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        60
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 30680903 213 RAAEVHNLSERKRRDRINERMKALQELIPRCNKSDKASMLDEAIEYMKSLQLQIQMMSMGC 273
Cdd:cd11445   1 RAAEVHNLSERRRRDRINEKMKALQELIPNCNKTDKASMLDEAIEYLKSLQLQVQMMSMGN 61

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        60
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 30680903 213 RAAEVHNLSERKRRDRINERMKALQELIPRCNKSDKASMLDEAIEYMKSLQLQIQMMSMGC 273
Cdd:cd11445   1 RAAEVHNLSERRRRDRINEKMKALQELIPNCNKTDKASMLDEAIEYLKSLQLQVQMMSMGN 61

Helix-loop-helix DNA-binding domain;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 30680903   216 EVHNLSERKRRDRINERMKALQELIPRCN---KSDKASMLDEAIEYMKSLQ 263
Cdd:pfam00010   3 EAHNERERRRRDRINDAFDELRELLPTLPpdkKLSKAEILRLAIEYIKHLQ 53

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        60
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 30680903 213 RAAEVHNLSERKRRDRINERMKALQELIPRCNKSDKASMLDEAIEYMKSLQLQIQMMSMGC 273
Cdd:cd11445   1 RAAEVHNLSERRRRDRINEKMKALQELIPNCNKTDKASMLDEAIEYLKSLQLQVQMMSMGN 61

basic helix-loop-helix (bHLH) domain found in Arabidopsis thaliana BIG PETAL (BPE) and similar proteins; The family includes several bHLH transcription factors from Arabidopsis thaliana, such as BPE, HBI1 and BEE proteins (BEE1-3). BPE, also termed AtbHLH31, or EN 88, is involved in the control of Arabidopsis petal size, by interfering with postmitotic cell expansion to limit final petal cell size. HBI1, also termed AtbHLH64, or homolog of bee2 interacting with IBH1, or EN 79, is an atypical bHLH transcription factor that acts as positive regulator of cell elongation downstream of multiple external and endogenous signals by direct binding to the promoters and activation of the two expansin genes EXPA1 and EXPA8, encoding cell wall loosening enzymes. BEEs, also termed protein Brassinosteroid enhanced expression, are positive regulators of brassinosteroid signaling.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 30680903 210 KRSRAAEVHNLSERKRRDRINERMKALQELIPRCNK-SDKASMLDEAIEYMKSLQLQIQMMSM 271
Cdd:cd18919   8 RRGQATDSHSLAERVRREKISERMKLLQDLVPGCNKvTGKALMLDEIINYVQSLQRQVEFLSM 70

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 30680903 220 LSERKRRDRINERMKALQELIPRCNKSDKASMLDEAIEYMKSLQLQIQMMSM 271
Cdd:cd11454   7 VAARHRRERISERIRILQRLVPGGTKMDTASMLDEAIHYVKFLQLQVKLLQS 58

Helix-loop-helix DNA-binding domain;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 30680903   216 EVHNLSERKRRDRINERMKALQELIPRCN---KSDKASMLDEAIEYMKSLQ 263
Cdd:pfam00010   3 EAHNERERRRRDRINDAFDELRELLPTLPpdkKLSKAEILRLAIEYIKHLQ 53

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 30680903 218 HNLSERKRRDRINERMKALQELIPRCNKSDKASMLDEAIEYMKSLQLQIQMM 269
Cdd:cd11452   6 HILAERKRREKLSQRFIALSALVPGLKKMDKASVLGDAIKHIKQLQERVKEL 57

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 30680903 218 HNLSERKRRDRINERMKALQELIPRCNKS------DKASMLDEAIEYMKSLQ 263
Cdd:cd11389   1 HKVIEKRRRDRINESLAELRRLVPEARKSkgsgklEKAEILEMTLQHLKALQ 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 30680903 218 HNLSERKRRDRINERMKALQELIPRCN------KSDKASMLDEAIEYMKSLQLQIQ 267
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 30680903 222 ERKRRDRINERMKALQELIPRCNKSDKASM---LDEAIEYMKSLQ 263
Cdd:cd00083   1 ERRRRDKINDAFEELKRLLPELPDSKKLSKasiLQKAVEYIRELQ 45

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 30680903 218 HNLSERKRRDRINERMKALQELIPRCNKSDKASMLDEAIEYMKSLQLQIQMMSM 271
Cdd:cd11449   9 HVEAERQRREKLNQRFYALRAVVPNVSKMDKASLLGDAISYINELKSKVQDMET 62

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in the microphthalmia-associated transcription factor family (MITF) family; The MITF (also known as microphthalmia-TFE, or MiT) family is a small family that contain a basic helix loop helix domain associated with a leucine zipper (bHLHZip). The MITF family comprises four genes in mammals (MITF, TFE3, TFEB, and TFEC); each gene has different functions. MITF is involved in neural crest melanocytes development as well as the pigmented retinal epithelium. TFEB is required for vascularization of the mouse placenta. TFE3 is involved in B cell function. TFEC regulates gene expression in macrophages. The MITF family can form homodimers or heterodimers with each other but not with other bHLH or bHLHzip proteins.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 30680903 218 HNLSERKRRDRINERMKALQELIPRCNKSD----KASMLDEAIEYMKSLQLQIQMM 269
Cdd:cd11397   9 HNMIERRRRFNINDRIKELGTLLPKSNDPDmrwnKGTILKASVDYIRKLQKEQERL 64

basic helix-loop-helix (bHLH) domain found in Arabidopsis thaliana Fe-deficiency induced transcription factor 1 (FIT) and similar proteins; The family includes bHLH transcription factors from Arabidopsis thaliana, such as FIT and DYT1. FIT, also termed FER-like iron deficiency-induced transcription factor, or FER-like regulator of iron uptake, or AtbHLH29, or EN 43, is a bHLH transcription factor that is required for the iron deficiency response in plant. It regulates FRO2 at the level of mRNA accumulation and IRT1 at the level of protein accumulation. DYT1, also termed AtbHLH22, or protein dysfunctional tapetum 1, or EN 49, is a bHLH transcription factor involved in the control of tapetum development. It is required for male fertility and pollen differentiation, especially during callose deposition.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*
gi 30680903 221 SERKRRDRINERMKALQELIPRCNKSDKASMLDEAIEYMKSLQLQ 265
Cdd:cd11450  10 SERNRRQKLNQRLFALRSVVPNITKMDKASIIKDAISYIQELQYQ 54

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 30680903 221 SERKRRDRINERMKALQELIPRCNKSDKASMLDEAIEYMKSLQLQIQ 267
Cdd:cd18917   4 NEKSRKEKIKKAVKLLRSIVPGGESMDTALVLDEAIDYLKSLKMELQ 50

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 30680903 215 AEVHNLSERKRRDRINERMKALQELIP----RCNKSDKASMLDEAIEYMKSLQL 264
Cdd:cd11391   1 REKSREAAKKRRDKENAEISELASLLPlppaVGSKLDKLSVLRLAVAYLRLKKF 54

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
                ....*....|....*....|....*....|....*....|....*...
gi 30680903 218 HNLSERKRRDRINERMKALQELIPRC--NKSDKASMLDEAIEYMKSLQ 263
Cdd:cd11404   6 HVRSEKKRRELIKKGYDELCALVPGLdpQKRTKADILQKAADWIQELK 53

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 30680903 222 ERKRRDRINERMKALQELIP--------RCNKSDKASMLDEAIEYMKSLQLQ 265
Cdd:cd11410   2 EKKRRARINKSLEQLKTLVLealnkdntRYSKLEKADILEMTVKYLKQLQRS 53

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in basic helix-loop-helix domain-containing protein USF3 and similar proteins; USF3, also termed upstream transcription factor 3, is a bHLHzip protein that is involved in the negative regulation of epithelial-mesenchymal transition, the process by which epithelial cells lose their polarity and adhesion properties to become mesenchymal cells with enhanced migration and invasive properties.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 30680903 210 KRSRAAEVHNLSERKRRDRINERMKALQELIPRCN--KSDKASMLDEAIEYMKSLQ 263
Cdd:cd18910   1 RREKKRESHNEVERRRKDKINAGINKIGELLPDRDakKQSKNMILEQAYKYIVELK 56

basic helix-loop-helix (bHLH) domain found in the spermatogenesis- and oogenesis-specific basic helix-loop-helix-containing protein (SOHLH) family; The SOHLH family includes two bHLH transcription factors, SOHLH1 and SOHLH2. They are specifically in spermatogonia and oocytes and essential for early spermatogonial and oocyte differentiation.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*
gi 30680903 215 AEVHNLSERKRRDRINERMKALQELIPRCN--KSDKASMLDEAIEYMKSLQLQIQ 267
Cdd:cd18908   3 ASSHSLKERLRRERIKSSCDQLRDLLPYIKgrKLDMASVLEMTVKYIRYIQERIP 57

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in microphthalmia-associated transcription factor (MITF) and similar proteins; MITF, also termed Class E basic helix-loop-helix protein 32 (bHLHe32), is a bHLHzip transcription factor that is involved in neural crest melanocytes development as well as the pigmented retinal epithelium. It regulates the expression of genes with essential roles in cell differentiation, proliferation and survival. It binds to M-boxes (5'-TCATGTG-3') and symmetrical DNA sequences (E-boxes) (5'-CACGTG-3') found in the promoters of target genes, such as BCL2 and tyrosinase (TYR).

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 30680903 210 KRSRAAEVHNLSERKRRDRINERMKALQELIPRCNKSD----KASMLDEAIEYMKSLQ 263
Cdd:cd18926   9 KERQKKDNHNLIERRRRFNINDRIKELGTLIPKSNDPDmrwnKGTILKASVDYIRKLQ 66

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
                ....*....|....*....|....*....|....*....|....
gi 30680903 219 NLSERKRRDRINERMKALQELIPRCN-KSDKASMLDEAIEYMKS 261
Cdd:cd11441   5 NLSEKKRRDQFNVLINELASMLPGRGrKMDKSTVLKKTIAFLRK 48

basic helix-loop-helix-Per-ARNT-Sim (bHLH-PAS) domain found in aryl hydrocarbon receptor nuclear translocator (ARNT) family; The ARNT family of bHLH-PAS transcription regulators includes ARNT, ARNT-like proteins (ARNTL and ARNTL2), and Drosophila melanogaster protein cycle. They act as the heterodimeric partner for bHLH-PAS proteins such as aryl hydrocarbon receptor (AhR), hypoxia-inducible factor (HIF), and single-minded (SIM). These bHLH-PAS transcription complexes are involved in transcriptional responses to xenobiotic, hypoxia, and developmental pathways. Heterodimerization of bHLH-PAS proteins with ARNT is mediated by contacts between both the bHLH and the tandem PAS domains. ARNT use bHLH and/or PAS domains to interact with several transcriptional coactivators. It is required for activity of the aryl hydrocarbon (dioxin) receptor. ARNTL, also termed Basic-helix-loop-helix-PAS protein MOP3, or brain and muscle ARNT-like 1 (BMAL1), or Class E basic helix-loop-helix protein 5 (bHLHe5), or member of PAS protein 3, or PAS domain-containing protein 3 (PASD3), or bHLH-PAS protein JAP3, is a member of the bHLH-PAS transcription factor family that forms heterodimers with another bHLH-PAS protein, CLOCK (circadian locomotor output cycle kaput), which regulates circadian rhythm. ARNTL-CLOCK heterodimer complex activates transcription from E-box (CANNTG) elements found in the promoter of circadian responsive genes. ARNTL is highly homologous to ARNT. ARNTL2, also termed Basic-helix-loop-helix-PAS protein MOP9, or brain and muscle ARNT-like 2 (BMAL2), or CYCLE-like factor (CLIF), or Class E basic helix-loop-helix protein 6 (bHLHe6), or member of PAS protein 9, or PAS domain-containing protein 9 (PASD9), is a neuronal bHLH-PAS transcriptional factor, regulating cell cycle progression and preventing cell death, whose sustained expression might ensure brain neuron survival. It also plays important roles in tumor angiogenesis. Protein cycle, also termed brain and muscle ARNT-like 1 (BMAL1), or MOP3, is a putative bHLH-PAS transcription factor involved in the generation of biological rhythms in Drosophila. It activates cycling transcription of Period (PER) and Timeless (TIM) by binding to the E-box (5'-CACGTG-3') present in their promoters.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*....
gi 30680903 218 HNLSERKRRDRINERMKALQELIPRCN----KSDKASMLDEAIEYMKSL 262
Cdd:cd11437   5 HSEIEKRRRDKMNAYIQELSALVPACNamsrKLDKLTVLRMAVQHLKSL 53

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 30680903 220 LSERKRRDRINERMKALQELIPR------CNKSDKASMLDEAIEYMKSLQ 263
Cdd:cd18916   6 MLERQRRARINKCLSELKTLVAEcsgddgCLRMDKAEMLETAVAFMRQQQ 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 30680903 210 KRSRAAevHNLSERKRRDRINERMKALQELIPRCN-----KSDKASMLDEAIEYMKSLQLQIQMM 269
Cdd:cd11405   1 EQRRLS--HISAEQKRRFNIKSGFDTLQSLIPSLGqnpnqKVSKAAMLQKAAEYIKSLKRERQQM 63

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 30680903 216 EVHNLSERKRRDRINERMKALQELIPRCN----KSDKASMLDEAIEYMKSLQ 263
Cdd:cd11469   3 EAHSQTEKRRRDKMNNLIEELSAMIPQCNpmarKLDKLTVLRMAVQHLKSLK 54

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 30680903 218 HNLSERKRRDRINERMKALQELIP--RCNKSDKASMLDEAIEYMKSLQLQIQMM 269
Cdd:cd19690   4 HKLAERKRRKEMKELFEDLRDALPqeRGTKASKWEILTKAISYIQQLKRHIREL 57

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in upstream stimulatory factor 2 (USF2) and similar proteins; USF2, also termed Class B basic helix-loop-helix protein 12 (bHLHb12), or major late transcription factor 2, or FOS-interacting protein (FIP), or upstream transcription factor 2, is a bHLHzip transcription factor that binds to a symmetrical DNA sequence (E-boxes) (5'-CACGTG-3') that is found in a variety of viral and cellular promoters.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30680903 206 TTSTKRSRAAevHNLSERKRRDRINERMKALQELIPRCNK------SDKASMLDEAIEYMKSLQLQIQMM 269
Cdd:cd18923   2 TPRDERRRAQ--HNEVERRRRDKINNWIVQLSKIIPDCNTdnsktgASKGGILSKACDYIRELRQTNQRM 69

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 30680903 210 KRSRAaEVHNLSERKRRDRINERMKALQELIPRCN--KSDKASMLDEAIEYMKSLQ 263
Cdd:cd11419   1 RRIRR-EIANSNERRRMQSINAGFQSLRTLLPHCDgeKLSKAAILQQTAEYIFSLE 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 30680903 222 ERKRRDRINERMKALQELIP-------RCNKSDKASMLDEAIEYMKSLQLQIQ 267
Cdd:cd18933   2 EKKRRARINVSLEQLKSLLEkhysnniRKRKLEKADILELTVKYLRSLQNSIQ 54

basic helix-loop-helix-orange (bHLH-O) domain found in differentially expressed in chondrocytes protein (DEC) family; The DEC family includes two bHLH-O transcriptional repressors, DEC1 and DEC2, which are widely expressed in both embryonic and adult tissues and have been implicated in apoptosis, cell proliferation, and circadian rhythms, as well as malignancy in various cancers. They mediate the circadian rhythm by negatively regulating the activity of the clock genes and clock-controlled genes. They are induced by CLOCK:BMAL1 heterodimer via the CACGTG E-box in the promoter.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|.
gi 30680903 218 HNLSERKRRDRINERMKALQELIPRCNK------SDKASMLDEAIEYMKSL 262
Cdd:cd11409   8 HRLIEKKRRDRINECIAQLKDLLPEHLKlttlghLEKAVVLELTLKHLKAL 58

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in upstream stimulatory factor 1 (USF1) and similar proteins; USF1, also termed Class B basic helix-loop-helix protein 11 (bHLHb11), or major late transcription factor 1, is a bHLHzip transcription factor that binds to a symmetrical DNA sequence (E-boxes) (5'-CACGTG-3') that is found in a variety of viral and cellular promoters. It is ubiquitously expressed and involved in the transcription activation of various functional genes implicated in lipid and glucose metabolism, stress response, immune response, cell cycle control and tumour suppression. USF-1 recruits chromatin remodeling enzymes and interact with co-activators and the members of the transcription pre-initiation complex. Genetic polymorphisms of USF1 are associated with some metabolic and cardiovascular diseases, like diabetes, atherosclerosis, coronary artery calcifications and familial combined hyperlipidaemia (FCHL).

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|..
gi 30680903 218 HNLSERKRRDRINERMKALQELIPRC------NKSDKASMLDEAIEYMKSLQ 263
Cdd:cd18924   9 HNEVERRRRDKINNWIVQLSKIIPDCsmestkSGQSKGGILSKACDYIQELR 60

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 30680903 208 STKRSRAAEV----HNLSERKRRDRINERMKALQELIPRCNK------SDKASMLDEAIEYMKSL 262
Cdd:cd19750   5 GLKRDESKEAyklpHRLIEKKRRDRINECIAQLKDLLPEHLKlttlghLEKAVVLELTLKHLKAL 69

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in sterol regulatory element-binding protein 2 (SREBP2) and similar proteins; SREBP2, also termed Class D basic helix-loop-helix protein 2 (bHLHd2), or sterol regulatory element-binding transcription factor 2 (SREBF2), is a member of a family of bHLHzip transcription factors that recognize sterol regulatory element 1 (SRE-1). It acts as a transcription activator of cholesterol biosynthesis.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*..
gi 30680903 218 HNLSERKRRDRINERMKALQELI-PRCNKSDKASMLDEAIEYMKSLQ 263
Cdd:cd18922  10 HNIIEKRYRSSINDKIIELKDLVmGTDAKMHKSGVLRKAIDYIKYLQ 56

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 30680903 218 HNLSERKRRDRINERMKALQELIPRC-----------------------NKSDKASMLDEAIEYMKSLQ 263
Cdd:cd11399   7 HNMIEKRYRSNINDRIAELRDSVPALreayksargededeedlggltpaTKLNKATILSKATEYIRHLE 75

basic helix-loop-helix-orange (bHLH-O) domain found in Drosophila melanogaster enhancer of split mbeta protein (ESMB) and similar proteins; ESMB, also termed E(spl)mbeta, or HLH-mbeta, or split locus enhancer protein mA, is a bHLH-O transcriptional repressor of genes that require a bHLH protein for their transcription. It is involved in the neural-epidermal lineage decision during early neurogenesis. The family also includes Enhancer of split m7 protein (also known as E(spl)m7), which acts as a transcriptional repressor that participates in the control of cell fate choice by uncommitted neuroectodermal cells in the embryo.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....
gi 30680903 220 LSERKRRDRINERMKALQELIPRC--------NKSDKASMLDEAIEYMKSLQLQ 265
Cdd:cd19741  14 LLERKRRARINKCLDELKDLMVEAlateaenvSKLEKADILELTVRHLKKLRRQ 67

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.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|.
gi 30680903 218 HNLSERKRRDRINERMKALQELI-PRCNKSDKASMLDEAIEYMKSLQLQIQ 267
Cdd:cd11394  10 HNAIEKRYRSSINDRIIELKDLVvGPDAKMNKSAVLRKAIDYIRYLQKVNQ 60

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
                ....*....|....*....|....*....|....*....|....
gi 30680903 219 NLSERKRRDRINERMKALQELIPRCN-KSDKASMLDEAIEYMKS 261
Cdd:cd19735  15 NLSEKKRRDQFNVLINELCSMVSTSNrKMDKSTVLKSTIAFLKN 58

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 30680903 219 NLSERKRRDRINERMKALQELIP---RCNKSDKASMLDEAIEYMKSLQ 263
Cdd:cd11418   6 NERERRRVQAVNDAFDRLRQHVPylkRRKKLSKVKTLRRAIEYIRHLQ 53

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

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|.
gi 30680903 218 HNLSERKRRDRINERMKALQELIPRCN-KSDKASMLDEAIEYMKSLQLQIQ 267
Cdd:cd18921  10 HNAIEKRYRSSINDKIIELKDLVVGTEaKLNKSAVLRKAIDYIRFLQQSNQ 60

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
                ....*....|....*....|....*....|....*....|...
gi 30680903 219 NLSERKRRDRINERMKALQELIP-RCNKSDKASMLDEAIEYMK 260
Cdd:cd19734  12 NKSEKKRRDQFNVLIKELGSMLPgNARKMDKSTVLQKSIDFLR 54

basic helix-loop-helix-orange (bHLH-O) domain found in hairy/enhancer-of-split related with YRPW motif-like protein (HEYL) and similar proteins; HEYL, also termed Class B basic helix-loop-helix protein 33 (bHLHb33), or hairy-related transcription factor 3 (HRT-3), is a bHLH-O transcriptional repressor that is strongly expressed in the presomitic mesoderm, the somites, the peripheral nervous system and smooth muscle of all arteries and is a downstream effector of the Notch and transforming growth factor-beta pathways. It promotes neuronal differentiation by activating proneural genes and inhibiting other hairy and enhancer of split (HES) and hairy/enhancer-of-split related with YRPW motif protein (HEY) proteins. HEYL also functions as a tumor suppressor involved in the progression of human cancers.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 30680903 206 TTSTKRSRAAEVHNLSERKRRDRINERMKALQELIPRC------NKSDKASMLDEAIEYMKSLQ 263
Cdd:cd11447   1 TTSSQIQARKKRRGIIEKRRRDRINSSLSELRRLVPTAfekqgsSKLEKAEILQMTVDHLKMLH 64