De novo inosine monophosphate biosynthesis

A reusable pathway that assembles the purine ring on 5-phosphoribosyl diphosphate (PRPP) to form inosine monophosphate (IMP). The module represents ten ordered reaction positions and separates reaction roles from lineage-specific protein fusions. It includes alternative folate-dependent PurN and ATP/formate-dependent PurT routes for GAR formylation, and alternative two-enzyme and direct routes for AIR carboxylation. Enzyme architecture varies widely: bacteria commonly use separate PurF, PurD, PurN/PurT, PurL, PurM, PurK, PurE, PurC, PurB and PurH proteins; animals fuse PurD, PurM and PurN in GART and direct AIR carboxylase with SAICAR synthetase in PAICS; fungi fuse PurD with PurM in a bifunctional GAR synthetase-AIR synthetase and PurK with PurE in a bifunctional AIR carboxylase that works through the N5-carboxyaminoimidazole ribonucleotide intermediate. In eukaryotes the pathway is cytosolic. The first enzyme, amidophosphoribosyltransferase, is feedback-inhibited by adenine nucleotides. IMP-to-AMP and IMP-to-GMP branches are outside the module, although PurB also has a second physiological role in AMP synthesis.

MODULE:de_novo_purine_synthesisDRAFTMetabolic Pathwaymodules/de_novo_purine_synthesis.yaml

'de novo' IMP biosynthetic processGO:0006189

YeastPathways:PWY-6122-1

5-aminoimidazole ribonucleotide biosynthesis II (S. cerevisiae, SGD YeastPathways)

First five reactions (PRPP to AIR) with ADE4, ADE5,7 (GAR synthetase and AIR synthetase), ADE8 and ADE6. Gene assignments are correct.

YeastPathways:PWY-6123-1

inosine-5'-phosphate biosynthesis I (S. cerevisiae, SGD YeastPathways)

AIR to IMP with ADE2, ADE1, ADE13 and the ADE16/ADE17 isozymes. AIR carboxylation is drawn as the single direct reaction AIRCARBOXY-RXN (EC 4.1.1.21), whereas fungal ADE2 works through the N5-CAIR intermediate (PMID:9500840).

YeastPathways:DENOVOPURINE2-PWY

superpathway of purine nucleotides de novo biosynthesis II (S. cerevisiae, SGD YeastPathways)

Superpathway joining this module with purine_nucleotide_interconversion (ADE12, ADE13, IMD2-4, GUA1, ADK1/ADK2, GUK1, YNK1) and ribonucleotide reduction (RNR1-4). It also lists two formate-dependent class III ribonucleotide reductase reactions (RXN0-745, RXN0-746) with no yeast gene; these are not part of yeast metabolism.

YeastPathways:DENOVOPURINE3-PWY

de novo biosynthesis of purine nucleotides (S. cerevisiae, SGD YeastPathways)

Same reaction set as DENOVOPURINE2-PWY plus an ammonia-dependent GMP synthase reaction; the comment describes the 10-step IMP pathway and its Bas1/Bas2 transcriptional control.

YeastPathways:PRPP-PWY-1

superpathway of histidine, purine, and pyrimidine biosynthesis (S. cerevisiae, SGD YeastPathways)

Union of PRPP synthesis (PRS1-PRS5), histidine biosynthesis, de novo purine and pyrimidine biosynthesis and nucleotide interconversion. Only the IMP reactions are modelled here; the other parts belong to pentose_phosphate_pathway, histidine_biosynthesis, de_novo_pyrimidine_synthesis, purine_nucleotide_interconversion and dntp_de_novo_synthesis.

GO:0006189

'de novo' IMP biosynthetic process

GO:0006189 defines the pathway from PRPP through purine-ring assembly to IMP.

file:modules/de_novo_purine_synthesis-deep-research-openscientist.md

OpenScientist research for de novo IMP biosynthesis

The generic pathway review supports the ordered reaction boundary, alternative GAR-formylation chemistry, AIR-carboxylation variants, and lineage-specific fusion architectures.

PMID:8501063

Evidence for a novel glycinamide ribonucleotide transformylase in Escherichia coli

Genetic analysis establishes PurN and PurT as alternative GAR transformylases at the same de novo purine-biosynthesis position.

PMID:10574791

Crystal structure of Escherichia coli PurE, an unusual mutase in the purine biosynthetic pathway

Structural and biochemical evidence distinguishes the bacterial PurK/PurE N5-CAIR route from direct AIR carboxylation.

PMID:9500840

Biochemical role of the Cryptococcus neoformans ADE2 protein in fungal de novo purine biosynthesis.

Fungal ADE2 is a two-domain bifunctional protein: an N-terminal PurK-like domain forms N5-CAIR from AIR, ATP and bicarbonate and a C-terminal PurE-like domain converts N5-CAIR to CAIR.

PMID:6376509

Glutamine nucleotide sequence of Saccharomyces cerevisiae ADE4 encoding phosphoribosylpyrophosphate amidotransferase.

ADE4 encodes yeast glutamine PRPP amidotransferase, homologous to the E. coli enzyme.

PMID:8082193

The ade4 gene of Schizosaccharomyces pombe: cloning, sequence and regulation.

S. pombe ade4 encodes the 533-residue amidophosphoribosyltransferase.

PMID:11689683

Yeast AMP pathway genes respond to adenine through regulated synthesis of a metabolic intermediate.

ATP feedback inhibition of Ade4p regulates flux and the synthesis of the pathway intermediate SAICAR, which promotes Bas1-Bas2 activation of the ADE genes.

PMID:3502942

Sequence of the bifunctional ade1 gene in the purine biosynthetic pathway of the fission yeast Schizosaccharomyces pombe.

S. pombe ade1 encodes a bifunctional protein carrying the second and fifth steps (GAR synthetase and AIR synthetase), homologous to S. cerevisiae ADE5,7.

PMID:9143321

Saccharomyces cerevisiae expresses two genes encoding isozymes of 5-aminoimidazole-4-carboxamide ribonucleotide transformylase.

ADE16 and ADE17 encode 84%-identical AICAR transformylase isozymes; disruption of both causes adenine auxotrophy.

PMID:10877846

Characterization of two 5-aminoimidazole-4-carboxamide ribonucleotide transformylase/inosine monophosphate cyclohydrolase isozymes from Saccharomyces cerevisiae.

Ade16p and Ade17p are cytosolic bifunctional AICAR transformylase/IMP cyclohydrolase homodimers; Ade17p is adenine-repressed and Ade16p is not.

PMID:15744050

Revisiting purine-histidine cross-pathway regulation in Saccharomyces cerevisiae: a central role for a small molecule.

AICAR, made both by this pathway and by histidine biosynthesis, acts as a regulatory metabolite; ade16 ade17 mutants are histidine auxotrophs.

PMID:22419079

Regulation of amino acid, nucleotide, and phosphate metabolism in Saccharomyces cerevisiae.

YeastBook review of purine pathway enzymes and their Bas1/Bas2 regulation.

file:human/PPAT/PPAT-ai-review.yaml

Human PPAT gene review

Q06203 provides a eukaryotic exemplar for the committed first reaction.

file:human/GART/GART-ai-review.yaml

Human GART gene review

P22102 exemplifies fusion of the PurD-, PurN-, and PurM-like reaction roles.

file:human/PFAS/PFAS-ai-review.yaml

Human PFAS gene review

O15067 provides a eukaryotic exemplar for FGAM synthase activity.

file:human/PAICS/PAICS-ai-review.yaml

Human PAICS gene review

P22234 exemplifies fusion of direct AIR carboxylase and SAICAR synthetase roles.

file:human/ADSL/ADSL-ai-review.yaml

Human ADSL gene review

P30566 provides a eukaryotic exemplar for the two physiological PurB lyase activities.

file:human/ATIC/ATIC-ai-review.yaml

Human ATIC gene review

P31939 exemplifies fusion of the final AICAR transformylase and IMP cyclohydrolase roles.

file:PSEPK/purF/purF-ai-review.yaml

PSEPK purF gene review

Q88LD5 supplies the committed amidophosphoribosyltransferase step.

file:PSEPK/purD/purD-ai-review.yaml

PSEPK purD gene review

Q88DK2 supplies phosphoribosylamine--glycine ligase activity.

file:PSEPK/purN/purN-ai-review.yaml

PSEPK purN gene review

Q88MB0 supplies the folate-dependent GAR transformylase route.

file:PSEPK/purT/purT-ai-review.yaml

PSEPK purT gene review

Q88MW1 supplies the ATP/formate-dependent GAR transformylase route.

file:PSEPK/purL/purL-ai-review.yaml

PSEPK purL gene review

Q88P16 supplies large-type FGAM synthase activity.

file:PSEPK/purM/purM-ai-review.yaml

PSEPK purM gene review

Q88MA9 supplies AIR synthetase activity.

file:PSEPK/purK/purK-ai-review.yaml

PSEPK purK gene review

Q88C48 supplies N5-CAIR synthetase activity.

file:PSEPK/purE/purE-ai-review.yaml

PSEPK purE gene review

Q88C47 supplies N5-CAIR mutase activity.

file:PSEPK/purC/purC-ai-review.yaml

PSEPK purC gene review

Q88NG9 supplies SAICAR synthetase activity.

file:PSEPK/purB/purB-ai-review.yaml

PSEPK purB gene review

Q88FR7 supplies SAICAR lyase activity in this module.

file:PSEPK/purH/purH-ai-review.yaml

PSEPK purH gene review

Q88DK3 supplies the final AICAR transformylase and IMP cyclohydrolase reactions.

20Nodes

14Parts

2Variant Sets

5Variants

15Annotons

11Connections

Derived QC

Recommended-field compliance

100.0% recommended fields populated

All recommended fields populated.

Module deep research

✓ present

de_novo_purine_synthesis-deep-research-openscientist.md (openscientist)

Leaf nodes lacking representative members

✓ every leaf node grounds to a representative protein.

Template conformance

✓ every declared conforms_to bundle matches its template motif.

Function consistency and core coverage

46 gene-function check(s) reflected in core functions · 0 conflict(s) · 13 evidence or coverage gap(s) (77 comparison(s))

Retained noncore functions are reported separately; they do not require promotion to core functions. Support from representative genes does not establish conservation across the whole family. Missing reviews or identifiers leave a claim unverified.

Annoton	Participant	Function	Assessment
purF_activity	purF (Pseudomonas putida KT2440) UniProtKB:Q88LD5 Family Representative	amidophosphoribosyltransferase activity GO:0004044	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
purF_activity	purF (Escherichia coli K-12) UniProtKB:P0AG16 Family Representative	amidophosphoribosyltransferase activity GO:0004044	Review Missing No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
purF_activity	PPAT (human) UniProtKB:Q06203 Family Representative	amidophosphoribosyltransferase activity GO:0004044	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
purF_activity	ADE4 (Saccharomyces cerevisiae) UniProtKB:P04046 Family Representative	amidophosphoribosyltransferase activity GO:0004044	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
purF_activity	ade4 (Schizosaccharomyces pombe) UniProtKB:P41390 Family Representative	amidophosphoribosyltransferase activity GO:0004044	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
purD_activity	purD (Pseudomonas putida KT2440) UniProtKB:Q88DK2 Family Representative	phosphoribosylamine-glycine ligase activity GO:0004637	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
purD_activity	purD (Escherichia coli K-12) UniProtKB:P15640 Family Representative	phosphoribosylamine-glycine ligase activity GO:0004637	Review Missing No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
purD_activity	GART (human) UniProtKB:P22102 Family Representative	phosphoribosylamine-glycine ligase activity GO:0004637	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
purD_activity	ADE57 (Saccharomyces cerevisiae) UniProtKB:P07244 Family Representative	phosphoribosylamine-glycine ligase activity GO:0004637	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
purD_activity	ade1 (Schizosaccharomyces pombe) UniProtKB:P20772 Family Representative	phosphoribosylamine-glycine ligase activity GO:0004637	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
purN_activity	purN (Pseudomonas putida KT2440) UniProtKB:Q88MB0 Family Representative	phosphoribosylglycinamide formyltransferase activity GO:0004644	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
purN_activity	purN (Escherichia coli K-12) UniProtKB:P08179 Family Representative	phosphoribosylglycinamide formyltransferase activity GO:0004644	Review Missing No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
purN_activity	GART (human) UniProtKB:P22102 Family Representative	phosphoribosylglycinamide formyltransferase activity GO:0004644	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
purN_activity	ADE8 (Saccharomyces cerevisiae) UniProtKB:P04161 Family Representative	phosphoribosylglycinamide formyltransferase activity GO:0004644	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
purN_activity	ade5 (Schizosaccharomyces pombe) UniProtKB:Q9UUK7 Family Representative	phosphoribosylglycinamide formyltransferase activity GO:0004644	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
purT_activity	purT (Pseudomonas putida KT2440) UniProtKB:Q88MW1 Family Representative	phosphoribosylglycinamide formyltransferase 2 activity GO:0043815	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
purT_activity	purT (Escherichia coli K-12) UniProtKB:P33221 Family Representative	phosphoribosylglycinamide formyltransferase 2 activity GO:0043815	Review Missing No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
purL_activity	purL (Pseudomonas putida KT2440) UniProtKB:Q88P16 Family Representative	phosphoribosylformylglycinamidine synthase activity GO:0004642	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
purL_activity	purL (Escherichia coli K-12) UniProtKB:P15254 Family Representative	phosphoribosylformylglycinamidine synthase activity GO:0004642	Review Missing No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
purL_activity	PFAS (human) UniProtKB:O15067 Family Representative	phosphoribosylformylglycinamidine synthase activity GO:0004642	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
purL_activity	ADE6 (Saccharomyces cerevisiae) UniProtKB:P38972 Family Representative	phosphoribosylformylglycinamidine synthase activity GO:0004642	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
purL_activity	ade3 (Schizosaccharomyces pombe) UniProtKB:O14228 Family Representative	phosphoribosylformylglycinamidine synthase activity GO:0004642	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
purM_activity	purM (Pseudomonas putida KT2440) UniProtKB:Q88MA9 Family Representative	phosphoribosylformylglycinamidine cyclo-ligase activity GO:0004641	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
purM_activity	purM (Escherichia coli K-12) UniProtKB:P08178 Family Representative	phosphoribosylformylglycinamidine cyclo-ligase activity GO:0004641	Review Missing No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
purM_activity	GART (human) UniProtKB:P22102 Family Representative	phosphoribosylformylglycinamidine cyclo-ligase activity GO:0004641	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
purM_activity	ADE57 (Saccharomyces cerevisiae) UniProtKB:P07244 Family Representative	phosphoribosylformylglycinamidine cyclo-ligase activity GO:0004641	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
purM_activity	ade1 (Schizosaccharomyces pombe) UniProtKB:P20772 Family Representative	phosphoribosylformylglycinamidine cyclo-ligase activity GO:0004641	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
purK_activity	purK (Pseudomonas putida KT2440) UniProtKB:Q88C48 Family Representative	5-(carboxyamino)imidazole ribonucleotide synthase activity GO:0034028	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
purK_activity	purK (Escherichia coli K-12) UniProtKB:P09029 Family Representative	5-(carboxyamino)imidazole ribonucleotide synthase activity GO:0034028	Review Missing No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
purE_activity	purE (Pseudomonas putida KT2440) UniProtKB:Q88C47 Family Representative	5-(carboxyamino)imidazole ribonucleotide mutase activity GO:0034023	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
purE_activity	purE (Escherichia coli K-12) UniProtKB:P0AG18 Family Representative	5-(carboxyamino)imidazole ribonucleotide mutase activity GO:0034023	Review Missing No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
ade2_n5_cair_synthetase_activity	ADE2 (Saccharomyces cerevisiae) UniProtKB:P21264 Family Representative	5-(carboxyamino)imidazole ribonucleotide synthase activity GO:0034028	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
ade2_n5_cair_synthetase_activity	ade6 (Schizosaccharomyces pombe) UniProtKB:P15567 Family Representative	5-(carboxyamino)imidazole ribonucleotide synthase activity GO:0034028	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
ade2_n5_cair_mutase_activity	ADE2 (Saccharomyces cerevisiae) UniProtKB:P21264 Family Representative	5-(carboxyamino)imidazole ribonucleotide mutase activity GO:0034023	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
ade2_n5_cair_mutase_activity	ade6 (Schizosaccharomyces pombe) UniProtKB:P15567 Family Representative	5-(carboxyamino)imidazole ribonucleotide mutase activity GO:0034023	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
direct_air_carboxylase_activity	PAICS (human) UniProtKB:P22234 Family Representative	phosphoribosylaminoimidazole carboxylase activity GO:0004638	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
purC_activity	purC (Pseudomonas putida KT2440) UniProtKB:Q88NG9 Family Representative	phosphoribosylaminoimidazolesuccinocarboxamide synthase activity GO:0004639	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
purC_activity	PAICS (human) UniProtKB:P22234 Family Representative	phosphoribosylaminoimidazolesuccinocarboxamide synthase activity GO:0004639	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
purC_activity	ADE1 (Saccharomyces cerevisiae) UniProtKB:P27616 Family Representative	phosphoribosylaminoimidazolesuccinocarboxamide synthase activity GO:0004639	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
purC_activity	ade7 (Schizosaccharomyces pombe) UniProtKB:Q9UUB4 Family Representative	phosphoribosylaminoimidazolesuccinocarboxamide synthase activity GO:0004639	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
purB_saicar_activity	purB (Pseudomonas putida KT2440) UniProtKB:Q88FR7 Family Representative	SAICAR lyase activity GO:0070626	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
purB_saicar_activity	purB (Escherichia coli K-12) UniProtKB:P0AB89 Family Representative	SAICAR lyase activity GO:0070626	Review Missing No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
purB_saicar_activity	ADSL (human) UniProtKB:P30566 Family Representative	SAICAR lyase activity GO:0070626	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
purB_saicar_activity	ADE13 (Saccharomyces cerevisiae) UniProtKB:Q05911 Family Representative	SAICAR lyase activity GO:0070626	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
purB_saicar_activity	ade8 (Schizosaccharomyces pombe) UniProtKB:O60105 Family Representative	SAICAR lyase activity GO:0070626	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
purH_transformylase_activity	purH (Pseudomonas putida KT2440) UniProtKB:Q88DK3 Family Representative	phosphoribosylaminoimidazolecarboxamide formyltransferase activity GO:0004643	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
purH_transformylase_activity	purH (Escherichia coli K-12) UniProtKB:P15639 Family Representative	phosphoribosylaminoimidazolecarboxamide formyltransferase activity GO:0004643	Review Missing No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
purH_transformylase_activity	ATIC (human) UniProtKB:P31939 Family Representative	phosphoribosylaminoimidazolecarboxamide formyltransferase activity GO:0004643	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
purH_transformylase_activity	ADE16 (Saccharomyces cerevisiae) UniProtKB:P54113 Family Representative	phosphoribosylaminoimidazolecarboxamide formyltransferase activity GO:0004643	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
purH_transformylase_activity	ADE17 (Saccharomyces cerevisiae) UniProtKB:P38009 Family Representative	phosphoribosylaminoimidazolecarboxamide formyltransferase activity GO:0004643	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
purH_transformylase_activity	ade10 (Schizosaccharomyces pombe) UniProtKB:O74928 Family Representative	phosphoribosylaminoimidazolecarboxamide formyltransferase activity GO:0004643	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
purH_cyclohydrolase_activity	purH (Pseudomonas putida KT2440) UniProtKB:Q88DK3 Family Representative	IMP cyclohydrolase activity GO:0003937	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
purH_cyclohydrolase_activity	purH (Escherichia coli K-12) UniProtKB:P15639 Family Representative	IMP cyclohydrolase activity GO:0003937	Review Missing No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
purH_cyclohydrolase_activity	ATIC (human) UniProtKB:P31939 Family Representative	IMP cyclohydrolase activity GO:0003937	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
purH_cyclohydrolase_activity	ADE16 (Saccharomyces cerevisiae) UniProtKB:P54113 Family Representative	IMP cyclohydrolase activity GO:0003937	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
purH_cyclohydrolase_activity	ADE17 (Saccharomyces cerevisiae) UniProtKB:P38009 Family Representative	IMP cyclohydrolase activity GO:0003937	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
purH_cyclohydrolase_activity	ade10 (Schizosaccharomyces pombe) UniProtKB:O74928 Family Representative	IMP cyclohydrolase activity GO:0003937	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
purF_activity	PurF amidophosphoribosyltransferases PANTHER:PTHR11907 Family	amidophosphoribosyltransferase activity GO:0004044	Family Supported Family review supports GO:0004044 FAMILY_WIDE. This is the defining activity of the family. It is shown for the yeast and fission-yeast enzymes and is inherited from PTN000225535, whose placement is sound. The module attaches it to the whole family. The exceptions are the GATase-domain-only members, which do not inherit the IBA anyway. FrzK keeps the full PurF architecture and is described as a PRPP amidotransferase, so it is not excepted.
purD_activity	PurD phosphoribosylamine--glycine ligases (standalone or fused) PANTHER:PTHR43472 Family	phosphoribosylamine-glycine ligase activity GO:0004637	Family Supported Family review supports GO:0004637 FAMILY_WIDE. This is the defining activity, shown for E. coli PurD and inherited through a sound node. It is the core function in the P. putida purD review. The de_novo_purine_synthesis module correctly uses this family for standalone PurD.
purD_activity	PurD phosphoribosylamine--glycine ligases (standalone or fused) PANTHER:PTHR10520:SF12 Family	phosphoribosylamine-glycine ligase activity GO:0004637	Family Function Unreviewed Family review leaves GO:0004637 UNRESOLVED. The term is safe only for the fusion members that carry a GARS domain: fungal ADE5,7/ade1-type proteins, Dictyostelium bifunctional purD, and animal GART. It is not safe for the standalone bacterial, archaeal and plant PurM proteins that make up most of SF12. All of these share the single subfamily SF12, so neither FAMILY_WIDE nor SUBFAMILY_ONLY fits. The clade-level fix is the TOO_DEEP correction at PTN000055158. In the module, the purD_activity leaf's use of PTHR10520:SF12 as a family_term is valid only together with its fusion exemplars (ADE57, ade1, GART). Standalone PurD is covered by PTHR43472.
purN_activity	PurN GAR transformylases (standalone or fused) PANTHER:PTHR43369 Family	phosphoribosylglycinamide formyltransferase activity GO:0004644	Family Supported Family review supports GO:0004644 FAMILY_WIDE. This is the defining activity of a coherent family, inherited from a sound node. The module uses it for the PurN leaf with PTHR43369 as selector, which is correct. The same leaf also lists PTHR10520:SF12, which is valid only for animal GART (see the PTHR10520 review).
purN_activity	PurN GAR transformylases (standalone or fused) PANTHER:PTHR10520:SF12 Family	phosphoribosylglycinamide formyltransferase activity GO:0004644	Family Function Unreviewed Family review leaves GO:0004644 UNRESOLVED. PAINT asserts no GAR transformylase term in this family. The module lists PTHR10520:SF12 as a family_term for the folate-dependent PurN leaf, but within SF12 only animal trifunctional GART (Pfam Formyl_trans_N) has the transformylase domain. Fungal ADE5,7/ade1 lack it, because fungi use the standalone ADE8/ade5 (PTHR43369). Standalone PurM lacks it as well. The term is safe for the GART clade only, which no subfamily delimits. As a family_term this is a module over-reach that the GART exemplar does not fix.
purT_activity	PurT formate-dependent GAR transformylases PANTHER:PTHR43055 Family	phosphoribosylglycinamide formyltransferase 2 activity GO:0043815	Family Supported Family review supports GO:0043815 FAMILY_WIDE. This is the defining activity, shown for E. coli PurT and attached to the family by the de_novo_purine_synthesis module for the PurT route. It is the core function in the P. putida purT review, which also removes the folate-dependent GO:0004644 on correct grounds. The only exceptions are the non-PurT ATP-grasp ligases in SF1. PylC is excepted on experimental evidence. The Methanobrevibacter carbamoyl-phosphate synthase is excepted on its UniProt functional annotation. Synechocystis P74724 is not excepted, because its PurK assignment comes only from a HAMAP rule.
purL_activity	large-type PurL FGAM synthases PANTHER:PTHR10099 Family	phosphoribosylformylglycinamidine synthase activity GO:0004642	Family Supported Family review supports GO:0004642 FAMILY_WIDE. The de_novo_purine_synthesis module uses PTHR10099 for the step-4 FGAM synthase annoton, and PAINT places this activity at PTN008493809. The activity holds for every single-chain large-PurL/PFAS member. Two caveats: an archaeal PurQ protein contributes only the glutaminase half-reaction to a PurQ/PurL/PurS complex, so for those proteins the activity is at most contributes_to; and the herpesvirus FGARAT-like tegument proteins have no demonstrated activity. Neither group receives the IBA. Read the family-wide scope as covering the cellular large-PurL enzymes that the module and PAINT actually address.
purM_activity	PurM AIR synthetases PANTHER:PTHR10520:SF12 Family	phosphoribosylformylglycinamidine cyclo-ligase activity GO:0004641	Family Supported Family review supports GO:0004641 FAMILY_WIDE. Every member carries the AIRS/AIRS_C domains that define the family, and the IBA comes from a sound node. This is the term the module attaches to PTHR10520:SF12 for the PurM leaf.
purK_activity	PurK N5-CAIR synthetases PANTHER:PTHR11609 Family	5-(carboxyamino)imidazole ribonucleotide synthase activity GO:0034028	Family Supported Family review supports GO:0034028 FAMILY_WIDE. The module asserts this term for the family (purK_activity) and for SF5 (the ADE2 PurK domain). The activity is defined by the PurK-type ATP-grasp domain (PF22660 pre-ATP-grasp, PF02222 ATP-grasp, PF17769 C-terminal domain), which bacterial PurK and the fungal and plant fusions all carry. The one reviewed member without it is B. cereus Pyl (Q814Z5), listed as an exception.
purE_activity	PurE N5-CAIR mutases PANTHER:PTHR23046 Family	5-(carboxyamino)imidazole ribonucleotide mutase activity GO:0034023	Family Supported Family review supports GO:0034023 FAMILY_WIDE. The module uses PTHR23046 for the bacterial N5-CAIR mutase annoton (purE_activity). The mutase holds for the class I majority, which is all the module representatives (E. coli and P. putida PurE) and all PAINT recipients. The class II members in the same subfamily are listed as exceptions. They bind AIR and CO2 rather than N5-CAIR, and their organisms lack PurK.
ade2_n5_cair_synthetase_activity	fungal ADE2-type bifunctional AIR carboxylases PANTHER:PTHR11609:SF5 Family	5-(carboxyamino)imidazole ribonucleotide synthase activity GO:0034028	Family Supported Family review supports GO:0034028 FAMILY_WIDE. The module asserts this term for the family (purK_activity) and for SF5 (the ADE2 PurK domain). The activity is defined by the PurK-type ATP-grasp domain (PF22660 pre-ATP-grasp, PF02222 ATP-grasp, PF17769 C-terminal domain), which bacterial PurK and the fungal and plant fusions all carry. The one reviewed member without it is B. cereus Pyl (Q814Z5), listed as an exception.
ade2_n5_cair_mutase_activity	fungal ADE2-type bifunctional AIR carboxylases PANTHER:PTHR11609:SF5 Family	5-(carboxyamino)imidazole ribonucleotide mutase activity GO:0034023	Family Supported Family review supports GO:0034023 for PANTHER:PTHR11609:SF5. The module asserts the mutase for PTHR11609:SF5 (the ADE2 PurE-like domain annoton). It holds only for SF5 members that carry the C-terminal class I PurE (PF00731) domain: fungal ADE2, plant PURKE and Dictyostelium purC/E. These are 68 of the 110 PTN000549205 recipients in the domain check. The bacterial standalone PurK proteins in the same subfamily have no PurE domain. Their mutase is a separate PurE protein in PTHR23046. They are listed as member exceptions, using the three reference bacteria, but the exception covers every standalone PurK in SF5. Applicability follows domain architecture, not the subfamily label, so the SF5 id alone does not select only mutases.
direct_air_carboxylase_activity	direct AIR carboxylases and PAICS-type fusion proteins PANTHER:PTHR43599:SF11 Family	phosphoribosylaminoimidazole carboxylase activity GO:0004638	Family Supported Family review supports GO:0004638 for PANTHER:PTHR43599:SF11. The module asserts the direct (class II) AIR carboxylase only for SF11 (direct_air_carboxylase_activity selects PANTHER:PTHR43599:SF11), matching this scope. The activity belongs to the C-terminal class II PurE domain (PF00731) of PAICS fusions. Every vertebrate PAICS in SF11 has that domain. Bacterial PurC, SF1 and SF8 proteins do not. The invertebrate PAICS fusions (Drosophila Paics, C. elegans pacs-1) also carry the domain but sit in SF3 with domain-less bacterial PurC, so SF3 cannot be granted as a whole. Applicability follows domain architecture. SF11 is the only subfamily for which the term is safe by label.
purC_activity	PurC and PAICS SAICAR synthetases PANTHER:PTHR43599:SF3 Family	phosphoribosylaminoimidazolesuccinocarboxamide synthase activity GO:0004639	Family Supported Family review supports GO:0004639 for PANTHER:PTHR43599:SF3. The module uses PTHR43599, together with PTHR43700, for the SAICAR synthetase annoton (purC_activity). The activity holds for SF11 (vertebrate PAICS) and for the PurC/invertebrate PAICS members of SF3. It does not hold for SF1 (RimK-like ATP-grasp proteins) or SF8 (Myb/SANT protein), which lack the PF01259 domain. Within SF3, the Myb/SANT-only proteins are exceptions.
purC_activity	PurC and PAICS SAICAR synthetases PANTHER:PTHR43599:SF11 Family	phosphoribosylaminoimidazolesuccinocarboxamide synthase activity GO:0004639	Family Supported Family review supports GO:0004639 for PANTHER:PTHR43599:SF11. The module uses PTHR43599, together with PTHR43700, for the SAICAR synthetase annoton (purC_activity). The activity holds for SF11 (vertebrate PAICS) and for the PurC/invertebrate PAICS members of SF3. It does not hold for SF1 (RimK-like ATP-grasp proteins) or SF8 (Myb/SANT protein), which lack the PF01259 domain. Within SF3, the Myb/SANT-only proteins are exceptions.
purC_activity	PurC and PAICS SAICAR synthetases PANTHER:PTHR43700 Family	phosphoribosylaminoimidazolesuccinocarboxamide synthase activity GO:0004639	Family Supported Family review supports GO:0004639 FAMILY_WIDE. The module uses PTHR43700, with PTHR43599, for the SAICAR synthetase annoton (purC_activity), with S. cerevisiae Ade1 and S. pombe ade7 as representatives. The activity is demonstrated for both yeast enzymes and is the annotated function of every reviewed member.
purB_saicar_activity	PurB adenylosuccinate lyases PANTHER:PTHR43411 Family	SAICAR lyase activity GO:0070626	Family Supported Family review supports GO:0070626 FAMILY_WIDE. The de_novo_purine_synthesis module uses PTHR43411, with PTHR43172:SF1, for the SAICAR lyase step (purB_saicar_activity). The PurB active site acts on both SAICAR and adenylosuccinate, and E. coli PurB is described as having this dual specificity. PAINT has no SAICAR lyase IBD in this family; its family-wide scope here rests on the dual-substrate chemistry, not on a PAINT node.
purB_saicar_activity	PurB adenylosuccinate lyases PANTHER:PTHR43172:SF1 Family	SAICAR lyase activity GO:0070626	Family Supported Family review supports GO:0070626 for PANTHER:PTHR43172:SF1. The de_novo_purine_synthesis module uses PTHR43172:SF1 (with PTHR43411) for the SAICAR lyase step (purB_saicar_activity), with human ADSL, yeast Ade13 and pombe ade8 as representatives. The same active site cleaves SAICAR and adenylosuccinate in true ADSLs, so the scope and exceptions match those for GO:0004018.
purH_transformylase_activity	PurH and ATIC AICAR transformylases PANTHER:PTHR11692 Family	phosphoribosylaminoimidazolecarboxamide formyltransferase activity GO:0004643	Family Supported Family review supports GO:0004643 FAMILY_WIDE. The C-terminal transformylase domain is present in every reviewed member. Activity has been measured on the purified yeast isozymes, and either yeast gene alone supports growth without adenine. This is the module's function for the purH_transformylase_activity annoton.
purH_cyclohydrolase_activity	PurH and ATIC IMP cyclohydrolases PANTHER:PTHR11692 Family	IMP cyclohydrolase activity GO:0003937	Family Supported Family review supports GO:0003937 FAMILY_WIDE. The N-terminal cyclohydrolase domain is present in every reviewed member, and both purified yeast isozymes carry the activity. This is the module's function for the purH_cyclohydrolase_activity annoton. Archaea that use the unrelated PurO cyclohydrolase are outside this family and are not affected.

Gene-review completeness (34/44 grounded genes reviewed)

33 complete review(s) · 13 with deep research · 10 missing review · 21 reviewed but lacking deep research

Gene	Review	Complete	Deep research
ade1 P20772	✓	✓	✗
ADE1 P27616	✓	✓	✓
ade10 O74928	✓	✓	✗
ADE13 Q05911	✓	✓	✓
ADE16 P54113	✓	✓	✓
ADE17 P38009	✓	✓	✓
ADE2 P21264	✓	✓	✓
ade3 O14228	✓	✓	✗
ADE4 P04046	✓	✓	✓
ade4 P41390	✓	✓	✗
ade5 Q9UUK7	✓	✓	✗
ADE57 P07244	✓	✓	✓
ade6 P15567	✓	✓	✗
ADE6 P38972	✓	✓	✓
ade7 Q9UUB4	✓	✓	✗
ade8 O60105	✓	✓	✗
ADE8 P04161	✓	✓	✓
ADSL P30566	✓	27/30	✗
ATIC P31939	✓	✓	✗
GART P22102	✓	✓	✗
purM (Escherichia coli K-12) P08178	✗	—	—
purN (Escherichia coli K-12) P08179	✗	—	—
purK (Escherichia coli K-12) P09029	✗	—	—
purB (Escherichia coli K-12) P0AB89	✗	—	—
purF (Escherichia coli K-12) P0AG16	✗	—	—
purE (Escherichia coli K-12) P0AG18	✗	—	—
purL (Escherichia coli K-12) P15254	✗	—	—
purH (Escherichia coli K-12) P15639	✗	—	—
purD (Escherichia coli K-12) P15640	✗	—	—
purT (Escherichia coli K-12) P33221	✗	—	—
PAICS P22234	✓	✓	✗
PFAS O15067	✓	✓	✗
PPAT Q06203	✓	✓	✗
purB Q88FR7	✓	✓	✗
purC Q88NG9	✓	✓	✓
purD Q88DK2	✓	✓	✓
purE Q88C47	✓	✓	✗
purF Q88LD5	✓	✓	✓
purH Q88DK3	✓	✓	✗
purK Q88C48	✓	✓	✗
purL Q88P16	✓	✓	✗
purM Q88MA9	✓	✓	✗
purN Q88MB0	✓	✓	✓
purT Q88MW1	✓	✓	✗

Tree

De novo inosine monophosphate biosynthesisMetabolic Pathwayde_novo_purine_synthesis

Parts
1. 1. committed phosphoribosylamine formation
2. AmidophosphoribosyltransferaseReactionpurF_step
  
  Annotons
  - Glutamine PRPP amidotransferase Family: PurF amidophosphoribosyltransferases
3. 2. glycinamide ribonucleotide formation
4. Phosphoribosylamine--glycine ligaseReactionpurD_step
  
  Annotons
  - GAR synthetase Family: PurD phosphoribosylamine--glycine ligases (standalone or fused)
5. 3. GAR formylation
6. Alternative GAR transformylation routesReactiongar_transformylation_step
  
  Variants
  1. GAR one-carbon donor route by one-carbon donor and energy coupling (One Or More)
    
    Folate-dependent PurN routeReactionpurN_folate_route
    
    Annotons
    
    Folate-dependent GAR transformylase Family: PurN GAR transformylases (standalone or fused)
    
    ATP/formate-dependent PurT routeReactionpurT_formate_route
    
    Annotons
    
    Formate-dependent GAR transformylase Family: PurT formate-dependent GAR transformylases
7. 4. formylglycinamidine ribonucleotide formation
8. Phosphoribosylformylglycinamidine synthaseReactionpurL_step
  
  Annotons
  - FGAM synthase Family: large-type PurL FGAM synthases
9. 5. aminoimidazole ribonucleotide formation
10. Phosphoribosylformylglycinamidine cyclo-ligaseReactionpurM_step
  
  Annotons
  - AIR synthetase Family: PurM AIR synthetases
11. 6. aminoimidazole ribonucleotide carboxylation
12. Alternative AIR carboxylation routesMetabolic Pathwayair_carboxylation_step
  
  Variants
  1. AIR-to-CAIR implementation by direct versus N5-CAIR intermediate (Exactly One)
    
    Separate PurK and PurE proteins (N5-CAIR route)Metabolic Pathwaytwo_enzyme_n5_cair_route
    
    Parts
    
    1. N5-CAIR formation
    
    N5-CAIR synthetaseReactionpurK_substep
    
    Annotons
    
    ATP-dependent N5-CAIR synthetase Family: PurK N5-CAIR synthetases
    
    2. CAIR rearrangement
    
    N5-CAIR mutaseReactionpurE_substep
    
    Annotons
    
    N5-CAIR mutase Family: PurE N5-CAIR mutases
    
    Fused PurK-PurE bifunctional AIR carboxylase (fungal ADE2 type; N5-CAIR route)Metabolic Pathwayfused_ade2_n5_cair_route
    
    Parts
    
    1. N5-CAIR formation by the PurK-like domain
    
    N5-CAIR synthetase (ADE2 PurK-like domain)Reactionade2_purK_domain_substep
    
    Annotons
    
    ADE2 N5-CAIR synthetase domain Family: fungal ADE2-type bifunctional AIR carboxylases
    
    2. CAIR formation by the PurE-like domain
    
    N5-CAIR mutase (ADE2 PurE-like domain)Reactionade2_purE_domain_substep
    
    Annotons
    
    ADE2 N5-CAIR mutase domain Family: fungal ADE2-type bifunctional AIR carboxylases
    
    Direct AIR carboxylase routeReactiondirect_air_carboxylase_route
    
    Annotons
    
    Direct AIR carboxylase Family: direct AIR carboxylases and PAICS-type fusion proteins
13. 7. succinylaminoimidazole carboxamide ribonucleotide formation
14. SAICAR synthetaseReactionpurC_step
  
  Annotons
  - SAICAR synthetase Family: PurC and PAICS SAICAR synthetases
15. 8. aminoimidazole carboxamide ribonucleotide formation
16. SAICAR lyaseReactionpurB_step
  
  Annotons
  - SAICAR lyase Family: PurB adenylosuccinate lyases
17. 9. formylaminoimidazole carboxamide ribonucleotide formation
18. AICAR transformylaseReactionpurH_transformylase_step
  
  Annotons
  - AICAR transformylase Family: PurH and ATIC AICAR transformylases
19. 10. inosine monophosphate formation
20. IMP cyclohydrolaseReactionpurH_cyclohydrolase_step
  
  Annotons
  - IMP cyclohydrolase Family: PurH and ATIC IMP cyclohydrolases

Details

Context

cytosolGO:0005829

De novo inosine monophosphate biosynthesisMetabolic Pathwayde_novo_purine_synthesis

'de novo' IMP biosynthetic processGO:0006189

Context

cytosolGO:0005829

Exact UniProt exemplars delimit each reaction role without restricting the module taxonomically. A multidomain protein may satisfy more than one leaf: GART combines PurD-, PurN-, and PurM-like roles, PAICS combines direct AIR carboxylase and SAICAR synthetase roles, and PurH/ATIC commonly combines the final two reactions. GART remains an exact fusion exemplar on the PurD and PurN leaves, where its reviewed domain descriptions establish those activities without using its whole-protein family as a reaction selector. The PurM leaf uses PTHR10520:SF12 because that whole-protein subfamily contains both standalone bacterial PurM proteins and the GART fusion; the leaf molecular function constrains it to the shared cyclo-ligase role. Separate bacterial and eukaryotic adenylosuccinate-lyase families are retained for the PurB leaf. Parent PANTHER families containing both standalone enzymes and fusion proteins are selector scaffolds constrained by the leaf molecular function and exemplars. No ancestral PTN node is asserted without verified PAINT IBD evidence. ALIGN with the YeastPathways crosswalk (PWY-6122-1, PWY-6123-1, DENOVOPURINE2-PWY, DENOVOPURINE3-PWY, PRPP-PWY-1) and the PomBase model 663d668500001911. Fungal architecture: ADE4 (PurF), ADE5,7 / S. pombe ade1 (PurD-PurM fusion, both leaves; PMID:3502942), ADE8 / ade5 (standalone PurN; fungi have no PurT), ADE6 / ade3 (large PurL), ADE2 / ade6 (fused PurK-PurE, modelled as the fused_ade2_n5_cair_route variant; PMID:9500840), ADE1 / ade7 (standalone PurC), ADE13 / ade8 (PurB) and the ADE16/ADE17 isozyme pair / ade10 (PurH-type bifunctional transformylase and cyclohydrolase; PMID:9143321, PMID:10877846). All YeastCyc catalysts are correct and none was missing. YeastCyc corrections: AIR carboxylation is drawn as the direct EC 4.1.1.21 reaction, and both YeastPathways and PomBase GO-CAMs annotate ADE2/ade6 with GO:0004638 (the direct, class II-type carboxylase term) rather than GO:0034028 + GO:0034023, although fungal ADE2 proceeds through free N5-CAIR. The YeastPathways models annotate the ADE13 SAICAR reaction with GO:0004018 (adenylosuccinate lyase) rather than GO:0070626. The superpathway frames DENOVOPURINE2-PWY and DENOVOPURINE3-PWY also contain IMP-to-AMP/GMP, NMP/NDP kinase and ribonucleotide reductase reactions (purine_nucleotide_interconversion, dntp_de_novo_synthesis) and two gene-less formate-dependent class III ribonucleotide reductase reactions that do not occur in yeast. PRPP-PWY-1 places every activity under the root-level GO:0009165 and the PomBase model additionally includes ade9 (one-carbon supply, folate_one_carbon_interconversion). Regulation (outside the module core): adenine nucleotides inhibit Ade4p, and the intermediates SAICAR and AICAR promote Bas1-Bas2 transcriptional activation of the ADE and HIS genes (PMID:11689683, PMID:15744050). PRPP supply (pentose_phosphate_pathway, PRS1-PRS5) and the 10-formyl-THF donor (folate_one_carbon_interconversion) are upstream inputs.

Connections

purF_step -> purD_step Provides Input For

PurF supplies phosphoribosylamine to PurD.

purD_step -> gar_transformylation_step Provides Input For

PurD supplies GAR to either transformylase route.

gar_transformylation_step -> purL_step Provides Input For

GAR formylation supplies FGAR to PurL.

purL_step -> purM_step Provides Input For

PurL supplies FGAM to PurM.

purM_step -> air_carboxylation_step Provides Input For

PurM supplies AIR to the selected carboxylation route.

air_carboxylation_step -> purC_step Provides Input For

AIR carboxylation supplies CAIR to SAICAR synthetase.

purC_step -> purB_step Provides Input For

PurC supplies SAICAR to PurB.

purB_step -> purH_transformylase_step Provides Input For

PurB supplies AICAR to the penultimate reaction.

purH_transformylase_step -> purH_cyclohydrolase_step Provides Input For

AICAR transformylation supplies FAICAR for ring closure.

Part 1: committed phosphoribosylamine formation

AmidophosphoribosyltransferaseReactionpurF_step

Annotons

Glutamine PRPP amidotransferase

purF_activity

Participant: Family: PurF amidophosphoribosyltransferases

Family:

PurF amidophosphoribosyltransferasesPANTHER:PTHR11907

Representative Members: purF (Pseudomonas putida KT2440)UniProtKB:Q88LD5 purF (Escherichia coli K-12)UniProtKB:P0AG16 PPAT (human)UniProtKB:Q06203 ADE4 (Saccharomyces cerevisiae)UniProtKB:P04046 ade4 (Schizosaccharomyces pombe)UniProtKB:P41390

Function

amidophosphoribosyltransferase activityGO:0004044

Substrates: 5-phosphoribosyl diphosphate L-glutamine water

Products: 5-phosphoribosylamine L-glutamate diphosphate

Commits PRPP to de novo purine-ring assembly. Feedback inhibition of the yeast enzyme by adenine nucleotides is the main flux control of the pathway (PMID:11689683).

Part 2: glycinamide ribonucleotide formation

Phosphoribosylamine--glycine ligaseReactionpurD_step

Annotons

GAR synthetase

purD_activity

Participant: Family: PurD phosphoribosylamine--glycine ligases (standalone or fused)

Family:

PurD phosphoribosylamine--glycine ligases (standalone or fused)

Representative Members: purD (Pseudomonas putida KT2440)UniProtKB:Q88DK2 purD (Escherichia coli K-12)UniProtKB:P15640 GART (human)UniProtKB:P22102 ADE57 (Saccharomyces cerevisiae)UniProtKB:P07244 ade1 (Schizosaccharomyces pombe)UniProtKB:P20772

Function

phosphoribosylamine-glycine ligase activityGO:0004637

Substrates: 5-phosphoribosylamine glycine ATP

Products: phosphoribosylglycinamide ADP phosphate

Adds glycine to the growing purine precursor.

Part 3: GAR formylation

Alternative GAR transformylation routesReactiongar_transformylation_step

Variant set: GAR one-carbon donor route by one-carbon donor and energy coupling (One Or More)

Folate-dependent PurN routeReactionpurN_folate_route

Annotons

Folate-dependent GAR transformylase

purN_activity

Participant: Family: PurN GAR transformylases (standalone or fused)

Family:

PurN GAR transformylases (standalone or fused)

Representative Members: purN (Pseudomonas putida KT2440)UniProtKB:Q88MB0 purN (Escherichia coli K-12)UniProtKB:P08179 GART (human)UniProtKB:P22102 ADE8 (Saccharomyces cerevisiae)UniProtKB:P04161 ade5 (Schizosaccharomyces pombe)UniProtKB:Q9UUK7

Function

phosphoribosylglycinamide formyltransferase activityGO:0004644

Substrates: phosphoribosylglycinamide 10-formyltetrahydrofolate

Products: phosphoribosyl-N-formylglycinamide tetrahydrofolate

Uses a folate-bound one-carbon unit to form FGAR. The only GAR transformylase route in fungi and animals.

ATP/formate-dependent PurT routeReactionpurT_formate_route

Annotons

Formate-dependent GAR transformylase

purT_activity

Participant: Family: PurT formate-dependent GAR transformylases

Family:

PurT formate-dependent GAR transformylasesPANTHER:PTHR43055

Representative Members: purT (Pseudomonas putida KT2440)UniProtKB:Q88MW1 purT (Escherichia coli K-12)UniProtKB:P33221

Function

phosphoribosylglycinamide formyltransferase 2 activityGO:0043815

Substrates: phosphoribosylglycinamide formate ATP

Products: phosphoribosyl-N-formylglycinamide ADP phosphate

Uses free formate and ATP to form FGAR (bacteria only).

Part 4: formylglycinamidine ribonucleotide formation

Phosphoribosylformylglycinamidine synthaseReactionpurL_step

Annotons

FGAM synthase

purL_activity

Participant: Family: large-type PurL FGAM synthases

Family:

large-type PurL FGAM synthasesPANTHER:PTHR10099

Representative Members: purL (Pseudomonas putida KT2440)UniProtKB:Q88P16 purL (Escherichia coli K-12)UniProtKB:P15254 PFAS (human)UniProtKB:O15067 ADE6 (Saccharomyces cerevisiae)UniProtKB:P38972 ade3 (Schizosaccharomyces pombe)UniProtKB:O14228

Function

phosphoribosylformylglycinamidine synthase activityGO:0004642

Substrates: phosphoribosyl-N-formylglycinamide L-glutamine ATP water

Products: phosphoribosylformylglycinamidine L-glutamate ADP phosphate

Introduces the second ring nitrogen to form FGAM.

Part 5: aminoimidazole ribonucleotide formation

Phosphoribosylformylglycinamidine cyclo-ligaseReactionpurM_step

Annotons

AIR synthetase

purM_activity

Participant: Family: PurM AIR synthetases

Family:

PurM AIR synthetasesPANTHER:PTHR10520:SF12 PTHR10520:SF12 contains standalone bacterial PurM proteins, animal GART and the fungal ADE5,7-type fusion. The leaf molecular function and exact exemplars constrain this whole-protein selector to the shared PurM cyclo-ligase role.

Representative Members: purM (Pseudomonas putida KT2440)UniProtKB:Q88MA9 purM (Escherichia coli K-12)UniProtKB:P08178 GART (human)UniProtKB:P22102 ADE57 (Saccharomyces cerevisiae)UniProtKB:P07244 ade1 (Schizosaccharomyces pombe)UniProtKB:P20772

Function

phosphoribosylformylglycinamidine cyclo-ligase activityGO:0004641

Substrates: phosphoribosylformylglycinamidine ATP

Products: 5-aminoimidazole ribonucleotide ADP phosphate

Cyclizes FGAM to form the first purine-ring intermediate AIR.

Part 6: aminoimidazole ribonucleotide carboxylation

Alternative AIR carboxylation routesMetabolic Pathwayair_carboxylation_step

Variant set: AIR-to-CAIR implementation by direct versus N5-CAIR intermediate (Exactly One)

Separate PurK and PurE proteins (N5-CAIR route)Metabolic Pathwaytwo_enzyme_n5_cair_route

Connections

purK_substep -> purE_substep Provides Input For

PurK supplies N5-CAIR to PurE.

Part 1: N5-CAIR formation

N5-CAIR synthetaseReactionpurK_substep

Annotons

ATP-dependent N5-CAIR synthetase

purK_activity

Participant: Family: PurK N5-CAIR synthetases

Family:

PurK N5-CAIR synthetasesPANTHER:PTHR11609

Representative Members: purK (Pseudomonas putida KT2440)UniProtKB:Q88C48 purK (Escherichia coli K-12)UniProtKB:P09029

Function

5-(carboxyamino)imidazole ribonucleotide synthase activityGO:0034028

Substrates: 5-aminoimidazole ribonucleotide hydrogencarbonate ATP

Products: N5-carboxyaminoimidazole ribonucleotide ADP phosphate

Part 2: CAIR rearrangement

N5-CAIR mutaseReactionpurE_substep

Annotons

N5-CAIR mutase

purE_activity

Participant: Family: PurE N5-CAIR mutases

Family:

PurE N5-CAIR mutasesPANTHER:PTHR23046

Representative Members: purE (Pseudomonas putida KT2440)UniProtKB:Q88C47 purE (Escherichia coli K-12)UniProtKB:P0AG18

Function

5-(carboxyamino)imidazole ribonucleotide mutase activityGO:0034023

Substrates: N5-carboxyaminoimidazole ribonucleotide

Products: 5-aminoimidazole-4-carboxylate ribonucleotide

Fused PurK-PurE bifunctional AIR carboxylase (fungal ADE2 type; N5-CAIR route)Metabolic Pathwayfused_ade2_n5_cair_route

One polypeptide with an N-terminal PurK-like N5-CAIR synthetase domain and a C-terminal class I PurE-like N5-CAIR mutase domain (PMID:9500840). Same chemistry as the separate PurK/PurE route.

Connections

ade2_purK_domain_substep -> ade2_purE_domain_substep Provides Input For

N5-CAIR passes from the PurK-like to the PurE-like domain.

Part 1: N5-CAIR formation by the PurK-like domain

N5-CAIR synthetase (ADE2 PurK-like domain)Reactionade2_purK_domain_substep

Annotons

ADE2 N5-CAIR synthetase domain

ade2_n5_cair_synthetase_activity

Participant: Family: fungal ADE2-type bifunctional AIR carboxylases

Family:

fungal ADE2-type bifunctional AIR carboxylasesPANTHER:PTHR11609:SF5

Representative Members: ADE2 (Saccharomyces cerevisiae)UniProtKB:P21264 ade6 (Schizosaccharomyces pombe)UniProtKB:P15567

Function

5-(carboxyamino)imidazole ribonucleotide synthase activityGO:0034028

Substrates: 5-aminoimidazole ribonucleotide hydrogencarbonate ATP

Products: N5-carboxyaminoimidazole ribonucleotide ADP phosphate

Part 2: CAIR formation by the PurE-like domain

N5-CAIR mutase (ADE2 PurE-like domain)Reactionade2_purE_domain_substep

Annotons

ADE2 N5-CAIR mutase domain

ade2_n5_cair_mutase_activity

Participant: Family: fungal ADE2-type bifunctional AIR carboxylases

Family:

fungal ADE2-type bifunctional AIR carboxylasesPANTHER:PTHR11609:SF5

Representative Members: ADE2 (Saccharomyces cerevisiae)UniProtKB:P21264 ade6 (Schizosaccharomyces pombe)UniProtKB:P15567

Function

5-(carboxyamino)imidazole ribonucleotide mutase activityGO:0034023

Substrates: N5-carboxyaminoimidazole ribonucleotide

Products: 5-aminoimidazole-4-carboxylate ribonucleotide

Direct AIR carboxylase routeReactiondirect_air_carboxylase_route

Annotons

Direct AIR carboxylase

direct_air_carboxylase_activity

Participant: Family: direct AIR carboxylases and PAICS-type fusion proteins

Family:

direct AIR carboxylases and PAICS-type fusion proteins

Representative Members: PAICS (human)UniProtKB:P22234

Function

phosphoribosylaminoimidazole carboxylase activityGO:0004638

Substrates: 5-aminoimidazole ribonucleotide carbon dioxide

Products: 5-aminoimidazole-4-carboxylate ribonucleotide

Directly forms CAIR without a free N5-CAIR intermediate (class II PurE, animals). Despite the PANTHER name "MULTIFUNCTIONAL PROTEIN ADE2", this family is the animal PAICS type, not fungal ADE2.

Part 7: succinylaminoimidazole carboxamide ribonucleotide formation

SAICAR synthetaseReactionpurC_step

Annotons

SAICAR synthetase

purC_activity

Participant: Family: PurC and PAICS SAICAR synthetases

Family:

PurC and PAICS SAICAR synthetases

Representative Members: purC (Pseudomonas putida KT2440)UniProtKB:Q88NG9 PAICS (human)UniProtKB:P22234 ADE1 (Saccharomyces cerevisiae)UniProtKB:P27616 ade7 (Schizosaccharomyces pombe)UniProtKB:Q9UUB4

Function

phosphoribosylaminoimidazolesuccinocarboxamide synthase activityGO:0004639

Substrates: 5-aminoimidazole-4-carboxylate ribonucleotide L-aspartate ATP

Products: SAICAR ADP phosphate

Adds aspartate to CAIR to form SAICAR. In yeast SAICAR also acts as the signal that promotes Bas1-Bas2 activation of the ADE genes (PMID:11689683).

Part 8: aminoimidazole carboxamide ribonucleotide formation

SAICAR lyaseReactionpurB_step

Annotons

SAICAR lyase

purB_saicar_activity

Participant: Family: PurB adenylosuccinate lyases

Family:

PurB adenylosuccinate lyases

Representative Members: purB (Pseudomonas putida KT2440)UniProtKB:Q88FR7 purB (Escherichia coli K-12)UniProtKB:P0AB89 ADSL (human)UniProtKB:P30566 ADE13 (Saccharomyces cerevisiae)UniProtKB:Q05911 ade8 (Schizosaccharomyces pombe)UniProtKB:O60105

Function

SAICAR lyase activityGO:0070626

Substrates: SAICAR

Products: AICAR fumarate

Removes fumarate from SAICAR to form AICAR.

Part 9: formylaminoimidazole carboxamide ribonucleotide formation

AICAR transformylaseReactionpurH_transformylase_step

Annotons

AICAR transformylase

purH_transformylase_activity

Participant: Family: PurH and ATIC AICAR transformylases

Family:

PurH and ATIC AICAR transformylasesPANTHER:PTHR11692

Representative Members: purH (Pseudomonas putida KT2440)UniProtKB:Q88DK3 purH (Escherichia coli K-12)UniProtKB:P15639 ATIC (human)UniProtKB:P31939 ADE16 (Saccharomyces cerevisiae)UniProtKB:P54113 ADE17 (Saccharomyces cerevisiae)UniProtKB:P38009 ade10 (Schizosaccharomyces pombe)UniProtKB:O74928

Function

phosphoribosylaminoimidazolecarboxamide formyltransferase activityGO:0004643

Substrates: AICAR 10-formyltetrahydrofolate

Products: FAICAR tetrahydrofolate

Adds the final folate-derived one-carbon unit. AICAR is also produced by histidine biosynthesis and acts as a regulatory metabolite in yeast (PMID:15744050).

Part 10: inosine monophosphate formation

IMP cyclohydrolaseReactionpurH_cyclohydrolase_step

Annotons

IMP cyclohydrolase

purH_cyclohydrolase_activity

Participant: Family: PurH and ATIC IMP cyclohydrolases

Family:

PurH and ATIC IMP cyclohydrolasesPANTHER:PTHR11692

Function

IMP cyclohydrolase activityGO:0003937

Substrates: FAICAR

Products: inosine monophosphate water

Closes the second purine ring to produce IMP.