CNOT1 is the large organizing subunit of the CCR4-NOT complex. Its repeated helical domains hold catalytic deadenylases and regulatory modules together and provide binding surfaces for RNA-associated recruitment factors, including tristetraprolin, GW182/TNRC6 and Nanos proteins. These assemblies coordinate poly(A)-tail shortening, mRNA decay and translational repression. CNOT1 acts in the cytoplasm and P-bodies and also participates in nuclear receptor-dependent transcriptional repression. It supplies scaffold and recruitment functions, while CNOT6/CNOT6L and CNOT7/CNOT8 provide the complexβs nuclease chemistry. Cellular effects on stem-cell identity and survival depend on this broader control of gene expression.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000122 negative regulation of transcription by RNA polymerase II | IDA PMID:16778766 Human Ccr4-Not complex is a ligand-dependent repressor of nu... | KEEP AS NON CORE | Summary: CNOT1 can repress RNA polymerase II transcription in a nuclear-receptor context. Reason: Human CNOT1 tethering and nuclear-receptor reporters show repression, and ligand-dependent promoter recruitment and target-gene changes in MCF7 cells corroborate a nuclear role. These experiments support a contextual transcriptional activity alongside the principal cytoplasmic scaffold function; they do not make every effect on mRNA abundance transcriptional. Supporting Evidence: |
| GO:0000288 nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay | IBA GO_REF:0000033 | ACCEPT | Summary: CNOT1 contributes to deadenylation-dependent mRNA decay. Reason: The exact fly, fungal and worm source identities resolve to Not1 orthologs. Current fly and budding-yeast records include experimental support, while the inspected pombe and worm same-term records remain propagated. Human recruitment, decay and complex-reconstitution experiments independently establish performed scaffold work in the pathway. The historical PAINT node and alignment were not reconstructed. Propagation Review Root cause: NO FAILURE CORE Sources checked: FB:FBgn0085436 SUPPORTS TRANSFER The exact identity and current same-term experimental records are verified. This supports the extant function without reconstructing historical node placement. PANTHER:PTN000322838 UNRESOLVED The historical ancestral node, family tree and alignment were not inspected; current experimental grounding is assessed separately. PomBase:SPAC20G8.06 UNRESOLVED The exact ortholog identity is resolved, but the inspected current same-term records are propagated; their historical experimental chain is not established here. Independent target experiments support the retained decision. SGD:S000000689 SUPPORTS TRANSFER The exact identity and current same-term experimental records are verified. This supports the extant function without reconstructing historical node placement. WB:WBGene00002845 UNRESOLVED The exact ortholog identity is resolved, but the inspected current same-term records are propagated; their historical experimental chain is not established here. Independent target experiments support the retained decision. |
| GO:0000289 nuclear-transcribed mRNA poly(A) tail shortening | NAS PMID:31320642 Reconstitution of recombinant human CCR4-NOT reveals molecul... | ACCEPT | Summary: CNOT1 helps the CCR4-NOT complex shorten mRNA poly(A) tails. Reason: Reconstitution of human CCR4-NOT from defined subcomplexes yields efficient poly(A)-tail removal. The CNOT1 scaffold organizes the catalytic and noncatalytic modules; the nuclease mutations locate hydrolysis in CCR4/CAF1 rather than CNOT1 itself. Supporting Evidence: |
| GO:0000932 P-body | IBA GO_REF:0000033 | ACCEPT | Summary: P-body activity has target and ortholog experimental grounding. Reason: The mouse donor maps to Cnot1 and has an experimental P-body record, and the human target has its own direct localization evidence. The targetβs appearance among PAINT sources is legitimate experimental grounding. Current records support the location without reconstructing the historical node. Propagation Review Root cause: NO FAILURE CORE Sources checked: MGI:MGI:2442402 SUPPORTS TRANSFER The exact identity and current same-term experimental records are verified. This supports the extant function without reconstructing historical node placement. PANTHER:PTN000322838 UNRESOLVED The historical ancestral node, family tree and alignment were not inspected; current experimental grounding is assessed separately. UniProtKB:A5YKK6 SUPPORTS TRANSFER The exact identity and current same-term experimental records are verified. This is direct target grounding, not circular evidence. This supports the extant function without reconstructing historical node placement. |
| GO:0000932 P-body | IDA PMID:21976065 The role of the CNOT1 subunit of the CCR4-NOT complex in mRN... | ACCEPT | Summary: CNOT1 localizes to cytoplasmic P-bodies. Reason: The original full paper shows FLAG-CNOT1 in the HeLa cytoplasm and P-body foci by immunofluorescence. This establishes the tested cellular location, not exclusive residence in P-bodies or equivalent localization of every alternative product. Supporting Evidence: |
| GO:0000932 P-body | IEA GO_REF:0000120 | ACCEPT | Summary: The combined electronic P-body assignment agrees with direct evidence. Reason: The actual mouse ortholog and Ensembl identifier resolve together, and the recorded ARBA and subcellular-location sources are preserved. Mouse Cnot1 localization and independent human FLAG-CNOT1 imaging corroborate the P-body call. |
| GO:0000932 P-body | ISS GO_REF:0000024 | ACCEPT | Summary: The mouse-to-human P-body transfer is supported. Reason: The named Q6ZQ08 donor is mouse Cnot1. Its gonadal localization evidence and the independent human HeLa experiment both support the term; the donorβs mouse tissue context is not relabeled as human germ-cell evidence. |
| GO:0001829 trophectodermal cell differentiation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: CNOT1 influences extraembryonic differentiation in stem-cell models. Reason: The Ensembl donor is mouse Cnot1, and the cited experiments show that depletion changes embryonic-stem-cell identity and trophectoderm-associated expression. Human H1 cells were also tested, with a milder CNOT1 phenotype than CNOT2/3. This is a context-dependent developmental consequence; the precise downstream molecular route remains unresolved. |
| GO:0003723 RNA binding | HDA PMID:22658674 Insights into RNA biology from an atlas of mammalian mRNA-bi... | MODIFY | Summary: The capture experiment supports mRNA binding. Reason: The original HeLa study combines covalent UV crosslinking with oligo(dT) capture and stringent LiCl/LiDS washes. Its Table S1 CNOT1 entry is enriched in crosslinked samples and absent from controls. The authors explain that this chemistry does not crosslink proteins to each other and discriminates against indirect mRNP subunits; they also recommend individual validation of high-probability screen hits. Retain mRNA binding at this high-throughput scope, without sequence specificity, an autonomous RNA-binding core, or proof for every product. Proposed replacements: mRNA binding Supporting Evidence: PMID:22658674 covalent UV crosslinking of RBPs to RNA |
| GO:0003723 RNA binding | HDA PMID:22681889 The mRNA-bound proteome and its global occupancy profile on ... | MODIFY | Summary: The independent HEK-cell capture supports mRNA binding. Reason: The original abstract describes photoreactive-nucleotide UV crosslinking and oligo(dT) purification. The first author's thesis reproduces the CNOT1 candidate-mRNA-binder row and specifies irradiated versus nonirradiated HEK293 controls with stringent detergent/salt purification in Methods section 3.5. The full journal Methods remain uninspected. Together with the independent HeLa capture, this supports mRNA contact at screening scope, without identifying a cognate sequence, a binding site or activity of every product. Proposed replacements: mRNA binding Supporting Evidence: PMID:22681889 photoreactive nucleotide-enhanced UV crosslinking and oligo(dT) purification |
| GO:0004535 poly(A)-specific ribonuclease activity | IDA PMID:21976065 The role of the CNOT1 subunit of the CCR4-NOT complex in mRN... | ACCEPT | Summary: CNOT1 contributes to the assembled complexβs poly(A)-specific RNase activity. Reason: The original contributes_to qualifier is essential. CNOT1 depletion reduces poly(A) degradation by EGFP-CNOT6L immunoprecipitates despite unchanged exogenous CNOT6L abundance. Human reconstitution independently supports the contribution of the scaffold-containing complex; no intrinsic CNOT1 hydrolysis is asserted. Supporting Evidence: PMID:21976065 specific activity of the CNOT6L immunoprecipitates-associated deadenylase from CNOT1-depleted cells was less than that from control cells |
| GO:0005515 protein binding | IPI PMID:10637334 Isolation and characterization of human orthologs of yeast C... | KEEP AS NON CORE | Summary: The CNOT2 association is retained. Reason: The original human study tests an N-terminally truncated CNOT1 fragment in yeast two-hybrid assays and finds the CNOT2 interaction. The result is retained at that construct scope. This source-specific association is retained as non-core rather than removed for genericity. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:10637334 Isolation and characterization of human orthologs of yeast C... | MODIFY | Summary: CNOT1 associates with the CNOT8 enzyme. Reason: The original human CNOT1-fragment yeast two-hybrid assay supports interaction with hCALIF/CNOT8. CNOT8 is an independently established poly(A) nuclease. The verified partner class supports enzyme binding; it does not assign the partnerβs catalytic activity to CNOT1. Proposed replacements: enzyme binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:16778766 Human Ccr4-Not complex is a ligand-dependent repressor of nu... | KEEP AS NON CORE | Summary: The CNOT3 association is retained. Reason: The exact source-linked anti-bait coimmunoprecipitation record supports association with CNOT3 in the nuclear-receptor study. This source-specific association is retained as non-core rather than removed for genericity. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:16778766 Human Ccr4-Not complex is a ligand-dependent repressor of nu... | KEEP AS NON CORE | Summary: The CNOT2 association is retained. Reason: Two source-linked anti-bait coimmunoprecipitation records support the CNOT2 association; receptor-specific repression differs among complex subunits. This source-specific association is retained as non-core rather than removed for genericity. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:16778766 Human Ccr4-Not complex is a ligand-dependent repressor of nu... | MODIFY | Summary: CNOT1 associates with the CNOT8 enzyme. Reason: Two source-linked anti-bait coimmunoprecipitation records preserve the CNOT8 association. Its nuclease identity supports an enzyme-binding refinement. The verified partner class supports enzyme binding; it does not assign the partnerβs catalytic activity to CNOT1. Proposed replacements: enzyme binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:17452450 Depletion of mammalian CCR4b deadenylase triggers elevation ... | KEEP AS NON CORE | Summary: CNOT1 associates with the CNOT6L enzyme. Reason: Human GFP-CCR4b/CNOT6L immunoprecipitation and mass spectrometry recovered CNOT1 with other CCR4-NOT subunits; endogenous mouse coimmunoprecipitation provides additional complex-level support. The positive association is retained. The source does not isolate a CNOT1βCNOT6L binary contact, and the human catalytic-module study identifies CAF1/POP2 as the bridge to CCR4a/b. Enzyme-binding specificity is therefore not added to this source assertion. Supporting Evidence: PMID:17452450 identified CNOT1, CNOT2, CNOT3, CAF1b/CNOT8, and CAF40/CNOT9 |
| GO:0005515 protein binding | IPI PMID:17452450 Depletion of mammalian CCR4b deadenylase triggers elevation ... | KEEP AS NON CORE | Summary: CNOT1 associates with the CNOT6 enzyme. Reason: Human GFP-CCR4a/CNOT6 immunoprecipitates contained a subunit pattern like the CCR4b complex, including CNOT1. This is positive complex-association evidence. The source does not distinguish CNOT1 contact with CNOT6 from linkage through CAF1/POP2, as described in the human catalytic-module study. Retain the original association without an enzyme-binding replacement. |
| GO:0005515 protein binding | IPI PMID:18377426 Interaction of antiproliferative protein Tob with the CCR4-N... | KEEP AS NON CORE | Summary: The TOB1 association is retained. Reason: The genuine original abstract explicitly reports interaction between the carboxyl-terminal half of Tob and Cnot1. Its NIH3T3 functional context and the limited access to detailed methods remain explicit. This source-specific association is retained as non-core rather than removed for genericity. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:20584987 Human Pat1b connects deadenylation with mRNA decapping and c... | KEEP AS NON CORE | Summary: The PATL1 association is retained. Reason: Human FLAG-NOT1 and YFP-Pat1b coimmunoprecipitation persists with RNase treatment and stringent washing. The study assigns the deadenylation-to-decapping bridging analysis to Pat1b, not automatically to every CNOT1 contact. This source-specific association is retained as non-core rather than removed for genericity. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:21278420 Not1 mediates recruitment of the deadenylase Caf1 to mRNAs t... | UNDECIDED | Summary: The exact ZFP36L1/BRF1 supporting assay remains unresolved. Reason: The complete main text centers on ZFP36/TTP and mentions BRF1 among ARE-binding proteins. The recovered original supplement contains TTP purification (Table S2) and TTP-fragment interaction assays (Figure S1), but does not identify a CNOT1βBRF1 assay. No exact pair was recovered from the inspected interaction databases. The source assertion is preserved pending its exact supporting record; absence from these inspected materials is not proof that the interaction is false. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:21278420 Not1 mediates recruitment of the deadenylase Caf1 to mRNAs t... | MODIFY | Summary: CNOT1 associates with the CNOT7 enzyme. Reason: Human NOT1 fragments associate with CAF1/CNOT7 in HEK/HeLa experiments, and NOT1 depletion disrupts TTPβCAF1 association. Independent recombinant human assays directly confirm the NOT1βCAF1 interface. The verified partner class supports enzyme binding; it does not assign the partnerβs catalytic activity to CNOT1. Proposed replacements: enzyme binding |
| GO:0005515 protein binding | IPI PMID:21981923 GW182 proteins directly recruit cytoplasmic deadenylase comp... | KEEP AS NON CORE | Summary: The TNRC6A association is retained. Reason: The original positive abstract reports direct recruitment of human NOT1 by GW182 proteins. Human TNRC6A binding and silencing are independently resolved in the later full-text study. This source-specific association is retained as non-core rather than removed for genericity. |
| GO:0005515 protein binding | IPI PMID:21981923 GW182 proteins directly recruit cytoplasmic deadenylase comp... | KEEP AS NON CORE | Summary: The TNRC6C association is retained. Reason: The original positive GW182 study supports the mapped TNRC6C association. The preserved abstract does not resolve every construct, so the result is not expanded to all isoforms or species. This source-specific association is retained as non-core rather than removed for genericity. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:21981923 GW182 proteins directly recruit cytoplasmic deadenylase comp... | KEEP AS NON CORE | Summary: The TNRC6B association is retained. Reason: The original positive GW182 study reports human recruitment of NOT1; the mapped TNRC6B source is retained. Detailed construct boundaries are not recoverable from the selected abstract. This source-specific association is retained as non-core rather than removed for genericity. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:21984185 miRNA-mediated deadenylation is orchestrated by GW182 throug... | KEEP AS NON CORE | Summary: CNOT1 associates with the CNOT6L enzyme. Reason: The original positive annotation and the accessible GW182 study abstract support CCR4-NOT recruitment; the original full assay was not recovered. Independent human coimmunoprecipitation and reconstitution support the CNOT6L-containing complex, while CAF1/POP2 can bridge CCR4 proteins to CNOT1. Retain the positive association without extending the limited source access to a direct CNOT1βCNOT6L contact or an enzyme-binding replacement. |
| GO:0005515 protein binding | IPI PMID:21984185 miRNA-mediated deadenylation is orchestrated by GW182 throug... | KEEP AS NON CORE | Summary: The TNRC6C association is retained. Reason: The source identifies conserved GW182 motifs that recruit CCR4-NOT. The positive mapped TNRC6C association is retained at the reported complex-recruitment scope. This source-specific association is retained as non-core rather than removed for genericity. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:21984185 miRNA-mediated deadenylation is orchestrated by GW182 throug... | KEEP AS NON CORE | Summary: The TNRC6C-1 association is retained. Reason: The original isoform-specific assertion is preserved. The source reports human GW182 recruitment of CCR4-NOT, but the selected abstract alone does not support extending the tested product to every TNRC6C isoform. This source-specific association is retained as non-core rather than removed for genericity. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:22977175 The structural basis for the interaction between the CAF1 nu... | KEEP AS NON CORE | Summary: CNOT1 associates with the CNOT6L enzyme. Reason: Human GFP-NOT1 coimmunoprecipitates HA-CCR4b/CNOT6L through the NOT1 middle region. The study explicitly distinguishes this association from recombinant binary pull-downs and structures for NOT1βCAF1/POP2, which bridge CCR4a/b to the NOT module. Preserve the CNOT6L association as non-core; the experiment does not establish a separate CNOT1βCNOT6L binding interface. Supporting Evidence: PMID:22977175 thereby bridging the interaction of CCR4a (or CCR4b) with the NOT module |
| GO:0005515 protein binding | IPI PMID:22977175 The structural basis for the interaction between the CAF1 nu... | MODIFY | Summary: CNOT1 associates with the CNOT8 enzyme. Reason: Recombinant human GST-POP2/CNOT8 pulls down the NOT1 middle domain, independently of other complex components; human-cell coimmunoprecipitation agrees. The verified partner class supports enzyme binding; it does not assign the partnerβs catalytic activity to CNOT1. Proposed replacements: enzyme binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:22977175 The structural basis for the interaction between the CAF1 nu... | MODIFY | Summary: CNOT1 associates with the CNOT7 enzyme. Reason: Recombinant human CAF1/CNOT7 binds the CNOT1 MIF4G domain, and the structure resolves their interface while leaving the CAF1 active site accessible. The verified partner class supports enzyme binding; it does not assign the partnerβs catalytic activity to CNOT1. Proposed replacements: enzyme binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:22977175 The structural basis for the interaction between the CAF1 nu... | KEEP AS NON CORE | Summary: CNOT1 associates with the CNOT6 enzyme. Reason: Human-cell coimmunoprecipitation recovers HA-CCR4a/CNOT6 with the NOT1 middle region. In the same study CAF1/POP2 connect CCR4a/b to the NOT module, whereas direct recombinant binding is demonstrated for NOT1βCAF1/POP2. Preserve the positive CNOT6 association without an enzyme-binding refinement from this co-complex assay. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:23232451 C2ORF29/CNOT11 and CNOT10 form a new module of the CCR4-NOT ... | KEEP AS NON CORE | Summary: The CNOT11 association is retained. Reason: Human CNOT11 affinity purification and yeast two-hybrid fragment mapping identify CNOT1βs N terminus as the CNOT11-interacting region. CNOT10 binds CNOT11 and is not inferred to contact that CNOT1 fragment directly. This source-specific association is retained as non-core rather than removed for genericity. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:23463101 GW182 proteins cause PABP dissociation from silenced miRNA t... | KEEP AS NON CORE | Summary: The TNRC6C-1 association is retained. Reason: The exact source-linked coimmunoprecipitation records support the mapped positive pair. The paperβs principal functional assays use Drosophila S2 cells and human TNRC6C silencing-domain constructs; independent human GW182βNOT1 evidence corroborates the association without relabeling those S2 assays. This source-specific association is retained as non-core rather than removed for genericity. |
| GO:0005515 protein binding | IPI PMID:23644599 Structural basis for the recruitment of the human CCR4-NOT d... | KEEP AS NON CORE | Summary: The ZFP36/TTP association is retained. Reason: Purified human CNOT1 fragments bind the TTP C-terminal motif, and a structure plus interface mutants identifies the contact. The paperβs historical isoform-C numbering and mouse Krebs-extract functional assay are kept distinct from human-cell reporter experiments. This source-specific association is retained as non-core rather than removed for genericity. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:24736845 Structural basis for the Nanos-mediated recruitment of the C... | KEEP AS NON CORE | Summary: The NANOS2 association is retained. Reason: Human NANOS2 pulls down endogenous CNOT1, and recombinant conserved Nanos motifs bind the human CNOT1 SHD. Motif deletion and interface mutations support specificity. This source-specific association is retained as non-core rather than removed for genericity. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:24736845 Structural basis for the Nanos-mediated recruitment of the C... | KEEP AS NON CORE | Summary: The NANOS1 association is retained. Reason: Human NANOS1 association is supported by cell pull-down and the recombinant NIMβCNOT1 SHD structure. The short isolated Nanos1 motif binds less strongly under stringent cell-lysate conditions than Nanos2/3. This source-specific association is retained as non-core rather than removed for genericity. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:24736845 Structural basis for the Nanos-mediated recruitment of the C... | KEEP AS NON CORE | Summary: The NANOS3 association is retained. Reason: Human NANOS3 cell pull-down, motif deletion and recombinant SHD binding support the association. Failure on one specific reporter does not negate the directly measured contact. This source-specific association is retained as non-core rather than removed for genericity. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:24768540 A DDX6-CNOT1 complex and W-binding pockets in CNOT9 reveal d... | KEEP AS NON CORE | Summary: The TNRC6A association is retained. Reason: The positive source describes the CNOT1βCNOT9 module that supplies GW182 recruitment surfaces. The tryptophan-binding pockets reside in CNOT9, so this association is not converted into a CNOT1 tryptophan-pocket claim. This source-specific association is retained as non-core rather than removed for genericity. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:24768540 A DDX6-CNOT1 complex and W-binding pockets in CNOT9 reveal d... | KEEP AS NON CORE | Summary: The TNRC6C association is retained. Reason: The source supports GW182 recruitment by the CNOT1βCNOT9 module. Its structural summary places the tryptophan pockets in CNOT9; the positive CNOT1 association does not by itself identify a direct CNOT1 pocket. This source-specific association is retained as non-core rather than removed for genericity. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:25038453 CNOT7/hCAF1 is involved in ICAM-1 and IL-8 regulation by tri... | KEEP AS NON CORE | Summary: The ZFP36/TTP association is retained. Reason: The original abstract explicitly reports TTP, CNOT7 and CNOT1 coimmunoprecipitation in human pulmonary microvascular endothelial cells. CNOT7 knockdown effects on inflammatory transcripts are not assigned as a new CNOT1 pathway. This source-specific association is retained as non-core rather than removed for genericity. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:26496610 A human interactome in three quantitative dimensions organiz... | KEEP AS NON CORE | Summary: The CNOT3 association is retained. Reason: The exact 2015 anti-tag coimmunoprecipitation record supports the CNOT3 pair in the quantitative HeLa interactome survey. This source-specific association is retained as non-core rather than removed for genericity. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:26496610 A human interactome in three quantitative dimensions organiz... | KEEP AS NON CORE | Summary: The TOB1 association is retained. Reason: The exact 2015 anti-tag coimmunoprecipitation record supports the TOB1 association; independent targeted Tob work corroborates the pair. This source-specific association is retained as non-core rather than removed for genericity. |
| GO:0005515 protein binding | IPI PMID:26496610 A human interactome in three quantitative dimensions organiz... | KEEP AS NON CORE | Summary: CNOT1 associates with the CNOT6L enzyme. Reason: The exact PMID:26496610 IntAct record is a positive anti-tag coimmunoprecipitation association in human HeLa cells, represented by spoke expansion from a complex. It supports the CNOT1βCNOT6L association but does not isolate their direct interface. In light of the experimentally characterized CAF1/POP2 bridge, retain the source assertion as non-core without the enzyme-binding replacement. |
| GO:0005515 protein binding | IPI PMID:26496610 A human interactome in three quantitative dimensions organiz... | KEEP AS NON CORE | Summary: The CNOT2 association is retained. Reason: Two exact 2015 source-linked anti-tag coimmunoprecipitation records support the CNOT2 association. This source-specific association is retained as non-core rather than removed for genericity. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:26496610 A human interactome in three quantitative dimensions organiz... | MODIFY | Summary: CNOT1 associates with the CNOT8 enzyme. Reason: The exact 2015 source-linked anti-tag coimmunoprecipitation record supports association with the CNOT8 deadenylase. The verified partner class supports enzyme binding; it does not assign the partnerβs catalytic activity to CNOT1. Proposed replacements: enzyme binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:26496610 A human interactome in three quantitative dimensions organiz... | MODIFY | Summary: CNOT1 associates with the CNOT7 enzyme. Reason: The exact 2015 source-linked anti-tag coimmunoprecipitation record supports association with the CNOT7 deadenylase. The verified partner class supports enzyme binding; it does not assign the partnerβs catalytic activity to CNOT1. Proposed replacements: enzyme binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:26496610 A human interactome in three quantitative dimensions organiz... | KEEP AS NON CORE | Summary: The CNOT11 association is retained. Reason: The exact 2015 source-linked anti-tag coimmunoprecipitation record supports CNOT11 association, consistent with the independently mapped N-terminal module. This source-specific association is retained as non-core rather than removed for genericity. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:26496610 A human interactome in three quantitative dimensions organiz... | KEEP AS NON CORE | Summary: CNOT1 associates with the CNOT6 enzyme. Reason: The exact PMID:26496610 IntAct record links CNOT1 and CNOT6 by positive anti-tag coimmunoprecipitation in human HeLa cells and is a spoke-expanded association. Retain that physical complex evidence. It does not distinguish direct CNOT1βCNOT6 contact from the characterized CAF1/POP2-mediated connection, so an enzyme-binding replacement is not added. |
| GO:0005515 protein binding | IPI PMID:27342281 The DDX6-4E-T interaction mediates translational repression ... | KEEP AS NON CORE | Summary: The EIF4ENIF1/4E-T association is retained. Reason: The paper reports the FLAG-CNOT1/4E-T interaction and enhanced complex association with an eIF4E-binding-site mutant. It distinguishes weak endogenous detection from the tagged-protein assays and does not establish direct purified CNOT1β4E-T binding. This source-specific association is retained as non-core rather than removed for genericity. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:28297718 DND1 maintains germline stem cells via recruitment of the CC... | MODIFY | Summary: CNOT1 associates with the CNOT7 enzyme. Reason: The source identifies CNOT1 and CNOT7 in the RNase-resistant DND1-associated CCR4-NOT machinery and tests their depletion. The direct recombinant interface resolved there is DND1βCNOT1; independent human NOT1βCAF1 structural work supports the enzyme-binding class. The verified partner class supports enzyme binding; it does not assign the partnerβs catalytic activity to CNOT1. Proposed replacements: enzyme binding |
| GO:0005515 protein binding | IPI PMID:30833792 A protein-interaction network of interferon-stimulated genes... | KEEP AS NON CORE | Summary: The ANXA2R association is retained. Reason: The exact source-linked records include positive pull-down evidence for ANXA2RβCNOT1 as well as a distinct microscopy record. Only the physical assay is used to support binding; the screen does not establish a native immune-signaling function for CNOT1. This source-specific association is retained as non-core rather than removed for genericity. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:31570513 HELZ directly interacts with CCR4-NOT and causes decay of bo... | KEEP AS NON CORE | Summary: The HELZ association is retained. Reason: Human GFP-HELZ coimmunoprecipitates endogenous NOT1, and recombinant HELZ C-terminal fragments bind the reconstituted NOT module. This establishes recruitment through a complex interface, not CNOT1 helicase catalysis. This source-specific association is retained as non-core rather than removed for genericity. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | KEEP AS NON CORE | Summary: The CNOT3 association is retained. Reason: The exact BioPlex anti-tag coimmunoprecipitation records support CNOT3 association. The selected publication text is partial; the literal assay records supply the target-specific evidence. This source-specific association is retained as non-core rather than removed for genericity. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | KEEP AS NON CORE | Summary: The TOB1 association is retained. Reason: The exact BioPlex anti-tag coimmunoprecipitation records support the positive TOB1 association, with targeted Tob studies providing independent context. This source-specific association is retained as non-core rather than removed for genericity. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | KEEP AS NON CORE | Summary: CNOT1 associates with the CNOT6L enzyme. Reason: The exact BioPlex records recover CNOT1 with CNOT6L by anti-tag coimmunoprecipitation in human 293T and HCT116 cells. Both are positive spoke-expanded associations; neither is a binary-contact assay. Retain the reproducible complex association as non-core, without inferring an additional CNOT1 enzyme-binding interface from these records. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MODIFY | Summary: CNOT1 associates with the CNOT7 enzyme. Reason: The exact BioPlex anti-tag coimmunoprecipitation record supports association with the CNOT7 deadenylase. The verified partner class supports enzyme binding; it does not assign the partnerβs catalytic activity to CNOT1. Proposed replacements: enzyme binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | KEEP AS NON CORE | Summary: The CNOT11 association is retained. Reason: The exact BioPlex anti-tag coimmunoprecipitation records support the CNOT11 association at the reported cell-screen scope. This source-specific association is retained as non-core rather than removed for genericity. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | KEEP AS NON CORE | Summary: The CNOT3 association is retained. Reason: The original U2OS AP-MS network contains the exact CNOT3βCNOT1 edge. C-terminal FlagβHA bait isolation and mass-spectrometric association support the pair, without establishing a purified binary contact. This source-specific association is retained as non-core rather than removed for genericity. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | KEEP AS NON CORE | Summary: The CNOT11 association is retained. Reason: The original U2OS AP-MS network contains the exact CNOT11βCNOT1 edge. This positive complex association is distinct from the studyβs separate imaging measurements. This source-specific association is retained as non-core rather than removed for genericity. Supporting Evidence: |
| GO:0005576 extracellular region | HDA PMID:22664934 Comparison of tear protein levels in breast cancer patients ... | KEEP AS NON CORE | Summary: CNOT1 was detected in the human tear proteome. Reason: Original Table II identifies CNOT1_HUMAN/CNOT1 in a merged list from pooled tear eluates of 25 breast-cancer patients and 25 controls. Tears were collected on Schirmer strips, extracted with detergent and analyzed by gel separation and MALDI-TOF/TOF. This supports extracellular sample detection, with cellular carryover and release mechanism unresolved. Neither a secretion pathway nor an extracellular function was tested. The spatial GO term does not require a signal peptide, and the study does not demonstrate that the CNOT1 identification is contamination; retain the original HDA located_in assertion as non-core. Supporting Evidence: PMID:22664934 Tear fluid was obtained from all participants using a Schirmer Strip. |
| GO:0005634 nucleus | IEA GO_REF:0000044 | ACCEPT | Summary: A nuclear CNOT1 population is supported. Reason: The fetched UniProt location mapping is consistent with ligand-dependent recruitment of CNOT1 to endogenous nuclear-receptor-regulated promoters. Predominantly cytoplasmic localization in another cell assay does not exclude this nuclear pool. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-429955 | ACCEPT | Summary: Reactome models CNOT1 in the cytosolic CCR4-NOT complex. Reason: The actual catalyst-to-complex chain contains the CNOT1 physical entity linked to A5YKK6 and cytosol. This supports the location; the reactionβs nuclease activity is performed by catalytic subunits. The broad database complex composition is not treated as a universal fixed stoichiometry. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-6798044 | ACCEPT | Summary: The BTG2 recruitment reaction retains cytosolic CNOT1 membership. Reason: The event includes the cytosolic CCR4-NOT complex, whose actual component chain resolves to A5YKK6. Its text assigns BTG2 binding to CNOT7/8, so this location assertion does not manufacture a direct CNOT1βBTG2 interaction. |
| GO:0010606 positive regulation of cytoplasmic mRNA processing body assembly | IDA PMID:21976065 The role of the CNOT1 subunit of the CCR4-NOT complex in mRN... | KEEP AS NON CORE | Summary: CNOT1 supports P-body abundance in the depletion assay. Reason: The original human experiment shows fewer AGO2-positive P-body foci after CNOT1 depletion while AGO2 abundance remains unchanged. This supports the existing regulatory annotation at cellular scope; it does not establish autonomous condensate nucleation by CNOT1. Supporting Evidence: |
| GO:0016020 membrane | HDA PMID:19946888 Defining the membrane proteome of NK cells. | UNDECIDED | Summary: The exact membrane-proteomics assignment remains unresolved. Reason: The genuine abstract describes fractionation and proteomics of human NK-like YTS cells, including proteins that may associate transiently with membranes. The CNOT1 target-table entry was not recovered, and the publisher attempt returned an access-error page. The assertion is retained without assuming integral-membrane topology or dismissing a possible peripheral association. Supporting Evidence: |
| GO:0017148 negative regulation of translation | IDA PMID:24736845 Structural basis for the Nanos-mediated recruitment of the C... | ACCEPT | Summary: CNOT1 recruitment contributes to translational repression. Reason: Human Nanos motifs bind the CNOT1 SHD, and interface mutations reduce repression. Nonpolyadenylated reporter assays separate repression from RNA loss. The recruitment interface performs work in assembling the silencing machinery; CNOT1 is not assigned the RNA-binding specificity of Nanos. Supporting Evidence: |
| GO:0017148 negative regulation of translation | IEA GO_REF:0000002 | ACCEPT | Summary: The family-based translation-regulation assignment is corroborated by target assays. Reason: The CNOT1 family mapping is consistent with human NanosβCNOT1 interface experiments and CNOT1-mediated recruitment of repression machinery. This target evidence supports the existing process independently of family membership alone. |
| GO:0019904 protein domain specific binding | IPI PMID:24768540 A DDX6-CNOT1 complex and W-binding pockets in CNOT9 reveal d... | MODIFY | Summary: CNOT1 binds the DEAD-box RNA helicase DDX6. Reason: The original structural summary explicitly identifies the CNOT1 MIF4GβDDX6 C-terminal RecA interface. The current specific partner-class term is more informative than generic domain-specific binding. DDX6 supplies helicase/ATPase functions; these are not transferred to CNOT1. Proposed replacements: DEAD/H-box RNA helicase binding Supporting Evidence: PMID:24768540 the CNOT1 MIF4G domain interacts with the C-terminal RecA domain of DDX6 |
| GO:0030014 CCR4-NOT complex | IDA PMID:19558367 Human Ccr4-Not complexes contain variable deadenylase subuni... | ACCEPT | Summary: CNOT1 is an organizing component of human CCR4-NOT. Reason: The original positive complex-isolation study describes human assemblies with mutually exclusive catalytic subunits. Independent structural and reconstitution experiments confirm CNOT1 membership and its scaffold role. The preserved abstract does not resolve every purification detail. |
| GO:0030014 CCR4-NOT complex | NAS PMID:19558367 Human Ccr4-Not complexes contain variable deadenylase subuni... | ACCEPT | Summary: The reported human complex membership is retained. Reason: This NAS assertion cites the same complex-isolation study as the separate IDA row. Both original source objects are preserved, and defined human reconstitution independently verifies membership. |
| GO:0030015 CCR4-NOT core complex | IBA GO_REF:0000033 | ACCEPT | Summary: The conserved CCR4-NOT core assignment has experimental grounding. Reason: The exact budding- and fission-yeast orthologs have current experimental core-complex records. Human structural and reconstitution experiments independently establish the retained central scaffold. Current source checks support the annotation without reconstructing the historical PAINT placement. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000322838 UNRESOLVED The historical ancestral node, family tree and alignment were not inspected; current experimental grounding is assessed separately. PomBase:SPAC20G8.06 SUPPORTS TRANSFER The exact identity and current same-term experimental records are verified. This supports the extant function without reconstructing historical node placement. SGD:S000000689 SUPPORTS TRANSFER The exact identity and current same-term experimental records are verified. This supports the extant function without reconstructing historical node placement. |
| GO:0030015 CCR4-NOT core complex | IEA GO_REF:0000002 | ACCEPT | Summary: The CNOT1 family assignment agrees with measured core-complex membership. Reason: The recorded InterPro family mapping is corroborated by purified human NOT1-containing modules and intact CCR4-NOT reconstitution. Family classification is not used to attribute nuclease catalysis to the scaffold. |
| GO:0030331 obsolete nuclear estrogen receptor binding | IDA PMID:16778766 Human Ccr4-Not complex is a ligand-dependent repressor of nu... | MODIFY | Summary: Use the current nuclear-receptor-binding class for the supported ER interaction. Reason: The original estrogen-receptor-binding term is obsolete because of gene-product-specific naming. The recommended current class is nuclear receptor binding. Human CNOT1 fragments show agonist-dependent ERΞ± ligand-binding-domain interaction, with independent full-length human receptor repression and promoter recruitment; the original source assertion remains intact. Proposed replacements: nuclear receptor binding Supporting Evidence: |
| GO:0033147 negative regulation of intracellular estrogen receptor signaling pathway | IDA PMID:16778766 Human Ccr4-Not complex is a ligand-dependent repressor of nu... | KEEP AS NON CORE | Summary: CNOT1 represses estrogen-receptor signaling in the tested systems. Reason: Reporter assays and ligand-dependent recruitment to endogenous estrogen-responsive promoters support a specific regulatory context. Endogenous CNOT1 depletion alters ERΞ± target expression. This does not imply a uniform repressive effect at every receptor target. Supporting Evidence: |
| GO:0035195 miRNA-mediated post-transcriptional gene silencing | IDA PMID:23172285 The interactions of GW182 proteins with PABP and deadenylase... | ACCEPT | Summary: CNOT1 helps execute miRNA-mediated silencing. Reason: Human TNRC6 recruitment and CNOT1 middle-domain interference demonstrate a role in both translational repression and target degradation. The paper also contains Drosophila experiments, but the human HeLa reporter and binding assays provide target-specific support. Supporting Evidence: |
| GO:0035195 miRNA-mediated post-transcriptional gene silencing | IDA PMID:24768540 A DDX6-CNOT1 complex and W-binding pockets in CNOT9 reveal d... | ACCEPT | Summary: The CNOT1βCNOT9 and CNOT1βDDX6 interfaces connect miRNA recruitment to repression. Reason: The original structural summary links GW182 recognition to CNOT1-associated regulatory modules. Human-cell recruitment and repression assays independently establish the broader silencing process. W-binding pockets are assigned to CNOT9, not to CNOT1 itself. |
| GO:0042974 obsolete nuclear retinoic acid receptor binding | IDA PMID:16778766 Human Ccr4-Not complex is a ligand-dependent repressor of nu... | MARK AS OVER ANNOTATED | Summary: The cited assay does not establish ligand-dependent RARΞ± binding. Reason: The original paper explicitly reports no ligand-dependent CNOT1 interaction with RARΞ±, while ERΞ± and RXRΞ± are positive. RAR-responsive reporter repression remains supported and may involve its RXR heterodimer partner. The obsolete RAR-specific binding assertion exceeds this evidence; this decision does not deny the demonstrated receptor regulation or broader nuclear-receptor binding. Supporting Evidence: PMID:16778766 CNOT1 did not display such interactions with RARΞ±, TRΞ², and PPARΞ³ |
| GO:0048387 negative regulation of retinoic acid receptor signaling pathway | IDA PMID:16778766 Human Ccr4-Not complex is a ligand-dependent repressor of nu... | KEEP AS NON CORE | Summary: RAR-pathway repression is supported even though direct RAR binding is unresolved. Reason: CNOT1 represses the RAR-responsive reporter in COS-7 cells. The authors distinguish that response from the negative ligand-dependent RARΞ± interaction assay and propose mediation through RXR. The pathway effect is retained without treating it as proof of a direct RAR contact. Supporting Evidence: |
| GO:0060090 molecular adaptor activity | IBA GO_REF:0000033 | MODIFY | Summary: Protein-complex scaffold activity captures CNOT1βs measured organizing role. Reason: The target itself provides experimental grounding for the broad adaptor annotation. Human structures and reconstitution establish a retained structural component organizing several CCR4-NOT modules, matching GO:0140378. This is a target-grounded term refinement, not a claim that the uninspected historical PAINT node was misplaced. Propagation Review Root cause: TERM SCOPING PROBLEM Sources checked: PANTHER:PTN000322838 UNRESOLVED The historical ancestral node, family tree and alignment were not inspected; current experimental grounding is assessed separately. UniProtKB:A5YKK6 SUPPORTS TRANSFER The exact identity and current same-term experimental records are verified. This is direct target grounding, not circular evidence. This supports the extant function without reconstructing historical node placement. Proposed replacements: protein complex scaffold activity |
| GO:0060090 molecular adaptor activity | IDA PMID:22977175 The structural basis for the interaction between the CAF1 nu... | MODIFY | Summary: The resolved human NOT1βCAF1 structure supports scaffold activity. Reason: CNOT1βs MIF4G domain holds CAF1 within the complex while leaving its catalytic site accessible. The broader adaptor label is refined to protein-complex scaffold activity; the functional decay reporter in this paper uses Drosophila S2 proteins and is not relabeled as a human assay. Proposed replacements: protein complex scaffold activity Supporting Evidence: PMID:22977175 NOT1 acts as a scaffold to arrange the position of CAF1 |
| GO:0060213 positive regulation of nuclear-transcribed mRNA poly(A) tail shortening | IDA PMID:23644599 Structural basis for the recruitment of the human CCR4-NOT d... | ACCEPT | Summary: The TTPβCNOT1 interface promotes productive deadenylase recruitment. Reason: The study resolves human CNOT1βTTP binding and tests interface mutants in mouse Krebs-extract deadenylation and a human-cell reporter. This supports the existing positive regulation term through recruitment of the catalytic machinery, without asserting that CNOT1 itself cleaves RNA. Supporting Evidence: |
| GO:0060213 positive regulation of nuclear-transcribed mRNA poly(A) tail shortening | IMP PMID:21278420 Not1 mediates recruitment of the deadenylase Caf1 to mRNAs t... | ACCEPT | Summary: CNOT1 promotes poly(A)-tail shortening through the recruited CAF1 module. Reason: In human HeLa reporter experiments, CNOT1 depletion impairs tail shortening and destabilizes TTPβCAF1 association. Direct human NOT1βCAF1 binding and reconstitution provide a molecular explanation beyond necessity alone. |
| GO:0061014 positive regulation of mRNA catabolic process | IMP PMID:22977175 The structural basis for the interaction between the CAF1 nu... | ACCEPT | Summary: The conserved NOT1βCAF1 interface promotes mRNA turnover. Reason: The cited study combines direct human binding/structure with Drosophila S2 decay reporters using fly NOT1/POP2 mutants. The human functional role is independently supported by CNOT1 depletion and reconstitution; the original IMP source is preserved with its actual species scope. |
| GO:0070016 armadillo repeat domain binding | IPI PMID:24768540 A DDX6-CNOT1 complex and W-binding pockets in CNOT9 reveal d... | ACCEPT | Summary: CNOT1 binds the armadillo-repeat CNOT9 module. Reason: The structural summary explicitly attaches CNOT9 to the CNOT1 DUF3819 region. The specific armadillo-repeat-domain binding assertion is consistent with the verified partner architecture. The adjacent GW182-binding pockets belong to CNOT9. Supporting Evidence: |
| GO:1900153 positive regulation of nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay | IMP PMID:21278420 Not1 mediates recruitment of the deadenylase Caf1 to mRNAs t... | ACCEPT | Summary: CNOT1 promotes deadenylation-dependent reporter decay. Reason: Human-cell decay time courses and tail-length measurements show impaired turnover after CNOT1 depletion, and interaction mapping demonstrates recruitment of CAF1 through CNOT1. This is performed scaffold work within the pathway, not an assignment of CAF1 catalysis to CNOT1. Supporting Evidence: |
| GO:2000036 regulation of stem cell population maintenance | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: The mouse-derived stem-cell maintenance context is supported. Reason: The exact Q6ZQ08/Ensembl donor identity and current experimental source record are resolved. Mouse ESC depletion alters pluripotency and extraembryonic markers, with distinct human H1 corroboration. The regulatory phenotype is retained as context-dependent rather than made a second molecular core. |
| 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: CNOT1 helps maintain embryonic-stem-cell identity in the tested cultures. Reason: The original study tests mouse ESCs and human H1 cells, with CNOT1 effects weaker than CNOT2/3 in the human assay. Cnot2/3 rescue and H9 follow-up experiments are not falsely attributed to CNOT1. The source supports a stem-cell regulatory context while leaving the exact effector route unresolved. Supporting Evidence: |
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Download this section (compressed HTML)Q: How do the four natural CNOT1 products differ in abundance, localization and recruitment of catalytic or regulatory modules?
Q: Which direct RNA contacts underlie the crosslink-capture findings, and how do they contribute relative to RNA recognition by recruited partner proteins?
Q: What is the precise original evidence for the ZFP36L1/BRF1 pair and for CNOT1 detection in the NK-cell membrane proteome?
Q: How does nuclear CNOT1 regulate receptor-dependent transcription, and when is RAR reporter repression mediated through RXR rather than a direct RAR contact?
Experiment: Reconstitute matched complexes with the sequence-verified natural CNOT1 products and compare module occupancy, RNA binding and deadenylation while holding catalytic-subunit abundance constant.
Hypothesis: Alternative CNOT1 sequence segments change recruitment or assembly without conferring intrinsic RNase catalysis.
Experiment: Measure CNOT1 binding to purified RAR/RXR heterodimers and isolated receptors with controlled ligands, followed by receptor-interface mutants in transcriptional reporters.
Hypothesis: RAR-pathway repression can be mediated by an RXR-facing interface despite absent ligand-dependent binding to isolated RARΞ± in the original assay.
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