Mad (Mothers against dpp) is the Drosophila receptor-regulated Smad (R-Smad) of the BMP pathway, the ortholog of vertebrate SMAD1/5/9. In unstimulated cells it is a cytosolic monomer. Dpp, Gbb and Scw ligands activate type I receptors (Tkv, Sax), which phosphorylate the C-terminal SSXS motif; phosphorylated Mad then forms a heteromeric complex with the co-Smad Medea and accumulates in the nucleus. There its MH1 domain binds GC-rich Smad-binding sites in Pol II enhancers. At activating elements Mad/Medea directly induce target genes such as vestigial, dad and Ubx. At silencer elements a trimeric Mad/Medea complex recruits the zinc-finger protein Schnurri to repress brinker and other genes, converting the extracellular Dpp gradient into graded transcriptional outputs. Mad activity is limited by Smurf-mediated ubiquitination, linker phosphorylation by CDK8 and GSK3/Shaggy, Nemo-dependent nuclear export and phosphatases. Through this signalling role Mad is required for embryonic dorsal-ventral patterning, midgut induction, imaginal disc patterning and growth, germline and somatic stem cell maintenance, and retrograde BMP signalling that promotes neuromuscular junction growth.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000122 negative regulation of transcription by RNA polymerase II | IDA PMID:12705870 Conversion of an extracellular Dpp/BMP morphogen gradient in... | ACCEPT | Summary: Mad/Medea/Shn complex directly represses brinker via the brk silencer. Reason: Mad, in a trimeric Mad/Medea complex that recruits Schnurri at silencer elements (SE), directly represses Pol II target genes such as brinker; this is a core mechanism of Dpp gradient read-out. Supporting Evidence: PMID:12705870 the brk silencer serves as a direct target for a protein complex consisting of the Smad homologs Mad/Medea and the zinc finger protein Schnurri file:DROME/Mad/Mad-uniprot.txt Mad-Med acts as a transcriptional activator but recruits shn/Shnurri to enhance its activity or switch to transcriptional repression |
| GO:0000122 negative regulation of transcription by RNA polymerase II | IDA PMID:17008448 Schnurri transcription factors from Drosophila and vertebrat... | ACCEPT | Summary: Shn/Smad repression complex on brk promoter elements. Reason: Mad, in a trimeric Mad/Medea complex that recruits Schnurri at silencer elements (SE), directly represses Pol II target genes such as brinker; this is a core mechanism of Dpp gradient read-out. Supporting Evidence: PMID:17008448 by forming a Shn/Smad repression complex on defined promoter elements in the brinker (brk) gene file:DROME/Mad/Mad-uniprot.txt Mad-Med acts as a transcriptional activator but recruits shn/Shnurri to enhance its activity or switch to transcriptional repression |
| GO:0000122 negative regulation of transcription by RNA polymerase II | IMP PMID:10094047 brinker is a target of Dpp in Drosophila that negatively reg... | ACCEPT | Summary: Dpp signalling represses brinker transcription; Mad is the transcriptional effector of this repression. Reason: Mad, in a trimeric Mad/Medea complex that recruits Schnurri at silencer elements (SE), directly represses Pol II target genes such as brinker; this is a core mechanism of Dpp gradient read-out. The cached abstract shows Dpp-dependent repression of brk; Mad requirement was assessed in the full text, which the curator read. Supporting Evidence: PMID:10094047 We report here the molecular cloning of brinker (brk), and show that brk expression is repressed by dpp. PMID:12705870 the brk silencer serves as a direct target for a protein complex consisting of the Smad homologs Mad/Medea and the zinc finger protein Schnurri |
| GO:0000902 cell morphogenesis | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: ARBA prediction of cell morphogenesis. Reason: ARBA machine-learning prediction. Mad is a transcription factor whose loss alters cell shape only indirectly through BMP target genes in specific tissues (e.g. pupal retina interommatidial cells). A generic cell morphogenesis process term overstates Mad's direct involvement. Supporting Evidence: file:DROME/Mad/Mad-uniprot.txt Component of the Mad-Med transcription factor complex involved in the dpp/BMP TGF-beta signal transduction pathway |
| GO:0000977 RNA polymerase II transcription regulatory region sequence-specific DNA binding | IDA PMID:11306550 Direct competition between Brinker and Drosophila Mad in Dpp... | ACCEPT | Summary: Mad binds Ubx midgut enhancer sites; Brinker competes for binding. Reason: Mad's MH1 domain binds GC-rich Smad-binding sites in Pol II enhancers and silencers of Dpp target genes (vestigial, Ubx, brinker, dad, tinman); this sequence-specific DNA binding is a core activity. Supporting Evidence: PMID:11306550 We show that Brinker efficiently competes with Mad in vitro, preventing the latter from binding to these sites. PMID:11306550 Brinker also competes with activated Mad in vivo, blocking the stimulation of the Ubx enhancer in response to simultaneous Dpp signalling. |
| GO:0000977 RNA polymerase II transcription regulatory region sequence-specific DNA binding | IDA PMID:12705870 Conversion of an extracellular Dpp/BMP morphogen gradient in... | ACCEPT | Summary: Mad/Medea binds the brk silencer. Reason: Mad's MH1 domain binds GC-rich Smad-binding sites in Pol II enhancers and silencers of Dpp target genes (vestigial, Ubx, brinker, dad, tinman); this sequence-specific DNA binding is a core activity. Supporting Evidence: PMID:12705870 the brk silencer serves as a direct target for a protein complex consisting of the Smad homologs Mad/Medea and the zinc finger protein Schnurri |
| GO:0000977 RNA polymerase II transcription regulatory region sequence-specific DNA binding | IDA PMID:15128656 Opposing inputs by Hedgehog and Brinker define a stripe of h... | ACCEPT | Summary: Mad binding to a Dpp-responsive hairy leg enhancer. Reason: Mad's MH1 domain binds GC-rich Smad-binding sites in Pol II enhancers and silencers of Dpp target genes (vestigial, Ubx, brinker, dad, tinman); this sequence-specific DNA binding is a core activity. The cached abstract does not describe the binding assay explicitly; deferring to the curator who read the full text, as the activity is well established. Supporting Evidence: PMID:15128656 In D-h-expressing cells, Dpp signaling is required to block Brk-mediated repression. file:DROME/Mad/Mad-uniprot.txt Binds GC-rich enhancer sites with consensus sequence 5'-GCCGNCG-3' in the enhancer region of dpp-responsive genes |
| GO:0000977 RNA polymerase II transcription regulatory region sequence-specific DNA binding | IDA PMID:20010841 A conserved activation element in BMP signaling during Droso... | ACCEPT | Summary: Mad/Medea bind the activating element (AE) of dad and other targets. Reason: Mad's MH1 domain binds GC-rich Smad-binding sites in Pol II enhancers and silencers of Dpp target genes (vestigial, Ubx, brinker, dad, tinman); this sequence-specific DNA binding is a core activity. Supporting Evidence: PMID:20010841 activating input by the Smad signal transducers Mothers against Dpp (Mad) and Medea via competitive DNA binding PMID:20010841 The AE is similar to the SE and recruits the Smad proteins via a conserved mechanism. |
| GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic inference of Pol II cis-regulatory DNA binding across R-Smads. Reason: Mad's MH1 domain binds GC-rich Smad-binding sites in Pol II enhancers and silencers of Dpp target genes (vestigial, Ubx, brinker, dad, tinman); this sequence-specific DNA binding is a core activity. The MH1 DNA-binding function is conserved across the SMAD family and Mad has direct experimental support. Supporting Evidence: PMID:9230443 possesses a sequence-specific DNA-binding activity that becomes apparent when carboxy-terminal residues are removed file:DROME/Mad/Mad-uniprot.txt Binds GC-rich enhancer sites with consensus sequence 5'-GCCGNCG-3' in the enhancer region of dpp-responsive genes |
| GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding | IDA PMID:9694800 Smad proteins act in combination with synergistic and antago... | ACCEPT | Summary: Smad binding sites in the tinman mesoderm enhancer. Reason: Mad's MH1 domain binds GC-rich Smad-binding sites in Pol II enhancers and silencers of Dpp target genes (vestigial, Ubx, brinker, dad, tinman); this sequence-specific DNA binding is a core activity. Supporting Evidence: PMID:9694800 We show that the binding and synergistic activities of Smad and Tinman proteins are critical for mesodermal tinman induction |
| GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific | IBA GO_REF:0000033 | ACCEPT | Summary: Conserved DNA-binding transcription factor activity of R-Smads. Reason: Mad is a bona fide sequence-specific DNA-binding transcription factor for Pol II genes, activated by receptor phosphorylation; this is its core molecular function. Supporting Evidence: PMID:9230443 possesses a sequence-specific DNA-binding activity that becomes apparent when carboxy-terminal residues are removed file:DROME/Mad/Mad-uniprot.txt Component of the Mad-Med transcription factor complex involved in the dpp/BMP TGF-beta signal transduction pathway |
| GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific | IDA PMID:24321690 Comparative gene expression analysis of Dtg, a novel target ... | ACCEPT | Summary: Mad binding motifs required for Dtg enhancer activity. Reason: Mad is a bona fide sequence-specific DNA-binding transcription factor for Pol II genes, activated by receptor phosphorylation; this is its core molecular function. Supporting Evidence: PMID:24321690 This enhancer contained a highly conserved region of 48-bp in which bioinformatic predictions and in vitro assays identified three Mad binding motifs. |
| GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific | IDA PMID:9230443 Drosophila Mad binds to DNA and directly mediates activation... | ACCEPT | Summary: Mad MH1 binds DNA and directly activates vestigial. Reason: Mad is a bona fide sequence-specific DNA-binding transcription factor for Pol II genes, activated by receptor phosphorylation; this is its core molecular function. Supporting Evidence: PMID:9230443 possesses a sequence-specific DNA-binding activity that becomes apparent when carboxy-terminal residues are removed PMID:9230443 Mad binds to and is required for the activation of an enhancer within the vestigial wing-patterning gene in cells across the entire developing wing blade. |
| GO:0001227 DNA-binding transcription repressor activity, RNA polymerase II-specific | IDA PMID:12705870 Conversion of an extracellular Dpp/BMP morphogen gradient in... | ACCEPT | Summary: Mad/Medea DNA binding at the brk silencer mediates repression. Reason: At silencer elements the Mad/Medea complex binds DNA and recruits Schnurri to repress transcription; the DNA-binding repressor activity is context-dependent but directly demonstrated. Supporting Evidence: PMID:12705870 the brk silencer serves as a direct target for a protein complex consisting of the Smad homologs Mad/Medea and the zinc finger protein Schnurri file:DROME/Mad/Mad-uniprot.txt Mad-Med acts as a transcriptional activator but recruits shn/Shnurri to enhance its activity or switch to transcriptional repression |
| GO:0001227 DNA-binding transcription repressor activity, RNA polymerase II-specific | IDA PMID:17008448 Schnurri transcription factors from Drosophila and vertebrat... | ACCEPT | Summary: Shn/Smad repression complex on brk. Reason: At silencer elements the Mad/Medea complex binds DNA and recruits Schnurri to repress transcription; the DNA-binding repressor activity is context-dependent but directly demonstrated. Supporting Evidence: PMID:17008448 by forming a Shn/Smad repression complex on defined promoter elements in the brinker (brk) gene |
| GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific | IDA PMID:11306550 Direct competition between Brinker and Drosophila Mad in Dpp... | ACCEPT | Summary: Activated Mad stimulates the Ubx midgut enhancer. Reason: Mad/Medea bind activating elements and directly activate Dpp target genes; DNA-binding transcription activator activity is a core function. Supporting Evidence: PMID:11306550 Brinker also competes with activated Mad in vivo, blocking the stimulation of the Ubx enhancer in response to simultaneous Dpp signalling. |
| GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific | IDA PMID:20010841 A conserved activation element in BMP signaling during Droso... | ACCEPT | Summary: Mad/Medea activate via the AE. Reason: Mad/Medea bind activating elements and directly activate Dpp target genes; DNA-binding transcription activator activity is a core function. Supporting Evidence: PMID:20010841 activating input by the Smad signal transducers Mothers against Dpp (Mad) and Medea via competitive DNA binding |
| GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific | IDA PMID:36029115 Dichotomous cis-regulatory motifs mediate the maturation of ... | ACCEPT | Summary: pMad/Med directly activate neuronal BMP targets via AE and SE motifs. Reason: Mad/Medea bind activating elements and directly activate Dpp target genes; DNA-binding transcription activator activity is a core function. Supporting Evidence: PMID:36029115 Unpredictably, both motifs mediate direct gene activation, with no involvement of the BMP derepression pathway regulators Schnurri and Brinker. |
| GO:0001745 compound eye morphogenesis | IGI PMID:8681796 Mad acts downstream of Dpp receptors, revealing a differenti... | KEEP AS NON CORE | Summary: Mad required for morphogenetic furrow initiation in the eye. Reason: Mad mediates Dpp signalling required for eye morphogenetic furrow initiation; a developmental outcome of BMP signalling, not a core function of Mad. Supporting Evidence: PMID:8681796 Mad-mediated dpp signaling is absolutely required for the initiation of the morphogenetic furrow in the eye PMID:8681796 Clonal analysis demonstrates a cell-autonomous function for Mad and genetic interactions indicate that Mad is an essential component of the signal transduction pathway downstream of the Dpp receptors in responding cells. |
| GO:0001745 compound eye morphogenesis | IMP PMID:17428827 Dynamic decapentaplegic signaling regulates patterning and a... | KEEP AS NON CORE | Summary: Mad required for pupal retina interommatidial cell patterning. Reason: Mad clones disrupt pupal retina patterning; developmental outcome of BMP signalling. Supporting Evidence: PMID:17428827 Also, the transcription factor Mad is required to regulate IPC patterning |
| GO:0003713 transcription coactivator activity | IDA PMID:11071761 The zinc finger protein schnurri acts as a Smad partner in m... | MODIFY | Summary: Mad and Shn synergistically activate transcription. Reason: GO transcription coactivator activity describes a coregulator recruited by a DNA-binding factor that does not itself bind DNA. Mad binds DNA directly through its MH1 domain, and in this study both Mad and Shn are DNA-binding factors acting cooperatively. The observed activity is better described as DNA-binding transcription activator activity, which the gene already carries. Proposed replacements: DNA-binding transcription activator activity, RNA polymerase II-specific Supporting Evidence: PMID:11071761 show that Shn and Mad act synergistically to induce transcription PMID:9230443 possesses a sequence-specific DNA-binding activity that becomes apparent when carboxy-terminal residues are removed |
| GO:0005515 protein binding | IPI PMID:11703946 The DSmurf ubiquitin-protein ligase restricts BMP signaling ... | MODIFY | Summary: Mad binds DSmurf. Reason: Bare protein binding is uninformative. Mad binds the HECT E3 ligase Smurf, which ubiquitinates phosphorylated Mad; the informative term is ubiquitin protein ligase binding. Proposed replacements: ubiquitin protein ligase binding Supporting Evidence: PMID:11703946 binds the Smad1/5 ortholog MAD and likely promotes its proteolysis |
| GO:0005515 protein binding | IPI PMID:12754252 dSmurf selectively degrades decapentaplegic-activated MAD, a... | MODIFY | Summary: Phosphorylated Mad binds dSmurf. Reason: Bare protein binding is uninformative. Mad binds the HECT E3 ligase Smurf, which ubiquitinates phosphorylated Mad; the informative term is ubiquitin protein ligase binding. Proposed replacements: ubiquitin protein ligase binding Supporting Evidence: PMID:12754252 dSmurf selectively interacted with MAD, but not Medea and Dad |
| GO:0005515 protein binding | IPI PMID:14645536 Drosophila TGIF proteins are transcriptional activators. | MODIFY | Summary: dTGIF co-precipitates with Mad. Reason: Bare protein binding is uninformative. The partner, dTGIF, is a homeodomain DNA-binding transcription activator in Drosophila; the interaction is better captured as RNA polymerase II-specific DNA-binding transcription factor binding (term already carried for Shn). Proposed replacements: RNA polymerase II-specific DNA-binding transcription factor binding Supporting Evidence: PMID:14645536 full-length dTGIFa (amino acids 2 to 424) coprecipitated with both dMad and dSmad2, but was not present in a control precipitate |
| GO:0005515 protein binding | IPI PMID:17115029 A novel function of Drosophila eIF4A as a negative regulator... | REMOVE | Summary: eIF4A associates with Mad. Reason: Bare protein binding is uninformative; eIF4A acts on Mad (promoting its degradation) and no informative molecular function of Mad is implied. Removal does not mean the interaction is false. Supporting Evidence: PMID:17115029 eIF4A physically associates with Mad and Medea, and promotes their degradation |
| GO:0005515 protein binding | IPI PMID:19914168 Nuclear CDKs drive Smad transcriptional activation and turno... | MODIFY | Summary: Yorkie binds linker-phosphorylated Mad. Reason: Bare protein binding is uninformative. Yorkie is a transcription coactivator recruited to linker-phosphorylated Mad to support Mad-dependent transcription; transcription coactivator binding is the informative term. Proposed replacements: transcription coactivator binding Supporting Evidence: PMID:19914168 Endogenous or transfected epitope-tagged Yorkie could be co-immunoprecipitated with wild-type Flag-Mad, but not with a linker phosphorylation site mutant |
| GO:0005515 protein binding | IPI PMID:21041636 Lissencephaly-1 controls germline stem cell self-renewal thr... | REMOVE | Summary: Lis1 binds and stabilises Mad. Reason: Bare protein binding is uninformative; Lis1 stabilises Mad as a client, which implies no specific molecular function of Mad. Removal does not mean the interaction is false. Supporting Evidence: PMID:21041636 Lis1 binds directly to and stabilizes the SMAD protein Mothers against decapentaplegic (Mad), facilitates its phosphorylation |
| GO:0005634 nucleus | EXP PMID:17507407 Drosophila Nemo antagonizes BMP signaling by phosphorylation... | ACCEPT | Summary: Nuclear Mad; Nemo promotes nuclear export. Reason: Activated Mad accumulates in the nucleus with Medea where it binds target enhancers; nucleus is a core location for its transcription factor activity. Supporting Evidence: PMID:17507407 In cell culture, phosphorylation by Nemo blocks the nuclear accumulation of Mad by promoting export of Mad from the nucleus in a kinase-dependent manner. |
| GO:0005634 nucleus | EXP PMID:22563507 R-Smad competition controls activin receptor output in Droso... | ACCEPT | Summary: Nuclear P-Mad in larval tissues. Reason: Activated Mad accumulates in the nucleus with Medea where it binds target enhancers; nucleus is a core location for its transcription factor activity. Supporting Evidence: PMID:22563507 Elevated P-Mad is seen in several tissues of dSmad2 protein-null mutant larvae |
| GO:0005634 nucleus | IDA PMID:16510868 Identification of phosphatases for Smad in the BMP/DPP pathw... | ACCEPT | Summary: Nuclear Mad in S2 cells (phosphatase study). Reason: Activated Mad accumulates in the nucleus with Medea where it binds target enhancers; nucleus is a core location for its transcription factor activity. Cached text is abstract-only; deferring to curator. Supporting Evidence: PMID:16510868 PDP directly dephosphorylates MAD and inhibits signal transduction of Decapentaplegic (DPP) file:DROME/Mad/Mad-uniprot.txt Localizes to the nucleus upon activation of the dpp/BMP signal transduction pathway |
| GO:0005634 nucleus | IDA PMID:17115029 A novel function of Drosophila eIF4A as a negative regulator... | ACCEPT | Summary: Nuclear Mad/pMad. Reason: Activated Mad accumulates in the nucleus with Medea where it binds target enhancers; nucleus is a core location for its transcription factor activity. Cached text is abstract-only; deferring to curator. Supporting Evidence: PMID:17115029 eIF4A physically associates with Mad and Medea, and promotes their degradation file:DROME/Mad/Mad-uniprot.txt Localizes to the nucleus upon activation of the dpp/BMP signal transduction pathway |
| GO:0005634 nucleus | IDA PMID:21696798 Drosophila nucleoporin Nup154 controls cell viability, proli... | ACCEPT | Summary: Mad nuclear accumulation depends on Nup154. Reason: Activated Mad accumulates in the nucleus with Medea where it binds target enhancers; nucleus is a core location for its transcription factor activity. Supporting Evidence: PMID:21696798 RNAi-mediated depletion of Nup154 in cultured cells prevented nuclear accumulation of the transcription factor Mothers against Dpp (Mad) |
| GO:0005634 nucleus | IDA PMID:24046358 Fragile X mental retardation protein regulates trans-synapti... | ACCEPT | Summary: Nuclear pMAD in motor neurons. Reason: Activated Mad accumulates in the nucleus with Medea where it binds target enhancers; nucleus is a core location for its transcription factor activity. Supporting Evidence: PMID:24046358 downstream signaling via phosphorylation of the transcription factor MAD (pMAD) seem not to be affected file:DROME/Mad/Mad-uniprot.txt Localizes to the nucleus upon activation of the dpp/BMP signal transduction pathway |
| GO:0005634 nucleus | IDA PMID:39494616 A genome-engineered tool set for Drosophila TGF-Ξ²/BMP signal... | ACCEPT | Summary: Endogenously tagged Mad; a minor fraction is nuclear. Reason: Activated Mad accumulates in the nucleus with Medea where it binds target enhancers; nucleus is a core location for its transcription factor activity. Supporting Evidence: PMID:39494616 the distribution of HA-Mad was uniform with no signs of nuclear enrichments in regions of high BMP signaling activity, suggesting that only a minor fraction of the protein accumulates in the nucleus upon phosphorylation |
| GO:0005634 nucleus | IDA PMID:9230443 Drosophila Mad binds to DNA and directly mediates activation... | ACCEPT | Summary: Nuclear Mad bound to target enhancers. Reason: Activated Mad accumulates in the nucleus with Medea where it binds target enhancers; nucleus is a core location for its transcription factor activity. Supporting Evidence: PMID:9230443 Mad binds to and is required for the activation of an enhancer within the vestigial wing-patterning gene in cells across the entire developing wing blade. file:DROME/Mad/Mad-uniprot.txt Localizes to the nucleus upon activation of the dpp/BMP signal transduction pathway |
| GO:0005634 nucleus | IDA PMID:9502724 Medea is a Drosophila Smad4 homolog that is differentially r... | ACCEPT | Summary: Mad/Medea nuclear translocation. Reason: Activated Mad accumulates in the nucleus with Medea where it binds target enhancers; nucleus is a core location for its transcription factor activity. Supporting Evidence: PMID:9502724 MEDEA is localized in the cytoplasm, is not regulated by phosphorylation, and requires physical association with MAD for nuclear translocation. |
| GO:0005634 nucleus | IDA PMID:9502733 The Drosophila gene Medea demonstrates the requirement for d... | ACCEPT | Summary: Mad translocates Medea into the nucleus. Reason: Activated Mad accumulates in the nucleus with Medea where it binds target enhancers; nucleus is a core location for its transcription factor activity. Supporting Evidence: PMID:9502733 upon activation of the Dpp pathway, Mad is required to actively translocate Medea into the nucleus |
| GO:0005634 nucleus | IDA PMID:9693372 Interplay of signal mediators of decapentaplegic (Dpp): mole... | ACCEPT | Summary: Dad blocks Mad nuclear translocation. Reason: Activated Mad accumulates in the nucleus with Medea where it binds target enhancers; nucleus is a core location for its transcription factor activity. Supporting Evidence: PMID:9693372 Dad also blocks hetero-oligomerization and nuclear translocation of Mad. |
| GO:0005634 nucleus | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt subcellular location mapping (nucleus). Reason: Activated Mad accumulates in the nucleus with Medea where it binds target enhancers; nucleus is a core location for its transcription factor activity. Supporting Evidence: file:DROME/Mad/Mad-uniprot.txt Localizes to the nucleus upon activation of the dpp/BMP signal transduction pathway |
| GO:0005667 transcription regulator complex | IEA GO_REF:0000002 | MODIFY | Summary: InterPro mapping to transcription regulator complex. Reason: Correct but general: Mad's transcription regulator complexes are the heteromeric Mad/Medea SMAD complex and, with Schnurri, the Pol II transcription repressor complex; both terms are already on the gene. Proposed replacements: heteromeric SMAD protein complex RNA polymerase II transcription repressor complex Supporting Evidence: file:DROME/Mad/Mad-uniprot.txt Component of a DNA binding Mad-Med complex composed of two copies of Mad and one copy of Med |
| GO:0005667 transcription regulator complex | IPI PMID:20010841 A conserved activation element in BMP signaling during Droso... | MODIFY | Summary: Mad/Medea complex at the AE. Reason: Correct but general: Mad's transcription regulator complexes are the heteromeric Mad/Medea SMAD complex and, with Schnurri, the Pol II transcription repressor complex; both terms are already on the gene. Proposed replacements: heteromeric SMAD protein complex RNA polymerase II transcription repressor complex Supporting Evidence: PMID:20010841 The AE is similar to the SE and recruits the Smad proteins via a conserved mechanism. |
| GO:0005737 cytoplasm | EXP PMID:17507407 Drosophila Nemo antagonizes BMP signaling by phosphorylation... | MODIFY | Summary: Cytoplasmic Mad (Nemo export). Reason: Correct but general: unstimulated Mad is a soluble cytoplasmic protein and the cytosol term (already on the gene, with IDA support) is the more precise location. Proposed replacements: cytosol Supporting Evidence: PMID:17507407 In cell culture, phosphorylation by Nemo blocks the nuclear accumulation of Mad by promoting export of Mad from the nucleus in a kinase-dependent manner. |
| GO:0005737 cytoplasm | EXP PMID:9502724 Medea is a Drosophila Smad4 homolog that is differentially r... | MODIFY | Summary: Cytoplasmic Mad. Reason: Correct but general: unstimulated Mad is a soluble cytoplasmic protein and the cytosol term (already on the gene, with IDA support) is the more precise location. Proposed replacements: cytosol Supporting Evidence: PMID:9502724 inactivating MEDEA mutations prevent nuclear translocation either by preventing interaction with MAD or by trapping MAD/MEDEA complexes in the cytosol |
| GO:0005737 cytoplasm | EXP PMID:9502733 The Drosophila gene Medea demonstrates the requirement for d... | MODIFY | Summary: Cytoplasmic Mad. Reason: Correct but general: unstimulated Mad is a soluble cytoplasmic protein and the cytosol term (already on the gene, with IDA support) is the more precise location. Proposed replacements: cytosol Supporting Evidence: PMID:9502733 upon activation of the Dpp pathway, Mad is required to actively translocate Medea into the nucleus |
| GO:0005737 cytoplasm | IDA PMID:16510868 Identification of phosphatases for Smad in the BMP/DPP pathw... | MODIFY | Summary: Cytoplasmic Mad. Reason: Correct but general: unstimulated Mad is a soluble cytoplasmic protein and the cytosol term (already on the gene, with IDA support) is the more precise location. Proposed replacements: cytosol Supporting Evidence: PMID:16510868 PDP directly dephosphorylates MAD and inhibits signal transduction of Decapentaplegic (DPP) |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | MODIFY | Summary: UniProt subcellular location mapping (cytoplasm). Reason: Correct but general: unstimulated Mad is a soluble cytoplasmic protein and the cytosol term (already on the gene, with IDA support) is the more precise location. Proposed replacements: cytosol Supporting Evidence: file:DROME/Mad/Mad-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0005829 cytosol | IDA PMID:17115029 A novel function of Drosophila eIF4A as a negative regulator... | ACCEPT | Summary: Cytosolic Mad. Reason: Inactive Mad resides in the cytosol, where it is phosphorylated by receptors and assembles with Medea before nuclear entry; a core location. Abstract-only cache; deferring to curator. Supporting Evidence: PMID:17115029 eIF4A physically associates with Mad and Medea, and promotes their degradation PMID:8681791 Immunohistochemical studies localize MAD to the cytoplasm in all tissues examined. |
| GO:0005829 cytosol | IDA PMID:39494616 A genome-engineered tool set for Drosophila TGF-Ξ²/BMP signal... | ACCEPT | Summary: Endogenously tagged Mad is largely cytosolic. Reason: Inactive Mad resides in the cytosol, where it is phosphorylated by receptors and assembles with Medea before nuclear entry; a core location. Supporting Evidence: PMID:39494616 the distribution of HA-Mad was uniform with no signs of nuclear enrichments in regions of high BMP signaling activity, suggesting that only a minor fraction of the protein accumulates in the nucleus upon phosphorylation |
| GO:0005829 cytosol | IDA PMID:8681791 Mothers against dpp encodes a conserved cytoplasmic protein ... | ACCEPT | Summary: MAD localises to the cytoplasm. Reason: Inactive Mad resides in the cytosol, where it is phosphorylated by receptors and assembles with Medea before nuclear entry; a core location. Supporting Evidence: PMID:8681791 Immunohistochemical studies localize MAD to the cytoplasm in all tissues examined. |
| GO:0005829 cytosol | IDA PMID:9502724 Medea is a Drosophila Smad4 homolog that is differentially r... | ACCEPT | Summary: MAD/MEDEA complexes in the cytosol. Reason: Inactive Mad resides in the cytosol, where it is phosphorylated by receptors and assembles with Medea before nuclear entry; a core location. Supporting Evidence: PMID:9502724 inactivating MEDEA mutations prevent nuclear translocation either by preventing interaction with MAD or by trapping MAD/MEDEA complexes in the cytosol |
| GO:0005829 cytosol | IDA PMID:9502733 The Drosophila gene Medea demonstrates the requirement for d... | ACCEPT | Summary: Cytosolic Mad prior to activation. Reason: Inactive Mad resides in the cytosol, where it is phosphorylated by receptors and assembles with Medea before nuclear entry; a core location. Supporting Evidence: PMID:9502733 upon activation of the Dpp pathway, Mad is required to actively translocate Medea into the nucleus |
| GO:0005829 cytosol | IEA GO_REF:0000117 | ACCEPT | Summary: ARBA cytosol. Reason: Inactive Mad resides in the cytosol, where it is phosphorylated by receptors and assembles with Medea before nuclear entry; a core location. The ARBA row agrees with experimental data. Supporting Evidence: PMID:8681791 Immunohistochemical studies localize MAD to the cytoplasm in all tissues examined. PMID:9502724 inactivating MEDEA mutations prevent nuclear translocation either by preventing interaction with MAD or by trapping MAD/MEDEA complexes in the cytosol |
| GO:0006355 regulation of DNA-templated transcription | IEA GO_REF:0000002 | MODIFY | Summary: InterPro mapping to regulation of transcription. Reason: Correct but general: Mad both activates and represses Pol II target genes; the specific terms are already on the gene. Proposed replacements: positive regulation of transcription by RNA polymerase II negative regulation of transcription by RNA polymerase II Supporting Evidence: file:DROME/Mad/Mad-uniprot.txt Mad-Med acts as a transcriptional activator but recruits shn/Shnurri to enhance its activity or switch to transcriptional repression |
| GO:0006357 regulation of transcription by RNA polymerase II | IBA GO_REF:0000033 | MODIFY | Summary: Phylogenetic inference of regulation of Pol II transcription. Reason: Correct but general: Mad both activates and represses Pol II target genes; the specific terms are already on the gene. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN000344419 SUPPORTS TRANSFER The SMAD ancestral node is correctly placed and Mad lies inside the clade; the inherited term is true for Mad but broader than the specific terms supported by Mad's own experimental evidence. Proposed replacements: positive regulation of transcription by RNA polymerase II negative regulation of transcription by RNA polymerase II Supporting Evidence: file:DROME/Mad/Mad-uniprot.txt Mad-Med acts as a transcriptional activator but recruits shn/Shnurri to enhance its activity or switch to transcriptional repression PMID:12705870 the brk silencer serves as a direct target for a protein complex consisting of the Smad homologs Mad/Medea and the zinc finger protein Schnurri PMID:9230443 Mad binds to and is required for the activation of an enhancer within the vestigial wing-patterning gene in cells across the entire developing wing blade. |
| GO:0007419 ventral cord development | HMP PMID:26092715 Novel Genes Involved in Controlling Specification of Drosoph... | KEEP AS NON CORE | Summary: Mad alleles recovered in a screen for FMRFa neuron specification in the ventral nerve cord. Reason: Mad mediates retrograde BMP signalling required for Ap4/FMRFa neuron terminal differentiation; a developmental outcome of BMP signalling. Supporting Evidence: PMID:26092715 we isolated mutants with global pMad staining reduction, all of which mapped to previously known genes: the BMP ligand-encoding gene gbb and the downstream effector Mad |
| GO:0007472 wing disc morphogenesis | IMP PMID:9230443 Drosophila Mad binds to DNA and directly mediates activation... | KEEP AS NON CORE | Summary: Mad required for wing disc vestigial enhancer activation. Reason: Mad is required for Dpp-dependent wing disc patterning and growth; a developmental outcome of BMP signalling, kept as non-core. Supporting Evidence: PMID:9230443 Mad binds to and is required for the activation of an enhancer within the vestigial wing-patterning gene in cells across the entire developing wing blade. |
| GO:0007476 imaginal disc-derived wing morphogenesis | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: ARBA wing morphogenesis. Reason: Mad is required for Dpp-dependent wing disc patterning and growth; a developmental outcome of BMP signalling, kept as non-core. Supporting Evidence: file:DROME/Mad/Mad-uniprot.txt Involved in anteroposterior patterning during wing imaginal disc growth |
| GO:0007476 imaginal disc-derived wing morphogenesis | IMP PMID:16648592 Epidermal growth factor receptor and transforming growth fac... | KEEP AS NON CORE | Summary: Mad insertion alleles alter wing shape as heterozygotes. Reason: Mad is required for Dpp-dependent wing disc patterning and growth; a developmental outcome of BMP signalling, kept as non-core. Supporting Evidence: PMID:16648592 the majority of these mutations have profound effects on shape but not size of the wing when measured as heterozygotes |
| GO:0007476 imaginal disc-derived wing morphogenesis | IMP PMID:8632795 Two distinct mechanisms for long-range patterning by Decapen... | KEEP AS NON CORE | Summary: Mad clonal analysis in wing A/P patterning. Reason: Mad is required for Dpp-dependent wing disc patterning and growth; a developmental outcome of BMP signalling, kept as non-core. Abstract-only cache does not name Mad; deferring to curator. Supporting Evidence: PMID:8632795 Evidence is presented that localized expression of Decapentaplegic instructs cells about their position along the anterior-posterior axis of the Drosophila wing in two distinct ways. file:DROME/Mad/Mad-uniprot.txt Involved in anteroposterior patterning during wing imaginal disc growth |
| GO:0007480 imaginal disc-derived leg morphogenesis | IMP PMID:11290719 Transgenic analysis of the Smad family of TGF-beta signal tr... | UNDECIDED | Summary: Phenotypes from Gal4/UAS overexpression of Smad transgenes. Reason: The cached abstract reports overexpression (gain-of-function) phenotypes of Smad transgenes; it is unclear whether a loss-of-function leg phenotype for Mad was shown. Full text not available. Supporting Evidence: PMID:11290719 We expressed six hSmad and four dSmad transgenes in Drosophila melanogaster using the Gal4/UAS system and compared their phenotypes. |
| GO:0007488 histoblast morphogenesis | IMP PMID:20226662 Dpp signaling directs cell motility and invasiveness during ... | KEEP AS NON CORE | Summary: Dpp signalling directs histoblast spreading. Reason: Developmental outcome of Dpp/Mad signalling in histoblasts. Supporting Evidence: PMID:20226662 Across nests, Dpp activity confers differential cellular behavior and motility by modulating cell-cell contacts, the organization and activity of the cytoskeleton, and histoblast attachment to the substrate. |
| GO:0007507 heart development | TAS PMID:12027431 Control of cardiac development by an evolutionarily conserve... | KEEP AS NON CORE | Summary: Heart development (review). Reason: Dpp signalling via Smads induces tinman in dorsal mesoderm, which gives rise to the heart; Mad's role is as the transcriptional effector. Non-core developmental outcome. Supporting Evidence: PMID:9694800 We show that the binding and synergistic activities of Smad and Tinman proteins are critical for mesodermal tinman induction |
| GO:0007560 imaginal disc morphogenesis | IMP PMID:7768443 Genetic characterization and cloning of mothers against dpp,... | KEEP AS NON CORE | Summary: Mad mutants have reduced imaginal discs. Reason: Developmental outcome of BMP signalling. Supporting Evidence: PMID:7768443 homozygous Mad mutant animals exhibit defects in midgut morphogenesis, imaginal disk development and embryonic dorsal-ventral patterning that are very reminiscent of dpp mutant phenotypes |
| GO:0008586 imaginal disc-derived wing vein morphogenesis | IMP PMID:11290719 Transgenic analysis of the Smad family of TGF-beta signal tr... | KEEP AS NON CORE | Summary: Wing vein phenotypes from Smad transgenes. Reason: Wing vein patterning depends on Dpp/Mad signalling; supported by Mad's established wing role. Non-core developmental outcome. Supporting Evidence: PMID:11290719 We expressed six hSmad and four dSmad transgenes in Drosophila melanogaster using the Gal4/UAS system and compared their phenotypes. file:DROME/Mad/Mad-uniprot.txt Involved in anteroposterior patterning during wing imaginal disc growth |
| GO:0009653 anatomical structure morphogenesis | IBA GO_REF:0000033 | MODIFY | Summary: Phylogenetic inference of anatomical structure morphogenesis. Reason: Correct but general: PAINT places morphogenesis on the R-Smad node; for Mad the supported specific processes are imaginal disc-derived wing morphogenesis and compound eye morphogenesis, both already on the gene. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN000344419 SUPPORTS TRANSFER The SMAD ancestral node is correctly placed and Mad lies inside the clade; the inherited term is true for Mad but broader than the specific terms supported by Mad's own experimental evidence. Proposed replacements: imaginal disc-derived wing morphogenesis compound eye morphogenesis Supporting Evidence: PMID:7768443 homozygous Mad mutant animals exhibit defects in midgut morphogenesis, imaginal disk development and embryonic dorsal-ventral patterning that are very reminiscent of dpp mutant phenotypes PMID:8681796 Mad-mediated dpp signaling is absolutely required for the initiation of the morphogenetic furrow in the eye |
| GO:0030154 cell differentiation | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Phylogenetic inference of cell differentiation. Reason: Smads regulate differentiation in many contexts; for Mad the process is a pleiotropic outcome of BMP signalling (e.g. intestinal progenitor and photoreceptor subtype differentiation). Kept as non-core. Supporting Evidence: PMID:20056890 both resulted in premature differentiation of AMPs into large, polyploid, enterocyte-like cells PMID:28853393 Concomitantly, two BMP ligands activate their receptor, Thickveins, and the transcriptional effector, Mad. |
| GO:0030509 BMP signaling pathway | IBA GO_REF:0000033 | ACCEPT | Summary: Mad acts as the transcriptional effector of BMP (Dpp/Gbb) signalling. Reason: Mad is the central receptor-regulated Smad transducing Dpp/Gbb (BMP) signals to the nucleus; BMP signaling pathway is its core process. Supporting Evidence: PMID:7705627 We propose that Mad and Medea encode rate-limiting components integral to dpp pathways throughout development. file:DROME/Mad/Mad-uniprot.txt Component of the Mad-Med transcription factor complex involved in the dpp/BMP TGF-beta signal transduction pathway |
| GO:0030509 BMP signaling pathway | IDA PMID:11071761 The zinc finger protein schnurri acts as a Smad partner in m... | ACCEPT | Summary: Mad acts as the transcriptional effector of BMP (Dpp/Gbb) signalling. Reason: Mad is the central receptor-regulated Smad transducing Dpp/Gbb (BMP) signals to the nucleus; BMP signaling pathway is its core process. Supporting Evidence: PMID:11071761 show that Shn and Mad act synergistically to induce transcription |
| GO:0030509 BMP signaling pathway | IDA PMID:12705870 Conversion of an extracellular Dpp/BMP morphogen gradient in... | ACCEPT | Summary: Mad acts as the transcriptional effector of BMP (Dpp/Gbb) signalling. Reason: Mad is the central receptor-regulated Smad transducing Dpp/Gbb (BMP) signals to the nucleus; BMP signaling pathway is its core process. Supporting Evidence: PMID:12705870 the brk silencer serves as a direct target for a protein complex consisting of the Smad homologs Mad/Medea and the zinc finger protein Schnurri |
| GO:0030509 BMP signaling pathway | IDA PMID:17008448 Schnurri transcription factors from Drosophila and vertebrat... | ACCEPT | Summary: Mad acts as the transcriptional effector of BMP (Dpp/Gbb) signalling. Reason: Mad is the central receptor-regulated Smad transducing Dpp/Gbb (BMP) signals to the nucleus; BMP signaling pathway is its core process. Supporting Evidence: PMID:17008448 by forming a Shn/Smad repression complex on defined promoter elements in the brinker (brk) gene |
| GO:0030509 BMP signaling pathway | IDA PMID:18588885 Specificity of the inhibitory effects of Dad on TGF-beta fam... | ACCEPT | Summary: Mad acts as the transcriptional effector of BMP (Dpp/Gbb) signalling. Reason: Mad is the central receptor-regulated Smad transducing Dpp/Gbb (BMP) signals to the nucleus; BMP signaling pathway is its core process. Supporting Evidence: PMID:18588885 Dad inhibited Saxophone (ALK-1/2 orthologue) and Thickveins (ALK-3/6 orthologue) but not Baboon (ALK-4/5/7 orthologue). PMID:9693372 Mad forms a heteromeric complex with Drosophila Smad4 (Medea) upon phosphorylation by Thick veins (Tkv), a type I receptor for Dpp. |
| GO:0030509 BMP signaling pathway | IDA PMID:20010841 A conserved activation element in BMP signaling during Droso... | ACCEPT | Summary: Mad acts as the transcriptional effector of BMP (Dpp/Gbb) signalling. Reason: Mad is the central receptor-regulated Smad transducing Dpp/Gbb (BMP) signals to the nucleus; BMP signaling pathway is its core process. Supporting Evidence: PMID:20010841 activating input by the Smad signal transducers Mothers against Dpp (Mad) and Medea via competitive DNA binding |
| GO:0030509 BMP signaling pathway | IDA PMID:25377173 Mad linker phosphorylations control the intensity and range ... | ACCEPT | Summary: Mad acts as the transcriptional effector of BMP (Dpp/Gbb) signalling. Reason: Mad is the central receptor-regulated Smad transducing Dpp/Gbb (BMP) signals to the nucleus; BMP signaling pathway is its core process. Supporting Evidence: PMID:25377173 The BMP signal is transduced intracellularly via C-terminal phosphorylation of the BMP transcription factor Mad |
| GO:0030509 BMP signaling pathway | IDA PMID:36029115 Dichotomous cis-regulatory motifs mediate the maturation of ... | ACCEPT | Summary: Mad acts as the transcriptional effector of BMP (Dpp/Gbb) signalling. Reason: Mad is the central receptor-regulated Smad transducing Dpp/Gbb (BMP) signals to the nucleus; BMP signaling pathway is its core process. Supporting Evidence: PMID:36029115 Unpredictably, both motifs mediate direct gene activation, with no involvement of the BMP derepression pathway regulators Schnurri and Brinker. |
| GO:0030509 BMP signaling pathway | IDA PMID:36641752 The Integrator complex desensitizes cellular response to TGF... | ACCEPT | Summary: Mad acts as the transcriptional effector of BMP (Dpp/Gbb) signalling. Reason: Mad is the central receptor-regulated Smad transducing Dpp/Gbb (BMP) signals to the nucleus; BMP signaling pathway is its core process. Supporting Evidence: PMID:36641752 Integrator works in various developmental contexts to desensitize the cellular response to Dpp/BMP signaling during Drosophila development |
| GO:0030509 BMP signaling pathway | IDA PMID:9502733 The Drosophila gene Medea demonstrates the requirement for d... | ACCEPT | Summary: Mad acts as the transcriptional effector of BMP (Dpp/Gbb) signalling. Reason: Mad is the central receptor-regulated Smad transducing Dpp/Gbb (BMP) signals to the nucleus; BMP signaling pathway is its core process. Supporting Evidence: PMID:9502733 upon activation of the Dpp pathway, Mad is required to actively translocate Medea into the nucleus |
| GO:0030509 BMP signaling pathway | IDA PMID:9693372 Interplay of signal mediators of decapentaplegic (Dpp): mole... | ACCEPT | Summary: Mad acts as the transcriptional effector of BMP (Dpp/Gbb) signalling. Reason: Mad is the central receptor-regulated Smad transducing Dpp/Gbb (BMP) signals to the nucleus; BMP signaling pathway is its core process. Supporting Evidence: PMID:9693372 Mad forms a heteromeric complex with Drosophila Smad4 (Medea) upon phosphorylation by Thick veins (Tkv), a type I receptor for Dpp. |
| GO:0030509 BMP signaling pathway | IGI PMID:28853393 Parallel Activin and BMP signaling coordinates R7/R8 photore... | ACCEPT | Summary: Mad acts as the transcriptional effector of BMP (Dpp/Gbb) signalling. Reason: Mad is the central receptor-regulated Smad transducing Dpp/Gbb (BMP) signals to the nucleus; BMP signaling pathway is its core process. Supporting Evidence: PMID:28853393 Concomitantly, two BMP ligands activate their receptor, Thickveins, and the transcriptional effector, Mad. |
| GO:0030509 BMP signaling pathway | IGI PMID:7705627 Genetic screens to identify elements of the decapentaplegic ... | ACCEPT | Summary: Mad acts as the transcriptional effector of BMP (Dpp/Gbb) signalling. Reason: Mad is the central receptor-regulated Smad transducing Dpp/Gbb (BMP) signals to the nucleus; BMP signaling pathway is its core process. Supporting Evidence: PMID:7705627 We propose that Mad and Medea encode rate-limiting components integral to dpp pathways throughout development. |
| GO:0030509 BMP signaling pathway | IGI PMID:7768443 Genetic characterization and cloning of mothers against dpp,... | ACCEPT | Summary: Mad acts as the transcriptional effector of BMP (Dpp/Gbb) signalling. Reason: Mad is the central receptor-regulated Smad transducing Dpp/Gbb (BMP) signals to the nucleus; BMP signaling pathway is its core process. Supporting Evidence: PMID:7768443 homozygous Mad mutant animals exhibit defects in midgut morphogenesis, imaginal disk development and embryonic dorsal-ventral patterning that are very reminiscent of dpp mutant phenotypes |
| GO:0030509 BMP signaling pathway | IGI PMID:8681791 Mothers against dpp encodes a conserved cytoplasmic protein ... | ACCEPT | Summary: Mad acts as the transcriptional effector of BMP (Dpp/Gbb) signalling. Reason: Mad is the central receptor-regulated Smad transducing Dpp/Gbb (BMP) signals to the nucleus; BMP signaling pathway is its core process. Supporting Evidence: PMID:8681791 Mad is required for any response of the visceral mesoderm or endoderm to DPP signals from the visceral mesoderm |
| GO:0030509 BMP signaling pathway | IGI PMID:8681796 Mad acts downstream of Dpp receptors, revealing a differenti... | ACCEPT | Summary: Mad acts as the transcriptional effector of BMP (Dpp/Gbb) signalling. Reason: Mad is the central receptor-regulated Smad transducing Dpp/Gbb (BMP) signals to the nucleus; BMP signaling pathway is its core process. Supporting Evidence: PMID:8681796 Clonal analysis demonstrates a cell-autonomous function for Mad and genetic interactions indicate that Mad is an essential component of the signal transduction pathway downstream of the Dpp receptors in responding cells. |
| GO:0030509 BMP signaling pathway | IGI PMID:8681796 Mad acts downstream of Dpp receptors, revealing a differenti... | ACCEPT | Summary: Mad acts as the transcriptional effector of BMP (Dpp/Gbb) signalling. Reason: Mad is the central receptor-regulated Smad transducing Dpp/Gbb (BMP) signals to the nucleus; BMP signaling pathway is its core process. Supporting Evidence: PMID:8681796 Clonal analysis demonstrates a cell-autonomous function for Mad and genetic interactions indicate that Mad is an essential component of the signal transduction pathway downstream of the Dpp receptors in responding cells. |
| GO:0030509 BMP signaling pathway | IGI PMID:8681796 Mad acts downstream of Dpp receptors, revealing a differenti... | ACCEPT | Summary: Mad acts as the transcriptional effector of BMP (Dpp/Gbb) signalling. Reason: Mad is the central receptor-regulated Smad transducing Dpp/Gbb (BMP) signals to the nucleus; BMP signaling pathway is its core process. Supporting Evidence: PMID:8681796 Clonal analysis demonstrates a cell-autonomous function for Mad and genetic interactions indicate that Mad is an essential component of the signal transduction pathway downstream of the Dpp receptors in responding cells. |
| GO:0030509 BMP signaling pathway | IGI PMID:9502724 Medea is a Drosophila Smad4 homolog that is differentially r... | ACCEPT | Summary: Mad acts as the transcriptional effector of BMP (Dpp/Gbb) signalling. Reason: Mad is the central receptor-regulated Smad transducing Dpp/Gbb (BMP) signals to the nucleus; BMP signaling pathway is its core process. Supporting Evidence: PMID:9502724 while MAD is essential for mediating all DPP signals, heteromeric MAD/MEDEA complexes function to modify or enhance DPP responses |
| GO:0030509 BMP signaling pathway | IGI PMID:9502733 The Drosophila gene Medea demonstrates the requirement for d... | ACCEPT | Summary: Mad acts as the transcriptional effector of BMP (Dpp/Gbb) signalling. Reason: Mad is the central receptor-regulated Smad transducing Dpp/Gbb (BMP) signals to the nucleus; BMP signaling pathway is its core process. Supporting Evidence: PMID:9502733 Embryos from germline clones of both Medea and Mad (a class I Smad) are ventralized, as are embryos null for the TGF-beta-like ligand decapentaplegic (dpp). |
| GO:0030509 BMP signaling pathway | IMP PMID:10094047 brinker is a target of Dpp in Drosophila that negatively reg... | ACCEPT | Summary: Mad acts as the transcriptional effector of BMP (Dpp/Gbb) signalling. Reason: Mad is the central receptor-regulated Smad transducing Dpp/Gbb (BMP) signals to the nucleus; BMP signaling pathway is its core process. Supporting Evidence: PMID:10094047 We report here the molecular cloning of brinker (brk), and show that brk expression is repressed by dpp. |
| GO:0030509 BMP signaling pathway | IMP PMID:15046722 Highwire regulates presynaptic BMP signaling essential for s... | ACCEPT | Summary: Mad acts as the transcriptional effector of BMP (Dpp/Gbb) signalling. Reason: Mad is the central receptor-regulated Smad transducing Dpp/Gbb (BMP) signals to the nucleus; BMP signaling pathway is its core process. Supporting Evidence: PMID:15046722 Med is part of a presynaptic bone morphogenetic protein (BMP) signaling cascade consisting of three receptor subunits, Wit, Tkv, and Sax, in addition to the Smad transcription factor Mad. |
| GO:0030509 BMP signaling pathway | IMP PMID:18820452 Distinct signaling of Drosophila Activin/TGF-beta family mem... | ACCEPT | Summary: Mad acts as the transcriptional effector of BMP (Dpp/Gbb) signalling. Reason: Mad is the central receptor-regulated Smad transducing Dpp/Gbb (BMP) signals to the nucleus; BMP signaling pathway is its core process. Supporting Evidence: PMID:18820452 Surprisingly, we find that activation of BABO can also lead to the phosphorylation of the "BMP-specific" MAD. |
| GO:0030509 BMP signaling pathway | IMP PMID:22959350 Integration of a retrograde signal during synapse formation ... | ACCEPT | Summary: Mad acts as the transcriptional effector of BMP (Dpp/Gbb) signalling. Reason: Mad is the central receptor-regulated Smad transducing Dpp/Gbb (BMP) signals to the nucleus; BMP signaling pathway is its core process. Supporting Evidence: PMID:22959350 This induces phosphorylation of Mad (P-Mad) in motor neurons, its translocation into the nucleus with a co-Smad, and activation of transcriptional programs controlling presynaptic bouton growth |
| GO:0030509 BMP signaling pathway | IMP PMID:39494616 A genome-engineered tool set for Drosophila TGF-Ξ²/BMP signal... | ACCEPT | Summary: Mad acts as the transcriptional effector of BMP (Dpp/Gbb) signalling. Reason: Mad is the central receptor-regulated Smad transducing Dpp/Gbb (BMP) signals to the nucleus; BMP signaling pathway is its core process. Supporting Evidence: PMID:39494616 We demonstrate that the generated alleles are biologically active |
| GO:0030509 BMP signaling pathway | IMP PMID:40955849 Drosophila Dpp and BMP signaling directly regulates dpp tran... | ACCEPT | Summary: Mad acts as the transcriptional effector of BMP (Dpp/Gbb) signalling. Reason: Mad is the central receptor-regulated Smad transducing Dpp/Gbb (BMP) signals to the nucleus; BMP signaling pathway is its core process. Supporting Evidence: PMID:40955849 This transcriptional negative-feedback mechanism primarily depends on the BMP-silencer-element (BMP-SE) complex binding to BMP-SE motifs at the dpp downstream distal cis-regulatory region. |
| GO:0030509 BMP signaling pathway | IMP PMID:8632795 Two distinct mechanisms for long-range patterning by Decapen... | ACCEPT | Summary: Mad acts as the transcriptional effector of BMP (Dpp/Gbb) signalling. Reason: Mad is the central receptor-regulated Smad transducing Dpp/Gbb (BMP) signals to the nucleus; BMP signaling pathway is its core process. Supporting Evidence: PMID:8632795 Evidence is presented that localized expression of Decapentaplegic instructs cells about their position along the anterior-posterior axis of the Drosophila wing in two distinct ways. file:DROME/Mad/Mad-uniprot.txt Component of the Mad-Med transcription factor complex involved in the dpp/BMP TGF-beta signal transduction pathway |
| GO:0030509 BMP signaling pathway | IMP PMID:8702167 Characterization of Medea, a gene required for maximal funct... | ACCEPT | Summary: Mad acts as the transcriptional effector of BMP (Dpp/Gbb) signalling. Reason: Mad is the central receptor-regulated Smad transducing Dpp/Gbb (BMP) signals to the nucleus; BMP signaling pathway is its core process. Supporting Evidence: file:DROME/Mad/Mad-uniprot.txt Component of the Mad-Med transcription factor complex involved in the dpp/BMP TGF-beta signal transduction pathway |
| GO:0030707 follicle cell of egg chamber development | IMP PMID:16256740 BMP signaling is required for controlling somatic stem cell ... | KEEP AS NON CORE | Summary: BMP signalling in ovarian somatic stem cells. Reason: Developmental outcome of BMP signalling in follicle stem cell lineage. Supporting Evidence: PMID:16256740 BMP signaling is required in SSCs to directly control their maintenance and division, but is dispensable for proliferation of their differentiated progeny. |
| GO:0030718 germ-line stem cell population maintenance | IMP PMID:9695953 decapentaplegic is essential for the maintenance and divisio... | KEEP AS NON CORE | Summary: Dpp signal is received directly by germline stem cells. Reason: Mad transduces the niche Dpp signal that maintains female GSCs (UniProt notes Mad is essential in the germline); a non-core developmental context. Supporting Evidence: PMID:9695953 We constructed mutant germline stem cell clones to show that the dpp signal is directly received by germline stem cells. PMID:9695953 dpp) is specifically required to maintain female germline stem cells and promote their division |
| GO:0035019 somatic stem cell population maintenance | IMP PMID:16256740 BMP signaling is required for controlling somatic stem cell ... | KEEP AS NON CORE | Summary: BMP signalling maintains ovarian somatic stem cells. Reason: Developmental outcome of BMP signalling. Supporting Evidence: PMID:16256740 BMP signaling is required in SSCs to directly control their maintenance and division, but is dispensable for proliferation of their differentiated progeny. |
| GO:0035290 trunk segmentation | IMP PMID:19657393 Mad is required for wingless signaling in wing development a... | KEEP AS NON CORE | Summary: Mad depletion produces segmentation phenotypes. Reason: Mad depletion gives Wingless-like segmentation phenotypes, attributed to Mad's integration of Wg/GSK3 signalling; a non-core developmental role. Supporting Evidence: PMID:19657393 Mad depletion or overexpression produced Wingless-like embryonic segmentation phenotypes. |
| GO:0036335 intestinal stem cell homeostasis | IEP PMID:23733344 Injury-induced BMP signaling negatively regulates Drosophila... | KEEP AS NON CORE | Summary: Injury-induced BMP signalling (pMad) in midgut ISCs. Reason: pMad is induced after injury and Mad clones show ISC phenotypes; BMP signalling limits ISC proliferation after injury. Non-core physiological context. Supporting Evidence: PMID:23733344 injury-induced BMP signaling acted autonomously in ISCs to limit proliferation and stem cell number after injury |
| GO:0042078 germ-line stem cell division | IMP PMID:9695953 decapentaplegic is essential for the maintenance and divisio... | KEEP AS NON CORE | Summary: Dpp signalling promotes GSC division. Reason: Developmental outcome of niche BMP signalling. Supporting Evidence: PMID:9695953 dpp) is specifically required to maintain female germline stem cells and promote their division |
| GO:0042592 homeostatic process | IEA GO_REF:0000117 | MODIFY | Summary: ARBA homeostatic process. Reason: Correct but general: the supported homeostatic role of Mad is in intestinal stem cell homeostasis, already on the gene. Proposed replacements: intestinal stem cell homeostasis Supporting Evidence: PMID:23733344 injury-induced BMP signaling acted autonomously in ISCs to limit proliferation and stem cell number after injury |
| GO:0043565 sequence-specific DNA binding | IDA PMID:14507783 Tgfbeta signaling acts on a Hox response element to confer s... | MODIFY | Summary: Mad binding to the wingless visceral mesoderm enhancer. Reason: Correct but general: the sites bound are Pol II cis-regulatory enhancer elements; the specific term is already on the gene. Proposed replacements: RNA polymerase II cis-regulatory region sequence-specific DNA binding Supporting Evidence: PMID:14507783 The signal, acting through Mad and Creb, provides spatial information that subdivides the domain of Abdominal A function through direct combinatorial action |
| GO:0043565 sequence-specific DNA binding | IDA PMID:17092951 Threshold response of C15 to the Dpp gradient in Drosophila ... | MODIFY | Summary: Smad-binding sites in the C15 enhancer. Reason: Correct but general: the sites bound are Pol II cis-regulatory enhancer elements; the specific term is already on the gene. Proposed replacements: RNA polymerase II cis-regulatory region sequence-specific DNA binding Supporting Evidence: PMID:17092951 The C15 regulatory element contains clusters of Smad- and Zen-binding sites in close proximity. |
| GO:0045464 R8 cell fate specification | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: ARBA R8 cell fate specification. Reason: Mad cooperates with dSmad2 in R8 to specify pale/yellow subtype (Rhodopsin choice); non-core developmental outcome. Supporting Evidence: PMID:28853393 Mad and dSmad2 cooperate to modulate the Hippo pathway kinase Warts and the growth regulator Melted |
| GO:0045464 R8 cell fate specification | IMP PMID:28853393 Parallel Activin and BMP signaling coordinates R7/R8 photore... | KEEP AS NON CORE | Summary: Mad required in R8 subtype specification. Reason: Mad cooperates with dSmad2 in R8 to specify pale/yellow subtype (Rhodopsin choice); non-core developmental outcome. Supporting Evidence: PMID:28853393 Concomitantly, two BMP ligands activate their receptor, Thickveins, and the transcriptional effector, Mad. PMID:28853393 Mad and dSmad2 cooperate to modulate the Hippo pathway kinase Warts and the growth regulator Melted |
| GO:0045595 regulation of cell differentiation | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: ARBA regulation of cell differentiation. Reason: Mad (BMP signalling) restrains or promotes differentiation depending on context; a pleiotropic, non-core outcome. Supporting Evidence: PMID:20056890 both resulted in premature differentiation of AMPs into large, polyploid, enterocyte-like cells |
| GO:0045595 regulation of cell differentiation | IMP PMID:20056890 A transient niche regulates the specification of Drosophila ... | KEEP AS NON CORE | Summary: Mad clones cause premature differentiation of adult midgut progenitors. Reason: Mad (BMP signalling) restrains or promotes differentiation depending on context; a pleiotropic, non-core outcome. Supporting Evidence: PMID:20056890 both resulted in premature differentiation of AMPs into large, polyploid, enterocyte-like cells |
| GO:0045705 negative regulation of salivary gland boundary specification | TAS PMID:11598957 Organ formation in Drosophila: specification and morphogenes... | UNDECIDED | Summary: Salivary gland boundary specification (review). Reason: The cited review abstract does not mention Mad and no primary evidence linking Mad to salivary gland boundary specification is available in the cache. |
| GO:0045887 positive regulation of synaptic assembly at neuromuscular junction | IMP PMID:15046722 Highwire regulates presynaptic BMP signaling essential for s... | KEEP AS NON CORE | Summary: BMP mutants including Mad have smaller NMJs. Reason: Mad mediates retrograde Gbb/BMP signalling in motor neurons that promotes NMJ synaptic growth; non-core developmental outcome. Supporting Evidence: PMID:15046722 When compared to wild-type, mutants of BMP signaling components have smaller NMJ size, reduced neurotransmitter release, and aberrant synaptic ultrastructure. PMID:15046722 Med is part of a presynaptic bone morphogenetic protein (BMP) signaling cascade consisting of three receptor subunits, Wit, Tkv, and Sax, in addition to the Smad transcription factor Mad. |
| GO:0045887 positive regulation of synaptic assembly at neuromuscular junction | IMP PMID:19451277 Nemo kinase interacts with Mad to coordinate synaptic growth... | KEEP AS NON CORE | Summary: Nemo phosphorylation of Mad required for normal NMJ. Reason: Mad mediates retrograde Gbb/BMP signalling in motor neurons that promotes NMJ synaptic growth; non-core developmental outcome. Supporting Evidence: PMID:19451277 Finally, our results indicate that Nmo phosphorylation of Mad at its N terminus, distinct from the BMP phosphorylation site, is required for normal function of Mad. |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IDA PMID:11071761 The zinc finger protein schnurri acts as a Smad partner in m... | ACCEPT | Summary: Mad and Shn synergistically activate transcription. Reason: Mad directly activates Pol II target genes (vestigial, Ubx, dad, tinman, neuronal targets); core process. Supporting Evidence: PMID:11071761 show that Shn and Mad act synergistically to induce transcription |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IDA PMID:11306550 Direct competition between Brinker and Drosophila Mad in Dpp... | ACCEPT | Summary: Activated Mad stimulates the Ubx enhancer. Reason: Mad directly activates Pol II target genes (vestigial, Ubx, dad, tinman, neuronal targets); core process. Supporting Evidence: PMID:11306550 Brinker also competes with activated Mad in vivo, blocking the stimulation of the Ubx enhancer in response to simultaneous Dpp signalling. |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IDA PMID:20010841 A conserved activation element in BMP signaling during Droso... | ACCEPT | Summary: Mad/Medea activate via AE. Reason: Mad directly activates Pol II target genes (vestigial, Ubx, dad, tinman, neuronal targets); core process. Supporting Evidence: PMID:20010841 activating input by the Smad signal transducers Mothers against Dpp (Mad) and Medea via competitive DNA binding |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IDA PMID:24321690 Comparative gene expression analysis of Dtg, a novel target ... | ACCEPT | Summary: Mad motifs required for Dtg enhancer expression. Reason: Mad directly activates Pol II target genes (vestigial, Ubx, dad, tinman, neuronal targets); core process. Supporting Evidence: PMID:24321690 This enhancer contained a highly conserved region of 48-bp in which bioinformatic predictions and in vitro assays identified three Mad binding motifs. |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IEP PMID:9230443 Drosophila Mad binds to DNA and directly mediates activation... | ACCEPT | Summary: Mad required for activation of the vg enhancer. Reason: Mad directly activates Pol II target genes (vestigial, Ubx, dad, tinman, neuronal targets); core process. Supporting Evidence: PMID:9230443 Mad binds to and is required for the activation of an enhancer within the vestigial wing-patterning gene in cells across the entire developing wing blade. |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IMP PMID:14507783 Tgfbeta signaling acts on a Hox response element to confer s... | ACCEPT | Summary: Mad required for wingless activation in visceral mesoderm. Reason: Mad directly activates Pol II target genes (vestigial, Ubx, dad, tinman, neuronal targets); core process. Supporting Evidence: PMID:14507783 The signal, acting through Mad and Creb, provides spatial information that subdivides the domain of Abdominal A function through direct combinatorial action |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IMP PMID:9694800 Smad proteins act in combination with synergistic and antago... | ACCEPT | Summary: Smad sites required for tinman induction. Reason: Mad directly activates Pol II target genes (vestigial, Ubx, dad, tinman, neuronal targets); core process. Supporting Evidence: PMID:9694800 We show that the binding and synergistic activities of Smad and Tinman proteins are critical for mesodermal tinman induction |
| GO:0048100 wing disc anterior/posterior pattern formation | IMP PMID:15708556 The role of Dpp signaling in maintaining the Drosophila ante... | KEEP AS NON CORE | Summary: Dpp signal transduction required in anterior cells for A/P boundary maintenance. Reason: Developmental outcome of Dpp/Mad signalling. Supporting Evidence: PMID:15708556 Further, we find that Dpp signal transduction is required in anterior cells, but not in posterior cells |
| GO:0048639 positive regulation of developmental growth | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: ARBA positive regulation of developmental growth. Reason: Dpp/Mad signalling promotes wing disc growth; Mad linker mutants enlarge wings. Non-core outcome of BMP signalling. Supporting Evidence: PMID:25377173 The BMP signal is transduced intracellularly via C-terminal phosphorylation of the BMP transcription factor Mad file:DROME/Mad/Mad-uniprot.txt Involved in anteroposterior patterning during wing imaginal disc growth |
| GO:0050803 regulation of synapse structure or activity | IEA GO_REF:0000117 | MODIFY | Summary: ARBA regulation of synapse structure or activity. Reason: Correct but general: Mad's supported synaptic role is positive regulation of synaptic assembly at the NMJ, already on the gene. Proposed replacements: positive regulation of synaptic assembly at neuromuscular junction Supporting Evidence: PMID:15046722 When compared to wild-type, mutants of BMP signaling components have smaller NMJ size, reduced neurotransmitter release, and aberrant synaptic ultrastructure. |
| GO:0051962 positive regulation of nervous system development | IEA GO_REF:0000117 | MODIFY | Summary: ARBA positive regulation of nervous system development. Reason: Correct but general: the supported role is positive regulation of neuromuscular junction development, already on the gene. Proposed replacements: positive regulation of neuromuscular junction development Supporting Evidence: PMID:22959350 This induces phosphorylation of Mad (P-Mad) in motor neurons, its translocation into the nucleus with a co-Smad, and activation of transcriptional programs controlling presynaptic bouton growth |
| GO:0060395 SMAD protein signal transduction | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic inference of SMAD protein signal transduction. Reason: Mad is the R-Smad that, once C-terminally phosphorylated, oligomerises with Medea and carries the signal into the nucleus; core process. Supporting Evidence: PMID:9693372 Mad forms a heteromeric complex with Drosophila Smad4 (Medea) upon phosphorylation by Thick veins (Tkv), a type I receptor for Dpp. file:DROME/Mad/Mad-uniprot.txt Component of the Mad-Med transcription factor complex involved in the dpp/BMP TGF-beta signal transduction pathway |
| GO:0060395 SMAD protein signal transduction | IDA PMID:9502733 The Drosophila gene Medea demonstrates the requirement for d... | ACCEPT | Summary: Mad translocates Medea to the nucleus upon Dpp signalling. Reason: Mad is the R-Smad that, once C-terminally phosphorylated, oligomerises with Medea and carries the signal into the nucleus; core process. Supporting Evidence: PMID:9502733 upon activation of the Dpp pathway, Mad is required to actively translocate Medea into the nucleus |
| GO:0061629 RNA polymerase II-specific DNA-binding transcription factor binding | IPI PMID:11071761 The zinc finger protein schnurri acts as a Smad partner in m... | ACCEPT | Summary: Mad binds Schnurri directly. Reason: Mad directly binds the zinc-finger DNA-binding transcription factor Schnurri, which it recruits to Dpp-responsive elements; an informative, mechanistically important interaction. Supporting Evidence: PMID:11071761 Furthermore we find that Shn and Mad can interact directly through discrete domains. |
| GO:0070410 co-SMAD binding | IEA GO_REF:0000117 | ACCEPT | Summary: ARBA co-SMAD binding. Reason: Mad associates with the co-Smad Medea upon receptor phosphorylation; co-SMAD binding is a core molecular function. Supporting Evidence: PMID:9693372 Mad forms a heteromeric complex with Drosophila Smad4 (Medea) upon phosphorylation by Thick veins (Tkv), a type I receptor for Dpp. PMID:9502724 MEDEA is most similar to mammalian Smad4 and forms heteromeric complexes with MAD. |
| GO:0070410 co-SMAD binding | IPI PMID:18588885 Specificity of the inhibitory effects of Dad on TGF-beta fam... | ACCEPT | Summary: Mad-Medea interaction. Reason: Mad associates with the co-Smad Medea upon receptor phosphorylation; co-SMAD binding is a core molecular function. Abstract-only cache; Mad/Medea association is well established. Supporting Evidence: PMID:9693372 Mad forms a heteromeric complex with Drosophila Smad4 (Medea) upon phosphorylation by Thick veins (Tkv), a type I receptor for Dpp. |
| GO:0070411 I-SMAD binding | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Phylogenetic inference of I-SMAD binding. Reason: Vertebrate BMP R-Smads bind I-Smads; in Drosophila, Dad blocks Mad hetero-oligomerisation and nuclear translocation, but direct Mad-Dad binding is not clearly documented. Plausible inherited property kept as non-core. Supporting Evidence: PMID:9693372 Dad also blocks hetero-oligomerization and nuclear translocation of Mad. |
| GO:0071144 heteromeric SMAD protein complex | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic inference of heteromeric SMAD complex. Reason: Phosphorylated Mad forms heteromeric complexes with Medea (two Mad, one Medea on DNA); core complex. Supporting Evidence: PMID:9693372 Mad forms a heteromeric complex with Drosophila Smad4 (Medea) upon phosphorylation by Thick veins (Tkv), a type I receptor for Dpp. file:DROME/Mad/Mad-uniprot.txt Component of a DNA binding Mad-Med complex composed of two copies of Mad and one copy of Med |
| GO:0071144 heteromeric SMAD protein complex | IDA PMID:9693372 Interplay of signal mediators of decapentaplegic (Dpp): mole... | ACCEPT | Summary: Tkv-induced Mad/Medea hetero-complex. Reason: Phosphorylated Mad forms heteromeric complexes with Medea (two Mad, one Medea on DNA); core complex. Supporting Evidence: PMID:9693372 Mad forms a heteromeric complex with Drosophila Smad4 (Medea) upon phosphorylation by Thick veins (Tkv), a type I receptor for Dpp. |
| GO:0071144 heteromeric SMAD protein complex | IEA GO_REF:0000117 | ACCEPT | Summary: ARBA heteromeric SMAD complex. Reason: Phosphorylated Mad forms heteromeric complexes with Medea (two Mad, one Medea on DNA); core complex. Supporting Evidence: PMID:9502724 MEDEA is most similar to mammalian Smad4 and forms heteromeric complexes with MAD. |
| GO:0071144 heteromeric SMAD protein complex | IPI PMID:18588885 Specificity of the inhibitory effects of Dad on TGF-beta fam... | ACCEPT | Summary: Mad/Medea complex. Reason: Phosphorylated Mad forms heteromeric complexes with Medea (two Mad, one Medea on DNA); core complex. Supporting Evidence: PMID:9693372 Mad forms a heteromeric complex with Drosophila Smad4 (Medea) upon phosphorylation by Thick veins (Tkv), a type I receptor for Dpp. |
| GO:0071144 heteromeric SMAD protein complex | IPI PMID:9502724 Medea is a Drosophila Smad4 homolog that is differentially r... | ACCEPT | Summary: MEDEA forms heteromeric complexes with MAD. Reason: Phosphorylated Mad forms heteromeric complexes with Medea (two Mad, one Medea on DNA); core complex. Supporting Evidence: PMID:9502724 MEDEA is most similar to mammalian Smad4 and forms heteromeric complexes with MAD. |
| GO:0090571 RNA polymerase II transcription repressor complex | IPI PMID:12705870 Conversion of an extracellular Dpp/BMP morphogen gradient in... | ACCEPT | Summary: Mad/Medea/Shn complex at the brk silencer. Reason: Mad/Medea with Schnurri forms a DNA-bound Pol II repressor complex at silencer elements; core complex for repression. Supporting Evidence: PMID:12705870 the brk silencer serves as a direct target for a protein complex consisting of the Smad homologs Mad/Medea and the zinc finger protein Schnurri |
| GO:0090571 RNA polymerase II transcription repressor complex | IPI PMID:17008448 Schnurri transcription factors from Drosophila and vertebrat... | ACCEPT | Summary: Shn/Smad repression complex. Reason: Mad/Medea with Schnurri forms a DNA-bound Pol II repressor complex at silencer elements; core complex for repression. Supporting Evidence: PMID:17008448 by forming a Shn/Smad repression complex on defined promoter elements in the brinker (brk) gene |
| GO:1904398 positive regulation of neuromuscular junction development | IMP PMID:22959350 Integration of a retrograde signal during synapse formation ... | KEEP AS NON CORE | Summary: Reduced P-Mad and NMJ growth when glial Mav is lost. Reason: Mad mediates retrograde Gbb/BMP signalling in motor neurons that promotes NMJ synaptic growth; non-core developmental outcome. Supporting Evidence: PMID:22959350 This induces phosphorylation of Mad (P-Mad) in motor neurons, its translocation into the nucleus with a co-Smad, and activation of transcriptional programs controlling presynaptic bouton growth |
| GO:2000134 negative regulation of G1/S transition of mitotic cell cycle | IMP PMID:15809036 Extracellular signals responsible for spatially regulated pr... | KEEP AS NON CORE | Summary: Dpp/Hh-dependent G1 arrest in the eye disc. Reason: Mad clones in the eye disc fail to arrest in G1 ahead of the furrow (redundantly with Hh); a context-specific outcome of BMP signalling. Supporting Evidence: PMID:15809036 Arrest depends on Dpp and Hh, acting redundantly. |
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Download this section (compressed HTML)Q: Should the Mad/Medea/Schnurri silencer complex be modelled as a distinct GO complex (or GO-CAM) rather than the generic RNA polymerase II transcription repressor complex?
Q: Does Mad bind the I-Smad Dad directly in vivo, as the IBA for I-SMAD binding implies, or does Dad act only at the receptor (Tkv) level?
Q: How does Mad's role in Wingless-dependent segmentation (via GSK3 linker phosphorylation) relate to its canonical BMP function, and is it independent of C-terminal phosphorylation?
Experiment: Map genome-wide occupancy of endogenously tagged Mad (CUT&RUN) in wing discs and motor neurons to separate AE-type activation from SE-type repression targets in vivo.
Experiment: Test direct Mad-Dad binding with purified proteins and endogenously tagged alleles to resolve the I-SMAD binding inference.
Mothers against dpp (Mad) encodes the primary transcription factor that mediates cellular response to the BMP like ligands encoded by dpp, scw and gbb. Upon phosphorylation by either the products of sax or tkv (type I BMP receptors), it forms a complex with the product of Med and translocates to the nucleus where, together with cofactors, it regulates expression of BMP response target genes.
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