Collection of 108 putative bHLH human TFs out of 112 considered proteins

DBD Alignment (Click to open/enlarge)


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Description
bHLH is the third largest group of TFs with over 100 TFs in human. As the name suggests, the bHLH protein domain is composed of two alpha helices that are connected to each other by a peptide loop. The shorter N-terminal helix inserts into the major groove of the DNA and makes the base-specific contacts, while the loop region adds to the binding by forming contacts with the DNA backbone. The C-terminal helix is used as a protein-protein interaction interface for contacting other bHLH proteins. DNA recognition of these TFs is in all known cases based on homo- or heterodimerization with other members of the same group. bHLH family has many prominent members such as MAX and MYC, which function in the control of the cell cycle, as well as CLOCK, which functions in the control of the circadian rhythm of the cells. 		Structure
Ensembl ID HGNC symbol DBD Family Is TF? TF Assessment Binding Mode Motif Status Notes Comments
AHR bHLH Yes Known motif 1 Monomer or homomultimer In vivo/Misc source Only known motifs are from Transfac or HocoMoco - origin is uncertain
AHRR bHLH Yes Inferred motif 1 Monomer or homomultimer In vivo/Misc source
ARNT bHLH Yes Known motif 1 Monomer or homomultimer 100 perc ID - in vitro
ARNT2 bHLH Yes Known motif 1 Monomer or homomultimer High-throughput in vitro
ARNTL bHLH Yes Known motif 1 Monomer or homomultimer High-throughput in vitro
ARNTL2 bHLH Yes Inferred motif 2 Obligate heteromer High-throughput in vitro ARNTL2 Forms heterodimers with CLOCK and NPAS2 (PMID:10864977 ).
ASCL1 bHLH Yes Known motif 1 Monomer or homomultimer High-throughput in vitro
ASCL2 bHLH Yes Known motif 1 Monomer or homomultimer High-throughput in vitro
ASCL3 bHLH Yes Inferred motif 2 Obligate heteromer High-throughput in vitro ASCL1 heterodimerizes with TCF3; TCF4 and TCF12 (PMID: 24835951).
ASCL4 bHLH Yes Inferred motif 1 Monomer or homomultimer High-throughput in vitro Probably heterodimerizes with TCF3; TCF4 or TCF12 like the other ASCL TFs
ASCL5 bHLH Yes Inferred motif 1 Monomer or homomultimer High-throughput in vitro Probably heterodimerizes with TCF3; TCF4 or TCF12 like the other ASCL TFs
ATOH1 bHLH Yes Known motif 1 Monomer or homomultimer High-throughput in vitro
ATOH7 bHLH Yes Known motif 1 Monomer or homomultimer High-throughput in vitro
ATOH8 bHLH Yes Inferred motif 1 Monomer or homomultimer High-throughput in vitro
BHLHA15 bHLH Yes Known motif 1 Monomer or homomultimer High-throughput in vitro
BHLHA9 bHLH Yes Likely to be sequence specific TF 2 Obligate heteromer No motif Protein heterodimerizes with TCF3; TCF4 and TCF12 (PMID: 25466284).
BHLHE22 bHLH Yes Known motif 1 Monomer or homomultimer High-throughput in vitro
BHLHE23 bHLH Yes Known motif 1 Monomer or homomultimer High-throughput in vitro
BHLHE40 bHLH Yes Known motif 1 Monomer or homomultimer High-throughput in vitro
BHLHE41 bHLH Yes Known motif 1 Monomer or homomultimer High-throughput in vitro
CCDC169-SOHLH2 bHLH Yes Known motif 1 Monomer or homomultimer 100 perc ID - in vitro
CLOCK bHLH Yes Known motif 1 Monomer or homomultimer High-throughput in vitro Can also bind as heterodimer with ARNTL.
EPAS1 bHLH Yes Known motif 1 Monomer or homomultimer In vivo/Misc source Only known motifs are from Transfac or HocoMoco - origin is uncertain
FERD3L bHLH Yes Known motif 1 Monomer or homomultimer High-throughput in vitro
FIGLA bHLH Yes Known motif 1 Monomer or homomultimer High-throughput in vitro
HAND1 bHLH Yes Known motif 2 Obligate heteromer In vivo/Misc source Only known motifs are from Transfac or HocoMoco - origin is uncertain Obligate heteromer (PMID: 10611232).
HAND2 bHLH Yes Known motif 1 Monomer or homomultimer High-throughput in vitro
HELT bHLH Yes Inferred motif 1 Monomer or homomultimer High-throughput in vitro Can form homodimers or heterodimers with HEY2 and HES5, suggesting also that the HELT homodimer is dependent of a additional Orange domain while the HEY2 heterodimer requires just the DBD (PMID: 14764602).
HES1 bHLH Yes Known motif 1 Monomer or homomultimer High-throughput in vitro
HES2 bHLH Yes Known motif 1 Monomer or homomultimer High-throughput in vitro
HES3 bHLH Yes Inferred motif 1 Monomer or homomultimer High-throughput in vitro
HES4 bHLH Yes Inferred motif 1 Monomer or homomultimer High-throughput in vitro
HES5 bHLH Yes Known motif 1 Monomer or homomultimer High-throughput in vitro
HES6 bHLH Yes Known motif 1 Monomer or homomultimer High-throughput in vitro
HES7 bHLH Yes Known motif 1 Monomer or homomultimer High-throughput in vitro Also forms heterodimers.
HEY1 bHLH Yes Known motif 1 Monomer or homomultimer High-throughput in vitro
HEY2 bHLH Yes Known motif 1 Monomer or homomultimer High-throughput in vitro
HEYL bHLH Yes Inferred motif 1 Monomer or homomultimer High-throughput in vitro
HIF1A bHLH Yes Known motif 2 Obligate heteromer In vivo/Misc source Only known motifs are from Transfac or HocoMoco - origin is uncertain Binds as obligate heteromer with ARNT (PMID: 9027737).
HIF3A bHLH Yes Inferred motif 2 Obligate heteromer In vivo/Misc source Binds DNA as a heterodimer with ARNT and ARNT2; reviewed in (PMID: 24099156).
ID1 bHLH No Unlikely to be sequence specific TF 4 Not a DNA binding protein No motif ID bHLH proteins lack the basic region and should not be able to bind DNA. The HT-SELEX motif for ID4 is likely by a co-precipitated protein or it is a contamination
ID2 bHLH No Unlikely to be sequence specific TF 4 Not a DNA binding protein No motif ID bHLH proteins lack the basic region and should not be able to bind DNA. The HT-SELEX motif for ID4 is likely by a co-precipitated protein or it is a contamination
ID3 bHLH No Unlikely to be sequence specific TF 4 Not a DNA binding protein No motif ID bHLH proteins lack the basic region and should not be able to bind DNA. The HT-SELEX motif for ID4 is likely by a co-precipitated protein or it is a contamination
ID4 bHLH No Unlikely to be sequence specific TF 4 Not a DNA binding protein No motif ID bHLH proteins lack the basic region and should not be able to bind DNA. The HT-SELEX motif for ID4 is likely by a co-precipitated protein or it is a contamination
LYL1 bHLH Yes Inferred motif 2 Obligate heteromer In vivo/Misc source TAL1, TAL2 and LYL are very similar and have a basic region with a bulky tryptophan inserting into the cluster of the basic residues. Binds DNA as a heterodimer with TCF3 (PDB:2YPB and PDB:2YPA).
MAX bHLH Yes Known motif 1 Monomer or homomultimer High-throughput in vitro
MESP1 bHLH Yes Known motif 1 Monomer or homomultimer High-throughput in vitro
MESP2 bHLH Yes Known motif 1 Monomer or homomultimer High-throughput in vitro
MITF bHLH Yes Known motif 1 Monomer or homomultimer 100 perc ID - in vitro Binds DNA both as homo- and heterodimers (PMID: 23207919). The structure 4ATI is a homodimer with DNA GTTAGCACATGACCCT.
MLX bHLH Yes Known motif 1 Monomer or homomultimer High-throughput in vitro
MLXIP bHLH Yes Inferred motif 2 Obligate heteromer High-throughput in vitro
MLXIPL bHLH Yes Known motif 1 Monomer or homomultimer High-throughput in vitro
MNT bHLH Yes Known motif 1 Monomer or homomultimer High-throughput in vitro Prefers to heterodimerize with MAX over homodimer formation (PMID: 9000049).
MSC bHLH Yes Known motif 1 Monomer or homomultimer High-throughput in vitro
MSGN1 bHLH Yes Known motif 1 Monomer or homomultimer High-throughput in vitro
MXD1 bHLH Yes Inferred motif 2 Obligate heteromer In vivo/Misc source All three MXD proteins have very similar sequences and should behave accordingly, making heterodimers with at least MAX (PMID:8521822).
MXD3 bHLH Yes Inferred motif 2 Obligate heteromer In vivo/Misc source All three MXD proteins have very similar sequences and should behave accordingly, making heterodimers with at least MAX (PMID:8521822).
MXD4 bHLH Yes Inferred motif 2 Obligate heteromer In vivo/Misc source All three MXD proteins have very similar sequences and should behave accordingly, making heterodimers with at least MAX (PMID:8521822).
MXI1 bHLH Yes Known motif 2 Obligate heteromer In vivo/Misc source Has a putative AT-hook Obligate heteromer (PMID: 8425219).
MYC bHLH Yes Known motif 2 Obligate heteromer In vivo/Misc source Functions as a heterodimer with MAX.
MYCL bHLH Yes Inferred motif 2 Obligate heteromer In vivo/Misc source Similar to MYC and thus likely to functions as a heterodimer with MAX.
MYCN bHLH Yes Known motif 1 Monomer or homomultimer High-throughput in vitro
MYF5 bHLH Yes Known motif 1 Monomer or homomultimer In vivo/Misc source Only known motifs are from Transfac or HocoMoco - origin is uncertain
MYF6 bHLH Yes Known motif 1 Monomer or homomultimer High-throughput in vitro
MYOD1 bHLH Yes Known motif 1 Monomer or homomultimer High-throughput in vitro
MYOG bHLH Yes Known motif 1 Monomer or homomultimer High-throughput in vitro
NCOA1 bHLH Yes Likely to be sequence specific TF 2 Obligate heteromer No motif NCOA1/2/3 all have been tested on PBMs and HT-SELEX without yielding a motif. All are co-activators, collectively suggesting they might be obligate heteromers.
NCOA2 bHLH Yes Likely to be sequence specific TF 2 Obligate heteromer No motif NCOA1/2/3 all have been tested on PBMs and HT-SELEX without yielding a motif. All are co-activators, collectively suggesting they might be obligate heteromers.
NCOA3 bHLH Yes Likely to be sequence specific TF 2 Obligate heteromer No motif NCOA1/2/3 all have been tested on PBMs and HT-SELEX without yielding a motif. All are co-activators, collectively suggesting they might be obligate heteromers.
NEUROD1 bHLH Yes Known motif 1 Monomer or homomultimer High-throughput in vitro
NEUROD2 bHLH Yes Known motif 1 Monomer or homomultimer High-throughput in vitro
NEUROD4 bHLH Yes Inferred motif 1 Monomer or homomultimer High-throughput in vitro
NEUROD6 bHLH Yes Inferred motif 1 Monomer or homomultimer High-throughput in vitro
NEUROG1 bHLH Yes Known motif 1 Monomer or homomultimer High-throughput in vitro
NEUROG2 bHLH Yes Known motif 1 Monomer or homomultimer High-throughput in vitro
NEUROG3 bHLH Yes Inferred motif 1 Monomer or homomultimer High-throughput in vitro
NHLH1 bHLH Yes Known motif 1 Monomer or homomultimer High-throughput in vitro
NHLH2 bHLH Yes Known motif 1 Monomer or homomultimer High-throughput in vitro
NPAS1 bHLH Yes Inferred motif 2 Obligate heteromer In vivo/Misc source Likely obligate heteromer (PMID: 27782878).
NPAS2 bHLH Yes Known motif 1 Monomer or homomultimer High-throughput in vitro
NPAS3 bHLH Yes Inferred motif 2 Obligate heteromer In vivo/Misc source Likely obligate heteromer (PMID: 9374395; PMID: 27782878).
NPAS4 bHLH Yes Inferred motif 2 Obligate heteromer High-throughput in vitro Likely dimerizes with ARNT2 (PMID:24263188).
OLIG1 bHLH Yes Known motif 1 Monomer or homomultimer High-throughput in vitro
OLIG2 bHLH Yes Known motif 1 Monomer or homomultimer High-throughput in vitro OLIG2 can homodimerize and heterodimerize with OLIG1 and NGN2 (PMID:15655114; PMID: 21382552).
OLIG3 bHLH Yes Known motif 1 Monomer or homomultimer High-throughput in vitro
PTF1A bHLH Yes Known motif 1 Monomer or homomultimer High-throughput in vitro
SCX bHLH Yes Inferred motif 1 Monomer or homomultimer High-throughput in vitro SCX heterodimerizes with TCF3 (PMID: 19828133). The Taipale lab has an unpublished HT-SELEX model; both it and the inferred B1H motif seem very weak, supporting the idea that the homodimer does not bind DNA well.
SIM1 bHLH Yes Inferred motif 2 Obligate heteromer In vivo/Misc source Similar to SIM2, which is a likely obligate heteromer.
SIM2 bHLH Yes Inferred motif 2 Obligate heteromer In vivo/Misc source Likely obligate hetereomer (PMID: 7592839)
SOHLH1 bHLH Yes Likely to be sequence specific TF 2 Obligate heteromer No motif Forms SOHLH1-SOHLH2 heterodimers (PMID: 22056784).
SOHLH2 bHLH Yes Known motif 1 Monomer or homomultimer High-throughput in vitro
SREBF1 bHLH Yes Known motif 1 Monomer or homomultimer High-throughput in vitro
SREBF2 bHLH Yes Known motif 1 Monomer or homomultimer High-throughput in vitro
TAL1 bHLH Yes Known motif 2 Obligate heteromer In vivo/Misc source Only known motifs are from Transfac or HocoMoco - origin is uncertain No motif yielded from PBMs or HT-SELEX. Binds DNA as heterodimer with TCF3 (PDB:2YPB and PDB:2YPA).
TAL2 bHLH Yes Inferred motif 2 Obligate heteromer In vivo/Misc source No motif yielded from PBMs or HT-SELEX. Similar to TAL1, which binds DNA as heterodimer with TCF3 (PDB:2YPB and PDB:2YPA).
TCF12 bHLH Yes Known motif 1 Monomer or homomultimer High-throughput in vitro
TCF15 bHLH Yes Inferred motif 1 Monomer or homomultimer High-throughput in vitro
TCF21 bHLH Yes Known motif 1 Monomer or homomultimer High-throughput in vitro
TCF23 bHLH Yes Inferred motif 1 Monomer or homomultimer High-throughput in vitro Basic region is very similar to TCF21, which binds DNA as a homodimer in HT-SELEX.
TCF24 bHLH Yes Inferred motif 1 Monomer or homomultimer High-throughput in vitro
TCF3 bHLH Yes Known motif 1 Monomer or homomultimer High-throughput in vitro
TCF4 bHLH Yes Known motif 1 Monomer or homomultimer High-throughput in vitro
TCFL5 bHLH Yes Known motif 1 Monomer or homomultimer High-throughput in vitro
TFAP4 bHLH Yes Known motif 1 Monomer or homomultimer High-throughput in vitro Also can form heterodimers (PMID: 26550823).
TFE3 bHLH Yes Known motif 1 Monomer or homomultimer High-throughput in vitro
TFEB bHLH Yes Known motif 1 Monomer or homomultimer High-throughput in vitro
TFEC bHLH Yes Known motif 1 Monomer or homomultimer High-throughput in vitro
TWIST1 bHLH Yes Known motif 1 Monomer or homomultimer In vivo/Misc source Only known motifs are from Transfac or HocoMoco - origin is uncertain Can form both homodimers and heterodimers with TCF3 (PMID: 16502419).
TWIST2 bHLH Yes Known motif 1 Monomer or homomultimer 100 perc ID - in vitro
USF1 bHLH Yes Known motif 1 Monomer or homomultimer High-throughput in vitro
USF2 bHLH Yes Known motif 1 Monomer or homomultimer High-throughput in vitro Has a putative AT-hook
USF3 bHLH Yes Likely to be sequence specific TF 1 Monomer or homomultimer No motif