helix loop helix domain;

                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|
gi 752893664     13 ERDRRKRMNTYFKTLADLLPPHQEGRKLNKVDILIHATKYIKDLHSRTEE 62
Cdd:smart00353    4 ERRRRRKINEAFDELRSLLPTLPKNKKLSKAEILRLAIEYIKSLQEELQK 53

helix loop helix domain;

                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|
gi 752893664     13 ERDRRKRMNTYFKTLADLLPPHQEGRKLNKVDILIHATKYIKDLHSRTEE 62
Cdd:smart00353    4 ERRRRRKINEAFDELRSLLPTLPKNKKLSKAEILRLAIEYIKSLQEELQK 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 752893664   13 ERDRRKRMNTYFKTLADLLPPHQEGRKLNKVDILIHATKYIKDLHS 58
Cdd:cd00083     1 ERRRRDKINDAFEELKRLLPELPDSKKLSKASILQKAVEYIRELQS 46

helix loop helix domain;

                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|
gi 752893664     13 ERDRRKRMNTYFKTLADLLPPHQEGRKLNKVDILIHATKYIKDLHSRTEE 62
Cdd:smart00353    4 ERRRRRKINEAFDELRSLLPTLPKNKKLSKAEILRLAIEYIKSLQEELQK 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 752893664   13 ERDRRKRMNTYFKTLADLLPPHQEGRKLNKVDILIHATKYIKDLHS 58
Cdd:cd00083     1 ERRRRDKINDAFEELKRLLPELPDSKKLSKASILQKAVEYIRELQS 46

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 752893664   13 ERDRRKRMNTYFKTLADLLPPHQEGRKLNKVDILIHATKYIKDL 56
Cdd:cd11390     8 ERRRMHDLNDAFEALRKVLPTVPPDKKLSKIETLRLAINYIAAL 51

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 752893664   13 ERDRRKRMNTYFKTLADLLPPhqeGRKLNKVDILIHATKYIKDLHSRTEEL 63
Cdd:cd11393     5 ERKRREKINERIRALRSLVPN---GGKTDKASILDEAIEYIKFLQEQVKVL 52

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 752893664   13 ERDRRKRMNTYFKTLADLLPPHQ---EGRKLNKVDILIHATKYIKDLHSRTEE 62
Cdd:cd11387     6 ERRRRDNINEKIQELGSLVPPSRletKDLKPNKGSILSKAVEYIRELQNQNQE 58

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in transcription factor AP-4 (TFAP4) and similar proteins; TFAP4, also termed activating enhancer-binding protein 4, or Class C basic helix-loop-helix protein 41 (bHLHc41), is a bHLHzip transcription factor that activates both viral and cellular genes involved in the regulation of cellular proliferation, stemness, and epithelial-mesenchymal transition by binding to the symmetrical DNA sequence 5'-CAGCTG-3'.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 752893664   13 ERDRRKRMNTYFKTLADLLPpHQEGRKLNKVDILIHATKYIKDLHSRTEEL 63
Cdd:cd11419    12 ERRRMQSINAGFQSLRTLLP-HCDGEKLSKAAILQQTAEYIFSLEQEKTRL 61

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        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 752893664    8 KAKTWERDRRKRMNTYFKTLADLLPPHQEGRKLNKVDILIHATKYIKDLH 57
Cdd:cd11422     3 VANARERERVRNLNSGFSKLRRIVPLIPRDRKPSKVDTLKGATEYIRLLQ 52

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        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 752893664   13 ERDRRKRMNTYFKTLADLLPPHQegrKLNKVDILIHATKYIKDLHSRTEELFSNRATEAHK 73
Cdd:cd11451    10 ERRRREKLNERFITLRSMVPFVT---KMDKVSILGDAIEYLKQLQRRVEELESRRKSSDTE 67

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 752893664   13 ERDRRKRMNTYFKTLADLLP-PHQEGRklnkVDILIHATKYIKDLHSRTEELFSNRATEAHKEE 75
Cdd:cd18918     5 ERERREKLNEKFSDLRNLIPnPTKNDR----ASILSDAIKYINELQRTVEELKSLVEKKRCGER 64

basic helix-loop-helix (bHLH) domain found in Fer3-like protein (FERD3L), pancreas transcription factor 1 subunit alpha (PTF1A) and similar proteins; The family corresponds to a group of bHLH transcription factors, including FERD3L and PTF1A. 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 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. 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 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
                  ....*....|....*....|....*....|....*....|....
gi 752893664   13 ERDRRKRMNTYFKTLADLLPPHQEGRKLNKVDILIHATKYIKDL 56
Cdd:cd19686     9 ERKRMRSINDAFDGLRRHIPTFPYEKRLSKVDTLRLAIQYINFL 52

basic helix-loop-helix (bHLH) domain found in transcription factor 15 (TCF-15) and similar proteins; 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 752893664    4 KENTKAKTWERDRRKRMNTYFKTLADLLPPHQEGRKLNKVDILIHATKYIKDL 56
Cdd:cd11470     7 KQRQAANARERDRTQSVNTAFTALRTLIPTEPVDRKLSKIETLRLASSYIAHL 59

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
                  ....*....|....*....|....*....|....*....|....
gi 752893664   13 ERDRRKRMNTYFKTLADLLPPHQEGRKLNKVDILIHATKYIKDL 56
Cdd:cd11418     9 ERRRVQAVNDAFDRLRQHVPYLKRRKKLSKVKTLRRAIEYIRHL 52

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 752893664   13 ERDRRKRMNTYFKTLADLLPP---HQEGRKLNKVDILIHATKYIKDLHS 58
Cdd:cd19685     2 EKRRRQRINDKLNQLKELLPPnlsKQSRSKLSKAEILEMAITELRRLQQ 50

basic helix-loop-helix-orange (bHLH-O) domain found in Drosophila melanogaster enhancer of split mbeta protein (ESMB) and similar proteins; ESMB, also termed E(spl)mbeta, or HLH-mbeta, or split locus enhancer protein mA, is a bHLH-O transcriptional repressor of genes that require a bHLH protein for their transcription. It is involved in the neural-epidermal lineage decision during early neurogenesis. The family also includes Enhancer of split m7 protein (also known as E(spl)m7), which acts as a transcriptional repressor that participates in the control of cell fate choice by uncommitted neuroectodermal cells in the embryo.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 752893664   13 ERDRRKRMNTYFKTLADLLPP--HQEGR---KLNKVDILIHATKYIKDLHSR 59
Cdd:cd19741    16 ERKRRARINKCLDELKDLMVEalATEAEnvsKLEKADILELTVRHLKKLRRQ 67

basic helix-loop-helix (bHLH) domain found in the DNA-binding protein inhibitor (ID) family; The ID family includes a dominant negative group of helix-loop-helix (dnHLH) proteins, ID1-4, that are negative regulators of bHLH transcription factors. They contain the HLH-dimerization domain but lack the basic domain necessary for DNA-binding. ID proteins inhibit binding to DNA and transcriptional transactivation by heterodimerization with bHLH proteins. They also interact with many non-bHLH proteins in complex networks. ID proteins have been implicated in regulating gene expression as well as cell-cycle progression. Whereas ID-1, ID-2 and ID-3, are generally considered as tumor promoters, ID4 on the contrary has emerged as a tumor suppressor.

                          10        20        30
                  ....*....|....*....|....*....|....*..
gi 752893664   20 MNTYFKTLADLLPPHQEGRKLNKVDILIHATKYIKDL 56
Cdd:cd19684     8 MQDCYSKLKELVPTIPQNKKVSKVEILQHVIDYILDL 44

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 752893664   13 ERDRRKRMNTYFKTLADLLPPHQEgRKLNKVDILIHATKYIKDLHSRTEELfsnRATEAH-KEELIRLKKLVTQLM 87
Cdd:cd11446     5 EKLRRDKLNERFMELSNVLEPGRP-PKTDKATILGDAIRMLKQLRGEVQKL---KEENSSlQEESKELKAEKNELR 76

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
                  ....*....|....*....|....*....|....*....|....*..
gi 752893664   13 ERDRRKRMNTYFKTLADLLpPHQEGRKLNKVDILIHATKYIKDLHSR 59
Cdd:cd18908    10 ERLRRERIKSSCDQLRDLL-PYIKGRKLDMASVLEMTVKYIRYIQER 55

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
                  ....*....|....*....|....*....|....*....|....*....|....
gi 752893664   10 KTWERDRRKRMNTYFKTLADLLpPHQEGRKLNKVDILIHATKYIKDLHSRTEEL 63
Cdd:cd19690     5 KLAERKRRKEMKELFEDLRDAL-PQERGTKASKWEILTKAISYIQQLKRHIREL 57

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in sterol regulatory element-binding protein (SREBP) family and similar proteins; 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. The family also includes Saccharomyces cerevisiae transcription factor HMS1 (also termed high-copy MEP suppressor protein 1) and serine-rich protein TYE7. HMS1 is a putative bHLHzip transcription factor involved in exit from mitosis and pseudohyphal differentiation. TYE7, also termed basic-helix-loop-helix protein SGC1, is a putative bHLHzip transcription activator required for Ty1-mediated glycolytic gene expression. TYE7 N-terminal is extremely rich in serine residues. It binds DNA on E-box motifs, 5'-CANNTG-3'. TYE7 is not essential for growth.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 752893664   13 ERDRRKRMNTYFKTLADLLPPHQ---------------EGRKLNKVDILIHATKYIKDLHSRTEEL 63
Cdd:cd11395    11 EKRYRSNLNTKIERLRDAIPSLRspegksddgglgglaPTTKLSKATILTKAIEYIRHLEQENERL 76