Helix-loop-helix DNA-binding domain;

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2481086926 268 RVSHNIIEKKYRSNINGKIEQLRRTVPTlrvaykkcndlpitsrdladldgLEPATKLNKASILTKSIEYICHLE 342
Cdd:pfam00010   2 REAHNERERRRRDRINDAFDELRELLPT-----------------------LPPDKKLSKAEILRLAIEYIKHLQ 53

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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2481086926 265 RTGRVSHNIIEKKYRSNINGKIEQLRRTVPTLRVAYKKCNDlpitsrdlADLDGLEPATKLNKASILTKSIEYICHLERK 344
Cdd:cd11395     1 PRKRLPHNAIEKRYRSNLNTKIERLRDAIPSLRSPEGKSDD--------GGLGGLAPTTKLSKATILTKAIEYIRHLEQE 72

                          90
                  ....*....|.
gi 2481086926 345 CLQLSLANQHL 355
Cdd:cd11395    73 NERLEEENEEL 83

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        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2481086926 268 RVSHNIIEKKYRSNINGKIEQLRRTVptlrvaykkcndlpitsrdladldgLEPATKLNKASILTKSIEYICHLERKCLQ 347
Cdd:cd11394     7 RSAHNAIEKRYRSSINDRIIELKDLV-------------------------VGPDAKMNKSAVLRKAIDYIRYLQKVNQK 61

                  ....*...
gi 2481086926 348 LSLANQHL 355
Cdd:cd11394    62 LKQENMAL 69

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2481086926 275 EKKYRSNINGKIEQLRRTVPTLRvaykkcndlpitsrdladldglePATKLNKASILTKSIEYICHLER 343
Cdd:cd00083     1 ERRRRDKINDAFEELKRLLPELP-----------------------DSKKLSKASILQKAVEYIRELQS 46

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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2481086926 268 RVSHNIIEKKYRSNINGKIEQLRRTVptlrvaykkcndlpitsrdladldgLEPATKLNKASILTKSIEYICHLERKCLQ 347
Cdd:cd18921     7 RTAHNAIEKRYRSSINDKIIELKDLV-------------------------VGTEAKLNKSAVLRKAIDYIRFLQQSNQK 61

                  ....*...
gi 2481086926 348 LSLANQHL 355
Cdd:cd18921    62 LKQENMAL 69

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'.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2481086926 268 RVSHNIIEKKYRSNINGKIEQLRRTVPTLRvaykkcndlpitsrdladldgLEPATKLNKASILTKSIEYICHLERKCLQ 347
Cdd:cd11405     4 RLSHISAEQKRRFNIKSGFDTLQSLIPSLG---------------------QNPNQKVSKAAMLQKAAEYIKSLKRERQQ 62

                  .
gi 2481086926 348 L 348
Cdd:cd11405    63 M 63

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2481086926 271 HNIIEKKYRSNINGKIEQLRRTVPTLRVaykkcndlpitsrdladldgLEPATKLNKASILTKSIEYICHL 341
Cdd:cd11389     1 HKVIEKRRRDRINESLAELRRLVPEARK--------------------SKGSGKLEKAEILEMTLQHLKAL 51

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2481086926 274 IEKKYRSNINGKIEQLRRTVPTLRvaykkcndlpitsrdladldGLEPATKLNKASILTKSIEYICHLER 343
Cdd:cd19685     1 SEKRRRQRINDKLNQLKELLPPNL--------------------SKQSRSKLSKAEILEMAITELRRLQQ 50

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in transcription factor EB (TFEB) and similar proteins; TFEB, also termed Class E basic helix-loop-helix protein 35 (bHLHe35), is a bHLHzip transcription factor that is required for vascularization of the mouse placenta. 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 TFE3 or MITF.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2481086926 259 KRITRVRTGRVSHNIIEKKYRSNINGKIEQLRRTVPtlrvaykKCNDLPitsrdladldglepaTKLNKASILTKSIEYI 338
Cdd:cd18927     3 RALAKERQKKDNHNLIERRRRFNINDRIKELGTLIP-------KTNDLD---------------VRWNKGTILKASVDYI 60

                  ....*
gi 2481086926 339 CHLER 343
Cdd:cd18927    61 KRMQK 65

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        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2481086926 256 VKPKRITRVRTGRVSHNIIEKKYRSNINGKIEQLRRTVPtlrvaykKCNDlpitsrdladldglePATKLNKASILTKSI 335
Cdd:cd18926     2 SEARALAKERQKKDNHNLIERRRRFNINDRIKELGTLIP-------KSND---------------PDMRWNKGTILKASV 59

                  ....*....
gi 2481086926 336 EYICHLERK 344
Cdd:cd18926    60 DYIRKLQRE 68

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).

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2481086926 268 RVSHNIIEKKYRSNINGKIEQLRRTVPTLRVAYKkcndlpitsrdladldglepATKLNkasILTKSIEYICHLERKCLQ 347
Cdd:cd11400     2 RRLHNVLERQRRNDLKNSFEKLRDLVPELADNEK--------------------ASKVV---ILKKATEYIKQLQQEEKK 58

                  ..
gi 2481086926 348 LS 349
Cdd:cd11400    59 LE 60

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 2481086926 268 RVSHNIIEKKYRSNINGKIEQLRRTVPTLRvaykkcndlpitsrdladldglepATKLNKASILTKSIEYICHLERK 344
Cdd:cd11406     2 RAHHNALERKRRDHIKDSFHSLRDSVPSLQ------------------------GEKASRAQILKKATEYIQYMRRK 54

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        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2481086926 269 VSHNIIEKKYRSNINGKIEQLRRTVPTLrvaykkcndlpitsrdladldglepaTKLNKASILTKSIEYICHLERKCLQL 348
Cdd:cd11451     4 GSHAMAERRRREKLNERFITLRSMVPFV--------------------------TKMDKVSILGDAIEYLKQLQRRVEEL 57

                          90
                  ....*....|..
gi 2481086926 349 SLANQHLSNDTR 360
Cdd:cd11451    58 ESRRKSSDTETR 69

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2481086926 268 RVSHNIIEKKYRSNINGKIEQLRRTVPtlrvaykkcndlpitsrdladldgLEPATKLNKASILTKSIEYICHLERKCLQ 347
Cdd:cd19690     1 RVSHKLAERKRRKEMKELFEDLRDALP------------------------QERGTKASKWEILTKAISYIQQLKRHIRE 56

                  .
gi 2481086926 348 L 348
Cdd:cd19690    57 L 57

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        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2481086926 263 RVRTGRVSHNIIEKKYRSNINGKIEQLRRTVPTLRVAYKKCNDLPITSRDLADLDGLEPAT 323
Cdd:cd11438     3 RIKNAREAHSQIEKRRRDKMNSFIDELASLVPTCNAMSRKLDKLTVLRMAVQHMKTLRGAT 63

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        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2481086926 268 RVSHNIIEKKYRSningkieqlrrtvpTLRVAYKKcndlpitsrdLADLDGLEPATKLNKASILTKSIEYICHLERKCLQ 347
Cdd:cd19682     1 RLRHKKRERERRS--------------ELRELFDK----------LKQLLGLDSDEKASKLAVLTEAIEEIQQLKREEDE 56

                  ....*...
gi 2481086926 348 LSLANQHL 355
Cdd:cd19682    57 LQKEKARL 64