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 58219048     86 QDYSEGYSWCLQEAVQFL-TLHAAS-DTQMKLLYHFQR 121
Cdd:smart00511   1 SSFRSGYRECANEVSRFLsQLPGTDpDVRARLLSHLQT 38

Helix-loop-helix DNA-binding domain;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 58219048    18 RLRKPVVEKMRRDRINSSIEQLKLLLEQefarHQPNSKLEKADILEMAVSYLKH 71
Cdd:pfam00010   2 REAHNERERRRRDRINDAFDELRELLPT----LPPDKKLSKAEILRLAIEYIKH 51

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

                           10        20        30
                   ....*....|....*....|....*....|....*...
gi 58219048     86 QDYSEGYSWCLQEAVQFL-TLHAAS-DTQMKLLYHFQR 121
Cdd:smart00511   1 SSFRSGYRECANEVSRFLsQLPGTDpDVRARLLSHLQT 38

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 58219048  24 VEKMRRDRINSSIEQLKLLLEQEFARHQP-NSKLEKADILEMAVSYLKHSKA 74
Cdd:cd11410   1 MEKKRRARINKSLEQLKTLVLEALNKDNTrYSKLEKADILEMTVKYLKQLQR 52

Helix-loop-helix DNA-binding domain;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 58219048    18 RLRKPVVEKMRRDRINSSIEQLKLLLEQefarHQPNSKLEKADILEMAVSYLKH 71
Cdd:pfam00010   2 REAHNERERRRRDRINDAFDELRELLPT----LPPDKKLSKAEILRLAIEYIKH 51

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
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 58219048  14 KEKNRLRKPVVEKMRRDRINSSIEQLKLLLEQEFAR-HQPNSKLEKADILEMAVSYLK 70
Cdd:cd19741   5 YQYRKVTKPLLERKRRARINKCLDELKDLMVEALATeAENVSKLEKADILELTVRHLK 62

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.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*
gi 58219048  20 RKPVVEKMRRDRINSSIEQLKLLLEQEFARhQPNSKLEKADILEMAVSYLKHSKA 74
Cdd:cd11407   4 RRGIIEKRRRDRINNSLAELRRLVPTAFEK-QGSAKLEKAEILQMTVDHLKMLHS 57

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 58219048  24 VEKMRRDRINSSIEQLKLLLEQEFARHQPNSKLEKADILEMAVSYLKH 71
Cdd:cd18933   1 MEKKRRARINVSLEQLKSLLEKHYSNNIRKRKLEKADILELTVKYLRS 48

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.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 58219048  15 EKNRLRKPVVEKMRRDRINSSIEQLKLL----LEQEFARHqpnSKLEKADILEMAVSYLK 70
Cdd:cd11459   1 EHRKSSKPIMEKRRRARINESLSQLKTLildaLKKDSSRH---SKLEKADILEMTVKHLR 57

helix loop helix domain;

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 58219048     22 PVVEKMRRDRINSSIEQLKLLLEQefarHQPNSKLEKADILEMAVSYLKH 71
Cdd:smart00353   1 NARERRRRRKINEAFDELRSLLPT----LPKNKKLSKAEILRLAIEYIKS 46

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 58219048  24 VEKMRRDRINSSIEQLKLLLeQEFARHQPNSKLEKADILEMAVSYLKH 71
Cdd:cd19685   1 SEKRRRQRINDKLNQLKELL-PPNLSKQSRSKLSKAEILEMAITELRR 47

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 58219048  18 RLRKPVVEKMRRDRINSSIEQLKLLLeqefARHQPNSKLEKADILEMAV 66
Cdd:cd11460   4 KARKPLVEKKRRARINESLQELRLIL----ADAELQSKMENAEVLELTV 48

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

                           10        20        30
                   ....*....|....*....|....*....|....*...
gi 58219048     86 QDYSEGYSWCLQEAVQFL-TLHAAS-DTQMKLLYHFQR 121
Cdd:smart00511   1 SSFRSGYRECANEVSRFLsQLPGTDpDVRARLLSHLQT 38

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 58219048  25 EKMRRDRINSSIEQLKLLLEQEFARhqpnsKLEKADILEMAVSYLK 70
Cdd:cd18908  10 ERLRRERIKSSCDQLRDLLPYIKGR-----KLDMASVLEMTVKYIR 50

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.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*..
gi 58219048  24 VEKMRRDRINSSIEQLKLLLEQEFARhqpNSKLEKADILEMAVSYLK 70
Cdd:cd11437   8 IEKRRRDKMNAYIQELSALVPACNAM---SRKLDKLTVLRMAVQHLK 51

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.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*...
gi 58219048  24 VEKMRRDRINSSIEQLKLLLEQEFaRHQPNSKLEKADILEMAVSYLKH 71
Cdd:cd11387   5 VERRRRDNINEKIQELGSLVPPSR-LETKDLKPNKGSILSKAVEYIRE 51

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 58219048  16 KNRLRKPVVEKMRRDRINSSIEQLKLLLeqefarhqP--NSKLEKADILEMAVSYLKH 71
Cdd:cd19683   1 KSRERHNAKERQRRERIKIACDQLRKLV--------PgcSRKTDKATVFEFTVAYIKF 50

basic helix-loop-helix (bHLH) domain found in Saccharomyces cerevisiae phosphate system positive regulatory protein PHO4 and similar proteins; PHO4 is a transcriptional activator that regulates the expression of repressible phosphatase under phosphate starvation conditions in Saccharomyces cerevisiae. The PHO4 protein has four functional domains with the bHLH domain at its carboxyl-terminal region. It regulates transcription by binding to promoter of the genes as a homodimer.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 58219048  23 VVEKMRRDRINSSIEQLKLLLEQEFAR----------HQPNSKLE-------KADILEMAVSYLKH 71
Cdd:cd11392   8 VAERGRRDRLNAALKELASLMPAEFVEgkmgadgsasDSNDKEKAaasaagsKAATVEMAIDYIKH 73

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 58219048    88 YSEGYSWCLQEAVQFLTLHAASDTQMK--LLYHFQR 121
Cdd:pfam07527   2 FRAGFNECANEVSRFLSTLEGVDPDLRqrLLNHLQR 37

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in MLX-interacting protein (MLXIP), MLX-interacting protein-like (MLXIPL) and similar proteins; The family includes MLXIP and MLXIPL. MLXIP, also termed Class E basic helix-loop-helix protein 36 (bHLHe36), or transcriptional activator MondoA, is a bHLHZip transcriptional activator that binds DNA as a heterodimer with Mlx. It binds to the canonical E box sequence 5'-CACGTG-3' and plays a role in transcriptional activation of glycolytic target genes. MLXIP is most highly expressed in skeletal muscle and functions as an indirect glucose sensor, by sensing glucose 6-phosphate and shuttling between the nucleus and the cytoplasm. MLXIPL, also termed carbohydrate-responsive element-binding protein (ChREBP), or Class D basic helix-loop-helix protein 14 (bHLHd14), or MLX interactor, or WS basic-helix-loop-helix leucine zipper protein (WS-bHLH), or Williams-Beuren syndrome chromosomal region 14 protein (WBSCR14), is a bHLHZip transcriptional factor integral to the regulation of glycolysis and lipogenesis in the liver. It forms heterodimers with the bHLHZip protein Mlx to bind the DNA sequence 5'-CACGTG-3'.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 58219048  15 EKNRLRKPVVEKMRRDRINSSIEQLKLLLEQefARHQPNSKLEKADILEMAVSYLKHSKA 74
Cdd:cd11405   1 EQRRLSHISAEQKRRFNIKSGFDTLQSLIPS--LGQNPNQKVSKAAMLQKAAEYIKSLKR 58

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        50
                ....*....|....*....|....*....|....*....|....*....|....*
gi 58219048  26 KMRRDRINSSIEQL-KLLLEQEFARhqpnSKLEKADILEMAVSYLkHSKAFVAAA 79
Cdd:cd19696   9 KRHRDRLNSELDELaSLLPFPEDVI----SKLDKLSVLRLSVSYL-RTKNYFQAV 58

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
                ....*....|....*....|....*....|....*....|....*..
gi 58219048  25 EKMRRDRINSSIEQLKLLLeqefarhqPNS-KLEKADILEMAVSYLK 70
Cdd:cd11393   5 ERKRREKINERIRALRSLV--------PNGgKTDKASILDEAIEYIK 43

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 58219048  24 VEKMRRDRINSSIEQLKLLLEQefaRHQPNSKLEKADILEMAVSYLKHSK 73
Cdd:cd11469   8 TEKRRRDKMNNLIEELSAMIPQ---CNPMARKLDKLTVLRMAVQHLKSLK 54

basic helix-loop-helix-Per-ARNT-Sim (bHLH-PAS) domain found in aryl hydrocarbon receptor nuclear translocator-like protein 1 (ARNTL) and similar proteins; 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.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*..
gi 58219048  24 VEKMRRDRINSSIEQLKLLLEQEFARHQpnsKLEKADILEMAVSYLK 70
Cdd:cd11438  14 IEKRRRDKMNSFIDELASLVPTCNAMSR---KLDKLTVLRMAVQHMK 57