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General Information
Symbol
Dmel\Mad
Species
D. melanogaster
Name
Mothers against dpp
Annotation Symbol
CG12399
Feature Type
FlyBase ID
FBgn0011648
Gene Model Status
Stock Availability
Gene Snapshot
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. [Date last reviewed: 2019-03-14]
Also Known As
pMad, Mothers Against Decapentaplegic, Smad, Mother against decapentaplegic, dMad
Key Links
Genomic Location
Cytogenetic map
Sequence location
2L:3,146,056..3,159,643 [-]
Recombination map
2-8
Sequence
Other Genome Views
The following external sites may use different assemblies or annotations than FlyBase.
Function
GO Summary Ribbons
Protein Family (UniProt)
Belongs to the dwarfin/SMAD family. (P42003)
Summaries
Gene Group (FlyBase)
MAD HOMOLOGY DOMAIN TRANSCRIPTION FACTORS -
The Mother against Dpp (MAD) homology (MH) domain transcription factors are sequence-specific DNA-binding proteins that regulate transcription. These members contain an N-terminal sequence-specific DNA-binding MH1 and a C-terminal MH2 domain that mediates the formation of oligomeric complexes. (Adapted from FBrf0208242 and FBrf0206210).
Pathway (FlyBase)
BMP Signaling Pathway Core Components -
The Bone Morphogenetic Protein (BMP) signaling pathway is one of two branches of Transforming Growth Factor-β family signaling in Drosophila. The binding of a BMP family dimer to a heterodimeric serine/threonine kinase receptor complex results in the phosphorylation of Mad, a member of the Smad family. Mad forms a complex with the co-Smad, Med. This complex translocates into the nucleus and regulates the transcription of target genes in concert with other nuclear cofactors. (Adapted from FBrf0236482.)
Protein Function (UniProtKB)
Required for the function of decapentaplegic. May play an important role in mediating Dpp signaling. Involved in the BMP signaling pathway.
(UniProt, P42003)
Phenotypic Description (Red Book; Lindsley and Zimm 1992)
apg: apang
Homozygotes when raised at 19 show occasional absence of one or both claws; veins L4 and L5 interrupted; fertile at 19 but become sterile when shifted to 28; produce embryos with range of germ band abnormalities. Homozygous pupal lethal when raised at 28; pharate adults show defective tarsal development of all six legs; condensed, poorly developed and curved metatarsus and tarsi; duplications in tibial and tarsal segments; claws absent. Temperature sensitive period first instar to early pupa.
Summary (Interactive Fly)
Smad family members convey TGFß signals from their receptors to the nucleus - Upon phosphorylation by either Sax or Tkv (type I BMP receptors), Mad forms a complex with Med and translocates to the nucleus where, together with cofactors, it regulates expression of BMP response target genes.
Gene Model and Products
Number of Transcripts
2
Number of Unique Polypeptides
2

Please see the GBrowse view of Dmel\Mad or the JBrowse view of Dmel\Mad for information on other features

To submit a correction to a gene model please use the Contact FlyBase form

Protein Domains (via Pfam)
Isoform displayed:
Pfam protein domains
InterPro name
classification
start
end
Protein Domains (via SMART)
Isoform displayed:
SMART protein domains
InterPro name
classification
start
end
Comments on Gene Model
Gene model reviewed during 5.45
Gene model reviewed during 5.46
Tissue-specific extension of 3' UTRs observed during later stages (FBrf0218523, FBrf0219848); all variants may not be annotated
Sequence Ontology: Class of Gene
Transcript Data
Annotated Transcripts
Name
FlyBase ID
RefSeq ID
Length (nt)
Assoc. CDS (aa)
FBtr0077616
2691
455
FBtr0332372
3262
525
Additional Transcript Data and Comments
Reported size (kB)
2.6 (northern blot)
Comments
External Data
Crossreferences
Polypeptide Data
Annotated Polypeptides
Name
FlyBase ID
Predicted MW (kDa)
Length (aa)
Theoretical pI
RefSeq ID
GenBank
FBpp0077302
50.5
455
7.04
FBpp0304648
57.9
525
7.20
Polypeptides with Identical Sequences

None of the polypeptides share 100% sequence identity.

Additional Polypeptide Data and Comments
Reported size (kDa)
Comments
External Data
Subunit Structure (UniProtKB)
Homotrimer (PubMed:19557331). Interacts with MAN1 (PubMed:20036230). Interacts with Sec13 and Nup93-1 (PubMed:20547758).
(UniProt, P42003)
Post Translational Modification
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 nucleus and antagonizes BMP signaling (PubMed:17507407). Ubiquitinated by Smurf upon phosphorylation; which promotes proteasomal degradation.
(UniProt, P42003)
Linkouts
Sequences Consistent with the Gene Model
Mapped Features

Click to get a list of regulatory features (enhancers, TFBS, etc.) and gene disruptions (point mutations, indels, etc.) within or overlapping Dmel\Mad using the Feature Mapper tool.

External Data
Crossreferences
Eukaryotic Promoter Database - A collection of databases of experimentally validated promoters for selected model organisms.
Linkouts
Gene Ontology (42 terms)
Molecular Function (10 terms)
Terms Based on Experimental Evidence (10 terms)
CV Term
Evidence
References
Terms Based on Predictions or Assertions (0 terms)
Biological Process (26 terms)
Terms Based on Experimental Evidence (23 terms)
CV Term
Evidence
References
inferred from mutant phenotype
inferred from genetic interaction with FLYBASE:dpp; FB:FBgn0000490
inferred from mutant phenotype
inferred from mutant phenotype
inferred from mutant phenotype
inferred from mutant phenotype
inferred from high throughput mutant phenotype
Terms Based on Predictions or Assertions (4 terms)
CV Term
Evidence
References
Cellular Component (6 terms)
Terms Based on Experimental Evidence (6 terms)
CV Term
Evidence
References
Terms Based on Predictions or Assertions (0 terms)
Expression Data
Expression Summary Ribbons
Colored tiles in ribbon indicate that expression data has been curated by FlyBase for that anatomical location. Colorless tiles indicate that there is no curated data for that location.
For complete stage-specific expression data, view the modENCODE Development RNA-Seq section under High-Throughput Expression below.
Transcript Expression
in situ
Stage
Tissue/Position (including subcellular localization)
Reference
organism

Comment: maternally deposited

northern blot
Stage
Tissue/Position (including subcellular localization)
Reference
Additional Descriptive Data
Mad 2.6kb transcripts are detected in all developmental stages but are most abundant in early embryos, pupae, and adult females. A minor slightly smaller transcript is also detected in 0-4hr embryos.
Marker for
 
Subcellular Localization
CV Term
Polypeptide Expression
immunolocalization
Stage
Tissue/Position (including subcellular localization)
Reference
organism | dorsal

Comment: Expressed in a dorsal midline stripe

female germline stem cell

Comment: high expression level

cystoblast

Comment: low expression level

in situ
Stage
Tissue/Position (including subcellular localization)
Reference
Additional Descriptive Data
pMad is expressed in CCAP-EN neurons but not in the CCAP-IN neurons.
The phosphorylated form of Mad protein is detected in two stripes in the eye disc: one corresponding to the morphogenetic furrow and the other anterior to it. No expression of phosphorylated Mad is detected in glial cells in the eye disc.
In the eye disc, antibody to phosphorylated Mad stains a broad band of cells anterior to and within the morphogenetic furrow, terminating in a stripe of more intensely labelled cells around columns 3 and 4 at the posterior edge of the furrow. In antennal disc, a broad band of nuclei in the ventral region of the disc is stained. Staining is observed in peripodial cells over the ventral region of the antennal disc and the dorsal region of the eye disc. In some preparations, nuclear pMad was also weakly detected in peripodial epithelium cells directly overlying the morphogenetic furrow.
Phosphorylated Mad protein is expressed in the presynaptic domain of type I boutons at the neuromuscular junction.
Phosphorylated Mad (pMAd) protein is detected in the spiracular chambers, spiracular branches, and dorsal trunk branches of the tracheal system. Expression is seen in the spiracular chamber form embryonic stage 13 and appears in the spriacular branch and dorsal trunk branches at stage 14 and persists through stage 17.
Mad is observed in the dorsal epidermis and the ventrolateral epidermis at embryonic stage 13.
Phosphorylated Mad (pMad) is detected in the amnioserosa and in the epidermis around the leading edge at embryonic stage 11. A ventral stripe is also seen. From stage 12 on, pMad levels decline in the amnioserosa but persist in epidermis stripes. At doral closure, expression is absent from the amnioserosa but persists in the epidermis.
Strong pMad staining is observed in the
precursor cells of the longitudinal veins around 19-22 hr after pupation. From 17-22 hr APF, pMAD accumulates in a broad patch of cells in the region of the presumptive posterior crossvein. During subsequent stages (13-28 hr APF), the pMAD staining becomes refined into a narrow stripe of cells that form the posterior crossvein.
Phosphorylated Mad protein is distributed in a gradient, with the highest levels near the anterior/posterior compartment boundary.
staining was for for pMad
In male adults, Mad protein is expressed in germline stem cells.
In female adults, Mad protein is expressed at a high level in germline stem cells, and at a low level in cystoblasts.
Phosphorylated Mad protein is localized to a subset of motor neurons in late stage embryos.
Phosphorylated Mad (pMad) is first detected at future sites of the crossveins at 19-21 hr APF and in portions of the longitudinal veins near the crossvein attachment sites and along wing vein L2. By 24-26 hr APF staining is seen all along the longitudinal veins but is stronger near the crossveins. At 36 hr APF, staining is seen throughout the wing but is stronger in the crossveins. Strong staining is also observed in the nuclei and axons of the PNS of the wing at 18-36 hr APF.
Mad protein is ubiquitously distributed in embryos.
Marker for
Subcellular Localization
CV Term
Evidence
References
Expression Deduced from Reporters
High-Throughput Expression Data
Associated Tools

GBrowse - Visual display of RNA-Seq signals

View Dmel\Mad in GBrowse 2
RNA-Seq by Region - Search RNA-Seq expression levels by exon or genomic region
Reference
See Gelbart and Emmert, 2013 for analysis details and data files for all genes.
Developmental Proteome: Life Cycle
Developmental Proteome: Embryogenesis
External Data and Images
Linkouts
BDGP expression data - Patterns of gene expression in Drosophila embryogenesis
FLIGHT - Cell culture data for RNAi and other high-throughput technologies
FlyAtlas - Adult expression by tissue, using Affymetrix Dros2 array
Fly-FISH - A database of Drosophila embryo and larvae mRNA localization patterns
Flygut - An atlas of the Drosophila adult midgut
Images
FlyExpress - Embryonic expression images (BDGP data)
  • Stages(s) 1-3
  • Stages(s) 4-6
  • Stages(s) 9-10
  • Stages(s) 11-12
Alleles, Insertions, and Transgenic Constructs
Classical and Insertion Alleles ( 53 )
For All Classical and Insertion Alleles Show
 
Other relevant insertions
Transgenic Constructs ( 44 )
For All Alleles Carried on Transgenic Constructs Show
Transgenic constructs containing/affecting coding region of Mad
Transgenic constructs containing regulatory region of Mad
Deletions and Duplications ( 20 )
Phenotypes
For more details about a specific phenotype click on the relevant allele symbol.
Lethality
Allele
Sterility
Allele
Other Phenotypes
Allele
Phenotype manifest in
Allele
Orthologs
Human Orthologs (via DIOPT v7.1)
Homo sapiens (Human) (9)
Species\Gene Symbol
Score
Best Score
Best Reverse Score
Alignment
Complementation?
Transgene?
13 of 15
Yes
Yes
 
 
10 of 15
No
Yes
9 of 15
No
Yes
2 of 15
No
No
 
2 of 15
No
No
 
1 of 15
No
No
 
1 of 15
No
No
 
1 of 15
No
No
 
1 of 15
No
Yes
Model Organism Orthologs (via DIOPT v7.1)
Mus musculus (laboratory mouse) (8)
Species\Gene Symbol
Score
Best Score
Best Reverse Score
Alignment
Complementation?
Transgene?
13 of 15
Yes
Yes
9 of 15
No
Yes
9 of 15
No
Yes
2 of 15
No
No
2 of 15
No
No
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
Rattus norvegicus (Norway rat) (8)
11 of 13
Yes
Yes
9 of 13
No
Yes
5 of 13
No
Yes
5 of 13
No
Yes
2 of 13
No
No
2 of 13
No
No
1 of 13
No
No
1 of 13
No
No
Xenopus tropicalis (Western clawed frog) (9)
10 of 12
Yes
Yes
7 of 12
No
Yes
1 of 12
No
No
1 of 12
No
No
1 of 12
No
No
1 of 12
No
No
1 of 12
No
No
1 of 12
No
No
1 of 12
No
No
Danio rerio (Zebrafish) (13)
10 of 15
Yes
Yes
9 of 15
No
Yes
9 of 15
No
Yes
2 of 15
No
No
2 of 15
No
No
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
Caenorhabditis elegans (Nematode, roundworm) (7)
12 of 15
Yes
Yes
8 of 15
No
Yes
2 of 15
No
No
2 of 15
No
No
1 of 15
No
No
1 of 15
No
Yes
1 of 15
No
No
Arabidopsis thaliana (thale-cress) (0)
No records found.
Saccharomyces cerevisiae (Brewer's yeast) (2)
1 of 15
Yes
No
1 of 15
Yes
No
Schizosaccharomyces pombe (Fission yeast) (0)
No records found.
Orthologs in Drosophila Species (via OrthoDB v9.1) ( EOG09190715 )
Organism
Common Name
Gene
AAA Syntenic Ortholog
Multiple Dmel Genes in this Orthologous Group
Drosophila melanogaster
fruit fly
Drosophila suzukii
Spotted wing Drosophila
Drosophila simulans
Drosophila sechellia
Drosophila erecta
Drosophila yakuba
Drosophila ananassae
Drosophila pseudoobscura pseudoobscura
Drosophila persimilis
Drosophila willistoni
Drosophila virilis
Drosophila mojavensis
Drosophila grimshawi
Orthologs in non-Drosophila Dipterans (via OrthoDB v9.1) ( EOG091504EB )
Organism
Common Name
Gene
Multiple Dmel Genes in this Orthologous Group
Musca domestica
House fly
Musca domestica
House fly
Glossina morsitans
Tsetse fly
Lucilia cuprina
Australian sheep blowfly
Mayetiola destructor
Hessian fly
Aedes aegypti
Yellow fever mosquito
Anopheles darlingi
American malaria mosquito
Anopheles gambiae
Malaria mosquito
Culex quinquefasciatus
Southern house mosquito
Orthologs in non-Dipteran Insects (via OrthoDB v9.1) ( EOG090W04Z6 )
Organism
Common Name
Gene
Multiple Dmel Genes in this Orthologous Group
Bombyx mori
Silkmoth
Bombyx mori
Silkmoth
Danaus plexippus
Monarch butterfly
Danaus plexippus
Monarch butterfly
Heliconius melpomene
Postman butterfly
Heliconius melpomene
Postman butterfly
Apis florea
Little honeybee
Apis florea
Little honeybee
Apis mellifera
Western honey bee
Apis mellifera
Western honey bee
Bombus impatiens
Common eastern bumble bee
Bombus impatiens
Common eastern bumble bee
Bombus terrestris
Buff-tailed bumblebee
Bombus terrestris
Buff-tailed bumblebee
Linepithema humile
Argentine ant
Linepithema humile
Argentine ant
Nasonia vitripennis
Parasitic wasp
Nasonia vitripennis
Parasitic wasp
Nasonia vitripennis
Parasitic wasp
Dendroctonus ponderosae
Mountain pine beetle
Tribolium castaneum
Red flour beetle
Tribolium castaneum
Red flour beetle
Tribolium castaneum
Red flour beetle
Pediculus humanus
Human body louse
Pediculus humanus
Human body louse
Rhodnius prolixus
Kissing bug
Rhodnius prolixus
Kissing bug
Cimex lectularius
Bed bug
Cimex lectularius
Bed bug
Acyrthosiphon pisum
Pea aphid
Acyrthosiphon pisum
Pea aphid
Acyrthosiphon pisum
Pea aphid
Zootermopsis nevadensis
Nevada dampwood termite
Zootermopsis nevadensis
Nevada dampwood termite
Orthologs in non-Insect Arthropods (via OrthoDB v9.1) ( EOG090X04JH )
Organism
Common Name
Gene
Multiple Dmel Genes in this Orthologous Group
Strigamia maritima
European centipede
Strigamia maritima
European centipede
Ixodes scapularis
Black-legged tick
Stegodyphus mimosarum
African social velvet spider
Stegodyphus mimosarum
African social velvet spider
Tetranychus urticae
Two-spotted spider mite
Tetranychus urticae
Two-spotted spider mite
Daphnia pulex
Water flea
Daphnia pulex
Water flea
Orthologs in non-Arthropod Metazoa (via OrthoDB v9.1) ( EOG091G082C )
Organism
Common Name
Gene
Multiple Dmel Genes in this Orthologous Group
Strongylocentrotus purpuratus
Purple sea urchin
Strongylocentrotus purpuratus
Purple sea urchin
Ciona intestinalis
Vase tunicate
Ciona intestinalis
Vase tunicate
Ciona intestinalis
Vase tunicate
Gallus gallus
Domestic chicken
Gallus gallus
Domestic chicken
Gallus gallus
Domestic chicken
Gallus gallus
Domestic chicken
Gallus gallus
Domestic chicken
Gallus gallus
Domestic chicken
Paralogs
Paralogs (via DIOPT v7.1)
Drosophila melanogaster (Fruit fly) (4)
5 of 10
3 of 10
3 of 10
1 of 10
Human Disease Associations
FlyBase Human Disease Model Reports
Disease Model Summary Ribbon
Disease Ontology (DO) Annotations
Models Based on Experimental Evidence ( 1 )
Allele
Disease
Evidence
References
Potential Models Based on Orthology ( 1 )
Human Ortholog
Disease
Evidence
References
Modifiers Based on Experimental Evidence ( 2 )
Allele
Disease
Interaction
References
Comments on Models/Modifiers Based on Experimental Evidence ( 1 )
 
Mad12 suppresses muscle dysfunction but not the heart tube dysfunction of muscular dystrophy in Scgδ840 flies.
Disease Associations of Human Orthologs (via DIOPT v7.1 and OMIM)
Note that ortholog calls supported by only 1 or 2 algorithms (DIOPT score < 3) are not shown.
Homo sapiens (Human)
Gene name
Score
OMIM
OMIM Phenotype
DO term
Complementation?
Transgene?
Functional Complementation Data
Functional complementation data is computed by FlyBase using a combination of the orthology data obtained from DIOPT and OrthoDB and the allele-level genetic interaction data curated from the literature.
Dmel gene
Ortholog showing functional complementation
Supporting References
Interactions
Summary of Physical Interactions
esyN Network Diagram
Show neighbor-neighbor interactions:
Select Layout:
Legend:
Protein
RNA
Selected Interactor(s)
Interactions Browser

Please see the Physical Interaction reports below for full details
RNA-RNA
Physical Interaction
Assay
References
RNA-protein
Physical Interaction
Assay
References
protein-protein
Physical Interaction
Assay
References
Summary of Genetic Interactions
esyN Network Diagram
esyN Network Key:
Suppression
Enhancement

Please look at the allele data for full details of the genetic interactions
Starting gene(s)
Interaction type
Interacting gene(s)
Reference
enhanceable
Starting gene(s)
Interaction type
Interacting gene(s)
Reference
suppressible
suppressible
External Data
Subunit Structure (UniProtKB)
Homotrimer (PubMed:19557331). Interacts with MAN1 (PubMed:20036230). Interacts with Sec13 and Nup93-1 (PubMed:20547758).
(UniProt, P42003 )
Linkouts
BioGRID - A database of protein and genetic interactions.
DroID - A comprehensive database of gene and protein interactions.
InterologFinder - Protein-protein interactions (PPI) from both known and predicted PPI data sets.
MIST (genetic) - An integrated Molecular Interaction Database
MIST (protein-protein) - An integrated Molecular Interaction Database
Pathways
Gene Group - Pathway Membership (FlyBase)
BMP Signaling Pathway Core Components -
The Bone Morphogenetic Protein (BMP) signaling pathway is one of two branches of Transforming Growth Factor-β family signaling in Drosophila. The binding of a BMP family dimer to a heterodimeric serine/threonine kinase receptor complex results in the phosphorylation of Mad, a member of the Smad family. Mad forms a complex with the co-Smad, Med. This complex translocates into the nucleus and regulates the transcription of target genes in concert with other nuclear cofactors. (Adapted from FBrf0236482.)
External Data
Linkouts
KEGG Pathways - Wiring diagrams of molecular interactions, reactions and relations.
SignaLink - A signaling pathway resource with multi-layered regulatory networks.
Genomic Location and Detailed Mapping Data
Chromosome (arm)
2L
Recombination map
2-8
Cytogenetic map
Sequence location
2L:3,146,056..3,159,643 [-]
FlyBase Computed Cytological Location
Cytogenetic map
Evidence for location
23D3-23D3
Limits computationally determined from genome sequence between P{PZ}toc01361 and P{lacW}Madk00237
Experimentally Determined Cytological Location
Cytogenetic map
Notes
References
23D3-23D4
(determined by in situ hybridisation)
23D4-23D6
(determined by in situ hybridisation)
23D-23D
(determined by in situ hybridisation)
The Mad gene is missing in Df(2L)S2590, although the distal break of the cytologically defined deficiency falls in the toc gene.
Experimentally Determined Recombination Data
Location
Notes
Stocks and Reagents
Stocks (28)
Genomic Clones (44)
cDNA Clones (130)
 

Please Note This section lists cDNAs and ESTs that fall within the genomic extent of the gene model, which may include cDNAs and ESTs of genes within introns, or of overlapping genes. Please see GBrowse for alignment of the cDNAs and ESTs to the gene model.

cDNA clones, fully sequences
BDGP DGC clones
Other clones
Drosophila Genomics Resource Center cDNA clones

For each fully sequenced cDNA the DGRC maintains various forms of the cDNA (e.g tagged or untagged) in several different host vectors for subsequent cloning and expression in Drosophila and Drosophila cell lines.

cDNA Clones, End Sequenced (ESTs)
RNAi and Array Information
Linkouts
DRSC - Results frm RNAi screens
GenomeRNAi - A database for cell-based and in vivo RNAi phenotypes and reagents
Antibody Information
Other Information
Relationship to Other Genes
Source for database identify of
Source for database merge of
Source for merge of: E(zen)2 Mad
Source for merge of: Mad l(2)k00237
Source for merge of: Mad apg
Additional comments
Other Comments
DNA-protein interactions: genome-wide binding profile assayed for Mad protein in stage 9-11 embryos; ArrayExpress accession number E-MTAB-1184.
Phosphorylation of Mad protein in the linker region by sgg regulates the development of sensory organs in the anterior-dorsal quadrant of the wing.
DNA-protein interactions: genome-wide binding profile assayed for Mad protein in 2-3 hr embryos; see BDTNP1_TFBS_Mad collection report.
The Mad product negatively regulates dac expression in the embryonic head.
dsRNA made from templates generated with primers directed against this gene tested in RNAi screen for effects on Kc167 and S2R+ cell morphology.
The brk silencer serves as a direct target for a protein complex consisting of Mad/Med and shn.
Hsap\MADH1 and Hsap\MADH4, as well as Mad and Med, can stimulate dpp signalling in limb development.
Overexpression of Mad or Hsap\MADH1 in the wing and leg causes a similar phenotype.
One of five genes identified as encoding downstream components of the dpp signalling cascade which is necessary for blocking salivary gland gene activation by Scr in the dorsal region of parasegment 2. Mad function is required to block salivary gland formation in dorsal regions of PS2.
Mad may recruit nej to effect the transcriptional activation of dpp responsive genes during development.
Loss of function alleles of tkv, put, Mad, Med and shn suppress the CycEJP mutant eye phenotype in combination with dppd-ho.
Mutants show no interaction with Df(2R)Pcl11B or Df(3L)66C-G28.
Mutants isolated in a screen of the second chromosome identifying genes affecting disc morphology.
Mad mediated nuclear translocation is essential for Med function.
Transcriptional activation of Ubx is subject to competition between dpp-activated Mad and another Smad whose function as a transcriptional repressor depends on high wg signalling.
The amino-terminal domain of the Mad protein contains a sequence-specific DNA-binding activity that becomes apparent when carboxy-terminal residues are removed. Mad protein binds to and is required for the activation of an enhancer within the vg gene in cells across the entire developing wing blade.
Mad protein functions downstream of the serine-threonine kinase activity of the tkv receptor.
Signalling by constitutively active tkv mutation is suppressed by heterozygosity for Mad mutations. These results indicate that Mad functions downstream of the tkv receptor.
Mad is required for any response of the visceral mesoderm or endoderm to dpp signals from the visceral mesoderm and is required specifically in cells responding to dpp. Mad can function in the signalling pathway of BMP-4 in Xenopus embryos, and is thus a highly conserved and essential element of the dpp signalling pathway.
Mad is required for dpp signalling during eye development. Clonal analysis demonstrated that this requirement is cell autonomous. Mad is an essential component of the signal transduction pathway downstream of the dpp receptors in responding cells. Mad-mediated dpp signaling is absolutely required for the initiation of the morphogenetic furrow in the eye, but has only a minor role in its subsequent propagation across the eye disc.
Dominant enhancer of zen.
Mad has been identified independently in two screens, one for dominant enhancers of the dpp mutant phenotype and dosage sensitive interactions with dpp. Mad mutant phenotypes show patterning defects that resemble many dpp mutant phenotypes. Studies of ectopic expression, tissue-specific expression and in situ hybridizations are consistent with a role for Mad downstream of dpp in the signalling pathway.
Genetic characterisation indicates Mad encodes a product essential for dpp function. Molecular analysis demonstrates the Mad protein is a member of a novel protein family that is highly conserved throughout metazoans.
A genetic enhancer of dpp.
Loss of function mutations of Mad are dominant maternal effect enhancers of dpp during early embryogenesis and dominant zygotic enhancers of dpp in imaginal discs.
Origin and Etymology
Discoverer
Etymology
The gene is named "apang" after the mutant phenotype ("apang" stands for an individual with mutilated and underdeveloped legs in Hindi).
Identification
External Crossreferences and Linkouts ( 54 )
Sequence Crossreferences
NCBI Gene - Gene integrates information from a wide range of species. A record may include nomenclature, Reference Sequences (RefSeqs), maps, pathways, variations, phenotypes, and links to genome-, phenotype-, and locus-specific resources worldwide.
GenBank Nucleotide - A collection of sequences from several sources, including GenBank, RefSeq, TPA, and PDB.
GenBank Protein - A collection of sequences from several sources, including translations from annotated coding regions in GenBank, RefSeq and TPA, as well as records from SwissProt, PIR, PRF, and PDB.
RefSeq - A comprehensive, integrated, non-redundant, well-annotated set of reference sequences including genomic, transcript, and protein.
UniProt/Swiss-Prot - Manually annotated and reviewed records of protein sequence and functional information
UniProt/TrEMBL - Automatically annotated and unreviewed records of protein sequence and functional information
Other crossreferences
BDGP expression data - Patterns of gene expression in Drosophila embryogenesis
Drosophila Genomics Resource Center - Drosophila Genomics Resource Center (DGRC) cDNA clones
Eukaryotic Promoter Database - A collection of databases of experimentally validated promoters for selected model organisms.
Fly-FISH - A database of Drosophila embryo and larvae mRNA localization patterns
Flygut - An atlas of the Drosophila adult midgut
GenomeRNAi - A database for cell-based and in vivo RNAi phenotypes and reagents
iBeetle-Base - RNAi phenotypes in the red flour beetle (Tribolium castaneum)
KEGG Genes - Molecular building blocks of life in the genomic space.
KEGG Pathways - Wiring diagrams of molecular interactions, reactions and relations.
modMine - A data warehouse for the modENCODE project
SignaLink - A signaling pathway resource with multi-layered regulatory networks.
Linkouts
ApoDroso - Functional genomic database for photoreceptor development, survival and function
BioGRID - A database of protein and genetic interactions.
DPiM - Drosophila Protein interaction map
DroID - A comprehensive database of gene and protein interactions.
DRSC - Results frm RNAi screens
FLIGHT - Cell culture data for RNAi and other high-throughput technologies
FlyAtlas - Adult expression by tissue, using Affymetrix Dros2 array
FlyMine - An integrated database for Drosophila genomics
Interactive Fly - A cyberspace guide to Drosophila development and metazoan evolution
InterologFinder - Protein-protein interactions (PPI) from both known and predicted PPI data sets.
KEGG Pathways - Wiring diagrams of molecular interactions, reactions and relations.
MIST (genetic) - An integrated Molecular Interaction Database
MIST (protein-protein) - An integrated Molecular Interaction Database
Synonyms and Secondary IDs (44)
Reported As
Symbol Synonym
E(zen)2
En(vvl)
Mad
(Chen, 2019, Kim et al., 2019, La Marca et al., 2019, Nakato et al., 2019, Shokri et al., 2019, Vuilleumier et al., 2019, Wang et al., 2019, Ahmed-de-Prado and Baonza, 2018, Ahmed-de-Prado et al., 2018, Ameku et al., 2018, Anreiter and Sokolowski, 2018, Bischof et al., 2018, Chandran et al., 2018, Levis, 2018.8.30, Liao et al., 2018, Newcomb et al., 2018, O'Hanlon et al., 2018, Powers and Srivastava, 2018, Prange et al., 2018, Roesley et al., 2018, Tseng et al., 2018, Wang et al., 2018, Aggarwal et al., 2017, Ahmad, 2017, Al Khatib et al., 2017, Banerjee et al., 2017, Follansbee et al., 2017, Golovnin et al., 2017, Houtz et al., 2017, Jeibmann et al., 2017, Jordán-Álvarez et al., 2017, Kim et al., 2017, Koenecke et al., 2017, Monsivais et al., 2017, Neuert et al., 2017, Requena et al., 2017, Richard et al., 2017, Romero-Pozuelo et al., 2017, Song et al., 2017, Tan et al., 2017, Transgenic RNAi Project members, 2017-, Zhou et al., 2017, Aggarwal et al., 2016, Bonfini et al., 2016, Djabrayan and Casanova, 2016, Fallahi et al., 2016, Frasch, 2016, Garaulet et al., 2016, Gui et al., 2016, Kwan et al., 2016, Li et al., 2016, Matsuda et al., 2016, Mbodj et al., 2016, Mottier-Pavie et al., 2016, Quijano et al., 2016, Sarov et al., 2016, Sharifkhodaei et al., 2016, Tauscher et al., 2016, Tsai et al., 2016, Urrutia et al., 2016, Akiyama and Gibson, 2015, Amoyel and Bach, 2015, Baëza et al., 2015, Ball et al., 2015, Bier and De Robertis, 2015, Bivik et al., 2015, Dolezal et al., 2015, Harmansa et al., 2015, Irvine and Harvey, 2015, Kakugawa et al., 2015, Kao et al., 2015, Kim et al., 2015, Liu et al., 2015, Newton et al., 2015, Sawala et al., 2015, Schertel et al., 2015, Schleede and Blair, 2015, Singh, 2015, Svendsen et al., 2015, Van Bortle et al., 2015, Yu et al., 2015, Zhou et al., 2015, Aleman et al., 2014, Alic et al., 2014, Archbold et al., 2014, Córdoba and Estella, 2014, Deshpande et al., 2014, Driver and Ohlstein, 2014, Esteves et al., 2014, Frank, 2014, Hamada-Kawaguchi et al., 2014, Herranz et al., 2014, Hodar et al., 2014, Jiang and Singh, 2014, Karandikar et al., 2014, Künnapuu et al., 2014, Navarro et al., 2014, Oh et al., 2014, Pichaud, 2014, Rhee et al., 2014, Rogers et al., 2014, Roy et al., 2014, Sulkowski et al., 2014, Tseng et al., 2014, White-Grindley et al., 2014, Wong et al., 2014, Zhang et al., 2014, Zhang et al., 2014, Bai et al., 2013, Bausek, 2013, Beckwith et al., 2013, Castellanos et al., 2013, Chang et al., 2013, Chauhan et al., 2013, Curtis et al., 2013, Doumpas et al., 2013, Enderle and McNeill, 2013, Guo et al., 2013, Ishitani and Ishitani, 2013, Jin et al., 2013, Jukam et al., 2013, Li and Gilmour, 2013, Li et al., 2013, Li et al., 2013, Marinho et al., 2013, Mbodj et al., 2013, Morozov and Ioshikhes, 2013, Nahm et al., 2013, Peterson and O'Connor, 2013, Saunders et al., 2013, Webber et al., 2013, Xin et al., 2013, Zhang et al., 2013, Aboukhalil and Bulyk, 2012, Agelopoulos et al., 2012, Akiyama et al., 2012, Beck et al., 2012, Boulanger et al., 2012, Cash and Andrews, 2012, Chen et al., 2012, Dahal et al., 2012, Dani et al., 2012, Fischer et al., 2012, Fuentes-Medel et al., 2012, Gomez et al., 2012, Kagey et al., 2012, Karim et al., 2012, Kim and Marqués, 2012, Le and Wharton, 2012, Lim et al., 2012, Liu et al., 2012, Pennetier et al., 2012, Peterson et al., 2012, Raftery and Umulis, 2012, Smith et al., 2012, Spokony and White, 2012.5.22, Stinchfield et al., 2012, Sun et al., 2012, Takaesu et al., 2012, Xia et al., 2012, Zhu et al., 2012, Abruzzi et al., 2011, Bayat et al., 2011, Ben-Zvi et al., 2011, Bhattacharya and Baker, 2011, Clark et al., 2011, de Cuevas and Matunis, 2011, Dejima et al., 2011, Dutko and Mullins, 2011, Eivers et al., 2011, Eliazer and Buszczak, 2011, Gancz et al., 2011, Giorgianni and Mann, 2011, Harris and Ashe, 2011, Issigonis and Matunis, 2011, König et al., 2011, Layalle et al., 2011, Li et al., 2011, Liu et al., 2011, Mikhaylova and Nurminsky, 2011, Miller et al., 2011, O'Keefe et al., 2011, Ogiso et al., 2011, Oh and Irvine, 2011, Peluso et al., 2011, Qian et al., 2011, Quijano et al., 2011, Rodal et al., 2011, Rodriguez, 2011, Veverytsa and Allan, 2011, Yang and Su, 2011, Yuva-Aydemir et al., 2011, Zhao et al., 2011, Ables and Drummond-Barbosa, 2010, Ballard et al., 2010, Ball et al., 2010, Chen et al., 2010, Ellis et al., 2010, Firth et al., 2010, Ishikawa et al., 2010, Li et al., 2010, Liu et al., 2010, Losada-Pérez et al., 2010, Mathur et al., 2010, Nahm et al., 2010, Neely et al., 2010, Padash-Barmchi et al., 2010, Portela et al., 2010, Quijano et al., 2010, Salzer et al., 2010, Sander et al., 2010, Sato et al., 2010, Su et al., 2010, Sun et al., 2010, Wagner et al., 2010, Wang and Ward, 2010, Weiss et al., 2010, Yagi et al., 2010, Alarcón et al., 2009, Eade and Allan, 2009, Eivers et al., 2009, Evans et al., 2009, Firth and Baker, 2009, Glavic et al., 2009, Guo and Wang, 2009, Guruharsha et al., 2009, Jensen et al., 2009, Künnapuu et al., 2009, Lembong et al., 2009, Liu et al., 2009, MacArthur et al., 2009, McKay et al., 2009, Merino et al., 2009, Pentek et al., 2009, Rhiner et al., 2009, Sellin et al., 2009, Smith-Bolton et al., 2009, Twombly et al., 2009, Umemori et al., 2009, Wang et al., 2009, Yu et al., 2009, Baena-Lopez et al., 2008, Bollenbach et al., 2008, Boylan et al., 2008, Brás-Pereira and Casares, 2008, Campbell and Moser, 2008, Casas-Tinto et al., 2008, Casas-Tinto et al., 2008, Chang et al., 2008, Christoforou et al., 2008, Erives et al., 2008, Estella and Mann, 2008, Estella et al., 2008, Fromental-Ramain et al., 2008, Fuentealba et al., 2008, Hao et al., 2008, Kamiya et al., 2008, Lembong et al., 2008, Lim et al., 2008, López-Onieva et al., 2008, Miguel-Aliaga et al., 2008, Miles et al., 2008, Newfeld et al., 2008, Ng, 2008, Pinto et al., 2008, Schwank et al., 2008, Serpe et al., 2008, Shcherbata et al., 2008, Shen et al., 2008, Takaesu et al., 2008, Tanaka-Matakatsu and Du, 2008, Tien et al., 2008, Tran and Doe, 2008, Ueyama et al., 2008, Vogler and Urban, 2008, Wang et al., 2008, Wang et al., 2008, Warrior et al., 2008, Yakoby et al., 2008, Yao et al., 2008, Yao et al., 2008, Zahedi et al., 2008, Zeng et al., 2008, Zhao et al., 2008, Aerts et al., 2007, Ambrus et al., 2007, Ballard and Wharton, 2007, Barrio et al., 2007, Baumgardt et al., 2007, Beltran et al., 2007, Christensen and Cook, 2007.3.22, Cordero et al., 2007, Crickmore and Mann, 2007, Escudero and Freeman, 2007, Fernández et al., 2007, Gao and Laughon, 2007, Gerlitz et al., 2007, Gonzales-Gaitan, 2007, Herrero et al., 2007, Hufnagel et al., 2007, Johnson et al., 2007, Kim et al., 2007, Korolchuk et al., 2007, Langille and Clark, 2007, Lecuit and Le Goff, 2007, Letizia et al., 2007, Liang et al., 2007, Li et al., 2007, Lilja et al., 2007, Makhijani et al., 2007, Manjon et al., 2007, Newfeld et al., 2007, Pistillo and Desplan, 2007, Ramel et al., 2007, Shcherbata et al., 2007, Shcherbata et al., 2007, Shirinian et al., 2007, Tyler and Baker, 2007, Tyler et al., 2007, Umemori et al., 2007, Walsh and Carroll, 2007, Xu et al., 2007, Yakoby et al., 2007, Zeng et al., 2007, Akasaka et al., 2006, Anderson et al., 2006, Bangi and Wharton, 2006, Bangi and Wharton, 2006, Bernardi et al., 2006, Bokel et al., 2006, Bokel et al., 2006, Bolivar et al., 2006, Brandt, 2006, Chen and Schupbach, 2006, Christensen and Cook, 2006.8.29, Christensen and Cook, 2006.8.29, Christensen and Cook, 2006.8.29, Christensen and Cook, 2006.12.5, Crickmore and Mann, 2006, Crickmore and Mann, 2006, Davidson and Erwin, 2006, de Navas et al., 2006, de Velasco et al., 2006, Dudu, 2006, Dudu et al., 2006, Dworkin and Gibson, 2006, Gao and Laughon, 2006, Garces and Thor, 2006, Jones et al., 2006, Joshi et al., 2006, Kirkpatrick et al., 2006, Knoblich, 2006, Layden et al., 2006, Li and Li, 2006, Lin et al., 2006, Mizutani et al., 2006, Niki, 2006, Niki et al., 2006, Oishi et al., 2006, Philippakis et al., 2006, Sotillos and de Celis, 2006, Takaesu et al., 2006, Umulis et al., 2006, van der Plas et al., 2006, Vrailas and Moses, 2006, Yao et al., 2006, Firth and Baker, 2005, Gao et al., 2005, Horabin, 2005, Kirilly et al., 2005, Marques, 2005, Mizutani et al., 2005, Sage et al., 2005, Stathopoulos and Levine, 2005, Takaesu et al., 2005, Xi and Xie, 2005, Yamashita et al., 2005, Koh et al., 2004, Pyrowolakis et al., 2004, Stanyon et al., 2004, Grienenberger et al., 2003, Jekely and Rorth, 2003, Rawson et al., 2003, Stefancsik and Sarkar, 2003, Wisotzkey et al., 2003, Saller and Bienz, 2001, Kyoda et al., 2000)
apg
l(2)k00237
mad
(Lu et al., 2019, Malik et al., 2019, Whittle and Extavour, 2019, Kang et al., 2018, Laugks et al., 2017, Wells et al., 2017, Zhang et al., 2017, Lee et al., 2016, Li et al., 2016, Moulton and Letsou, 2016, Testa and Dworkin, 2016, Ayyaz et al., 2015, Charbonnier et al., 2015, Dong et al., 2015, Luo et al., 2015, Zhao et al., 2015, Kang et al., 2014, Liu et al., 2014, Atkins et al., 2013, Gafner et al., 2013, Jukam et al., 2013, Jukam et al., 2013, Shi et al., 2013, Chen et al., 2012, Fischer et al., 2012, Peterson et al., 2012, Xia et al., 2012, Dworkin et al., 2011, Giorgianni and Mann, 2011, Kaneko et al., 2011, Nègre et al., 2011, Reddy and Irvine, 2011, Vlachos and Harden, 2011, Wang et al., 2011, Kim et al., 2010, Ninov et al., 2010, Terriente-Félix et al., 2010, The modENCODE Consortium, 2010, The modENCODE Consortium, 2010, Vuilleumier et al., 2010, Debat et al., 2009, Twombly et al., 2009, Umemori et al., 2009, Widmann and Dahmann, 2009, Jiang et al., 2008, Ng, 2008, O'Connor-Giles et al., 2008, Seppa et al., 2008, Ulvklo et al., 2008, Zeng et al., 2008, Corrigall et al., 2007, Goold and Davis, 2007, Terriente and de Celis, 2007, Tyler and Baker, 2007, Dworkin and Gibson., 2006, Kirilly et al., 2006, Serpe and O'Connor, 2006, Eaton and Davis, 2005, Gibson and Perrimon, 2005, Kirilly et al., 2005, Li et al., 2005, Pappu et al., 2005, Xie et al., 2005, Dunlop et al., 2004, Kalinovsky and Scheiffele, 2004, Luschnig et al., 2004, Luschnig et al., 2004, Kawase and Xie, 2003, Kirilly et al., 2003, Shivdasani and Ingham, 2003, Zhu and Xie, 2003, Bessa et al., 2002, McCabe et al., 2002, Deng and Lin, 2001, Dorfman and Shilo, 2001, Affolter, 2000, Jordan et al., 2000, Marty et al., 2000, Zhang et al., 1999, Certel and Johnson, 1998, Cho and Blitz, 1998, Henderson and Andrew, 1998, Horsfield et al., 1998, Lin, 1998, Xie and Spradling, 1998, Yu et al., 1998, Henderson and Andrew, 1997, Mehler et al., 1997, Dean, 1996, Haerry et al., 1996, Hill, 1996, Hogan, 1996)
Name Synonyms
Mother against DPP
Mother against Dpp
Mother against decapentaplegic
Mothers against Decapentaplegic
Mothers against decapentaplegi
Mothers-against-decapentaplegic
apang
mothers against DPP
mothers against decapentaplegi
mothers against decapentaplegic
phosphorylated Smad
Secondary FlyBase IDs
  • FBgn0000105
  • FBgn0013945
  • FBgn0022270
  • FBgn0024356
Datasets (3)
Study focus (3)
Experimental Role
Project
Project Type
Title
  • bait_protein
ChIP-chip identification of binding sites for transcription factors that regulate mesodermal development.
  • bait_protein
ChIP characterization of transcription factor genome binding, Berkeley Drosophila Transcription Factor Network Project.
  • bait_protein
Genome-wide localization of transcription factors by ChIP-chip and ChIP-Seq.
References (1,023)