basic helix-loop-helix (bHLH) domain found in DNA-binding protein inhibitor ID3 and similar proteins; ID3, also termed Class B basic helix-loop-helix protein 25 (bHLHb25), or helix-loop-helix protein HEIR-1, or ID-like protein inhibitor HLH 1R21, or inhibitor of DNA binding 3, or inhibitor of differentiation 3, is a dominant negative helix-loop-helix (dnHLH) transcriptional regulator (lacking a basic DNA binding domain) which negatively regulates the bHLH transcription factors by forming heterodimers and inhibiting their DNA binding and transcriptional activity. It negatively regulates muscle differentiation by inhibiting the DNA-binding activities of the myogenic regulatory factors.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 156119621  23 AIARGRGKGPAAEEPLSLLDDMNHCYSRLRELVPGVPRGTQLSQVEILQRVIDYILDLQVV 83
Cdd:cd19693    1 SSRNGSNKGPALEEPVSLLYDMNDCYSRLRELVPGVPQGTKLSQVEILQHVIDYILDLQIV 61

basic helix-loop-helix (bHLH) domain found in DNA-binding protein inhibitor ID3 and similar proteins; ID3, also termed Class B basic helix-loop-helix protein 25 (bHLHb25), or helix-loop-helix protein HEIR-1, or ID-like protein inhibitor HLH 1R21, or inhibitor of DNA binding 3, or inhibitor of differentiation 3, is a dominant negative helix-loop-helix (dnHLH) transcriptional regulator (lacking a basic DNA binding domain) which negatively regulates the bHLH transcription factors by forming heterodimers and inhibiting their DNA binding and transcriptional activity. It negatively regulates muscle differentiation by inhibiting the DNA-binding activities of the myogenic regulatory factors.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 156119621  23 AIARGRGKGPAAEEPLSLLDDMNHCYSRLRELVPGVPRGTQLSQVEILQRVIDYILDLQVV 83
Cdd:cd19693    1 SSRNGSNKGPALEEPVSLLYDMNDCYSRLRELVPGVPQGTKLSQVEILQHVIDYILDLQIV 61

helix loop helix domain;

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*
gi 156119621    42 DDMNHCYSRLRELVPGVPRGTQLSQVEILQRVIDYILDLQVVLAE 86
Cdd:smart00353   9 RKINEAFDELRSLLPTLPKNKKLSKAEILRLAIEYIKSLQEELQK 53

basic helix-loop-helix (bHLH) domain found in DNA-binding protein inhibitor ID3 and similar proteins; ID3, also termed Class B basic helix-loop-helix protein 25 (bHLHb25), or helix-loop-helix protein HEIR-1, or ID-like protein inhibitor HLH 1R21, or inhibitor of DNA binding 3, or inhibitor of differentiation 3, is a dominant negative helix-loop-helix (dnHLH) transcriptional regulator (lacking a basic DNA binding domain) which negatively regulates the bHLH transcription factors by forming heterodimers and inhibiting their DNA binding and transcriptional activity. It negatively regulates muscle differentiation by inhibiting the DNA-binding activities of the myogenic regulatory factors.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 156119621  23 AIARGRGKGPAAEEPLSLLDDMNHCYSRLRELVPGVPRGTQLSQVEILQRVIDYILDLQVV 83
Cdd:cd19693    1 SSRNGSNKGPALEEPVSLLYDMNDCYSRLRELVPGVPQGTKLSQVEILQHVIDYILDLQIV 61

basic helix-loop-helix (bHLH) domain found in DNA-binding protein inhibitor ID2 and similar proteins; ID2, also termed Class B basic helix-loop-helix protein 26 (bHLHb26), or inhibitor of DNA binding 2, or inhibitor of differentiation 2, is a dominant negative helix-loop-helix (dnHLH) transcriptional regulator (lacking a basic DNA binding domain) which negatively regulates the bHLH transcription factors by forming heterodimers and inhibiting their DNA binding and transcriptional activity. It has been implicated in the regulation of cell proliferation and differentiation in myogenesis, neurogenesis, and/or hematopoiesis.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 156119621  21 SLAIARGrgKGPAaEEPLSLLDDMNHCYSRLRELVPGVPRGTQLSQVEILQRVIDYILDLQVVL 84
Cdd:cd19692    2 SLGISRS--KTPV-DDPMSLLYNMNDCYSKLKELVPSIPQNKKVSKMEILQHVIDYILDLQIAL 62

basic helix-loop-helix (bHLH) domain found in DNA-binding protein inhibitor ID4 and similar proteins; ID4, also termed Class B basic helix-loop-helix protein 27 (bHLHb27), or inhibitor of DNA binding 4, or inhibitor of differentiation 4, is a dominant negative helix-loop-helix (dnHLH) transcriptional regulator (lacking a basic DNA binding domain) which negatively regulates the bHLH transcription factors by forming heterodimers and inhibiting their DNA binding and transcriptional activity. It plays a role in adipose cell differentiation.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 156119621  35 EEPLSLLDDMNHCYSRLRELVPGVPRGTQLSQVEILQRVIDYILDLQVVL 84
Cdd:cd19694    2 EEALCLQYDMNDCYSRLKRLVPTIPPNKKVSKVEILQHVIDYILDLQLAL 51

helix loop helix domain;

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*
gi 156119621    42 DDMNHCYSRLRELVPGVPRGTQLSQVEILQRVIDYILDLQVVLAE 86
Cdd:smart00353   9 RKINEAFDELRSLLPTLPKNKKLSKAEILRLAIEYIKSLQEELQK 53

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 156119621  42 DDMNHCYSRLRELVPGVPRGTQLSQVEILQRVIDYILDLQ 81
Cdd:cd00083    6 DKINDAFEELKRLLPELPDSKKLSKASILQKAVEYIRELQ 45

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
                 ....*....|....*....|....*....|....*....|..
gi 156119621  43 DMNHCYSRLRELVPGVPRGTQLSQVEILQRVIDYILDLQVVL 84
Cdd:cd11390   14 DLNDAFEALRKVLPTVPPDKKLSKIETLRLAINYIAALSDLL 55

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
                 ....*....|....*....|....*....|....*....|
gi 156119621  45 NHCYSRLRELVPGVPRGTQLSQVEILQRVIDYILDLQVVL 84
Cdd:cd19723   17 NLGFATLREHVPNGRANKKMSKVETLRSAVEYIRQLQQLL 56

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 156119621  21 SLAIARGRGKGPAAEEPlSLLDDMNHCYSRLRELVPGVPRGTQLSQVEILQRVIDYILDLQVVLAE 86
Cdd:cd19714    1 RLESAARRRLAANARER-RRMQGLNTAFDRLRKVVPQWGQDKKLSKYETLQMALSYIMALTRILAE 65

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
                 ....*....|....*....|....*....|....*....|....*.
gi 156119621  44 MNHCYSRLRELVPGVPRGTQLSQVEILQRVIDYILDLQVVLAEPAP 89
Cdd:cd11471   16 INSAFAELRECIPNVPADTKLSKIKTLRLATSYIAYLMDLLAKDDQ 61

basic helix-loop-helix (bHLH) domain found in achaete-scute-like protein 4 (ASCL-4) and similar proteins; ASCL-4, also termed Class A basic helix-loop-helix protein 44 (bHLHa44), or achaete-scute homolog 4 (ASH-4), or Hash4, is a bHLH transcriptional regulator that may be involved in skin development.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|.
gi 156119621  44 MNHCYSRLRELVPGVPRGTQLSQVEILQRVIDYILDLQVVL 84
Cdd:cd19746   23 VNEGYARLREHLPQELADKRLSKVETLRAAIDYIKHLQELL 63

basic helix-loop-helix (bHLH) domain found in heart- and neural crest derivatives-expressed protein (HAND) family; The HAND family includes two bHLH transcription factors, HAND1 and HAND2. 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), plays an essential role in both trophoblast-giant cells differentiation and in cardiac morphogenesis. 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 essential for cardiac morphogenesis, particularly for the formation of the right ventricle and of the aortic arch arteries.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|.
gi 156119621  44 MNHCYSRLRELVPGVPRGTQLSQVEILQRVIDYILDLQVVL 84
Cdd:cd11466   16 INSAFADLRECIPNVPADTKLSKIKTLRLATSYIAYLMDVL 56

basic helix-loop-helix (bHLH) domain found in Arabidopsis thaliana paclobutrazol resistance (PRE) family; The PRE family includes several bHLH transcription factors from Arabidopsis thaliana, such as PRE1-6. PRE1 (also termed AtbHLH136, or protein banquo 1), PRE2 (also termed AtbHLH134, or protein banquo 2, or EN 52), PRE4 (also termed AtbHLH161, or protein banquo 3), and PRE5 (also termed AtbHLH164) are atypical and probable non DNA-binding bHLH transcription factors that integrate multiple signaling pathways to regulate cell elongation and plant development. PRE3 (also termed AtbHLH135, or protein activation-tagged BRI1 suppressor 1, or ATBS1, or protein target of MOOPTEROS 7, or EN 67) is an atypical and probable non DNA-binding bHLH transcription factor required for MONOPTEROS-dependent root initiation in embryo. It promotes the correct definition of the hypophysis cell division plane. PRE5 (also termed AtbHLH163, or protein KIDARI) is an atypical and probable non DNA-binding bHLH transcription factor that regulates light-mediated responses in day light conditions by binding and inhibiting the activity of the bHLH transcription factor HFR1, a critical regulator of light signaling and shade avoidance.

                         10        20        30
                 ....*....|....*....|....*....|....*..
gi 156119621  48 YSRLRELVPGVPRGTQLSQVEILQRVIDYILDLQVVL 84
Cdd:cd11442   16 YSRLRALLPSIATSDKVSKATVLEEACNYIRNLHREV 52

basic helix-loop-helix (bHLH) domain found in Drosophila melanogaster helix loop helix protein 3B (dHLH3B) and similar proteins; Drosophila HLH3B is an uncharacterized bHLH transcription factor that belongs to the T-cell acute lymphocytic leukemia protein/ lymphoblastic leukemia-derived sequence (TAL/LYL) family.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|..
gi 156119621  43 DMNHCYSRLRELVPGVPRGTQLSQVEILQRVIDYILDLQVVL 84
Cdd:cd19708   15 NVNGAFAELRKLVPTHPPDKKLSKNEILRLAIKYIRLLSNVL 56

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
                 ....*....|....*....|....*....|....*....
gi 156119621  43 DMNHCYSRLRELVPgVPRGTQLSQVEILQRVIDYILDLQ 81
Cdd:cd19690   14 EMKELFEDLRDALP-QERGTKASKWEILTKAISYIQQLK 51

basic helix-loop-helix (bHLH) domain found in musculin and similar proteins; Musculin, also termed activated B-cell factor 1 (ABF-1), or Class A basic helix-loop-helix protein 22 (bHLHa22), is a bHLH transcription factor expressed in activated B lymphocytes. It acts as a transcription repressor capable of inhibiting the transactivation capability of TCF3/E47. Musculin may play a role in regulating antigen-dependent B-cell differentiation. The mouse homolog, musculin, is suggested to be a repressor of myogenesis that is expressed in developing muscle and in the spleen. Musculin heterodimerizes with products of the E2A gene.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 156119621  18 SERSLAIARGRGKgpaaeeplslLDDMNHCYSRLRELVPGVPRGTQLSQVEILQRVIDYILDLQVVLAE 86
Cdd:cd19703    3 SQRNAANARERAR----------MRVLSKAFSRLKTSLPWVPPDTKLSKLDTLRLASSYIAHLRQLLQE 61

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
                 ....*....|....*....|....*....|....*....|.
gi 156119621  44 MNHCYSRLRELVP---GVPRGTQLSQVEILQRVIDYILDLQ 81
Cdd:cd19685    9 INDKLNQLKELLPpnlSKQSRSKLSKAEILEMAITELRRLQ 49

basic helix-loop-helix-orange (bHLH-O) domain found in hairy and enhancer of split (HES)-related repressor protein (HERP) family; HERP (also called Hey/Hesr/HRT/CHF/gridlock) proteins corresponds to a family of bHLH-O transcriptional repressors that are related to the Drosophila hairy and Enhancer-of-split proteins and act as downstream effectors of Notch signaling. 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 are involved in cardiovascular development and have roles in somitogenesis, myogenesis and gliogenesis.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|...
gi 156119621  42 DDMNHCYSRLRELVPGV--PRGTQ-LSQVEILQRVIDYILDLQ 81
Cdd:cd11407   14 DRINNSLAELRRLVPTAfeKQGSAkLEKAEILQMTVDHLKMLH 56