TF Info Page for SMAD4 (SMAD)


Assessment Binding Mode Motif Status Notes Comments
Known motif 1 Monomer or homomultimer 100 perc ID - in vitro


Description: SMAD family member 4 [Source:HGNC Symbol;Acc:HGNC:6770]
Entrez Summary This gene encodes a member of the Smad family of signal transduction proteins. Smad proteins are phosphorylated and activated by transmembrane serine-threonine receptor kinases in response to transforming growth factor (TGF)-beta signaling. The product of this gene forms homomeric complexes and heteromeric complexes with other activated Smad proteins, which then accumulate in the nucleus and regulate the transcription of target genes. This protein binds to DNA and recognizes an 8-bp palindromic sequence (GTCTAGAC) called the Smad-binding element (SBE). The protein acts as a tumor suppressor and inhibits epithelial cell proliferation. It may also have an inhibitory effect on tumors by reducing angiogenesis and increasng blood vessel hyperpermeability. The encoded protein is a crucial component of the bone morphogenetic protein signaling pathway. The Smad proteins are subject to complex regulation by post-translational modifications. Mutations or deletions in this gene have been shown to result in pancreatic cancer, juvenile polyposis syndrome, and hereditary hemorrhagic telangiectasia syndrome. [provided by RefSeq, Aug 2017]
Ensembl ID: ENSG00000141646
External Link: CisBP
Interpro IPR001132; IPR003619; IPR008984; IPR013019;
Protein Domain: ENSP00000465874
Protein Domain: ENSP00000466941
Protein Domain: ENSP00000466118
Protein: ENSP00000465874DBD: MH1 Family DBDsOther:
Protein: ENSP00000466941DBD: MH1 Family DBDsOther:
Protein: ENSP00000466118DBD: MH1 Family DBDsOther: MH2

Previous Annotations

Source Annotation
TF-CAT classification No
Vaquerizas 2009 TF classification
"a" Has direct evidence of TF function;
"b" Has evidence for an orthologous TF;
"c" contains likely DBDs, but has no functional evidence;
"x" is an unlikely TF such as predicted gene, genes with likely non-specific DBDs or that have function outside transcription;
"other" category contains proteins without clear DBDs they curated from external sources.
CisBP considers it as a TF? Yes
TFclass considers it as a TF? Yes
Has GO:0003700 "transcription factor activity, sequence-specific DNA binding" Yes
GO-Info GO:0001077
RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor a
IDA - PMID:9389648
sequence-specific DNA binding transcription factor activity
IDA - PMID:10823886, PMID:17438144
Initial Assessment
1a1 Protein has a high confidence PWM (HT-SELEX, PBM or B1H model) or there is a crystal structure that supports sequence specific DNA binding;
1a2 There is high confidence data for a close ortholog (as defined in CisBP);
2a1 There is lower confidence direct evidence, such as a Jaspar, Hocomoco or Transfac model;
2a2 There is lower confidence evidence for an close ortholog;
3a There is decent circumstantial evidence for its role as a TF or not;
4a Two or more datasets predict it as a TF;
5a One of the source datasets predicts is as a TF
1a1, Direct HQ evidence
TF has conditional DNA-binding requirements


Published Motif Data

Source Annotation Motif Evidence
TransfacTransfacLicense requiredDirect
TransfacTransfacLicense requiredDirect
TransfacTransfacLicense requiredDirect
SMiLE-seqIsakova2017Inferred - SMAD4 (100% AA Identity, Mus musculus)
MisciDMMPMMInferred - Med (96% AA Identity, Drosophila melanogaster)


Structure PDB 3QSV

Experimental History

Method Constructs
Tried in PBM?
(Whether the protein was tried in PBM or not)
Tried in HT-SELEX
(Whether the protein was tried in HT-SELEX or not, and if so, then what kind of clones were tested)
Other Information?
(Tried with another method and failed?)

External Contribution