ADSS1

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0004019 adenylosuccinate synthase activity	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetically inferred adenylosuccinate synthase activity, the defining molecular function of ADSS1 and the entire adenylosuccinate synthetase family. This is directly confirmed experimentally for the human protein. Reason: This is the core, well-supported molecular function. The IBA is grounded in a broad set of orthologs (E. coli purA, yeast, mouse muscle/non-muscle isozymes) and is confirmed for the human enzyme by direct assay (PMID:15786719) and by a mutation study (PMID:26506222). Supporting Evidence: PMID:15786719 Recombinant AdSSL1 protein possesses typical enzymatic activity to catalyze adenylosuccinate formation.
GO:0005737 cytoplasm	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetically inferred cytoplasmic localization, consistent with the experimentally observed cytoplasmic localization of the human protein. Reason: Adenylosuccinate synthetase is a soluble cytosolic enzyme across the family; the human protein was directly observed in the cytoplasm when overexpressed (PMID:15786719). Cytosol (GO:0005829) is the more precise term captured elsewhere. Supporting Evidence: PMID:15786719 Overexpressed AdSSL1 protein in COS-7 cells locates in cytoplasm.
GO:0044208 'de novo' AMP biosynthetic process	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetically inferred role in de novo AMP biosynthesis. ADSS1 catalyzes step 1 of 2 of the conversion of IMP to AMP, the first committed step of the de novo AMP branch of purine metabolism. Reason: This is a core biological process for the gene, matching the UniProt-annotated pathway (AMP biosynthesis via the de novo pathway, AMP from IMP, step 1 of 2). Well supported by orthology and by the enzyme's characterized reaction. Supporting Evidence: file:human/ADSS1/ADSS1-uniprot.txt Purine metabolism; AMP biosynthesis via de novo pathway; AMP from IMP
GO:0046040 IMP metabolic process	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetically inferred involvement in IMP metabolism. IMP is the direct substrate of adenylosuccinate synthase, consumed in the first committed step of AMP synthesis. Reason: Accurate; ADSS1 consumes IMP (with GTP and aspartate) and, as part of the purine nucleotide cycle, contributes to IMP/AMP interconversion. Broader than the specific catalytic function but a correct process annotation. Supporting Evidence: PMID:15786719 which catalyzes the first committed step in AMP synthesis
GO:0000166 nucleotide binding	IEA GO_REF:0000002	ACCEPT	Summary: InterPro-based inference of nucleotide binding. ADSS1 binds GTP (and its product GDP) and IMP as substrates; nucleotide binding is a general parent of these specific activities. Reason: Correct but general. The enzyme has a P-loop NTPase fold and documented GTP/IMP binding sites (UniProt BINDING features). More specific GTP binding (GO:0005525) is also annotated. Retained as an accurate, if broad, molecular-function annotation. Supporting Evidence: file:human/ADSS1/ADSS1-uniprot.txt Nucleotide-binding
GO:0000287 magnesium ion binding	IEA GO_REF:0000104	ACCEPT	Summary: Rule-based inference of magnesium ion binding. Adenylosuccinate synthase is a Mg2+-dependent enzyme that binds one Mg2+ ion per subunit, coordinating the GTP/phosphoryl-transfer chemistry. Reason: Supported by UniProt cofactor and binding-site annotations (Mg2+ bound at residues 43 and 70), consistent with the conserved catalytic mechanism of the family. Supporting Evidence: file:human/ADSS1/ADSS1-uniprot.txt Binds 1 Mg(2+) ion per subunit.
GO:0004019 adenylosuccinate synthase activity	IEA GO_REF:0000120	ACCEPT	Summary: Automated (ARBA/UniRule/InterPro/RHEA/EC) inference of the core adenylosuccinate synthase activity, duplicating the experimentally and phylogenetically supported molecular function. Reason: Correct core molecular function (EC 6.3.4.4; RHEA 15753), consistent with the IDA, IMP, and IBA annotations for the same term. Supporting Evidence: PMID:15786719 Recombinant AdSSL1 protein possesses typical enzymatic activity to catalyze adenylosuccinate formation.
GO:0005525 GTP binding	IEA GO_REF:0000120	ACCEPT	Summary: Automated inference of GTP binding. GTP is a required co-substrate of the adenylosuccinate synthase reaction, providing the energy for the ligation and being converted to GDP + phosphate. Reason: Well supported; UniProt documents multiple GTP-binding regions (residues 42-48, 70-72, 337, 363-365, 445-448) and the reaction consumes GTP. Also independently annotated NAS from PMID:15786719. Supporting Evidence: file:human/ADSS1/ADSS1-uniprot.txt N(6)-(1,2-dicarboxyethyl)-AMP + GDP
GO:0005737 cytoplasm	IEA GO_REF:0000120	ACCEPT	Summary: Automated inference of cytoplasmic localization, matching the experimental cytoplasmic localization and the cytosol annotation. Reason: Consistent with UniProt subcellular location (Cytoplasm) and the direct experimental observation in PMID:15786719. Supporting Evidence: PMID:15786719 Overexpressed AdSSL1 protein in COS-7 cells locates in cytoplasm.
GO:0006164 purine nucleotide biosynthetic process	IEA GO_REF:0000002	ACCEPT	Summary: InterPro-based inference of involvement in purine nucleotide biosynthesis. ADSS1 acts in the IMP-to-AMP branch, producing the purine nucleotide AMP. Reason: Correct but general parent of the more specific AMP biosynthesis terms; retained as an accurate process annotation. Supporting Evidence: PMID:15786719 which catalyzes the first committed step in AMP synthesis
GO:0006167 AMP biosynthetic process	IEA GO_REF:0000120	ACCEPT	Summary: Automated inference of involvement in AMP biosynthesis, the direct downstream product process of the adenylosuccinate synthase reaction (via ADSL cleavage of S-AMP to AMP). Also independently supported by IDA (PMID:15786719). Reason: Core biological process; the enzyme catalyzes the committed step producing the AMP precursor adenylosuccinate. Supporting Evidence: PMID:15786719 which catalyzes the first committed step in AMP synthesis
GO:0044208 'de novo' AMP biosynthetic process	IEA GO_REF:0000120	ACCEPT	Summary: Automated (UniRule/UniPathway) inference of the de novo AMP biosynthetic process, matching the IBA annotation and the UniProt pathway assignment. Reason: Correct and specific core process (de novo AMP-from-IMP pathway, step 1 of 2). Supporting Evidence: file:human/ADSS1/ADSS1-uniprot.txt AMP biosynthesis via de novo pathway
GO:0005515 protein binding	IPI PMID:28514442 Architecture of the human interactome defines protein commun...	MARK AS OVER ANNOTATED	Summary: IntAct proteome-scale interaction annotation (WITH/FROM UniProtKB:P30520, the paralog ADSS2). "Protein binding" is uninformative as a molecular function. Reason: The bare GO:0005515 term conveys no specific function. The recorded partner is the paralog ADSS2, consistent with the UniProt-documented ADSS1-ADSS2 interaction, but this is a large-scale interactome dataset that does not establish a discrete functional MF for ADSS1. Per curation policy, retained (not removed) but flagged as over-annotation; the informative function is captured by GO:0004019. Supporting Evidence: file:human/ADSS1/ADSS1-uniprot.txt Q8N142; P30520: ADSS2; NbExp=4
GO:0005515 protein binding	IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling...	MARK AS OVER ANNOTATED	Summary: IntAct proteome-scale interaction annotation (WITH/FROM UniProtKB:P30520, the paralog ADSS2). Uninformative bare protein-binding term. Reason: As above, a high-throughput interactome mapping to the paralog ADSS2. Retained per policy but flagged as over-annotation; adds no specific molecular function beyond the adenylosuccinate synthase activity. Supporting Evidence: file:human/ADSS1/ADSS1-uniprot.txt Q8N142; P30520: ADSS2; NbExp=4
GO:0005515 protein binding	IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func...	MARK AS OVER ANNOTATED	Summary: IntAct proteome-scale interaction annotation (WITH/FROM UniProtKB:P30520, the paralog ADSS2). Uninformative bare protein-binding term. Reason: As above, a multimodal cell-map / interactome dataset mapping to ADSS2. Retained per policy but flagged as over-annotation. Supporting Evidence: file:human/ADSS1/ADSS1-uniprot.txt Q8N142; P30520: ADSS2; NbExp=4
GO:0044209 AMP salvage	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Ensembl-orthology inference of involvement in AMP salvage. ADSS1 in muscle operates the AMP-regenerating limb of the purine nucleotide cycle (IMP to AMP), which recycles the purine nucleotide pool. Reason: The primary and precise characterization of ADSS1 is de novo AMP biosynthesis (AMP from IMP, step 1 of 2). AMP salvage (reuse of preformed adenine/adenosine) is not the enzyme's committed-step chemistry; the overlap is via the purine nucleotide cycle that regenerates AMP from IMP. Kept as it is not strictly wrong, but flagged as a less precise, orthology-transferred process; GO:0044208 is the accurate term. Supporting Evidence: file:human/ADSS1/ADSS1-uniprot.txt which interconverts IMP and AMP to regulate the nucleotide levels
GO:0004019 adenylosuccinate synthase activity	IMP PMID:26506222 ADSSL1 mutation relevant to autosomal recessive adolescent o...	ACCEPT	Summary: Adenylosuccinate synthase activity inferred from mutant phenotype; disease variants in ADSSL1 reduce catalytic activity, confirming that the wild-type protein provides this function. Reason: Direct genetic/functional evidence. Both MPD5 mutations (p.D304N and p.I350fs) decreased enzymatic activity, and the D261N variant characterized in UniProt shows decreased adenylosuccinate synthase activity, tying the human gene product's core catalytic function to disease. Supporting Evidence: PMID:26506222 Both the D304N and I350fs mutations in ADSSL1 led to decreased enzymatic activity.
GO:0005829 cytosol	TAS Reactome:R-HSA-111524	ACCEPT	Summary: Cytosolic localization asserted by Reactome for the adenylosuccinate synthase reaction, consistent with the soluble cytosolic nature of the enzyme. Reason: Cytosol is the precise cellular component for this soluble enzyme, agreeing with the experimental cytoplasm localization (PMID:15786719) and UniProt subcellular location. This is the preferred specific location term. Supporting Evidence: Reactome:R-HSA-111524 Two isoforms of adenylosuccinate synthetase, ADSS and ADSSL1, catalyze the reaction of IMP, aspartate, and GTP to form adenylosuccinate, GDP, and orthophosphate
GO:0002376 immune system process	NAS PMID:15786719 Molecular cloning and characterization of a novel muscle ade...	KEEP AS NON CORE	Summary: Non-traceable author statement based on the observation that AdSSL1 is expressed in hematopoietic/leukemia cell lines in a stimulation-dependent manner. This is an expression correlation, not an established immune function. Reason: ADSS1 is fundamentally a purine-metabolism enzyme predominantly expressed in muscle; the immune-system link rests only on expression in leukemia cells after stimulation, with no demonstrated mechanistic immune role. Kept as a non-core, weakly-supported process rather than a core function. Supporting Evidence: PMID:15786719 After stimulation, leukemia cells express AdSSL1 in a time-dependent manner
GO:0004019 adenylosuccinate synthase activity	IDA PMID:15786719 Molecular cloning and characterization of a novel muscle ade...	ACCEPT	Summary: Direct assay of recombinant human AdSSL1 demonstrating adenylosuccinate synthase activity (adenylosuccinate formation). This is the primary experimental evidence for the core molecular function. Reason: Strong direct experimental support for the defining catalytic activity of the gene product. Supporting Evidence: PMID:15786719 Recombinant AdSSL1 protein possesses typical enzymatic activity to catalyze adenylosuccinate formation.
GO:0005525 GTP binding	NAS PMID:15786719 Molecular cloning and characterization of a novel muscle ade...	ACCEPT	Summary: Author statement of GTP binding, reflecting the conserved GTP-dependent mechanism of adenylosuccinate synthetase; GTP is a co-substrate of the reaction. Reason: Consistent with the well-characterized GTP-dependent catalytic mechanism and the multiple GTP-binding regions annotated in UniProt; also independently supported by IEA. Supporting Evidence: file:human/ADSS1/ADSS1-uniprot.txt N(6)-(1,2-dicarboxyethyl)-AMP + GDP
GO:0005737 cytoplasm	IDA PMID:15786719 Molecular cloning and characterization of a novel muscle ade...	ACCEPT	Summary: Direct experimental observation that overexpressed AdSSL1 localizes to the cytoplasm in COS-7 cells. Reason: Direct localization evidence for the human protein; cytosol (GO:0005829) is the more granular equivalent captured from Reactome. Supporting Evidence: PMID:15786719 Overexpressed AdSSL1 protein in COS-7 cells locates in cytoplasm.
GO:0006167 AMP biosynthetic process	IDA PMID:15786719 Molecular cloning and characterization of a novel muscle ade...	ACCEPT	Summary: Direct evidence linking ADSS1 to AMP biosynthesis via its characterized adenylosuccinate-forming activity, the committed step in AMP synthesis. Reason: Core biological process, directly supported by the enzyme assay and the description of AdSSL1 as catalyzing the first committed step in AMP synthesis. Supporting Evidence: PMID:15786719 which catalyzes the first committed step in AMP synthesis
GO:0042301 phosphate ion binding	NAS PMID:15786719 Molecular cloning and characterization of a novel muscle ade...	MARK AS OVER ANNOTATED	Summary: Author statement of phosphate ion binding. Phosphate is a reaction product and the enzyme binds the phosphate groups of its GTP/GDP and IMP ligands, but a standalone phosphate-ion-binding molecular function is not informative for this enzyme. Reason: The enzyme's phosphate handling is part of GTP binding and the ligase catalytic mechanism (phosphate is released as a product). A discrete phosphate-ion-binding MF annotation adds little and risks over-representing an incidental feature; the informative functions are GO:0004019 and GO:0005525. Kept (not wrong) but flagged. Supporting Evidence: file:human/ADSS1/ADSS1-uniprot.txt N(6)-(1,2-dicarboxyethyl)-AMP + GDP + phosphate

Gene Description

Existing Annotations Review

Core Functions

Catalyzes the first committed step of AMP biosynthesis from IMP - the Mg2+-dependent, GTP-driven condensation of IMP with L-aspartate to yield adenylosuccinate (N6-(1,2-dicarboxyethyl)-AMP), GDP and phosphate (EC 6.3.4.4) - as the muscle isozyme of adenylosuccinate synthetase.

References

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Notes

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