Affinage

ATIC

Bifunctional purine biosynthesis protein ATIC · UniProt P31939

Length
592 aa
Mass
64.6 kDa
Annotated
2026-06-09
69 papers in source corpus 21 papers cited in narrative 20 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ATIC is a homodimeric bifunctional enzyme that catalyzes the final two steps of de novo IMP (purine) biosynthesis, harboring AICAR transformylase (AICARFT) activity in its C-terminal domain and IMP cyclohydrolase (IMPCHase) activity in its N-terminal domain, which can be expressed independently from truncation mutants (PMID:8567683). Transient and steady-state kinetics establish that tetrahydrofolate release from the AICARFT site is rate-limiting, the cyclohydrolase step is essentially irreversible, and the FAICAR intermediate is not channeled between the two active sites (PMID:11948179); ligand-binding analyses further show that nucleotides bind selectively to one of the two sites, with XMP exceptionally engaging both and exhibiting cooperative communication between symmetry-related IMPCHase domains (PMID:29042184). Homodimerization is required for the terminal AICARFT step, and blocking it raises intracellular ZMP (AICAR monophosphate), which activates AMPK (PMID:26144885). Through control of ZMP levels and ATP supply, ATIC integrates purine synthesis with downstream signaling and proliferative physiology: its loss causes G2/M arrest, ATP depletion and impaired DNA double-strand break repair (PMID:29029884), it suppresses AMPK to sustain mTOR-S6K1 signaling in hepatocellular carcinoma (PMID:29246230), and genetic deletion blocks vascular smooth muscle cell proliferation and arterial/atherosclerotic disease in mice (PMID:36073366). ATIC also has non-enzymatic roles, directly binding the muscle-specific splicing enhancer MSE3 to promote cardiac troponin T exon inclusion (PMID:10801888) and accumulating in Golgi/endosome fractions where it supports insulin receptor phosphorylation and endocytosis (PMID:25687571). Loss-of-function mutations in ATIC cause AICA-ribosiduria, a metabolic disorder driven by abolition of AICARFT activity and accumulation of ZMP/AICA-riboside (PMID:15114530), and these mutations destabilize purinosome assembly in patient fibroblasts (PMID:22180458). The N-terminal ALK fusion partner role arises when an inv(2) chromosomal rearrangement fuses ATIC to ALK, with ATIC-mediated dimerization driving constitutive ALK kinase activation and oncogenic signaling in anaplastic large cell lymphoma (PMID:10706887, PMID:10702393, PMID:10706082).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 1996 High

    Established that ATIC is a single polypeptide carrying two distinct catalytic activities, defining its bifunctional architecture in de novo purine biosynthesis.

    Evidence cDNA cloning, recombinant protein purification, truncation and site-directed mutagenesis with steady-state kinetics

    PMID:8567683

    Open questions at the time
    • Did not resolve whether the two activities act sequentially via channeling
    • No structural model of the dimer
    • Folate-binding motif role left undefined functionally
  2. 2000 High

    Revealed an oncogenic gain-of-function: chromosomal fusion of ATIC to ALK creates a constitutively active tyrosine kinase, with ATIC dimerization as the activating mechanism.

    Evidence RT-PCR/inverse PCR cloning, expression in BaF3 and fibroblasts, cytokine-independence and focus-formation assays, Co-IP of Grb2/Shc

    PMID:10702393 PMID:10706082 PMID:10706887

    Open questions at the time
    • Whether ATIC enzymatic function contributes to transformation is not addressed
    • Full downstream signaling network beyond Grb2/Shc not mapped
  3. 2000 Medium

    Uncovered a moonlighting non-enzymatic role in which ATIC acts as an RNA-binding splicing co-regulator.

    Evidence RNA affinity purification, recombinant PurH RNA-binding assay, in vitro splicing and in vivo exon-inclusion correlation

    PMID:10801888

    Open questions at the time
    • Physiological relevance in muscle in vivo not demonstrated
    • RNA-binding interface on ATIC not mapped
    • Relationship to enzymatic function unknown
  4. 2002 High

    Defined the detailed kinetic mechanism and ruled out substrate channeling, settling how the two active sites operate.

    Evidence Rapid chemical quench, stopped-flow absorbance, steady-state kinetics, KINSIM simulation

    PMID:11948179

    Open questions at the time
    • No structural basis for rate-limiting THF release
    • Allosteric communication between sites not yet probed
  5. 2004 High

    Linked ATIC directly to a Mendelian disease, showing loss of AICARFT activity causes AICA-ribosiduria with ZMP accumulation.

    Evidence Patient metabolite assays, gene sequencing, recombinant mutant enzyme activity measurement

    PMID:15114530

    Open questions at the time
    • Mechanism linking ZMP accumulation to clinical phenotype not fully resolved
    • IMPCHase retention consequences unclear
  6. 2011 Medium

    Connected ATIC structural integrity to assembly of the purinosome multienzyme complex.

    Evidence Immunofluorescence/confocal imaging of purinosome assembly in patient fibroblasts and multiple cell lines

    PMID:22180458

    Open questions at the time
    • Single lab
    • Direct interactions stabilizing the purinosome not biochemically defined
    • Causality between assembly defect and metabolic phenotype correlational
  7. 2015 Medium

    Demonstrated that ATIC homodimerization controls intracellular ZMP and thereby AMPK activity, linking the terminal biosynthetic step to metabolic signaling.

    Evidence Peptide/small-molecule dimerization inhibitor, cellular ZMP quantification, AMPK phosphorylation assay, mouse metabolic model

    PMID:26144885

    Open questions at the time
    • Single lab
    • Off-target effects of inhibitor on other ZMP-dependent processes not excluded
  8. 2015 Medium

    Implicated ATIC in insulin receptor endocytosis at Golgi/endosome compartments, beyond its cytosolic biosynthetic role.

    Evidence Subcellular fractionation, siRNA knockdown, IR phosphorylation assays, AICAR treatment in cells and liver

    PMID:25687571

    Open questions at the time
    • Direct binding partners at the endosome not identified
    • Whether ATIC enzymatic activity is required is unclear
    • Single lab
  9. 2017 Medium

    Showed that ATIC-dependent purine synthesis maintains ATP pools required for DNA double-strand break repair and cell cycle progression.

    Evidence siRNA knockdown, AICARFT inhibitor, comet/γH2AX assays, cell cycle analysis, ATP rescue

    PMID:29029884

    Open questions at the time
    • Single lab
    • Whether ZMP/AMPK contributes independently of ATP not separated
  10. 2017 Medium

    Positioned ATIC upstream of AMPK to drive mTOR signaling and tumor cell proliferation in hepatocellular carcinoma.

    Evidence Lentiviral shRNA knockdown, Western blots, Compound C rescue, proliferation/migration assays

    PMID:29246230

    Open questions at the time
    • Mechanism by which ATIC suppresses AMPK not defined at molecular level
    • Single lab
  11. 2017 Medium

    Resolved active-site selectivity of ligand binding and identified XMP-dependent inter-domain cooperativity in the dimer.

    Evidence Site-directed mutagenesis (S10W), truncation mutants, isothermal calorimetry

    PMID:29042184

    Open questions at the time
    • Single lab, no independent replication
    • Physiological role of XMP cooperativity unknown
  12. 2022 High

    Provided definitive in vivo genetic evidence that ATIC-dependent purine synthesis drives vascular smooth muscle proliferation and arterial disease.

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

    PMID:36073366

    Open questions at the time
    • Whether ZMP signaling or nucleotide supply is the operative mechanism not fully separated
  13. 2022 Low

    Extended ATIC pro-tumorigenic roles to additional cancers via PI3K/AKT and Myc programs.

    Evidence Knockdown/overexpression, SC79 and Myc-knockdown rescue, luciferase reporter, xenografts (HCC and lung adenocarcinoma)

    PMID:35251351 PMID:39001904

    Open questions at the time
    • Single labs, partial rescues
    • No direct link between ATIC enzymatic activity and AKT/Myc established
  14. 2022 High

    Identified the fungal ATIC ortholog as essential for purine synthesis and virulence, with structural and kinetic divergence from the human enzyme.

    Evidence ADE16 deletion, auxotrophy and murine infection assays, X-ray crystallography, recombinant kinetics in C. neoformans

    PMID:36063996

    Open questions at the time
    • Selective inhibitor exploiting the active-site difference not yet developed
  15. 2023 Medium

    Showed the ATIC substrate AICAR acts as a small-molecule signal regulating LRRK2 mRNA stability, linking purine metabolism to neurodegeneration.

    Evidence AICAr treatment, AUF1 RIP, mRNA decay and DCP1/2 recruitment assays, Drosophila and mouse PD models

    PMID:37366237

    Open questions at the time
    • This is a substrate effect, not a direct ATIC molecular activity
    • Cell-type specificity mechanism incompletely defined
  16. 2025 Medium

    Linked ATIC loss to skeletal muscle atrophy through AICAR accumulation, mitochondrial OXPHOS failure, ROS, and ubiquitin-proteasome activation.

    Evidence CRISPR atic knockout zebrafish, siRNA in C2C12, mitochondrial/OXPHOS/ROS assays

    PMID:40623538

    Open questions at the time
    • Single lab
    • Whether AICAR accumulation or IMP/ATP depletion is the primary driver not separated
  17. 2025 Medium

    Defined transcriptional and proteomic regulatory contexts in which ATIC drives cancer progression.

    Evidence TPT1-AS1/CBP Co-IP and H3K27Ac ChIP at ATIC promoter (breast cancer); TMT proteomics of ATIC/B7-H3 axis (urothelial carcinoma)

    PMID:40091780 PMID:41771578

    Open questions at the time
    • Connection between ATIC enzymatic function and the B7-H3 axis not mechanistically established (Low confidence for #19)
    • Single labs

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved which ATIC outputs — nucleotide/ATP supply, ZMP/AMPK signaling, or non-enzymatic moonlighting functions — dominate in each disease context, and how its enzymatic and non-catalytic roles are coordinated.
  • No study cleanly separates catalytic from non-catalytic contributions in vivo
  • Full-length human dimer structural mechanism of inter-domain cooperativity not resolved
  • Recruitment mechanism to Golgi/endosome and to splicing complexes undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016740 transferase activity 3 GO:0016787 hydrolase activity 2 GO:0003723 RNA binding 1
Localization
GO:0005829 cytosol 2 GO:0005768 endosome 1 GO:0005794 Golgi apparatus 1
Pathway
R-HSA-1430728 Metabolism 4 R-HSA-162582 Signal Transduction 3 R-HSA-1643685 Disease 3
Partners
ALKGRB2SHC
Complex memberships
ATIC homodimerATIC-ALK fusionpurinosome

Evidence

Reading pass · 20 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1996 Human ATIC (purH gene product) is a bifunctional enzyme with two separable 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 that independently express each activity. Km values for AICAR and (6R,6S)10-formyltetrahydrofolate were determined for the purified recombinant human enzyme. Site-directed mutagenesis of a putative folate-binding motif showed it plays no role in enzymatic activity. cDNA cloning, recombinant protein purification, steady-state kinetics, truncation mutagenesis, site-directed mutagenesis The Journal of biological chemistry High 8567683
2002 Detailed kinetic mechanism of human ATIC established by rapid chemical quench, stopped-flow, and steady-state kinetics: (1) rate-limiting step is tetrahydrofolate release from the AICARFT active site (~2.9 s⁻¹); (2) the reverse transformylase reaction (~6.7 s⁻¹) is faster than forward; (3) the cyclohydrolase reaction is essentially unidirectional; (4) there is no kinetic evidence of substrate channeling of the FAICAR intermediate between the two active sites. Rapid chemical quench, stopped-flow absorbance, steady-state kinetics, kinetic simulation (KINSIM) The Journal of biological chemistry High 11948179
2000 ATIC fuses to ALK via inv(2)(p23q35) in anaplastic large cell lymphoma, producing an ~87 kDa ATIC-ALK chimeric protein localized exclusively to the cytoplasm (unlike NPM-ALK which is cytoplasmic and nuclear). The fusion protein is constitutively tyrosine-phosphorylated and converts the IL-3-dependent BaF3 cell line to cytokine-independent growth. ATIC-mediated homodimerization is proposed as the mechanism of ALK activation. RT-PCR, inverse PCR, transient expression in BaF3 cells, cytokine-independence assay, subcellular localization by immunostaining Blood High 10702393 10706082 10706887
2000 ATIC-ALK fusion protein possesses constitutive tyrosine kinase activity, forms stable complexes with the signaling adaptor proteins Grb2 and Shc (detected by co-immunoprecipitation), induces tyrosine phosphorylation of Shc, and provokes oncogenic transformation of mouse fibroblasts. Full-length cDNA expression in mouse fibroblasts, co-immunoprecipitation of Grb2 and Shc, tyrosine phosphorylation assay, focus-formation/transformation assay Cancer research High 10706082
2004 Loss-of-function mutations in ATIC cause AICA-ribosiduria: a K426R missense mutation in the transformylase region completely abolishes AICARFT activity in recombinant protein, while a frameshift mutation causes loss of the other allele. Patients accumulate ZMP (AICAR) and its di/triphosphates in erythrocytes and excrete AICA-riboside in urine. Impaired AICARFT activity is the primary enzymatic defect; IMPCHase activity is partially retained (~40% of normal). Fibroblast metabolite accumulation assay, ATIC gene sequencing, recombinant mutant protein expression and enzymatic activity assay American journal of human genetics High 15114530
2011 Mutations in ATIC destabilize purinosome assembly in cultured skin fibroblasts from AICA-ribosiduria patients. The ability to form purinosomes (multienzyme de novo purine synthesis complexes) in purine-depleted medium correlates with structural integrity of ATIC protein. Purinosome assembly was confirmed in multiple cell types (HeLa, HepG2, Saos-2, HEK293, skin fibroblasts, keratinocytes) by parallel immunolabeling and confocal fluorescence microscopy. Immunofluorescence/confocal microscopy of purinosome assembly in primary patient fibroblasts and multiple cell lines, parallel immunolabeling of multiple DNPS enzymes Human molecular genetics Medium 22180458
2015 Endogenous ZMP (produced when ATIC homodimerization is blocked by a small-molecule inhibitor) can activate AMPK and its downstream signaling pathways. Inhibition of ATIC homodimerization with a peptide-based inhibitor increases intracellular ZMP and activates AMPK in cells and in a mouse model of metabolic disorder, establishing ATIC homodimerization as necessary for the final step of de novo purine biosynthesis. Small-molecule ATIC homodimerization inhibitor, cellular ZMP quantification, AMPK phosphorylation assay, in vivo mouse metabolic disorder model Chemistry & biology Medium 26144885
2015 ATIC accumulates in Golgi/endosome fractions after insulin stimulation in hepatocytes. siRNA-mediated knockdown of ATIC in HEK293 cells reduces insulin receptor (IR) tyrosine phosphorylation and endocytosis. ATIC knockdown increases AMPK-Thr172 phosphorylation in IR complexes. Treatment with AICAR (the ATIC substrate) increases IR endocytosis in cells and in liver. These results suggest ATIC participates in a signaling mechanism linking purine biosynthesis to IR endocytosis. Subcellular fractionation, siRNA knockdown, IR phosphorylation assay, in vitro reconstitution system, AICAR treatment in cultured cells and mouse liver Molecular & cellular proteomics Medium 25687571
2017 ATIC knockdown or chemical inhibition of its transformylase activity in cancer cells causes G2/M cell cycle arrest, ATP depletion, and increased DNA double-strand breaks after ionizing radiation, with delayed repair. Exogenous ATP supplementation rescues the DNA repair defect, linking ATIC function in purine synthesis to DNA damage response via ATP levels. siRNA knockdown, small-molecule AICARFT inhibitor, clonogenic survival assay, neutral comet assay, γH2AX staining, cell cycle analysis, ATP rescue experiment International journal of radiation oncology, biology, physics Medium 29029884
2017 ATIC suppresses AMPK activation in hepatocellular carcinoma cells, thereby activating the downstream mTOR-S6K1-S6 signaling axis. ATIC knockdown by lentiviral shRNA reduces proliferation, colony formation, and migration of HCC cells; these effects are rescued by the AMPK inhibitor Compound C, placing ATIC upstream of AMPK in this pathway. Lentiviral shRNA knockdown, Western blot for AMPK/mTOR/S6K1 phosphorylation, Compound C rescue assay, cell proliferation/apoptosis/migration assays Cell communication and signaling Medium 29246230
2000 ATIC (PurH) directly binds the muscle-specific splicing enhancer MSE3 RNA element downstream of cardiac troponin T exon 5, and the in vitro binding affinity of recombinant human PurH to MSE3 directly correlates with functional activation of exon 5 inclusion in vivo, identifying a non-enzymatic, moonlighting role for ATIC as a splicing co-regulator. RNA affinity purification/protein identification, recombinant PurH direct RNA-binding assay, in vitro splicing competition assay, in vivo exon inclusion assay with binding affinity correlation The Journal of biological chemistry Medium 10801888
2017 Analysis of individual active sites of dimeric human ATIC using site-directed mutagenesis (S10W blocks the IMPCHase site) and isothermal calorimetry showed that most nucleotide ligands bind selectively to one of the two active sites. XMP is exceptional in binding both AICARFT and IMPCHase active sites and shows evidence of cooperative binding with communication between symmetrically-related IMPCHase domains. No positive cooperativity was detected in the AICARFT site with the model ligands tested. Site-directed mutagenesis, truncation mutants, isothermal calorimetry (ITC) Biochimica et biophysica acta. Proteins and proteomics Medium 29042184
2022 ATIC promotes hepatocellular carcinoma cell proliferation and migration via the PI3K/AKT signaling pathway. ATIC knockdown inhibited cell proliferation and migration; AKT activator SC79 partially reversed these effects. LncRNA ZFAS1 was shown to directly interact with ATIC and regulate its transcription. siRNA/shRNA knockdown, luciferase reporter assay, SC79 (AKT activator) rescue, colony formation, wound-healing and Transwell assays, in vivo xenograft Journal of cancer research and clinical oncology Low 39001904
2022 ATIC promotes lung adenocarcinoma cell growth and migration by upregulating Myc expression. ATIC overexpression-induced growth and migration were abrogated by Myc knockdown in HCC827 and NCI-H1435 cells, establishing ATIC as upstream of Myc in this context. ATIC overexpression, Myc siRNA knockdown rescue experiment, cell proliferation, migration and invasion assays Oncology letters Low 35251351
2022 Global and vascular smooth muscle cell (VSMC)-specific knockout of Atic in mice inhibited VSMC proliferation and attenuated arterial neointima formation and atherosclerotic lesion development, demonstrating a cell-autonomous role for ATIC-dependent de novo purine synthesis in proliferative arterial disease. VSMC-specific and global Atic knockout mouse models, arterial injury models, atherosclerosis models, liquid chromatography-tandem mass spectrometry for purine metabolites Circulation High 36073366
2022 Cryptococcus neoformans ATIC (encoded by ADE16) is essential for de novo purine synthesis; atic null mutants are adenine and histidine auxotrophs unable to establish infection in a murine model. Crystal structure of C. neoformans ATIC was determined, revealing a serine-to-tyrosine substitution in the active site compared to human ATIC, and fungal Km values for AICAR and FAICAR are 8-fold and 20-fold higher, respectively, than human ortholog. Genetic deletion (ΔaDE16), auxotrophy assay, murine infection model, X-ray crystallography, recombinant enzyme kinetics The Journal of biological chemistry High 36063996
2023 ATIC substrate AICAR (as its ribonucleoside AICAr) regulates LRRK2 mRNA stability in a cell-type-specific manner. AICAr treatment recruits the RNA-binding protein AUF1 to AU-rich elements (AREs) in LRRK2 mRNA, leading to recruitment of the decapping complex DCP1/2 and mRNA decay, thereby reducing LRRK2 protein levels. This pathway rescues LRRK2-induced dopaminergic neurodegeneration and neuroinflammation in Drosophila and mouse PD models. AICAr treatment in cells and mouse tissue, AUF1 RNA immunoprecipitation, mRNA stability assay, DCP1/2 recruitment assay, Drosophila PD model, mouse PD model The EMBO journal Medium 37366237
2025 ATIC deletion in zebrafish causes skeletal muscle atrophy through disruption of de novo purine synthesis, abnormal AICAR accumulation, blockade of IMP synthesis, mitochondrial structural damage, dysfunction of oxidative phosphorylation (OXPHOS) complexes I–V, and reactive oxygen species burst, ultimately activating the ubiquitin-proteasome system to drive muscle atrophy. CRISPR/Cas9 atic knockout zebrafish, siRNA knockdown in C2C12 myoblasts, mitochondrial function assays, ROS measurement, OXPHOS complex activity assays, ubiquitin-proteasome pathway readouts 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 and suppression of ATIC transcription, thereby blocking de novo purine biosynthesis and breast cancer progression. ATIC knockdown mimicked the tumor-suppressive effects of TPT1-AS1. Mass spectrometry (MS) identification of TPT1-AS1 interactome, Co-IP of TPT1-AS1/CBP, ChIP for H3K27Ac at ATIC promoter, siRNA knockdown, xenograft tumor model Cancer science Medium 40091780
2025 ATIC knockdown in upper tract urothelial carcinoma (UTUC) cells reduces B7-H3 (CD276), PRNP, RAC2, and NT5E expression as determined by TMT-based quantitative proteomics. The ATIC/B7-H3 axis modulates mTOR, AKT, ERK, and p38 phosphorylation. B7-H3 appears upstream of PRNP and RAC2 in this network. TMT-based quantitative proteomics after ATIC knockdown, Western blot for signaling proteins, siRNA epistasis experiments, cell proliferation/migration/invasion assays Cancer genomics & proteomics Low 41771578

Source papers

Stage 0 corpus · 69 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
2015 AMPK Activation via Modulation of De Novo Purine Biosynthesis with an Inhibitor of ATIC Homodimerization. Chemistry & biology 75 26144885
2001 The NPM-ALK and the ATIC-ALK fusion genes can be detected in non-neoplastic cells. The American journal of pathology 75 11395396
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 40 36073366
2016 Association of the ATIC 347 C/G polymorphism with responsiveness to and toxicity of methotrexate in rheumatoid arthritis: a meta-analysis. Rheumatology international 36 27379764
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
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
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 22 30546311
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
2016 ATIC 347C>G gene polymorphism may be associated with methotrexate-induced adverse events in south Indian Tamil rheumatoid arthritis. Pharmacogenomics 20 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 16 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
2020 Cyclic Peptide Mimotopes for the Detection of Serum Anti-ATIC Autoantibody Biomarker in Hepato-Cellular Carcinoma. International journal of molecular sciences 11 33352757
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
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 Hydrodynamic Enhancement of p-atic Defect Dynamics. Physical review letters 5 36930922
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
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 4 38071832
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
2008 Association and haplotype analysis of purH gene with inosine monophosphate content in chickens. Animal biotechnology 4 18855251
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 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
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
2026 ATIC facilitates the malignant progression of bladder cancer by modulating AMPK-mTOR-S6K1 axis under folate reprogramming. Journal of translational medicine 1 41723491
2025 Lnc-TPT1-AS1/CBP/ATIC Axis Mediated Purine Metabolism Activation Promotes Breast Cancer Progression. Cancer science 1 40091780
2025 miR-944 inhibits malignant progression of bladder cancer through ATIC/AKT/FOXO3 A axis mediated by SHMT1. In vitro cellular & developmental biology. Animal 1 40442541
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 Knockdown Reduces B7-H3 Expression and Oncogenic Signaling in Upper Tract Urothelial Carcinoma Cells. Cancer genomics & proteomics 0 41771578
2026 Integrative machine learning and multi-omics analysis reveals ATIC as a promoter of hepatocellular carcinoma progression. Scientific reports 0 42259854
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 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

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