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        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13540521  31 KPKRSMKRDDTKDTYKLPHRLIEKKRRDRINECIAQLKDLLPEHLKLTTLGHLEKAVVLELTLKHLKALTALTEQQHQKI 110
Cdd:cd19750   1 KPKRGLKRDESKEAYKLPHRLIEKKRRDRINECIAQLKDLLPEHLKLTTLGHLEKAVVLELTLKHLKALTALTEQQHQKI 80

                        90
                ....*....|..
gi 13540521 111 IALQNGERSLKS 122
Cdd:cd19750  81 IALQNGERSLKS 92

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        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13540521  31 KPKRSMKRDDTKDTYKLPHRLIEKKRRDRINECIAQLKDLLPEHLKLTTLGHLEKAVVLELTLKHLKALTALTEQQHQKI 110
Cdd:cd19750   1 KPKRGLKRDESKEAYKLPHRLIEKKRRDRINECIAQLKDLLPEHLKLTTLGHLEKAVVLELTLKHLKALTALTEQQHQKI 80

                        90
                ....*....|..
gi 13540521 111 IALQNGERSLKS 122
Cdd:cd19750  81 IALQNGERSLKS 92

Helix-loop-helix DNA-binding domain;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 13540521    45 YKLPHRLIEKKRRDRINECIAQLKDLLPEHLKLTtlgHLEKAVVLELTLKHLKALT 100
Cdd:pfam00010   1 RREAHNERERRRRDRINDAFDELRELLPTLPPDK---KLSKAEILRLAIEYIKHLQ 53

Hairy Orange; The Orange domain is found in the Drosophila proteins Hesr-1, Hairy, and Enhancer of Split. The Orange domain is proposed to mediate specific protein-protein interaction between Hairy and Scute.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|.
gi 13540521   131 FHSGFQTCAKEVLQYLSRFESWTPrePRCVQLINHLHAVAT 171
Cdd:pfam07527   2 FRAGFNECANEVSRFLSTLEGVDP--DLRQRLLNHLQRCLA 40

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        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13540521  31 KPKRSMKRDDTKDTYKLPHRLIEKKRRDRINECIAQLKDLLPEHLKLTTLGHLEKAVVLELTLKHLKALTALTEQQHQKI 110
Cdd:cd19750   1 KPKRGLKRDESKEAYKLPHRLIEKKRRDRINECIAQLKDLLPEHLKLTTLGHLEKAVVLELTLKHLKALTALTEQQHQKI 80

                        90
                ....*....|..
gi 13540521 111 IALQNGERSLKS 122
Cdd:cd19750  81 IALQNGERSLKS 92

basic helix-loop-helix-orange (bHLH-O) domain found in differentially expressed in chondrocytes protein 1 (DEC1) and similar proteins; DEC1, also termed Class E basic helix-loop-helix protein 40 (bHLHe40), or Class B basic helix-loop-helix protein 2 (bHLHb2), or enhancer-of-split and hairy-related protein 2 (SHARP-2), or stimulated by retinoic acid gene 13 protein (STRA13), 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        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13540521  33 KRSMKR-DDTKDTYKLPHRLIEKKRRDRINECIAQLKDLLPEHLKLTTLGHLEKAVVLELTLKHLKALTALTEQQHQKII 111
Cdd:cd19749   1 RRGLKRsEDSKDTYKLPHRLIEKKRRDRINECIAQLKDLLPEHLKLTTLGHLEKAVVLELTLKHVKALTSLIEQQQQKIL 80

                ....*
gi 13540521 112 ALQNG 116
Cdd:cd19749  81 ALQSG 85

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 13540521  52 IEKKRRDRINECIAQLKDLLPEHLKLTTLGH--LEKAVVLELTLKHLKALTA 101
Cdd:cd11410   1 MEKKRRARINKSLEQLKTLVLEALNKDNTRYskLEKADILEMTVKYLKQLQR 52

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 13540521  41 TKDTYKLPHRLIEKKRRDRINECIAQLKDLLPEHLKLTTLGH--LEKAVVLELTLKHLKAL 99
Cdd:cd19741   4 TYQYRKVTKPLLERKRRARINKCLDELKDLMVEALATEAENVskLEKADILELTVRHLKKL 64

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 13540521  52 IEKKRRDRINECIAQLKDLLPEHLKLTTLGHLEKAVVLELTLKHLKAL 99
Cdd:cd19685   1 SEKRRRQRINDKLNQLKELLPPNLSKQSRSKLSKAEILEMAITELRRL 48

Helix-loop-helix DNA-binding domain;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 13540521    45 YKLPHRLIEKKRRDRINECIAQLKDLLPEHLKLTtlgHLEKAVVLELTLKHLKALT 100
Cdd:pfam00010   1 RREAHNERERRRRDRINDAFDELRELLPTLPPDK---KLSKAEILRLAIEYIKHLQ 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
                ....*....|....*....|....*....|....*....|....*....|.
gi 13540521  51 LIEKKRRDRINECIAQLKDLLPEHLKLTTLGH--LEKAVVLELTLKHLKAL 99
Cdd:cd11459   9 IMEKRRRARINESLSQLKTLILDALKKDSSRHskLEKADILEMTVKHLRNL 59

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

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 13540521    129 DAFHSGFQTCAKEVLQYLSRFESWTPrePRCVQLINHLHAVATQFLP 175
Cdd:smart00511   1 SSFRSGYRECANEVSRFLSQLPGTDP--DVRARLLSHLQTHLNQLLQ 45

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 13540521  46 KLPHRLIEKKRRDRINECIAQLKDLL-PEHLKLTTLGHLEKAVVLELTLKHLK 97
Cdd:cd11461   1 KLRKPVVEKTRRDRINSSIEQLKTLLeKEFQRHQPNSKLEKADILEMTVSFLK 53

basic helix-loop-helix-orange (bHLH-O) domain found in hairy and enhancer of split 7 (HES-7) and similar proteins; HES-7, also termed Class B basic helix-loop-helix protein 37 (bHLHb37), or bHLH factor Hes7, is a bHLH-O transcriptional repressor that is expressed in an oscillatory manner and acts as a key regulator of the pace of the segmentation clock. It is regulated by the Notch and Fgf/Mapk pathways. HES-7 is one mammalian counterpart of the Hairy and Enhancer of split proteins that play a critical role in many physiological processes including cellular differentiation, cell cycle arrest, apoptosis and self-renewal ability.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 13540521  46 KLPHRLIEKKRRDRINECIAQLKDLLPEHLKLTTL--GHLEKAVVLELTLKHLKALTA 101
Cdd:cd11462   2 KLLKPLVEKRRRDRINRSLEELRVLLLQNTQDEKLknPKVEKAEILELTVQFLRNSSL 59

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        50
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 13540521  49 HRLIEKKRRDRINECIAQLKDLLPEHLKLTTLGHLEKAVVLELTLKHLKALTALTE 104
Cdd:cd11387   2 HNAVERRRRDNINEKIQELGSLVPPSRLETKDLKPNKGSILSKAVEYIRELQNQNQ 57

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 13540521  53 EKKRRDRINECIAQLKDLLPEHLKLTTlghLEKAVVLELTLKHLKAL 99
Cdd:cd00083   1 ERRRRDKINDAFEELKRLLPELPDSKK---LSKASILQKAVEYIREL 44

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 13540521  46 KLPHRLIEKKRRDRINECIAQLKDLLPEHLKLTTlgHLEKAVVLELTLKHLKALTAL 102
Cdd:cd11391   1 REKSREAAKKRRDKENAEISELASLLPLPPAVGS--KLDKLSVLRLAVAYLRLKKFL 55

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
                ....*....|....*....|....*....|....*....|....*..
gi 13540521  51 LIEKKRRDRINECIAQLKDLLPEHLKLTTLGHLEKAVVLELTLKHLK 97
Cdd:cd18916   6 MLERQRRARINKCLSELKTLVAECSGDDGCLRMDKAEMLETAVAFMR 52

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        60
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 13540521  49 HRLIEKKRRDRINECIAQLKDLLPehlkltTLGHLEKAVVLELTLKHLKALtaltEQQHQK 109
Cdd:cd11393   1 HSIAERKRREKINERIRALRSLVP------NGGKTDKASILDEAIEYIKFL----QEQVKV 51

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 13540521  48 PHRLIEKKRRDRINECIAQLKDLLPEHLKLTTlgHLEKAVVLELTLKHLKALTALT 103
Cdd:cd11469   4 AHSQTEKRRRDKMNNLIEELSAMIPQCNPMAR--KLDKLTVLRMAVQHLKSLKGST 57

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        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13540521  44 TYKLPHRLIEKKRRDRINECIAQLKDLLPEhlkltTLGHLEKAVVLELTLKHLKAL---TALTEQQHQKIialqNGERSL 120
Cdd:cd11453   2 TPRSKHSATEQRRRSKINERLQALRDLIPH-----SDQKRDKASFLLEVIEYIQALqekVAKLEEQVQGW----GGEPAK 72

                ....*
gi 13540521 121 KSPIQ 125
Cdd:cd11453  73 LTPWA 77

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 13540521  49 HRLIEKKRRDRINECIAQLKDLLPEHLKLTTlgHLEKAVVLELTLKHLKALTALT 103
Cdd:cd11438  11 HSQIEKRRRDKMNSFIDELASLVPTCNAMSR--KLDKLTVLRMAVQHMKTLRGAT 63

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 13540521  51 LIEKKRRDRINECIAQLKDL-LPEHLKLTT-LGHLEKAVVLELTLKHLKALTA 101
Cdd:cd11463  11 LMEKRRRARINESLNQLKTLiLPLVGKDSSrYSKLEKADILEMTVRFLQDLPA 63

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 13540521  49 HRLIEKKRRDRINECIAQLKDLLPEHLKLTtlghleKAVVLELTLKHLKAL 99
Cdd:cd11445   6 HNLSERRRRDRINEKMKALQELIPNCNKTD------KASMLDEAIEYLKSL 50

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 13540521  46 KLPHRLIEKKRRDRINECIAQLKDLLPEhlkLTTLGHlEKAVVLELTLKHLKALTALTEQQHQKIIAL 113
Cdd:cd11404   3 RLNHVRSEKKRRELIKKGYDELCALVPG---LDPQKR-TKADILQKAADWIQELKEENEKLEEQLDEL 66

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        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 13540521  46 KLPHRLIEKKRRDRINECIAQLKDLLPEhLKLTTLGHLEKAVVLELTLKHLKALTalTEQQhqkiiALQNGERSLKSPI 124
Cdd:cd11405   4 RLSHISAEQKRRFNIKSGFDTLQSLIPS-LGQNPNQKVSKAAMLQKAAEYIKSLK--RERQ-----QMQEEAEQLRQEI 74

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
                ....*....|....*....|....*....|....*....|
gi 13540521  33 KRSMKRDDtkdtyklpHRLIEKKRRDRINECIAQLKDLLP 72
Cdd:cd11397   1 KDRQKKDN--------HNMIERRRRFNINDRIKELGTLLP 32

basic helix-loop-helix-Per-ARNT-Sim (bHLH-PAS) domain found in Drosophila melanogaster Circadian locomotor output cycles protein kaput (dCLOCK) and similar proteins; dCLOCK, also termed dPAS1, is a bHLH-PAS Circadian regulator that acts as a transcription factor and generates a rhythmic output with a period of about 24 hours.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 13540521  39 DDTKDTYKLPHR-LIEKKRRDRINECIAQLKDLLPehlklTTLGHLEKAVVLELTLKHLKALTALTEQQHQ 108
Cdd:cd19735   3 EDEKDTIKRKSRnLSEKKRRDQFNVLINELCSMVS-----TSNRKMDKSTVLKSTIAFLKNHNEVTMQSHQ 68

basic helix-loop-helix (bHLH) domain found in Arabidopsis thaliana protein IAA-leucine resistant 3 (ILR3) and similar proteins; ILR3, also termed AtbHLH105, or EN 133, is a bHLH transcription factor that plays a role in resistance to amide-linked indole-3-acetic acid (IAA) conjugates such as IAA-Leu and IAA-Phe. It may regulate gene expression in response to metal homeostasis changes.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 13540521  53 EKKRRDRINECIAQLKDLL-PEHLKLTtlghlEKAVVLELTLKHLKALTALTEQQHQKIIALQNGERSLKS 122
Cdd:cd11446   5 EKLRRDKLNERFMELSNVLePGRPPKT-----DKATILGDAIRMLKQLRGEVQKLKEENSSLQEESKELKA 70

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 13540521  53 EKKRRDRINECIAQLKDLLPEHLKlttlgHLEKAVVLELT---LKHLKALTA 101
Cdd:cd11441   8 EKKRRDQFNVLINELASMLPGRGR-----KMDKSTVLKKTiafLRKHKELTA 54

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in Saccharomyces cerevisiae transcription factor HMS1 and similar proteins; HMS1, also termed high-copy MEP suppressor protein 1, is a putative bHLHzip transcription factor involved in exit from mitosis and pseudohyphal differentiation.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13540521  46 KLPHRLIEKKRRDRINECIAQLKDLLP--------------EHLKLTTLG---HLEKAVVLELTLKHLKALTALTEQQHQ 108
Cdd:cd11399   4 KTAHNMIEKRYRSNINDRIAELRDSVPalreayksargedeDEEDLGGLTpatKLNKATILSKATEYIRHLEKKNKRLSR 83

                ....*..
gi 13540521 109 KIIALQN 115
Cdd:cd11399  84 ENASLRE 90