Helix-loop-helix DNA-binding domain;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 281359791  249 REVHNKLEKERRAQLKECYDLLKKVLPmGDEDRKKTSNLTILDTAHKYVNSL 300
Cdd:pfam00010   2 REAHNERERRRRDRINDAFDELRELLP-TLPPDKKLSKAEILRLAIEYIKHL 52

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        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281359791 249 REVHNKLEKERRAQLKECYDLLKKVLPmGDEDRKKTSNLTILDTAHKYVNSLSHEVCEQEAKIEKLAKQKIELQKRLKQL 328
Cdd:cd11400    2 RRLHNVLERQRRNDLKNSFEKLRDLVP-ELADNEKASKVVILKKATEYIKQLQQEEKKLEKEKDKLKARNEQLRKKLERL 80

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in MAX gene-associated protein (MGA) family; The MGA family includes MGA, Schizosaccharomyces pombe ESC1 (spESC1) and similar proteins. MGA, also termed MAX dimerization protein 5 (MAD5), is a dual specificity T-box/ bHLHzip transcription factor that regulates the expression of both Max-network and T-box family target genes. It contains a Myc-like bHLHZip motif and requires heterodimerization with Max for binding to the preferred Myc-Max-binding site CACGTG. In addition to the bHLHZip domain, MGA harbors a second DNA-binding domain, the T-box or T-domain. It thus binds the preferred Brachyury-binding sequence and represses transcription of reporter genes containing promoter-proximal Brachyury-binding sites. spESC1 is a bHLHzip protein with homology to human MyoD and Myf-5 myogenic differentiation inducers. It is involved in the sexual differentiation process.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 281359791 249 REVHNKLEKERRAQLKECYDLLKKVLPMGDEDrkKTSNLTILDTAHKYVNSLshevceqEAKIEKLAKQKIELQ 322
Cdd:cd19682    1 RLRHKKRERERRSELRELFDKLKQLLGLDSDE--KASKLAVLTEAIEEIQQL-------KREEDELQKEKARLT 65

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in Max-interacting protein 1 (MXI1) and similar proteins; MXI1, also termed Max interactor 1, or Class C basic helix-loop-helix protein 11 (bHLHc11), is a bHLHZip transcriptional repressor that binds with MAX to form a sequence-specific DNA-binding protein complex which recognizes the core sequence 5'-CAC[GA]TG-3'. It thus antagonizes MYC transcriptional activity by competing for MAX. It plays an important role in the regulation of cell proliferation.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281359791 249 REVHNKLEKERRAQLKECYDLLKKVLPMGDEDRKKTSnLTILDTAHKYVNSLSHEVCEQEAKIEKLAKQKIELQKRLKQL 328
Cdd:cd18930    2 RSTHNELEKNRRAHLRLCLERLKVLIPLGPDCTRHTT-LGLLNKAKAHIKKLEEADRKSQHQLENLEREQRFLKRRLEQL 80

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in Max-associated protein 3 (Mad3) and similar proteins; Mad3, also termed Max dimerization protein 3, or Max dimerizer 3 (MXD3), or Class C basic helix-loop-helix protein 13 (bHLHc13), or Max-interacting transcriptional repressor MAD3, or Myx, is a bHLHZip Max-interacting transcriptional repressor that plays an important role in cellular proliferation. It suppresses c-myc dependent transformation and is expressed during neural and epidermal differentiation.

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281359791 249 REVHNKLEKERRAQLKECYDLLKKVLPMGDEDRKKTSnLTILDTAHKYVNSLshevCEQEAKI----EKLAKQKIELQKR 324
Cdd:cd18932    7 RSVHNELEKHRRAQLRRCLEQLKQQVPLGADCSRYTT-LSLLRRARLHIQKL----EEQEQRAqqlkERLRWEQQKLRRR 81

                 ....
gi 281359791 325 LKQL 328
Cdd:cd18932   82 LESL 85

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in Max-associated protein 4 (Mad4) and similar proteins; Mad4, also termed Max dimerization protein 4, or Max dimerizer 4 (MXD4), or Class C basic helix-loop-helix protein 12 (bHLHc12), or Max-interacting transcriptional repressor MAD4, is a bHLHZip Max-interacting transcriptional repressor that suppresses c-myc dependent transformation and is expressed during neural and epidermal differentiation. It is regulated by a transcriptional repressor complex that contains Miz-1 and c-Myc.

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281359791 249 REVHNKLEKERRAQLKECYDLLKKVLPMGDEDRKKTSnLTILDTAHKYVNSLShevcEQEAKI----EKLAKQKIELQKR 324
Cdd:cd18929    3 RSSHNELEKHRRAKLRLYLEQLKQLVPLGPDSTRHTT-LSLLKRAKMHIKKLE----EQDRKAlnikEQLQREHRYLKRR 77

                 ....*..
gi 281359791 325 LKQLSLR 331
Cdd:cd18929   78 LEQLSVQ 84

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        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 281359791 252 HNKLEKERRAQLKECYDLLKKVLP-MGDEDRKKTSNLTILDTAHKYVNSLSHEVCEQEAKIEKLaKQKI 319
Cdd:cd11405    7 HISAEQKRRFNIKSGFDTLQSLIPsLGQNPNQKVSKAAMLQKAAEYIKSLKRERQQMQEEAEQL-RQEI 74

basic helix-loop-helix (bHLH) domain found in Arabidopsis thaliana OBP3-responsive gene 2 (ORG2), 3 (ORG3) and similar proteins; The family includes ORG2 (also termed AtbHLH38, or EN 8) and ORG3 (also termed AtbHLH39, or EN 9), both of which act as bHLH transcription factors.

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 281359791 249 REVHNKLEKERRAQLKECYDLLKKVLPMGDEDRKKTSNLTIlDTAHKYVNslshevcEQEAKIEKLAKQKIELQKRL 325
Cdd:cd18914    2 KLLHNDVERQRRQEMASLFSSLRSLLPLQYIKGKLSVSDHV-DEAVNYIK-------ELQEKIKELSEKRDELLKLI 70

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.

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 281359791 249 REVHNKLEKERRAQLKECYDLLKKVLPMGDEDrkKTSNLTILDTAHKYVNSLSHEVCEQEAKIEKLAKQ 317
Cdd:cd11406    2 RAHHNALERKRRDHIKDSFHSLRDSVPSLQGE--KASRAQILKKATEYIQYMRRKNHTHQQDIDDLKRQ 68

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in L-Myc and similar proteins; L-Myc, also termed Class E basic helix-loop-helix protein 38 (bHLHe38), or protein L-Myc-1, or V-myc myelocytomatosis viral oncogene homolog, is a bHLHZip oncoprotein belonging to the Myc oncogene protein family. It binds DNA as a heterodimer with MAX. L-Myc is co-expressed with another Myc family member and has weaker transformation/transactivation activities. L-Myc knockout mouse did not exhibit any phenotypic abnormalities.

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281359791 248 TREVHNKLEKERRAQLKECYDLLKKVLPmGDEDRKKTSNLTILDTAHKYVNSLSHEVCEQEAKIEKLAKQKIELQKRLKQ 327
Cdd:cd11457    7 KRKNHNFLERKRRNDLRSRFLALRDEVP-GLASCSKTPKVVILSKATEYLRGLVSAERRMAAEKRQLKSRQQQLLRRIAQ 85

                 ..
gi 281359791 328 LS 329
Cdd:cd11457   86 LK 87

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in Schizosaccharomyces pombe ESC1 (spESC1) and similar proteins; spESC1 is a bHLHzip protein with homology to human MyoD and Myf-5 myogenic differentiation inducers. It is involved in the sexual differentiation process.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 281359791 249 REVHNKLEKERRAQLKECYDLLKKVLPmgDEDRKKTSNLTILDTAHKYVNSLSHEVCEQEAKIEKL 314
Cdd:cd19690    1 RVSHKLAERKRRKEMKELFEDLRDALP--QERGTKASKWEILTKAISYIQQLKRHIRELRSEVNDL 64

basic helix-loop-helix (bHLH) domain found in Saccharomyces cerevisiae protein INO2 and similar proteins; INO2 is a positive regulatory factor required for depression of the co-regulated phospholipid biosynthetic enzymes in Saccharomyces cerevisiae. It is also involved in the expression of ITR1.

                         10        20        30        40        50        60        70
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gi 281359791 249 REVHNKLEKERRAQLKECYDLLKKVLPM-GDEDRKKTSNLTILdtahkyvnslsHEVCEQeakIEKLAKQKIELQKRLK 326
Cdd:cd11388    4 KWKHVEAEKKRRNQIKKGFEDLINLINYpRNNNEKRISKSELL-----------NKAVDD---IRGLLKANEQLQEEIN 68

basic helix-loop-helix (bHLH) domain found in Arabidopsis thaliana protein IAA-leucine resistant 3 (ILR3) and similar proteins; ILR3, also termed AtbHLH105, or EN 133, is a bHLH transcription factor that plays a role in resistance to amide-linked indole-3-acetic acid (IAA) conjugates such as IAA-Leu and IAA-Phe. It may regulate gene expression in response to metal homeostasis changes.

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gi 281359791 256 EKERRAQLKECYDLLKKVLpmgDEDRK-KTSNLTILDTAHKYVNSLSHEVCEQEAKIEKLAKQKIELQKRLKQL 328
Cdd:cd11446    5 EKLRRDKLNERFMELSNVL---EPGRPpKTDKATILGDAIRMLKQLRGEVQKLKEENSSLQEESKELKAEKNEL 75

basic helix-loop-helix (bHLH) domain found in transcription factor-like 5 protein (TCFL5) and similar proteins; TCFL5, also termed Cha transcription factor, or HPV-16 E2-binding protein 1 (E2BP-1), is a bHLH transcription factor that plays a crucial role in spermatogenesis. It regulates cell proliferation or differentiation of cells through binding to a specific DNA sequence like other bHLH molecules.

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                 ....*....|....*....|....*....|....*....
gi 281359791 249 REVHNKLEKERRAQLKECYDLLKKVLPMGDEDRKKTSNL 287
Cdd:cd18909    3 RERHNRMERDRRRRIRICCDELNLLVPFCNAETDKATTL 41

basic helix-loop-helix-Per-ARNT-Sim (bHLH-PAS) domain found in aryl hydrocarbon receptor nuclear translocator-like protein 1 (ARNTL) and similar proteins; ARNTL, also termed Basic-helix-loop-helix-PAS protein MOP3, or brain and muscle ARNT-like 1 (BMAL1), or Class E basic helix-loop-helix protein 5 (bHLHe5), or member of PAS protein 3, or PAS domain-containing protein 3 (PASD3), or bHLH-PAS protein JAP3, is a member of the bHLH-PAS transcription factor family that forms heterodimers with another bHLH-PAS protein, CLOCK (circadian locomotor output cycle kaput), which regulates circadian rhythm. ARNTL-CLOCK heterodimer complex activates transcription from E-box (CANNTG) elements found in the promoter of circadian responsive genes. ARNTL is highly homologous to ARNT.

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                 ....*....|....*....|....*....|....*....|....*....|..
gi 281359791 249 REVHNKLEKERRAQLKECYDLLKKVLPMGDEDRKKTSNLTILDTAHKYVNSL 300
Cdd:cd11438    8 REAHSQIEKRRRDKMNSFIDELASLVPTCNAMSRKLDKLTVLRMAVQHMKTL 59

basic helix-loop-helix-orange (bHLH-O) domain found in HERP/HES-like family; The HERP/HES-like family includes bHLH-O transcriptional regulators that are related to the Drosophila hairy and Enhancer-of-split (HES) proteins. The HERP (HES-related repressor protein) subfamily proteins contain a basic helix-loop-helix (bHLH) domain with an invariant glycine residue in its basic region, an orange domain in the central region and YXXW sequence motif at its C-terminal region. Hairy and enhancer of split (HES)-related repressor protein (HERP) proteins (HEY1, HEY2 and HEYL) act as downstream effectors of Notch signaling. They are involved in cardiovascular development and have roles in somitogenesis, myogenesis and gliogenesis. Hairy and enhancer of split-related protein HELT is a transcriptional repressor expressed in the developing central nervous system. It binds preferentially to the canonical E box sequence 5'-CACGCG-3' and regulates neuronal differentiation and/or identity. Differentially expressed in chondrocytes proteins, DEC1 and DEC2, are widely expressed in both embryonic and adult tissues and have been implicated in apoptosis, cell proliferation, and circadian rhythms, as well as malignancy in various cancers. Drosophila melanogaster protein clockwork orange (Cwo) is also included in this subfamily. It is involved in the regulation of Drosophila circadian rhythms. It functions as both an activator and a repressor of clock gene expression. The HES subfamily proteins contain a basic helix-loop-helix (bHLH) domain with an invariant proline residue in its basic region, an orange domain in the central region and a conserved tetrapeptide motif, WRPW, at its C-terminal region. They form heterodimers or homodimers via their HLH domain and bind DNA to repress gene transcription that play an essential role in development of both compartment and boundary cells of the central nervous system.

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                 ....*....|....*....|....*....|....*....|....*....|.
gi 281359791 256 EKERRAQLKECYDLLKKVLPM--GDEDRKKTSNLTILDTAHKYVNSLSHEV 304
Cdd:cd19685    2 EKRRRQRINDKLNQLKELLPPnlSKQSRSKLSKAEILEMAITELRRLQQEV 52