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Protein

Protein mothers against dpp

Gene

Mad

Organism
Drosophila melanogaster (Fruit fly)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Required for the function of decapentaplegic. May play an important role in mediating Dpp signaling. Involved in the BMP signaling pathway.2 Publications

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi78 – 781ZincBy similarity
Metal bindingi123 – 1231ZincBy similarity
Metal bindingi135 – 1351ZincBy similarity
Metal bindingi140 – 1401ZincBy similarity

GO - Molecular functioni

  • DNA binding Source: FlyBase
  • metal ion binding Source: UniProtKB-KW
  • RNA polymerase II activating transcription factor binding Source: FlyBase
  • RNA polymerase II distal enhancer sequence-specific DNA binding Source: FlyBase
  • RNA polymerase II transcription coactivator activity Source: FlyBase
  • sequence-specific DNA binding Source: FlyBase
  • transcription factor activity, RNA polymerase II distal enhancer sequence-specific binding Source: FlyBase
  • transforming growth factor beta receptor, pathway-specific cytoplasmic mediator activity Source: FlyBase

GO - Biological processi

  • BMP signaling pathway involved in Malpighian tubule cell chemotaxis Source: FlyBase
  • compound eye morphogenesis Source: FlyBase
  • dorsal closure Source: FlyBase
  • germ-line stem cell division Source: FlyBase
  • germ-line stem cell population maintenance Source: FlyBase
  • heart development Source: FlyBase
  • histoblast morphogenesis Source: FlyBase
  • imaginal disc-derived leg morphogenesis Source: FlyBase
  • imaginal disc-derived wing morphogenesis Source: FlyBase
  • imaginal disc-derived wing vein morphogenesis Source: FlyBase
  • negative regulation of G1/S transition of mitotic cell cycle Source: FlyBase
  • negative regulation of gene expression Source: FlyBase
  • negative regulation of salivary gland boundary specification Source: FlyBase
  • open tracheal system development Source: FlyBase
  • ovarian follicle cell development Source: FlyBase
  • positive regulation of synaptic growth at neuromuscular junction Source: FlyBase
  • positive regulation of transcription from RNA polymerase II promoter Source: FlyBase
  • regulation of cell differentiation Source: FlyBase
  • regulation of synapse structure or activity Source: FlyBase
  • regulation of transcription from RNA polymerase II promoter Source: FlyBase
  • somatic stem cell population maintenance Source: FlyBase
  • transforming growth factor beta receptor signaling pathway Source: FlyBase
  • transforming growth factor beta receptor signaling pathway involved in endodermal cell fate specification Source: FlyBase
  • trunk segmentation Source: FlyBase
  • ventral cord development Source: FlyBase
  • wing disc anterior/posterior pattern formation Source: FlyBase
Complete GO annotation...

Keywords - Molecular functioni

Developmental protein

Keywords - Biological processi

Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding, Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-DME-201451. Signaling by BMP.
SignaLinkiP42003.

Names & Taxonomyi

Protein namesi
Recommended name:
Protein mothers against dpp
Gene namesi
Name:Mad
ORF Names:CG12399
OrganismiDrosophila melanogaster (Fruit fly)
Taxonomic identifieri7227 [NCBI]
Taxonomic lineageiEukaryotaMetazoaEcdysozoaArthropodaHexapodaInsectaPterygotaNeopteraEndopterygotaDipteraBrachyceraMuscomorphaEphydroideaDrosophilidaeDrosophilaSophophora
Proteomesi
  • UP000000803 Componenti: Chromosome 2L

Organism-specific databases

FlyBaseiFBgn0011648. Mad.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: FlyBase
  • nucleus Source: FlyBase
  • transcription factor complex Source: InterPro
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Disruption phenotypei

Mutants exhibit defects in midgut morphogenesis, imaginal disk development and embryonic dorsal-ventral patterning that are very reminiscent of dpp mutant phenotypes.1 Publication

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi25 – 251S → A: Abolishes phosphorylation.
Mutagenesisi409 – 4091G → S in allele Mad-10; pupal lethal. 1 Publication
Mutagenesisi421 – 4211S → L in allele Mad-9; lethal. 1 Publication
Mutagenesisi453 – 4531S → A: Abolishes interaction with lack; when associated with A-455. 1 Publication
Mutagenesisi455 – 4551S → A: Abolishes interaction with lack; when associated with A-453. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 455455Protein mothers against dppPRO_0000090878Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei25 – 251PhosphoserinePROSITE-ProRule annotation1 Publication
Modified residuei453 – 4531PhosphoserinePROSITE-ProRule annotation2 Publications
Modified residuei455 – 4551PhosphoserinePROSITE-ProRule annotation2 Publications

Post-translational modificationi

Phosphorylation on Ser-453 and/or Ser-455 is required for interaction with lack. Phosphorylation on Ser-25 by key/Nemo promotes export from nucleus and antagonizes BMP signaling.3 Publications
Ubiquitinated by lack/SMURF1 upon phosphorylatiom; which promotes proteasomal degradation.1 Publication

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiP42003.
PRIDEiP42003.

PTM databases

iPTMnetiP42003.

Expressioni

Developmental stagei

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.1 Publication

Gene expression databases

BgeeiP42003.
ExpressionAtlasiP42003. differential.
GenevisibleiP42003. DM.

Interactioni

Subunit structurei

Homotrimer.1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
ykiQ45VV32EBI-162238,EBI-141254

GO - Molecular functioni

  • RNA polymerase II activating transcription factor binding Source: FlyBase

Protein-protein interaction databases

BioGridi59745. 54 interactions.
DIPiDIP-18256N.
IntActiP42003. 32 interactions.
MINTiMINT-280063.
STRINGi7227.FBpp0304648.

Structurei

Secondary structure

1
455
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi261 – 2688Combined sources
Beta strandi271 – 2799Combined sources
Beta strandi281 – 2899Combined sources
Turni294 – 2963Combined sources
Beta strandi297 – 3004Combined sources
Helixi301 – 3033Combined sources
Helixi311 – 32010Combined sources
Beta strandi324 – 3296Combined sources
Beta strandi332 – 3376Combined sources
Beta strandi339 – 3413Combined sources
Beta strandi343 – 3464Combined sources
Helixi348 – 3536Combined sources
Beta strandi362 – 3643Combined sources
Beta strandi369 – 3735Combined sources
Helixi375 – 38410Combined sources
Helixi386 – 3883Combined sources
Helixi391 – 3966Combined sources
Helixi397 – 4004Combined sources
Beta strandi401 – 4088Combined sources
Beta strandi411 – 4155Combined sources
Helixi419 – 4213Combined sources
Beta strandi422 – 4309Combined sources
Helixi431 – 44111Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
3DITX-ray3.20A/B/C259-446[»]
3GMJX-ray2.80A/B/C/D215-455[»]
ProteinModelPortaliP42003.
SMRiP42003. Positions 23-146, 259-446.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP42003.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini26 – 150125MH1PROSITE-ProRule annotationAdd
BLAST
Domaini261 – 455195MH2PROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni221 – 2255Interaction with lack

Sequence similaritiesi

Belongs to the dwarfin/SMAD family.Curated
Contains 1 MH1 (MAD homology 1) domain.PROSITE-ProRule annotation
Contains 1 MH2 (MAD homology 2) domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG3701. Eukaryota.
ENOG410XQKU. LUCA.
GeneTreeiENSGT00760000119091.
InParanoidiP42003.
OrthoDBiEOG7W1540.
PhylomeDBiP42003.

Family and domain databases

Gene3Di2.60.200.10. 1 hit.
3.90.520.10. 1 hit.
InterProiIPR013790. Dwarfin.
IPR003619. MAD_homology1_Dwarfin-type.
IPR013019. MAD_homology_MH1.
IPR017855. SMAD_dom-like.
IPR001132. SMAD_dom_Dwarfin-type.
IPR008984. SMAD_FHA_domain.
[Graphical view]
PANTHERiPTHR13703. PTHR13703. 1 hit.
PfamiPF03165. MH1. 1 hit.
PF03166. MH2. 1 hit.
[Graphical view]
SMARTiSM00523. DWA. 1 hit.
SM00524. DWB. 1 hit.
[Graphical view]
SUPFAMiSSF49879. SSF49879. 1 hit.
SSF56366. SSF56366. 1 hit.
PROSITEiPS51075. MH1. 1 hit.
PS51076. MH2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P42003-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MDTDDVESNT SSAMSTLGSL FSFTSPAVKK LLGWKQGDEE EKWAEKAVDS
60 70 80 90 100
LVKKLKKRKG AIEELERALS CPGQPSKCVT IPRSLDGRLQ VSHRKGLPHV
110 120 130 140 150
IYCRVWRWPD LQSHHELKPL ELCQYPFSAK QKEVCINPYH YKRVESPVLP
160 170 180 190 200
PVLVPRHSEF APGHSMLQFN HVAEPSMPHN VSYSNSGFNS HSLSTSNTSV
210 220 230 240 250
GSPSSVNSNP NSPYDSLAGT PPPAYSPSED GNSNNPNDGG QLLDAQMGDV
260 270 280 290 300
AQVSYSEPAF WASIAYYELN CRVGEVFHCN NNSVIVDGFT NPSNNSDRCC
310 320 330 340 350
LGQLSNVNRN STIENTRRHI GKGVHLYYVT GEVYAECLSD SAIFVQSRNC
360 370 380 390 400
NYHHGFHPST VCKIPPGCSL KIFNNQEFAQ LLSQSVNNGF EAVYELTKMC
410 420 430 440 450
TIRMSFVKGW GAEYHRQDVT STPCWIEIHL HGPLQWLDKV LTQMGSPHNA

ISSVS
Length:455
Mass (Da):50,505
Last modified:November 1, 1995 - v1
Checksum:i6C8570674C3AB9D8
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U10328 mRNA. Translation: AAB60230.1.
AE014134 Genomic DNA. Translation: AAF51142.1.
BT004845 mRNA. Translation: AAO45201.1.
PIRiS55019.
RefSeqiNP_477017.1. NM_057669.3.
UniGeneiDm.7367.

Genome annotation databases

EnsemblMetazoaiFBtr0077616; FBpp0077302; FBgn0011648.
GeneIDi33529.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U10328 mRNA. Translation: AAB60230.1.
AE014134 Genomic DNA. Translation: AAF51142.1.
BT004845 mRNA. Translation: AAO45201.1.
PIRiS55019.
RefSeqiNP_477017.1. NM_057669.3.
UniGeneiDm.7367.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
3DITX-ray3.20A/B/C259-446[»]
3GMJX-ray2.80A/B/C/D215-455[»]
ProteinModelPortaliP42003.
SMRiP42003. Positions 23-146, 259-446.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi59745. 54 interactions.
DIPiDIP-18256N.
IntActiP42003. 32 interactions.
MINTiMINT-280063.
STRINGi7227.FBpp0304648.

PTM databases

iPTMnetiP42003.

Proteomic databases

PaxDbiP42003.
PRIDEiP42003.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsemblMetazoaiFBtr0077616; FBpp0077302; FBgn0011648.
GeneIDi33529.

Organism-specific databases

CTDi33529.
FlyBaseiFBgn0011648. Mad.

Phylogenomic databases

eggNOGiKOG3701. Eukaryota.
ENOG410XQKU. LUCA.
GeneTreeiENSGT00760000119091.
InParanoidiP42003.
OrthoDBiEOG7W1540.
PhylomeDBiP42003.

Enzyme and pathway databases

ReactomeiR-DME-201451. Signaling by BMP.
SignaLinkiP42003.

Miscellaneous databases

EvolutionaryTraceiP42003.
GenomeRNAii33529.
NextBioi784055.
PROiP42003.

Gene expression databases

BgeeiP42003.
ExpressionAtlasiP42003. differential.
GenevisibleiP42003. DM.

Family and domain databases

Gene3Di2.60.200.10. 1 hit.
3.90.520.10. 1 hit.
InterProiIPR013790. Dwarfin.
IPR003619. MAD_homology1_Dwarfin-type.
IPR013019. MAD_homology_MH1.
IPR017855. SMAD_dom-like.
IPR001132. SMAD_dom_Dwarfin-type.
IPR008984. SMAD_FHA_domain.
[Graphical view]
PANTHERiPTHR13703. PTHR13703. 1 hit.
PfamiPF03165. MH1. 1 hit.
PF03166. MH2. 1 hit.
[Graphical view]
SMARTiSM00523. DWA. 1 hit.
SM00524. DWB. 1 hit.
[Graphical view]
SUPFAMiSSF49879. SSF49879. 1 hit.
SSF56366. SSF56366. 1 hit.
PROSITEiPS51075. MH1. 1 hit.
PS51076. MH2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Genetic characterization and cloning of mothers against dpp, a gene required for decapentaplegic function in Drosophila melanogaster."
    Sekelsky J.J., Newfeld S.J., Raftery L.A., Chartoff E.H., Gelbart W.M.
    Genetics 139:1347-1358(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, DEVELOPMENTAL STAGE, MUTAGENESIS OF GLY-409 AND SER-421, DISRUPTION PHENOTYPE.
  2. "The genome sequence of Drosophila melanogaster."
    Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D., Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F., George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N., Sutton G.G., Wortman J.R., Yandell M.D.
    , Zhang Q., Chen L.X., Brandon R.C., Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C., Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A., An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A., Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V., Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J., Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E., Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B., Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I., Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C., Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S., Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M., Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M., Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D., Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F., Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D., Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A., Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C., McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C., Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L., Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R., Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V., Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F., Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J., Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R., Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y., Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T., Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S., Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W., Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M., Venter J.C.
    Science 287:2185-2195(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: Berkeley.
  3. Cited for: GENOME REANNOTATION.
    Strain: Berkeley.
  4. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: Berkeley.
    Tissue: Embryo.
  5. "The DSmurf ubiquitin-protein ligase restricts BMP signaling spatially and temporally during Drosophila embryogenesis."
    Podos S.D., Hanson K.K., Wang Y.-C., Ferguson E.L.
    Dev. Cell 1:567-578(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH LACK.
  6. "DSmurf selectively degrades decapentaplegic-activated MAD, and its overexpression disrupts imaginal disc development."
    Liang Y.-Y., Lin X., Liang M., Brunicardi F.C., ten Dijke P., Chen Z., Choi K.-W., Feng X.-H.
    J. Biol. Chem. 278:26307-26310(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH LACK, PHOSPHORYLATION AT SER-453 AND SER-455, MUTAGENESIS OF SER-453 AND SER-455, UBIQUITINATION.
  7. "Drosophila Nemo antagonizes BMP signaling by phosphorylation of Mad and inhibition of its nuclear accumulation."
    Zeng Y.A., Rahnama M., Wang S., Sosu-Sedzorme W., Verheyen E.M.
    Development 134:2061-2071(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION, PHOSPHORYLATION AT SER-25.
  8. "Phosphoproteome analysis of Drosophila melanogaster embryos."
    Zhai B., Villen J., Beausoleil S.A., Mintseris J., Gygi S.P.
    J. Proteome Res. 7:1675-1682(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-453 AND SER-455, IDENTIFICATION BY MASS SPECTROMETRY.
    Tissue: Embryo.
  9. "Crystal structure of the MH2 domain of Drosophila Mad."
    Wang C., Chen L., Wang L., Wu J.
    Sci. China, Ser. C, Life Sci. 52:539-544(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 215-455, SUBUNIT.

Entry informationi

Entry nameiMAD_DROME
AccessioniPrimary (citable) accession number: P42003
Secondary accession number(s): Q9VQM3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: November 1, 1995
Last modified: May 11, 2016
This is version 151 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programDrosophila annotation project

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Drosophila
    Drosophila: entries, gene names and cross-references to FlyBase
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.