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). (6S)-10-formyltetrahydrofolate + 5-amino-1-(5-phospho-beta-D-ribosyl)imidazole-4-carboxamide = (6S)-5,6,7,8-tetrahydrofolate + 5-formamido-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide 10-formyldihydrofolate + 5-amino-1-(5-phospho-beta-D-ribosyl)imidazole-4-carboxamide = 5-formamido-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide + 7,8-dihydrofolate H2O + IMP = 5-formamido-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide 10-formyldihydrofolate + 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-thiocarboxamide = 6-thio-IMP + 7,8-dihydrofolate + H2O AMP and XMP inhibit AICAR formyltransferase activity (PubMed:10985775). AICAR formyltransferase activity is inhibited by N-(6-fluoro-1-oxo-1,2-dihydroisoquinolin-7-yl)-5- [(3R)-3-hydroxypyrrolidin-1-yl]thiophene-2-sulfonamide (LSN 3213128), which acts as a tumor suppression in cancer cell lines (PubMed:29072452). kcat is 3.7 sec(-1) for AICAR formyltransferase activity with (6S)-10-formyltetrahydrofolate as substrate (PubMed:10985775). kcat is 4.1 sec(-1) for AICAR formyltransferase activity with 10-formyldihydrofolate as substrate (PubMed:10985775). kcat is 2.9 sec(-1) for AICAR formyltransferase activity with (6S)-10-formyltetrahydrofolate as substrate (PubMed:11948179). kcat is 6.0 sec(-1) for FAICAR cyclization activity (PubMed:11948179). kcat is 8.6 sec(-1) for FAICAR cyclization activity (PubMed:14756554). Purine metabolism; IMP biosynthesis via de novo pathway; 5-formamido-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide from 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide (10-formyl THF route): step 1/1. Purine metabolism; IMP biosynthesis via de novo pathway; IMP from 5-formamido-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide: step 1/1. Homodimer (PubMed:14756553, PubMed:14966129). Associates with internalized INSR complexes on Golgi/endosomal membranes (PubMed:25687571). Interacts with INSR; ATIC together with PRKAA2/AMPK2 and HACD3/PTPLAD1 is proposed to be part of a signaling network regulating INSR autophosphorylation and endocytosis (PubMed:25687571). Present in the heart, brain, placenta, lung, liver, skeletal muscle, kidney, pancreas. The IMP cyclohydrolase activity resides in the N-terminal region. The disease is caused by variants affecting the gene represented in this entry. The de novo purine synthesis pathway includes 10 sequential steps, beginning with phosphoribosyl pyrophosphate and ending with inositol monophosphate (IMP), the first purin compound of the pathway. Belongs to the PurH family.