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Protein structural motif From Wikipedia, the free encyclopedia
A basic helix–loop–helix (bHLH) is a protein structural motif that characterizes one of the largest families of dimerizing transcription factors.[2][3][4][5] The word "basic" does not refer to complexity but to the chemistry of the motif because transcription factors in general contain basic amino acid residues in order to facilitate DNA binding.[6]
Basic helix–loop–helix DNA-binding domain | |||||||||||
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Identifiers | |||||||||||
Symbol | bHLH | ||||||||||
Pfam | PF00010 | ||||||||||
InterPro | IPR001092 | ||||||||||
SMART | SM00353 | ||||||||||
PROSITE | PDOC00038 | ||||||||||
SCOP2 | 1mdy / SCOPe / SUPFAM | ||||||||||
CDD | cd00083 | ||||||||||
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bHLH transcription factors are often important in development or cell activity. For one, BMAL1-Clock (also called ARNTL) is a core transcription complex in the molecular circadian clock. Other genes, like c-Myc and HIF-1, have been linked to cancer due to their effects on cell growth and metabolism.
The motif is characterized by two α-helices connected by a loop. In general, transcription factors (including this type) are dimeric, each with one helix containing basic amino acid residues that facilitate DNA binding.[6] In general, one helix is smaller, and due to the flexibility of this loop, allows dimerization by folding and packing against another helix. The larger helix typically contains the DNA-binding regions. bHLH proteins typically bind to a consensus sequence called an E-box, CANNTG.[7] The canonical E-box is CACGTG (palindromic), however some bHLH transcription factors, notably those of the bHLH-PAS family, bind to related non-palindromic sequences, which are similar to the E-box. bHLH TFs may homodimerize or heterodimerize with other bHLH TFs and form a large variety of dimers, each one with specific functions.[8]
A phylogenetic analysis suggested that bHLH proteins fall into 6 major groups, indicated by letters A through F. [9] Examples of transcription factors containing a bHLH include:
These proteins contain two additional PAS domains after the bHLH domain.
These proteins contain an additional COE domain
Since many bHLH transcription factors are heterodimeric,[8] their activity is often highly regulated by the dimerization of the subunits. One subunit's expression or availability is often controlled, whereas the other subunit is constitutively expressed. Many of the known regulatory proteins, such as the Drosophila extramacrochaetae protein, have the helix-loop-helix structure but lack the basic region, making them unable to bind to DNA on their own. They are, however, able to form heterodimers with proteins that have the bHLH structure, and inactivate their abilities as transcription factors.[10]
AHR; AHRR; ARNT; ARNT2; ARNTL; ARNTL2; ASCL1; ASCL2; ASCL3; ASCL4; ATOH1; ATOH7; ATOH8; BHLHB2; BHLHB3; BHLHB4; BHLHB5; BHLHB8; CLOCK; EPAS1; FERD3L; FIGLA; HAND1; HAND2; HES1; HES2; HES3; HES4; HES5; HES6; HES7; HEY1; HEY2; HIF1A; ID1; ID2; ID3; ID4; KIAA2018; LYL1; MASH1; MATH2; MAX; MESP1; MESP2; MIST1; MITF; MLX; MLXIP; MLXIPL; MNT; MSC; MSGN1; MXD1; MXD3; MXD4; MXI1; MYC; MYCL1; MYCL2; MYCN; MYF5; MYF6; MYOD1; MYOG; NCOA1; NCOA3; NEUROD1; NEUROD2; NEUROD4; NEUROD6; NEUROG1; NEUROG2; NEUROG3; NHLH1; NHLH2; NPAS1; NPAS2; NPAS3; NPAS4; OAF1; OLIG1; OLIG2; OLIG3; PTF1A; SCL; SCXB; SIM1; SIM2; SOHLH1; SOHLH2; SREBF1; SREBF2; TAL1; TAL2; TCF12; TCF15; TCF21; TCF3; TCF4; TCFL5; TFAP4; TFE3; TFEB; TFEC; TWIST1; TWIST2; USF1; USF2.
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