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        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 127604   378 EDSERRRNHNILERQRRNDLRSSFLTLRDHVPELVKNEKAAKVVILKKATEYVHSLQAEEHQLLLEKEKLQARQQQLLKK 457
Cdd:cd11456   1 EDSERRRNHNILERQRRNDLRSSFLTLRDHVPELVKNEKAAKVVILKKATEYVHSLQAEEQKLLLEKEKLQARQQQLLKK 80

                ....*..
gi 127604   458 IEHARTC 464
Cdd:cd11456  81 IEQARTC 87

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        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 127604   378 EDSERRRNHNILERQRRNDLRSSFLTLRDHVPELVKNEKAAKVVILKKATEYVHSLQAEEHQLLLEKEKLQARQQQLLKK 457
Cdd:cd11456   1 EDSERRRNHNILERQRRNDLRSSFLTLRDHVPELVKNEKAAKVVILKKATEYVHSLQAEEQKLLLEKEKLQARQQQLLKK 80

                ....*..
gi 127604   458 IEHARTC 464
Cdd:cd11456  81 IEQARTC 87

Helix-loop-helix DNA-binding domain;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 127604     382 RRRNHNILERQRRNDLRSSFLTLRDHVPELVKNEKAAKVVILKKATEYVHSLQ 434
Cdd:pfam00010   1 RREAHNERERRRRDRINDAFDELRELLPTLPPDKKLSKAEILRLAIEYIKHLQ 53

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        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 127604   378 EDSERRRNHNILERQRRNDLRSSFLTLRDHVPELVKNEKAAKVVILKKATEYVHSLQAEEHQLLLEKEKLQARQQQLLKK 457
Cdd:cd11456   1 EDSERRRNHNILERQRRNDLRSSFLTLRDHVPELVKNEKAAKVVILKKATEYVHSLQAEEQKLLLEKEKLQARQQQLLKK 80

                ....*..
gi 127604   458 IEHARTC 464
Cdd:cd11456  81 IEQARTC 87

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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 127604   376 DSEDSERRRNHNILERQRRNDLRSSFLTLRDHVPELVKNEKAAKVVILKKATEYVHSLQAEEHQLLLEKEKLQARQQQLL 455
Cdd:cd11457   1 DTEDVAKRKNHNFLERKRRNDLRSRFLALRDEVPGLASCSKTPKVVILSKATEYLRGLVSAERRMAAEKRQLKSRQQQLL 80

                ....*
gi 127604   456 KKIEH 460
Cdd:cd11457  81 RRIAQ 85

helix loop helix domain;

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 127604      387 NILERQRRNDLRSSFLTLRDHVPELVKNEKAAKVVILKKATEYVHSLQAEEHQ 439
Cdd:smart00353   1 NARERRRRRKINEAFDELRSLLPTLPKNKKLSKAEILRLAIEYIKSLQEELQK 53

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 127604   382 RRRNHNILERQRRNDLRSSFLTLRDHVPELvKNEKAAKVVILKKATEYVHSLQAE--EHQLLLEKEKLQ 448
Cdd:cd11406   1 KRAHHNALERKRRDHIKDSFHSLRDSVPSL-QGEKASRAQILKKATEYIQYMRRKnhTHQQDIDDLKRQ 68

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 127604   383 RRNHNILERQRRNDLRSSFLTLRDHVPeLVKNEKAAKVVILKKATEYVHSLQAEEHQLLLEKEKLQ 448
Cdd:cd19682   1 RLRHKKRERERRSELRELFDKLKQLLG-LDSDEKASKLAVLTEAIEEIQQLKREEDELQKEKARLT 65

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 127604   382 RRRNHNILERQRRNDLRSSFLTLRDHVPELvKNEKAAKVVILKKATEYVHSLQAEehQLLLEKEKLQARQQ 452
Cdd:cd11404   2 RRLNHVRSEKKRRELIKKGYDELCALVPGL-DPQKRTKADILQKAADWIQELKEE--NEKLEEQLDELKEA 69

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 127604   383 RRNHNILERQRRNDLRSSFLTLRDHVPELVKNEKAAKVVILKKATEYVHSLQAEEHQLLLEKEKLQARQQQLLKKI 458
Cdd:cd11401   1 RSTHNELEKNRRAHLRLCLERLKELVPLGPDATRHTTLSLLTKAKAYIKNLEDKEKRQRQQKEQLRREQRELKRRL 76

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in Saccharomyces cerevisiae centromere-binding protein 1 (CBP-1) and similar proteins; CBP-1, also termed centromere promoter factor 1 (CPF1), or centromere-binding factor 1 (CBF1), is a bHLHzip protein that is required for chromosome stability and methionine prototrophy. It binds as a homodimer to the centromere DNA elements I (CDEI, GTCACATG) region of the centromere that is required for optimal centromere function.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 127604   381 ERRRNHNILERQRRNDLRSSFLTLRDHVPelVKNEKAAKVVILKKATEYVHSLQAEEHQLLLE--KEKLQARQ 451
Cdd:cd11398   6 QRRDNHKEVERRRRENINEGINELAALVP--GNAREKNKGAILARAVEYIQELQETEAKNIEKwtLEKLLTDQ 76

basic helix-loop-helix (bHLH) domain found in Drosophila melanogaster achaete-scute complex (AS-C) proteins, achaete-scute-like proteins, ASCL1-2, and similar proteins; This subfamily includes Drosophila melanogaster AS-C proteins and two ASCL family of transcription factors, ASCL-1 and ASCL-2. Drosophila melanogaster AS-C proteins includes 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. 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 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 involved in Schwann cell differentiation and control of proliferation in adult peripheral nerves.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|..
gi 127604   383 RRNHNilERQRRNDLRSSFLTLRDHVPELVKNEKAAKVVILKKATEYVHSLQ 434
Cdd:cd19723   4 RRNER--ERNRVKLVNLGFATLREHVPNGRANKKMSKVETLRSAVEYIRQLQ 53

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        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 127604   381 ERRRNHNILERQRRNDLRSSFLTLRDHV-PELVKNEKAAkvvILKKATEYVHSLQAEEHQLLLEKEKLQARQ 451
Cdd:cd11394   5 EKRSAHNAIEKRYRSSINDRIIELKDLVvGPDAKMNKSA---VLRKAIDYIRYLQKVNQKLKQENMALKKAL 73

basic helix-loop-helix (bHLH) domain found in achaete-scute-like protein 1 (ASCL-1) and similar proteins; 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.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 127604   383 RRNHNilERQRRNDLRSSFLTLRDHVPELVKNEKAAKVVILKKATEYVHSLQaeehQLLLEKEKLQARQQ 452
Cdd:cd19742   8 RRNER--ERNRVKLVNMGFATLREHVPNGAANKKMSKVETLRSAVEYIRALQ----QLLDEHDAVSAAFQ 71

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 127604   383 RRNHNilERQRRNDLRSSFLTLRDHVPELVKNEKAAKVVILKKATEYVHSLQ 434
Cdd:cd11418   4 RRNER--ERRRVQAVNDAFDRLRQHVPYLKRRKKLSKVKTLRRAIEYIRHLQ 53

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        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 127604   382 RRRNHNILERQRRNDLRSSFLTLRDHVPELVKNEKAAKVVILKKATEYVHSLQAEEHQLLLEKEKLQ 448
Cdd:cd19688   3 RRMKHISAEQKRRFNIKICFDTLNSLVSTLKNSKPISNAITLQKTVEYIAKLQQERTQMQEETKRLR 69

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        50
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 127604   382 RRRNHNILERQRRNDLRSSFLTLRDHVPELV---KNEKAAKVVILKKATEYVHSLQ 434
Cdd:cd11431   1 RRKTANARERDRMREINDAFEALRRAVPEYPvagKDGKLTKITTLRLAMNYIKALT 56

basic helix-loop-helix (bHLH) domain found in Arabidopsis thaliana protein transparent testa 8 (TT8) and similar proteins; The family includes several bHLH transcription factors from Arabidopsis thaliana, such as TT8, EGL1, and GL3. TT8, also termed AtbHLH42, or EN 32, is involved in the control of flavonoid pigmentation and plays a key role in regulating leucoanthocyanidin reductase (BANYULS) and dihydroflavonol-4-reductase (DFR). EGL1, also termed AtbHLH2, or EN 30, or AtMYC146, or protein enhancer of GLABRA 3, is involved in epidermal cell fate specification and regulates negatively stomata formation but promotes trichome formation. GL3, also termed AtbHLH1, or AtMYC6, or protein shapeshifter, or EN 31, is involved in epidermal cell fate specification. It regulates negatively stomata formation, but, in association with TTG1 and MYB0/GL1, promotes trichome formation, branching and endoreplication.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 127604   385 NHNILERQRRNDLRSSFLTLRDHVPELVKNEkaaKVVILKKATEYVHSLQAEEHQL 440
Cdd:cd11451   5 SHAMAERRRREKLNERFITLRSMVPFVTKMD---KVSILGDAIEYLKQLQRRVEEL 57

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 127604   383 RRNHNILERQRRNDLRSSFLTLRDHVPeLVKNEKAAKVVILKKATEYVHSLQAEEHQLLLEKEKLQ 448
Cdd:cd19690   1 RVSHKLAERKRRKEMKELFEDLRDALP-QERGTKASKWEILTKAISYIQQLKRHIRELRSEVNDLR 65

basic helix-loop-helix (bHLH) domain found in achaete-scute-like protein 2 (ASCL-2) and similar proteins; 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.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 127604   377 SEDSERRrnhNILERQRRNDLRSSFLTLRDHVPELVKNEKAAKVVILKKATEYVHSLQA 435
Cdd:cd19743   1 AAAVERR---NERERNRVKLVNLGFAALRQHVPQGGASKKMSKVETLRSAVEYIRALQR 56

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 127604   386 HNILERQRRNDLRSSFLTLRDHVPELVKNEKAAkvvILKKATEYVHSLQAEEHQL 440
Cdd:cd11393   1 HSIAERKRREKINERIRALRSLVPNGGKTDKAS---ILDEAIEYIKFLQEQVKVL 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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 127604   383 RRNHNILERQRRNDLRSSFLTLRdHVPELVKNEKAAKVVILKKATEYVHSLQAEEHQLLLEKEKL 447
Cdd:cd18911   1 RRTHTANERRRRNEMRDLFEKLK-RTLGLHNLPKVSKYYILKQAFEEIQGLTDQADRLIGQKTLL 64

basic helix-loop-helix (bHLH) domain found in achaete-scute-like proteins, ASCL3-5, and similar proteins; This subfamily includes three ASCL family of transcription factors, ASCL-3, ASCL-4 and ASCL-5. 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 specifically localized in the duct cells of the salivary glands. It may act as transcriptional repressor that inhibits myogenesis. ASCL-4, also termed Class A basic helix-loop-helix protein 44 (bHLHa44), or achaete-scute homolog 4 (ASH-4), or Hash4, may be involved in skin development. ASCL-5, also termed Class A basic helix-loop-helix protein 47 (bHLHa47), or achaete-scute homolog 5 (ASH-5), is an uncharacterized bHLH transcription factor that is close related to ASCL-3 and ASCL-4.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....
gi 127604   382 RRRNHNilERQRRNDLRSSFLTLRDHVPELVKNEKAAKVVILKKATEYVHSLQA 435
Cdd:cd19724   3 RKRNER--ERQRVRCVNEGYARLRRHLPLENKDKRLSKVETLRAAIRYIKHLQE 54

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.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 127604   383 RRNHNILERQRRNDLRSSFLTLRDHVPELVKNEKAAKVVILKKATEYVHSLQAEEHQLLLEKEKLQARQQQLLKKIEH 460
Cdd:cd18929   3 RSSHNELEKHRRAKLRLYLEQLKQLVPLGPDSTRHTTLSLLKRAKMHIKKLEEQDRKALNIKEQLQREHRYLKRRLEQ 80

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 127604   382 RRRNHNILERQRRNDLRSSFLTLRDHVPELVKNEKAAKVVILKKATEYVHSLQA 435
Cdd:cd19711   1 RRLESNERERQRMHKLNNAFQALREVIPHVRAEKKLSKIETLTLAKNYIKSLTT 54

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 127604   379 DSERRRNHNILERQRRNDLRSSFLTLRDHVPEL-VKNEK--AAKVVILKKATEYVHSLQAEEHQL---LLEKEKLQ 448
Cdd:cd18923   5 DERRRAQHNEVERRRRDKINNWIVQLSKIIPDCnTDNSKtgASKGGILSKACDYIRELRQTNQRMqetYKEAERLQ 80

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 127604   379 DSERRRNHNILERQRRNDLRSSFLTLRDHVPEL-VKNEKA--AKVVILKKATEYVHSLQAEEHQ 439
Cdd:cd18924   2 DEKRRAQHNEVERRRRDKINNWIVQLSKIIPDCsMESTKSgqSKGGILSKACDYIQELRQSNHR 65

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in USF/MITF family; The USF (upstream stimulatory factor)/MITF (microphthalmia-associated transcription factor) family includes two bHLHzip transcription factor subfamilies. USFs are ubiquitously expressed and key regulators of a wide number of gene regulation networks, including the stress and immune responses, cell cycle and proliferation, lipid and glucid metabolism. USFs recruit chromatin remodeling enzymes and interact with co-activators and the members of the transcription pre-initiation complex. USFs interact with high affinity to E-box regulatory elements. The MITF (also known as microphthalmia-TFE, or MiT) subfamily comprises four genes in mammals (MITF, TFE3, TFEB, and TFEC); each gene has different functions. MITF is involved in neural crest melanocytes development as well as the pigmented retinal epithelium. TFEB is required for vascularization of the mouse placenta. TFE3 is involved in B cell function. TFEC regulates gene expression in macrophages. The MITF subfamily proteins can form homodimers or heterodimers with each other but not with other bHLH or bHLHzip proteins.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 127604   385 NHNILERQRRNDLRSSFLTLRDHVPEL---VKNEKAAKVVILKKATEYVHSLQAEEH 438
Cdd:cd11387   1 SHNAVERRRRDNINEKIQELGSLVPPSrleTKDLKPNKGSILSKAVEYIRELQNQNQ 57

basic helix-loop-helix (bHLH) domain found in protein atonal homolog 8 (ATOH8) and similar proteins; ATOH8, also termed Class A basic helix-loop-helix protein 21 (bHLHa21), or helix-loop-helix protein hATH-6 (hATH6), is a bHLH shear-stress-responsive transcription factor expressed in activated satellite cells and proliferating myoblasts of human skeletal muscle tissue. It regulates endothelial cell proliferation, migration and tube-like structures formation. ATOH8 binds a palindromic (canonical) core consensus DNA sequence 5'-CANNTG- 3' known as an E-box element, possibly as a heterodimer with other bHLH proteins.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|...
gi 127604   381 ERRRNHNILERQRRNDLRSSFLTLRDHVPELVKNEKAAKVVILKKATEYVHSL 433
Cdd:cd11421   7 QRRIEANARERTRVHTISAAFEALRKAVPSYSYNQKLSKLAILRIACSYILAL 59

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in protein Max-associated protein 1 (Mad1) and similar proteins; Mad1, also termed Max dimerization protein 1 (MXD1), or Max dimerizer 1, or protein MAD, 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.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 127604   383 RRNHNILERQRRNDLRSSFLTLRDHVPELVKNEKAAKVVILKKATEYVHSLQAEEHQLLLEKEKLQARQQQLLKKIE 459
Cdd:cd18931   2 RSTHNEMEKNRRAHLRLCLEKLKMLVPLGPESNRHTTLSLLMKAKLHIKKLEDSDRKAVHQIDQLQREQRHLKRQLE 78

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        60
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 127604   382 RRRNHNILERQRRNDLRSSFLTLRDHVPElVKNEKAAKVVILKKATEYVHSLQAEEHQLLLE 443
Cdd:cd18910   5 KRESHNEVERRRKDKINAGINKIGELLPD-RDAKKQSKNMILEQAYKYIVELKKKNDKLLLN 65

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 127604   380 SERRRNHNILERQRRNDLRSSFLTLRD--HVPELVKNEKAAKVVILKKATEYVHSLQAEEHQLLLE 443
Cdd:cd11388   1 PVKKWKHVEAEKKRRNQIKKGFEDLINliNYPRNNNEKRISKSELLNKAVDDIRGLLKANEQLQEE 66

basic helix-loop-helix (bHLH) domain found in scleraxis, transcription factor 15 (TCF-15) and similar proteins; The family includes scleraxis and transcription factor 15 (TCF-15). Scleraxis, also termed SCX, or Class A basic helix-loop-helix protein 41 (bHLHa41), or Class A basic helix-loop-helix protein 48 (bHLHa48), is a bHLH transcription factor that is expressed in sclerotome limb bud cranial and body wall mesenchyme, pericardium and heart valves, ligaments and tendons. It is required for tendon formation ligaments, connective tissue, the diaphragm, and testis development. Scleraxis plays a central role in promoting fibroblast proliferation and matrix synthesis during the embryonic development of tendons. TCF-15, also termed Class A basic helix-loop-helix protein 40 (bHLHa40), or paraxis, or protein bHLH-EC2, is a bHLH transcription factor expressed in caudal lateral and paraxial mesoderm dermomyotome and sclerotome fore limb buds during embryo development. It may function as an early transcriptional regulator involved in the patterning of the mesoderm and in lineage determination of cell types derived from the mesoderm.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|.
gi 127604   383 RRNHNILERQRRNDLRSSFLTLRDHVPELVKNEKAAKVVILKKATEYVHSL 433
Cdd:cd11465   1 RQAANARERDRTHSVNSAFTALRTLIPTEPADRKLSKIETLRLASSYISHL 51

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 127604   386 HNILERQRRNDLRSSFLTLRDHVPE------LVKNEKAakvVILKKATEYVHSLQAE 436
Cdd:cd11389   1 HKVIEKRRRDRINESLAELRRLVPEarkskgSGKLEKA---EILEMTLQHLKALQSS 54

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 127604   382 RRRNHNILERQRRNDLRSSFLTLRDHVPELVKNE--KAAKVVILKKATEYVHSLQAEEHQLLLEKEKLQ 448
Cdd:cd19689   5 RRITHISAEQKRRFNIKLGFDTLHSLVTTLSSQPsiKISKATTLQKTAEYISKLQQERAQLQEEAQRLR 73

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 127604   382 RRRNHNILERQRRNDLRSSFLTLRDHVPELVKNEKAAKVVILKKATEYVHSLQ 434
Cdd:cd11417   1 QRQAANLRERRRMQSINDAFEGLRSHIPTLPYEKRLSKVDTLRLAIGYINFLS 53

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in transcription factor EC (TFEC) and similar proteins; TFEC, also termed Class E basic helix-loop-helix protein 34 (bHLHe34), or transcription factor EC-like (TFEC-L), is a bHLHzip transcriptional regulator that acts as a repressor or an activator and regulates gene expression in macrophages. It plays an important role in the niche to expand hematopoietic progenitors through the modulation of several cytokines.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 127604   378 EDSERRRNHNILERQRRNDLRSSFLTLRDHVPELVKNE-KAAKVVILKKATEYVHSLQAEEHQllleKEKLQARQQQL 454
Cdd:cd18925   1 KERQKKDNHNLIERRRRYNINYRIKELGTLIPKSNDPDmRWNKGTILKASVEYIKWLQKEQQR----ARELEHRQKKL 74