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 24650606  71 RRREAHTQAEQKRRDAIKKGYDSLQELVPRCQPND-SSGYKLSKALILQKSIEYIGYLNQQKLKQEDEGSALQKEV 145
Cdd:cd19687   1 RRREAHTQAEQKRRDAIKKGYDDLQDIVPTCQQQDdIGSQKLSKATILQRSIDYIQFLHQQKKKQEEELSALRKEV 76

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 24650606  71 RRREAHTQAEQKRRDAIKKGYDSLQELVPRCQPND-SSGYKLSKALILQKSIEYIGYLNQQKLKQEDEGSALQKEV 145
Cdd:cd19687   1 RRREAHTQAEQKRRDAIKKGYDDLQDIVPTCQQQDdIGSQKLSKATILQRSIDYIQFLHQQKKKQEEELSALRKEV 76

helix loop helix domain;

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 24650606     79 AEQKRRDAIKKGYDSLQELVPRCQPNDssgyKLSKALILQKSIEYIGYLNQQ 130
Cdd:smart00353   3 RERRRRRKINEAFDELRSLLPTLPKNK----KLSKAEILRLAIEYIKSLQEE 50

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 24650606  71 RRREAHTQAEQKRRDAIKKGYDSLQELVPRCQPND-SSGYKLSKALILQKSIEYIGYLNQQKLKQEDEGSALQKEV 145
Cdd:cd19687   1 RRREAHTQAEQKRRDAIKKGYDDLQDIVPTCQQQDdIGSQKLSKATILQRSIDYIQFLHQQKKKQEEELSALRKEV 76

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 24650606  70 ERRREAHTQAEQKRRDAIKKGYDSLQELVPRCQPNDSSgyKLSKALILQKSIEYIGYLNQQKLKQEDEGSALQKEV 145
Cdd:cd11405   1 EQRRLSHISAEQKRRFNIKSGFDTLQSLIPSLGQNPNQ--KVSKAAMLQKAAEYIKSLKRERQQMQEEAEQLRQEI 74

helix loop helix domain;

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 24650606     79 AEQKRRDAIKKGYDSLQELVPRCQPNDssgyKLSKALILQKSIEYIGYLNQQ 130
Cdd:smart00353   3 RERRRRRKINEAFDELRSLLPTLPKNK----KLSKAEILRLAIEYIKSLQEE 50

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in MLX-interacting protein-like (MLXIPL) and similar proteins; 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 24650606  70 ERRREAHTQAEQKRRDAIKKGYDSLQELVPRCQPNDSSgyKLSKALILQKSIEYIGYLNQQKLKQEDEGSALQKEV 145
Cdd:cd19689   3 ETRRITHISAEQKRRFNIKLGFDTLHSLVTTLSSQPSI--KISKATTLQKTAEYISKLQQERAQLQEEAQRLRDQI 76

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        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 24650606  69 KERRREAHTQAEQKRRDAIKKGYDSLQELVPRCQpndssGYKLSKALILQKSIEYIGYLNQQKLKQ 134
Cdd:cd11419   1 RRIRREIANSNERRRMQSINAGFQSLRTLLPHCD-----GEKLSKAAILQQTAEYIFSLEQEKTRL 61

basic Helix-Loop-Helix (bHLH) domain found in Saccharomyces cerevisiae INO4 and similar proteins; INO4 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. INO4 dimerizes with INO2 and binds to an UAS DNA element to control expression of the genes whose expression is inositol-responsive.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 24650606  72 RREAHTQAEQKRRDAIKKGYDSLQELVPRCQPNDSSgyklSKALILQKSIEYIGYLNQQKLK 133
Cdd:cd11403   2 KKENHISSEHKRREAIREGFDRLCAIVPALSSSQSR----SEAVVYVKTVEYLKELYERRAK 59

basic helix-loop-helix (bHLH) domain found in Saccharomyces cerevisiae protein INO2 and similar proteins; INO2 is a positive regulatory factor required for depression of the co-regulated phospholipid biosynthetic enzymes in Saccharomyces cerevisiae. It is also involved in the expression of ITR1.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 24650606  70 ERRREAHTQAEQKRRDAIKKGYDSLQELVPrcQPNDSSGYKLSKALILQKSIEYIGYLNQQKLKQEDE 137
Cdd:cd11388   1 PVKKWKHVEAEKKRRNQIKKGFEDLINLIN--YPRNNNEKRISKSELLNKAVDDIRGLLKANEQLQEE 66

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 24650606  76 HTQAEQKRRDAIKKGYDSLQELVPRCQPNDSSGyKLSKALILQKSIEYIGYLNQQ 130
Cdd:cd11387   2 HNAVERRRRDNINEKIQELGSLVPPSRLETKDL-KPNKGSILSKAVEYIRELQNQ 55

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 24650606  69 KERRREAHTQAEQKRRDAIKKGYDSLQELVPRCQPNdssgyKLSKALILQKSIEYIGYLNQQ 130
Cdd:cd18910   2 REKKRESHNEVERRRKDKINAGINKIGELLPDRDAK-----KQSKNMILEQAYKYIVELKKK 58

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 24650606  76 HTQAEQKRRDAIKKGYDSLQELVPRCQPNDSSGyKLSKALILQKSIEYIGYLNQQ 130
Cdd:cd11389   1 HKVIEKRRRDRINESLAELRRLVPEARKSKGSG-KLEKAEILEMTLQHLKALQSS 54

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 24650606  70 ERRREAHTQAEQKRRDAIKKGYDSLQELVPRCQpNDSSGYKLSKALILQKSIEYIGYLNQQKLKQED 136
Cdd:cd18923   6 ERRRAQHNEVERRRRDKINNWIVQLSKIIPDCN-TDNSKTGASKGGILSKACDYIRELRQTNQRMQE 71

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 24650606  71 RRREAHTQAEQKRRDAIKKGYDSLQELVPRCqpndssgYKLSKALILQKSIEYIGYLNQQ 130
Cdd:cd11445   1 RAAEVHNLSERRRRDRINEKMKALQELIPNC-------NKTDKASMLDEAIEYLKSLQLQ 53

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        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 24650606  68 YKERRREAhtqaEQKRRDAIKKGYDSLQELVPRCQPNDssgyKLSKALILQKSIEYIGYLNQQ 130
Cdd:cd11418   1 RVARRNER----ERRRVQAVNDAFDRLRQHVPYLKRRK----KLSKVKTLRRAIEYIRHLQKL 55

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        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 24650606  70 ERRREAHTQAEQKRRDAIKKGYDSLQELVPRCQpNDSSGYKLSKALILQKSIEYIGYLNQQKLK 133
Cdd:cd18924   3 EKRRAQHNEVERRRRDKINNWIVQLSKIIPDCS-MESTKSGQSKGGILSKACDYIQELRQSNHR 65

basic helix-loop-helix (bHLH) domain found in Arabidopsis thaliana BES1-interacting Myc-like proteins (BIMs) and similar proteins; The family includes Arabidopsis thaliana BIM1 and its homologs (BIM2 and BIM3), which are bHLH transcription factors that interact with BES1 to regulate transcription of Brassinosteroid (BR)-induced gene. BR regulates many growth and developmental processes such as cell elongation, vascular development, senescence stress responses, and photomorphogenesis. BIM1 heterodimerize with BES1 and bind to E-box sequences present in many BR-induced promoters to regulated BR-induced genes.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 24650606  72 RREAHTQAEQKRRDAIKKGYDSLQELVPrcqpndSSGYKLSKALILQKSIEYIGYLNQQKLKQED 136
Cdd:cd11453   3 PRSKHSATEQRRRSKINERLQALRDLIP------HSDQKRDKASFLLEVIEYIQALQEKVAKLEE 61

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 24650606  73 REAHTQAEQKRRDAIKKGYDSLQELVPRCQPNDSsgyKLSKALILQKSIEYIGYL 127
Cdd:cd11469   2 REAHSQTEKRRRDKMNNLIEELSAMIPQCNPMAR---KLDKLTVLRMAVQHLKSL 53

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 24650606  76 HTQAEQKRRDAIKKGYDSLQELVPRCQpndssGYKLSKALILQKSIEYIGYLN 128
Cdd:cd18908   6 HSLKERLRRERIKSSCDQLRDLLPYIK-----GRKLDMASVLEMTVKYIRYIQ 53

basic helix-loop-helix (bHLH) domain found in heart- and neural crest derivatives-expressed protein 1 (HAND1) and similar proteins; HAND1, also termed Class A basic helix-loop-helix protein 27 (bHLHa27), or extraembryonic tissues, heart, autonomic nervous system and neural crest derivatives-expressed protein 1 (eHAND), is a bHLH transcription factor that plays an essential role in both trophoblast-giant cells differentiation and in cardiac morphogenesis.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 24650606  71 RRREAHTQAEQKRRDAIKKGYDSLQElvprCQPNDSSGYKLSKALILQKSIEYIGYL 127
Cdd:cd18952   1 RRKGAGPKKERRRTESINSAFAELRE----CIPNVPADTKLSKIKTLRLATSYIAYL 53

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 24650606  80 EQKRRDAIKKGYDSLQELVPRCQPNDSSGyKLSKALILQKSIEYIGYLNQ 129
Cdd:cd19685   2 EKRRRQRINDKLNQLKELLPPNLSKQSRS-KLSKAEILEMAITELRRLQQ 50

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        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 24650606  72 RREAHTQAEQKRRDAIKKGYDSLQELVprcQPNDSsgyKLSKALILQKSIEYIGYLNQ--QKLKQED 136
Cdd:cd18922   6 RRTTHNIIEKRYRSSINDKIIELKDLV---MGTDA---KMHKSGVLRKAIDYIKYLQQvnHKLRQEN 66

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in MAX gene-associated protein (MGA) family; The MGA family includes MGA, Schizosaccharomyces pombe ESC1 (spESC1) and similar proteins. MGA, also termed MAX dimerization protein 5 (MAD5), is a dual specificity T-box/ bHLHzip transcription factor that regulates the expression of both Max-network and T-box family target genes. It contains a Myc-like bHLHZip motif and requires heterodimerization with Max for binding to the preferred Myc-Max-binding site CACGTG. In addition to the bHLHZip domain, MGA harbors a second DNA-binding domain, the T-box or T-domain. It thus binds the preferred Brachyury-binding sequence and represses transcription of reporter genes containing promoter-proximal Brachyury-binding sites. 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 24650606  73 REAHTQAEQKRRDAIKKGYDSLQELVprcqpNDSSGYKLSKALILQKSIEYIGYLNQQ 130
Cdd:cd19682   1 RLRHKKRERERRSELRELFDKLKQLL-----GLDSDEKASKLAVLTEAIEEIQQLKRE 53

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

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 24650606  72 RREAHTQAEQKRRDAIKKGYDSLQELVPRCQPNDSSGyKLSKALILQKSIEYIGYLNQ 129
Cdd:cd11407   1 RKKRRGIIEKRRRDRINNSLAELRRLVPTAFEKQGSA-KLEKAEILQMTVDHLKMLHS 57

basic helix-loop-helix (bHLH) domain found in protein atonal homolog 7 (ATOH7) and similar proteins; ATOH7, also termed Class A basic helix-loop-helix protein 13 (bHLHa13), or helix-loop-helix protein hATH-5 (hATH5), or Math5, is a bHLH transcription factor involved in the differentiation of retinal ganglion cells.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 24650606  71 RRREAHTQAEQKRRDAIKKGYDSLQELVPRCqpndSSGYKLSKALILQKSIEYIGYLNQ 129
Cdd:cd19714   7 RRRLAANARERRRMQGLNTAFDRLRKVVPQW----GQDKKLSKYETLQMALSYIMALTR 61

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        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 24650606  69 KERRR-EAHTQAEQKRR----DAIKKgydsLQELVPRcqpNDSSGYKLSKALILQKSIEYIGYL--NQQKLKQEDE 137
Cdd:cd11397   1 KDRQKkDNHNMIERRRRfninDRIKE----LGTLLPK---SNDPDMRWNKGTILKASVDYIRKLqkEQERLRQLEE 69

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 24650606  72 RREAHTQAEQKRRDAIKKGYDSLQELVPRCQPNDssgyKLSKALILQKSIEYIGYLNQQKLKQEDEGSALQ 142
Cdd:cd11456   5 RRRNHNILERQRRNDLRSSFLTLRDHVPELVKNE----KAAKVVILKKATEYVHSLQAEEQKLLLEKEKLQ 71

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 24650606  73 REAHTQAEQKRRDAIKKGYDSLQELVPRCQPNdssgyKLSKALILQKSIEYIGYLNQQKLKQEDEGSALQKEVTALR 149
Cdd:cd11402   3 REVHNKLEKNRRAHLKECFETLKRQIPNLDDK-----KTSNLNILRSALRYIQILKRKEKEYEHEMERLAREKIALQ 74