CNOT3 is a noncatalytic subunit of the CCR4–NOT complex that connects translation to mRNA turnover. Its N-terminal region recognizes ribosomes with a vacant E-site and contacts the P-site tRNA, while its C-terminal region assembles with CNOT2 on the CNOT1 scaffold. Recognition of particular tRNA features helps recruit CCR4–NOT to slowly decoded transcripts and promotes their decay. The CNOT3-containing NOT module also supports efficient deadenylation by the complex’s catalytic subunits. CNOT3 acts in cytosolic RNA-regulatory assemblies, including context-dependent P-body pools, and has a nuclear pool associated with transcription regulation. Its RNA-regulatory functions support stem-cell maintenance and tissue-specific developmental and metabolic programs. Heterozygous pathogenic variants can cause a neurodevelopmental disorder with developmental delay, intellectual disability and hypotonia.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000289 nuclear-transcribed mRNA poly(A) tail shortening | IBA GO_REF:0000033 | ACCEPT | Summary: CNOT3 structurally participates in CCR4–NOT-mediated poly(A) shortening. Reason: The mapped fly, fungal and yeast donors include positive deadenylation experiments. Human recombinant-complex dissection independently shows that the noncatalytic NOT module containing CNOT3 stimulates the exonucleases together with other modules. This is structural participation in shortening, not an assertion that CNOT3 cleaves RNA. Current donor records corroborate the function without reconstructing the original PAINT ancestral placement. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000595684 UNRESOLVED Experimental donor shortening and independent human structural participation support the process; the historical IBD placement is not reconstructed. |
| GO:0000289 nuclear-transcribed mRNA poly(A) tail shortening | NAS PMID:31320642 Reconstitution of recombinant human CCR4-NOT reveals molecul... | ACCEPT | Summary: The human NOT module supports efficient deadenylation. Reason: The reconstituted human complex retains strong poly(A) shortening with the C-terminal CNOT3 structural core and CNOT2 on the CNOT1 scaffold. Removing nonenzymatic modules reduces activity. The original NAS assertion is retained: CNOT3 contributes structural work to the process while CNOT6/CNOT7 provide the catalytic activities. Supporting Evidence: PMID:31320642 non-enzymatic CAF40 and NOT modules are together necessary and sufficient to fully stimulate deadenylation in vitro |
| GO:0000932 P-body | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: P-body localization is supported in the mouse ortholog. Reason: The exact Q8K0V4 donor has an IDA localization premise from PMID:20133598. Original mouse gonad immunostaining shows CNOT3 colocalizing with NANOS2 and DCP1A, with recruitment altered after Nanos2 loss. Retain the human inference as a contextual compartment, without treating it as the exclusive location or a demonstrated endogenous human germ-cell experiment. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: PANTHER:PTN000595684 UNRESOLVED The mouse donor has an actual germ-cell P-body localization premise; ancestral placement is not reconstructed. |
| GO:0000932 P-body | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: P-body localization is supported in the mouse ortholog. Reason: The exact Q8K0V4 donor has an IDA localization premise from PMID:20133598. Original mouse gonad immunostaining shows CNOT3 colocalizing with NANOS2 and DCP1A, with recruitment altered after Nanos2 loss. Retain the human inference as a contextual compartment, without treating it as the exclusive location or a demonstrated endogenous human germ-cell experiment. |
| GO:0000932 P-body | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: P-body localization is supported in the mouse ortholog. Reason: The exact Q8K0V4 donor has an IDA localization premise from PMID:20133598. Original mouse gonad immunostaining shows CNOT3 colocalizing with NANOS2 and DCP1A, with recruitment altered after Nanos2 loss. Retain the human inference as a contextual compartment, without treating it as the exclusive location or a demonstrated endogenous human germ-cell experiment. |
| GO:0001829 trophectodermal cell differentiation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: CNOT3 regulates the trophectoderm differentiation context. Reason: Mouse ESC depletion and rescue experiments show that Cnot3 restrains extraembryonic differentiation; human H1/H9 depletion also induces extraembryonic markers. The donor assertion is retained as developmental regulation, with the direction made explicit. It does not imply that CNOT3 itself is a trophectoderm-specific differentiation factor or that all cellular effects are direct transcriptional effects. |
| GO:0005515 protein binding | IPI PMID:10637334 Isolation and characterization of human orthologs of yeast C... | MODIFY | Summary: CNOT3 associates with CNOT8. Reason: The original human CALIF/CNOT8 study contains a positive two-hybrid interaction and endogenous coimmunoprecipitation with NOT3. Its historical 609-residue cloned NOT3 is distinct from the current 753-residue sequence, whereas endogenous association supplies independent support. CNOT8 is a catalytic deadenylase, so enzyme binding is more informative than the broad parent. Proposed replacements: enzyme binding |
| GO:0005515 protein binding | IPI PMID:12207886 TBP-interacting protein 120B, which is induced in relation t... | KEEP AS NON CORE | Summary: CNOT3 associates with human CAND2. Reason: The authentic abstract reports GST pull-down and two-hybrid binding between TIP120B/CAND2 and the extended NOT3L form, mapping regions on both partners. Retain the positive association without assigning CNOT3 a CAND2-specific transcriptional or myogenic molecular activity; full construct details were not recovered. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:12207886 TBP-interacting protein 120B, which is induced in relation t... | KEEP AS NON CORE | Summary: CNOT3 associates with mouse Cand2. Reason: The source reports TIP120B binding to NOT3L and explicitly discusses mouse myogenic expression. Preserve the mouse Q6ZQ73 participant and the positive curated association; the abstract does not independently settle every construct-to-species assignment, and it is not evidence for a physiological human myogenesis function. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:16189514 Towards a proteome-scale map of the human protein-protein in... | MODIFY | Summary: CNOT3 associates with CNOT2. Reason: The positive two-hybrid-pooling record supports this pair. Independent human NOT-module structural work identifies the CNOT2–CNOT3 heterodimer and its assembly contacts, supporting a specific heterodimerization refinement without assigning the screen a native-cell structural measurement. Proposed replacements: protein heterodimerization activity Supporting Evidence: PMID:24121232 heterodimerize through their SH3-like NOT-box domains file:human/CNOT3/CNOT3-source-evidence.json |
| GO:0005515 protein binding | IPI PMID:16778766 Human Ccr4-Not complex is a ligand-dependent repressor of nu... | KEEP AS NON CORE | Summary: CNOT3 associates with CNOT1. Reason: The original human antibody coimmunoprecipitations recover CNOT3 with CNOT1, with control immunoprecipitations negative. This is complex association; CNOT1 is the principal CCR4–NOT scaffold, and this pair alone does not establish a separate adaptor activity of CNOT3. |
| GO:0005515 protein binding | IPI PMID:16778766 Human Ccr4-Not complex is a ligand-dependent repressor of nu... | MODIFY | Summary: CNOT3 associates with CNOT2. Reason: The original endogenous coimmunoprecipitation is positive and agrees with independent human NOT-module structures showing the CNOT2–CNOT3 heterodimer. The specific structural relationship is supported without claiming that coimmunoprecipitation alone proves a binary interface. Proposed replacements: protein heterodimerization activity |
| GO:0005515 protein binding | IPI PMID:16778766 Human Ccr4-Not complex is a ligand-dependent repressor of nu... | MODIFY | Summary: CNOT3 associates with CNOT8. Reason: The original endogenous human coimmunoprecipitation recovers CNOT3 with catalytic CNOT8. Enzyme binding captures the authenticated partner class; association in CCR4–NOT does not make CNOT3 an intrinsic nuclease. Proposed replacements: enzyme binding |
| GO:0005515 protein binding | IPI PMID:17452450 Depletion of mammalian CCR4b deadenylase triggers elevation ... | MODIFY | Summary: CNOT3 associates with CNOT6L. Reason: Human CCR4b/CNOT6L pull-downs and reciprocal tagged CNOT3 experiments support association. CNOT6L is the catalytic deadenylase partner, so enzyme binding is an appropriate class refinement; mouse endogenous corroboration is kept distinct from the human expression experiments. Proposed replacements: enzyme binding |
| GO:0005515 protein binding | IPI PMID:17452450 Depletion of mammalian CCR4b deadenylase triggers elevation ... | MODIFY | Summary: CNOT3 associates with CNOT6. Reason: Human CCR4a/CNOT6 pull-downs identify CNOT3 by mass spectrometry and immunoblotting relative to GFP controls. The catalytic partner class supports enzyme binding without inferring direct catalytic activity in CNOT3. Proposed replacements: enzyme binding |
| GO:0005515 protein binding | IPI PMID:18377426 Interaction of antiproliferative protein Tob with the CCR4-N... | KEEP AS NON CORE | Summary: CNOT3 associates with TOB1. Reason: The genuine full source reports tagged Tob and Cnot3 coimmunoprecipitation. Deadenylation of the immunoprecipitated assembly belongs to the associated complex and does not identify CNOT3 as the catalytic protein or the direct Tob-recognition site. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:20211142 An atlas of combinatorial transcriptional regulation in mous... | MODIFY | Summary: CNOT3 associates with CNOT2. Reason: The archived reciprocal pair records are positive. The original mammalian two-hybrid methodology includes self-activation exclusions and pairwise retesting; the curated assay labels are retained literally. Independent human NOT-module structures supply the specific heterodimer relationship. Proposed replacements: protein heterodimerization activity |
| GO:0005515 protein binding | IPI PMID:21981923 GW182 proteins directly recruit cytoplasmic deadenylase comp... | KEEP AS NON CORE | Summary: CNOT3 associates with TNRC6C. Reason: The source establishes GW182 recruitment of deadenylase complexes. Its inspected abstract identifies direct contacts with NOT1 and PAN3; it does not independently map a CNOT3–TNRC6C binary interface. Retain the curated complex-association observation without inferring that CNOT3 directly recruits GW182. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:21984185 miRNA-mediated deadenylation is orchestrated by GW182 throug... | KEEP AS NON CORE | Summary: CNOT3 associates with TNRC6C. Reason: The complete abstract supports hGW182-dependent CCR4–NOT recruitment through conserved motifs. The exact CNOT3 interface and full assay details remain uninspected, so the positive curated association is retained at complex scope rather than converted into a distinct adaptor activity. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:21984185 miRNA-mediated deadenylation is orchestrated by GW182 throug... | MODIFY | Summary: CNOT3 associates with CNOT2. Reason: The original curated association is consistent with the human NOT-module heterodimer established independently. The replacement is grounded in that direct structural evidence, while the protected original reference remains an abstract-only cache with its exact pair-specific assay unresolved. Proposed replacements: protein heterodimerization activity |
| GO:0005515 protein binding | IPI PMID:24736845 Structural basis for the Nanos-mediated recruitment of the C... | KEEP AS NON CORE | Summary: CNOT3 associates with NANOS2. Reason: Human NANOS2 pulls down endogenous CNOT3 within CCR4–NOT, but the purified CNOT2–CNOT3 module does not bind the NANOS interaction motif. The direct recognition site is on CNOT1. Retain the positive association without assigning CNOT3 the NANOS-recruitment interface. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:24736845 Structural basis for the Nanos-mediated recruitment of the C... | KEEP AS NON CORE | Summary: CNOT3 associates with NANOS1. Reason: Human NANOS1 pull-downs recover CNOT3 as part of CCR4–NOT. The original purified-module experiment places the NANOS motif-binding site on CNOT1, not isolated CNOT2–CNOT3; the association remains valid without a CNOT3-specific adaptor inference. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:24736845 Structural basis for the Nanos-mediated recruitment of the C... | KEEP AS NON CORE | Summary: CNOT3 associates with NANOS3. Reason: Human NANOS3 pull-downs recover endogenous CNOT3, with interaction-motif dependence. Purified subcomplex experiments assign motif recognition to CNOT1 rather than the CNOT2–CNOT3 module. Preserve the positive complex association and that molecular boundary. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:26496610 A human interactome in three quantitative dimensions organiz... | KEEP AS NON CORE | Summary: CNOT3 associates with CNOT1. Reason: The exact anti-tag coimmunoprecipitation record has CNOT1 as tagged bait and CNOT3 as prey. This supports complex association in the systematic human interaction study, without resolving a separate CNOT3-specific signaling or adaptor mechanism. |
| GO:0005515 protein binding | IPI PMID:26496610 A human interactome in three quantitative dimensions organiz... | MODIFY | Summary: CNOT3 associates with CNOT2. Reason: The exact anti-tag coimmunoprecipitation record supports the CNOT2–CNOT3 association. Independent human NOT-module structure identifies the heterodimer, providing a more specific relationship than the source parent term. Proposed replacements: protein heterodimerization activity |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | KEEP AS NON CORE | Summary: CNOT3 associates with TOB1. Reason: The exact BioPlex affinity-purification record identifies tagged TOB1 bait and CNOT3 prey. Retain the positive association as non-core; this screen does not assign a binary interface or establish a distinct TOB1-dependent activity of CNOT3. |
| GO:0005515 protein binding | IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari... | MODIFY | Summary: CNOT3 associates with CNOT2. Reason: The literal two-hybrid record preserves the tested CNOT3 position-491 variant and its no-effect annotation. This is a positive interaction, not loss of binding. Independent human NOT-module structural evidence supports the heterodimer refinement; the screen does not establish native complex dynamics. Proposed replacements: protein heterodimerization activity |
| GO:0005515 protein binding | IPI PMID:31570513 HELZ directly interacts with CCR4-NOT and causes decay of bo... | KEEP AS NON CORE | Summary: CNOT3 associates with HELZ. Reason: The original human pull-downs and purified proteins show HELZ C-terminal segments associating with the NOT1–NOT2–NOT3 module. These assays do not isolate CNOT3 as the sole interface. HELZ is a superfamily-1 helicase, so a DEAD/H-box-helicase-binding label would be inappropriate; retain the specific association without that misclassification. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | MODIFY | Summary: CNOT3 associates with CNOT2. Reason: Three positive HuRI records preserve array, prey-pooling and validated two-hybrid roles. They agree with the independent human CNOT2–CNOT3 structural heterodimer. General MAPPIT/GPCA validation rates are not assigned as pair-specific experiments. Proposed replacements: protein heterodimerization activity |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | MODIFY | Summary: CNOT3 binds the cell adhesion molecule PECAM1 in binary screening assays. Reason: Three positive yeast two-hybrid records identify CNOT3 and canonical human PECAM1 in array, pooling and validated-pair assays. The tested partner sequence matches the 738-residue P16284 record, whose curated function explicitly establishes the cell-adhesion-molecule class; GO:0050839 therefore gives the bound-partner specificity at this assay scope. The records have no mapped fragment boundary and do not resolve precursor processing, the contact interface, a native cellular encounter or an adhesion/signaling function of CNOT3. Proposed replacements: cell adhesion molecule binding |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | MODIFY | Summary: CNOT3 associates with calreticulin. Reason: Three positive yeast two-hybrid records identify CNOT3 and canonical CALR, whose official function is protein-folding chaperone. GO:0051087 describes binding to that partner class; it does not require CNOT3 to fold proteins or modulate chaperone activity. Retain this assay-scoped refinement without a native ER-complex claim. CALR is predominantly ER-luminal but its official record also includes cytosol; compartment labels alone do not contradict the positive binary assay. Precursor processing and the contact site were not resolved. Proposed replacements: protein-folding chaperone binding Supporting Evidence: PMID:32814053 systematic yeast two-hybrid interaction screening file:human/CNOT3/CNOT3-source-evidence.json |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | MODIFY | Summary: CNOT3 associates with DLST. Reason: Three positive yeast two-hybrid records identify CNOT3 and canonical DLST. The authenticated partner is the catalytic succinyltransferase component of 2-oxoglutarate dehydrogenase, supporting enzyme-binding specificity at assay scope. Neither mitochondrial localization of CNOT3 nor metabolic regulation by CNOT3 follows. The official DLST record describes a predominant mitochondrial pool and a nuclear fraction; these locations do not establish a native CNOT3 encounter, but are not evidence that the positive assay is false. The tested precursor processing state and interface remain unresolved. Proposed replacements: enzyme binding |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | MODIFY | Summary: CNOT3 associates with VCP. Reason: Three positive yeast two-hybrid records identify CNOT3 and canonical VCP, an experimentally characterized ATP-hydrolyzing enzyme in the official partner record. This supports ATPase binding at the recorded heterologous assay scope. GO:0051117 requires binding to an ATPase, not stimulation of that ATPase or ATP hydrolysis by CNOT3. No endogenous VCP mechanism, substrate relationship or pair-specific orthogonal validation is inferred. Proposed replacements: ATPase binding |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | MODIFY | Summary: CNOT3 associates with NEK7. Reason: Three positive yeast two-hybrid records identify CNOT3 and canonical NEK7, an experimentally characterized protein kinase in the official partner record. Retain protein kinase binding at assay scope. The term describes the bound partner class; it does not assert that CNOT3 is phosphorylated, changes NEK7 activity, or participates in a native NEK7 pathway. The screen does not resolve the contact domain or a physiological complex. Proposed replacements: protein kinase binding |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | KEEP AS NON CORE | Summary: CNOT3 associates with CNOT1. Reason: The two positive BioPlex records use CNOT3 as tagged bait and recover CNOT1. Retain the complex association without calling the AP-MS result a purified binary interface or equating CNOT3 with the main scaffold. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | KEEP AS NON CORE | Summary: CNOT3 associates with TOB1. Reason: The BioPlex records use tagged TOB1 bait and recover CNOT3. This corroborates association with the deadenylase complex, with no pair-specific catalytic or adaptor mechanism established by the screen. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MODIFY | Summary: CNOT3 associates with CNOT6L. Reason: The exact positive BioPlex records recover catalytic CNOT6L with tagged CNOT3. The enzyme class provides a specific refinement, while AP-MS remains evidence of association rather than CNOT3 catalysis. Proposed replacements: enzyme binding |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MODIFY | Summary: CNOT3 associates with CNOT2. Reason: The positive BioPlex pair agrees with the direct human NOT-module heterodimer. Refine the relationship using that independent structural evidence while preserving the AP-MS assay and source fields. Proposed replacements: protein heterodimerization activity |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MODIFY | Summary: CNOT3 associates with CNOT8. Reason: The positive BioPlex records recover catalytic CNOT8 with CNOT3. Enzyme binding is supported by the partner identity and association; no nuclease activity is assigned to CNOT3. Proposed replacements: enzyme binding |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MODIFY | Summary: CNOT3 associates with CNOT6. Reason: The positive BioPlex records recover catalytic CNOT6 with CNOT3. The specific enzyme-binding class is retained at the measured association scope and does not imply an isolated binary complex or CNOT3 catalysis. Proposed replacements: enzyme binding |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | KEEP AS NON CORE | Summary: CNOT3 associates with CNOT1. Reason: The original U2OS AP-MS network has the exact CNOT3–CNOT1 edge 556154. This independently supports the association, with imaging and affinity-purification results kept separate; it does not by itself establish a CNOT3-specific adaptor activity. |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | MODIFY | Summary: CNOT3 associates with CNOT2. Reason: The original U2OS AP-MS network has the exact CNOT3–CNOT2 edge 556242. Independent human structural work resolves their heterodimer, supporting the specific replacement without presenting the network itself as a structural assay. Proposed replacements: protein heterodimerization activity |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | MODIFY | Summary: CNOT3 associates with CNOT6. Reason: The selected CNOT3 U2OS subnetwork recovers CNOT6L but does not resolve the exact CNOT6 pair cited in this source row. That limited retrieval is not proof of miscitation. Independent original human CNOT6 pull-downs and exact BioPlex CNOT6 records support the enzyme-binding refinement; preserve the original assertion and its unresolved 2025 pair linkage. Proposed replacements: enzyme binding Supporting Evidence: file:human/CNOT3/CNOT3-source-evidence.json |
| GO:0005634 nucleus | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: A nuclear CNOT3 pool is supported. Reason: Human endogenous complex purification and nuclear-receptor transcription experiments support a nuclear pool in addition to the cytosolic RNA-turnover machinery. The source combines a NOT-family domain mapping with the UniProt location; neither implies exclusive nuclear localization or autonomous DNA binding. Supporting Evidence: GO_REF:0000120 file:human/CNOT3/CNOT3-source-evidence.json |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | MODIFY | Summary: Refine the broad cytoplasmic location to cytosol. Reason: Human cytosolic translation reactions, endogenous ribosome association and the specific Reactome target entities support a cytosolic pool. Cytosol is more informative than the broad cytoplasm parent, without excluding nuclear or P-body-associated pools. Proposed replacements: cytosol |
| GO:0005829 cytosol | IEA GO_REF:0000117 | ACCEPT | Summary: The ARBA cytosol mapping is experimentally corroborated. Reason: The target matches the actual ARBA00029243 FunFam route. Human CNOT3 associates with translating ribosomes in cytosolic lysates, providing independent biological support beyond the computational rule. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-429955 | ACCEPT | Summary: The curated reaction explicitly places CNOT3 in cytosol. Reason: The exact reaction-to-complex trace reaches physical entity R-HSA-429872, mapped to human O75175 residues 1–753 and the cytosol compartment. This is model provenance for location; the reaction title alone is not used as proof of an intrinsic CNOT3 enzyme or BTG2-binding activity. Supporting Evidence: Reactome:R-HSA-429955 file:human/CNOT3/CNOT3-source-evidence.json |
| GO:0005829 cytosol | TAS Reactome:R-HSA-6798044 | ACCEPT | Summary: The curated reaction explicitly places CNOT3 in cytosol. Reason: The exact reaction-to-complex trace reaches physical entity R-HSA-429872, mapped to human O75175 residues 1–753 and the cytosol compartment. This is model provenance for location; the reaction title alone is not used as proof of an intrinsic CNOT3 enzyme or BTG2-binding activity. Supporting Evidence: Reactome:R-HSA-6798044 file:human/CNOT3/CNOT3-source-evidence.json |
| GO:0006355 regulation of DNA-templated transcription | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: CNOT3 has a contextual transcription-regulatory role. Reason: The original human MCF7 depletion study changes estrogen-responsive transcript output, and CNOT3 is recovered in the CCR4–NOT complex. Retain the domain-derived broad regulatory process as non-core. These assays do not demonstrate CNOT3 binding DNA or identify it as the direct nuclear-receptor-binding subunit. |
| GO:0006402 mRNA catabolic process | IEA GO_REF:0000107 | ACCEPT | Summary: CNOT3 contributes to regulated mRNA decay. Reason: The exact mouse donor has positive Cnot3-dependent Dand5 mRNA decay in the embryonic node. Independent human codon-dependent recruitment and transcript half-life measurements establish a direct CNOT3 recognition role in mRNA turnover. Retain the broad process without assigning the nuclease chemistry to CNOT3. Supporting Evidence: GO_REF:0000107 file:human/CNOT3/CNOT3-source-evidence.json |
| GO:0006402 mRNA catabolic process | ISS GO_REF:0000024 | ACCEPT | Summary: CNOT3 contributes to regulated mRNA decay. Reason: The exact mouse donor has positive Cnot3-dependent Dand5 mRNA decay in the embryonic node. Independent human codon-dependent recruitment and transcript half-life measurements establish a direct CNOT3 recognition role in mRNA turnover. Retain the broad process without assigning the nuclease chemistry to CNOT3. Supporting Evidence: GO_REF:0000024 file:human/CNOT3/CNOT3-source-evidence.json |
| GO:0007368 determination of left/right symmetry | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: The mouse ortholog supports left–right patterning through RNA regulation. Reason: Node-restricted Cnot3 loss attenuates asymmetric Dand5 mRNA decay and perturbs laterality readouts. This is a supported developmental role of the RNA-regulatory machinery, retained at ortholog scope rather than an additional molecular activity or direct human embryonic experiment. |
| GO:0007368 determination of left/right symmetry | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: The mouse ortholog supports left–right patterning through RNA regulation. Reason: Node-restricted Cnot3 loss attenuates asymmetric Dand5 mRNA decay and perturbs laterality readouts. This is a supported developmental role of the RNA-regulatory machinery, retained at ortholog scope rather than an additional molecular activity or direct human embryonic experiment. |
| GO:0030014 CCR4-NOT complex | IDA PMID:19558367 Human Ccr4-Not complexes contain variable deadenylase subuni... | ACCEPT | Summary: CNOT3 is a constitutive member of the CCR4–NOT core. Reason: Retain the original IDA membership in the CCR4-NOT complex. The authentic original abstract reports proteomic purification from stable human cell lines and several complex variants containing stable core proteins plus alternative deadenylase subunits; the full original Methods remain uninspected. Independent human assembly and reconstitution corroborate CNOT3 membership. They do not require replacing this source assertion with the narrower core-complex term, which is already supported by separate annotations. Supporting Evidence: PMID:19558367 consisting of seven stable core proteins |
| GO:0030014 CCR4-NOT complex | NAS PMID:19558367 Human Ccr4-Not complexes contain variable deadenylase subuni... | ACCEPT | Summary: CNOT3 is a constitutive member of the CCR4–NOT core. Reason: Retain the original NAS membership in the CCR4-NOT complex at the source scope of the human composition study. Its authentic abstract describes heterogeneous complexes with stable core proteins and alternative deadenylases; no new full-text access is claimed. The independently characterized CNOT1–CNOT2–CNOT3 module explains CNOT3 assembly, while the separate core-complex annotations remain intact. No source-specific narrowing is necessary. |
| GO:0030015 CCR4-NOT core complex | IBA GO_REF:0000033 | ACCEPT | Summary: The conserved core-complex assignment is supported. Reason: The named fungal and yeast donors carry genuine experimental core-complex premises. Human structural and biochemical work independently establishes CNOT3 in the core NOT module. The historical PAINT node placement remains unreplicated; donor membership does not mean all paralogs have identical molecular interfaces. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000595684 UNRESOLVED Experimental fungal and yeast core-complex records and direct human assembly support the compartment; the ancestral placement is not reconstructed. Supporting Evidence: GO_REF:0000033 file:human/CNOT3/CNOT3-source-evidence.json |
| GO:0030015 CCR4-NOT core complex | IEA GO_REF:0000002 | ACCEPT | Summary: Official NOT-family features agree with core-complex membership. Reason: The exact target contains IPR012270 and IPR040168, and independent human structures and recombinant-complex assembly support core membership. The InterPro mapping is retained without transferring catalytic deadenylase activity to the noncatalytic subunit. Supporting Evidence: GO_REF:0000002 file:human/CNOT3/CNOT3-source-evidence.json |
| GO:0120162 positive regulation of cold-induced thermogenesis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Adipocyte Cnot3 supports cold-induced thermogenesis in mice. Reason: The original adipocyte-specific knockout has lower BAT Ucp1 RNA/protein and a greater fall in body temperature during a 4 °C challenge, with baseline-temperature controls. Retain this positive regulatory phenotype as a tissue-context role. The accompanying lipodystrophy and altered lipid handling do not establish a direct thermogenic catalytic step or a matched human adipocyte experiment. |
| GO:0120162 positive regulation of cold-induced thermogenesis | ISS PMID:28032897 Adipocyte-specific disruption of mouse Cnot3 causes lipodyst... | KEEP AS NON CORE | Summary: Adipocyte Cnot3 supports cold-induced thermogenesis in mice. Reason: The original adipocyte-specific knockout has lower BAT Ucp1 RNA/protein and a greater fall in body temperature during a 4 °C challenge, with baseline-temperature controls. Retain this positive regulatory phenotype as a tissue-context role. The accompanying lipodystrophy and altered lipid handling do not establish a direct thermogenic catalytic step or a matched human adipocyte experiment. |
| GO:2000036 regulation of stem cell population maintenance | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: CNOT3 supports embryonic stem-cell population maintenance. Reason: The original mouse knockdown/rescue experiments and human H1/H9 depletion show loss of self-renewal and extraembryonic marker induction when CNOT3 is reduced. Retain this supported cell-state regulation as non-core. Its PAINT target self-inclusion is legitimate experimental grounding, not circularity; the historical node placement remains separate from the direct target result. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: PANTHER:PTN000595760 UNRESOLVED Human and mouse ESC experiments support the cell-state role. Target self-inclusion is expected; historical IBD placement is not reconstructed. |
| GO:2000036 regulation of stem cell population maintenance | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: CNOT3 supports embryonic stem-cell population maintenance. Reason: The original mouse knockdown/rescue experiments and human H1/H9 depletion show loss of self-renewal and extraembryonic marker induction when CNOT3 is reduced. Retain this supported cell-state regulation as non-core. Its PAINT target self-inclusion is legitimate experimental grounding, not circularity; the historical node placement remains separate from the direct target result. |
| GO:2000036 regulation of stem cell population maintenance | IMP PMID:22367759 Cnot1, Cnot2, and Cnot3 maintain mouse and human ESC identit... | KEEP AS NON CORE | Summary: CNOT3 supports embryonic stem-cell population maintenance. Reason: The original mouse knockdown/rescue experiments and human H1/H9 depletion show loss of self-renewal and extraembryonic marker induction when CNOT3 is reduced. Retain this supported cell-state regulation as non-core. Its PAINT target self-inclusion is legitimate experimental grounding, not circularity; the historical node placement remains separate from the direct target result. Supporting Evidence: |
| GO:0180014 protein-tRNA adaptor activity | IDA PMID:39571015 Specific tRNAs promote mRNA decay by recruiting the CCR4-NOT... | NEW | Summary: CNOT3 couples P-site tRNA recognition to CCR4–NOT recruitment. Reason: Human HEK293T translation, cryo-EM and mutagenesis show that CNOT3 contacts the P-site tRNA through its N terminus and recruits the CCR4-NOT assembly in a tRNA-dependent manner. Its C terminus is independently resolved with CNOT1 and CNOT2. This fits the current protein-tRNA adaptor definition: protein and tRNA are brought into coordinated function; the definition is not restricted to presenting tRNA to a modifying enzyme. Direct tRNA contact is established in the ribosome-bound context, without a free-tRNA affinity claim. GO:0000049 is neither ancestor nor descendant of this term; not adding it separately is a conservative choice to describe this same recognition activity once, not a claim of typed ontology redundancy. Supporting Evidence: PMID:39571015 contacts the D-loop, D-stem, and anticodon stem of the P-site tRNA file:human/CNOT3/CNOT3-source-evidence.json |
| GO:0043022 ribosome binding | IDA PMID:39571015 Specific tRNAs promote mRNA decay by recruiting the CCR4-NOT... | NEW | Summary: CNOT3 directly recognizes translating ribosomes. Reason: The human HEK293T translation system and cryo-EM reconstruction resolve CNOT3 contacting both ribosomal subunits in the vacant E-site. An independent study combines recombinant human CCR4–NOT with rabbit ribosomes and resolves the same recognition region. These are direct binding observations with defined complexes, not a claim that isolated CNOT3 arrests every ribosome or that all tRNAs recruit it equally. Supporting Evidence: PMID:37653243 The N-terminal region (NTR) of CNOT3 (residues 1-236) binds the vacant E site of the 80S ribosome file:human/CNOT3/CNOT3-source-evidence.json |
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Download this section (compressed HTML)Q: How do the N-terminal ribosome/tRNA-recognition region and C-terminal NOT assembly module coordinate transcript selection in native human tissues?
Q: Which disease-associated variants primarily disrupt tRNA recognition, ribosome binding, complex assembly or the regulation of particular transcript classes?
Q: Which nuclear and P-body pools of CNOT3 have functions separable from its cytosolic cotranslational mRNA-decay role?
Experiment: Compare sequence-verified CNOT3 tRNA-contact and assembly mutants in human cells using selective ribosome profiling, transcript half-life measurements and matched complex-assembly controls.
Experiment: Use endogenous tagging and tissue-relevant cells to relate CNOT3 compartment-specific interactions to RNA targets, separating direct recruitment from secondary differentiation or metabolic effects.
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