The Human Transcription Factors

Conclusion

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

Description

Description:

hes family bHLH transcription factor 5 [Source:HGNC Symbol;Acc:HGNC:19764]

Entrez Summary

This gene encodes a member of a family of basic helix-loop-helix transcriptional repressors. The protein product of this gene, which is activated downstream of the Notch pathway, regulates cell differentiation in multiple tissues. Disruptions in the normal expression of this gene have been associated with developmental diseases and cancer. [provided by RefSeq, Dec 2008]

Ensembl ID:

ENSG00000197921

External Link:

CisBP

Interpro

IPR003650; IPR011598;

Protein Domain:

ENSP00000367714

Domain:

Protein: ENSP00000367714	DBD: bHLH	Other: Hairy_orange

Previous Annotations

Source	Annotation
TF-CAT classification	TF Gene_DNA-Binding sequence-specific_TF PPI_ PMIDS:15156153
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.	b
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:0001078 RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor a ISS - GO_REF:0000024
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	Yin2017		Direct
Methyl-HT-SELEX	Yin2017		Direct
Methyl-HT-SELEX	Yin2017		Direct
HT-SELEX	Yin2017		Inferred - HES5 (100% AA Identity, Homo sapiens)
Methyl-HT-SELEX	Yin2017		Inferred - HES5 (100% AA Identity, Homo sapiens)
Methyl-HT-SELEX	Yin2017		Inferred - HES5 (100% AA Identity, Homo sapiens)
PBM	Zoo_01		Inferred - Hes5 (100% AA Identity, Mus musculus)
HT-SELEX	Yin2017		Inferred - HES7 (51% AA Identity, Homo sapiens)
Methyl-HT-SELEX	Yin2017		Inferred - HES7 (51% AA Identity, Homo sapiens)
PBM	Zoo_01		Inferred - Hes7 (51% AA Identity, Mus musculus)
Transfac	Transfac	License required	Inferred - Hes7 (51% AA Identity, Mus musculus)

Structure

Structure	PDB	Not_Covered

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

{"regions": [{"startStyle": "curved", "end": 73, "endStyle": "curved", "aliStart": 18, "text": "HLH", "colour": "#2cb42c", "aliEnd": 71, "start": 17, "href": "http://pfam.xfam.org/family/PF00010.24", "type": "pfama", "display": "true", "metadata": {"end": 73, "description": "A number of eukaryotic proteins, which probably are sequence specific DNA-binding proteins that act as transcription factors, share a conserved domain of 40 to 50 amino acid residues. It has been proposed [PUBMED:2493990] that this domain is formed of two amphipathic helices joined by a variable length linker region that could form a loop. This 'helix-loop-helix' (HLH) domain mediates protein dimerization and has been found in the proteins listed below [PUBMED:1521738]. Most of these proteins have an extra basic region of about 15 amino acid residues that is adjacent to the HLH domain and specifically binds to DNA. They are refered as basic helix-loop-helix proteins (bHLH), and are classified in two groups: class A (ubiquitous) and class B (tissue-specific). Members of the bHLH family bind variations on the core sequence 'CANNTG', also refered to as the E-box motif. The homo- or heterodimerization mediated by the HLH domain is independent of, but necessary for DNA binding, as two basic regions are required for DNA binding activity. The HLH proteins lacking the basic domain (Emc, Id) function as negative regulators, since they form heterodimers, but fail to bind DNA. The hairy-related proteins (hairy, E(spl), deadpan) also repress transcription although they can bind DNA. The proteins of this subfamily act together with co-repressor proteins, like groucho, through their C-terminal motif WRPW.", "database": "PfamA", "aliStart": 18, "scoreName": "E-value", "accession": "PF00010.24", "start": 17, "score": 2.4e-15, "identifier": "Helix-loop-helix DNA-binding domain", "type": "DBD", "aliEnd": 71}}, {"startStyle": "straight", "end": 122, "endStyle": "straight", "aliStart": 87, "text": "Hairy_orange", "colour": "#9999ff", "aliEnd": 121, "start": 87, "href": "http://pfam.xfam.org/family/PF07527.11", "type": "pfama", "display": "true", "metadata": {"end": 122, "description": "The Orange domain is found in the Drosophila proteins Hesr-1, Hairy, and Enhancer of Split [1,2].  The Orange domain is proposed to mediate specific protein-protein interaction between Hairy and Scute[2].", "database": "PfamA", "aliStart": 87, "scoreName": "E-value", "accession": "PF07527.11", "start": 87, "score": 1.4e-08, "identifier": "Hairy Orange", "type": "DBD", "aliEnd": 121}}], "length": 167}

TF Info Page for HES5 (bHLH)