Mouse anti-Human/Mouse/Rat sapiens (Human) ATIC Monoclonal Antibody

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)

Subcellular Location

Cytoplasm, cytosol

Disease Association

AICA-ribosuria due to ATIC 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. Clinical features include profound intellectual disability, epilepsy, dysmorphic features and congenital blindness. AICAR inheritance is autosomal recessive. [The disease is caused by variants affecting the gene represented in this entry]

Tissue Specificity

Present in the heart, brain, placenta, lung, liver, skeletal muscle, kidney, pancreas

Subunit

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)

Pathway

Purine metabolism; IMP biosynthesis via de novo pathway; IMP from 5-formamido-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide: step 1/1

• Rayl E.A. et al. The human purH gene product, 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/IMP cyclohydrolase. Cloning, sequencing, expression, purification, kinetic analysis, and domain mapping. — J. Biol. Chem. (1996)
• Yamauchi M. et al. Isolation of human purH gene expressed in the rodent transformant cells by subtractive enrichment of 3'-untranslated region of human transcript. — DNA Res. (1995)
• Sugita T. et al. Characterization of molecularly cloned human 5-aminoimidazole-4-carboxamide ribonucleotide transformylase. — J. Biochem. (1997)
• Shichijo S. et al. Identification of immuno-peptidmics that are recognized by tumor-reactive CTL generated from TIL of colon cancer patients. (MAY-)
• Ota T. et al. Complete sequencing and characterization of 21,243 full-length human cDNAs. — Nat. Genet. (2004)
• Hillier L.W. et al. Generation and annotation of the DNA sequences of human chromosomes 2 and 4. — Nature (2005)
• Mural R.J. et al. PubMed: CI-56FT96O07V0QG (JUL-)
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). — Genome Res. (2004)