basic Helix Loop Helix (bHLH) domain superfamily; bHLH proteins are transcriptional regulators that are found in organisms from yeast to humans. Members of the bHLH superfamily have two highly conserved and functionally distinct regions. The basic part is at the amino end of the bHLH that may bind DNA to a consensus hexanucleotide sequence known as the E box (CANNTG). Different families of bHLH proteins recognize different E-box consensus sequences. At the carboxyl-terminal end of the region is the HLH region that interacts with other proteins to form homo- and heterodimers. bHLH proteins function as a diverse set of regulatory factors because they recognize different DNA sequences and dimerize with different proteins. The bHLH proteins can be divided to cell-type specific and widely expressed proteins. The cell-type specific members of bHLH superfamily are involved in cell-fate determination and act in neurogenesis, cardiogenesis, myogenesis, and hematopoiesis.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2241061111 162 MTHIAVERNRRKQMNEYLSVLRSLMPESYVQRGDQASIIGGAINFVKELEQRLQLLGGHKEIKGKSDHGEH 232
Cdd:cd11448     1 MTHIAVERNRRKQMNEHLNVLRSLMPGSYIQRGDQASIVGGAIEFVKELEQLLQSLEAQKRRRTLNESSVP 71

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        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2241061111 162 MTHIAVERNRRKQMNEYLSVLRSLMPESYVQRGDQASIIGGAINFVKELEQRLQLLGGHKEIKGKSDHGEH 232
Cdd:cd11448     1 MTHIAVERNRRKQMNEHLNVLRSLMPGSYIQRGDQASIVGGAIEFVKELEQLLQSLEAQKRRRTLNESSVP 71

helix loop helix domain;

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2241061111  166 AVERNRRKQMNEYLSVLRSLMPESY-VQRGDQASIIGGAINFVKELEQRLQ 215
Cdd:smart00353   2 ARERRRRRKINEAFDELRSLLPTLPkNKKLSKAEILRLAIEYIKSLQEELQ 52

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        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2241061111 162 MTHIAVERNRRKQMNEYLSVLRSLMPESYVQRGDQASIIGGAINFVKELEQRLQLLGGHKEIKGKSDHGEH 232
Cdd:cd11448     1 MTHIAVERNRRKQMNEHLNVLRSLMPGSYIQRGDQASIVGGAIEFVKELEQLLQSLEAQKRRRTLNESSVP 71

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 2241061111 168 ERNRRKQMNEYLSVLRSLMPEsyVQRGDQASIIGGAINFVKELEQRLQLLGGHKEIKGKSDHGEHHAS 235
Cdd:cd11443     7 ERRRRKKLNDRLYMLRSVVPK--ITKMDRASILGDAIDYVKELLQEINELQDELEGLPESESGETLSQ 72

basic helix-loop-helix (bHLH) domain found in Arabidopsis thaliana OBP3-responsive gene 2 (ORG2), 3 (ORG3) and similar proteins; The family includes ORG2 (also termed AtbHLH38, or EN 8) and ORG3 (also termed AtbHLH39, or EN 9), both of which act as bHLH transcription factors.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 2241061111 161 RMTHIAVERNRRKQMNEYLSVLRSLMPESYVQRGDQAS-IIGGAINFVKELEQRLQLL 217
Cdd:cd18914     2 KLLHNDVERQRRQEMASLFSSLRSLLPLQYIKGKLSVSdHVDEAVNYIKELQEKIKEL 59

basic Helix-Loop-Helix (bHLH) domain found in Arabidopsis thaliana MYC1 and similar proteins; MYC1, also termed AtbHLH12, or EN 58, acts as a transcription activator, when associated with MYB75/PAP1 or MYB90/PAP2.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2241061111 164 HIAVERNRRKQMNEYLSVLRSLMPESYvqRGDQASIIGGAINFVKELEQRLQLLGGHKEIK 224
Cdd:cd18918     1 LFATERERREKLNEKFSDLRNLIPNPT--KNDRASILSDAIKYINELQRTVEELKSLVEKK 59

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        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 2241061111 158 ENQRMTHIAVERNRRKQMNEYLSVLRSLMPEsyVQRGDQASIIGGAINFVKELE 211
Cdd:cd11450     1 SSPASKNLVSERNRRQKLNQRLFALRSVVPN--ITKMDKASIIKDAISYIQELQ 52

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        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2241061111 164 HIAVERNRRKQMNEYLSVLRSLMPEsyVQRGDQASIIGGAINFVKELEQRLQLLGGHKEIKGKS 227
Cdd:cd11449     9 HVEAERQRREKLNQRFYALRAVVPN--VSKMDKASLLGDAISYINELKSKVQDMETEKKEMKRQ 70

basic helix-loop-helix (bHLH) domain found in Arabidopsis thaliana protein AIG1 and similar proteins; AIG1, also termed AtbHLH32, or EN 54, or protein target of MOOPTEROS 5, is a transcription factor required for MONOPTEROS-dependent root initiation in embryo.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 2241061111 163 THIAVERNRRKQMNEYLSVLRSLMPESyvQRGDQASIIGGAINFVKELEQ 212
Cdd:cd11455    10 SHSEAERRRRERINSHLATLRTLLPNL--SKTDKASLLAEVVQHVKELKR 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 2241061111 164 HIAVERNRRKQMNEYLSVLRSLMPESYVQRG----DQASIIGGAINFVKELEQRL 214
Cdd:cd11389     1 HKVIEKRRRDRINESLAELRRLVPEARKSKGsgklEKAEILEMTLQHLKALQSST 55

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        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2241061111 161 RMTHIAVERNRRKQMNEYLSVLRSLMPESyvqRGDQAS---IIGGAINFVKELEQRLQLLggHKEIK 224
Cdd:cd19690     1 RVSHKLAERKRRKEMKELFEDLRDALPQE---RGTKASkweILTKAISYIQQLKRHIREL--RSEVN 62

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 2241061111 163 THIAVERNRRKQMNEYLSVLRSLMPESYVQRGDQ----ASIIGGAINFVKELEQRLQ 215
Cdd:cd11387     1 SHNAVERRRRDNINEKIQELGSLVPPSRLETKDLkpnkGSILSKAVEYIRELQNQNQ 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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2241061111 158 ENQRMTHIAVERNRRKQMNEYLSVLRSLMPESYVQRGDQASIIGG----AINFVKELE---QRLQ 215
Cdd:cd18923     6 ERRRAQHNEVERRRRDKINNWIVQLSKIIPDCNTDNSKTGASKGGilskACDYIRELRqtnQRMQ 70

basic helix-loop-helix (bHLH) domain found in Saccharomyces cerevisiae phosphate system positive regulatory protein PHO4 and similar proteins; PHO4 is a transcriptional activator that regulates the expression of repressible phosphatase under phosphate starvation conditions in Saccharomyces cerevisiae. The PHO4 protein has four functional domains with the bHLH domain at its carboxyl-terminal region. It regulates transcription by binding to promoter of the genes as a homodimer.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 2241061111 160 QRMTHIAVERNRRKQMNEYLSVLRSLMPESYVQRGDQASIIGGAINFVKE 209
Cdd:cd11392     2 KRTAHKVAERGRRDRLNAALKELASLMPAEFVEGKMGADGSASDSNDKEK 51

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 2241061111 156 EIENQRMTHIAVERNRRKQMNEYLSVLRSLMP--ESYVQRGDQASIIGGAINFVKEL 210
Cdd:cd11438     3 RIKNAREAHSQIEKRRRDKMNSFIDELASLVPtcNAMSRKLDKLTVLRMAVQHMKTL 59