CTBP1 (C-terminal-binding protein 1) is a transcriptional corepressor that functions as a scaffold to nucleate multi-protein chromatin-modifying complexes. It lacks intrinsic DNA-binding activity and is instead recruited to target gene promoters by DNA-binding transcription factors (e.g. ZEB1/2, KLFs, BCL6, MECOM) that present PXDLS/PLDLS short linear motifs. Once recruited, CTBP1 assembles corepressor complexes containing HDAC1/2, LSD1/KDM1A, and RCOR1/CoREST to mediate transcriptional silencing through histone modification. CTBP1 contains a D-isomer-specific 2-hydroxyacid dehydrogenase-like domain with a Rossmann fold that binds NAD+/NADH, and NADH binding allosterically promotes dimerization/oligomerization critical for corepressor function, establishing CTBP1 as a metabolic/redox sensor in transcriptional regulation. CTBP1 also has roles in Golgi membrane fission (as CtBP1/BARS) and has been reported at presynaptic terminals in neurons. It is predominantly nuclear but shuttles between nucleus and cytoplasm depending on cellular context.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005634 nucleus | IBA GO_REF:0000033 | ACCEPT | Summary: CTBP1 is well established as a nuclear transcriptional corepressor. UniProt confirms nuclear localization (PMID:12679040). IBA is appropriate as this is conserved across the CtBP family. |
| GO:0003714 transcription corepressor activity | IBA GO_REF:0000033 | ACCEPT | Summary: Transcription corepressor activity is the primary molecular function of CTBP1. It is recruited by PXDLS-motif-containing transcription factors and assembles HDAC/LSD1/CoREST complexes to silence gene expression. IBA is well-supported and represents the core function. Supporting Evidence: PMID:12419229 CtBP is an NAD(+)-regulated component of critical complexes for specific repression events in cells. |
| GO:0006357 regulation of transcription by RNA polymerase II | IBA GO_REF:0000033 | ACCEPT | Summary: CTBP1 regulates RNA Pol II-dependent transcription as a corepressor. This is a core biological process annotation consistent with its well-established role. IBA annotation is well-supported. |
| GO:0140297 DNA-binding transcription factor binding | IBA GO_REF:0000033 | ACCEPT | Summary: CTBP1 binds numerous DNA-binding transcription factors via their PXDLS motifs (ZEB1/2, KLFs, BCL6, MECOM, FOXP1, etc.). This is a core molecular function. IBA is well-supported. Supporting Evidence: PMID:10359772 ZEB represses transcription through interaction with the corepressor CtBP. |
| GO:0001221 transcription coregulator binding | IBA GO_REF:0000033 | ACCEPT | Summary: CTBP1 binds other coregulators such as HDAC1/2, LSD1/KDM1A, RCOR1/CoREST within its corepressor complexes. It also heterodimerizes with CTBP2. IBA is appropriate. |
| GO:0003713 transcription coactivator activity | IBA GO_REF:0000033 | ACCEPT | Summary: While CTBP1 is primarily a corepressor, there is evidence that CtBP proteins can also have coactivator functions in certain contexts. The IBA annotation suggests this is phylogenetically conserved. Chen 2021 describes both transrepression and transactivation roles for CtBPs. Accepting as a secondary function. Reason: Chen 2021 (J Mol Med) describes transactivation roles of CtBPs in certain pathways, supporting the IBA annotation of coactivator activity as a conserved property. |
| GO:0045893 positive regulation of DNA-templated transcription | IEA GO_REF:0000108 | ACCEPT | Summary: IEA annotation consistent with the coactivator role noted above for CtBP family. Logically inferred from the coactivator activity annotation. Acceptable as a broader annotation. |
| GO:0003714 transcription corepressor activity | IEA GO_REF:0000002 | ACCEPT | Summary: IEA annotation for transcription corepressor activity is redundant with the IBA (index 1) but correct. CTBP1 is well established as a transcriptional corepressor. |
| GO:0005634 nucleus | IEA GO_REF:0000120 | ACCEPT | Summary: IEA annotation for nucleus is redundant with the IBA and IDA annotations but correct. |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: CTBP1 localizes to both nucleus and cytoplasm. UniProt confirms cytoplasmic localization (PMID:12679040). CTBP1/BARS has well-described cytoplasmic roles in Golgi membrane dynamics. |
| GO:0016491 oxidoreductase activity | IEA GO_REF:0000043 | ACCEPT | Summary: CTBP1 has a D-2-hydroxyacid dehydrogenase domain and demonstrated dehydrogenase activity (PMID:12419229). This IEA is a parent term of the more specific GO:0016616 annotation and is correct. Supporting Evidence: PMID:12419229 CtBP is a functional dehydrogenase. |
| GO:0016616 oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor | IEA GO_REF:0000002 | ACCEPT | Summary: Correct IEA annotation consistent with the IDA annotation from PMID:12419229. CTBP1 has demonstrated dehydrogenase activity with NAD as cofactor. |
| GO:0030154 cell differentiation | IEA GO_REF:0000043 | KEEP AS NON CORE | Summary: CTBP1 is involved in differentiation processes (BAT/WAT differentiation, developmental programs) as a pleiotropic consequence of its transcriptional corepressor function. This is a very general term. Keeping as non-core. Reason: Cell differentiation is too general and represents pleiotropic effects of CTBP1 corepressor activity rather than a core function. |
| GO:0051287 NAD binding | IEA GO_REF:0000002 | ACCEPT | Summary: NAD binding is well established for CTBP1. Its Rossmann fold binds NAD+/NADH, which allosterically regulates oligomerization and corepressor function. Supported by crystal structure (PMID:12419229). |
| GO:0005515 protein binding | IPI PMID:10359772 ZEB represses transcription through interaction with the cor... | MODIFY | Summary: PMID:10359772 demonstrates CTBP1 interaction with ZEB1, a DNA-binding transcription factor. "protein binding" is too vague. Should be annotated as DNA-binding transcription factor binding. Proposed replacements: DNA-binding transcription factor binding Supporting Evidence: PMID:10359772 ZEB represses transcription through interaction with the corepressor CtBP. |
| GO:0005515 protein binding | IPI PMID:10995736 The interaction of the carboxyl terminus-binding protein wit... | MODIFY | Summary: PMID:10995736 describes CTBP1 interaction with TGIF, a Smad corepressor/transcription factor. Should be annotated more specifically. Proposed replacements: DNA-binding transcription factor binding Supporting Evidence: PMID:10995736 The interaction of the carboxyl terminus-binding protein with the Smad corepressor TGIF is disrupted by a holoprosencephaly mutation in TGIF. |
| GO:0005515 protein binding | IPI PMID:11462050 Physical and functional interactions between the corepressor... | MODIFY | Summary: PMID:11462050 describes physical interaction between CTBP1 and Epstein-Barr virus EBNA3C. This is a viral protein interaction relevant to host-virus biology. Protein binding is too vague. Reason: EBNA3C is a viral transcriptional regulator that recruits CTBP1 corepressor activity. Proposed replacements: DNA-binding transcription factor binding Supporting Evidence: PMID:11462050 Physical and functional interactions between the corepressor CtBP and the Epstein-Barr virus nuclear antigen EBNA3C. |
| GO:0005515 protein binding | IPI PMID:16762039 A L225A substitution in the human tumour suppressor HIC1 abo... | MODIFY | Summary: PMID:16762039 demonstrates CTBP1 interaction with HIC1 tumor suppressor. HIC1 is a DNA-binding transcription factor. Protein binding is too vague. Proposed replacements: DNA-binding transcription factor binding Supporting Evidence: PMID:16762039 2006 Jun 7. A L225A substitution in the human tumour suppressor HIC1 abolishes its interaction with the corepressor CtBP. |
| GO:0005515 protein binding | IPI PMID:17085477 ZNF366 is an estrogen receptor corepressor that acts through... | MODIFY | Summary: PMID:17085477 shows ZNF366 is an estrogen receptor corepressor that acts through CtBP. ZNF366 is a DNA-binding zinc-finger transcription factor. Protein binding is too vague. Proposed replacements: DNA-binding transcription factor binding Supporting Evidence: PMID:17085477 ZNF366 is an estrogen receptor corepressor that acts through CtBP and histone deacetylases. |
| GO:0005515 protein binding | IPI PMID:19486893 HIC1 interacts with a specific subunit of SWI/SNF complexes,... | UNDECIDED | Summary: PMID:19486893 is about HIC1 interacting with SWI/SNF subunit ARID1A. The direct relevance to CTBP1 protein binding is unclear from the title alone. Unable to fully assess without reading the full publication. Reason: Cannot determine the specific CTBP1 interaction described in this paper from the available abstract alone. Supporting Evidence: PMID:19486893 HIC1 interacts with a specific subunit of SWI/SNF complexes, ARID1A/BAF250A. |
| GO:0005515 protein binding | IPI PMID:19751731 C-terminal binding proteins (CtBPs) attenuate KLF4-mediated ... | MODIFY | Summary: PMID:19751731 describes CtBPs attenuating KLF4-mediated transcriptional activation. KLF4 is a DNA-binding transcription factor. Protein binding is too vague. Proposed replacements: DNA-binding transcription factor binding Supporting Evidence: PMID:19751731 Epub 2009 Sep 12. C-terminal binding proteins (CtBPs) attenuate KLF4-mediated transcriptional activation. |
| GO:0005515 protein binding | IPI PMID:20098713 A role for non-covalent SUMO interaction motifs in Pc2/CBX4 ... | MODIFY | Summary: PMID:20098713 describes CTBP1 interaction with Pc2/CBX4 in the context of SUMOylation. CBX4 is a Polycomb group protein that SUMOylates CTBP1. This could be more specifically annotated. Reason: CBX4/Pc2 functions as a transcriptional coregulator and SUMO E3 ligase for CTBP1. Proposed replacements: transcription coregulator binding Supporting Evidence: PMID:20098713 A role for non-covalent SUMO interaction motifs in Pc2/CBX4 E3 activity. |
| GO:0005515 protein binding | IPI PMID:20211142 An atlas of combinatorial transcriptional regulation in mous... | MARK AS OVER ANNOTATED | Summary: PMID:20211142 is a large-scale atlas study of combinatorial transcriptional regulation. Protein binding from HTP studies is uninformative for CTBP1 annotation. Reason: High-throughput study; protein binding is too vague to be useful. Supporting Evidence: PMID:20211142 An atlas of combinatorial transcriptional regulation in mouse and man. |
| GO:0005515 protein binding | IPI PMID:21044950 Genome-wide YFP fluorescence complementation screen identifi... | MARK AS OVER ANNOTATED | Summary: PMID:21044950 is a genome-wide YFP fluorescence complementation screen for telomere signaling. CTBP1 is not primarily involved in telomere signaling. This is a HTP screen result. Reason: High-throughput screen; protein binding is too vague and telomere function is not core to CTBP1. Supporting Evidence: PMID:21044950 Epub 2010 Nov 2. Genome-wide YFP fluorescence complementation screen identifies new regulators for telomere signaling in human cells. |
| GO:0005515 protein binding | IPI PMID:21900206 A directed protein interaction network for investigating int... | MARK AS OVER ANNOTATED | Summary: PMID:21900206 is a directed protein interaction network study. Protein binding from HTP studies is uninformative. Reason: High-throughput study; protein binding is too vague. Supporting Evidence: PMID:21900206 A directed protein interaction network for investigating intracellular signal transduction. |
| GO:0005515 protein binding | IPI PMID:21903422 Mapping a dynamic innate immunity protein interaction networ... | MARK AS OVER ANNOTATED | Summary: PMID:21903422 is a HTP mapping study of innate immunity protein interaction network. Protein binding is uninformative. Reason: High-throughput study; protein binding is too vague. Supporting Evidence: PMID:21903422 2011 Sep 8. Mapping a dynamic innate immunity protein interaction network regulating type I interferon production. |
| GO:0005515 protein binding | IPI PMID:21988832 Toward an understanding of the protein interaction network o... | MARK AS OVER ANNOTATED | Summary: PMID:21988832 is a HTP protein interaction network study of human liver. Protein binding is uninformative. Reason: High-throughput study; protein binding is too vague. Supporting Evidence: PMID:21988832 Toward an understanding of the protein interaction network of the human liver. |
| GO:0005515 protein binding | IPI PMID:24722188 Protein interaction network of alternatively spliced isoform... | MARK AS OVER ANNOTATED | Summary: PMID:24722188 is a HTP isoform interaction network study from brain. Protein binding is uninformative. Reason: High-throughput study; protein binding is too vague. Supporting Evidence: PMID:24722188 Protein interaction network of alternatively spliced isoforms from brain links genetic risk factors for autism. |
| GO:0005515 protein binding | IPI PMID:24981860 Human-chromatin-related protein interactions identify a deme... | MODIFY | Summary: PMID:24981860 identifies chromatin-related protein interactions including a demethylase complex. CTBP1 is known to associate with chromatin-modifying complexes (LSD1/CoREST). More specifically annotated as transcription coregulator binding. Proposed replacements: transcription coregulator binding Supporting Evidence: PMID:24981860 2014 Jun 26. Human-chromatin-related protein interactions identify a demethylase complex required for chromosome segregation. |
| GO:0005515 protein binding | IPI PMID:26496610 A human interactome in three quantitative dimensions organiz... | MARK AS OVER ANNOTATED | Summary: PMID:26496610 is a large-scale quantitative interactome study. Protein binding is uninformative. Reason: High-throughput study; protein binding is too vague. Supporting Evidence: PMID:26496610 Oct 22. A human interactome in three quantitative dimensions organized by stoichiometries and abundances. |
| GO:0005515 protein binding | IPI PMID:26807646 EXD2 promotes homologous recombination by facilitating DNA e... | MARK AS OVER ANNOTATED | Summary: PMID:26807646 is about EXD2 promoting homologous recombination. CTBP1 is not primarily a DNA repair protein. This likely reflects a HTP interaction. Reason: Tangential interaction; protein binding is too vague. Supporting Evidence: PMID:26807646 EXD2 promotes homologous recombination by facilitating DNA end resection. |
| GO:0005515 protein binding | IPI PMID:27705803 A High-Density Map for Navigating the Human Polycomb Complex... | MODIFY | Summary: PMID:27705803 maps the Polycomb complexome. CTBP1 is known to interact with Polycomb proteins (CBX4/Pc2). More informative than generic protein binding. Proposed replacements: transcription coregulator binding Supporting Evidence: PMID:27705803 A High-Density Map for Navigating the Human Polycomb Complexome. |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | MARK AS OVER ANNOTATED | Summary: PMID:28514442 is a large-scale interactome architecture study. Protein binding is uninformative. Reason: High-throughput study; protein binding is too vague. Supporting Evidence: PMID:28514442 Architecture of the human interactome defines protein communities and disease networks. |
| GO:0005515 protein binding | IPI PMID:28947780 ZNF516 suppresses EGFR by targeting the CtBP/LSD1/CoREST com... | MODIFY | Summary: PMID:28947780 shows ZNF516 suppresses EGFR by targeting the CtBP/LSD1/CoREST complex to chromatin. ZNF516 is a DNA-binding transcription factor recruiting the CTBP1 complex. Protein binding is too vague. Proposed replacements: DNA-binding transcription factor binding Supporting Evidence: PMID:28947780 ZNF516 suppresses EGFR by targeting the CtBP/LSD1/CoREST complex to chromatin. |
| GO:0005515 protein binding | IPI PMID:31041561 A pathogenic CtBP1 missense mutation causes altered cofactor... | MODIFY | Summary: PMID:31041561 describes a pathogenic CtBP1 missense mutation affecting cofactor binding and transcriptional activity. The protein binding here likely refers to self-association and partner interactions. Given CtBP1 forms homodimers, identical protein binding is already annotated. Protein binding is too vague. Proposed replacements: identical protein binding Supporting Evidence: PMID:31041561 2019 Apr 30. A pathogenic CtBP1 missense mutation causes altered cofactor binding and transcriptional activity. |
| GO:0005515 protein binding | IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari... | MARK AS OVER ANNOTATED | Summary: PMID:31515488 is a large-scale study of genetic variant effects on protein interactions. Protein binding is uninformative. Reason: High-throughput study; protein binding is too vague. Supporting Evidence: PMID:31515488 Extensive disruption of protein interactions by genetic variants across the allele frequency spectrum in human populations. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MARK AS OVER ANNOTATED | Summary: PMID:33961781 is a large-scale proteome network study. Protein binding is uninformative. Reason: High-throughput study; protein binding is too vague. Supporting Evidence: PMID:33961781 2021 May 6. Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. |
| GO:0005515 protein binding | IPI PMID:35016035 Identification and functional characterization of transcript... | MARK AS OVER ANNOTATED | Summary: PMID:35016035 is a large-scale study identifying transcriptional activators. Protein binding from HTP is uninformative. Reason: High-throughput study; protein binding is too vague. Supporting Evidence: PMID:35016035 2022 Jan 10. Identification and functional characterization of transcriptional activators in human cells. |
| GO:0005515 protein binding | IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce... | MARK AS OVER ANNOTATED | Summary: PMID:35271311 is the OpenCell large-scale endogenous tagging study. Protein binding is uninformative. Reason: High-throughput study; protein binding is too vague. Supporting Evidence: PMID:35271311 2022 Mar 11. OpenCell: Endogenous tagging for the cartography of human cellular organization. |
| GO:0005515 protein binding | IPI PMID:36414381 ZBTB18 inhibits SREBP-dependent lipid synthesis by halting C... | MODIFY | Summary: PMID:36414381 shows ZBTB18 inhibits lipid synthesis by halting CTBPs and LSD1 activity in glioblastoma. ZBTB18 is a DNA-binding transcription factor. Protein binding is too vague. Proposed replacements: DNA-binding transcription factor binding Supporting Evidence: PMID:36414381 Print 2023 Jan. ZBTB18 inhibits SREBP-dependent lipid synthesis by halting CTBPs and LSD1 activity in glioblastoma. |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | MARK AS OVER ANNOTATED | Summary: PMID:40205054 is a large-scale multimodal cell map study. Protein binding is uninformative. Reason: High-throughput study; protein binding is too vague. Supporting Evidence: PMID:40205054 Apr 9. Multimodal cell maps as a foundation for structural and functional genomics. |
| GO:0005515 protein binding | IPI PMID:7479821 Molecular cloning and characterization of a cellular phospho... | MODIFY | Summary: PMID:7479821 is the original cloning paper showing CTBP1 interacts with adenovirus E1A C-terminal domain. This is a specific viral protein interaction. Protein binding is too vague for this well-characterized interaction. Reason: E1A is a viral transcriptional regulator. The CTBP1-E1A interaction via PXDLS motif is the founding interaction for this protein. Proposed replacements: DNA-binding transcription factor binding Supporting Evidence: PMID:7479821 Molecular cloning and characterization of a cellular phosphoprotein that interacts with a conserved C-terminal domain of adenovirus E1A involved in negative modulation of oncogenic transformation. |
| GO:0005515 protein binding | IPI PMID:9535825 Interaction between a cellular protein that binds to the C-t... | MODIFY | Summary: PMID:9535825 describes the interaction between CTBP1 and a novel cellular protein (CtIP/RBBP8) disrupted by E1A through a PLDLS motif. This is a specific corepressor complex interaction. Reason: CtIP/RBBP8 participates in CtBP corepressor complexes. Proposed replacements: transcription coregulator binding Supporting Evidence: PMID:9535825 Interaction between a cellular protein that binds to the C-terminal region of adenovirus E1A (CtBP) and a novel cellular protein is disrupted by E1A through a conserved PLDLS motif. |
| GO:0042802 identical protein binding | IPI PMID:21988832 Toward an understanding of the protein interaction network o... | ACCEPT | Summary: CTBP1 forms homodimers, which is critical for its corepressor function. NAD/NADH binding promotes dimerization. Identical protein binding is well supported by crystal structures and biochemical data (PMID:12419229). Supporting Evidence: PMID:12419229 both a cofactor-dependent conformational change, with NAD(+) and NADH being equivalently effective, and the active site residues are linked to the binding of the PXDLS consensus recognition motif |
| GO:0042802 identical protein binding | IPI PMID:24722188 Protein interaction network of alternatively spliced isoform... | ACCEPT | Summary: CTBP1 homodimerization is well established. Duplicate evidence source is acceptable. Supporting Evidence: PMID:24722188 Protein interaction network of alternatively spliced isoforms from brain links genetic risk factors for autism. |
| GO:0042802 identical protein binding | IPI PMID:31041561 A pathogenic CtBP1 missense mutation causes altered cofactor... | ACCEPT | Summary: PMID:31041561 describes a pathogenic CTBP1 mutation affecting cofactor binding and transcriptional activity, which includes effects on self-association. Homodimerization is a core property. Supporting Evidence: PMID:31041561 2019 Apr 30. A pathogenic CtBP1 missense mutation causes altered cofactor binding and transcriptional activity. |
| GO:0042802 identical protein binding | IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari... | ACCEPT | Summary: Additional evidence for CTBP1 homodimerization from genetic variant disruption study. Homodimerization is well established. Supporting Evidence: PMID:31515488 Extensive disruption of protein interactions by genetic variants across the allele frequency spectrum in human populations. |
| GO:0003682 chromatin binding | IEA GO_REF:0000107 | ACCEPT | Summary: CTBP1 associates with chromatin as part of its corepressor complexes containing HDAC1/2, LSD1, CoREST. While it does not bind DNA directly, it is recruited to chromatin by DNA-binding partners. IEA from Ensembl ortholog transfer is reasonable. |
| GO:0017053 transcription repressor complex | IEA GO_REF:0000107 | ACCEPT | Summary: CTBP1 is a component of transcription repressor complexes. It assembles multi-protein corepressor complexes with HDAC1/2, LSD1/KDM1A, CoREST. IEA is consistent with IDA evidence from other annotations. |
| GO:0045892 negative regulation of DNA-templated transcription | IEA GO_REF:0000107 | ACCEPT | Summary: CTBP1 negatively regulates transcription by assembling corepressor complexes. IEA is consistent with extensive experimental evidence including PMID:19162039, PMID:21102443, and PMID:16287852. |
| GO:0048488 synaptic vesicle endocytosis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: CTBP1 has been reported to interact with presynaptic scaffold proteins (Bassoon) in neurons. Synaptic vesicle endocytosis is based on ortholog data. This is not the core function of CTBP1 but may reflect a specialized neuronal role. Reason: Neuronal-specific function transferred from mouse ortholog. Not a core function of CTBP1. |
| GO:0050872 white fat cell differentiation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: CTBP1 interacts with PRDM16 to repress WAT-specific genes. UniProt notes it functions in BAT differentiation. This is a pleiotropic consequence of corepressor activity, not a core function. Reason: Differentiation role is a downstream consequence of corepressor function. |
| GO:0061629 RNA polymerase II-specific DNA-binding transcription factor binding | IEA GO_REF:0000107 | ACCEPT | Summary: CTBP1 binds RNA Pol II-specific transcription factors like ZEB1/2, KLFs, BCL6 via PXDLS motifs. This is a more specific child of GO:0140297. IEA from Ensembl is appropriate. |
| GO:0097091 synaptic vesicle clustering | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: CTBP1 has reported synaptic roles through Bassoon interaction. This is a specialized neuronal function, not the core function of CTBP1. Reason: Neuronal-specific function. Not core to CTBP1. |
| GO:0098831 presynaptic active zone cytoplasmic component | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Based on ortholog evidence from mouse CTBP1 at presynaptic terminals via Bassoon interaction. Not a core localization for CTBP1. Reason: Neuronal-specific localization. Not core. |
| GO:0098978 glutamatergic synapse | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Synaptic localization is a specialized neuronal function of CTBP1, not its core localization. Reason: Neuronal-specific localization. Not core. |
| GO:0098982 GABA-ergic synapse | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Synaptic localization is a specialized neuronal function of CTBP1, not its core localization. Reason: Neuronal-specific localization. Not core. |
| GO:0106222 lncRNA binding | IEA GO_REF:0000107 | UNDECIDED | Summary: lncRNA binding for CTBP1 is not well supported in the literature reviewed. This may come from ortholog evidence but lacks clear validation for human CTBP1. Reason: Insufficient evidence in the reviewed literature to confirm lncRNA binding as a function of CTBP1. |
| GO:0005654 nucleoplasm | IDA GO_REF:0000052 | ACCEPT | Summary: Nucleoplasm localization is well supported by immunofluorescence data (HPA). CTBP1 is predominantly nuclear in its corepressor function. |
| GO:0016616 oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor | IDA PMID:12419229 Transcription corepressor CtBP is an NAD(+)-regulated dehydr... | ACCEPT | Summary: PMID:12419229 directly demonstrates CTBP1 dehydrogenase activity by biochemical and crystallographic methods. This is a core molecular function. Supporting Evidence: PMID:12419229 CtBP is a functional dehydrogenase. In addition, both a cofactor-dependent conformational change, with NAD(+) and NADH being equivalently effective, and the active site residues are linked to the binding of the PXDLS consensus recognition motif on repressors |
| GO:0051287 NAD binding | IDA PMID:12419229 Transcription corepressor CtBP is an NAD(+)-regulated dehydr... | ACCEPT | Summary: PMID:12419229 provides crystal structure (1.95A) of CTBP1 in complex with NAD, directly demonstrating NAD binding. This is a core molecular function. Supporting Evidence: PMID:12419229 CtBP is an NAD(+)-regulated component of critical complexes for specific repression events in cells. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-3108209 | ACCEPT | Summary: Nucleoplasm localization from Reactome SUMOylation pathway. CTBP1 is SUMOylated at Lys-428 by CBX4 in the nucleus (PMID:12679040). Consistent with nuclear localization. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-3108203 | ACCEPT | Summary: Same as above. Nucleoplasm is the site of CTBP1 SUMOylation events. Consistent with established nuclear localization. |
| GO:0140297 DNA-binding transcription factor binding | IPI PMID:16609867 The FoxP subclass in Xenopus laevis development. | ACCEPT | Summary: PMID:16609867 describes interaction of CTBP1 with FOXP1. UniProt confirms this interaction. FOXP1 is a DNA-binding transcription factor. Directly supports this annotation. Supporting Evidence: PMID:16609867 The FoxP subclass in Xenopus laevis development. |
| GO:0005515 protein binding | IPI PMID:23707407 PLEIAD/SIMC1/C5orf25, a novel autolysis regulator for a skel... | MODIFY | Summary: PMID:23707407 describes interaction between SIMC1 and CTBP1, where SIMC1 scaffolds CAPN3-mediated cleavage of CTBP1. This is a specific protein interaction but protein binding is too vague. Reason: SIMC1 interacts with CTBP1 through specific domains. UniProt confirms the interaction and identifies specific mutagenesis sites that disrupt it. Proposed replacements: protein domain specific binding Supporting Evidence: PMID:23707407 2013 May 21. PLEIAD/SIMC1/C5orf25, a novel autolysis regulator for a skeletal-muscle-specific calpain, CAPN3, scaffolds a CAPN3 substrate, CTBP1. |
| GO:0001222 transcription corepressor binding | IPI PMID:29628311 A Family of Vertebrate-Specific Polycombs Encoded by the LCO... | ACCEPT | Summary: PMID:29628311 describes LCOR/LCORL family as vertebrate-specific Polycombs that interact with CTBP1. LCOR functions as a corepressor. This annotation correctly captures CTBP1 binding to a transcription corepressor. Supporting Evidence: PMID:29628311 A Family of Vertebrate-Specific Polycombs Encoded by the LCOR/LCORL Genes Balance PRC2 Subtype Activities. |
| GO:0005515 protein binding | IPI PMID:25728771 MCRIP1, an ERK substrate, mediates ERK-induced gene silencin... | MODIFY | Summary: PMID:25728771 describes MCRIP1 as an ERK substrate that competitively inhibits CtBP-ZEB1 interaction via its PXDLS motif. This is a specific coregulator interaction. Protein binding is too vague. Reason: MCRIP1 regulates CTBP1 corepressor function through competitive binding. Proposed replacements: transcription coregulator binding Supporting Evidence: PMID:25728771 Feb 26. MCRIP1, an ERK substrate, mediates ERK-induced gene silencing during epithelial-mesenchymal transition by regulating the co-repressor CtBP. |
| GO:0005634 nucleus | IDA PMID:16702210 Zinc finger protein Wiz links G9a/GLP histone methyltransfer... | ACCEPT | Summary: PMID:16702210 shows CTBP1 in the nucleus via its interaction with WIZ, which links G9a/GLP histone methyltransferases to CTBP1. Nuclear localization is well established. Supporting Evidence: PMID:16702210 Zinc finger protein Wiz links G9a/GLP histone methyltransferases to the co-repressor molecule CtBP. |
| GO:0005515 protein binding | IPI PMID:16702210 Zinc finger protein Wiz links G9a/GLP histone methyltransfer... | MODIFY | Summary: PMID:16702210 demonstrates WIZ links G9a/GLP histone methyltransferases to CtBP. WIZ is a zinc finger protein functioning as a transcriptional coregulator. Protein binding is too vague. Proposed replacements: transcription coregulator binding Supporting Evidence: PMID:16702210 2006 May 15. Zinc finger protein Wiz links G9a/GLP histone methyltransferases to the co-repressor molecule CtBP. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-3361751 | ACCEPT | Summary: Nucleoplasm localization from Reactome pathway Reactome:R-HSA-3361751. CTBP1 functions in the nucleoplasm as a transcriptional corepressor in Wnt signaling and other pathways. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-3364042 | ACCEPT | Summary: Nucleoplasm localization from Reactome pathway Reactome:R-HSA-3364042. CTBP1 functions in the nucleoplasm as a transcriptional corepressor in Wnt signaling and other pathways. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5334050 | ACCEPT | Summary: Nucleoplasm localization from Reactome pathway Reactome:R-HSA-5334050. CTBP1 functions in the nucleoplasm as a transcriptional corepressor in Wnt signaling and other pathways. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5334052 | ACCEPT | Summary: Nucleoplasm localization from Reactome pathway Reactome:R-HSA-5334052. CTBP1 functions in the nucleoplasm as a transcriptional corepressor in Wnt signaling and other pathways. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9765973 | ACCEPT | Summary: Nucleoplasm localization from Reactome pathway Reactome:R-HSA-9765973. CTBP1 functions in the nucleoplasm as a transcriptional corepressor in Wnt signaling and other pathways. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9765974 | ACCEPT | Summary: Nucleoplasm localization from Reactome pathway Reactome:R-HSA-9765974. CTBP1 functions in the nucleoplasm as a transcriptional corepressor in Wnt signaling and other pathways. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9768477 | ACCEPT | Summary: Nucleoplasm localization from Reactome pathway Reactome:R-HSA-9768477. CTBP1 functions in the nucleoplasm as a transcriptional corepressor in Wnt signaling and other pathways. |
| GO:0003714 transcription corepressor activity | IDA PMID:19162039 Hepatoma-derived growth factor represses SET and MYND domain... | ACCEPT | Summary: PMID:19162039 directly demonstrates CTBP1 corepressor activity. HDGF represses SMYD1 gene transcription through interaction with CtBP. Over-expression of CtBP potentiated the trans-repressive activity of HDGF; knocking down CtBP attenuated the effect. Supporting Evidence: PMID:19162039 Over-expression of CtBP potentiated the trans-repressive activity of HDGF; on the other hand, knocking down CtBP attenuated the trans-repressive effect of HDGF. |
| GO:0140297 DNA-binding transcription factor binding | IPI PMID:19162039 Hepatoma-derived growth factor represses SET and MYND domain... | ACCEPT | Summary: PMID:19162039 demonstrates CTBP1 binding to HDGF via a non-canonical PXDLS motif (PKDLF). HDGF acts as a transcriptional repressor. Directly supports this annotation. Supporting Evidence: PMID:19162039 HDGF binds CtBP through a non-canonical binding motif (PKDLF) within the PWWP domain, as mutation of DL to AS abolished HDGF and CtBP interaction |
| GO:0000122 negative regulation of transcription by RNA polymerase II | IMP PMID:19162039 Hepatoma-derived growth factor represses SET and MYND domain... | ACCEPT | Summary: PMID:19162039 demonstrates CTBP1 participates in negative regulation of SMYD1 transcription. HDGF-CtBP complex represses SMYD1 promoter activity. IMP evidence is appropriate. Supporting Evidence: PMID:19162039 in G-7 myoblast cells, over-expression of a GFP-HDGF fusion specifically downregulated SMYD1 mRNA expression and the activity of the human SMYD1 promoter |
| GO:0017053 transcription repressor complex | IDA PMID:19162039 Hepatoma-derived growth factor represses SET and MYND domain... | ACCEPT | Summary: PMID:19162039 demonstrates CTBP1 forms a transcriptional complex with HDGF for gene repression. CTBP1 is a well-established component of transcription repressor complexes. Supporting Evidence: PMID:19162039 fluorescent microscopy showed that HDGF induced the nuclear accumulation of CtBP, suggesting that HDGF forms a transcriptional complex with CtBP |
| GO:0019904 protein domain specific binding | IDA PMID:19162039 Hepatoma-derived growth factor represses SET and MYND domain... | ACCEPT | Summary: PMID:19162039 demonstrates CTBP1 binds specifically to the PKDLF motif within the PWWP domain of HDGF. Mutation of this motif abolishes the interaction. This is protein domain specific binding. Supporting Evidence: PMID:19162039 HDGF binds CtBP through a non-canonical binding motif (PKDLF) within the PWWP domain, as mutation of DL to AS abolished HDGF and CtBP interaction |
| GO:0003714 transcription corepressor activity | IDA PMID:16287852 RBP-Jkappa/SHARP recruits CtIP/CtBP corepressors to silence ... | ACCEPT | Summary: PMID:16287852 demonstrates CtBP corepressor activity in the context of Notch signaling. CtBP augments SHARP-mediated repression and is required for repression of Notch target gene Hey1. Supporting Evidence: PMID:16287852 Transcriptional repression of the Notch target gene Hey1 is abolished in CtBP-deficient cells or after the functional knockout of CtBP. |
| GO:0005515 protein binding | IPI PMID:16287852 RBP-Jkappa/SHARP recruits CtIP/CtBP corepressors to silence ... | MODIFY | Summary: PMID:16287852 shows CTBP1 interaction with CtIP and SHARP within the RBP-Jkappa/SHARP corepressor complex. Protein binding is too vague for this specific corepressor complex interaction. Reason: CtIP and SHARP are corepressor complex components that interact with CTBP1. Proposed replacements: transcription coregulator binding Supporting Evidence: PMID:16287852 RBP-Jkappa/SHARP recruits CtIP/CtBP corepressors to silence Notch target genes. |
| GO:0017053 transcription repressor complex | IDA PMID:16287852 RBP-Jkappa/SHARP recruits CtIP/CtBP corepressors to silence ... | ACCEPT | Summary: PMID:16287852 directly demonstrates CTBP1 as a component of the RBP-Jkappa/SHARP-CtIP-CtBP corepressor complex that silences Notch target genes. Supporting Evidence: PMID:16287852 We identify the CtIP and CtBP corepressors as novel components of the human RBP-Jkappa/SHARP-corepressor complex |
| GO:0000122 negative regulation of transcription by RNA polymerase II | IMP PMID:21102443 Transcriptional regulation of BRCA1 expression by a metaboli... | ACCEPT | Summary: PMID:21102443 directly demonstrates CTBP1 negatively regulates BRCA1 transcription. CtBP assembles at the BRCA1 promoter as part of a corepressor complex containing HDAC1. CtBP depletion increases BRCA1 expression. Supporting Evidence: PMID:21102443 Silencing of CtBP expression in MCF-7 cells results in a significant increase in both BRCA1 protein and BRCA1 RNA message (nascent and mature). |
| GO:0051726 regulation of cell cycle | IMP PMID:21102443 Transcriptional regulation of BRCA1 expression by a metaboli... | KEEP AS NON CORE | Summary: PMID:21102443 shows CtBP depletion induces a cell cycle block in G2 phase, mimicking BRCA1 over-expression effects. This is a downstream consequence of CTBP1 corepressor activity on cell cycle regulators, not a direct cell cycle function. Reason: Cell cycle regulation is an indirect consequence of CTBP1 transcriptional corepression of BRCA1 and other targets. Supporting Evidence: PMID:21102443 CtBP depletion also mimics the functional influences of BRCA1 over-expression 12 by inducing a cell cycle block in G2 phase (Fig |
| GO:0005515 protein binding | IPI PMID:19505873 Complementary quantitative proteomics reveals that transcrip... | MODIFY | Summary: PMID:19505873 identifies CTBP1 in an AP-4 mediated transcriptional repression complex for HDM2. AP-4/TFAP4 is a DNA-binding transcription factor. Protein binding is too vague. Proposed replacements: DNA-binding transcription factor binding Supporting Evidence: PMID:19505873 Epub 2009 Jun 7. Complementary quantitative proteomics reveals that transcription factor AP-4 mediates E-box-dependent complex formation for transcriptional repression of HDM2. |
| GO:0005515 protein binding | IPI PMID:11568182 Interaction of EVI1 with cAMP-responsive element-binding pro... | MODIFY | Summary: PMID:11568182 describes CTBP1 interaction with MECOM/EVI1. MECOM is a DNA-binding transcription factor. Protein binding is too vague. Proposed replacements: DNA-binding transcription factor binding Supporting Evidence: PMID:11568182 2001 Sep 21. Interaction of EVI1 with cAMP-responsive element-binding protein-binding protein (CBP) and p300/CBP-associated factor (P/CAF) results in reversible acetylation of EVI1 and in co-localization in nuclear speckles. |
| GO:0005515 protein binding | IPI PMID:15897867 Oligomerization of Evi-1 regulated by the PR domain contribu... | MODIFY | Summary: PMID:15897867 shows oligomerization of Evi-1/MECOM regulated by the PR domain contributes to recruitment of corepressor CtBP. MECOM is a DNA-binding transcription factor. Protein binding is too vague. Proposed replacements: DNA-binding transcription factor binding Supporting Evidence: PMID:15897867 Oligomerization of Evi-1 regulated by the PR domain contributes to recruitment of corepressor CtBP. |
| GO:0051287 NAD binding | ISS GO_REF:0000024 | ACCEPT | Summary: NAD binding is well established for CTBP1 by crystal structure and biochemistry (PMID:12419229). ISS annotation is consistent with IDA evidence. |
| GO:0019904 protein domain specific binding | IPI PMID:18374649 TBL1 and TBLR1 phosphorylation on regulated gene promoters o... | ACCEPT | Summary: PMID:18374649 describes TBL1/TBLR1 phosphorylation overcoming dual CtBP and NCoR/SMRT repression checkpoints. CTBP1 recognizes PXDLS domains specifically, supporting protein domain specific binding. Supporting Evidence: PMID:18374649 TBL1 and TBLR1 phosphorylation on regulated gene promoters overcomes dual CtBP and NCoR/SMRT transcriptional repression checkpoints. |
| GO:0005634 nucleus | ISS GO_REF:0000024 | ACCEPT | Summary: Nuclear localization is well established for CTBP1. ISS is consistent with IDA and IBA evidence. |
| GO:0017053 transcription repressor complex | ISS GO_REF:0000024 | ACCEPT | Summary: CTBP1 is a well-established component of transcription repressor complexes. ISS is consistent with IDA evidence from multiple publications. |
| GO:0045892 negative regulation of DNA-templated transcription | ISS GO_REF:0000024 | ACCEPT | Summary: CTBP1 negatively regulates DNA-templated transcription. ISS is consistent with extensive experimental evidence. |
| GO:0050872 white fat cell differentiation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: CTBP1 interacts with PRDM16 to repress WAT-specific genes. UniProt confirms function in BAT differentiation. This is a pleiotropic consequence of corepressor activity. Reason: WAT differentiation is a downstream consequence of CTBP1 corepressor function, not a core function. |
| GO:0019079 viral genome replication | TAS PMID:7479821 Molecular cloning and characterization of a cellular phospho... | MARK AS OVER ANNOTATED | Summary: PMID:7479821 describes CTBP1 interaction with adenovirus E1A and suggests a role in adenovirus replication. However, CTBP1 is not directly involved in viral genome replication; rather, the E1A-CtBP interaction modulates transformation and indirectly affects replication. The annotation over-attributes a direct viral replication function. Reason: CTBP1 does not directly participate in viral genome replication. The E1A interaction modulates cellular transcription. PMID:23747199 suggests the interaction potentiates viral replication but CTBP1 is a host transcriptional corepressor, not a replication factor. Supporting Evidence: PMID:7479821 These results suggest that interaction of CtBP with the E1A proteins may play a critical role in adenovirus replication and oncogenic transformation. |
| GO:0005515 protein binding | TAS PMID:8440238 A region in the C-terminus of adenovirus 2/5 E1a protein is ... | MODIFY | Summary: PMID:8440238 describes the interaction between CTBP1 and adenovirus E1A C-terminal domain. E1A is a viral transcriptional regulator. Protein binding is too vague. Proposed replacements: DNA-binding transcription factor binding Supporting Evidence: PMID:8440238 A region in the C-terminus of adenovirus 2/5 E1a protein is required for association with a cellular phosphoprotein and important for the negative modulation of T24-ras mediated transformation, tumorigenesis and metastasis. |
| GO:0006468 protein phosphorylation | TAS PMID:8440238 A region in the C-terminus of adenovirus 2/5 E1a protein is ... | REMOVE | Summary: MISANNOTATION: CTBP1 is a transcriptional corepressor, NOT a kinase. PMID:8440238 explicitly describes CTBP1 as being phosphorylated: "CtBP is a phosphoprotein and the level of phosphorylation of CtBP appears to be regulated during the cell cycle". UniProt shows CTBP1 is "phosphorylated by HIPK2" at Ser-422. CTBP1 is a SUBSTRATE of kinases, not an enzyme that performs phosphorylation. Supporting Evidence: PMID:8440238 A region in the C-terminus of adenovirus 2/5 E1a protein is required for association with a cellular phosphoprotein and important for the negative modulation of T24-ras mediated transformation, tumorigenesis and metastasis. |
| GO:0008285 negative regulation of cell population proliferation | TAS PMID:7479821 Molecular cloning and characterization of a cellular phospho... | MARK AS OVER ANNOTATED | Summary: PMID:7479821 describes CTBP1 in the context of E1A-mediated modulation of oncogenic transformation. The paper does not directly demonstrate CTBP1 negatively regulates cell proliferation; rather, the E1A-CtBP interaction modulates transformation. This over-attributes a direct antiproliferative function to CTBP1. Reason: The negative regulation of proliferation is attributed to the E1A-CtBP interaction in the context of transformation, not to CTBP1 alone. Supporting Evidence: PMID:7479821 a region located between residues 225 and 238 of the 243R E1A protein negatively modulates in vitro T24 ras cooperative transformation as well as the tumorigenic potential of E1A/T24 ras-transformed cells |
| GO:0005515 protein binding | IPI PMID:12052894 The human candidate tumor suppressor gene HIC1 recruits CtBP... | MODIFY | Summary: PMID:12052894 demonstrates CTBP1 interaction with HIC1 through a degenerate GLDLSKK motif. HIC1 is a DNA-binding transcription factor/tumor suppressor. Protein binding is too vague. Proposed replacements: DNA-binding transcription factor binding Supporting Evidence: PMID:12052894 The human candidate tumor suppressor gene HIC1 recruits CtBP through a degenerate GLDLSKK motif. |
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