basic Helix-Loop-Helix-zipper (bHLHzip) domain found in Max-binding protein Mnt and similar proteins; Mnt, also termed Class D basic helix-loop-helix protein 3 (bHLHd3), or Myc antagonist MNT, or protein ROX, is a bHLHZip transcriptional repressor that binds DNA as a heterodimer with MAX. It binds to the canonical E box sequence 5'-CACGTG-3' and, with higher affinity, to 5'-CACGCG-3'. Mnt has an important role as an antagonist and regulator of Myc activities and it is a potential tumor suppressor. Mnt is ubiquitously expressed. Mnt-deficient mice shown to exhibit early postnatal lethality.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 281359797 455 GTREVHNKLEKERRAQLKECYDLLKKVLPMGDedRKKTSNLTILDTAHKYVNSLSHEVCEQEAKIEKLAKQKIELQKRL 533
Cdd:cd11402    1 GTREVHNKLEKNRRAHLKECFETLKRQIPNLD--DKKTSNLNILRSALRYIQILKRKEKEYEHEMERLAREKIALQQRL 77

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in Max-binding protein Mnt and similar proteins; Mnt, also termed Class D basic helix-loop-helix protein 3 (bHLHd3), or Myc antagonist MNT, or protein ROX, is a bHLHZip transcriptional repressor that binds DNA as a heterodimer with MAX. It binds to the canonical E box sequence 5'-CACGTG-3' and, with higher affinity, to 5'-CACGCG-3'. Mnt has an important role as an antagonist and regulator of Myc activities and it is a potential tumor suppressor. Mnt is ubiquitously expressed. Mnt-deficient mice shown to exhibit early postnatal lethality.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 281359797 455 GTREVHNKLEKERRAQLKECYDLLKKVLPMGDedRKKTSNLTILDTAHKYVNSLSHEVCEQEAKIEKLAKQKIELQKRL 533
Cdd:cd11402    1 GTREVHNKLEKNRRAHLKECFETLKRQIPNLD--DKKTSNLNILRSALRYIQILKRKEKEYEHEMERLAREKIALQQRL 77

helix loop helix domain;

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 281359797   461 NKLEKERRAQLKECYDLLKKVLPMGDEDrKKTSNLTILDTAHKYVNSLSHEV 512
Cdd:smart00353   1 NARERRRRRKINEAFDELRSLLPTLPKN-KKLSKAEILRLAIEYIKSLQEEL 51

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in Max-binding protein Mnt and similar proteins; Mnt, also termed Class D basic helix-loop-helix protein 3 (bHLHd3), or Myc antagonist MNT, or protein ROX, is a bHLHZip transcriptional repressor that binds DNA as a heterodimer with MAX. It binds to the canonical E box sequence 5'-CACGTG-3' and, with higher affinity, to 5'-CACGCG-3'. Mnt has an important role as an antagonist and regulator of Myc activities and it is a potential tumor suppressor. Mnt is ubiquitously expressed. Mnt-deficient mice shown to exhibit early postnatal lethality.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 281359797 455 GTREVHNKLEKERRAQLKECYDLLKKVLPMGDedRKKTSNLTILDTAHKYVNSLSHEVCEQEAKIEKLAKQKIELQKRL 533
Cdd:cd11402    1 GTREVHNKLEKNRRAHLKECFETLKRQIPNLD--DKKTSNLNILRSALRYIQILKRKEKEYEHEMERLAREKIALQQRL 77

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in the Mad family; Members of the Mad family (Mad1, Mxi, Mad3, and Mad4) bear the bHLHzip domain (also known as basic-helix-loop-helix-leucine-zipper or bHLH-LZ domain), which mediates heterodimerization to Max and the sequence-specific DNA binding ability to E-box DNA. Mad family proteins can repress transcription at the E-box through their interaction with co-repressors. Mad family proteins antagonize Myc function in transactivation and transformation and they are growth/tumor suppressors. The developmental phenotypes of the individual Mad family member knockout mice are relatively mild- all these mice have been shown to be viable and normal.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 281359797 457 REVHNKLEKERRAQLKECYDLLKKVLPMGDEDRKKTSnLTILDTAHKYVNSLSHEVCEQEAKIEKLAKQKIELQKRL 533
Cdd:cd11401    1 RSTHNELEKNRRAHLRLCLERLKELVPLGPDATRHTT-LSLLTKAKAYIKNLEDKEKRQRQQKEQLRREQRELKRRL 76

Helix-loop-helix DNA-binding domain;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 281359797  457 REVHNKLEKERRAQLKECYDLLKKVLPmGDEDRKKTSNLTILDTAHKYVNSL 508
Cdd:pfam00010   2 REAHNERERRRRDRINDAFDELRELLP-TLPPDKKLSKAEILRLAIEYIKHL 52

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281359797 457 REVHNKLEKERRAQLKECYDLLKKVLPMGDEDRKKTSnLTILDTAHKYVNSLshevCEQEAKI----EKLAKQKIELQKR 532
Cdd:cd18932    7 RSVHNELEKHRRAQLRRCLEQLKQQVPLGADCSRYTT-LSLLRRARLHIQKL----EEQEQRAqqlkERLRWEQQKLRRR 81

                 ....
gi 281359797 533 LKQL 536
Cdd:cd18932   82 LESL 85

helix loop helix domain;

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 281359797   461 NKLEKERRAQLKECYDLLKKVLPMGDEDrKKTSNLTILDTAHKYVNSLSHEV 512
Cdd:smart00353   1 NARERRRRRKINEAFDELRSLLPTLPKN-KKLSKAEILRLAIEYIKSLQEEL 51

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in c-Myc and similar proteins; c-Myc, also termed Myc proto-oncogene protein, or Class E basic helix-loop-helix protein 39 (bHLHe39), or transcription factor p64, a bHLHZip proto-oncogene protein that functions as a transcription factor, which binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. It activates the transcription of growth-related genes.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281359797 457 REVHNKLEKERRAQLKECYDLLKKVLPMGdEDRKKTSNLTILDTAHKYVNSLSHEVCEQEAKIEKLAKQKIELQKRLKQL 536
Cdd:cd11458    6 RRTHNVLERQRRNELKLSFFALRDQIPEV-ANNEKAPKVVILKKATEYILSMQADEQRLISEKEQLRRRREQLKHRLEQL 84

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 281359797 464 EKERRAQLKECYDLLKKVLPMGdEDRKKTSNLTILDTAHKYVNSL 508
Cdd:cd00083    1 ERRRRDKINDAFEELKRLLPEL-PDSKKLSKASILQKAVEYIREL 44

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        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 281359797 457 REVHNKLEKERRAQLKECYDLLKKVLPMGDEDrkKTSNLTILDTAHKYVNSLSHEVCEQEAKIEKLAKQ 525
Cdd:cd11406    2 RAHHNALERKRRDHIKDSFHSLRDSVPSLQGE--KASRAQILKKATEYIQYMRRKNHTHQQDIDDLKRQ 68

basic helix-loop-helix (bHLH) domain found in the spermatogenesis- and oogenesis-specific basic helix-loop-helix-containing protein (SOHLH) family and similar proteins; The SOHLH family includes two bHLH transcription factors, SOHLH1 and SOHLH2. They are specifically in spermatogonia and oocytes and essential for early spermatogonial and oocyte differentiation. The family also includes 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.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 281359797 457 REVHNKLEKERRAQLKECYDLLKKVLPMGDEdrkKTSNLTILDTAHKYV 505
Cdd:cd19683    3 RERHNAKERQRRERIKIACDQLRKLVPGCSR---KTDKATVFEFTVAYI 48

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in Max-like protein X (Mlx) family; Mlx, also termed Class D basic helix-loop-helix protein 13 (bHLHd13), or Max-like bHLHZip protein, or protein BigMax, or transcription factor-like protein 4, is a Max-like bHLHZip transcription regulator that interacts with the Max network of transcription factors. It forms a sequence-specific DNA-binding protein complex with some member of Mad family (Mad1 and Mad4) and Mondo family but not the Myc family and bind the E-box DNA to control transcription. The family also includes Saccharomyces cerevisiae INO4, which is a bHLH transcriptional activator of phospholipid synthetic genes (such as INO1, CHO1/PSS, CHO2/PEM1, OPI3/PEM2, etc.). It is required for de-repression of phospholipid biosynthetic gene expression in response to inositol deprivation in yeast.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 281359797 457 REVHNKLEKERRAQLKECYDLLKKVLPmgDEDRKKTSNLTILDTAHKYVNSLShevceqeAKIEKLAKQKIELQKR 532
Cdd:cd11404    3 RLNHVRSEKKRRELIKKGYDELCALVP--GLDPQKRTKADILQKAADWIQELK-------EENEKLEEQLDELKEA 69

basic helix-loop-helix (bHLH) domain found in Arabidopsis thaliana genes coding transcription factors and similar proteins; bHLH proteins are the second largest class of plant transcription factors that regulate transcription of genes that are involve in many essential physiological and developmental process. bHLH proteins are transcriptional regulators that are found in organisms from yeast to humans. The Arabidopsis bHLH proteins that have been characterized so far have roles in regulation of fruit dehiscence, cell development (carpel, anther and epidermal), phytochrome signaling, flavonoid biosynthesis, hormone signaling and stress responses.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 281359797 460 HNKLEKERRAQLKECYDLLKKVLPMGdedrKKTSNLTILDTAHKYVNSLSHEV 512
Cdd:cd11393    1 HSIAERKRREKINERIRALRSLVPNG----GKTDKASILDEAIEYIKFLQEQV 49

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in basic helix-loop-helix domain-containing protein USF3 and similar proteins; USF3, also termed upstream transcription factor 3, is a bHLHzip protein that is involved in the negative regulation of epithelial-mesenchymal transition, the process by which epithelial cells lose their polarity and adhesion properties to become mesenchymal cells with enhanced migration and invasive properties.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 281359797 457 REVHNKLEKERRAQLKECYDLLKKVLPmgDEDRKKTSNLTILDTAHKYVNSLShEVCEQ 515
Cdd:cd18910    6 RESHNEVERRRKDKINAGINKIGELLP--DRDAKKQSKNMILEQAYKYIVELK-KKNDK 61

basic Helix-Loop-Helix (bHLH) domain found in Arabidopsis thaliana MYC1 and similar proteins; MYC1, also termed AtbHLH12, or EN 58, acts as a transcription activator, when associated with MYB75/PAP1 or MYB90/PAP2.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 281359797 460 HNKLEKERRAQLKECYDLLKKVLPmgdeDRKKTSNLTILDTAHKYVNSLSHEVCEQEAKIEK 521
Cdd:cd18918    1 LFATERERREKLNEKFSDLRNLIP----NPTKNDRASILSDAIKYINELQRTVEELKSLVEK 58

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.

                         10        20        30
                 ....*....|....*....|....*....|....*....
gi 281359797 457 REVHNKLEKERRAQLKECYDLLKKVLPMGDEDRKKTSNL 495
Cdd:cd18909    3 RERHNRMERDRRRRIRICCDELNLLVPFCNAETDKATTL 41

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.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 281359797 464 EKERRAQLKECYDLLKKVLPM--GDEDRKKTSNLTILDTAHKYVNSLSHEV 512
Cdd:cd19685    2 EKRRRQRINDKLNQLKELLPPnlSKQSRSKLSKAEILEMAITELRRLQQEV 52