Conclusion
Assessment
Binding Mode
Motif Status
Notes
Comments
Known motif
2 Obligate heteromer
In vivo/Misc source
Only known motifs are from Transfac or HocoMoco - origin is uncertain
Well-established obligate heteromer
Description
Description:
SMAD family member 1 [Source:HGNC Symbol;Acc:HGNC:6767]
Entrez Summary
TBA
Ensembl ID:
ENSG00000170365
External Link:
T141888_1.02
Interpro
IPR001132 ; IPR003619 ; IPR008984 ; IPR013019 ;
Protein Domain:
Protein: ENSP00000305769DBD: MH1 Family DBDsOther: IRF-3, MH2Protein: ENSP00000377652DBD: MH1 Family DBDsOther: IRF-3, MH2Protein: ENSP00000427002DBD: MH1 Family DBDsOther: Protein: ENSP00000425270DBD: MH1 Family DBDsOther: Protein: ENSP00000426568DBD: MH1 Family DBDsOther: IRF-3, MH2Protein: ENSP00000421601DBD: MH1 Family DBDsOther:
Previous Annotations
Source
Annotation
TF-CAT classification
No PMIDS:
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.
a
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:12270938 GO:0003700 sequence-specific DNA binding transcription factor activity IDA - PMID:9389648
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
DNA-Binding
Published Motif Data
Structure
Experimental History
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{"regions": [{"startStyle": "curved", "end": 131, "endStyle": "curved", "aliStart": 31, "text": "MH1", "colour": "#009900", "aliEnd": 131, "start": 30, "href": "http://pfam.xfam.org/family/PF03165.14", "type": "pfama", "display": "true", "metadata": {"end": 131, "description": "The MH1 (MAD homology 1) domain is found at the amino terminus of MAD related proteins such as Smads. This domain is separated from the MH2 domain by a non-conserved linker region. The crystal structure of the MH1 domain shows that a highly conserved 11 residue beta hairpin is used to bind the DNA consensus sequence GNCN in the major groove, shown to be vital for the transcriptional activation of target genes. Not all examples of MH1 can bind to DNA however. Smad2 cannot bind DNA and has a large insertion within the hairpin that presumably abolishes DNA binding. A basic helix (H2) in MH1 with the nuclear localisation signal KKLKK has been shown to be essential for Smad3 nuclear import. Smads also use the MH1 domain to interact with transcription factors such as Jun, TFE3, Sp1, and Runx [1,3].", "database": "PfamA", "aliStart": 31, "scoreName": "E-value", "accession": "PF03165.14", "start": 30, "score": 1.8999999999999998e-42, "identifier": "MH1 domain", "type": "DBD", "aliEnd": 131}}, {"startStyle": "straight", "end": 441, "endStyle": "straight", "aliStart": 269, "text": "MH2", "colour": "#9999ff", "aliEnd": 441, "start": 269, "href": "http://pfam.xfam.org/family/PF03166.12", "type": "pfama", "display": "true", "metadata": {"end": 441, "description": "This is the MH2 (MAD homology 2) domain found at the carboxy terminus of MAD related proteins such as Smads. This domain is separated from the MH1 domain by a non-conserved linker region. The MH2 domain mediates interaction with a wide variety of proteins and provides specificity and selectivity to Smad function and also is critical for mediating interactions in Smad oligomers. Unlike MH1, MH2 does not bind DNA. The well-studied MH2 domain of Smad4 is composed of five alpha helices and three loops enclosing a beta sandwich. Smads are involved in the propagation of TGF-beta signals by direct association with the TGF-beta receptor kinase which phosphorylates the last two Ser of a conserved 'SSXS' motif located at the C-terminus of MH2 [1-3].", "database": "PfamA", "aliStart": 269, "scoreName": "E-value", "accession": "PF03166.12", "start": 269, "score": 2.0999999999999996e-76, "identifier": "MH2 domain", "type": "DBD", "aliEnd": 441}}, {"startStyle": "jagged", "end": 428, "endStyle": "jagged", "aliStart": 320, "text": "IRF-3", "colour": "#9999ff", "aliEnd": 402, "start": 310, "href": "http://pfam.xfam.org/family/PF10401.7", "type": "pfama", "display": "true", "metadata": {"end": 428, "description": "This is the interferon-regulatory factor 3 chain of the hetero-dimeric structure which also contains the shorter chain CREB-binding protein. These two subunits make up the DRAF1 (double-stranded RNA-activated factor 1). Viral dsRNA produced during viral transcription or replication leads to the activation of DRAF1. The DNA-binding specificity of DRAF1 correlates with transcriptional induction of ISG (interferon-alpha,beta-stimulated gene). IRF-3 preexists in the cytoplasm of uninfected cells and translocates to the nucleus following viral infection. Translocation of IRF-3 is accompanied by an increase in serine and threonine phosphorylation, and association with the CREB coactivator occurs only after infection.", "database": "PfamA", "aliStart": 320, "scoreName": "E-value", "accession": "PF10401.7", "start": 310, "score": 0.00014, "identifier": "Interferon-regulatory factor 3", "type": "DBD", "aliEnd": 402}}], "length": 466}