GART

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0004641 phosphoribosylformylglycinamidine cyclo-ligase activity	IBA GO_REF:0000033	ACCEPT	Summary: AIR synthetase (EC 6.3.3.1), the central AIRS domain activity of the trifunctional GART protein, catalyzing the ATP-dependent cyclization of FGAM to AIR (step 5 of de novo IMP biosynthesis). A core molecular function, well supported phylogenetically. Reason: This is one of the three defining catalytic activities of GART, carried by the central AIRS domain, and is consistent across IBA, IDA, IEA, and TAS lines. Supporting Evidence: file:human/GART/GART-uniprot.txt The central AIRS domain carries the phosphoribosylformylglycinamidine cyclo-ligase activity.
GO:0006164 purine nucleotide biosynthetic process	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: GART participates in de novo purine nucleotide biosynthesis. This is a correct but broad parent of the more specific 'de novo' IMP biosynthetic process (GO:0006189). Reason: Accurate but general; the specific process for GART is 'de novo' IMP biosynthetic process (GO:0006189), which is captured separately and is the core process term. Retain this broader IBA parent as supporting, non-core context. Supporting Evidence: file:human/GART/GART-uniprot.txt Trifunctional enzyme that catalyzes three distinct reactions as part of the 'de novo' inosine monophosphate biosynthetic pathway.
GO:0005829 cytosol	IBA GO_REF:0000033	ACCEPT	Summary: GART is a cytosolic enzyme; the de novo purine pathway operates in the cytosol (with transient purinosome assembly under low-purine conditions). Reason: Cytosolic localization is the core location for this pathway, consistent across IBA, IDA (PMID:2183217), IEA, and Reactome TAS lines. Supporting Evidence: Reactome:R-HSA-73814 The active form of the protein is cytosolic
GO:0004637 phosphoribosylamine-glycine ligase activity	IBA GO_REF:0000033	ACCEPT	Summary: GAR synthetase (EC 6.3.4.13), the N-terminal ATP-grasp domain activity, condensing phosphoribosylamine, glycine, and ATP to GAR (step 2 of de novo IMP biosynthesis). A core molecular function. Reason: One of the three defining catalytic activities of GART, carried by the N-terminal ATP-grasp domain; well supported phylogenetically and by structure. Supporting Evidence: file:human/GART/GART-uniprot.txt The N-terminal ATP-grasp domain carries the phosphoribosylamine--glycine ligase activity.
GO:0046084 adenine biosynthetic process	IBA GO_REF:0000033	MARK AS OVER ANNOTATED	Summary: IBA-projected term for synthesis of the free purine base adenine. Human GART contributes to de novo purine NUCLEOTIDE synthesis (IMP and downstream AMP), not to synthesis of the free adenine base. Reason: Human de novo purine biosynthesis produces IMP and thence the nucleotides AMP/GMP, not free adenine base; adenine biosynthetic process is a taxonomically skewed projection (CGD/PANTHER) that does not accurately describe GART's role. The correct process is 'de novo' IMP biosynthetic process (GO:0006189). Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: LINEAGE OR TAXON MISMATCH GRANULARITY MISMATCH Sources checked: PANTHER:PTN000055158 · Trifunctional purine biosynthetic protein family node The 'adenine biosynthetic process' projection is contributed via a Candida (CGD:CAL0000199243) family member; in human, GART makes the nucleotide IMP, not the free adenine base, so the term mis-scopes the biosynthetic product. Supporting Evidence: file:human/GART/GART-uniprot.txt Trifunctional enzyme that catalyzes three distinct reactions as part of the 'de novo' inosine monophosphate biosynthetic pathway.
GO:0003824 catalytic activity	IEA GO_REF:0000117	MARK AS OVER ANNOTATED	Summary: Root-level molecular function term; correct but uninformative given that the three specific catalytic activities of GART are annotated explicitly. Reason: GART is an enzyme, so this ARBA-derived term is not wrong, but it is far too general to be informative when the specific EC 6.3.4.13 / 2.1.2.2 / 6.3.3.1 activities are already annotated. Supporting Evidence: file:human/GART/GART-uniprot.txt Trifunctional enzyme that catalyzes three distinct reactions as part of the 'de novo' inosine monophosphate biosynthetic pathway.
GO:0004637 phosphoribosylamine-glycine ligase activity	IEA GO_REF:0000120	ACCEPT	Summary: Electronic (InterPro/RHEA/EC) support for GAR synthetase activity (EC 6.3.4.13), duplicating the IBA/IDA/TAS lines for this core activity. Reason: Correct and specific; the IEA mapping via InterPro, RHEA:17453 and EC:6.3.4.13 is consistent with the experimentally supported activity. Supporting Evidence: file:human/GART/GART-uniprot.txt The N-terminal ATP-grasp domain carries the phosphoribosylamine--glycine ligase activity.
GO:0004641 phosphoribosylformylglycinamidine cyclo-ligase activity	IEA GO_REF:0000120	ACCEPT	Summary: Electronic (InterPro/RHEA/EC) support for AIR synthetase activity (EC 6.3.3.1), duplicating the IBA/IDA/TAS lines for this core activity. Reason: Correct and specific; the IEA mapping via InterPro:IPR004733, RHEA:23032 and EC:6.3.3.1 is consistent with the experimentally supported activity. Supporting Evidence: file:human/GART/GART-uniprot.txt The central AIRS domain carries the phosphoribosylformylglycinamidine cyclo-ligase activity.
GO:0004644 phosphoribosylglycinamide formyltransferase activity	IEA GO_REF:0000120	ACCEPT	Summary: Electronic (InterPro/RHEA/EC) support for GAR transformylase activity (EC 2.1.2.2), duplicating the EXP/IDA/TAS lines for this core, experimentally validated activity. Reason: Correct and specific; the IEA mapping via InterPro:IPR004607, RHEA:15053 and EC:2.1.2.2 agrees with the experimental (EXP) annotations of this activity. Supporting Evidence: file:human/GART/GART-uniprot.txt The C-terminal GART domain carries the phosphoribosylglycinamide formyltransferase activity.
GO:0005524 ATP binding	IEA GO_REF:0000002	ACCEPT	Summary: ATP is a substrate of both the GAR synthetase (ATP-grasp) and AIR synthetase domains; ATP-binding residues are defined in the ATP-grasp domain by crystallography. Reason: Supported by the ATP-grasp domain and mapped ATP-binding residues (BINDING 190-193, 197, 220, 229 to ATP); a genuine, if supporting rather than defining, molecular function. Supporting Evidence: file:human/GART/GART-uniprot.txt The N-terminal ATP-grasp domain carries the phosphoribosylamine--glycine ligase activity.
GO:0006189 'de novo' IMP biosynthetic process	IEA GO_REF:0000120	ACCEPT	Summary: The core biological process for GART: it catalyzes three consecutive steps of the de novo IMP biosynthesis pathway. Reason: This is the defining process for GART. Electronic support here is corroborated by the IDA annotations from PMID:2183217 and the UniProt PATHWAY statements. Supporting Evidence: file:human/GART/GART-uniprot.txt Trifunctional enzyme that catalyzes three distinct reactions as part of the 'de novo' inosine monophosphate biosynthetic pathway.
GO:0009113 purine nucleobase biosynthetic process	IEA GO_REF:0000002	KEEP AS NON CORE	Summary: InterPro-derived term for synthesis of purine nucleobases. GART's role is in de novo purine NUCLEOTIDE (IMP) biosynthesis rather than free nucleobase synthesis. Reason: Broad and slightly imprecise (nucleobase vs nucleotide), but defensible as an ancestor of the purine-synthesis role. The precise term is 'de novo' IMP biosynthetic process (GO:0006189); retain this as non-core. Supporting Evidence: file:human/GART/GART-uniprot.txt Trifunctional enzyme that catalyzes three distinct reactions as part of the 'de novo' inosine monophosphate biosynthetic pathway.
GO:0046872 metal ion binding	IEA GO_REF:0000002	ACCEPT	Summary: GART binds one divalent metal ion (Mg2+ or Mn2+) per subunit, required for the ATP-dependent ligase/synthetase reactions. Reason: Supported by the UniProt cofactor annotation and mapped Mg2+-binding residues (BINDING 288, 290). A genuine supporting molecular function. Supporting Evidence: file:human/GART/GART-uniprot.txt Binds 1 magnesium or manganese ion per subunit.
GO:0003360 brainstem development	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Developmental term transferred electronically from a rat ortholog via Ensembl Compara (GO_REF:0000107). GART is a broadly expressed housekeeping de novo purine enzyme, not a brainstem-specific developmental regulator. Reason: This reflects expression/phenotype transfer from a rodent ortholog, not a specific molecular role of GART in brainstem development. A ubiquitous nucleotide-metabolism enzyme; the term over-specifies a generic housekeeping requirement. Supporting Evidence: file:human/GART/GART-uniprot.txt Trifunctional enzyme that catalyzes three distinct reactions as part of the 'de novo' inosine monophosphate biosynthetic pathway.
GO:0005829 cytosol	IEA GO_REF:0000107	ACCEPT	Summary: Cytosolic localization transferred electronically from a mouse ortholog; consistent with the experimentally supported cytosolic localization of human GART. Reason: Redundant with the IDA/IBA/TAS cytosol annotations but correct; cytosol is the core location. Supporting Evidence: Reactome:R-HSA-73814 The active form of the protein is cytosolic
GO:0006177 GMP biosynthetic process	IEA GO_REF:0000120	MARK AS OVER ANNOTATED	Summary: GMP is synthesized from IMP, downstream of the GART-catalyzed steps. GART supplies the IMP precursor but does not itself perform GMP-specific biosynthetic reactions. Reason: GART acts before the IMP branch point; GMP biosynthesis (IMP -> XMP -> GMP) is carried out by IMPDH and GMPS. involved_in overstates GART's participation; its contribution is upstream provision of IMP, better captured by GO:0006189. Supporting Evidence: file:human/GART/GART-uniprot.txt Trifunctional enzyme that catalyzes three distinct reactions as part of the 'de novo' inosine monophosphate biosynthetic pathway.
GO:0021549 cerebellum development	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Developmental term transferred electronically from a rat ortholog via Ensembl Compara. GART is a broadly expressed housekeeping enzyme, not a cerebellum-specific developmental regulator. Reason: As with the other brain-development terms, this is ortholog expression/phenotype transfer, not a specific developmental function of GART. Supporting Evidence: file:human/GART/GART-uniprot.txt Trifunctional enzyme that catalyzes three distinct reactions as part of the 'de novo' inosine monophosphate biosynthetic pathway.
GO:0021987 cerebral cortex development	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Developmental term transferred electronically from a rat ortholog via Ensembl Compara. GART is a broadly expressed housekeeping enzyme, not a cortex-specific developmental regulator. Reason: Ortholog expression/phenotype transfer, not a specific molecular role of GART in cerebral cortex development. Supporting Evidence: file:human/GART/GART-uniprot.txt Trifunctional enzyme that catalyzes three distinct reactions as part of the 'de novo' inosine monophosphate biosynthetic pathway.
GO:0044208 'de novo' AMP biosynthetic process	IEA GO_REF:0000120	MARK AS OVER ANNOTATED	Summary: AMP is synthesized from IMP, downstream of the GART-catalyzed steps. GART supplies the IMP precursor but does not itself perform AMP-specific biosynthetic reactions. Reason: GART acts before the IMP branch point; AMP biosynthesis (IMP -> adenylosuccinate -> AMP) is carried out by ADSS and ADSL. involved_in overstates its participation; the accurate role is upstream IMP provision (GO:0006189). Supporting Evidence: file:human/GART/GART-uniprot.txt Trifunctional enzyme that catalyzes three distinct reactions as part of the 'de novo' inosine monophosphate biosynthetic pathway.
GO:0097294 'de novo' XMP biosynthetic process	IEA GO_REF:0000120	MARK AS OVER ANNOTATED	Summary: XMP is synthesized from IMP, downstream of the GART-catalyzed steps. GART supplies the IMP precursor but does not itself perform XMP-specific biosynthetic reactions. Reason: GART acts before the IMP branch point; XMP biosynthesis (IMP -> XMP) is carried out by IMPDH. involved_in overstates its participation; the accurate role is upstream IMP provision (GO:0006189). Supporting Evidence: file:human/GART/GART-uniprot.txt Trifunctional enzyme that catalyzes three distinct reactions as part of the 'de novo' inosine monophosphate biosynthetic pathway.
GO:0009168 purine ribonucleoside monophosphate biosynthetic process	TAS Reactome:R-HSA-73817	KEEP AS NON CORE	Summary: Reactome-asserted involvement in purine ribonucleoside monophosphate (IMP) biosynthesis; the pathway assembles IMP on PRPP, and GART catalyzes three of its steps. Reason: Correct but a broader parent of 'de novo' IMP biosynthetic process (GO:0006189). Retain as supporting, non-core context; the specific IMP term is the core process. Supporting Evidence: Reactome:R-HSA-73817 The purine ribonucleotide inosine 5'-monophosphate (IMP) is assembled on 5-phospho-alpha-D-ribose 1-diphosphate (PRPP)
GO:0004637 phosphoribosylamine-glycine ligase activity	TAS Reactome:R-HSA-73814	ACCEPT	Summary: Reactome (TAS) annotation of GAR synthetase activity: synthesis of GAR from 5-phosphoribosylamine, glycine and ATP. A core catalytic activity. Reason: Matches the experimentally and phylogenetically supported GAR synthetase activity of the N-terminal ATP-grasp domain. Supporting Evidence: Reactome:R-HSA-73814 is catalyzed by the phosphoribosylglycinamide synthetase domain of the trifunctional protein
GO:0004641 phosphoribosylformylglycinamidine cyclo-ligase activity	TAS Reactome:R-HSA-73810	ACCEPT	Summary: Reactome (TAS) annotation of AIR synthetase activity: irreversible ATP-dependent synthesis of AIR from FGAM. A core catalytic activity. Reason: Matches the experimentally and phylogenetically supported AIR synthetase activity of the central AIRS domain. Supporting Evidence: Reactome:R-HSA-73810 is catalyzed by the phosphoribosylaminoimidazole synthetase domain of the trifunctional protein
GO:0004644 phosphoribosylglycinamide formyltransferase activity	TAS Reactome:R-HSA-73813	ACCEPT	Summary: Reactome (TAS) annotation of GAR transformylase activity: folate-dependent formyl transfer from 10-formyl-THF to GAR to give FGAR. A core catalytic activity. Reason: Matches the experimentally supported (EXP; PMID:12450384, PMID:12755606) GAR transformylase activity of the C-terminal GART domain. Supporting Evidence: Reactome:R-HSA-73813 is catalyzed by the phosphoribosylglycinamide formyltransferase domain of the trifunctional protein
GO:0004644 phosphoribosylglycinamide formyltransferase activity	EXP PMID:12450384 Crystal structures of human GAR Tfase at low and high pH and...	ACCEPT	Summary: GAR transformylase (GAR Tfase) activity established by crystal structures of the human enzyme with its substrate beta-GAR and pH-dependent activity measurements. A core, experimentally validated catalytic activity and antitumor drug target. Reason: Strong experimental support: structures of the human purN domain with substrate and pH-dependent enzyme activity. This is the best-supported of GART's three activities. Supporting Evidence: PMID:12450384 Glycinamide ribonucleotide transformylase (GAR Tfase) is a key folate-dependent enzyme in the de novo purine biosynthesis pathway
GO:0004644 phosphoribosylglycinamide formyltransferase activity	EXP PMID:12755606 Rational design, synthesis, evaluation, and crystal structur...	ACCEPT	Summary: GAR transformylase activity confirmed via a structure-based folate-analogue inhibitor (Ki=15 nM) and its crystal structure with human GAR Tfase; reinforces the folate-dependent catalytic activity and antifolate-target role. Reason: Experimental support for GO:0004644 through selective inhibition of recombinant human GAR Tfase and co-crystal structure. Consistent with the other EXP/IDA/TAS lines. Supporting Evidence: PMID:12755606 which specifically inhibits recombinant human GAR Tfase (K(i) = 15 nM)
GO:0004641 phosphoribosylformylglycinamidine cyclo-ligase activity	IDA PMID:2183217 Cloning of three human multifunctional de novo purine biosyn...	ACCEPT	Summary: AIR synthetase activity demonstrated by functional complementation of a yeast ade7 (AIRS) mutation by the human GART cDNA, establishing this as one of GART's three activities. Reason: Complementation of the yeast ade7 (AIRS/PAIS) mutation by the human trifunctional cDNA directly supports the AIR synthetase activity. Curator (MGI) IDA annotation. Supporting Evidence: PMID:2183217 also complemented the ade5 (phosphoribosylglycinamide synthetase) and ade7 [phosphoribosylaminoimidazole synthetase (AIRS; also known as PAIS)] mutations, indicating that it is the human trifunctional GART gene
GO:0004644 phosphoribosylglycinamide formyltransferase activity	IDA PMID:2183217 Cloning of three human multifunctional de novo purine biosyn...	ACCEPT	Summary: GAR transformylase activity demonstrated by functional complementation of a yeast ade8 (GART) mutation by the human GART cDNA. Reason: Complementation of the yeast ade8 (phosphoribosylglycinamide formyltransferase, GART) mutation by the human cDNA directly supports this activity. Curator (MGI) IDA annotation, also independently supported by EXP structures. Supporting Evidence: PMID:2183217 The cDNA that complemented the ade8 (phosphoribosylglycinamide formyltransferase, GART) mutation
GO:0005829 cytosol	IDA PMID:2183217 Cloning of three human multifunctional de novo purine biosyn...	ACCEPT	Summary: Cytosolic localization of GART; the core location of the de novo purine biosynthesis machinery. Reason: Curator IDA annotation for cytosolic localization, consistent with all other location evidence (IBA, IEA, Reactome TAS). Supporting Evidence: Reactome:R-HSA-73814 The active form of the protein is cytosolic
GO:0006177 GMP biosynthetic process	IDA PMID:2183217 Cloning of three human multifunctional de novo purine biosyn...	MARK AS OVER ANNOTATED	Summary: GART provides IMP, the precursor from which GMP is made. GART does not itself perform GMP-specific biosynthetic reactions; GMP synthesis (IMP -> XMP -> GMP) is carried out by IMPDH and GMPS downstream of GART. Reason: GART acts before the IMP branch point and is not part of GMP-specific biosynthesis. Even with the acts_upstream_of_or_within qualifier this term over-specifies GART's role; its accurate direct process is de novo IMP biosynthesis (GO:0006189). Marked over-annotated to keep review actions consistent across all GO:0006177 lines. Supporting Evidence: file:human/GART/GART-uniprot.txt Trifunctional enzyme that catalyzes three distinct reactions as part of the 'de novo' inosine monophosphate biosynthetic pathway.
GO:0006189 'de novo' IMP biosynthetic process	IDA PMID:2183217 Cloning of three human multifunctional de novo purine biosyn...	ACCEPT	Summary: GART catalyzes three consecutive steps of de novo IMP biosynthesis; established by complementation of yeast ade5/ade7/ade8 mutations by the single human cDNA. Reason: The defining biological process for GART, directly supported by the complementation experiments. (The involved_in duplicate of this term is the core-process form.) Supporting Evidence: PMID:2183217 clone three multifunctional human genes involved in de novo purine biosynthesis
GO:0044208 'de novo' AMP biosynthetic process	IDA PMID:2183217 Cloning of three human multifunctional de novo purine biosyn...	MARK AS OVER ANNOTATED	Summary: GART provides IMP, the precursor from which AMP is made. GART does not itself perform AMP-specific biosynthetic reactions; AMP synthesis (IMP -> adenylosuccinate -> AMP) is carried out by ADSS and ADSL downstream of GART. Reason: GART acts before the IMP branch point and is not part of AMP-specific biosynthesis. Even with the acts_upstream_of_or_within qualifier this over-specifies GART's role; its accurate direct process is de novo IMP biosynthesis (GO:0006189). Marked over-annotated to keep review actions consistent across all GO:0044208 lines. Supporting Evidence: file:human/GART/GART-uniprot.txt Trifunctional enzyme that catalyzes three distinct reactions as part of the 'de novo' inosine monophosphate biosynthetic pathway.
GO:0097294 'de novo' XMP biosynthetic process	IDA PMID:2183217 Cloning of three human multifunctional de novo purine biosyn...	MARK AS OVER ANNOTATED	Summary: GART provides IMP, the precursor from which XMP is made. GART does not itself perform XMP-specific biosynthetic reactions; XMP synthesis (IMP -> XMP) is carried out by IMPDH downstream of GART. Reason: GART acts before the IMP branch point and is not part of XMP-specific biosynthesis. Even with the acts_upstream_of_or_within qualifier this over-specifies GART's role; its accurate direct process is de novo IMP biosynthesis (GO:0006189). Marked over-annotated to keep review actions consistent across all GO:0097294 lines. Supporting Evidence: file:human/GART/GART-uniprot.txt Trifunctional enzyme that catalyzes three distinct reactions as part of the 'de novo' inosine monophosphate biosynthetic pathway.
GO:0097294 'de novo' XMP biosynthetic process	IDA PMID:2183217 Cloning of three human multifunctional de novo purine biosyn...	MARK AS OVER ANNOTATED	Summary: involved_in duplicate of the XMP biosynthesis annotation. XMP is made from IMP, downstream of GART; GART does not perform XMP-specific reactions. Reason: The involved_in qualifier asserts GART is part of XMP-specific biosynthesis, which overstates its role. GART's direct process is de novo IMP biosynthesis (GO:0006189); XMP synthesis (IMP -> XMP) is done by IMPDH. Supporting Evidence: file:human/GART/GART-uniprot.txt Trifunctional enzyme that catalyzes three distinct reactions as part of the 'de novo' inosine monophosphate biosynthetic pathway.
GO:0006177 GMP biosynthetic process	IDA PMID:2183217 Cloning of three human multifunctional de novo purine biosyn...	MARK AS OVER ANNOTATED	Summary: involved_in duplicate of the GMP biosynthesis annotation. GMP is made from IMP, downstream of GART; GART does not perform GMP-specific reactions. Reason: The involved_in qualifier asserts GART is part of GMP-specific biosynthesis, which overstates its role. GART's direct process is de novo IMP biosynthesis (GO:0006189); GMP synthesis is done by IMPDH and GMPS. Supporting Evidence: file:human/GART/GART-uniprot.txt Trifunctional enzyme that catalyzes three distinct reactions as part of the 'de novo' inosine monophosphate biosynthetic pathway.
GO:0006189 'de novo' IMP biosynthetic process	IDA PMID:2183217 Cloning of three human multifunctional de novo purine biosyn...	ACCEPT	Summary: The core biological process for GART: it catalyzes three consecutive steps of de novo IMP biosynthesis (GAR synthetase, GAR transformylase, AIR synthetase). Reason: Directly supported by the yeast-complementation experiments establishing the trifunctional de novo purine enzyme; this is the core process term for GART. Supporting Evidence: PMID:2183217 clone three multifunctional human genes involved in de novo purine biosynthesis
GO:0005829 cytosol	IDA PMID:2183217 Cloning of three human multifunctional de novo purine biosyn...	ACCEPT	Summary: GART is active in the cytosol; the core location of de novo purine biosynthesis. Reason: Consistent with all other cytosol evidence; is_active_in appropriately captures where the enzyme functions. Supporting Evidence: Reactome:R-HSA-73814 The active form of the protein is cytosolic
GO:0044208 'de novo' AMP biosynthetic process	IDA PMID:2183217 Cloning of three human multifunctional de novo purine biosyn...	MARK AS OVER ANNOTATED	Summary: involved_in duplicate of the AMP biosynthesis annotation. AMP is made from IMP, downstream of GART; GART does not perform AMP-specific reactions. Reason: The involved_in qualifier asserts GART is part of AMP-specific biosynthesis, which overstates its role. GART's direct process is de novo IMP biosynthesis (GO:0006189); AMP synthesis is done by ADSS and ADSL. Supporting Evidence: file:human/GART/GART-uniprot.txt Trifunctional enzyme that catalyzes three distinct reactions as part of the 'de novo' inosine monophosphate biosynthetic pathway.
GO:0070062 extracellular exosome	HDA PMID:20458337 MHC class II-associated proteins in B-cell exosomes and pote...	MARK AS OVER ANNOTATED	Summary: Detected in a high-throughput MS survey of the B-cell exosome proteome (539 proteins), not a specific localization study. GART is a cytosolic de novo purine enzyme. Reason: This HDA annotation derives from bulk exosome proteomics; cytosolic enzymes are common passenger contaminants in such datasets. It does not represent a specific or core extracellular/exosomal function of GART, whose established location is the cytosol. Supporting Evidence: PMID:20458337 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-73810	ACCEPT	Summary: Reactome (TAS) cytosolic localization associated with the AIR synthetase reaction; the core location of GART. Reason: Consistent with all other cytosol evidence. Supporting Evidence: Reactome:R-HSA-73810 The active form of the protein is cytosolic
GO:0005829 cytosol	TAS Reactome:R-HSA-73813	ACCEPT	Summary: Reactome (TAS) cytosolic localization associated with the GAR transformylase reaction; the core location of GART. Reason: Consistent with all other cytosol evidence. Supporting Evidence: Reactome:R-HSA-73813 Fluoresence microscopy studies of cultured human cells have shown that GART is cytosolic
GO:0005829 cytosol	TAS Reactome:R-HSA-73814	ACCEPT	Summary: Reactome (TAS) cytosolic localization associated with the GAR synthetase reaction; the core location of GART. Reason: Consistent with all other cytosol evidence. Supporting Evidence: Reactome:R-HSA-73814 The active form of the protein is cytosolic
GO:0004644 phosphoribosylglycinamide formyltransferase activity	TAS PMID:2050105 Cloning and in vivo expression of the human GART gene using ...	ACCEPT	Summary: Traceable author statement (TAS) for GAR transformylase activity from the paper cloning the full-length human GART gene, which describes the trifunctional GARS-GART-AIRS protein. Reason: Consistent with the EXP/IDA/TAS/IEA support for GO:0004644; the reference describes the trifunctional protein including the GART (formyltransferase) function. Supporting Evidence: PMID:2050105 the trifunctional protein containing phosphoribosylglycinamide synthetase (GARS), phosphoribosylglycinamide formyltransferase (GART) and phosphoribosylaminoimidazole synthetase (AIRS)

Gene Description

Existing Annotations Review

Core Functions

Phosphoribosylamine--glycine ligase (GAR synthetase, EC 6.3.4.13) activity of the N-terminal ATP-grasp domain, catalyzing step 2 of de novo IMP biosynthesis (5-phospho-beta-D-ribosylamine + glycine + ATP -> GAR + ADP + Pi).

Phosphoribosylglycinamide formyltransferase (GAR transformylase, EC 2.1.2.2) activity of the C-terminal GART domain, the folate-dependent step 3 of de novo IMP biosynthesis (GAR + 10-formyl-THF -> FGAR + THF) and a validated antifolate chemotherapy target.

Phosphoribosylformylglycinamidine cyclo-ligase (AIR synthetase, EC 6.3.3.1) activity of the central AIRS domain, catalyzing step 5 of de novo IMP biosynthesis (FGAM + ATP -> AIR + ADP + Pi).

References

Suggested Questions for Experts

Suggested Experiments

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Notes

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