate of this complex. This places gigaxonin within the BTB-Kelch/Cul3 ubiquitin ligase system. Three other BTB-Kelch proteins (Keap1, ENC1, Sarcosin) are similarly ubiquitinated by Cul3-dependent complexes. In vivo ubiquitination assays, cell-based ubiquitination with Cul3 constructs, immunoblotting The Journal of biological chemistry Medium 15983046
2007 Genotype-phenotype analysis of GAN patients confirms that gigaxonin binds N-terminally to ubiquitin activating enzyme E1 and C-terminally to various microtubule-associated proteins, causing their ubiquitin-mediated degradation. Multiple GAN mutations (splice-site and missense in BTB, BACK, and kelch domains) impede this degradation process, leading to accumulation of microtubule-associated proteins and impaired cellular functions. Molecular genetic analysis, mutation sequencing across patient cohort (10 patients), literature synthesis with functional interpretation Neuromuscular disorders Medium 17587580
2013 Gigaxonin is responsible for ubiquitin-proteasome-dependent degradation of vimentin intermediate filaments (IFs) in fibroblasts and of peripherin and neurofilament IF proteins in neurons. Using GAN patient fibroblasts and Gan-/- mice, gigaxonin loss causes IF protein accumulation. Proteasome inhibition with MG-132 reverses gigaxonin-induced IF clearance, confirming proteasomal involvement. This identifies gigaxonin as a major regulator of cytoskeletal IF degradation and provides a molecular explanation for IF aggregate accumulation in GAN. Patient fibroblast cultures, Gan-/- mouse neurons, gigaxonin overexpression, MG-132 proteasome inhibition, immunofluorescence, immunoblotting The Journal of clinical investigation High 23585478
2016 GAN mutations occur in domains associated with protein homodimerization and substrate interaction: the BTB domain, BTB-associated C-terminal BACK domain, and KELCH repeats. Gigaxonin functions as an E3 ubiquitin ligase adaptor protein involved in intermediate filament processing in neural cells and vimentin filaments in fibroblasts. Identical missense and nonsense GAN mutations are found in both GAN patients and cancer cell lines/primary tumors, suggesting shared pathological mechanisms. Database analysis of cancer genomic sequences (COSMIC, DriverDB, IDGC), comparison with GAN patient mutation database, domain mapping Human genetics Low 27023907
2023 GAN (KLHL16) patient-derived iPSCs reprogrammed to astrocytes, neural progenitor cells (NPCs), and brain organoids reveal that gigaxonin deficiency causes striking perinuclear vimentin and GFAP accumulations and abnormal nuclear morphology in astrocytes. GAN NPCs have lower nestin expression. GAN brain organoids show neurofilament and GFAP aggregates. In overexpression systems, GFAP oligomerization and perinuclear aggregation are augmented in the presence of vimentin. Cells with large perinuclear vimentin aggregates accumulate significantly more nuclear KLHL16 mRNA, suggesting vimentin aggregates trap KLHL16 mRNA. Vimentin is identified as an early effector of KLHL16/gigaxonin mutations. iPSC reprogramming from GAN patient fibroblasts, CRISPR/Cas9 isogenic controls, NPC and astrocyte differentiation, brain organoids, overexpression assays, immunofluorescence, RNA FISH Molecular biology of the cell High 37672338
2009 Downregulation of Gan1 gene expression and gigaxonin protein levels occurs in mouse spinal dorsal horn in a model of NRTI-induced peripheral neuropathy, suggesting gigaxonin loss-of-function contributes to nerve pathology beyond inherited GAN mutations. Whole-genome microarray screen, quantitative PCR validation, Western blot in mouse spinal dorsal horn tissue Biological research for nursing Low 19398414

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. Cell 2861 17081983
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2010 Network organization of the human autophagy system. Nature 1286 20562859
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1118 26186194
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2018 VIRMA mediates preferential m6A mRNA methylation in 3'UTR and near stop codon and associates with alternative polyadenylation. Cell discovery 829 29507755
2003 Complete sequencing and characterization of 21,243 full-length human cDNAs. Nature genetics 754 14702039
2012 Quantitative analysis of HSP90-client interactions reveals principles of substrate recognition. Cell 708 22939624
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2022 OpenCell: Endogenous tagging for the cartography of human cellular organization. Science (New York, N.Y.) 432 35271311
2004 14-3-3-affinity purification of over 200 human phosphoproteins reveals new links to regulation of cellular metabolism, proliferation and trafficking. The Biochemical journal 372 14744259
2014 A quantitative chaperone interaction network reveals the architecture of cellular protein homeostasis pathways. Cell 325 25036637
2000 The gene encoding gigaxonin, a new member of the cytoskeletal BTB/kelch repeat family, is mutated in giant axonal neuropathy. Nature genetics 322 11062483
2010 Dynamics of cullin-RING ubiquitin ligase network revealed by systematic quantitative proteomics. Cell 318 21145461
2005 Ubiquitination of Keap1, a BTB-Kelch substrate adaptor protein for Cul3, targets Keap1 for degradation by a proteasome-independent pathway. The Journal of biological chemistry 256 15983046
2016 An organelle-specific protein landscape identifies novel diseases and molecular mechanisms. Nature communications 211 27173435
2013 Update on the Kelch-like (KLHL) gene family. Human genomics 211 23676014
1993 (CT)n (GA)n repeats and heat shock elements have distinct roles in chromatin structure and transcriptional activation of the Drosophila hsp26 gene. Molecular and cellular biology 210 8474442
2005 Targeted proteomic analysis of 14-3-3 sigma, a p53 effector commonly silenced in cancer. Molecular & cellular proteomics : MCP 153 15778465
2022 A comprehensive SARS-CoV-2-human protein-protein interactome reveals COVID-19 pathobiology and potential host therapeutic targets. Nature biotechnology 140 36217030
2005 Gigaxonin-controlled degradation of MAP1B light chain is critical to neuronal survival. Nature 114 16227972
2013 Giant axonal neuropathy-associated gigaxonin mutations impair intermediate filament protein degradation. The Journal of clinical investigation 108 23585478
2010 Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score. Molecular medicine (Cambridge, Mass.) 108 20379614
2012 Mechanism by which ma-xing-shi-gan-tang inhibits the entry of influenza virus. Journal of ethnopharmacology 100 22710290
2020 Human translatability of the GAN diet-induced obese mouse model of non-alcoholic steatohepatitis. BMC gastroenterology 98 32631250
1990 Optimal heat-induced expression of the Drosophila hsp26 gene requires a promoter sequence containing (CT)n.(GA)n repeats. Journal of molecular biology 85 2313697
2020 Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains. Cell reports 79 32814053
2002 Microtubule-associated protein 1B: a neuronal binding partner for gigaxonin. The Journal of cell biology 79 12147674
2005 Gigaxonin interacts with tubulin folding cofactor B and controls its degradation through the ubiquitin-proteasome pathway. Current biology : CB 75 16303566
2018 E3 Ligase Trim21 Ubiquitylates and Stabilizes Keratin 17 to Induce STAT3 Activation in Psoriasis. The Journal of investigative dermatology 73 29859926
2022 Scalable multiplex co-fractionation/mass spectrometry platform for accelerated protein interactome discovery. Nature communications 65 35831314
2019 TOP-GAN: Stain-free cancer cell classification using deep learning with a small training set. Medical image analysis 63 31325721
2022 Hepatoprotective effects of semaglutide, lanifibranor and dietary intervention in the GAN diet-induced obese and biopsy-confirmed mouse model of NASH. Clinical and translational science 59 35143711
2017 Cullin 3-Based Ubiquitin Ligases as Master Regulators of Mammalian Cell Differentiation. Trends in biochemical sciences 59 29249570
2019 PINK1 Content in Mitochondria is Regulated by ER-Associated Degradation. The Journal of neuroscience : the official journal of the Society for Neuroscience 58 31300519
2013 Chromatographic isolation of nanoparticles from Ma-Xing-Shi-Gan-Tang decoction and their characterization. Journal of ethnopharmacology 52 24384378
2020 Highly Sensitive and Selective Photoelectrochemical Aptasensor for Cancer Biomarker CA125 Based on AuNPs/GaN Schottky Junction. Analytical chemistry 48 32580543
2020 Ling-gui-zhu-gan decoction alleviates hepatic steatosis through SOCS2 modification by N6-methyladenosine. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 47 32559839
2022 PHIAF: prediction of phage-host interactions with GAN-based data augmentation and sequence-based feature fusion. Briefings in bioinformatics 37 34472593
2006 The UAA/GAN internal loop motif: a new RNA structural element that forms a cross-strand AAA stack and long-range tertiary interactions. Journal of molecular biology 36 16828489
2020 Combining DC-GAN with ResNet for blood cell image classification. Medical & biological engineering & computing 35 32221797
2021 Highly Sensitive and Selective Photoelectrochemical Aptasensors for Cancer Biomarkers Based on MoS2/Au/GaN Photoelectrodes. Analytical chemistry 34 33961398
2017 Accurate recognition and feature qualify for flavonoid extracts from Liang-wai Gan Cao by liquid chromatography-high resolution-mass spectrometry and computational MS/MS fragmentation. Journal of pharmaceutical and biomedical analysis 31 28850862
2008 Functional reconstitution of the human chemokine receptor CXCR4 with G(i)/G (o)-proteins in Sf9 insect cells. Naunyn-Schmiedeberg's archives of pharmacology 30 18523757
2004 A study on the effects to diabetic nephropathy of Hachimi-jio-gan in rats. Nephron. Experimental nephrology 30 15218322
2023 Semaglutide reduces tumor burden in the GAN diet-induced obese and biopsy-confirmed mouse model of NASH-HCC with advanced fibrosis. Scientific reports 29 38155202
2020 Qiang-Gan formula extract improves non-alcoholic steatohepatitis via regulating bile acid metabolism and gut microbiota in mice. Journal of ethnopharmacology 29 32325178
2019 The traditional Chinese formulae Ling-gui-zhu-gan decoction alleviated non-alcoholic fatty liver disease via inhibiting PPP1R3C mediated molecules. BMC complementary and alternative medicine 29 30616587
2021 iEnhancer-GAN: A Deep Learning Framework in Combination with Word Embedding and Sequence Generative Adversarial Net to Identify Enhancers and Their Strength. International journal of molecular sciences 28 33808317
2007 Genotype-phenotype analysis in patients with giant axonal neuropathy (GAN). Neuromuscular disorders : NMD 27 17587580
2021 Lnc-GAN1 expression is associated with good survival and suppresses tumor progression by sponging mir-26a-5p to activate PTEN signaling in non-small cell lung cancer. Journal of experimental & clinical cancer research : CR 26 33407724
2021 The TCM prescription Ma-xing-shi-gan-tang inhibits Streptococcus pneumoniae pathogenesis by targeting pneumolysin. Journal of ethnopharmacology 24 33892068
2008 Gosha-jinki-gan reduces transmitter proteins and sensory receptors associated with C fiber activation induced by acetic acid in rat urinary bladder. Neurourology and urodynamics 24 18551569
2020 Optimization of O-GIG for O-Glycopeptide Characterization with Sialic Acid Linkage Determination. Analytical chemistry 23 32663021
2013 Direct label free ultrasensitive impedimetric DNA biosensor using dendrimer functionalized GaN nanowires. Biosensors & bioelectronics 23 23425555
2018 Yu Gan Long reduces rat liver fibrosis by blocking TGF-β1/Smad pathway and modulating the immunity. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 21 30119204
2016 A review of gigaxonin mutations in giant axonal neuropathy (GAN) and cancer. Human genetics 20 27023907
2007 Effects of Hachimi-jio-gan (Ba-Wei-Di-Huang-Wan) on hyperglycemia in streptozotocin-induced diabetic rats. Biological & pharmaceutical bulletin 20 17473455
2019 Daiokanzoto (Da-Huang-Gan-Cao-Tang) is an effective laxative in gut microbiota associated with constipation. Scientific reports 19 30846728
2017 The GAN Exonuclease or the Flap Endonuclease Fen1 and RNase HII Are Necessary for Viability of Thermococcus kodakarensis. Journal of bacteriology 19 28416706
2009 Genome-wide screen identifies drug-induced regulation of the gene giant axonal neuropathy (Gan) in a mouse model of antiretroviral-induced painful peripheral neuropathy. Biological research for nursing 19 19398414
2004 Gosha-jinki-gan (a Herbal Complex) Corrects Abnormal Insulin Signaling. Evidence-based complementary and alternative medicine : eCAM 19 15841260
2018 Gosha-Jinki-Gan Recovers Spermatogenesis in Mice with Busulfan-Induced Aspermatogenesis. International journal of molecular sciences 17 30177609
2023 GAN-based data augmentation for transcriptomics: survey and comparative assessment. Bioinformatics (Oxford, England) 16 37387181
2015 Protective effect of Huang Gan formula in 5/6 nephrectomized rats by depressing the Wnt/β-catenin signaling pathway. Drug design, development and therapy 16 26082617
2018 Effect of Soothing Gan (Liver) and Invigorating Pi (Spleen) Recipes on TLR4-p38 MAPK Pathway in Kupffer Cells of Non-alcoholic Steatohepatitis Rats. Chinese journal of integrative medicine 15 29335857
2016 Gan-Lu-Siao-Du-yin, a prescription of traditional Chinese medicine, inhibited enterovirus 71 replication, translation, and virus-induced cell apoptosis. Journal of ethnopharmacology 15 26993050
2010 Effects of a Chinese herbal health formula, "Gan-Lu-Yin", on angiogenesis. Journal of agricultural and food chemistry 15 20527984
2024 Huang Gan Formula Alleviates Systemic Inflammation and Uremia in Adenine-Induced Chronic Kidney Disease Rats May Associate with Modification of Gut Microbiota and Colonic Microenvironment. Drug design, development and therapy 14 38205394
2024 Dietary intervention reverses molecular markers of hepatocellular senescence in the GAN diet-induced obese and biopsy-confirmed mouse model of NASH. BMC gastroenterology 14 38308212
2022 Single-cell multi-modal GAN reveals spatial patterns in single-cell data from triple-negative breast cancer. Patterns (New York, N.Y.) 14 36124302
2020 Ma xing shi gan decoction eliminates PM2.5-induced lung injury by reducing pulmonary cell apoptosis through Akt/mTOR/p70S6K pathway in rats. Bioscience reports 14 32627816
2018 Two novel mutations in the GAN gene causing giant axonal neuropathy. World journal of pediatrics : WJP 14 29876741
2022 Effector-GAN: prediction of fungal effector proteins based on pretrained deep representation learning methods and generative adversarial networks. Bioinformatics (Oxford, England) 13 35640972
2013 A novel mutation in the GAN gene causes an intermediate form of giant axonal neuropathy in an Arab-Israeli family. European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society 13 23332420
2024 Ling-Gui-Zhu-Gan decoction ameliorates nonalcoholic fatty liver disease via modulating the gut microbiota. Microbiology spectrum 12 38647315
2022 iPro-GAN: A novel model based on generative adversarial learning for identifying promoters and their strength. Computer methods and programs in biomedicine 12 35038653
2016 Electronic and chemical structure of the H2O/GaN(0001) interface under ambient conditions. Scientific reports 12 27108711
2010 Herb medicine Gan-fu-kang attenuates liver injury in a rat fibrotic model. Journal of ethnopharmacology 12 20056141
2024 The potential linkage between sediment oxygen demand and microbes and its contribution to the dissolved oxygen depletion in the Gan River. Frontiers in microbiology 11 39144217
2024 Pharmacological mechanisms of Ma Xing Shi Gan Decoction in treating influenza virus-induced pneumonia: intestinal microbiota and pulmonary glycolysis. Frontiers in pharmacology 11 39161892
2023 MutaGAN: A sequence-to-sequence GAN framework to predict mutations of evolving protein populations. Virus evolution 11 37066021
2020 Co-Administration of the Traditional Medicines Hachimi-Jio-Gan and Hochu-Ekki-To Can Reverse Busulfan-Induced Aspermatogenesis. International journal of molecular sciences 11 32138301
2022 The effect of Ma-Xin-Gan-Shi decoction on asthma exacerbated by respiratory syncytial virus through regulating TRPV1 channel. Journal of ethnopharmacology 10 35247474
2022 Network pharmacology analysis on mechanism of Jian Pi Qing Gan Yin decoction ameliorating high fat diet-induced non-alcoholic fatty liver disease and validated in vivo. Journal of ethnopharmacology 10 35577161
2014 Anti-tumor effect of Shu-Gan-Liang-Xue decoction in breast cancer is related to the inhibition of aromatase and steroid sulfatase expression. Journal of ethnopharmacology 10 24809288
2008 Herbal medicine, Hachimi-jio-gan, and its component cinnamomi cortex activate the peroxisome proliferator-activated receptor alpha in renal cells. Endocrine journal 10 18469482
2024 AGImpute: imputation of scRNA-seq data based on a hybrid GAN with dropouts identification. Bioinformatics (Oxford, England) 9 38317025
2021 From rumor to genetic mutation detection with explanations: a GAN approach. Scientific reports 9 33712675
2021 Increasing prediction accuracy of pathogenic staging by sample augmentation with a GAN. PloS one 9 33905431
2021 Comprehensive RNA-Seq Analysis of Potential Therapeutic Targets of Gan-Dou-Fu-Mu Decoction for Treatment of Wilson Disease Using a Toxic Milk Mouse Model. Frontiers in pharmacology 9 33935715
2020 Vimentin's side gig: Regulating cellular proteostasis in mammalian systems. Cytoskeleton (Hoboken, N.J.) 9 33190414
2016 Bo-Gan-Whan regulates proliferation and migration of vascular smooth muscle cells. BMC complementary and alternative medicine 9 27549769
2007 AlGaN/GaN heterostructures for non-invasive cell electrophysiological measurements. Biosensors & bioelectronics 9 17766103
2025 Vitality attributes and their associations with intrinsic capacity, resilience, and happiness in community-dwelling adults: Results from Gan-Dau Healthy Longevity Plan Wave 2. The journal of nutrition, health & aging 8 40305974
2025 Intestinal IL-17 family orchestrates microbiota-driven histone deacetylation and promotes Treg differentiation to mediate the alleviation of asthma by Ma-Xing-Shi-Gan decoction. Phytomedicine : international journal of phytotherapy and phytopharmacology 8 40311598
2023 Therapeutic effects and mechanisms of Ku-Gan formula on atopic dermatitis: A pilot clinical study and modular pharmacology analysis with animal validation. Journal of ethnopharmacology 8 36716903
2022 3D GAN image synthesis and dataset quality assessment for bacterial biofilm. Bioinformatics (Oxford, England) 8 35924980
2020 Go-sha-jinki-Gan Alleviates Inflammation in Neurological Disorders via p38-TNF Signaling in the Central Nervous System. Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics 8 33083995
2020 Glycyrrhizin, the active compound of the TCM drug Gan Cao stimulates actin remodelling and defence in grapevine. Plant science : an international journal of experimental plant biology 8 33288019
2017 The Legionella pneumophila GIG operon responds to gold and copper in planktonic and biofilm cultures. PloS one 8 28463986
2013 Gan-Lu-Yin Inhibits Proliferation and Migration of Murine WEHI-3 Leukemia Cells and Tumor Growth in BALB/C Allograft Tumor Model. Evidence-based complementary and alternative medicine : eCAM 8 23573143
2005 Hepatoprotective mechanisms of Yan-gan-wan. Hepatology research : the official journal of the Japan Society of Hepatology 8 16107322
2024 Ling-Gui-Zhu-Gan decoction protects against doxorubicin-induced myocardial injury by downregulating ferroptosis. The Journal of pharmacy and pharmacology 7 38241142
2023 The protective effects of Zhi-Gan-Cao-Tang against diabetic myocardial infarction injury and identification of its effective constituents. Journal of ethnopharmacology 7 36828197
2023 First-principles study of controllable contact types in Janus MoSH/GaN van der Waals heterostructure. The Journal of chemical physics 7 37655766
2023 Intermediate filament dysregulation in astrocytes in the human disease model of KLHL16 mutation in giant axonal neuropathy (GAN). Molecular biology of the cell 7 37672338
2023 SIGANEO: Similarity network with GAN enhancement for immunogenic neoepitope prediction. Computational and structural biotechnology journal 7 38034402
2022 Major Plant in Herbal Mixture Gan-Mai-Da-Zao for the Alleviation of Depression in Rat Models. Plants (Basel, Switzerland) 7 35161241
2022 A Versatile, Incubator-Compatible, Monolithic GaN Photonic Chipscope for Label-Free Monitoring of Live Cell Activities. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 7 35404518
2021 Giant axonal neuropathy (GAN) in an 8-year-old girl caused by a homozygous pathogenic splicing variant in GAN gene. American journal of medical genetics. Part A 7 34889507
2014 Enhanced cell growth on nanotextured GaN surface treated by UV illumination and fibronectin adsorption. Colloids and surfaces. B, Biointerfaces 7 25264283
2012 Effect and mechanisms of Gong-tone music on the immunological function in rats with Liver (Gan)-qi depression and Spleen (Pi)-qi deficiency syndrome in rats. Chinese journal of integrative medicine 7 22241503
2012 Rokumi-jio-gan-Containing Prescriptions Attenuate Oxidative Stress, Inflammation, and Apoptosis in the Remnant Kidney. Evidence-based complementary and alternative medicine : eCAM 7 23243456
2025 Novel dual gland GAN architecture improves human protein localization classification using salivary and pituitary gland inspired loss functions. Scientific reports 6 40750975
2024 Metabolic profile and bioactivity of the peel of Zhoupigan (Citrus reticulata cv. Manau Gan), a special citrus variety in China, based on GC-MS, UPLC-ESI-MS/MS analysis, and in vitro assay. Food chemistry: X 6 39224696
2024 Intrinsic Capacity Impairments (ICOPE Step 1 and Step 2), Cardiometabolic Risk and Immune Resilience: An Exploratory Analysis from the Gan-Dau Healthy Longevity Plan. The Journal of frailty & aging 6 39574280
2023 Exploring the molecular mechanism of Gan Shuang granules for the treatment of non-alcoholic steatohepatitis using network pharmacology, molecular docking, and experimental verification. Frontiers in pharmacology 6 36762105
2023 HER2GAN: Overcome the Scarcity of HER2 Breast Cancer Dataset Based on Transfer Learning and GAN Model. Clinical breast cancer 6 37926662
2021 Shu-Di-Huang and Gan-Cao Herb Pair Restored the Differentiation Potentials of Mesenchymal Stem Progenitors in Treating Osteoporosis via Downregulation of NF-κB Signaling Pathway. Evidence-based complementary and alternative medicine : eCAM 6 34950216
2011 Shu-Gan-Liang-Xue Decoction Simultaneously Down-regulates Expressions of Aromatase and Steroid Sulfatase in Estrogen Receptor Positive Breast Cancer Cells. Chinese journal of cancer research = Chung-kuo yen cheng yen chiu 6 23467843
2023 Exploring the molecular mechanism of Ling-Gui-Zhu-Gan decoction for the treatment of type 2 diabetes mellitus based on network pharmacology and molecular docking: A review. Medicine 5 36961137
2023 Role of PGC-1α mediated synaptic plasticity, mitochondrial function, and neuroinflammation in the antidepressant effect of Zi-Shui-Qing-Gan-Yin. Frontiers in neurology 5 37251232
2023 Molecular mechanism of Gan-song Yin inhibiting the proliferation of renal tubular epithelial cells by regulating miR-21-5p in adipocyte exosomes. Journal of ethnopharmacology 5 38043753
2022 Clinical Evidence and Potential Mechanisms of Complementary Treatment of Ling Gui Zhu Gan Formula for the Management of Serum Lipids and Obesity. Evidence-based complementary and alternative medicine : eCAM 5 35586687
2022 Integrating UPLC-HR-MS/MS, Network Pharmacology, and Experimental Validation to Uncover the Mechanisms of Jin'gan Capsules against Breast Cancer. ACS omega 5 35990498
2020 Modified p-GaN Microwells with Vertically Aligned 2D-MoS2 for Enhanced Photoelectrochemical Water Splitting. ACS applied materials & interfaces 5 32150368
2020 Identification of Novel Compound Heterozygous Mutations in the GAN Gene of a Chinese Patient Diagnosed With Giant Axonal Neuropathy. Frontiers in neuroscience 5 32158379
2013 Detection of Severe Acute Respiratory Syndrome (SARS) Coronavirus Nucleocapsid Protein Using AlGaN/GaN High Electron Mobility Transistors. ECS transactions 5 32288936