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 672074856 137 RDEKRRAQHNEVERRRRDKINNWIVQLSKIIPDCSMESTKSGQSKGGILSKACDYIQELRQSNHR 201
Cdd:cd18924    1 RDEKRRAQHNEVERRRRDKINNWIVQLSKIIPDCSMESTKSGQSKGGILSKACDYIQELRQSNHR 65

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 672074856 137 RDEKRRAQHNEVERRRRDKINNWIVQLSKIIPDCSMESTKSGQSKGGILSKACDYIQELRQSNHR 201
Cdd:cd18924    1 RDEKRRAQHNEVERRRRDKINNWIVQLSKIIPDCSMESTKSGQSKGGILSKACDYIQELRQSNHR 65

helix loop helix domain;

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 672074856   146 NEVERRRRDKINNWIVQLSKIIPDCSmESTKsgQSKGGILSKACDYIQELRQSNH 200
Cdd:smart00353   1 NARERRRRRKINEAFDELRSLLPTLP-KNKK--LSKAEILRLAIEYIKSLQEELQ 52

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 672074856 137 RDEKRRAQHNEVERRRRDKINNWIVQLSKIIPDCSMESTKSGQSKGGILSKACDYIQELRQSNHR 201
Cdd:cd18924    1 RDEKRRAQHNEVERRRRDKINNWIVQLSKIIPDCSMESTKSGQSKGGILSKACDYIQELRQSNHR 65

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 672074856 144 QHNEVERRRRDKINNWIVQLSKIIPDCSMESTKSGQSKGGILSKACDYIQELRQSNHR 201
Cdd:cd11396    1 THNEVERRRRDKINNWIVKLAKIVPDCEKDNSKQGQSKGGILSKACDYIQELRSQNER 58

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 672074856 137 RDEKRRAQHNEVERRRRDKINNWIVQLSKIIPDCSmestKSGQSKGGILSKACDYIQELRQSNHRL 202
Cdd:cd18910    1 RREKKRESHNEVERRRKDKINAGINKIGELLPDRD----AKKQSKNMILEQAYKYIVELKKKNDKL 62

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 672074856 141 RRAQHNEVERRRRDKINNWIVQLSKII--PDCSMestksgqSKGGILSKACDYIQELRQSNHRLSEELQGL 209
Cdd:cd11394    6 KRSAHNAIEKRYRSSINDRIIELKDLVvgPDAKM-------NKSAVLRKAIDYIRYLQKVNQKLKQENMAL 69

Helix-loop-helix DNA-binding domain;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 672074856  141 RRAQHNEVERRRRDKINNWIVQLSKIIPdCSMESTKsgQSKGGILSKACDYIQELR 196
Cdd:pfam00010   1 RREAHNERERRRRDRINDAFDELRELLP-TLPPDKK--LSKAEILRLAIEYIKHLQ 53

helix loop helix domain;

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 672074856   146 NEVERRRRDKINNWIVQLSKIIPDCSmESTKsgQSKGGILSKACDYIQELRQSNH 200
Cdd:smart00353   1 NARERRRRRKINEAFDELRSLLPTLP-KNKK--LSKAEILRLAIEYIKSLQEELQ 52

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 672074856 149 ERRRRDKINNWIVQLSKIIPDCsmeSTKSGQSKGGILSKACDYIQELRQ 197
Cdd:cd00083    1 ERRRRDKINDAFEELKRLLPEL---PDSKKLSKASILQKAVEYIRELQS 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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 672074856 137 RDEKRRAqHNEVERRRRDKINNWIVQLSKIIpdcsmESTKSGQSKGGILSKACDYIQELRQSNHRLSEE 205
Cdd:cd18921    3 KGEKRTA-HNAIEKRYRSSINDKIIELKDLV-----VGTEAKLNKSAVLRKAIDYIRFLQQSNQKLKQE 65

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 672074856 137 RDEKRRAQHNEVERRRRDKINNWIVQLSKIIPDCSMESTKsgQSKGGILSKACDYIQELR--QSNHRLSEE 205
Cdd:cd11397    1 KDRQKKDNHNMIERRRRFNINDRIKELGTLLPKSNDPDMR--WNKGTILKASVDYIRKLQkeQERLRQLEE 69

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 672074856 129 KSEAPRTTRDEKRRAQHNEVERRRRDKINNWIVQLSKIIPDCSMESTKsgQSKGGILSKACDYIQELRQSNHRLSEelqg 208
Cdd:cd18926    1 ESEARALAKERQKKDNHNLIERRRRFNINDRIKELGTLIPKSNDPDMR--WNKGTILKASVDYIRKLQREQQRAKE---- 74

                         90       100
                 ....*....|....*....|....*...
gi 672074856 209 ldqlqLDNdvlRQQVEDLKNKNLLLRAQ 236
Cdd:cd18926   75 -----LEN---RQKKLEHANRHLLLRIQ 94

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 672074856 139 EKRRAqHNEVERRRRDKINNWIVQLSKIIPDCSMESTKSGQ-----------------SKGGILSKACDYIQELRQSNHR 201
Cdd:cd11399    2 SKKTA-HNMIEKRYRSNINDRIAELRDSVPALREAYKSARGededeedlggltpatklNKATILSKATEYIRHLEKKNKR 80

                 ....*...
gi 672074856 202 LSEELQGL 209
Cdd:cd11399   81 LSRENASL 88

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 672074856 139 EKRRAQHNEVERRRRDKINNWIVQLSKIIPdcSMESTKSGQ-SKGGILSKACDYIQELRQSNHRLSEELQGLDQ 211
Cdd:cd11405    1 EQRRLSHISAEQKRRFNIKSGFDTLQSLIP--SLGQNPNQKvSKAAMLQKAAEYIKSLKRERQQMQEEAEQLRQ 72

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 672074856 131 EAPRTTRDEKRRAQHNEVERRRRDKINNWIVQLSKIIPDCSMESTKsgQSKGGILSKACDYIQELRQSNHRlSEELQgld 210
Cdd:cd18928    1 EAKAFLKERQKKDNHNLIERRRRFNINDRIKELGTLIPKSTDPEMR--WNKGTILKASVDYIRKLQKEQQR-SKEIE--- 74

                         90       100
                 ....*....|....*....|....
gi 672074856 211 qlqldndvLRQQVEDLKNKNLLLR 234
Cdd:cd18928   75 --------MRQRKLEQANRSLQLR 90

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 672074856 145 HNEVERRRRDKINNWIVQLSKIIPDCSMESTKSGQSKGGILSKACDYIQELRQS 198
Cdd:cd11389    1 HKVIEKRRRDRINESLAELRRLVPEARKSKGSGKLEKAEILEMTLQHLKALQSS 54

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        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 672074856 141 RRAQHNEVERRRRDKINNWIVQLSKIIPdcsmeSTKSGQSKGGILSKACDYIQELRQSNHRLSEELQGLDQ 211
Cdd:cd11453    3 PRSKHSATEQRRRSKINERLQALRDLIP-----HSDQKRDKASFLLEVIEYIQALQEKVAKLEEQVQGWGG 68

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 672074856 142 RAQHNEVERRRRDKINNWIVQLSKIIPDCSMESTKsgQSKGGILSKACDYIQELRQSN 199
Cdd:cd11469    2 REAHSQTEKRRRDKMNNLIEELSAMIPQCNPMARK--LDKLTVLRMAVQHLKSLKGST 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 672074856 137 RDEKRRAQHNEVERRRRDKINNWIVQLSKIIPDCSMESTKsgQSKGGILSKACDYIQELR 196
Cdd:cd11438    3 RIKNAREAHSQIEKRRRDKMNSFIDELASLVPTCNAMSRK--LDKLTVLRMAVQHMKTLR 60

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in the Mad family; Members of the Mad family (Mad1, Mxi, Mad3, and Mad4) bear the bHLHzip domain (also known as basic-helix-loop-helix-leucine-zipper or bHLH-LZ domain), which mediates heterodimerization to Max and the sequence-specific DNA binding ability to E-box DNA. Mad family proteins can repress transcription at the E-box through their interaction with co-repressors. Mad family proteins antagonize Myc function in transactivation and transformation and they are growth/tumor suppressors. The developmental phenotypes of the individual Mad family member knockout mice are relatively mild- all these mice have been shown to be viable and normal.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672074856 142 RAQHNEVERRRRDKINNWIVQLSKIIP---DCSMESTKSgqskggILSKACDYIQELRQSNHRLSEElqgLDQLQLDNDV 218
Cdd:cd11401    1 RSTHNELEKNRRAHLRLCLERLKELVPlgpDATRHTTLS------LLTKAKAYIKNLEDKEKRQRQQ---KEQLRREQRE 71

                 ....*
gi 672074856 219 LRQQV 223
Cdd:cd11401   72 LKRRL 76

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 672074856 148 VERRRRDKINNWIVQLSKIIPDCSMESTKSGQSKGGILSKACDYIQELRQSN 199
Cdd:cd19685    1 SEKRRRQRINDKLNQLKELLPPNLSKQSRSKLSKAEILEMAITELRRLQQEV 52

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in Max-associated protein 4 (Mad4) and similar proteins; Mad4, also termed Max dimerization protein 4, or Max dimerizer 4 (MXD4), or Class C basic helix-loop-helix protein 12 (bHLHc12), or Max-interacting transcriptional repressor MAD4, is a bHLHZip Max-interacting transcriptional repressor that suppresses c-myc dependent transformation and is expressed during neural and epidermal differentiation. It is regulated by a transcriptional repressor complex that contains Miz-1 and c-Myc.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672074856 142 RAQHNEVERRRRDKINNWIVQLSKII---PDCSMESTKSgqskggILSKACDYIQELRQSNHRlseELQGLDQLQLDNDV 218
Cdd:cd18929    3 RSSHNELEKHRRAKLRLYLEQLKQLVplgPDSTRHTTLS------LLKRAKMHIKKLEEQDRK---ALNIKEQLQREHRY 73

                 ....*...
gi 672074856 219 LRQQVEDL 226
Cdd:cd18929   74 LKRRLEQL 81

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 672074856 142 RAQHNEVERRRRDKINNWIVQLSKIIPDCsmESTKSGQSKGGILSKACDYIQ 193
Cdd:cd11391    1 REKSREAAKKRRDKENAEISELASLLPLP--PAVGSKLDKLSVLRLAVAYLR 50

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 672074856 141 RRAQHNEVERRRRDKINNWIVQLSKIIPDCSMEStksgQSKGGILSKACDYIQELRQSNHRL 202
Cdd:cd11419    4 RREIANSNERRRMQSINAGFQSLRTLLPHCDGEK----LSKAAILQQTAEYIFSLEQEKTRL 61

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 672074856 140 KRRAQHNEVERRRRDKINNWIVQLSKIIPDCSMESTKSgqskgGILSKACDYIQELR 196
Cdd:cd19683    1 KSRERHNAKERQRRERIKIACDQLRKLVPGCSRKTDKA-----TVFEFTVAYIKFLR 52

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in Max-interacting protein 1 (MXI1) and similar proteins; MXI1, also termed Max interactor 1, or Class C basic helix-loop-helix protein 11 (bHLHc11), is a bHLHZip transcriptional repressor that binds with MAX to form a sequence-specific DNA-binding protein complex which recognizes the core sequence 5'-CAC[GA]TG-3'. It thus antagonizes MYC transcriptional activity by competing for MAX. It plays an important role in the regulation of cell proliferation.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672074856 142 RAQHNEVERRRRDKINNWIVQLSKIIPdcsMESTKSGQSKGGILSKACDYIQELRQSNHRlseELQGLDQLQLDNDVLRQ 221
Cdd:cd18930    2 RSTHNELEKNRRAHLRLCLERLKVLIP---LGPDCTRHTTLGLLNKAKAHIKKLEEADRK---SQHQLENLEREQRFLKR 75

                 ....*
gi 672074856 222 QVEDL 226
Cdd:cd18930   76 RLEQL 80

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 672074856 138 DEKRRAQHNEVERRRRDKINNWIVQLSKIIPDCsMESTKSgqSKGGILSKACDYIQELRQSNHRLseeLQGLDQLQLDND 217
Cdd:cd11456    2 DSERRRNHNILERQRRNDLRSSFLTLRDHVPEL-VKNEKA--AKVVILKKATEYVHSLQAEEQKL---LLEKEKLQARQQ 75

                         90
                 ....*....|
gi 672074856 218 VLRQQVEDLK 227
Cdd:cd11456   76 QLLKKIEQAR 85

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

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 672074856 145 HNEVERRRRDKINNWIVQLSKIIPDCSMESTKSgqskggILSKACDYIQELRqsnhRLSEELQGL 209
Cdd:cd18918    1 LFATERERREKLNEKFSDLRNLIPNPTKNDRAS------ILSDAIKYINELQ----RTVEELKSL 55

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

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 672074856 145 HNEVERRRRDKINNWIVQLSKIIPDcsmeSTKsgQSKGGILSKACDYIQELRQ 197
Cdd:cd11455   11 HSEAERRRRERINSHLATLRTLLPN----LSK--TDKASLLAEVVQHVKELKR 57

basic helix-loop-helix-Per-ARNT-Sim (bHLH-PAS) domain found in Circadian locomotor output cycles protein kaput (CLOCK) and similar proteins; CLOCK, also termed Class E basic helix-loop-helix protein 8 (bHLHe8), is a bHLH-PAS transcriptional activator which forms a core component of the circadian clock. It forms heterodimers with another bHLH-PAS protein, Brain-Muscle-Arnt-Like (also known as BMAL or ARNT3 or mop3), which regulates circadian rhythm. BMAL1-CLOCK heterodimer complex activates transcription from E-box (CANNTG) elements found in the promoter of circadian responsive genes.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 672074856 137 RDEKRRAQHNEVERRRRDKINNWIVQLSKIIPDCSMESTKSgqskgGILSKACDYIQELRQ 197
Cdd:cd19734    3 KDKAKRVSRNKSEKKRRDQFNVLIKELGSMLPGNARKMDKS-----TVLQKSIDFLRKHKE 58

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
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 672074856 145 HNEVERRRRDKINNWIVQLSKIIPDCSMestksgQSKGGILSKACDYIQELRQSNHRL 202
Cdd:cd11451    6 HAMAERRRREKLNERFITLRSMVPFVTK------MDKVSILGDAIEYLKQLQRRVEEL 57

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
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 672074856 141 RRAQHNEVERRRRDKINNWIVQLSKIIPDCSmESTKSgqSKGGILSKACDYIQELRQ 197
Cdd:cd11418    1 RVARRNERERRRVQAVNDAFDRLRQHVPYLK-RRKKL--SKVKTLRRAIEYIRHLQK 54

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in c-Myc and similar proteins; c-Myc, also termed Myc proto-oncogene protein, or Class E basic helix-loop-helix protein 39 (bHLHe39), or transcription factor p64, a bHLHZip proto-oncogene protein that functions as a transcription factor, which binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. It activates the transcription of growth-related genes.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672074856 138 DEKRRAqHNEVERRRRDKINNWIVQLSKIIPDCsmeSTKSGQSKGGILSKACDYIQELRQSNHRLSEElqgLDQLQLDND 217
Cdd:cd11458    3 NDKRRT-HNVLERQRRNELKLSFFALRDQIPEV---ANNEKAPKVVILKKATEYILSMQADEQRLISE---KEQLRRRRE 75

                 ....*....
gi 672074856 218 VLRQQVEDL 226
Cdd:cd11458   76 QLKHRLEQL 84

basic helix-loop-helix (bHLH) domain found in Arabidopsis thaliana protein ABA-INDUCIBLE bHLH-TYPE (AIB) and similar proteins; The family includes several bHLH transcription factors from Arabidopsis thaliana, such as AIB and MYC proteins (MYC2, MYC3 and MYC4). AIB, also termed AtbHLH17, or EN 35, is a transcription activator that regulates positively abscisic acid (ABA) response. MYC2, also termed protein jasmonate insensitive 1, or R-homologous Arabidopsis protein 1 (RAP-1), or AtbHLH6, or EN 38, or Z-box binding factor 1 protein, is a transcriptional activator involved in abscisic acid (ABA), jasmonic acid (JA), and light signaling pathways. MYC3, also termed protein altered tryptophan regulation 2, or AtbHLH5, or transcription factor ATR2, or EN 36, is a transcription factor involved in tryptophan, jasmonic acid (JA) and other stress-responsive gene regulation. MYC4, also termed AtbHLH4, or EN 37, is a transcription factor involved in jasmonic acid (JA) gene regulation. MYC2, together with MYC3 and MYC4, controls additively subsets of JA-dependent responses.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 672074856 145 HNEVERRRRDKINNWIVQLSKIIPDCS-MEstksgqsKGGILSKACDYIQELRQSNHRLSEELQGLdQLQLDN 216
Cdd:cd11449    9 HVEAERQRREKLNQRFYALRAVVPNVSkMD-------KASLLGDAISYINELKSKVQDMETEKKEM-KRQESE 73

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 672074856 141 RRAQHNEVERRRRDKINNWIVQLSKIIPDCSMESTKsgqSKGGILSKACDYIQELRQSNHRLSEEL 206
Cdd:cd11403    2 KKENHISSEHKRREAIREGFDRLCAIVPALSSSQSR---SEAVVYVKTVEYLKELYERRAKLRSQL 64

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in protein Max-associated protein 1 (Mad1) and similar proteins; Mad1, also termed Max dimerization protein 1 (MXD1), or Max dimerizer 1, or protein MAD, is a bHLHZip transcriptional repressor that binds with MAX to form a sequence-specific DNA-binding protein complex which recognizes the core sequence 5'-CAC[GA]TG-3'. It thus antagonizes MYC transcriptional activity by competing for MAX.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672074856 142 RAQHNEVERRRRDKINNWIVQLSKII---PDCSMESTKSgqskggILSKACDYIQELRQSNHRlseELQGLDQLQLDNDV 218
Cdd:cd18931    2 RSTHNEMEKNRRAHLRLCLEKLKMLVplgPESNRHTTLS------LLMKAKLHIKKLEDSDRK---AVHQIDQLQREQRH 72

                 ....*...
gi 672074856 219 LRQQVEDL 226
Cdd:cd18931   73 LKRQLEKL 80