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        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1395447074 184 RDRRKKDIHNMIERRRRYNINDRIKELGQMLPKNTSEDMKLNKGTILKASCDYIRVLQKDREQAMKTQQ 252
Cdd:cd11397     1 KDRQKKDNHNMIERRRRFNINDRIKELGTLLPKSNDPDMRWNKGTILKASVDYIRKLQKEQERLRQLEE 69

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        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1395447074 184 RDRRKKDIHNMIERRRRYNINDRIKELGQMLPKNTSEDMKLNKGTILKASCDYIRVLQKDREQAMKTQQ 252
Cdd:cd11397     1 KDRQKKDNHNMIERRRRFNINDRIKELGTLLPKSNDPDMRWNKGTILKASVDYIRKLQKEQERLRQLEE 69

helix loop helix domain;

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1395447074  193 NMIERRRRYNINDRIKELGQMLPKNTSeDMKLNKGTILKASCDYIRVLQK 242
Cdd:smart00353   1 NARERRRRRKINEAFDELRSLLPTLPK-NKKLSKAEILRLAIEYIKSLQE 49

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        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1395447074 184 RDRRKKDIHNMIERRRRYNINDRIKELGQMLPKNTSEDMKLNKGTILKASCDYIRVLQKDREQAMKTQQ 252
Cdd:cd11397     1 KDRQKKDNHNMIERRRRFNINDRIKELGTLLPKSNDPDMRWNKGTILKASVDYIRKLQKEQERLRQLEE 69

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        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1395447074 182 YYRDRRKKDIHNMIERRRRYNINDRIKELGQMLPKNTSEDMKLNKGTILKASCDYIRVLQKDREQAMKTQQQQKSLESTA 261
Cdd:cd18928     5 FLKERQKKDNHNLIERRRRFNINDRIKELGTLIPKSTDPEMRWNKGTILKASVDYIRKLQKEQQRSKEIEMRQRKLEQAN 84

                  ....*..
gi 1395447074 262 HKYADRV 268
Cdd:cd18928    85 RSLQLRI 91

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in transcription factor EC (TFEC) and similar proteins; TFEC, also termed Class E basic helix-loop-helix protein 34 (bHLHe34), or transcription factor EC-like (TFEC-L), is a bHLHzip transcriptional regulator that acts as a repressor or an activator and regulates gene expression in macrophages. It plays an important role in the niche to expand hematopoietic progenitors through the modulation of several cytokines.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1395447074 184 RDRRKKDIHNMIERRRRYNINDRIKELGQMLPKNTSEDMKLNKGTILKASCDYIRVLQKDREQAMKTQQQQKSLESTAHK 263
Cdd:cd18925     1 KERQKKDNHNLIERRRRYNINYRIKELGTLIPKSNDPDMRWNKGTILKASVEYIKWLQKEQQRARELEHRQKKLEQANRR 80

                  ....*
gi 1395447074 264 YADRV 268
Cdd:cd18925    81 LLLRI 85

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1395447074 186 RRKKDIHNMIERRRRYNINDRIKELGQMLPKNTSEDmklNKGTILKASCDYIRVLQKDREQAMKTQQQQKSLestahkya 265
Cdd:cd11398     5 RQRRDNHKEVERRRRENINEGINELAALVPGNAREK---NKGAILARAVEYIQELQETEAKNIEKWTLEKLL-------- 73

                          90
                  ....*....|...
gi 1395447074 266 drVKELEEMLARQ 278
Cdd:cd11398    74 --TDQAIAELAAL 84

Helix-loop-helix DNA-binding domain;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1395447074 186 RRKKdiHNMIERRRRYNINDRIKELGQMLPKNTSeDMKLNKGTILKASCDYIRVLQ 241
Cdd:pfam00010   1 RREA--HNERERRRRDRINDAFDELRELLPTLPP-DKKLSKAEILRLAIEYIKHLQ 53

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1395447074 188 KKDIHNMIERRRRYNINDRIKELGQMLP------------KNTSEDM-------KLNKGTILKASCDYIRVLQKDREQAM 248
Cdd:cd11399     3 KKTAHNMIEKRYRSNINDRIAELRDSVPalreayksargeDEDEEDLggltpatKLNKATILSKATEYIRHLEKKNKRLS 82

                  ....*
gi 1395447074 249 KTQQQ 253
Cdd:cd11399    83 RENAS 87

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        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1395447074 188 KKDIHNMIERRRRYNINDRIKELGQMLpknTSEDMKLNKGTILKASCDYIRVLQkdrEQAMKTQQQQKSLESTAHK 263
Cdd:cd18921     6 KRTAHNAIEKRYRSSINDKIIELKDLV---VGTEAKLNKSAVLRKAIDYIRFLQ---QSNQKLKQENMALKMAVQK 75

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 1395447074 196 ERRRRYNINDRIKELGQMLPkNTSEDMKLNKGTILKASCDYIRVLQK 242
Cdd:cd00083     1 ERRRRDKINDAFEELKRLLP-ELPDSKKLSKASILQKAVEYIRELQS 46

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in sterol regulatory element-binding protein (SREBP) family and similar proteins; The SREBP family includes SREBP1 and SREBP2, which are bHLHzip transcriptional activator of genes encoding proteins essential for cholesterol biosynthesis/uptake and fatty acid biosynthesis. SREBP1 and SREBP2 are principally found in the liver and in adipocytes and made up of an N-terminal transcription factor portion (composed of an activation domain, a bHLHzip domain, and a nuclear localization signal), a hydrophobic region containing two membrane spanning regions, and a C-terminal regulatory segment. They recognize a symmetric sterol regulatory element (TCACNCCAC) instead of E-box. The family also includes Saccharomyces cerevisiae transcription factor HMS1 (also termed high-copy MEP suppressor protein 1) and serine-rich protein TYE7. HMS1 is a putative bHLHzip transcription factor involved in exit from mitosis and pseudohyphal differentiation. TYE7, also termed basic-helix-loop-helix protein SGC1, is a putative bHLHzip transcription activator required for Ty1-mediated glycolytic gene expression. TYE7 N-terminal is extremely rich in serine residues. It binds DNA on E-box motifs, 5'-CANNTG-3'. TYE7 is not essential for growth.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1395447074 186 RRKKDIHNMIERRRRYNINDRIKELGQMLPKNTSEDM--------------KLNKGTILKASCDYIRVLQKDREQ 246
Cdd:cd11395     1 PRKRLPHNAIEKRYRSNLNTKIERLRDAIPSLRSPEGksddgglgglapttKLSKATILTKAIEYIRHLEQENER 75

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        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1395447074 184 RDRRKKDIHNMIERRRRYNINDRIKELGQMLPKntSEDMKLNKGTILKASCDYIRVLQKDREQAM 248
Cdd:cd18910     1 RREKKRESHNEVERRRKDKINAGINKIGELLPD--RDAKKQSKNMILEQAYKYIVELKKKNDKLL 63

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in MLX-interacting protein (MLXIP), MLX-interacting protein-like (MLXIPL) and similar proteins; The family includes MLXIP and MLXIPL. MLXIP, also termed Class E basic helix-loop-helix protein 36 (bHLHe36), or transcriptional activator MondoA, is a bHLHZip transcriptional activator that binds DNA as a heterodimer with Mlx. It binds to the canonical E box sequence 5'-CACGTG-3' and plays a role in transcriptional activation of glycolytic target genes. MLXIP is most highly expressed in skeletal muscle and functions as an indirect glucose sensor, by sensing glucose 6-phosphate and shuttling between the nucleus and the cytoplasm. MLXIPL, also termed carbohydrate-responsive element-binding protein (ChREBP), or Class D basic helix-loop-helix protein 14 (bHLHd14), or MLX interactor, or WS basic-helix-loop-helix leucine zipper protein (WS-bHLH), or Williams-Beuren syndrome chromosomal region 14 protein (WBSCR14), is a bHLHZip transcriptional factor integral to the regulation of glycolysis and lipogenesis in the liver. It forms heterodimers with the bHLHZip protein Mlx to bind the DNA sequence 5'-CACGTG-3'.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1395447074 186 RRKKDIHNMIERRRRYNINDRIKELGQMLPKNTS-EDMKLNKGTILKASCDYIRVLQKDReQAMKTQQQQ 254
Cdd:cd11405     1 EQRRLSHISAEQKRRFNIKSGFDTLQSLIPSLGQnPNQKVSKAAMLQKAAEYIKSLKRER-QQMQEEAEQ 69

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

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 1395447074 195 IERRRRYNINDRIKELGQMLPKNTSEDM--KLNKGTILKASCDYIRVLQK 242
Cdd:cd19685     1 SEKRRRQRINDKLNQLKELLPPNLSKQSrsKLSKAEILEMAITELRRLQQ 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 1395447074 189 KDIHNMIERRRRYNINDRIKELGQMLPKNTSEDMKLNKGTILKASCDYIRVLQ 241
Cdd:cd11391     1 REKSREAAKKRRDKENAEISELASLLPLPPAVGSKLDKLSVLRLAVAYLRLKK 53

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 1395447074 192 HNMIERRRRYNINDRIKELGQMLP--KNTSEDMKLNKGTILKASCDYIRVLQK 242
Cdd:cd11389     1 HKVIEKRRRDRINESLAELRRLVPeaRKSKGSGKLEKAEILEMTLQHLKALQS 53

basic helix-loop-helix-Per-ARNT-Sim (bHLH-PAS) domain found in circadian clock protein PASD1; PASD1, also termed PAS domain-containing protein 1, 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. Mammalian PASD1 doesn't harbor the bHLH-PAS domain and is not included in this family.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1395447074 184 RDRRKKDIHNMIERRRRYNINDRIKELGQMLpKNTSEDMKLNKGTILKASCDYirvLQKDREQAMKTQ 251
Cdd:cd19736     6 KDRAKRASRNKSEKKRRDQFNVLIKELCTML-QGHGHPLKMDKSTILQRTIDF---LQKQKEITAQTE 69

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        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1395447074 194 MIERRRRYNINDRIKELGQMLPKNTsedmKLNKGTILKASCDYIRVLQkdrEQAMKTQQQQKSLESTAHK 263
Cdd:cd11443     5 MAERRRRKKLNDRLYMLRSVVPKIT----KMDRASILGDAIDYVKELL---QEINELQDELEGLPESESG 67

basic helix-loop-helix-Per-ARNT-Sim (bHLH-PAS) domain found in neuronal PAS domain-containing protein 2 (NPAS2) and similar proteins; 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 (PASD4), is a bHLH-PAS transcriptional activator which forms a core component of the circadian clock.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1395447074 184 RDRRKKDIHNMIERRRRYNINDRIKELGQMLPKNTSedmKLNKGTILKASCDYirvLQKDREQAMKTQ 251
Cdd:cd19737     6 KDRAKRASRNKSEKKRRDQFNVLIKELSSMLPGNTR---KMDKTTVLEKVIGF---LQKHNEVSAQTE 67

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in Max-like protein X (Mlx) and similar proteins; 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.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1395447074 187 RKKDIHNMIERRRRYNINDRIKELGQMLPKNTSEDM----KLNKGTILKASCDYIRVLQKDReqamKTQQQQKS 256
Cdd:cd19687     1 RRREAHTQAEQKRRDAIKKGYDDLQDIVPTCQQQDDigsqKLSKATILQRSIDYIQFLHQQK----KKQEEELS 70

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        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1395447074 196 ERRRRYNINDRIKELGQMLPKNTsedmKLNKGTILKASCDYIRVLqkdreqamktQQQQKSLESTAHKYADRVKELEEM 274
Cdd:cd11450    11 ERNRRQKLNQRLFALRSVVPNIT----KMDKASIIKDAISYIQEL----------QYQEKKLEAEIRELESRPPSTLSF 75

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in Max-like protein X (Mlx) family; Mlx, also termed Class D basic helix-loop-helix protein 13 (bHLHd13), or Max-like bHLHZip protein, or protein BigMax, or transcription factor-like protein 4, is a Max-like bHLHZip transcription regulator that interacts with the Max network of transcription factors. It forms a sequence-specific DNA-binding protein complex with some member of Mad family (Mad1 and Mad4) and Mondo family but not the Myc family and bind the E-box DNA to control transcription. The family also includes Saccharomyces cerevisiae INO4, which is a bHLH transcriptional activator of phospholipid synthetic genes (such as INO1, CHO1/PSS, CHO2/PEM1, OPI3/PEM2, etc.). It is required for de-repression of phospholipid biosynthetic gene expression in response to inositol deprivation in yeast.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1395447074 187 RKKDIHNMIERRRRYNINDRIKELGQMLPKNTSEdmKLNKGTILKASCDYIRVLQKDREQAMK 249
Cdd:cd11404     1 QRRLNHVRSEKKRRELIKKGYDELCALVPGLDPQ--KRTKADILQKAADWIQELKEENEKLEE 61

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in protein Max and similar proteins; Max, also termed Class D basic helix-loop-helix protein 4 (bHLHd4), or Myc-associated factor X, is a bHLHZip transcription regulator that forms a sequence-specific DNA-binding protein complex with MYC or MAD which recognizes the core sequence 5'-CAC[GA]TG-3'. The MYC:MAX complex is a transcriptional activator, whereas the MAD:MAX complex is a transcriptional repressor. Max homodimer bind DNA but is transcriptionally inactive. Targeted deletion of max results in early embryonic lethality in mice.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1395447074 188 KKDIHNMIERRRRYNINDRIKELGQMLPKNTSEdmKLNKGTILKASCDYIRVLQKdreqamKTQQQQKSLE 258
Cdd:cd11406     1 KRAHHNALERKRRDHIKDSFHSLRDSVPSLQGE--KASRAQILKKATEYIQYMRR------KNHTHQQDID 63

basic helix-loop-helix (bHLH) domain found in Arabidopsis thaliana protein transparent testa 8 (TT8) and similar proteins; The family includes several bHLH transcription factors from Arabidopsis thaliana, such as TT8, EGL1, and GL3. TT8, also termed AtbHLH42, or EN 32, is involved in the control of flavonoid pigmentation and plays a key role in regulating leucoanthocyanidin reductase (BANYULS) and dihydroflavonol-4-reductase (DFR). EGL1, also termed AtbHLH2, or EN 30, or AtMYC146, or protein enhancer of GLABRA 3, is involved in epidermal cell fate specification and regulates negatively stomata formation but promotes trichome formation. GL3, also termed AtbHLH1, or AtMYC6, or protein shapeshifter, or EN 31, is involved in epidermal cell fate specification. It regulates negatively stomata formation, but, in association with TTG1 and MYB0/GL1, promotes trichome formation, branching and endoreplication.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1395447074 192 HNMIERRRRYNINDRIKELGQMLPKNTsedmKLNKGTILKASCDYIRVLQK---DREQAMKTQQ 252
Cdd:cd11451     6 HAMAERRRREKLNERFITLRSMVPFVT----KMDKVSILGDAIEYLKQLQRrveELESRRKSSD 65

basic helix-loop-helix-Per-ARNT-Sim (bHLH-PAS) domain found in aryl hydrocarbon receptor nuclear translocator (ARNT) and similar proteins; ARNT, also termed Class E basic helix-loop-helix protein 2 (bHLHe2), or Dioxin receptor, nuclear translocator, or hypoxia-inducible factor 1-beta (HIF1b), or HIF-1-beta, or HIF1-beta, is a member of bHLH-PAS transcription regulators that acts 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.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1395447074 184 RDRRKKDIHNMIERRRRYNINDRIKELGQMLPKNTSEDMKLNKGTILKASCDYIRVLQK 242
Cdd:cd18947     1 KERFARENHSEIERRRRNKMTAYITELSDMVPTCSALARKPDKLTILRMAVSHMKSLRG 59

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in MLX-interacting protein (MLXIP) and similar proteins; 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.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1395447074 184 RDRRKKdiHNMIERRRRYNINDRIKELGQMLPKNTSEDMKLNKGTiLKASCDYIRVLQKDREQamkTQQQQKSL 257
Cdd:cd19688     1 KNRRMK--HISAEQKRRFNIKICFDTLNSLVSTLKNSKPISNAIT-LQKTVEYIAKLQQERTQ---MQEETKRL 68

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        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1395447074 192 HNMIERRRRYNINDRIKELGQMLPkntsEDMKLN------KGTILKASCDYIRVLqkdreQAMKTQQQQKSL 257
Cdd:cd11409     8 HRLIEKKRRDRINECIAQLKDLLP----EHLKLTtlghleKAVVLELTLKHLKAL-----TALTEQQQQKII 70

basic helix-loop-helix (bHLH) domain found in T-cell acute lymphocytic leukemia protein/ lymphoblastic leukemia-derived sequence (TAL/LYL) family; The TAL/LYL family includes a group of bHLH transcription factors (TAL1, TAL2 and LYL1) implicated in T cell acute leukaemia. They act as mediators of T cell leukaemogenesis. TAL-1, also termed Class A basic helix-loop-helix protein 17 (bHLHa17), or stem cell protein (SCL), or T-cell leukemia/lymphoma protein 5, is a hematopoietic-specific bHLH transcription factor that functions in embryonic and adult hematopoiesis in vertebrates. It is also required for embryonic vascular remodeling. It acts as a regulator of erythroid differentiation and binds to regulatory regions of a large cohort of erythroid genes as part of a complex with GATA-1, LMO2 and Ldb1. TAL-2, also termed Class A basic helix-loop-helix protein 19 (bHLHa19), is a bHLH transcription factor essential for the normal brain development. Lyl-1, also termed Class A basic helix-loop-helix protein 18 (bHLHa18), or lymphoblastic leukemia-derived sequence 1, is a proto-oncogenic bHLH transcription factor that plays an important role in hematopoietic stem cell function and is required for the late stages of postnatal angiogenesis to limit the formation of new blood vessels, notably by regulating the activity of the small GTPase Rap1. LYL-1 deficiency induces a stress erythropoiesis.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 1395447074 193 NMIERRRRYNINDRIKELGQMLPKNTSeDMKLNKGTILKASCDYIRVLQK 242
Cdd:cd11413     6 NTRERWRQQNVNGAFAELRKLIPTHPP-DKKLSKNEILRLAMKYIKFLEK 54

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in N-Myc and similar proteins; N-Myc, also termed Class E basic helix-loop-helix protein 37 (bHLHe37), is a bHLHZip proto-oncogene protein that positively regulates the transcription of MYCNOS in neuroblastoma cells. It is also essential during embryonic development. N-Myc has a critical role in regulating the switch between proliferation and differentiation of progenitor cells. It binds DNA as a heterodimer with MAX. The family also includes S-Myc, encoded by rat or mouse intronless myc gene, which has apoptosis-inducing activity.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1395447074 185 DRRKKdiHNMIERRRRYNINDRIKELGQMLPKNTSEDmKLNKGTILKASCDYIRVLQKDREqamKTQQQQKSLESTAHKY 264
Cdd:cd11456     4 ERRRN--HNILERQRRNDLRSSFLTLRDHVPELVKNE-KAAKVVILKKATEYVHSLQAEEQ---KLLLEKEKLQARQQQL 77

                  ....*..
gi 1395447074 265 ADRVKEL 271
Cdd:cd11456    78 LKKIEQA 84

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 1395447074 188 KKDIHNMIERRRRyninDRIKE----LGQMLPKNTSEdmKLNKGTILKASCDYIRVLQ 241
Cdd:cd18908     2 DASSHSLKERLRR----ERIKSscdqLRDLLPYIKGR--KLDMASVLEMTVKYIRYIQ 53

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 1395447074 195 IERRRRYNINDRIKELGQMLPKNTSEDM---KLNKGTILKASCDYIRVLQ 241
Cdd:cd18933     1 MEKKRRARINVSLEQLKSLLEKHYSNNIrkrKLEKADILELTVKYLRSLQ 50

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        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1395447074 184 RDRRKkdihNMIERRRRYNINDRIKELGQMLP----KNTSEdmKLNKGTILKASCDYIRVLQ 241
Cdd:cd19748     9 RKRRR----GIIEKRRRDRINNSLSELRRLVPsafeKQGSA--KLEKAEILQMTVDHLKMLH 64

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in the Myc family; The Myc family is a member of the bHLHzip family of transcription factors that play important roles in the control of normal cell proliferation, growth, survival and differentiation. All Myc isoforms contain two independently functioning polypeptide chain regions: N-terminal transactivating residues and a C-terminal bHLHzip segment. The bHLHzip family of bHLH transcription factors are characterized by a highly conserved N-terminal basic region that may bind DNA at a consensus hexanucleotide sequence known as the E-box (CANNTG) followed by HLH and leucine zipper motifs that may interact with other proteins to form homo- and heterodimers. Myc heterodimerizes with Max enabling specific binding to E-box DNA sequences in the promoters of target genes. The Myc proto-oncoprotein family includes at least five different functional members: c-, N-, L-, S- and B-Myc (which is lacking the bHLH domain).

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1395447074 188 KKDIHNMIERRRRYNINDRIKELGQMLPKNTSEDmKLNKGTILKASCDYIRVLQkDREQAMKTQQQQ 254
Cdd:cd11400     1 KRRLHNVLERQRRNDLKNSFEKLRDLVPELADNE-KASKVVILKKATEYIKQLQ-QEEKKLEKEKDK 65

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in Max-binding protein Mnt and similar proteins; Mnt, also termed Class D basic helix-loop-helix protein 3 (bHLHd3), or Myc antagonist MNT, or protein ROX, is a bHLHZip transcriptional repressor that binds DNA as a heterodimer with MAX. It binds to the canonical E box sequence 5'-CACGTG-3' and, with higher affinity, to 5'-CACGCG-3'. Mnt has an important role as an antagonist and regulator of Myc activities and it is a potential tumor suppressor. Mnt is ubiquitously expressed. Mnt-deficient mice shown to exhibit early postnatal lethality.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1395447074 189 KDIHNMIERRRRYNINDRIKELGQMLPknTSEDMKLNKGTILKASCDYIRVLQK---------DREQAMKTQQQQK 255
Cdd:cd11402     3 REVHNKLEKNRRAHLKECFETLKRQIP--NLDDKKTSNLNILRSALRYIQILKRkekeyehemERLAREKIALQQR 76

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.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 1395447074 193 NMIERRRRYNINDRIKELGQMLPKNtSEDMKLNKGTILKASCDYIRVLQK 242
Cdd:cd19686     6 NIRERKRMRSINDAFDGLRRHIPTF-PYEKRLSKVDTLRLAIQYINFLTE 54

basic helix-loop-helix (bHLH) domain found in factor in the germline alpha (FIGLA) and similar proteins; FIGLA, also termed FIGalpha, or Class C basic helix-loop-helix protein 8 (bHLHc8), or folliculogenesis-specific basic helix-loop-helix protein, or transcription factor FIGa, is a germ-cell-specific bHLH transcription factor expressed abundantly in female and less so in male germ cells. It is essential for primordial follicle formation and expression of many genes required for folliculogenesis, fertilization and early embryonic survival. FIGLA knockout mice cannot form primordial follicles and lose oocytes rapidly after birth, whereas male gonads are unaffected.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 1395447074 193 NMIERRRRYNINDRIKELGQMLPKNTsEDMKLNKGTILKASCDYIRVLQ 241
Cdd:cd11422     5 NARERERVRNLNSGFSKLRRIVPLIP-RDRKPSKVDTLKGATEYIRLLQ 52

basic helix-loop-helix (bHLH) domain found in Drosophila melanogaster helix loop helix protein 3B (dHLH3B) and similar proteins; Drosophila HLH3B is an uncharacterized bHLH transcription factor that belongs to the T-cell acute lymphocytic leukemia protein/ lymphoblastic leukemia-derived sequence (TAL/LYL) family.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1395447074 188 KKDIHNMIERRRRYNINDRIKELGQMLPKNTSeDMKLNKGTILKASCDYIRVL 240
Cdd:cd19708     1 RRMFTNSRERWRQQNVNGAFAELRKLVPTHPP-DKKLSKNEILRLAIKYIRLL 52

basic helix-loop-helix-orange (bHLH-O) domain found in Drosophila melanogaster Enhancer of split proteins, E(spl)m5, E(spl)m8 and similar proteins; The family includes two bHLH-O transcriptional repressors, E(spl)m5 and E(spl)m8, which participate in the control of cell fate choice by uncommitted neuroectodermal cells in the embryo. They bind DNA on N-box motifs, 5'-CACNAG-3'.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 1395447074 194 MIERRRRYNINDRIKELGQMLPKNTSED--MKLNKGTILKASCDYIR 238
Cdd:cd18916     6 MLERQRRARINKCLSELKTLVAECSGDDgcLRMDKAEMLETAVAFMR 52

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 1395447074 192 HNMIERRRRYNINDRIKELGQMLPKNTSeDMKLNKGTILKASCDYIRVLQK 242
Cdd:cd11390     4 ANARERRRMHDLNDAFEALRKVLPTVPP-DKKLSKIETLRLAINYIAALSD 53

basic helix-loop-helix (bHLH) domain found in Arabidopsis thaliana paclobutrazol resistance (PRE) family; The PRE family includes several bHLH transcription factors from Arabidopsis thaliana, such as PRE1-6. PRE1 (also termed AtbHLH136, or protein banquo 1), PRE2 (also termed AtbHLH134, or protein banquo 2, or EN 52), PRE4 (also termed AtbHLH161, or protein banquo 3), and PRE5 (also termed AtbHLH164) are atypical and probable non DNA-binding bHLH transcription factors that integrate multiple signaling pathways to regulate cell elongation and plant development. PRE3 (also termed AtbHLH135, or protein activation-tagged BRI1 suppressor 1, or ATBS1, or protein target of MOOPTEROS 7, or EN 67) is an atypical and probable non DNA-binding bHLH transcription factor required for MONOPTEROS-dependent root initiation in embryo. It promotes the correct definition of the hypophysis cell division plane. PRE5 (also termed AtbHLH163, or protein KIDARI) is an atypical and probable non DNA-binding bHLH transcription factor that regulates light-mediated responses in day light conditions by binding and inhibiting the activity of the bHLH transcription factor HFR1, a critical regulator of light signaling and shade avoidance.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1395447074 203 INDRIKELGQMLPKNTSEDmKLNKGTILKASCDYIRVLQkdreQAMKTQQQQKSLEST 260
Cdd:cd11442    12 KNDLYSRLRALLPSIATSD-KVSKATVLEEACNYIRNLH----REVDDLSERLSRLLT 64