Orange domain; This domain confers specificity among members of the Hairy/E(SPL) family.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*
gi 55715331     97 ESFRAGYVHAANEVSKTLAAVPGVSVDLGTQLMSHLGHRLNYLQV 141
Cdd:smart00511   1 SSFRSGYRECANEVSRFLSQLPGTDPDVRARLLSHLQTHLNQLLQ 45

Orange domain; This domain confers specificity among members of the Hairy/E(SPL) family.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*
gi 55715331     97 ESFRAGYVHAANEVSKTLAAVPGVSVDLGTQLMSHLGHRLNYLQV 141
Cdd:smart00511   1 SSFRSGYRECANEVSRFLSQLPGTDPDVRARLLSHLQTHLNQLLQ 45

helix loop helix domain;

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 55715331     19 PMLERKRRARINKCLDELKDIMVECLTqegehITRLEKADILELTVEHMKKLRAQKQ 75
Cdd:smart00353   1 NARERRRRRKINEAFDELRSLLPTLPK-----NKKLSKAEILRLAIEYIKSLQEELQ 52

basic helix-loop-helix-orange (bHLH-O) domain found in hairy and enhancer of split (HES) family; The HES family includes bHLH-O transcriptional regulators that are related to the Drosophila hairy and Enhancer-of-split (HES) proteins. They contain a basic helix-loop-helix (bHLH) domain with an invariant proline residue in its basic region, an orange domain in the central region and a conserved tetrapeptide motif, WRPW, at its C-terminal region. HES family proteins form heterodimers or homodimers via their HLH domain and bind DNA to repress gene transcription that play an essential role in development of both compartment and boundary cells of the central nervous system.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....
gi 55715331  21 LERKRRARINKCLDELKDIMVECLTQEGEHITRLEKADILELTVEHMKKLRAQK 74
Cdd:cd11410   1 MEKKRRARINKSLEQLKTLVLEALNKDNTRYSKLEKADILEMTVKYLKQLQRSK 54

basic helix-loop-helix-orange (bHLH-O) domain found in Drosophila melanogaster protein hairy, protein deadpan and similar proteins; Protein hairy is a bHLH transcriptional repressor of genes that require a bHLH-O protein for their transcription. It acts as a pair-rule protein that regulates embryonic segmentation and adult bristle patterning. Protein deadpan is closely related to the product of the segmentation gene hairy. It is a direct target of Notch signaling and regulates neuroblast self-renewal in Drosophila.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 55715331  12 QYRKVMKPMLERKRRARINKCLDELKDIMVECLTQEGEHITRLEKADILELTVEHMKKLRAQK 74
Cdd:cd18913   1 ESRKSSKPIMEKRRRARINASLNELKSLLLDALKKDGTRHSKLEKADILEMTVKHLRQVQRQQ 63

basic helix-loop-helix-orange (bHLH-O) domain found in hairy and enhancer of split HES-1, HES-4 and similar proteins; The family includes two bHLH-O transcriptional repressors, HES-1 and HES-4. HES-1, also termed Class B basic helix-loop-helix protein 39 (bHLHb39), or hairy homolog, or hairy-like protein (HL), plays an essential role in development of both compartment and boundary cells of the central nervous system. It regulates the maintenance of neural stem/progenitor cells by inhibiting proneural gene expression via Notch signaling. HES-4, also termed Class B basic helix-loop-helix protein 42 (bHLHb42), or bHLH factor Hes4, antagonizes the function of Twist-1 to regulate lineage commitment of bone marrow stromal/stem cells (BMSC). Epigenetic dysregulation of HES-4 is associated with striatal degeneration in postmortem Huntington brains. Both HES-1 and HES-4 are mammalian counterparts 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        60
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 55715331  12 QYRKVMKPMLERKRRARINKCLDELKDIMVECLTQEGEHITRLEKADILELTVEHMKKLRAQK 74
Cdd:cd11459   1 EHRKSSKPIMEKRRRARINESLSQLKTLILDALKKDSSRHSKLEKADILEMTVKHLRNLQRQQ 63

basic helix-loop-helix-orange (bHLH-O) domain found in hairy and enhancer of split 7 (HES-7) and similar proteins; HES-7, also termed Class B basic helix-loop-helix protein 37 (bHLHb37), or bHLH factor Hes7, is a bHLH-O transcriptional repressor that is expressed in an oscillatory manner and acts as a key regulator of the pace of the segmentation clock. It is regulated by the Notch and Fgf/Mapk pathways. HES-7 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 55715331  14 RKVMKPMLERKRRARINKCLDELKDIMVECLTQEGEHITRLEKADILELTVEHMKK 69
Cdd:cd11462   1 RKLLKPLVEKRRRDRINRSLEELRVLLLQNTQDEKLKNPKVEKAEILELTVQFLRN 56

helix loop helix domain;

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 55715331     19 PMLERKRRARINKCLDELKDIMVECLTqegehITRLEKADILELTVEHMKKLRAQKQ 75
Cdd:smart00353   1 NARERRRRRKINEAFDELRSLLPTLPK-----NKKLSKAEILRLAIEYIKSLQEELQ 52

basic helix-loop-helix-orange (bHLH-O) domain found in transcription factor HES-5 and similar proteins; HES-5, also termed Class B basic helix-loop-helix protein 38 (bHLHb38), or hairy and enhancer of split 5, is a bHLH-O transcription factor that is involved in cell differentiation and proliferation in a variety of tissues. HES-5 is an essential effector for Notch signaling. It acts as a transducer of Notch signals in brain vascular development. It also acts as a key mediator of Wnt-3a-induced neuronal differentiation and plays a crucial role in normal inner ear hair cell development. HES-5 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 55715331  15 KVMKPMLERKRRARINKCLDELKDIMvECLTQEGEHITRLEKADILELTVEHMKKLRAQ 73
Cdd:cd11461   1 KLRKPVVEKTRRDRINSSIEQLKTLL-EKEFQRHQPNSKLEKADILEMTVSFLKQSAKL 58

Hairy Orange; The Orange domain is found in the Drosophila proteins Hesr-1, Hairy, and Enhancer of Split. The Orange domain is proposed to mediate specific protein-protein interaction between Hairy and Scute.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|
gi 55715331    98 SFRAGYVHAANEVSKTLAAVPGVSVDLGTQLMSHLGHRLN 137
Cdd:pfam07527   1 RFRAGFNECANEVSRFLSTLEGVDPDLRQRLLNHLQRCLA 40

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 55715331  22 ERKRRARINKCLDELKDIMVECLTQEGEhiTRLEKADILELTVEHMKKLRA 72
Cdd:cd19685   2 EKRRRQRINDKLNQLKELLPPNLSKQSR--SKLSKAEILEMAITELRRLQQ 50

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 55715331  20 MLERKRRARINKCLDELKDIMVECLTQEGehITRLEKADILELTVEHMKKLRA---QKQLRLSSVTGG 84
Cdd:cd11409  10 LIEKKRRDRINECIAQLKDLLPEHLKLTT--LGHLEKAVVLELTLKHLKALTAlteQQQQKIIALQNG 75

basic helix-loop-helix-orange (bHLH-O) domain found in differentially expressed in chondrocytes protein 2 (DEC2) and similar proteins; DEC2, also termed Class E basic helix-loop-helix protein 41 (bHLHe41), or Class B basic helix-loop-helix protein 3 (bHLHb3), or enhancer-of-split and hairy-related protein 1 (SHARP-1), is a bHLH-O transcriptional repressor involved in the regulation of the circadian rhythm by negatively regulating the activity of the clock genes and clock-controlled genes.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|...
gi 55715331  20 MLERKRRARINKCLDELKDIMVECLTQEGehITRLEKADILELTVEHMKKLRA 72
Cdd:cd19750  21 LIEKKRRDRINECIAQLKDLLPEHLKLTT--LGHLEKAVVLELTLKHLKALTA 71

basic helix-loop-helix-orange (bHLH-O) domain found in transcription factor HES-6 and similar proteins; HES-6, also termed Class B basic helix-loop-helix protein 41 (bHLHb41), or hairy and enhancer of split 6, or C-HAIRY1, is a bHLH-O transcription factor that is expressed in developing muscle and involved in angiogenesis, myogenesis, neural differentiation and neurogenesis. HES-6 antagonizes Notch signaling but is not regulated by Notch signaling. It is a transcription co-factor associated with stem cell characteristics in neural tissue. It may act as an inhibitor of Hes-1 during neuronal development and forms a heterodimer with HES-1 to prevent its association with transcriptional co-repressors. The overexpression of HES-6 has been reported in metastatic cancers of different origins. HES-6 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        60
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 55715331  14 RKVMKPMLERKRRARINKCLDELKDIMVECLTQegehiTRLEKADILELTVEHMKKLRAQK 74
Cdd:cd11460   3 RKARKPLVEKKRRARINESLQELRLILADAELQ-----SKMENAEVLELTVKRVQGILRNR 58

basic helix-loop-helix-orange (bHLH-O) domain found in hairy and enhancer of split-related protein HELT and similar proteins; HELT, also termed HES/HEY-like transcription factor, is a bHLH-O 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. HELT could homodimerize and heterodimerize with other bHLH-O protein such as HES-5 or HEY-2 and bound to E box to repress gene transcription.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|...
gi 55715331  20 MLERKRRARINKCLDELKDIMVECLTQEGEhiTRLEKADILELTVEHMKKLRA 72
Cdd:cd11408   4 VIEKRRRDRINRCLNELGKTVPMALAKQTS--GKLEKAEILEMTVQYLRALHS 54

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
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 55715331  22 ERKRRARINKCLDELKDiMVECLTQEGEhiTRLEKADILELTVEHMKKLRAQKQLRL 78
Cdd:cd11405  11 EQKRRFNIKSGFDTLQS-LIPSLGQNPN--QKVSKAAMLQKAAEYIKSLKRERQQMQ 64

basic helix-loop-helix (bHLH) domain found in the spermatogenesis- and oogenesis-specific basic helix-loop-helix-containing protein (SOHLH) family and similar proteins; 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. The family also includes transcription factor-like 5 protein (TCFL5) and similar proteins. TCFL5, also termed Cha transcription factor, or HPV-16 E2-binding protein 1 (E2BP-1), is a bHLH transcription factor that plays a crucial role in spermatogenesis. It regulates cell proliferation or differentiation of cells through binding to a specific DNA sequence like other bHLH molecules.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|..
gi 55715331  22 ERKRRARINKCLDELKDiMVECLTQEgehitrLEKADILELTVEHMKKLRAQ 73
Cdd:cd19683  10 ERQRRERIKIACDQLRK-LVPGCSRK------TDKATVFEFTVAYIKFLREK 54

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
                ....*....|....*....|....*....|....*....|....*....|...
gi 55715331  22 ERKRRARINKCLDELKDIMVECLTQEGEHITRLEKADILELTVEHMKKLRAQK 74
Cdd:cd19687  10 EQKRRDAIKKGYDDLQDIVPTCQQQDDIGSQKLSKATILQRSIDYIQFLHQQK 62

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in upstream stimulatory factors, USF1, USF2 and similar proteins; Upstream stimulatory factor 1 and 2 (USF-1 and USF-2) are members of bHLHzip transcription factor family. 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.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....
gi 55715331  22 ERKRRARINKCLDELKDIMVECLTQEGEHITrlEKADILELTVEHMKKLRAQKQ 75
Cdd:cd11396   6 ERRRRDKINNWIVKLAKIVPDCEKDNSKQGQ--SKGGILSKACDYIQELRSQNE 57

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 55715331  22 ERKRRARINKCLDELKDImVECLTQEGEHitrleKADILELTVEHMKKL-----RAQKQLR 77
Cdd:cd11404  10 EKKRRELIKKGYDELCAL-VPGLDPQKRT-----KADILQKAADWIQELkeeneKLEEQLD 64

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 55715331  22 ERKRRARINKCLDELKDIMVECLTQEGE----------HITRLEKADILELTVEHMKKLRAQKQL 76
Cdd:cd11395  11 EKRYRSNLNTKIERLRDAIPSLRSPEGKsddgglgglaPTTKLSKATILTKAIEYIRHLEQENER 75

basic helix-loop-helix (bHLH) domain found in Arabidopsis thaliana protein maternal effect embryo arrest 8 (AtMEE8) and similar proteins; AtMEE8, also termed AtbHLH108, or EN 132, is a bHLH transcription factor required during early embryo development, for the endosperm formation.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 55715331  20 MLERKRRARINKCLDELKDIMVECLTQEgehitrlEKADILELTVEHMKKLRAQKQ 75
Cdd:cd19698   3 LLEKKRRERIKDKIEILKGLTPNCTPKS-------DIASILSCVIDYIKSLLLQVE 51

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

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|..
gi 55715331  21 LERKRRARINKCLDELKDIMVECLTqegeHITRLEKADILELTVEHMKKLRA 72
Cdd:cd11437   8 IEKRRRDKMNAYIQELSALVPACNA----MSRKLDKLTVLRMAVQHLKSLRG 55

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 55715331  21 LERKRRARINKCLDELKDIM-----------VECLTQEGEHITRLEKADIlELTvEHMKKLRA-QKQLR 77
Cdd:cd11400   8 LERQRRNDLKNSFEKLRDLVpeladnekaskVVILKKATEYIKQLQQEEK-KLE-KEKDKLKArNEQLR 74

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

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 55715331  20 MLERKRRARINKCLDELKDImvecLTQEGEHITRLEKADILELTVEHMKKLRAQKQ 75
Cdd:cd11397  11 MIERRRRFNINDRIKELGTL----LPKSNDPDMRWNKGTILKASVDYIRKLQKEQE 62