basic Helix Loop Helix (bHLH) domain superfamily; bHLH proteins are transcriptional regulators that are found in organisms from yeast to humans. Members of the bHLH superfamily have two highly conserved and functionally distinct regions. The basic part is at the amino end of the bHLH that may bind DNA to a consensus hexanucleotide sequence known as the E box (CANNTG). Different families of bHLH proteins recognize different E-box consensus sequences. At the carboxyl-terminal end of the region is the HLH region that interacts with other proteins to form homo- and heterodimers. bHLH proteins function as a diverse set of regulatory factors because they recognize different DNA sequences and dimerize with different proteins. The bHLH proteins can be divided to cell-type specific and widely expressed proteins. The cell-type specific members of bHLH superfamily are involved in cell-fate determination and act in neurogenesis, cardiogenesis, myogenesis, and hematopoiesis.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*.
gi 568996658   1 MQSINAGFQSLKTLIPHTDGEKLSKAAILQQTAEYIFSLEQEKTRL 46
Cdd:cd11419   16 MQSINAGFQSLRTLLPHCDGEKLSKAAILQQTAEYIFSLEQEKTRL 61

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in transcription factor AP-4 (TFAP4) and similar proteins; TFAP4, also termed activating enhancer-binding protein 4, or Class C basic helix-loop-helix protein 41 (bHLHc41), is a bHLHzip transcription factor that activates both viral and cellular genes involved in the regulation of cellular proliferation, stemness, and epithelial-mesenchymal transition by binding to the symmetrical DNA sequence 5'-CAGCTG-3'.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*.
gi 568996658   1 MQSINAGFQSLKTLIPHTDGEKLSKAAILQQTAEYIFSLEQEKTRL 46
Cdd:cd11419   16 MQSINAGFQSLRTLLPHCDGEKLSKAAILQQTAEYIFSLEQEKTRL 61

Helix-loop-helix DNA-binding domain;

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|.
gi 568996658    1 MQSINAGFQSLKTLIP-HTDGEKLSKAAILQQTAEYIFSLE 40
Cdd:pfam00010  13 RDRINDAFDELRELLPtLPPDKKLSKAEILRLAIEYIKHLQ 53

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in transcription factor AP-4 (TFAP4) and similar proteins; TFAP4, also termed activating enhancer-binding protein 4, or Class C basic helix-loop-helix protein 41 (bHLHc41), is a bHLHzip transcription factor that activates both viral and cellular genes involved in the regulation of cellular proliferation, stemness, and epithelial-mesenchymal transition by binding to the symmetrical DNA sequence 5'-CAGCTG-3'.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*.
gi 568996658   1 MQSINAGFQSLKTLIPHTDGEKLSKAAILQQTAEYIFSLEQEKTRL 46
Cdd:cd11419   16 MQSINAGFQSLRTLLPHCDGEKLSKAAILQQTAEYIFSLEQEKTRL 61

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in MLX-interacting protein (MLXIP), MLX-interacting protein-like (MLXIPL) and similar proteins; The family includes MLXIP and MLXIPL. MLXIP, also termed Class E basic helix-loop-helix protein 36 (bHLHe36), or transcriptional activator MondoA, is a bHLHZip transcriptional activator that binds DNA as a heterodimer with Mlx. It binds to the canonical E box sequence 5'-CACGTG-3' and plays a role in transcriptional activation of glycolytic target genes. MLXIP is most highly expressed in skeletal muscle and functions as an indirect glucose sensor, by sensing glucose 6-phosphate and shuttling between the nucleus and the cytoplasm. MLXIPL, also termed carbohydrate-responsive element-binding protein (ChREBP), or Class D basic helix-loop-helix protein 14 (bHLHd14), or MLX interactor, or WS basic-helix-loop-helix leucine zipper protein (WS-bHLH), or Williams-Beuren syndrome chromosomal region 14 protein (WBSCR14), is a bHLHZip transcriptional factor integral to the regulation of glycolysis and lipogenesis in the liver. It forms heterodimers with the bHLHZip protein Mlx to bind the DNA sequence 5'-CACGTG-3'.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 568996658   3 SINAGFQSLKTLIP---HTDGEKLSKAAILQQTAEYIFSLEQEKTRLLQQNTQLKRFI 57
Cdd:cd11405   17 NIKSGFDTLQSLIPslgQNPNQKVSKAAMLQKAAEYIKSLKRERQQMQEEAEQLRQEI 74

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in sterol regulatory element-binding protein (SREBP) family; The SREBP family includes SREBP1 and SREBP2, which are bHLHzip transcriptional activator of genes encoding proteins essential for cholesterol biosynthesis/uptake and fatty acid biosynthesis. SREBP1 and SREBP2 are principally found in the liver and in adipocytes and made up of an N-terminal transcription factor portion (composed of an activation domain, a bHLHzip domain, and a nuclear localization signal), a hydrophobic region containing two membrane spanning regions, and a C-terminal regulatory segment. They recognize a symmetric sterol regulatory element (TCACNCCAC) instead of E-box.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 568996658   3 SINAGFQSLKTLIPHTDGeKLSKAAILQQTAEYIFSLEQEKTRLLQQNTQLKR 55
Cdd:cd11394   20 SINDRIIELKDLVVGPDA-KMNKSAVLRKAIDYIRYLQKVNQKLKQENMALKK 71

basic Helix Loop Helix (bHLH) domain superfamily; bHLH proteins are transcriptional regulators that are found in organisms from yeast to humans. Members of the bHLH superfamily have two highly conserved and functionally distinct regions. The basic part is at the amino end of the bHLH that may bind DNA to a consensus hexanucleotide sequence known as the E box (CANNTG). Different families of bHLH proteins recognize different E-box consensus sequences. At the carboxyl-terminal end of the region is the HLH region that interacts with other proteins to form homo- and heterodimers. bHLH proteins function as a diverse set of regulatory factors because they recognize different DNA sequences and dimerize with different proteins. The bHLH proteins can be divided to cell-type specific and widely expressed proteins. The cell-type specific members of bHLH superfamily are involved in cell-fate determination and act in neurogenesis, cardiogenesis, myogenesis, and hematopoiesis.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|..
gi 568996658   1 MQSINAGFQSLKTLIP-HTDGEKLSKAAILQQTAEYIFSLEQ 41
Cdd:cd00083    5 RDKINDAFEELKRLLPeLPDSKKLSKASILQKAVEYIRELQS 46

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in sterol regulatory element-binding protein 1 (SREBP1) and similar proteins; SREBP1, also termed Class D basic helix-loop-helix protein 1 (bHLHd1), or sterol regulatory element-binding transcription factor 1 (SREBF1), is a member of a family of bHLHzip transcription factors that recognize sterol regulatory element 1 (SRE-1). It acts as a transcriptional activator required for lipid homeostasis. It may control transcription of the low-density lipoprotein receptor gene as well as the fatty acid. SREBP1 has dual sequence specificity binding to both an E-box motif (5'-ATCACGTGA-3') and to SRE-1 (5'-ATCACCCCAC-3').

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 568996658   3 SINAGFQSLKTLIPHTDGeKLSKAAILQQTAEYIFSLEQEKTRLLQQNTQLKRFIQE 59
Cdd:cd18921   20 SINDKIIELKDLVVGTEA-KLNKSAVLRKAIDYIRFLQQSNQKLKQENMALKMAVQK 75

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in protein Max and similar proteins; Max, also termed Class D basic helix-loop-helix protein 4 (bHLHd4), or Myc-associated factor X, is a bHLHZip transcription regulator that forms a sequence-specific DNA-binding protein complex with MYC or MAD which recognizes the core sequence 5'-CAC[GA]TG-3'. The MYC:MAX complex is a transcriptional activator, whereas the MAD:MAX complex is a transcriptional repressor. Max homodimer bind DNA but is transcriptionally inactive. Targeted deletion of max results in early embryonic lethality in mice.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 568996658   3 SINAGFQSLKTLIPHTDGEKLSKAAILQQTAEYIFSLEQEKTRLLQQNTQLKR 55
Cdd:cd11406   15 HIKDSFHSLRDSVPSLQGEKASRAQILKKATEYIQYMRRKNHTHQQDIDDLKR 67

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in MLX-interacting protein-like (MLXIPL) and similar proteins; MLXIPL, also termed carbohydrate-responsive element-binding protein (ChREBP), or Class D basic helix-loop-helix protein 14 (bHLHd14), or MLX interactor, or WS basic-helix-loop-helix leucine zipper protein (WS-bHLH), or Williams-Beuren syndrome chromosomal region 14 protein (WBSCR14), is a bHLHZip transcriptional factor integral to the regulation of glycolysis and lipogenesis in the liver. It forms heterodimers with the bHLHZip protein Mlx to bind the DNA sequence 5'-CACGTG-3'.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 568996658   3 SINAGFQSLKTLIPHTDGE---KLSKAAILQQTAEYIFSLEQEKTRLLQQNTQLK 54
Cdd:cd19689   19 NIKLGFDTLHSLVTTLSSQpsiKISKATTLQKTAEYISKLQQERAQLQEEAQRLR 73

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in sterol regulatory element-binding protein (SREBP) family and similar proteins; The SREBP family includes SREBP1 and SREBP2, which are bHLHzip transcriptional activator of genes encoding proteins essential for cholesterol biosynthesis/uptake and fatty acid biosynthesis. SREBP1 and SREBP2 are principally found in the liver and in adipocytes and made up of an N-terminal transcription factor portion (composed of an activation domain, a bHLHzip domain, and a nuclear localization signal), a hydrophobic region containing two membrane spanning regions, and a C-terminal regulatory segment. They recognize a symmetric sterol regulatory element (TCACNCCAC) instead of E-box. The family also includes Saccharomyces cerevisiae transcription factor HMS1 (also termed high-copy MEP suppressor protein 1) and serine-rich protein TYE7. HMS1 is a putative bHLHzip transcription factor involved in exit from mitosis and pseudohyphal differentiation. TYE7, also termed basic-helix-loop-helix protein SGC1, is a putative bHLHzip transcription activator required for Ty1-mediated glycolytic gene expression. TYE7 N-terminal is extremely rich in serine residues. It binds DNA on E-box motifs, 5'-CANNTG-3'. TYE7 is not essential for growth.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 568996658   2 QSINAGFQSLKTLIP----------------HTDGEKLSKAAILQQTAEYIFSLEQEKTRLLQQNTQLKRFI 57
Cdd:cd11395   16 SNLNTKIERLRDAIPslrspegksddgglggLAPTTKLSKATILTKAIEYIRHLEQENERLEEENEELRQQV 87

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in the Myc family; The Myc family is a member of the bHLHzip family of transcription factors that play important roles in the control of normal cell proliferation, growth, survival and differentiation. All Myc isoforms contain two independently functioning polypeptide chain regions: N-terminal transactivating residues and a C-terminal bHLHzip segment. The bHLHzip family of bHLH transcription factors are characterized by a highly conserved N-terminal basic region that may bind DNA at a consensus hexanucleotide sequence known as the E-box (CANNTG) followed by HLH and leucine zipper motifs that may interact with other proteins to form homo- and heterodimers. Myc heterodimerizes with Max enabling specific binding to E-box DNA sequences in the promoters of target genes. The Myc proto-oncoprotein family includes at least five different functional members: c-, N-, L-, S- and B-Myc (which is lacking the bHLH domain).

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 568996658   8 FQSLKTLIPHT-DGEKLSKAAILQQTAEYIFSLEQEKTRLLQQNTQLKRFIQELS 61
Cdd:cd11400   20 FEKLRDLVPELaDNEKASKVVILKKATEYIKQLQQEEKKLEKEKDKLKARNEQLR 74

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in MLX-interacting protein (MLXIP) and similar proteins; MLXIP, also termed Class E basic helix-loop-helix protein 36 (bHLHe36), or transcriptional activator MondoA, is a bHLHZip transcriptional activator that binds DNA as a heterodimer with Mlx. It binds to the canonical E box sequence 5'-CACGTG-3' and plays a role in transcriptional activation of glycolytic target genes. MLXIP is most highly expressed in skeletal muscle and functions as an indirect glucose sensor, by sensing glucose 6-phosphate and shuttling between the nucleus and the cytoplasm.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 568996658   3 SINAGFQSLKTLIPHTDGEK-LSKAAILQQTAEYIFSLEQEKTRLLQQNTQLKRFI 57
Cdd:cd19688   17 NIKICFDTLNSLVSTLKNSKpISNAITLQKTVEYIAKLQQERTQMQEETKRLREEI 72

basic helix-loop-helix (bHLH) domain found in Drosophila melanogaster protein taxi and similar proteins; Protein taxi, also termed protein delilah (Dei), is a bHLH transcription factor that is involved in regulation of cell adhesion and attachment that is expressed in specialized cells that provide anchoring sites to either muscles (tendon cells), or proprioceptors (chordotonal attachment cells) during embryonic development. It probably plays an important role in the differentiation of epidermal cells into the tendon cells that form the attachment sites for all muscles.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*
gi 568996658   1 MQSINAGFQSLKTLIP----HTDGEKLSKAAILQQTAEYIFSLEQ 41
Cdd:cd11431   13 MREINDAFEALRRAVPeypvAGKDGKLTKITTLRLAMNYIKALTD 57