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        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 658309882 342 AKNLMAERRRRKKLNDRLYMLRSVVPKISKMDRASILGDAIEYLKELLQRINNLHNELESIPPGS 406
Cdd:cd11443    1 SKNLMAERRRRKKLNDRLYMLRSVVPKITKMDRASILGDAIDYVKELLQEINELQDELEGLPESE 65

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        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 658309882 342 AKNLMAERRRRKKLNDRLYMLRSVVPKISKMDRASILGDAIEYLKELLQRINNLHNELESIPPGS 406
Cdd:cd11443    1 SKNLMAERRRRKKLNDRLYMLRSVVPKITKMDRASILGDAIDYVKELLQEINELQDELEGLPESE 65

Helix-loop-helix DNA-binding domain;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 658309882  342 AKNLMaERRRRKKLNDRLYMLRSVVPKI---SKMDRASILGDAIEYLKEL 388
Cdd:pfam00010   4 AHNER-ERRRRDRINDAFDELRELLPTLppdKKLSKAEILRLAIEYIKHL 52

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        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 658309882 342 AKNLMAERRRRKKLNDRLYMLRSVVPKISKMDRASILGDAIEYLKELLQRINNLHNELESIPPGS 406
Cdd:cd11443    1 SKNLMAERRRRKKLNDRLYMLRSVVPKITKMDRASILGDAIDYVKELLQEINELQDELEGLPESE 65

basic helix-loop-helix (bHLH) domain found in Arabidopsis thaliana protein ABA-INDUCIBLE bHLH-TYPE (AIB) and similar proteins; The family includes several bHLH transcription factors from Arabidopsis thaliana, such as AIB and MYC proteins (MYC2, MYC3 and MYC4). AIB, also termed AtbHLH17, or EN 35, is a transcription activator that regulates positively abscisic acid (ABA) response. MYC2, also termed protein jasmonate insensitive 1, or R-homologous Arabidopsis protein 1 (RAP-1), or AtbHLH6, or EN 38, or Z-box binding factor 1 protein, is a transcriptional activator involved in abscisic acid (ABA), jasmonic acid (JA), and light signaling pathways. MYC3, also termed protein altered tryptophan regulation 2, or AtbHLH5, or transcription factor ATR2, or EN 36, is a transcription factor involved in tryptophan, jasmonic acid (JA) and other stress-responsive gene regulation. MYC4, also termed AtbHLH4, or EN 37, is a transcription factor involved in jasmonic acid (JA) gene regulation. MYC2, together with MYC3 and MYC4, controls additively subsets of JA-dependent responses.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 658309882 347 AERRRRKKLNDRLYMLRSVVPKISKMDRASILGDAIEYLKELLQRINNLHNELESI 402
Cdd:cd11449   12 AERQRREKLNQRFYALRAVVPNVSKMDKASLLGDAISYINELKSKVQDMETEKKEM 67

basic helix-loop-helix (bHLH) domain found in Arabidopsis thaliana genes coding transcription factors and similar proteins; bHLH proteins are the second largest class of plant transcription factors that regulate transcription of genes that are involve in many essential physiological and developmental process. bHLH proteins are transcriptional regulators that are found in organisms from yeast to humans. The Arabidopsis bHLH proteins that have been characterized so far have roles in regulation of fruit dehiscence, cell development (carpel, anther and epidermal), phytochrome signaling, flavonoid biosynthesis, hormone signaling and stress responses.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 658309882 344 NLMAERRRRKKLNDRLYMLRSVVPKISKMDRASILGDAIEYLKELLQRINNL 395
Cdd:cd11393    1 HSIAERKRREKINERIRALRSLVPNGGKTDKASILDEAIEYIKFLQEQVKVL 52

basic helix-loop-helix (bHLH) domain found in Arabidopsis thaliana protein NAI1 and similar proteins; NAI1, also termed AtbHLH20, or EN 27, is a bHLH transcription activator that regulates the expression of at least NAI2, PYK10 and PBP1. It is required for and mediates the formation of endoplasmic reticulum bodies (ER bodies). It plays a role in the symbiotic interactions with the endophytes of the Sebacinaceae fungus family, such as Piriformospora indica and Sebacina.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 658309882 345 LMAERRRRKKLNDRLYMLRSVVPKISKMDRASILGDAIEYLKELLQRINNLHNELE 400
Cdd:cd11452    7 ILAERKRREKLSQRFIALSALVPGLKKMDKASVLGDAIKHIKQLQERVKELEEEKK 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
                 ....*....|....*....|....*....|....*....|..
gi 658309882 347 AERRRRKKLNDRLYMLRSVVPKISKMDRASILGDAIEYLKEL 388
Cdd:cd11455   14 AERRRRERINSHLATLRTLLPNLSKTDKASLLAEVVQHVKEL 55

basic helix-loop-helix (bHLH) domain found in Arabidopsis thaliana protein FAMA and similar proteins; The family includes several bHLH transcription factors from Arabidopsis thaliana, such as FAMA, MUTE and SPEECHLESS, which work together to regulate the sequential cell fate specification during stomatal development and differentiation. FAMA, also termed AtbHLH97, or EN 14, is a transcription activator required to promote differentiation and morphogenesis of stomatal guard cells and to halt proliferative divisions in their immediate precursors. It mediates the formation of stomata. MUTE, also termed AtbHLH45, or EN 20, is required for the differentiation of stomatal guard cells, by promoting successive asymmetric cell divisions and the formation of guard mother cells. It promotes the conversion of the leaf epidermis into stomata. SPEECHLESS, also termed AtbHLH98, or EN 19, is required for the initiation and the formation of stomata, by promoting the first asymmetric cell divisions. FAMA, MUTE and SPEECHLESS form heterodimers with SCREAM/ICE1 and SCRM2 to regulate transcription of genes during stomatal development.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 658309882 348 ERRRRKKLNDRLYMLRSVVPK--ISKMDRASILGDAIEYLKELLQRINNL 395
Cdd:cd11448    7 ERNRRKQMNEHLNVLRSLMPGsyIQRGDQASIVGGAIEFVKELEQLLQSL 56

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 658309882 342 AKNLMAERRRRKKLNDRLYMLRSVVPKISKM-DRASILGDAIEYLKELLQRInnlhNELESIPPGSALTPTGNT 414
Cdd:cd11453    5 SKHSATEQRRRSKINERLQALRDLIPHSDQKrDKASFLLEVIEYIQALQEKV----AKLEEQVQGWGGEPAKLT 74

basic helix-loop-helix (bHLH) domain found in Arabidopsis thaliana protein INDEHISCENT (IND) and similar proteins; The family includes several bHLH transcription factors from Arabidopsis thaliana, such as IND, HEC proteins (HEC1, HEC2 and HEC3) and UNE12. IND, also termed AtbHLH40, or EN 120, is a bHLH transcription regulator required for seed dispersal. It is involved in the differentiation of all three cell types required for fruit dehiscence. HEC1 (also termed AtbHLH88, or protein HECATE 1, or EN 118), HEC2 (also termed AtbHLH37, or protein HECATE 2, or EN 117) and HEC3 (also termed AtbHLH43, or protein HECATE 3, or EN 119) are required for the female reproductive tract development and fertility. Both IND and HEC proteins have been implicated in regulation of auxin signaling. They heterodimerize with SPATULA (SPT) bHLH transcription factor to regulate reproductive tract development in plant. UNE12, also termed AtbHLH59, or protein UNFERTILIZED EMBRYO SAC 12, or EN 93, is required for ovule fertilization.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 658309882 346 MAERRRRKKLNDRLYMLRSVVPKISKMDRASILGDAIEYLKeLLQRINNLHNELESIP 403
Cdd:cd11454    7 VAARHRRERISERIRILQRLVPGGTKMDTASMLDEAIHYVK-FLQLQVKLLQSDDLWM 63

ACT domains of the bacterial signal-transducing uridylyltransferase /uridylyl-removing (UUR) enzyme, GlnD; This ACT domain family, ACT_UUR_ACR-like, includes the two C-terminal ACT domains of the bacterial signal-transducing uridylyltransferase /uridylyl-removing (UUR) enzyme, GlnD; including those enzymes similar to the GlnD found in enteric Escherichia coli and those found in photosynthetic, nitrogen-fixing bacterium Rhodospirillum rubrum. Also included in this CD are the four ACT domains of a novel protein composed almost entirely of ACT domain repeats (the ACR protein) and like proteins. These ACR proteins, found in Arabidopsis and Oryza, are proposed to function as novel regulatory or sensor proteins in plants. This CD also includes the first of the two ACT domains that comprise the Glycine Cleavage System Transcriptional Repressor (GcvR) protein and related domains, as well as, the N-terminal ACT domain of a yet characterized Arabidopsis/Oryza predicted tyrosine kinase. Members of this CD belong to the superfamily of ACT regulatory domains.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 658309882 460 IHMFCGRRPGLLLSTMRTLDNLGLDIQQAVISCFNGFAMDVFRAEQcKEGQDVHPDQIKAV 520
Cdd:cd04873    3 VEVYAPDRPGLLADITRVLADLGLNIHDARISTTGERALDVFYVTD-SDGRPLDPERIARL 62

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 658309882 348 ERRRRKKLNDRLYMLRSVVPKI--SKMDRASILGDAIEYLKELLQRINNLHNELESI 402
Cdd:cd11406    9 ERKRRDHIKDSFHSLRDSVPSLqgEKASRAQILKKATEYIQYMRRKNHTHQQDIDDL 65

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 658309882 346 MAERRRRKKLNDRLYMLRSVVPKISKMD----RASILGDAIEYLKEL 388
Cdd:cd11397   11 MIERRRRFNINDRIKELGTLLPKSNDPDmrwnKGTILKASVDYIRKL 57

basic helix-loop-helix (bHLH) domain found in Arabidopsis thaliana suppressor of acaulis 51 (SAC51) and similar proteins; SAC51, also termed AtbHLH142, or EN 128, is a bHLH transcription factor that is involved in stem elongation, probably by regulating a subset of genes involved in this process.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*...
gi 658309882 348 ERRRRKKLNDRLYMLRSVVPKISKMDRASILGDAIEYLKELLQRINNL 395
Cdd:cd18917    5 EKSRKEKIKKAVKLLRSIVPGGESMDTALVLDEAIDYLKSLKMELQSL 52

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in Schizosaccharomyces pombe ESC1 (spESC1) and similar proteins; spESC1 is a bHLHzip protein with homology to human MyoD and Myf-5 myogenic differentiation inducers. It is involved in the sexual differentiation process.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 658309882 346 MAERRRRKKLNDRLYMLRSVVP--KISKMDRASILGDAIEYLKELLQRINNLHNELES 401
Cdd:cd19690    6 LAERKRRKEMKELFEDLRDALPqeRGTKASKWEILTKAISYIQQLKRHIRELRSEVND 63

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
                 ....*....|....*....|....*....|....*....|....
gi 658309882 347 AERRRRKKLNDRLYMLRSVVP----KISKMDRASILGDAIEYLK 386
Cdd:cd11391    7 AAKKRRDKENAEISELASLLPlppaVGSKLDKLSVLRLAVAYLR 50

basic helix-loop-helix (bHLH) domain found in Arabidopsis thaliana protein maternal effect embryo arrest 8 (AtMEE8) and similar proteins; AtMEE8, also termed AtbHLH108, or EN 132, is a bHLH transcription factor required during early embryo development, for the endosperm formation.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*
gi 658309882 346 MAERRRRKKLNDRLYMLRSVVPKIS-KMDRASILGDAIEYLKELL 389
Cdd:cd19698    3 LLEKKRRERIKDKIEILKGLTPNCTpKSDIASILSCVIDYIKSLL 47

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in Saccharomyces cerevisiae centromere-binding protein 1 (CBP-1) and similar proteins; CBP-1, also termed centromere promoter factor 1 (CPF1), or centromere-binding factor 1 (CBF1), is a bHLHzip protein that is required for chromosome stability and methionine prototrophy. It binds as a homodimer to the centromere DNA elements I (CDEI, GTCACATG) region of the centromere that is required for optimal centromere function.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|..
gi 658309882 348 ERRRRKKLNDRLYMLRSVVPKIS-KMDRASILGDAIEYLKEL 388
Cdd:cd11398   15 ERRRRENINEGINELAALVPGNArEKNKGAILARAVEYIQEL 56

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
                 ....*....|....*....|....*....|....*....|....*..
gi 658309882 348 ERRRRKKLNDRLYMLRSVVPKI------SKMDRASILGDAIEYLKEL 388
Cdd:cd11407    9 EKRRRDRINNSLAELRRLVPTAfekqgsAKLEKAEILQMTVDHLKML 55

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 658309882 347 AERRRRKKLNDRLYMLRSVVPKI-----SKMDRASILGDAIEYLKELLQRINNLHNELESI 402
Cdd:cd11405   10 AEQKRRFNIKSGFDTLQSLIPSLgqnpnQKVSKAAMLQKAAEYIKSLKRERQQMQEEAEQL 70

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 658309882 346 MAERRRRKKLNDRLYMLRSVVPK------ISKMDRASILGDAIEYLKE 387
Cdd:cd18916    6 MLERQRRARINKCLSELKTLVAEcsgddgCLRMDKAEMLETAVAFMRQ 53

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        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 658309882 346 MAERRRRKKLNDRLYMLRSVVPKIS------------------KMDRASILGDAIEYLKELLQRINNLHNELES 401
Cdd:cd11395    9 AIEKRYRSNLNTKIERLRDAIPSLRspegksddgglgglapttKLSKATILTKAIEYIRHLEQENERLEEENEE 82

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 658309882 348 ERRRRKKLNDRLYMLRSVVP------KISKMDRASILGDAIEYLKELLQ 390
Cdd:cd19685    2 EKRRRQRINDKLNQLKELLPpnlskqSRSKLSKAEILEMAITELRRLQQ 50

basic helix-loop-helix (bHLH) domain found in achaete-scute complex-like (ASCL) family; The achaete-scute complex-like (ASCL, also known as achaete-scute complex homolog or ASH) family of bHLH transcription factors, ASCL1-5, have been implicated in cell fate specification and differentiation. They are critical for proper development of the nervous system. The deregulation of ASCL plays a key role in psychiatric and neurological disorders. ASCL-1, also termed Class A basic helix-loop-helix protein 46 (bHLHa46), or achaete-scute homolog 1 (ASH-1), or mammalian achaete-scute homolog 1 (Mash1), is a neural-specific bHLH transcription factor that is expressed in subsets of neural progenitors in both the central and peripheral nervous system. It plays a key role in neuronal differentiation and specification in the nervous system. ASCL-2, also termed achaete-scute homolog 2 (ASH-2), or Class A basic helix-loop-helix protein 45 (bHLHa45), or mammalian achaete-scute homolog 2 (Mash2), is a bHLH transcription factor that is involved in Schwann cell differentiation and control of proliferation in adult peripheral nerves. ASCL-3, also termed Class A basic helix-loop-helix protein 42 (bHLHa42), or bHLH transcriptional regulator Sgn-1, or achaete-scute homolog 3 (ASH-3), is a bHLH transcription factor specifically localized in the duct cells of the salivary glands. It may act as transcriptional repressor that inhibits myogenesis. The family also includes Drosophila melanogaster achaete-scute complex (AS-C) proteins, which consists of lethal of scute (also known as achaete-scute complex protein T3 or AST3), scute (also known as achaete-scute complex protein T4 or AST4), achaete (also known as achaete-scute complex protein T5 or AST5), and asense (also known as achaete-scute complex protein T8 or AST8). They are involved in the determination of the neuronal precursors in the peripheral nervous system and the central nervous system, as well as in sex determination and dosage compensation.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*..
gi 658309882 348 ERRRRKKLNDRLYMLRSVVP------KISKMdraSILGDAIEYLKEL 388
Cdd:cd11418    9 ERRRVQAVNDAFDRLRQHVPylkrrkKLSKV---KTLRRAIEYIRHL 52

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 658309882 346 MAERRRRKKLNDRLYMLRSVVPKIS----KMDRASILGDAIEYLKElLQRINNLHNELES 401
Cdd:cd18928   17 LIERRRRFNINDRIKELGTLIPKSTdpemRWNKGTILKASVDYIRK-LQKEQQRSKEIEM 75

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in transcription factor AP-4 (TFAP4) and similar proteins; TFAP4, also termed activating enhancer-binding protein 4, or Class C basic helix-loop-helix protein 41 (bHLHc41), is a bHLHzip transcription factor that activates both viral and cellular genes involved in the regulation of cellular proliferation, stemness, and epithelial-mesenchymal transition by binding to the symmetrical DNA sequence 5'-CAGCTG-3'.

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gi 658309882 348 ERRRRKKLNDRLYMLRSVVPKI--SKMDRASILGDAIEYLKELLQRINNL 395
Cdd:cd11419   12 ERRRMQSINAGFQSLRTLLPHCdgEKLSKAAILQQTAEYIFSLEQEKTRL 61

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.

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gi 658309882 346 MAERRRRKKLNDRLYMLRSVVPKIS-KMDRASILGDAIEYLKELLQRINN 394
Cdd:cd19683    8 AKERQRRERIKIACDQLRKLVPGCSrKTDKATVFEFTVAYIKFLREKLGD 57

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').

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gi 658309882 348 ERRRRKKLNDRLYMLRS-VVPKISKMDRASILGDAIEYLKELLQRINNLHNE 398
Cdd:cd18921   14 EKRYRSSINDKIIELKDlVVGTEAKLNKSAVLRKAIDYIRFLQQSNQKLKQE 65

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.

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gi 658309882 343 KNLMaERRRRKKLNDRLYMLRSVV--------PKISKMDRASILGDAIEYLKEL 388
Cdd:cd11463    9 KPLM-EKRRRARINESLNQLKTLIlplvgkdsSRYSKLEKADILEMTVRFLQDL 61