GLUL

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0004356 glutamine synthetase activity	IBA GO_REF:0000033	ACCEPT	Summary: Core molecular function. Phylogenetic (IBA) propagation of glutamine synthetase activity across the family, fully concordant with the human experimental annotations (IDA/EXP) and the UniProt catalytic activity. Supporting Evidence: file:human/GLUL/GLUL-uniprot.txt Glutamine synthetase that catalyzes the ATP-dependent
GO:0005737 cytoplasm	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: GS is active in the cytoplasm; correct but non-specific. The more precise cytosol term (GO:0005829) is supported experimentally (IDA) and is used in core_functions. Proposed replacements: cytosol Supporting Evidence: file:human/GLUL/GLUL-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm, cytosol
GO:1901704 L-glutamine biosynthetic process	IBA GO_REF:0000033	ACCEPT	Summary: Core biological process. Glutamine biosynthesis is the canonical output of GS activity; IBA propagation is consistent with human experimental evidence and UniProt. This is the current (non-obsolete) term for glutamine biosynthesis. Supporting Evidence: file:human/GLUL/GLUL-uniprot.txt conversion of glutamate and ammonia to glutamine
GO:0003824 catalytic activity	IEA GO_REF:0000002	MARK AS OVER ANNOTATED	Summary: Root-level catalytic activity from InterPro2GO; correct but far too general given the specific, experimentally supported glutamine synthetase activity. Proposed replacements: glutamine synthetase activity
GO:0004356 glutamine synthetase activity	IEA GO_REF:0000120	ACCEPT	Summary: Core molecular function, here from automated InterPro/ARBA/RHEA/EC mapping (EC 6.3.1.2, RHEA:16169). Redundant with the experimental IDA/EXP annotations but correct. Supporting Evidence: file:human/GLUL/GLUL-uniprot.txt Glutamine synthetase that catalyzes the ATP-dependent
GO:0005739 mitochondrion	IEA GO_REF:0000044	REMOVE	Summary: Mitochondrial localization derived from UniProt Subcellular Location mapping, but the UniProt mitochondrion assignment is itself only by-similarity to the sheep enzyme (ECO:0000250\|UniProtKB:P09606), not human-experimental. The mammalian enzyme is overwhelmingly cytosolic; this IEA is a low-confidence over-propagation.
GO:0005829 cytosol	IEA GO_REF:0000044	ACCEPT	Summary: Correct core localization from UniProt Subcellular Location mapping; redundant with the experimental IDA cytosol annotations. Supporting Evidence: file:human/GLUL/GLUL-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm, cytosol
GO:0005886 plasma membrane	IEA GO_REF:0000044	KEEP AS NON CORE	Summary: Plasma membrane localization from UniProt Subcellular Location mapping; corresponds to the palmitoylation-anchored fraction and is independently supported by experimental IDA (PMID:30158707). A minor, non-core location. Supporting Evidence: file:human/GLUL/GLUL-uniprot.txt with a fraction associated with the cell membrane
GO:0019706 protein-cysteine S-palmitoyltransferase activity	IEA GO_REF:0000120	KEEP AS NON CORE	Summary: Palmitoyltransferase activity from automated RHEA/EC (EC 2.3.1.225) mapping. This is a real but non-canonical moonlighting activity (autopalmitoylation / RHOJ palmitoylation) also supported by experimental IDA (PMID:30158707); the EC assignment in UniProt is ECO:0000305 (inferred). Keep as non-core. Supporting Evidence: file:human/GLUL/GLUL-uniprot.txt then transfer the palmitoyl group to RHOJ
GO:1901704 L-glutamine biosynthetic process	IEA GO_REF:0000002	ACCEPT	Summary: Core biological process (glutamine biosynthesis) from InterPro2GO; redundant with the IBA and experimental evidence but correct. Supporting Evidence: file:human/GLUL/GLUL-uniprot.txt conversion of glutamate and ammonia to glutamine
GO:0005515 protein binding	IPI PMID:25910212 Widespread macromolecular interaction perturbations in human...	MARK AS OVER ANNOTATED	Summary: Bare protein binding from a large-scale interactome perturbation study (a systematic HIV TAT / disease-variant interaction screen). The cached full text does not mention GLUL by name; the interaction (with TAT, P17735) carries no functional context. Uninformative per curation policy.
GO:0005515 protein binding	IPI PMID:30158707 Role of glutamine synthetase in angiogenesis beyond glutamin...	MARK AS OVER ANNOTATED	Summary: Binding to the GTPase RHOJ (Q9H4E5). This is a functionally meaningful interaction underlying GLUL-mediated RHOJ palmitoylation and endothelial migration, but as a bare protein binding term it is uninformative; the functional consequences are captured by the palmitoylation and angiogenesis annotations. Mark the generic binding term as over-annotated. Supporting Evidence: file:human/GLUL/GLUL-uniprot.txt interacts with RHOJ to sustain RHOJ palmitoylation
GO:0042802 identical protein binding	IPI PMID:16189514 Towards a proteome-scale map of the human protein-protein in...	KEEP AS NON CORE	Summary: Self-interaction (homo-oligomerization) from a proteome-scale Y2H interactome map. GS is genuinely a homo-oligomer (decamer of two pentamers), so identical protein binding is biologically real, but this high-throughput annotation adds little beyond the known quaternary structure. Keep as non-core. Supporting Evidence: file:human/GLUL/GLUL-uniprot.txt Decamer; composed of two pentamers
GO:0042802 identical protein binding	IPI PMID:19447967 Shifted Transversal Design smart-pooling for high coverage i...	KEEP AS NON CORE	Summary: Self-interaction from a smart-pooling interactome screen; consistent with the known homo-oligomeric (decameric) assembly. Redundant high-throughput evidence, kept as non-core. Supporting Evidence: file:human/GLUL/GLUL-uniprot.txt Decamer; composed of two pentamers
GO:0042802 identical protein binding	IPI PMID:21988832 Toward an understanding of the protein interaction network o...	KEEP AS NON CORE	Summary: Self-interaction from a human liver protein-interaction network study; consistent with GS homo-oligomerization. Redundant high-throughput evidence, kept as non-core. Supporting Evidence: file:human/GLUL/GLUL-uniprot.txt Decamer; composed of two pentamers
GO:0042802 identical protein binding	IPI PMID:25416956 A proteome-scale map of the human interactome network.	KEEP AS NON CORE	Summary: Self-interaction from a proteome-scale interactome map; consistent with the known decameric assembly. Redundant high-throughput evidence, kept as non-core. Supporting Evidence: file:human/GLUL/GLUL-uniprot.txt Decamer; composed of two pentamers
GO:0042802 identical protein binding	IPI PMID:25502805 A massively parallel pipeline to clone DNA variants and exam...	KEEP AS NON CORE	Summary: Self-interaction from a parallel variant-cloning / interaction study; consistent with GS homo-oligomerization. Redundant high-throughput evidence, kept as non-core. Supporting Evidence: file:human/GLUL/GLUL-uniprot.txt Decamer; composed of two pentamers
GO:0042802 identical protein binding	IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari...	KEEP AS NON CORE	Summary: Self-interaction from an allele-frequency interactome perturbation study; consistent with the decameric quaternary structure. Redundant high-throughput evidence, kept as non-core. Supporting Evidence: file:human/GLUL/GLUL-uniprot.txt Decamer; composed of two pentamers
GO:0004356 glutamine synthetase activity	EXP PMID:16267323 Congenital glutamine deficiency with glutamine synthetase mu...	ACCEPT	Summary: Core molecular function with direct experimental support: patient variants R324C and R341C reduce GS activity in expression studies, establishing the human enzyme's glutamine synthetase activity and its clinical relevance (congenital glutamine deficiency). Supporting Evidence: PMID:16267323 these mutations are associated with reduced glutamine synthetase activity
GO:0005739 mitochondrion	ISS GO_REF:0000024	MARK AS OVER ANNOTATED	Summary: Mitochondrial localization transferred by sequence similarity from the sheep enzyme (P09606). The human enzyme is a cytosolic protein; UniProt itself flags mitochondrion only by-similarity. Not supported by human experimental data and biologically doubtful as a functional location.
GO:0045648 positive regulation of erythrocyte differentiation	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: Role in ammonium detoxification during erythropoiesis, transferred by similarity from mouse (P15105): GS activity removes ammonium generated by HMBS during heme biosynthesis. Plausible but indirect and species-inferred; a downstream consequence of the enzymatic activity. Keep as non-core. Supporting Evidence: file:human/GLUL/GLUL-uniprot.txt Plays a key role in ammonium detoxification during
GO:0097275 intracellular ammonium homeostasis	ISS GO_REF:0000024	ACCEPT	Summary: Intracellular ammonium homeostasis is a direct, core consequence of GS activity (it consumes free ammonium to make glutamine). Transferred by similarity from mouse but strongly consistent with the enzyme's role in ammonia detoxification. Retained as a core biological process. Supporting Evidence: file:human/GLUL/GLUL-uniprot.txt it regulates the levels of toxic ammonia
GO:0004356 glutamine synthetase activity	IDA PMID:36289327 Bestrophin-2 and glutamine synthetase form a complex for glu...	ACCEPT	Summary: Core molecular function; direct assay of GS catalytic activity in the study of the GLUL-BEST2 complex (R299E abolishes glutamine synthase activity).
GO:0005515 protein binding	IPI PMID:36289327 Bestrophin-2 and glutamine synthetase form a complex for glu...	MARK AS OVER ANNOTATED	Summary: Binding to bestrophin-2 (BEST2, Q8NFU1). A functionally meaningful complex (tethers GS to membrane and reciprocally gates BEST2 for glutamate release), but the bare protein binding term is uninformative; the functional role is described in the notes and captured by the cytosol/complex context. Supporting Evidence: file:human/GLUL/GLUL-uniprot.txt Interacts with BEST2
GO:0005829 cytosol	IDA PMID:36289327 Bestrophin-2 and glutamine synthetase form a complex for glu...	ACCEPT	Summary: Core localization; direct experimental demonstration that GS is cytosolic (with a membrane-tethered fraction via BEST2). Supporting Evidence: file:human/GLUL/GLUL-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm, cytosol
GO:0008283 cell population proliferation	IDA PMID:18662667 Glutamine synthetase is essential for proliferation of fetal...	KEEP AS NON CORE	Summary: GS activity is required for proliferation of fetal skin fibroblasts; loss of activity (patient R324C or MSO inhibition) reduces proliferation without affecting apoptosis. This is a downstream cellular consequence of glutamine supply rather than a distinct molecular function. Keep as non-core. Supporting Evidence: PMID:18662667 results in a significant drop in the proliferation rate but has no effect on apoptosis
GO:0042254 ribosome biogenesis	IMP PMID:26711351 Genome-wide RNAi Screening Identifies Protein Modules Requir...	KEEP AS NON CORE	Summary: Genome-wide RNAi screen identified GS/GLUL as supporting 40S ribosomal subunit production; the R324A mutant reduces 40S synthesis. The authors attribute this to intracellular glutamine synthesis, i.e. a downstream consequence of the core enzymatic activity. Valid experimental annotation, kept as non-core. Supporting Evidence: PMID:26711351 intracellular glutamine synthesis supports 40S subunit production
GO:1904749 regulation of protein localization to nucleolus	IMP PMID:26711351 Genome-wide RNAi Screening Identifies Protein Modules Requir...	KEEP AS NON CORE	Summary: From the same 40S-biogenesis screen: GLUL knockdown / R324A mutation causes loss of nucleolar localization of the biogenesis factor BYSL. A specific but downstream, moonlighting-context phenotype. Keep as non-core. Supporting Evidence: file:human/GLUL/GLUL-uniprot.txt loss of nucleolar location of BYSL
GO:0004356 glutamine synthetase activity	IDA PMID:30158707 Role of glutamine synthetase in angiogenesis beyond glutamin...	ACCEPT	Summary: Core molecular function; the enzyme's glutamine synthetase activity was directly assayed (and shown to be MSO-inhibitable) in the angiogenesis study. Supporting Evidence: file:human/GLUL/GLUL-uniprot.txt Glutamine synthetase activity is inhibited by
GO:0005829 cytosol	IDA PMID:30158707 Role of glutamine synthetase in angiogenesis beyond glutamin...	ACCEPT	Summary: Core localization; direct experimental evidence that GS is mainly cytosolic in endothelial cells. Supporting Evidence: file:human/GLUL/GLUL-uniprot.txt Mainly localizes in the cytosol
GO:0005886 plasma membrane	IDA PMID:30158707 Role of glutamine synthetase in angiogenesis beyond glutamin...	KEEP AS NON CORE	Summary: A fraction of GS is lipid-anchored (palmitoylated) at the plasma membrane, shown experimentally in endothelial cells. Minor, non-core location tied to the palmitoyltransferase moonlighting function. Supporting Evidence: file:human/GLUL/GLUL-uniprot.txt with a fraction associated with the cell membrane
GO:0010594 regulation of endothelial cell migration	IDA PMID:30158707 Role of glutamine synthetase in angiogenesis beyond glutamin...	KEEP AS NON CORE	Summary: Glutamine-synthesis-independent role: GS controls endothelial cell migration by palmitoylating RHOJ, sustaining its membrane localization and activation. Genuine moonlighting function distinct from the core catalytic role; keep as non-core. Supporting Evidence: file:human/GLUL/GLUL-uniprot.txt required for endothelial cell migration during vascular development
GO:0018345 protein palmitoylation	IDA PMID:30158707 Role of glutamine synthetase in angiogenesis beyond glutamin...	KEEP AS NON CORE	Summary: GS autopalmitoylates and transfers the palmitoyl group to RHOJ; the biological process (protein palmitoylation) directly reflects this moonlighting acyltransferase activity. Keep as non-core. Supporting Evidence: file:human/GLUL/GLUL-uniprot.txt then transfer the palmitoyl group to RHOJ
GO:0019706 protein-cysteine S-palmitoyltransferase activity	IDA PMID:30158707 Role of glutamine synthetase in angiogenesis beyond glutamin...	KEEP AS NON CORE	Summary: Direct experimental evidence for palmitoyltransferase activity (autopalmitoylation and RHOJ palmitoylation). A real non-canonical moonlighting molecular function; kept as non-core relative to the dominant glutamine synthetase activity. Supporting Evidence: file:human/GLUL/GLUL-uniprot.txt able to autopalmitoylate and
GO:1903670 regulation of sprouting angiogenesis	IDA PMID:30158707 Role of glutamine synthetase in angiogenesis beyond glutamin...	KEEP AS NON CORE	Summary: GS (via RHOJ palmitoylation and endothelial migration control) regulates vessel sprouting; genetic deletion of Glul in endothelial cells impairs sprouting during vascular development. Moonlighting biological role, kept as non-core. Supporting Evidence: PMID:30158707 impairs vessel sprouting during vascular development
GO:0005634 nucleus	HDA PMID:21630459 Proteomic characterization of the human sperm nucleus.	MARK AS OVER ANNOTATED	Summary: Nuclear localization from a high-throughput sperm-nucleus proteomics dataset. Typical of abundant cytosolic enzymes detected in bulk proteomic fractions; not a genuine functional location for GS. Over-annotation.
GO:0070062 extracellular exosome	HDA PMID:19056867 Large-scale proteomics and phosphoproteomics of urinary exos...	MARK AS OVER ANNOTATED	Summary: Extracellular exosome localization from a large-scale urinary-exosome proteomics dataset. A common high-throughput detection of abundant cytosolic proteins; not indicative of a functional exosomal role. Over-annotation.
GO:0005829 cytosol	TAS Reactome:R-HSA-70606	ACCEPT	Summary: Core cytosolic localization asserted by Reactome for the GS-catalyzed reaction. Concordant with experimental IDA evidence. Supporting Evidence: Reactome:R-HSA-70606 Cytosolic glutamine synthetase
GO:0006538 L-glutamate catabolic process	TAS PMID:21757002 The nuclear receptor FXR regulates hepatic transport and met...	KEEP AS NON CORE	Summary: GS consumes L-glutamate as a substrate, so its reaction contributes to glutamate turnover; the perivenous hepatic GS uses glutamate as the main source for glutamine. Correct but a secondary framing of the same reaction whose primary output is glutamine biosynthesis. Keep as non-core. Supporting Evidence: PMID:21757002 Glutamate is taken up by perivenous hepatocytes and is the main source for the synthesis of glutamine, catalyzed by glutamine synthase (GS)
GO:1901704 L-glutamine biosynthetic process	TAS PMID:21757002 The nuclear receptor FXR regulates hepatic transport and met...	ACCEPT	Summary: Core biological process: hepatic (perivenous) glutamine synthesis catalyzed by GS, author-asserted (TAS). Concordant with the IBA/IEA/experimental evidence. Supporting Evidence: PMID:21757002 the main source for the synthesis of glutamine, catalyzed by glutamine synthase (GS)

Gene Description

Existing Annotations Review

Core Functions

ATP binding: GLUL binds ATP as an essential co-substrate, phosphorylating glutamate to the gamma-glutamyl phosphate intermediate before ammonia incorporation. Required for the glutamine synthetase reaction.

References

📚 Additional Documentation

Notes

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