ATIC

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0004643 phosphoribosylaminoimidazolecarboxamide formyltransferase activity	IBA GO_REF:0000033	ACCEPT	Summary: AICAR transformylase (phosphoribosylaminoimidazolecarboxamide formyltransferase, EC 2.1.2.3) activity is a core, phylogenetically conserved molecular function of ATIC, catalyzing the penultimate step of de novo IMP biosynthesis. This IBA is well supported by direct experimental characterization of the human enzyme. Reason: Core molecular function of the C-terminal domain, confirmed by kinetic and structural studies of the human protein. The IBA sensibly transfers the family-conserved activity to human ATIC. Supporting Evidence: PMID:9378707 With the cloned cDNA fragment, we constructed expression vectors for mature and GST-fused AICAR transformylase. Both recombinant molecules possessing AICAR transformylase activity were overproduced in Escherichia coli. PMID:8567683 IMPCHase and AICARFT activities are located within the NH2-terminal 223 and COOH-terminal 406 amino acids, respectively.
GO:0005829 cytosol	IBA GO_REF:0000033	ACCEPT	Summary: ATIC is a cytosolic enzyme of the de novo purine biosynthesis pathway; cytosolic localization is conserved across the PurH family and is where the enzyme carries out its catalytic activities. Reason: Cytosol is the established subcellular location of ATIC (UniProt Cytoplasm, cytosol), consistent with its role in the soluble purine biosynthesis pathway. The is_active_in qualifier is appropriate because the enzyme performs its function in the cytosol. Supporting Evidence: file:human/ATIC/ATIC-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm, cytosol
GO:0003937 IMP cyclohydrolase activity	IBA GO_REF:0000033	ACCEPT	Summary: IMP cyclohydrolase (EC 3.5.4.10) activity is a core, conserved molecular function of ATIC, catalyzing the final step of de novo IMP biosynthesis (cyclization of FAICAR to IMP). Directly confirmed for the human enzyme by kinetics and mutagenesis. Reason: Core molecular function residing in the N-terminal domain; the IBA correctly propagates this family-conserved activity to human ATIC. Supporting Evidence: PMID:14756554 The bifunctional enzyme aminoimidazole carboxamide ribonucleotide transformylase/inosine monophosphate cyclohydrolase (ATIC) is responsible for catalysis of the last two steps in the de novo purine pathway. PMID:8567683 IMPCHase and AICARFT activities are located within the NH2-terminal 223 and COOH-terminal 406 amino acids, respectively.
GO:0006189 'de novo' IMP biosynthetic process	IBA GO_REF:0000033	ACCEPT	Summary: ATIC catalyzes the last two steps of the de novo IMP biosynthesis pathway, so involvement in de novo IMP biosynthesis is a core biological process for this gene. Reason: Directly supported process; ATIC is the terminal bifunctional enzyme of the de novo purine (IMP) pathway. The IBA is at the correct level of specificity. Supporting Evidence: PMID:11948179 is a bifunctional protein possessing two enzymatic activities that sequentially catalyze the last two steps in the pathway for de novo synthesis of inosine 5'-monophosphate
GO:0003937 IMP cyclohydrolase activity	IEA GO_REF:0000120	ACCEPT	Summary: Electronic assertion (ARBA/RHEA/EC mapping) of IMP cyclohydrolase activity. This is the same core catalytic function established experimentally for human ATIC. Reason: The IEA (EC 3.5.4.10 / RHEA:18445) correctly maps to ATIC's experimentally confirmed IMP cyclohydrolase activity. Supporting Evidence: PMID:14756554 transformylase/inosine monophosphate cyclohydrolase (ATIC) is responsible for catalysis of the last two steps in the de novo purine pathway
GO:0004643 phosphoribosylaminoimidazolecarboxamide formyltransferase activity	IEA GO_REF:0000120	ACCEPT	Summary: Electronic assertion (RHEA:22192 / EC 2.1.2.3) of AICAR transformylase activity, matching the experimentally confirmed core function of ATIC. Reason: The IEA correctly maps EC 2.1.2.3 to ATIC's experimentally confirmed AICAR transformylase activity. Supporting Evidence: PMID:10985775 It is proposed that the conformation of the carboxamide moiety required for binding to AICAR Tfase is different than the conformation required for binding to IMP CHase
GO:0005829 cytosol	IEA GO_REF:0000044	ACCEPT	Summary: Electronic assertion of cytosol localization from UniProt Subcellular Location mapping (SL-0091). Consistent with the established cytosolic localization of ATIC. Reason: Matches the curated UniProt subcellular location (Cytoplasm, cytosol) and the IBA cytosol annotation. Supporting Evidence: file:human/ATIC/ATIC-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm, cytosol
GO:0006164 purine nucleotide biosynthetic process	IEA GO_REF:0000002	ACCEPT	Summary: InterPro2GO mapping (IPR002695, PurH-like) to the general process of purine nucleotide biosynthesis. Correct but less specific than the de novo IMP biosynthetic process annotation. Reason: Biologically correct; ATIC functions in purine nucleotide biosynthesis. This is a broader parent of the more specific de novo IMP biosynthetic process annotation, and acceptable as an IEA that is deliberately conservative. Supporting Evidence: PMID:11948179 sequentially catalyze the last two steps in the pathway for de novo synthesis of inosine 5'-monophosphate
GO:0003360 brainstem development	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Electronic transfer of a rat/mouse ortholog annotation (Ensembl Compara) asserting involvement in brainstem development. There is no direct evidence that ATIC has a dedicated developmental role in the brainstem; any neurodevelopmental phenotype is a downstream consequence of impaired purine supply (AICA-ribosiduria), not a distinct molecular process ATIC participates in. Reason: This is an over-propagated ortholog-transfer IEA. ATIC's neurological involvement is indirect, via its housekeeping purine-biosynthesis function; a specific brainstem developmental process annotation over-interprets an electronic ortholog transfer and is not a core function.
GO:0006177 GMP biosynthetic process	IEA GO_REF:0000120	KEEP AS NON CORE	Summary: Electronic assertion that ATIC is involved in GMP biosynthesis. ATIC produces IMP, the common precursor from which GMP (and AMP) are subsequently derived; ATIC itself does not catalyze any GMP-specific step. Reason: ATIC acts upstream of GMP biosynthesis by generating the shared IMP precursor, so an acts-upstream-of style relationship is defensible, but GMP biosynthesis is not a core function of ATIC (its core outputs are the two enzymatic steps that make IMP). Keep as non-core rather than remove. Supporting Evidence: PMID:11948179 sequentially catalyze the last two steps in the pathway for de novo synthesis of inosine 5'-monophosphate
GO:0006189 'de novo' IMP biosynthetic process	IEA GO_REF:0000120	ACCEPT	Summary: Electronic assertion (ARBA / UniPathway UPA00074) of involvement in de novo IMP biosynthesis, matching the core biological process of ATIC. Reason: Correct core process, redundant with the IBA/IDA de novo IMP biosynthesis annotations. Supporting Evidence: PMID:11948179 sequentially catalyze the last two steps in the pathway for de novo synthesis of inosine 5'-monophosphate
GO:0021549 cerebellum development	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Ortholog-transfer IEA (Ensembl Compara) asserting cerebellum development. As with brainstem development, there is no evidence for a dedicated ATIC role in cerebellar development beyond its general housekeeping purine-biosynthesis function. Reason: Over-propagated developmental IEA; neurodevelopmental effects of ATIC deficiency are indirect consequences of purine insufficiency, not a distinct cerebellum-development function.
GO:0021987 cerebral cortex development	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Ortholog-transfer IEA (Ensembl Compara) asserting cerebral cortex development. No direct evidence for a specific cortical developmental role of ATIC distinct from its metabolic housekeeping function. Reason: Over-propagated developmental IEA; not a core function of ATIC.
GO:0031100 animal organ regeneration	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Ortholog-transfer IEA (Ensembl Compara) asserting involvement in organ regeneration, likely reflecting increased purine demand in regenerating rodent tissue rather than a specific regenerative function of ATIC. Reason: Over-propagated IEA; any association with regeneration is an indirect consequence of proliferation-driven purine demand, not a dedicated molecular role of ATIC.
GO:0044208 'de novo' AMP biosynthetic process	IEA GO_REF:0000120	KEEP AS NON CORE	Summary: Electronic assertion of involvement in de novo AMP biosynthesis. ATIC produces IMP, from which AMP is subsequently synthesized; ATIC does not catalyze an AMP-specific step. Reason: ATIC acts upstream of AMP biosynthesis via the shared IMP precursor. Defensible as an upstream involvement but not a core function; keep as non-core. Supporting Evidence: PMID:11948179 sequentially catalyze the last two steps in the pathway for de novo synthesis of inosine 5'-monophosphate
GO:0046452 dihydrofolate metabolic process	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Ortholog-transfer IEA (Ensembl Compara) asserting dihydrofolate metabolic process. ATIC's transformylase reaction consumes 10-formyltetrahydrofolate (and can use 10-formyldihydrofolate) and releases tetrahydrofolate (or dihydrofolate), so it participates in folate one-carbon metabolism, but it is not a canonical enzyme of dihydrofolate metabolism. Reason: ATIC consumes a formyl-folate cofactor rather than performing dedicated dihydrofolate metabolism; the term over-interprets the cofactor usage. Its folate link is that its AICAR-transformylase step depends on 10-formyl-THF, making it an antifolate target, not a dihydrofolate-metabolizing enzyme. Supporting Evidence: file:human/ATIC/ATIC-uniprot.txt Can use both 10-formyldihydrofolate
GO:0046654 tetrahydrofolate biosynthetic process	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Ortholog-transfer IEA (Ensembl Compara) asserting tetrahydrofolate biosynthesis. ATIC releases tetrahydrofolate as a product of the transformylase reaction (from 10-formyl-THF) but does not synthesize the tetrahydrofolate scaffold; this is not a biosynthetic role for THF. Reason: Regenerating THF from a formyl-THF donor during formyl transfer is not tetrahydrofolate biosynthesis. Over-propagated cofactor-based IEA. Supporting Evidence: file:human/ATIC/ATIC-uniprot.txt and 10-formyltetrahydrofolate as the formyl donor in this reaction
GO:0097294 'de novo' XMP biosynthetic process	IEA GO_REF:0000120	KEEP AS NON CORE	Summary: Electronic assertion of involvement in de novo XMP biosynthesis. XMP is derived from IMP (via IMP dehydrogenase) downstream of ATIC; ATIC does not catalyze an XMP-specific step. Reason: ATIC acts upstream of XMP biosynthesis through the shared IMP precursor. Not a core function; keep as non-core. Supporting Evidence: PMID:11948179 sequentially catalyze the last two steps in the pathway for de novo synthesis of inosine 5'-monophosphate
GO:0003937 IMP cyclohydrolase activity	EXP PMID:11948179 The kinetic mechanism of the human bifunctional enzyme ATIC ...	ACCEPT	Summary: Direct kinetic characterization of the human bifunctional enzyme established the IMP cyclohydrolase activity (cyclization of FAICAR to IMP), which is essentially unidirectional and draws the overall reaction toward IMP. Reason: Experimental (EXP) evidence directly demonstrating the core IMP cyclohydrolase function of human ATIC via complete kinetic analysis. Supporting Evidence: PMID:11948179 the cyclohydrolase reaction is essentially unidirectional in the forward sense. The cyclohydrolase reaction thus draws the overall bifunctional reaction toward the production of inosine monophosphate.
GO:0003937 IMP cyclohydrolase activity	EXP PMID:14756554 Catalytic mechanism of the cyclohydrolase activity of human ...	ACCEPT	Summary: Site-directed mutagenesis and steady-state kinetics of the human enzyme dissected the catalytic mechanism of the IMP cyclohydrolase activity, directly confirming this core function. Reason: Experimental evidence directly characterizing ATIC's IMP cyclohydrolase catalytic mechanism in the human enzyme. Supporting Evidence: PMID:14756554 four candidate residues, Lys66, Tyr104, Asp125, and Lys137, were identified for site-directed mutagenesis to study the cyclohydrolase activity of this bifunctional enzyme
GO:0004643 phosphoribosylaminoimidazolecarboxamide formyltransferase activity	EXP PMID:10985775 Human AICAR transformylase: role of the 4-carboxamide of AIC...	ACCEPT	Summary: Mechanistic study of human AICAR transformylase using AICAR analogues, establishing the specificity and catalytic role of the 4-carboxamide and directly confirming AICAR transformylase (formyltransferase) activity. Reason: Experimental evidence directly characterizing the human AICAR transformylase catalytic activity. Supporting Evidence: PMID:10985775 The results show that the 4-carboxamide of AICAR is essential for catalysis, and it is proposed to assist in mediating proton transfer
GO:0004643 phosphoribosylaminoimidazolecarboxamide formyltransferase activity	EXP PMID:11948179 The kinetic mechanism of the human bifunctional enzyme ATIC ...	ACCEPT	Summary: The complete kinetic mechanism study of human ATIC directly measured the AICAR transformylase reaction (forward/reverse rates, rate-limiting THF release), confirming formyltransferase activity. Reason: Experimental evidence directly demonstrating human ATIC AICAR transformylase activity within the bifunctional enzyme. Supporting Evidence: PMID:11948179 The rate-limiting step in the overall reaction (2.9 +/- 0.4 s(-1)) is likely the release of tetrahydrofolate from the formyltransferase active site
GO:0004643 phosphoribosylaminoimidazolecarboxamide formyltransferase activity	EXP PMID:9378707 Characterization of molecularly cloned human 5-aminoimidazol...	ACCEPT	Summary: Molecular cloning and expression of human AICAR transformylase with mutagenesis identifying His213 and His267 as essential for activity, directly confirming the formyltransferase function. Reason: Experimental evidence: recombinant human enzyme with demonstrated AICAR transformylase activity and essential catalytic residues identified. Supporting Evidence: PMID:9378707 Mutational analysis, utilizing this expression system, showed that His213 and His267 were essential for AICAR transformylase activity.
GO:0005829 cytosol	TAS Reactome:R-HSA-9700181	ACCEPT	Summary: Reactome cytosol localization annotation. Consistent with the established cytosolic localization of ATIC, though attached to an ALK-fusion signaling event module (see reference). Reason: Cytosol is the correct location for ATIC; TAS from Reactome is consistent with curated UniProt subcellular location. Supporting Evidence: file:human/ATIC/ATIC-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm, cytosol
GO:0005829 cytosol	TAS Reactome:R-HSA-9700190	ACCEPT	Summary: Reactome cytosol localization annotation (ALK-fusion module). Consistent with ATIC's cytosolic localization. Reason: Cytosol is the correct location for ATIC. Supporting Evidence: file:human/ATIC/ATIC-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm, cytosol
GO:0005829 cytosol	TAS Reactome:R-HSA-9700193	ACCEPT	Summary: Reactome cytosol localization annotation (ALK-fusion module). Consistent with ATIC's cytosolic localization. Reason: Cytosol is the correct location for ATIC. Supporting Evidence: file:human/ATIC/ATIC-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm, cytosol
GO:0005829 cytosol	TAS Reactome:R-HSA-9710914	ACCEPT	Summary: Reactome cytosol localization annotation (ALK-fusion module). Consistent with ATIC's cytosolic localization. Reason: Cytosol is the correct location for ATIC. Supporting Evidence: file:human/ATIC/ATIC-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm, cytosol
GO:0005829 cytosol	TAS Reactome:R-HSA-9710917	ACCEPT	Summary: Reactome cytosol localization annotation (ALK-fusion module). Consistent with ATIC's cytosolic localization. Reason: Cytosol is the correct location for ATIC. Supporting Evidence: file:human/ATIC/ATIC-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm, cytosol
GO:0005829 cytosol	TAS Reactome:R-HSA-9712086	ACCEPT	Summary: Reactome cytosol localization annotation (ALK-fusion module). Consistent with ATIC's cytosolic localization. Reason: Cytosol is the correct location for ATIC. Supporting Evidence: file:human/ATIC/ATIC-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm, cytosol
GO:0005829 cytosol	TAS Reactome:R-HSA-9724099	ACCEPT	Summary: Reactome cytosol localization annotation (ALK-fusion module). Consistent with ATIC's cytosolic localization. Reason: Cytosol is the correct location for ATIC. Supporting Evidence: file:human/ATIC/ATIC-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm, cytosol
GO:0003937 IMP cyclohydrolase activity	IDA PMID:26588576 Colocalization and Sequential Enzyme Activity in Aqueous Bip...	ACCEPT	Summary: In this study ATIC (with ASL) was used as a de novo purine pathway enzyme to study sequential enzyme colocalization; ATIC catalyzes steps 9 and 10 (AICAR transformylase then IMP cyclohydrolase). Supports IMP cyclohydrolase activity. Reason: Direct assay context confirming ATIC's IMP cyclohydrolase (step 10) activity; redundant with the EXP annotations but consistent and correct. Supporting Evidence: PMID:26588576 ATIC (5-aminoimidazole-4-carboxamide ribonucleotide transformylase/inosine monophosphate cyclohydrolase, Steps 9 and 10)
GO:0006177 GMP biosynthetic process	IDA PMID:26588576 Colocalization and Sequential Enzyme Activity in Aqueous Bip...	KEEP AS NON CORE	Summary: ATIC acts upstream of GMP biosynthesis by producing IMP, the common precursor of GMP and AMP. The acts_upstream_of_or_within qualifier captures this indirect relationship. Reason: Correct upstream relationship (IMP is the precursor of GMP) but GMP biosynthesis is not a core function of ATIC. Keep as non-core. Supporting Evidence: PMID:26588576 Two proteins of the de novo purine biosynthesis pathway, ASL (adenylosuccinate lyase, Step 8) and ATIC
GO:0006189 'de novo' IMP biosynthetic process	IDA PMID:26588576 Colocalization and Sequential Enzyme Activity in Aqueous Bip...	ACCEPT	Summary: ATIC catalyzes the final two steps (9 and 10) of de novo IMP biosynthesis; the acts_upstream_of_or_within relation is consistent with its participation in this pathway. Reason: Core biological process; ATIC produces IMP, the end product of de novo purine biosynthesis. Supporting Evidence: PMID:26588576 Two proteins of the de novo purine biosynthesis pathway, ASL (adenylosuccinate lyase, Step 8) and ATIC
GO:0044208 'de novo' AMP biosynthetic process	IDA PMID:26588576 Colocalization and Sequential Enzyme Activity in Aqueous Bip...	KEEP AS NON CORE	Summary: ATIC acts upstream of AMP biosynthesis by producing IMP, the precursor of AMP. The acts_upstream_of_or_within qualifier captures this indirect relationship. Reason: Correct upstream relationship but not a core function of ATIC; keep as non-core. Supporting Evidence: PMID:26588576 Two proteins of the de novo purine biosynthesis pathway, ASL (adenylosuccinate lyase, Step 8) and ATIC
GO:0097294 'de novo' XMP biosynthetic process	IDA PMID:26588576 Colocalization and Sequential Enzyme Activity in Aqueous Bip...	KEEP AS NON CORE	Summary: ATIC acts upstream of XMP biosynthesis by producing IMP, the precursor from which XMP is made (via IMP dehydrogenase). Reason: Correct upstream relationship but not a core function of ATIC; keep as non-core. Supporting Evidence: PMID:26588576 Two proteins of the de novo purine biosynthesis pathway, ASL (adenylosuccinate lyase, Step 8) and ATIC
GO:0097294 'de novo' XMP biosynthetic process	IDA PMID:26588576 Colocalization and Sequential Enzyme Activity in Aqueous Bip...	KEEP AS NON CORE	Summary: involved_in variant of the XMP biosynthesis annotation from the same study. ATIC provides the IMP precursor upstream of XMP synthesis but does not itself catalyze XMP formation. Reason: ATIC's contribution to XMP biosynthesis is indirect (via IMP); not a core function. Keep as non-core rather than accept as core process. Supporting Evidence: PMID:26588576 Two proteins of the de novo purine biosynthesis pathway, ASL (adenylosuccinate lyase, Step 8) and ATIC
GO:0006177 GMP biosynthetic process	IDA PMID:26588576 Colocalization and Sequential Enzyme Activity in Aqueous Bip...	KEEP AS NON CORE	Summary: involved_in variant of the GMP biosynthesis annotation. ATIC provides the IMP precursor upstream of GMP synthesis but does not itself catalyze a GMP-specific step. Reason: Indirect (upstream) relationship; not a core function of ATIC. Keep as non-core. Supporting Evidence: PMID:26588576 Two proteins of the de novo purine biosynthesis pathway, ASL (adenylosuccinate lyase, Step 8) and ATIC
GO:0006189 'de novo' IMP biosynthetic process	IDA PMID:26588576 Colocalization and Sequential Enzyme Activity in Aqueous Bip...	ACCEPT	Summary: involved_in variant of the de novo IMP biosynthesis annotation. ATIC catalyzes the last two steps of this pathway, making this a core biological process. Reason: Core biological process for ATIC (production of IMP), directly supported. Supporting Evidence: PMID:26588576 Two proteins of the de novo purine biosynthesis pathway, ASL (adenylosuccinate lyase, Step 8) and ATIC
GO:0044208 'de novo' AMP biosynthetic process	IDA PMID:26588576 Colocalization and Sequential Enzyme Activity in Aqueous Bip...	KEEP AS NON CORE	Summary: involved_in variant of the AMP biosynthesis annotation. ATIC provides the IMP precursor upstream of AMP synthesis but does not catalyze an AMP-specific step. Reason: Indirect (upstream) relationship; not a core function. Keep as non-core. Supporting Evidence: PMID:26588576 Two proteins of the de novo purine biosynthesis pathway, ASL (adenylosuccinate lyase, Step 8) and ATIC
GO:0005829 cytosol	TAS Reactome:R-HSA-9700179	ACCEPT	Summary: Reactome cytosol localization annotation (ALK-fusion module). Consistent with ATIC's cytosolic localization. Reason: Cytosol is the correct location for ATIC. Supporting Evidence: file:human/ATIC/ATIC-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm, cytosol
GO:0045296 cadherin binding	HDA PMID:25468996 E-cadherin interactome complexity and robustness resolved by...	MARK AS OVER ANNOTATED	Summary: ATIC was identified among the proteins in the vicinity of the E-cadherin cytoplasmic tail in a high-throughput BioID proximity-biotinylation proteomic screen. This is a proximity-labeling co-detection, not evidence of a specific, functionally meaningful cadherin-binding activity of ATIC. Reason: The authors themselves note the screen captured many proteins that do not localize to junctions and are found elsewhere in the cell; ATIC is a soluble cytosolic metabolic enzyme with no independent evidence of a cadherin-binding function. This is a non-specific proximity-proteomics hit, not a core molecular function. Per policy, an HDA is not removed outright. Supporting Evidence: PMID:25468996 employed proximity biotinylation and quantitative proteomics to isolate and identify 612 proteins in the vicinity of E-cadherin’s cytoplasmic tail PMID:25468996 the expression of GFP-tagged candidates clearly showed that many of the E-cad-BirA* interactome proteins are found in other locations in the cell
GO:0070062 extracellular exosome	HDA PMID:23533145 In-depth proteomic analyses of exosomes isolated from expres...	MARK AS OVER ANNOTATED	Summary: ATIC was detected among ~900 proteins in a shotgun proteomic survey of exosomes from expressed prostatic secretions in urine. This is a bulk-proteomics co-detection typical for abundant cytosolic housekeeping enzymes and does not reflect ATIC's genuine functional localization. Reason: Detection in an exosome proteome is a common non-specific finding for abundant cytosolic enzymes and does not indicate a functional extracellular/exosomal role for ATIC, whose established localization is cytosol. Not a core function. Supporting Evidence: PMID:23533145 In pooled EPS-urine exosome samples, ~900 proteins were detected.
GO:0016020 membrane	HDA PMID:19946888 Defining the membrane proteome of NK cells.	MARK AS OVER ANNOTATED	Summary: ATIC was identified in a mass-spectrometry membrane-proteome survey of an NK-like cell line; the authors explicitly note that many identified species are not integral membrane proteins but are transiently or peripherally associated. ATIC is a soluble cytosolic enzyme. Reason: Non-specific co-purification in a membrane fraction; the study itself flags that a large fraction of hits are not genuine membrane proteins. ATIC is cytosolic; not a core membrane localization. Supporting Evidence: PMID:19946888 The remaining species were largely involved in cellular processes and molecular functions that could be predicted to be transiently associated with membranes.
GO:0070062 extracellular exosome	HDA PMID:19056867 Large-scale proteomics and phosphoproteomics of urinary exos...	MARK AS OVER ANNOTATED	Summary: ATIC was detected among 1132 proteins in a large-scale proteomic profile of human urinary exosomes. As above, this is a bulk-proteomics co-detection of an abundant cytosolic enzyme, not evidence of a functional exosomal role. Reason: Non-specific exosome-proteome detection; ATIC's established localization is cytosol. Not a core function. Supporting Evidence: PMID:19056867 the analysis identified 1132 proteins unambiguously
GO:0070062 extracellular exosome	HDA PMID:20458337 MHC class II-associated proteins in B-cell exosomes and pote...	MARK AS OVER ANNOTATED	Summary: ATIC was detected among 539 proteins in a proteomic analysis of purified B-cell-derived exosomes. Again a bulk-proteomics co-detection, not a functional exosomal localization for this cytosolic enzyme. Reason: Non-specific exosome-proteome detection; ATIC is cytosolic. Not a core function. Supporting Evidence: PMID:20458337 we first analyzed the total proteome of highly purified B cell-derived exosomes using sensitive and accurate mass spectrometry (MS), and identified 539 proteins
GO:0005829 cytosol	TAS Reactome:R-HSA-73797	ACCEPT	Summary: Reactome cytosol localization for the reaction "FAICAR => IMP + H2O" (the IMP cyclohydrolase step). This correctly places ATIC's catalytic activity in the cytosol. Reason: Cytosol is the correct location for ATIC, and this Reactome event corresponds directly to ATIC's IMP cyclohydrolase reaction. Supporting Evidence: file:human/ATIC/ATIC-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm, cytosol
GO:0005829 cytosol	TAS Reactome:R-HSA-73798	ACCEPT	Summary: Reactome cytosol localization for the reaction "AICAR + 10-Formyl-THF => FAICAR + THF" (the AICAR transformylase step). Correctly places ATIC's catalytic activity in the cytosol. Reason: Cytosol is the correct location for ATIC, and this Reactome event corresponds directly to ATIC's AICAR transformylase reaction. Supporting Evidence: file:human/ATIC/ATIC-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm, cytosol
GO:0042803 protein homodimerization activity	IPI PMID:14756553 Structural insights into the human and avian IMP cyclohydrol...	ACCEPT	Summary: Crystal structures of human ATIC establish that the enzyme is a homodimer, with the AICAR transformylase active site formed at the dimer interface (substrate shared between dimeric partners). Homodimerization is functionally important because the dimeric form has enhanced cyclohydrolase activity. Reason: ATIC functions as an obligate homodimer; structural evidence (PDB 1PKX) confirms the homodimeric assembly. This is a genuine, functionally relevant quaternary-structure activity, not a bare protein-binding annotation. Supporting Evidence: PMID:14756553 crystal structures of XMP inhibitor complexes of human ATIC at 1.9 A resolution file:human/ATIC/ATIC-uniprot.txt SUBUNIT: Homodimer (PubMed:14756553, PubMed:14966129)
GO:0042803 protein homodimerization activity	IPI PMID:14966129 Crystal structures of human bifunctional enzyme aminoimidazo...	ACCEPT	Summary: Crystal structures of human ATIC in complex with AICAR and sulfonyl- containing antifolates confirm the homodimeric assembly, with the transformylase active site (Lys266, His267, Asn431') built at the dimer interface. Reason: Structural confirmation of the functionally required homodimer. This is a meaningful quaternary-structure annotation, not a vague protein-binding term. Supporting Evidence: PMID:14966129 now implicate Asn(431') in the reaction mechanism along with previously identified key catalytic residues Lys(266) and His(267) file:human/ATIC/ATIC-uniprot.txt SUBUNIT: Homodimer (PubMed:14756553, PubMed:14966129)
GO:0003937 IMP cyclohydrolase activity	TAS PMID:8567683 The human purH gene product, 5-aminoimidazole-4-carboxamide ...	ACCEPT	Summary: Cloning, purification, kinetic analysis and domain mapping of the human purH (ATIC) gene product established both enzymatic activities, localizing IMP cyclohydrolase (IMPCHase) to the N-terminal region. Reason: Author-asserted (TAS) and directly supported by the same paper's domain-mapping and kinetic data; core IMP cyclohydrolase function. Supporting Evidence: PMID:8567683 IMPCHase and AICARFT activities are located within the NH2-terminal 223 and COOH-terminal 406 amino acids, respectively.
GO:0004643 phosphoribosylaminoimidazolecarboxamide formyltransferase activity	TAS PMID:8567683 The human purH gene product, 5-aminoimidazole-4-carboxamide ...	ACCEPT	Summary: The same cloning/domain-mapping study established the AICAR formyltransferase (AICARFT) activity of human ATIC and localized it to the C-terminal region. Reason: Author-asserted and directly supported; core AICAR transformylase function. Supporting Evidence: PMID:8567683 IMPCHase and AICARFT activities are located within the NH2-terminal 223 and COOH-terminal 406 amino acids, respectively.
GO:0006139 nucleobase-containing compound metabolic process	TAS PMID:8567683 The human purH gene product, 5-aminoimidazole-4-carboxamide ...	MODIFY	Summary: Author-asserted involvement in nucleobase-containing compound metabolism. This is a very general parent term; ATIC's specific role is in de novo IMP/purine nucleotide biosynthesis. Reason: The term is correct but far too general given that ATIC's specific process is de novo IMP biosynthesis (and, more broadly, purine nucleotide biosynthesis). Replace with the more informative specific process term. Proposed replacements: 'de novo' IMP biosynthetic process Supporting Evidence: PMID:8567683 These steps of de novo purine biosynthesis, respectively.

Gene Description

Existing Annotations Review

Core Functions

AICAR transformylase (phosphoribosylaminoimidazolecarboxamide formyltransferase, EC 2.1.2.3) that transfers a formyl group from 10-formyltetrahydrofolate to AICAR to form FAICAR -- the penultimate step of de novo IMP biosynthesis. Acts as a cytosolic homodimer.

References

📄 View Raw YAML