Affinage

ATIC

Bifunctional purine biosynthesis protein ATIC · UniProt P31939

Length
592 aa
Mass
64.6 kDa
Annotated
2026-04-28
68 papers in source corpus 20 papers cited in narrative 19 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ATIC is a homodimeric bifunctional enzyme that catalyzes the penultimate and final steps of de novo purine biosynthesis—AICAR transformylase (C-terminal domain) and IMP cyclohydrolase (N-terminal domain)—with each catalytic activity operating at spatially distinct active sites without substrate channeling, and with tetrahydrofolate release as the rate-limiting step (PMID:8567683, PMID:11948179). Loss-of-function mutations cause AICA-ribosiduria with massive ZMP/AICAR accumulation, and structurally intact ATIC is required for purinosome assembly (PMID:15114530, PMID:22180458). Pharmacological or genetic disruption of ATIC triggers ZMP accumulation that activates AMPK signaling—linking purine flux to mTOR, PI3K/AKT, and metabolic regulation—while ATIC deletion in vivo impairs de novo purine supply required for vascular smooth muscle cell proliferation and causes mitochondrial dysfunction with skeletal muscle atrophy (PMID:26144885, PMID:36073366, PMID:40623538). The ATIC homodimerization domain drives constitutive ALK kinase activation in the oncogenic ATIC-ALK fusion found in anaplastic large-cell lymphoma (PMID:10706887, PMID:10706082).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 1996 High

    Establishing that a single human gene encodes both terminal steps of de novo purine biosynthesis resolved the long-standing question of whether AICAR transformylase and IMP cyclohydrolase are separate or fused enzymes, and localized each activity to an independent protein domain.

    Evidence Truncation mutagenesis and steady-state kinetics of purified recombinant human ATIC

    PMID:8567683

    Open questions at the time
    • No structural information on domain arrangement at this stage
    • Quaternary structure not yet characterized
  2. 2000 High

    Discovery that the ATIC homodimerization domain fused to ALK creates a constitutively active oncogenic kinase established a direct role for ATIC's oligomerization interface in driving anaplastic large-cell lymphoma, and showed the fusion protein engages Grb2/Shc signaling to induce transformation.

    Evidence Identification of inv(2)(p23q35) in ALCL patients; expression of ATIC-ALK in BaF3 and fibroblast cells with co-IP, transformation assays, and cytokine-independence assays across three independent laboratories

    PMID:10702393 PMID:10706082 PMID:10706887

    Open questions at the time
    • Structural basis for how ATIC dimerization activates ALK kinase not resolved
    • Relative contribution of ATIC enzymatic loss vs. ALK gain to oncogenesis unclear
  3. 2000 Medium

    Identification of ATIC (avian PurH) as a direct RNA-binding protein that activates muscle-specific exon inclusion revealed an unexpected moonlighting function beyond purine metabolism.

    Evidence Purification from muscle extracts, recombinant protein-RNA binding assays, and in vivo splicing reporter assays in avian system

    PMID:10801888

    Open questions at the time
    • Only demonstrated with avian ortholog; not confirmed for human ATIC
    • Structural basis for RNA binding unknown
    • Relationship between enzymatic and splicing activities not addressed
  4. 2002 High

    Pre-steady-state kinetic dissection showed that tetrahydrofolate release is rate-limiting and that the two active sites operate independently without substrate channeling, establishing the catalytic logic of the bifunctional enzyme.

    Evidence Rapid chemical quench, stopped-flow absorbance, and kinetic simulation (KINSIM) on purified human ATIC

    PMID:11948179

    Open questions at the time
    • Structural basis for lack of channeling not yet visualized
    • Whether cellular purinosome context alters channeling behavior unknown
  5. 2004 High

    Identification of causative ATIC mutations in AICA-ribosiduria patients—with recombinant K426R protein lacking transformylase activity—proved ATIC is essential for purine biosynthesis in humans and established K426 as a critical catalytic residue.

    Evidence Patient fibroblast metabolite analysis, ATIC sequencing, and recombinant mutant enzyme activity assays

    PMID:15114530

    Open questions at the time
    • Extremely rare disease with very few patients characterized
    • IMP cyclohydrolase retained partial activity—independent pathological contribution of each domain unclear
  6. 2011 Medium

    Patient-derived ATIC mutant fibroblasts showed impaired purinosome assembly, establishing that structurally intact ATIC is required for the higher-order metabolon organizing de novo purine synthesis.

    Evidence Immunolabeling and confocal microscopy of de novo purine synthesis enzymes in patient vs. control fibroblasts

    PMID:22180458

    Open questions at the time
    • Whether ATIC is a scaffold for purinosome nucleation or its loss indirectly destabilizes the complex is unresolved
    • Single lab observation
  7. 2015 High

    Chemical inhibition of ATIC homodimerization caused ZMP accumulation and AMPK activation both in cells and in vivo, establishing a direct metabolic link from ATIC catalytic flux to AMPK-dependent energy sensing.

    Evidence Small-molecule ATIC homodimerization inhibitor with ZMP and AMPK measurements in cells and a mouse metabolic disorder model

    PMID:26144885

    Open questions at the time
    • Inhibitor selectivity not fully profiled; off-target effects possible
    • Whether ZMP-AMPK axis fully accounts for downstream effects not delineated
  8. 2017 Medium

    Multiple studies converged on ATIC's role in cancer cell proliferation: ATIC knockdown suppresses AMPK and activates mTOR-S6K1 in hepatocellular carcinoma, while ATIC depletion depletes ATP and sensitizes cancer cells to ionizing radiation by impairing DNA repair, and cooperative XMP binding between IMPCHase active sites was revealed by ITC.

    Evidence Lentiviral/siRNA knockdown with Compound C rescue in HCC cells; siRNA plus small-molecule inhibitors with ATP rescue and γH2AX/comet assays in cancer cells; ITC with site-directed mutants

    PMID:29029884 PMID:29042184 PMID:29246230

    Open questions at the time
    • Direction of ATIC–AMPK relationship appears opposite between studies (KD suppresses AMPK in HCC vs. KD increases AMPK in inhibitor study)—context dependence unresolved
    • No structural basis for XMP cooperativity
  9. 2022 High

    Genetic knockout of Atic in vascular smooth muscle cells in mice demonstrated that ATIC-dependent purine synthesis is required for VSMC proliferation and arterial neointima formation, translating the enzyme's metabolic role to cardiovascular disease.

    Evidence Global and VSMC-specific Atic knockout mice with arterial injury models and LC-MS/MS metabolomics

    PMID:36073366

    Open questions at the time
    • Whether AMPK activation or purine depletion is the dominant anti-proliferative mechanism in VSMCs not separated
    • No pharmacological validation in vascular disease models
  10. 2023 Medium

    The ATIC substrate precursor AICAr was shown to suppress LRRK2 expression via AUF1-mediated mRNA decay, rescuing dopaminergic neurodegeneration in PD models—extending ATIC's metabolic influence to neurodegeneration through metabolite-driven gene regulation.

    Evidence RNA immunoprecipitation, mRNA decay assays, Drosophila and mouse PD models

    PMID:37366237

    Open questions at the time
    • ATIC itself was not directly manipulated; effect attributed to its substrate AICAR/AICAr
    • Cell-type specificity of LRRK2 regulation not fully defined
  11. 2025 Medium

    ATIC deletion in zebrafish and knockdown in myoblasts revealed that AICAR accumulation from ATIC loss causes mitochondrial respiratory chain dysfunction and skeletal muscle atrophy via ubiquitin-proteasome activation, establishing a purine-mitochondria-proteostasis axis.

    Evidence CRISPR/Cas9 zebrafish knockout, siRNA in C2C12 cells, metabolomics, mitochondrial function assays, transcriptomics

    PMID:40623538

    Open questions at the time
    • Whether AICAR directly damages mitochondria or acts through AMPK hyperactivation not resolved
    • Single lab; no rescue with exogenous purines reported

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: the structural basis for ATIC's role in purinosome assembly; whether the apparently contradictory directions of AMPK modulation upon ATIC loss reflect tissue-specific contexts or methodological differences; whether the RNA-binding/splicing function is conserved in mammals and its relationship to enzymatic activity; and the precise mechanism linking ATIC to PI3K/AKT signaling independent of AMPK.
  • No high-resolution structure of ATIC within a purinosome
  • AMPK activation vs. suppression upon ATIC loss not reconciled across tissues
  • Mammalian splicing regulatory role not confirmed

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016740 transferase activity 3 GO:0016853 isomerase activity 2 GO:0003723 RNA binding 1
Localization
GO:0005829 cytosol 2 GO:0005794 Golgi apparatus 1
Pathway
R-HSA-1430728 Metabolism 6 R-HSA-1643685 Disease 4 R-HSA-162582 Signal Transduction 3
Partners
ALKAUF1GRB2INSRSHC1ZFAS1
Complex memberships
ATIC homodimerpurinosome

Evidence

Reading pass · 19 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1996 Human ATIC (purH gene product) encodes a bifunctional enzyme with two independent catalytic activities: AICAR transformylase (AICARFT) in the C-terminal 406 amino acids and IMP cyclohydrolase (IMPCHase) in the N-terminal 223 amino acids, as demonstrated by truncation mutants showing each activity can be expressed independently. Km values for AICAR and 10-formyltetrahydrofolate were determined as 16.8 µM and 60.2 µM respectively. Cloning, purification, steady-state kinetics, truncation mutagenesis, site-directed mutagenesis The Journal of biological chemistry High 8567683
2000 ATIC-ALK fusion protein arising from inv(2)(p23q35) in ALCL fuses the amino-terminus of ATIC (including its homodimerization domain) to the intracellular portion of ALK, resulting in constitutive cytoplasmic tyrosine kinase activity and ATIC-mediated homodimerization of ALK, converting IL-3-dependent BaF3 cells to cytokine-independent growth. Inverse PCR, RT-PCR, transient expression in BaF3 cells, cytokine independence assay, subcellular localization Blood High 10702393 10706082 10706887
2000 Full-length ATIC-ALK cDNA expressed in mouse fibroblasts produces a ~96 kDa fusion protein that possesses constitutive tyrosine kinase activity, forms stable complexes with signaling proteins Grb2 and Shc, induces tyrosine-phosphorylation of Shc, and provokes oncogenic transformation. Expression in mouse fibroblasts, co-immunoprecipitation, tyrosine phosphorylation assay, transformation assay, 5'-RACE Cancer research High 10706082
2002 Detailed kinetic mechanism of human ATIC established: the rate-limiting step is tetrahydrofolate release from the formyltransferase active site (2.9 s⁻¹); the reverse transformylase reaction (6.7 s⁻¹) is faster than forward; the cyclohydrolase reaction is essentially unidirectional driving IMP production; and there is no kinetic evidence for substrate channeling of the FAICAR intermediate between the two active sites. Rapid chemical quench, stopped-flow absorbance, steady-state kinetics, kinetic simulation with KINSIM The Journal of biological chemistry High 11948179
2004 ATIC is the enzyme responsible for AICAR transformylase and IMP cyclohydrolase activities in human cells; loss-of-function mutations (K426R in the transformylase region, and a frameshift) cause AICA-ribosiduria with massive AICAR/ZMP accumulation. The K426R recombinant protein completely lacks AICAR transformylase activity while IMP cyclohydrolase retains ~40% activity. Patient fibroblast incubation with AICA-riboside showing AICAR accumulation, ATIC sequencing, recombinant protein expression and enzyme activity assay American journal of human genetics High 15114530
2000 Avian ATIC (PurH) protein directly binds a muscle-specific splicing enhancer (MSE3) RNA element in cardiac troponin T pre-mRNA, and binding affinity of both the native MSE3 complex and recombinant PurH correlates directly with functional activation of muscle-specific exon inclusion in vivo, revealing a moonlighting RNA-binding/splicing regulatory role for ATIC. Purification from muscle extracts, recombinant protein binding assays, in vivo splicing reporter assays, affinity correlation The Journal of biological chemistry Medium 10801888
2011 ATIC mutations causing AICA-ribosiduria destabilize purinosome assembly in patient fibroblasts, demonstrating that structurally intact ATIC complexes are required for de novo purine synthesis purinosome formation. The ability to form purinosomes correlated with clinical phenotype severity. Immunolabeling of DNPS enzymes, confocal fluorescence microscopy in patient fibroblasts vs. controls across multiple cell lines Human molecular genetics Medium 22180458
2015 Inhibition of ATIC homodimerization blocks the ninth step of de novo purine biosynthesis, causing accumulation of endogenous ZMP (ATIC's substrate), which in turn activates AMPK and its downstream signaling pathways in cells and in an in vivo mouse model for metabolic disorders. ATIC homodimerization inhibitor treatment, ZMP measurement, AMPK activation assay, in vivo mouse metabolic disorder model Chemistry & biology High 26144885
2015 ATIC accumulates in the Golgi/endosome fraction after insulin stimulation and interacts with the insulin receptor (IR) complex. siRNA knockdown of ATIC affects IR tyrosine phosphorylation and endocytosis; ATIC knockdown increases AMPK-Thr172 phosphorylation in IR complexes, and AICAR (ATIC's substrate) increases IR endocytosis. In vitro reconstitution system, siRNA knockdown, subcellular fractionation, insulin receptor tyrosine phosphorylation assay, endocytosis assay, bioinformatic screen of Golgi/endosome fractions Molecular & cellular proteomics Medium 25687571
2017 ATIC knockdown in hepatocellular carcinoma cells suppresses AMPK activation, thereby activating mTOR-S6K1-S6 signaling to support tumor cell growth and motility; Compound C (AMPK inhibitor) rescue confirmed AMPK dependence of the phenotype. Lentivirus-mediated knockdown, proliferation/colony/migration assays, western blot, Compound C rescue Cell communication and signaling Medium 29246230
2017 ATIC depletion (siRNA) or inhibition of its transformylase activity shifts cancer cells to G2/M phase, depletes cellular ATP without causing direct DNA damage, and sensitizes cells to ionizing radiation by increasing DNA double-strand breaks and delaying their repair; exogenous ATP supplementation rescues the DNA repair phenotype, implicating ATP depletion as the mechanism. siRNA knockdown, small molecule inhibitors, clonogenic survival assay, neutral comet assay, γH2AX staining, cell cycle analysis, exogenous ATP rescue International journal of radiation oncology, biology, physics Medium 29029884
2017 Analysis of substrate binding using S10W mutation (blocks IMPCHase active site) and truncation mutants reveals that nucleotide ligands bind selectively at one of the two active sites; XMP uniquely shows cooperative binding with communication between symmetrically-related IMPCHase active sites in the ATIC dimer; no evidence for cooperative binding in the AICARFT site. Site-directed mutagenesis, truncation mutants, isothermal titration calorimetry (ITC) Biochimica et biophysica acta. Proteins and proteomics Medium 29042184
2022 VSMC-specific or global knockout of Atic in mice inhibits VSMC proliferation, reduces de novo purine synthesis, and attenuates arterial neointima formation in mouse models of atherosclerosis and arterial restenosis, establishing ATIC-associated purine synthesis as required for VSMC proliferative phenotype in arterial disease. Global and VSMC-specific Atic knockout mice, arterial injury models, LC-MS/MS metabolomics, cell proliferation assays Circulation High 36073366
2022 ATIC promotes cell growth and migration in lung adenocarcinoma by upregulating Myc expression; Myc knockdown abrogates the pro-growth and pro-migratory effects of ATIC overexpression, placing ATIC upstream of Myc in a regulatory axis. siRNA knockdown, overexpression, rescue (Myc knockdown) experiments, proliferation/migration/invasion assays in HCC827 and NCI-H1435 cells Oncology letters Medium 35251351
2023 ATIC's substrate AICAr (AICAR precursor) regulates LRRK2 mRNA levels in a cell-type-specific manner via AUF1-mediated mRNA decay: upon AICAr treatment, the RNA-binding protein AUF1 is recruited to AU-rich elements in LRRK2 mRNA, recruiting the decapping enzyme complex DCP1/2 leading to LRRK2 mRNA degradation; this suppresses LRRK2 expression and rescues dopaminergic neurodegeneration in Drosophila and mouse PD models. Cell-based assays, RNA immunoprecipitation, mRNA decay assays, Drosophila and mouse PD models, LRRK2 expression measurements The EMBO journal Medium 37366237
2024 lncRNA ZFAS1 directly interacts with ATIC and regulates its transcription; ATIC knockdown suppresses hepatocellular carcinoma cell proliferation and migration through the PI3K/AKT signaling pathway; SC79 (AKT activator) partially restores the effects of ZFAS1/ATIC knockdown. Luciferase reporter assay, siRNA knockdown, colony formation, CCK-8, wound healing and Transwell assays, in vivo xenograft model, AKT activator rescue Journal of cancer research and clinical oncology Medium 39001904
2025 ATIC deletion in zebrafish and siRNA knockdown in C2C12 myoblasts causes AICAR accumulation and IMP synthesis blockage, leading to mitochondrial structural damage, dysfunction of respiratory chain complexes I-V, ROS burst, and skeletal muscle atrophy through activation of the ubiquitin-proteasome system. CRISPR/Cas9 zebrafish knockout, siRNA knockdown in C2C12 cells, metabolomic analysis, mitochondrial function assays, transcriptome sequencing Free radical biology & medicine Medium 40623538
2025 lncRNA TPT1-AS1 physically interacts with CBP (CREB-binding protein), leading to loss of H3K27Ac at the ATIC promoter, thereby suppressing ATIC transcription and blocking de novo purine biosynthesis (IMP synthesis) in breast cancer cells; ATIC knockdown inhibits breast cancer tumor growth and metastasis. Mass spectrometry identification, ChIP assay for H3K27Ac, siRNA knockdown, in vivo xenograft model, IMP measurement Cancer science Medium 40091780
2026 ATIC knockdown in upper tract urothelial carcinoma cells downregulates B7-H3 (CD276), PRNP, RAC2, and NT5E (CD73); ATIC silencing modulates mTOR, AKT, ERK, and p38 phosphorylation; B7-H3 may lie upstream of PRNP and RAC2 in this axis. TMT proteomics identified these as downstream effectors. TMT-based quantitative proteomics, RNA interference, functional assays (proliferation, migration, invasion), western blot for signaling Cancer genomics & proteomics Medium 41771578

Source papers

Stage 0 corpus · 68 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2008 EML4-ALK fusion transcripts, but no NPM-, TPM3-, CLTC-, ATIC-, or TFG-ALK fusion transcripts, in non-small cell lung carcinomas. Lung cancer (Amsterdam, Netherlands) 135 18242762
2000 ATIC-ALK: A novel variant ALK gene fusion in anaplastic large cell lymphoma resulting from the recurrent cryptic chromosomal inversion, inv(2)(p23q35). The American journal of pathology 129 10702393
2004 AICA-ribosiduria: a novel, neurologically devastating inborn error of purine biosynthesis caused by mutation of ATIC. American journal of human genetics 123 15114530
2000 A new variant anaplastic lymphoma kinase (ALK)-fusion protein (ATIC-ALK) in a case of ALK-positive anaplastic large cell lymphoma. Cancer research 115 10706082
1994 Five Listeria monocytogenes genes preferentially expressed in infected mammalian cells: plcA, purH, purD, pyrE and an arginine ABC transporter gene, arpJ. Molecular microbiology 111 7997171
2000 Inv(2)(p23q35) in anaplastic large-cell lymphoma induces constitutive anaplastic lymphoma kinase (ALK) tyrosine kinase activation by fusion to ATIC, an enzyme involved in purine nucleotide biosynthesis. Blood 110 10706887
2003 ALK-ATIC fusion in urinary bladder inflammatory myofibroblastic tumor. Genes, chromosomes & cancer 98 12939746
1996 The human purH gene product, 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/IMP cyclohydrolase. Cloning, sequencing, expression, purification, kinetic analysis, and domain mapping. The Journal of biological chemistry 85 8567683
2001 The NPM-ALK and the ATIC-ALK fusion genes can be detected in non-neoplastic cells. The American journal of pathology 75 11395396
2015 AMPK Activation via Modulation of De Novo Purine Biosynthesis with an Inhibitor of ATIC Homodimerization. Chemistry & biology 74 26144885
2017 Bifunctional enzyme ATIC promotes propagation of hepatocellular carcinoma by regulating AMPK-mTOR-S6 K1 signaling. Cell communication and signaling : CCS 65 29246230
2011 Mutations of ATIC and ADSL affect purinosome assembly in cultured skin fibroblasts from patients with AICA-ribosiduria and ADSL deficiency. Human molecular genetics 59 22180458
1989 Nucleotide sequence analysis of genes purH and purD involved in the de novo purine nucleotide biosynthesis of Escherichia coli. The Journal of biological chemistry 47 2687276
2022 ATIC-Associated De Novo Purine Synthesis Is Critically Involved in Proliferative Arterial Disease. Circulation 39 36073366
2002 The kinetic mechanism of the human bifunctional enzyme ATIC (5-amino-4-imidazolecarboxamide ribonucleotide transformylase/inosine 5'-monophosphate cyclohydrolase). A surprising lack of substrate channeling. The Journal of biological chemistry 36 11948179
1991 De novo purine nucleotide biosynthesis: cloning, sequencing and expression of a chicken PurH cDNA encoding 5-aminoimidazole-4-carboxamide-ribonucleotide transformylase-IMP cyclohydrolase. Gene 36 1937050
2016 Association of the ATIC 347 C/G polymorphism with responsiveness to and toxicity of methotrexate in rheumatoid arthritis: a meta-analysis. Rheumatology international 35 27379764
2020 AICA-ribosiduria due to ATIC deficiency: Delineation of the phenotype with three novel cases, and long-term update on the first case. Journal of inherited metabolic disease 29 32557644
2017 Anaplastic lymphoma kinase-positive anaplastic large cell lymphoma with the variant RNF213-, ATIC- and TPM3-ALK fusions is characterized by copy number gain of the rearranged ALK gene. Haematologica 26 28659337
2015 The last enzyme of the de novo purine synthesis pathway 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/IMP cyclohydrolase (ATIC) plays a central role in insulin signaling and the Golgi/endosomes protein network. Molecular & cellular proteomics : MCP 26 25687571
2017 Identification of ATIC as a Novel Target for Chemoradiosensitization. International journal of radiation oncology, biology, physics 25 29029884
2022 ATIC facilitates cell growth and migration by upregulating Myc expression in lung adenocarcinoma. Oncology letters 22 35251351
2017 Discovery of N-(6-Fluoro-1-oxo-1,2-dihydroisoquinolin-7-yl)-5-[(3R)-3-hydroxypyrrolidin-1-yl]thiophene-2-sulfonamide (LSN 3213128), a Potent and Selective Nonclassical Antifolate Aminoimidazole-4-carboxamide Ribonucleotide Formyltransferase (AICARFT) Inhibitor Effective at Tumor Suppression in a Cancer Xenograft Model. Journal of medicinal chemistry 22 29072452
2018 Genetic Polymorphisms of TYMS, MTHFR, ATIC, MTR, and MTRR Are Related to the Outcome of Methotrexate Therapy for Rheumatoid Arthritis in a Chinese Population. Frontiers in pharmacology 20 30546311
2016 ATIC 347C>G gene polymorphism may be associated with methotrexate-induced adverse events in south Indian Tamil rheumatoid arthritis. Pharmacogenomics 19 26799664
2018 Characterization of a novel AICARFT inhibitor which potently elevates ZMP and has anti-tumor activity in murine models. Scientific reports 18 30337562
2006 Inhibition of fructose-1,6-bisphosphatase by aminoimidazole carboxamide ribotide prevents growth of Salmonella enterica purH mutants on glycerol. The Journal of biological chemistry 18 16987812
1991 Nucleotide sequence analysis of purH and purD genes from Salmonella typhimurium. Biochimica et biophysica acta 18 1954258
2017 Characterization of AICAR transformylase/IMP cyclohydrolase (ATIC) from Staphylococcus lugdunensis. The FEBS journal 16 29063699
2016 ATIC missense variant affects response to methotrexate treatment in rheumatoid arthritis patients. Pharmacogenomics 15 27885916
2020 Coexistence of a novel CCNY-ALK and ATIC-ALK double-fusion in one patient with ALK-positive NSCLC and response to crizotinib: a case report. Translational lung cancer research 13 33489809
2020 Upregulation of ATIC in multiple myeloma tissues based on tissue microarray and gene microarrays. International journal of laboratory hematology 12 33226193
2023 Case report: ATIC-ALK fusion in infant-type hemispheric glioma and response to lorlatinib. Frontiers in oncology 11 36910660
2005 Virulence deficiency caused by a transposon insertion in the purH gene of Xanthomonas oryzae pv. oryzae. Canadian journal of microbiology 11 16175206
2023 Circ-ATIC regulates esophageal squamous cell carcinoma growth and metastasis through miR-1294/PBX3 pathway. Heliyon 10 36699282
2023 Regulation of LRRK2 mRNA stability by ATIC and its substrate AICAR through ARE-mediated mRNA decay in Parkinson's disease. The EMBO journal 10 37366237
2022 AICAR transformylase/IMP cyclohydrolase (ATIC) is essential for de novo purine biosynthesis and infection by Cryptococcus neoformans. The Journal of biological chemistry 10 36063996
2020 Cyclic Peptide Mimotopes for the Detection of Serum Anti-ATIC Autoantibody Biomarker in Hepato-Cellular Carcinoma. International journal of molecular sciences 10 33352757
2017 ATIC Gene Polymorphism and Histologic Response to Chemotherapy in Pediatric Osteosarcoma. Journal of pediatric hematology/oncology 10 28267080
2016 Intraosseous inflammatory myofibroblastic tumor of the mandible with a novel ATIC-ALK fusion mutation: a case report. Diagnostic pathology 10 27846861
2022 Circ-ATIC Serves as a Sponge of miR-326 to Accelerate Esophageal Squamous Cell Carcinoma Progression by Targeting ID1. Biochemical genetics 9 35064360
2024 LncRNA ZFAS1 regulates ATIC transcription and promotes the proliferation and migration of hepatocellular carcinoma through the PI3K/AKT signaling pathway. Journal of cancer research and clinical oncology 7 39001904
2021 Genetic polymorphism in ATIC is associated with effectiveness and toxicity of pemetrexed in non-small-cell lung cancer. Thorax 7 33859051
2020 The CRISPR-Cas9 crATIC HeLa transcriptome: Characterization of a novel cellular model of ATIC deficiency and ZMP accumulation. Molecular genetics and metabolism reports 7 32939338
2017 Analysis of substrate binding in individual active sites of bifunctional human ATIC. Biochimica et biophysica acta. Proteins and proteomics 7 29042184
2022 Impact of Variants in the ATIC and ARID5B Genes on Therapeutic Failure with Imatinib in Patients with Chronic Myeloid Leukemia. Genes 6 35205374
2018 Utilisation of 10-formyldihydrofolate as substrate by dihydrofolate reductase (DHFR) and 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) tranformylase/IMP cyclohydrolase (PurH) in Escherichia coli. Microbiology (Reading, England) 6 29799386
2023 Promoter methylation levels of RASSF1 and ATIC genes are associated with lung cancer in Iranian patients. Hormone molecular biology and clinical investigation 4 36584330
2022 Expanding the spectrum of clinical severity of AICA-ribosiduria: Report of two siblings with mild phenotype caused by a novel pathogenic variant in ATIC gene. American journal of medical genetics. Part A 4 36367252
2012 Regular Multivitamin Supplement Use, Single Nucleotide Polymorphisms in ATIC, SHMT2, and SLC46A1, and Risk of Ovarian Carcinoma. Frontiers in genetics 4 22461784
2011 Expression, purification, crystallization and preliminary X-ray diffraction crystallographic study of PurH from Escherichia coli. Acta crystallographica. Section F, Structural biology and crystallization communications 4 22139174
2000 Binding of PurH to a muscle-specific splicing enhancer functionally correlates with exon inclusion in vivo. The Journal of biological chemistry 4 10801888
2023 Hydrodynamic Enhancement of p-atic Defect Dynamics. Physical review letters 3 36930922
2023 NOTCH2, ATIC, MRI1, SLC6A13, ATP13A2 Genetic Variations are Associated with Ventricular Septal Defect in the Chinese Tibetan Population Through Whole-Exome Sequencing. Pharmacogenomics and personalized medicine 3 37138656
2023 A meta-analysis of the association between the ATIC 347 C/G polymorphism and methotrexate responsiveness and toxicity in rheumatoid arthritis. Seminars in arthritis and rheumatism 3 38071832
2008 Association and haplotype analysis of purH gene with inosine monophosphate content in chickens. Animal biotechnology 3 18855251
2008 [ATIC-ALK-positive anaplastic large cell lymphoma: a case report and review of the literature]. [Rinsho ketsueki] The Japanese journal of clinical hematology 2 18572809
1995 Isolation of human purH gene expressed in the rodent transformant cells by subtractive enrichment of 3'-untranslated region of human transcript. DNA research : an international journal for rapid publication of reports on genes and genomes 2 8867801
2025 Lnc-TPT1-AS1/CBP/ATIC Axis Mediated Purine Metabolism Activation Promotes Breast Cancer Progression. Cancer science 1 40091780
2025 Quantifying the shape of cells, from Minkowski tensors to p-atic orders. eLife 1 41257512
2024 Anaplastic large cell lymphoma with ALK::ATIC fusion mimicking a histiocytic sarcoma debuting as an anterior thoracic soft tissue tumor with exceptional clinicopathological, morphological and molecular features. Thoracic cancer 1 38523398
2026 ATIC facilitates the malignant progression of bladder cancer by modulating AMPK-mTOR-S6K1 axis under folate reprogramming. Journal of translational medicine 0 41723491
2026 ATIC Knockdown Reduces B7-H3 Expression and Oncogenic Signaling in Upper Tract Urothelial Carcinoma Cells. Cancer genomics & proteomics 0 41771578
2025 Genetic Variants of the ATIC Gene and Therapeutic Response to Methotrexate in Patients with Rheumatoid Arthritis. International journal of molecular sciences 0 40362255
2025 miR-944 inhibits malignant progression of bladder cancer through ATIC/AKT/FOXO3 A axis mediated by SHMT1. In vitro cellular & developmental biology. Animal 0 40442541
2025 Aerobic exercise ameliorates skeletal muscle atrophy in atic knockout zebrafish through the oxidative phosphorylation pathway. Free radical biology & medicine 0 40623538
2025 Construction of a Zebrafish Model of Cardiac Hypertrophy Caused by ATIC Gene Deletion and Preliminary Exploration of Aerobic Exercise Improvement. International journal of molecular sciences 0 41226290
2024 Characterization of AICAR transformylase/IMP cyclohydrolase (ATIC) bifunctional enzyme from Candidatus Liberibacer asiaticus. Biochimica et biophysica acta. Proteins and proteomics 0 38615986