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Reviewed, UniProtKB/Swiss-Prot P97471 (SMAD4_MOUSE)

Last modified January 19, 2010. Version 99. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

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Names and origin

Protein namesRecommended name:
    Mothers against decapentaplegic homolog 4
      Short name=Mothers against DPP homolog 4
Alternative name(s):
    SMAD 4
      Short name=Smad4
    Deletion target in pancreatic carcinoma 4 homolog
Gene names
Name: Smad4
Synonyms: Dpc4, Madh4
OrganismMus musculus (Mouse)
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus

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Protein attributes

Sequence length551 AA.
Sequence statusComplete.
Protein existenceEvidence at transcript level.

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General annotation (Comments)

Function

Common mediator of signal transduction by TGF-beta (transforming growth factor) superfamily; SMAD4 is the common SMAD (co-SMAD) By similarity. Required for gastrulation. May act as a tumor suppressor.

Subunit structure

May form trimers with receptor-regulated SMAD (R-SMAD). Found in a ternary complex composed of SMAD4, STK11 and STK11IP. Interacts with ATF2, COPS5, DACH1, MSG1, SKI, STK11, STK11IP and TRIM33. Associates with ZNF423 or ZNF521 in response to BMP2 leading to activate transcription of BMP target genes. Interacts with USP9X. Interacts with RBPMS; the interaction is direct By similarity.

Subcellular location

Cytoplasm By similarity. Nucleus By similarity. Note: In the cytoplasm in the absence of ligand. Migration to the nucleus when complexed with R-SMAD By similarity.

Tissue specificity

Ubiquitous.

Post-translational modification

Monoubiquitinated on Lys-518 by E3 ubiquitin-protein ligase TRIM33. Monoubiquitination hampers its ability to form a stable complex with activated SMAD2/3 resulting in inhibition of TGF-beta/BMP signaling cascade By similarity.

Sequence similarities

Belongs to the dwarfin/SMAD family.

Contains 1 MH1 (MAD homology 1) domain.

Contains 1 MH2 (MAD homology 2) domain.

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Ontologies

Keywords
   Biological processTranscription
Transcription regulation
   Cellular componentCytoplasm
Nucleus
   PTMAcetylation
Isopeptide bond
Ubl conjugation
Gene Ontology (GO)
   Biological processanterior/posterior pattern formation

Inferred from mutant phenotype. Source: MGI

branching involved in ureteric bud morphogenesis

Inferred from genetic interaction. Source: MGI

gastrulation with mouth forming second

Inferred from mutant phenotype. Source: MGI

negative regulation of cell proliferation

Inferred from genetic interaction. Source: MGI

neuron fate commitment

Inferred from mutant phenotype. Source: MGI

palate development

Inferred from mutant phenotype. Source: UniProtKB

positive regulation of SMAD protein nuclear translocation

Inferred from mutant phenotype. Source: UniProtKB

positive regulation of epithelial to mesenchymal transition

Inferred from mutant phenotype. Source: UniProtKB

positive regulation of pathway-restricted SMAD protein phosphorylation

Inferred from mutant phenotype. Source: UniProtKB

positive regulation of transcription from RNA polymerase II promoter

Inferred from direct assay. Source: MGI

regulation of binding

Inferred from direct assay. Source: MGI

transcription

Inferred from electronic annotation. Source: UniProtKB-KW

transforming growth factor beta receptor signaling pathway

Inferred from genetic interaction. Source: MGI

   Cellular componentcytoplasm

Inferred from direct assay. Source: UniProtKB

   Molecular functionchromatin binding

Inferred from direct assay. Source: MGI

collagen binding

Inferred from physical interaction. Source: MGI

transcription activator activity

Inferred from direct assay. Source: MGI

transcription factor activity

Inferred from direct assay. Source: MGI

Complete GO annotation...

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Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 551551Mothers against decapentaplegic homolog 4
PRO_0000090862

Regions

Domain18 – 142125MH1
Domain322 – 551230MH2
Region274 – 31946SAD
Compositional bias450 – 46516Poly-Ala

Amino acid modifications

Modified residue371N6-acetyllysine By similarity
Modified residue4271N6-acetyllysine By similarity
Modified residue5061N6-acetyllysine By similarity
Cross-link518Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity

Experimental info

Sequence conflict2571S → A in BAB23576. Ref.2
Sequence conflict2921R → P in BAB23576. Ref.2

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Sequences

Sequence LengthMass (Da)Tools
P97471-1 [UniParc].

Last modified May 1, 1997. Version 1.
Checksum: 0835EF88D9C1C980

FASTA55160,417
        10         20         30         40         50         60 
MDNMSITNTP TSNDACLSIV HSLMCHRQGG ESETFAKRAI ESLVKKLKEK KDELDSLITA 

        70         80         90        100        110        120 
ITTNGAHPSK CVTIQRTLDG RLQVAGRKGF PHVIYARLWR WPDLHKNELK HVKYCQYAFD 

       130        140        150        160        170        180 
LKCDSVCVNP YHYERVVSPG IDLSGLTLQS NAPSMLVKDE YVHDFEGQPS LPTEGHSIQT 

       190        200        210        220        230        240 
IQHPPSNRAS TETYSAPALL APAESNATST TNFPNIPVAS TSQPASILAG SHSEGLLQIA 

       250        260        270        280        290        300 
SGPQPGQQQN GFTAQPSTYH HNSTTTWTGS RTAPYTPNLP HHQNGHLQHH PRMPPHPGHY 

       310        320        330        340        350        360 
WPVHNELAFQ PPISNHPAPE YWCSIAYFEM DVQVGETFKV PSSCPVVTVD GYVDPSGGDR 

       370        380        390        400        410        420 
FCLGQLSNVH RTEAIERARL HIGKGVQLEC KGEGDVWVRC LSDHAVFVQS YYLDREAGRA 

       430        440        450        460        470        480 
PGDAVHKIYP SAYIKVFDLR QCHRQMQQQA ATAQAAAAAQ AAAVAGNIPG PGSVGGIAPA 

       490        500        510        520        530        540 
ISLSAAAGIG VDDLRRLCIL RMSFVKGWGP DYPRQSIKET PCWIEIHLHR ALQLLDEVLH 

       550 
TMPIADPQPL D

« Hide

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References

« Hide 'large scale' references
[1]"Sequence and chromosomal mapping of the mouse homolog (Madh4) of the human DPC4/MADH4 gene."
Anna C.H., Devereux T.R.
Mamm. Genome 8:443-444(1997) [PubMed: 9166592] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Strain: A/J.
Tissue: Lung.
[2]"The transcriptional landscape of the mammalian genome."
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. expand/collapse author list , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
Science 309:1559-1563(2005) [PubMed: 16141072] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 67-551.
Strain: C57BL/6J.
Tissue: Lung.
[3]"Functions of mammalian Smad genes as revealed by targeted gene disruption in mice."
Weinstein M., Yang X., Deng C.-X.
Cytokine Growth Factor Rev. 11:49-58(2000) [PubMed: 10708952] [Abstract]
Cited for: REVIEW.
+Additional computationally mapped references.

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Cross-references

Sequence databases

EMBL
GenBank
DDBJ		U79748 mRNA. Translation: AAB57905.1.
AK004804 mRNA. Translation: BAB23576.1.
IPIIPI00125567.
UniGeneMm.100399

3D structure databases

SMRP97471. Positions 19-138, 284-551.
ModBaseSearch...

Protein-protein interaction databases

DIPDIP-29718N.
STRINGP97471.

PTM databases

PhosphoSiteP97471.

Proteomic databases

PRIDEP97471.

Genome annotation databases

EnsemblENSMUST00000025393; ENSMUSP00000025393; ENSMUSG00000024515; Mus musculus. [Genome view]
ENSMUST00000114939; ENSMUSP00000110589; ENSMUSG00000024515; Mus musculus. [Genome view]

Organism-specific databases

MGIMGI:894293. Smad4.

Phylogenomic databases

eggNOGroNOG04669.
HOGENOMHBG443554.
HOVERGENP97471.
InParanoidP97471.

Gene expression databases

ArrayExpressP97471.
BgeeP97471.
CleanExMM_SMAD4.
GenevestigatorP97471.
GermOnlineENSMUSG00000024515. Mus musculus.

Family and domain databases

InterProIPR013790. 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]
Gene3DG3DSA:3.90.520.10. MAD_MH1. 1 hit.
G3DSA:2.60.200.10. MH2_Dwarfin-type. 1 hit.
PANTHERPTHR13703. Dwarfin. 1 hit.
PfamPF03165. MH1. 1 hit.
PF03166. MH2. 1 hit.
[Graphical view]
SMARTSM00523. DWA. 1 hit.
SM00524. DWB. 1 hit.
[Graphical view]
PROSITEPS51075. MH1. 1 hit.
PS51076. MH2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

SOURCESearch...

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Entry information

Entry nameSMAD4_MOUSE
AccessionPrimary (citable) accession number: P97471
Secondary accession number(s): Q9CW56
Entry history
Integrated into UniProtKB/Swiss-Prot: May 4, 2001
Last sequence update: May 1, 1997
Last modified: January 19, 2010
This is version 99 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)

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Relevant documents

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents