Purine ribonucleotide interconversion (IMP to AMP/GMP and their di- and triphosphates)

Inosine monophosphate (IMP), the first complete purine nucleotide made by de novo synthesis or by salvage, is the branch point from which the adenine and guanine ribonucleotides are made. Toward AMP, adenylosuccinate synthetase condenses IMP with L-aspartate using GTP to form adenylosuccinate, which adenylosuccinate lyase cleaves to AMP and fumarate. Toward GMP, IMP dehydrogenase oxidises IMP to xanthosine monophosphate (XMP) with NAD+ (the committed, rate-limiting step of guanine-nucleotide synthesis) and GMP synthase aminates XMP to GMP using the amide nitrogen of glutamine. The monophosphates are then phosphorylated by adenylate kinase (AMP to ADP) and guanylate kinase (GMP to GDP), and nucleoside-diphosphate kinase transfers the gamma-phosphate of ATP to GDP (and other diphosphates) to make GTP; ADP is converted to ATP mainly by energy metabolism. AMP deaminase hydrolytically deaminates AMP back to IMP; with adenylosuccinate synthetase and lyase this forms the purine nucleotide cycle, which in animal muscle buffers the adenylate energy charge and releases fumarate and ammonia. Because GTP is required to make AMP and ATP to make GMP, these reactions cross-regulate the adenine and guanine nucleotide pools. The enzymes are cytosolic and conserved from bacteria to fungi and animals, with lineage-specific isozymes (for example, muscle and liver adenylosuccinate synthetases and three AMP deaminases in mammals, and three expressed IMP dehydrogenases in budding yeast). Inherited defects of the human enzymes include ADSS1 distal myopathy, IMPDH1 retinitis pigmentosa, IMPDH2 neurodevelopmental dystonia, myoadenylate deaminase (AMPD1) deficiency and AMPD2 pontocerebellar hypoplasia; IMP dehydrogenase is the target of mycophenolic acid and ribavirin.

MODULE:purine_nucleotide_interconversionDRAFTMetabolic Pathwaymodules/purine_nucleotide_interconversion.yaml
purine ribonucleotide interconversionGO:0015951 'de novo' AMP biosynthetic processGO:0044208 'de novo' GMP biosynthetic processGO:0106387
YeastPathways:PWY-7219
adenosine ribonucleotides de novo biosynthesis (S. cerevisiae, SGD YeastPathways)
IMP to ADP with ADE12, ADE13 and ADK1/ADK2. ADK2 is the mitochondrial GTP:AMP phosphotransferase (PMID:15753074), not the main cytosolic ATP:AMP adenylate kinase; it is kept only as a note.
YeastPathways:PWY-7221
guanosine ribonucleotides de novo biosynthesis (S. cerevisiae, SGD YeastPathways)
IMP to GTP with IMD2/IMD3/IMD4, GUA1, GUK1 and YNK1.
YeastPathways:PWY-6126-1
superpathway of adenosine nucleotides de novo biosynthesis II (S. cerevisiae, SGD YeastPathways)
PWY-7219 plus ADP reduction by ribonucleotide reductase and dADP phosphorylation (modelled in dntp_de_novo_synthesis) and a gene-less formate-dependent class III reductase reaction not present in yeast.
YeastPathways:PWY-6125
superpathway of guanosine nucleotides de novo biosynthesis II (S. cerevisiae, SGD YeastPathways)
PWY-7221 plus GDP reduction and dGDP phosphorylation (dntp_de_novo_synthesis) and a gene-less class III reductase reaction.
GO:0015951
purine ribonucleotide interconversion
Module-level process term for the IMP/AMP/GMP interconversion network.
GO:0044208
'de novo' AMP biosynthetic process
Process term for the IMP-to-AMP arm.
GO:0106387
'de novo' GMP biosynthetic process
Process term for the IMP-to-GMP arm.
Reactome:R-HSA-73817
Purine ribonucleoside monophosphate biosynthesis
Reactions follow the human Reactome purine-metabolism reactions R-HSA-111524 (ADSS), R-HSA-73794 (IMPDH), R-HSA-73792 (GMPS) and R-HSA-76590 (AMPD).
PMID:10417315
Adenylosuccinate synthase from Saccharomyces cerevisiae: homologous overexpression, purification and characterization of the recombinant protein.
ADE12 encodes yeast adenylosuccinate synthase, the first committed step of AMP synthesis.
PMID:22419079
Regulation of amino acid, nucleotide, and phosphate metabolism in Saccharomyces cerevisiae.
YeastBook review: ADE13 encodes adenylosuccinate lyase, used in both the de novo IMP pathway and the AMP branch; regulation of the AMP and GMP branches.
PMID:12746440
Functional distinctions between IMP dehydrogenase genes in providing mycophenolate resistance and guanine prototrophy to yeast.
IMD1 is a transcriptionally silent pseudogene; IMD2, IMD3 and IMD4 encode IMP dehydrogenase, either IMD3 or IMD4 suffices for guanine prototrophy, and IMD2 provides inducible, mycophenolate-resistant activity. Deletion of all four genes causes guanine auxotrophy.
PMID:11035032
Transcriptional regulation of the yeast gmp synthesis pathway by its end products.
Only the IMD (IMP dehydrogenase) genes of the GMP branch are repressed by guanine; GUA1 and GUK1 are guanine-insensitive.
PMID:8112582
Cloning and sequencing of the GMP synthetase-encoding gene of Saccharomyces cerevisiae.
GUA1 encodes GMP synthetase; its disruption causes guanine auxotrophy.
PMID:2690949
Characterization of AMD, the AMP deaminase gene in yeast. Production of amd strain, cloning, nucleotide sequence, and properties of the protein.
AMD1 encodes yeast AMP deaminase; amd strains grow at near normal rates.
PMID:1334480
Cloning and expression of the essential gene for guanylate kinase from yeast.
GUK1 encodes guanylate kinase and is essential for vegetative growth.
PMID:11063676
Yeast GMP kinase mutants constitutively express AMP biosynthesis genes by phenocopying a hypoxanthine-guanine phosphoribosyltransferase defect.
Low GMP kinase activity in guk1 (bra3) mutants causes GMP accumulation and feedback inhibition of HGPRT, linking guanylate kinase to purine pool balance.
PMID:1333436
The adenylate kinase family in yeast: identification of URA6 as a multicopy suppressor of deficiency in major AMP kinase.
AKY2 (ADK1) encodes the major yeast AMP kinase and is also imported into the mitochondrial intermembrane space.
PMID:15753074
A GTP:AMP phosphotransferase, Adk2p, in Saccharomyces cerevisiae. Role of the C terminus in protein folding/stabilization, thermal tolerance, and enzymatic activity.
ADK2 encodes a mitochondrial-matrix GTP:AMP phosphotransferase.
PMID:1659321
Saccharomyces cerevisiae nucleoside-diphosphate kinase: purification, characterization, and substrate specificity.
Yeast NDP kinase is a tetramer with broad specificity for ribo- and deoxyribonucleoside diphosphates.
PMID:12472466
Nucleoside diphosphate kinase of Saccharomyces cerevisiae, Ynk1p: localization to the mitochondrial intermembrane space.
Ynk1p is predominantly cytosolic with a small fraction in the mitochondrial intermembrane space.
file:human/ADSS1/ADSS1-ai-review.yaml
ADSS1 gene review (human)
The IMP -> adenylosuccinate step (UniProtKB:Q8N142, GO:0004019) matches the completed human ADSS1 review.
file:human/ADSL/ADSL-ai-review.yaml
ADSL gene review (human)
The adenylosuccinate -> AMP step (UniProtKB:P30566, GO:0004018) matches the completed human ADSL review (also in the de novo purine module).
file:human/IMPDH1/IMPDH1-ai-review.yaml
IMPDH1 gene review (human)
The IMP -> XMP step (UniProtKB:P20839, GO:0003938) matches the completed human IMPDH1 review.
file:human/IMPDH2/IMPDH2-ai-review.yaml
IMPDH2 gene review (human)
The ubiquitous IMP -> XMP isozyme (UniProtKB:P12268, GO:0003938) matches the completed human IMPDH2 review.
file:human/GMPS/GMPS-ai-review.yaml
GMPS gene review (human)
The XMP -> GMP step (UniProtKB:P49915, GO:0003922) matches the completed human GMPS review.
file:human/AMPD1/AMPD1-ai-review.yaml
AMPD1 gene review (human)
The AMP -> IMP step (UniProtKB:P23109, GO:0003876) matches the completed human AMPD1 review.
file:human/AMPD2/AMPD2-ai-review.yaml
AMPD2 gene review (human)
The broad/neuronal AMP -> IMP isozyme (UniProtKB:Q01433, GO:0003876) matches the completed human AMPD2 review.
file:human/AMPD3/AMPD3-ai-review.yaml
AMPD3 gene review (human)
The erythrocyte AMP -> IMP isozyme (UniProtKB:Q01432, GO:0003876) matches the completed human AMPD3 review.
9Nodes
8Parts
0Variant Sets
0Variants
8Annotons
8Connections

Derived QC

Recommended-field compliance

100.0% recommended fields populated

All recommended fields populated.

Module deep research

✗ none found

No MODULE:purine_nucleotide_interconversion deep-research report alongside the module YAML.

Leaf nodes lacking representative members

✓ every leaf node grounds to a representative protein.

Template conformance

✓ every declared conforms_to bundle matches its template motif.

Reaction chaining (advisory)

✓ every PRECEDES step chains, or its break is acknowledged via chaining_status.

  • adss_step → adsl_amp_step [NOT_CHECKED]
    No CoA-carrier intermediate; continuity is via adenylosuccinate.
  • impdh_step → gmps_step [NOT_CHECKED]
    No CoA-carrier intermediate; continuity is via XMP.

Function consistency and core coverage

18 gene-function check(s) reflected in core functions · 0 conflict(s) · 5 evidence or coverage gap(s) (45 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.

AnnotonParticipantFunctionAssessment
adss_activity ADSS1 (human, muscle isozyme)
UniProtKB:Q8N142
Family Representative 		adenylosuccinate synthase activity
GO:0004019 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
adss_activity ADE12 (Saccharomyces cerevisiae)
UniProtKB:P80210
Family Representative 		adenylosuccinate synthase activity
GO:0004019 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
adsl_amp_activity ADSL (human)
UniProtKB:P30566
Family Representative 		N6-(1,2-dicarboxyethyl)AMP AMP-lyase (fumarate-forming) activity
GO:0004018 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
adsl_amp_activity ADE13 (Saccharomyces cerevisiae)
UniProtKB:Q05911
Family Representative 		N6-(1,2-dicarboxyethyl)AMP AMP-lyase (fumarate-forming) activity
GO:0004018 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
adsl_amp_activity purB (Escherichia coli K-12)
UniProtKB:P0AB89
Family Representative 		N6-(1,2-dicarboxyethyl)AMP AMP-lyase (fumarate-forming) activity
GO:0004018 		Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
impdh_activity IMPDH2 (human, ubiquitous/proliferation-associated)
UniProtKB:P12268
Family Representative 		IMP dehydrogenase activity
GO:0003938 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
impdh_activity IMPDH1 (human, retina-enriched)
UniProtKB:P20839
Family Representative 		IMP dehydrogenase activity
GO:0003938 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
impdh_activity IMD2 (Saccharomyces cerevisiae)
UniProtKB:P38697
Family Representative 		IMP dehydrogenase activity
GO:0003938 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
impdh_activity IMD3 (Saccharomyces cerevisiae)
UniProtKB:P50095
Family Representative 		IMP dehydrogenase activity
GO:0003938 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
impdh_activity IMD4 (Saccharomyces cerevisiae)
UniProtKB:P50094
Family Representative 		IMP dehydrogenase activity
GO:0003938 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
gmps_activity GMPS (human)
UniProtKB:P49915
Family Representative 		GMP synthase (glutamine-hydrolyzing) activity
GO:0003922 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
gmps_activity GUA1 (Saccharomyces cerevisiae)
UniProtKB:P38625
Family Representative 		GMP synthase (glutamine-hydrolyzing) activity
GO:0003922 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
adenylate_kinase_activity ADK1 (Saccharomyces cerevisiae)
UniProtKB:P07170
Family Representative 		AMP kinase activity
GO:0004017 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
adenylate_kinase_activity AK1 (human)
UniProtKB:P00568
Family Representative 		AMP kinase activity
GO:0004017 		Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
guanylate_kinase_activity GUK1 (Saccharomyces cerevisiae)
UniProtKB:P15454
Family Representative 		GMP kinase activity
GO:0004385 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
guanylate_kinase_activity GUK1 (human)
UniProtKB:Q16774
Family Representative 		GMP kinase activity
GO:0004385 		Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
ndp_kinase_activity YNK1 (Saccharomyces cerevisiae)
UniProtKB:P36010
Family Representative 		nucleoside diphosphate kinase activity
GO:0004550 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
ndp_kinase_activity NME1 (human)
UniProtKB:P15531
Family Representative 		nucleoside diphosphate kinase activity
GO:0004550 		Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
ampd_activity AMPD1 (human, muscle)
UniProtKB:P23109
Family Representative 		AMP deaminase activity
GO:0003876 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
ampd_activity AMPD2 (human, liver/neuronal)
UniProtKB:Q01433
Family Representative 		AMP deaminase activity
GO:0003876 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
ampd_activity AMPD3 (human, erythrocyte)
UniProtKB:Q01432
Family Representative 		AMP deaminase activity
GO:0003876 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
ampd_activity AMD1 (Saccharomyces cerevisiae)
UniProtKB:P15274
Family Representative 		AMP deaminase activity
GO:0003876 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
adss_activity Adenylosuccinate synthetase family (PurA/ADSS)
PANTHER:PTHR11846
Family 		adenylosuccinate synthase activity
GO:0004019 		Family Supported
Family review supports GO:0004019 FAMILY_WIDE. Asserted by purine_nucleotide_interconversion; accepted by ADE12, ADSS1, zebrafish adss1 and poplar PURA.
adsl_amp_activity PurB adenylosuccinate lyases
PANTHER:PTHR43411
Family 		N6-(1,2-dicarboxyethyl)AMP AMP-lyase (fumarate-forming) activity
GO:0004018 		Family Supported
Family review supports GO:0004018 FAMILY_WIDE. The purine_nucleotide_interconversion module uses PTHR43411, together with PTHR43172:SF1, for the AMP-forming lyase step (adsl_amp_activity), with E. coli PurB as a representative. Every reviewed member is a PurB, and the E. coli enzyme has been characterized structurally with its adenylosuccinate substrate and AMP/fumarate products.
adsl_amp_activity PurB adenylosuccinate lyases
PANTHER:PTHR43172:SF1
Family 		N6-(1,2-dicarboxyethyl)AMP AMP-lyase (fumarate-forming) activity
GO:0004018 		Family Supported
Family review supports GO:0004018 for PANTHER:PTHR43172:SF1. The purine_nucleotide_interconversion module uses PTHR43172:SF1 (with PTHR43411) for the AMP-forming lyase step, with human ADSL and yeast Ade13 as representatives. The activity holds for the ADSL members of SF1, but not for SF2 or for the non-ADSL paralogs inside SF1. Those paralogs are listed as exceptions.
impdh_activity IMP dehydrogenase family
PANTHER:PTHR11911:SF111
Family 		IMP dehydrogenase activity
GO:0003938 		Family Supported
Family review supports GO:0003938 for PANTHER:PTHR11911:SF111. IMPDH subfamilies; purine_nucleotide_interconversion selects the base family, which also takes in GMP reductase.
impdh_activity IMP dehydrogenase family
PANTHER:PTHR11911:SF121
Family 		IMP dehydrogenase activity
GO:0003938 		Family Supported
Family review supports GO:0003938 for PANTHER:PTHR11911:SF121. IMPDH subfamilies; purine_nucleotide_interconversion selects the base family, which also takes in GMP reductase.
impdh_activity IMP dehydrogenase family
PANTHER:PTHR11911:SF74
Family 		IMP dehydrogenase activity
GO:0003938 		Family Supported
Family review supports GO:0003938 for PANTHER:PTHR11911:SF74. IMPDH subfamilies; purine_nucleotide_interconversion selects the base family, which also takes in GMP reductase.
impdh_activity IMP dehydrogenase family
PANTHER:PTHR11911:SF85
Family 		IMP dehydrogenase activity
GO:0003938 		Family Supported
Family review supports GO:0003938 for PANTHER:PTHR11911:SF85. IMPDH subfamilies; purine_nucleotide_interconversion selects the base family, which also takes in GMP reductase.
impdh_activity IMP dehydrogenase family
PANTHER:PTHR11911:SF124
Family 		IMP dehydrogenase activity
GO:0003938 		Family Supported
Family review supports GO:0003938 for PANTHER:PTHR11911:SF124. IMPDH subfamilies; purine_nucleotide_interconversion selects the base family, which also takes in GMP reductase.
impdh_activity IMP dehydrogenase family
PANTHER:PTHR11911:SF129
Family 		IMP dehydrogenase activity
GO:0003938 		Family Supported
Family review supports GO:0003938 for PANTHER:PTHR11911:SF129. IMPDH subfamilies; purine_nucleotide_interconversion selects the base family, which also takes in GMP reductase.
gmps_activity GMP synthase family (GuaA/GMPS)
PANTHER:PTHR11922
Family 		GMP synthase (glutamine-hydrolyzing) activity
GO:0003922 		Family Supported
Family review supports GO:0003922 FAMILY_WIDE. Asserted by purine_nucleotide_interconversion; core function of GUA1 and GMPS.
adenylate_kinase_activity adenylate kinase family (ADK/AK1-type)
PANTHER:PTHR23359:SF234
Family 		AMP kinase activity
GO:0004017 		Family Supported
Family review supports GO:0004017 for PANTHER:PTHR23359:SF234. This is the module's function for the adenylate_kinase_activity annoton (ADK1, AK1), which selects exactly the subfamilies listed here. Within the mixed SF206 the annoton's function, not the selector, restricts the claim to ATP:AMP phosphotransfer. The listed subfamilies hold the canonical ATP:AMP kinases with checked experimental seeds: ADK1 and adk1 (SF234), AK2 (SF227), AK1 (SF59), AK7 (SF105), AK8 (SF167), and the bacterial Adk in the mixed SF206. Excluded are the GTP:AMP AK3-type groups (SF242, SF68), inactive AK4 (SF58), and AK5 (SF79) and AK9 (SF148), which PAINT negates. In SF206 the eukaryotic UMP/CMP kinases are not primarily AMP kinases (IRD at PTN000599579), but URA6 has a measured secondary AMP kinase activity. Plant isoform subfamilies were not individually checked.
adenylate_kinase_activity adenylate kinase family (ADK/AK1-type)
PANTHER:PTHR23359:SF227
Family 		AMP kinase activity
GO:0004017 		Family Supported
Family review supports GO:0004017 for PANTHER:PTHR23359:SF227. This is the module's function for the adenylate_kinase_activity annoton (ADK1, AK1), which selects exactly the subfamilies listed here. Within the mixed SF206 the annoton's function, not the selector, restricts the claim to ATP:AMP phosphotransfer. The listed subfamilies hold the canonical ATP:AMP kinases with checked experimental seeds: ADK1 and adk1 (SF234), AK2 (SF227), AK1 (SF59), AK7 (SF105), AK8 (SF167), and the bacterial Adk in the mixed SF206. Excluded are the GTP:AMP AK3-type groups (SF242, SF68), inactive AK4 (SF58), and AK5 (SF79) and AK9 (SF148), which PAINT negates. In SF206 the eukaryotic UMP/CMP kinases are not primarily AMP kinases (IRD at PTN000599579), but URA6 has a measured secondary AMP kinase activity. Plant isoform subfamilies were not individually checked.
adenylate_kinase_activity adenylate kinase family (ADK/AK1-type)
PANTHER:PTHR23359:SF59
Family 		AMP kinase activity
GO:0004017 		Family Supported
Family review supports GO:0004017 for PANTHER:PTHR23359:SF59. This is the module's function for the adenylate_kinase_activity annoton (ADK1, AK1), which selects exactly the subfamilies listed here. Within the mixed SF206 the annoton's function, not the selector, restricts the claim to ATP:AMP phosphotransfer. The listed subfamilies hold the canonical ATP:AMP kinases with checked experimental seeds: ADK1 and adk1 (SF234), AK2 (SF227), AK1 (SF59), AK7 (SF105), AK8 (SF167), and the bacterial Adk in the mixed SF206. Excluded are the GTP:AMP AK3-type groups (SF242, SF68), inactive AK4 (SF58), and AK5 (SF79) and AK9 (SF148), which PAINT negates. In SF206 the eukaryotic UMP/CMP kinases are not primarily AMP kinases (IRD at PTN000599579), but URA6 has a measured secondary AMP kinase activity. Plant isoform subfamilies were not individually checked.
adenylate_kinase_activity adenylate kinase family (ADK/AK1-type)
PANTHER:PTHR23359:SF105
Family 		AMP kinase activity
GO:0004017 		Family Supported
Family review supports GO:0004017 for PANTHER:PTHR23359:SF105. This is the module's function for the adenylate_kinase_activity annoton (ADK1, AK1), which selects exactly the subfamilies listed here. Within the mixed SF206 the annoton's function, not the selector, restricts the claim to ATP:AMP phosphotransfer. The listed subfamilies hold the canonical ATP:AMP kinases with checked experimental seeds: ADK1 and adk1 (SF234), AK2 (SF227), AK1 (SF59), AK7 (SF105), AK8 (SF167), and the bacterial Adk in the mixed SF206. Excluded are the GTP:AMP AK3-type groups (SF242, SF68), inactive AK4 (SF58), and AK5 (SF79) and AK9 (SF148), which PAINT negates. In SF206 the eukaryotic UMP/CMP kinases are not primarily AMP kinases (IRD at PTN000599579), but URA6 has a measured secondary AMP kinase activity. Plant isoform subfamilies were not individually checked.
adenylate_kinase_activity adenylate kinase family (ADK/AK1-type)
PANTHER:PTHR23359:SF167
Family 		AMP kinase activity
GO:0004017 		Family Supported
Family review supports GO:0004017 for PANTHER:PTHR23359:SF167. This is the module's function for the adenylate_kinase_activity annoton (ADK1, AK1), which selects exactly the subfamilies listed here. Within the mixed SF206 the annoton's function, not the selector, restricts the claim to ATP:AMP phosphotransfer. The listed subfamilies hold the canonical ATP:AMP kinases with checked experimental seeds: ADK1 and adk1 (SF234), AK2 (SF227), AK1 (SF59), AK7 (SF105), AK8 (SF167), and the bacterial Adk in the mixed SF206. Excluded are the GTP:AMP AK3-type groups (SF242, SF68), inactive AK4 (SF58), and AK5 (SF79) and AK9 (SF148), which PAINT negates. In SF206 the eukaryotic UMP/CMP kinases are not primarily AMP kinases (IRD at PTN000599579), but URA6 has a measured secondary AMP kinase activity. Plant isoform subfamilies were not individually checked.
adenylate_kinase_activity adenylate kinase family (ADK/AK1-type)
PANTHER:PTHR23359:SF206
Family 		AMP kinase activity
GO:0004017 		Family Supported
Family review supports GO:0004017 for PANTHER:PTHR23359:SF206. This is the module's function for the adenylate_kinase_activity annoton (ADK1, AK1), which selects exactly the subfamilies listed here. Within the mixed SF206 the annoton's function, not the selector, restricts the claim to ATP:AMP phosphotransfer. The listed subfamilies hold the canonical ATP:AMP kinases with checked experimental seeds: ADK1 and adk1 (SF234), AK2 (SF227), AK1 (SF59), AK7 (SF105), AK8 (SF167), and the bacterial Adk in the mixed SF206. Excluded are the GTP:AMP AK3-type groups (SF242, SF68), inactive AK4 (SF58), and AK5 (SF79) and AK9 (SF148), which PAINT negates. In SF206 the eukaryotic UMP/CMP kinases are not primarily AMP kinases (IRD at PTN000599579), but URA6 has a measured secondary AMP kinase activity. Plant isoform subfamilies were not individually checked.
guanylate_kinase_activity guanylate kinases
PANTHER:PTHR23117:SF13
Family 		GMP kinase activity
GO:0004385 		Family Supported
Family review supports GO:0004385 for PANTHER:PTHR23117:SF13. SF13, as purine_nucleotide_interconversion selects.
ndp_kinase_activity nucleoside-diphosphate kinases (NDK/NME)
PANTHER:PTHR11349
Family 		nucleoside diphosphate kinase activity
GO:0004550 		Family Function Unreviewed
Family review leaves GO:0004550 UNRESOLVED. Awd and classical NDKs catalyze nucleoside-diphosphate phosphorylation; the Awd killer-of-prune mutation changes protein stability without abolishing catalytic efficiency (PMID:1320004). The classification also includes NDK-like/domain-containing branches for which this source does not resolve a complete active-site and biochemical boundary. Awd activity is supported, but an unconditional grant to all classified NDK-like proteins remains unresolved. Notch regulation and other Awd-specific pathways are not universal NDK functions.
ampd_activity AMP deaminase family
PANTHER:PTHR11359:SF0
Family 		AMP deaminase activity
GO:0003876 		Family Supported
Family review supports GO:0003876 for PANTHER:PTHR11359:SF0. The catalytic subfamilies, not SF7. Both modules select the base family.
ampd_activity AMP deaminase family
PANTHER:PTHR11359:SF1
Family 		AMP deaminase activity
GO:0003876 		Family Supported
Family review supports GO:0003876 for PANTHER:PTHR11359:SF1. The catalytic subfamilies, not SF7. Both modules select the base family.
ampd_activity AMP deaminase family
PANTHER:PTHR11359:SF2
Family 		AMP deaminase activity
GO:0003876 		Family Supported
Family review supports GO:0003876 for PANTHER:PTHR11359:SF2. The catalytic subfamilies, not SF7. Both modules select the base family.
ampd_activity AMP deaminase family
PANTHER:PTHR11359:SF3
Family 		AMP deaminase activity
GO:0003876 		Family Supported
Family review supports GO:0003876 for PANTHER:PTHR11359:SF3. The catalytic subfamilies, not SF7. Both modules select the base family.
ampd_activity AMP deaminase family
PANTHER:PTHR11359:SF10
Family 		AMP deaminase activity
GO:0003876 		Family Supported
Family review supports GO:0003876 for PANTHER:PTHR11359:SF10. The catalytic subfamilies, not SF7. Both modules select the base family.

Gene-review completeness (18/22 grounded genes reviewed)

17 complete review(s) · 10 with deep research · 4 missing review · 8 reviewed but lacking deep research

Gene Review Complete Deep research
ADE12 P80210 ✓ ✓ ✓
ADE13 Q05911 ✓ ✓ ✓
ADK1 P07170 ✓ ✓ ✓
ADSL P30566 ✓ 27/30 ✗
ADSS1 Q8N142 ✓ ✓ ✗
AMD1 P15274 ✓ ✓ ✓
AMPD1 P23109 ✓ ✓ ✗
AMPD2 Q01433 ✓ ✓ ✗
AMPD3 Q01432 ✓ ✓ ✗
GMPS P49915 ✓ ✓ ✗
GUA1 P38625 ✓ ✓ ✓
GUK1 P15454 ✓ ✓ ✓
IMD2 P38697 ✓ ✓ ✓
IMD3 P50095 ✓ ✓ ✓
IMD4 P50094 ✓ ✓ ✓
IMPDH1 P20839 ✓ ✓ ✗
IMPDH2 P12268 ✓ ✓ ✗
AK1 (human) P00568 ✗ — —
purB (Escherichia coli K-12) P0AB89 ✗ — —
NME1 (human) P15531 ✗ — —
GUK1 (human) Q16774 ✗ — —
YNK1 P36010 ✓ ✓ ✓

Details

Context
cytosolGO:0005829
Purine ribonucleotide interconversion (IMP to AMP/GMP, ADP/GDP and GTP)Metabolic Pathwaypurine_nucleotide_interconversion
purine ribonucleotide interconversionGO:0015951 'de novo' AMP biosynthetic processGO:0044208 'de novo' GMP biosynthetic processGO:0106387
Context
cytosolGO:0005829

GENERALIZE from the earlier human-only module. The human enzymes and disorders are retained (ADSS1 Q8N142, ADSL P30566, IMPDH1 P20839 / IMPDH2 P12268, GMPS P49915, AMPD1 P23109 / AMPD2 Q01433 / AMPD3 Q01432; GO molecular-function terms from the human GOA records; Reactome reaction ids verified against the local reactome cache) and S. cerevisiae exemplars added from the YeastPathways crosswalk (PWY-7219, PWY-7221, PWY-6126-1, PWY-6125): ADE12, ADE13, IMD2/IMD3/IMD4, GUA1, ADK1, GUK1, YNK1 and AMD1. Boundary changes: the adenylosuccinate lyase AMP step (previously only mentioned) is now an explicit part, and the adenylate kinase, guanylate kinase and NDP kinase steps that complete ADP/GTP formation in the YeastCyc frames were added; ATP formation from ADP (oxidative and substrate-level phosphorylation) stays outside. The ribonucleotide reductase and dNDP kinase reactions of the YeastCyc superpathways are modelled in dntp_de_novo_synthesis, and the gene-less formate-dependent class III reductase reactions (RXN0-745, RXN0-746) do not occur in yeast. YeastCyc corrections: IMD1 (pseudogene, PMID:12746440) is correctly absent; ADK2 is listed as an ATP:AMP adenylate kinase in PWY-7219 but is a mitochondrial-matrix GTP:AMP phosphotransferase (PMID:15753074), so it is not used as an exemplar; AMD1 is placed by YeastCyc only in the salvage frames but is the AMP deaminase of this network. GO-CAM disagreement: YeastPathways_PWY-7219 and PWY-6126-1 annotate every activity as part_of GO:0046086 adenosine biosynthetic process (a nucleoside term) instead of AMP/ADP synthesis. No S. pombe GO-CAM is listed for this group; the S. pombe orthologs (ada1 AMP deaminase, gua1 IMP dehydrogenase, gua2 GMP synthase) appear in the PomBase purine salvage model 680ad14200001682 (see purine_salvage_and_catabolism). Upstream, IMP comes from de_novo_purine_synthesis and from hypoxanthine salvage (purine_salvage_and_catabolism); purine_nucleotide_catabolism covers degradation of these nucleotides.

Connections

Adenylosuccinate is cleaved to AMP and fumarate.
adsl_amp_step -> adenylate_kinase_step Provides Input For
AMP is phosphorylated to ADP.
impdh_step -> gmps_step Precedes
XMP from IMP dehydrogenase is aminated to GMP by GMP synthase.
gmps_step -> guanylate_kinase_step Provides Input For
GMP is phosphorylated to GDP.
guanylate_kinase_step -> ndp_kinase_step Provides Input For
GDP is phosphorylated to GTP.
ndp_kinase_step -> adss_step Provides Input For
GTP is the phosphate donor of adenylosuccinate synthetase (cross-regulation of the two arms).
ampd_step -> adss_step Provides Input For
AMP deaminase regenerates IMP, which adenylosuccinate synthetase re-uses toward AMP (the purine nucleotide cycle).
ampd_step -> impdh_step Provides Input For
IMP regenerated by AMP deaminase can also be routed to GMP synthesis via IMP dehydrogenase.
Part 1: IMP -> AMP (committed adenylosuccinate step)
IMP + L-aspartate + GTP to adenylosuccinate + GDP + PiReactionadss_step

Annotons

Adenylosuccinate synthetase
adss_activity
Participant: Family: Adenylosuccinate synthetase family (PurA/ADSS)
Family:
Adenylosuccinate synthetase family (PurA/ADSS)PANTHER:PTHR11846
Representative Members: ADSS1 (human, muscle isozyme)UniProtKB:Q8N142 ADE12 (Saccharomyces cerevisiae)UniProtKB:P80210

Function

adenylosuccinate synthase activityGO:0004019
Substrates: IMP L-aspartate GTP
Products: adenylosuccinate (N6-(1,2-dicarboxyethyl)-AMP) GDP phosphate

Locations

cytosolGO:0005829

GTP-dependent, committed first step toward AMP. In mammals ADSS1 is the muscle isozyme (distal myopathy on deficiency) and ADSS2 the ubiquitous isozyme; yeast has a single enzyme, ADE12.

Part 2: adenylosuccinate -> AMP + fumarate
Adenylosuccinate to AMP + fumarateReactionadsl_amp_step

Annotons

Adenylosuccinate lyase (AMP-forming reaction)
adsl_amp_activity
Participant: Family: PurB adenylosuccinate lyases
Family:
PurB adenylosuccinate lyases
Representative Members: ADSL (human)UniProtKB:P30566 ADE13 (Saccharomyces cerevisiae)UniProtKB:Q05911 purB (Escherichia coli K-12)UniProtKB:P0AB89

Function

N6-(1,2-dicarboxyethyl)AMP AMP-lyase (fumarate-forming) activityGO:0004018
Substrates: adenylosuccinate
Products: AMP fumarate

Locations

cytosolGO:0005829

Completes AMP synthesis. The same protein performs the SAICAR lyase step of de_novo_purine_synthesis; human ADSL deficiency causes adenylosuccinate lyase deficiency.

Part 3: IMP -> XMP (committed, rate-limiting GMP step)
IMP + NAD+ + H2O to XMP + NADHReactionimpdh_step

Annotons

IMP dehydrogenase
impdh_activity
Participant: Family: IMP dehydrogenase family
Family:
IMP dehydrogenase family
Representative Members: IMPDH2 (human, ubiquitous/proliferation-associated)UniProtKB:P12268 IMPDH1 (human, retina-enriched)UniProtKB:P20839 IMD2 (Saccharomyces cerevisiae)UniProtKB:P38697 IMD3 (Saccharomyces cerevisiae)UniProtKB:P50095 IMD4 (Saccharomyces cerevisiae)UniProtKB:P50094

Function

IMP dehydrogenase activityGO:0003938
Substrates: IMP NAD+
Products: xanthosine 5'-monophosphate (XMP) NADH

Locations

cytosolGO:0005829

Committed, rate-limiting step of GMP synthesis and the only step of the GMP branch that is transcriptionally repressed by guanine in yeast (PMID:11035032). Human IMPDH1 (retina; RP10/LCA) and IMPDH2 (ubiquitous; neurodevelopmental dystonia; mycophenolate/ribavirin target) form regulated tetramers/filaments. Yeast IMD1 is a pseudogene.

Part 4: XMP -> GMP (glutamine amination)
XMP + L-glutamine + ATP to GMP + L-glutamate + AMP + PPiReactiongmps_step

Annotons

GMP synthase (glutamine-hydrolysing)
gmps_activity
Participant: Family: GMP synthase family (GuaA/GMPS)
Family:
GMP synthase family (GuaA/GMPS)PANTHER:PTHR11922
Representative Members: GMPS (human)UniProtKB:P49915 GUA1 (Saccharomyces cerevisiae)UniProtKB:P38625

Function

GMP synthase (glutamine-hydrolyzing) activityGO:0003922
Substrates: XMP L-glutamine ATP
Products: GMP L-glutamate AMP + diphosphate

Locations

cytosolGO:0005829

Aminates XMP to GMP using glutamine and ATP. Also the route by which salvaged xanthine (via XMP) enters the guanine nucleotide pool. Human GMPS has a reported USP7/p53-regulatory nuclear moonlighting role (non-core).

Part 5: AMP -> ADP
AMP + ATP to 2 ADPReactionadenylate_kinase_step

Annotons

Adenylate kinase (ATP:AMP phosphotransferase)
adenylate_kinase_activity
Participant: Family: adenylate kinase family (ADK/AK1-type)
Family:
adenylate kinase family (ADK/AK1-type) Only the ATP:AMP adenylate kinase subfamilies of the broad nucleoside-monophosphate kinase family PTHR23359 are selected, excluding the GTP:AMP phosphotransferase ADK2 groups. The mixed SF206 also holds the UMP/CMP kinases (URA6, CMPK1); the leaf function restricts it to ATP:AMP phosphotransfer.
Representative Members: ADK1 (Saccharomyces cerevisiae)UniProtKB:P07170 AK1 (human)UniProtKB:P00568

Function

AMP kinase activityGO:0004017
Substrates: AMP ATP
Products: ADP

Locations

cytosolGO:0005829 mitochondrial intermembrane spaceGO:0005758

Converts AMP to ADP and equilibrates the adenylate pool; ADP is then phosphorylated to ATP by energy metabolism.

Part 6: GMP -> GDP
GMP + ATP to GDP + ADPReactionguanylate_kinase_step

Annotons

Guanylate kinase
guanylate_kinase_activity
Participant: Family: guanylate kinases
Family:
guanylate kinasesPANTHER:PTHR23117:SF13
Representative Members: GUK1 (Saccharomyces cerevisiae)UniProtKB:P15454 GUK1 (human)UniProtKB:Q16774

Function

GMP kinase activityGO:0004385
Substrates: GMP ATP
Products: GDP ADP

Locations

cytosolGO:0005829

Single essential GMP kinase for both de novo and salvaged GMP; reduced activity causes GMP accumulation and HGPRT feedback inhibition in yeast (PMID:11063676).

Part 7: GDP -> GTP (and other NDPs to NTPs)
GDP + ATP to GTP + ADPReactionndp_kinase_step

Annotons

Nucleoside-diphosphate kinase
ndp_kinase_activity
Participant: Family: nucleoside-diphosphate kinases (NDK/NME)
Family:
nucleoside-diphosphate kinases (NDK/NME)PANTHER:PTHR11349
Representative Members: YNK1 (Saccharomyces cerevisiae)UniProtKB:P36010 NME1 (human)UniProtKB:P15531

Function

nucleoside diphosphate kinase activityGO:0004550
Substrates: GDP (or another ribo- or deoxyribonucleoside diphosphate) ATP
Products: GTP (or the corresponding triphosphate) ADP

Locations

cytosolGO:0005829 mitochondrial intermembrane spaceGO:0005758

Broad-specificity terminal phosphorylation; the same enzyme makes UTP, CTP and the dNTPs (de_novo_pyrimidine_synthesis, dntp_de_novo_synthesis). YNK1 is not essential, so other phosphotransferases can supply NTPs in its absence.

Part 8: AMP -> IMP (purine nucleotide cycle / regeneration)
AMP + H2O to IMP + ammoniaReactionampd_step

Annotons

AMP deaminase
ampd_activity
Participant: Family: AMP deaminase family
Family:
AMP deaminase family
Representative Members: AMPD1 (human, muscle)UniProtKB:P23109 AMPD2 (human, liver/neuronal)UniProtKB:Q01433 AMPD3 (human, erythrocyte)UniProtKB:Q01432 AMD1 (Saccharomyces cerevisiae)UniProtKB:P15274

Function

AMP deaminase activityGO:0003876
Substrates: AMP water
Products: IMP ammonia

Locations

cytosolGO:0005829

Deaminates AMP back to IMP, closing the purine nucleotide cycle (with adenylosuccinate synthetase and lyase) and lowering AMP when energy charge falls. Human isozymes AMPD1 (muscle; myoadenylate deaminase deficiency), AMPD2 (broad/neuronal; PCH9/SPG63), AMPD3 (erythrocyte; benign).