Helix-loop-helix DNA-binding domain;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 767980574   24 KRAHHNALERKRRDHIKDSFHSLRDSVPSL-QGEKASRAQILDKATEYIQYMR 75
Cdd:pfam00010   1 RREAHNERERRRRDRINDAFDELRELLPTLpPDKKLSKAEILRLAIEYIKHLQ 53

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 767980574  24 KRAHHNALERKRRDHIKDSFHSLRDSVPSL-QGEKASRAQILDKATEYIQYMRRKNHTHQQDIDDLKRQNALLEQQ 98
Cdd:cd11400    1 KRRLHNVLERQRRNDLKNSFEKLRDLVPELaDNEKASKVVILKKATEYIKQLQQEEKKLEKEKDKLKARNEQLRKK 76

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 767980574  32 ERKRRDHIKDSFHSLRDSVPSL-QGEKASRAQILDKATEYIQYMRR 76
Cdd:cd00083    1 ERRRRDKINDAFEELKRLLPELpDSKKLSKASILQKAVEYIRELQS 46

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 767980574  25 RAHHNALERKRRDHIKDSFHSLRDSVPSLQGEKASRAQILDKATEYIQYMRRKNHTHQQDIDDLKRQNALLEQQ 98
Cdd:cd11402    3 REVHNKLEKNRRAHLKECFETLKRQIPNLDDKKTSNLNILRSALRYIQILKRKEKEYEHEMERLAREKIALQQR 76

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 767980574  24 KRAHHNALERKRRDHIKDSFHSLRDSVPSLQGEKASRAQILDKATEYIQYMrrknhthQQDIDDLKRQNALLEQQ 98
Cdd:cd11404    2 RRLNHVRSEKKRRELIKKGYDELCALVPGLDPQKRTKADILQKAADWIQEL-------KEENEKLEEQLDELKEA 69

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in N-Myc and similar proteins; N-Myc, also termed Class E basic helix-loop-helix protein 37 (bHLHe37), is a bHLHZip proto-oncogene protein that positively regulates the transcription of MYCNOS in neuroblastoma cells. It is also essential during embryonic development. N-Myc has a critical role in regulating the switch between proliferation and differentiation of progenitor cells. It binds DNA as a heterodimer with MAX. The family also includes S-Myc, encoded by rat or mouse intronless myc gene, which has apoptosis-inducing activity.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 767980574  23 DKRAHHNALERKRRDHIKDSFHSLRDSVPSL-QGEKASRAQILDKATEYIQYMRRKNHTHQQDIDDLK-RQNALLEQ 97
Cdd:cd11456    4 ERRRNHNILERQRRNDLRSSFLTLRDHVPELvKNEKAAKVVILKKATEYVHSLQAEEQKLLLEKEKLQaRQQQLLKK 80

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        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 767980574  24 KRAHHNALERKRRDHIKDSFHSLRDSVPSLQGE---KASRAQILDKATEYIQYMRRKNHTHQQDIDDLKRQ 91
Cdd:cd11405    3 RRLSHISAEQKRRFNIKSGFDTLQSLIPSLGQNpnqKVSKAAMLQKAAEYIKSLKRERQQMQEEAEQLRQE 73

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 767980574  25 RAHHNALERKRRDHIKDSFHSLRDSVPSLQGEKASRAQILDKATEYIQYMRRKNHTHQQDIDDLK 89
Cdd:cd19690    1 RVSHKLAERKRRKEMKELFEDLRDALPQERGTKASKWEILTKAISYIQQLKRHIRELRSEVNDLR 65

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 767980574  25 RAHHNALERKRRDHIKDSFHSLRDSVPSLQGEKASRAQILDKATEYIQYMRRKNhthqqdiDDLKRQNALLE 96
Cdd:cd19682    1 RLRHKKRERERRSELRELFDKLKQLLGLDSDEKASKLAVLTEAIEEIQQLKREE-------DELQKEKARLT 65

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 767980574  24 KRAHHNALERKRRDHIKDSFHSLRDSVPSLQGEKASRAQILDKATEYIQYMRRKN 78
Cdd:cd18910    5 KRESHNEVERRRKDKINAGINKIGELLPDRDAKKQSKNMILEQAYKYIVELKKKN 59

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        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 767980574  24 KRAHHNALERKRRDHIKDSFHSLRDSVPSLQGeKASRAQILDKATEYIQYMRRKNHTHQQDIDDLKRQN 92
Cdd:cd11394    6 KRSAHNAIEKRYRSSINDRIIELKDLVVGPDA-KMNKSAVLRKAIDYIRYLQKVNQKLKQENMALKKAL 73

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 767980574  25 RAHHNALERKRRDHIKDSFHSLRDSVPSlqGEKASRAQ---ILDKATEYIQYMRRKNHTHQQDIDDLKRQNALL 95
Cdd:cd11401    1 RSTHNELEKNRRAHLRLCLERLKELVPL--GPDATRHTtlsLLTKAKAYIKNLEDKEKRQRQQKEQLRREQREL 72

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in upstream stimulatory factor 1 (USF1) and similar proteins; USF1, also termed Class B basic helix-loop-helix protein 11 (bHLHb11), or major late transcription factor 1, is a bHLHzip transcription factor that binds to a symmetrical DNA sequence (E-boxes) (5'-CACGTG-3') that is found in a variety of viral and cellular promoters. It is ubiquitously expressed and involved in the transcription activation of various functional genes implicated in lipid and glucose metabolism, stress response, immune response, cell cycle control and tumour suppression. USF-1 recruits chromatin remodeling enzymes and interact with co-activators and the members of the transcription pre-initiation complex. Genetic polymorphisms of USF1 are associated with some metabolic and cardiovascular diseases, like diabetes, atherosclerosis, coronary artery calcifications and familial combined hyperlipidaemia (FCHL).

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 767980574  24 KRAHHNALERKRRDHIKDSFHSLRDSVP--SLQGEKA--SRAQILDKATEYIQYMRRKNH 79
Cdd:cd18924    5 RRAQHNEVERRRRDKINNWIVQLSKIIPdcSMESTKSgqSKGGILSKACDYIQELRQSNH 64

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in upstream stimulatory factor 2 (USF2) and similar proteins; USF2, also termed Class B basic helix-loop-helix protein 12 (bHLHb12), or major late transcription factor 2, or FOS-interacting protein (FIP), or upstream transcription factor 2, is a bHLHzip transcription factor that binds to a symmetrical DNA sequence (E-boxes) (5'-CACGTG-3') that is found in a variety of viral and cellular promoters.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 767980574  24 KRAHHNALERKRRDHIKDSFHSLRDSVPSLQGEK----ASRAQILDKATEYIQYMRRKNHTHQQDIDDLKR 90
Cdd:cd18923    8 RRAQHNEVERRRRDKINNWIVQLSKIIPDCNTDNsktgASKGGILSKACDYIRELRQTNQRMQETYKEAER 78

basic helix-loop-helix (bHLH) domain found in the spermatogenesis- and oogenesis-specific basic helix-loop-helix-containing protein (SOHLH) family; 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.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 767980574  28 HNALERKRRDHIKDSFHSLRDSVPSLQGEKASRAQILDKATEYIQYMRRKNH 79
Cdd:cd18908    6 HSLKERLRRERIKSSCDQLRDLLPYIKGRKLDMASVLEMTVKYIRYIQERIP 57

tissue specific basic helix-loop-helix (bHLH-TS) domain family; Tissue specific bHLH domain family includes transcription regulators whose expression are restricted to certain tissues. They are involved in cell-fate determination and process in neurogenesis, cardiogenesis, myogenesis, and hematopoiesis and include proteins from myogenic regulatory factor (MRF) family, twist-related protein (TWIST) family, scleraxis-like family, heart- and neural crest derivatives-expressed protein (HAND) family, helix-loop-helix protein (HEN) family, musculin-like family, germline alpha (FIGLA) family, T-cell acute lymphocytic leukemia protein/ lymphoblastic leukemia-derived sequence (TAL/LYL) family, ovary, uterus and testis protein (OUT) family, mesoderm posterior protein (Mesp) family, muscle, intestine and stomach expression 1 (MIST-1) family, protein atonal homologs (ATOH) family, neurogenin (NGN) family, neurogenic differentiation factor (NeuroD) family, achaete-scute complex-like (ASCL) family, Fer3-like protein (FERD3L)-like family, and Oligodendrocyte lineage genes (OLIG) family of transcription factors.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 767980574  25 RAHHNALERKRRDHIKDSFHSLRDSVPSLQ-GEKASRAQILDKATEYIQYMRR 76
Cdd:cd11390    1 RNAANARERRRMHDLNDAFEALRKVLPTVPpDKKLSKIETLRLAINYIAALSD 53

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 767980574  28 HNALERKRRDHIKDSFHSLRDSVPSLQgeKASRAQILDKATEYIQYMRRK 77
Cdd:cd11393    1 HSIAERKRREKINERIRALRSLVPNGG--KTDKASILDEAIEYIKFLQEQ 48

basic helix-loop-helix (bHLH) domain found in twist-related protein 1 (TWIST1) and similar proteins; TWIST1, also termed Class A basic helix-loop-helix protein 38 (bHLHa38), or H-twist, is a bHLH transcriptional regulator that inhibits myogenesis by sequestrating E proteins, inhibiting trans-activation by MEF2, and inhibiting DNA-binding by MYOD1 through physical interaction. It also represses expression of proinflammatory cytokines such as TNFA and IL1B. In addition, TWIST1 is involved in cancer development and progression.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 767980574  18 FQSAADKRAHHNALERKRRDHIKDSFHSLRDSVPSLQGEKASRAQILDKATEYIQYM 74
Cdd:cd11412    6 FEELQTQRVMANVRERQRTQSLNEAFAALRKIIPTLPSDKLSKIQTLKLAARYIDFL 62

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 767980574  24 KRAHHNALERKRRDHIKDSFHSLRDSVPSLQGE---KASRAQILDKATEYIQYMRRKNHTHQQDID 86
Cdd:cd11388    3 KKWKHVEAEKKRRNQIKKGFEDLINLINYPRNNnekRISKSELLNKAVDDIRGLLKANEQLQEEIN 68

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.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 767980574  24 KRAHHNALERKRRDHIKDSFHSLRDSVP-SLQGEKASRAQILDKATEYIQYMRRK 77
Cdd:cd18914    1 KKLLHNDVERQRRQEMASLFSSLRSLLPlQYIKGKLSVSDHVDEAVNYIKELQEK 55

basic helix-loop-helix (bHLH) domain found in protein atonal homolog 7 (ATOH7) and similar proteins; ATOH7, also termed Class A basic helix-loop-helix protein 13 (bHLHa13), or helix-loop-helix protein hATH-5 (hATH5), or Math5, is a bHLH transcription factor involved in the differentiation of retinal ganglion cells.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 767980574  17 RFQSAADKRAHHNALERKRRDHIKDSFHSLRDSVPSL-QGEKASRAQILDKATEYIQYMRR 76
Cdd:cd19714    1 RLESAARRRLAANARERRRMQGLNTAFDRLRKVVPQWgQDKKLSKYETLQMALSYIMALTR 61

basic helix-loop-helix (bHLH) domain found in achaete-scute complex-like (ASCL) family; The achaete-scute complex-like (ASCL, also known as achaete-scute complex homolog or ASH) family of bHLH transcription factors, ASCL1-5, have been implicated in cell fate specification and differentiation. They are critical for proper development of the nervous system. The deregulation of ASCL plays a key role in psychiatric and neurological disorders. ASCL-1, also termed Class A basic helix-loop-helix protein 46 (bHLHa46), or achaete-scute homolog 1 (ASH-1), or mammalian achaete-scute homolog 1 (Mash1), is a neural-specific bHLH transcription factor that is expressed in subsets of neural progenitors in both the central and peripheral nervous system. It plays a key role in neuronal differentiation and specification in the nervous system. ASCL-2, also termed achaete-scute homolog 2 (ASH-2), or Class A basic helix-loop-helix protein 45 (bHLHa45), or mammalian achaete-scute homolog 2 (Mash2), is a bHLH transcription factor that is involved in Schwann cell differentiation and control of proliferation in adult peripheral nerves. ASCL-3, also termed Class A basic helix-loop-helix protein 42 (bHLHa42), or bHLH transcriptional regulator Sgn-1, or achaete-scute homolog 3 (ASH-3), is a bHLH transcription factor specifically localized in the duct cells of the salivary glands. It may act as transcriptional repressor that inhibits myogenesis. The family also includes Drosophila melanogaster achaete-scute complex (AS-C) proteins, which consists of lethal of scute (also known as achaete-scute complex protein T3 or AST3), scute (also known as achaete-scute complex protein T4 or AST4), achaete (also known as achaete-scute complex protein T5 or AST5), and asense (also known as achaete-scute complex protein T8 or AST8). They are involved in the determination of the neuronal precursors in the peripheral nervous system and the central nervous system, as well as in sex determination and dosage compensation.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 767980574  24 KRAHHNALERKRRDHIKDSFHSLRDSVPSLQGEKA-SRAQILDKATEYIQYMRR 76
Cdd:cd11418    1 RVARRNERERRRVQAVNDAFDRLRQHVPYLKRRKKlSKVKTLRRAIEYIRHLQK 54

basic helix-loop-helix-orange (bHLH-O) domain found in hairy and enhancer of split (HES)-related repressor protein (HERP)-like family; The HERP-like family includes bHLH-O transcriptional regulators that are related to the Drosophila hairy and Enhancer-of-split proteins. They 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. 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 family. It is involved in the regulation of Drosophila circadian rhythms. It functions as both an activator and a repressor of clock gene expression.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 767980574  28 HNALERKRRDHIKDSFHSLRDSVP----SLQGEKASRAQILDKATEYIQYM 74
Cdd:cd11389    1 HKVIEKRRRDRINESLAELRRLVPearkSKGSGKLEKAEILEMTLQHLKAL 51

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        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 767980574  24 KRAHHNALERKRRDHIK---DSFHSLRDSVPSLQGEKASRAQILDKATEYIQYMRRKNHTHQQDIDDLKRQ 91
Cdd:cd19689    5 RRITHISAEQKRRFNIKlgfDTLHSLVTTLSSQPSIKISKATTLQKTAEYISKLQQERAQLQEEAQRLRDQ 75

basic helix-loop-helix (bHLH) domain found in factor in the germline alpha (FIGLA) and similar proteins; FIGLA, also termed FIGalpha, or Class C basic helix-loop-helix protein 8 (bHLHc8), or folliculogenesis-specific basic helix-loop-helix protein, or transcription factor FIGa, is a germ-cell-specific bHLH transcription factor expressed abundantly in female and less so in male germ cells. It is essential for primordial follicle formation and expression of many genes required for folliculogenesis, fertilization and early embryonic survival. FIGLA knockout mice cannot form primordial follicles and lose oocytes rapidly after birth, whereas male gonads are unaffected.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 767980574  29 NALERKRRDHIKDSFHSLRDSVP-SLQGEKASRAQILDKATEYIQYMRR 76
Cdd:cd11422    5 NARERERVRNLNSGFSKLRRIVPlIPRDRKPSKVDTLKGATEYIRLLQR 53

basic helix-loop-helix (bHLH) domain found in heart- and neural crest derivatives-expressed protein 1 (HAND1) and similar proteins; HAND1, also termed Class A basic helix-loop-helix protein 27 (bHLHa27), or extraembryonic tissues, heart, autonomic nervous system and neural crest derivatives-expressed protein 1 (eHAND), is a bHLH transcription factor that plays an essential role in both trophoblast-giant cells differentiation and in cardiac morphogenesis.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....
gi 767980574  32 ERKRRDHIKDSFHSLRDSVPSLQGE-KASRAQILDKATEYIQYM 74
Cdd:cd18952   10 ERRRTESINSAFAELRECIPNVPADtKLSKIKTLRLATSYIAYL 53

basic helix-loop-helix (bHLH) domain found in heart- and neural crest derivatives-expressed protein 2 (HAND2) and similar proteins; HAND2, also termed Class A basic helix-loop-helix protein 26 (bHLHa26), or deciduum, heart, autonomic nervous system and neural crest derivatives-expressed protein 2 (dHAND), is a bHLH transcription factor that is essential for cardiac morphogenesis, particularly for the formation of the right ventricle and of the aortic arch arteries.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 767980574  24 KRAHHNALERKRRDHIKDSFHSLRDSVPSLQGE-KASRAQILDKATEYIQYM 74
Cdd:cd11471    1 RRGTANRKERRRTQSINSAFAELRECIPNVPADtKLSKIKTLRLATSYIAYL 52

basic helix-loop-helix (bHLH) domain found in Fer3-like protein (FERD3L) and similar proteins; FERD3L, also termed basic helix-loop-helix protein N-twist, or Class A basic helix-loop-helix protein 31 (bHLHa31), or nephew of atonal 3 (NATO3), or Neuronal twist (NTWIST), is a bHLH transcription factor expressed in the developing central nervous system (CNS). It regulates floor plate (FP) cells development. FP is a critical organizing center located at the ventral-most midline of the neural tube. FERD3L binds to the E-box and functions as inhibitor of transcription.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 767980574  17 RFQSAADKRAHhNALERKRRDHIKDSFHSLRDSVPSLQGEKA-SRAQILDKATEYIQYM 74
Cdd:cd11415    3 RVITYAQRQAA-NIRERRRMFNLNEAFDKLRKKVPTFAYEKRlSRIETLRLAIVYISFM 60

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 767980574  25 RAHHNALERKRRDHIKDSFHSLRDSVPsLQGEKASRAQ--ILDKATEYIQYMRRKNHTHQQDIDDLKRQNALLEQQ 98
Cdd:cd18930    2 RSTHNELEKNRRAHLRLCLERLKVLIP-LGPDCTRHTTlgLLNKAKAHIKKLEEADRKSQHQLENLEREQRFLKRR 76

basic helix-loop-helix (bHLH) domain found in muscle, intestine and stomach expression 1 (MIST-1) and similar proteins; MIST-1, also termed Class A basic helix-loop-helix protein 15 (bHLHa15), or Class B basic helix-loop-helix protein 8 (bHLHb8), is a bHLH transcription factor expressed in pancreatic acinar cells and other serous exocrine cells. It is essential for cytoskeletal organization and secretory activity. It also functions as a potent endoplasmic reticulum (ER) stress-inducible transcriptional regulator. MIST-1 is capable of binding to E-box (CANNTG) motifs as a homodimer or a heterodimer with E-proteins (E12 and E47) to regulate transcription.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 767980574  24 KRAHHNALERKRRDHIKDSFHSLRDSVPSLQGEKA-SRAQILDKATEYIQ 72
Cdd:cd19711    1 RRLESNERERQRMHKLNNAFQALREVIPHVRAEKKlSKIETLTLAKNYIK 50

basic helix-loop-helix (bHLH) domain found in pancreas transcription factor 1 subunit alpha (PTF1A) and similar proteins; PTF1A, also termed Class A basic helix-loop-helix protein 29 (bHLHa29), or pancreas-specific transcription factor 1a, or bHLH transcription factor p48, or p48 DNA-binding subunit of transcription factor PTF1 (PTF1-p48), is a bHLH transcription factor implicated in the cell fate determination in various organs. It binds to the E-box consensus sequence 5'-CANNTG-3' and plays a role in early and late pancreas development and differentiation.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 767980574  24 KRAHHNALERKRRDHIKDSFHSLRDSVPSLQGEKA-SRAQILDKATEYIQYM 74
Cdd:cd11417    1 QRQAANLRERRRMQSINDAFEGLRSHIPTLPYEKRlSKVDTLRLAIGYINFL 52

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in MAX gene-associated protein (MGA) 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.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 767980574  25 RAHHNALERKRRDHIKDSFHSLRDSVPSLQGEKASRAQILDKATEYIQYMrrknhthQQDIDDLKRQNALL 95
Cdd:cd18911    1 RRTHTANERRRRNEMRDLFEKLKRTLGLHNLPKVSKYYILKQAFEEIQGL-------TDQADRLIGQKTLL 64