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

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....
gi 62008685     86 DSFKNGYMNAVSEISRVMACTPAMSVDVGKTVMTHLGVEFQRML 129
Cdd:smart00511   1 SSFRSGYRECANEVSRFLSQLPGTDPDVRARLLSHLQTHLNQLL 44

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

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....
gi 62008685     86 DSFKNGYMNAVSEISRVMACTPAMSVDVGKTVMTHLGVEFQRML 129
Cdd:smart00511   1 SSFRSGYRECANEVSRFLSQLPGTDPDVRARLLSHLQTHLNQLL 44

Helix-loop-helix DNA-binding domain;

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 62008685    19 KVKKPLLERQRRARMNKCLDTLKTLVAEFQGDDailRMDKAEMLEAA 65
Cdd:pfam00010   2 REAHNERERRRRDRINDAFDELRELLPTLPPDK---KLSKAEILRLA 45

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 62008685  11 VSKTQHYLKVKKPLLERQRRARMNKCLDTLKTLVAEFQGDDA--ILRMDKAEMLEAALVFMRKQ 72
Cdd:cd19741   1 MSKTYQYRKVTKPLLERKRRARINKCLDELKDLMVEALATEAenVSKLEKADILELTVRHLKKL 64

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

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....
gi 62008685     86 DSFKNGYMNAVSEISRVMACTPAMSVDVGKTVMTHLGVEFQRML 129
Cdd:smart00511   1 SSFRSGYRECANEVSRFLSQLPGTDPDVRARLLSHLQTHLNQLL 44

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 62008685  19 KVKKPLLERQRRARMNKCLDTLKTLVA-EFQGDDAILRMDKAEMLEAALVFMRKQ 72
Cdd:cd11461   1 KLRKPVVEKTRRDRINSSIEQLKTLLEkEFQRHQPNSKLEKADILEMTVSFLKQS 55

basic helix-loop-helix-orange (bHLH-O) domain found in hairy and enhancer of split 2 (HES-2) and similar proteins; HES-2, also termed Class B basic helix-loop-helix protein 40 (bHLHb40), is a bHLH-O transcriptional repressor of genes that require a bHLH protein for their transcription. It acts as a negative regulator through interaction with both E-box and N-box sequences. HES-2 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 62008685  19 KVKKPLLERQRRARMNKCLDTLKTLVAEFQGDDA--ILRMDKAEMLEAALVFMR 70
Cdd:cd11463   6 KTLKPLMEKRRRARINESLNQLKTLILPLVGKDSsrYSKLEKADILEMTVRFLQ 59

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 62008685  19 KVKKPLLERQRRARMNKCLDTLKTLVAEFQGDDAIL--RMDKAEMLEAALVFMRkQVVKQQAPVS 81
Cdd:cd18913   4 KSSKPIMEKRRRARINASLNELKSLLLDALKKDGTRhsKLEKADILEMTVKHLR-QVQRQQLAVA 67

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 62008685  24 LLERQRRARMNKCLDTLKTLVAEFQGDDAILRMDKAEMLEAALVFMRKQ 72
Cdd:cd11389   3 VIEKRRRDRINESLAELRRLVPEARKSKGSGKLEKAEILEMTLQHLKAL 51

basic helix-loop-helix-orange (bHLH-O) domain found in transcription factor HES-6 and similar proteins; HES-6, also termed Class B basic helix-loop-helix protein 41 (bHLHb41), or hairy and enhancer of split 6, or C-HAIRY1, is a bHLH-O transcription factor that is expressed in developing muscle and involved in angiogenesis, myogenesis, neural differentiation and neurogenesis. HES-6 antagonizes Notch signaling but is not regulated by Notch signaling. It is a transcription co-factor associated with stem cell characteristics in neural tissue. It may act as an inhibitor of Hes-1 during neuronal development and forms a heterodimer with HES-1 to prevent its association with transcriptional co-repressors. The overexpression of HES-6 has been reported in metastatic cancers of different origins. HES-6 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
                ....*....|....*....|....*....|....*....|....*
gi 62008685  19 KVKKPLLERQRRARMNKCLDTLKTLVAefqGDDAILRMDKAEMLE 63
Cdd:cd11460   4 KARKPLVEKKRRARINESLQELRLILA---DAELQSKMENAEVLE 45

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 62008685  26 ERQRRARMNKCLDTLKTLVAEFQGDDailRMDKAEMLEAA 65
Cdd:cd00083   1 ERRRRDKINDAFEELKRLLPELPDSK---KLSKASILQKA 37

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
                ....*....|....*....|....*....|....*....|....*...
gi 62008685  25 LERQRRARMNKCLDTLKTLVaEFQGDDAI--LRMDKAEMLEAALVFMR 70
Cdd:cd18933   1 MEKKRRARINVSLEQLKSLL-EKHYSNNIrkRKLEKADILELTVKYLR 47

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 62008685  19 KVKKPLLERQRRARMNKCLDTLKTLVAEFQGDDAILRMDKAEMLEAALVFMR--KQVVKQQ 77
Cdd:cd11409   5 KLPHRLIEKKRRDRINECIAQLKDLLPEHLKLTTLGHLEKAVVLELTLKHLKalTALTEQQ 65

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 62008685  22 KPLLERQRRARMNKCLDTLKTLVAEFQGddailrMDKAEMLEAA---LVFMRKQV 73
Cdd:cd11393   1 HSIAERKRREKINERIRALRSLVPNGGK------TDKASILDEAieyIKFLQEQV 49

basic helix-loop-helix-orange (bHLH-O) domain found in differentially expressed in chondrocytes protein 2 (DEC2) and similar proteins; DEC2, also termed Class E basic helix-loop-helix protein 41 (bHLHe41), or Class B basic helix-loop-helix protein 3 (bHLHb3), or enhancer-of-split and hairy-related protein 1 (SHARP-1), is a bHLH-O transcriptional repressor involved in the regulation of the circadian rhythm by negatively regulating the activity of the clock genes and clock-controlled genes.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*...
gi 62008685  19 KVKKPLLERQRRARMNKCLDTLKTLVAEFQGDDAILRMDKAEMLEAAL 66
Cdd:cd19750  16 KLPHRLIEKKRRDRINECIAQLKDLLPEHLKLTTLGHLEKAVVLELTL 63