MAML1 is a nuclear transcriptional coactivator in the canonical Notch transcription activation complex. It binds Notch intracellular domains with RBPJ/CSL to promote transcription of Notch target genes such as HES1, and can recruit additional coactivator machinery including CREBBP/EP300 and CDK8.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005654 nucleoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: MAML1 is consistently described as a nuclear coactivator that functions in DNA-bound Notch transcription complexes. Reason: Nucleoplasm/nucleus localization is the supported cellular context for the core transcriptional coactivator function. Supporting Evidence: PMID:11101851 Here we clone MAML1, a human homologue of the Drosophila gene Mastermind, and show that it encodes a protein of 130 kD localizing to nuclear bodies. file:human/MAML1/MAML1-deep-research-falcon.md Nuclear localization is well supported; “nucleoplasm” is reasonable, but exact subnuclear assignment depends on assay context. |
| GO:0003713 transcription coactivator activity | IBA GO_REF:0000033 | ACCEPT | Summary: MAML1 is a transcriptional coactivator for Notch intracellular domain complexes and also has evidence for p53 coactivator activity. Reason: The term captures the principal molecular role of MAML1. Direct experiments show MAML1 amplifies Notch-induced HES1 transcription and acts as a coactivator in p53-dependent transcription. Supporting Evidence: PMID:11101851 MAML1 binds to the ankyrin repeat domain of all four mammalian NOTCH receptors, forms a DNA-binding complex with ICN and RBP-Jkappa, and amplifies NOTCH-induced transcription of HES1. PMID:17317671 Overexpression of wild-type MAML1 as well as a mutant, defective in Notch signaling, enhanced the p53-dependent gene induction in mammalian cells, whereas MAML1 knockdown reduced the p53-dependent gene expression. |
| GO:0007221 positive regulation of transcription of Notch receptor target | IBA GO_REF:0000033 | ACCEPT | Summary: MAML1 positively regulates transcription of Notch receptor target genes through the ICN-RBPJ/CSL-MAML transcriptional activation complex. Reason: Direct reporter and complex-assembly evidence supports MAML1-dependent activation of HES1-class Notch target transcription. Supporting Evidence: PMID:11101851 MAML1 binds to the ankyrin repeat domain of all four mammalian NOTCH receptors, forms a DNA-binding complex with ICN and RBP-Jkappa, and amplifies NOTCH-induced transcription of HES1. file:human/MAML1/MAML1-deep-research-falcon.md The strongest direct evidence for MAML1 typically reads out **transcriptional activation** (HES/HES4/DTX1 reporters; chromatin templates; ChIP-linked acetylation changes), supporting specific transcriptional regulation terms rather than broad pathway-level terms (which can be context- and tissue-dependent). |
| GO:0003713 transcription coactivator activity | IEA GO_REF:0000120 | ACCEPT | Summary: MAML1's transcription coactivator activity is supported by direct experimental evidence and is not just an automated inference. Reason: This is the core molecular function of MAML1 in Notch transcriptional activation. Supporting Evidence: PMID:11101851 MAML1 binds to the ankyrin repeat domain of all four mammalian NOTCH receptors, forms a DNA-binding complex with ICN and RBP-Jkappa, and amplifies NOTCH-induced transcription of HES1. |
| GO:0007219 Notch signaling pathway | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: MAML1 participates in canonical Notch signaling through the nuclear transcriptional activation step. Reason: The broad pathway term is defensible, but Falcon and the primary literature indicate the more precise curatable process is positive regulation of transcription of Notch target genes. Supporting Evidence: PMID:11390662 hMam-1 stabilizes and participates in the DNA binding complex of the intracellular domain of human Notch1 and a CSL protein. file:human/MAML1/MAML1-deep-research-falcon.md **Prefer “Notch target gene transcription” over broad “Notch signaling pathway”** unless direct pathway-level phenotypes are tied specifically to human MAML1 (not dnMAML pan-inhibition, not paralog redundancy). |
| GO:0007221 positive regulation of transcription of Notch receptor target | IEA GO_REF:0000002 | ACCEPT | Summary: MAML1 positively regulates transcription of Notch receptor target genes through the ICN-RBPJ/CSL-MAML transcriptional activation complex. Reason: This term is more specific than broad Notch signaling pathway and is directly supported by HES1 activation evidence. Supporting Evidence: PMID:11101851 MAML1 binds to the ankyrin repeat domain of all four mammalian NOTCH receptors, forms a DNA-binding complex with ICN and RBP-Jkappa, and amplifies NOTCH-induced transcription of HES1. |
| GO:0016607 nuclear speck | IEA GO_REF:0000120 | MARK AS OVER ANNOTATED | Summary: Nuclear subcompartment localization has been reported, but Falcon cautions that nuclear-body/speck evidence is often overexpression-based. Reason: The broader nuclear/nucleoplasm localization is well supported, whereas nuclear speck is more specific than the strongest direct evidence warrants for a core annotation. Supporting Evidence: file:human/MAML1/MAML1-deep-research-falcon.md **Nuclear bodies/specks:** nuclear-body localization is supported but is **often overexpression-linked**; annotate cautiously at specific subnuclear compartments. |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IEA GO_REF:0000120 | ACCEPT | Summary: MAML1 positively regulates RNA polymerase II transcription by acting as a coactivator in Notch and p53-responsive transcriptional complexes. Reason: The term is broad, but it is directly supported by MAML1-dependent activation of Notch target transcription and p53-dependent gene induction. Supporting Evidence: PMID:11101851 MAML1 binds to the ankyrin repeat domain of all four mammalian NOTCH receptors, forms a DNA-binding complex with ICN and RBP-Jkappa, and amplifies NOTCH-induced transcription of HES1. PMID:17317671 Overexpression of wild-type MAML1 as well as a mutant, defective in Notch signaling, enhanced the p53-dependent gene induction in mammalian cells, whereas MAML1 knockdown reduced the p53-dependent gene expression. |
| GO:0005515 protein binding | IPI PMID:12370315 Identification of a family of mastermind-like transcriptiona... | MARK AS OVER ANNOTATED | Summary: Bare protein binding row from an IntAct interaction with RBPJ/CSL (UniProtKB:P46531). The underlying interaction is real, but the term is uninformative. Reason: Per curation guidelines, bare protein binding (GO:0005515) is not informative about MAML1's molecular function. The biological substance of this RBPJ/CSL interaction (assembly of the Notch transcription activation complex) is captured by the accepted transcription coactivator activity (GO:0003713) and the MAML1-RBP-Jkappa-ICN1 complex (GO:0002193) annotations. Supporting Evidence: PMID:12370315 Identification of a family of mastermind-like transcriptional coactivators for mammalian notch receptors. |
| GO:0005515 protein binding | IPI PMID:16530044 Structural basis for cooperativity in recruitment of MAML co... | MARK AS OVER ANNOTATED | Summary: Bare protein binding row from the crystal structure of the Notch transcription complex showing MAML recruitment to NICD-RBPJ. The interaction is well established but the term is uninformative. Reason: GO:0005515 protein binding is uninformative. The structurally characterized MAML1 recruitment to the NICD-RBPJ complex is captured by the accepted transcription coactivator activity and the MAML1-RBP-Jkappa-ICN1 complex annotations. Supporting Evidence: PMID:16530044 Structural basis for cooperativity in recruitment of MAML coactivators to Notch transcription complexes. |
| GO:0005515 protein binding | IPI PMID:18427106 Notch signaling mediates hypoxia-induced tumor cell migratio... | MARK AS OVER ANNOTATED | Summary: Bare protein binding row derived from an IntAct interaction with RBPJ/CSL (UniProtKB:P46531) catalogued in a Notch/hypoxia paper. The term is uninformative. Reason: GO:0005515 protein binding does not describe a molecular function. The MAML1-RBPJ interaction underlying these IntAct rows is already represented by the accepted Notch transcription coactivator and complex membership annotations. Supporting Evidence: PMID:18427106 Notch signaling mediates hypoxia-induced tumor cell migration and invasion. |
| GO:0005515 protein binding | IPI PMID:19907488 Direct inhibition of the NOTCH transcription factor complex. | MARK AS OVER ANNOTATED | Summary: Bare protein binding row from the SAHM1 stapled-peptide study that targets the MAML1-NICD-RBPJ transcription complex. The interaction is genuine but the term is uninformative. Reason: GO:0005515 protein binding is uninformative; the functional content (MAML1 as a coactivator within the Notch transcription factor complex) is captured by accepted MF and complex annotations. Supporting Evidence: PMID:19907488 Direct inhibition of the NOTCH transcription factor complex. |
| GO:0005515 protein binding | IPI PMID:20972443 Structural and mechanistic insights into cooperative assembl... | MARK AS OVER ANNOTATED | Summary: Bare protein binding row from a structural study of dimeric Notch transcription complexes that include MAML. The interaction is genuine but the term is uninformative. Reason: GO:0005515 protein binding adds no functional information beyond the accepted coactivator and Notch transcription complex annotations. Supporting Evidence: PMID:20972443 Structural and mechanistic insights into cooperative assembly of dimeric Notch transcription complexes. |
| GO:0005515 protein binding | IPI PMID:22325781 Conformational locking upon cooperative assembly of notch tr... | MARK AS OVER ANNOTATED | Summary: Bare protein binding row from an X-ray/HX-MS structural study of the human MAML1/RAM/ANK/CSL/DNA Notch transcription complex. The interaction is well established but the term is uninformative. Reason: GO:0005515 protein binding is uninformative about molecular function. The structurally characterized MAML1 recruitment to the NICD-CSL complex is already captured by the accepted transcription coactivator activity (GO:0003713) and MAML1-RBP-Jkappa-ICN1 complex (GO:0002193) annotations. Supporting Evidence: PMID:22325781 we report the X-ray structure of a human MAML1/RAM/ANK/CSL/DNA complex, and probe changes in component dynamics upon stepwise assembly of a MAML1/NICD/CSL complex using HX-MS. |
| GO:0005515 protein binding | IPI PMID:23022380 NOTCH1 nuclear interactome reveals key regulators of its tra... | MARK AS OVER ANNOTATED | Summary: Bare protein binding row derived from a NOTCH1 nuclear interactome study that confirms MAML1 as part of the core ICN1-CSL-MAML1 activation complex. The interaction is genuine but the term is uninformative. Reason: GO:0005515 protein binding does not describe a molecular function. The MAML1 membership in the Notch core activation complex described here is already captured by the accepted transcription coactivator activity and MAML1-RBP-Jkappa-ICN1 complex annotations. Supporting Evidence: PMID:23022380 beyond the well-characterized core activation complex (ICN1-CSL-MAML1), NOTCH1 assembles a multifunctional complex |
| GO:0005634 nucleus | IEA GO_REF:0000120 | ACCEPT | Summary: MAML1 is a nuclear protein with an NLS that functions in DNA-bound Notch transcription complexes; nuclear localization is well supported. Reason: Nuclear localization is robustly supported by direct experimental evidence (PMID:11101851) and is consistent with the core transcriptional coactivator function. The IEA term is appropriate, if broader than the nucleoplasm assignment. Supporting Evidence: PMID:11101851 Here we clone MAML1, a human homologue of the Drosophila gene Mastermind, and show that it encodes a protein of 130 kD localizing to nuclear bodies. |
| GO:0010831 positive regulation of myotube differentiation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: MAML1 promotes myotube formation as a coactivator for MEF2C, an activity documented in mouse and transferred to human by ortholog inference. Reason: Maml1-null fibroblasts fail MyoD-induced differentiation and MAML1 overexpression enhances myotube formation, supporting positive regulation of myotube differentiation. This is a genuine Notch- independent (MEF2C) function but is peripheral to the core Notch coactivator role. Supporting Evidence: PMID:16510869 overexpression of MAML1 in C2C12 cells dramatically enhanced myotube formation and increased the expression of muscle-specific genes, while RNA interference (RNAi)-mediated MAML1 knockdown abrogated differentiation. |
| GO:0045445 myoblast differentiation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: MAML1 is required for myogenic differentiation, documented in mouse and transferred to human by ortholog inference. Reason: Maml1-null embryonic fibroblasts fail to undergo MyoD-induced myogenic differentiation, supporting a role in myoblast/muscle differentiation. This is a genuine but non-core (MEF2C-mediated, Notch-independent) process relative to the core Notch coactivator function. Supporting Evidence: PMID:16510869 In vitro, Maml1-null embryonic fibroblasts failed to undergo MyoD-induced myogenic differentiation, further suggesting that Maml1 is required for muscle development. |
| GO:0051149 positive regulation of muscle cell differentiation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: MAML1 positively regulates muscle cell differentiation via MEF2C coactivation, documented in mouse and transferred by ortholog inference. Reason: MAML1 enhances muscle-specific gene expression and myotube formation and is required for myogenesis. This supports positive regulation of muscle cell differentiation, a genuine but non-core function relative to the core Notch coactivator role. Supporting Evidence: PMID:16510869 overexpression of MAML1 in C2C12 cells dramatically enhanced myotube formation and increased the expression of muscle-specific genes |
| GO:0060928 atrioventricular node cell development | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Cardiac/atrioventricular node development is attributed to MAML1 via Notch-pathway roles in the mouse ortholog and transferred to human by automated ortholog inference. Reason: AV node development is a plausible developmental output of MAML-dependent Notch signaling, but direct attribution to human MAML1 is indirect (ortholog/pathway-based, with potential MAML paralog redundancy). Keep as a non-core developmental annotation rather than a core function. Supporting Evidence: file:human/MAML1/MAML1-deep-research-falcon.md Avoid over-broad human MAML1 developmental annotations unless supported by direct gene-specific experiments; dnMAML affects multiple MAML paralogs/pathway output. |
| GO:0005654 nucleoplasm | IDA GO_REF:0000052 | ACCEPT | Summary: Direct immunofluorescence localization (Human Protein Atlas) places MAML1 in the nucleoplasm, consistent with its nuclear coactivator role. Reason: Nucleoplasm is the supported subnuclear compartment for MAML1's DNA-bound transcriptional coactivator function, corroborated by direct experimental nuclear localization in the primary literature. Supporting Evidence: PMID:11101851 Here we clone MAML1, a human homologue of the Drosophila gene Mastermind, and show that it encodes a protein of 130 kD localizing to nuclear bodies. |
| GO:0005634 nucleus | IDA PMID:32601208 Pharmacological disruption of the Notch transcription factor... | ACCEPT | Summary: MAML1 acts as part of the nuclear Notch transcription factor complex, the target of the small-molecule inhibitor characterized in this study. Reason: Nuclear localization is the supported cellular context for MAML1's function within the Notch transcription activation complex. Supporting Evidence: PMID:32601208 the use of drug-like small molecules to target the downstream mediators of Notch signaling, the Notch transcription activation complex |
| GO:0007219 Notch signaling pathway | IDA PMID:32601208 Pharmacological disruption of the Notch transcription factor... | KEEP AS NON CORE | Summary: MAML1 is a component of the Notch transcription activation complex whose pharmacological disruption inhibits Notch signaling output. Reason: The broad pathway term is defensible as context, but the more precise curatable process for MAML1's direct role is positive regulation of transcription of Notch target genes. Keep this as non-core. Supporting Evidence: PMID:32601208 we describe a pharmacological strategy that interferes with Notch signaling by disrupting the Notch transcription complex |
| GO:0045893 positive regulation of DNA-templated transcription | IDA PMID:32601208 Pharmacological disruption of the Notch transcription factor... | ACCEPT | Summary: As a component of the Notch transcription activation complex, MAML1 positively regulates transcription of Notch target genes. Reason: Positive regulation of DNA-templated transcription is supported by MAML1's coactivator role in the Notch transcription complex; disrupting the complex reduces this transcriptional output. The more specific RNA Pol II and Notch-target-gene terms are also annotated. Supporting Evidence: PMID:32601208 we describe a pharmacological strategy that interferes with Notch signaling by disrupting the Notch transcription complex |
| GO:0003162 atrioventricular node development | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Atrioventricular node development is inferred for MAML1 by curator sequence-similarity transfer (ISS) from Notch pathway components, not from direct human MAML1 experiments. Reason: AV node development is a plausible developmental consequence of MAML-dependent Notch signaling, but the attribution to human MAML1 is indirect (ISS from NOTCH/ortholog) and subject to MAML paralog redundancy. Retain as a non-core developmental annotation. Supporting Evidence: file:human/MAML1/MAML1-deep-research-falcon.md Avoid over-broad human MAML1 developmental annotations unless supported by direct gene-specific experiments; dnMAML affects multiple MAML paralogs/pathway output. |
| GO:0060928 atrioventricular node cell development | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Atrioventricular node cell development is inferred for MAML1 by curator sequence-similarity transfer (ISS) from the mouse Maml1 ortholog, not from direct human MAML1 experiments. Reason: This duplicates the IEA AV node cell development annotation and rests on ortholog-based Notch developmental roles rather than direct human MAML1 evidence. Retain as a non-core developmental annotation. Supporting Evidence: file:human/MAML1/MAML1-deep-research-falcon.md Avoid over-broad human MAML1 developmental annotations unless supported by direct gene-specific experiments; dnMAML affects multiple MAML paralogs/pathway output. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-1912394 | ACCEPT | Summary: Reactome traceable assertion placing MAML in the nucleoplasm as part of the NICD-RBPJ coactivator complex assembly reaction. Reason: Nucleoplasm is the correct subnuclear compartment for MAML1's role in the Notch transcription activation complex, consistent with direct experimental nuclear localization. One of many redundant Reactome rows. Supporting Evidence: PMID:11101851 MAML1 binds to the ankyrin repeat domain of all four mammalian NOTCH receptors, forms a DNA-binding complex with ICN and RBP-Jkappa, and amplifies NOTCH-induced transcription of HES1. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-212356 | ACCEPT | Summary: Reactome traceable assertion placing MAML in the nucleoplasm as part of a NICD-RBPJ-MAML Notch coactivator complex reaction. Reason: Nucleoplasm is the correct subnuclear compartment for MAML1's role in the Notch transcription activation complex, consistent with direct experimental nuclear localization. One of many redundant Reactome rows. Supporting Evidence: PMID:11101851 MAML1 binds to the ankyrin repeat domain of all four mammalian NOTCH receptors, forms a DNA-binding complex with ICN and RBP-Jkappa, and amplifies NOTCH-induced transcription of HES1. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-2197588 | ACCEPT | Summary: Reactome traceable assertion placing MAML in the nucleoplasm as part of a NICD-RBPJ-MAML Notch coactivator complex reaction. Reason: Nucleoplasm is the correct subnuclear compartment for MAML1's role in the Notch transcription activation complex, consistent with direct experimental nuclear localization. One of many redundant Reactome rows. Supporting Evidence: PMID:11101851 MAML1 binds to the ankyrin repeat domain of all four mammalian NOTCH receptors, forms a DNA-binding complex with ICN and RBP-Jkappa, and amplifies NOTCH-induced transcription of HES1. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-2220957 | ACCEPT | Summary: Reactome traceable assertion placing MAML in the nucleoplasm as part of a NICD-RBPJ-MAML Notch coactivator complex reaction. Reason: Nucleoplasm is the correct subnuclear compartment for MAML1's role in the Notch transcription activation complex, consistent with direct experimental nuclear localization. One of many redundant Reactome rows. Supporting Evidence: PMID:11101851 MAML1 binds to the ankyrin repeat domain of all four mammalian NOTCH receptors, forms a DNA-binding complex with ICN and RBP-Jkappa, and amplifies NOTCH-induced transcription of HES1. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-2220964 | ACCEPT | Summary: Reactome traceable assertion placing MAML in the nucleoplasm as part of a NICD-RBPJ-MAML Notch coactivator complex reaction. Reason: Nucleoplasm is the correct subnuclear compartment for MAML1's role in the Notch transcription activation complex, consistent with direct experimental nuclear localization. One of many redundant Reactome rows. Supporting Evidence: PMID:11101851 MAML1 binds to the ankyrin repeat domain of all four mammalian NOTCH receptors, forms a DNA-binding complex with ICN and RBP-Jkappa, and amplifies NOTCH-induced transcription of HES1. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-2220971 | ACCEPT | Summary: Reactome traceable assertion placing MAML in the nucleoplasm as part of a NICD-RBPJ-MAML Notch coactivator complex reaction. Reason: Nucleoplasm is the correct subnuclear compartment for MAML1's role in the Notch transcription activation complex, consistent with direct experimental nuclear localization. One of many redundant Reactome rows. Supporting Evidence: PMID:11101851 MAML1 binds to the ankyrin repeat domain of all four mammalian NOTCH receptors, forms a DNA-binding complex with ICN and RBP-Jkappa, and amplifies NOTCH-induced transcription of HES1. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-2976742 | ACCEPT | Summary: Reactome traceable assertion placing MAML in the nucleoplasm as part of a NICD-RBPJ-MAML Notch coactivator complex reaction. Reason: Nucleoplasm is the correct subnuclear compartment for MAML1's role in the Notch transcription activation complex, consistent with direct experimental nuclear localization. One of many redundant Reactome rows. Supporting Evidence: PMID:11101851 MAML1 binds to the ankyrin repeat domain of all four mammalian NOTCH receptors, forms a DNA-binding complex with ICN and RBP-Jkappa, and amplifies NOTCH-induced transcription of HES1. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-4396371 | ACCEPT | Summary: Reactome traceable assertion placing MAML in the nucleoplasm as part of a NICD-RBPJ-MAML Notch coactivator complex reaction. Reason: Nucleoplasm is the correct subnuclear compartment for MAML1's role in the Notch transcription activation complex, consistent with direct experimental nuclear localization. One of many redundant Reactome rows. Supporting Evidence: PMID:11101851 MAML1 binds to the ankyrin repeat domain of all four mammalian NOTCH receptors, forms a DNA-binding complex with ICN and RBP-Jkappa, and amplifies NOTCH-induced transcription of HES1. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-4396379 | ACCEPT | Summary: Reactome traceable assertion placing MAML in the nucleoplasm as part of a NICD-RBPJ-MAML Notch coactivator complex reaction. Reason: Nucleoplasm is the correct subnuclear compartment for MAML1's role in the Notch transcription activation complex, consistent with direct experimental nuclear localization. One of many redundant Reactome rows. Supporting Evidence: PMID:11101851 MAML1 binds to the ankyrin repeat domain of all four mammalian NOTCH receptors, forms a DNA-binding complex with ICN and RBP-Jkappa, and amplifies NOTCH-induced transcription of HES1. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-4396392 | ACCEPT | Summary: Reactome traceable assertion placing MAML in the nucleoplasm as part of a NICD-RBPJ-MAML Notch coactivator complex reaction. Reason: Nucleoplasm is the correct subnuclear compartment for MAML1's role in the Notch transcription activation complex, consistent with direct experimental nuclear localization. One of many redundant Reactome rows. Supporting Evidence: PMID:11101851 MAML1 binds to the ankyrin repeat domain of all four mammalian NOTCH receptors, forms a DNA-binding complex with ICN and RBP-Jkappa, and amplifies NOTCH-induced transcription of HES1. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-4396393 | ACCEPT | Summary: Reactome traceable assertion placing MAML in the nucleoplasm as part of a NICD-RBPJ-MAML Notch coactivator complex reaction. Reason: Nucleoplasm is the correct subnuclear compartment for MAML1's role in the Notch transcription activation complex, consistent with direct experimental nuclear localization. One of many redundant Reactome rows. Supporting Evidence: PMID:11101851 MAML1 binds to the ankyrin repeat domain of all four mammalian NOTCH receptors, forms a DNA-binding complex with ICN and RBP-Jkappa, and amplifies NOTCH-induced transcription of HES1. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-4396401 | ACCEPT | Summary: Reactome traceable assertion placing MAML in the nucleoplasm as part of a NICD-RBPJ-MAML Notch coactivator complex reaction. Reason: Nucleoplasm is the correct subnuclear compartment for MAML1's role in the Notch transcription activation complex, consistent with direct experimental nuclear localization. One of many redundant Reactome rows. Supporting Evidence: PMID:11101851 MAML1 binds to the ankyrin repeat domain of all four mammalian NOTCH receptors, forms a DNA-binding complex with ICN and RBP-Jkappa, and amplifies NOTCH-induced transcription of HES1. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-4396402 | ACCEPT | Summary: Reactome traceable assertion placing MAML in the nucleoplasm as part of a NICD-RBPJ-MAML Notch coactivator complex reaction. Reason: Nucleoplasm is the correct subnuclear compartment for MAML1's role in the Notch transcription activation complex, consistent with direct experimental nuclear localization. One of many redundant Reactome rows. Supporting Evidence: PMID:11101851 MAML1 binds to the ankyrin repeat domain of all four mammalian NOTCH receptors, forms a DNA-binding complex with ICN and RBP-Jkappa, and amplifies NOTCH-induced transcription of HES1. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-8878220 | ACCEPT | Summary: Reactome traceable assertion placing MAML in the nucleoplasm as part of a NICD-RBPJ-MAML Notch coactivator complex reaction. Reason: Nucleoplasm is the correct subnuclear compartment for MAML1's role in the Notch transcription activation complex, consistent with direct experimental nuclear localization. One of many redundant Reactome rows. Supporting Evidence: PMID:11101851 MAML1 binds to the ankyrin repeat domain of all four mammalian NOTCH receptors, forms a DNA-binding complex with ICN and RBP-Jkappa, and amplifies NOTCH-induced transcription of HES1. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-8878237 | ACCEPT | Summary: Reactome traceable assertion placing MAML in the nucleoplasm as part of a NICD-RBPJ-MAML Notch coactivator complex reaction. Reason: Nucleoplasm is the correct subnuclear compartment for MAML1's role in the Notch transcription activation complex, consistent with direct experimental nuclear localization. One of many redundant Reactome rows. Supporting Evidence: PMID:11101851 MAML1 binds to the ankyrin repeat domain of all four mammalian NOTCH receptors, forms a DNA-binding complex with ICN and RBP-Jkappa, and amplifies NOTCH-induced transcription of HES1. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9017835 | ACCEPT | Summary: Reactome traceable assertion placing MAML in the nucleoplasm as part of a NICD-RBPJ-MAML Notch coactivator complex reaction. Reason: Nucleoplasm is the correct subnuclear compartment for MAML1's role in the Notch transcription activation complex, consistent with direct experimental nuclear localization. One of many redundant Reactome rows. Supporting Evidence: PMID:11101851 MAML1 binds to the ankyrin repeat domain of all four mammalian NOTCH receptors, forms a DNA-binding complex with ICN and RBP-Jkappa, and amplifies NOTCH-induced transcription of HES1. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9018542 | ACCEPT | Summary: Reactome traceable assertion placing MAML in the nucleoplasm as part of a NICD-RBPJ-MAML Notch coactivator complex reaction. Reason: Nucleoplasm is the correct subnuclear compartment for MAML1's role in the Notch transcription activation complex, consistent with direct experimental nuclear localization. One of many redundant Reactome rows. Supporting Evidence: PMID:11101851 MAML1 binds to the ankyrin repeat domain of all four mammalian NOTCH receptors, forms a DNA-binding complex with ICN and RBP-Jkappa, and amplifies NOTCH-induced transcription of HES1. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9021406 | ACCEPT | Summary: Reactome traceable assertion placing MAML in the nucleoplasm as part of a NICD-RBPJ-MAML Notch coactivator complex reaction. Reason: Nucleoplasm is the correct subnuclear compartment for MAML1's role in the Notch transcription activation complex, consistent with direct experimental nuclear localization. One of many redundant Reactome rows. Supporting Evidence: PMID:11101851 MAML1 binds to the ankyrin repeat domain of all four mammalian NOTCH receptors, forms a DNA-binding complex with ICN and RBP-Jkappa, and amplifies NOTCH-induced transcription of HES1. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9021451 | ACCEPT | Summary: Reactome traceable assertion placing MAML in the nucleoplasm as part of a NICD-RBPJ-MAML Notch coactivator complex reaction. Reason: Nucleoplasm is the correct subnuclear compartment for MAML1's role in the Notch transcription activation complex, consistent with direct experimental nuclear localization. One of many redundant Reactome rows. Supporting Evidence: PMID:11101851 MAML1 binds to the ankyrin repeat domain of all four mammalian NOTCH receptors, forms a DNA-binding complex with ICN and RBP-Jkappa, and amplifies NOTCH-induced transcription of HES1. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9021480 | ACCEPT | Summary: Reactome traceable assertion placing MAML in the nucleoplasm as part of a NICD-RBPJ-MAML Notch coactivator complex reaction. Reason: Nucleoplasm is the correct subnuclear compartment for MAML1's role in the Notch transcription activation complex, consistent with direct experimental nuclear localization. One of many redundant Reactome rows. Supporting Evidence: PMID:11101851 MAML1 binds to the ankyrin repeat domain of all four mammalian NOTCH receptors, forms a DNA-binding complex with ICN and RBP-Jkappa, and amplifies NOTCH-induced transcription of HES1. |
| GO:0005654 nucleoplasm | TAS Reactome:R-NUL-2064916 | ACCEPT | Summary: Reactome traceable assertion placing MAML in the nucleoplasm as part of a NICD-RBPJ-MAML Notch coactivator complex reaction. Reason: Nucleoplasm is the correct subnuclear compartment for MAML1's role in the Notch transcription activation complex, consistent with direct experimental nuclear localization. One of many redundant Reactome rows. Supporting Evidence: PMID:11101851 MAML1 binds to the ankyrin repeat domain of all four mammalian NOTCH receptors, forms a DNA-binding complex with ICN and RBP-Jkappa, and amplifies NOTCH-induced transcription of HES1. |
| GO:0005654 nucleoplasm | TAS Reactome:R-NUL-2065178 | ACCEPT | Summary: Reactome traceable assertion placing MAML in the nucleoplasm as part of a NICD-RBPJ-MAML Notch coactivator complex reaction. Reason: Nucleoplasm is the correct subnuclear compartment for MAML1's role in the Notch transcription activation complex, consistent with direct experimental nuclear localization. One of many redundant Reactome rows. Supporting Evidence: PMID:11101851 MAML1 binds to the ankyrin repeat domain of all four mammalian NOTCH receptors, forms a DNA-binding complex with ICN and RBP-Jkappa, and amplifies NOTCH-induced transcription of HES1. |
| GO:0005654 nucleoplasm | TAS Reactome:R-NUL-4396363 | ACCEPT | Summary: Reactome traceable assertion placing MAML in the nucleoplasm as part of a NICD-RBPJ-MAML Notch coactivator complex reaction. Reason: Nucleoplasm is the correct subnuclear compartment for MAML1's role in the Notch transcription activation complex, consistent with direct experimental nuclear localization. One of many redundant Reactome rows. Supporting Evidence: PMID:11101851 MAML1 binds to the ankyrin repeat domain of all four mammalian NOTCH receptors, forms a DNA-binding complex with ICN and RBP-Jkappa, and amplifies NOTCH-induced transcription of HES1. |
| GO:0005654 nucleoplasm | TAS Reactome:R-NUL-9013647 | ACCEPT | Summary: Reactome traceable assertion placing MAML in the nucleoplasm as part of a NICD-RBPJ-MAML Notch coactivator complex reaction. Reason: Nucleoplasm is the correct subnuclear compartment for MAML1's role in the Notch transcription activation complex, consistent with direct experimental nuclear localization. One of many redundant Reactome rows. Supporting Evidence: PMID:11101851 MAML1 binds to the ankyrin repeat domain of all four mammalian NOTCH receptors, forms a DNA-binding complex with ICN and RBP-Jkappa, and amplifies NOTCH-induced transcription of HES1. |
| GO:0005654 nucleoplasm | TAS Reactome:R-NUL-9013660 | ACCEPT | Summary: Reactome traceable assertion placing MAML in the nucleoplasm as part of a NICD-RBPJ-MAML Notch coactivator complex reaction. Reason: Nucleoplasm is the correct subnuclear compartment for MAML1's role in the Notch transcription activation complex, consistent with direct experimental nuclear localization. One of many redundant Reactome rows. Supporting Evidence: PMID:11101851 MAML1 binds to the ankyrin repeat domain of all four mammalian NOTCH receptors, forms a DNA-binding complex with ICN and RBP-Jkappa, and amplifies NOTCH-induced transcription of HES1. |
| GO:0005654 nucleoplasm | TAS Reactome:R-NUL-9013699 | ACCEPT | Summary: Reactome traceable assertion placing MAML in the nucleoplasm as part of a NICD-RBPJ-MAML Notch coactivator complex reaction. Reason: Nucleoplasm is the correct subnuclear compartment for MAML1's role in the Notch transcription activation complex, consistent with direct experimental nuclear localization. One of many redundant Reactome rows. Supporting Evidence: PMID:11101851 MAML1 binds to the ankyrin repeat domain of all four mammalian NOTCH receptors, forms a DNA-binding complex with ICN and RBP-Jkappa, and amplifies NOTCH-induced transcription of HES1. |
| GO:0005654 nucleoplasm | TAS Reactome:R-NUL-9604511 | ACCEPT | Summary: Reactome traceable assertion placing MAML in the nucleoplasm as part of a NICD-RBPJ-MAML Notch coactivator complex reaction. Reason: Nucleoplasm is the correct subnuclear compartment for MAML1's role in the Notch transcription activation complex, consistent with direct experimental nuclear localization. One of many redundant Reactome rows. Supporting Evidence: PMID:11101851 MAML1 binds to the ankyrin repeat domain of all four mammalian NOTCH receptors, forms a DNA-binding complex with ICN and RBP-Jkappa, and amplifies NOTCH-induced transcription of HES1. |
| GO:0002193 MAML1-RBP-Jkappa- ICN1 complex | IDA PMID:16510869 The Notch coactivator, MAML1, functions as a novel coactivat... | ACCEPT | Summary: MAML1 is a component of the Notch intracellular domain-RBPJ/CSL transcriptional activation complex. Reason: The term is a specific cellular component representation of the canonical Notch transcription activation complex. The original cited PMID is myogenesis-focused, so the support should rely on the direct Notch complex papers. Supporting Evidence: PMID:11390662 hMam-1 stabilizes and participates in the DNA binding complex of the intracellular domain of human Notch1 and a CSL protein. file:human/MAML1/MAML1-deep-research-falcon.md Specific complex membership: NICD–RBPJ–MAML1. |
| GO:0005515 protein binding | IPI PMID:16510869 The Notch coactivator, MAML1, functions as a novel coactivat... | MARK AS OVER ANNOTATED | Summary: Bare protein binding rows from the myogenesis paper capturing the MAML1 interactions with MEF2C and RBPJ. The interactions are real but the term is uninformative. Reason: GO:0005515 protein binding is uninformative about molecular function. The functional content (MAML1 coactivation of MEF2C-mediated muscle transcription, and Notch complex membership) is captured by the transcription coactivator activity and muscle-differentiation annotations. Supporting Evidence: PMID:16510869 we determined that MAML1 interacts with MEF2C (myocyte enhancer factor 2C), functioning as its potent co-transcriptional regulator. |
| GO:0005634 nucleus | IDA PMID:16510869 The Notch coactivator, MAML1, functions as a novel coactivat... | ACCEPT | Summary: MAML1 functions as a nuclear coactivator (for MEF2C and Notch), placing it in the nucleus. Reason: Nuclear localization is the supported cellular context for MAML1's coactivator function, consistent across the Notch and MEF2C literature. Supporting Evidence: PMID:16510869 we determined that MAML1 interacts with MEF2C (myocyte enhancer factor 2C), functioning as its potent co-transcriptional regulator. |
| GO:0006468 protein phosphorylation | IDA PMID:16510869 The Notch coactivator, MAML1, functions as a novel coactivat... | REMOVE | Summary: MISANNOTATION: MAML1 is a transcriptional coactivator, not a kinase, and the cited PMID:16510869 supports MEF2C coactivation/myogenesis rather than protein phosphorylation. Reason: The essence of the annotation is not sound: MAML1 does not catalyze protein phosphorylation in this paper. MAML1's non-catalytic CDK8 recruitment role is already captured separately by the accepted GO:0019901 protein kinase binding row based on PMID:15546612. Supporting Evidence: PMID:16510869 Our study thus reveals novel and nonredundant functions for MAML1: It acts as a coactivator for MEF2C transcription and is essential for proper muscle development. |
| GO:0010831 positive regulation of myotube differentiation | IGI PMID:16510869 The Notch coactivator, MAML1, functions as a novel coactivat... | KEEP AS NON CORE | Summary: MAML1 promotes myotube differentiation as a MEF2C coactivator, demonstrated by gain- and loss-of-function in C2C12 cells and Maml1-null fibroblasts. Reason: This is a directly supported (IGI, MyoD genetic interaction) muscle differentiation function, but it is a Notch-independent MEF2C-mediated activity peripheral to MAML1's core Notch coactivator role. Supporting Evidence: PMID:16510869 overexpression of MAML1 in C2C12 cells dramatically enhanced myotube formation and increased the expression of muscle-specific genes, while RNA interference (RNAi)-mediated MAML1 knockdown abrogated differentiation. |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IDA PMID:16510869 The Notch coactivator, MAML1, functions as a novel coactivat... | ACCEPT | Summary: MAML1 positively regulates RNA polymerase II transcription as a coactivator for MEF2C-mediated muscle-specific gene expression. Reason: Direct evidence that MAML1 acts as a potent co-transcriptional regulator of MEF2C and increases muscle-specific gene expression supports positive regulation of RNA Pol II transcription. Supporting Evidence: PMID:16510869 we determined that MAML1 interacts with MEF2C (myocyte enhancer factor 2C), functioning as its potent co-transcriptional regulator. |
| GO:0005515 protein binding | IPI PMID:11101851 MAML1, a human homologue of Drosophila mastermind, is a tran... | MARK AS OVER ANNOTATED | Summary: Bare protein binding rows from the founding MAML1 paper capturing interactions with NOTCH intracellular domains and RBPJ. The interactions are central but the term is uninformative. Reason: GO:0005515 protein binding does not describe MAML1's molecular function. The functionally meaningful content (binding the Notch ANK domain to assemble the ICN-RBPJ-MAML transcription complex) is captured by the accepted transcription coactivator activity and MAML1-RBP-Jkappa-ICN1 complex annotations. Supporting Evidence: PMID:11101851 MAML1 binds to the ankyrin repeat domain of all four mammalian NOTCH receptors, forms a DNA-binding complex with ICN and RBP-Jkappa, and amplifies NOTCH-induced transcription of HES1. |
| GO:0005515 protein binding | IPI PMID:11390662 A human protein with sequence similarity to Drosophila maste... | MARK AS OVER ANNOTATED | Summary: Bare protein binding row from a paper showing hMam-1 coordinates nuclear Notch and CSL into a transcriptional activator complex. The interaction is real but the term is uninformative. Reason: GO:0005515 protein binding is uninformative. The substance of this MAML1-Notch-CSL interaction (assembly/stabilization of the DNA-bound Notch transcription activation complex) is already captured by the accepted coactivator and complex-membership annotations. Supporting Evidence: PMID:11390662 hMam-1 stabilizes and participates in the DNA binding complex of the intracellular domain of human Notch1 and a CSL protein. |
| GO:0005634 nucleus | IDA PMID:9874765 CIR, a corepressor linking the DNA binding factor CBF1 to th... | ACCEPT | Summary: Nucleus localization annotation; the cited PMID:9874765 is a CIR/CBF1 corepressor paper only tangentially related to MAML1, but nuclear localization of MAML1 is independently well established. Reason: Although the original reference is principally about the CBF1/CSL corepressor CIR rather than direct MAML1 localization, the nucleus assignment is correct and robustly supported by direct MAML1 experiments (PMID:11101851). Supporting Evidence: PMID:11101851 Here we clone MAML1, a human homologue of the Drosophila gene Mastermind, and show that it encodes a protein of 130 kD localizing to nuclear bodies. |
| GO:0019901 protein kinase binding | IPI PMID:15546612 Mastermind recruits CycC:CDK8 to phosphorylate the Notch ICD... | ACCEPT | Summary: MAML1 binds/recruits CDK8 in the Notch transcription complex to promote Notch intracellular domain phosphorylation and turnover. Reason: This is a specific and informative interaction term supported by the CDK8 recruitment paper, unlike generic protein binding rows. Supporting Evidence: PMID:15546612 MAM interacts directly with CDK8 and can cause it to localize to subnuclear foci. file:human/MAML1/MAML1-deep-research-falcon.md Mediator kinase module recruitment and NICD phosphorylation/turnover. |
| GO:0042605 peptide antigen binding | IPI PMID:17317671 The notch regulator MAML1 interacts with p53 and functions a... | REMOVE | Summary: The cited paper shows MAML1 interaction with p53 and transcriptional coactivator activity, not peptide antigen binding. Reason: Peptide antigen binding is unsupported and appears to be an erroneous interpretation of a p53 interaction/coactivator paper. Supporting Evidence: PMID:17317671 MAML1-p53 interaction involves the N-terminal region of MAML1 and the DNA-binding domain of p53, and we use a chromatin immunoprecipitation assay to show that MAML1 is part of the activator complex that binds to native p53-response elements within the promoter of the p53 target genes. |
| GO:0003713 transcription coactivator activity | IDA PMID:11101851 MAML1, a human homologue of Drosophila mastermind, is a tran... | ACCEPT | Summary: MAML1 is a transcriptional coactivator for Notch receptor intracellular domains and RBPJ/CSL. Reason: This direct experimental annotation captures the principal molecular function of MAML1. Supporting Evidence: PMID:11101851 MAML1 binds to the ankyrin repeat domain of all four mammalian NOTCH receptors, forms a DNA-binding complex with ICN and RBP-Jkappa, and amplifies NOTCH-induced transcription of HES1. |
| GO:0005634 nucleus | IDA PMID:11101851 MAML1, a human homologue of Drosophila mastermind, is a tran... | ACCEPT | Summary: MAML1 is a nuclear protein that acts in nuclear Notch transcription complexes. Reason: Nuclear localization is the supported cellular context for the core transcriptional coactivator function. Supporting Evidence: PMID:11101851 MAML1 binds to the ankyrin repeat domain of all four mammalian NOTCH receptors, forms a DNA-binding complex with ICN and RBP-Jkappa, and amplifies NOTCH-induced transcription of HES1. |
| GO:0007219 Notch signaling pathway | IDA PMID:11101851 MAML1, a human homologue of Drosophila mastermind, is a tran... | KEEP AS NON CORE | Summary: MAML1 acts in the nuclear transcriptional arm of the Notch signaling pathway. Reason: The broad pathway term is acceptable as context, but the more specific curated process is activation of Notch target gene transcription. Supporting Evidence: PMID:11101851 MAML1 binds to the ankyrin repeat domain of all four mammalian NOTCH receptors, forms a DNA-binding complex with ICN and RBP-Jkappa, and amplifies NOTCH-induced transcription of HES1. |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IDA PMID:11101851 MAML1, a human homologue of Drosophila mastermind, is a tran... | ACCEPT | Summary: MAML1 positively regulates RNA polymerase II transcription as a Notch transcriptional coactivator. Reason: Reporter and complex-assembly evidence support MAML1-dependent activation of Notch target transcription. Supporting Evidence: PMID:11101851 MAML1 binds to the ankyrin repeat domain of all four mammalian NOTCH receptors, forms a DNA-binding complex with ICN and RBP-Jkappa, and amplifies NOTCH-induced transcription of HES1. |
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Download this section (compressed HTML)Q: Which MAML1 developmental annotations are directly supported by human MAML1-specific experiments rather than pan-MAML or Notch pathway perturbation?
Q: Are endogenous MAML1 nuclear bodies equivalent to nuclear specks in the contexts represented by GOA annotations?
Experiment: Use endogenous-tagged MAML1 with Notch activation time courses to map nuclear subcompartment localization and distinguish nucleoplasm, nuclear body, and nuclear speck assignments.
Experiment: Perform MAML1-specific rescue after knockout at representative Notch, p53, and myogenic target genes to separate direct MAML1 functions from broader Notch pathway or paralog-redundant effects.
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