Orange domain; This domain confers specificity among members of the Hairy/E(SPL) family.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....
gi 63055047     84 DSYREGYSACVARLARVLPACRVLEPAVSARLLEHLWRRAASAT 127
Cdd:smart00511   1 SSFRSGYRECANEVSRFLSQLPGTDPDVRARLLSHLQTHLNQLL 44

Helix-loop-helix DNA-binding domain;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 63055047    14 RKSLKPLLEKRRRARINQSLSQLKGLIlPLLGrensNCSKLEKADVLEMTVRFLQEL 70
Cdd:pfam00010   1 RREAHNERERRRRDRINDAFDELRELL-PTLP----PDKKLSKAEILRLAIEYIKHL 52

helix loop helix domain;

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 63055047     19 PLLEKRRRARINQSLSQLKGLILPLLgrensNCSKLEKADVLEMTVRFLQEL 70
Cdd:smart00353   1 NARERRRRRKINEAFDELRSLLPTLP-----KNKKLSKAEILRLAIEYIKSL 47

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.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|
gi 63055047  21 LEKRRRARINQSLSQLKGLILPLLGRENSNCSKLEKADVLEMTVRFLQEL 70
Cdd:cd11410   1 MEKKRRARINKSLEQLKTLVLEALNKDNTRYSKLEKADILEMTVKYLKQL 50

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
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 63055047  12 ELRKSLKPLLEKRRRARINQSLSQLKGLILPLLGRENSNCSKLEKADVLEMTVRFLQEL 70
Cdd:cd18913   1 ESRKSSKPIMEKRRRARINASLNELKSLLLDALKKDGTRHSKLEKADILEMTVKHLRQV 59

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
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 63055047  18 KPLLEKRRRARINQSLSQLKGLILPLLGRENSNcSKLEKADVLEMTVRFLQELPASS 74
Cdd:cd11461   4 KPVVEKTRRDRINSSIEQLKTLLEKEFQRHQPN-SKLEKADILEMTVSFLKQSAKLS 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 63055047  15 KSLKPLLEKRRRARINQSLSQLKGLILPLLGreNSNCSKLEKADVLEMTVRFLQE 69
Cdd:cd18916   1 KSKKPMLERQRRARINKCLSELKTLVAECSG--DDGCLRMDKAEMLETAVAFMRQ 53

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        60
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 63055047  14 RKSLKPLLEKRRRARINQSLSQLKGLILPLLGRENSncSKLEKADVLEMTVRFLQELPAS 73
Cdd:cd11447   9 RKKRRGIIEKRRRDRINSSLSELRRLVPTAFEKQGS--SKLEKAEILQMTVDHLKMLHAT 66

Helix-loop-helix DNA-binding domain;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 63055047    14 RKSLKPLLEKRRRARINQSLSQLKGLIlPLLGrensNCSKLEKADVLEMTVRFLQEL 70
Cdd:pfam00010   1 RREAHNERERRRRDRINDAFDELRELL-PTLP----PDKKLSKAEILRLAIEYIKHL 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 63055047  22 EKRRRARINQSLSQLKGLILPLLGRENSncSKLEKADVLEMTVRFLQEL 70
Cdd:cd19685   2 EKRRRQRINDKLNQLKELLPPNLSKQSR--SKLSKAEILEMAITELRRL 48

Orange domain; This domain confers specificity among members of the Hairy/E(SPL) family.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....
gi 63055047     84 DSYREGYSACVARLARVLPACRVLEPAVSARLLEHLWRRAASAT 127
Cdd:smart00511   1 SSFRSGYRECANEVSRFLSQLPGTDPDVRARLLSHLQTHLNQLL 44

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 63055047  14 RKSLKPLLEKRRRARINQSLSQLKGLILPLLGRENSncSKLEKADVLEMTVRFLQELPA 72
Cdd:cd19748   9 RKRRRGIIEKRRRDRINNSLSELRRLVPSAFEKQGS--AKLEKAEILQMTVDHLKMLHA 65

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        60
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 63055047  14 RKSLKPLLEKRRRARINQSLSQLKGLILPLLGRENSncSKLEKADVLEMTVRFLQELPAS 73
Cdd:cd18920  10 RKKRRGIIEKRRRDRINNSLSELRRLVPTAFEKQGS--AKLEKAEILQMTVDHLKMLQAT 67

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 63055047  22 EKRRRARINQSLSQLKGLIlpllgRENSNCSKLEKADVLEMTVRFLQEL 70
Cdd:cd00083   1 ERRRRDKINDAFEELKRLL-----PELPDSKKLSKASILQKAVEYIREL 44

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
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 63055047  20 LLEKRRRARINQSLSQLKGLI-----LPLLGRensncskLEKADVLEMTVRFLQELPA 72
Cdd:cd11409  10 LIEKKRRDRINECIAQLKDLLpehlkLTTLGH-------LEKAVVLELTLKHLKALTA 60

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        50
                ....*....|....*....|....*....|....*....|....*....|...
gi 63055047  15 KSLKPLLEKRRRARINQSLSQLKGLILPLLGRensncsKLEKADVLEMTVRFL 67
Cdd:cd18908   3 ASSHSLKERLRRERIKSSCDQLRDLLPYIKGR------KLDMASVLEMTVKYI 49

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        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 63055047  22 EKRRRARINQSLSQLKGLIlpllgrenSNCSKLEKADVLEMTVRFLQELP----ASSWPTAAPLPCDS 85
Cdd:cd11455  15 ERRRRERINSHLATLRTLL--------PNLSKTDKASLLAEVVQHVKELKrqaaEITTPPDVPTEDEE 74

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
                ....*....|....*....|....*....|....*....|....*.
gi 63055047  22 EKRRRARINQSLSQLKGLIlPLLGRENsncsklEKADVLEMTVRFL 67
Cdd:cd19683  10 ERQRRERIKIACDQLRKLV-PGCSRKT------DKATVFEFTVAYI 48

basic helix-loop-helix-Per-ARNT-Sim (bHLH-PAS) domain found in the aryl hydrocarbon receptor (AhR) family; The AhR family includes AhR, AhR repressor (AhRR) and Drosophila melanogaster protein spineless. AhR, also termed Ah receptor, or Dioxin receptor (DR), or Class E basic helix-loop-helix protein 76 (bHLHe76), is the only member of bHLH-PAS transcription regulators that bind and be activated by small chemical ligands. It is activated by Dioxin to control the expression of certain genes to influence biological processes such as apoptosis, proliferation, cell growth and differentiation. To form active DNA binding complexes AhR dimerizes with a bHLH-PAS factor ARNT (Aryl hydrocarbon Nuclear Receptor Translocator). AhRR, also termed Class E basic helix-loop-helix protein 77 (bHLHe77), is a member of bHLH-PAS transcription factors that acts as a negative regulator of AhR, playing key roles in development and environmental sensing. AhRR functions by competing with AhR for its partner ARNT. AhRR-ARNT complexes are transcriptionally inactive. Spineless is a bHLH-PAS transcription factor that plays an important role in fly morphogenesis. It is both necessary and sufficient for the formation of the ommatidial mosaic.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*.
gi 63055047  23 KRRRARINQSLSQLKGLiLPLlgrENSNCSKLEKADVLEMTVRFLQ 68
Cdd:cd19696   9 KRHRDRLNSELDELASL-LPF---PEDVISKLDKLSVLRLSVSYLR 50

basic helix-loop-helix (bHLH) domain found in Arabidopsis thaliana phytochrome interacting factors (PIFs) and similar proteins; The family includes several bHLH transcription factors from Arabidopsis thaliana, such as PIFs, ALC, PIL1, SPATULA, and UNE10. PIFs (PIF1, PIF3, PIF4, PIF5, PIF6 and PIF7) have been shown to control light-regulated gene expression. They directly bind to the photoactivated phytochromes and are degraded in response to light signals. ALC, also termed AtbHLH73, or protein ALCATRAZ, or EN 98, is required for the dehiscence of fruit, especially for the separation of the valve cells from the replum. It promotes the differentiation of a strip of labile non-lignified cells sandwiched between layers of lignified cells. PIL1, also termed AtbHLH124, or protein phytochrome interacting factor 3-like 1, or EN 110, is involved in responses to transient and long-term shade. It is required for the light-mediated inhibition of hypocotyl elongation and necessary for rapid light-induced expression of the photomorphogenesis- and circadian-related gene APRR9. PIL1 seems to play a role in multiple PHYB responses, such as flowering transition and petiole elongation. SPATULA, also termed AtbHLH24, or EN 99, plays a role in floral organogenesis. It promotes the growth of carpel margins and of pollen tract tissues derived from them. UNE10, also termed AtbHLH16, or protein UNFERTILIZED EMBRYO SAC 10, or EN 99, is required during the fertilization of ovules by pollen.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|.
gi 63055047  20 LLEKRRRARINQSLSQLKGLIlpllgrenSNCSKLEKADVLEMTVRFLQEL 70
Cdd:cd11445   8 LSERRRRDRINEKMKALQELI--------PNCNKTDKASMLDEAIEYLKSL 50

basic helix-loop-helix-Per-ARNT-Sim (bHLH-PAS) domain found in aryl hydrocarbon receptor nuclear translocator-like protein 2 (ARNTL2) and similar proteins; 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. ARNT-2 heterodimerize with other bHLH-PAS proteins such as aryl hydrocarbon receptor (AhR), hypoxia-inducible factor (HIF), and single-minded (SIM).

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....
gi 63055047  21 LEKRRRARINQSLSQLKGLILPLlgreNSNCSKLEKADVLEMTVRFLQELPASS 74
Cdd:cd11469   8 TEKRRRDKMNNLIEELSAMIPQC----NPMARKLDKLTVLRMAVQHLKSLKGST 57

basic helix-loop-helix (bHLH) domain found in Arabidopsis thaliana Fe-deficiency induced transcription factor 1 (FIT) and similar proteins; The family includes bHLH transcription factors from Arabidopsis thaliana, such as FIT and DYT1. FIT, also termed FER-like iron deficiency-induced transcription factor, or FER-like regulator of iron uptake, or AtbHLH29, or EN 43, is a bHLH transcription factor that is required for the iron deficiency response in plant. It regulates FRO2 at the level of mRNA accumulation and IRT1 at the level of protein accumulation. DYT1, also termed AtbHLH22, or protein dysfunctional tapetum 1, or EN 49, is a bHLH transcription factor involved in the control of tapetum development. It is required for male fertility and pollen differentiation, especially during callose deposition.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*....
gi 63055047  22 EKRRRARINQSLSQLKGLIlpllgrenSNCSKLEKADVLEMTVRFLQEL 70
Cdd:cd11450  11 ERNRRQKLNQRLFALRSVV--------PNITKMDKASIIKDAISYIQEL 51