Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0003735 structural constituent of ribosome	IBA GO_REF:0000033	ACCEPT	Summary: RPS3/uS3 is a canonical structural protein of the human cytosolic small ribosomal subunit. Reason: This is the core molecular function of RPS3 and is supported by human ribosome structural studies and Falcon's synthesis. Supporting Evidence: PMID:23636399 Here we present structures of Drosophila melanogaster and Homo sapiens 80S ribosomes in complex with the translation factor eEF2, E-site transfer RNA and Stm1-like proteins, based on high-resolution cryo-electron-microscopy density maps. file:human/RPS3/RPS3-deep-research-falcon.md RPS3 is a core protein of the cytosolic small ribosomal subunit (40S) and therefore supports GO annotations centered on (i) structural constituent of ribosome, (ii) cytoplasmic translation, and (iii) localization to cytosolic ribosome / small ribosomal subunit / cytosol (cytoplasm).
GO:0005634 nucleus	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: RPS3 can localize to the nucleus in ribosome-biogenesis trafficking and regulated extra-ribosomal signaling contexts. Reason: Nuclear localization is supported but is not the primary cellular context of the core ribosomal function. Supporting Evidence: file:human/RPS3/RPS3-deep-research-falcon.md Nuclear localization is real but context-dependent: supported for ribosome biogenesis trafficking and for NF-κB/apoptosis responses; annotate nuclear location but avoid implying constitutive transcription factor behavior.
GO:0022627 cytosolic small ribosomal subunit	IBA GO_REF:0000033	ACCEPT	Summary: RPS3 is a component of the cytosolic small ribosomal subunit. Reason: This is the core cellular component for RPS3's ribosomal structural function. Supporting Evidence: PMID:23636399 Here we present structures of Drosophila melanogaster and Homo sapiens 80S ribosomes in complex with the translation factor eEF2, E-site transfer RNA and Stm1-like proteins, based on high-resolution cryo-electron-microscopy density maps. file:human/RPS3/RPS3-deep-research-falcon.md RPS3 is a core protein of the cytosolic small ribosomal subunit (40S) and therefore supports GO annotations centered on (i) structural constituent of ribosome, (ii) cytoplasmic translation, and (iii) localization to cytosolic ribosome / small ribosomal subunit / cytosol (cytoplasm).
GO:2001235 positive regulation of apoptotic signaling pathway	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: RPS3 has reported pro-apoptotic effects in overexpression/cytokine treatment assays, but this is a context-dependent secondary function. Reason: The apoptosis evidence is real enough to retain cautiously, but it should not be treated as the core function of this ribosomal protein. Supporting Evidence: PMID:14988002 Transient expression of GFP-rpS3 activates caspase-8/caspase-3 and sensitizes cytokine-induced apoptosis. file:human/RPS3/RPS3-deep-research-falcon.md Likely context-dependent moonlighting effect; do not overextend to generic apoptosis/development terms without genetic/physiologic evidence.
GO:0045944 positive regulation of transcription by RNA polymerase II	IEA GO_REF:0000108	KEEP AS NON CORE	Summary: RPS3 can act as an NF-kB-associated transcriptional specificity factor, but broad RNA polymerase II transcription regulation is not its core function. Reason: Falcon supports a context-specific NF-kB cofactor/specifier role and cautions against broad generic transcription terms. Supporting Evidence: file:human/RPS3/RPS3-deep-research-falcon.md Strong for NF-κB cofactor/specifier in selected promoters; weaker for generic “RNA polymerase II transcription” or “DNA-binding transcription factor binding/coactivator” across all contexts.
GO:0003677 DNA binding	IEA GO_REF:0000043	MODIFY	Summary: RPS3 binds damaged DNA lesions including AP sites and 8-oxoG, but generic DNA binding is less informative than damaged DNA binding. Reason: The broad DNA binding term should be replaced by the more specific damaged DNA binding term that is supported by primary binding assays. Proposed replacements: damaged DNA binding Supporting Evidence: PMID:14706345 An even more dramatic five orders of magnitude higher binding affinity for AP DNA was found for hS3 as opposed to hOGG1.
GO:0003723 RNA binding	IEA GO_REF:0000120	KEEP AS NON CORE	Summary: RNA binding is plausible for RPS3 through its KH domain, but this is secondary to its ribosomal structural role. Reason: Falcon supports RNA-binding capacity in a mechanistic/domain context but cautions against overextending it to sequence-specific RNA regulation. Supporting Evidence: file:human/RPS3/RPS3-deep-research-falcon.md RPS3’s KH domain is described as capable of binding single-stranded RNA/DNA and is required for NF-κB complex association; this supports GO:RNA binding in a mechanistically grounded way.
GO:0003735 structural constituent of ribosome	IEA GO_REF:0000120	ACCEPT	Summary: RPS3/uS3 is a canonical structural protein of the human cytosolic small ribosomal subunit. Reason: This automated annotation matches the core experimentally supported ribosomal function. Supporting Evidence: PMID:23636399 Here we present structures of Drosophila melanogaster and Homo sapiens 80S ribosomes in complex with the translation factor eEF2, E-site transfer RNA and Stm1-like proteins, based on high-resolution cryo-electron-microscopy density maps.
GO:0005634 nucleus	IEA GO_REF:0000044	KEEP AS NON CORE	Summary: RPS3 can localize to the nucleus in ribosome-biogenesis trafficking and regulated extra-ribosomal signaling contexts. Reason: Nuclear localization is supported but secondary to the cytosolic ribosome location of the core function. Supporting Evidence: file:human/RPS3/RPS3-deep-research-falcon.md Nuclear localization is real but context-dependent: supported for ribosome biogenesis trafficking and for NF-κB/apoptosis responses; annotate nuclear location but avoid implying constitutive transcription factor behavior.
GO:0005730 nucleolus	IEA GO_REF:0000044	MARK AS OVER ANNOTATED	Summary: Nucleolar relevance is plausible in ribosome biogenesis, but Falcon found weaker direct evidence for RPS3 protein localization in nucleoli. Reason: The evidence is more about ribosome biogenesis/gene context than direct RPS3 protein localization to the nucleolus. Supporting Evidence: file:human/RPS3/RPS3-deep-research-falcon.md Caveat: this is not direct imaging of RPS3 protein in nucleoli; nucleolar protein localization should be annotated conservatively unless supported by direct localization assays.
GO:0005737 cytoplasm	IEA GO_REF:0000120	ACCEPT	Summary: Cytoplasm/cytosol is the expected location for RPS3's core cytosolic ribosomal function. Reason: The cytoplasmic location is consistent with accepted cytosolic ribosome and translation annotations. Supporting Evidence: file:human/RPS3/RPS3-deep-research-falcon.md RPS3 is a core protein of the cytosolic small ribosomal subunit (40S) and therefore supports GO annotations centered on (i) structural constituent of ribosome, (ii) cytoplasmic translation, and (iii) localization to cytosolic ribosome / small ribosomal subunit / cytosol (cytoplasm).
GO:0005743 mitochondrial inner membrane	IEA GO_REF:0000044	REMOVE	Summary: The automated mitochondrial inner membrane annotation overstates stable, constitutive localization. Direct evidence supports stress-induced RPS3 accumulation in mitochondria, which is represented by separate IDA annotations from PMID:23911537. Reason: This IEA annotation should not be retained as evidence for stable mitochondrial inner membrane localization. PMID:23911537 supports ROS-induced mitochondrial accumulation for DNA repair, but not constitutive inner membrane residency; the PMID:23911537 IDA mitochondrial annotations should be evaluated separately. Supporting Evidence: file:human/RPS3/RPS3-deep-research-falcon.md Mitochondrial inner membrane / ER: no direct, RPS3-specific evidence in the retrieved corpus supports stable mitochondrial inner membrane or ER localization; avoid those CC annotations without targeted localization data. PMID:23911537 Increased ROS induces rpS3 accumulation in the mitochondria for DNA repair while significantly decreasing the cellular protein synthesis.
GO:0005819 spindle	IEA GO_REF:0000044	KEEP AS NON CORE	Summary: RPS3 has been reported to localize on the mitotic spindle and act as a microtubule-associated protein during mitosis, so spindle localization has experimental support. Reason: Spindle localization is supported by direct imaging (PMID:23131551) but is a context-dependent extra-ribosomal/mitotic function rather than the core cytosolic ribosomal location; the more specific mitotic spindle IDA annotation captures it. Supporting Evidence: PMID:23131551 When we examined localization of ribosomal proteins in mitosis, we found that rpS3 specifically localizes on the mitotic spindle.
GO:0005840 ribosome	IEA GO_REF:0000043	ACCEPT	Summary: Ribosome localization is core to RPS3's function as a small-subunit ribosomal protein. Reason: RPS3 is a structural protein of the human cytosolic ribosome. Supporting Evidence: PMID:23636399 Here we present structures of Drosophila melanogaster and Homo sapiens 80S ribosomes in complex with the translation factor eEF2, E-site transfer RNA and Stm1-like proteins, based on high-resolution cryo-electron-microscopy density maps.
GO:0006281 DNA repair	IEA GO_REF:0000043	KEEP AS NON CORE	Summary: RPS3 has secondary evidence for participation in DNA damage processing and base-excision repair contexts. Reason: DNA repair is supported as an extra-ribosomal function, but Falcon emphasizes that damaged-DNA binding and cofactor-like BER roles are better supported than treating DNA repair as the core function. Supporting Evidence: PMID:15518571 These results raise the possibility that hS3 not only functions as a ribosomal protein but, in addition, may influence repair activities at sites of DNA damage.
GO:0006412 translation	IEA GO_REF:0000002	ACCEPT	Summary: RPS3's core role in the cytosolic ribosome supports translation. Reason: Translation is the principal biological process associated with RPS3's structural ribosome function. Supporting Evidence: PMID:23636399 Protein synthesis in all cells is carried out by macromolecular machines called ribosomes. file:human/RPS3/RPS3-deep-research-falcon.md RPS3 is a core protein of the cytosolic small ribosomal subunit (40S) and therefore supports GO annotations centered on (i) structural constituent of ribosome, (ii) cytoplasmic translation, and (iii) localization to cytosolic ribosome / small ribosomal subunit / cytosol (cytoplasm).
GO:0006417 regulation of translation	IEA GO_REF:0000043	KEEP AS NON CORE	Summary: RPS3 has been reported to autoregulate its own translation and to be part of translational control mechanisms, but the broad regulation of translation term applied by keyword mapping is loosely supported. Reason: A specific autoregulatory negative-regulation-of-translation activity is documented (PMID:20217897), so a generic regulation-of-translation term is not wrong but is non-core relative to the structural ribosomal role and is better represented by the specific IDA negative-regulation annotation. Supporting Evidence: PMID:20217897 We here report an additional function of rpS3 in which it represses its own translation by binding to its cognate mRNA.
GO:0006915 apoptotic process	IEA GO_REF:0000043	KEEP AS NON CORE	Summary: RPS3 has context-dependent pro-apoptotic evidence from overexpression and cytokine-treatment assays. Reason: Apoptosis is an extra-ribosomal moonlighting context and should not be treated as the core function. Supporting Evidence: PMID:14988002 Transient expression of GFP-rpS3 activates caspase-8/caspase-3 and sensitizes cytokine-induced apoptosis.
GO:0006974 DNA damage response	IEA GO_REF:0000043	KEEP AS NON CORE	Summary: RPS3 has reported roles in DNA damage response through damaged-DNA binding and BER-associated interactions. Reason: This is a secondary extra-ribosomal function and should be interpreted cautiously relative to the core ribosomal role. Supporting Evidence: PMID:15518571 These results raise the possibility that hS3 not only functions as a ribosomal protein but, in addition, may influence repair activities at sites of DNA damage.
GO:0015935 small ribosomal subunit	IEA GO_REF:0000002	ACCEPT	Summary: RPS3 is a component of the small ribosomal subunit. Reason: This cellular component matches the core ribosomal role of RPS3. Supporting Evidence: PMID:23636399 Here we present structures of Drosophila melanogaster and Homo sapiens 80S ribosomes in complex with the translation factor eEF2, E-site transfer RNA and Stm1-like proteins, based on high-resolution cryo-electron-microscopy density maps.
GO:0016829 lyase activity	IEA GO_REF:0000043	MARK AS OVER ANNOTATED	Summary: RPS3 has historical AP lyase/endonuclease activity claims, but this broad lyase activity annotation is not the best-supported framing for human RPS3 function. Reason: The better-supported non-ribosomal activity is damaged-DNA binding and possible BER cofactor activity; intrinsic human AP lyase/endonuclease activity remains secondary and unresolved relative to the core ribosomal role. Supporting Evidence: file:human/RPS3/RPS3-deep-research-falcon.md Multiple sources describe RPS3 as a DNA repair endonuclease/AP lyase and map repair activity to the C-terminus, but the excerpts show that the most definitive catalytic evidence often arises from non-human orthologs (e.g., Drosophila/yeast) or engineered conversions, and human intrinsic catalytic status is not resolved here.
GO:0022626 cytosolic ribosome	IEA GO_REF:0000117	ACCEPT	Summary: RPS3 is a component of the cytosolic ribosome, specifically the 40S small ribosomal subunit. Reason: This parent cellular component is consistent with the accepted, more specific cytosolic small ribosomal subunit annotation. Supporting Evidence: PMID:23636399 Here we present structures of Drosophila melanogaster and Homo sapiens 80S ribosomes in complex with the translation factor eEF2, E-site transfer RNA and Stm1-like proteins, based on high-resolution cryo-electron-microscopy density maps. file:human/RPS3/RPS3-deep-research-falcon.md RPS3 is a core protein of the cytosolic small ribosomal subunit (40S) and therefore supports GO annotations centered on (i) structural constituent of ribosome, (ii) cytoplasmic translation, and (iii) localization to cytosolic ribosome / small ribosomal subunit / cytosol (cytoplasm).
GO:0051301 cell division	IEA GO_REF:0000043	KEEP AS NON CORE	Summary: A keyword-derived generic cell division annotation. RPS3 has reported mitotic-spindle/microtubule functions (PMID:23131551), but the broad cell division term is non-core relative to its ribosomal role and is better represented by the specific spindle assembly/mitotic spindle IMP/IDA annotations. Reason: RPS3 has documented mitotic roles as a microtubule-associated/spindle protein, so cell division is not wrong, but it is an extra-ribosomal moonlighting context rather than the core function and is captured more specifically by GO:0051225 (spindle assembly) and GO:0072686 (mitotic spindle). Supporting Evidence: PMID:23131551 Depletion of the rpS3 proteins caused mitotic arrest during the metaphase.
GO:0140078 class I DNA-(apurinic or apyrimidinic site) endonuclease activity	IEA GO_REF:0000120	MARK AS OVER ANNOTATED	Summary: Direct class I AP endonuclease activity for human RPS3 is historically claimed but remains less secure than damaged-DNA binding and possible BER cofactor activity. Reason: The annotation likely overstates a debated secondary activity; RPS3's core function is ribosomal, and the stronger DNA repair evidence supports lesion binding/cofactor framing rather than intrinsic class I AP endonuclease activity. Supporting Evidence: file:human/RPS3/RPS3-deep-research-falcon.md Annotation guidance: treat DNA lesion binding and BER cofactor roles as better-supported than broad “wide-range base-damage endonuclease” claims unless primary human biochemistry is directly cited.
GO:1990904 ribonucleoprotein complex	IEA GO_REF:0000043	ACCEPT	Summary: RPS3 is a constituent of the ribosome, which is a ribonucleoprotein complex; this parent term is consistent with its core ribosomal role. Reason: As a 40S small-subunit protein, RPS3 is part of a ribonucleoprotein complex (the ribosome). This broad term is correct but is subsumed by the more specific cytosolic small ribosomal subunit annotation. Supporting Evidence: PMID:23636399 Here we present structures of Drosophila melanogaster and Homo sapiens 80S ribosomes in complex with the translation factor eEF2, E-site transfer RNA and Stm1-like proteins, based on high-resolution cryo-electron-microscopy density maps.
GO:0005515 protein binding	IPI PMID:15161933 Comprehensive proteomic analysis of interphase and mitotic 1...	KEEP AS NON CORE	Summary: RPS3 was identified as a 14-3-3-binding protein in a large-scale proteomic survey of interphase and mitotic 14-3-3 interactors. Reason: This is a generic protein binding annotation derived from a high-throughput interactome screen. Per curation guidelines protein binding is uninformative, and a single proteomic co-purification does not establish a specific, physiologically core molecular function. Retained as non-core documentation of the interaction. Supporting Evidence: PMID:15161933 Comprehensive proteomic analysis of interphase and mitotic 14-3-3-binding proteins.
GO:0005515 protein binding	IPI PMID:18045535 Ribosomal protein S3: a KH domain subunit in NF-kappaB compl...	MODIFY	Summary: This annotation captures RPS3's interaction with RELA (p65) of the NF-kappaB complex. While 'protein binding' is a very general term, the specific interaction with RELA is functionally significant for RPS3's role as a transcription coactivator in NF-kappaB signaling. A more informative annotation would specify the binding partner (RELA). Reason: The generic 'protein binding' term is too vague. PMID:18045535 specifically demonstrates interaction with RELA/p65 subunit of NF-kappaB. A more appropriate annotation would be to a more specific binding term that captures the functionally relevant interaction with a transcription factor. GO:0140297 (DNA-binding transcription factor binding) or GO:0061629 (RNA polymerase II-specific DNA-binding transcription factor binding) would be more informative. Proposed replacements: DNA-binding transcription factor binding RNA polymerase II-specific DNA-binding transcription factor binding Supporting Evidence: PMID:18045535 We identified ribosomal protein S3 (RPS3), a KH domain protein, as a non-Rel subunit of p65 homodimer and p65-p50 heterodimer DNA-binding complexes that synergistically enhances DNA binding.
GO:0005515 protein binding	IPI PMID:18274552 Ribosomal proteins are targets for the NEDD8 pathway.	KEEP AS NON CORE	Summary: RPS3 was identified as one of a subset of ribosomal proteins targeted by the NEDD8 conjugation pathway in a proteomic/in vivo NEDDylation screen; NEDDylation protects ribosomal proteins from destabilization. Reason: Generic protein binding from a proteomic NEDDylation screen. This is uninformative as a molecular function (it reflects RPS3 being a NEDD8 substrate rather than a specific binding activity), so it is retained only as non-core documentation of the interaction/modification. Supporting Evidence: PMID:18274552 we identified a subset of ribosomal proteins as novel targets for the NEDD8 pathway. We further show that the lack of NEDDylation in cells causes ribosomal protein instability.
GO:0005515 protein binding	IPI PMID:19656744 Ribosomal protein S3: A multi-functional protein that intera...	KEEP AS NON CORE	Summary: RPS3 interacts with both p53 and MDM2 through its KH domain and acts as a scaffold on 8-oxoG-containing DNA for binding of MDM2 and p53. Reason: Generic protein binding term; the specific p53/MDM2 interactions are an extra-ribosomal moonlighting context. Retained as non-core; the more informative MF aspects of this paper are captured by the separate oxidized-pyrimidine DNA binding and negative-regulation-of-ubiquitination annotations from the same reference. Supporting Evidence: PMID:19656744 We identified ribosomal protein S3 (RPS3), whose interaction with MDM2, and notably p53, was further established by His and GST pull-down assays
GO:0005515 protein binding	IPI PMID:20618440 Proteomic and biochemical analysis of 14-3-3-binding protein...	KEEP AS NON CORE	Summary: RPS3 was recovered among 14-3-3-binding proteins in a proteomic survey during C2-ceramide-induced apoptosis. Reason: Generic protein binding from a high-throughput 14-3-3 affinity proteomics study; uninformative as a specific molecular function and not validated as a physiologically core interaction. Retained as non-core. Supporting Evidence: PMID:20618440 Proteomic and biochemical analysis of 14-3-3-binding proteins during C2-ceramide-induced apoptosis
GO:0005515 protein binding	IPI PMID:21145461 Dynamics of cullin-RING ubiquitin ligase network revealed by...	KEEP AS NON CORE	Summary: RPS3 was detected as an interactor in a systematic quantitative proteomic study of the cullin-RING ubiquitin ligase (CRL) network. Reason: Generic protein binding from a large-scale CRL interactome study; uninformative as a specific molecular function and not independently validated for RPS3. Retained as non-core. Supporting Evidence: PMID:21145461 Dynamics of cullin-RING ubiquitin ligase network revealed by systematic quantitative proteomics
GO:0005515 protein binding	IPI PMID:21146485 Identification of cyclophilin-40-interacting proteins reveal...	KEEP AS NON CORE	Summary: RPS3 was identified among cyclophilin-40 (CyP40)-interacting proteins in a proteomic pull-down survey. Reason: Generic protein binding from a single-bait interaction proteomics study; uninformative as a specific molecular function and not validated as a physiologically core interaction for RPS3. Retained as non-core. Supporting Evidence: PMID:21146485 Identification of cyclophilin-40-interacting proteins reveals potential cellular function of cyclophilin-40
GO:0005515 protein binding	IPI PMID:21399639 IKKβ phosphorylation regulates RPS3 nuclear translocation an...	KEEP AS NON CORE	Summary: In the context of NF-kB signaling, RPS3 nuclear translocation depends on IKKβ-mediated phosphorylation of RPS3 Ser209 and association with the nuclear import machinery (importin-α), as demonstrated by co-IP and functional assays. Reason: Generic protein binding term. The underlying interactions (IKKβ, importin) are part of RPS3's regulated extra-ribosomal NF-kB role, which is captured more informatively by the NF-kB complex and transcription-regulation annotations. Retained as non-core. Supporting Evidence: PMID:21399639 phosphorylation of RPS3 Ser209 by the kinase IKKβ was crucial for nuclear localization of RPS3 in response to activating stimuli
GO:0005515 protein binding	IPI PMID:22113938 A bead-based approach for large-scale identification of in v...	KEEP AS NON CORE	Summary: RPS3 was detected in a bead-based large-scale screen for in vitro kinase substrates. Reason: Generic protein binding from a high-throughput in vitro kinase-substrate screen; uninformative as a specific molecular function and not validated physiologically. Retained as non-core. Supporting Evidence: PMID:22113938 A bead-based approach for large-scale identification of in vitro kinase substrates
GO:0005515 protein binding	IPI PMID:24457201 Ribosomal protein S3 interacts with the NF-κB inhibitor IκBα...	KEEP AS NON CORE	Summary: RPS3 interacts directly with the NF-kB inhibitor IκBα, which sequesters both p65 and RPS3 in the cytoplasm, maintaining an RPS3 pool for the NF-kB pathway. Reason: Generic protein binding term, but the specific IκBα interaction is part of RPS3's regulated extra-ribosomal NF-kB role. This is non-core relative to the ribosomal function; the NF-kB role is captured by the NF-kB complex and transcription-regulation annotations. Supporting Evidence: PMID:24457201 in resting HEK293 cells, RPS3 interacts with NF-κB inhibitor IκBα
GO:0005515 protein binding	IPI PMID:24725412 Ribosomal protein s15 phosphorylation mediates LRRK2 neurode...	KEEP AS NON CORE	Summary: RPS3 was detected as an interactor in a study centered on LRRK2-mediated phosphorylation of ribosomal protein S15 in Parkinson's disease models. Reason: Generic protein binding from a study whose focus is RPS15, not RPS3; uninformative as a specific molecular function for RPS3 and not validated as a physiologically core interaction. Retained as non-core. Supporting Evidence: PMID:24725412 Ribosomal protein s15 phosphorylation mediates LRRK2 neurodegeneration in Parkinson's disease
GO:0005515 protein binding	IPI PMID:25609649 Proteomic analyses reveal distinct chromatin-associated and ...	KEEP AS NON CORE	Summary: RPS3 was identified in a proteomic analysis of chromatin-associated and soluble transcription factor complexes. Reason: Generic protein binding from a large-scale complex proteomics study; uninformative as a specific molecular function and not independently validated for RPS3. Retained as non-core. Supporting Evidence: PMID:25609649 Proteomic analyses reveal distinct chromatin-associated and soluble transcription factor complexes
GO:0005515 protein binding	IPI PMID:26526615 Caspase-3 cleaved p65 fragment dampens NF-κB-mediated anti-a...	KEEP AS NON CORE	Summary: The caspase-3-generated p65(1-97) fragment interferes with RPS3 and retards its nuclear translocation, dampening RPS3/NF-kB-dependent anti-apoptotic gene expression, supporting a physical RPS3-p65 interaction in NF-kB signaling. Reason: Generic protein binding term; the specific RPS3-p65 interaction is part of RPS3's extra-ribosomal NF-kB specifier role, captured more informatively by the NF-kB complex and transcription-regulation annotations. Retained as non-core. Supporting Evidence: PMID:26526615 the p65(1-97) fragment generated by Caspase-3 cleavage interferes with ribosomal protein S3 (RPS3), an NF-κB "specifier" subunit, and selectively retards the nuclear translocation of RPS3
GO:0005515 protein binding	IPI PMID:30021884 Histone Interaction Landscapes Visualized by Crosslinking Ma...	KEEP AS NON CORE	Summary: RPS3 was detected among histone-interacting proteins by crosslinking mass spectrometry in intact cell nuclei. Reason: Generic protein binding from a high-throughput crosslinking-MS histone interactome study; uninformative as a specific molecular function and not independently validated for RPS3. Retained as non-core. Supporting Evidence: PMID:30021884 Histone Interaction Landscapes Visualized by Crosslinking Mass Spectrometry in Intact Cell Nuclei
GO:0005515 protein binding	IPI PMID:31046837 Parkinson's disease-associated LRRK2-G2019S mutant acts thro...	KEEP AS NON CORE	Summary: RPS3 was detected as an interactor in a study of LRRK2-G2019S regulation of SERCA activity and ER stress in astrocytes. Reason: Generic protein binding from a study not focused on RPS3; uninformative as a specific molecular function for RPS3 and not validated as a physiologically core interaction. Retained as non-core. Supporting Evidence: PMID:31046837 Parkinson's disease-associated LRRK2-G2019S mutant acts through regulation of SERCA activity to control ER stress in astrocytes
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	KEEP AS NON CORE	Summary: RPS3 appears in the HuRI reference map of the human binary protein interactome (yeast two-hybrid). Reason: Generic protein binding from a genome-scale binary interactome map; uninformative as a specific molecular function and not individually validated for RPS3. Retained as non-core. Supporting Evidence: PMID:32296183 A reference map of the human binary protein interactome
GO:0005515 protein binding	IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ...	KEEP AS NON CORE	Summary: RPS3 was detected in an interactome map of neurodegenerative disease proteins. Reason: Generic protein binding from a large-scale neurodegenerative-disease interactome study; uninformative as a specific molecular function and not independently validated for RPS3. Retained as non-core. Supporting Evidence: PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains
GO:0005515 protein binding	IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling...	KEEP AS NON CORE	Summary: RPS3 appears in the BioPlex dual proteome-scale AP-MS interaction networks. Reason: Generic protein binding from a genome-scale AP-MS interactome; for an abundant ribosomal protein such co-purifications are expected and uninformative as a specific molecular function. Retained as non-core. Supporting Evidence: PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome
GO:0005515 protein binding	IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce...	KEEP AS NON CORE	Summary: RPS3 was characterized in the OpenCell endogenous-tagging interaction/ localization atlas of human cellular organization. Reason: Generic protein binding from a systematic endogenous-tagging interactome atlas; uninformative as a specific molecular function. Retained as non-core. Supporting Evidence: PMID:35271311 OpenCell: Endogenous tagging for the cartography of human cellular organization
GO:0005515 protein binding	IPI PMID:39251607 Systematic identification of post-transcriptional regulatory...	KEEP AS NON CORE	Summary: RPS3 was identified in a systematic study of post-transcriptional regulatory modules. Reason: Generic protein binding from a high-throughput post-transcriptional regulatory network study; uninformative as a specific molecular function and not independently validated for RPS3. Retained as non-core. Supporting Evidence: PMID:39251607 Systematic identification of post-transcriptional regulatory modules
GO:0005515 protein binding	IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func...	KEEP AS NON CORE	Summary: RPS3 was included in multimodal cell maps integrating imaging and AP-MS data for structural and functional genomics. Reason: Generic protein binding from a large-scale multimodal interactome/imaging study; uninformative as a specific molecular function. Retained as non-core. Supporting Evidence: PMID:40205054 Multimodal cell maps as a foundation for structural and functional genomics
GO:0003906 DNA-(apurinic or apyrimidinic site) endonuclease activity	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: RPS3 has historical AP-site endonuclease activity claims, but intrinsic human AP endonuclease activity is not as well supported as damaged-DNA binding and possible BER cofactor activity. Reason: This automated AP-site endonuclease annotation likely overstates a debated secondary activity. The current synthesis supports lesion binding and BER-associated cofactor roles more strongly than intrinsic human AP-site endonuclease activity. Supporting Evidence: file:human/RPS3/RPS3-deep-research-falcon.md Annotation guidance: treat DNA lesion binding and BER cofactor roles as better-supported than broad “wide-range base-damage endonuclease” claims unless primary human biochemistry is directly cited.
GO:0022627 cytosolic small ribosomal subunit	IEA GO_REF:0000107	ACCEPT	Summary: RPS3 is a component of the cytosolic small ribosomal subunit (40S). Reason: This automated orthology-based annotation matches the core ribosomal cellular component, consistent with the accepted IBA/IDA cytosolic small ribosomal subunit annotations. Supporting Evidence: PMID:23636399 Here we present structures of Drosophila melanogaster and Homo sapiens 80S ribosomes in complex with the translation factor eEF2, E-site transfer RNA and Stm1-like proteins, based on high-resolution cryo-electron-microscopy density maps.
GO:0045202 synapse	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: RPS3 appears in synapse/postsynaptic density proteomic datasets and is used as a ribosome marker in synaptic compartments, but this most likely reflects local translation machinery near synapses rather than a stable, RPS3-specific synaptic component. Reason: The synapse localization is an orthology-transferred annotation based on ribosome/translation-machinery presence in synaptic compartments. Per the deep-research synthesis, evidence is indirect for RPS3-specific synaptic residency, so this is better treated as an over-annotation relative to the core cytosolic ribosome location. Supporting Evidence: file:human/RPS3/RPS3-deep-research-falcon.md Evidence is indirect for human RPS3-specific PSD residency; better treated as synaptic ribosome/local translation association, not a definitive stable PSD component.
GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific	IMP PMID:18045535 Ribosomal protein S3: a KH domain subunit in NF-kappaB compl...	MODIFY	Summary: This annotation is an over-annotation. PMID:18045535 demonstrates that RPS3 acts as a non-Rel subunit of NF-kappaB complexes that synergistically enhances DNA binding of p65 homodimer and p65-p50 heterodimer complexes. RPS3 contains a KH domain (an RNA-binding domain, not a DNA-binding transcription factor domain) and interacts with the NF-kappaB complex via protein-protein interactions with RELA/p65. The study shows RPS3 forms part of the NF-kappaB complex bound to regulatory DNA sites, but RPS3 itself does not directly bind DNA with sequence specificity. This is transcription coactivator activity, not DNA-binding transcription factor activity. The term GO:0001228 requires intrinsic sequence-specific DNA binding, which RPS3 lacks. Reason: The annotation to GO:0001228 (DNA-binding transcription activator activity, RNA polymerase II-specific) is incorrect because this term requires the protein to directly bind DNA in a sequence-specific manner to modulate transcription. RPS3 does not possess a canonical DNA-binding domain for transcriptional regulation - its KH domain is an RNA-binding motif. Per PMID:18045535, RPS3 functions as "a non-Rel subunit of p65 homodimer and p65-p50 heterodimer DNA-binding complexes that synergistically enhances DNA binding." RPS3 acts through protein-protein interactions with the NF-kappaB transcription factors, enhancing their activity. This is the definition of transcription coactivator activity (GO:0003713), not DNA-binding transcription factor activity. The appropriate replacement annotation is GO:0003713 (transcription coactivator activity); DNA-binding transcription factor binding is captured by a separate accepted GO:0140297 annotation. Proposed replacements: transcription coactivator activity Supporting Evidence: PMID:18045535 We identified ribosomal protein S3 (RPS3), a KH domain protein, as a non-Rel subunit of p65 homodimer and p65-p50 heterodimer DNA-binding complexes that synergistically enhances DNA binding.
GO:0005783 endoplasmic reticulum	IDA GO_REF:0000052	MARK AS OVER ANNOTATED	Summary: An immunofluorescence-based ER annotation. Ribosomes engaged in co-translational translocation associate with the rough ER, but there is no direct RPS3-specific evidence supporting stable ER residency as a distinct function. Reason: ER signal for a ribosomal protein most plausibly reflects ER-associated (rough ER) ribosomes rather than an RPS3-specific ER localization. The deep-research synthesis found no direct RPS3-specific support for stable ER localization, so this is treated as an over-annotation relative to the core cytosolic ribosome location. Supporting Evidence: file:human/RPS3/RPS3-deep-research-falcon.md ER-related translation appears generic/translatome-level, not RPS3-specific
GO:0005829 cytosol	IDA GO_REF:0000052	ACCEPT	Summary: RPS3 localizes to the cytosol as part of the cytosolic ribosome. Reason: Cytosol is the expected cellular location for RPS3's core cytosolic ribosomal function and is consistent with the accepted cytosolic ribosome annotation. Supporting Evidence: file:human/RPS3/RPS3-deep-research-falcon.md RPS3 is a core protein of the cytosolic small ribosomal subunit (40S) and therefore supports GO annotations centered on (i) structural constituent of ribosome, (ii) cytoplasmic translation, and (iii) localization to cytosolic ribosome / small ribosomal subunit / cytosol (cytoplasm).
GO:0002181 cytoplasmic translation	NAS PMID:25901680 Structure of the human 80S ribosome.	ACCEPT	Summary: RPS3 is a 40S small-subunit protein of the human cytosolic ribosome and thereby participates in cytoplasmic translation. Reason: Cytoplasmic translation is the core biological process for RPS3's structural ribosomal role, supported by the near-atomic structure of the human 80S ribosome. Supporting Evidence: PMID:25901680 Ribosomes are translational machineries that catalyse protein synthesis.
GO:0005737 cytoplasm	NAS PMID:25901680 Structure of the human 80S ribosome.	ACCEPT	Summary: RPS3 is located in the cytoplasm as part of the cytosolic ribosome. Reason: Cytoplasm is the expected, core cellular location for RPS3's cytosolic ribosomal function, consistent with the human 80S ribosome structure and accepted cytosol/cytosolic ribosome annotations. Supporting Evidence: PMID:25901680 Structure of the human 80S ribosome.
GO:0002181 cytoplasmic translation	NAS PMID:1712897 Ribosomal protein genes are overexpressed in colorectal canc...	ACCEPT	Summary: RPS3 was cloned as the human S3 ribosomal protein, a component of the translation machinery, overexpressed in colorectal cancer. Reason: Cytoplasmic translation is the core process for this small-subunit ribosomal protein. The reference establishes RPS3 as the human S3 ribosomal protein. Supporting Evidence: PMID:1712897 isolation of a cDNA clone encoding the human S3 ribosomal protein
GO:0002181 cytoplasmic translation	IC PMID:8706699 Characterization of the human small-ribosomal-subunit protei...	ACCEPT	Summary: RPS3 was identified by protein sequencing and mass spectrometry as one of the proteins of the human 40S ribosomal subunit, supporting its role in cytoplasmic translation. Reason: Cytoplasmic translation is the core process inferred from RPS3's experimentally confirmed identity as a 40S small-subunit ribosomal protein. Supporting Evidence: PMID:8706699 Characterization of the human small-ribosomal-subunit proteins by N-terminal and internal sequencing, and mass spectrometry.
GO:0002183 cytoplasmic translational initiation	NAS PMID:15883184 Mass spectrometric analysis of the human 40S ribosomal subun...	ACCEPT	Summary: RPS3 is a 40S small-subunit protein located at the mRNA entry channel and is part of the 40S complex recruited during cap-independent (HCV IRES) and canonical translation initiation. Reason: RPS3 sits at the mRNA entry channel of the 40S subunit and contacts mRNA in initiation complexes (PMID:18464793), so participation in cytoplasmic translational initiation is consistent with its core ribosomal role. The reference identifies RPS3 as part of native and IRES-bound 40S complexes. Supporting Evidence: PMID:15883184 a global protein composition analysis of native and IRES-bound 40S ribosomal complexes has been conducted PMID:18464793 Crosslinking of mRNA positions (+)11 to ribosomal protein (rp) rpS2(S5p) and rpS3(S3p)
GO:2000144 positive regulation of DNA-templated transcription initiation	IMP PMID:18045535 Ribosomal protein S3: a KH domain subunit in NF-kappaB compl...	ACCEPT	Summary: This annotation reflects RPS3's role in enhancing NF-kappaB-mediated transcription as demonstrated in PMID:18045535. The study showed that RPS3 knockdown impaired NF-kappaB-mediated transcription of selected p65 target genes, and lymphocyte-activating stimuli caused nuclear translocation of RPS3 to form part of NF-kappaB bound to specific regulatory sites in chromatin. While this is a biological process annotation that could be retained, it should be noted that RPS3's effect on transcription is indirect - through its role as a coactivator of NF-kappaB rather than as a direct transcription factor. Reason: The biological process annotation to positive regulation of DNA-templated transcription initiation is appropriate because RPS3 does positively regulate transcription through its role in the NF-kappaB complex, even though this regulation is through protein-protein interactions rather than direct DNA binding. PMID:18045535 demonstrates that RPS3 is "an essential but previously unknown subunit of NF-kappaB involved in the regulation of key genes in rapid cellular activation responses." Supporting Evidence: PMID:18045535 RPS3 knockdown impaired NF-kappaB-mediated transcription of selected p65 target genes but not nuclear shuttling or global protein translation. Rather, lymphocyte-activating stimuli caused nuclear translocation of RPS3, parallel to p65, to form part of NF-kappaB bound to specific regulatory sites in chromatin.
GO:0014069 postsynaptic density	EXP PMID:21170055 Characterization of the proteome, diseases and evolution of ...	KEEP AS NON CORE	Summary: RPS3 was detected in a proteomic characterization of the isolated human postsynaptic density, consistent with ribosome/local-translation machinery at synapses. Reason: Detection in an isolated PSD proteome most likely reflects synaptic ribosomes/local translation machinery rather than an RPS3-specific structural role at the postsynaptic density. Retained as non-core given the indirect, proteome-survey nature of the evidence. Supporting Evidence: PMID:21170055 We isolated the postsynaptic density from human neocortex (hPSD) and identified 1,461 proteins.
GO:0014069 postsynaptic density	IDA PMID:21170055 Characterization of the proteome, diseases and evolution of ...	KEEP AS NON CORE	Summary: Duplicate (IDA) of the postsynaptic density detection from the same human PSD proteome study. Reason: Same rationale as the EXP-coded postsynaptic density annotation from this reference: most likely reflects synaptic ribosomes/local translation machinery rather than an RPS3-specific PSD structural role. Retained as non-core. Supporting Evidence: PMID:21170055 We isolated the postsynaptic density from human neocortex (hPSD) and identified 1,461 proteins.
GO:0022626 cytosolic ribosome	IDA PMID:23636399 Structures of the human and Drosophila 80S ribosome.	ACCEPT	Summary: RPS3 is a component of the cytosolic ribosome, specifically the 40S small ribosomal subunit. Reason: This cellular component is supported by structural evidence for the human cytosolic 80S ribosome and is consistent with the accepted cytosolic small ribosomal subunit annotation. Supporting Evidence: PMID:23636399 Here we present structures of Drosophila melanogaster and Homo sapiens 80S ribosomes in complex with the translation factor eEF2, E-site transfer RNA and Stm1-like proteins, based on high-resolution cryo-electron-microscopy density maps. file:human/RPS3/RPS3-deep-research-falcon.md RPS3 is a core protein of the cytosolic small ribosomal subunit (40S) and therefore supports GO annotations centered on (i) structural constituent of ribosome, (ii) cytoplasmic translation, and (iii) localization to cytosolic ribosome / small ribosomal subunit / cytosol (cytoplasm).
GO:0003684 damaged DNA binding	IDA PMID:15518571 Human ribosomal protein S3 interacts with DNA base excision ...	KEEP AS NON CORE	Summary: Human RPS3 binds damaged DNA, including abasic (AP) sites and 8-oxoG lesions, with high apparent affinity as shown by surface plasmon resonance. Reason: Damaged DNA binding is a well-supported extra-ribosomal molecular function of human RPS3 (multiple independent IDA assays: PMID:14706345, PMID:18610840, PMID:16737853). It is a genuine moonlighting activity but secondary to the core ribosomal structural function, so retained as non-core. Supporting Evidence: PMID:14706345 An even more dramatic five orders of magnitude higher binding affinity for AP DNA was found for hS3 as opposed to hOGG1.
GO:0006284 base-excision repair	IDA PMID:15518571 Human ribosomal protein S3 interacts with DNA base excision ...	KEEP AS NON CORE	Summary: Human RPS3 physically interacts with the BER enzymes OGG1 and APE1/Ref-1 and can stimulate OGG1 N-glycosylase activity, supporting participation in base-excision repair as a binding partner/modulator rather than as a core BER enzyme. Reason: RPS3 participates in BER through cofactor-like interactions (binding and stimulating OGG1/APE1; PMID:18973764 shows it also stimulates UNG), but this is an extra-ribosomal moonlighting role; note that under some conditions bound RPS3 can inhibit OGG1 repair (PMID:16737853), so the role is context-dependent. Retained as non-core. Supporting Evidence: PMID:15518571 hOGG1 N-glycosylase activity becomes increasingly more robust in the presence of hS3. Human S3 was found to co-immunoprecipitate with both hOGG1 and APE/Ref-1
GO:0005515 protein binding	IPI PMID:19059439 PKCdelta-dependent functional switch of rpS3 between transla...	KEEP AS NON CORE	Summary: RPS3 is phosphorylated by PKCdelta, which interacts with RPS3 and mobilizes non-ribosomal RPS3 to the nucleus for DNA repair. Reason: Generic protein binding term; the specific PKCdelta interaction is part of the regulated extra-ribosomal DNA-repair switch and is non-core relative to the ribosomal function. Retained as non-core documentation. Supporting Evidence: PMID:19059439 PKCdelta phosphorylates rpS3 resulting in its mobilization in the nucleus to repair damaged DNA
GO:0006281 DNA repair	IMP PMID:19059439 PKCdelta-dependent functional switch of rpS3 between transla...	KEEP AS NON CORE	Summary: RPS3 knockdown increased sensitivity to genotoxic stress, and the phosphorylation-dependent repair endonuclease activity of non-ribosomal RPS3 was required for this protection, supporting an extra-ribosomal DNA repair role. Reason: DNA repair is a documented extra-ribosomal moonlighting function but is secondary to the core ribosomal role. Note that other work reports RPS3 knockdown protects cells from genotoxic stress (PMID:17049931), so the net effect on repair is context-dependent. Supporting Evidence: PMID:19059439 rpS3 knock-down cells showed more sensitivity to genotoxic stress than control cells, and this sensitivity was corrected by overexpressed wild-type rpS3 but not by phosphorylation defective rpS3
GO:0007059 chromosome segregation	IMP PMID:23131551 Ribosomal protein S3 localizes on the mitotic spindle and fu...	KEEP AS NON CORE	Summary: RPS3 depletion caused mitotic arrest at metaphase with abnormal spindle shape and chromosome movement, consistent with a role in proper chromosome segregation via its mitotic-spindle/microtubule function. Reason: The chromosome segregation phenotype is downstream of RPS3's reported microtubule-associated/spindle role during mitosis, an extra-ribosomal moonlighting context rather than the core ribosomal function. Retained as non-core. Supporting Evidence: PMID:23131551 Depletion of the rpS3 proteins caused mitotic arrest during the metaphase. Furthermore, the shape of the spindle and chromosome movement in the rpS3 depleted cell was abnormal.
GO:0010628 positive regulation of gene expression	IMP PMID:20605787 Ribosomal protein S3, a new substrate of Akt, serves as a si...	KEEP AS NON CORE	Summary: RPS3 up-regulated the proapoptotic proteins Dp5/Hrk and Bim by binding to and acting synergistically with the transcription factor E2F1 in neuronal apoptosis. Reason: This positive regulation of gene expression is an extra-ribosomal transcriptional-coregulator activity (via E2F1), context-specific to neuronal apoptosis, and non-core relative to the ribosomal role. The mechanistic E2F1 interaction is captured by the DNA-binding transcription factor binding annotation from the same reference. Supporting Evidence: PMID:20605787 RPS3 induced neuronal apoptosis, up-regulating proapoptotic proteins Dp5/Hrk and Bim by binding to E2F1 and acting synergistically with it.
GO:0005743 mitochondrial inner membrane	IDA PMID:23911537 Cytoplasmic ribosomal protein S3 (rpS3) plays a pivotal role...	KEEP AS NON CORE	Summary: Under elevated ROS, RPS3 accumulates in the mitochondria (entry mediated by HSP90/HSP70/TOM70) to participate in mtDNA damage repair. Reason: This IDA captures stress-induced (ROS-triggered) mitochondrial accumulation of RPS3 for mtDNA damage surveillance, a regulated extra-ribosomal context, not constitutive inner-membrane residency. It is kept as non-core, distinct from the broad IEA mitochondrial inner membrane annotation that was removed. Supporting Evidence: PMID:23911537 Increased ROS induces rpS3 accumulation in the mitochondria for DNA repair while significantly decreasing the cellular protein synthesis.
GO:0005759 mitochondrial matrix	IDA PMID:23911537 Cytoplasmic ribosomal protein S3 (rpS3) plays a pivotal role...	KEEP AS NON CORE	Summary: RPS3 accumulates within mitochondria under oxidative stress to repair mitochondrial DNA, consistent with localization to the mitochondrial matrix where the mtDNA resides. Reason: Stress-induced mitochondrial localization for mtDNA repair is a regulated extra-ribosomal moonlighting role, secondary to the core cytosolic ribosomal function. Retained as non-core. Supporting Evidence: PMID:23911537 rpS3 accumulates in the mitochondria to repair damaged DNA due to the decreased interaction between rpS3 and HSP90 in the cytosol.
GO:0005515 protein binding	IPI PMID:22510408 Ribosomal protein S3 interacts with TRADD to induce apoptosi...	KEEP AS NON CORE	Summary: RPS3 physically interacts with TRADD and is recruited to the death-inducing signaling complex (DISC) to promote caspase-dependent JNK activation and apoptosis under stress. Reason: Generic protein binding term; the specific TRADD interaction underlies an extra-ribosomal pro-apoptotic moonlighting role and is non-core relative to the ribosomal function. Retained as non-core. Supporting Evidence: PMID:22510408 This apoptotic effect was shown to result from the physical interaction between rpS3 and TRADD, as assessed by coimmunoprecipitation.
GO:0005515 protein binding	IPI PMID:20041225 Bacterial effector binding to ribosomal protein s3 subverts ...	KEEP AS NON CORE	Summary: The enterohemorrhagic E. coli type III secretion effectors NleH1/NleH2 bind the N-terminus of human RPS3 to subvert RPS3-dependent NF-kB function. Reason: Generic protein binding term capturing a host-pathogen interaction relevant to RPS3's NF-kB role; non-core relative to the ribosomal function. Retained as non-core. Supporting Evidence: PMID:20041225 the E. coli O157:H7 nleH1 and nleH2 genes encode T3SS effectors that bind to the human ribosomal protein S3 (RPS3), a subunit of ... NF-kappaB transcriptional complexes
GO:0140297 DNA-binding transcription factor binding	IPI PMID:20605787 Ribosomal protein S3, a new substrate of Akt, serves as a si...	ACCEPT	Summary: Well-supported annotation. PMID:20605787 demonstrates that RPS3 binds to the E2F1 transcription factor and acts synergistically with E2F1 to up-regulate proapoptotic proteins Dp5/Hrk and Bim. This interaction is regulated by Akt-mediated phosphorylation of RPS3, which perturbs its interaction with E2F1. This annotation is appropriate and supports the role of RPS3 as a transcriptional coregulator that binds transcription factors rather than DNA directly. Reason: The annotation to DNA-binding transcription factor binding is correct based on the evidence in PMID:20605787 showing RPS3 physically interacts with E2F1, a DNA-binding transcription factor. This is consistent with RPS3's role as a transcriptional coregulator that modulates transcription through protein-protein interactions with transcription factors (both E2F1 and NF-kappaB/RELA). Supporting Evidence: PMID:20605787 RPS3 induced neuronal apoptosis, up-regulating proapoptotic proteins Dp5/Hrk and Bim by binding to E2F1 and acting synergistically with it. Akt-dependent phosphorylation of RPS3 inhibited its proapoptotic function and perturbed its interaction with E2F1.
GO:0002181 cytoplasmic translation	IC PMID:23636399 Structures of the human and Drosophila 80S ribosome.	ACCEPT	Summary: RPS3 is part of the human 80S ribosome resolved by cryo-EM, supporting its role in cytoplasmic translation. Reason: Cytoplasmic translation is the core biological process for RPS3, inferred from its experimentally confirmed structural presence in the human cytosolic ribosome. Supporting Evidence: PMID:23636399 Protein synthesis in all cells is carried out by macromolecular machines called ribosomes.
GO:0003735 structural constituent of ribosome	IDA PMID:23636399 Structures of the human and Drosophila 80S ribosome.	ACCEPT	Summary: RPS3/uS3 is resolved as a structural protein of the human cytosolic small ribosomal subunit in the 80S ribosome cryo-EM structure. Reason: This is the core, directly-evidenced molecular function of RPS3. Supporting Evidence: PMID:23636399 Here we present structures of Drosophila melanogaster and Homo sapiens 80S ribosomes in complex with the translation factor eEF2, E-site transfer RNA and Stm1-like proteins, based on high-resolution cryo-electron-microscopy density maps.
GO:0030544 Hsp70 protein binding	IDA PMID:23911537 Cytoplasmic ribosomal protein S3 (rpS3) plays a pivotal role...	KEEP AS NON CORE	Summary: RPS3 interacts with HSP70 (with HSP90 and TOM70) to regulate its entry into mitochondria during oxidative stress. Reason: This is a specific, directly-evidenced chaperone interaction supporting RPS3's stress-induced mitochondrial trafficking, an extra-ribosomal moonlighting context. More informative than generic protein binding, but non-core relative to the ribosomal function. Supporting Evidence: PMID:23911537 the accumulation of rpS3 was regulated by interaction with HSP90, HSP70, and TOM70.
GO:0034614 cellular response to reactive oxygen species	IDA PMID:23911537 Cytoplasmic ribosomal protein S3 (rpS3) plays a pivotal role...	KEEP AS NON CORE	Summary: Elevated cellular ROS triggers RPS3 accumulation in mitochondria for mtDNA repair and a decrease in protein synthesis, indicating a cellular response to reactive oxygen species. Reason: RPS3's ROS-responsive mitochondrial relocalization is a regulated extra-ribosomal stress response, non-core relative to its ribosomal function. Retained as non-core. Supporting Evidence: PMID:23911537 When cellular ROS levels increase, the mitochondrial genes are highly vulnerable to DNA damage. Increased ROS induces rpS3 accumulation in the mitochondria for DNA repair
GO:0019899 enzyme binding	IPI PMID:18973764 Human ribosomal protein S3 (hRpS3) interacts with uracil-DNA...	KEEP AS NON CORE	Summary: Human RPS3 interacts with uracil-DNA glycosylase (UNG) and stimulates its glycosylase activity, as shown by co-IP and GST pull-down assays. Reason: Enzyme binding here captures a specific, directly-evidenced interaction with a BER enzyme (UNG); more informative than generic protein binding but part of RPS3's extra-ribosomal BER-cofactor moonlighting role, so non-core. Supporting Evidence: PMID:18973764 We identified, for the first time, the interaction between hRpS3 and human uracil-DNA glycosylase (hUNG) ... hRpS3 dramatically stimulated the uracil-excision activity of hUNG, whereas hRpS3 alone had no cleavage activity.
GO:0005515 protein binding	IPI PMID:28065601 Initiation of Quality Control during Poly(A) Translation Req...	KEEP AS NON CORE	Summary: Study of ZNF598-mediated site-specific 40S ribosomal ubiquitination initiating ribosome-associated quality control; RPS3/uS3 is a 40S component in this context. Reason: Generic protein binding term arising from a ribosome-associated quality control study; for an abundant 40S protein this association is expected and uninformative as a specific molecular function. Retained as non-core. Supporting Evidence: PMID:28065601 Initiation of Quality Control during Poly(A) Translation Requires Site-Specific Ribosome Ubiquitination.
GO:0005515 protein binding	IPI PMID:28132843 ZNF598 and RACK1 Regulate Mammalian Ribosome-Associated Qual...	KEEP AS NON CORE	Summary: ZNF598 and RACK1 regulate 40S ribosomal ubiquitylation during ribosome-associated quality control; RACK1 regulates ubiquitination of RPS2, RPS3, and RPS20. Reason: Generic protein binding term from a ribosome-associated quality control study. The specific finding (RACK1-regulated RPS3 ubiquitylation) is part of ribosome regulation rather than a discrete RPS3 binding function; retained as non-core. Supporting Evidence: PMID:28132843 RACK1 regulates RPS2, RPS3, and RPS20 ubiquitylation
GO:0005634 nucleus	IDA PMID:17560175 Translocation of human ribosomal protein S3 to sites of DNA ...	KEEP AS NON CORE	Summary: Following genotoxic stress, human RPS3 translocates from the cytoplasm to the nucleus (dependent on ERK-mediated T42 phosphorylation), where it co-localizes with 8-oxoG damage foci. Reason: Stimulus-dependent nuclear translocation is well documented but represents a regulated extra-ribosomal DNA-damage-response context rather than the core cytosolic ribosomal location. Retained as non-core. Supporting Evidence: PMID:17560175 hS3 is capable of carrying out both roles by its ex vivo translocation from the cytoplasm to the nucleus as a consequence of genotoxic stress.
GO:0005634 nucleus	IMP PMID:21399639 IKKβ phosphorylation regulates RPS3 nuclear translocation an...	KEEP AS NON CORE	Summary: Nuclear localization of RPS3 in response to activating stimuli requires IKKβ-mediated phosphorylation of RPS3 Ser209, as shown using phospho-mutant analysis. Reason: Regulated, stimulus-dependent nuclear localization tied to NF-kB signaling; non-core relative to the cytosolic ribosomal location. Retained as non-core. Supporting Evidence: PMID:21399639 phosphorylation of RPS3 Ser209 by the kinase IKKβ was crucial for nuclear localization of RPS3 in response to activating stimuli
GO:0005925 focal adhesion	HDA PMID:21423176 Analysis of the myosin-II-responsive focal adhesion proteome...	MARK AS OVER ANNOTATED	Summary: RPS3 was detected in a high-throughput proteomic analysis of isolated focal adhesions. Reason: Detection of an abundant ribosomal protein in a focal-adhesion proteome is most plausibly a co-isolation/contaminant signal rather than evidence of an RPS3-specific focal adhesion role. No targeted validation supports stable focal-adhesion localization, so this is treated as an over-annotation. Supporting Evidence: PMID:21423176 we performed proteomic analysis of isolated focal adhesions ... We identified 905 focal adhesion proteins
GO:0071159 NF-kappaB complex	IDA PMID:18045535 Ribosomal protein S3: a KH domain subunit in NF-kappaB compl...	ACCEPT	Summary: Well-supported annotation. PMID:18045535 used tandem affinity purification and mass spectrometry to identify RPS3 as a component of the NF-kappaB complex. The study clearly shows that RPS3 is "a non-Rel subunit of p65 homodimer and p65-p50 heterodimer DNA-binding complexes." RPS3 interacts with RELA (p65) and forms part of the NF-kappaB transcription factor complex bound to chromatin in response to activating stimuli. Reason: The proteomic approach in PMID:18045535 directly demonstrates RPS3 is a component of NF-kappaB complexes. This was validated by co-IP experiments and functional studies showing RPS3 is essential for NF-kappaB function in gene regulation. Supporting Evidence: PMID:18045535 We identified ribosomal protein S3 (RPS3), a KH domain protein, as a non-Rel subunit of p65 homodimer and p65-p50 heterodimer DNA-binding complexes that synergistically enhances DNA binding.
GO:0005829 cytosol	IDA PMID:18045535 Ribosomal protein S3: a KH domain subunit in NF-kappaB compl...	ACCEPT	Summary: RPS3 is present in the cytosol, where it associates with NF-kB inhibitory complexes prior to stimulus-induced nuclear translocation. Reason: Cytosol is the expected, core cellular location for RPS3 (cytosolic ribosome), consistent with the accepted cytosol/cytosolic ribosome annotations. Supporting Evidence: PMID:18045535 lymphocyte-activating stimuli caused nuclear translocation of RPS3, parallel to p65
GO:1905053 positive regulation of base-excision repair	IDA PMID:18973764 Human ribosomal protein S3 (hRpS3) interacts with uracil-DNA...	KEEP AS NON CORE	Summary: RPS3 stimulates the uracil-excision (glycosylase) activity of UNG and its knockdown reduces uracil-excision activity in cell extracts, supporting positive regulation of base-excision repair. Reason: RPS3 positively regulates BER as a cofactor that stimulates UNG (and OGG1, PMID:15518571) rather than acting as a core BER enzyme. This is a genuine extra-ribosomal moonlighting role, retained as non-core. Note that under conditions where RPS3 binds 8-oxoG it can instead inhibit OGG1 repair (PMID:16737853), so the regulation is context-dependent. Supporting Evidence: PMID:18973764 The disruption of hRpS3 by small-interfering RNA (siRNA-hRpS3) transfection reduced the uracil-excision activity preserved in cell extracts, whereas the supplement of purified hRpS3 retained uracil-excision activity.
GO:0005515 protein binding	IPI PMID:24965446 Host factors that interact with the pestivirus N-terminal pr...	KEEP AS NON CORE	Summary: RPS3 was identified among ribosomal proteins/ribonucleoproteins that co-purify with the pestivirus N-terminal protease Npro in the ribonucleoprotein complex. Reason: Generic protein binding from a viral-protein interaction proteomics study; for an abundant ribosomal protein this co-purification is expected and uninformative as a specific molecular function. Retained as non-core. Supporting Evidence: PMID:24965446 Host factors that interact with the pestivirus N-terminal protease, Npro, are components of the ribonucleoprotein complex
GO:0017148 negative regulation of translation	IDA PMID:20217897 RpS3 translation is repressed by interaction with its own mR...	KEEP AS NON CORE	Summary: Free (non-ribosomal) RPS3 binds its own cognate mRNA via its C-terminal domain and represses its own translation in a feedback mechanism. Reason: This is a specific, directly-evidenced autoregulatory negative regulation of translation. It is a genuine but specialized function distinct from the core structural ribosomal role, so retained as non-core. Supporting Evidence: PMID:20217897 We here report an additional function of rpS3 in which it represses its own translation by binding to its cognate mRNA.
GO:0061481 response to TNF agonist	IDA PMID:20041225 Bacterial effector binding to ribosomal protein s3 subverts ...	KEEP AS NON CORE	Summary: RPS3 participates in NF-kB-dependent transcriptional responses; in this study its nuclear abundance and RPS3/NF-kB-dependent reporter activity are modulated, and RPS3 functions within TNF/NF-kB activation pathways. Reason: This term reflects RPS3's extra-ribosomal participation in NF-kB-mediated cytokine responses, a context-dependent moonlighting role rather than the core ribosomal function. Retained as non-core. Supporting Evidence: PMID:20041225 NleH1 repressed the transcription of a RPS3/NF-kappaB-dependent reporter plasmid
GO:0005634 nucleus	IDA PMID:20041225 Bacterial effector binding to ribosomal protein s3 subverts ...	KEEP AS NON CORE	Summary: RPS3 has a nuclear pool whose abundance is modulated during NF-kB signaling (NleH1 reduced the nuclear abundance of RPS3). Reason: Nuclear localization in the NF-kB context is a regulated extra-ribosomal pool, non-core relative to the cytosolic ribosomal location. Retained as non-core. Supporting Evidence: PMID:20041225 NleH1, but not NleH2, reduced the nuclear abundance of RPS3 without altering the p50 or p65 NF-kappaB subunits
GO:1901224 positive regulation of non-canonical NF-kappaB signal transduction	IDA PMID:20041225 Bacterial effector binding to ribosomal protein s3 subverts ...	KEEP AS NON CORE	Summary: RPS3 acts as a specifier subunit that positively contributes to NF-kB-dependent transcription; bacterial effector binding to RPS3 subverts this NF-kB function. Reason: RPS3's positive contribution to NF-kB-dependent transcription is a well-supported extra-ribosomal moonlighting role. The specific "non-canonical" qualifier is not strongly distinguished in this reference (which centers on RPS3/p65 transcriptional complexes), but the broad positive NF-kB regulation is supported; retained as non-core. Supporting Evidence: PMID:20041225 Bacterial effector binding to ribosomal protein s3 subverts NF-kappaB function.
GO:0005515 protein binding	IPI PMID:23911537 Cytoplasmic ribosomal protein S3 (rpS3) plays a pivotal role...	KEEP AS NON CORE	Summary: RPS3's mitochondrial entry under oxidative stress is regulated by interaction with HSP90, HSP70, and TOM70. Reason: Generic protein binding term from the mitochondrial mtDNA-surveillance study; the specific chaperone/TOM70 interactions are captured more informatively by the Hsp70/Hsp90 binding annotations from the same reference. Retained as non-core. Supporting Evidence: PMID:23911537 the accumulation of rpS3 was regulated by interaction with HSP90, HSP70, and TOM70.
GO:0045739 positive regulation of DNA repair	IDA PMID:23911537 Cytoplasmic ribosomal protein S3 (rpS3) plays a pivotal role...	KEEP AS NON CORE	Summary: Increasing mitochondrial RPS3 levels reduced cellular ROS and rescued mtDNA damage, indicating RPS3 positively contributes to repair of damaged mitochondrial DNA under oxidative stress. Reason: Positive regulation of (mitochondrial) DNA repair is a stress-induced extra-ribosomal moonlighting role, non-core relative to the ribosomal function. Retained as non-core. Supporting Evidence: PMID:23911537 cellular ROS was decreased and mtDNA damage was rescued when levels of rpS3 were increased in the mitochondria.
GO:0051879 Hsp90 protein binding	IDA PMID:23911537 Cytoplasmic ribosomal protein S3 (rpS3) plays a pivotal role...	KEEP AS NON CORE	Summary: RPS3 interacts with HSP90 in the cytosol; geldanamycin disruption of this interaction stimulates RPS3 accumulation in mitochondria. Reason: Specific, directly-evidenced HSP90 interaction governing RPS3's stress-induced mitochondrial trafficking; more informative than generic protein binding but part of an extra-ribosomal context, so non-core. Supporting Evidence: PMID:23911537 Pretreatment with geldanamycin, which binds to the ATP pocket of HSP90, significantly decreased the interaction of rpS3 with HSP90 and stimulated the accumulation of rpS3 in the mitochondria.
GO:0070301 cellular response to hydrogen peroxide	IDA PMID:23911537 Cytoplasmic ribosomal protein S3 (rpS3) plays a pivotal role...	KEEP AS NON CORE	Summary: RPS3 relocalizes to mitochondria in response to oxidative (ROS/H2O2) stress to participate in mtDNA damage surveillance. Reason: Specific oxidative-stress (hydrogen peroxide) response captured by RPS3's stress-induced mitochondrial trafficking, an extra-ribosomal role; non-core relative to the ribosomal function. Retained as non-core. Supporting Evidence: PMID:23911537 Increased ROS induces rpS3 accumulation in the mitochondria for DNA repair while significantly decreasing the cellular protein synthesis.
GO:0005886 plasma membrane	IDA PMID:22510408 Ribosomal protein S3 interacts with TRADD to induce apoptosi...	KEEP AS NON CORE	Summary: During stress-induced apoptosis, GFP-RPS3 co-localized with TRADD around the plasma membrane (and in the cytoplasm) at the death-inducing signaling complex. Reason: Plasma-membrane-proximal localization is a transient, apoptosis-context observation tied to DISC recruitment, not a stable RPS3 plasma membrane residency. Retained as non-core given the specialized, context-dependent nature. Supporting Evidence: PMID:22510408 GFP-rpS3 colocalized with TRADD around the plasma membrane and in the cytoplasm during apoptosis.
GO:0008017 microtubule binding	IDA PMID:23131551 Ribosomal protein S3 localizes on the mitotic spindle and fu...	KEEP AS NON CORE	Summary: RPS3 localizes on the mitotic spindle and functions as a microtubule-associated protein, with its depletion decreasing microtubule polymerization. Reason: Microtubule binding supports a directly-evidenced mitotic microtubule-associated-protein moonlighting role, distinct from and secondary to the core ribosomal function. Retained as non-core. Supporting Evidence: PMID:23131551 we concluded that rpS3 acts as a microtubule associated protein (MAP) and regulates spindle dynamics during mitosis.
GO:0015631 tubulin binding	IDA PMID:23131551 Ribosomal protein S3 localizes on the mitotic spindle and fu...	KEEP AS NON CORE	Summary: RPS3 associates with the mitotic spindle and microtubules as a microtubule-associated protein. Reason: Tubulin/microtubule binding supports RPS3's directly-evidenced mitotic MAP role, an extra-ribosomal moonlighting function secondary to the core ribosomal role. Retained as non-core. Supporting Evidence: PMID:23131551 rpS3 specifically localizes on the mitotic spindle ... rpS3 acts as a microtubule associated protein (MAP)
GO:0031116 positive regulation of microtubule polymerization	IMP PMID:23131551 Ribosomal protein S3 localizes on the mitotic spindle and fu...	KEEP AS NON CORE	Summary: RPS3 depletion decreased microtubule polymerization, indicating RPS3 promotes microtubule polymerization during mitosis. Reason: Directly supported by loss-of-function evidence, but part of RPS3's mitotic microtubule moonlighting role rather than the core ribosomal function. Retained as non-core. Supporting Evidence: PMID:23131551 Microtubule (MT) polymerization also decreased in rpS3 depleted cells, suggesting that rpS3 is involved in spindle dynamics.
GO:0051225 spindle assembly	IMP PMID:23131551 Ribosomal protein S3 localizes on the mitotic spindle and fu...	KEEP AS NON CORE	Summary: RPS3 depletion produced abnormal spindle shape and mitotic arrest, consistent with a role in proper spindle assembly. Reason: Spindle assembly is supported by loss-of-function data but reflects RPS3's mitotic microtubule moonlighting role, secondary to the core ribosomal function. Retained as non-core. Supporting Evidence: PMID:23131551 the shape of the spindle and chromosome movement in the rpS3 depleted cell was abnormal.
GO:0072686 mitotic spindle	IDA PMID:23131551 Ribosomal protein S3 localizes on the mitotic spindle and fu...	KEEP AS NON CORE	Summary: RPS3 specifically localizes on the mitotic spindle during mitosis as shown by direct imaging. Reason: Direct imaging supports mitotic spindle localization, an extra-ribosomal moonlighting context distinct from and secondary to the cytosolic ribosomal location. Retained as non-core. Supporting Evidence: PMID:23131551 When we examined localization of ribosomal proteins in mitosis, we found that rpS3 specifically localizes on the mitotic spindle.
GO:1902231 positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage	IMP PMID:22510408 Ribosomal protein S3 interacts with TRADD to induce apoptosi...	KEEP AS NON CORE	Summary: RPS3 sensitizes genotoxic (DNA-damage) stress-induced apoptosis by activating JNK in a caspase-dependent manner through interaction with TRADD at the DISC. Reason: RPS3's pro-apoptotic activity in response to genotoxic stress is an extra-ribosomal moonlighting role demonstrated by overexpression/interaction experiments, secondary to the core ribosomal function. Retained as non-core. Supporting Evidence: PMID:22510408 rpS3 sensitizes genotoxic stress-induced apoptosis by activating JNK through a caspase dependent manner.
GO:0003723 RNA binding	IDA PMID:20217897 RpS3 translation is repressed by interaction with its own mR...	KEEP AS NON CORE	Summary: Free RPS3 binds RNA, including its own cognate mRNA and 18S rRNA, via its C-terminal domain (independent of the KH domain). Reason: RNA binding is a directly-evidenced activity consistent with RPS3's KH domain and its rRNA contacts in the ribosome, and underlies its translational autoregulation. It is secondary to the core structural ribosomal role; retained as non-core. Supporting Evidence: PMID:20217897 rpS3 protein was found to interact with various RNAs-endogenous rpS3, 18S rRNA. The S3-C terminal domain was shown to be the major mRNA binding domain of rpS3
GO:0004520 DNA endonuclease activity	IDA PMID:20605787 Ribosomal protein S3, a new substrate of Akt, serves as a si...	KEEP AS NON CORE	Summary: Nuclear-accumulated RPS3 is reported to function as an endonuclease, contributing to DNA repair activity in neuronal cells. Reason: DNA endonuclease activity reflects RPS3's historically reported AP/base-damage endonuclease moonlighting activity. The intrinsic catalytic status of human RPS3 remains debated (PMID:18610840 finds only AP-site beta-elimination and questions in vivo relevance), so this is retained as a non-core, context-dependent activity rather than a core function. Supporting Evidence: PMID:20605787 nuclear translocation and accumulation of RPS3, where it functions as an endonuclease.
GO:0005634 nucleus	IMP PMID:21871177 Ribosomal protein S3 is phosphorylated by Cdk1/cdc2 during G...	KEEP AS NON CORE	Summary: Cdk1-mediated phosphorylation of RPS3 at Thr221 during G2/M promotes its nuclear accumulation. Reason: Regulated, cell-cycle-dependent nuclear accumulation is an extra-ribosomal context, non-core relative to the cytosolic ribosomal location. Retained as non-core. Supporting Evidence: PMID:21871177 the phosphorylation of rpS3 by Cdk1 occurs at Thr221 during G2/M phase and, moreover, that this event is important for nuclear accumulation of rpS3.
GO:0005737 cytoplasm	IDA PMID:20217897 RpS3 translation is repressed by interaction with its own mR...	ACCEPT	Summary: A pool of free RPS3 exists in the cytoplasm (outside ribosomes), where it binds its own mRNA to autoregulate translation. Reason: Cytoplasm is the expected, core location for RPS3 (cytosolic ribosome and free cytoplasmic pool), consistent with accepted cytosol/cytoplasm annotations. Supporting Evidence: PMID:20217897 Most of the rpS3 pool is located in the ribosome while the minority exists in free form in the cytoplasm.
GO:0005737 cytoplasm	IMP PMID:21871177 Ribosomal protein S3 is phosphorylated by Cdk1/cdc2 during G...	ACCEPT	Summary: RPS3 is present in the cytoplasm, with a phosphorylation-regulated shift to nuclear accumulation during G2/M. Reason: Cytoplasm is the expected, core cellular location for RPS3, consistent with its cytosolic ribosomal function. Supporting Evidence: PMID:21871177 Decreased phosphorylation and nuclear accumulation of T221A was much more pronounced in G2/M phase.
GO:0005840 ribosome	IDA PMID:20217897 RpS3 translation is repressed by interaction with its own mR...	ACCEPT	Summary: Most of the cellular RPS3 pool is located in the ribosome, consistent with its core role as a ribosomal protein. Reason: Ribosome localization is core to RPS3's function as a 40S small-subunit protein. Supporting Evidence: PMID:20217897 Most of the rpS3 pool is located in the ribosome while the minority exists in free form in the cytoplasm.
GO:0019900 kinase binding	IPI PMID:20605787 Ribosomal protein S3, a new substrate of Akt, serves as a si...	KEEP AS NON CORE	Summary: RPS3 is a physiological target of Akt kinase; NGF-stimulated Akt phosphorylates RPS3 at Thr70, and this phosphorylation is required for Akt binding to RPS3. Reason: Kinase binding captures the directly-evidenced Akt interaction that regulates RPS3's pro-apoptotic/DNA-repair switch, an extra-ribosomal regulatory context. More informative than generic protein binding but non-core relative to the ribosomal role. Supporting Evidence: PMID:20605787 NGF stimulation resulted in phosphorylation of threonine 70 of RPS3 by Akt, and this phosphorylation was required for Akt binding to RPS3.
GO:0019901 protein kinase binding	IPI PMID:21871177 Ribosomal protein S3 is phosphorylated by Cdk1/cdc2 during G...	KEEP AS NON CORE	Summary: RPS3 interacts with the cell-cycle kinase Cdk1, which phosphorylates it during G2/M phase, as shown by co-IP and GST pull-down. Reason: Protein kinase binding captures the directly-evidenced Cdk1 interaction that regulates RPS3's mitotic phosphorylation/nuclear accumulation, an extra-ribosomal regulatory context. More informative than generic protein binding but non-core. Supporting Evidence: PMID:21871177 Co-immunoprecipitation and GST pull-down assays revealed that Cdk1 interacted with rpS3.
GO:0042981 regulation of apoptotic process	IMP PMID:20605787 Ribosomal protein S3, a new substrate of Akt, serves as a si...	KEEP AS NON CORE	Summary: RPS3 acts as an Akt-regulated molecular switch in neuronal apoptosis; abolishing Akt-mediated phosphorylation accelerated apoptotic cell death, while RPS3 induced apoptosis via E2F1-dependent gene up-regulation. Reason: Regulation of apoptosis is a context-dependent extra-ribosomal moonlighting role of RPS3, secondary to the core ribosomal function. Retained as non-core. Supporting Evidence: PMID:20605787 Akt-dependent phosphorylation of RPS3 inhibited its proapoptotic function ... Abolishment of Akt-mediated RPS3 phosphorylation ... accelerated apoptotic cell death
GO:0044390 ubiquitin-like protein conjugating enzyme binding	IPI PMID:21968017 Ribosomal protein S3 is stabilized by sumoylation.	KEEP AS NON CORE	Summary: RPS3 interacts with SUMO-1 (identified by yeast two-hybrid) and is sumoylated, which increases its protein stability. Reason: This captures a specific interaction with the SUMO modification machinery that regulates RPS3 stability, an extra-ribosomal regulatory context. Retained as non-core. [Note: the interactor identified is SUMO-1 itself; the "conjugating enzyme binding" framing is a curation interpretation of the SUMO-pathway interaction.] Supporting Evidence: PMID:21968017 we identified small ubiquitin-related modifier-1 (SUMO-1) as a new interacting partner of rpS3.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-6791223	KEEP AS NON CORE	Summary: Reactome places RPS3 in the nucleoplasm in the context of pre-40S particle processing during ribosome biogenesis (pre-rRNA processing en route from nucleus to cytosol). Reason: Nucleoplasmic localization reflects the transient nuclear phase of ribosome biogenesis/pre-40S trafficking, not the mature cytosolic ribosomal location. Retained as non-core. Supporting Evidence: Reactome:R-HSA-6791223 18SE pre-rRNA in pre-40S particles is nucleolytically processed during translocation from the nucleus to the cytosol
GO:0031397 negative regulation of protein ubiquitination	IDA PMID:19656744 Ribosomal protein S3: A multi-functional protein that intera...	KEEP AS NON CORE	Summary: RPS3 interacts with MDM2 and p53; under oxidative stress, RPS3 knockdown led to loss of the MDM2 E3 ubiquitin ligase domain and decreased p53, implicating RPS3 in regulating MDM2-mediated ubiquitination of p53. Reason: This is an extra-ribosomal moonlighting role in the p53/MDM2 axis. The evidence is indirect (effects on MDM2/p53 levels under stress) rather than a direct ubiquitination assay, and is secondary to the core ribosomal function. Retained as non-core. Supporting Evidence: PMID:19656744 in cells exposed to oxidative stress and harboring siRNA to knockdown RPS3 expression, decreased p53 levels and loss of the E3 ubiquitin ligase domain possessed by MDM2 were observed.
GO:0032358 oxidized pyrimidine DNA binding	IDA PMID:19656744 Ribosomal protein S3: A multi-functional protein that intera...	KEEP AS NON CORE	Summary: RPS3 binds an 8-oxoG-containing duplex oligonucleotide and acts as a scaffold for binding of MDM2 and p53 at the damaged DNA. Reason: Damaged/oxidized DNA binding by RPS3 is well-supported (PMID:14706345, PMID:18610840), and DNA-pull-down here shows binding to an 8-oxoG duplex. This is an extra-ribosomal moonlighting activity, secondary to the core ribosomal function. [The 8-oxoG lesion is an oxidized purine; the term used is oxidized pyrimidine DNA binding, a minor mismatch, but binding to oxidatively damaged DNA is supported.] Supporting Evidence: PMID:19656744 DNA pull-down assays using a 7,8-dihydro-8-oxoguanine duplex oligonucleotide as a substrate found that RPS3 acted as a scaffold for the additional binding of MDM2 and p53
GO:0003906 DNA-(apurinic or apyrimidinic site) endonuclease activity	IDA PMID:19059439 PKCdelta-dependent functional switch of rpS3 between transla...	KEEP AS NON CORE	Summary: Phosphorylation of non-ribosomal RPS3 by PKCdelta increased its repair (AP/damage) endonuclease activity. Reason: AP-site endonuclease activity is a historically reported moonlighting activity of RPS3. Its intrinsic catalytic relevance in human cells remains debated (PMID:18610840 finds only AP-site beta-elimination and questions global in vivo repair), so this is retained as a non-core, context-dependent activity rather than a core function. Supporting Evidence: PMID:19059439 the repair endonuclease activity of rpS3 was increased by its phosphorylation.
GO:0005634 nucleus	IDA PMID:19059439 PKCdelta-dependent functional switch of rpS3 between transla...	KEEP AS NON CORE	Summary: PKCdelta phosphorylation mobilizes non-ribosomal RPS3 to the nucleus to repair damaged DNA. Reason: Stimulus/phosphorylation-dependent nuclear localization is a regulated extra-ribosomal context, non-core relative to the cytosolic ribosomal location. Retained as non-core. Supporting Evidence: PMID:19059439 PKCdelta phosphorylates rpS3 resulting in its mobilization in the nucleus to repair damaged DNA.
GO:0005737 cytoplasm	IDA PMID:19059439 PKCdelta-dependent functional switch of rpS3 between transla...	ACCEPT	Summary: RPS3 is present in the cytoplasm, with a phosphorylation-regulated non-ribosomal pool that relocates to the nucleus upon DNA damage. Reason: Cytoplasm is the expected, core cellular location for RPS3, consistent with its cytosolic ribosomal function. Supporting Evidence: PMID:19059439 Phosphorylated rpS3 was only detected in non-ribosomal rpS3
GO:0005840 ribosome	IDA PMID:19059439 PKCdelta-dependent functional switch of rpS3 between transla...	ACCEPT	Summary: RPS3 is a component of the 40S ribosomal subunit involved in translation. Reason: Ribosome localization is core to RPS3's role as a small-subunit ribosomal protein. Supporting Evidence: PMID:19059439 Ribosomal protein S3 (rpS3) is critically involved in translation as a component of the 40S ribosomal subunit
GO:0003677 DNA binding	IDA PMID:18610840 [Interactions of human ribosomal protein S3 with undamaged a...	MODIFY	Summary: Recombinant human RPS3 binds DNA, including undamaged DNA; in this study binding to undamaged DNA was actually more efficient than to several damaged lesions. Reason: Generic DNA binding is less informative than the specific damaged-DNA binding activity that is the functionally relevant moonlighting feature of RPS3; the same reference also documents damaged DNA binding. Recommend the more specific damaged DNA binding term (also separately annotated from this reference). Proposed replacements: damaged DNA binding Supporting Evidence: PMID:18610840 Binding of hS3 to DNA ligands containing oxidized and deaminated bases was less efficient than its binding to undamaged DNA.
GO:0003684 damaged DNA binding	IDA PMID:18610840 [Interactions of human ribosomal protein S3 with undamaged a...	KEEP AS NON CORE	Summary: Recombinant human RPS3 binds and cleaves AP-site-containing DNA substrates (via beta-elimination), confirming damaged-DNA binding. Reason: Damaged DNA binding is a well-supported extra-ribosomal activity, secondary to the core ribosomal function. Retained as non-core. Supporting Evidence: PMID:18610840 hS3 catalyzed cleavage of apurine/apyrimidine sites through beta-elimination mechanism forming a transient Schiff base covalent intermediate
GO:0003906 DNA-(apurinic or apyrimidinic site) endonuclease activity	IDA PMID:18610840 [Interactions of human ribosomal protein S3 with undamaged a...	KEEP AS NON CORE	Summary: Recombinant human RPS3 cleaves AP sites via a beta-elimination (AP lyase) mechanism but does not cleave substrates containing other lesions, and the authors question its in vivo global repair relevance. Reason: AP-site cleavage activity is supported in vitro but is mechanistically an AP lyase (beta-elimination) and its physiological/global in vivo relevance is doubted by the authors. It is a context-dependent moonlighting activity, secondary to the core ribosomal function; retained as non-core. Supporting Evidence: PMID:18610840 the activity of hS3 on apurine/apyrimidine sites is not likely to be involved in the global in vivo DNA repair but could have a role in the repair in some specific locations in the genome.
GO:0005634 nucleus	IDA PMID:19460357 Arginine methylation of ribosomal protein S3 affects ribosom...	KEEP AS NON CORE	Summary: Arginine methylation of RPS3 by PRMT1 is required for its import into the nucleus/nucleolus and subsequent incorporation into the ribosome. Reason: Nuclear/nucleolar localization here reflects the ribosome-biogenesis trafficking phase, not the mature cytosolic ribosomal location. Retained as non-core. Supporting Evidence: PMID:19460357 mutant rpS3 (3RA), which cannot be methylated at these sites, cannot be transported into the nucleolus and subsequently incorporated into the ribosome.
GO:0005730 nucleolus	IDA PMID:19460357 Arginine methylation of ribosomal protein S3 affects ribosom...	KEEP AS NON CORE	Summary: RPS3 is imported into the nucleolus (dependent on PRMT1 arginine methylation) for small-subunit ribosome assembly. Reason: Nucleolar localization reflects the ribosome-biogenesis/assembly phase of RPS3, distinct from the mature cytosolic ribosomal location. This is a direct functional study (unlike the weaker IEA nucleolus annotation that was marked over-annotated), so retained as non-core. Supporting Evidence: PMID:19460357 arginine methylation of rpS3 plays a critical role in its import into the nucleolus, as well as in small subunit assembly of the ribosome.
GO:0005840 ribosome	IDA PMID:19460357 Arginine methylation of ribosomal protein S3 affects ribosom...	ACCEPT	Summary: RPS3 is incorporated into the ribosome (40S small subunit), a process that depends on its PRMT1-mediated arginine methylation. Reason: Ribosome localization/incorporation is core to RPS3's function as a 40S small-subunit ribosomal protein. Supporting Evidence: PMID:19460357 The human ribosomal protein S3 (rpS3), a component of the 40S small subunit in the ribosome
GO:0019104 DNA N-glycosylase activity	IDA NOT PMID:18610840 [Interactions of human ribosomal protein S3 with undamaged a...	ACCEPT	Summary: Recombinant human RPS3 cleaved AP sites by beta-elimination but did NOT cleave substrates containing oxidized/deaminated bases (8-oxoguanine, uracil, hypoxanthine, etc.), so it lacks DNA glycosylase activity. Reason: The NOT annotation is well-supported: despite sequence-based predictions, RPS3 has no detectable DNA N-glycosylase activity. Accept the negation as correctly representing the experimental result. Supporting Evidence: PMID:18610840 hS3 catalyzed cleavage of apurine/apyrimidine sites through beta-elimination mechanism forming a transient Schiff base covalent intermediate, but did not cleave substrates containing other lesions.
GO:0019899 enzyme binding	IPI PMID:19460357 Arginine methylation of ribosomal protein S3 affects ribosom...	KEEP AS NON CORE	Summary: RPS3 is methylated by and interacts with protein arginine methyltransferase 1 (PRMT1), which regulates its nucleolar import and ribosome assembly. Reason: Enzyme binding here captures the directly-evidenced PRMT1 interaction that governs RPS3 modification and ribosome assembly. More informative than generic protein binding; it relates to ribosome biogenesis regulation but is retained as non-core relative to the structural ribosomal function. Supporting Evidence: PMID:19460357 the arginine residue(s) of rpS3 are methylated by protein arginine methyltransferase 1 (PRMT1).
GO:0070181 small ribosomal subunit rRNA binding	IDA PMID:18610840 [Interactions of human ribosomal protein S3 with undamaged a...	ACCEPT	Summary: RPS3 interacts with 18S rRNA, the rRNA of the small (40S) ribosomal subunit, consistent with its structural role in the small subunit. Reason: Small-subunit rRNA binding is consistent with RPS3's core structural role in the 40S subunit, where it contacts 18S rRNA. The 18S rRNA interaction is directly documented (PMID:20217897), supporting this MF as core. Supporting Evidence: PMID:20217897 rpS3 protein was found to interact with various RNAs-endogenous rpS3, 18S rRNA.
GO:0003906 DNA-(apurinic or apyrimidinic site) endonuclease activity	IDA PMID:15707971 Characterization of a wide range base-damage-endonuclease ac...	KEEP AS NON CORE	Summary: Mammalian RPS3 nicks DNA containing AP sites and a wide range of base-damage lesions (thymine glycols, UV-damaged lesions) as a base-damage-endonuclease. Reason: AP-site endonuclease activity is a historically reported moonlighting activity. Its intrinsic catalytic relevance for human RPS3 in vivo is debated (PMID:18610840), so it is retained as a context-dependent non-core activity rather than a core function. Supporting Evidence: PMID:15707971 rpS3 cleaves the lesions including AP sites, thymine glycols, and other UV damaged lesions such as pyrimidine dimers.
GO:0004520 DNA endonuclease activity	IDA PMID:15707971 Characterization of a wide range base-damage-endonuclease ac...	KEEP AS NON CORE	Summary: Mammalian RPS3 acts as a wide-range base-damage endonuclease, cleaving phosphodiester bonds in DNA containing various altered bases. Reason: DNA endonuclease activity is a historically reported moonlighting activity whose physiological relevance in human cells is debated. Retained as a non-core, context-dependent activity. Supporting Evidence: PMID:15707971 rpS3 cleaves phosphodiester bonds of DNAs containing altered bases with broad specificity acting as a base-damage-endonuclease.
GO:0019104 DNA N-glycosylase activity	TAS NOT PMID:15707971 Characterization of a wide range base-damage-endonuclease ac...	ACCEPT	Summary: Despite a sequence prediction of glycosylase activity, RPS3 does not have glycosylase activity; it acts as an endonuclease on damaged DNA. Reason: The NOT annotation is well-supported and consistent with PMID:18610840: RPS3 lacks DNA glycosylase activity. Accept the negation. Supporting Evidence: PMID:15707971 This enzyme does not have a glycosylase activity as predicted from its amino acid sequence.
GO:0097100 supercoiled DNA binding	IDA PMID:15707971 Characterization of a wide range base-damage-endonuclease ac...	KEEP AS NON CORE	Summary: RPS3 cleaves supercoiled UV-damaged DNA more efficiently than the relaxed counterpart, indicating a preference for/interaction with supercoiled DNA. Reason: Supercoiled DNA binding is inferred from the preferential cleavage of supercoiled damaged DNA, part of RPS3's debated extra-ribosomal base-damage-endonuclease activity. Retained as non-core. Supporting Evidence: PMID:15707971 RpS3 cleaves supercoiled UV damaged DNA more efficiently than the relaxed counterpart
GO:0003684 damaged DNA binding	IDA PMID:14706345 Characterization of human ribosomal protein S3 binding to 7,...	KEEP AS NON CORE	Summary: By surface plasmon resonance, human RPS3 binds 8-oxoG and AP sites with very high apparent affinity (orders of magnitude higher than OGG1). Reason: Damaged DNA binding is among the best-supported extra-ribosomal activities of human RPS3, with quantitative binding data. It is secondary to the core ribosomal role; retained as non-core. Supporting Evidence: PMID:14706345 An even more dramatic five orders of magnitude higher binding affinity for AP DNA was found for hS3 as opposed to hOGG1.
GO:0032357 oxidized purine DNA binding	IDA PMID:14706345 Characterization of human ribosomal protein S3 binding to 7,...	KEEP AS NON CORE	Summary: Human RPS3 binds 7,8-dihydro-8-oxoguanine (8-oxoG), an oxidized purine lesion, with high apparent affinity. Reason: Oxidized purine (8-oxoG) DNA binding is directly and quantitatively supported; this term is more specific and accurate than the generic oxidized-pyrimidine term used elsewhere. It is an extra-ribosomal moonlighting activity, secondary to the core ribosomal function. Retained as non-core. Supporting Evidence: PMID:14706345 hS3 was found to have an apparent three orders of magnitude higher binding affinity (KD) for 8-oxoG than the human N-glycosylase/AP lyase base excision repair (BER) enzyme OGG1.
GO:0003906 DNA-(apurinic or apyrimidinic site) endonuclease activity	IDA PMID:7775413 Implication of mammalian ribosomal protein S3 in the process...	KEEP AS NON CORE	Summary: The earliest report implicating mammalian RPS3 in DNA damage processing identified an AP/UV endonuclease activity co-purifying with ribosomal protein S3. Reason: This historical biochemical evidence connects RPS3 with AP/UV endonuclease activity, but the physiological relevance for human RPS3 is debated (PMID:18610840). Retained as a non-core, context-dependent activity. Supporting Evidence: PMID:7775413 The nuclease activities have been purified from mouse cells to yield a peptide of M(r) = 32,000, whose sequence indicates identity with ribosomal protein S3.
GO:0016020 membrane	HDA PMID:19946888 Defining the membrane proteome of NK cells.	MARK AS OVER ANNOTATED	Summary: RPS3 was detected in a high-throughput proteomic study of the membrane proteome of NK cells. Reason: Detection of an abundant ribosomal protein in a membrane proteome most plausibly reflects co-isolation (e.g., membrane-associated ribosomes) or contamination rather than an RPS3-specific integral/peripheral membrane role. Treated as an over-annotation. Supporting Evidence: PMID:19946888 Defining the membrane proteome of NK cells.
GO:0005515 protein binding	IPI PMID:24423872 AUF1 contributes to Cryptochrome1 mRNA degradation and rhyth...	KEEP AS NON CORE	Summary: RPS3 directly associates with AUF1 and contributes to 3'UTR-dependent translation of Cry1 mRNA in the circadian clock context. Reason: Generic protein binding term; the specific AUF1 association relates to translational regulation but is non-core relative to the structural ribosomal function and not a defining RPS3 molecular function. Retained as non-core. Supporting Evidence: PMID:24423872 AUF1 ... directly associated with ribosomal protein S3 or ribosomal protein S14, resulting in translation of Cry1 mRNA in a 3'UTR-dependent manner.
GO:2001235 positive regulation of apoptotic signaling pathway	IDA PMID:14988002 RpS3, a DNA repair endonuclease and ribosomal protein, is in...	KEEP AS NON CORE	Summary: Overexpression of GFP-RPS3 activates caspase-8/caspase-3 and sensitizes cells to cytokine-induced apoptosis, indicating a pro-apoptotic activity. Reason: Pro-apoptotic activity is a context-dependent extra-ribosomal moonlighting function shown by overexpression/cytokine paradigms, secondary to the core ribosomal role. Retained as non-core. Supporting Evidence: PMID:14988002 Transient expression of GFP-rpS3 activates caspase-8/caspase-3 and sensitizes cytokine-induced apoptosis.
GO:0003723 RNA binding	HDA PMID:22658674 Insights into RNA biology from an atlas of mammalian mRNA-bi...	KEEP AS NON CORE	Summary: RPS3 was identified as an mRNA-binding protein in a high-throughput interactome-capture atlas of mammalian mRNA-binding proteins. Reason: RNA binding is consistent with RPS3's KH domain and its direct rRNA/mRNA contacts in the ribosome and in autoregulation (PMID:20217897). It is a real activity but, as captured by these broad mRNA-interactome screens, is secondary to the core structural ribosomal role; kept non-core for consistency with the other RNA binding annotations. Supporting Evidence: PMID:22658674 We identify 860 proteins that qualify as RBPs by biochemical and statistical criteria
GO:0003723 RNA binding	HDA PMID:22681889 The mRNA-bound proteome and its global occupancy profile on ...	KEEP AS NON CORE	Summary: RPS3 was identified among the mRNA-bound proteome in a second high-throughput RNA-interactome study. Reason: Independent HDA support for RPS3 RNA binding, consistent with its KH domain and rRNA/mRNA contacts. A real but broad MF, secondary to the structural ribosomal function; kept non-core for consistency with the other RNA binding annotations. Supporting Evidence: PMID:22681889 We developed a photoreactive nucleotide-enhanced UV crosslinking and oligo(dT) purification approach to identify the mRNA-bound proteome
GO:0003684 damaged DNA binding	IDA PMID:17560175 Translocation of human ribosomal protein S3 to sites of DNA ...	KEEP AS NON CORE	Summary: Human RPS3 has affinity for abasic sites and 8-oxoG residues and co-localizes with 8-oxoG damage foci after genotoxic stress. Reason: Damaged DNA binding is a well-supported extra-ribosomal activity here complemented by in-cell co-localization with damage foci. Secondary to the core ribosomal role; retained as non-core. Supporting Evidence: PMID:17560175 hS3 was traced in exposed cells to its co-localization with 8-oxoG foci
GO:0005634 nucleus	IDA PMID:16814409 Reduction of invasion in human fibrosarcoma cells by ribosom...	KEEP AS NON CORE	Summary: RPS3 was observed in the nucleus as well as cytoplasm/cell periphery; in this study it colocalized with Nm23-H1 in the cell periphery and cytoplasm. Reason: Nuclear localization is a regulated extra-ribosomal pool, non-core relative to the cytosolic ribosomal location. Retained as non-core. Supporting Evidence: PMID:16814409 RpS3 interacted with nm23-H1, and the two proteins were colocalized in the cell periphery and cytoplasm.
GO:0005829 cytosol	IDA PMID:17560175 Translocation of human ribosomal protein S3 to sites of DNA ...	ACCEPT	Summary: Under basal conditions RPS3 is cytoplasmic/cytosolic, translocating to the nucleus only upon genotoxic stress. Reason: Cytosol is the expected, core cellular location for RPS3's cytosolic ribosomal function, consistent with accepted cytosol annotations. Supporting Evidence: PMID:17560175 hS3 is capable of carrying out both roles by its ex vivo translocation from the cytoplasm to the nucleus as a consequence of genotoxic stress.
GO:0019899 enzyme binding	IPI PMID:15518571 Human ribosomal protein S3 interacts with DNA base excision ...	KEEP AS NON CORE	Summary: Human RPS3 physically interacts with the BER enzymes OGG1 and APE1/Ref-1 (co-immunoprecipitation and SPR). Reason: Enzyme binding captures the directly-evidenced interactions with BER enzymes (OGG1, APE1), more informative than generic protein binding but part of RPS3's extra-ribosomal BER-cofactor role. Retained as non-core. Supporting Evidence: PMID:15518571 Human S3 was found to co-immunoprecipitate with both hOGG1 and APE/Ref-1, indicating that these proteins physically interact with one another.
GO:0070062 extracellular exosome	HDA PMID:20458337 MHC class II-associated proteins in B-cell exosomes and pote...	MARK AS OVER ANNOTATED	Summary: RPS3 was detected in a proteomic study of MHC class II-associated proteins in B-cell exosomes. Reason: Detection of an abundant ribosomal protein in an exosome proteome is a common, non-specific finding and does not establish a discrete RPS3-specific exosomal function. Treated as an over-annotation. Supporting Evidence: PMID:20458337 MHC class II-associated proteins in B-cell exosomes and potential functional implications for exosome biogenesis.
GO:0005829 cytosol	TAS Reactome:R-HSA-156808	ACCEPT	Summary: Reactome places RPS3 (as a 40S/cytosolic ribosome component) in the cytosol within this translation/ribosome-associated pathway step. Reason: Cytosol is the expected, core cellular location for RPS3 as part of the cytosolic ribosome participating in translation and ribosome-associated processes. Consistent with the accepted cytosol/cytosolic ribosome annotations. Supporting Evidence: Reactome:R-HSA-156808 Formation of translation initiation complexes yielding circularized Ceruloplasmin mRNA in a 'closed-loop' conformation
GO:0005829 cytosol	TAS Reactome:R-HSA-156823	ACCEPT	Summary: Reactome places RPS3 (as a 40S/cytosolic ribosome component) in the cytosol within this translation/ribosome-associated pathway step. Reason: Cytosol is the expected, core cellular location for RPS3 as part of the cytosolic ribosome participating in translation and ribosome-associated processes. Consistent with the accepted cytosol/cytosolic ribosome annotations. Supporting Evidence: Reactome:R-HSA-156823 Association of phospho-L13a with GAIT element of Ceruloplasmin mRNA
GO:0005829 cytosol	TAS Reactome:R-HSA-157849	ACCEPT	Summary: Reactome places RPS3 (as a 40S/cytosolic ribosome component) in the cytosol within this translation/ribosome-associated pathway step. Reason: Cytosol is the expected, core cellular location for RPS3 as part of the cytosolic ribosome participating in translation and ribosome-associated processes. Consistent with the accepted cytosol/cytosolic ribosome annotations. Supporting Evidence: Reactome:R-HSA-157849 Formation of translation initiation complexes containing mRNA that does not circularize
GO:0005829 cytosol	TAS Reactome:R-HSA-1799332	ACCEPT	Summary: Reactome places RPS3 (as a 40S/cytosolic ribosome component) in the cytosol within this translation/ribosome-associated pathway step. Reason: Cytosol is the expected, core cellular location for RPS3 as part of the cytosolic ribosome participating in translation and ribosome-associated processes. Consistent with the accepted cytosol/cytosolic ribosome annotations. Supporting Evidence: Reactome:R-HSA-1799332 Nascent polypeptide:mRNA:ribosome complex binds signal recognition particle (SRP)
GO:0005829 cytosol	TAS Reactome:R-HSA-1799335	ACCEPT	Summary: Reactome places RPS3 (as a 40S/cytosolic ribosome component) in the cytosol within this translation/ribosome-associated pathway step. Reason: Cytosol is the expected, core cellular location for RPS3 as part of the cytosolic ribosome participating in translation and ribosome-associated processes. Consistent with the accepted cytosol/cytosolic ribosome annotations. Supporting Evidence: Reactome:R-HSA-1799335 Synthesis of nascent polypeptide containing signal sequence
GO:0005829 cytosol	TAS Reactome:R-HSA-192704	ACCEPT	Summary: Reactome places RPS3 (as a 40S/cytosolic ribosome component) in the cytosol within this translation/ribosome-associated pathway step. Reason: Cytosol is the expected, core cellular location for RPS3 as part of the cytosolic ribosome participating in translation and ribosome-associated processes. Consistent with the accepted cytosol/cytosolic ribosome annotations. Supporting Evidence: Reactome:R-HSA-192704 Synthesis of PB1-F2
GO:0005829 cytosol	TAS Reactome:R-HSA-192841	ACCEPT	Summary: Reactome places RPS3 (as a 40S/cytosolic ribosome component) in the cytosol within this translation/ribosome-associated pathway step. Reason: Cytosol is the expected, core cellular location for RPS3 as part of the cytosolic ribosome participating in translation and ribosome-associated processes. Consistent with the accepted cytosol/cytosolic ribosome annotations. Supporting Evidence: Reactome:R-HSA-192841 Viral Protein Synthesis
GO:0005829 cytosol	TAS Reactome:R-HSA-6791223	ACCEPT	Summary: Reactome places RPS3 (as a pre-40S/40S ribosome component) in the cytosol in the context of pre-rRNA processing during nucleus-to-cytosol translocation of pre-40S particles. Reason: Cytosol is the expected, core cellular location for RPS3 as part of the cytosolic ribosome, consistent with the accepted cytosol/cytosolic ribosome annotations. Supporting Evidence: Reactome:R-HSA-6791223 18SE pre-rRNA in pre-40S particles is nucleolytically processed during translocation from the nucleus to the cytosol
GO:0005829 cytosol	TAS Reactome:R-HSA-72619	ACCEPT	Summary: Reactome places RPS3 (as a 40S/cytosolic ribosome component) in the cytosol within this translation/ribosome-associated pathway step. Reason: Cytosol is the expected, core cellular location for RPS3 as part of the cytosolic ribosome participating in translation and ribosome-associated processes. Consistent with the accepted cytosol/cytosolic ribosome annotations. Supporting Evidence: Reactome:R-HSA-72619 eIF2:GTP is hydrolyzed, eIFs are released
GO:0005829 cytosol	TAS Reactome:R-HSA-72621	ACCEPT	Summary: Reactome places RPS3 (as a 40S/cytosolic ribosome component) in the cytosol within this translation/ribosome-associated pathway step. Reason: Cytosol is the expected, core cellular location for RPS3 as part of the cytosolic ribosome participating in translation and ribosome-associated processes. Consistent with the accepted cytosol/cytosolic ribosome annotations. Supporting Evidence: Reactome:R-HSA-72621 Ribosomal scanning
GO:0005829 cytosol	TAS Reactome:R-HSA-72671	ACCEPT	Summary: Reactome places RPS3 (as a 40S/cytosolic ribosome component) in the cytosol within this translation/ribosome-associated pathway step. Reason: Cytosol is the expected, core cellular location for RPS3 as part of the cytosolic ribosome participating in translation and ribosome-associated processes. Consistent with the accepted cytosol/cytosolic ribosome annotations. Supporting Evidence: Reactome:R-HSA-72671 eIF5B:GTP is hydrolyzed and released
GO:0005829 cytosol	TAS Reactome:R-HSA-72672	ACCEPT	Summary: Reactome places RPS3 (as a 40S/cytosolic ribosome component) in the cytosol within this translation/ribosome-associated pathway step. Reason: Cytosol is the expected, core cellular location for RPS3 as part of the cytosolic ribosome participating in translation and ribosome-associated processes. Consistent with the accepted cytosol/cytosolic ribosome annotations. Supporting Evidence: Reactome:R-HSA-72672 The 60S subunit joins the translation initiation complex
GO:0005829 cytosol	TAS Reactome:R-HSA-72673	ACCEPT	Summary: Reactome places RPS3 (as a 40S/cytosolic ribosome component) in the cytosol within this translation/ribosome-associated pathway step. Reason: Cytosol is the expected, core cellular location for RPS3 as part of the cytosolic ribosome participating in translation and ribosome-associated processes. Consistent with the accepted cytosol/cytosolic ribosome annotations. Supporting Evidence: Reactome:R-HSA-72673 Release of 40S and 60S subunits from the 80S ribosome
GO:0005829 cytosol	TAS Reactome:R-HSA-72676	ACCEPT	Summary: Reactome places RPS3 (as a 40S/cytosolic ribosome component) in the cytosol within this translation/ribosome-associated pathway step. Reason: Cytosol is the expected, core cellular location for RPS3 as part of the cytosolic ribosome participating in translation and ribosome-associated processes. Consistent with the accepted cytosol/cytosolic ribosome annotations. Supporting Evidence: Reactome:R-HSA-72676 eIF3 and eIF1A bind to the 40S subunit
GO:0005829 cytosol	TAS Reactome:R-HSA-72691	ACCEPT	Summary: Reactome places RPS3 (as a 40S/cytosolic ribosome component) in the cytosol within this translation/ribosome-associated pathway step. Reason: Cytosol is the expected, core cellular location for RPS3 as part of the cytosolic ribosome participating in translation and ribosome-associated processes. Consistent with the accepted cytosol/cytosolic ribosome annotations. Supporting Evidence: Reactome:R-HSA-72691 Formation of the 43S pre-initiation complex
GO:0005829 cytosol	TAS Reactome:R-HSA-72697	ACCEPT	Summary: Reactome places RPS3 (as a 40S/cytosolic ribosome component) in the cytosol within this translation/ribosome-associated pathway step. Reason: Cytosol is the expected, core cellular location for RPS3 as part of the cytosolic ribosome participating in translation and ribosome-associated processes. Consistent with the accepted cytosol/cytosolic ribosome annotations. Supporting Evidence: Reactome:R-HSA-72697 Start codon recognition
GO:0005829 cytosol	TAS Reactome:R-HSA-927789	ACCEPT	Summary: Reactome places RPS3 (as a 40S/cytosolic ribosome component) in the cytosol within this translation/ribosome-associated pathway step. Reason: Cytosol is the expected, core cellular location for RPS3 as part of the cytosolic ribosome participating in translation and ribosome-associated processes. Consistent with the accepted cytosol/cytosolic ribosome annotations. Supporting Evidence: Reactome:R-HSA-927789 Formation of UPF1:eRF3 complex on mRNA with a premature termination codon and no Exon Junction Complex
GO:0005829 cytosol	TAS Reactome:R-HSA-927813	ACCEPT	Summary: Reactome places RPS3 (as a 40S/cytosolic ribosome component) in the cytosol within this translation/ribosome-associated pathway step. Reason: Cytosol is the expected, core cellular location for RPS3 as part of the cytosolic ribosome participating in translation and ribosome-associated processes. Consistent with the accepted cytosol/cytosolic ribosome annotations. Supporting Evidence: Reactome:R-HSA-927813 p-4S-UPF1 recruits SMG5, SMG7, SMG6, PNRC2, DCP1A, and PP2A
GO:0005829 cytosol	TAS Reactome:R-HSA-927832	ACCEPT	Summary: Reactome places RPS3 (as a 40S/cytosolic ribosome component) in the cytosol within this translation/ribosome-associated pathway step. Reason: Cytosol is the expected, core cellular location for RPS3 as part of the cytosolic ribosome participating in translation and ribosome-associated processes. Consistent with the accepted cytosol/cytosolic ribosome annotations. Supporting Evidence: Reactome:R-HSA-927832 UPF1 binds an mRNP with a termination codon preceding an Exon Junction Complex
GO:0005829 cytosol	TAS Reactome:R-HSA-927836	ACCEPT	Summary: Reactome places RPS3 (as a 40S/cytosolic ribosome component) in the cytosol within this translation/ribosome-associated pathway step. Reason: Cytosol is the expected, core cellular location for RPS3 as part of the cytosolic ribosome participating in translation and ribosome-associated processes. Consistent with the accepted cytosol/cytosolic ribosome annotations. Supporting Evidence: Reactome:R-HSA-927836 SMG6 hydrolyzes mRNA with premature termination codon
GO:0005829 cytosol	TAS Reactome:R-HSA-927889	ACCEPT	Summary: Reactome places RPS3 (as a 40S/cytosolic ribosome component) in the cytosol within this translation/ribosome-associated pathway step. Reason: Cytosol is the expected, core cellular location for RPS3 as part of the cytosolic ribosome participating in translation and ribosome-associated processes. Consistent with the accepted cytosol/cytosolic ribosome annotations. Supporting Evidence: Reactome:R-HSA-927889 SMG1 phosphorylates UPF1 (enhanced by Exon Junction Complex)
GO:0005829 cytosol	TAS Reactome:R-HSA-9729232	ACCEPT	Summary: Reactome places RPS3 (as a 40S/cytosolic ribosome component) in the cytosol within this translation/ribosome-associated pathway step. Reason: Cytosol is the expected, core cellular location for RPS3 as part of the cytosolic ribosome participating in translation and ribosome-associated processes. Consistent with the accepted cytosol/cytosolic ribosome annotations. Supporting Evidence: Reactome:R-HSA-9729232 SARS-CoV-1 nsp1 binds to 40S ribosomal subunit
GO:0005829 cytosol	TAS Reactome:R-HSA-9729849	ACCEPT	Summary: Reactome places RPS3 (as a 40S/cytosolic ribosome component) in the cytosol within this translation/ribosome-associated pathway step. Reason: Cytosol is the expected, core cellular location for RPS3 as part of the cytosolic ribosome participating in translation and ribosome-associated processes. Consistent with the accepted cytosol/cytosolic ribosome annotations. Supporting Evidence: Reactome:R-HSA-9729849 SARS-CoV-2 nsp1 binds to 40S ribosomal complex
GO:0005829 cytosol	TAS Reactome:R-HSA-9948291	ACCEPT	Summary: Reactome places RPS3 (as a 40S/cytosolic ribosome component) in the cytosol within this translation/ribosome-associated pathway step. Reason: Cytosol is the expected, core cellular location for RPS3 as part of the cytosolic ribosome participating in translation and ribosome-associated processes. Consistent with the accepted cytosol/cytosolic ribosome annotations. Supporting Evidence: Reactome:R-HSA-9948291 RQT complex binds K63polyUb-80S ribosome:no-go mRNA:peptidyl-tRNA with nascent peptide
GO:0005829 cytosol	TAS Reactome:R-HSA-9948300	ACCEPT	Summary: Reactome places RPS3 (as a 40S/cytosolic ribosome component) in the cytosol within this translation/ribosome-associated pathway step. Reason: Cytosol is the expected, core cellular location for RPS3 as part of the cytosolic ribosome participating in translation and ribosome-associated processes. Consistent with the accepted cytosol/cytosolic ribosome annotations. Supporting Evidence: Reactome:R-HSA-9948300 RQT complex:K63polyUb-80S ribosome dissociates yielding K63polyUb-40S subunit and 60S subunit:peptidyl-tRNA with nascent peptide
GO:0005829 cytosol	TAS Reactome:R-HSA-9948301	ACCEPT	Summary: Reactome places RPS3 (as a 40S/cytosolic ribosome component) in the cytosol within this translation/ribosome-associated pathway step. Reason: Cytosol is the expected, core cellular location for RPS3 as part of the cytosolic ribosome participating in translation and ribosome-associated processes. Consistent with the accepted cytosol/cytosolic ribosome annotations. Supporting Evidence: Reactome:R-HSA-9948301 ZNF598 K63 polyubiquitinates RPS10 (eS10) and RPS20 (uS10) of the 40S ribosomal subunit
GO:0005829 cytosol	TAS Reactome:R-HSA-9948317	ACCEPT	Summary: Reactome places RPS3 (as a 40S/cytosolic ribosome component) in the cytosol within this translation/ribosome-associated pathway step. Reason: Cytosol is the expected, core cellular location for RPS3 as part of the cytosolic ribosome participating in translation and ribosome-associated processes. Consistent with the accepted cytosol/cytosolic ribosome annotations. Supporting Evidence: Reactome:R-HSA-9948317 ZNF598 and Ub:UBE2D1,2,3 bind stalled 80S ribosome
GO:0005829 cytosol	TAS Reactome:R-HSA-9954730	ACCEPT	Summary: Reactome places RPS3 (as a 40S/cytosolic ribosome component) in the cytosol within this translation/ribosome-associated pathway step. Reason: Cytosol is the expected, core cellular location for RPS3 as part of the cytosolic ribosome participating in translation and ribosome-associated processes. Consistent with the accepted cytosol/cytosolic ribosome annotations. Supporting Evidence: Reactome:R-HSA-9954730 PELO:HBS1L-1:GTP binds 80S ribosome:non-stop mRNA:peptidyl-tRNA with nascent peptide
GO:0005829 cytosol	TAS Reactome:R-HSA-9954919	ACCEPT	Summary: Reactome places RPS3 (as a 40S/cytosolic ribosome component) in the cytosol within this translation/ribosome-associated pathway step. Reason: Cytosol is the expected, core cellular location for RPS3 as part of the cytosolic ribosome participating in translation and ribosome-associated processes. Consistent with the accepted cytosol/cytosolic ribosome annotations. Supporting Evidence: Reactome:R-HSA-9954919 ABCE1:ATP binds PELO:HBS1L-1:GTP:80S ribosome:non-stop mRNA:peptidyl-tRNA with nascent peptide and HBS1L-1:GDP is released
GO:0005829 cytosol	TAS Reactome:R-HSA-9955731	ACCEPT	Summary: Reactome places RPS3 (as a 40S/cytosolic ribosome component) in the cytosol within this translation/ribosome-associated pathway step. Reason: Cytosol is the expected, core cellular location for RPS3 as part of the cytosolic ribosome participating in translation and ribosome-associated processes. Consistent with the accepted cytosol/cytosolic ribosome annotations. Supporting Evidence: Reactome:R-HSA-9955731 ABCE1:PELO:80S Ribosome:non-stop mRNA:peptidyl-tRNA with elongating peptide dissociates yielding ABCE1:40S ribosomal subunit, PELO, and 60S ribosomal subunit:peptidyl-tRNA with nascent peptide
GO:0051018 protein kinase A binding	IPI PMID:16814409 Reduction of invasion in human fibrosarcoma cells by ribosom...	KEEP AS NON CORE	Summary: RPS3 interacts with Nm23-H1 (a nucleoside diphosphate kinase) and modulates ERK signaling, reducing invasion of fibrosarcoma cells. Reason: The specific kinase-related interaction documented in this reference is with Nm23-H1/ERK, not protein kinase A; the protein kinase A binding term is a questionable mapping. The genuine interaction (Nm23-H1) is an extra-ribosomal moonlighting context. Retained as non-core given the evidence supports a kinase-pathway interaction rather than this exact term. Supporting Evidence: PMID:16814409 RpS3 interacted with nm23-H1, and the two proteins were colocalized in the cell periphery and cytoplasm.
GO:0005515 protein binding	IPI PMID:22244329 Hydrogen sulfide-linked sulfhydration of NF-κB mediates its ...	KEEP AS NON CORE	Summary: H2S-mediated sulfhydration of the NF-kB p65 subunit at Cys38 promotes its binding to the coactivator RPS3, supporting an RPS3-p65 interaction in antiapoptotic NF-kB signaling. Reason: Generic protein binding term; the specific RPS3-p65 interaction is part of RPS3's extra-ribosomal NF-kB coactivator role, captured more informatively by the NF-kB complex and transcription-regulation annotations. Retained as non-core. Supporting Evidence: PMID:22244329 sulfhydrating the p65 subunit of NF-κB at cysteine-38, which promotes its binding to the coactivator ribosomal protein S3 (RPS3).
GO:1990904 ribonucleoprotein complex	IDA PMID:17289661 Molecular composition of IMP1 ribonucleoprotein granules.	ACCEPT	Summary: RPS3 was identified as a component of IMP1 (IGF2BP1) mRNP granules, which contain ribosomal proteins and translation machinery. Reason: RPS3 is a ribonucleoprotein-complex component (the ribosome itself is an RNP), so this broad term is correct; it is subsumed by the more specific cytosolic ribosome annotations. Consistent with the accepted IEA ribonucleoprotein complex annotation. Supporting Evidence: PMID:17289661 Molecular composition of IMP1 ribonucleoprotein granules.
GO:0022627 cytosolic small ribosomal subunit	IDA PMID:8706699 Characterization of the human small-ribosomal-subunit protei...	ACCEPT	Summary: RPS3 was identified by protein sequencing and mass spectrometry as one of the proteins of the human 40S (small) ribosomal subunit. Reason: This is the core cellular component for RPS3, directly evidenced by characterization of the human 40S ribosomal subunit proteins. Supporting Evidence: PMID:8706699 This allowed us to identify all proteins from the 40S human ribosomal subunit in the HPLC elution profile.
GO:0003729 mRNA binding	IDA PMID:18464793 Ribosomal position and contacts of mRNA in eukaryotic transl...	ACCEPT	Summary: In eukaryotic initiation complexes, mRNA crosslinks to RPS3 (rpS3/S3p) at the mRNA entry channel of the 40S subunit, indicating direct mRNA contact. Reason: RPS3 sits at the mRNA entry channel and directly contacts mRNA in the 40S subunit during initiation; mRNA binding is thus part of its core ribosomal structural/functional role at the decoding/entry site. Supporting Evidence: PMID:18464793 Crosslinking of mRNA positions (+)11 to ribosomal protein (rp) rpS2(S5p) and rpS3(S3p)
GO:0003735 structural constituent of ribosome	NAS PMID:1712897 Ribosomal protein genes are overexpressed in colorectal canc...	ACCEPT	Summary: RPS3 was cloned and identified as the human S3 ribosomal protein, a structural component of the ribosome. Reason: Structural constituent of ribosome is the core molecular function of RPS3, supported here by its identification as the human S3 ribosomal protein. Supporting Evidence: PMID:1712897 isolation of a cDNA clone encoding the human S3 ribosomal protein
GO:0005634 nucleus	IDA PMID:14988002 RpS3, a DNA repair endonuclease and ribosomal protein, is in...	KEEP AS NON CORE	Summary: Endogenous RPS3 translocated into nuclei in cytokine-treated cells undergoing apoptosis. Reason: Stimulus-dependent nuclear translocation in an apoptosis context is a regulated extra-ribosomal pool, non-core relative to the cytosolic ribosomal location. Retained as non-core. Supporting Evidence: PMID:14988002 RpS3, a DNA repair endonuclease and ribosomal protein, is involved in apoptosis.
GO:0005737 cytoplasm	IDA PMID:14988002 RpS3, a DNA repair endonuclease and ribosomal protein, is in...	ACCEPT	Summary: RPS3 is present in the cytoplasm under basal conditions, with translocation to the nucleus during cytokine-induced apoptosis. Reason: Cytoplasm is the expected, core cellular location for RPS3's cytosolic ribosomal function. Supporting Evidence: PMID:14988002 RpS3, a DNA repair endonuclease and ribosomal protein, is involved in apoptosis.
GO:0005829 cytosol	IDA PMID:16814409 Reduction of invasion in human fibrosarcoma cells by ribosom...	ACCEPT	Summary: RPS3 localizes to the cytoplasm/cytosol and cell periphery, where it colocalizes with Nm23-H1. Reason: Cytosol is the expected, core cellular location for RPS3's cytosolic ribosomal function. Supporting Evidence: PMID:16814409 the two proteins were colocalized in the cell periphery and cytoplasm.
GO:0019901 protein kinase binding	IPI PMID:15950189 Erk phosphorylates threonine 42 residue of ribosomal protein...	KEEP AS NON CORE	Summary: RPS3 has an FXFP motif that serves as an ERK (MAP kinase) binding site, and ERK phosphorylates RPS3 at Thr42, as confirmed by co-immunoprecipitation. Reason: Protein kinase binding captures the directly-evidenced ERK interaction that regulates RPS3 phosphorylation and its stress-induced nuclear translocation, an extra-ribosomal regulatory context. More informative than generic protein binding but non-core. Supporting Evidence: PMID:15950189 the motif was demonstrated as an Erk binding site by co-immunoprecipitation. In addition to this, it was revealed that Erk specifically phosphorylated Thr 42 residue of rpS3
GO:0032587 ruffle membrane	IDA PMID:16814409 Reduction of invasion in human fibrosarcoma cells by ribosom...	MARK AS OVER ANNOTATED	Summary: RPS3 was observed at the cell periphery in the context of its Nm23-H1 interaction and inhibition of invasion. Reason: Ruffle membrane localization is a very specific term inferred from cell-periphery colocalization in an invasion assay; the evidence does not robustly establish stable ruffle-membrane residency of RPS3. Treated as an over-annotation. Supporting Evidence: PMID:16814409 the two proteins were colocalized in the cell periphery and cytoplasm.
GO:0051536 iron-sulfur cluster binding	NAS PMID:11911468 Electron paramagnetic resonance study reveals a putative iro...	MARK AS OVER ANNOTATED	Summary: An EPR study reported an apparent iron-sulfur-cluster signal in human RPS3, proposed in analogy to E. coli endonuclease III. Reason: The iron-sulfur cluster claim is weakly supported and was not reproduced: refolding RPS3 with Fe2+/S2- did not increase activity and the protein's AP-lyase mechanism does not require a cluster (PMID:18610840). This is best treated as an over-annotation of a putative cofactor. Supporting Evidence: PMID:18610840 Refolding of hS3 in the presence of Fe2+ and S2- ions did not increase its activity, despite the earlier suggestions that this protein could contain an iron-sulfur cluster.
GO:0003684 damaged DNA binding	IDA PMID:16737853 The high binding affinity of human ribosomal protein S3 to 7...	KEEP AS NON CORE	Summary: Human RPS3 binds 8-oxoG with high affinity; a single K132A change in its helix-hairpin-helix motif abolishes 8-oxoG binding while retaining AP-DNA-cleavage activity. Reason: Damaged DNA binding is well-supported and mapped to a specific HhH DNA binding residue (K132). It is an extra-ribosomal moonlighting activity, secondary to the core ribosomal function. Retained as non-core. Supporting Evidence: PMID:16737853 One putative site, lysine 132 (K132), located in a helix-hairpin-helix DNA binding motif, was mutated to alanine (K132A). The hS3-K132A mutant retained the ability to cleave abasic DNA, but its capacity to bind 8-oxoG was abrogated completely.
GO:0003906 DNA-(apurinic or apyrimidinic site) endonuclease activity	IDA PMID:16737853 The high binding affinity of human ribosomal protein S3 to 7...	KEEP AS NON CORE	Summary: Human RPS3 (and its K132A mutant) cleaves abasic DNA, an AP-lyase/AP- endonuclease-type activity; importantly, RPS3 binding to 8-oxoG can inhibit OGG1-mediated repair. Reason: AP-site cleavage is supported, but the broader physiological significance of this activity is debated and context-dependent (RPS3 can inhibit rather than promote OGG1 repair). Retained as a non-core, context-dependent activity. Supporting Evidence: PMID:16737853 The hS3-K132A mutant retained the ability to cleave abasic DNA
GO:0005634 nucleus	IDA PMID:18045535 Ribosomal protein S3: a KH domain subunit in NF-kappaB compl...	KEEP AS NON CORE	Summary: Lymphocyte-activating stimuli cause nuclear translocation of RPS3 (parallel to p65), where it forms part of NF-kB bound to specific chromatin regulatory sites. Reason: Stimulus-dependent nuclear localization in the NF-kB context is a regulated extra-ribosomal pool, non-core relative to the cytosolic ribosomal location. Retained as non-core. Supporting Evidence: PMID:18045535 lymphocyte-activating stimuli caused nuclear translocation of RPS3, parallel to p65, to form part of NF-kappaB bound to specific regulatory sites in chromatin.
GO:0006974 DNA damage response	IEP PMID:17560175 Translocation of human ribosomal protein S3 to sites of DNA ...	KEEP AS NON CORE	Summary: Genotoxic stress triggers ERK-dependent phosphorylation and nuclear translocation of RPS3 and its co-localization with 8-oxoG damage foci, placing it in a cellular DNA damage response pathway. Reason: Participation in the DNA damage response is a regulated extra-ribosomal moonlighting role (damaged-DNA binding/relocalization), secondary to the core ribosomal function. Retained as non-core. Supporting Evidence: PMID:17560175 hS3 is a member of a cellular DNA damage response pathway that results in its interaction with sites of DNA damage.
GO:0045738 negative regulation of DNA repair	IMP PMID:17049931 Knockdown of ribosomal protein S3 protects human cells from ...	KEEP AS NON CORE	Summary: RPS3 knockdown increased survival of cells exposed to oxidative/alkylating genotoxic agents, and RPS3 inhibits OGG1 from liberating 8-oxoG, indicating RPS3 can negatively affect base-excision repair. Reason: RPS3 can negatively regulate repair (by sequestering 8-oxoG lesions from OGG1), a context-dependent extra-ribosomal activity. Note this is opposite in sign to other reports where RPS3 stimulates repair (PMID:18973764), so the net effect is context-dependent. Retained as non-core. Supporting Evidence: PMID:17049931 a 40% knockdown of hS3 resulted in as much as a seven-fold increase in the 24h survival-rate of HEK293 cells exposed to hydrogen peroxide.
GO:0003735 structural constituent of ribosome	HDA PMID:15883184 Mass spectrometric analysis of the human 40S ribosomal subun...	ACCEPT	Summary: RPS3 was identified by mass spectrometry as a protein of the human 40S ribosomal subunit in native and HCV IRES-bound complexes. Reason: Structural constituent of ribosome is the core molecular function of RPS3, supported here by direct identification within the human 40S subunit. Supporting Evidence: PMID:15883184 Thirty-one out of a possible 32 ribosomal proteins were identified by combining top-down and bottom-up mass spectrometry techniques.
GO:0022627 cytosolic small ribosomal subunit	HDA PMID:15883184 Mass spectrometric analysis of the human 40S ribosomal subun...	ACCEPT	Summary: RPS3 is a component of the human 40S (cytosolic small) ribosomal subunit, as identified by mass spectrometry of native and IRES-bound 40S complexes. Reason: This is the core cellular component for RPS3, directly supported by compositional analysis of the human 40S subunit. Supporting Evidence: PMID:15883184 a global protein composition analysis of native and IRES-bound 40S ribosomal complexes has been conducted

Core Functions

RPS3/uS3 is a structural component of the human cytosolic small ribosomal subunit and supports cytoplasmic translation. This ribosomal role is the physiological primary function; DNA repair, NF-kB/transcription, and apoptosis annotations should be treated as context-dependent extra-ribosomal functions.

Molecular Function:

structural constituent of ribosome

Directly Involved In:

translation

Cellular Locations:

cytosolic ribosome cytosol

Supporting Evidence:

PMID:23636399
Here we present structures of Drosophila melanogaster and Homo sapiens 80S ribosomes in complex with the translation factor eEF2, E-site transfer RNA and Stm1-like proteins, based on high-resolution cryo-electron-microscopy density maps.
file:human/RPS3/RPS3-deep-research-falcon.md
RPS3 is a core protein of the **cytosolic small ribosomal subunit (40S)** and therefore supports GO annotations centered on (i) **structural constituent of ribosome**, (ii) **cytoplasmic translation**, and (iii) localization to **cytosolic ribosome / small ribosomal subunit / cytosol (cytoplasm)**.

References

GO_REF:0000002

Gene Ontology annotation through association of InterPro records with GO terms

GO_REF:0000033

Annotation inferences using phylogenetic trees

GO_REF:0000043

Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping

GO_REF:0000044

Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt

GO_REF:0000052

Gene Ontology annotation based on curation of immunofluorescence data

GO_REF:0000107

Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara

GO_REF:0000108

Automatic assignment of GO terms using logical inference, based on on inter-ontology links

GO_REF:0000117

Electronic Gene Ontology annotations created by ARBA machine learning models

GO_REF:0000120

Combined Automated Annotation using Multiple IEA Methods

PMID:11911468

Electron paramagnetic resonance study reveals a putative iron-sulfur cluster in human rpS3 protein.

PMID:14706345

Characterization of human ribosomal protein S3 binding to 7,8-dihydro-8-oxoguanine and abasic sites by surface plasmon resonance.

RPS3/hS3 binds damaged DNA lesions, including 8-oxoG and AP DNA, with high affinity.

"An even more dramatic five orders of magnitude higher binding affinity for AP DNA was found for hS3 as opposed to hOGG1."

PMID:14988002

RpS3, a DNA repair endonuclease and ribosomal protein, is involved in apoptosis.

RPS3 overexpression can activate caspase-dependent apoptosis in a cytokine-treatment context.

"Transient expression of GFP-rpS3 activates caspase-8/caspase-3 and sensitizes cytokine-induced apoptosis."

PMID:15161933

Comprehensive proteomic analysis of interphase and mitotic 14-3-3-binding proteins.

PMID:15518571

Human ribosomal protein S3 interacts with DNA base excision repair proteins hAPE/Ref-1 and hOGG1.

Human RPS3/hS3 interacts with OGG1 and APE/Ref-1 and may influence DNA repair activities at damage sites.

"These results raise the possibility that hS3 not only functions as a ribosomal protein but, in addition, may influence repair activities at sites of DNA damage."

PMID:15707971

Characterization of a wide range base-damage-endonuclease activity of mammalian rpS3.

PMID:15883184

Mass spectrometric analysis of the human 40S ribosomal subunit: native and HCV IRES-bound complexes.

PMID:15950189

Erk phosphorylates threonine 42 residue of ribosomal protein S3.

PMID:16737853

The high binding affinity of human ribosomal protein S3 to 7,8-dihydro-8-oxoguanine is abrogated by a single amino acid change.

PMID:16814409

Reduction of invasion in human fibrosarcoma cells by ribosomal protein S3 in conjunction with Nm23-H1 and ERK.

PMID:17049931

Knockdown of ribosomal protein S3 protects human cells from genotoxic stress.

PMID:1712897

Ribosomal protein genes are overexpressed in colorectal cancer: isolation of a cDNA clone encoding the human S3 ribosomal protein.

PMID:17289661

Molecular composition of IMP1 ribonucleoprotein granules.

PMID:17560175

Translocation of human ribosomal protein S3 to sites of DNA damage is dependant on ERK-mediated phosphorylation following genotoxic stress.

PMID:18045535

Ribosomal protein S3: a KH domain subunit in NF-kappaB complexes that mediates selective gene regulation.

PMID:18274552

Ribosomal proteins are targets for the NEDD8 pathway.

PMID:18464793

Ribosomal position and contacts of mRNA in eukaryotic translation initiation complexes.

PMID:18610840

[Interactions of human ribosomal protein S3 with undamaged and damaged DNA].

PMID:18973764

Human ribosomal protein S3 (hRpS3) interacts with uracil-DNA glycosylase (hUNG) and stimulates its glycosylase activity.

PMID:19059439

PKCdelta-dependent functional switch of rpS3 between translation and DNA repair.

PMID:19460357

Arginine methylation of ribosomal protein S3 affects ribosome assembly.

PMID:19656744

Ribosomal protein S3: A multi-functional protein that interacts with both p53 and MDM2 through its KH domain.

PMID:19946888

Defining the membrane proteome of NK cells.

PMID:20041225

Bacterial effector binding to ribosomal protein s3 subverts NF-kappaB function.

PMID:20217897

RpS3 translation is repressed by interaction with its own mRNA.

PMID:20458337

MHC class II-associated proteins in B-cell exosomes and potential functional implications for exosome biogenesis.

PMID:20605787

Ribosomal protein S3, a new substrate of Akt, serves as a signal mediator between neuronal apoptosis and DNA repair.

PMID:20618440

Proteomic and biochemical analysis of 14-3-3-binding proteins during C2-ceramide-induced apoptosis.

PMID:21145461

Dynamics of cullin-RING ubiquitin ligase network revealed by systematic quantitative proteomics.

PMID:21146485

Identification of cyclophilin-40-interacting proteins reveals potential cellular function of cyclophilin-40.

PMID:21170055

Characterization of the proteome, diseases and evolution of the human postsynaptic density.

PMID:21399639

IKKβ phosphorylation regulates RPS3 nuclear translocation and NF-κB function during infection with Escherichia coli strain O157:H7.

PMID:21423176

Analysis of the myosin-II-responsive focal adhesion proteome reveals a role for β-Pix in negative regulation of focal adhesion maturation.

PMID:21871177

Ribosomal protein S3 is phosphorylated by Cdk1/cdc2 during G2/M phase.

PMID:21968017

Ribosomal protein S3 is stabilized by sumoylation.

PMID:22113938

A bead-based approach for large-scale identification of in vitro kinase substrates.

PMID:22244329

Hydrogen sulfide-linked sulfhydration of NF-κB mediates its antiapoptotic actions.

PMID:22510408

Ribosomal protein S3 interacts with TRADD to induce apoptosis through caspase dependent JNK activation.

PMID:22658674

Insights into RNA biology from an atlas of mammalian mRNA-binding proteins.

PMID:22681889

The mRNA-bound proteome and its global occupancy profile on protein-coding transcripts.

PMID:23131551

Ribosomal protein S3 localizes on the mitotic spindle and functions as a microtubule associated protein in mitosis.

PMID:23636399

Structures of the human and Drosophila 80S ribosome.

Human 80S ribosome structures support RPS3's core role as a structural constituent of the cytosolic ribosome/small ribosomal subunit.

"Here we present structures of Drosophila melanogaster and Homo sapiens 80S ribosomes in complex with the translation factor eEF2, E-site transfer RNA and Stm1-like proteins, based on high-resolution cryo-electron-microscopy density maps."

PMID:23911537

Cytoplasmic ribosomal protein S3 (rpS3) plays a pivotal role in mitochondrial DNA damage surveillance.

PMID:24423872

AUF1 contributes to Cryptochrome1 mRNA degradation and rhythmic translation.

PMID:24457201

Ribosomal protein S3 interacts with the NF-κB inhibitor IκBα.

PMID:24725412

Ribosomal protein s15 phosphorylation mediates LRRK2 neurodegeneration in Parkinson's disease.

PMID:24965446

Host factors that interact with the pestivirus N-terminal protease, Npro, are components of the ribonucleoprotein complex.

PMID:25609649

Proteomic analyses reveal distinct chromatin-associated and soluble transcription factor complexes.

PMID:25901680

Structure of the human 80S ribosome.

PMID:26526615

Caspase-3 cleaved p65 fragment dampens NF-κB-mediated anti-apoptotic transcription by interfering with the p65/RPS3 interaction.

PMID:28065601

Initiation of Quality Control during Poly(A) Translation Requires Site-Specific Ribosome Ubiquitination.

PMID:28132843

ZNF598 and RACK1 Regulate Mammalian Ribosome-Associated Quality Control Function by Mediating Regulatory 40S Ribosomal Ubiquitylation.

PMID:30021884

Histone Interaction Landscapes Visualized by Crosslinking Mass Spectrometry in Intact Cell Nuclei.

PMID:31046837

Parkinson's disease-associated LRRK2-G2019S mutant acts through regulation of SERCA activity to control ER stress in astrocytes.

PMID:32296183

A reference map of the human binary protein interactome.

PMID:32814053

Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains.

PMID:33961781

Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.

PMID:35271311

OpenCell: Endogenous tagging for the cartography of human cellular organization.

PMID:39251607

Systematic identification of post-transcriptional regulatory modules.

PMID:40205054

Multimodal cell maps as a foundation for structural and functional genomics.

PMID:7775413

Implication of mammalian ribosomal protein S3 in the processing of DNA damage.

Historical biochemical evidence connects mammalian ribosomal protein S3 with AP/UV endonuclease activities, but this is secondary to the core ribosomal role.

"The unexpected role of a ribosomal protein in DNA damage processing and the unexplained inability to detect the nuclease activities in complementation group-D xeroderma pigmentosum cells suggest that these activities may be important to cellular DNA repair."

PMID:8706699

Characterization of the human small-ribosomal-subunit proteins by N-terminal and internal sequencing, and mass spectrometry.

file:human/RPS3/RPS3-deep-research-falcon.md

Falcon deep research on RPS3 GO-relevant functions

RPS3's core GO annotations should prioritize ribosome structure, cytosolic small ribosomal subunit localization, and translation.

"RPS3 is a core protein of the **cytosolic small ribosomal subunit (40S)** and therefore supports GO annotations centered on (i) **structural constituent of ribosome**, (ii) **cytoplasmic translation**, and (iii) localization to **cytosolic ribosome / small ribosomal subunit / cytosol (cytoplasm)**."
DNA repair and NF-kB/apoptosis annotations are secondary moonlighting contexts that require cautious evidence handling.

"A second tier of GO-relevant “extra-ribosomal” evidence (DNA lesion binding/BER cofactor activity, NF-κB transcriptional specificity, apoptosis) exists, but requires careful caveats about direct catalytic activity vs **cofactor/interaction** roles, species extrapolations, and the frequent reliance on **review synthesis** rather than modern physiological genetics."
Mitochondrial inner membrane and ER localization should not be retained without direct RPS3-specific localization evidence.

"**Mitochondrial inner membrane / ER:** no direct, RPS3-specific evidence in the retrieved corpus supports stable mitochondrial inner membrane or ER localization; avoid those CC annotations without targeted localization data."

Reactome:R-HSA-156808

Formation of translation initiation complexes yielding circularized Ceruloplasmin mRNA in a 'closed-loop' conformation

Reactome:R-HSA-156823

Association of phospho-L13a with GAIT element of Ceruloplasmin mRNA

Reactome:R-HSA-157849

Formation of translation initiation complexes containing mRNA that does not circularize

Reactome:R-HSA-1799332

Nascent polypeptide:mRNA:ribosome complex binds signal recognition particle (SRP)

Reactome:R-HSA-1799335

Synthesis of nascent polypeptide containing signal sequence

Reactome:R-HSA-192704

Synthesis of PB1-F2

Reactome:R-HSA-192841

Viral Protein Synthesis

Reactome:R-HSA-6791223

18SE pre-rRNA in pre-40S particles is nucleolytically processed during translocation from the nucleus to the cytosol

Reactome:R-HSA-72619

eIF2:GTP is hydrolyzed, eIFs are released

Reactome:R-HSA-72621

Ribosomal scanning

Reactome:R-HSA-72671

eIF5B:GTP is hydrolyzed and released

Reactome:R-HSA-72672

The 60S subunit joins the translation initiation complex

Reactome:R-HSA-72673

Release of 40S and 60S subunits from the 80S ribosome

Reactome:R-HSA-72676

eIF3 and eIF1A bind to the 40S subunit

Reactome:R-HSA-72691

Formation of the 43S pre-initiation complex

Reactome:R-HSA-72697

Start codon recognition

Reactome:R-HSA-927789

Formation of UPF1:eRF3 complex on mRNA with a premature termination codon and no Exon Junction Complex

Reactome:R-HSA-927813

p-4S-UPF1 recruits SMG5, SMG7, SMG6, PNRC2, DCP1A, and PP2A

Reactome:R-HSA-927832

UPF1 binds an mRNP with a termination codon preceding an Exon Junction Complex

Reactome:R-HSA-927836

SMG6 hydrolyzes mRNA with premature termination codon

Reactome:R-HSA-927889

SMG1 phosphorylates UPF1 (enhanced by Exon Junction Complex)

Reactome:R-HSA-9729232

SARS-CoV-1 nsp1 binds to 40S ribosomal subunit

Reactome:R-HSA-9729849

SARS-CoV-2 nsp1 binds to 40S ribosomal complex

Reactome:R-HSA-9948291

RQT complex binds K63polyUb-80S ribosome:no-go mRNA:peptidyl-tRNA with nascent peptide

Reactome:R-HSA-9948300

RQT complex:K63polyUb-80S ribosome dissociates yielding K63polyUb-40S subunit and 60S subunit:peptidyl-tRNA with nascent peptide

Reactome:R-HSA-9948301

ZNF598 K63 polyubiquitinates RPS10 (eS10) and RPS20 (uS10) of the 40S ribosomal subunit

Reactome:R-HSA-9948317

ZNF598 and Ub:UBE2D1,2,3 bind stalled 80S ribosome

Reactome:R-HSA-9954730

PELO:HBS1L-1:GTP binds 80S ribosome:non-stop mRNA:peptidyl-tRNA with nascent peptide

Reactome:R-HSA-9954919

ABCE1:ATP binds PELO:HBS1L-1:GTP:80S ribosome:non-stop mRNA:peptidyl-tRNA with nascent peptide and HBS1L-1:GDP is released

Reactome:R-HSA-9955731

ABCE1:PELO:80S Ribosome:non-stop mRNA:peptidyl-tRNA with elongating peptide dissociates yielding ABCE1:40S ribosomal subunit, PELO, and 60S ribosomal subunit:peptidyl-tRNA with nascent peptide

Suggested Experiments

Experiment: Use endogenous-tagged RPS3 with ribosome and nuclear stress markers to quantify steady-state cytosolic ribosome localization versus inducible nuclear NF-kB/apoptosis-associated translocation.

Experiment: Reconstitute purified human RPS3 with defined AP and 8-oxoG substrates plus APE1/OGG1 to separate damaged-DNA binding, enzyme stimulation, and intrinsic AP lyase/endonuclease activity.

Deep Research

Falcon

(RPS3-deep-research-falcon.md)

Question: You are an expert researcher providing comprehensive, well-cited information. Falcon Edison Scientific Literature 30 citations 2026-05-12T19:38:03.653005

Question: You are an expert researcher providing comprehensive, well-cited information.

Provide detailed information focusing on:
1. Key concepts and definitions with current understanding
2. Recent developments and latest research (prioritize 2023-2024 sources)
3. Current applications and real-world implementations
4. Expert opinions and analysis from authoritative sources
5. Relevant statistics and data from recent studies

Format as a comprehensive research report with proper citations. Include URLs and publication dates where available.
Always prioritize recent, authoritative sources and provide specific citations for all major claims.

Concise GO annotation research for human RPS3 / UniProt P23396 (40S ribosomal protein S3, uS3). Focus only on GO-relevant evidence: core role as structural constituent of the small ribosomal subunit/cytosolic ribosome and cytoplasmic translation; cellular locations cytosolic small ribosomal subunit, ribosome, cytosol/cytoplasm, nucleus/nucleolus, synapse/postsynaptic density, mitochondrial inner membrane or ER if supported; non-ribosomal activities including damaged DNA binding, class I DNA-(apurinic/apyrimidinic site) endonuclease/AP lyase activity, base-excision repair/DNA damage response, interactions with APEX1/OGG1, wide-range base-damage endonuclease claims; regulation of NF-kB or transcription by RNA polymerase II, DNA-binding transcription factor binding/coactivator caveats; apoptosis regulation; RNA binding. Include caveats for generic protein binding, high-throughput interactome rows, over-broad cell division/apoptosis/development terms, and whether DNA repair enzymatic activity is direct and physiologically core or secondary. Include PMID/DOI citations and keep under 1500 words.

Concise GO annotation research report: Human RPS3 (UniProt P23396, 40S ribosomal protein S3 / uS3)

Scope and key GO concepts

RPS3 is a core protein of the cytosolic small ribosomal subunit (40S) and therefore supports GO annotations centered on (i) structural constituent of ribosome, (ii) cytoplasmic translation, and (iii) localization to cytosolic ribosome / small ribosomal subunit / cytosol (cytoplasm). Evidence also supports nuclear (and more cautiously nucleolar) presence tied to ribosome biogenesis and to stimulus-dependent “moonlighting” signaling roles. (dionne2018characterizationofzinc pages 26-29, dionne2018characterizationofzinc pages 10-15)

A second tier of GO-relevant “extra-ribosomal” evidence (DNA lesion binding/BER cofactor activity, NF-κB transcriptional specificity, apoptosis) exists, but requires careful caveats about direct catalytic activity vs cofactor/interaction roles, species extrapolations, and the frequent reliance on review synthesis rather than modern physiological genetics. (gao2011ribosomalproteins3 pages 2-3, wan2011ikkβphosphorylationregulates pages 1-3)

GO aspect	Suggested GO term name	Evidence summary	Evidence type	Key citations	Caveats
MF	structural constituent of ribosome	RPS3/uS3 is a canonical 40S small-subunit protein; assembly literature supports incorporation into pre-40S particles and mature cytosolic ribosomes (dionne2018characterizationofzinc pages 26-29, dionne2018characterizationofzinc pages 10-15)	low-throughput + background/review	Wan et al., Nat Immunol. 2011, doi:10.1038/ni.2007, Mar 2011, https://doi.org/10.1038/ni.2007 (wan2011ikkβphosphorylationregulates pages 1-3); Dionne 2018 thesis excerpts (dionne2018characterizationofzinc pages 26-29, dionne2018characterizationofzinc pages 10-15)	Core/physiologic role; strongest GO support. Some assembly details derive from yeast-conserved pathways rather than direct human perturbation.
BP	cytoplasmic translation	Proteomics and ribosome-biology sources place RPS3 in the cytosolic 40S machinery supporting translation; 2024 tumor proteomics enriched DEPs in cytoplasmic translation/cytosolic ribosome/structural constituent of ribosome (tan2019theinteractomeof pages 13-15, tong2024proteomicsshowsthat pages 3-5)	high-throughput + background	Tong et al., Sci Rep 2024-07, doi:10.1038/s41598-024-58967-y, https://doi.org/10.1038/s41598-024-58967-y (tong2024proteomicsshowsthat pages 3-5)	Enrichment/proteomics is indirect for RPS3-specific function, but aligns with canonical biology.
CC	cytosolic small ribosomal subunit / cytosolic ribosome / cytosol	RPS3 detected with multiple ribosomal proteins in AP-MS/proteomics datasets; consistent with 40S/cytosolic ribosome localization (tan2019theinteractomeof pages 13-15, zeng2023spatiallyresolvedsinglecell pages 3-5)	high-throughput + orthogonal method use	Zeng et al., Science 2023-06, doi:10.1126/science.add3067, https://doi.org/10.1126/science.add3067 (zeng2023spatiallyresolvedsinglecell pages 3-5); Tong et al. 2024 (tong2024proteomicsshowsthat pages 3-5)	AP-MS and antibody-based ribosome targeting support localization/association, not independent proof of all subcellular contexts.
CC	nucleus	uS3/RPS3 is imported to the nucleus for pre-40S incorporation; multiple studies show stimulus-dependent nuclear translocation in extra-ribosomal contexts (NF-κB, apoptosis, DNA damage) (dionne2018characterizationofzinc pages 26-29, gao2011ribosomalproteins3 pages 2-3, jang2004rps3adna pages 3-4, wan2011ikkβphosphorylationregulates pages 1-3)	low-throughput	Wan et al., Nat Immunol. 2011, doi:10.1038/ni.2007, https://doi.org/10.1038/ni.2007 (wan2011ikkβphosphorylationregulates pages 1-3); Jang et al., FEBS Lett. 2004-02, doi:10.1016/S0014-5793(04)00074-2, https://doi.org/10.1016/S0014-5793(04)00074-2 (jang2004rps3adna pages 3-4)	Nuclear localization is well supported, but occurs in both ribosome biogenesis and moonlighting pathways; annotation should avoid overgeneralizing to transcription regulation per se.
CC	nucleolus	Ribosome-biogenesis context and intronic snoRNA biology of human RPS3 support nucleolar relevance during ribosome assembly/processing (lim2002completegenomicstructure pages 7-7)	low-throughput + background	Lim et al., Gene 2002-03, doi:10.1016/S0378-1119(02)00502-4, https://doi.org/10.1016/S0378-1119(02)00502-4 (lim2002completegenomicstructure pages 7-7)	Evidence is more about RPS3 gene-associated snoRNA/biogenesis context than direct imaging of RPS3 protein in nucleoli. Use cautiously.
CC	synapse / postsynaptic density	Recent data support ribosome/translation machinery near synaptic compartments; RPS3 was used as a ribosome marker in spatial translatomics, and synaptosome proteomics supports synaptic local translation context (gorski2025insightsintosynaptic pages 71-74, zeng2023spatiallyresolvedsinglecell pages 3-5)	high-throughput	Zeng et al., Science 2023-06, doi:10.1126/science.add3067, https://doi.org/10.1126/science.add3067 (zeng2023spatiallyresolvedsinglecell pages 3-5)	Evidence is indirect for human RPS3-specific PSD residency; better treated as synaptic ribosome/local translation association, not a definitive stable PSD component.
MF	RNA binding	RPS3 contains a KH domain; review/primary NF-κB literature notes KH-domain-mediated ssRNA/ssDNA binding and association with p65 (wan2010thenuclearsignaling pages 1-2, gao2011ribosomalproteins3 pages 1-2)	review + low-throughput	Wan & Lenardo, Cell Res. 2010-12, doi:10.1038/cr.2009.137, https://doi.org/10.1038/cr.2009.137 (wan2010thenuclearsignaling pages 1-2)	RNA binding is credible, but much evidence is domain-based or in NF-κB context; avoid broad annotations to sequence-specific RNA regulation without direct assays.
MF	damaged DNA binding	Human RPS3 binds tightly to abasic (AP) and 8-oxoG lesions; cited as damaged-DNA recognition in BER-related studies (gao2011ribosomalproteins3 pages 2-3, wan2011ikkβphosphorylationregulates pages 11-13)	review summarizing primary low-throughput	Gao & Hardwidge, Front Microbiol. 2011-06, doi:10.3389/fmicb.2011.00137, https://doi.org/10.3389/fmicb.2011.00137 (gao2011ribosomalproteins3 pages 2-3); Wan et al. 2011 cites Hegde 2004 PMID:14706345 (wan2011ikkβphosphorylationregulates pages 11-13)	Stronger for lesion binding than for direct catalytic repair in vivo. Much wording comes through reviews citing older primary papers.
MF	AP lyase / DNA-(apurinic or apyrimidinic site) endonuclease activity	Historical literature reports human RPS3 as a DNA repair endonuclease and phosphorylation-enhanced endonuclease activity; C-terminus implicated in repair function (gao2011ribosomalproteins3 pages 3-4, jang2004rps3adna pages 3-4, jang2004rps3adna pages 1-2)	low-throughput + review	Jang et al., FEBS Lett. 2004-02, doi:10.1016/S0014-5793(04)00074-2, https://doi.org/10.1016/S0014-5793(04)00074-2 (jang2004rps3adna pages 3-4); Lim et al. 2002, https://doi.org/10.1016/S0378-1119(02)00502-4 (lim2002completegenomicstructure pages 7-7)	Major caveat: direct intrinsic human AP-lyase/endonuclease activity remains debated/secondary; some strongest catalytic evidence is from Drosophila/yeast or engineered variants, not clear core human physiology.
BP / MF	base-excision repair; BER enzyme activator/cofactor	Human RPS3 reportedly stimulates uracil-DNA glycosylase, hOGG1, and APE1/Ref-1 while lacking its own glycosylase activity; supports BER participation via cofactor-like action (gao2011ribosomalproteins3 pages 2-3)	review summarizing primary low-throughput	Gao & Hardwidge, Front Microbiol. 2011-06, doi:10.3389/fmicb.2011.00137, https://doi.org/10.3389/fmicb.2011.00137 (gao2011ribosomalproteins3 pages 2-3)	Best framed as interaction/stimulation within BER, not core BER enzyme. Direct physical interaction details with OGG1/APEX1 should be annotated cautiously unless curators verify original primary assays.
BP / MF	NF-κB complex cofactor; transcription coactivator activity caveat	RPS3 is a non-Rel NF-κB subunit/specifier that binds p65, enhances selective κB-site occupancy, and requires IKKβ-dependent S209 phosphorylation for nuclear import (wan2010thenuclearsignaling pages 1-2, wan2011ikkβphosphorylationregulates pages 1-3, wan2011ikkβphosphorylationregulates media cf840cd8)	low-throughput + review	Wan et al., Nat Immunol. 2011-03, doi:10.1038/ni.2007, https://doi.org/10.1038/ni.2007 (wan2011ikkβphosphorylationregulates pages 1-3); Wan & Lenardo, Cell Res. 2010-12, doi:10.1038/cr.2009.137, https://doi.org/10.1038/cr.2009.137 (wan2010thenuclearsignaling pages 1-2); Sen et al., Mol Cell 2012-01, doi:10.1016/j.molcel.2011.10.021, https://doi.org/10.1016/j.molcel.2011.10.021 (gao2011ribosomalproteins3 pages 5-6)	Strong for NF-κB cofactor/specifier in selected promoters; weaker for generic “RNA polymerase II transcription” or “DNA-binding transcription factor binding/coactivator” across all contexts.
CC / BP	nuclear translocation in NF-κB signaling	Co-IP, phospho-specific blots, microscopy, and fractionation show TNF/PMA-induced S209 phosphorylation, importin-α association, and reduced nuclear entry of S209A mutant (wan2011ikkβphosphorylationregulates pages 1-3, wan2011ikkβphosphorylationregulates media cf840cd8)	low-throughput	Wan et al., Nat Immunol. 2011-03, doi:10.1038/ni.2007, https://doi.org/10.1038/ni.2007 (wan2011ikkβphosphorylationregulates pages 1-3)	Supports regulated nuclear trafficking, not broad chromatin residency.
BP	regulation of apoptotic process	RPS3 overexpression/transfection induces apoptosis with caspase-8/caspase-3 dependence; endogenous rpS3 accumulates in nuclei during cytokine-treated apoptosis (jang2004rps3adna pages 3-4, gao2011ribosomalproteins3 pages 3-4)	low-throughput	Jang et al., FEBS Lett. 2004-02, doi:10.1016/S0014-5793(04)00074-2, https://doi.org/10.1016/S0014-5793(04)00074-2 (jang2004rps3adna pages 3-4)	Likely context-dependent moonlighting effect; do not overextend to generic apoptosis/development terms without genetic/physiologic evidence.
CC / misc. caution	mitochondrial inner membrane / ER	No convincing direct evidence in gathered RPS3-specific sources for stable mitochondrial inner membrane localization; ER-related translation appears generic/translatome-level, not RPS3-specific (zeng2023spatiallyresolvedsinglecell pages 13-18, zeng2023spatiallyresolvedsinglecell pages 3-5)	negative / insufficient	Zeng et al., Science 2023-06, https://doi.org/10.1126/science.add3067 (zeng2023spatiallyresolvedsinglecell pages 13-18, zeng2023spatiallyresolvedsinglecell pages 3-5)	Avoid GO annotation to mitochondrial inner membrane or ER unless supported by direct targeted localization evidence for human RPS3.
misc. caution	generic protein binding / cell division / development terms	Interactome/AP-MS rows detect RPS3 in many complexes but are insufficient for specific GO molecular functions or broad processes without orthogonal validation (rahim2018globalinteractomicsconnect pages 11-12, tan2019theinteractomeof pages 13-15)	high-throughput	Rahim et al., Viruses 2018-12, doi:10.3390/v10120731, https://doi.org/10.3390/v10120731 (rahim2018globalinteractomicsconnect pages 11-12); Tan et al., 2019 preprint, doi:10.21203/rs.2.12355/v1, https://doi.org/10.21203/rs.2.12355/v1 (tan2019theinteractomeof pages 13-15)	Curate generic binding/over-broad process terms conservatively; HTP co-purification does not establish direct function, physiological relevance, or stable localization.

Table: This table compiles GO-relevant evidence for human RPS3/P23396 across canonical ribosomal functions, cellular locations, and reported moonlighting activities. It emphasizes evidence strength and caveats to help distinguish core annotations from context-dependent or indirect claims.

1) Core ribosomal function (highest-confidence GO)

Structural constituent of cytosolic ribosome / small ribosomal subunit (MF/CC)
- Ribosome assembly/biogenesis literature supports that uS3/RPS3 is a canonical 40S protein that is handled by dedicated chaperone pathways and imported for pre-40S incorporation, consistent with core ribosome structure. (dionne2018characterizationofzinc pages 26-29)

Cytoplasmic translation (BP)
- A 2024 clinical proteomics study of lung adenocarcinoma (LUAD) brain metastases after gamma knife radiosurgery (GKRS) shows differentially expressed proteins enriched in cytoplasmic translation, and in CC/MF categories including cytosolic ribosome and structural constituent of ribosome—consistent with RPS3’s canonical GO placement in translation/ribosome. (Tong et al., 2024-07, Scientific Reports; https://doi.org/10.1038/s41598-024-58967-y) (tong2024proteomicsshowsthat pages 3-5)

Recent quantitative statistic (2024): proteomics detected 70 ribosomal proteins, with 53/70 (75.7%) significantly upregulated after GKRS; no ribosomal protein was significantly downregulated. RPS3 was among proteins reported to accumulate after GKRS. (Tong et al., 2024-07) (tong2024proteomicsshowsthat pages 5-7)

2) Cellular component annotations: cytosol/cytosolic ribosome; nucleus/nucleolus; synapse/PSD

Cytosol / cytoplasm / cytosolic ribosome (CC)
- High-throughput interactome/proteomics studies consistently recover RPS3 alongside many ribosomal proteins, supporting cytosolic ribosome association (but not fine-grained localization). (tan2019theinteractomeof pages 13-15)

Nucleus (CC)
- Primary evidence shows stimulus-dependent nuclear translocation in non-ribosomal contexts.
- In NF-κB signaling, RPS3 nuclear entry depends on IKKβ phosphorylation (S209) and association with the nuclear import machinery (importin-α). (Wan et al., 2011-03, Nature Immunology; https://doi.org/10.1038/ni.2007) (wan2011ikkβphosphorylationregulates pages 1-3)
- In apoptosis paradigms, endogenous rpS3 translocated into nuclei in cytokine-treated cells, and rpS3 overexpression induced caspase-dependent apoptosis. (Jang et al., 2004-02, FEBS Letters; https://doi.org/10.1016/S0014-5793(04)00074-2) (jang2004rps3adna pages 3-4)

Image-supported evidence (NF-κB/nuclear translocation): figure panels from Wan et al. (2011) show phosphorylation, co-IP interactions, and nuclear translocation behavior. (wan2011ikkβphosphorylationregulates media cf840cd8, wan2011ikkβphosphorylationregulates media 7c78b978, wan2011ikkβphosphorylationregulates media b6da7309, wan2011ikkβphosphorylationregulates media de8959ff, wan2011ikkβphosphorylationregulates media 799fbec1)

Nucleolus (CC; cautious)
- Human RPS3 gene contains an intronic snoRNA (U15b) relevant to nucleolar rRNA processing/biogenesis programs, supporting a nucleolus-linked gene architecture/biogenesis context. (Lim et al., 2002-03, Gene; https://doi.org/10.1016/S0378-1119(02)00502-4) (lim2002completegenomicstructure pages 7-7)
- Caveat: this is not direct imaging of RPS3 protein in nucleoli; nucleolar protein localization should be annotated conservatively unless supported by direct localization assays. (lim2002completegenomicstructure pages 7-7)

Synapse / postsynaptic density (CC; limited RPS3-specific evidence)
- Synaptic/PSD association is currently best supported as ribosome/translation machinery near synapses, not as a definitive stable PSD component of RPS3.
- A mouse synaptosome proteomics study reports ribosomal proteins including an Rps3-family entry among local translation machinery in synaptosomes, consistent with synaptic ribosomes. (gorski2025insightsintosynaptic pages 71-74)
- In 2023, RPS3 was used as an antibody target to label ribosomes in a spatial translatomics method (RIBOmap), reinforcing its role as a ribosomal marker but not proving PSD residency. (Zeng et al., 2023-06, Science; https://doi.org/10.1126/science.add3067) (zeng2023spatiallyresolvedsinglecell pages 3-5)

Mitochondrial inner membrane / ER: no direct, RPS3-specific evidence in the retrieved corpus supports stable mitochondrial inner membrane or ER localization; avoid those CC annotations without targeted localization data. (zeng2023spatiallyresolvedsinglecell pages 13-18)

3) Non-ribosomal (moonlighting) functions relevant to GO: DNA damage/BER, NF-κB, apoptosis, RNA binding

Damaged DNA binding (MF): AP sites and 8-oxoG
- Review-synthesized evidence states human RPS3 binds tightly to abasic (AP) sites and 8-oxoG lesions. (Gao & Hardwidge, 2011-06; https://doi.org/10.3389/fmicb.2011.00137) (gao2011ribosomalproteins3 pages 2-3)

Interaction with BER enzymes (MF/BP; cofactor framing)
- The same review summarizes that human RPS3 lacks its own glycosylase activity but can stimulate a uracil-DNA glycosylase and BER enzymes hOGG1 and APE/Ref-1 (APE1). (gao2011ribosomalproteins3 pages 2-3)
- Caveat: because this statement is mediated through a review excerpt here, GO curators should confirm the original primary interaction/enzymology experiments before asserting “direct physical interaction” annotations; best annotated as modulates/stimulates BER enzyme activity if primary evidence is verified. (gao2011ribosomalproteins3 pages 2-3)

AP lyase / AP endonuclease claims (MF; strong caveats)
- Multiple sources describe RPS3 as a DNA repair endonuclease/AP lyase and map repair activity to the C-terminus, but the excerpts show that the most definitive catalytic evidence often arises from non-human orthologs (e.g., Drosophila/yeast) or engineered conversions, and human intrinsic catalytic status is not resolved here. (jang2004rps3adna pages 1-2, lim2002completegenomicstructure pages 7-7)
- Annotation guidance: treat DNA lesion binding and BER cofactor roles as better-supported than broad “wide-range base-damage endonuclease” claims unless primary human biochemistry is directly cited. (gao2011ribosomalproteins3 pages 2-3, lim2002completegenomicstructure pages 7-7)

3.2 NF-κB signaling and transcriptional specificity

NF-κB complex cofactor/specifier (BP/MF; avoid overly broad transcription terms)
- RPS3 is described as a non-Rel NF-κB subunit that cooperates with Rel dimers for DNA binding and promoter selectivity; its KH domain is important for association with p65, and RPS3 translocates to the nucleus upon stimulation. (Wan & Lenardo, 2010-12, Cell Research; https://doi.org/10.1038/cr.2009.137) (wan2010thenuclearsignaling pages 1-2)

Mechanistic primary evidence (2011): IKKβ→RPS3 S209 phosphorylation→importin-α association→nuclear translocation
- Wan et al. demonstrate RPS3 phosphorylation and nuclear import regulation, supporting GO terms related to NF-κB signaling and regulated nuclear localization, and justifying cautionary, context-specific annotations such as “positive regulation of NF-κB transcription factor activity” rather than generic “RNA polymerase II transcription.” (Wan et al., 2011-03; https://doi.org/10.1038/ni.2007) (wan2011ikkβphosphorylationregulates pages 1-3)
- Supporting figure panels are available. (wan2011ikkβphosphorylationregulates media cf840cd8, wan2011ikkβphosphorylationregulates media 7c78b978, wan2011ikkβphosphorylationregulates media b6da7309, wan2011ikkβphosphorylationregulates media de8959ff, wan2011ikkβphosphorylationregulates media 799fbec1)

3.3 Apoptosis regulation

RPS3/rpS3 overexpression induces apoptosis with caspase-8 and caspase-3 dependence, and endogenous rpS3 accumulates in nuclei during cytokine-induced apoptosis; separable N-terminal death-inducing vs C-terminal repair domains were proposed. (Jang et al., 2004-02; https://doi.org/10.1016/S0014-5793(04)00074-2) (jang2004rps3adna pages 3-4)
Caveat: these are overexpression/transfection and cytokine-treatment paradigms; avoid over-broad developmental/cell-cycle/apoptosis GO terms without genetic physiological evidence. (jang2004rps3adna pages 3-4)

3.4 RNA binding

RPS3’s KH domain is described as capable of binding single-stranded RNA/DNA and is required for NF-κB complex association; this supports GO:RNA binding in a mechanistically grounded way. (wan2010thenuclearsignaling pages 1-2)

4) Expert/authoritative interpretation and caveats for GO curation

Core GO annotations should prioritize ribosome/translation: structural constituent of ribosome, cytosolic small ribosomal subunit/cytosolic ribosome, cytoplasm/cytosol, and cytoplasmic translation are strongly supported and are the physiological primary function. (dionne2018characterizationofzinc pages 26-29, tong2024proteomicsshowsthat pages 3-5)
Nuclear localization is real but context-dependent: supported for ribosome biogenesis trafficking and for NF-κB/apoptosis responses; annotate nuclear location but avoid implying constitutive transcription factor behavior. (wan2011ikkβphosphorylationregulates pages 1-3, jang2004rps3adna pages 3-4)
DNA repair enzymatic activity claims require caution: evidence in the retrieved excerpts supports damaged-DNA binding and cofactor-like stimulation of BER enzymes (OGG1/APE1), while direct intrinsic AP-lyase/endonuclease activity for human RPS3 appears historically claimed and may be secondary or context-dependent; species and engineered-variant literature complicates interpretation. (gao2011ribosomalproteins3 pages 2-3, lim2002completegenomicstructure pages 7-7)
Avoid “generic protein binding” and HTP-only overreach: AP-MS/interactome detections are useful for association but do not establish direct functions, subcellular compartments (e.g., PSD), or broad biological processes. (rahim2018globalinteractomicsconnect pages 11-12, tan2019theinteractomeof pages 13-15)

5) Recent applications / real-world implementations (2023–2024)

Spatial translatomics (methodological application): RIBOmap (Science 2023) is an in situ translation profiling platform; RPS3 was trialed as an antibody ribosome target (as a ribosomal marker), illustrating real-world use of RPS3 as a translation machinery handle (though the authors preferred rRNA targeting due to signal-to-noise). (Zeng et al., 2023-06; https://doi.org/10.1126/science.add3067) (zeng2023spatiallyresolvedsinglecell pages 3-5)
Clinical proteomics (biomedical application): In LUAD brain metastasis tissue collected in a clinical setting post-GKRS, ribosomal proteins (including RPS3) were prominently upregulated and used in downstream prognostic modeling. (Tong et al., 2024-07; https://doi.org/10.1038/s41598-024-58967-y) (tong2024proteomicsshowsthat pages 5-7)

References (URLs and dates available in evidence)

Wan F. et al. Nature Immunology (2011-03). IKKβ phosphorylation regulates RPS3 nuclear translocation and NF-κB function… https://doi.org/10.1038/ni.2007 (wan2011ikkβphosphorylationregulates pages 1-3)
Wan F., Lenardo MJ. Cell Research (2010-12). The nuclear signaling of NF-κB… https://doi.org/10.1038/cr.2009.137 (wan2010thenuclearsignaling pages 1-2)
Gao X., Hardwidge PR. Frontiers in Microbiology (2011-06). Ribosomal Protein S3: A Multifunctional Target… https://doi.org/10.3389/fmicb.2011.00137 (gao2011ribosomalproteins3 pages 2-3)
Jang C-Y. et al. FEBS Letters (2004-02). RpS3… is involved in apoptosis https://doi.org/10.1016/S0014-5793(04)00074-2 (jang2004rps3adna pages 3-4)
Lim Y. et al. Gene (2002-03). Complete genomic structure of human rpS3… https://doi.org/10.1016/S0378-1119(02)00502-4 (lim2002completegenomicstructure pages 7-7)
Zeng H. et al. Science (2023-06). Spatially resolved single-cell translatomics at molecular resolution https://doi.org/10.1126/science.add3067 (zeng2023spatiallyresolvedsinglecell pages 3-5)
Tong L. et al. Scientific Reports (2024-07). Proteomics shows that brain metastases… overexpress ribosomal proteins… https://doi.org/10.1038/s41598-024-58967-y (tong2024proteomicsshowsthat pages 5-7)

References

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(tan2019theinteractomeof pages 13-15): Min Tan, Guofei Ding, Xinna Cai, Shengliang Cao, Fangyuan Cong, Jiaqi Liu, Yuzhong Zhao, Sidang Liu, Guangliang Liu, and Yihong Xiao. The interactome of porcine epidemic diarrhea virus nucleocapsid protein. ArXiv, Aug 2019. URL: https://doi.org/10.21203/rs.2.12355/v1, doi:10.21203/rs.2.12355/v1. This article has 0 citations.
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(lim2002completegenomicstructure pages 7-7): Yoon Lim, Seong Min Lee, Mijin Kim, Jae Yung Lee, Eun Pyo Moon, Byeong Jae Lee, and Joon Kim. Complete genomic structure of human rps3: identification of functional u15b snorna in the fifth intron. Gene, 286 2:291-7, Mar 2002. URL: https://doi.org/10.1016/s0378-1119(02)00502-4, doi:10.1016/s0378-1119(02)00502-4. This article has 24 citations and is from a peer-reviewed journal.
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(gao2011ribosomalproteins3 pages 1-2): Xiaofei Gao and Philip R. Hardwidge. Ribosomal protein s3: a multifunctional target of attaching/effacing bacterial pathogens. Frontiers in Microbiology, Jun 2011. URL: https://doi.org/10.3389/fmicb.2011.00137, doi:10.3389/fmicb.2011.00137. This article has 80 citations and is from a peer-reviewed journal.
(wan2011ikkβphosphorylationregulates pages 11-13): Fengyi Wan, Amanda Weaver, Xiaofei Gao, Michael Bern, Philip R Hardwidge, and Michael J Lenardo. Ikkβ phosphorylation regulates rps3 nuclear translocation and nf-κb function during infection with escherichia coli strain o157:h7. Mar 2011. URL: https://doi.org/10.1038/ni.2007, doi:10.1038/ni.2007. This article has 170 citations and is from a highest quality peer-reviewed journal.
(gao2011ribosomalproteins3 pages 3-4): Xiaofei Gao and Philip R. Hardwidge. Ribosomal protein s3: a multifunctional target of attaching/effacing bacterial pathogens. Frontiers in Microbiology, Jun 2011. URL: https://doi.org/10.3389/fmicb.2011.00137, doi:10.3389/fmicb.2011.00137. This article has 80 citations and is from a peer-reviewed journal.
(jang2004rps3adna pages 1-2): Chang-Young Jang, Jae Yung Lee, and Joonhee Kim. Rps3, a dna repair endonuclease and ribosomal protein, is involved in apoptosis. FEBS Letters, 560:81-85, Feb 2004. URL: https://doi.org/10.1016/s0014-5793(04)00074-2, doi:10.1016/s0014-5793(04)00074-2. This article has 186 citations and is from a peer-reviewed journal.
(wan2011ikkβphosphorylationregulates media cf840cd8): Fengyi Wan, Amanda Weaver, Xiaofei Gao, Michael Bern, Philip R Hardwidge, and Michael J Lenardo. Ikkβ phosphorylation regulates rps3 nuclear translocation and nf-κb function during infection with escherichia coli strain o157:h7. Mar 2011. URL: https://doi.org/10.1038/ni.2007, doi:10.1038/ni.2007. This article has 170 citations and is from a highest quality peer-reviewed journal.
(gao2011ribosomalproteins3 pages 5-6): Xiaofei Gao and Philip R. Hardwidge. Ribosomal protein s3: a multifunctional target of attaching/effacing bacterial pathogens. Frontiers in Microbiology, Jun 2011. URL: https://doi.org/10.3389/fmicb.2011.00137, doi:10.3389/fmicb.2011.00137. This article has 80 citations and is from a peer-reviewed journal.
(zeng2023spatiallyresolvedsinglecell pages 13-18): Hu Zeng, Jiahao Huang, Jingyi Ren, Connie Kangni Wang, Zefang Tang, Haowen Zhou, Yiming Zhou, Hailing Shi, Abhishek Aditham, Xin Sui, Hongyu Chen, Jennifer A. Lo, and Xiao Wang. Spatially resolved single-cell translatomics at molecular resolution. Science, Jun 2023. URL: https://doi.org/10.1126/science.add3067, doi:10.1126/science.add3067. This article has 190 citations and is from a highest quality peer-reviewed journal.
(rahim2018globalinteractomicsconnect pages 11-12): Md Niaz Rahim, Ludger Klewes, Ali Zahedi-Amiri, Sabine Mai, and Kevin M. Coombs. Global interactomics connect nuclear mitotic apparatus protein numa1 to influenza virus maturation. Viruses, 10:731, Dec 2018. URL: https://doi.org/10.3390/v10120731, doi:10.3390/v10120731. This article has 12 citations.
(tong2024proteomicsshowsthat pages 5-7): Luqing Tong, Ke Ye, Qun Chen, Xiaoxi Wang, Chi Hu, Qingsheng Xu, Lihui Zhou, Renya Zhan, and Ying Tong. Proteomics shows that brain metastases of lung adenocarcinoma overexpress ribosomal proteins in response to gamma knife radiosurgery. Scientific Reports, Jul 2024. URL: https://doi.org/10.1038/s41598-024-58967-y, doi:10.1038/s41598-024-58967-y. This article has 4 citations and is from a peer-reviewed journal.
(wan2011ikkβphosphorylationregulates media 7c78b978): Fengyi Wan, Amanda Weaver, Xiaofei Gao, Michael Bern, Philip R Hardwidge, and Michael J Lenardo. Ikkβ phosphorylation regulates rps3 nuclear translocation and nf-κb function during infection with escherichia coli strain o157:h7. Mar 2011. URL: https://doi.org/10.1038/ni.2007, doi:10.1038/ni.2007. This article has 170 citations and is from a highest quality peer-reviewed journal.
(wan2011ikkβphosphorylationregulates media b6da7309): Fengyi Wan, Amanda Weaver, Xiaofei Gao, Michael Bern, Philip R Hardwidge, and Michael J Lenardo. Ikkβ phosphorylation regulates rps3 nuclear translocation and nf-κb function during infection with escherichia coli strain o157:h7. Mar 2011. URL: https://doi.org/10.1038/ni.2007, doi:10.1038/ni.2007. This article has 170 citations and is from a highest quality peer-reviewed journal.
(wan2011ikkβphosphorylationregulates media de8959ff): Fengyi Wan, Amanda Weaver, Xiaofei Gao, Michael Bern, Philip R Hardwidge, and Michael J Lenardo. Ikkβ phosphorylation regulates rps3 nuclear translocation and nf-κb function during infection with escherichia coli strain o157:h7. Mar 2011. URL: https://doi.org/10.1038/ni.2007, doi:10.1038/ni.2007. This article has 170 citations and is from a highest quality peer-reviewed journal.
(wan2011ikkβphosphorylationregulates media 799fbec1): Fengyi Wan, Amanda Weaver, Xiaofei Gao, Michael Bern, Philip R Hardwidge, and Michael J Lenardo. Ikkβ phosphorylation regulates rps3 nuclear translocation and nf-κb function during infection with escherichia coli strain o157:h7. Mar 2011. URL: https://doi.org/10.1038/ni.2007, doi:10.1038/ni.2007. This article has 170 citations and is from a highest quality peer-reviewed journal.

Citations

tong2024proteomicsshowsthat pages 3-5
zeng2023spatiallyresolvedsinglecell pages 3-5
lim2002completegenomicstructure pages 7-7
wan2010thenuclearsignaling pages 1-2
rahim2018globalinteractomicsconnect pages 11-12
tan2019theinteractomeof pages 13-15
dionne2018characterizationofzinc pages 26-29
tong2024proteomicsshowsthat pages 5-7
gorski2025insightsintosynaptic pages 71-74
zeng2023spatiallyresolvedsinglecell pages 13-18
dionne2018characterizationofzinc pages 10-15
https://doi.org/10.1038/ni.2007
https://doi.org/10.1038/s41598-024-58967-y
https://doi.org/10.1126/science.add3067
https://doi.org/10.1016/S0014-5793(04
https://doi.org/10.1016/S0378-1119(02
https://doi.org/10.1038/cr.2009.137
https://doi.org/10.3389/fmicb.2011.00137
https://doi.org/10.1016/j.molcel.2011.10.021
https://doi.org/10.3390/v10120731
https://doi.org/10.21203/rs.2.12355/v1
https://doi.org/10.3389/fmicb.2011.00137,
https://doi.org/10.1038/ni.2007,
https://doi.org/10.21203/rs.2.12355/v1,
https://doi.org/10.1038/s41598-024-58967-y,
https://doi.org/10.1126/science.add3067,
https://doi.org/10.1016/s0014-5793(04
https://doi.org/10.1016/s0378-1119(02
https://doi.org/10.1038/cr.2009.137,
https://doi.org/10.3390/v10120731,

📚 Additional Documentation

Notes

(RPS3-notes.md)

RPS3 notes

Falcon integration, 2026-05-12

Falcon identifies the core function as the canonical 40S/uS3 ribosomal role: structural constituent of the cytosolic small ribosomal subunit supporting translation [file:human/RPS3/RPS3-deep-research-falcon.md "RPS3 is a core protein of the cytosolic small ribosomal subunit (40S) and therefore supports GO annotations centered on (i) structural constituent of ribosome, (ii) cytoplasmic translation, and (iii) localization to cytosolic ribosome / small ribosomal subunit / cytosol (cytoplasm)."].
Human ribosome structural work supports the ribosome/small-subunit context PMID:23636399.
Damaged-DNA binding and BER roles are real but secondary to the ribosomal function; hS3 binds AP DNA strongly PMID:14706345 and may influence repair at DNA damage sites PMID:15518571.
Apoptosis annotations should be kept non-core because the evidence is context-dependent overexpression/cytokine treatment PMID:14988002.
Falcon found no direct RPS3-specific support for stable mitochondrial inner membrane or ER localization in the retrieved corpus, so the automated mitochondrial inner membrane row was removed [file:human/RPS3/RPS3-deep-research-falcon.md "Mitochondrial inner membrane / ER: no direct, RPS3-specific evidence in the retrieved corpus supports stable mitochondrial inner membrane or ER localization; avoid those CC annotations without targeted localization data."].

📄 View Raw YAML

id: P23396
gene_symbol: RPS3
product_type: PROTEIN
status: INITIALIZED
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: >-
  RPS3 is human 40S ribosomal protein uS3, a structural component of the
  cytosolic small ribosomal subunit that supports cytoplasmic translation. It
  also has reported extra-ribosomal roles in damaged-DNA binding/base-excision
  repair contexts, NF-kB-associated transcriptional regulation, and apoptosis,
  but these are secondary and context-dependent relative to its core ribosomal
  function.
alternative_products:
- name: '1'
  id: P23396-1
- name: '2'
  id: P23396-2
  sequence_note: VSP_046667
existing_annotations:
- term:
    id: GO:0003735
    label: structural constituent of ribosome
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: >-
      RPS3/uS3 is a canonical structural protein of the human cytosolic small
      ribosomal subunit.
    action: ACCEPT
    reason: >-
      This is the core molecular function of RPS3 and is supported by human
      ribosome structural studies and Falcon's synthesis.
    supported_by:
    - reference_id: PMID:23636399
      supporting_text: >-
        Here we present structures of Drosophila melanogaster and Homo sapiens
        80S ribosomes in complex with the translation factor eEF2, E-site
        transfer RNA and Stm1-like proteins, based on high-resolution
        cryo-electron-microscopy density maps.
    - reference_id: file:human/RPS3/RPS3-deep-research-falcon.md
      supporting_text: >-
        RPS3 is a core protein of the **cytosolic small ribosomal subunit
        (40S)** and therefore supports GO annotations centered on (i)
        **structural constituent of ribosome**, (ii) **cytoplasmic
        translation**, and (iii) localization to **cytosolic ribosome / small
        ribosomal subunit / cytosol (cytoplasm)**.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: >-
      RPS3 can localize to the nucleus in ribosome-biogenesis trafficking and
      regulated extra-ribosomal signaling contexts.
    action: KEEP_AS_NON_CORE
    reason: >-
      Nuclear localization is supported but is not the primary cellular context
      of the core ribosomal function.
    supported_by:
    - reference_id: file:human/RPS3/RPS3-deep-research-falcon.md
      supporting_text: >-
        **Nuclear localization is real but context-dependent**: supported for
        ribosome biogenesis trafficking and for NF-κB/apoptosis responses;
        annotate nuclear location but avoid implying constitutive transcription
        factor behavior.
- term:
    id: GO:0022627
    label: cytosolic small ribosomal subunit
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: >-
      RPS3 is a component of the cytosolic small ribosomal subunit.
    action: ACCEPT
    reason: >-
      This is the core cellular component for RPS3's ribosomal structural
      function.
    supported_by:
    - reference_id: PMID:23636399
      supporting_text: >-
        Here we present structures of Drosophila melanogaster and Homo sapiens
        80S ribosomes in complex with the translation factor eEF2, E-site
        transfer RNA and Stm1-like proteins, based on high-resolution
        cryo-electron-microscopy density maps.
    - reference_id: file:human/RPS3/RPS3-deep-research-falcon.md
      supporting_text: >-
        RPS3 is a core protein of the **cytosolic small ribosomal subunit
        (40S)** and therefore supports GO annotations centered on (i)
        **structural constituent of ribosome**, (ii) **cytoplasmic
        translation**, and (iii) localization to **cytosolic ribosome / small
        ribosomal subunit / cytosol (cytoplasm)**.
- term:
    id: GO:2001235
    label: positive regulation of apoptotic signaling pathway
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: >-
      RPS3 has reported pro-apoptotic effects in overexpression/cytokine
      treatment assays, but this is a context-dependent secondary function.
    action: KEEP_AS_NON_CORE
    reason: >-
      The apoptosis evidence is real enough to retain cautiously, but it should
      not be treated as the core function of this ribosomal protein.
    supported_by:
    - reference_id: PMID:14988002
      supporting_text: >-
        Transient expression of GFP-rpS3 activates caspase-8/caspase-3 and
        sensitizes cytokine-induced apoptosis.
    - reference_id: file:human/RPS3/RPS3-deep-research-falcon.md
      supporting_text: >-
        Likely context-dependent moonlighting effect; do not overextend to
        generic apoptosis/development terms without genetic/physiologic
        evidence.
- term:
    id: GO:0045944
    label: positive regulation of transcription by RNA polymerase II
  evidence_type: IEA
  original_reference_id: GO_REF:0000108
  review:
    summary: >-
      RPS3 can act as an NF-kB-associated transcriptional specificity factor,
      but broad RNA polymerase II transcription regulation is not its core
      function.
    action: KEEP_AS_NON_CORE
    reason: >-
      Falcon supports a context-specific NF-kB cofactor/specifier role and
      cautions against broad generic transcription terms.
    supported_by:
    - reference_id: file:human/RPS3/RPS3-deep-research-falcon.md
      supporting_text: >-
        Strong for NF-κB cofactor/specifier in selected promoters; weaker for
        generic “RNA polymerase II transcription” or “DNA-binding transcription
        factor binding/coactivator” across all contexts.
- term:
    id: GO:0003677
    label: DNA binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: >-
      RPS3 binds damaged DNA lesions including AP sites and 8-oxoG, but generic
      DNA binding is less informative than damaged DNA binding.
    action: MODIFY
    reason: >-
      The broad DNA binding term should be replaced by the more specific
      damaged DNA binding term that is supported by primary binding assays.
    proposed_replacement_terms:
    - id: GO:0003684
      label: damaged DNA binding
    supported_by:
    - reference_id: PMID:14706345
      supporting_text: >-
        An even more dramatic five orders of magnitude higher binding affinity
        for AP DNA was found for hS3 as opposed to hOGG1.
- term:
    id: GO:0003723
    label: RNA binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: >-
      RNA binding is plausible for RPS3 through its KH domain, but this is
      secondary to its ribosomal structural role.
    action: KEEP_AS_NON_CORE
    reason: >-
      Falcon supports RNA-binding capacity in a mechanistic/domain context but
      cautions against overextending it to sequence-specific RNA regulation.
    supported_by:
    - reference_id: file:human/RPS3/RPS3-deep-research-falcon.md
      supporting_text: >-
        RPS3’s KH domain is described as capable of binding single-stranded
        RNA/DNA and is required for NF-κB complex association; this supports
        GO:RNA binding in a mechanistically grounded way.
- term:
    id: GO:0003735
    label: structural constituent of ribosome
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: >-
      RPS3/uS3 is a canonical structural protein of the human cytosolic small
      ribosomal subunit.
    action: ACCEPT
    reason: >-
      This automated annotation matches the core experimentally supported
      ribosomal function.
    supported_by:
    - reference_id: PMID:23636399
      supporting_text: >-
        Here we present structures of Drosophila melanogaster and Homo sapiens
        80S ribosomes in complex with the translation factor eEF2, E-site
        transfer RNA and Stm1-like proteins, based on high-resolution
        cryo-electron-microscopy density maps.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    summary: >-
      RPS3 can localize to the nucleus in ribosome-biogenesis trafficking and
      regulated extra-ribosomal signaling contexts.
    action: KEEP_AS_NON_CORE
    reason: >-
      Nuclear localization is supported but secondary to the cytosolic ribosome
      location of the core function.
    supported_by:
    - reference_id: file:human/RPS3/RPS3-deep-research-falcon.md
      supporting_text: >-
        **Nuclear localization is real but context-dependent**: supported for
        ribosome biogenesis trafficking and for NF-κB/apoptosis responses;
        annotate nuclear location but avoid implying constitutive transcription
        factor behavior.
- term:
    id: GO:0005730
    label: nucleolus
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    summary: >-
      Nucleolar relevance is plausible in ribosome biogenesis, but Falcon found
      weaker direct evidence for RPS3 protein localization in nucleoli.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      The evidence is more about ribosome biogenesis/gene context than direct
      RPS3 protein localization to the nucleolus.
    supported_by:
    - reference_id: file:human/RPS3/RPS3-deep-research-falcon.md
      supporting_text: >-
        Caveat: this is not direct imaging of RPS3 protein in nucleoli;
        nucleolar **protein** localization should be annotated conservatively
        unless supported by direct localization assays.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: >-
      Cytoplasm/cytosol is the expected location for RPS3's core cytosolic
      ribosomal function.
    action: ACCEPT
    reason: >-
      The cytoplasmic location is consistent with accepted cytosolic ribosome
      and translation annotations.
    supported_by:
    - reference_id: file:human/RPS3/RPS3-deep-research-falcon.md
      supporting_text: >-
        RPS3 is a core protein of the **cytosolic small ribosomal subunit
        (40S)** and therefore supports GO annotations centered on (i)
        **structural constituent of ribosome**, (ii) **cytoplasmic
        translation**, and (iii) localization to **cytosolic ribosome / small
        ribosomal subunit / cytosol (cytoplasm)**.
- term:
    id: GO:0005743
    label: mitochondrial inner membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    summary: >-
      The automated mitochondrial inner membrane annotation overstates stable,
      constitutive localization. Direct evidence supports stress-induced RPS3
      accumulation in mitochondria, which is represented by separate IDA
      annotations from PMID:23911537.
    action: REMOVE
    reason: >-
      This IEA annotation should not be retained as evidence for stable
      mitochondrial inner membrane localization. PMID:23911537 supports
      ROS-induced mitochondrial accumulation for DNA repair, but not
      constitutive inner membrane residency; the PMID:23911537 IDA
      mitochondrial annotations should be evaluated separately.
    supported_by:
    - reference_id: file:human/RPS3/RPS3-deep-research-falcon.md
      supporting_text: >-
        **Mitochondrial inner membrane / ER:** no direct, RPS3-specific
        evidence in the retrieved corpus supports stable mitochondrial inner
        membrane or ER localization; avoid those CC annotations without
        targeted localization data.
    - reference_id: PMID:23911537
      supporting_text: >-
        Increased ROS induces rpS3 accumulation in the mitochondria for DNA
        repair while significantly decreasing the cellular protein synthesis.
- term:
    id: GO:0005819
    label: spindle
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    summary: >-
      RPS3 has been reported to localize on the mitotic spindle and act as a
      microtubule-associated protein during mitosis, so spindle localization has
      experimental support.
    action: KEEP_AS_NON_CORE
    reason: >-
      Spindle localization is supported by direct imaging (PMID:23131551) but is
      a context-dependent extra-ribosomal/mitotic function rather than the core
      cytosolic ribosomal location; the more specific mitotic spindle IDA
      annotation captures it.
    supported_by:
    - reference_id: PMID:23131551
      supporting_text: >-
        When we examined localization of ribosomal proteins in mitosis, we
        found that rpS3 specifically localizes on the mitotic spindle.
- term:
    id: GO:0005840
    label: ribosome
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: >-
      Ribosome localization is core to RPS3's function as a small-subunit
      ribosomal protein.
    action: ACCEPT
    reason: >-
      RPS3 is a structural protein of the human cytosolic ribosome.
    supported_by:
    - reference_id: PMID:23636399
      supporting_text: >-
        Here we present structures of Drosophila melanogaster and Homo sapiens
        80S ribosomes in complex with the translation factor eEF2, E-site
        transfer RNA and Stm1-like proteins, based on high-resolution
        cryo-electron-microscopy density maps.
- term:
    id: GO:0006281
    label: DNA repair
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: >-
      RPS3 has secondary evidence for participation in DNA damage processing
      and base-excision repair contexts.
    action: KEEP_AS_NON_CORE
    reason: >-
      DNA repair is supported as an extra-ribosomal function, but Falcon
      emphasizes that damaged-DNA binding and cofactor-like BER roles are better
      supported than treating DNA repair as the core function.
    supported_by:
    - reference_id: PMID:15518571
      supporting_text: >-
        These results raise the possibility that hS3 not only functions as a
        ribosomal protein but, in addition, may influence repair activities at
        sites of DNA damage.
- term:
    id: GO:0006412
    label: translation
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: >-
      RPS3's core role in the cytosolic ribosome supports translation.
    action: ACCEPT
    reason: >-
      Translation is the principal biological process associated with RPS3's
      structural ribosome function.
    supported_by:
    - reference_id: PMID:23636399
      supporting_text: >-
        Protein synthesis in all cells is carried out by macromolecular
        machines called ribosomes.
    - reference_id: file:human/RPS3/RPS3-deep-research-falcon.md
      supporting_text: >-
        RPS3 is a core protein of the **cytosolic small ribosomal subunit
        (40S)** and therefore supports GO annotations centered on (i)
        **structural constituent of ribosome**, (ii) **cytoplasmic
        translation**, and (iii) localization to **cytosolic ribosome / small
        ribosomal subunit / cytosol (cytoplasm)**.
- term:
    id: GO:0006417
    label: regulation of translation
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: >-
      RPS3 has been reported to autoregulate its own translation and to be part
      of translational control mechanisms, but the broad regulation of
      translation term applied by keyword mapping is loosely supported.
    action: KEEP_AS_NON_CORE
    reason: >-
      A specific autoregulatory negative-regulation-of-translation activity is
      documented (PMID:20217897), so a generic regulation-of-translation term is
      not wrong but is non-core relative to the structural ribosomal role and is
      better represented by the specific IDA negative-regulation annotation.
    supported_by:
    - reference_id: PMID:20217897
      supporting_text: >-
        We here report an additional function of rpS3 in which it represses its
        own translation by binding to its cognate mRNA.
- term:
    id: GO:0006915
    label: apoptotic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: >-
      RPS3 has context-dependent pro-apoptotic evidence from overexpression and
      cytokine-treatment assays.
    action: KEEP_AS_NON_CORE
    reason: >-
      Apoptosis is an extra-ribosomal moonlighting context and should not be
      treated as the core function.
    supported_by:
    - reference_id: PMID:14988002
      supporting_text: >-
        Transient expression of GFP-rpS3 activates caspase-8/caspase-3 and
        sensitizes cytokine-induced apoptosis.
- term:
    id: GO:0006974
    label: DNA damage response
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: >-
      RPS3 has reported roles in DNA damage response through damaged-DNA
      binding and BER-associated interactions.
    action: KEEP_AS_NON_CORE
    reason: >-
      This is a secondary extra-ribosomal function and should be interpreted
      cautiously relative to the core ribosomal role.
    supported_by:
    - reference_id: PMID:15518571
      supporting_text: >-
        These results raise the possibility that hS3 not only functions as a
        ribosomal protein but, in addition, may influence repair activities at
        sites of DNA damage.
- term:
    id: GO:0015935
    label: small ribosomal subunit
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: >-
      RPS3 is a component of the small ribosomal subunit.
    action: ACCEPT
    reason: >-
      This cellular component matches the core ribosomal role of RPS3.
    supported_by:
    - reference_id: PMID:23636399
      supporting_text: >-
        Here we present structures of Drosophila melanogaster and Homo sapiens
        80S ribosomes in complex with the translation factor eEF2, E-site
        transfer RNA and Stm1-like proteins, based on high-resolution
        cryo-electron-microscopy density maps.
- term:
    id: GO:0016829
    label: lyase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: >-
      RPS3 has historical AP lyase/endonuclease activity claims, but this broad
      lyase activity annotation is not the best-supported framing for human
      RPS3 function.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      The better-supported non-ribosomal activity is damaged-DNA binding and
      possible BER cofactor activity; intrinsic human AP lyase/endonuclease
      activity remains secondary and unresolved relative to the core ribosomal
      role.
    supported_by:
    - reference_id: file:human/RPS3/RPS3-deep-research-falcon.md
      supporting_text: >-
        Multiple sources describe RPS3 as a DNA repair endonuclease/AP lyase
        and map repair activity to the C-terminus, but the excerpts show that
        the most definitive catalytic evidence often arises from non-human
        orthologs (e.g., Drosophila/yeast) or engineered conversions, and human
        intrinsic catalytic status is not resolved here.
- term:
    id: GO:0022626
    label: cytosolic ribosome
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: >-
      RPS3 is a component of the cytosolic ribosome, specifically the 40S small
      ribosomal subunit.
    action: ACCEPT
    reason: >-
      This parent cellular component is consistent with the accepted, more
      specific cytosolic small ribosomal subunit annotation.
    supported_by:
    - reference_id: PMID:23636399
      supporting_text: >-
        Here we present structures of Drosophila melanogaster and Homo sapiens
        80S ribosomes in complex with the translation factor eEF2, E-site
        transfer RNA and Stm1-like proteins, based on high-resolution
        cryo-electron-microscopy density maps.
    - reference_id: file:human/RPS3/RPS3-deep-research-falcon.md
      supporting_text: >-
        RPS3 is a core protein of the **cytosolic small ribosomal subunit
        (40S)** and therefore supports GO annotations centered on (i)
        **structural constituent of ribosome**, (ii) **cytoplasmic
        translation**, and (iii) localization to **cytosolic ribosome / small
        ribosomal subunit / cytosol (cytoplasm)**.
- term:
    id: GO:0051301
    label: cell division
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: >-
      A keyword-derived generic cell division annotation. RPS3 has reported
      mitotic-spindle/microtubule functions (PMID:23131551), but the broad cell
      division term is non-core relative to its ribosomal role and is better
      represented by the specific spindle assembly/mitotic spindle IMP/IDA
      annotations.
    action: KEEP_AS_NON_CORE
    reason: >-
      RPS3 has documented mitotic roles as a microtubule-associated/spindle
      protein, so cell division is not wrong, but it is an extra-ribosomal
      moonlighting context rather than the core function and is captured more
      specifically by GO:0051225 (spindle assembly) and GO:0072686 (mitotic
      spindle).
    supported_by:
    - reference_id: PMID:23131551
      supporting_text: >-
        Depletion of the rpS3 proteins caused mitotic arrest during the
        metaphase.
- term:
    id: GO:0140078
    label: class I DNA-(apurinic or apyrimidinic site) endonuclease activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: >-
      Direct class I AP endonuclease activity for human RPS3 is historically
      claimed but remains less secure than damaged-DNA binding and possible BER
      cofactor activity.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      The annotation likely overstates a debated secondary activity; RPS3's
      core function is ribosomal, and the stronger DNA repair evidence supports
      lesion binding/cofactor framing rather than intrinsic class I AP
      endonuclease activity.
    supported_by:
    - reference_id: file:human/RPS3/RPS3-deep-research-falcon.md
      supporting_text: >-
        Annotation guidance: treat **DNA lesion binding** and **BER cofactor
        roles** as better-supported than broad “wide-range base-damage
        endonuclease” claims unless primary human biochemistry is directly
        cited.
- term:
    id: GO:1990904
    label: ribonucleoprotein complex
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: >-
      RPS3 is a constituent of the ribosome, which is a ribonucleoprotein
      complex; this parent term is consistent with its core ribosomal role.
    action: ACCEPT
    reason: >-
      As a 40S small-subunit protein, RPS3 is part of a ribonucleoprotein
      complex (the ribosome). This broad term is correct but is subsumed by the
      more specific cytosolic small ribosomal subunit annotation.
    supported_by:
    - reference_id: PMID:23636399
      supporting_text: >-
        Here we present structures of Drosophila melanogaster and Homo sapiens
        80S ribosomes in complex with the translation factor eEF2, E-site
        transfer RNA and Stm1-like proteins, based on high-resolution
        cryo-electron-microscopy density maps.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:15161933
  review:
    summary: >-
      RPS3 was identified as a 14-3-3-binding protein in a large-scale
      proteomic survey of interphase and mitotic 14-3-3 interactors.
    action: KEEP_AS_NON_CORE
    reason: >-
      This is a generic protein binding annotation derived from a
      high-throughput interactome screen. Per curation guidelines protein
      binding is uninformative, and a single proteomic co-purification does not
      establish a specific, physiologically core molecular function. Retained as
      non-core documentation of the interaction.
    supported_by:
    - reference_id: PMID:15161933
      supporting_text: >-
        Comprehensive proteomic analysis of interphase and mitotic
        14-3-3-binding proteins.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:18045535
  review:
    summary: >-
      This annotation captures RPS3's interaction with RELA (p65) of the NF-kappaB complex.
      While 'protein binding' is a very general term, the specific interaction with RELA
      is functionally significant for RPS3's role as a transcription coactivator in NF-kappaB
      signaling. A more informative annotation would specify the binding partner (RELA).
    action: MODIFY
    reason: >-
      The generic 'protein binding' term is too vague. PMID:18045535 specifically demonstrates
      interaction with RELA/p65 subunit of NF-kappaB. A more appropriate annotation would be
      to a more specific binding term that captures the functionally relevant interaction
      with a transcription factor. GO:0140297 (DNA-binding transcription factor binding) or
      GO:0061629 (RNA polymerase II-specific DNA-binding transcription factor binding)
      would be more informative.
    proposed_replacement_terms:
      - id: GO:0140297
        label: DNA-binding transcription factor binding
      - id: GO:0061629
        label: RNA polymerase II-specific DNA-binding transcription factor binding
    supported_by:
      - reference_id: PMID:18045535
        supporting_text: >-
          We identified ribosomal protein S3 (RPS3), a KH domain protein, as a non-Rel subunit
          of p65 homodimer and p65-p50 heterodimer DNA-binding complexes that synergistically
          enhances DNA binding.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:18274552
  review:
    summary: >-
      RPS3 was identified as one of a subset of ribosomal proteins targeted by
      the NEDD8 conjugation pathway in a proteomic/in vivo NEDDylation screen;
      NEDDylation protects ribosomal proteins from destabilization.
    action: KEEP_AS_NON_CORE
    reason: >-
      Generic protein binding from a proteomic NEDDylation screen. This is
      uninformative as a molecular function (it reflects RPS3 being a NEDD8
      substrate rather than a specific binding activity), so it is retained only
      as non-core documentation of the interaction/modification.
    supported_by:
    - reference_id: PMID:18274552
      supporting_text: >-
        we identified a subset of ribosomal proteins as novel targets for the
        NEDD8 pathway. We further show that the lack of NEDDylation in cells
        causes ribosomal protein instability.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:19656744
  review:
    summary: >-
      RPS3 interacts with both p53 and MDM2 through its KH domain and acts as a
      scaffold on 8-oxoG-containing DNA for binding of MDM2 and p53.
    action: KEEP_AS_NON_CORE
    reason: >-
      Generic protein binding term; the specific p53/MDM2 interactions are an
      extra-ribosomal moonlighting context. Retained as non-core; the more
      informative MF aspects of this paper are captured by the separate
      oxidized-pyrimidine DNA binding and negative-regulation-of-ubiquitination
      annotations from the same reference.
    supported_by:
    - reference_id: PMID:19656744
      supporting_text: >-
        We identified ribosomal protein S3 (RPS3), whose interaction with MDM2,
        and notably p53, was further established by His and GST pull-down assays
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:20618440
  review:
    summary: >-
      RPS3 was recovered among 14-3-3-binding proteins in a proteomic survey
      during C2-ceramide-induced apoptosis.
    action: KEEP_AS_NON_CORE
    reason: >-
      Generic protein binding from a high-throughput 14-3-3 affinity proteomics
      study; uninformative as a specific molecular function and not validated as
      a physiologically core interaction. Retained as non-core.
    supported_by:
    - reference_id: PMID:20618440
      supporting_text: >-
        Proteomic and biochemical analysis of 14-3-3-binding proteins during
        C2-ceramide-induced apoptosis
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:21145461
  review:
    summary: >-
      RPS3 was detected as an interactor in a systematic quantitative proteomic
      study of the cullin-RING ubiquitin ligase (CRL) network.
    action: KEEP_AS_NON_CORE
    reason: >-
      Generic protein binding from a large-scale CRL interactome study;
      uninformative as a specific molecular function and not independently
      validated for RPS3. Retained as non-core.
    supported_by:
    - reference_id: PMID:21145461
      supporting_text: >-
        Dynamics of cullin-RING ubiquitin ligase network revealed by systematic
        quantitative proteomics
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:21146485
  review:
    summary: >-
      RPS3 was identified among cyclophilin-40 (CyP40)-interacting proteins in a
      proteomic pull-down survey.
    action: KEEP_AS_NON_CORE
    reason: >-
      Generic protein binding from a single-bait interaction proteomics study;
      uninformative as a specific molecular function and not validated as a
      physiologically core interaction for RPS3. Retained as non-core.
    supported_by:
    - reference_id: PMID:21146485
      supporting_text: >-
        Identification of cyclophilin-40-interacting proteins reveals potential
        cellular function of cyclophilin-40
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:21399639
  review:
    summary: >-
      In the context of NF-kB signaling, RPS3 nuclear translocation depends on
      IKKβ-mediated phosphorylation of RPS3 Ser209 and association with the
      nuclear import machinery (importin-α), as demonstrated by co-IP and
      functional assays.
    action: KEEP_AS_NON_CORE
    reason: >-
      Generic protein binding term. The underlying interactions (IKKβ, importin)
      are part of RPS3's regulated extra-ribosomal NF-kB role, which is captured
      more informatively by the NF-kB complex and transcription-regulation
      annotations. Retained as non-core.
    supported_by:
    - reference_id: PMID:21399639
      supporting_text: >-
        phosphorylation of RPS3 Ser209 by the kinase IKKβ was crucial for
        nuclear localization of RPS3 in response to activating stimuli
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:22113938
  review:
    summary: >-
      RPS3 was detected in a bead-based large-scale screen for in vitro kinase
      substrates.
    action: KEEP_AS_NON_CORE
    reason: >-
      Generic protein binding from a high-throughput in vitro kinase-substrate
      screen; uninformative as a specific molecular function and not validated
      physiologically. Retained as non-core.
    supported_by:
    - reference_id: PMID:22113938
      supporting_text: >-
        A bead-based approach for large-scale identification of in vitro kinase
        substrates
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:24457201
  review:
    summary: >-
      RPS3 interacts directly with the NF-kB inhibitor IκBα, which sequesters
      both p65 and RPS3 in the cytoplasm, maintaining an RPS3 pool for the NF-kB
      pathway.
    action: KEEP_AS_NON_CORE
    reason: >-
      Generic protein binding term, but the specific IκBα interaction is part of
      RPS3's regulated extra-ribosomal NF-kB role. This is non-core relative to
      the ribosomal function; the NF-kB role is captured by the NF-kB complex
      and transcription-regulation annotations.
    supported_by:
    - reference_id: PMID:24457201
      supporting_text: >-
        in resting HEK293 cells, RPS3 interacts with NF-κB inhibitor IκBα
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:24725412
  review:
    summary: >-
      RPS3 was detected as an interactor in a study centered on LRRK2-mediated
      phosphorylation of ribosomal protein S15 in Parkinson's disease models.
    action: KEEP_AS_NON_CORE
    reason: >-
      Generic protein binding from a study whose focus is RPS15, not RPS3;
      uninformative as a specific molecular function for RPS3 and not validated
      as a physiologically core interaction. Retained as non-core.
    supported_by:
    - reference_id: PMID:24725412
      supporting_text: >-
        Ribosomal protein s15 phosphorylation mediates LRRK2 neurodegeneration
        in Parkinson's disease
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25609649
  review:
    summary: >-
      RPS3 was identified in a proteomic analysis of chromatin-associated and
      soluble transcription factor complexes.
    action: KEEP_AS_NON_CORE
    reason: >-
      Generic protein binding from a large-scale complex proteomics study;
      uninformative as a specific molecular function and not independently
      validated for RPS3. Retained as non-core.
    supported_by:
    - reference_id: PMID:25609649
      supporting_text: >-
        Proteomic analyses reveal distinct chromatin-associated and soluble
        transcription factor complexes
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:26526615
  review:
    summary: >-
      The caspase-3-generated p65(1-97) fragment interferes with RPS3 and
      retards its nuclear translocation, dampening RPS3/NF-kB-dependent
      anti-apoptotic gene expression, supporting a physical RPS3-p65 interaction
      in NF-kB signaling.
    action: KEEP_AS_NON_CORE
    reason: >-
      Generic protein binding term; the specific RPS3-p65 interaction is part of
      RPS3's extra-ribosomal NF-kB specifier role, captured more informatively by
      the NF-kB complex and transcription-regulation annotations. Retained as
      non-core.
    supported_by:
    - reference_id: PMID:26526615
      supporting_text: >-
        the p65(1-97) fragment generated by Caspase-3 cleavage interferes with
        ribosomal protein S3 (RPS3), an NF-κB "specifier" subunit, and
        selectively retards the nuclear translocation of RPS3
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:30021884
  review:
    summary: >-
      RPS3 was detected among histone-interacting proteins by crosslinking mass
      spectrometry in intact cell nuclei.
    action: KEEP_AS_NON_CORE
    reason: >-
      Generic protein binding from a high-throughput crosslinking-MS histone
      interactome study; uninformative as a specific molecular function and not
      independently validated for RPS3. Retained as non-core.
    supported_by:
    - reference_id: PMID:30021884
      supporting_text: >-
        Histone Interaction Landscapes Visualized by Crosslinking Mass
        Spectrometry in Intact Cell Nuclei
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:31046837
  review:
    summary: >-
      RPS3 was detected as an interactor in a study of LRRK2-G2019S regulation
      of SERCA activity and ER stress in astrocytes.
    action: KEEP_AS_NON_CORE
    reason: >-
      Generic protein binding from a study not focused on RPS3; uninformative as
      a specific molecular function for RPS3 and not validated as a
      physiologically core interaction. Retained as non-core.
    supported_by:
    - reference_id: PMID:31046837
      supporting_text: >-
        Parkinson's disease-associated LRRK2-G2019S mutant acts through
        regulation of SERCA activity to control ER stress in astrocytes
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32296183
  review:
    summary: >-
      RPS3 appears in the HuRI reference map of the human binary protein
      interactome (yeast two-hybrid).
    action: KEEP_AS_NON_CORE
    reason: >-
      Generic protein binding from a genome-scale binary interactome map;
      uninformative as a specific molecular function and not individually
      validated for RPS3. Retained as non-core.
    supported_by:
    - reference_id: PMID:32296183
      supporting_text: >-
        A reference map of the human binary protein interactome
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32814053
  review:
    summary: >-
      RPS3 was detected in an interactome map of neurodegenerative disease
      proteins.
    action: KEEP_AS_NON_CORE
    reason: >-
      Generic protein binding from a large-scale neurodegenerative-disease
      interactome study; uninformative as a specific molecular function and not
      independently validated for RPS3. Retained as non-core.
    supported_by:
    - reference_id: PMID:32814053
      supporting_text: >-
        Interactome Mapping Provides a Network of Neurodegenerative Disease
        Proteins and Uncovers Widespread Protein Aggregation in Affected Brains
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:33961781
  review:
    summary: >-
      RPS3 appears in the BioPlex dual proteome-scale AP-MS interaction networks.
    action: KEEP_AS_NON_CORE
    reason: >-
      Generic protein binding from a genome-scale AP-MS interactome; for an
      abundant ribosomal protein such co-purifications are expected and
      uninformative as a specific molecular function. Retained as non-core.
    supported_by:
    - reference_id: PMID:33961781
      supporting_text: >-
        Dual proteome-scale networks reveal cell-specific remodeling of the
        human interactome
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:35271311
  review:
    summary: >-
      RPS3 was characterized in the OpenCell endogenous-tagging interaction/
      localization atlas of human cellular organization.
    action: KEEP_AS_NON_CORE
    reason: >-
      Generic protein binding from a systematic endogenous-tagging interactome
      atlas; uninformative as a specific molecular function. Retained as
      non-core.
    supported_by:
    - reference_id: PMID:35271311
      supporting_text: >-
        OpenCell: Endogenous tagging for the cartography of human cellular
        organization
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:39251607
  review:
    summary: >-
      RPS3 was identified in a systematic study of post-transcriptional
      regulatory modules.
    action: KEEP_AS_NON_CORE
    reason: >-
      Generic protein binding from a high-throughput post-transcriptional
      regulatory network study; uninformative as a specific molecular function
      and not independently validated for RPS3. Retained as non-core.
    supported_by:
    - reference_id: PMID:39251607
      supporting_text: >-
        Systematic identification of post-transcriptional regulatory modules
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:40205054
  review:
    summary: >-
      RPS3 was included in multimodal cell maps integrating imaging and AP-MS
      data for structural and functional genomics.
    action: KEEP_AS_NON_CORE
    reason: >-
      Generic protein binding from a large-scale multimodal interactome/imaging
      study; uninformative as a specific molecular function. Retained as
      non-core.
    supported_by:
    - reference_id: PMID:40205054
      supporting_text: >-
        Multimodal cell maps as a foundation for structural and functional
        genomics
- term:
    id: GO:0003906
    label: DNA-(apurinic or apyrimidinic site) endonuclease activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: >-
      RPS3 has historical AP-site endonuclease activity claims, but intrinsic
      human AP endonuclease activity is not as well supported as damaged-DNA
      binding and possible BER cofactor activity.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      This automated AP-site endonuclease annotation likely overstates a debated
      secondary activity. The current synthesis supports lesion binding and
      BER-associated cofactor roles more strongly than intrinsic human AP-site
      endonuclease activity.
    supported_by:
    - reference_id: file:human/RPS3/RPS3-deep-research-falcon.md
      supporting_text: >-
        Annotation guidance: treat **DNA lesion binding** and **BER cofactor
        roles** as better-supported than broad “wide-range base-damage
        endonuclease” claims unless primary human biochemistry is directly
        cited.
- term:
    id: GO:0022627
    label: cytosolic small ribosomal subunit
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: >-
      RPS3 is a component of the cytosolic small ribosomal subunit (40S).
    action: ACCEPT
    reason: >-
      This automated orthology-based annotation matches the core ribosomal
      cellular component, consistent with the accepted IBA/IDA cytosolic small
      ribosomal subunit annotations.
    supported_by:
    - reference_id: PMID:23636399
      supporting_text: >-
        Here we present structures of Drosophila melanogaster and Homo sapiens
        80S ribosomes in complex with the translation factor eEF2, E-site
        transfer RNA and Stm1-like proteins, based on high-resolution
        cryo-electron-microscopy density maps.
- term:
    id: GO:0045202
    label: synapse
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: >-
      RPS3 appears in synapse/postsynaptic density proteomic datasets and is
      used as a ribosome marker in synaptic compartments, but this most likely
      reflects local translation machinery near synapses rather than a stable,
      RPS3-specific synaptic component.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      The synapse localization is an orthology-transferred annotation based on
      ribosome/translation-machinery presence in synaptic compartments. Per the
      deep-research synthesis, evidence is indirect for RPS3-specific synaptic
      residency, so this is better treated as an over-annotation relative to the
      core cytosolic ribosome location.
    supported_by:
    - reference_id: file:human/RPS3/RPS3-deep-research-falcon.md
      supporting_text: >-
        Evidence is indirect for human RPS3-specific PSD residency; better
        treated as synaptic ribosome/local translation association, not a
        definitive stable PSD component.
- term:
    id: GO:0001228
    label: DNA-binding transcription activator activity, RNA polymerase II-specific
  evidence_type: IMP
  original_reference_id: PMID:18045535
  review:
    summary: >-
      This annotation is an over-annotation. PMID:18045535 demonstrates that RPS3 acts as a
      non-Rel subunit of NF-kappaB complexes that synergistically enhances DNA binding of
      p65 homodimer and p65-p50 heterodimer complexes. RPS3 contains a KH domain (an RNA-binding
      domain, not a DNA-binding transcription factor domain) and interacts with the NF-kappaB
      complex via protein-protein interactions with RELA/p65. The study shows RPS3 forms part
      of the NF-kappaB complex bound to regulatory DNA sites, but RPS3 itself does not directly
      bind DNA with sequence specificity. This is transcription coactivator activity, not
      DNA-binding transcription factor activity. The term GO:0001228 requires intrinsic
      sequence-specific DNA binding, which RPS3 lacks.
    action: MODIFY
    reason: >-
      The annotation to GO:0001228 (DNA-binding transcription activator activity, RNA polymerase
      II-specific) is incorrect because this term requires the protein to directly bind DNA in
      a sequence-specific manner to modulate transcription. RPS3 does not possess a canonical
      DNA-binding domain for transcriptional regulation - its KH domain is an RNA-binding motif.
      Per PMID:18045535, RPS3 functions as "a non-Rel subunit of p65 homodimer and p65-p50
      heterodimer DNA-binding complexes that synergistically enhances DNA binding." RPS3 acts
      through protein-protein interactions with the NF-kappaB transcription factors, enhancing
      their activity. This is the definition of transcription coactivator activity (GO:0003713),
      not DNA-binding transcription factor activity. The appropriate replacement annotation is
      GO:0003713 (transcription coactivator activity); DNA-binding transcription factor binding
      is captured by a separate accepted GO:0140297 annotation.
    proposed_replacement_terms:
      - id: GO:0003713
        label: transcription coactivator activity
    additional_reference_ids:
      - PMID:18045535
    supported_by:
      - reference_id: PMID:18045535
        supporting_text: >-
          We identified ribosomal protein S3 (RPS3), a KH domain protein, as a non-Rel subunit
          of p65 homodimer and p65-p50 heterodimer DNA-binding complexes that synergistically
          enhances DNA binding.
- term:
    id: GO:0005783
    label: endoplasmic reticulum
  evidence_type: IDA
  original_reference_id: GO_REF:0000052
  review:
    summary: >-
      An immunofluorescence-based ER annotation. Ribosomes engaged in
      co-translational translocation associate with the rough ER, but there is
      no direct RPS3-specific evidence supporting stable ER residency as a
      distinct function.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      ER signal for a ribosomal protein most plausibly reflects ER-associated
      (rough ER) ribosomes rather than an RPS3-specific ER localization. The
      deep-research synthesis found no direct RPS3-specific support for stable ER
      localization, so this is treated as an over-annotation relative to the core
      cytosolic ribosome location.
    supported_by:
    - reference_id: file:human/RPS3/RPS3-deep-research-falcon.md
      supporting_text: >-
        ER-related translation appears generic/translatome-level, not
        RPS3-specific
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IDA
  original_reference_id: GO_REF:0000052
  review:
    summary: >-
      RPS3 localizes to the cytosol as part of the cytosolic ribosome.
    action: ACCEPT
    reason: >-
      Cytosol is the expected cellular location for RPS3's core cytosolic
      ribosomal function and is consistent with the accepted cytosolic ribosome
      annotation.
    supported_by:
    - reference_id: file:human/RPS3/RPS3-deep-research-falcon.md
      supporting_text: >-
        RPS3 is a core protein of the **cytosolic small ribosomal subunit
        (40S)** and therefore supports GO annotations centered on (i)
        **structural constituent of ribosome**, (ii) **cytoplasmic
        translation**, and (iii) localization to **cytosolic ribosome / small
        ribosomal subunit / cytosol (cytoplasm)**.
- term:
    id: GO:0002181
    label: cytoplasmic translation
  evidence_type: NAS
  original_reference_id: PMID:25901680
  review:
    summary: >-
      RPS3 is a 40S small-subunit protein of the human cytosolic ribosome and
      thereby participates in cytoplasmic translation.
    action: ACCEPT
    reason: >-
      Cytoplasmic translation is the core biological process for RPS3's
      structural ribosomal role, supported by the near-atomic structure of the
      human 80S ribosome.
    supported_by:
    - reference_id: PMID:25901680
      supporting_text: >-
        Ribosomes are translational machineries that catalyse protein synthesis.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: NAS
  original_reference_id: PMID:25901680
  review:
    summary: >-
      RPS3 is located in the cytoplasm as part of the cytosolic ribosome.
    action: ACCEPT
    reason: >-
      Cytoplasm is the expected, core cellular location for RPS3's cytosolic
      ribosomal function, consistent with the human 80S ribosome structure and
      accepted cytosol/cytosolic ribosome annotations.
    supported_by:
    - reference_id: PMID:25901680
      supporting_text: >-
        Structure of the human 80S ribosome.
- term:
    id: GO:0002181
    label: cytoplasmic translation
  evidence_type: NAS
  original_reference_id: PMID:1712897
  review:
    summary: >-
      RPS3 was cloned as the human S3 ribosomal protein, a component of the
      translation machinery, overexpressed in colorectal cancer.
    action: ACCEPT
    reason: >-
      Cytoplasmic translation is the core process for this small-subunit
      ribosomal protein. The reference establishes RPS3 as the human S3
      ribosomal protein.
    supported_by:
    - reference_id: PMID:1712897
      supporting_text: >-
        isolation of a cDNA clone encoding the human S3 ribosomal protein
- term:
    id: GO:0002181
    label: cytoplasmic translation
  evidence_type: IC
  original_reference_id: PMID:8706699
  review:
    summary: >-
      RPS3 was identified by protein sequencing and mass spectrometry as one of
      the proteins of the human 40S ribosomal subunit, supporting its role in
      cytoplasmic translation.
    action: ACCEPT
    reason: >-
      Cytoplasmic translation is the core process inferred from RPS3's
      experimentally confirmed identity as a 40S small-subunit ribosomal
      protein.
    supported_by:
    - reference_id: PMID:8706699
      supporting_text: >-
        Characterization of the human small-ribosomal-subunit proteins by
        N-terminal and internal sequencing, and mass spectrometry.
- term:
    id: GO:0002183
    label: cytoplasmic translational initiation
  evidence_type: NAS
  original_reference_id: PMID:15883184
  review:
    summary: >-
      RPS3 is a 40S small-subunit protein located at the mRNA entry channel and
      is part of the 40S complex recruited during cap-independent (HCV IRES) and
      canonical translation initiation.
    action: ACCEPT
    reason: >-
      RPS3 sits at the mRNA entry channel of the 40S subunit and contacts mRNA
      in initiation complexes (PMID:18464793), so participation in cytoplasmic
      translational initiation is consistent with its core ribosomal role. The
      reference identifies RPS3 as part of native and IRES-bound 40S complexes.
    supported_by:
    - reference_id: PMID:15883184
      supporting_text: >-
        a global protein composition analysis of native and IRES-bound 40S
        ribosomal complexes has been conducted
    - reference_id: PMID:18464793
      supporting_text: >-
        Crosslinking of mRNA positions (+)11 to ribosomal protein (rp) rpS2(S5p)
        and rpS3(S3p)
- term:
    id: GO:2000144
    label: positive regulation of DNA-templated transcription initiation
  evidence_type: IMP
  original_reference_id: PMID:18045535
  review:
    summary: >-
      This annotation reflects RPS3's role in enhancing NF-kappaB-mediated transcription as
      demonstrated in PMID:18045535. The study showed that RPS3 knockdown impaired NF-kappaB-mediated
      transcription of selected p65 target genes, and lymphocyte-activating stimuli caused nuclear
      translocation of RPS3 to form part of NF-kappaB bound to specific regulatory sites in chromatin.
      While this is a biological process annotation that could be retained, it should be noted that
      RPS3's effect on transcription is indirect - through its role as a coactivator of NF-kappaB
      rather than as a direct transcription factor.
    action: ACCEPT
    reason: >-
      The biological process annotation to positive regulation of DNA-templated transcription
      initiation is appropriate because RPS3 does positively regulate transcription through its
      role in the NF-kappaB complex, even though this regulation is through protein-protein
      interactions rather than direct DNA binding. PMID:18045535 demonstrates that RPS3 is
      "an essential but previously unknown subunit of NF-kappaB involved in the regulation of
      key genes in rapid cellular activation responses."
    supported_by:
      - reference_id: PMID:18045535
        supporting_text: >-
          RPS3 knockdown impaired NF-kappaB-mediated transcription of selected p65 target genes
          but not nuclear shuttling or global protein translation. Rather, lymphocyte-activating
          stimuli caused nuclear translocation of RPS3, parallel to p65, to form part of NF-kappaB
          bound to specific regulatory sites in chromatin.
- term:
    id: GO:0014069
    label: postsynaptic density
  evidence_type: EXP
  original_reference_id: PMID:21170055
  review:
    summary: >-
      RPS3 was detected in a proteomic characterization of the isolated human
      postsynaptic density, consistent with ribosome/local-translation machinery
      at synapses.
    action: KEEP_AS_NON_CORE
    reason: >-
      Detection in an isolated PSD proteome most likely reflects synaptic
      ribosomes/local translation machinery rather than an RPS3-specific
      structural role at the postsynaptic density. Retained as non-core given the
      indirect, proteome-survey nature of the evidence.
    supported_by:
    - reference_id: PMID:21170055
      supporting_text: >-
        We isolated the postsynaptic density from human neocortex (hPSD) and
        identified 1,461 proteins.
- term:
    id: GO:0014069
    label: postsynaptic density
  evidence_type: IDA
  original_reference_id: PMID:21170055
  review:
    summary: >-
      Duplicate (IDA) of the postsynaptic density detection from the same human
      PSD proteome study.
    action: KEEP_AS_NON_CORE
    reason: >-
      Same rationale as the EXP-coded postsynaptic density annotation from this
      reference: most likely reflects synaptic ribosomes/local translation
      machinery rather than an RPS3-specific PSD structural role. Retained as
      non-core.
    supported_by:
    - reference_id: PMID:21170055
      supporting_text: >-
        We isolated the postsynaptic density from human neocortex (hPSD) and
        identified 1,461 proteins.
- term:
    id: GO:0022626
    label: cytosolic ribosome
  evidence_type: IDA
  original_reference_id: PMID:23636399
  review:
    summary: >-
      RPS3 is a component of the cytosolic ribosome, specifically the 40S small
      ribosomal subunit.
    action: ACCEPT
    reason: >-
      This cellular component is supported by structural evidence for the human
      cytosolic 80S ribosome and is consistent with the accepted cytosolic
      small ribosomal subunit annotation.
    supported_by:
    - reference_id: PMID:23636399
      supporting_text: >-
        Here we present structures of Drosophila melanogaster and Homo sapiens
        80S ribosomes in complex with the translation factor eEF2, E-site
        transfer RNA and Stm1-like proteins, based on high-resolution
        cryo-electron-microscopy density maps.
    - reference_id: file:human/RPS3/RPS3-deep-research-falcon.md
      supporting_text: >-
        RPS3 is a core protein of the **cytosolic small ribosomal subunit
        (40S)** and therefore supports GO annotations centered on (i)
        **structural constituent of ribosome**, (ii) **cytoplasmic
        translation**, and (iii) localization to **cytosolic ribosome / small
        ribosomal subunit / cytosol (cytoplasm)**.
- term:
    id: GO:0003684
    label: damaged DNA binding
  evidence_type: IDA
  original_reference_id: PMID:15518571
  review:
    summary: >-
      Human RPS3 binds damaged DNA, including abasic (AP) sites and 8-oxoG
      lesions, with high apparent affinity as shown by surface plasmon resonance.
    action: KEEP_AS_NON_CORE
    reason: >-
      Damaged DNA binding is a well-supported extra-ribosomal molecular function
      of human RPS3 (multiple independent IDA assays: PMID:14706345,
      PMID:18610840, PMID:16737853). It is a genuine moonlighting activity but
      secondary to the core ribosomal structural function, so retained as
      non-core.
    supported_by:
    - reference_id: PMID:14706345
      supporting_text: >-
        An even more dramatic five orders of magnitude higher binding affinity
        for AP DNA was found for hS3 as opposed to hOGG1.
- term:
    id: GO:0006284
    label: base-excision repair
  evidence_type: IDA
  original_reference_id: PMID:15518571
  review:
    summary: >-
      Human RPS3 physically interacts with the BER enzymes OGG1 and APE1/Ref-1
      and can stimulate OGG1 N-glycosylase activity, supporting participation in
      base-excision repair as a binding partner/modulator rather than as a core
      BER enzyme.
    action: KEEP_AS_NON_CORE
    reason: >-
      RPS3 participates in BER through cofactor-like interactions (binding and
      stimulating OGG1/APE1; PMID:18973764 shows it also stimulates UNG), but
      this is an extra-ribosomal moonlighting role; note that under some
      conditions bound RPS3 can inhibit OGG1 repair (PMID:16737853), so the role
      is context-dependent. Retained as non-core.
    supported_by:
    - reference_id: PMID:15518571
      supporting_text: >-
        hOGG1 N-glycosylase activity becomes increasingly more robust in the
        presence of hS3. Human S3 was found to co-immunoprecipitate with both
        hOGG1 and APE/Ref-1
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:19059439
  review:
    summary: >-
      RPS3 is phosphorylated by PKCdelta, which interacts with RPS3 and
      mobilizes non-ribosomal RPS3 to the nucleus for DNA repair.
    action: KEEP_AS_NON_CORE
    reason: >-
      Generic protein binding term; the specific PKCdelta interaction is part of
      the regulated extra-ribosomal DNA-repair switch and is non-core relative
      to the ribosomal function. Retained as non-core documentation.
    supported_by:
    - reference_id: PMID:19059439
      supporting_text: >-
        PKCdelta phosphorylates rpS3 resulting in its mobilization in the
        nucleus to repair damaged DNA
- term:
    id: GO:0006281
    label: DNA repair
  evidence_type: IMP
  original_reference_id: PMID:19059439
  review:
    summary: >-
      RPS3 knockdown increased sensitivity to genotoxic stress, and the
      phosphorylation-dependent repair endonuclease activity of non-ribosomal
      RPS3 was required for this protection, supporting an extra-ribosomal DNA
      repair role.
    action: KEEP_AS_NON_CORE
    reason: >-
      DNA repair is a documented extra-ribosomal moonlighting function but is
      secondary to the core ribosomal role. Note that other work reports RPS3
      knockdown protects cells from genotoxic stress (PMID:17049931), so the net
      effect on repair is context-dependent.
    supported_by:
    - reference_id: PMID:19059439
      supporting_text: >-
        rpS3 knock-down cells showed more sensitivity to genotoxic stress than
        control cells, and this sensitivity was corrected by overexpressed
        wild-type rpS3 but not by phosphorylation defective rpS3
- term:
    id: GO:0007059
    label: chromosome segregation
  evidence_type: IMP
  original_reference_id: PMID:23131551
  review:
    summary: >-
      RPS3 depletion caused mitotic arrest at metaphase with abnormal spindle
      shape and chromosome movement, consistent with a role in proper
      chromosome segregation via its mitotic-spindle/microtubule function.
    action: KEEP_AS_NON_CORE
    reason: >-
      The chromosome segregation phenotype is downstream of RPS3's reported
      microtubule-associated/spindle role during mitosis, an extra-ribosomal
      moonlighting context rather than the core ribosomal function. Retained as
      non-core.
    supported_by:
    - reference_id: PMID:23131551
      supporting_text: >-
        Depletion of the rpS3 proteins caused mitotic arrest during the
        metaphase. Furthermore, the shape of the spindle and chromosome movement
        in the rpS3 depleted cell was abnormal.
- term:
    id: GO:0010628
    label: positive regulation of gene expression
  evidence_type: IMP
  original_reference_id: PMID:20605787
  review:
    summary: >-
      RPS3 up-regulated the proapoptotic proteins Dp5/Hrk and Bim by binding to
      and acting synergistically with the transcription factor E2F1 in neuronal
      apoptosis.
    action: KEEP_AS_NON_CORE
    reason: >-
      This positive regulation of gene expression is an extra-ribosomal
      transcriptional-coregulator activity (via E2F1), context-specific to
      neuronal apoptosis, and non-core relative to the ribosomal role. The
      mechanistic E2F1 interaction is captured by the DNA-binding transcription
      factor binding annotation from the same reference.
    supported_by:
    - reference_id: PMID:20605787
      supporting_text: >-
        RPS3 induced neuronal apoptosis, up-regulating proapoptotic proteins
        Dp5/Hrk and Bim by binding to E2F1 and acting synergistically with it.
- term:
    id: GO:0005743
    label: mitochondrial inner membrane
  evidence_type: IDA
  original_reference_id: PMID:23911537
  review:
    summary: >-
      Under elevated ROS, RPS3 accumulates in the mitochondria (entry mediated
      by HSP90/HSP70/TOM70) to participate in mtDNA damage repair.
    action: KEEP_AS_NON_CORE
    reason: >-
      This IDA captures stress-induced (ROS-triggered) mitochondrial
      accumulation of RPS3 for mtDNA damage surveillance, a regulated
      extra-ribosomal context, not constitutive inner-membrane residency. It is
      kept as non-core, distinct from the broad IEA mitochondrial inner membrane
      annotation that was removed.
    supported_by:
    - reference_id: PMID:23911537
      supporting_text: >-
        Increased ROS induces rpS3 accumulation in the mitochondria for DNA
        repair while significantly decreasing the cellular protein synthesis.
- term:
    id: GO:0005759
    label: mitochondrial matrix
  evidence_type: IDA
  original_reference_id: PMID:23911537
  review:
    summary: >-
      RPS3 accumulates within mitochondria under oxidative stress to repair
      mitochondrial DNA, consistent with localization to the mitochondrial
      matrix where the mtDNA resides.
    action: KEEP_AS_NON_CORE
    reason: >-
      Stress-induced mitochondrial localization for mtDNA repair is a regulated
      extra-ribosomal moonlighting role, secondary to the core cytosolic
      ribosomal function. Retained as non-core.
    supported_by:
    - reference_id: PMID:23911537
      supporting_text: >-
        rpS3 accumulates in the mitochondria to repair damaged DNA due to the
        decreased interaction between rpS3 and HSP90 in the cytosol.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:22510408
  review:
    summary: >-
      RPS3 physically interacts with TRADD and is recruited to the
      death-inducing signaling complex (DISC) to promote caspase-dependent JNK
      activation and apoptosis under stress.
    action: KEEP_AS_NON_CORE
    reason: >-
      Generic protein binding term; the specific TRADD interaction underlies an
      extra-ribosomal pro-apoptotic moonlighting role and is non-core relative to
      the ribosomal function. Retained as non-core.
    supported_by:
    - reference_id: PMID:22510408
      supporting_text: >-
        This apoptotic effect was shown to result from the physical interaction
        between rpS3 and TRADD, as assessed by coimmunoprecipitation.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:20041225
  review:
    summary: >-
      The enterohemorrhagic E. coli type III secretion effectors NleH1/NleH2
      bind the N-terminus of human RPS3 to subvert RPS3-dependent NF-kB function.
    action: KEEP_AS_NON_CORE
    reason: >-
      Generic protein binding term capturing a host-pathogen interaction
      relevant to RPS3's NF-kB role; non-core relative to the ribosomal
      function. Retained as non-core.
    supported_by:
    - reference_id: PMID:20041225
      supporting_text: >-
        the E. coli O157:H7 nleH1 and nleH2 genes encode T3SS effectors that
        bind to the human ribosomal protein S3 (RPS3), a subunit of ... NF-kappaB
        transcriptional complexes
- term:
    id: GO:0140297
    label: DNA-binding transcription factor binding
  evidence_type: IPI
  original_reference_id: PMID:20605787
  review:
    summary: >-
      Well-supported annotation. PMID:20605787 demonstrates that RPS3 binds to the E2F1
      transcription factor and acts synergistically with E2F1 to up-regulate proapoptotic
      proteins Dp5/Hrk and Bim. This interaction is regulated by Akt-mediated phosphorylation
      of RPS3, which perturbs its interaction with E2F1. This annotation is appropriate and
      supports the role of RPS3 as a transcriptional coregulator that binds transcription
      factors rather than DNA directly.
    action: ACCEPT
    reason: >-
      The annotation to DNA-binding transcription factor binding is correct based on the
      evidence in PMID:20605787 showing RPS3 physically interacts with E2F1, a DNA-binding
      transcription factor. This is consistent with RPS3's role as a transcriptional
      coregulator that modulates transcription through protein-protein interactions with
      transcription factors (both E2F1 and NF-kappaB/RELA).
    supported_by:
      - reference_id: PMID:20605787
        supporting_text: >-
          RPS3 induced neuronal apoptosis, up-regulating proapoptotic proteins Dp5/Hrk and Bim
          by binding to E2F1 and acting synergistically with it. Akt-dependent phosphorylation
          of RPS3 inhibited its proapoptotic function and perturbed its interaction with E2F1.
- term:
    id: GO:0002181
    label: cytoplasmic translation
  evidence_type: IC
  original_reference_id: PMID:23636399
  review:
    summary: >-
      RPS3 is part of the human 80S ribosome resolved by cryo-EM, supporting its
      role in cytoplasmic translation.
    action: ACCEPT
    reason: >-
      Cytoplasmic translation is the core biological process for RPS3, inferred
      from its experimentally confirmed structural presence in the human
      cytosolic ribosome.
    supported_by:
    - reference_id: PMID:23636399
      supporting_text: >-
        Protein synthesis in all cells is carried out by macromolecular machines
        called ribosomes.
- term:
    id: GO:0003735
    label: structural constituent of ribosome
  evidence_type: IDA
  original_reference_id: PMID:23636399
  review:
    summary: >-
      RPS3/uS3 is resolved as a structural protein of the human cytosolic small
      ribosomal subunit in the 80S ribosome cryo-EM structure.
    action: ACCEPT
    reason: >-
      This is the core, directly-evidenced molecular function of RPS3.
    supported_by:
    - reference_id: PMID:23636399
      supporting_text: >-
        Here we present structures of Drosophila melanogaster and Homo sapiens
        80S ribosomes in complex with the translation factor eEF2, E-site
        transfer RNA and Stm1-like proteins, based on high-resolution
        cryo-electron-microscopy density maps.
- term:
    id: GO:0030544
    label: Hsp70 protein binding
  evidence_type: IDA
  original_reference_id: PMID:23911537
  review:
    summary: >-
      RPS3 interacts with HSP70 (with HSP90 and TOM70) to regulate its entry
      into mitochondria during oxidative stress.
    action: KEEP_AS_NON_CORE
    reason: >-
      This is a specific, directly-evidenced chaperone interaction supporting
      RPS3's stress-induced mitochondrial trafficking, an extra-ribosomal
      moonlighting context. More informative than generic protein binding, but
      non-core relative to the ribosomal function.
    supported_by:
    - reference_id: PMID:23911537
      supporting_text: >-
        the accumulation of rpS3 was regulated by interaction with HSP90, HSP70,
        and TOM70.
- term:
    id: GO:0034614
    label: cellular response to reactive oxygen species
  evidence_type: IDA
  original_reference_id: PMID:23911537
  review:
    summary: >-
      Elevated cellular ROS triggers RPS3 accumulation in mitochondria for mtDNA
      repair and a decrease in protein synthesis, indicating a cellular response
      to reactive oxygen species.
    action: KEEP_AS_NON_CORE
    reason: >-
      RPS3's ROS-responsive mitochondrial relocalization is a regulated
      extra-ribosomal stress response, non-core relative to its ribosomal
      function. Retained as non-core.
    supported_by:
    - reference_id: PMID:23911537
      supporting_text: >-
        When cellular ROS levels increase, the mitochondrial genes are highly
        vulnerable to DNA damage. Increased ROS induces rpS3 accumulation in the
        mitochondria for DNA repair
- term:
    id: GO:0019899
    label: enzyme binding
  evidence_type: IPI
  original_reference_id: PMID:18973764
  review:
    summary: >-
      Human RPS3 interacts with uracil-DNA glycosylase (UNG) and stimulates its
      glycosylase activity, as shown by co-IP and GST pull-down assays.
    action: KEEP_AS_NON_CORE
    reason: >-
      Enzyme binding here captures a specific, directly-evidenced interaction
      with a BER enzyme (UNG); more informative than generic protein binding but
      part of RPS3's extra-ribosomal BER-cofactor moonlighting role, so non-core.
    supported_by:
    - reference_id: PMID:18973764
      supporting_text: >-
        We identified, for the first time, the interaction between hRpS3 and
        human uracil-DNA glycosylase (hUNG) ... hRpS3 dramatically stimulated the
        uracil-excision activity of hUNG, whereas hRpS3 alone had no cleavage
        activity.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:28065601
  review:
    summary: >-
      Study of ZNF598-mediated site-specific 40S ribosomal ubiquitination
      initiating ribosome-associated quality control; RPS3/uS3 is a 40S
      component in this context.
    action: KEEP_AS_NON_CORE
    reason: >-
      Generic protein binding term arising from a ribosome-associated quality
      control study; for an abundant 40S protein this association is expected and
      uninformative as a specific molecular function. Retained as non-core.
    supported_by:
    - reference_id: PMID:28065601
      supporting_text: >-
        Initiation of Quality Control during Poly(A) Translation Requires
        Site-Specific Ribosome Ubiquitination.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:28132843
  review:
    summary: >-
      ZNF598 and RACK1 regulate 40S ribosomal ubiquitylation during
      ribosome-associated quality control; RACK1 regulates ubiquitination of
      RPS2, RPS3, and RPS20.
    action: KEEP_AS_NON_CORE
    reason: >-
      Generic protein binding term from a ribosome-associated quality control
      study. The specific finding (RACK1-regulated RPS3 ubiquitylation) is part
      of ribosome regulation rather than a discrete RPS3 binding function;
      retained as non-core.
    supported_by:
    - reference_id: PMID:28132843
      supporting_text: >-
        RACK1 regulates RPS2, RPS3, and RPS20 ubiquitylation
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:17560175
  review:
    summary: >-
      Following genotoxic stress, human RPS3 translocates from the cytoplasm to
      the nucleus (dependent on ERK-mediated T42 phosphorylation), where it
      co-localizes with 8-oxoG damage foci.
    action: KEEP_AS_NON_CORE
    reason: >-
      Stimulus-dependent nuclear translocation is well documented but represents
      a regulated extra-ribosomal DNA-damage-response context rather than the
      core cytosolic ribosomal location. Retained as non-core.
    supported_by:
    - reference_id: PMID:17560175
      supporting_text: >-
        hS3 is capable of carrying out both roles by its ex vivo translocation
        from the cytoplasm to the nucleus as a consequence of genotoxic stress.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IMP
  original_reference_id: PMID:21399639
  review:
    summary: >-
      Nuclear localization of RPS3 in response to activating stimuli requires
      IKKβ-mediated phosphorylation of RPS3 Ser209, as shown using
      phospho-mutant analysis.
    action: KEEP_AS_NON_CORE
    reason: >-
      Regulated, stimulus-dependent nuclear localization tied to NF-kB
      signaling; non-core relative to the cytosolic ribosomal location. Retained
      as non-core.
    supported_by:
    - reference_id: PMID:21399639
      supporting_text: >-
        phosphorylation of RPS3 Ser209 by the kinase IKKβ was crucial for
        nuclear localization of RPS3 in response to activating stimuli
- term:
    id: GO:0005925
    label: focal adhesion
  evidence_type: HDA
  original_reference_id: PMID:21423176
  review:
    summary: >-
      RPS3 was detected in a high-throughput proteomic analysis of isolated
      focal adhesions.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Detection of an abundant ribosomal protein in a focal-adhesion proteome is
      most plausibly a co-isolation/contaminant signal rather than evidence of an
      RPS3-specific focal adhesion role. No targeted validation supports stable
      focal-adhesion localization, so this is treated as an over-annotation.
    supported_by:
    - reference_id: PMID:21423176
      supporting_text: >-
        we performed proteomic analysis of isolated focal adhesions ... We
        identified 905 focal adhesion proteins
- term:
    id: GO:0071159
    label: NF-kappaB complex
  evidence_type: IDA
  original_reference_id: PMID:18045535
  review:
    summary: >-
      Well-supported annotation. PMID:18045535 used tandem affinity purification and mass
      spectrometry to identify RPS3 as a component of the NF-kappaB complex. The study clearly
      shows that RPS3 is "a non-Rel subunit of p65 homodimer and p65-p50 heterodimer DNA-binding
      complexes." RPS3 interacts with RELA (p65) and forms part of the NF-kappaB transcription
      factor complex bound to chromatin in response to activating stimuli.
    action: ACCEPT
    reason: >-
      The proteomic approach in PMID:18045535 directly demonstrates RPS3 is a component of
      NF-kappaB complexes. This was validated by co-IP experiments and functional studies showing
      RPS3 is essential for NF-kappaB function in gene regulation.
    supported_by:
      - reference_id: PMID:18045535
        supporting_text: >-
          We identified ribosomal protein S3 (RPS3), a KH domain protein, as a non-Rel subunit
          of p65 homodimer and p65-p50 heterodimer DNA-binding complexes that synergistically
          enhances DNA binding.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IDA
  original_reference_id: PMID:18045535
  review:
    summary: >-
      RPS3 is present in the cytosol, where it associates with NF-kB inhibitory
      complexes prior to stimulus-induced nuclear translocation.
    action: ACCEPT
    reason: >-
      Cytosol is the expected, core cellular location for RPS3 (cytosolic
      ribosome), consistent with the accepted cytosol/cytosolic ribosome
      annotations.
    supported_by:
    - reference_id: PMID:18045535
      supporting_text: >-
        lymphocyte-activating stimuli caused nuclear translocation of RPS3,
        parallel to p65
- term:
    id: GO:1905053
    label: positive regulation of base-excision repair
  evidence_type: IDA
  original_reference_id: PMID:18973764
  review:
    summary: >-
      RPS3 stimulates the uracil-excision (glycosylase) activity of UNG and its
      knockdown reduces uracil-excision activity in cell extracts, supporting
      positive regulation of base-excision repair.
    action: KEEP_AS_NON_CORE
    reason: >-
      RPS3 positively regulates BER as a cofactor that stimulates UNG (and OGG1,
      PMID:15518571) rather than acting as a core BER enzyme. This is a genuine
      extra-ribosomal moonlighting role, retained as non-core. Note that under
      conditions where RPS3 binds 8-oxoG it can instead inhibit OGG1 repair
      (PMID:16737853), so the regulation is context-dependent.
    supported_by:
    - reference_id: PMID:18973764
      supporting_text: >-
        The disruption of hRpS3 by small-interfering RNA (siRNA-hRpS3)
        transfection reduced the uracil-excision activity preserved in cell
        extracts, whereas the supplement of purified hRpS3 retained
        uracil-excision activity.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:24965446
  review:
    summary: >-
      RPS3 was identified among ribosomal proteins/ribonucleoproteins that
      co-purify with the pestivirus N-terminal protease Npro in the
      ribonucleoprotein complex.
    action: KEEP_AS_NON_CORE
    reason: >-
      Generic protein binding from a viral-protein interaction proteomics study;
      for an abundant ribosomal protein this co-purification is expected and
      uninformative as a specific molecular function. Retained as non-core.
    supported_by:
    - reference_id: PMID:24965446
      supporting_text: >-
        Host factors that interact with the pestivirus N-terminal protease,
        Npro, are components of the ribonucleoprotein complex
- term:
    id: GO:0017148
    label: negative regulation of translation
  evidence_type: IDA
  original_reference_id: PMID:20217897
  review:
    summary: >-
      Free (non-ribosomal) RPS3 binds its own cognate mRNA via its C-terminal
      domain and represses its own translation in a feedback mechanism.
    action: KEEP_AS_NON_CORE
    reason: >-
      This is a specific, directly-evidenced autoregulatory negative regulation
      of translation. It is a genuine but specialized function distinct from the
      core structural ribosomal role, so retained as non-core.
    supported_by:
    - reference_id: PMID:20217897
      supporting_text: >-
        We here report an additional function of rpS3 in which it represses its
        own translation by binding to its cognate mRNA.
- term:
    id: GO:0061481
    label: response to TNF agonist
  evidence_type: IDA
  original_reference_id: PMID:20041225
  review:
    summary: >-
      RPS3 participates in NF-kB-dependent transcriptional responses; in this
      study its nuclear abundance and RPS3/NF-kB-dependent reporter activity are
      modulated, and RPS3 functions within TNF/NF-kB activation pathways.
    action: KEEP_AS_NON_CORE
    reason: >-
      This term reflects RPS3's extra-ribosomal participation in NF-kB-mediated
      cytokine responses, a context-dependent moonlighting role rather than the
      core ribosomal function. Retained as non-core.
    supported_by:
    - reference_id: PMID:20041225
      supporting_text: >-
        NleH1 repressed the transcription of a RPS3/NF-kappaB-dependent reporter
        plasmid
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:20041225
  review:
    summary: >-
      RPS3 has a nuclear pool whose abundance is modulated during NF-kB
      signaling (NleH1 reduced the nuclear abundance of RPS3).
    action: KEEP_AS_NON_CORE
    reason: >-
      Nuclear localization in the NF-kB context is a regulated extra-ribosomal
      pool, non-core relative to the cytosolic ribosomal location. Retained as
      non-core.
    supported_by:
    - reference_id: PMID:20041225
      supporting_text: >-
        NleH1, but not NleH2, reduced the nuclear abundance of RPS3 without
        altering the p50 or p65 NF-kappaB subunits
- term:
    id: GO:1901224
    label: positive regulation of non-canonical NF-kappaB signal transduction
  evidence_type: IDA
  original_reference_id: PMID:20041225
  review:
    summary: >-
      RPS3 acts as a specifier subunit that positively contributes to
      NF-kB-dependent transcription; bacterial effector binding to RPS3 subverts
      this NF-kB function.
    action: KEEP_AS_NON_CORE
    reason: >-
      RPS3's positive contribution to NF-kB-dependent transcription is a
      well-supported extra-ribosomal moonlighting role. The specific
      "non-canonical" qualifier is not strongly distinguished in this reference
      (which centers on RPS3/p65 transcriptional complexes), but the broad
      positive NF-kB regulation is supported; retained as non-core.
    supported_by:
    - reference_id: PMID:20041225
      supporting_text: >-
        Bacterial effector binding to ribosomal protein s3 subverts NF-kappaB
        function.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:23911537
  review:
    summary: >-
      RPS3's mitochondrial entry under oxidative stress is regulated by
      interaction with HSP90, HSP70, and TOM70.
    action: KEEP_AS_NON_CORE
    reason: >-
      Generic protein binding term from the mitochondrial mtDNA-surveillance
      study; the specific chaperone/TOM70 interactions are captured more
      informatively by the Hsp70/Hsp90 binding annotations from the same
      reference. Retained as non-core.
    supported_by:
    - reference_id: PMID:23911537
      supporting_text: >-
        the accumulation of rpS3 was regulated by interaction with HSP90, HSP70,
        and TOM70.
- term:
    id: GO:0045739
    label: positive regulation of DNA repair
  evidence_type: IDA
  original_reference_id: PMID:23911537
  review:
    summary: >-
      Increasing mitochondrial RPS3 levels reduced cellular ROS and rescued
      mtDNA damage, indicating RPS3 positively contributes to repair of damaged
      mitochondrial DNA under oxidative stress.
    action: KEEP_AS_NON_CORE
    reason: >-
      Positive regulation of (mitochondrial) DNA repair is a stress-induced
      extra-ribosomal moonlighting role, non-core relative to the ribosomal
      function. Retained as non-core.
    supported_by:
    - reference_id: PMID:23911537
      supporting_text: >-
        cellular ROS was decreased and mtDNA damage was rescued when levels of
        rpS3 were increased in the mitochondria.
- term:
    id: GO:0051879
    label: Hsp90 protein binding
  evidence_type: IDA
  original_reference_id: PMID:23911537
  review:
    summary: >-
      RPS3 interacts with HSP90 in the cytosol; geldanamycin disruption of this
      interaction stimulates RPS3 accumulation in mitochondria.
    action: KEEP_AS_NON_CORE
    reason: >-
      Specific, directly-evidenced HSP90 interaction governing RPS3's
      stress-induced mitochondrial trafficking; more informative than generic
      protein binding but part of an extra-ribosomal context, so non-core.
    supported_by:
    - reference_id: PMID:23911537
      supporting_text: >-
        Pretreatment with geldanamycin, which binds to the ATP pocket of HSP90,
        significantly decreased the interaction of rpS3 with HSP90 and stimulated
        the accumulation of rpS3 in the mitochondria.
- term:
    id: GO:0070301
    label: cellular response to hydrogen peroxide
  evidence_type: IDA
  original_reference_id: PMID:23911537
  review:
    summary: >-
      RPS3 relocalizes to mitochondria in response to oxidative (ROS/H2O2)
      stress to participate in mtDNA damage surveillance.
    action: KEEP_AS_NON_CORE
    reason: >-
      Specific oxidative-stress (hydrogen peroxide) response captured by RPS3's
      stress-induced mitochondrial trafficking, an extra-ribosomal role; non-core
      relative to the ribosomal function. Retained as non-core.
    supported_by:
    - reference_id: PMID:23911537
      supporting_text: >-
        Increased ROS induces rpS3 accumulation in the mitochondria for DNA
        repair while significantly decreasing the cellular protein synthesis.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IDA
  original_reference_id: PMID:22510408
  review:
    summary: >-
      During stress-induced apoptosis, GFP-RPS3 co-localized with TRADD around
      the plasma membrane (and in the cytoplasm) at the death-inducing signaling
      complex.
    action: KEEP_AS_NON_CORE
    reason: >-
      Plasma-membrane-proximal localization is a transient, apoptosis-context
      observation tied to DISC recruitment, not a stable RPS3 plasma membrane
      residency. Retained as non-core given the specialized, context-dependent
      nature.
    supported_by:
    - reference_id: PMID:22510408
      supporting_text: >-
        GFP-rpS3 colocalized with TRADD around the plasma membrane and in the
        cytoplasm during apoptosis.
- term:
    id: GO:0008017
    label: microtubule binding
  evidence_type: IDA
  original_reference_id: PMID:23131551
  review:
    summary: >-
      RPS3 localizes on the mitotic spindle and functions as a
      microtubule-associated protein, with its depletion decreasing microtubule
      polymerization.
    action: KEEP_AS_NON_CORE
    reason: >-
      Microtubule binding supports a directly-evidenced mitotic
      microtubule-associated-protein moonlighting role, distinct from and
      secondary to the core ribosomal function. Retained as non-core.
    supported_by:
    - reference_id: PMID:23131551
      supporting_text: >-
        we concluded that rpS3 acts as a microtubule associated protein (MAP)
        and regulates spindle dynamics during mitosis.
- term:
    id: GO:0015631
    label: tubulin binding
  evidence_type: IDA
  original_reference_id: PMID:23131551
  review:
    summary: >-
      RPS3 associates with the mitotic spindle and microtubules as a
      microtubule-associated protein.
    action: KEEP_AS_NON_CORE
    reason: >-
      Tubulin/microtubule binding supports RPS3's directly-evidenced mitotic
      MAP role, an extra-ribosomal moonlighting function secondary to the core
      ribosomal role. Retained as non-core.
    supported_by:
    - reference_id: PMID:23131551
      supporting_text: >-
        rpS3 specifically localizes on the mitotic spindle ... rpS3 acts as a
        microtubule associated protein (MAP)
- term:
    id: GO:0031116
    label: positive regulation of microtubule polymerization
  evidence_type: IMP
  original_reference_id: PMID:23131551
  review:
    summary: >-
      RPS3 depletion decreased microtubule polymerization, indicating RPS3
      promotes microtubule polymerization during mitosis.
    action: KEEP_AS_NON_CORE
    reason: >-
      Directly supported by loss-of-function evidence, but part of RPS3's mitotic
      microtubule moonlighting role rather than the core ribosomal function.
      Retained as non-core.
    supported_by:
    - reference_id: PMID:23131551
      supporting_text: >-
        Microtubule (MT) polymerization also decreased in rpS3 depleted cells,
        suggesting that rpS3 is involved in spindle dynamics.
- term:
    id: GO:0051225
    label: spindle assembly
  evidence_type: IMP
  original_reference_id: PMID:23131551
  review:
    summary: >-
      RPS3 depletion produced abnormal spindle shape and mitotic arrest,
      consistent with a role in proper spindle assembly.
    action: KEEP_AS_NON_CORE
    reason: >-
      Spindle assembly is supported by loss-of-function data but reflects RPS3's
      mitotic microtubule moonlighting role, secondary to the core ribosomal
      function. Retained as non-core.
    supported_by:
    - reference_id: PMID:23131551
      supporting_text: >-
        the shape of the spindle and chromosome movement in the rpS3 depleted
        cell was abnormal.
- term:
    id: GO:0072686
    label: mitotic spindle
  evidence_type: IDA
  original_reference_id: PMID:23131551
  review:
    summary: >-
      RPS3 specifically localizes on the mitotic spindle during mitosis as shown
      by direct imaging.
    action: KEEP_AS_NON_CORE
    reason: >-
      Direct imaging supports mitotic spindle localization, an extra-ribosomal
      moonlighting context distinct from and secondary to the cytosolic
      ribosomal location. Retained as non-core.
    supported_by:
    - reference_id: PMID:23131551
      supporting_text: >-
        When we examined localization of ribosomal proteins in mitosis, we found
        that rpS3 specifically localizes on the mitotic spindle.
- term:
    id: GO:1902231
    label: positive regulation of intrinsic apoptotic signaling pathway in response
      to DNA damage
  evidence_type: IMP
  original_reference_id: PMID:22510408
  review:
    summary: >-
      RPS3 sensitizes genotoxic (DNA-damage) stress-induced apoptosis by
      activating JNK in a caspase-dependent manner through interaction with
      TRADD at the DISC.
    action: KEEP_AS_NON_CORE
    reason: >-
      RPS3's pro-apoptotic activity in response to genotoxic stress is an
      extra-ribosomal moonlighting role demonstrated by overexpression/interaction
      experiments, secondary to the core ribosomal function. Retained as
      non-core.
    supported_by:
    - reference_id: PMID:22510408
      supporting_text: >-
        rpS3 sensitizes genotoxic stress-induced apoptosis by activating JNK
        through a caspase dependent manner.
- term:
    id: GO:0003723
    label: RNA binding
  evidence_type: IDA
  original_reference_id: PMID:20217897
  review:
    summary: >-
      Free RPS3 binds RNA, including its own cognate mRNA and 18S rRNA, via its
      C-terminal domain (independent of the KH domain).
    action: KEEP_AS_NON_CORE
    reason: >-
      RNA binding is a directly-evidenced activity consistent with RPS3's KH
      domain and its rRNA contacts in the ribosome, and underlies its
      translational autoregulation. It is secondary to the core structural
      ribosomal role; retained as non-core.
    supported_by:
    - reference_id: PMID:20217897
      supporting_text: >-
        rpS3 protein was found to interact with various RNAs-endogenous rpS3,
        18S rRNA. The S3-C terminal domain was shown to be the major mRNA
        binding domain of rpS3
- term:
    id: GO:0004520
    label: DNA endonuclease activity
  evidence_type: IDA
  original_reference_id: PMID:20605787
  review:
    summary: >-
      Nuclear-accumulated RPS3 is reported to function as an endonuclease,
      contributing to DNA repair activity in neuronal cells.
    action: KEEP_AS_NON_CORE
    reason: >-
      DNA endonuclease activity reflects RPS3's historically reported
      AP/base-damage endonuclease moonlighting activity. The intrinsic catalytic
      status of human RPS3 remains debated (PMID:18610840 finds only AP-site
      beta-elimination and questions in vivo relevance), so this is retained as a
      non-core, context-dependent activity rather than a core function.
    supported_by:
    - reference_id: PMID:20605787
      supporting_text: >-
        nuclear translocation and accumulation of RPS3, where it functions as an
        endonuclease.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IMP
  original_reference_id: PMID:21871177
  review:
    summary: >-
      Cdk1-mediated phosphorylation of RPS3 at Thr221 during G2/M promotes its
      nuclear accumulation.
    action: KEEP_AS_NON_CORE
    reason: >-
      Regulated, cell-cycle-dependent nuclear accumulation is an extra-ribosomal
      context, non-core relative to the cytosolic ribosomal location. Retained as
      non-core.
    supported_by:
    - reference_id: PMID:21871177
      supporting_text: >-
        the phosphorylation of rpS3 by Cdk1 occurs at Thr221 during G2/M phase
        and, moreover, that this event is important for nuclear accumulation of
        rpS3.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:20217897
  review:
    summary: >-
      A pool of free RPS3 exists in the cytoplasm (outside ribosomes), where it
      binds its own mRNA to autoregulate translation.
    action: ACCEPT
    reason: >-
      Cytoplasm is the expected, core location for RPS3 (cytosolic ribosome and
      free cytoplasmic pool), consistent with accepted cytosol/cytoplasm
      annotations.
    supported_by:
    - reference_id: PMID:20217897
      supporting_text: >-
        Most of the rpS3 pool is located in the ribosome while the minority
        exists in free form in the cytoplasm.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IMP
  original_reference_id: PMID:21871177
  review:
    summary: >-
      RPS3 is present in the cytoplasm, with a phosphorylation-regulated shift to
      nuclear accumulation during G2/M.
    action: ACCEPT
    reason: >-
      Cytoplasm is the expected, core cellular location for RPS3, consistent with
      its cytosolic ribosomal function.
    supported_by:
    - reference_id: PMID:21871177
      supporting_text: >-
        Decreased phosphorylation and nuclear accumulation of T221A was much
        more pronounced in G2/M phase.
- term:
    id: GO:0005840
    label: ribosome
  evidence_type: IDA
  original_reference_id: PMID:20217897
  review:
    summary: >-
      Most of the cellular RPS3 pool is located in the ribosome, consistent with
      its core role as a ribosomal protein.
    action: ACCEPT
    reason: >-
      Ribosome localization is core to RPS3's function as a 40S small-subunit
      protein.
    supported_by:
    - reference_id: PMID:20217897
      supporting_text: >-
        Most of the rpS3 pool is located in the ribosome while the minority
        exists in free form in the cytoplasm.
- term:
    id: GO:0019900
    label: kinase binding
  evidence_type: IPI
  original_reference_id: PMID:20605787
  review:
    summary: >-
      RPS3 is a physiological target of Akt kinase; NGF-stimulated Akt
      phosphorylates RPS3 at Thr70, and this phosphorylation is required for Akt
      binding to RPS3.
    action: KEEP_AS_NON_CORE
    reason: >-
      Kinase binding captures the directly-evidenced Akt interaction that
      regulates RPS3's pro-apoptotic/DNA-repair switch, an extra-ribosomal
      regulatory context. More informative than generic protein binding but
      non-core relative to the ribosomal role.
    supported_by:
    - reference_id: PMID:20605787
      supporting_text: >-
        NGF stimulation resulted in phosphorylation of threonine 70 of RPS3 by
        Akt, and this phosphorylation was required for Akt binding to RPS3.
- term:
    id: GO:0019901
    label: protein kinase binding
  evidence_type: IPI
  original_reference_id: PMID:21871177
  review:
    summary: >-
      RPS3 interacts with the cell-cycle kinase Cdk1, which phosphorylates it
      during G2/M phase, as shown by co-IP and GST pull-down.
    action: KEEP_AS_NON_CORE
    reason: >-
      Protein kinase binding captures the directly-evidenced Cdk1 interaction
      that regulates RPS3's mitotic phosphorylation/nuclear accumulation, an
      extra-ribosomal regulatory context. More informative than generic protein
      binding but non-core.
    supported_by:
    - reference_id: PMID:21871177
      supporting_text: >-
        Co-immunoprecipitation and GST pull-down assays revealed that Cdk1
        interacted with rpS3.
- term:
    id: GO:0042981
    label: regulation of apoptotic process
  evidence_type: IMP
  original_reference_id: PMID:20605787
  review:
    summary: >-
      RPS3 acts as an Akt-regulated molecular switch in neuronal apoptosis;
      abolishing Akt-mediated phosphorylation accelerated apoptotic cell death,
      while RPS3 induced apoptosis via E2F1-dependent gene up-regulation.
    action: KEEP_AS_NON_CORE
    reason: >-
      Regulation of apoptosis is a context-dependent extra-ribosomal moonlighting
      role of RPS3, secondary to the core ribosomal function. Retained as
      non-core.
    supported_by:
    - reference_id: PMID:20605787
      supporting_text: >-
        Akt-dependent phosphorylation of RPS3 inhibited its proapoptotic
        function ... Abolishment of Akt-mediated RPS3 phosphorylation ...
        accelerated apoptotic cell death
- term:
    id: GO:0044390
    label: ubiquitin-like protein conjugating enzyme binding
  evidence_type: IPI
  original_reference_id: PMID:21968017
  review:
    summary: >-
      RPS3 interacts with SUMO-1 (identified by yeast two-hybrid) and is
      sumoylated, which increases its protein stability.
    action: KEEP_AS_NON_CORE
    reason: >-
      This captures a specific interaction with the SUMO modification machinery
      that regulates RPS3 stability, an extra-ribosomal regulatory context.
      Retained as non-core. [Note: the interactor identified is SUMO-1 itself; the
      "conjugating enzyme binding" framing is a curation interpretation of the
      SUMO-pathway interaction.]
    supported_by:
    - reference_id: PMID:21968017
      supporting_text: >-
        we identified small ubiquitin-related modifier-1 (SUMO-1) as a new
        interacting partner of rpS3.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6791223
  review:
    summary: >-
      Reactome places RPS3 in the nucleoplasm in the context of pre-40S particle
      processing during ribosome biogenesis (pre-rRNA processing en route from
      nucleus to cytosol).
    action: KEEP_AS_NON_CORE
    reason: >-
      Nucleoplasmic localization reflects the transient nuclear phase of
      ribosome biogenesis/pre-40S trafficking, not the mature cytosolic
      ribosomal location. Retained as non-core.
    supported_by:
    - reference_id: Reactome:R-HSA-6791223
      supporting_text: >-
        18SE pre-rRNA in pre-40S particles is nucleolytically processed during
        translocation from the nucleus to the cytosol
- term:
    id: GO:0031397
    label: negative regulation of protein ubiquitination
  evidence_type: IDA
  original_reference_id: PMID:19656744
  review:
    summary: >-
      RPS3 interacts with MDM2 and p53; under oxidative stress, RPS3 knockdown
      led to loss of the MDM2 E3 ubiquitin ligase domain and decreased p53,
      implicating RPS3 in regulating MDM2-mediated ubiquitination of p53.
    action: KEEP_AS_NON_CORE
    reason: >-
      This is an extra-ribosomal moonlighting role in the p53/MDM2 axis. The
      evidence is indirect (effects on MDM2/p53 levels under stress) rather than
      a direct ubiquitination assay, and is secondary to the core ribosomal
      function. Retained as non-core.
    supported_by:
    - reference_id: PMID:19656744
      supporting_text: >-
        in cells exposed to oxidative stress and harboring siRNA to knockdown
        RPS3 expression, decreased p53 levels and loss of the E3 ubiquitin ligase
        domain possessed by MDM2 were observed.
- term:
    id: GO:0032358
    label: oxidized pyrimidine DNA binding
  evidence_type: IDA
  original_reference_id: PMID:19656744
  review:
    summary: >-
      RPS3 binds an 8-oxoG-containing duplex oligonucleotide and acts as a
      scaffold for binding of MDM2 and p53 at the damaged DNA.
    action: KEEP_AS_NON_CORE
    reason: >-
      Damaged/oxidized DNA binding by RPS3 is well-supported (PMID:14706345,
      PMID:18610840), and DNA-pull-down here shows binding to an 8-oxoG duplex.
      This is an extra-ribosomal moonlighting activity, secondary to the core
      ribosomal function. [The 8-oxoG lesion is an oxidized purine; the term used
      is oxidized pyrimidine DNA binding, a minor mismatch, but binding to
      oxidatively damaged DNA is supported.]
    supported_by:
    - reference_id: PMID:19656744
      supporting_text: >-
        DNA pull-down assays using a 7,8-dihydro-8-oxoguanine duplex
        oligonucleotide as a substrate found that RPS3 acted as a scaffold for
        the additional binding of MDM2 and p53
- term:
    id: GO:0003906
    label: DNA-(apurinic or apyrimidinic site) endonuclease activity
  evidence_type: IDA
  original_reference_id: PMID:19059439
  review:
    summary: >-
      Phosphorylation of non-ribosomal RPS3 by PKCdelta increased its repair
      (AP/damage) endonuclease activity.
    action: KEEP_AS_NON_CORE
    reason: >-
      AP-site endonuclease activity is a historically reported moonlighting
      activity of RPS3. Its intrinsic catalytic relevance in human cells remains
      debated (PMID:18610840 finds only AP-site beta-elimination and questions
      global in vivo repair), so this is retained as a non-core, context-dependent
      activity rather than a core function.
    supported_by:
    - reference_id: PMID:19059439
      supporting_text: >-
        the repair endonuclease activity of rpS3 was increased by its
        phosphorylation.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:19059439
  review:
    summary: >-
      PKCdelta phosphorylation mobilizes non-ribosomal RPS3 to the nucleus to
      repair damaged DNA.
    action: KEEP_AS_NON_CORE
    reason: >-
      Stimulus/phosphorylation-dependent nuclear localization is a regulated
      extra-ribosomal context, non-core relative to the cytosolic ribosomal
      location. Retained as non-core.
    supported_by:
    - reference_id: PMID:19059439
      supporting_text: >-
        PKCdelta phosphorylates rpS3 resulting in its mobilization in the
        nucleus to repair damaged DNA.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:19059439
  review:
    summary: >-
      RPS3 is present in the cytoplasm, with a phosphorylation-regulated
      non-ribosomal pool that relocates to the nucleus upon DNA damage.
    action: ACCEPT
    reason: >-
      Cytoplasm is the expected, core cellular location for RPS3, consistent with
      its cytosolic ribosomal function.
    supported_by:
    - reference_id: PMID:19059439
      supporting_text: >-
        Phosphorylated rpS3 was only detected in non-ribosomal rpS3
- term:
    id: GO:0005840
    label: ribosome
  evidence_type: IDA
  original_reference_id: PMID:19059439
  review:
    summary: >-
      RPS3 is a component of the 40S ribosomal subunit involved in translation.
    action: ACCEPT
    reason: >-
      Ribosome localization is core to RPS3's role as a small-subunit ribosomal
      protein.
    supported_by:
    - reference_id: PMID:19059439
      supporting_text: >-
        Ribosomal protein S3 (rpS3) is critically involved in translation as a
        component of the 40S ribosomal subunit
- term:
    id: GO:0003677
    label: DNA binding
  evidence_type: IDA
  original_reference_id: PMID:18610840
  review:
    summary: >-
      Recombinant human RPS3 binds DNA, including undamaged DNA; in this study
      binding to undamaged DNA was actually more efficient than to several
      damaged lesions.
    action: MODIFY
    reason: >-
      Generic DNA binding is less informative than the specific damaged-DNA
      binding activity that is the functionally relevant moonlighting feature of
      RPS3; the same reference also documents damaged DNA binding. Recommend the
      more specific damaged DNA binding term (also separately annotated from this
      reference).
    proposed_replacement_terms:
    - id: GO:0003684
      label: damaged DNA binding
    supported_by:
    - reference_id: PMID:18610840
      supporting_text: >-
        Binding of hS3 to DNA ligands containing oxidized and deaminated bases
        was less efficient than its binding to undamaged DNA.
- term:
    id: GO:0003684
    label: damaged DNA binding
  evidence_type: IDA
  original_reference_id: PMID:18610840
  review:
    summary: >-
      Recombinant human RPS3 binds and cleaves AP-site-containing DNA substrates
      (via beta-elimination), confirming damaged-DNA binding.
    action: KEEP_AS_NON_CORE
    reason: >-
      Damaged DNA binding is a well-supported extra-ribosomal activity, secondary
      to the core ribosomal function. Retained as non-core.
    supported_by:
    - reference_id: PMID:18610840
      supporting_text: >-
        hS3 catalyzed cleavage of apurine/apyrimidine sites through
        beta-elimination mechanism forming a transient Schiff base covalent
        intermediate
- term:
    id: GO:0003906
    label: DNA-(apurinic or apyrimidinic site) endonuclease activity
  evidence_type: IDA
  original_reference_id: PMID:18610840
  review:
    summary: >-
      Recombinant human RPS3 cleaves AP sites via a beta-elimination (AP lyase)
      mechanism but does not cleave substrates containing other lesions, and the
      authors question its in vivo global repair relevance.
    action: KEEP_AS_NON_CORE
    reason: >-
      AP-site cleavage activity is supported in vitro but is mechanistically an
      AP lyase (beta-elimination) and its physiological/global in vivo relevance
      is doubted by the authors. It is a context-dependent moonlighting activity,
      secondary to the core ribosomal function; retained as non-core.
    supported_by:
    - reference_id: PMID:18610840
      supporting_text: >-
        the activity of hS3 on apurine/apyrimidine sites is not likely to be
        involved in the global in vivo DNA repair but could have a role in the
        repair in some specific locations in the genome.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:19460357
  review:
    summary: >-
      Arginine methylation of RPS3 by PRMT1 is required for its import into the
      nucleus/nucleolus and subsequent incorporation into the ribosome.
    action: KEEP_AS_NON_CORE
    reason: >-
      Nuclear/nucleolar localization here reflects the ribosome-biogenesis
      trafficking phase, not the mature cytosolic ribosomal location. Retained as
      non-core.
    supported_by:
    - reference_id: PMID:19460357
      supporting_text: >-
        mutant rpS3 (3RA), which cannot be methylated at these sites, cannot be
        transported into the nucleolus and subsequently incorporated into the
        ribosome.
- term:
    id: GO:0005730
    label: nucleolus
  evidence_type: IDA
  original_reference_id: PMID:19460357
  review:
    summary: >-
      RPS3 is imported into the nucleolus (dependent on PRMT1 arginine
      methylation) for small-subunit ribosome assembly.
    action: KEEP_AS_NON_CORE
    reason: >-
      Nucleolar localization reflects the ribosome-biogenesis/assembly phase of
      RPS3, distinct from the mature cytosolic ribosomal location. This is a
      direct functional study (unlike the weaker IEA nucleolus annotation that was
      marked over-annotated), so retained as non-core.
    supported_by:
    - reference_id: PMID:19460357
      supporting_text: >-
        arginine methylation of rpS3 plays a critical role in its import into the
        nucleolus, as well as in small subunit assembly of the ribosome.
- term:
    id: GO:0005840
    label: ribosome
  evidence_type: IDA
  original_reference_id: PMID:19460357
  review:
    summary: >-
      RPS3 is incorporated into the ribosome (40S small subunit), a process that
      depends on its PRMT1-mediated arginine methylation.
    action: ACCEPT
    reason: >-
      Ribosome localization/incorporation is core to RPS3's function as a 40S
      small-subunit ribosomal protein.
    supported_by:
    - reference_id: PMID:19460357
      supporting_text: >-
        The human ribosomal protein S3 (rpS3), a component of the 40S small
        subunit in the ribosome
- term:
    id: GO:0019104
    label: DNA N-glycosylase activity
  evidence_type: IDA
  original_reference_id: PMID:18610840
  negated: true
  review:
    summary: >-
      Recombinant human RPS3 cleaved AP sites by beta-elimination but did NOT
      cleave substrates containing oxidized/deaminated bases (8-oxoguanine,
      uracil, hypoxanthine, etc.), so it lacks DNA glycosylase activity.
    action: ACCEPT
    reason: >-
      The NOT annotation is well-supported: despite sequence-based predictions,
      RPS3 has no detectable DNA N-glycosylase activity. Accept the negation as
      correctly representing the experimental result.
    supported_by:
    - reference_id: PMID:18610840
      supporting_text: >-
        hS3 catalyzed cleavage of apurine/apyrimidine sites through
        beta-elimination mechanism forming a transient Schiff base covalent
        intermediate, but did not cleave substrates containing other lesions.
- term:
    id: GO:0019899
    label: enzyme binding
  evidence_type: IPI
  original_reference_id: PMID:19460357
  review:
    summary: >-
      RPS3 is methylated by and interacts with protein arginine
      methyltransferase 1 (PRMT1), which regulates its nucleolar import and
      ribosome assembly.
    action: KEEP_AS_NON_CORE
    reason: >-
      Enzyme binding here captures the directly-evidenced PRMT1 interaction that
      governs RPS3 modification and ribosome assembly. More informative than
      generic protein binding; it relates to ribosome biogenesis regulation but
      is retained as non-core relative to the structural ribosomal function.
    supported_by:
    - reference_id: PMID:19460357
      supporting_text: >-
        the arginine residue(s) of rpS3 are methylated by protein arginine
        methyltransferase 1 (PRMT1).
- term:
    id: GO:0070181
    label: small ribosomal subunit rRNA binding
  evidence_type: IDA
  original_reference_id: PMID:18610840
  review:
    summary: >-
      RPS3 interacts with 18S rRNA, the rRNA of the small (40S) ribosomal
      subunit, consistent with its structural role in the small subunit.
    action: ACCEPT
    reason: >-
      Small-subunit rRNA binding is consistent with RPS3's core structural role
      in the 40S subunit, where it contacts 18S rRNA. The 18S rRNA interaction
      is directly documented (PMID:20217897), supporting this MF as core.
    supported_by:
    - reference_id: PMID:20217897
      supporting_text: >-
        rpS3 protein was found to interact with various RNAs-endogenous rpS3,
        18S rRNA.
- term:
    id: GO:0003906
    label: DNA-(apurinic or apyrimidinic site) endonuclease activity
  evidence_type: IDA
  original_reference_id: PMID:15707971
  review:
    summary: >-
      Mammalian RPS3 nicks DNA containing AP sites and a wide range of
      base-damage lesions (thymine glycols, UV-damaged lesions) as a
      base-damage-endonuclease.
    action: KEEP_AS_NON_CORE
    reason: >-
      AP-site endonuclease activity is a historically reported moonlighting
      activity. Its intrinsic catalytic relevance for human RPS3 in vivo is
      debated (PMID:18610840), so it is retained as a context-dependent non-core
      activity rather than a core function.
    supported_by:
    - reference_id: PMID:15707971
      supporting_text: >-
        rpS3 cleaves the lesions including AP sites, thymine glycols, and other
        UV damaged lesions such as pyrimidine dimers.
- term:
    id: GO:0004520
    label: DNA endonuclease activity
  evidence_type: IDA
  original_reference_id: PMID:15707971
  review:
    summary: >-
      Mammalian RPS3 acts as a wide-range base-damage endonuclease, cleaving
      phosphodiester bonds in DNA containing various altered bases.
    action: KEEP_AS_NON_CORE
    reason: >-
      DNA endonuclease activity is a historically reported moonlighting activity
      whose physiological relevance in human cells is debated. Retained as a
      non-core, context-dependent activity.
    supported_by:
    - reference_id: PMID:15707971
      supporting_text: >-
        rpS3 cleaves phosphodiester bonds of DNAs containing altered bases with
        broad specificity acting as a base-damage-endonuclease.
- term:
    id: GO:0019104
    label: DNA N-glycosylase activity
  evidence_type: TAS
  original_reference_id: PMID:15707971
  negated: true
  review:
    summary: >-
      Despite a sequence prediction of glycosylase activity, RPS3 does not have
      glycosylase activity; it acts as an endonuclease on damaged DNA.
    action: ACCEPT
    reason: >-
      The NOT annotation is well-supported and consistent with PMID:18610840:
      RPS3 lacks DNA glycosylase activity. Accept the negation.
    supported_by:
    - reference_id: PMID:15707971
      supporting_text: >-
        This enzyme does not have a glycosylase activity as predicted from its
        amino acid sequence.
- term:
    id: GO:0097100
    label: supercoiled DNA binding
  evidence_type: IDA
  original_reference_id: PMID:15707971
  review:
    summary: >-
      RPS3 cleaves supercoiled UV-damaged DNA more efficiently than the relaxed
      counterpart, indicating a preference for/interaction with supercoiled DNA.
    action: KEEP_AS_NON_CORE
    reason: >-
      Supercoiled DNA binding is inferred from the preferential cleavage of
      supercoiled damaged DNA, part of RPS3's debated extra-ribosomal
      base-damage-endonuclease activity. Retained as non-core.
    supported_by:
    - reference_id: PMID:15707971
      supporting_text: >-
        RpS3 cleaves supercoiled UV damaged DNA more efficiently than the relaxed
        counterpart
- term:
    id: GO:0003684
    label: damaged DNA binding
  evidence_type: IDA
  original_reference_id: PMID:14706345
  review:
    summary: >-
      By surface plasmon resonance, human RPS3 binds 8-oxoG and AP sites with
      very high apparent affinity (orders of magnitude higher than OGG1).
    action: KEEP_AS_NON_CORE
    reason: >-
      Damaged DNA binding is among the best-supported extra-ribosomal activities
      of human RPS3, with quantitative binding data. It is secondary to the core
      ribosomal role; retained as non-core.
    supported_by:
    - reference_id: PMID:14706345
      supporting_text: >-
        An even more dramatic five orders of magnitude higher binding affinity
        for AP DNA was found for hS3 as opposed to hOGG1.
- term:
    id: GO:0032357
    label: oxidized purine DNA binding
  evidence_type: IDA
  original_reference_id: PMID:14706345
  review:
    summary: >-
      Human RPS3 binds 7,8-dihydro-8-oxoguanine (8-oxoG), an oxidized purine
      lesion, with high apparent affinity.
    action: KEEP_AS_NON_CORE
    reason: >-
      Oxidized purine (8-oxoG) DNA binding is directly and quantitatively
      supported; this term is more specific and accurate than the generic
      oxidized-pyrimidine term used elsewhere. It is an extra-ribosomal
      moonlighting activity, secondary to the core ribosomal function. Retained
      as non-core.
    supported_by:
    - reference_id: PMID:14706345
      supporting_text: >-
        hS3 was found to have an apparent three orders of magnitude higher
        binding affinity (KD) for 8-oxoG than the human N-glycosylase/AP lyase
        base excision repair (BER) enzyme OGG1.
- term:
    id: GO:0003906
    label: DNA-(apurinic or apyrimidinic site) endonuclease activity
  evidence_type: IDA
  original_reference_id: PMID:7775413
  review:
    summary: >-
      The earliest report implicating mammalian RPS3 in DNA damage processing
      identified an AP/UV endonuclease activity co-purifying with ribosomal
      protein S3.
    action: KEEP_AS_NON_CORE
    reason: >-
      This historical biochemical evidence connects RPS3 with AP/UV endonuclease
      activity, but the physiological relevance for human RPS3 is debated
      (PMID:18610840). Retained as a non-core, context-dependent activity.
    supported_by:
    - reference_id: PMID:7775413
      supporting_text: >-
        The nuclease activities have been purified from mouse cells to yield a
        peptide of M(r) = 32,000, whose sequence indicates identity with
        ribosomal protein S3.
- term:
    id: GO:0016020
    label: membrane
  evidence_type: HDA
  original_reference_id: PMID:19946888
  review:
    summary: >-
      RPS3 was detected in a high-throughput proteomic study of the membrane
      proteome of NK cells.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Detection of an abundant ribosomal protein in a membrane proteome most
      plausibly reflects co-isolation (e.g., membrane-associated ribosomes) or
      contamination rather than an RPS3-specific integral/peripheral membrane
      role. Treated as an over-annotation.
    supported_by:
    - reference_id: PMID:19946888
      supporting_text: >-
        Defining the membrane proteome of NK cells.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:24423872
  review:
    summary: >-
      RPS3 directly associates with AUF1 and contributes to 3'UTR-dependent
      translation of Cry1 mRNA in the circadian clock context.
    action: KEEP_AS_NON_CORE
    reason: >-
      Generic protein binding term; the specific AUF1 association relates to
      translational regulation but is non-core relative to the structural
      ribosomal function and not a defining RPS3 molecular function. Retained as
      non-core.
    supported_by:
    - reference_id: PMID:24423872
      supporting_text: >-
        AUF1 ... directly associated with ribosomal protein S3 or ribosomal
        protein S14, resulting in translation of Cry1 mRNA in a 3'UTR-dependent
        manner.
- term:
    id: GO:2001235
    label: positive regulation of apoptotic signaling pathway
  evidence_type: IDA
  original_reference_id: PMID:14988002
  review:
    summary: >-
      Overexpression of GFP-RPS3 activates caspase-8/caspase-3 and sensitizes
      cells to cytokine-induced apoptosis, indicating a pro-apoptotic activity.
    action: KEEP_AS_NON_CORE
    reason: >-
      Pro-apoptotic activity is a context-dependent extra-ribosomal moonlighting
      function shown by overexpression/cytokine paradigms, secondary to the core
      ribosomal role. Retained as non-core.
    supported_by:
    - reference_id: PMID:14988002
      supporting_text: >-
        Transient expression of GFP-rpS3 activates caspase-8/caspase-3 and
        sensitizes cytokine-induced apoptosis.
- term:
    id: GO:0003723
    label: RNA binding
  evidence_type: HDA
  original_reference_id: PMID:22658674
  review:
    summary: >-
      RPS3 was identified as an mRNA-binding protein in a high-throughput
      interactome-capture atlas of mammalian mRNA-binding proteins.
    action: KEEP_AS_NON_CORE
    reason: >-
      RNA binding is consistent with RPS3's KH domain and its direct rRNA/mRNA
      contacts in the ribosome and in autoregulation (PMID:20217897). It is a real
      activity but, as captured by these broad mRNA-interactome screens, is
      secondary to the core structural ribosomal role; kept non-core for
      consistency with the other RNA binding annotations.
    supported_by:
    - reference_id: PMID:22658674
      supporting_text: >-
        We identify 860 proteins that qualify as RBPs by biochemical and
        statistical criteria
- term:
    id: GO:0003723
    label: RNA binding
  evidence_type: HDA
  original_reference_id: PMID:22681889
  review:
    summary: >-
      RPS3 was identified among the mRNA-bound proteome in a second
      high-throughput RNA-interactome study.
    action: KEEP_AS_NON_CORE
    reason: >-
      Independent HDA support for RPS3 RNA binding, consistent with its KH domain
      and rRNA/mRNA contacts. A real but broad MF, secondary to the structural
      ribosomal function; kept non-core for consistency with the other RNA binding
      annotations.
    supported_by:
    - reference_id: PMID:22681889
      supporting_text: >-
        We developed a photoreactive nucleotide-enhanced UV crosslinking and
        oligo(dT) purification approach to identify the mRNA-bound proteome
- term:
    id: GO:0003684
    label: damaged DNA binding
  evidence_type: IDA
  original_reference_id: PMID:17560175
  review:
    summary: >-
      Human RPS3 has affinity for abasic sites and 8-oxoG residues and
      co-localizes with 8-oxoG damage foci after genotoxic stress.
    action: KEEP_AS_NON_CORE
    reason: >-
      Damaged DNA binding is a well-supported extra-ribosomal activity here
      complemented by in-cell co-localization with damage foci. Secondary to the
      core ribosomal role; retained as non-core.
    supported_by:
    - reference_id: PMID:17560175
      supporting_text: >-
        hS3 was traced in exposed cells to its co-localization with 8-oxoG foci
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:16814409
  review:
    summary: >-
      RPS3 was observed in the nucleus as well as cytoplasm/cell periphery; in
      this study it colocalized with Nm23-H1 in the cell periphery and cytoplasm.
    action: KEEP_AS_NON_CORE
    reason: >-
      Nuclear localization is a regulated extra-ribosomal pool, non-core relative
      to the cytosolic ribosomal location. Retained as non-core.
    supported_by:
    - reference_id: PMID:16814409
      supporting_text: >-
        RpS3 interacted with nm23-H1, and the two proteins were colocalized in
        the cell periphery and cytoplasm.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IDA
  original_reference_id: PMID:17560175
  review:
    summary: >-
      Under basal conditions RPS3 is cytoplasmic/cytosolic, translocating to the
      nucleus only upon genotoxic stress.
    action: ACCEPT
    reason: >-
      Cytosol is the expected, core cellular location for RPS3's cytosolic
      ribosomal function, consistent with accepted cytosol annotations.
    supported_by:
    - reference_id: PMID:17560175
      supporting_text: >-
        hS3 is capable of carrying out both roles by its ex vivo translocation
        from the cytoplasm to the nucleus as a consequence of genotoxic stress.
- term:
    id: GO:0019899
    label: enzyme binding
  evidence_type: IPI
  original_reference_id: PMID:15518571
  review:
    summary: >-
      Human RPS3 physically interacts with the BER enzymes OGG1 and APE1/Ref-1
      (co-immunoprecipitation and SPR).
    action: KEEP_AS_NON_CORE
    reason: >-
      Enzyme binding captures the directly-evidenced interactions with BER
      enzymes (OGG1, APE1), more informative than generic protein binding but
      part of RPS3's extra-ribosomal BER-cofactor role. Retained as non-core.
    supported_by:
    - reference_id: PMID:15518571
      supporting_text: >-
        Human S3 was found to co-immunoprecipitate with both hOGG1 and
        APE/Ref-1, indicating that these proteins physically interact with one
        another.
- term:
    id: GO:0070062
    label: extracellular exosome
  evidence_type: HDA
  original_reference_id: PMID:20458337
  review:
    summary: >-
      RPS3 was detected in a proteomic study of MHC class II-associated proteins
      in B-cell exosomes.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Detection of an abundant ribosomal protein in an exosome proteome is a
      common, non-specific finding and does not establish a discrete
      RPS3-specific exosomal function. Treated as an over-annotation.
    supported_by:
    - reference_id: PMID:20458337
      supporting_text: >-
        MHC class II-associated proteins in B-cell exosomes and potential
        functional implications for exosome biogenesis.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-156808
  review:
    summary: >-
      Reactome places RPS3 (as a 40S/cytosolic ribosome component) in the cytosol
      within this translation/ribosome-associated pathway step.
    action: ACCEPT
    reason: >-
      Cytosol is the expected, core cellular location for RPS3 as part of the
      cytosolic ribosome participating in translation and ribosome-associated
      processes. Consistent with the accepted cytosol/cytosolic ribosome
      annotations.
    supported_by:
    - reference_id: Reactome:R-HSA-156808
      supporting_text: >-
        Formation of translation initiation complexes yielding circularized Ceruloplasmin mRNA in a  'closed-loop' conformation
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-156823
  review:
    summary: >-
      Reactome places RPS3 (as a 40S/cytosolic ribosome component) in the cytosol
      within this translation/ribosome-associated pathway step.
    action: ACCEPT
    reason: >-
      Cytosol is the expected, core cellular location for RPS3 as part of the
      cytosolic ribosome participating in translation and ribosome-associated
      processes. Consistent with the accepted cytosol/cytosolic ribosome
      annotations.
    supported_by:
    - reference_id: Reactome:R-HSA-156823
      supporting_text: >-
        Association of phospho-L13a with GAIT element of Ceruloplasmin mRNA
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-157849
  review:
    summary: >-
      Reactome places RPS3 (as a 40S/cytosolic ribosome component) in the cytosol
      within this translation/ribosome-associated pathway step.
    action: ACCEPT
    reason: >-
      Cytosol is the expected, core cellular location for RPS3 as part of the
      cytosolic ribosome participating in translation and ribosome-associated
      processes. Consistent with the accepted cytosol/cytosolic ribosome
      annotations.
    supported_by:
    - reference_id: Reactome:R-HSA-157849
      supporting_text: >-
        Formation of translation initiation complexes containing mRNA that does not circularize
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-1799332
  review:
    summary: >-
      Reactome places RPS3 (as a 40S/cytosolic ribosome component) in the cytosol
      within this translation/ribosome-associated pathway step.
    action: ACCEPT
    reason: >-
      Cytosol is the expected, core cellular location for RPS3 as part of the
      cytosolic ribosome participating in translation and ribosome-associated
      processes. Consistent with the accepted cytosol/cytosolic ribosome
      annotations.
    supported_by:
    - reference_id: Reactome:R-HSA-1799332
      supporting_text: >-
        Nascent polypeptide:mRNA:ribosome complex binds signal recognition particle (SRP)
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-1799335
  review:
    summary: >-
      Reactome places RPS3 (as a 40S/cytosolic ribosome component) in the cytosol
      within this translation/ribosome-associated pathway step.
    action: ACCEPT
    reason: >-
      Cytosol is the expected, core cellular location for RPS3 as part of the
      cytosolic ribosome participating in translation and ribosome-associated
      processes. Consistent with the accepted cytosol/cytosolic ribosome
      annotations.
    supported_by:
    - reference_id: Reactome:R-HSA-1799335
      supporting_text: >-
        Synthesis of nascent polypeptide containing signal sequence
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-192704
  review:
    summary: >-
      Reactome places RPS3 (as a 40S/cytosolic ribosome component) in the cytosol
      within this translation/ribosome-associated pathway step.
    action: ACCEPT
    reason: >-
      Cytosol is the expected, core cellular location for RPS3 as part of the
      cytosolic ribosome participating in translation and ribosome-associated
      processes. Consistent with the accepted cytosol/cytosolic ribosome
      annotations.
    supported_by:
    - reference_id: Reactome:R-HSA-192704
      supporting_text: >-
        Synthesis of PB1-F2
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-192841
  review:
    summary: >-
      Reactome places RPS3 (as a 40S/cytosolic ribosome component) in the cytosol
      within this translation/ribosome-associated pathway step.
    action: ACCEPT
    reason: >-
      Cytosol is the expected, core cellular location for RPS3 as part of the
      cytosolic ribosome participating in translation and ribosome-associated
      processes. Consistent with the accepted cytosol/cytosolic ribosome
      annotations.
    supported_by:
    - reference_id: Reactome:R-HSA-192841
      supporting_text: >-
        Viral Protein Synthesis
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6791223
  review:
    summary: >-
      Reactome places RPS3 (as a pre-40S/40S ribosome component) in the cytosol
      in the context of pre-rRNA processing during nucleus-to-cytosol
      translocation of pre-40S particles.
    action: ACCEPT
    reason: >-
      Cytosol is the expected, core cellular location for RPS3 as part of the
      cytosolic ribosome, consistent with the accepted cytosol/cytosolic ribosome
      annotations.
    supported_by:
    - reference_id: Reactome:R-HSA-6791223
      supporting_text: >-
        18SE pre-rRNA in pre-40S particles is nucleolytically processed during
        translocation from the nucleus to the cytosol
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-72619
  review:
    summary: >-
      Reactome places RPS3 (as a 40S/cytosolic ribosome component) in the cytosol
      within this translation/ribosome-associated pathway step.
    action: ACCEPT
    reason: >-
      Cytosol is the expected, core cellular location for RPS3 as part of the
      cytosolic ribosome participating in translation and ribosome-associated
      processes. Consistent with the accepted cytosol/cytosolic ribosome
      annotations.
    supported_by:
    - reference_id: Reactome:R-HSA-72619
      supporting_text: >-
        eIF2:GTP is hydrolyzed, eIFs are released
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-72621
  review:
    summary: >-
      Reactome places RPS3 (as a 40S/cytosolic ribosome component) in the cytosol
      within this translation/ribosome-associated pathway step.
    action: ACCEPT
    reason: >-
      Cytosol is the expected, core cellular location for RPS3 as part of the
      cytosolic ribosome participating in translation and ribosome-associated
      processes. Consistent with the accepted cytosol/cytosolic ribosome
      annotations.
    supported_by:
    - reference_id: Reactome:R-HSA-72621
      supporting_text: >-
        Ribosomal scanning
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-72671
  review:
    summary: >-
      Reactome places RPS3 (as a 40S/cytosolic ribosome component) in the cytosol
      within this translation/ribosome-associated pathway step.
    action: ACCEPT
    reason: >-
      Cytosol is the expected, core cellular location for RPS3 as part of the
      cytosolic ribosome participating in translation and ribosome-associated
      processes. Consistent with the accepted cytosol/cytosolic ribosome
      annotations.
    supported_by:
    - reference_id: Reactome:R-HSA-72671
      supporting_text: >-
        eIF5B:GTP is hydrolyzed and released
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-72672
  review:
    summary: >-
      Reactome places RPS3 (as a 40S/cytosolic ribosome component) in the cytosol
      within this translation/ribosome-associated pathway step.
    action: ACCEPT
    reason: >-
      Cytosol is the expected, core cellular location for RPS3 as part of the
      cytosolic ribosome participating in translation and ribosome-associated
      processes. Consistent with the accepted cytosol/cytosolic ribosome
      annotations.
    supported_by:
    - reference_id: Reactome:R-HSA-72672
      supporting_text: >-
        The 60S subunit joins the translation initiation complex
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-72673
  review:
    summary: >-
      Reactome places RPS3 (as a 40S/cytosolic ribosome component) in the cytosol
      within this translation/ribosome-associated pathway step.
    action: ACCEPT
    reason: >-
      Cytosol is the expected, core cellular location for RPS3 as part of the
      cytosolic ribosome participating in translation and ribosome-associated
      processes. Consistent with the accepted cytosol/cytosolic ribosome
      annotations.
    supported_by:
    - reference_id: Reactome:R-HSA-72673
      supporting_text: >-
        Release of 40S and 60S subunits from the 80S ribosome
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-72676
  review:
    summary: >-
      Reactome places RPS3 (as a 40S/cytosolic ribosome component) in the cytosol
      within this translation/ribosome-associated pathway step.
    action: ACCEPT
    reason: >-
      Cytosol is the expected, core cellular location for RPS3 as part of the
      cytosolic ribosome participating in translation and ribosome-associated
      processes. Consistent with the accepted cytosol/cytosolic ribosome
      annotations.
    supported_by:
    - reference_id: Reactome:R-HSA-72676
      supporting_text: >-
        eIF3 and eIF1A bind to the 40S subunit
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-72691
  review:
    summary: >-
      Reactome places RPS3 (as a 40S/cytosolic ribosome component) in the cytosol
      within this translation/ribosome-associated pathway step.
    action: ACCEPT
    reason: >-
      Cytosol is the expected, core cellular location for RPS3 as part of the
      cytosolic ribosome participating in translation and ribosome-associated
      processes. Consistent with the accepted cytosol/cytosolic ribosome
      annotations.
    supported_by:
    - reference_id: Reactome:R-HSA-72691
      supporting_text: >-
        Formation of the 43S pre-initiation complex
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-72697
  review:
    summary: >-
      Reactome places RPS3 (as a 40S/cytosolic ribosome component) in the cytosol
      within this translation/ribosome-associated pathway step.
    action: ACCEPT
    reason: >-
      Cytosol is the expected, core cellular location for RPS3 as part of the
      cytosolic ribosome participating in translation and ribosome-associated
      processes. Consistent with the accepted cytosol/cytosolic ribosome
      annotations.
    supported_by:
    - reference_id: Reactome:R-HSA-72697
      supporting_text: >-
        Start codon recognition
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-927789
  review:
    summary: >-
      Reactome places RPS3 (as a 40S/cytosolic ribosome component) in the cytosol
      within this translation/ribosome-associated pathway step.
    action: ACCEPT
    reason: >-
      Cytosol is the expected, core cellular location for RPS3 as part of the
      cytosolic ribosome participating in translation and ribosome-associated
      processes. Consistent with the accepted cytosol/cytosolic ribosome
      annotations.
    supported_by:
    - reference_id: Reactome:R-HSA-927789
      supporting_text: >-
        Formation of UPF1:eRF3 complex on mRNA with a premature termination codon and no Exon Junction Complex
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-927813
  review:
    summary: >-
      Reactome places RPS3 (as a 40S/cytosolic ribosome component) in the cytosol
      within this translation/ribosome-associated pathway step.
    action: ACCEPT
    reason: >-
      Cytosol is the expected, core cellular location for RPS3 as part of the
      cytosolic ribosome participating in translation and ribosome-associated
      processes. Consistent with the accepted cytosol/cytosolic ribosome
      annotations.
    supported_by:
    - reference_id: Reactome:R-HSA-927813
      supporting_text: >-
        p-4S-UPF1 recruits SMG5, SMG7, SMG6, PNRC2, DCP1A, and PP2A
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-927832
  review:
    summary: >-
      Reactome places RPS3 (as a 40S/cytosolic ribosome component) in the cytosol
      within this translation/ribosome-associated pathway step.
    action: ACCEPT
    reason: >-
      Cytosol is the expected, core cellular location for RPS3 as part of the
      cytosolic ribosome participating in translation and ribosome-associated
      processes. Consistent with the accepted cytosol/cytosolic ribosome
      annotations.
    supported_by:
    - reference_id: Reactome:R-HSA-927832
      supporting_text: >-
        UPF1 binds an mRNP with a termination codon preceding an Exon Junction Complex
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-927836
  review:
    summary: >-
      Reactome places RPS3 (as a 40S/cytosolic ribosome component) in the cytosol
      within this translation/ribosome-associated pathway step.
    action: ACCEPT
    reason: >-
      Cytosol is the expected, core cellular location for RPS3 as part of the
      cytosolic ribosome participating in translation and ribosome-associated
      processes. Consistent with the accepted cytosol/cytosolic ribosome
      annotations.
    supported_by:
    - reference_id: Reactome:R-HSA-927836
      supporting_text: >-
        SMG6 hydrolyzes mRNA with premature termination codon
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-927889
  review:
    summary: >-
      Reactome places RPS3 (as a 40S/cytosolic ribosome component) in the cytosol
      within this translation/ribosome-associated pathway step.
    action: ACCEPT
    reason: >-
      Cytosol is the expected, core cellular location for RPS3 as part of the
      cytosolic ribosome participating in translation and ribosome-associated
      processes. Consistent with the accepted cytosol/cytosolic ribosome
      annotations.
    supported_by:
    - reference_id: Reactome:R-HSA-927889
      supporting_text: >-
        SMG1 phosphorylates UPF1 (enhanced by Exon Junction Complex)
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9729232
  review:
    summary: >-
      Reactome places RPS3 (as a 40S/cytosolic ribosome component) in the cytosol
      within this translation/ribosome-associated pathway step.
    action: ACCEPT
    reason: >-
      Cytosol is the expected, core cellular location for RPS3 as part of the
      cytosolic ribosome participating in translation and ribosome-associated
      processes. Consistent with the accepted cytosol/cytosolic ribosome
      annotations.
    supported_by:
    - reference_id: Reactome:R-HSA-9729232
      supporting_text: >-
        SARS-CoV-1 nsp1 binds to 40S ribosomal subunit
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9729849
  review:
    summary: >-
      Reactome places RPS3 (as a 40S/cytosolic ribosome component) in the cytosol
      within this translation/ribosome-associated pathway step.
    action: ACCEPT
    reason: >-
      Cytosol is the expected, core cellular location for RPS3 as part of the
      cytosolic ribosome participating in translation and ribosome-associated
      processes. Consistent with the accepted cytosol/cytosolic ribosome
      annotations.
    supported_by:
    - reference_id: Reactome:R-HSA-9729849
      supporting_text: >-
        SARS-CoV-2 nsp1 binds to 40S ribosomal complex
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9948291
  review:
    summary: >-
      Reactome places RPS3 (as a 40S/cytosolic ribosome component) in the cytosol
      within this translation/ribosome-associated pathway step.
    action: ACCEPT
    reason: >-
      Cytosol is the expected, core cellular location for RPS3 as part of the
      cytosolic ribosome participating in translation and ribosome-associated
      processes. Consistent with the accepted cytosol/cytosolic ribosome
      annotations.
    supported_by:
    - reference_id: Reactome:R-HSA-9948291
      supporting_text: >-
        RQT complex binds K63polyUb-80S ribosome:no-go mRNA:peptidyl-tRNA with nascent peptide
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9948300
  review:
    summary: >-
      Reactome places RPS3 (as a 40S/cytosolic ribosome component) in the cytosol
      within this translation/ribosome-associated pathway step.
    action: ACCEPT
    reason: >-
      Cytosol is the expected, core cellular location for RPS3 as part of the
      cytosolic ribosome participating in translation and ribosome-associated
      processes. Consistent with the accepted cytosol/cytosolic ribosome
      annotations.
    supported_by:
    - reference_id: Reactome:R-HSA-9948300
      supporting_text: >-
        RQT complex:K63polyUb-80S ribosome dissociates yielding K63polyUb-40S subunit and 60S subunit:peptidyl-tRNA with nascent peptide
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9948301
  review:
    summary: >-
      Reactome places RPS3 (as a 40S/cytosolic ribosome component) in the cytosol
      within this translation/ribosome-associated pathway step.
    action: ACCEPT
    reason: >-
      Cytosol is the expected, core cellular location for RPS3 as part of the
      cytosolic ribosome participating in translation and ribosome-associated
      processes. Consistent with the accepted cytosol/cytosolic ribosome
      annotations.
    supported_by:
    - reference_id: Reactome:R-HSA-9948301
      supporting_text: >-
        ZNF598 K63 polyubiquitinates RPS10 (eS10) and RPS20 (uS10) of the 40S ribosomal subunit
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9948317
  review:
    summary: >-
      Reactome places RPS3 (as a 40S/cytosolic ribosome component) in the cytosol
      within this translation/ribosome-associated pathway step.
    action: ACCEPT
    reason: >-
      Cytosol is the expected, core cellular location for RPS3 as part of the
      cytosolic ribosome participating in translation and ribosome-associated
      processes. Consistent with the accepted cytosol/cytosolic ribosome
      annotations.
    supported_by:
    - reference_id: Reactome:R-HSA-9948317
      supporting_text: >-
        ZNF598 and Ub:UBE2D1,2,3 bind stalled 80S ribosome
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9954730
  review:
    summary: >-
      Reactome places RPS3 (as a 40S/cytosolic ribosome component) in the cytosol
      within this translation/ribosome-associated pathway step.
    action: ACCEPT
    reason: >-
      Cytosol is the expected, core cellular location for RPS3 as part of the
      cytosolic ribosome participating in translation and ribosome-associated
      processes. Consistent with the accepted cytosol/cytosolic ribosome
      annotations.
    supported_by:
    - reference_id: Reactome:R-HSA-9954730
      supporting_text: >-
        PELO:HBS1L-1:GTP binds 80S ribosome:non-stop mRNA:peptidyl-tRNA with nascent peptide
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9954919
  review:
    summary: >-
      Reactome places RPS3 (as a 40S/cytosolic ribosome component) in the cytosol
      within this translation/ribosome-associated pathway step.
    action: ACCEPT
    reason: >-
      Cytosol is the expected, core cellular location for RPS3 as part of the
      cytosolic ribosome participating in translation and ribosome-associated
      processes. Consistent with the accepted cytosol/cytosolic ribosome
      annotations.
    supported_by:
    - reference_id: Reactome:R-HSA-9954919
      supporting_text: >-
        ABCE1:ATP binds PELO:HBS1L-1:GTP:80S ribosome:non-stop mRNA:peptidyl-tRNA with nascent peptide and HBS1L-1:GDP is released
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9955731
  review:
    summary: >-
      Reactome places RPS3 (as a 40S/cytosolic ribosome component) in the cytosol
      within this translation/ribosome-associated pathway step.
    action: ACCEPT
    reason: >-
      Cytosol is the expected, core cellular location for RPS3 as part of the
      cytosolic ribosome participating in translation and ribosome-associated
      processes. Consistent with the accepted cytosol/cytosolic ribosome
      annotations.
    supported_by:
    - reference_id: Reactome:R-HSA-9955731
      supporting_text: >-
        ABCE1:PELO:80S Ribosome:non-stop mRNA:peptidyl-tRNA with elongating peptide dissociates yielding ABCE1:40S ribosomal subunit, PELO, and 60S ribosomal subunit:peptidyl-tRNA with nascent peptide
- term:
    id: GO:0051018
    label: protein kinase A binding
  evidence_type: IPI
  original_reference_id: PMID:16814409
  review:
    summary: >-
      RPS3 interacts with Nm23-H1 (a nucleoside diphosphate kinase) and modulates
      ERK signaling, reducing invasion of fibrosarcoma cells.
    action: KEEP_AS_NON_CORE
    reason: >-
      The specific kinase-related interaction documented in this reference is with
      Nm23-H1/ERK, not protein kinase A; the protein kinase A binding term is a
      questionable mapping. The genuine interaction (Nm23-H1) is an extra-ribosomal
      moonlighting context. Retained as non-core given the evidence supports a
      kinase-pathway interaction rather than this exact term.
    supported_by:
    - reference_id: PMID:16814409
      supporting_text: >-
        RpS3 interacted with nm23-H1, and the two proteins were colocalized in
        the cell periphery and cytoplasm.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:22244329
  review:
    summary: >-
      H2S-mediated sulfhydration of the NF-kB p65 subunit at Cys38 promotes its
      binding to the coactivator RPS3, supporting an RPS3-p65 interaction in
      antiapoptotic NF-kB signaling.
    action: KEEP_AS_NON_CORE
    reason: >-
      Generic protein binding term; the specific RPS3-p65 interaction is part of
      RPS3's extra-ribosomal NF-kB coactivator role, captured more informatively by
      the NF-kB complex and transcription-regulation annotations. Retained as
      non-core.
    supported_by:
    - reference_id: PMID:22244329
      supporting_text: >-
        sulfhydrating the p65 subunit of NF-κB at cysteine-38, which promotes its
        binding to the coactivator ribosomal protein S3 (RPS3).
- term:
    id: GO:1990904
    label: ribonucleoprotein complex
  evidence_type: IDA
  original_reference_id: PMID:17289661
  review:
    summary: >-
      RPS3 was identified as a component of IMP1 (IGF2BP1) mRNP granules, which
      contain ribosomal proteins and translation machinery.
    action: ACCEPT
    reason: >-
      RPS3 is a ribonucleoprotein-complex component (the ribosome itself is an
      RNP), so this broad term is correct; it is subsumed by the more specific
      cytosolic ribosome annotations. Consistent with the accepted IEA
      ribonucleoprotein complex annotation.
    supported_by:
    - reference_id: PMID:17289661
      supporting_text: >-
        Molecular composition of IMP1 ribonucleoprotein granules.
- term:
    id: GO:0022627
    label: cytosolic small ribosomal subunit
  evidence_type: IDA
  original_reference_id: PMID:8706699
  review:
    summary: >-
      RPS3 was identified by protein sequencing and mass spectrometry as one of
      the proteins of the human 40S (small) ribosomal subunit.
    action: ACCEPT
    reason: >-
      This is the core cellular component for RPS3, directly evidenced by
      characterization of the human 40S ribosomal subunit proteins.
    supported_by:
    - reference_id: PMID:8706699
      supporting_text: >-
        This allowed us to identify all proteins from the 40S human ribosomal
        subunit in the HPLC elution profile.
- term:
    id: GO:0003729
    label: mRNA binding
  evidence_type: IDA
  original_reference_id: PMID:18464793
  review:
    summary: >-
      In eukaryotic initiation complexes, mRNA crosslinks to RPS3 (rpS3/S3p) at
      the mRNA entry channel of the 40S subunit, indicating direct mRNA contact.
    action: ACCEPT
    reason: >-
      RPS3 sits at the mRNA entry channel and directly contacts mRNA in the 40S
      subunit during initiation; mRNA binding is thus part of its core ribosomal
      structural/functional role at the decoding/entry site.
    supported_by:
    - reference_id: PMID:18464793
      supporting_text: >-
        Crosslinking of mRNA positions (+)11 to ribosomal protein (rp) rpS2(S5p)
        and rpS3(S3p)
- term:
    id: GO:0003735
    label: structural constituent of ribosome
  evidence_type: NAS
  original_reference_id: PMID:1712897
  review:
    summary: >-
      RPS3 was cloned and identified as the human S3 ribosomal protein, a
      structural component of the ribosome.
    action: ACCEPT
    reason: >-
      Structural constituent of ribosome is the core molecular function of RPS3,
      supported here by its identification as the human S3 ribosomal protein.
    supported_by:
    - reference_id: PMID:1712897
      supporting_text: >-
        isolation of a cDNA clone encoding the human S3 ribosomal protein
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:14988002
  review:
    summary: >-
      Endogenous RPS3 translocated into nuclei in cytokine-treated cells
      undergoing apoptosis.
    action: KEEP_AS_NON_CORE
    reason: >-
      Stimulus-dependent nuclear translocation in an apoptosis context is a
      regulated extra-ribosomal pool, non-core relative to the cytosolic ribosomal
      location. Retained as non-core.
    supported_by:
    - reference_id: PMID:14988002
      supporting_text: >-
        RpS3, a DNA repair endonuclease and ribosomal protein, is involved in
        apoptosis.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:14988002
  review:
    summary: >-
      RPS3 is present in the cytoplasm under basal conditions, with translocation
      to the nucleus during cytokine-induced apoptosis.
    action: ACCEPT
    reason: >-
      Cytoplasm is the expected, core cellular location for RPS3's cytosolic
      ribosomal function.
    supported_by:
    - reference_id: PMID:14988002
      supporting_text: >-
        RpS3, a DNA repair endonuclease and ribosomal protein, is involved in
        apoptosis.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IDA
  original_reference_id: PMID:16814409
  review:
    summary: >-
      RPS3 localizes to the cytoplasm/cytosol and cell periphery, where it
      colocalizes with Nm23-H1.
    action: ACCEPT
    reason: >-
      Cytosol is the expected, core cellular location for RPS3's cytosolic
      ribosomal function.
    supported_by:
    - reference_id: PMID:16814409
      supporting_text: >-
        the two proteins were colocalized in the cell periphery and cytoplasm.
- term:
    id: GO:0019901
    label: protein kinase binding
  evidence_type: IPI
  original_reference_id: PMID:15950189
  review:
    summary: >-
      RPS3 has an FXFP motif that serves as an ERK (MAP kinase) binding site, and
      ERK phosphorylates RPS3 at Thr42, as confirmed by co-immunoprecipitation.
    action: KEEP_AS_NON_CORE
    reason: >-
      Protein kinase binding captures the directly-evidenced ERK interaction that
      regulates RPS3 phosphorylation and its stress-induced nuclear translocation,
      an extra-ribosomal regulatory context. More informative than generic protein
      binding but non-core.
    supported_by:
    - reference_id: PMID:15950189
      supporting_text: >-
        the motif was demonstrated as an Erk binding site by
        co-immunoprecipitation. In addition to this, it was revealed that Erk
        specifically phosphorylated Thr 42 residue of rpS3
- term:
    id: GO:0032587
    label: ruffle membrane
  evidence_type: IDA
  original_reference_id: PMID:16814409
  review:
    summary: >-
      RPS3 was observed at the cell periphery in the context of its Nm23-H1
      interaction and inhibition of invasion.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Ruffle membrane localization is a very specific term inferred from
      cell-periphery colocalization in an invasion assay; the evidence does not
      robustly establish stable ruffle-membrane residency of RPS3. Treated as an
      over-annotation.
    supported_by:
    - reference_id: PMID:16814409
      supporting_text: >-
        the two proteins were colocalized in the cell periphery and cytoplasm.
- term:
    id: GO:0051536
    label: iron-sulfur cluster binding
  evidence_type: NAS
  original_reference_id: PMID:11911468
  review:
    summary: >-
      An EPR study reported an apparent iron-sulfur-cluster signal in human RPS3,
      proposed in analogy to E. coli endonuclease III.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      The iron-sulfur cluster claim is weakly supported and was not reproduced:
      refolding RPS3 with Fe2+/S2- did not increase activity and the protein's
      AP-lyase mechanism does not require a cluster (PMID:18610840). This is best
      treated as an over-annotation of a putative cofactor.
    supported_by:
    - reference_id: PMID:18610840
      supporting_text: >-
        Refolding of hS3 in the presence of Fe2+ and S2- ions did not increase
        its activity, despite the earlier suggestions that this protein could
        contain an iron-sulfur cluster.
- term:
    id: GO:0003684
    label: damaged DNA binding
  evidence_type: IDA
  original_reference_id: PMID:16737853
  review:
    summary: >-
      Human RPS3 binds 8-oxoG with high affinity; a single K132A change in its
      helix-hairpin-helix motif abolishes 8-oxoG binding while retaining
      AP-DNA-cleavage activity.
    action: KEEP_AS_NON_CORE
    reason: >-
      Damaged DNA binding is well-supported and mapped to a specific HhH DNA
      binding residue (K132). It is an extra-ribosomal moonlighting activity,
      secondary to the core ribosomal function. Retained as non-core.
    supported_by:
    - reference_id: PMID:16737853
      supporting_text: >-
        One putative site, lysine 132 (K132), located in a helix-hairpin-helix
        DNA binding motif, was mutated to alanine (K132A). The hS3-K132A mutant
        retained the ability to cleave abasic DNA, but its capacity to bind
        8-oxoG was abrogated completely.
- term:
    id: GO:0003906
    label: DNA-(apurinic or apyrimidinic site) endonuclease activity
  evidence_type: IDA
  original_reference_id: PMID:16737853
  review:
    summary: >-
      Human RPS3 (and its K132A mutant) cleaves abasic DNA, an AP-lyase/AP-
      endonuclease-type activity; importantly, RPS3 binding to 8-oxoG can inhibit
      OGG1-mediated repair.
    action: KEEP_AS_NON_CORE
    reason: >-
      AP-site cleavage is supported, but the broader physiological significance of
      this activity is debated and context-dependent (RPS3 can inhibit rather than
      promote OGG1 repair). Retained as a non-core, context-dependent activity.
    supported_by:
    - reference_id: PMID:16737853
      supporting_text: >-
        The hS3-K132A mutant retained the ability to cleave abasic DNA
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:18045535
  review:
    summary: >-
      Lymphocyte-activating stimuli cause nuclear translocation of RPS3 (parallel
      to p65), where it forms part of NF-kB bound to specific chromatin regulatory
      sites.
    action: KEEP_AS_NON_CORE
    reason: >-
      Stimulus-dependent nuclear localization in the NF-kB context is a regulated
      extra-ribosomal pool, non-core relative to the cytosolic ribosomal location.
      Retained as non-core.
    supported_by:
    - reference_id: PMID:18045535
      supporting_text: >-
        lymphocyte-activating stimuli caused nuclear translocation of RPS3,
        parallel to p65, to form part of NF-kappaB bound to specific regulatory
        sites in chromatin.
- term:
    id: GO:0006974
    label: DNA damage response
  evidence_type: IEP
  original_reference_id: PMID:17560175
  review:
    summary: >-
      Genotoxic stress triggers ERK-dependent phosphorylation and nuclear
      translocation of RPS3 and its co-localization with 8-oxoG damage foci,
      placing it in a cellular DNA damage response pathway.
    action: KEEP_AS_NON_CORE
    reason: >-
      Participation in the DNA damage response is a regulated extra-ribosomal
      moonlighting role (damaged-DNA binding/relocalization), secondary to the core
      ribosomal function. Retained as non-core.
    supported_by:
    - reference_id: PMID:17560175
      supporting_text: >-
        hS3 is a member of a cellular DNA damage response pathway that results in
        its interaction with sites of DNA damage.
- term:
    id: GO:0045738
    label: negative regulation of DNA repair
  evidence_type: IMP
  original_reference_id: PMID:17049931
  review:
    summary: >-
      RPS3 knockdown increased survival of cells exposed to oxidative/alkylating
      genotoxic agents, and RPS3 inhibits OGG1 from liberating 8-oxoG, indicating
      RPS3 can negatively affect base-excision repair.
    action: KEEP_AS_NON_CORE
    reason: >-
      RPS3 can negatively regulate repair (by sequestering 8-oxoG lesions from
      OGG1), a context-dependent extra-ribosomal activity. Note this is opposite in
      sign to other reports where RPS3 stimulates repair (PMID:18973764), so the
      net effect is context-dependent. Retained as non-core.
    supported_by:
    - reference_id: PMID:17049931
      supporting_text: >-
        a 40% knockdown of hS3 resulted in as much as a seven-fold increase in
        the 24h survival-rate of HEK293 cells exposed to hydrogen peroxide.
- term:
    id: GO:0003735
    label: structural constituent of ribosome
  evidence_type: HDA
  original_reference_id: PMID:15883184
  review:
    summary: >-
      RPS3 was identified by mass spectrometry as a protein of the human 40S
      ribosomal subunit in native and HCV IRES-bound complexes.
    action: ACCEPT
    reason: >-
      Structural constituent of ribosome is the core molecular function of RPS3,
      supported here by direct identification within the human 40S subunit.
    supported_by:
    - reference_id: PMID:15883184
      supporting_text: >-
        Thirty-one out of a possible 32 ribosomal proteins were identified by
        combining top-down and bottom-up mass spectrometry techniques.
- term:
    id: GO:0022627
    label: cytosolic small ribosomal subunit
  evidence_type: HDA
  original_reference_id: PMID:15883184
  review:
    summary: >-
      RPS3 is a component of the human 40S (cytosolic small) ribosomal subunit, as
      identified by mass spectrometry of native and IRES-bound 40S complexes.
    action: ACCEPT
    reason: >-
      This is the core cellular component for RPS3, directly supported by
      compositional analysis of the human 40S subunit.
    supported_by:
    - reference_id: PMID:15883184
      supporting_text: >-
        a global protein composition analysis of native and IRES-bound 40S
        ribosomal complexes has been conducted
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO
    terms
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000043
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping
  findings: []
- id: GO_REF:0000044
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location
    vocabulary mapping, accompanied by conservative changes to GO terms applied by
    UniProt
  findings: []
- id: GO_REF:0000052
  title: Gene Ontology annotation based on curation of immunofluorescence data
  findings: []
- id: GO_REF:0000107
  title: Automatic transfer of experimentally verified manual GO annotation data to
    orthologs using Ensembl Compara
  findings: []
- id: GO_REF:0000108
  title: Automatic assignment of GO terms using logical inference, based on on inter-ontology
    links
  findings: []
- id: GO_REF:0000117
  title: Electronic Gene Ontology annotations created by ARBA machine learning models
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: PMID:11911468
  title: Electron paramagnetic resonance study reveals a putative iron-sulfur cluster
    in human rpS3 protein.
  findings: []
- id: PMID:14706345
  title: Characterization of human ribosomal protein S3 binding to 7,8-dihydro-8-oxoguanine
    and abasic sites by surface plasmon resonance.
  findings:
  - statement: >-
      RPS3/hS3 binds damaged DNA lesions, including 8-oxoG and AP DNA, with high
      affinity.
    supporting_text: >-
      An even more dramatic five orders of magnitude higher binding affinity
      for AP DNA was found for hS3 as opposed to hOGG1.
- id: PMID:14988002
  title: RpS3, a DNA repair endonuclease and ribosomal protein, is involved in apoptosis.
  findings:
  - statement: >-
      RPS3 overexpression can activate caspase-dependent apoptosis in a
      cytokine-treatment context.
    supporting_text: >-
      Transient expression of GFP-rpS3 activates caspase-8/caspase-3 and
      sensitizes cytokine-induced apoptosis.
- id: PMID:15161933
  title: Comprehensive proteomic analysis of interphase and mitotic 14-3-3-binding
    proteins.
  findings: []
- id: PMID:15518571
  title: Human ribosomal protein S3 interacts with DNA base excision repair proteins
    hAPE/Ref-1 and hOGG1.
  findings:
  - statement: >-
      Human RPS3/hS3 interacts with OGG1 and APE/Ref-1 and may influence DNA
      repair activities at damage sites.
    supporting_text: >-
      These results raise the possibility that hS3 not only functions as a
      ribosomal protein but, in addition, may influence repair activities at
      sites of DNA damage.
- id: PMID:15707971
  title: Characterization of a wide range base-damage-endonuclease activity of mammalian
    rpS3.
  findings: []
- id: PMID:15883184
  title: 'Mass spectrometric analysis of the human 40S ribosomal subunit: native and
    HCV IRES-bound complexes.'
  findings: []
- id: PMID:15950189
  title: Erk phosphorylates threonine 42 residue of ribosomal protein S3.
  findings: []
- id: PMID:16737853
  title: The high binding affinity of human ribosomal protein S3 to 7,8-dihydro-8-oxoguanine
    is abrogated by a single amino acid change.
  findings: []
- id: PMID:16814409
  title: Reduction of invasion in human fibrosarcoma cells by ribosomal protein S3
    in conjunction with Nm23-H1 and ERK.
  findings: []
- id: PMID:17049931
  title: Knockdown of ribosomal protein S3 protects human cells from genotoxic stress.
  findings: []
- id: PMID:1712897
  title: 'Ribosomal protein genes are overexpressed in colorectal cancer: isolation
    of a cDNA clone encoding the human S3 ribosomal protein.'
  findings: []
- id: PMID:17289661
  title: Molecular composition of IMP1 ribonucleoprotein granules.
  findings: []
- id: PMID:17560175
  title: Translocation of human ribosomal protein S3 to sites of DNA damage is dependant
    on ERK-mediated phosphorylation following genotoxic stress.
  findings: []
- id: PMID:18045535
  title: 'Ribosomal protein S3: a KH domain subunit in NF-kappaB complexes that mediates
    selective gene regulation.'
  findings: []
- id: PMID:18274552
  title: Ribosomal proteins are targets for the NEDD8 pathway.
  findings: []
- id: PMID:18464793
  title: Ribosomal position and contacts of mRNA in eukaryotic translation initiation
    complexes.
  findings: []
- id: PMID:18610840
  title: '[Interactions of human ribosomal protein S3 with undamaged and damaged DNA].'
  findings: []
- id: PMID:18973764
  title: Human ribosomal protein S3 (hRpS3) interacts with uracil-DNA glycosylase
    (hUNG) and stimulates its glycosylase activity.
  findings: []
- id: PMID:19059439
  title: PKCdelta-dependent functional switch of rpS3 between translation and DNA
    repair.
  findings: []
- id: PMID:19460357
  title: Arginine methylation of ribosomal protein S3 affects ribosome assembly.
  findings: []
- id: PMID:19656744
  title: 'Ribosomal protein S3: A multi-functional protein that interacts with both
    p53 and MDM2 through its KH domain.'
  findings: []
- id: PMID:19946888
  title: Defining the membrane proteome of NK cells.
  findings: []
- id: PMID:20041225
  title: Bacterial effector binding to ribosomal protein s3 subverts NF-kappaB function.
  findings: []
- id: PMID:20217897
  title: RpS3 translation is repressed by interaction with its own mRNA.
  findings: []
- id: PMID:20458337
  title: MHC class II-associated proteins in B-cell exosomes and potential functional
    implications for exosome biogenesis.
  findings: []
- id: PMID:20605787
  title: Ribosomal protein S3, a new substrate of Akt, serves as a signal mediator
    between neuronal apoptosis and DNA repair.
  findings: []
- id: PMID:20618440
  title: Proteomic and biochemical analysis of 14-3-3-binding proteins during C2-ceramide-induced
    apoptosis.
  findings: []
- id: PMID:21145461
  title: Dynamics of cullin-RING ubiquitin ligase network revealed by systematic quantitative
    proteomics.
  findings: []
- id: PMID:21146485
  title: Identification of cyclophilin-40-interacting proteins reveals potential cellular
    function of cyclophilin-40.
  findings: []
- id: PMID:21170055
  title: Characterization of the proteome, diseases and evolution of the human postsynaptic
    density.
  findings: []
- id: PMID:21399639
  title: IKKβ phosphorylation regulates RPS3 nuclear translocation and NF-κB function
    during infection with Escherichia coli strain O157:H7.
  findings: []
- id: PMID:21423176
  title: Analysis of the myosin-II-responsive focal adhesion proteome reveals a role
    for β-Pix in negative regulation of focal adhesion maturation.
  findings: []
- id: PMID:21871177
  title: Ribosomal protein S3 is phosphorylated by Cdk1/cdc2 during G2/M phase.
  findings: []
- id: PMID:21968017
  title: Ribosomal protein S3 is stabilized by sumoylation.
  findings: []
- id: PMID:22113938
  title: A bead-based approach for large-scale identification of in vitro kinase substrates.
  findings: []
- id: PMID:22244329
  title: Hydrogen sulfide-linked sulfhydration of NF-κB mediates its antiapoptotic
    actions.
  findings: []
- id: PMID:22510408
  title: Ribosomal protein S3 interacts with TRADD to induce apoptosis through caspase
    dependent JNK activation.
  findings: []
- id: PMID:22658674
  title: Insights into RNA biology from an atlas of mammalian mRNA-binding proteins.
  findings: []
- id: PMID:22681889
  title: The mRNA-bound proteome and its global occupancy profile on protein-coding
    transcripts.
  findings: []
- id: PMID:23131551
  title: Ribosomal protein S3 localizes on the mitotic spindle and functions as a
    microtubule associated protein in mitosis.
  findings: []
- id: PMID:23636399
  title: Structures of the human and Drosophila 80S ribosome.
  findings:
  - statement: >-
      Human 80S ribosome structures support RPS3's core role as a structural
      constituent of the cytosolic ribosome/small ribosomal subunit.
    supporting_text: >-
      Here we present structures of Drosophila melanogaster and Homo sapiens
      80S ribosomes in complex with the translation factor eEF2, E-site
      transfer RNA and Stm1-like proteins, based on high-resolution
      cryo-electron-microscopy density maps.
- id: PMID:23911537
  title: Cytoplasmic ribosomal protein S3 (rpS3) plays a pivotal role in mitochondrial
    DNA damage surveillance.
  findings: []
- id: PMID:24423872
  title: AUF1 contributes to Cryptochrome1 mRNA degradation and rhythmic translation.
  findings: []
- id: PMID:24457201
  title: Ribosomal protein S3 interacts with the NF-κB inhibitor IκBα.
  findings: []
- id: PMID:24725412
  title: Ribosomal protein s15 phosphorylation mediates LRRK2 neurodegeneration in
    Parkinson's disease.
  findings: []
- id: PMID:24965446
  title: Host factors that interact with the pestivirus N-terminal protease, Npro,
    are components of the ribonucleoprotein complex.
  findings: []
- id: PMID:25609649
  title: Proteomic analyses reveal distinct chromatin-associated and soluble transcription
    factor complexes.
  findings: []
- id: PMID:25901680
  title: Structure of the human 80S ribosome.
  findings: []
- id: PMID:26526615
  title: Caspase-3 cleaved p65 fragment dampens NF-κB-mediated anti-apoptotic transcription
    by interfering with the p65/RPS3 interaction.
  findings: []
- id: PMID:28065601
  title: Initiation of Quality Control during Poly(A) Translation Requires Site-Specific
    Ribosome Ubiquitination.
  findings: []
- id: PMID:28132843
  title: ZNF598 and RACK1 Regulate Mammalian Ribosome-Associated Quality Control Function
    by Mediating Regulatory 40S Ribosomal Ubiquitylation.
  findings: []
- id: PMID:30021884
  title: Histone Interaction Landscapes Visualized by Crosslinking Mass Spectrometry
    in Intact Cell Nuclei.
  findings: []
- id: PMID:31046837
  title: Parkinson's disease-associated LRRK2-G2019S mutant acts through regulation
    of SERCA activity to control ER stress in astrocytes.
  findings: []
- id: PMID:32296183
  title: A reference map of the human binary protein interactome.
  findings: []
- id: PMID:32814053
  title: Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins
    and Uncovers Widespread Protein Aggregation in Affected Brains.
  findings: []
- id: PMID:33961781
  title: Dual proteome-scale networks reveal cell-specific remodeling of the human
    interactome.
  findings: []
- id: PMID:35271311
  title: 'OpenCell: Endogenous tagging for the cartography of human cellular organization.'
  findings: []
- id: PMID:39251607
  title: Systematic identification of post-transcriptional regulatory modules.
  findings: []
- id: PMID:40205054
  title: Multimodal cell maps as a foundation for structural and functional genomics.
  findings: []
- id: PMID:7775413
  title: Implication of mammalian ribosomal protein S3 in the processing of DNA damage.
  findings:
  - statement: >-
      Historical biochemical evidence connects mammalian ribosomal protein S3
      with AP/UV endonuclease activities, but this is secondary to the core
      ribosomal role.
    supporting_text: >-
      The unexpected role of a ribosomal protein in DNA damage processing and
      the unexplained inability to detect the nuclease activities in
      complementation group-D xeroderma pigmentosum cells suggest that these
      activities may be important to cellular DNA repair.
- id: PMID:8706699
  title: Characterization of the human small-ribosomal-subunit proteins by N-terminal
    and internal sequencing, and mass spectrometry.
  findings: []
- id: file:human/RPS3/RPS3-deep-research-falcon.md
  title: Falcon deep research on RPS3 GO-relevant functions
  findings:
  - statement: >-
      RPS3's core GO annotations should prioritize ribosome structure,
      cytosolic small ribosomal subunit localization, and translation.
    supporting_text: >-
      RPS3 is a core protein of the **cytosolic small ribosomal subunit
      (40S)** and therefore supports GO annotations centered on (i)
      **structural constituent of ribosome**, (ii) **cytoplasmic
      translation**, and (iii) localization to **cytosolic ribosome / small
      ribosomal subunit / cytosol (cytoplasm)**.
  - statement: >-
      DNA repair and NF-kB/apoptosis annotations are secondary moonlighting
      contexts that require cautious evidence handling.
    supporting_text: >-
      A second tier of GO-relevant “extra-ribosomal” evidence (DNA lesion
      binding/BER cofactor activity, NF-κB transcriptional specificity,
      apoptosis) exists, but requires careful caveats about direct catalytic
      activity vs **cofactor/interaction** roles, species extrapolations, and
      the frequent reliance on **review synthesis** rather than modern
      physiological genetics.
  - statement: >-
      Mitochondrial inner membrane and ER localization should not be retained
      without direct RPS3-specific localization evidence.
    supporting_text: >-
      **Mitochondrial inner membrane / ER:** no direct, RPS3-specific evidence
      in the retrieved corpus supports stable mitochondrial inner membrane or
      ER localization; avoid those CC annotations without targeted localization
      data.
- id: Reactome:R-HSA-156808
  title: Formation of translation initiation complexes yielding circularized Ceruloplasmin
    mRNA in a  'closed-loop' conformation
  findings: []
- id: Reactome:R-HSA-156823
  title: Association of phospho-L13a with GAIT element of Ceruloplasmin mRNA
  findings: []
- id: Reactome:R-HSA-157849
  title: Formation of translation initiation complexes containing mRNA that does not
    circularize
  findings: []
- id: Reactome:R-HSA-1799332
  title: Nascent polypeptide:mRNA:ribosome complex binds signal recognition particle
    (SRP)
  findings: []
- id: Reactome:R-HSA-1799335
  title: Synthesis of nascent polypeptide containing signal sequence
  findings: []
- id: Reactome:R-HSA-192704
  title: Synthesis of PB1-F2
  findings: []
- id: Reactome:R-HSA-192841
  title: Viral Protein Synthesis
  findings: []
- id: Reactome:R-HSA-6791223
  title: 18SE pre-rRNA in pre-40S particles is nucleolytically processed during translocation
    from the nucleus to the cytosol
  findings: []
- id: Reactome:R-HSA-72619
  title: eIF2:GTP is hydrolyzed, eIFs are released
  findings: []
- id: Reactome:R-HSA-72621
  title: Ribosomal scanning
  findings: []
- id: Reactome:R-HSA-72671
  title: eIF5B:GTP is hydrolyzed and released
  findings: []
- id: Reactome:R-HSA-72672
  title: The 60S subunit joins the translation initiation complex
  findings: []
- id: Reactome:R-HSA-72673
  title: Release of 40S and 60S subunits from the 80S ribosome
  findings: []
- id: Reactome:R-HSA-72676
  title: eIF3 and eIF1A bind to the 40S subunit
  findings: []
- id: Reactome:R-HSA-72691
  title: Formation of the 43S pre-initiation complex
  findings: []
- id: Reactome:R-HSA-72697
  title: Start codon recognition
  findings: []
- id: Reactome:R-HSA-927789
  title: Formation of UPF1:eRF3 complex on mRNA with a premature termination codon
    and no Exon Junction Complex
  findings: []
- id: Reactome:R-HSA-927813
  title: p-4S-UPF1 recruits SMG5, SMG7, SMG6, PNRC2, DCP1A, and PP2A
  findings: []
- id: Reactome:R-HSA-927832
  title: UPF1 binds an mRNP with a termination codon preceding an Exon Junction Complex
  findings: []
- id: Reactome:R-HSA-927836
  title: SMG6 hydrolyzes mRNA with premature termination codon
  findings: []
- id: Reactome:R-HSA-927889
  title: SMG1 phosphorylates UPF1 (enhanced by Exon Junction Complex)
  findings: []
- id: Reactome:R-HSA-9729232
  title: SARS-CoV-1 nsp1 binds to 40S ribosomal subunit
  findings: []
- id: Reactome:R-HSA-9729849
  title: SARS-CoV-2 nsp1 binds to 40S ribosomal complex
  findings: []
- id: Reactome:R-HSA-9948291
  title: RQT complex binds K63polyUb-80S ribosome:no-go mRNA:peptidyl-tRNA with nascent
    peptide
  findings: []
- id: Reactome:R-HSA-9948300
  title: RQT complex:K63polyUb-80S ribosome dissociates yielding K63polyUb-40S subunit
    and 60S subunit:peptidyl-tRNA with nascent peptide
  findings: []
- id: Reactome:R-HSA-9948301
  title: ZNF598 K63 polyubiquitinates RPS10 (eS10) and RPS20 (uS10) of the 40S ribosomal
    subunit
  findings: []
- id: Reactome:R-HSA-9948317
  title: ZNF598 and Ub:UBE2D1,2,3 bind stalled 80S ribosome
  findings: []
- id: Reactome:R-HSA-9954730
  title: PELO:HBS1L-1:GTP binds 80S ribosome:non-stop mRNA:peptidyl-tRNA with nascent
    peptide
  findings: []
- id: Reactome:R-HSA-9954919
  title: ABCE1:ATP binds PELO:HBS1L-1:GTP:80S ribosome:non-stop mRNA:peptidyl-tRNA
    with nascent peptide and HBS1L-1:GDP is released
  findings: []
- id: Reactome:R-HSA-9955731
  title: ABCE1:PELO:80S Ribosome:non-stop mRNA:peptidyl-tRNA with elongating peptide
    dissociates yielding ABCE1:40S ribosomal subunit, PELO, and 60S ribosomal subunit:peptidyl-tRNA
    with nascent peptide
  findings: []
core_functions:
- molecular_function:
    id: GO:0003735
    label: structural constituent of ribosome
  description: >-
    RPS3/uS3 is a structural component of the human cytosolic small ribosomal
    subunit and supports cytoplasmic translation. This ribosomal role is the
    physiological primary function; DNA repair, NF-kB/transcription, and
    apoptosis annotations should be treated as context-dependent extra-ribosomal
    functions.
  directly_involved_in:
  - id: GO:0006412
    label: translation
  locations:
  - id: GO:0022626
    label: cytosolic ribosome
  - id: GO:0005829
    label: cytosol
  supported_by:
  - reference_id: PMID:23636399
    supporting_text: >-
      Here we present structures of Drosophila melanogaster and Homo sapiens
      80S ribosomes in complex with the translation factor eEF2, E-site
      transfer RNA and Stm1-like proteins, based on high-resolution
      cryo-electron-microscopy density maps.
  - reference_id: file:human/RPS3/RPS3-deep-research-falcon.md
    supporting_text: >-
      RPS3 is a core protein of the **cytosolic small ribosomal subunit
      (40S)** and therefore supports GO annotations centered on (i)
      **structural constituent of ribosome**, (ii) **cytoplasmic
      translation**, and (iii) localization to **cytosolic ribosome / small
      ribosomal subunit / cytosol (cytoplasm)**.
proposed_new_terms: []
suggested_questions:
- question: >-
    Which RPS3 DNA repair annotations are supported by direct human enzymology
    rather than historical, orthologous, or review-summarized evidence?
- question: >-
    Are synapse/postsynaptic density annotations reporting stable RPS3 protein
    localization or only local ribosome/translation machinery near synapses?
suggested_experiments:
- description: >-
    Use endogenous-tagged RPS3 with ribosome and nuclear stress markers to
    quantify steady-state cytosolic ribosome localization versus inducible
    nuclear NF-kB/apoptosis-associated translocation.
- description: >-
    Reconstitute purified human RPS3 with defined AP and 8-oxoG substrates plus
    APE1/OGG1 to separate damaged-DNA binding, enzyme stimulation, and intrinsic
    AP lyase/endonuclease activity.

RPS3

Gene Description

Existing Annotations Review

Core Functions

References

Suggested Questions for Experts

Suggested Experiments

Deep Research

Falcon

Concise GO annotation research report: Human RPS3 (UniProt P23396, 40S ribosomal protein S3 / uS3)

Scope and key GO concepts

1) Core ribosomal function (highest-confidence GO)

2) Cellular component annotations: cytosol/cytosolic ribosome; nucleus/nucleolus; synapse/PSD

3) Non-ribosomal (moonlighting) functions relevant to GO: DNA damage/BER, NF-κB, apoptosis, RNA binding

3.2 NF-κB signaling and transcriptional specificity

3.3 Apoptosis regulation

3.4 RNA binding

4) Expert/authoritative interpretation and caveats for GO curation

5) Recent applications / real-world implementations (2023–2024)

References (URLs and dates available in evidence)

Citations

📚 Additional Documentation

Notes

RPS3 notes

Falcon integration, 2026-05-12

📄 View Raw YAML

RPS3

Gene Description

Existing Annotations Review

Core Functions

References

Suggested Questions for Experts

Suggested Experiments

Deep Research

Falcon

Concise GO annotation research report: Human RPS3 (UniProt P23396, 40S ribosomal protein S3 / uS3)

Scope and key GO concepts

1) Core ribosomal function (highest-confidence GO)

2) Cellular component annotations: cytosol/cytosolic ribosome; nucleus/nucleolus; synapse/PSD

3) Non-ribosomal (moonlighting) functions relevant to GO: DNA damage/BER, NF-κB, apoptosis, RNA binding

3.1 Damaged DNA binding and BER-related roles

3.2 NF-κB signaling and transcriptional specificity

3.3 Apoptosis regulation

3.4 RNA binding

4) Expert/authoritative interpretation and caveats for GO curation

5) Recent applications / real-world implementations (2023–2024)

References (URLs and dates available in evidence)

Citations

📚 Additional Documentation

Notes

RPS3 notes

Falcon integration, 2026-05-12

📄 View Raw YAML