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Details on Person UniProt:P42003 Mad
| Class:Id | ReferenceGeneProduct:94819 |
|---|---|
| _chainChangeLog | chain:1-455 added on Fri February 6 2015 |
| _displayName | UniProt:P42003 Mad |
| _timestamp | 2026-02-20 21:41:14 |
| chain | chain:1-455 |
| checksum | 6C8570674C3AB9D8 |
| comment | FUNCTION Component of the Mad-Med transcription factor complex involved in the dpp/BMP TGF-beta signal transduction pathway (PubMed:15296719, PubMed:16109720, PubMed:7705627, PubMed:7768443, PubMed:8702167, PubMed:9230443, PubMed:9502724, PubMed:9694800). Acts downstream of the dpp-receptor protein serine/threonine kinase tkv/thickvein (PubMed:10320478). Becomes phosphorylated upon dpp-signaling, triggering association with Med and nuclear localization (PubMed:9502724, PubMed:9502733). Binds GC-rich enhancer sites with consensus sequence 5'-GCCGNCG-3' in the enhancer region of dpp-responsive genes (PubMed:15296719, PubMed:16109720, PubMed:9230443, PubMed:9694800). Mad-Med acts as a transcriptional activator but recruits shn/Shnurri to enhance its activity or switch to transcriptional repression (PubMed:11071761, PubMed:16109720). Regulates dpp-responsive genes by directly activating their expression or by repressing the transcriptional repressor brk/brinker (PubMed:12705870). Also involved in repression of other key developmental genes including bam and gsb (PubMed:15296719). Essential in the germline during oogenesis (PubMed:9502724). Required for dpp-signaling during dorsoventral patterning of the embryo (PubMed:14534137, PubMed:7768443, PubMed:9502733). Involved in anteroposterior patterning during wing imaginal disc growth (PubMed:17507407, PubMed:18820452, PubMed:7768443, PubMed:9230443).ACTIVITY REGULATION DNA binding of the Mad-Med complex, specifically of the enhancer region of the brk gene, is activated by dpp-signaling (PubMed:15296719). Dpp-signaling induces phosphorylation of Mad by dpp-specific receptor serine/threonine kinase complexes, which in turn induces interaction of Mad with Med and nuclear localization of the Mad-Med complex, where it can bind the enhancer regions of dpp-responsive genes (PubMed:9502724).SUBUNIT Homotrimer (PubMed:19557331). Component of a DNA binding Mad-Med complex composed of two copies of Mad and one copy of Med (PubMed:16109720, PubMed:9502724). May form heterodimers composed of one copy of Mad and one copy of Med when associated with certain gene enhancer regions such as the enhancer for brk (PubMed:15296719). Interacts (when phosphorylated at the C-terminus) with Med (via C-terminus) (PubMed:16109720, PubMed:16951053, PubMed:9502724). The Mad-Med complex associates with shn/Shnurri; recruitment of shn to DNA enhancer elements can result in transcriptional repression (PubMed:15296719, PubMed:16109720). Interacts (via MH2 or linker domains) with shn (via the region upstream of C2H2-type zinc-finger 3); the interaction is direct (PubMed:11071761). Interacts with MAN1 (PubMed:20036230). Interacts with Sec13 and Nup93-1 (PubMed:20547758).INTERACTION Localizes to the nucleus upon activation of the dpp/BMP signal transduction pathway (PubMed:9502724). Phosphorylated when in the nucleus (PubMed:22563507). Phosphorylation on Ser-25 by key/Nemo promotes export from nucleus (PubMed:17507407).TISSUE SPECIFICITY Stage 13 embryos display expression in the dorsal epidermis (at protein level).DEVELOPMENTAL STAGE Is detected in all developmental stages, though it appears most abundant in pupae, adult stages and early embryos. Its abundance decreases throughout embryonic and larval development and then returns to high levels in pupae and adult females.DOMAIN The MH1 domain mediates DNA binding within specific enhancer elements (consensus sequence 5'-GCCGNCG-3') (PubMed:9230443, PubMed:9694800). DNA interaction is mediated by a conserved beta-hairpin DNA binding motif (PubMed:16109720).DOMAIN The MH2 domain has an inhibitory effect on DNA binding.PTM Phosphorylated on multiple positions (PubMed:9502724). Phosphorylated on a C-terminal SSXS motif by a receptor serine/threonine kinase complex containing the type I receptors tkv or sax in response to BMP-like signaling by dpp or gbb and to a lower extent by babo in response to activin-like TGF-beta signaling by Actbeta/activin or daw; requires the type II receptor put/punt or wit/wishful thinking (PubMed:10320478, PubMed:14534137, PubMed:18820452, PubMed:19766717, PubMed:22563507, PubMed:9502724). Phosphorylation of the C-terminal SSXS motif is required for interaction with Med and nuclear localization (PubMed:9502724). Phosphorylation on Ser-453 and/or Ser-455 is required for interaction with Smurf (PubMed:12754252, PubMed:18327897). Phosphorylation on Ser-25 by key/Nemo promotes export from the nucleus and antagonizes BMP signaling (PubMed:17507407).PTM Ubiquitinated by Smurf upon phosphorylation; which promotes proteasomal degradation.DISRUPTION PHENOTYPE Mutants exhibit defects in midgut morphogenesis, imaginal disk development and embryonic dorsal-ventral patterning that are reminiscent of dpp mutant phenotypes (PubMed:7768443, PubMed:9502733). RNAi-mediated knockdown in wings results in small flat wings lacking some veins (PubMed:22563507).MISCELLANEOUS Named 'Mothers against dpp' because of the dominant maternal effect of mutation on the lethality of defects in dpp signaling.SIMILARITY Belongs to the dwarfin/SMAD family. |
| description | recommendedName: fullName evidence="29 32"Protein mothers against dpp |
| geneName | Mad CG12399 |
| identifier | P42003 |
| isSequenceChanged | FALSE |
| keyword | 3D-structure Cytoplasm Developmental protein DNA-binding Metal-binding Nucleus Phosphoprotein Reference proteome Transcription Transcription regulation Ubl conjugation Zinc |
| modified | [InstanceEdit:143527] Schmidt, EE, 2004-11-12 07:45:10 [InstanceEdit:217385] Schmidt, EE, 2008-03-27 06:23:53 [InstanceEdit:354386] Schmidt, EE, 2008-06-18 04:45:12 [InstanceEdit:384350] Kanapin, AA, 2008-11-26 14:00:39 [InstanceEdit:392885] Kanapin, AA, 2009-03-09 12:07:18 [InstanceEdit:400710] Schmidt, EE, 2009-03-25 05:33:35 [InstanceEdit:423310] Kanapin, AA [InstanceEdit:435478] Kanapin, AA [InstanceEdit:435871] Kanapin, AA [InstanceEdit:447347] Kanapin, AA [InstanceEdit:525883] Kanapin, AA [InstanceEdit:613449] Kanapin, AA [InstanceEdit:797602] Kanapin, AA [InstanceEdit:937368] Yung, CK [InstanceEdit:1042053] Yung, CK [InstanceEdit:1220657] Yung, CK [InstanceEdit:1300696] Yung, CK [InstanceEdit:1301627] Yung, CK [InstanceEdit:1551960] Weiser, JD [InstanceEdit:1995863] Weiser, JD [InstanceEdit:2132304] Weiser, JD [InstanceEdit:2265580] Weiser, JD [InstanceEdit:3132113] Weiser, JD [InstanceEdit:5433710] Weiser, JD [InstanceEdit:5618410] Weiser, JD [InstanceEdit:5618413] Weiser, JD [InstanceEdit:5618415] Weiser, JD [InstanceEdit:5634237] Weiser, JD [InstanceEdit:5673015] Weiser, JD [InstanceEdit:9037114] Weiser, JD [InstanceEdit:9607352] Weiser, JD [InstanceEdit:9637257] Weiser, JD [InstanceEdit:9676415] Weiser, JD [InstanceEdit:9698430] Weiser, JD [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9983091] Weiser, Joel, 2026-02-20 |
| name | Mad |
| referenceDatabase | [ReferenceDatabase:2] UniProt |
| secondaryIdentifier | MAD_DROME Q9VQM3 |
| sequenceLength | 455 |
| species | [Species:56210] Drosophila melanogaster |
| (referenceEntity) | [EntityWithAccessionedSequence:205892] Phospho MAD [cytosol] [Drosophila melanogaster] [EntityWithAccessionedSequence:206084] MAD [nucleoplasm] [Drosophila melanogaster] [EntityWithAccessionedSequence:206101] MAD [cytosol] [Drosophila melanogaster] [EntityWithAccessionedSequence:206207] Phospho MAD [nucleoplasm] [Drosophila melanogaster] |
| (referenceSequence) | [ModifiedResidue:205728] O-phospho-L-serine at 453 [ModifiedResidue:206297] O-phospho-L-serine at 455 |
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No pathways have been reviewed or authored by UniProt:P42003 Mad (94819)
