P42003 (MAD_DROME) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Protein mothers against dpp

Gene names

Name:	Mad
ORF Names:	CG12399

Organism

Drosophila melanogaster (Fruit fly)

Taxonomic identifier

7227 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Arthropoda › Hexapoda › Insecta › Pterygota › Neoptera › Endopterygota › Diptera › Brachycera › Muscomorpha › Ephydroidea › Drosophilidae › Drosophila › Sophophora

Protein attributes

Sequence length	455 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Required for the function of decapentaplegic. May play an important role in mediating Dpp signaling. Involved in the BMP signaling pathway. Ref.1 Ref.7
Subunit structure	Phosphorylated form interacts with lack/SMURF1. Ref.5 Ref.6
Subcellular location	Cytoplasm. Nucleus Ref.7.
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. Ref.1
Post-translational modification	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. Ubiquitinated by lack; which promotes proteasomal degradation. Ref.6
Disruption phenotype	Mutants exhibit defects in midgut morphogenesis, imaginal disk development and embryonic dorsal-ventral patterning that are very reminiscent of dpp mutant phenotypes. Ref.1
Sequence similarities	Belongs to the dwarfin/SMAD family. Contains 1 MH1 (MAD homology 1) domain. Contains 1 MH2 (MAD homology 2) domain.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Cytoplasm Nucleus
Molecular function	Developmental protein
PTM	Phosphoprotein Ubl conjugation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	compound eye morphogenesis Inferred from mutant phenotype. Source: FlyBase dorsal closure Non-traceable author statement. Source: FlyBase germ-line stem cell division Inferred from mutant phenotype. Source: FlyBase germ-line stem cell maintenance Inferred from mutant phenotype. Source: FlyBase heart development Traceable author statement. Source: FlyBase histoblast morphogenesis Inferred from mutant phenotype. Source: FlyBase imaginal disc-derived leg morphogenesis Inferred from mutant phenotype. Source: FlyBase imaginal disc-derived wing vein morphogenesis Inferred from mutant phenotype. Source: FlyBase negative regulation of S phase of mitotic cell cycle Inferred from mutant phenotype. Source: FlyBase negative regulation of salivary gland boundary specification Traceable author statement. Source: FlyBase open tracheal system development Traceable author statement. Source: FlyBase ovarian follicle cell development Inferred from mutant phenotype. Source: FlyBase positive regulation of synaptic growth at neuromuscular junction Inferred from mutant phenotype. Source: FlyBase positive regulation of transcription from RNA polymerase II promoter Inferred from mutant phenotype. Source: FlyBase somatic stem cell maintenance Inferred from mutant phenotype. Source: FlyBase transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW transforming growth factor beta receptor signaling pathway Inferred from genetic interaction. Source: FlyBase trunk segmentation Inferred from mutant phenotype. Source: FlyBase wing disc anterior/posterior pattern formation Inferred from mutant phenotype. Source: FlyBase
Cellular component	cytoplasm Inferred from direct assay. Source: FlyBase transcription factor complex Inferred from electronic annotation. Source: InterPro
Molecular function	protein binding Inferred from physical interaction Ref.5Ref.6. Source: UniProtKB sequence-specific DNA binding Inferred from direct assay. Source: FlyBase sequence-specific DNA binding transcription factor activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
yki	Q45VV3	2	EBI-162238,EBI-141254

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 455

455

Protein mothers against dpp

PRO_0000090878

Regions

Domain

26 – 150

125

MH1

Domain

261 – 455

195

MH2

Region

221 – 225

5

Interaction with lack

Amino acid modifications

Modified residue

25

1

Phosphoserine Ref.7

Modified residue

453

1

Phosphoserine Ref.6 Ref.8

Modified residue

455

1

Phosphoserine Ref.6 Ref.8

Experimental info

Mutagenesis

25

1

S → A: Abolishes phosphorylation.

Mutagenesis

409

1

G → S in allele Mad-10; pupal lethal. Ref.1

Mutagenesis

421

1

S → L in allele Mad-9; lethal. Ref.1

Mutagenesis

453

1

S → A: Abolishes interaction with lack; when associated with A-455. Ref.6

Mutagenesis

455

1

S → A: Abolishes interaction with lack; when associated with A-453. Ref.6

Secondary structure

1

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455

Helix Strand Turn

Details...

Beta strand

261 – 268

8

Beta strand

277 – 279

3

Beta strand

281 – 287

7

Beta strand

296 – 300

5

Helix

311 – 316

6

Turn

317 – 319

3

Beta strand

325 – 328

4

Beta strand

333 – 336

4

Beta strand

339 – 341

3

Beta strand

343 – 346

4

Helix

348 – 353

6

Beta strand

369 – 373

5

Helix

375 – 386

12

Helix

391 – 395

5

Helix

396 – 400

5

Beta strand

401 – 406

6

Helix

419 – 421

3

Beta strand

422 – 430

9

Helix

434 – 443

10

Sequences

	Sequence		Length	Mass (Da)
	P42003 [UniParc]. Last modified November 1, 1995. Version 1. Checksum: 6C8570674C3AB9D8	FASTA	455	50,505
	10 20 30 40 50 60 MDTDDVESNT SSAMSTLGSL FSFTSPAVKK LLGWKQGDEE EKWAEKAVDS LVKKLKKRKG 70 80 90 100 110 120 AIEELERALS CPGQPSKCVT IPRSLDGRLQ VSHRKGLPHV IYCRVWRWPD LQSHHELKPL 130 140 150 160 170 180 ELCQYPFSAK QKEVCINPYH YKRVESPVLP PVLVPRHSEF APGHSMLQFN HVAEPSMPHN 190 200 210 220 230 240 VSYSNSGFNS HSLSTSNTSV GSPSSVNSNP NSPYDSLAGT PPPAYSPSED GNSNNPNDGG 250 260 270 280 290 300 QLLDAQMGDV AQVSYSEPAF WASIAYYELN CRVGEVFHCN NNSVIVDGFT NPSNNSDRCC 310 320 330 340 350 360 LGQLSNVNRN STIENTRRHI GKGVHLYYVT GEVYAECLSD SAIFVQSRNC NYHHGFHPST 370 380 390 400 410 420 VCKIPPGCSL KIFNNQEFAQ LLSQSVNNGF EAVYELTKMC TIRMSFVKGW GAEYHRQDVT 430 440 450 STPCWIEIHL HGPLQWLDKV LTQMGSPHNA ISSVS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[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: 7768443] [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: 10731132] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: Berkeley.
[3]	"Annotation of the Drosophila melanogaster euchromatic genome: a systematic review." Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S., Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E., Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P., Bettencourt B.R., Celniker S.E., de Grey A.D.N.J. , Drysdale R.A., Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M., Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E. Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002) [PubMed: 12537572] [Abstract] Cited for: GENOME REANNOTATION. Strain: Berkeley.
[4]	Stapleton M., Brokstein P., Hong L., Agbayani A., Carlson J.W., Champe M., Chavez C., Dorsett V., Dresnek D., Farfan D., Frise E., George R.A., Gonzalez M., Guarin H., Kronmiller B., Li P.W., Liao G., Miranda A. , Mungall C.J., Nunoo J., Pacleb J.M., Paragas V., Park S., Patel S., Phouanenavong S., Wan K.H., Yu C., Lewis S.E., Rubin G.M., Celniker S.E. Submitted (FEB-2003) to the EMBL/GenBank/DDBJ databases 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: 11703946] [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: 12754252] [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: 17507407] [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: 18327897] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-453 AND SER-455, MASS SPECTROMETRY. Tissue: Embryo.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U10328 mRNA. Translation: AAB60230.1.
AE014134 Genomic DNA. Translation: AAF51142.1.
BT004845 mRNA. Translation: AAO45201.1.

PIR

S55019.

RefSeq

NP_477017.1. NM_057669.2.

UniGene

Dm.7367.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3DIT	X-ray	3.20	A/B/C	259-446	[»]
3GMJ	X-ray	2.80	A/B/C/D	215-455	[»]

ProteinModelPortal

P42003.

SMR

P42003. Positions 23-146, 259-446.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-18256N.

IntAct

P42003. 32 interactions.

MINT

MINT-280063.

STRING

P42003.

Proteomic databases

PRIDE

P42003.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

EnsemblMetazoa

FBtr0077616; FBpp0077302; FBgn0011648.

GeneID

33529.

KEGG

dme:Dmel_CG12399.

NMPDR

fig|7227.3.peg.542.

Organism-specific databases

CTD

33529.

FlyBase

FBgn0011648. Mad.

Phylogenomic databases

eggNOG

inNOG05372.

GeneTree

EMGT00050000000290.

InParanoid

P42003.

OMA

RWPDISS.

OrthoDB

EOG49GHXZ.

PhylomeDB

P42003.

Gene expression databases

ArrayExpress

P42003.

Bgee

P42003.

GermOnline

CG12399. Drosophila melanogaster.

Family and domain databases

InterPro

IPR013790. 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]

Gene3D

G3DSA:3.90.520.10. MAD_MH1. 1 hit.
G3DSA:2.60.200.10. MH2_Dwarfin-type. 1 hit.

KO

K04676.

PANTHER

PTHR13703. Dwarfin. 1 hit.

Pfam

PF03165. MH1. 1 hit.
PF03166. MH2. 1 hit.
[Graphical view]

SMART

SM00523. DWA. 1 hit.
SM00524. DWB. 1 hit.
[Graphical view]

SUPFAM

SSF56366. MAD_MH1. 1 hit.
SSF49879. SMAD_FHA. 1 hit.

PROSITE

PS51075. MH1. 1 hit.
PS51076. MH2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

NextBio

784055.

Entry information

Entry name

MAD_DROME

Accession

Primary (citable) accession number: P42003
Secondary accession number(s): Q9VQM3

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1995
Last sequence update:	November 1, 1995
Last modified:	January 25, 2012
This is version 113 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Drosophila annotation project