protein
Bifunctional purine biosynthesis protein ATIC
Gene
ATIC
Organism
Homo sapiens(9606)
Length
592 aa
Mass
64,616 Da
ATIC (Bifunctional purine biosynthesis protein ATIC) is a 592-amino-acid enzyme catalyzing the final two steps of purine biosynthesis (UniProt: P31939). It functions as a transformylase and cyclase, converting AICAR to FAICAR and then to IMP, using either 10-formyldihydrofolate or 10-formyltetrahydrofolate as a formyl donor. The enzyme also processes thio-AICAR to 6-mercaptopurine ribonucleotide, a chemotherapeutic agent, and independently promotes insulin receptor autophosphorylation and internalization.
ATIC deficiency causes AICA-ribosuria, a severe autosomal recessive inborn error of purine metabolism characterized by neurological devastation, intellectual disability, epilepsy, and congenital blindness (UniProt: P31939, MIM 608688). The protein is central to purine biosynthesis and nucleotide metabolism pathways essential for neuronal function.
ATIC shows ambiguous regulation in Alzheimer's Disease, with a mean log2 fold-change of −0.0195 across three subcellular fractions from TMT-labeled post-mortem AD brain versus age-matched controls (Chaparral AD proteomics). This minimal change suggests no clear directional dysregulation in AD, though subcellular redistribution across the four fractions examined may warrant further investigation.
Generated from the curated entity record below. May contain errors — verify against source links.
Proteomics Evidence · AD
⚠ Ambiguous — detected in AD samples, direction unclear across fractionsP3
+0.415
P2
+0.200
S2
-0.673
S3
not detected
Mean log₂FC across detected fractions: -0.0195 (3 of 4 fractions detected)
Human post-mortem AD brain vs age-matched controls, TMT-labeled, 4 subcellular fractions (P2, P3, S2, S3), DDA proteomics.
Related Publications
Browse all →Tau molecular diversity contributes to clinical heterogeneity in Alzheimer's disease.
Dujardin Simon et al.Nature medicine2020PMID 32572268Deep Multilayer Brain Proteomics Identifies Molecular Networks in Alzheimer's Disease Progression.
Bai Bing et al.Neuron2020PMID 31926610A Multi-network Approach Identifies Protein-Specific Co-expression in Asymptomatic and Symptomatic Alzheimer's Disease.
Seyfried Nicholas T et al.Cell systems2017PMID 27989508Large-scale deep multi-layer analysis of Alzheimer's disease brain reveals strong proteomic disease-related changes not observed at the RNA level.
Johnson Erik C B et al.Nature neuroscience2022PMID 35115731Organization and regulation of gene transcription.
Cramer PatrickNature2019PMID 31462772
Function
Bifunctional enzyme that catalyzes the last two steps of purine biosynthesis (PubMed:11948179, PubMed:14756554). Acts as a transformylase that incorporates a formyl group to the AMP analog AICAR (5-amino-1-(5-phospho-beta-D-ribosyl)imidazole-4-carboxamide) to produce the intermediate formyl-AICAR (FAICAR) (PubMed:10985775, PubMed:11948179, PubMed:9378707). Can use both 10-formyldihydrofolate and 10-formyltetrahydrofolate as the formyl donor in this reaction (PubMed:10985775). Also catalyzes the cyclization of FAICAR to inosine monophosphate (IMP) (PubMed:11948179, PubMed:14756554). Is able to convert thio-AICAR to 6-mercaptopurine ribonucleotide, an inhibitor of purine biosynthesis used in the treatment of human leukemias (PubMed:10985775). Promotes insulin receptor/INSR autophosphorylation and is involved in INSR internalization (PubMed:25687571)
Disease associations
AICA-ribosuria due to ATIC deficiencyAICAR
A neurologically devastating inborn error of purine biosynthesis. Patients excrete massive amounts of AICA-riboside in the urine and accumulate AICA-ribotide and its derivatives in erythrocytes and fibroblasts. Clinical features include profound intellectual disability, epilepsy, dysmorphic features and congenital blindness. AICAR inheritance is autosomal recessive.
Sources
Last updated 5/8/2026, 6:28:38 AM