ATIC

This gene encodes a bifunctional protein that catalyzes the last two steps of the de novo purine biosynthetic pathway. The N-terminal domain has phosphoribosylaminoimidazolecarboxamide formyltransferase activity, and the C-terminal domain has IMP cyclohydrolase activity. A mutation in this gene results in AICA-ribosiduria. [provided by RefSeq, Sep 2009]

5-Aminoimidazole-4-Carboxamide Ribonucleotide Formyltransferase/IMP Cyclohydrolase

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:9378707, PubMed:11948179, PubMed:10985775).
Can use both 10-formyldihydrofolate and 10-formyltetrahydrofolate as the formyl donor in this reaction (PubMed:10985775).
Also catalyzes the cyclization of FAICAR to 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).

de novo' IMP biosynthetic process Source: GO_Central
Animal organ regeneration Source: Ensembl
Brainstem development Source: Ensembl
Cellular response to interleukin-7 Source: Ensembl
Cerebellum development Source: Ensembl
Cerebral cortex development Source: Ensembl
Dihydrofolate metabolic process Source: Ensembl
Nucleobase-containing compound metabolic process Source: ProtInc
Nucleoside metabolic process Source: Ensembl
Purine ribonucleoside monophosphate biosynthetic process Source: Reactome
Response to inorganic substance Source: Ensembl
Tetrahydrofolate biosynthetic process Source: Ensembl

Cytosol; Extracellular exosome; Plasma membrane; Membrane

AICAR transformylase/IMP cyclohydrolase deficiency (AICAR): 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. AICAR causes profound mental retardation, epilepsy, dysmorphic features and congenital blindness.