basic helix-loop-helix-orange (bHLH-O) domain found in transcription factor HES-3 and similar proteins; HES-3, also termed Class B basic helix-loop-helix protein 43 (bHLHb43), or hairy and enhancer of split 3, is a bHLH-O transcription factor expressed in neural stem and progenitor cells that is involved in tissue regeneration. It regulates gene expression, cell growth, and insulin release. HES-3 is one mammalian counterpart of the Hairy and Enhancer of split proteins that play a critical role in many physiological processes including cellular differentiation, cell cycle arrest, apoptosis and self-renewal ability.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 755509282  26 MEKKRRARINVSLEQLRSLLERHYSHQIRKRKLEKADILELSVKYMRSLQNSLQG 80
Cdd:cd18933    1 MEKKRRARINVSLEQLKSLLEKHYSNNIRKRKLEKADILELTVKYLRSLQNSIQG 55

basic helix-loop-helix-orange (bHLH-O) domain found in transcription factor HES-3 and similar proteins; HES-3, also termed Class B basic helix-loop-helix protein 43 (bHLHb43), or hairy and enhancer of split 3, is a bHLH-O transcription factor expressed in neural stem and progenitor cells that is involved in tissue regeneration. It regulates gene expression, cell growth, and insulin release. HES-3 is one mammalian counterpart of the Hairy and Enhancer of split proteins that play a critical role in many physiological processes including cellular differentiation, cell cycle arrest, apoptosis and self-renewal ability.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 755509282  26 MEKKRRARINVSLEQLRSLLERHYSHQIRKRKLEKADILELSVKYMRSLQNSLQG 80
Cdd:cd18933    1 MEKKRRARINVSLEQLKSLLEKHYSNNIRKRKLEKADILELTVKYLRSLQNSIQG 55

helix loop helix domain;

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 755509282    24 PLMEKKRRARINVSLEQLRSLLERHYSHqirkRKLEKADILELSVKYMRSLQNSLQ 79
Cdd:smart00353   1 NARERRRRRKINEAFDELRSLLPTLPKN----KKLSKAEILRLAIEYIKSLQEELQ 52

basic helix-loop-helix-orange (bHLH-O) domain found in transcription factor HES-3 and similar proteins; HES-3, also termed Class B basic helix-loop-helix protein 43 (bHLHb43), or hairy and enhancer of split 3, is a bHLH-O transcription factor expressed in neural stem and progenitor cells that is involved in tissue regeneration. It regulates gene expression, cell growth, and insulin release. HES-3 is one mammalian counterpart of the Hairy and Enhancer of split proteins that play a critical role in many physiological processes including cellular differentiation, cell cycle arrest, apoptosis and self-renewal ability.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 755509282  26 MEKKRRARINVSLEQLRSLLERHYSHQIRKRKLEKADILELSVKYMRSLQNSLQG 80
Cdd:cd18933    1 MEKKRRARINVSLEQLKSLLEKHYSNNIRKRKLEKADILELTVKYLRSLQNSIQG 55

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 755509282  14 PASSFRKISKPLMEKKRRARINVSLEQLRSLL-----ERHYSHQirkrKLEKADILELSVKYMRSLQ 75
Cdd:cd19741    3 KTYQYRKVTKPLLERKRRARINKCLDELKDLMvealaTEAENVS----KLEKADILELTVRHLKKLR 65

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 755509282  19 RKISKPLMEKKRRARINVSLEQLRSL-LERHYSHQIRKRKLEKADILELSVKYMRSLQ 75
Cdd:cd18913    3 RKSSKPIMEKRRRARINASLNELKSLlLDALKKDGTRHSKLEKADILEMTVKHLRQVQ 60

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 755509282  20 KISKPLMEKKRRARINVSLEQLRSLLERHYSHQIRKRKLEKADILELSVKYMR 72
Cdd:cd11461    1 KLRKPVVEKTRRDRINSSIEQLKTLLEKEFQRHQPNSKLEKADILEMTVSFLK 53

helix loop helix domain;

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 755509282    24 PLMEKKRRARINVSLEQLRSLLERHYSHqirkRKLEKADILELSVKYMRSLQNSLQ 79
Cdd:smart00353   1 NARERRRRRKINEAFDELRSLLPTLPKN----KKLSKAEILRLAIEYIKSLQEELQ 52

basic helix-loop-helix-orange (bHLH-O) domain found in hairy and enhancer of split (HES)-related repressor protein (HERP)-like family; The HERP-like family includes bHLH-O transcriptional regulators that are related to the Drosophila hairy and Enhancer-of-split proteins. They contain a basic helix-loop-helix (bHLH) domain with an invariant glycine residue in its basic region, an orange domain in the central region and YXXW sequence motif at its C-terminal region. HERP proteins (HEY1, HEY2 and HEYL) act as downstream effectors of Notch signaling. They are involved in cardiovascular development and have roles in somitogenesis, myogenesis and gliogenesis. Hairy and enhancer of split-related protein HELT is a transcriptional repressor expressed in the developing central nervous system. It binds preferentially to the canonical E box sequence 5'-CACGCG-3' and regulates neuronal differentiation and/or identity. Differentially expressed in chondrocytes proteins, DEC1 and DEC2, are widely expressed in both embryonic and adult tissues and have been implicated in apoptosis, cell proliferation, and circadian rhythms, as well as malignancy in various cancers. Drosophila melanogaster protein clockwork orange (Cwo) is also included in this family. It is involved in the regulation of Drosophila circadian rhythms. It functions as both an activator and a repressor of clock gene expression.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 755509282  25 LMEKKRRARINVSLEQLRSLLERHYSHQIRKrKLEKADILELSVKYMRSLQNSL 78
Cdd:cd11389    3 VIEKRRRDRINESLAELRRLVPEARKSKGSG-KLEKAEILEMTLQHLKALQSST 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        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 755509282  20 KISKPLMEKKRRARINVSLEQLRSL-LERHYSHQIrkRKLEKADILELSVKYMRSLQ 75
Cdd:cd18916    1 KSKKPMLERQRRARINKCLSELKTLvAECSGDDGC--LRMDKAEMLETAVAFMRQQQ 55

basic helix-loop-helix-orange (bHLH-O) domain found in hairy and enhancer of split (HES)-related repressor protein (HERP) family; HERP (also called Hey/Hesr/HRT/CHF/gridlock) proteins corresponds to a family of bHLH-O transcriptional repressors that are related to the Drosophila hairy and Enhancer-of-split proteins and act as downstream effectors of Notch signaling. They contain a basic helix-loop-helix (bHLH) domain with an invariant glycine residue in its basic region, an orange domain in the central region and YXXW sequence motif at its C-terminal region. HERP proteins are involved in cardiovascular development and have roles in somitogenesis, myogenesis and gliogenesis.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 755509282  19 RKISKPLMEKKRRARINVSLEQLRSLLERHYSHQiRKRKLEKADILELSVKYMRSLQ 75
Cdd:cd11407    1 RKKRRGIIEKRRRDRINNSLAELRRLVPTAFEKQ-GSAKLEKAEILQMTVDHLKMLH 56

basic helix-loop-helix-orange (bHLH-O) domain found in hairy and enhancer of split-related protein HELT and similar proteins; HELT, also termed HES/HEY-like transcription factor, is a bHLH-O 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. HELT could homodimerize and heterodimerize with other bHLH-O protein such as HES-5 or HEY-2 and bound to E box to repress gene transcription.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 755509282  22 SKPLMEKKRRARINVSLEQLRSLLERHYSHQiRKRKLEKADILELSVKYMRSLQNS 77
Cdd:cd11408    1 SHKVIEKRRRDRINRCLNELGKTVPMALAKQ-TSGKLEKAEILEMTVQYLRALHSA 55

basic helix-loop-helix-orange (bHLH-O) domain found in hairy/enhancer-of-split related with YRPW motif protein 1 (HEY1) and similar proteins; HEY1, also termed cardiovascular helix-loop-helix factor 2 (CHF-2), or Class B basic helix-loop-helix protein 31 (bHLHb31), or HES-related repressor protein 1, or hairy and enhancer of split-related protein 1 (HESR-1), or hairy-related transcription factor 1 (HRT-1), is a bHLH-O transcriptional repressor that acts as an essential downstream effector of the Notch signaling pathway and may play a fundamental role in vascular development. HEY1 also participates several cancer-related pathways. It acts as a positive regulator of the tumor suppressor p53.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 755509282  19 RKISKPLMEKKRRARINVSLEQLRSLLERHYSHQiRKRKLEKADILELSVKYMRSLQ 75
Cdd:cd19748    9 RKRRRGIIEKRRRDRINNSLSELRRLVPSAFEKQ-GSAKLEKAEILQMTVDHLKMLH 64

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
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 755509282  19 RKISKPLMEKKRRARINVSLEQLRSLLERHYSHQiRKRKLEKADILELSVKYMRSLQ 75
Cdd:cd11447    9 RKKRRGIIEKRRRDRINSSLSELRRLVPTAFEKQ-GSSKLEKAEILQMTVDHLKMLH 64

basic helix-loop-helix-orange (bHLH-O) domain found in hairy/enhancer-of-split related with YRPW motif protein 2 (HEY2) and similar proteins; HEY2, also termed cardiovascular helix-loop-helix factor 1 (CHF-1), or Class B basic helix-loop-helix protein 32 (bHLHb32), or HES-related repressor protein 2, or hairy and enhancer of split-related protein 2 (HESR-2), or hairy-related transcription factor 2 (HRT-2), or protein gridlock homolog, is a bHLH-O transcriptional repressor expressed preferentially in the developing and adult cardiovascular system. As a downstream effector of Notch signaling, HEY2 may be required for cardiovascular development. It also plays an important role in neurologic development, as well as in the progression of human cancers.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 755509282  19 RKISKPLMEKKRRARINVSLEQLRSLLERHYSHQiRKRKLEKADILELSVKYMRSLQ 75
Cdd:cd18920   10 RKKRRGIIEKRRRDRINNSLSELRRLVPTAFEKQ-GSAKLEKAEILQMTVDHLKMLQ 65

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

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 755509282  27 EKKRRARINVSLEQLRSLLERHyshqirkRKLEKADILELSVKYMRSLQNSLQGL 81
Cdd:cd11393    5 ERKRREKINERIRALRSLVPNG-------GKTDKASILDEAIEYIKFLQEQVKVL 52

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 755509282  27 EKKRRARINVSLEQLRSLLERHYSHQIRKrKLEKADILELSVKYMRSLQNSLQ 79
Cdd:cd11387    6 ERRRRDNINEKIQELGSLVPPSRLETKDL-KPNKGSILSKAVEYIRELQNQNQ 57

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 755509282  25 LMEKKRRARINVSLEQLRSLLERHYshqirkrKLEKADILELSVKYMRSLQNSLQGLWP 83
Cdd:cd11445    8 LSERRRRDRINEKMKALQELIPNCN-------KTDKASMLDEAIEYLKSLQLQVQMMSM 59

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
                 ....*....|....*....|....*....|....*....|....*....|
gi 755509282  27 EKKRRARINVSLEQLRSLLERhySHQIRKRKLEKADILELSVKYMRSLQN 76
Cdd:cd11405   11 EQKRRFNIKSGFDTLQSLIPS--LGQNPNQKVSKAAMLQKAAEYIKSLKR 58

basic helix-loop-helix (bHLH) domain found in the spermatogenesis- and oogenesis-specific basic helix-loop-helix-containing protein (SOHLH) family and similar proteins; The SOHLH family includes two bHLH transcription factors, SOHLH1 and SOHLH2. They are specifically in spermatogonia and oocytes and essential for early spermatogonial and oocyte differentiation. The family also includes transcription factor-like 5 protein (TCFL5) and similar proteins. TCFL5, also termed Cha transcription factor, or HPV-16 E2-binding protein 1 (E2BP-1), is a bHLH transcription factor that plays a crucial role in spermatogenesis. It regulates cell proliferation or differentiation of cells through binding to a specific DNA sequence like other bHLH molecules.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 755509282  26 MEKKRRARINVSLEQLRSLLErhyshqIRKRKLEKADILELSVKYMRSLQNSL 78
Cdd:cd19683    9 KERQRRERIKIACDQLRKLVP------GCSRKTDKATVFEFTVAYIKFLREKL 55

tissue specific basic helix-loop-helix (bHLH-TS) domain family; Tissue specific bHLH domain family includes transcription regulators whose expression are restricted to certain tissues. They are involved in cell-fate determination and process in neurogenesis, cardiogenesis, myogenesis, and hematopoiesis and include proteins from myogenic regulatory factor (MRF) family, twist-related protein (TWIST) family, scleraxis-like family, heart- and neural crest derivatives-expressed protein (HAND) family, helix-loop-helix protein (HEN) family, musculin-like family, germline alpha (FIGLA) family, T-cell acute lymphocytic leukemia protein/ lymphoblastic leukemia-derived sequence (TAL/LYL) family, ovary, uterus and testis protein (OUT) family, mesoderm posterior protein (Mesp) family, muscle, intestine and stomach expression 1 (MIST-1) family, protein atonal homologs (ATOH) family, neurogenin (NGN) family, neurogenic differentiation factor (NeuroD) family, achaete-scute complex-like (ASCL) family, Fer3-like protein (FERD3L)-like family, and Oligodendrocyte lineage genes (OLIG) family of transcription factors.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 755509282  27 EKKRRARINVSLEQLRSLLerhySHQIRKRKLEKADILELSVKYMRSLQNSL 78
Cdd:cd11390    8 ERRRMHDLNDAFEALRKVL----PTVPPDKKLSKIETLRLAINYIAALSDLL 55

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 755509282  22 SKPLMEKKRRARINVSLEQLRSLLERhyshqiRKRKLEKADILELSVKYMRS 73
Cdd:cd11441    3 SRNLSEKKRRDQFNVLINELASMLPG------RGRKMDKSTVLKKTIAFLRK 48

basic helix-loop-helix-Per-ARNT-Sim (bHLH-PAS) domain found in Circadian locomotor output cycles protein kaput (CLOCK) and similar proteins; CLOCK, also termed Class E basic helix-loop-helix protein 8 (bHLHe8), is a bHLH-PAS transcriptional activator which forms a core component of the circadian clock. It forms heterodimers with another bHLH-PAS protein, Brain-Muscle-Arnt-Like (also known as BMAL or ARNT3 or mop3), which regulates circadian rhythm. BMAL1-CLOCK heterodimer complex activates transcription from E-box (CANNTG) elements found in the promoter of circadian responsive genes.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 755509282  19 RKISKPLMEKKRRARINVSLEQLRSLLERHyshqirKRKLEKADILELSVKYMR 72
Cdd:cd19734    7 KRVSRNKSEKKRRDQFNVLIKELGSMLPGN------ARKMDKSTVLQKSIDFLR 54

basic helix-loop-helix (bHLH) domain found in Drosophila melanogaster achaete-scute complex (AS-C) proteins, achaete-scute-like proteins, ASCL1-2, and similar proteins; This subfamily includes Drosophila melanogaster AS-C proteins and two ASCL family of transcription factors, ASCL-1 and ASCL-2. Drosophila melanogaster AS-C proteins includes 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. 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 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 involved in Schwann cell differentiation and control of proliferation in adult peripheral nerves.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 755509282  27 EKKRRARINVSLEQLRSllerHYSHQIRKRKLEKADILELSVKYMRSLQNSL 78
Cdd:cd19723    9 ERNRVKLVNLGFATLRE----HVPNGRANKKMSKVETLRSAVEYIRQLQQLL 56

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 755509282  26 MEKKRRARINVSLEQLRSLLErhySHQIRKRKLEKADILELSVKYMRSLQNS 77
Cdd:cd11438   14 IEKRRRDKMNSFIDELASLVP---TCNAMSRKLDKLTVLRMAVQHMKTLRGA 62

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'.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 755509282  27 EKKRRARINVSLEQLRSLLERHyshqiRKRKLEKADILELSVKYMRSLQNSLQGL 81
Cdd:cd11419   12 ERRRMQSINAGFQSLRTLLPHC-----DGEKLSKAAILQQTAEYIFSLEQEKTRL 61

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 755509282  19 RKISKPLMEKKRRARINVSLEQLRSLLERHYSHQIRkrkLEKADILELSVKYMRSLQNSLQ 79
Cdd:cd18928   11 KKDNHNLIERRRRFNINDRIKELGTLIPKSTDPEMR---WNKGTILKASVDYIRKLQKEQQ 68

basic helix-loop-helix (bHLH) domain found in Fer3-like protein (FERD3L), pancreas transcription factor 1 subunit alpha (PTF1A) and similar proteins; The family corresponds to a group of bHLH transcription factors, including FERD3L and PTF1A. FERD3L, also termed basic helix-loop-helix protein N-twist, or Class A basic helix-loop-helix protein 31 (bHLHa31), or nephew of atonal 3 (NATO3), or Neuronal twist (NTWIST), is expressed in the developing central nervous system (CNS). It regulates floor plate (FP) cells development. FP is a critical organizing center located at the ventral-most midline of the neural tube. FERD3L binds to the E-box and functions as inhibitor of transcription. PTF1A, also termed Class A basic helix-loop-helix protein 29 (bHLHa29), or pancreas-specific transcription factor 1a, or bHLH transcription factor p48, or p48 DNA-binding subunit of transcription factor PTF1 (PTF1-p48), is implicated in the cell fate determination in various organs. It binds to the E-box consensus sequence 5'-CANNTG-3' and plays a role in early and late pancreas development and differentiation.

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                 ....*....|....*....|....*....|....*....|....*....|..
gi 755509282  27 EKKRRARINVSLEQLRslleRHYSHQIRKRKLEKADILELSVKYMRSLQNSL 78
Cdd:cd19686    9 ERKRMRSINDAFDGLR----RHIPTFPYEKRLSKVDTLRLAIQYINFLTELL 56

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in sterol regulatory element-binding protein (SREBP) family; 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.

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                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 755509282  19 RKISKPLMEKKRRARINVSLEQLRSLLERHYShqirkrKLEKADILELSVKYMRSLQNSLQGL 81
Cdd:cd11394    6 KRSAHNAIEKRYRSSINDRIIELKDLVVGPDA------KMNKSAVLRKAIDYIRYLQKVNQKL 62