The Human Transcription Factors

Conclusion

Assessment	Binding Mode	Motif Status	Notes	Comments
Known motif	1 Monomer or homomultimer	High-throughput in vitro

Description

Description:	forkhead box O4 [Source:HGNC Symbol;Acc:HGNC:7139]
Entrez Summary	TBA
Ensembl ID:	ENSG00000184481
External Link:
Interpro	IPR001766; ;
Protein Domain:
Protein: ENSP00000363377	DBD: Forkhead	Other: FOXO-TAD, FOXO_KIX_bdg
Protein: ENSP00000342209	DBD: Forkhead	Other: FOXO-TAD, FOXO_KIX_bdg

Previous Annotations

Source	Annotation
TF-CAT classification	TF Gene Candidate_DNA-Binding sequence-specific_DNA Binding Transactivation_ PMIDS:11777915
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:0000981 sequence-specific DNA binding RNA polymerase II transcription factor activity IBA - GO_REF:0000033 GO:0003700 sequence-specific DNA binding transcription factor activity IDA - PMID:10783894
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

Source	Annotation	Motif	Evidence
HT-SELEX	Jolma2013		Direct
HT-SELEX	Jolma2013		Direct
HT-SELEX	Jolma2013		Direct
HT-SELEX	Yin2017		Direct
Methyl-HT-SELEX	Yin2017		Direct
Transfac	Transfac	License required	Direct
Transfac	Transfac	License required	Direct
Misc	HocoMoco		Direct
PBM	DREAM_contest		Inferred - Foxo4 (85% AA Identity, Mus musculus)
PBM	DREAM_contest		Inferred - Foxo1 (81% AA Identity, Mus musculus)
Transfac	Transfac	License required	Inferred - FOXO1 (81% AA Identity, Homo sapiens)
Transfac	Transfac	License required	Inferred - FOXO1 (81% AA Identity, Homo sapiens)
Transfac	Transfac	License required	Inferred - FOXO1 (81% AA Identity, Homo sapiens)
Transfac	Transfac	License required	Inferred - FOXO1 (81% AA Identity, Homo sapiens)
Transfac	Transfac	License required	Inferred - FOXO1 (81% AA Identity, Homo sapiens)
Transfac	Transfac	License required	Inferred - FOXO1 (81% AA Identity, Homo sapiens)
ChIP-seq	JASPAR		Inferred - Foxo1 (81% AA Identity, Mus musculus)
Misc	HocoMoco		Inferred - FOXO1 (81% AA Identity, Homo sapiens)
Misc	HOMER		Inferred - Foxo1 (81% AA Identity, Mus musculus)
PBM	DREAM_contest		Inferred - Foxo6 (78% AA Identity, Mus musculus)
HT-SELEX	Yin2017		Inferred - FOXO3 (75% AA Identity, Homo sapiens)
Methyl-HT-SELEX	Yin2017		Inferred - FOXO3 (75% AA Identity, Homo sapiens)
PBM	DREAM_contest		Inferred - Foxo3 (75% AA Identity, Mus musculus)
Transfac	Transfac	License required	Inferred - FOXO3 (75% AA Identity, Homo sapiens)
Transfac	Transfac	License required	Inferred - FOXO3 (75% AA Identity, Homo sapiens)
Transfac	Transfac	License required	Inferred - FOXO3 (75% AA Identity, Homo sapiens)
Misc	HocoMoco		Inferred - FOXO3 (75% AA Identity, Homo sapiens)

Structure

Structure	PDB	3L2C

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

Name
Email
Comment
Reference

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{"regions": [{"startStyle": "jagged", "end": 133, "endStyle": "curved", "aliStart": 57, "text": "Frkh", "colour": "#228B22", "aliEnd": 129, "start": 50, "href": "http://pfam.xfam.org/family/PF00250.16", "type": "pfama", "display": "true", "metadata": {"end": 133, "description": "The fork head domain is a conserved DNA-binding domain (also known as a \"winged helix\") of about 100 amino-acid residues.", "database": "PfamA", "aliStart": 57, "scoreName": "E-value", "accession": "PF00250.16", "start": 50, "score": 8.7e-21, "identifier": "Forkhead domain", "type": "DBD", "aliEnd": 129}}, {"startStyle": "straight", "end": 449, "endStyle": "straight", "aliStart": 408, "text": "FOXO-TAD", "colour": "#9999ff", "aliEnd": 448, "start": 408, "href": "http://pfam.xfam.org/family/PF16676.3", "type": "pfama", "display": "true", "metadata": {"end": 449, "description": "TAD is a promiscuous binding domain that mediates the association of the transcription factor FOXO with the coactivator CBP/p300. Both this domain and the FOXO-KIX_bd family Pfam:PF16675 bind simultaneously the KIX domain of CBP/p300. Coactivator CBP/p300 is recruited by FOXO3 though binding to these two regions.  The promiscuity of the TAD is further evidenced by that the finding that they also bind the TAZ1 and TAZ2 domains of CBP/p300.", "database": "PfamA", "aliStart": 408, "scoreName": "E-value", "accession": "PF16676.3", "start": 408, "score": 1.9e-17, "identifier": "Transactivation domain of FOXO protein family", "type": "DBD", "aliEnd": 448}}, {"startStyle": "jagged", "end": 351, "endStyle": "jagged", "aliStart": 304, "text": "FOXO_KIX_bdg", "colour": "#9999ff", "aliEnd": 340, "start": 298, "href": "http://pfam.xfam.org/family/PF16675.3", "type": "pfama", "display": "true", "metadata": {"end": 351, "description": "FOXO_KIX_bd is the first part of the region of transcription factor forkhead box O family proteins that binds to the CREB-binding proteins via the KIX domain. Coactivator CBP/p300 is recruited by FOXO3 via the binding of this domain as well as the simultaneous binding of the more C-terminal TAD domain.", "database": "PfamA", "aliStart": 304, "scoreName": "E-value", "accession": "PF16675.3", "start": 298, "score": 1.6e-06, "identifier": "KIX-binding domain of forkhead box O, CR2", "type": "DBD", "aliEnd": 340}}], "length": 451}

TF Info Page for FOXO4 (Forkhead)