Helix-loop-helix DNA-binding domain;

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                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2068648109  23 RRIRKPLMERKRRERINTSLNDLARLLteahlvnaEAPGKQTKLEKADILELTVKHLKDLK 83
Cdd:pfam00010   1 RREAHNERERRRRDRINDAFDELRELL--------PTLPPDKKLSKAEILRLAIEYIKHLQ 53

basic helix-loop-helix-orange (bHLH-O) domain found in hairy and enhancer of split (HES) family; The HES family includes bHLH-O transcriptional regulators that are related to the Drosophila hairy and Enhancer-of-split (HES) proteins. They 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. HES family proteins 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.

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                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 2068648109  30 MERKRRERINTSLNDLARLLTEAHlvnAEAPGKQTKLEKADILELTVKHLKDLKTQQ 86
Cdd:cd11410     1 MEKKRRARINKSLEQLKTLVLEAL---NKDNTRYSKLEKADILEMTVKYLKQLQRSK 54

basic helix-loop-helix-orange (bHLH-O) domain found in hairy and enhancer of split HES-1, HES-4 and similar proteins; The family includes two bHLH-O transcriptional repressors, HES-1 and HES-4. HES-1, also termed Class B basic helix-loop-helix protein 39 (bHLHb39), or hairy homolog, or hairy-like protein (HL), plays an essential role in development of both compartment and boundary cells of the central nervous system. It regulates the maintenance of neural stem/progenitor cells by inhibiting proneural gene expression via Notch signaling. HES-4, also termed Class B basic helix-loop-helix protein 42 (bHLHb42), or bHLH factor Hes4, antagonizes the function of Twist-1 to regulate lineage commitment of bone marrow stromal/stem cells (BMSC). Epigenetic dysregulation of HES-4 is associated with striatal degeneration in postmortem Huntington brains. Both HES-1 and HES-4 are mammalian counterparts of the Hairy and Enhancer of split proteins that play a critical role in many physiological processes including cellular differentiation, cell cycle arrest, apoptosis and self-renewal ability.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2068648109  21 EARRIRKPLMERKRRERINTSLNDLARLLTEAhlvNAEAPGKQTKLEKADILELTVKHLKDLKTQQ 86
Cdd:cd11459     1 EHRKSSKPIMEKRRRARINESLSQLKTLILDA---LKKDSSRHSKLEKADILEMTVKHLRNLQRQQ 63

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.

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gi 2068648109  29 LMERKRRERINTSLNDLARLLTEAHLVNAEApgkqtKLEKADILELTVKHLKDLKTQQ 86
Cdd:cd11389     3 VIEKRRRDRINESLAELRRLVPEARKSKGSG-----KLEKAEILEMTLQHLKALQSST 55

Helix-loop-helix DNA-binding domain;

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                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2068648109  23 RRIRKPLMERKRRERINTSLNDLARLLteahlvnaEAPGKQTKLEKADILELTVKHLKDLK 83
Cdd:pfam00010   1 RREAHNERERRRRDRINDAFDELRELL--------PTLPPDKKLSKAEILRLAIEYIKHLQ 53

basic helix-loop-helix-orange (bHLH-O) domain found in transcription factor HES-3 and similar proteins; HES-3, also termed Class B basic helix-loop-helix protein 43 (bHLHb43), or hairy and enhancer of split 3, is a bHLH-O transcription factor expressed in neural stem and progenitor cells that is involved in tissue regeneration. It regulates gene expression, cell growth, and insulin release. HES-3 is one mammalian counterpart of the Hairy and Enhancer of split proteins that play a critical role in many physiological processes including cellular differentiation, cell cycle arrest, apoptosis and self-renewal ability.

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                  ....*....|....*....|....*....|....*....|....*....|....
gi 2068648109  30 MERKRRERINTSLNDLARLLTEAHLVNAeapgKQTKLEKADILELTVKHLKDLK 83
Cdd:cd18933     1 MEKKRRARINVSLEQLKSLLEKHYSNNI----RKRKLEKADILELTVKYLRSLQ 50

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.

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gi 2068648109  23 RRIRKPLMERKRRERINTSLNDLARLLTEAHlvnaEAPGkQTKLEKADILELTVKHLKDLKT 84
Cdd:cd11407     1 RKKRRGIIEKRRRDRINNSLAELRRLVPTAF----EKQG-SAKLEKAEILQMTVDHLKMLHS 57

basic helix-loop-helix-orange (bHLH-O) domain found in hairy/enhancer-of-split related with YRPW motif-like protein (HEYL) and similar proteins; HEYL, also termed Class B basic helix-loop-helix protein 33 (bHLHb33), or hairy-related transcription factor 3 (HRT-3), is a bHLH-O transcriptional repressor that is strongly expressed in the presomitic mesoderm, the somites, the peripheral nervous system and smooth muscle of all arteries and is a downstream effector of the Notch and transforming growth factor-beta pathways. It promotes neuronal differentiation by activating proneural genes and inhibiting other hairy and enhancer of split (HES) and hairy/enhancer-of-split related with YRPW motif protein (HEY) proteins. HEYL also functions as a tumor suppressor involved in the progression of human cancers.

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gi 2068648109  21 EARRIRKPLMERKRRERINTSLNDLARLLTEAHlvnaEAPGkQTKLEKADILELTVKHLKDL 82
Cdd:cd11447     7 QARKKRRGIIEKRRRDRINSSLSELRRLVPTAF----EKQG-SSKLEKAEILQMTVDHLKML 63

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.

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                  ....*....|....*....|....*....|....*....|....*....|...
gi 2068648109  30 MERKRRERINTSLNDLARLlteahLVNAEAPGKQTKLEKADILELTVKHLKDL 82
Cdd:cd19685     1 SEKRRRQRINDKLNQLKEL-----LPPNLSKQSRSKLSKAEILEMAITELRRL 48

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 2068648109  31 ERKRRERINTSLNDLARLLTEAHLVnaeapGKQTKLEKADILELTVKHLKDLKTQQ 86
Cdd:cd11387     6 ERRRRDNINEKIQELGSLVPPSRLE-----TKDLKPNKGSILSKAVEYIRELQNQN 56

basic helix-loop-helix (bHLH) domain found in Arabidopsis thaliana protein AIG1 and similar proteins; AIG1, also termed AtbHLH32, or EN 54, or protein target of MOOPTEROS 5, is a transcription factor required for MONOPTEROS-dependent root initiation in embryo.

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gi 2068648109  31 ERKRRERINTSLNDLARLLTEAhlvnaeapgkqTKLEKADILELTVKHLKDLKTQ--QVPDGGDDKQPEETAK 101
Cdd:cd11455    15 ERRRRERINSHLATLRTLLPNL-----------SKTDKASLLAEVVQHVKELKRQaaEITTPPDVPTEDEEDT 76

basic helix-loop-helix-orange (bHLH-O) domain found in Drosophila melanogaster protein clockwork orange (Cwo) and similar proteins; Cwo is a bHLH-O transcriptional regulator involved in the regulation of Drosophila circadian rhythms. It functions as both an activator and a repressor of clock gene expression.

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                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 2068648109  29 LMERKRRERINTSLNDLARLLTEAHLVNAeapgkQTKLEKADILELTVKHLKDLKTQ 85
Cdd:cd11440     8 IIEKRRRDRMNNCLADLSRLIPPTYLKKG-----RGRIEKTEIIEMAIKHIKHLQQH 59

basic helix-loop-helix-orange (bHLH-O) domain found in differentially expressed in chondrocytes protein (DEC) family; The DEC family includes two bHLH-O transcriptional repressors, DEC1 and DEC2, which 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. They mediate the circadian rhythm by negatively regulating the activity of the clock genes and clock-controlled genes. They are induced by CLOCK:BMAL1 heterodimer via the CACGTG E-box in the promoter.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2068648109  21 EARRIRKPLMERKRRERINTSLNDLARLLTEaHLvnaeapgKQTKL---EKADILELTVKHLKDL 82
Cdd:cd11409     2 ETYKLPHRLIEKKRRDRINECIAQLKDLLPE-HL-------KLTTLghlEKAVVLELTLKHLKAL 58

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in upstream stimulatory factors, USF1, USF2 and similar proteins; Upstream stimulatory factor 1 and 2 (USF-1 and USF-2) are members of bHLHzip transcription factor family. 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.

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                  ....*....|....*....|....*....|....*....|....*....|....*
gi 2068648109  31 ERKRRERINTSLNDLARLLTeahlvNAEAPGKQTKLEKADILELTVKHLKDLKTQ 85
Cdd:cd11396     6 ERRRRDKINNWIVKLAKIVP-----DCEKDNSKQGQSKGGILSKACDYIQELRSQ 55

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*
gi 2068648109  31 ERKRRERINTSLNDLARLLteahlvnaeaPGkQTKLEKADILELTVKHLKDLKTQ 85
Cdd:cd11393     5 ERKRREKINERIRALRSLV----------PN-GGKTDKASILDEAIEYIKFLQEQ 48

basic helix-loop-helix-Per-ARNT-Sim (bHLH-PAS) domain found in aryl hydrocarbon receptor nuclear translocator (ARNT) family; The ARNT family of bHLH-PAS transcription regulators includes ARNT, ARNT-like proteins (ARNTL and ARNTL2), and Drosophila melanogaster protein cycle. They act as the heterodimeric partner for bHLH-PAS proteins such as aryl hydrocarbon receptor (AhR), hypoxia-inducible factor (HIF), and single-minded (SIM). These bHLH-PAS transcription complexes are involved in transcriptional responses to xenobiotic, hypoxia, and developmental pathways. Heterodimerization of bHLH-PAS proteins with ARNT is mediated by contacts between both the bHLH and the tandem PAS domains. ARNT use bHLH and/or PAS domains to interact with several transcriptional coactivators. It is required for activity of the aryl hydrocarbon (dioxin) receptor. ARNTL, also termed Basic-helix-loop-helix-PAS protein MOP3, or brain and muscle ARNT-like 1 (BMAL1), or Class E basic helix-loop-helix protein 5 (bHLHe5), or member of PAS protein 3, or PAS domain-containing protein 3 (PASD3), or bHLH-PAS protein JAP3, is a member of the bHLH-PAS transcription factor family that forms heterodimers with another bHLH-PAS protein, CLOCK (circadian locomotor output cycle kaput), which regulates circadian rhythm. ARNTL-CLOCK heterodimer complex activates transcription from E-box (CANNTG) elements found in the promoter of circadian responsive genes. ARNTL is highly homologous to ARNT. ARNTL2, also termed Basic-helix-loop-helix-PAS protein MOP9, or brain and muscle ARNT-like 2 (BMAL2), or CYCLE-like factor (CLIF), or Class E basic helix-loop-helix protein 6 (bHLHe6), or member of PAS protein 9, or PAS domain-containing protein 9 (PASD9), is a neuronal bHLH-PAS transcriptional factor, regulating cell cycle progression and preventing cell death, whose sustained expression might ensure brain neuron survival. It also plays important roles in tumor angiogenesis. Protein cycle, also termed brain and muscle ARNT-like 1 (BMAL1), or MOP3, is a putative bHLH-PAS transcription factor involved in the generation of biological rhythms in Drosophila. It activates cycling transcription of Period (PER) and Timeless (TIM) by binding to the E-box (5'-CACGTG-3') present in their promoters.

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                  ....*....|....*....|....*....|....*....|....*....|...
gi 2068648109  31 ERKRRERINTSLNDLARLLTeahLVNAEAPgkqtKLEKADILELTVKHLKDLK 83
Cdd:cd11437     9 EKRRRDKMNAYIQELSALVP---ACNAMSR----KLDKLTVLRMAVQHLKSLR 54

basic helix-loop-helix (bHLH) domain found in the spermatogenesis- and oogenesis-specific basic helix-loop-helix-containing protein (SOHLH) family and similar proteins; The SOHLH family includes two bHLH transcription factors, SOHLH1 and SOHLH2. They are specifically in spermatogonia and oocytes and essential for early spermatogonial and oocyte differentiation. The family also includes transcription factor-like 5 protein (TCFL5) and similar proteins. TCFL5, also termed Cha transcription factor, or HPV-16 E2-binding protein 1 (E2BP-1), is a bHLH transcription factor that plays a crucial role in spermatogenesis. It regulates cell proliferation or differentiation of cells through binding to a specific DNA sequence like other bHLH molecules.

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                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 2068648109  30 MERKRRERINTSLNDLARLLteahlvnaeaPGKQTKLEKADILELTVKHLKDLKTQ 85
Cdd:cd19683     9 KERQRRERIKIACDQLRKLV----------PGCSRKTDKATVFEFTVAYIKFLREK 54

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 2068648109  30 MERKRRERINTSLNDLARLLteahlvnaeaPGKQTKLE-KADILELTVKHLKDLKTQ 85
Cdd:cd18910    12 VERRRKDKINAGINKIGELL----------PDRDAKKQsKNMILEQAYKYIVELKKK 58

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*
gi 2068648109  31 ERKRRERINTSLNDLARLLTeahlvnaeaPGKQTKLEKADILELTVKHLKDLKTQ 85
Cdd:cd11446     5 EKLRRDKLNERFMELSNVLE---------PGRPPKTDKATILGDAIRMLKQLRGE 50