basic helix-loop-helix-orange (bHLH-O) domain found in Drosophila melanogaster Enhancer of split proteins, E(spl)m5, E(spl)m8 and similar proteins; The family includes two bHLH-O transcriptional repressors, E(spl)m5 and E(spl)m8, which participate in the control of cell fate choice by uncommitted neuroectodermal cells in the embryo. They bind DNA on N-box motifs, 5'-CACNAG-3'.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 113205017  12 KVKKPMLERQRRARMNKCLDNLKTLVAELRGDDGILRMDKAEMLESAVIFMRQQKTPKK 70
Cdd:cd18916    1 KSKKPMLERQRRARINKCLSELKTLVAECSGDDGCLRMDKAEMLETAVAFMRQQQTAKN 59

basic helix-loop-helix-orange (bHLH-O) domain found in Drosophila melanogaster Enhancer of split proteins, E(spl)m5, E(spl)m8 and similar proteins; The family includes two bHLH-O transcriptional repressors, E(spl)m5 and E(spl)m8, which participate in the control of cell fate choice by uncommitted neuroectodermal cells in the embryo. They bind DNA on N-box motifs, 5'-CACNAG-3'.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 113205017  12 KVKKPMLERQRRARMNKCLDNLKTLVAELRGDDGILRMDKAEMLESAVIFMRQQKTPKK 70
Cdd:cd18916    1 KSKKPMLERQRRARINKCLSELKTLVAECSGDDGCLRMDKAEMLETAVAFMRQQQTAKN 59

helix loop helix domain;

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 113205017    16 PMLERQRRARMNKCLDNLKTLVAELRGDDgilRMDKAEMLESAVIFMRQQK 66
Cdd:smart00353   1 NARERRRRRKINEAFDELRSLLPTLPKNK---KLSKAEILRLAIEYIKSLQ 48

Helix-loop-helix DNA-binding domain;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 113205017   11 QKVKKPMLERQRRARMNKCLDNLKTLVAELRGDDgilRMDKAEMLESAVIFMRQ 64
Cdd:pfam00010   1 RREAHNERERRRRDRINDAFDELRELLPTLPPDK---KLSKAEILRLAIEYIKH 51

basic helix-loop-helix-orange (bHLH-O) domain found in Drosophila melanogaster Enhancer of split proteins, E(spl)m5, E(spl)m8 and similar proteins; The family includes two bHLH-O transcriptional repressors, E(spl)m5 and E(spl)m8, which participate in the control of cell fate choice by uncommitted neuroectodermal cells in the embryo. They bind DNA on N-box motifs, 5'-CACNAG-3'.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 113205017  12 KVKKPMLERQRRARMNKCLDNLKTLVAELRGDDGILRMDKAEMLESAVIFMRQQKTPKK 70
Cdd:cd18916    1 KSKKPMLERQRRARINKCLSELKTLVAECSGDDGCLRMDKAEMLETAVAFMRQQQTAKN 59

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        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 113205017   4 TTKTQIYQKVKKPMLERQRRARMNKCLDNLKTLVAE--LRGDDGILRMDKAEMLESAVIFMRQQKTPKK 70
Cdd:cd19741    1 MSKTYQYRKVTKPLLERKRRARINKCLDELKDLMVEalATEAENVSKLEKADILELTVRHLKKLRRQKS 69

basic helix-loop-helix-orange (bHLH-O) domain found in hairy and enhancer of split 7 (HES-7) and similar proteins; HES-7, also termed Class B basic helix-loop-helix protein 37 (bHLHb37), or bHLH factor Hes7, is a bHLH-O transcriptional repressor that is expressed in an oscillatory manner and acts as a key regulator of the pace of the segmentation clock. It is regulated by the Notch and Fgf/Mapk pathways. HES-7 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.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 113205017  12 KVKKPMLERQRRARMNKCLDNLKTLVAELRGDDGIL--RMDKAEMLESAVIFMRQQKT 67
Cdd:cd11462    2 KLLKPLVEKRRRDRINRSLEELRVLLLQNTQDEKLKnpKVEKAEILELTVQFLRNSSL 59

Hairy Orange; The Orange domain is found in the Drosophila proteins Hesr-1, Hairy, and Enhancer of Split. The Orange domain is proposed to mediate specific protein-protein interaction between Hairy and Scute.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|
gi 113205017   82 SFKNGYMNAVNEVSRVMASTPGMSVDLGKSVMTHLGRVYK 121
Cdd:pfam07527   1 RFRAGFNECANEVSRFLSTLEGVDPDLRQRLLNHLQRCLA 40

Helix-loop-helix DNA-binding domain;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 113205017   11 QKVKKPMLERQRRARMNKCLDNLKTLVAELRGDDgilRMDKAEMLESAVIFMRQ 64
Cdd:pfam00010   1 RREAHNERERRRRDRINDAFDELRELLPTLPPDK---KLSKAEILRLAIEYIKH 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
                 ....*....|....*....|....*....|....*....|....*..
gi 113205017  19 ERQRRARMNKCLDNLKTLVAELRGDDGILRMDKAEMLESAVIFMRQQ 65
Cdd:cd11389    5 EKRRRDRINESLAELRRLVPEARKSKGSGKLEKAEILEMTLQHLKAL 51

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 113205017  19 ERQRRARMNKCLDNLKTLVAELRGDDgilRMDKAEMLESAVIFMRQQK 66
Cdd:cd00083    1 ERRRRDKINDAFEELKRLLPELPDSK---KLSKASILQKAVEYIRELQ 45

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 113205017  19 ERQRRARMNKCLDNLKTLVAELRGDDGILRMDKAEMLESAVIFMR 63
Cdd:cd19685    2 EKRRRQRINDKLNQLKELLPPNLSKQSRSKLSKAEILEMAITELR 46

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.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 113205017  19 ERQRRARMNKCLDNLKTLVAeLRGDDgilrMDKAEMLESAV---IFMRQQ 65
Cdd:cd19683   10 ERQRRERIKIACDQLRKLVP-GCSRK----TDKATVFEFTVayiKFLREK 54

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.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 113205017  17 MLERQRRARMNKCLDNLKTLVAELRGDDGILRMDKAEMLESAVIFMRQQK 66
Cdd:cd11440    8 IIEKRRRDRMNNCLADLSRLIPPTYLKKGRGRIEKTEIIEMAIKHIKHLQ 57

basic helix-loop-helix-orange (bHLH-O) domain found in hairy and enhancer of split-related protein HELT and similar proteins; HELT, also termed HES/HEY-like transcription factor, is a bHLH-O 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. HELT could homodimerize and heterodimerize with other bHLH-O protein such as HES-5 or HEY-2 and bound to E box to repress gene transcription.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*..
gi 113205017  17 MLERQRRARMNKCLDNLKTLVAELRGDDGILRMDKAEMLESAVIFMR 63
Cdd:cd11408    4 VIEKRRRDRINRCLNELGKTVPMALAKQTSGKLEKAEILEMTVQYLR 50

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.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 113205017   4 TTKTQIY-QKVKKPMLERQRRARMNKCLDNLKTLVAELRGDDGILRMDKAEMLESAV 59
Cdd:cd11447    1 TTSSQIQaRKKRRGIIEKRRRDRINSSLSELRRLVPTAFEKQGSSKLEKAEILQMTV 57

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.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 113205017  19 ERQRRARMNKCLDNLKTLVAELrgddgiLRMDKAEMLESAVifmRQQKTPKKVAQE 74
Cdd:cd11455   15 ERRRRERINSHLATLRTLLPNL------SKTDKASLLAEVV---QHVKELKRQAAE 61