ASL

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0004056 argininosuccinate lyase activity	IBA GO_REF:0000033	ACCEPT	Summary: Retain the phylogenetically inferred argininosuccinate lyase activity as core. Reason: The PAINT assertion is concordant with independent human enzyme, pathway and localization evidence. Preserve its ancestral node and descendant evidence: a human self-donor is not circular, and donor count does not measure the strength of an IBA. The exact family tree and alignment were not independently reconstructed. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000154674 UNRESOLVED The exact ancestral node and alignment were not independently replayed. Concordant human function corroborates the transfer but does not independently establish node placement. Supporting Evidence: PMID:11747433 Argininosuccinate lyase (ASL) is a homotetrameric enzyme that catalyzes the reversible cleavage of argininosuccinate to arginine and fumarate.
GO:0006526 L-arginine biosynthetic process	IBA GO_REF:0000033	ACCEPT	Summary: Retain the phylogenetically inferred arginine biosynthesis as core. Reason: The PAINT assertion is concordant with independent human enzyme, pathway and localization evidence. Preserve its ancestral node and descendant evidence: a human self-donor is not circular, and donor count does not measure the strength of an IBA. The exact family tree and alignment were not independently reconstructed. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000154674 UNRESOLVED The exact ancestral node and alignment were not independently replayed. Concordant human function corroborates the transfer but does not independently establish node placement. Supporting Evidence: PMID:11747432 a reaction involved in the biosynthesis of arginine in all species and in the production of urea in ureotelic species
GO:0005829 cytosol	IBA GO_REF:0000033	ACCEPT	Summary: Retain the phylogenetically inferred cytosolic localization as core. Reason: The PAINT assertion is concordant with independent human enzyme, pathway and localization evidence. Preserve its ancestral node and descendant evidence: a human self-donor is not circular, and donor count does not measure the strength of an IBA. The exact family tree and alignment were not independently reconstructed. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000154674 UNRESOLVED The exact ancestral node and alignment were not independently replayed. Concordant human function corroborates the transfer but does not independently establish node placement.
GO:0003824 catalytic activity	IEA GO_REF:0000002	MODIFY	Summary: Refine broad catalytic activity to argininosuccinate lyase activity. Reason: The InterPro-based assertion of catalysis is correct but broad. Human enzyme assays support GO:0004056. Generality calls for a more precise term, not a claim that the catalytic function is false or over-annotated. Proposed replacements: argininosuccinate lyase activity Supporting Evidence: PMID:11747433 Argininosuccinate lyase (ASL) is a homotetrameric enzyme that catalyzes the reversible cleavage of argininosuccinate to arginine and fumarate.
GO:0004056 argininosuccinate lyase activity	IEA GO_REF:0000120	ACCEPT	Summary: Retain the combined electronic lyase assignment as core. Reason: The preserved InterPro, Rhea and EC mappings describe argininosuccinate cleavage into arginine and fumarate, which is independently established for human ASL. Distinct electronic and experimental assertions remain separate.
GO:0006526 L-arginine biosynthetic process	IEA GO_REF:0000120	ACCEPT	Summary: Retain the combined electronic arginine-biosynthesis assignment as core. Reason: The preserved mouse, Ensembl, InterPro and UniPathway sources agree with human ASL catalysis. ASL itself executes the arginine-producing step; this is direct participation rather than a substrate or downstream phenotype inference.
GO:0005515 protein binding	IPI PMID:25416956 A proteome-scale map of the human interactome network.	UNDECIDED	Summary: Leave the source-specific interaction with UniProtKB:Q96HA8 unresolved. Reason: The PMID:25416956 annotation names NTAQ1 (UniProtKB:Q96HA8) as the ASL partner. The exact source-specific pair record and assay context remain uninspected, so the interaction and any narrower molecular function remain unresolved for this assertion. The shipped UniProt interaction list corroborates the partner association across studies but does not resolve this individual citation.
GO:0005515 protein binding	IPI PMID:26871637 Widespread Expansion of Protein Interaction Capabilities by ...	UNDECIDED	Summary: Leave the source-specific interaction with UniProtKB:Q9BTE3-2 unresolved. Reason: The PMID:26871637 annotation names MCMBP isoform 2 (UniProtKB:Q9BTE3-2) as the ASL partner. The exact source-specific pair record and assay context remain uninspected, so the interaction and any narrower molecular function remain unresolved for this assertion. The shipped UniProt interaction list corroborates the partner association across studies but does not resolve this individual citation.
GO:0005515 protein binding	IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari...	UNDECIDED	Summary: Leave the source-specific interaction with UniProtKB:Q96HA8 unresolved. Reason: The PMID:31515488 annotation names NTAQ1 (UniProtKB:Q96HA8) as the ASL partner. The exact source-specific pair record and assay context remain uninspected, so the interaction and any narrower molecular function remain unresolved for this assertion. The shipped UniProt interaction list corroborates the partner association across studies but does not resolve this individual citation.
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	UNDECIDED	Summary: Leave the source-specific interaction with UniProtKB:O75382 unresolved. Reason: The PMID:32296183 annotation names TRIM3 (UniProtKB:O75382) as the ASL partner. The exact source-specific pair record and assay context remain uninspected, so the interaction and any narrower molecular function remain unresolved for this assertion. The shipped UniProt interaction list corroborates the partner association across studies but does not resolve this individual citation.
GO:0042802 identical protein binding	IPI PMID:21988832 Toward an understanding of the protein interaction network o...	ACCEPT	Summary: Retain curated ASL self-association, independently corroborated by its homotetramer. Reason: ASL is a homotetramer whose subunits contribute to catalytic sites, independently supporting self-association as part of the enzyme mechanism. The PMID:21988832 IPI assertion is retained with that biochemical corroboration; its individual screen record remains uninspected. Supporting Evidence: PMID:11747433 Argininosuccinate lyase (ASL) is a homotetrameric enzyme that catalyzes the reversible cleavage of argininosuccinate to arginine and fumarate.
GO:0042802 identical protein binding	IPI PMID:25416956 A proteome-scale map of the human interactome network.	ACCEPT	Summary: Retain curated ASL self-association, independently corroborated by its homotetramer. Reason: ASL is a homotetramer whose subunits contribute to catalytic sites, independently supporting self-association as part of the enzyme mechanism. The PMID:25416956 IPI assertion is retained with that biochemical corroboration; its individual screen record remains uninspected. Supporting Evidence: PMID:11747433 Argininosuccinate lyase (ASL) is a homotetrameric enzyme that catalyzes the reversible cleavage of argininosuccinate to arginine and fumarate.
GO:0042802 identical protein binding	IPI PMID:25502805 A massively parallel pipeline to clone DNA variants and exam...	ACCEPT	Summary: Retain curated ASL self-association, independently corroborated by its homotetramer. Reason: ASL is a homotetramer whose subunits contribute to catalytic sites, independently supporting self-association as part of the enzyme mechanism. The PMID:25502805 IPI assertion is retained with that biochemical corroboration; its individual screen record remains uninspected. Supporting Evidence: PMID:11747433 Argininosuccinate lyase (ASL) is a homotetrameric enzyme that catalyzes the reversible cleavage of argininosuccinate to arginine and fumarate.
GO:0042802 identical protein binding	IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari...	ACCEPT	Summary: Retain curated ASL self-association, independently corroborated by its homotetramer. Reason: ASL is a homotetramer whose subunits contribute to catalytic sites, independently supporting self-association as part of the enzyme mechanism. The PMID:31515488 IPI assertion is retained with that biochemical corroboration; its individual screen record remains uninspected. Supporting Evidence: PMID:11747433 Argininosuccinate lyase (ASL) is a homotetrameric enzyme that catalyzes the reversible cleavage of argininosuccinate to arginine and fumarate.
GO:0042802 identical protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	ACCEPT	Summary: Retain curated ASL self-association, independently corroborated by its homotetramer. Reason: ASL is a homotetramer whose subunits contribute to catalytic sites, independently supporting self-association as part of the enzyme mechanism. The PMID:32296183 IPI assertion is retained with that biochemical corroboration; its individual screen record remains uninspected. Supporting Evidence: PMID:11747433 Argininosuccinate lyase (ASL) is a homotetrameric enzyme that catalyzes the reversible cleavage of argininosuccinate to arginine and fumarate.
GO:0045429 positive regulation of nitric oxide biosynthetic process	IEA GO_REF:0000107	ACCEPT	Summary: Retain the mouse-derived nitric-oxide regulation inference as a second core role. Reason: The preserved mouse Q91YI0/Ensembl transfer agrees with reduced NOS-complex recovery in Asl-deficient mouse lung and brain and with independent human ASL rescue experiments. ASL supports nitric oxide production through both arginine synthesis and complex assembly. The exact mouse donor annotation chain was not replayed. Supporting Evidence: PMID:22081021 AslNeo/Neo mouse lung and brain showed significantly decreased quantities of both Nos3 and Nos1 isoforms, respectively, as well as other proteins involved in the complex (Fig. 6a, Supplementary Fig.8); this is despite increased abundance of the individual components (other than Asl) in tissues of AslNeo/Neo mice compared to WT on Western analysis (Figure 2c, Supplementary Fig.8). PMID:22081021 absence of ASL prevented efficient immunoprecipitation of the proteins involved in the NOS complex by either one of these antibodies (Fig. 6b). PMID:22081021 when we overexpressed human ASL with the R113Q mutation in vitro, ASA fibroblasts were able to generate nitrite at a level comparable to control cells when supplemented with arginine
GO:0000050 urea cycle	IEA GO_REF:0000041	ACCEPT	Summary: Retain the mapped urea-cycle participation as core. Reason: ASL directly catalyzes the argininosuccinate-cleavage step that regenerates arginine in the urea cycle. The original UniPathway source is preserved and agrees with human biochemical evidence. Supporting Evidence: PMID:11747432 a reaction involved in the biosynthesis of arginine in all species and in the production of urea in ureotelic species
GO:0005829 cytosol	TAS Reactome:R-HSA-9956524	ACCEPT	Summary: Retain the cytosolic location from the Reactome loss-of-function variant reaction. Reason: The official human reaction page identifies the ASL tetramer in the cytosol. This verifies the modeled compartment, not an independent assay of every variant or catalytic competence of the variant set. The recovered normal summary distinguishes candidate from characterized variant members; it does not itself state the compartment, which was checked on the official event and catalyst pages.
GO:0004056 argininosuccinate lyase activity	EXP PMID:2263616 Molecular analysis of human argininosuccinate lyase: mutant ...	ACCEPT	Summary: Retain the experimentally established human ASL enzyme activity. Reason: The cited study expressed human ASL R95C in COS cells and observed normal mRNA, little protein and less than 1% enzyme activity. Together with independent enzyme studies, this supports the core lyase assignment. The cached abstract was read; no claim of complete article inspection is made. Supporting Evidence: PMID:2263616 Expression in COS cells demonstrated that the R95C mutation produces normal amounts of ASAL mRNA but little protein and less than 1% ASAL activity.
GO:0004056 argininosuccinate lyase activity	IDA PMID:9045711 Intragenic complementation at the human argininosuccinate ly...	ACCEPT	Summary: Retain human ASL activity supported by mutant complementation. Reason: Human Q286R and D87G constructs each reduced ASL activity in COS-cell assays; joint expression partially restored activity. This directly supports the enzyme assignment and interallelic complementation. The accessible abstract, rather than the complete experimental record, was inspected. Supporting Evidence: PMID:9045711 each conferred loss of ASL activity in COS cell transfection assays
GO:0006525 arginine metabolic process	IDA PMID:9045711 Intragenic complementation at the human argininosuccinate ly...	MODIFY	Summary: Refine broad arginine metabolism to arginine biosynthesis. Reason: The cited human complementation study supports ASL catalytic function. Independent human structure and enzymology describe the same arginine-producing reaction as part of arginine biosynthesis. GO:0006526 therefore refines the broad metabolic assertion while retaining the original PMID:9045711 source and IDA code; the added process quote is corroboration from PMID:11747432, not a relabeling of the original experiment. Proposed replacements: L-arginine biosynthetic process Supporting Evidence: PMID:9045711 each conferred loss of ASL activity in COS cell transfection assays PMID:11747432 a reaction involved in the biosynthesis of arginine in all species and in the production of urea in ureotelic species
GO:0045429 positive regulation of nitric oxide biosynthetic process	IMP PMID:22081021 Requirement of argininosuccinate lyase for systemic nitric o...	ACCEPT	Summary: Retain experimentally supported nitric-oxide regulation as a second core role. Reason: Human ASL expression restores arginine-stimulated nitrite production in ASL-deficient patient fibroblasts even with a catalytic-site mutant. Separate COS7 experiments show impaired NOS/ASS co-immunoprecipitation without ASL and maintained assembly with human R236W ASL. Together these support a structural contribution to NO production in addition to arginine synthesis. Mouse Nos3 and Nos1 assembly results concern lung and brain, respectively. The Results/caption mutant-label discrepancy is retained once in the reference assessment and notes. Supporting Evidence: PMID:22081021 absence of ASL prevented efficient immunoprecipitation of the proteins involved in the NOS complex by either one of these antibodies (Fig. 6b). PMID:22081021 in vitro over-expression of mutated ASL in COS7 cells did not prevent NOS protein assembly with ASS as shown by IP using antibodies against ASS or NOS. PMID:22081021 when we overexpressed human ASL with the R113Q mutation in vitro, ASA fibroblasts were able to generate nitrite at a level comparable to control cells when supplemented with arginine
GO:0004056 argininosuccinate lyase activity	IDA PMID:11747433 Mechanisms for intragenic complementation at the human argin...	ACCEPT	Summary: Retain lyase activity established in human complementation studies. Reason: The cited abstract describes recombinant-protein reconstruction of catalytic complementation in vivo and in vitro. It distinguishes restoration of active sites in Q286R/D87G heteromers from stabilization involving M360T or A398D. This supports the enzyme activity without claiming that all alleles have the same mechanism. Supporting Evidence: PMID:11747433 Argininosuccinate lyase (ASL) is a homotetrameric enzyme that catalyzes the reversible cleavage of argininosuccinate to arginine and fumarate.
GO:0006526 L-arginine biosynthetic process	IDA PMID:11747432 Three-dimensional structure of the argininosuccinate lyase f...	ACCEPT	Summary: Retain ASL participation in the arginine-producing reaction. Reason: The human Q286R structure paper explicitly identifies argininosuccinate cleavage as an arginine-biosynthetic reaction. The abstract corroborates the biological function; the experimental curator has fuller access to the underlying assays. Supporting Evidence: PMID:11747432 a reaction involved in the biosynthesis of arginine in all species and in the production of urea in ureotelic species
GO:0006526 L-arginine biosynthetic process	IDA PMID:11747433 Mechanisms for intragenic complementation at the human argin...	ACCEPT	Summary: Retain arginine biosynthesis supported by enzyme complementation. Reason: Human ASL directly produces arginine from argininosuccinate. The accessible recombinant-complementation abstract corroborates the curated process assertion and the enzyme assignment; this is a catalytic participant, not a passive substrate. Supporting Evidence: PMID:11747433 Argininosuccinate lyase (ASL) is a homotetrameric enzyme that catalyzes the reversible cleavage of argininosuccinate to arginine and fumarate.
GO:0004056 argininosuccinate lyase activity	IDA PMID:11747432 Three-dimensional structure of the argininosuccinate lyase f...	ACCEPT	Summary: Retain the human lyase activity associated with the Q286R structure study. Reason: The abstract explicitly describes the ASL reaction and human structure. Retain the curated activity with independent biochemical corroboration. The earlier exact Km claim was not verified from this abstract and is omitted; no complete kinetic-table inspection is claimed. Supporting Evidence: PMID:11747432 Argininosuccinate lyase (ASL) catalyzes the reversible breakdown of argininosuccinate to arginine and fumarate
GO:0070062 extracellular exosome	HDA PMID:19056867 Large-scale proteomics and phosphoproteomics of urinary exos...	KEEP AS NON CORE	Summary: Retain the directly identified urinary-exosome localization as non-core. Reason: The study-authored NHLBI Urinary Exosome Protein Database explicitly lists ASL NP_001020117 with one peptide and reference 2, which links PMID:19056867. This verifies target detection in that human urinary-exosome study. It supports a non-core location, without demonstrating catalytic work in exosomes or contamination. The database isoform label does not change the original source assertion or establish peptide uniqueness for a modern ASL isoform.
GO:0005829 cytosol	TAS Reactome:R-HSA-70573	ACCEPT	Summary: Retain the cytosolic location from the Reactome normal reversible reaction. Reason: The official human reaction page identifies the ASL tetramer in the cytosol. This verifies the modeled compartment, not an independent assay of every variant or catalytic competence of the variant set. Supporting Evidence: Reactome:R-HSA-70573 Cytosolic argininosuccinate lyase (ASL) catalyzes the reversible reaction of argininosuccinate to form fumarate and arginine.
GO:0004056 argininosuccinate lyase activity	TAS PMID:282632 Argininosuccinic aciduria: assignment of the argininosuccina...	ACCEPT	Summary: Retain the traceable human ASL enzyme assertion. Reason: The human genetic-mapping study detected ASL activity by bioautography. Its abstract and independent enzyme studies support the lyase function; no additional localization assay is inferred from the electrophoretic detection method. Supporting Evidence: PMID:282632 associated with a deficiency of argininosuccinate lyase (ASL; L-argininosuccinate arginine-lyase, EC 4.3.2.1)
GO:0005737 cytoplasm	TAS PMID:282632 Argininosuccinic aciduria: assignment of the argininosuccina...	ACCEPT	Summary: Retain the broad curated cytoplasmic location. Reason: The cytoplasmic assertion agrees with the independently established cytosolic enzyme and Reactome compartment. The cited bioautography abstract does not itself demonstrate subcellular fractionation, so retention relies on concordant localization and curator deference rather than an invented localization experiment.
GO:0140378 protein complex scaffold activity	IMP PMID:22081021 Requirement of argininosuccinate lyase for systemic nitric o...	NEW	Summary: ASL supports the structural integrity of NOS-containing protein assemblies. Reason: NOS-complex co-immunoprecipitation decreases without ASL, while human catalytically inactive R236W ASL supports assembly in COS7 cells. Mouse lung and brain show reduced complex-associated components despite increased abundance of the individual proteins. These assembly observations, together with catalytic-mutant rescue of nitrite production in patient fibroblasts, support a structural scaffold contribution rather than catalytic necessity alone. The evidence does not establish a single universal complex containing every NOS isoform or direct pairwise contact with every component. The Results/caption mutant-label discrepancy is retained once in the reference assessment and notes. Supporting Evidence: PMID:22081021 Mechanistic studies showed that ASL has a structural function in addition to its catalytic activity, by which it contributes to the formation of a multiprotein complex required for NO production. PMID:22081021 absence of ASL prevented efficient immunoprecipitation of the proteins involved in the NOS complex by either one of these antibodies (Fig. 6b). PMID:22081021 AslNeo/Neo mouse lung and brain showed significantly decreased quantities of both Nos3 and Nos1 isoforms, respectively, as well as other proteins involved in the complex (Fig. 6a, Supplementary Fig.8); this is despite increased abundance of the individual components (other than Asl) in tissues of AslNeo/Neo mice compared to WT on Western analysis (Figure 2c, Supplementary Fig.8). PMID:22081021 in vitro over-expression of mutated ASL in COS7 cells did not prevent NOS protein assembly with ASS as shown by IP using antibodies against ASS or NOS. PMID:22081021 when we overexpressed human ASL with the R113Q mutation in vitro, ASA fibroblasts were able to generate nitrite at a level comparable to control cells when supplemented with arginine
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	UNDECIDED	Summary: Leave the source-specific interaction with UniProtKB:Q96HA8 unresolved. Reason: The PMID:32296183 annotation names NTAQ1 (UniProtKB:Q96HA8) as the ASL partner. The exact source-specific pair record and assay context remain uninspected, so the interaction and any narrower molecular function remain unresolved for this assertion. The shipped UniProt interaction list corroborates the partner association across studies but does not resolve this individual citation.
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	UNDECIDED	Summary: Leave the source-specific interaction with UniProtKB:Q9BTE3-2 unresolved. Reason: The PMID:32296183 annotation names MCMBP isoform 2 (UniProtKB:Q9BTE3-2) as the ASL partner. The exact source-specific pair record and assay context remain uninspected, so the interaction and any narrower molecular function remain unresolved for this assertion. The shipped UniProt interaction list corroborates the partner association across studies but does not resolve this individual citation.

Gene Description

Existing Annotations Review

Core Functions

Catalyzes the reversible cleavage of argininosuccinate into arginine and fumarate as a cytosolic homotetramer, contributing directly to the urea cycle and arginine biosynthesis. Self-association assembles the catalytic sites and is part of this enzyme mechanism.

Contributes a structural scaffold to nitric oxide synthase protein assemblies, supporting utilization of arginine for nitric oxide production independently of its arginine-generating catalytic reaction.

References

Deep Research

Falcon

📚 Additional Documentation

Notes

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