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

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 105990526   124 MDYRSlGFRECLAEVARYLSIIEGLDasDPLRVRLVSHLNNYASQRE 170
Cdd:smart00511   1 SSFRS-GYRECANEVSRFLSQLPGTD--PDVRARLLSHLQTHLNQLL 44

Helix-loop-helix DNA-binding domain;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 105990526   50 RKRRRGIIEKRRRDRINNSLSELRRLVPSAFEKQvmeqgsaKLEKAEILQMTVDHLKMLH 109
Cdd:pfam00010   1 RREAHNERERRRRDRINDAFDELRELLPTLPPDK-------KLSKAEILRLAIEYIKHLQ 53

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

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 105990526   124 MDYRSlGFRECLAEVARYLSIIEGLDasDPLRVRLVSHLNNYASQRE 170
Cdd:smart00511   1 SSFRS-GYRECANEVSRFLSQLPGTD--PDVRARLLSHLQTHLNQLL 44

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        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 105990526  42 TTSSQILARKRRRGIIEKRRRDRINNSLSELRRLVPSAFEKqvmeQGSAKLEKAEILQMTVDHLKMLHTAGGKGYFDA 119
Cdd:cd11447    1 TTSSQIQARKKRRGIIEKRRRDRINSSLSELRRLVPTAFEK----QGSSKLEKAEILQMTVDHLKMLHATGGAGKFDA 74

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        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 105990526  50 RKRRRGIIEKRRRDRINNSLSELRRLVPSAFEKqvmeQGSAKLEKAEILQMTVDHLKMLHTAG 112
Cdd:cd11407    1 RKKRRGIIEKRRRDRINNSLAELRRLVPTAFEK----QGSAKLEKAEILQMTVDHLKMLHSKG 59

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 105990526  57 IEKRRRDRINNSLSELRRLVPSAFEKQVMEQgsAKLEKAEILQMTVDHLKMLH 109
Cdd:cd11410    1 MEKKRRARINKSLEQLKTLVLEALNKDNTRY--SKLEKADILEMTVKYLKQLQ 51

Helix-loop-helix DNA-binding domain;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 105990526   50 RKRRRGIIEKRRRDRINNSLSELRRLVPSAFEKQvmeqgsaKLEKAEILQMTVDHLKMLH 109
Cdd:pfam00010   1 RREAHNERERRRRDRINDAFDELRELLPTLPPDK-------KLSKAEILRLAIEYIKHLQ 53

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 105990526  51 KRRRGIIEKRRRDRINNSLSELRRLvpsaFEKQ-VMEQGSAKLEKAEILQMTVDHLK 106
Cdd:cd11461    1 KLRKPVVEKTRRDRINSSIEQLKTL----LEKEfQRHQPNSKLEKADILEMTVSFLK 53

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 105990526  49 ARKRRRGIIEKRRRDRINNSLSELRRLVPSAFEKQVMEQgsAKLEKAEILQMTVDHLKML 108
Cdd:cd11459    2 HRKSSKPIMEKRRRARINESLSQLKTLILDALKKDSSRH--SKLEKADILEMTVKHLRNL 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
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 105990526  50 RKRRRGIIEKRRRDRINNSLSELRRLVPSAFEKQVMEQgsAKLEKAEILQMTVDHLKML 108
Cdd:cd18913    3 RKSSKPIMEKRRRARINASLNELKSLLLDALKKDGTRH--SKLEKADILEMTVKHLRQV 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        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 105990526  39 MSPTTSSqilaRKRRRGIIEKRRRDRINNSLSELRRLVPSAFEKQvmEQGSAKLEKAEILQMTVDHLKMLH 109
Cdd:cd19741    1 MSKTYQY----RKVTKPLLERKRRARINKCLDELKDLMVEALATE--AENVSKLEKADILELTVRHLKKLR 65

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 105990526  58 EKRRRDRINNSLSELRRLVPSafekqvmEQGSAKLEKAEILQMTVDHLKMLH 109
Cdd:cd00083    1 ERRRRDKINDAFEELKRLLPE-------LPDSKKLSKASILQKAVEYIRELQ 45

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        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 105990526  57 IEKRRRDRINNSLSELRRLVPSAFekqvmeQGSAKLEKAEILQMTVDHLKMLHTAG 112
Cdd:cd11437    8 IEKRRRDKMNAYIQELSALVPACN------AMSRKLDKLTVLRMAVQHLKSLRGTG 57

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        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 105990526  50 RKRRRGIIEKRRRDRINNSLSELRRLVPSAfEKQvmeqgsAKLEKAEILQMTV 102
Cdd:cd11460    3 RKARKPLVEKKRRARINESLQELRLILADA-ELQ------SKMENAEVLELTV 48

basic helix-loop-helix-Per-ARNT-Sim (bHLH-PAS) domain found in Drosophila melanogaster protein cycle and similar proteins; 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        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 105990526  57 IEKRRRDRINNSLSELRRLVPSAFEKqvmeqgSAKLEKAEILQMTVDHLKMLHTAG 112
Cdd:cd19726    8 IEKRRRDKMNTYITELSSMIPMCNAM------SRKLDKLTVLRMAVQHMKTLRGSL 57

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 105990526  50 RKRRRGIIEKRRRDRINNSLSELRRLVPSAFEKQvmEQGSAKLEKAEILQMTVDHLKML 108
Cdd:cd11463    5 RKTLKPLMEKRRRARINESLNQLKTLILPLVGKD--SSRYSKLEKADILEMTVRFLQDL 61

basic helix-loop-helix-Per-ARNT-Sim (bHLH-PAS) domain family; bHLH-PAS domain has been found in a large group of bHLH transcription regulators that are involved in gene expression responding to environmental change and controlling aspects of neural development, including proteins from aryl hydrocarbon receptor nuclear translocator (ARNT) family, hypoxia-inducible factor (HIF) family, aryl hydrocarbon receptor (AhR) family, neuronal PAS domain-containing protein (NPAS) family, Circadian locomotor output cycles protein kaput (CLOCK)-like family, and single-minded (SIM) family. bHLH-PAS transcriptional regulatory factors have a bHLH DNA-binding domain followed by two PAS domains and a C-terminal activation or repression domain. bHLH-PAS family members can be divided into class I and class II based on their dimerization partner. bHLH-PAS class I factors include AhR, HIF and SIM. The best characterized bHLH-PAS Class II protein is the ubiquitous ARNT. Some members of bHLH-PAS family act as transcriptional coactivators (such as NCoA) that lack the ability to dimerize and bind DNA.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 105990526  50 RKRRRGIiEKRRRDRINNSLSELRRLVPSAfekqvmEQGSAKLEKAEILQMTVDHLKM 107
Cdd:cd11391    1 REKSREA-AKKRRDKENAEISELASLLPLP------PAVGSKLDKLSVLRLAVAYLRL 51

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 105990526  56 IIEKRRRDRINNSLSELRRLVPSAFEKQVMeqgsAKLEKAEILQMTVDHLKML 108
Cdd:cd11409   10 LIEKKRRDRINECIAQLKDLLPEHLKLTTL----GHLEKAVVLELTLKHLKAL 58

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        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 105990526  57 IEKRRRDRINNSLSELRRLVPSAfekQVMeqgSAKLEKAEILQMTVDHLKMLHTA 111
Cdd:cd11438   14 IEKRRRDKMNSFIDELASLVPTC---NAM---SRKLDKLTVLRMAVQHMKTLRGA 62

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 105990526  58 EKRRRDRINNSLSELRRLVPsafekqvmeqGSAKLEKAEILQMTVDHLKML 108
Cdd:cd11455   15 ERRRRERINSHLATLRTLLP----------NLSKTDKASLLAEVVQHVKEL 55

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in sterol regulatory element-binding protein (SREBP) family and similar proteins; The SREBP family includes SREBP1 and SREBP2, which are bHLHzip transcriptional activator of genes encoding proteins essential for cholesterol biosynthesis/uptake and fatty acid biosynthesis. SREBP1 and SREBP2 are principally found in the liver and in adipocytes and made up of an N-terminal transcription factor portion (composed of an activation domain, a bHLHzip domain, and a nuclear localization signal), a hydrophobic region containing two membrane spanning regions, and a C-terminal regulatory segment. They recognize a symmetric sterol regulatory element (TCACNCCAC) instead of E-box. The family also includes Saccharomyces cerevisiae transcription factor HMS1 (also termed high-copy MEP suppressor protein 1) and serine-rich protein TYE7. HMS1 is a putative bHLHzip transcription factor involved in exit from mitosis and pseudohyphal differentiation. TYE7, also termed basic-helix-loop-helix protein SGC1, is a putative bHLHzip transcription activator required for Ty1-mediated glycolytic gene expression. TYE7 N-terminal is extremely rich in serine residues. It binds DNA on E-box motifs, 5'-CANNTG-3'. TYE7 is not essential for growth.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 105990526  50 RKRRRGIIEKRRRDRINNSLSELRRLVPSAF-------EKQVMEQGSA-KLEKAEILQMTVDHLKML 108
Cdd:cd11395    3 KRLPHNAIEKRYRSNLNTKIERLRDAIPSLRspegksdDGGLGGLAPTtKLSKATILTKAIEYIRHL 69

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 105990526  51 KRRRGIIEKRRRDRINNSLSELRRLVPsAFEkqvmeqgSAKLEKAEILQMTVDHLKML 108
Cdd:cd18908    3 ASSHSLKERLRRERIKSSCDQLRDLLP-YIK-------GRKLDMASVLEMTVKYIRYI 52

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 105990526  57 IEKRRRDRINNSLSELRRLVPSAfekqvmEQGSAKLEKAEILQMTVDHLKMLHTA 111
Cdd:cd11469    8 TEKRRRDKMNNLIEELSAMIPQC------NPMARKLDKLTVLRMAVQHLKSLKGS 56

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in the microphthalmia-associated transcription factor family (MITF) family; The MITF (also known as microphthalmia-TFE, or MiT) family is a small family that contain a basic helix loop helix domain associated with a leucine zipper (bHLHZip). The MITF family 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 family can form homodimers or heterodimers with each other but not with other bHLH or bHLHzip proteins.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 105990526  56 IIEKRRRDRINNSLSELRRLVPSAFEKQVmeqgsaKLEKAEILQMTVDHLKML 108
Cdd:cd11397   11 MIERRRRFNINDRIKELGTLLPKSNDPDM------RWNKGTILKASVDYIRKL 57

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        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 105990526  50 RKRRRGIIEKRRRDRINNSLSELRRLVPSAFEKQVMEQGSAKLE--------------KAEILQMTVDHLKMLH 109
Cdd:cd11392    2 KRTAHKVAERGRRDRLNAALKELASLMPAEFVEGKMGADGSASDsndkekaaasaagsKAATVEMAIDYIKHLQ 75

basic helix-loop-helix-Per-ARNT-Sim (bHLH-PAS) domain found in Circadian locomotor output cycles protein kaput (CLOCK) and similar proteins; The family includes CLOCK, neuronal PAS domain-containing protein 2 (NPAS2) and non-mammalian circadian clock protein PASD1. CLOCK, also termed Class E basic helix-loop-helix protein 8 (bHLHe8), is a transcriptional activator which forms a core component of the circadian clock. NPAS2, also termed neuronal PAS2, or basic-helix-loop-helix-PAS protein MOP4, or Class E basic helix-loop-helix protein 9 (bHLHe9), or member of PAS protein 4, or PAS domain-containing protein 4, is a transcriptional activator which forms a core component of the circadian clock. PASD1 is evolutionarily related to Circadian locomotor output cycles protein kaput (CLOCK)and functions as a suppressor of the biological clock that drives the daily circadian rhythms of cells throughout the body.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 105990526  51 KRRRGIIEKRRRDRINNSLSELRRLVPSAfekqvmeqgSAKLEKAEILQMTVDHLK 106
Cdd:cd11441    1 RKSRNLSEKKRRDQFNVLINELASMLPGR---------GRKMDKSTVLKKTIAFLR 47

basic helix-loop-helix (bHLH) domain found in Arabidopsis thaliana protein aborted microspores (AMS) and similar proteins; The family includes several bHLH transcription factors from Arabidopsis thaliana, such as AMS, ICE1 and SCREAM2. AMS, also termed AtbHLH21, or EN 48, plays a crucial role in tapetum development and it is required for male fertility and pollen differentiation. ICE1, also termed inducer of CBF expression 1, or AtbHLH116, or EN 45, or SCREAM, acts as a transcriptional activator that regulates the cold-induced transcription of CBF/DREB1 genes. It binds specifically to the MYC recognition sites (5'-CANNTG-3') found in the CBF3/DREB1A promoter. SCREAM2, also termed AtbHLH33, or EN 44, mediates stomatal differentiation in the epidermis probably by controlling successive roles of SPCH, MUTE, and FAMA.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 105990526  58 EKRRRDRINNSLSELRRLVPSAfekqvmeqgsAKLEKAEILQMTVDHLKML 108
Cdd:cd11443    7 ERRRRKKLNDRLYMLRSVVPKI----------TKMDRASILGDAIDYVKEL 47

basic helix-loop-helix (bHLH) domain found in Arabidopsis thaliana BES1-interacting Myc-like proteins (BIMs) and similar proteins; The family includes Arabidopsis thaliana BIM1 and its homologs (BIM2 and BIM3), which are bHLH transcription factors that interact with BES1 to regulate transcription of Brassinosteroid (BR)-induced gene. BR regulates many growth and developmental processes such as cell elongation, vascular development, senescence stress responses, and photomorphogenesis. BIM1 heterodimerize with BES1 and bind to E-box sequences present in many BR-induced promoters to regulated BR-induced genes.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 105990526  49 ARKRRRGIIEKRRRDRINNSLSELRRLVPsafekqvmeQGSAKLEKAEILQMTVDHLKML 108
Cdd:cd11453    2 TPRSKHSATEQRRRSKINERLQALRDLIP---------HSDQKRDKASFLLEVIEYIQAL 52

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in Max-like protein X (Mlx) family; Mlx, also termed Class D basic helix-loop-helix protein 13 (bHLHd13), or Max-like bHLHZip protein, or protein BigMax, or transcription factor-like protein 4, is a Max-like bHLHZip transcription regulator that interacts with the Max network of transcription factors. It forms a sequence-specific DNA-binding protein complex with some member of Mad family (Mad1 and Mad4) and Mondo family but not the Myc family and bind the E-box DNA to control transcription. The family also includes Saccharomyces cerevisiae INO4, which is a bHLH transcriptional activator of phospholipid synthetic genes (such as INO1, CHO1/PSS, CHO2/PEM1, OPI3/PEM2, etc.). It is required for de-repression of phospholipid biosynthetic gene expression in response to inositol deprivation in yeast.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 105990526  50 RKRRRGIIEKRRRDRINNSLSELRRLVPSAFEKqvmeqgsaKLEKAEILQMTVDHLKMLHT 110
Cdd:cd11404    2 RRLNHVRSEKKRRELIKKGYDELCALVPGLDPQ--------KRTKADILQKAADWIQELKE 54

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        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 105990526  59 KRRRDRINNSLSELRRLVPsaFEKQVmeqgSAKLEKAEILQMTVDHLKMlhtaggKGYFDA 119
Cdd:cd19696    9 KRHRDRLNSELDELASLLP--FPEDV----ISKLDKLSVLRLSVSYLRT------KNYFQA 57

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in transcription factor EB (TFEB) and similar proteins; TFEB, also termed Class E basic helix-loop-helix protein 35 (bHLHe35), is a bHLHzip transcription factor that is required for vascularization of the mouse placenta. It specifically recognizes and binds E-box sequences (5'-CANNTG-3'). Its efficient DNA-binding requires dimerization with itself or with another MiT/TFE family member such as TFE3 or MITF.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 105990526  45 SQILARKRRR----GIIEKRRRDRINNSLSELRRLVPSAFEKQVmeqgsaKLEKAEILQMTVDHLKMLH 109
Cdd:cd18927    2 ARALAKERQKkdnhNLIERRRRFNINDRIKELGTLIPKTNDLDV------RWNKGTILKASVDYIKRMQ 64

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in transcription factor E3 (TFE3) and similar proteins; TFE3, also termed Class E basic helix-loop-helix protein 33 (bHLHe33), is a bHLHzip transcription factor that is involved in B cell function. It specifically recognizes and binds E-box sequences (5'-CANNTG-3'). Its efficient DNA-binding requires dimerization with itself or with another MiT/TFE family member such as TFEB or MITF.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 105990526  50 RKRRRGIIEKRRRDRINNSLSELRRLVPSAFEKQVmeqgsaKLEKAEILQMTVDHLKMLH 109
Cdd:cd18928   11 KKDNHNLIERRRRFNINDRIKELGTLIPKSTDPEM------RWNKGTILKASVDYIRKLQ 64

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in sterol regulatory element-binding protein 1 (SREBP1) and similar proteins; SREBP1, also termed Class D basic helix-loop-helix protein 1 (bHLHd1), or sterol regulatory element-binding transcription factor 1 (SREBF1), is a member of a family of bHLHzip transcription factors that recognize sterol regulatory element 1 (SRE-1). It acts as a transcriptional activator required for lipid homeostasis. It may control transcription of the low-density lipoprotein receptor gene as well as the fatty acid. SREBP1 has dual sequence specificity binding to both an E-box motif (5'-ATCACGTGA-3') and to SRE-1 (5'-ATCACCCCAC-3').

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 105990526  57 IEKRRRDRINNSLSELRRLVPSAfekqvmeqgSAKLEKAEILQMTVDHLKMLHTAGGKGYFDAHALAM 124
Cdd:cd18921   13 IEKRYRSSINDKIIELKDLVVGT---------EAKLNKSAVLRKAIDYIRFLQQSNQKLKQENMALKM 71

basic helix-loop-helix-Per-ARNT-Sim (bHLH-PAS) domain found in aryl hydrocarbon receptor repressor (AhRR) and similar proteins; AhRR, also termed AhR repressor, or 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 (or Dioxin Receptor), playing key roles in development and environmental sensing. AhR 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 functions by competing with AhR for its partner ARNT. AhRR-ARNT complexes are transcriptionally inactive.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 105990526  59 KRRRDRINNSLSELRRLVPsaFEKQVMeqgsAKLEKAEILQMTVDHLKMlhtaggKGYFDA 119
Cdd:cd11435    9 KRHRDRLNAELDHLASLLP--FPPDII----SKLDKLSVLRLSVSYLRV------KSFFQA 57

basic helix-loop-helix-Per-ARNT-Sim (bHLH-PAS) domain found in aryl hydrocarbon receptor nuclear translocator (ARNT) and similar proteins; ARNT, also termed Class E basic helix-loop-helix protein 2 (bHLHe2), or Dioxin receptor, nuclear translocator, or hypoxia-inducible factor 1-beta (HIF1b), or HIF-1-beta, or HIF1-beta, is a member of bHLH-PAS transcription regulators that acts 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.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 105990526  57 IEKRRRDRINNSLSELRRLVP--SAFEKqvmeqgsaKLEKAEILQMTVDHLKMLHTAGG 113
Cdd:cd18947   12 IERRRRNKMTAYITELSDMVPtcSALAR--------KPDKLTILRMAVSHMKSLRGTGN 62

basic helix-loop-helix (bHLH) domain found in Saccharomyces cerevisiae protein INO2 and similar proteins; INO2 is a positive regulatory factor required for depression of the co-regulated phospholipid biosynthetic enzymes in Saccharomyces cerevisiae. It is also involved in the expression of ITR1.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 105990526  50 RKRRRGIIEKRRRDRINNSLSELRRLVPSAfekqvMEQGSAKLEKAEILQMTVDHLKML 108
Cdd:cd11388    3 KKWKHVEAEKKRRNQIKKGFEDLINLINYP-----RNNNEKRISKSELLNKAVDDIRGL 56

basic helix-loop-helix (bHLH) domain found in Arabidopsis thaliana protein transparent testa 8 (TT8) and similar proteins; The family includes several bHLH transcription factors from Arabidopsis thaliana, such as TT8, EGL1, and GL3. TT8, also termed AtbHLH42, or EN 32, is involved in the control of flavonoid pigmentation and plays a key role in regulating leucoanthocyanidin reductase (BANYULS) and dihydroflavonol-4-reductase (DFR). EGL1, also termed AtbHLH2, or EN 30, or AtMYC146, or protein enhancer of GLABRA 3, is involved in epidermal cell fate specification and regulates negatively stomata formation but promotes trichome formation. GL3, also termed AtbHLH1, or AtMYC6, or protein shapeshifter, or EN 31, is involved in epidermal cell fate specification. It regulates negatively stomata formation, but, in association with TTG1 and MYB0/GL1, promotes trichome formation, branching and endoreplication.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 105990526  56 IIEKRRRDRINNSLSELRRLVPSAfekqvmeqgsAKLEKAEILQMTVDHLKML 108
Cdd:cd11451    8 MAERRRREKLNERFITLRSMVPFV----------TKMDKVSILGDAIEYLKQL 50

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in protein Max and similar proteins; Max, also termed Class D basic helix-loop-helix protein 4 (bHLHd4), or Myc-associated factor X, is a bHLHZip transcription regulator that forms a sequence-specific DNA-binding protein complex with MYC or MAD which recognizes the core sequence 5'-CAC[GA]TG-3'. The MYC:MAX complex is a transcriptional activator, whereas the MAD:MAX complex is a transcriptional repressor. Max homodimer bind DNA but is transcriptionally inactive. Targeted deletion of max results in early embryonic lethality in mice.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 105990526  57 IEKRRRDRINNSLSELRRLVPSAfekqvmeQGSaKLEKAEILQMTVDHLKML 108
Cdd:cd11406    8 LERKRRDHIKDSFHSLRDSVPSL-------QGE-KASRAQILKKATEYIQYM 51