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 55715330   9 MSKTYQYRKVMKPMLERKRRARINKCLDELKDLMVATLESEGEHVTRLEKADILELTVTHLQKMKQQRQ 77
Cdd:cd19741   1 MSKTYQYRKVTKPLLERKRRARINKCLDELKDLMVEALATEAENVSKLEKADILELTVRHLKKLRRQKS 69

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 55715330   9 MSKTYQYRKVMKPMLERKRRARINKCLDELKDLMVATLESEGEHVTRLEKADILELTVTHLQKMKQQRQ 77
Cdd:cd19741   1 MSKTYQYRKVTKPLLERKRRARINKCLDELKDLMVEALATEAENVSKLEKADILELTVRHLKKLRRQKS 69

Helix-loop-helix DNA-binding domain;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 55715330    16 RKVMKPMLERKRRARINKCLDELKDLMVATLESegehvTRLEKADILELTVTHLQKMK 73
Cdd:pfam00010   1 RREAHNERERRRRDRINDAFDELRELLPTLPPD-----KKLSKAEILRLAIEYIKHLQ 53

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
                  ....*....|....*....|....*....|....*....
gi 55715330    93 FRSGYIHAVNEVSRSLSQLPGMNVSLGTQLMTHLGQRLN 131
Cdd:pfam07527   2 FRAGFNECANEVSRFLSTLEGVDPDLRQRLLNHLQRCLA 40

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 55715330   9 MSKTYQYRKVMKPMLERKRRARINKCLDELKDLMVATLESEGEHVTRLEKADILELTVTHLQKMKQQRQ 77
Cdd:cd19741   1 MSKTYQYRKVTKPLLERKRRARINKCLDELKDLMVEALATEAENVSKLEKADILELTVRHLKKLRRQKS 69

basic helix-loop-helix-orange (bHLH-O) domain found in Drosophila melanogaster protein hairy, protein deadpan and similar proteins; Protein hairy is a bHLH transcriptional repressor of genes that require a bHLH-O protein for their transcription. It acts as a pair-rule protein that regulates embryonic segmentation and adult bristle patterning. Protein deadpan is closely related to the product of the segmentation gene hairy. It is a direct target of Notch signaling and regulates neuroblast self-renewal in Drosophila.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 55715330  14 QYRKVMKPMLERKRRARINKCLDELKDLMVATLESEGEHVTRLEKADILELTVTHLQKMKQQR 76
Cdd:cd18913   1 ESRKSSKPIMEKRRRARINASLNELKSLLLDALKKDGTRHSKLEKADILEMTVKHLRQVQRQQ 63

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        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 55715330  17 KVMKPMLERKRRARINKCLDELKDLMVATLESEGehVTRLEKADILELTVTHlqkMKQQRQHKR 80
Cdd:cd18916   1 KSKKPMLERQRRARINKCLSELKTLVAECSGDDG--CLRMDKAEMLETAVAF---MRQQQTAKN 59

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 55715330  16 RKVMKPMLERKRRARINKCLDELKDLMVATLESEGEHVTRLEKADILELTVTHLQK 71
Cdd:cd11462   1 RKLLKPLVEKRRRDRINRSLEELRVLLLQNTQDEKLKNPKVEKAEILELTVQFLRN 56

basic helix-loop-helix-orange (bHLH-O) domain found in transcription factor HES-5 and similar proteins; HES-5, also termed Class B basic helix-loop-helix protein 38 (bHLHb38), or hairy and enhancer of split 5, is a bHLH-O transcription factor that is involved in cell differentiation and proliferation in a variety of tissues. HES-5 is an essential effector for Notch signaling. It acts as a transducer of Notch signals in brain vascular development. It also acts as a key mediator of Wnt-3a-induced neuronal differentiation and plays a crucial role in normal inner ear hair cell development. HES-5 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        60
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 55715330  17 KVMKPMLERKRRARINKCLDELKDLMVATLESEgEHVTRLEKADILELTVTHLQKMKQQR 76
Cdd:cd11461   1 KLRKPVVEKTRRDRINSSIEQLKTLLEKEFQRH-QPNSKLEKADILEMTVSFLKQSAKLS 59

Helix-loop-helix DNA-binding domain;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 55715330    16 RKVMKPMLERKRRARINKCLDELKDLMVATLESegehvTRLEKADILELTVTHLQKMK 73
Cdd:pfam00010   1 RREAHNERERRRRDRINDAFDELRELLPTLPPD-----KKLSKAEILRLAIEYIKHLQ 53

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
                  ....*....|....*....|....*....|....*....
gi 55715330    93 FRSGYIHAVNEVSRSLSQLPGMNVSLGTQLMTHLGQRLN 131
Cdd:pfam07527   2 FRAGFNECANEVSRFLSTLEGVDPDLRQRLLNHLQRCLA 40

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.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 55715330  23 LERKRRARINKCLDELKDLmvatLESEGEHVTR---LEKADILELTVTHLQKMKQQRQ 77
Cdd:cd18933   1 MEKKRRARINVSLEQLKSL----LEKHYSNNIRkrkLEKADILELTVKYLRSLQNSIQ 54

basic helix-loop-helix-orange (bHLH-O) domain found in hairy/enhancer-of-split related with YRPW motif protein 1 (HEY1) and similar proteins; HEY1, also termed cardiovascular helix-loop-helix factor 2 (CHF-2), or Class B basic helix-loop-helix protein 31 (bHLHb31), or HES-related repressor protein 1, or hairy and enhancer of split-related protein 1 (HESR-1), or hairy-related transcription factor 1 (HRT-1), is a bHLH-O transcriptional repressor that acts as an essential downstream effector of the Notch signaling pathway and may play a fundamental role in vascular development. HEY1 also participates several cancer-related pathways. It acts as a positive regulator of the tumor suppressor p53.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*
gi 55715330  16 RKVMKPMLERKRRARINKCLDELKDLMVATLESEGEhvTRLEKADILELTVTHLQ 70
Cdd:cd19748   9 RKRRRGIIEKRRRDRINNSLSELRRLVPSAFEKQGS--AKLEKAEILQMTVDHLK 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        50
                ....*....|....*....|....*....|....*....|....*....|.
gi 55715330  24 ERKRRARINKCLDELKDLMVATLESEGEhvTRLEKADILELTVTHLQKMKQ 74
Cdd:cd19685   2 EKRRRQRINDKLNQLKELLPPNLSKQSR--SKLSKAEILEMAITELRRLQQ 50

basic helix-loop-helix-orange (bHLH-O) domain found in hairy/enhancer-of-split related with YRPW motif protein 2 (HEY2) and similar proteins; HEY2, also termed cardiovascular helix-loop-helix factor 1 (CHF-1), or Class B basic helix-loop-helix protein 32 (bHLHb32), or HES-related repressor protein 2, or hairy and enhancer of split-related protein 2 (HESR-2), or hairy-related transcription factor 2 (HRT-2), or protein gridlock homolog, is a bHLH-O transcriptional repressor expressed preferentially in the developing and adult cardiovascular system. As a downstream effector of Notch signaling, HEY2 may be required for cardiovascular development. It also plays an important role in neurologic development, as well as in the progression of human cancers.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 55715330  16 RKVMKPMLERKRRARINKCLDELKDLMVATLESEGEhvTRLEKADILELTVTHLQKMK 73
Cdd:cd18920  10 RKKRRGIIEKRRRDRINNSLSELRRLVPTAFEKQGS--AKLEKAEILQMTVDHLKMLQ 65

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.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 55715330  22 MLERKRRARINKCLDELKDLMVATLESEGehVTRLEKADILELTVTHLQKMK---QQRQHK 79
Cdd:cd11409  10 LIEKKRRDRINECIAQLKDLLPEHLKLTT--LGHLEKAVVLELTLKHLKALTaltEQQQQK 68

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        50
                ....*....|....*....|....*....|....*....|....*....|.
gi 55715330  24 ERKRRARINKCLDELKDLMvatleSEGEHVTRLEKADILELTVTHLQKMKQ 74
Cdd:cd00083   1 ERRRRDKINDAFEELKRLL-----PELPDSKKLSKASILQKAVEYIRELQS 46

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 55715330  22 MLERKRRARINKCLDELKDLMVATLESEGEhvTRLEKADILELTVTHLQKMKQQ 75
Cdd:cd11440   8 IIEKRRRDRMNNCLADLSRLIPPTYLKKGR--GRIEKTEIIEMAIKHIKHLQQH 59

basic helix-loop-helix-Per-ARNT-Sim (bHLH-PAS) domain found in nuclear receptor coactivator 1 (NCoA-1) and similar proteins; NCoA-1, also termed Class E basic helix-loop-helix protein 74 (bHLHe74), or protein Hin-2, or RIP160, or renal carcinoma antigen NY-REN-52, or steroid receptor coactivator 1 (SRC-1), is a bHLH-PAS nuclear receptor coactivator that directly binds nuclear receptors and stimulates the transcriptional activities in a hormone-dependent fashion.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 55715330  21 PMLERKRRARINKCLDELKDLMVATLESEGEHVTRLEKADILELTVTHLQKMKQQRQHK 79
Cdd:cd18948   3 QSTEKRRREQENKYLEELAELLSANIGDIDSLSVKPDKCKILKKTVDQIQQMKRLEQEK 61

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 55715330  24 ERKRRARINKCLDELKDLMVATlesegeHVTRLEKADILELTVTHLQK 71
Cdd:cd18908  10 ERLRRERIKSSCDQLRDLLPYI------KGRKLDMASVLEMTVKYIRY 51

basic helix-loop-helix-Per-ARNT-Sim (bHLH-PAS) domain found in steroid receptor coactivator (SRC) family; The SRC family of coactivators includes SRC-1 (NcoA-1/p160), SRC-2(TIF2/GRIP1/NcoA-2) and SRC-3(NcoA-3/pCIP/RAC3/ACTR/pCIP/AIB1/TRAM1), which are critical mediators of steroid receptor action. They contain bHLH-PAS domain at the N-terminal that is followed by receptor interacting domain and C-terminal transcriptional activation domain. SRC coactivators interact with nuclear receptors in a ligand-dependent manner and enhance transcriptional activation by the receptor via histone acetylation/methylation.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|..
gi 55715330  24 ERKRRARINKCLDELKDLMVATLESEGEHVTRLEKADILELTVTHLQKMKQQ 75
Cdd:cd11439   6 EKRRREQENKYIEELAELISASISDMDSLSVKPDKCAILQETVKQIRQIKEQ 57