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O70437 (SMAD4_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified January 25, 2012. Version 92. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
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Names and origin

Protein namesRecommended name:
Mothers against decapentaplegic homolog 4

Short name=MAD homolog 4
Short name=Mothers against DPP homolog 4
Alternative name(s):
SMAD family member 4
Short name=SMAD 4
Short name=Smad4
Gene names
Name:Smad4
Synonyms:Madh4
OrganismRattus norvegicus (Rat)
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length552 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Common SMAD (co-SMAD) is the coactivator and mediator of signal transduction by TGF-beta (transforming growth factor). Component of the heterotrimeric SMAD2/SMAD3-SMAD4 complex that forms in the nucleus and is required for the TGF-mediated signaling. Promotes binding of the SMAD2/SMAD4/FAST-1 complex to DNA and provides an activation function required for SMAD1 or SMAD2 to stimulate transcription. Component of the multimeric SMAD3/SMAD4/JUN/FOS complex which forms at the AP1 promoter site; required for syngernistic transcriptional activity in response to TGF-beta. May act as a tumor suppressor. Positively regulates PDPK1 kinase activity by stimulating its dissociation from the 14-3-3 protein YWHAQ which acts as a negative regulator By similarity.

Subunit structure

Monomer By similarity. Heterotrimer; with a C-terminally phosphorylated R-SMAD molecule and to form the transcriptionally active SMAD2/3-SMAD4 complex By similarity. Found in a ternary complex composed of SMAD4, STK11/LKB1 and STK11IP. Interacts with ATF2, COPS5, DACH1, MSG1, SKI, STK11/LKB1, 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. Interacts with WWTR1 (via coiled-coil domain). Interacts with CITED1 By similarity. Interacts with CITED2. Interacts with PDPK1 (via PH domain) By similarity. Ref.3

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. PDPK1 prevents its nuclear translocation By similarity.

Domain

The MH1 domain is required for DNA binding By similarity.

The MH2 domain is required for both homomeric and heteromeric interactions and for transcriptional regulation. Sufficient for nuclear import By similarity.

Post-translational modification

Phosphorylated by PDPK1 By similarity.

Monoubiquitinated on Lys-519 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. Deubiqitination by USP9X restores its competence to mediate TGF-beta signaling By similarity.

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 processTranscription
Transcription regulation
   Cellular componentCytoplasm
Nucleus
   PTMAcetylation
Isopeptide bond
Ubl conjugation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological processtranscription, DNA-dependent

Inferred from electronic annotation. Source: UniProtKB-KW

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 552552Mothers against decapentaplegic homolog 4
PRO_0000090864

Regions

Domain18 – 142125MH1
Domain323 – 552230MH2
Region275 – 32046SAD
Compositional bias451 – 46616Poly-Ala

Sites

Site5151Necessary for heterotrimerization By similarity

Amino acid modifications

Modified residue371N6-acetyllysine By similarity
Modified residue4281N6-acetyllysine By similarity
Modified residue5071N6-acetyllysine By similarity
Cross-link519Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity

Sequences

Sequence LengthMass (Da)Tools
O70437 [UniParc].

Last modified August 1, 1998. Version 1.
Checksum: 7AE0540AB4DF0E77

FASTA55260,469
        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 NAPPSMLVKD EYVHDFEGQP SLPTEGHSIQ 

       190        200        210        220        230        240 
TIQHPPSNRA STETYSAPAL LAPSESNATS TTNFPNIPVA STSQPASILA GSHSEGLLQI 

       250        260        270        280        290        300 
ASGPQPGQQQ NGFTAQPATY HHNSTTTWTG SRTAPYTPNL PHHQNGHLQH HPPMPPHPGH 

       310        320        330        340        350        360 
YWPVHNELAF QPPISNHPAP EYWCSIAYFE MDVQVGETFK VPSSCPIVTV DGYVDPSGGD 

       370        380        390        400        410        420 
RFCLGQLSNV HRTEAIERAR LHIGKGVQLE CKGEGDVWVR CLSDHAVFVQ SYYLDREAGR 

       430        440        450        460        470        480 
APGDAVHKIY PSAYIKVFDL RQCHRQMQQQ AATAQAAAAA QAAAVAGNIP GPGSVGGIAP 

       490        500        510        520        530        540 
AISLSAAAGI GVDDLRRLCI LRMSFVKGWG PDYPRQSIKE TPCWIEIHLH RALQLLDEVL 

       550 
HTMPIADPQP LD 

« Hide

References

[1]"Molecular cloning of rat Smad4 gene."
Miyakita A., Okuno S., Watanabe T.K., Oga K., Tsuji A., Hishigaki H., Suto T., Nakagawa K., Nakahara Y., Higashi K.
Submitted (FEB-1998) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Skeletal muscle.
[2]"cDNA cloning and chromosomal mapping of rat Smad2 and Smad4 and their expression in cultured rat articular chondrocytes."
Osaki M., Tsukazaki T., Ono N., Yonekura A., Hirota Y., Miyazaki Y., Shindo H., Sonta S., Yamashita S.
Endocr. J. 46:695-701(1999) [PubMed: 10670756] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]"Cited2 modulates TGF-beta-mediated upregulation of MMP9."
Chou Y.T., Wang H., Chen Y., Danielpour D., Yang Y.C.
Oncogene 25:5547-5560(2006) [PubMed: 16619037] [Abstract]
Cited for: INTERACTION WITH CITED2.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AB010954 mRNA. Translation: BAA83092.1.
AF056002 mRNA. Translation: AAC12781.1.
IPIIPI00198545.
RefSeqNP_062148.1. NM_019275.2.
UniGeneRn.9774.

3D structure databases

ProteinModelPortalO70437.
SMRO70437. Positions 19-138, 285-552.
ModBaseSearch...

Protein-protein interaction databases

MINTMINT-2739642.
STRINGO70437.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID50554.
KEGGrno:50554.
UCSCNM_019275. rat.

Organism-specific databases

CTD4089.
RGD3033. Smad4.

Phylogenomic databases

eggNOGroNOG04669.
GeneTreeENSGT00600000084353.
HOVERGENHBG053353.
InParanoidO70437.
OrthoDBEOG4KPT9S.

Gene expression databases

ArrayExpressO70437.
GenevestigatorO70437.
GermOnlineENSRNOG00000015634. Rattus norvegicus.

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.
KOK04501.
PANTHERPTHR13703. Dwarfin. 1 hit.
PfamPF03165. MH1. 1 hit.
PF03166. MH2. 1 hit.
[Graphical view]
SMARTSM00523. DWA. 1 hit.
SM00524. DWB. 1 hit.
[Graphical view]
SUPFAMSSF56366. MAD_MH1. 1 hit.
SSF49879. SMAD_FHA. 1 hit.
PROSITEPS51075. MH1. 1 hit.
PS51076. MH2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio610352.

Entry information

Entry nameSMAD4_RAT
AccessionPrimary (citable) accession number: O70437
Entry history
Integrated into UniProtKB/Swiss-Prot: May 4, 2001
Last sequence update: August 1, 1998
Last modified: January 25, 2012
This is version 92 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families