SOD1 encodes Cu/Zn superoxide dismutase, a highly abundant homodimeric metalloenzyme that catalyzes the dismutation of superoxide radical (O2.-) into molecular oxygen and hydrogen peroxide (EC 1.15.1.1), providing a first line of antioxidant defense. Each ~16 kDa subunit adopts an eight-stranded Greek-key beta-barrel and binds one catalytic copper ion and one structural zinc ion; an intrasubunit disulfide bond (Cys58-Cys147) and zinc binding stabilize the unusually robust dimer. Catalytic copper is delivered by the copper chaperone CCS, which also promotes intramolecular disulfide formation during maturation. SOD1 is predominantly cytosolic, with a functional minor pool in the mitochondrial intermembrane space (imported with CCS) that detoxifies mitochondria-derived superoxide, and additional pools detected in the nucleus and extracellularly. Beyond its dismutase activity, SOD1 has been reported to oxidize hydrogen sulfide to sulfate (a reactive-sulfur-species detoxifying activity) and to act as a redox sensor that binds Rac1 to modulate NADPH oxidase. Loss of SOD1 activity causes a recessive neurological syndrome (STAHP), whereas dominant missense variants cause familial amyotrophic lateral sclerosis through a toxic gain-of-function involving destabilization, misfolding, and aggregation of the protein.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005634 nucleus | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: IBA across the Cu/Zn-SOD family annotates SOD1 active in the nucleus; SOD1 has a reproducible secondary nuclear pool that participates in the oxidative stress response and has been linked to roles in transcription and ribosome biogenesis. Reason: Nuclear localization is genuine but secondary to the predominant cytosolic site of catalysis; kept as non-core. Supporting Evidence: PMID:1332049 Cu,Zn-SOD was found widely distributed in the cell cytosol and in the cell nucleus file:human/SOD1/SOD1-deep-research-falcon.md substantial nuclear localization of SOD1 under both normal and pathological conditions, where it participates in oxidative stress response and may have regulatory roles in transcription and ribosome biogenesis |
| GO:0019430 removal of superoxide radicals | IBA GO_REF:0000033 | ACCEPT | Summary: IBA: removal of superoxide radicals; the direct process consequence of dismutase activity. Reason: Strongly phylogenetically supported and equivalent to the core enzymatic role. Supporting Evidence: PMID:16790527 Superoxide dismutases (SODs) represent the first line of defense against oxidative stress |
| GO:0005739 mitochondrion | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: IBA: SOD1 active in mitochondrion; reflects the intermembrane-space pool. Reason: The functional mitochondrial pool is specifically the intermembrane space (GO:0005758); the generic 'mitochondrion' is a broader, non-core localization. Supporting Evidence: PMID:24026195 both localize to the cytosol and the mitochondrial intermembrane space where they specifically counteract mitochondria-derived superoxide |
| GO:0005507 copper ion binding | IBA GO_REF:0000033 | ACCEPT | Summary: IBA: copper ion binding, the catalytic metal of SOD1. Reason: Phylogenetically well-supported; copper is the catalytic cofactor. Supporting Evidence: PMID:31292775 Copper-zinc superoxide dismutase (Sod1) is a critical antioxidant enzyme that rids the cell of reactive oxygen through the redox cycling of a catalytic copper ion provided by its copper chaperone (Ccs). |
| GO:0005777 peroxisome | IBA GO_REF:0000033 | MARK AS OVER ANNOTATED | Summary: IBA: SOD1 active in peroxisome; weakly supported in human cells. Reason: Peroxisomal localization is poorly supported; EM immunocytochemistry found SOD1 primarily cytosolic with peroxisome labeling near background. Likely over-annotation. Supporting Evidence: PMID:1332049 Copper,zinc superoxide dismutase is primarily a cytosolic protein in human cells. |
| GO:0005829 cytosol | IBA GO_REF:0000033 | ACCEPT | Summary: IBA: cytosol; SOD1 is principally cytosolic. Reason: Core compartment; matches direct human-cell localization. Supporting Evidence: PMID:1332049 Copper,zinc superoxide dismutase is primarily a cytosolic protein in human cells. |
| GO:0004784 superoxide dismutase activity | IEA GO_REF:0000120 | ACCEPT | Summary: SOD1 catalyzes dismutation of superoxide to O2 + H2O2 (EC 1.15.1.1); the defining molecular function. Reason: IEA mapping from RHEA/EC is correct and matches direct experimental evidence. Supporting Evidence: PMID:24140062 Cu/Zn superoxide dismutase (SOD1) is a key antioxidant enzyme. |
| GO:0005507 copper ion binding | IEA GO_REF:0000120 | ACCEPT | Summary: Copper ion binding (IEA); the catalytic copper cofactor. Reason: Correct metal-binding mapping. Supporting Evidence: PMID:31292775 Copper-zinc superoxide dismutase (Sod1) is a critical antioxidant enzyme that rids the cell of reactive oxygen through the redox cycling of a catalytic copper ion provided by its copper chaperone (Ccs). |
| GO:0005634 nucleus | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Nucleus (IEA, SubCell). Reason: Secondary nuclear pool; non-core. Supporting Evidence: PMID:1332049 Cu,Zn-SOD was found widely distributed in the cell cytosol and in the cell nucleus |
| GO:0005737 cytoplasm | IEA GO_REF:0000120 | ACCEPT | Summary: Cytoplasm (IEA, SubCell). Reason: Consistent with predominant cytosolic localization. Supporting Evidence: PMID:1332049 Copper,zinc superoxide dismutase is primarily a cytosolic protein in human cells. |
| GO:0006801 superoxide metabolic process | IEA GO_REF:0000120 | ACCEPT | Summary: Superoxide metabolic process (IEA); core process parent of dismutation. Reason: Correct broad parent of the reaction. |
| GO:0046872 metal ion binding | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: Broad 'metal ion binding' (IEA, InterPro). Reason: Correct but less informative than the specific copper (GO:0005507) and zinc (GO:0008270) ion binding annotations; retained as a broader parent. |
| GO:1904115 axon cytoplasm | IEA GO_REF:0000108 | MARK AS OVER ANNOTATED | Summary: Axon cytoplasm (IEA), inferred from axonal-transport annotations of the rodent ortholog. Reason: Derived computationally from ortholog axonal-transport annotations; not a core human SOD1 localization. |
| GO:0005515 protein binding | IPI PMID:12968035 The copper toxicosis gene product Murr1 directly interacts w... | MARK AS OVER ANNOTATED | Summary: Generic protein-binding interaction (IPI) from interaction proteomics/two-hybrid datasets. Reason: Bare 'protein binding' (GO:0005515) is uninformative per curation guidelines; these IPI entries are largely high-throughput or disease/aggregation-context interactions. Marked as over-annotated in favor of specific informative terms (copper ion binding, identical protein binding, protein-folding chaperone binding, small GTPase binding). |
| GO:0005515 protein binding | IPI PMID:16369483 Chromogranin-mediated secretion of mutant superoxide dismuta... | MARK AS OVER ANNOTATED | Summary: Generic protein-binding interaction (IPI) from interaction proteomics/two-hybrid datasets. Reason: Bare 'protein binding' (GO:0005515) is uninformative per curation guidelines; these IPI entries are largely high-throughput or disease/aggregation-context interactions. Marked as over-annotated in favor of specific informative terms (copper ion binding, identical protein binding, protein-folding chaperone binding, small GTPase binding). |
| GO:0005515 protein binding | IPI PMID:16595634 Spinal cord endoplasmic reticulum stress associated with a m... | MARK AS OVER ANNOTATED | Summary: Generic protein-binding interaction (IPI) from interaction proteomics/two-hybrid datasets. Reason: Bare 'protein binding' (GO:0005515) is uninformative per curation guidelines; these IPI entries are largely high-throughput or disease/aggregation-context interactions. Marked as over-annotated in favor of specific informative terms (copper ion binding, identical protein binding, protein-folding chaperone binding, small GTPase binding). |
| GO:0005515 protein binding | IPI PMID:19171884 Progressive aggregation despite chaperone associations of a ... | MARK AS OVER ANNOTATED | Summary: Generic protein-binding interaction (IPI) from interaction proteomics/two-hybrid datasets. Reason: Bare 'protein binding' (GO:0005515) is uninformative per curation guidelines; these IPI entries are largely high-throughput or disease/aggregation-context interactions. Marked as over-annotated in favor of specific informative terms (copper ion binding, identical protein binding, protein-folding chaperone binding, small GTPase binding). |
| GO:0005515 protein binding | IPI PMID:20195357 A comprehensive resource of interacting protein regions for ... | MARK AS OVER ANNOTATED | Summary: Generic protein-binding interaction (IPI) from interaction proteomics/two-hybrid datasets. Reason: Bare 'protein binding' (GO:0005515) is uninformative per curation guidelines; these IPI entries are largely high-throughput or disease/aggregation-context interactions. Marked as over-annotated in favor of specific informative terms (copper ion binding, identical protein binding, protein-folding chaperone binding, small GTPase binding). |
| GO:0005515 protein binding | IPI PMID:21252941 BAG3 mediates chaperone-based aggresome-targeting and select... | MARK AS OVER ANNOTATED | Summary: Generic protein-binding interaction (IPI) from interaction proteomics/two-hybrid datasets. Reason: Bare 'protein binding' (GO:0005515) is uninformative per curation guidelines; these IPI entries are largely high-throughput or disease/aggregation-context interactions. Marked as over-annotated in favor of specific informative terms (copper ion binding, identical protein binding, protein-folding chaperone binding, small GTPase binding). |
| GO:0005515 protein binding | IPI PMID:22508683 Molecular and biochemical characterization of a unique mutat... | MARK AS OVER ANNOTATED | Summary: Generic protein-binding interaction (IPI) from interaction proteomics/two-hybrid datasets. Reason: Bare 'protein binding' (GO:0005515) is uninformative per curation guidelines; these IPI entries are largely high-throughput or disease/aggregation-context interactions. Marked as over-annotated in favor of specific informative terms (copper ion binding, identical protein binding, protein-folding chaperone binding, small GTPase binding). |
| GO:0005515 protein binding | IPI PMID:24234043 Cystatin B and SOD1: proteinβprotein interaction and possibl... | MARK AS OVER ANNOTATED | Summary: Generic protein-binding interaction (IPI) from interaction proteomics/two-hybrid datasets. Reason: Bare 'protein binding' (GO:0005515) is uninformative per curation guidelines; these IPI entries are largely high-throughput or disease/aggregation-context interactions. Marked as over-annotated in favor of specific informative terms (copper ion binding, identical protein binding, protein-folding chaperone binding, small GTPase binding). |
| GO:0005515 protein binding | IPI PMID:24981860 Human-chromatin-related protein interactions identify a deme... | MARK AS OVER ANNOTATED | Summary: Generic protein-binding interaction (IPI) from interaction proteomics/two-hybrid datasets. Reason: Bare 'protein binding' (GO:0005515) is uninformative per curation guidelines; these IPI entries are largely high-throughput or disease/aggregation-context interactions. Marked as over-annotated in favor of specific informative terms (copper ion binding, identical protein binding, protein-folding chaperone binding, small GTPase binding). |
| GO:0005515 protein binding | IPI PMID:26643113 alpha-synuclein interacts with SOD1 and promotes its oligome... | MARK AS OVER ANNOTATED | Summary: Generic protein-binding interaction (IPI) from interaction proteomics/two-hybrid datasets. Reason: Bare 'protein binding' (GO:0005515) is uninformative per curation guidelines; these IPI entries are largely high-throughput or disease/aggregation-context interactions. Marked as over-annotated in favor of specific informative terms (copper ion binding, identical protein binding, protein-folding chaperone binding, small GTPase binding). Supporting Evidence: PMID:26643113 Ξ±-synuclein interacts with SOD1 and promotes its oligomerization. |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | MARK AS OVER ANNOTATED | Summary: Generic protein-binding interaction (IPI) from interaction proteomics/two-hybrid datasets. Reason: Bare 'protein binding' (GO:0005515) is uninformative per curation guidelines; these IPI entries are largely high-throughput or disease/aggregation-context interactions. Marked as over-annotated in favor of specific informative terms (copper ion binding, identical protein binding, protein-folding chaperone binding, small GTPase binding). |
| GO:0005515 protein binding | IPI PMID:29128334 A Map of Human Mitochondrial Protein Interactions Linked to ... | MARK AS OVER ANNOTATED | Summary: Generic protein-binding interaction (IPI) from interaction proteomics/two-hybrid datasets. Reason: Bare 'protein binding' (GO:0005515) is uninformative per curation guidelines; these IPI entries are largely high-throughput or disease/aggregation-context interactions. Marked as over-annotated in favor of specific informative terms (copper ion binding, identical protein binding, protein-folding chaperone binding, small GTPase binding). |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | MARK AS OVER ANNOTATED | Summary: Generic protein-binding interaction (IPI) from interaction proteomics/two-hybrid datasets. Reason: Bare 'protein binding' (GO:0005515) is uninformative per curation guidelines; these IPI entries are largely high-throughput or disease/aggregation-context interactions. Marked as over-annotated in favor of specific informative terms (copper ion binding, identical protein binding, protein-folding chaperone binding, small GTPase binding). |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MARK AS OVER ANNOTATED | Summary: Generic protein-binding interaction (IPI) from interaction proteomics/two-hybrid datasets. Reason: Bare 'protein binding' (GO:0005515) is uninformative per curation guidelines; these IPI entries are largely high-throughput or disease/aggregation-context interactions. Marked as over-annotated in favor of specific informative terms (copper ion binding, identical protein binding, protein-folding chaperone binding, small GTPase binding). |
| GO:0042802 identical protein binding | IPI PMID:17592131 Metal-free superoxide dismutase forms soluble oligomers unde... | ACCEPT | Summary: SOD1 self-association (identical protein binding); SOD1 functions as a homodimer. Reason: SOD1 is an obligate homodimer; identical protein binding (homodimerization) is a genuine and informative molecular function supported by structural and interaction studies. |
| GO:0042802 identical protein binding | IPI PMID:19022905 Initiation and elongation in fibrillation of ALS-linked supe... | ACCEPT | Summary: SOD1 self-association (identical protein binding); SOD1 functions as a homodimer. Reason: SOD1 is an obligate homodimer; identical protein binding (homodimerization) is a genuine and informative molecular function supported by structural and interaction studies. |
| GO:0042802 identical protein binding | IPI PMID:19171884 Progressive aggregation despite chaperone associations of a ... | ACCEPT | Summary: SOD1 self-association (identical protein binding); SOD1 functions as a homodimer. Reason: SOD1 is an obligate homodimer; identical protein binding (homodimerization) is a genuine and informative molecular function supported by structural and interaction studies. Supporting Evidence: PMID:19171884 superoxide dismutase 1 (SOD1)-linked amyotrophic |
| GO:0042802 identical protein binding | IPI PMID:19369197 Structural and dynamic aspects related to oligomerization of... | ACCEPT | Summary: SOD1 self-association (identical protein binding); SOD1 functions as a homodimer. Reason: SOD1 is an obligate homodimer; identical protein binding (homodimerization) is a genuine and informative molecular function supported by structural and interaction studies. |
| GO:0042802 identical protein binding | IPI PMID:19828437 Transient structural distortion of metal-free Cu/Zn superoxi... | ACCEPT | Summary: SOD1 self-association (identical protein binding); SOD1 functions as a homodimer. Reason: SOD1 is an obligate homodimer; identical protein binding (homodimerization) is a genuine and informative molecular function supported by structural and interaction studies. |
| GO:0042802 identical protein binding | IPI PMID:21257910 Decreased stability and increased formation of soluble aggre... | ACCEPT | Summary: SOD1 self-association (identical protein binding); SOD1 functions as a homodimer. Reason: SOD1 is an obligate homodimer; identical protein binding (homodimerization) is a genuine and informative molecular function supported by structural and interaction studies. |
| GO:0042802 identical protein binding | IPI PMID:23831581 Intracellular seeded aggregation of mutant Cu,Zn-superoxide ... | ACCEPT | Summary: SOD1 self-association (identical protein binding); SOD1 functions as a homodimer. Reason: SOD1 is an obligate homodimer; identical protein binding (homodimerization) is a genuine and informative molecular function supported by structural and interaction studies. |
| GO:0042802 identical protein binding | IPI PMID:26643113 alpha-synuclein interacts with SOD1 and promotes its oligome... | ACCEPT | Summary: SOD1 self-association (identical protein binding); SOD1 functions as a homodimer. Reason: SOD1 is an obligate homodimer; identical protein binding (homodimerization) is a genuine and informative molecular function supported by structural and interaction studies. |
| GO:0042802 identical protein binding | IPI PMID:31999698 Tryptophan residue 32 in human Cu-Zn superoxide dismutase mo... | ACCEPT | Summary: SOD1 self-association (identical protein binding); SOD1 functions as a homodimer. Reason: SOD1 is an obligate homodimer; identical protein binding (homodimerization) is a genuine and informative molecular function supported by structural and interaction studies. |
| GO:0001975 response to amphetamine | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Response to amphetamine (IEA, ortholog). Reason: Transferred from the rodent ortholog (electronic/ortholog evidence); reflects a pleiotropic organismal response to the loss of antioxidant protection rather than a core molecular function. Kept as non-core. |
| GO:0005576 extracellular region | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Extracellular region (IEA). Reason: A minor secreted/extracellular pool of SOD1 (including exosomes) exists but is peripheral to the cytosolic antioxidant function. |
| GO:0005764 lysosome | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Lysosome (IEA, ortholog). Reason: Minor/ortholog-transferred localization; non-core. |
| GO:0005777 peroxisome | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Peroxisome (IEA, ortholog). Reason: Weakly supported in human; same concern as the IBA peroxisome call. Supporting Evidence: PMID:1332049 Copper,zinc superoxide dismutase is primarily a cytosolic protein in human cells. |
| GO:0006979 response to oxidative stress | IEA GO_REF:0000107 | ACCEPT | Summary: Response to oxidative stress (IEA, ortholog); SOD1 is a first-line antioxidant defense. Reason: Core defensive role against oxidative stress. Supporting Evidence: PMID:16790527 Superoxide dismutases (SODs) represent the first line of defense against oxidative stress |
| GO:0008089 anterograde axonal transport | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Anterograde axonal transport (IEA, ortholog). Reason: Transferred from the rodent ortholog (electronic/ortholog evidence); reflects a pleiotropic organismal response to the loss of antioxidant protection rather than a core molecular function. Kept as non-core. |
| GO:0008090 retrograde axonal transport | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retrograde axonal transport (IEA, ortholog). Reason: Transferred from the rodent ortholog (electronic/ortholog evidence); reflects a pleiotropic organismal response to the loss of antioxidant protection rather than a core molecular function. Kept as non-core. |
| GO:0019430 removal of superoxide radicals | IEA GO_REF:0000107 | ACCEPT | Summary: Removal of superoxide radicals (IEA, ortholog); core process. Reason: Equivalent to the core enzymatic role. Supporting Evidence: PMID:16790527 Superoxide dismutases (SODs) represent the first line of defense against oxidative stress |
| GO:0019899 enzyme binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Enzyme binding (IEA, ortholog). Reason: Generic and uninformative; more specific informative binding (e.g. calcineurin/PP2B, Rac1, CCS) is captured elsewhere. Non-core. |
| GO:0030141 secretory granule | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Secretory granule (IEA, ortholog). Reason: Minor ortholog-transferred localization; non-core. |
| GO:0030346 protein phosphatase 2B binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Protein phosphatase 2B (calcineurin) binding (IEA, ortholog). Reason: SOD1 directly binds and activates calcineurin (protein phosphatase 2B); a specific, experimentally supported interaction, though peripheral to the core antioxidant function. |
| GO:0031045 dense core granule | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Dense core granule (IEA, ortholog). Reason: Minor ortholog-transferred localization; non-core. |
| GO:0031667 response to nutrient levels | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Response to nutrient levels (IEA, ortholog). Reason: Transferred from the rodent ortholog (electronic/ortholog evidence); reflects a pleiotropic organismal response to the loss of antioxidant protection rather than a core molecular function. Kept as non-core. |
| GO:0032991 protein-containing complex | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Protein-containing complex (IEA, ortholog). Reason: Very generic; SOD1's specific complexes (homodimer, CCS chaperone complex) are captured by more precise terms. Non-core. |
| GO:0034465 response to carbon monoxide | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Response to carbon monoxide (IEA, ortholog). Reason: Transferred from the rodent ortholog (electronic/ortholog evidence); reflects a pleiotropic organismal response to the loss of antioxidant protection rather than a core molecular function. Kept as non-core. |
| GO:0034599 cellular response to oxidative stress | IEA GO_REF:0000107 | ACCEPT | Summary: Cellular response to oxidative stress (IEA, ortholog). Reason: Consistent with SOD1's antioxidant defense role. Supporting Evidence: PMID:16790527 Superoxide dismutases (SODs) represent the first line of defense against oxidative stress |
| GO:0035865 cellular response to potassium ion | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Cellular response to potassium ion (IEA, ortholog). Reason: Transferred from the rodent ortholog (electronic/ortholog evidence); reflects a pleiotropic organismal response to the loss of antioxidant protection rather than a core molecular function. Kept as non-core. |
| GO:0043025 neuronal cell body | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Neuronal cell body (IEA, ortholog). Reason: Cell-type-specific localization; non-core. |
| GO:0043066 negative regulation of apoptotic process | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Negative regulation of apoptotic process (IEA, ortholog). Reason: SOD1 is broadly cytoprotective/anti-apoptotic via ROS removal; this downstream process is non-core. |
| GO:0046688 response to copper ion | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Response to copper ion (IEA, ortholog). Reason: Transferred from the rodent ortholog (electronic/ortholog evidence); reflects a pleiotropic organismal response to the loss of antioxidant protection rather than a core molecular function. Kept as non-core. |
| GO:0050665 hydrogen peroxide biosynthetic process | IEA GO_REF:0000120 | ACCEPT | Summary: Hydrogen peroxide biosynthetic process (IEA); H2O2 is the SOD reaction product. Reason: H2O2 is the direct product of dismutation; correct consequence of SOD1 activity. |
| GO:0050728 negative regulation of inflammatory response | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Negative regulation of inflammatory response (IEA, ortholog). Reason: Transferred from the rodent ortholog (electronic/ortholog evidence); reflects a pleiotropic organismal response to the loss of antioxidant protection rather than a core molecular function. Kept as non-core. |
| GO:0050766 positive regulation of phagocytosis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Positive regulation of phagocytosis (IEA, ortholog). Reason: Transferred from the rodent ortholog (electronic/ortholog evidence); reflects a pleiotropic organismal response to the loss of antioxidant protection rather than a core molecular function. Kept as non-core. |
| GO:0071276 cellular response to cadmium ion | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Cellular response to cadmium ion (IEA, ortholog). Reason: Transferred from the rodent ortholog (electronic/ortholog evidence); reflects a pleiotropic organismal response to the loss of antioxidant protection rather than a core molecular function. Kept as non-core. |
| GO:0071318 cellular response to ATP | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Cellular response to ATP (IEA, ortholog). Reason: Transferred from the rodent ortholog (electronic/ortholog evidence); reflects a pleiotropic organismal response to the loss of antioxidant protection rather than a core molecular function. Kept as non-core. |
| GO:0097332 response to antipsychotic drug | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Response to antipsychotic drug (IEA, ortholog). Reason: Transferred from the rodent ortholog (electronic/ortholog evidence); reflects a pleiotropic organismal response to the loss of antioxidant protection rather than a core molecular function. Kept as non-core. |
| GO:0005758 mitochondrial intermembrane space | IDA PMID:24026195 Human copper chaperone for superoxide dismutase 1 mediates i... | ACCEPT | Summary: Mitochondrial intermembrane space as active location (IDA). Reason: Direct evidence for a functional IMS pool dismutating mitochondria-derived superoxide. Supporting Evidence: PMID:24026195 both localize to the cytosol and the mitochondrial intermembrane space where they specifically counteract mitochondria-derived superoxide |
| GO:0005829 cytosol | TAS PMID:24026195 Human copper chaperone for superoxide dismutase 1 mediates i... | ACCEPT | Summary: Cytosol as active location (TAS). Reason: Core compartment. Supporting Evidence: PMID:1332049 Copper,zinc superoxide dismutase is primarily a cytosolic protein in human cells. |
| GO:0019430 removal of superoxide radicals | NAS PMID:31292775 Copper-zinc superoxide dismutase (Sod1) activation terminate... | ACCEPT | Summary: Removal of superoxide radicals asserted for the SOD1/CCS complex (NAS). Reason: Equivalent to the core process. Supporting Evidence: PMID:31292775 Copper-zinc superoxide dismutase (Sod1) is a critical antioxidant enzyme that rids the cell of reactive oxygen through the redox cycling of a catalytic copper ion provided by its copper chaperone (Ccs). |
| GO:1902694 superoxide dismutase copper chaperone complex | IPI PMID:30735496 Molecular recognition and maturation of SOD1 by its evolutio... | ACCEPT | Summary: SOD1 is part of the superoxide dismutase copper chaperone complex (with CCS). Reason: Directly supported: hCCS recognizes and matures SOD1 (copper insertion, disulfide formation) via a defined heterocomplex. Supporting Evidence: PMID:30735496 Molecular recognition and maturation of SOD1 by its evolutionarily destabilised cognate chaperone hCCS. |
| GO:0005654 nucleoplasm | IDA GO_REF:0000052 | KEEP AS NON CORE | Summary: Nucleoplasm (IDA, HPA). Reason: Secondary nuclear pool; non-core. Supporting Evidence: PMID:1332049 Cu,Zn-SOD was found widely distributed in the cell cytosol and in the cell nucleus |
| GO:0005829 cytosol | IDA GO_REF:0000052 | ACCEPT | Summary: Cytosol (IDA, HPA immunofluorescence). Reason: Core compartment. Supporting Evidence: PMID:1332049 Copper,zinc superoxide dismutase is primarily a cytosolic protein in human cells. |
| GO:0005739 mitochondrion | HTP PMID:34800366 Quantitative high-confidence human mitochondrial proteome an... | KEEP AS NON CORE | Summary: Mitochondrion (HTP proteomics). Reason: High-throughput; consistent with IMS pool but non-specific. |
| GO:0019430 removal of superoxide radicals | IDA PMID:24567322 DJ-1 is a copper chaperone acting on SOD1 activation. | ACCEPT | Summary: DJ-1/PARK7 copper chaperone activates SOD1, restoring superoxide removal. Reason: Direct demonstration of SOD1 activation and superoxide removal. Supporting Evidence: PMID:24567322 DJ-1 is a copper chaperone acting on SOD1 activation. |
| GO:0042803 protein homodimerization activity | IPI PMID:24567322 DJ-1 is a copper chaperone acting on SOD1 activation. | ACCEPT | Summary: Protein homodimerization activity (IPI); SOD1 is an obligate homodimer. Reason: Homodimerization is a core structural property required for activity. Supporting Evidence: PMID:24567322 DJ-1 is a copper chaperone acting on SOD1 activation. |
| GO:0019430 removal of superoxide radicals | IDA PMID:16254550 Expression of superoxide dismutase in whole lens prevents ca... | ACCEPT | Summary: SOD1 expression in lens prevents oxidative cataract via superoxide removal. Reason: Functional demonstration of antioxidant protection. Supporting Evidence: PMID:16254550 overexpression of superoxide dismutase (SOD) in intact lenses could prevent cataract formation induced by oxidative stress |
| GO:0005515 protein binding | IPI PMID:31292775 Copper-zinc superoxide dismutase (Sod1) activation terminate... | KEEP AS NON CORE | Summary: Protein-binding interaction with CCS (IPI). Reason: Bare 'protein binding', but the partner (copper chaperone CCS) is functionally central; the informative aspect is captured by the copper chaperone complex and chaperone-binding annotations. Kept non-core. Supporting Evidence: PMID:31292775 provided by its copper chaperone (Ccs) |
| GO:0043410 positive regulation of MAPK cascade | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Positive regulation of MAPK cascade (ISS, ortholog). Reason: Transferred from the rodent ortholog (electronic/ortholog evidence); reflects a pleiotropic organismal response to the loss of antioxidant protection rather than a core molecular function. Kept as non-core. |
| GO:0005737 cytoplasm | IDA PMID:24784232 A new transcriptional role for matrix metalloproteinase-12 i... | ACCEPT | Summary: Cytoplasm (IDA). Reason: Core compartment. Supporting Evidence: PMID:1332049 Copper,zinc superoxide dismutase is primarily a cytosolic protein in human cells. |
| GO:0005515 protein binding | IPI PMID:24023695 Molecular chaperone mediated late-stage neuroprotection in t... | KEEP AS NON CORE | Summary: Protein-binding interaction with the chaperone HSJ1/DNAJB2 (IPI). Reason: Disease-context chaperone interaction (mutant SOD1 aggregation); bare protein binding, non-core. Supporting Evidence: PMID:24023695 HSJ1a preferentially bound to mutant SOD1 |
| GO:0005634 nucleus | IDA PMID:24023695 Molecular chaperone mediated late-stage neuroprotection in t... | KEEP AS NON CORE | Summary: Nucleus (IDA). Reason: Secondary nuclear pool; non-core. Supporting Evidence: PMID:1332049 Cu,Zn-SOD was found widely distributed in the cell cytosol and in the cell nucleus |
| GO:0005737 cytoplasm | IDA PMID:24023695 Molecular chaperone mediated late-stage neuroprotection in t... | ACCEPT | Summary: Cytoplasm (IDA). Reason: Core compartment. Supporting Evidence: PMID:1332049 Copper,zinc superoxide dismutase is primarily a cytosolic protein in human cells. |
| GO:0005634 nucleus | IDA PMID:22496122 Endothelial cell palmitoylproteomic identifies novel lipid-m... | KEEP AS NON CORE | Summary: Nucleus (IDA); Cys7 palmitoylation promotes nuclear targeting. Reason: Genuine secondary nuclear pool regulated by palmitoylation; non-core. Supporting Evidence: PMID:22496122 palmitoylproteins identified is superoxide dismutase-1, an intensively studied enzyme that protects all cells from oxidative damage |
| GO:0005739 mitochondrion | IDA PMID:19741096 Mitochondrial ubiquitin ligase MITOL ubiquitinates mutant SO... | KEEP AS NON CORE | Summary: Mitochondrion (IDA); ALS-mutant SOD1 accumulates in mitochondria. Reason: Derives from mutant SOD1 aggregation/accumulation in mitochondria, a disease context rather than the core wild-type location. |
| GO:0070062 extracellular exosome | HDA PMID:23533145 In-depth proteomic analyses of exosomes isolated from expres... | KEEP AS NON CORE | Summary: Extracellular exosome (HDA proteomics). Reason: A minor secreted/extracellular pool of SOD1 (including exosomes) exists but is peripheral to the cytosolic antioxidant function. |
| GO:0004784 superoxide dismutase activity | IDA PMID:24567322 DJ-1 is a copper chaperone acting on SOD1 activation. | ACCEPT | Summary: Direct SOD activity assay (DJ-1/SOD1 study). Reason: Confirms the core molecular function. Supporting Evidence: PMID:24567322 DJ-1 is a copper chaperone acting on SOD1 activation. |
| GO:0005634 nucleus | HDA PMID:21630459 Proteomic characterization of the human sperm nucleus. | KEEP AS NON CORE | Summary: Nucleus (HDA proteomics). Reason: Secondary nuclear pool; non-core. Supporting Evidence: PMID:1332049 Cu,Zn-SOD was found widely distributed in the cell cytosol and in the cell nucleus |
| GO:0004784 superoxide dismutase activity | IDA PMID:24140062 SIRT5 desuccinylates and activates SOD1 to eliminate ROS. | ACCEPT | Summary: Direct SOD activity assay; succinylation/SIRT5 regulation study. Reason: Confirms core function. Supporting Evidence: PMID:24140062 Cu/Zn superoxide dismutase (SOD1) is a key antioxidant enzyme. |
| GO:0072593 reactive oxygen species metabolic process | IDA PMID:24140062 SIRT5 desuccinylates and activates SOD1 to eliminate ROS. | ACCEPT | Summary: Reactive oxygen species metabolic process (IDA). Beyond consuming superoxide, SOD1-derived H2O2 itself acts as a diffusible redox-signaling species, reinforcing SOD1's central role in cellular ROS metabolism. Reason: SOD1 directly governs cellular ROS levels; it both removes superoxide and generates H2O2, which functions in redox signaling, so the broad ROS metabolic process term is well supported. Supporting Evidence: PMID:24140062 SOD1-mediated ROS reduction is increased when SIRT5 is co-expressed. file:human/SOD1/SOD1-deep-research-falcon.md H2O2 generated by SOD1 can diffuse across cellular membranes and oxidize specific protein thiols, thereby regulating enzyme activities, transcription factors, and signaling pathways |
| GO:0070062 extracellular exosome | HDA PMID:19056867 Large-scale proteomics and phosphoproteomics of urinary exos... | KEEP AS NON CORE | Summary: Extracellular exosome (HDA proteomics). Reason: A minor secreted/extracellular pool of SOD1 (including exosomes) exists but is peripheral to the cytosolic antioxidant function. |
| GO:0005758 mitochondrial intermembrane space | TAS Reactome:R-HSA-3777112 | ACCEPT | Summary: Mitochondrial IMS (TAS, Reactome) dismutation. Reason: Functional IMS pool. Supporting Evidence: PMID:24026195 both localize to the cytosol and the mitochondrial intermembrane space where they specifically counteract mitochondria-derived superoxide |
| GO:0005758 mitochondrial intermembrane space | TAS Reactome:R-HSA-8950771 | ACCEPT | Summary: Mitochondrial IMS (TAS, Reactome) detoxification of ROS. Reason: Functional IMS pool. Supporting Evidence: PMID:24026195 both localize to the cytosol and the mitochondrial intermembrane space where they specifically counteract mitochondria-derived superoxide |
| GO:0005829 cytosol | TAS Reactome:R-HSA-3299691 | ACCEPT | Summary: Cytosol (TAS, Reactome). Reason: Core compartment. Supporting Evidence: PMID:1332049 Copper,zinc superoxide dismutase is primarily a cytosolic protein in human cells. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-3299753 | ACCEPT | Summary: Cytosol (TAS, Reactome). Reason: Core compartment. Supporting Evidence: PMID:1332049 Copper,zinc superoxide dismutase is primarily a cytosolic protein in human cells. |
| GO:0004784 superoxide dismutase activity | IDA PMID:12551919 Differential effects of superoxide dismutase isoform express... | ACCEPT | Summary: Direct SOD activity (CuZn-SOD overexpression in PC-12). Reason: Confirms core function. Supporting Evidence: PMID:12551919 stably overexpress the human mitochondrial or cytoplasmic forms of superoxide |
| GO:0006801 superoxide metabolic process | IDA PMID:12551919 Differential effects of superoxide dismutase isoform express... | ACCEPT | Summary: Superoxide metabolic process (IDA). Reason: SOD1 governs superoxide handling. Supporting Evidence: PMID:12551919 Stable overexpression of SOD isoforms |
| GO:1902177 positive regulation of oxidative stress-induced intrinsic apoptotic signaling pathway | IMP PMID:12551919 Differential effects of superoxide dismutase isoform express... | MARK AS OVER ANNOTATED | Summary: Positive regulation of oxidative-stress-induced intrinsic apoptotic signaling (IMP). Reason: Derived from SOD isoform overexpression effects on hydroperoxide-induced apoptosis; SOD1 is canonically cytoprotective/antioxidant, so a 'positive regulation of apoptosis' process annotation is a context-specific over-annotation. Supporting Evidence: PMID:12551919 hydroperoxide-induced apoptosis |
| GO:0031267 small GTPase binding | IDA PMID:18219391 SOD1 mutations disrupt redox-sensitive Rac regulation of NAD... | KEEP AS NON CORE | Summary: Small GTPase (Rac1) binding (IDA). Reason: SOD1 directly binds Rac1 as a redox sensor regulating NADPH oxidase; specific and experimentally supported but a specialized moonlighting role, non-core. Supporting Evidence: PMID:18219391 SOD1 is not just a catabolic enzyme, but can also directly regulate NADPH oxidase-dependent (Nox-dependent) O(2)(*-) production by binding Rac1 and inhibiting its GTPase activity. |
| GO:0032930 positive regulation of superoxide anion generation | IDA PMID:18219391 SOD1 mutations disrupt redox-sensitive Rac regulation of NAD... | KEEP AS NON CORE | Summary: Positive regulation of superoxide anion generation (IDA), via Rac1/Nox regulation. Reason: Paradoxical relative to SOD1's superoxide-consuming activity; reflects the specialized Rac1/Nox redox-sensor role rather than the core function. Non-core. Supporting Evidence: PMID:18219391 SOD1 is not just a catabolic enzyme, but can also directly regulate NADPH oxidase-dependent (Nox-dependent) O(2)(*-) production by binding Rac1 and inhibiting its GTPase activity. |
| GO:0043087 regulation of GTPase activity | IDA PMID:18219391 SOD1 mutations disrupt redox-sensitive Rac regulation of NAD... | KEEP AS NON CORE | Summary: Regulation of GTPase activity (IDA); SOD1 inhibits Rac1 GTPase. Reason: Specialized Rac1/Nox redox-sensor moonlighting role; non-core. Supporting Evidence: PMID:18219391 SOD1 is not just a catabolic enzyme, but can also directly regulate NADPH oxidase-dependent (Nox-dependent) O(2)(*-) production by binding Rac1 and inhibiting its GTPase activity. |
| GO:0005634 nucleus | IDA PMID:1332049 Copper,zinc superoxide dismutase is primarily a cytosolic pr... | KEEP AS NON CORE | Summary: Nucleus (IDA, EM immunocytochemistry). Reason: Secondary nuclear pool; non-core. Supporting Evidence: PMID:1332049 Cu,Zn-SOD was found widely distributed in the cell cytosol and in the cell nucleus |
| GO:0005777 peroxisome | IDA PMID:1332049 Copper,zinc superoxide dismutase is primarily a cytosolic pr... | MARK AS OVER ANNOTATED | Summary: Peroxisome (IDA, EM immunocytochemistry). Reason: The original EM immunocytochemistry study found SOD1 primarily cytosolic with peroxisome labeling only slightly above background; peroxisomal localization is weakly supported and treated as an over-annotation, consistent with the IBA/IEA/ISS peroxisome calls. Supporting Evidence: PMID:1332049 Copper,zinc superoxide dismutase is primarily a cytosolic protein in human cells. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-482772 | KEEP AS NON CORE | Summary: Extracellular region (TAS, Reactome). Reason: A minor secreted/extracellular pool of SOD1 (including exosomes) exists but is peripheral to the cytosolic antioxidant function. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-3697860 | ACCEPT | Summary: Cytosol (TAS, Reactome). Reason: Core compartment. Supporting Evidence: PMID:1332049 Copper,zinc superoxide dismutase is primarily a cytosolic protein in human cells. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-482772 | ACCEPT | Summary: Cytosol (TAS, Reactome). Reason: Core compartment. Supporting Evidence: PMID:1332049 Copper,zinc superoxide dismutase is primarily a cytosolic protein in human cells. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8951723 | ACCEPT | Summary: Cytosol (TAS, Reactome). Reason: Core compartment. Supporting Evidence: PMID:1332049 Copper,zinc superoxide dismutase is primarily a cytosolic protein in human cells. |
| GO:0008089 anterograde axonal transport | ISS PMID:20510358 Effects of ALS-related SOD1 mutants on dynein- and KIF5-medi... | KEEP AS NON CORE | Summary: Anterograde axonal transport (ISS, ortholog). Reason: Transferred from the rodent ortholog (electronic/ortholog evidence); reflects a pleiotropic organismal response to the loss of antioxidant protection rather than a core molecular function. Kept as non-core. |
| GO:0008090 retrograde axonal transport | ISS PMID:20510358 Effects of ALS-related SOD1 mutants on dynein- and KIF5-medi... | KEEP AS NON CORE | Summary: Retrograde axonal transport (ISS, ortholog). Reason: Transferred from the rodent ortholog (electronic/ortholog evidence); reflects a pleiotropic organismal response to the loss of antioxidant protection rather than a core molecular function. Kept as non-core. |
| GO:0005737 cytoplasm | IDA PMID:19741096 Mitochondrial ubiquitin ligase MITOL ubiquitinates mutant SO... | ACCEPT | Summary: Cytoplasm (IDA). Reason: Core compartment. Supporting Evidence: PMID:1332049 Copper,zinc superoxide dismutase is primarily a cytosolic protein in human cells. |
| GO:0005777 peroxisome | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: Peroxisome (ISS, ortholog). Reason: Weakly supported in human; over-annotation. Supporting Evidence: PMID:1332049 Copper,zinc superoxide dismutase is primarily a cytosolic protein in human cells. |
| GO:0005737 cytoplasm | IDA PMID:18809582 Nucleophosmin serves as a rate-limiting nuclear export chape... | ACCEPT | Summary: Cytoplasm (IDA). Reason: Core compartment. Supporting Evidence: PMID:1332049 Copper,zinc superoxide dismutase is primarily a cytosolic protein in human cells. |
| GO:0001541 ovarian follicle development | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Ovarian follicle development (ISS, ortholog). Reason: Transferred from the rodent ortholog (electronic/ortholog evidence); reflects a pleiotropic organismal response to the loss of antioxidant protection rather than a core molecular function. Kept as non-core. |
| GO:0001890 placenta development | NAS PMID:12485882 Implication of copper zinc superoxide dismutase (SOD-1) in h... | KEEP AS NON CORE | Summary: Placenta development (NAS). Reason: Transferred from the rodent ortholog (electronic/ortholog evidence); reflects a pleiotropic organismal response to the loss of antioxidant protection rather than a core molecular function. Kept as non-core. |
| GO:0001895 retina homeostasis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Retina homeostasis (ISS, ortholog). Reason: Transferred from the rodent ortholog (electronic/ortholog evidence); reflects a pleiotropic organismal response to the loss of antioxidant protection rather than a core molecular function. Kept as non-core. |
| GO:0002262 myeloid cell homeostasis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Myeloid cell homeostasis (ISS, ortholog). Reason: Transferred from the rodent ortholog (electronic/ortholog evidence); reflects a pleiotropic organismal response to the loss of antioxidant protection rather than a core molecular function. Kept as non-core. |
| GO:0005737 cytoplasm | IDA PMID:11527942 Superoxide dismutase isoenzymes in the normal and diseased h... | ACCEPT | Summary: Cytoplasm (IDA). Reason: Core compartment. Supporting Evidence: PMID:1332049 Copper,zinc superoxide dismutase is primarily a cytosolic protein in human cells. |
| GO:0006749 glutathione metabolic process | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Glutathione metabolic process (ISS, ortholog). Reason: Transferred from the rodent ortholog (electronic/ortholog evidence); reflects a pleiotropic organismal response to the loss of antioxidant protection rather than a core molecular function. Kept as non-core. |
| GO:0006801 superoxide metabolic process | ISS GO_REF:0000024 | ACCEPT | Summary: Superoxide metabolic process (ISS, ortholog); core process. Reason: Equivalent to the core role. |
| GO:0006879 intracellular iron ion homeostasis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Intracellular iron ion homeostasis (ISS, ortholog). Reason: Transferred from the rodent ortholog (electronic/ortholog evidence); reflects a pleiotropic organismal response to the loss of antioxidant protection rather than a core molecular function. Kept as non-core. |
| GO:0007283 spermatogenesis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Spermatogenesis (ISS, ortholog). Reason: Transferred from the rodent ortholog (electronic/ortholog evidence); reflects a pleiotropic organismal response to the loss of antioxidant protection rather than a core molecular function. Kept as non-core. |
| GO:0007566 embryo implantation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Embryo implantation (ISS, ortholog). Reason: Transferred from the rodent ortholog (electronic/ortholog evidence); reflects a pleiotropic organismal response to the loss of antioxidant protection rather than a core molecular function. Kept as non-core. |
| GO:0007566 embryo implantation | NAS PMID:10920331 Differential localization of placental extracellular superox... | KEEP AS NON CORE | Summary: Embryo implantation (NAS). Reason: Transferred from the rodent ortholog (electronic/ortholog evidence); reflects a pleiotropic organismal response to the loss of antioxidant protection rather than a core molecular function. Kept as non-core. |
| GO:0007605 sensory perception of sound | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Sensory perception of sound (ISS, ortholog). Reason: Transferred from the rodent ortholog (electronic/ortholog evidence); reflects a pleiotropic organismal response to the loss of antioxidant protection rather than a core molecular function. Kept as non-core. |
| GO:0007626 locomotory behavior | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Locomotory behavior (ISS, ortholog). Reason: Transferred from the rodent ortholog (electronic/ortholog evidence); reflects a pleiotropic organismal response to the loss of antioxidant protection rather than a core molecular function. Kept as non-core. |
| GO:0008217 regulation of blood pressure | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Regulation of blood pressure (ISS, ortholog). Reason: Transferred from the rodent ortholog (electronic/ortholog evidence); reflects a pleiotropic organismal response to the loss of antioxidant protection rather than a core molecular function. Kept as non-core. |
| GO:0008270 zinc ion binding | IDA PMID:17381088 Binding of a single zinc ion to one subunit of copper-zinc s... | ACCEPT | Summary: SOD1 binds one structural zinc ion per subunit (IDA). Reason: Direct biochemical evidence; zinc is the structural cofactor stabilizing the dimer/active site. Supporting Evidence: PMID:17381088 Binding of a single zinc ion to one subunit of copper-zinc superoxide dismutase apoprotein substantially influences the structure and stability of the entire homodimeric protein. |
| GO:0009408 response to heat | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Response to heat (ISS, ortholog). Reason: Transferred from the rodent ortholog (electronic/ortholog evidence); reflects a pleiotropic organismal response to the loss of antioxidant protection rather than a core molecular function. Kept as non-core. |
| GO:0019226 transmission of nerve impulse | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Transmission of nerve impulse (ISS, ortholog). Reason: Transferred from the rodent ortholog (electronic/ortholog evidence); reflects a pleiotropic organismal response to the loss of antioxidant protection rather than a core molecular function. Kept as non-core. |
| GO:0019430 removal of superoxide radicals | ISS GO_REF:0000024 | ACCEPT | Summary: Removal of superoxide radicals (ISS, ortholog); core process. Reason: Equivalent to the core role. |
| GO:0032287 peripheral nervous system myelin maintenance | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Peripheral nervous system myelin maintenance (ISS, ortholog). Reason: Transferred from the rodent ortholog (electronic/ortholog evidence); reflects a pleiotropic organismal response to the loss of antioxidant protection rather than a core molecular function. Kept as non-core. |
| GO:0033081 regulation of T cell differentiation in thymus | NAS PMID:16716898 Early thymic T cell development in young transgenic mice ove... | KEEP AS NON CORE | Summary: Regulation of T cell differentiation in thymus (NAS). Reason: Transferred from the rodent ortholog (electronic/ortholog evidence); reflects a pleiotropic organismal response to the loss of antioxidant protection rather than a core molecular function. Kept as non-core. |
| GO:0040014 regulation of multicellular organism growth | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Regulation of multicellular organism growth (ISS, ortholog). Reason: Transferred from the rodent ortholog (electronic/ortholog evidence); reflects a pleiotropic organismal response to the loss of antioxidant protection rather than a core molecular function. Kept as non-core. |
| GO:0042542 response to hydrogen peroxide | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Response to hydrogen peroxide (ISS, ortholog). Reason: Transferred from the rodent ortholog (electronic/ortholog evidence); reflects a pleiotropic organismal response to the loss of antioxidant protection rather than a core molecular function. Kept as non-core. |
| GO:0043524 negative regulation of neuron apoptotic process | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Negative regulation of neuron apoptotic process (ISS, ortholog). Reason: SOD1 is broadly neuroprotective via ROS removal; downstream process, non-core. |
| GO:0045471 response to ethanol | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Response to ethanol (ISS, ortholog). Reason: Transferred from the rodent ortholog (electronic/ortholog evidence); reflects a pleiotropic organismal response to the loss of antioxidant protection rather than a core molecular function. Kept as non-core. |
| GO:0046620 regulation of organ growth | NAS PMID:16716898 Early thymic T cell development in young transgenic mice ove... | KEEP AS NON CORE | Summary: Regulation of organ growth (NAS). Reason: Transferred from the rodent ortholog (electronic/ortholog evidence); reflects a pleiotropic organismal response to the loss of antioxidant protection rather than a core molecular function. Kept as non-core. |
| GO:0046716 muscle cell cellular homeostasis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Muscle cell cellular homeostasis (ISS, ortholog). Reason: Transferred from the rodent ortholog (electronic/ortholog evidence); reflects a pleiotropic organismal response to the loss of antioxidant protection rather than a core molecular function. Kept as non-core. |
| GO:0048538 thymus development | NAS PMID:16716898 Early thymic T cell development in young transgenic mice ove... | KEEP AS NON CORE | Summary: Thymus development (NAS). Reason: Transferred from the rodent ortholog (electronic/ortholog evidence); reflects a pleiotropic organismal response to the loss of antioxidant protection rather than a core molecular function. Kept as non-core. |
| GO:0048678 response to axon injury | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Response to axon injury (ISS, ortholog). Reason: Transferred from the rodent ortholog (electronic/ortholog evidence); reflects a pleiotropic organismal response to the loss of antioxidant protection rather than a core molecular function. Kept as non-core. |
| GO:0050665 hydrogen peroxide biosynthetic process | ISS GO_REF:0000024 | ACCEPT | Summary: Hydrogen peroxide biosynthetic process (ISS); H2O2 is the SOD reaction product. Reason: H2O2 is the direct product of dismutation. |
| GO:0060047 heart contraction | IDA PMID:9539776 Overexpression of human copper, zinc-superoxide dismutase (S... | KEEP AS NON CORE | Summary: Heart contraction (IDA, ortholog/physiology). Reason: Organ-physiology phenotype downstream of antioxidant protection; non-core. |
| GO:0060052 neurofilament cytoskeleton organization | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Neurofilament cytoskeleton organization (ISS, ortholog). Reason: Transferred from the rodent ortholog (electronic/ortholog evidence); reflects a pleiotropic organismal response to the loss of antioxidant protection rather than a core molecular function. Kept as non-core. |
| GO:0060087 relaxation of vascular associated smooth muscle | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Relaxation of vascular associated smooth muscle (ISS, ortholog). Reason: Transferred from the rodent ortholog (electronic/ortholog evidence); reflects a pleiotropic organismal response to the loss of antioxidant protection rather than a core molecular function. Kept as non-core. |
| GO:0060088 auditory receptor cell stereocilium organization | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Auditory receptor cell stereocilium organization (ISS, ortholog). Reason: Transferred from the rodent ortholog (electronic/ortholog evidence); reflects a pleiotropic organismal response to the loss of antioxidant protection rather than a core molecular function. Kept as non-core. |
| GO:0001819 positive regulation of cytokine production | IDA PMID:15544046 Gene transfer of CuZn superoxide dismutase enhances the synt... | KEEP AS NON CORE | Summary: Positive regulation of cytokine production (IDA). Reason: Single-study immunomodulatory effect; downstream/peripheral, non-core. Supporting Evidence: PMID:15544046 Gene transfer of CuZn superoxide dismutase enhances the synthesis of vascular endothelial growth factor. |
| GO:0004784 superoxide dismutase activity | IDA PMID:15544046 Gene transfer of CuZn superoxide dismutase enhances the synt... | ACCEPT | Summary: Direct SOD activity assay. Reason: Confirms core function. Supporting Evidence: PMID:15544046 dismutase (CuZnSOD, SOD1). Overexpression of human SOD1 |
| GO:0004784 superoxide dismutase activity | IDA PMID:17324120 Activation of brain calcineurin (Cn) by Cu-Zn superoxide dis... | ACCEPT | Summary: Direct SOD activity assay (calcineurin study). Reason: Confirms core function. Supporting Evidence: PMID:17324120 Cu-Zn superoxide dismutase (SOD1) |
| GO:0005507 copper ion binding | IDA PMID:17008312 Mitochondrial matrix copper complex used in metallation of c... | ACCEPT | Summary: Copper ion binding (IDA); SOD1 metallation in mitochondrial IMS. Reason: Direct evidence SOD1 acquires its catalytic copper. Supporting Evidence: PMID:31292775 Copper-zinc superoxide dismutase (Sod1) is a critical antioxidant enzyme that rids the cell of reactive oxygen through the redox cycling of a catalytic copper ion provided by its copper chaperone (Ccs). |
| GO:0005759 mitochondrial matrix | NAS PMID:17008312 Mitochondrial matrix copper complex used in metallation of c... | REMOVE | Summary: Mitochondrial matrix (NAS). Reason: The functional and metallation pools of SOD1 are in the cytosol and mitochondrial intermembrane space, not the matrix; the matrix call appears to be a misassignment. Supporting Evidence: PMID:24026195 both localize to the cytosol and the mitochondrial intermembrane space where they specifically counteract mitochondria-derived superoxide |
| GO:0005886 plasma membrane | IDA PMID:17324120 Activation of brain calcineurin (Cn) by Cu-Zn superoxide dis... | KEEP AS NON CORE | Summary: Plasma membrane colocalization (IDA). Reason: Colocalization observed on endocytosis/specialized contexts; peripheral, non-core. |
| GO:0030346 protein phosphatase 2B binding | IDA PMID:17324120 Activation of brain calcineurin (Cn) by Cu-Zn superoxide dis... | KEEP AS NON CORE | Summary: Protein phosphatase 2B (calcineurin) binding (IDA). Reason: SOD1 directly binds and activates calcineurin (protein phosphatase 2B); a specific, experimentally supported interaction, though peripheral to the core antioxidant function. Supporting Evidence: PMID:17324120 Activation of brain calcineurin (Cn) by Cu-Zn superoxide dismutase (SOD1) depends on direct SOD1-Cn protein interactions occurring in vitro and in vivo. |
| GO:0032839 dendrite cytoplasm | IDA PMID:17324120 Activation of brain calcineurin (Cn) by Cu-Zn superoxide dis... | KEEP AS NON CORE | Summary: Dendrite cytoplasm (IDA). Reason: Cell-type-specific cytoplasmic localization; non-core. |
| GO:0032991 protein-containing complex | IDA PMID:17324120 Activation of brain calcineurin (Cn) by Cu-Zn superoxide dis... | KEEP AS NON CORE | Summary: Protein-containing complex (IDA). Reason: Generic; SOD1's specific complexes are captured by precise terms. Non-core. |
| GO:0043025 neuronal cell body | IDA PMID:17324120 Activation of brain calcineurin (Cn) by Cu-Zn superoxide dis... | KEEP AS NON CORE | Summary: Neuronal cell body (IDA). Reason: Cell-type-specific localization; non-core. |
| GO:0050665 hydrogen peroxide biosynthetic process | IDA PMID:15544046 Gene transfer of CuZn superoxide dismutase enhances the synt... | ACCEPT | Summary: Hydrogen peroxide biosynthetic process (IDA); H2O2 produced by SOD1. Reason: H2O2 is the direct product of dismutation. Supporting Evidence: PMID:15544046 Overexpression of human SOD1 |
| GO:0000303 response to superoxide | IDA PMID:16790527 Mitochondrial damage due to SOD1 deficiency in SH-SY5Y neuro... | KEEP AS NON CORE | Summary: Response to superoxide (IDA); SOD1 deficiency raises steady-state superoxide. Reason: Real, but a downstream cellular-response framing; the core process is removal of superoxide. Supporting Evidence: PMID:16790527 The steady-state concentration of superoxide was significantly increased |
| GO:0005515 protein binding | IPI PMID:16790527 Mitochondrial damage due to SOD1 deficiency in SH-SY5Y neuro... | MARK AS OVER ANNOTATED | Summary: Generic protein-binding interaction (IPI). Reason: Bare 'protein binding' (GO:0005515) is uninformative per curation guidelines; these IPI entries are largely high-throughput or disease/aggregation-context interactions. Marked as over-annotated in favor of specific informative terms (copper ion binding, identical protein binding, protein-folding chaperone binding, small GTPase binding). |
| GO:0005576 extracellular region | IDA PMID:9453566 CuZn-superoxide dismutase, extracellular superoxide dismutas... | KEEP AS NON CORE | Summary: Extracellular region (IDA); SOD1 detected extracellularly. Reason: A minor secreted/extracellular pool of SOD1 (including exosomes) exists but is peripheral to the cytosolic antioxidant function. |
| GO:0005634 nucleus | IDA PMID:17504823 Mutation of SOD1 in ALS: a gain of a loss of function. | KEEP AS NON CORE | Summary: Nucleus (IDA). Reason: Secondary nuclear pool; non-core. Supporting Evidence: PMID:1332049 Cu,Zn-SOD was found widely distributed in the cell cytosol and in the cell nucleus |
| GO:0005634 nucleus | IDA PMID:9726962 The copper chaperone CCS directly interacts with copper/zinc... | KEEP AS NON CORE | Summary: Nucleus (IDA); SOD1/CCS study. Reason: Secondary nuclear pool; non-core. Supporting Evidence: PMID:1332049 Cu,Zn-SOD was found widely distributed in the cell cytosol and in the cell nucleus |
| GO:0005737 cytoplasm | IDA PMID:17077646 Rapid endocytosis of copper-zinc superoxide dismutase into h... | ACCEPT | Summary: Cytoplasm (IDA). Reason: Core compartment. Supporting Evidence: PMID:1332049 Copper,zinc superoxide dismutase is primarily a cytosolic protein in human cells. |
| GO:0005737 cytoplasm | IDA PMID:17504823 Mutation of SOD1 in ALS: a gain of a loss of function. | ACCEPT | Summary: Cytoplasm (IDA). Reason: Core compartment. Supporting Evidence: PMID:1332049 Copper,zinc superoxide dismutase is primarily a cytosolic protein in human cells. |
| GO:0005737 cytoplasm | IDA PMID:9726962 The copper chaperone CCS directly interacts with copper/zinc... | ACCEPT | Summary: Cytoplasm (IDA). Reason: Core compartment. Supporting Evidence: PMID:1332049 Copper,zinc superoxide dismutase is primarily a cytosolic protein in human cells. |
| GO:0005739 mitochondrion | IDA PMID:16790527 Mitochondrial damage due to SOD1 deficiency in SH-SY5Y neuro... | KEEP AS NON CORE | Summary: Mitochondrion (IDA); SOD1 deficiency causes mitochondrial damage. Reason: Reflects functional impact on mitochondria; the specific functional pool is the IMS. Supporting Evidence: PMID:16790527 Mitochondrial damage due to SOD1 deficiency in SH-SY5Y neuroblastoma cells |
| GO:0005829 cytosol | IDA PMID:16790527 Mitochondrial damage due to SOD1 deficiency in SH-SY5Y neuro... | ACCEPT | Summary: Cytosol (IDA). Reason: Core compartment. Supporting Evidence: PMID:1332049 Copper,zinc superoxide dismutase is primarily a cytosolic protein in human cells. |
| GO:0005886 plasma membrane | IDA PMID:17077646 Rapid endocytosis of copper-zinc superoxide dismutase into h... | KEEP AS NON CORE | Summary: Plasma membrane colocalization (IDA); endocytic uptake context. Reason: Colocalization on endocytosis into endothelial cells; peripheral, non-core. |
| GO:0031410 cytoplasmic vesicle | IDA PMID:17077646 Rapid endocytosis of copper-zinc superoxide dismutase into h... | KEEP AS NON CORE | Summary: Cytoplasmic vesicle (IDA); endocytic uptake context. Reason: Vesicular localization in an uptake/endocytosis context; non-core. |
| GO:0043065 positive regulation of apoptotic process | IC PMID:16790527 Mitochondrial damage due to SOD1 deficiency in SH-SY5Y neuro... | MARK AS OVER ANNOTATED | Summary: Positive regulation of apoptotic process (IC, chained off protein binding). Reason: Inferred (IC) from a protein-binding annotation; SOD1 is canonically anti-apoptotic/cytoprotective, so a positive-apoptosis process annotation is a context-specific over-annotation. |
| GO:0051087 protein-folding chaperone binding | IPI PMID:9726962 The copper chaperone CCS directly interacts with copper/zinc... | ACCEPT | Summary: Protein-folding chaperone binding (IPI); SOD1 binds its CCS chaperone. Reason: Direct, informative interaction with the copper chaperone CCS that matures SOD1. Supporting Evidence: PMID:30735496 maturation of SOD1 by its evolutionarily destabilised cognate chaperone hCCS |
| GO:0051881 regulation of mitochondrial membrane potential | IMP PMID:16790527 Mitochondrial damage due to SOD1 deficiency in SH-SY5Y neuro... | KEEP AS NON CORE | Summary: Regulation of mitochondrial membrane potential (IMP). Reason: SOD1 knockdown impairs mitochondrial membrane potential; a downstream consequence of lost antioxidant protection, non-core. Supporting Evidence: PMID:16790527 impairment of the mitochondrial transmembrane potential |
| GO:0005737 cytoplasm | IDA PMID:1332049 Copper,zinc superoxide dismutase is primarily a cytosolic pr... | ACCEPT | Summary: Cytoplasm (IDA, EM immunocytochemistry). Reason: Core compartment. Supporting Evidence: PMID:1332049 Copper,zinc superoxide dismutase is primarily a cytosolic protein in human cells. |
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Download this section (compressed HTML)Q: Is the hydrogen sulfide oxidase activity (EC 1.8.-.-) of SOD1 a physiologically significant function in human tissues, and should it be captured by a distinct molecular-function annotation alongside superoxide dismutase activity?
Suggested experts: Switzer CH, Eaton P
Q: To what extent does the mitochondrial intermembrane-space pool of SOD1 contribute to total cellular superoxide detoxification versus the cytosolic pool in human neurons?
Suggested experts: Riemer J
Experiment: Use SOD1 separation-of-function variants (catalytically inactive but Rac1-binding competent, and vice versa) in human cells to dissociate dismutase activity from Rac1/Nox regulation, measuring superoxide flux and Rac1 GTPase activity.
Hypothesis: SOD1's Rac1-binding redox-sensor function modulates NADPH oxidase output independently of its bulk dismutase activity.
Type: structure-function mutagenesis with redox/GTPase readouts
Experiment: Compare superoxide levels, mitochondrial membrane potential, and viability in human iPSC-derived motor neurons with IMS-targeting-deficient versus wild-type SOD1, using CCS-dependent import mutants.
Hypothesis: The mitochondrial intermembrane-space SOD1 pool is required to protect against mitochondria-derived superoxide in human motor neurons.
Type: organelle-targeted rescue in iPSC-derived neurons
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