The Human Transcription Factors

Conclusion

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

Description

Description:	nescient helix-loop-helix 2 [Source:HGNC Symbol;Acc:HGNC:7818]
Entrez Summary	TBA
Ensembl ID:	ENSG00000177551
External Link:	T014244_1.02
Interpro	IPR011598; ;
Protein Domain:
Protein: ENSP00000322087	DBD: bHLH	Other:
Protein: ENSP00000405062	DBD: bHLH	Other:
Protein: ENSP00000358519	DBD: bHLH	Other:

Previous Annotations

Source	Annotation
TF-CAT classification	TF Gene_DNA-Binding sequence-specific_DNA Binding_ PMIDS:15470499
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:0000981 sequence-specific DNA binding RNA polymerase II transcription factor activity IBA - GO_REF:0000033 GO:0051091 positive regulation of sequence-specific DNA binding transcription factor activity TAS - PMID:16314316
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	Yin2017		Direct
Methyl-HT-SELEX	Yin2017		Direct
PBM	DREAM_contest		Inferred - Nhlh2 (100% AA Identity, Mus musculus)
Transfac	Transfac	License required	Inferred - Nhlh2 (100% AA Identity, Mus musculus)
HT-SELEX	Yin2017		Inferred - NHLH1 (98% AA Identity, Homo sapiens)
HT-SELEX	Yin2017		Inferred - NHLH1 (98% AA Identity, Homo sapiens)
Methyl-HT-SELEX	Yin2017		Inferred - NHLH1 (98% AA Identity, Homo sapiens)
Methyl-HT-SELEX	Yin2017		Inferred - NHLH1 (98% AA Identity, Homo sapiens)
SELEX	JASPAR		Inferred - NHLH1 (98% AA Identity, Homo sapiens)
Transfac	Transfac	License required	Inferred - NHLH1 (98% AA Identity, Homo sapiens)
Transfac	Transfac	License required	Inferred - NHLH1 (98% AA Identity, Homo sapiens)
Misc	HocoMoco		Inferred - NHLH1 (98% AA Identity, Homo sapiens)
HT-SELEX	Nitta2015		Inferred - HLH4C (90% AA Identity, Drosophila melanogaster)
HT-SELEX	Nitta2015		Inferred - HLH4C (90% AA Identity, Drosophila melanogaster)
HT-SELEX	Nitta2015		Inferred - HLH4C (90% AA Identity, Drosophila melanogaster)
Transfac	Transfac	License required	Inferred - TAL1 (62% AA Identity, Homo sapiens)
Transfac	Transfac	License required	Inferred - TAL1 (62% AA Identity, Homo sapiens)
Transfac	Transfac	License required	Inferred - TAL1 (62% AA Identity, Homo sapiens)
Misc	HocoMoco		Inferred - TAL1 (62% AA Identity, Homo sapiens)
Misc	HocoMoco		Inferred - TAL1 (62% AA Identity, Homo sapiens)
Misc	HOMER		Inferred - Tal1 (62% AA Identity, Mus musculus)
Misc	HOMER		Inferred - Tal1 (62% AA Identity, Mus musculus)
HT-SELEX	Yin2017		Inferred - HAND2 (50% AA Identity, Homo sapiens)
Methyl-HT-SELEX	Yin2017		Inferred - HAND2 (50% AA Identity, Homo sapiens)
Misc	HocoMoco		Inferred - HAND1 (50% AA Identity, Homo sapiens)

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": 130, "endStyle": "curved", "aliStart": 79, "text": "HLH", "colour": "#2cb42c", "aliEnd": 129, "start": 78, "href": "http://pfam.xfam.org/family/PF00010.24", "type": "pfama", "display": "true", "metadata": {"end": 130, "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": 79, "scoreName": "E-value", "accession": "PF00010.24", "start": 78, "score": 5.4000000000000005e-18, "identifier": "Helix-loop-helix DNA-binding domain", "type": "DBD", "aliEnd": 129}}], "length": 136}

{"regions": [{"startStyle": "curved", "end": 107, "endStyle": "jagged", "aliStart": 79, "text": "HLH", "colour": "#2cb42c", "aliEnd": 107, "start": 78, "href": "http://pfam.xfam.org/family/PF00010.24", "type": "pfama", "display": "true", "metadata": {"end": 107, "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": 79, "scoreName": "E-value", "accession": "PF00010.24", "start": 78, "score": 3.7000000000000006e-06, "identifier": "Helix-loop-helix DNA-binding domain", "type": "DBD", "aliEnd": 107}}], "length": 107}

TF Info Page for NHLH2 (bHLH)