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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)DescriptionActionsGraphical viewLength
Metal bindingi78ZincBy similarity1
Metal bindingi123ZincBy similarity1
Metal bindingi135ZincBy similarity1
Metal bindingi140ZincBy similarity1

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)DescriptionActionsGraphical viewLength
Mutagenesisi25S → A: Abolishes phosphorylation. 1
Mutagenesisi409G → S in allele Mad-10; pupal lethal. 1 Publication1
Mutagenesisi421S → L in allele Mad-9; lethal. 1 Publication1
Mutagenesisi453S → A: Abolishes interaction with lack; when associated with A-455. 1 Publication1
Mutagenesisi455S → A: Abolishes interaction with lack; when associated with A-453. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000908781 – 455Protein mothers against dppAdd BLAST455

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei25PhosphoserinePROSITE-ProRule annotation1 Publication1
Modified residuei453PhosphoserinePROSITE-ProRule annotation2 Publications1
Modified residuei455PhosphoserinePROSITE-ProRule annotation2 Publications1

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

BgeeiFBgn0011648.
ExpressionAtlasiP42003. baseline.
GenevisibleiP42003. DM.

Interactioni

Subunit structurei

Homotrimer (PubMed:19557331). Interacts with MAD1 (PubMed:20036230).2 Publications

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 interactors.
DIPiDIP-18256N.
IntActiP42003. 32 interactors.
MINTiMINT-280063.
STRINGi7227.FBpp0304648.

Structurei

Secondary structure

1455
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi261 – 268Combined sources8
Beta strandi271 – 279Combined sources9
Beta strandi281 – 289Combined sources9
Turni294 – 296Combined sources3
Beta strandi297 – 300Combined sources4
Helixi301 – 303Combined sources3
Helixi311 – 320Combined sources10
Beta strandi324 – 329Combined sources6
Beta strandi332 – 337Combined sources6
Beta strandi339 – 341Combined sources3
Beta strandi343 – 346Combined sources4
Helixi348 – 353Combined sources6
Beta strandi362 – 364Combined sources3
Beta strandi369 – 373Combined sources5
Helixi375 – 384Combined sources10
Helixi386 – 388Combined sources3
Helixi391 – 396Combined sources6
Helixi397 – 400Combined sources4
Beta strandi401 – 408Combined sources8
Beta strandi411 – 415Combined sources5
Helixi419 – 421Combined sources3
Beta strandi422 – 430Combined sources9
Helixi431 – 441Combined sources11

3D structure databases

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

Miscellaneous databases

EvolutionaryTraceiP42003.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini26 – 150MH1PROSITE-ProRule annotationAdd BLAST125
Domaini261 – 455MH2PROSITE-ProRule annotationAdd BLAST195

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni221 – 225Interaction with lack5

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.
KOiK04676.
OrthoDBiEOG091G082C.
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.
KEGGidme:Dmel_CG12399.

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
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3DITX-ray3.20A/B/C259-446[»]
3GMJX-ray2.80A/B/C/D215-455[»]
ProteinModelPortaliP42003.
SMRiP42003.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi59745. 54 interactors.
DIPiDIP-18256N.
IntActiP42003. 32 interactors.
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.
KEGGidme:Dmel_CG12399.

Organism-specific databases

CTDi33529.
FlyBaseiFBgn0011648. Mad.

Phylogenomic databases

eggNOGiKOG3701. Eukaryota.
ENOG410XQKU. LUCA.
GeneTreeiENSGT00760000119091.
InParanoidiP42003.
KOiK04676.
OrthoDBiEOG091G082C.
PhylomeDBiP42003.

Enzyme and pathway databases

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

Miscellaneous databases

EvolutionaryTraceiP42003.
GenomeRNAii33529.
PROiP42003.

Gene expression databases

BgeeiFBgn0011648.
ExpressionAtlasiP42003. baseline.
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...

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: November 30, 2016
This is version 157 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.