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

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*
gi 332815975   140 EMFCSGFQTCAREVLQYLAKHENTRDLKSSQLVTHLHRVVSELLQ 184
Cdd:smart00511   1 SSFRSGYRECANEVSRFLSQLPGTDPDVRARLLSHLQTHLNQLLQ 45

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

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*
gi 332815975   140 EMFCSGFQTCAREVLQYLAKHENTRDLKSSQLVTHLHRVVSELLQ 184
Cdd:smart00511   1 SSFRSGYRECANEVSRFLSQLPGTDPDVRARLLSHLQTHLNQLLQ 45

Helix-loop-helix DNA-binding domain;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 332815975   53 YKLPHRLIEKKRRDRINECIAQLKDLLPEHLKLTtlgHLEKAVVLELTLKHVKALT 108
Cdd:pfam00010   1 RREAHNERERRRRDRINDAFDELRELLPTLPPDK---KLSKAEILRLAIEYIKHLQ 53

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        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 332815975  38 KSRRGIKRsEDSKETYKLPHRLIEKKRRDRINECIAQLKDLLPEHLKLTTLGHLEKAVVLELTLKHVKALTNLIDQQQQK 117
Cdd:cd19750    1 KPKRGLKR-DESKEAYKLPHRLIEKKRRDRINECIAQLKDLLPEHLKLTTLGHLEKAVVLELTLKHLKALTALTEQQHQK 79

                         90
                 ....*....|
gi 332815975 118 IIALQSGLQA 127
Cdd:cd19750   80 IIALQNGERS 89

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 332815975  57 HRLIEKKRRDRINECIAQLKDLLPEHLKLTTLGHLEKAVVLELTLKHVKALT 108
Cdd:cd11389    1 HKVIEKRRRDRINESLAELRRLVPEARKSKGSGKLEKAEILEMTLQHLKALQ 52

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 332815975  57 HRLIEKKRRDRINECIAQLKDLLPEHLKLTTLGHLEKAVVLELTLKHVKAL 107
Cdd:cd11408    2 HKVIEKRRRDRINRCLNELGKTVPMALAKQTSGKLEKAEILEMTVQYLRAL 52

basic helix-loop-helix-orange (bHLH-O) domain found in Drosophila melanogaster enhancer of split mbeta protein (ESMB) and similar proteins; ESMB, also termed E(spl)mbeta, or HLH-mbeta, or split locus enhancer protein mA, is a bHLH-O transcriptional repressor of genes that require a bHLH protein for their transcription. It is involved in the neural-epidermal lineage decision during early neurogenesis. The family also includes Enhancer of split m7 protein (also known as E(spl)m7), which acts as a transcriptional repressor that participates in the control of cell fate choice by uncommitted neuroectodermal cells in the embryo.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 332815975  50 KETYKLPHRLIEKKRRDRINECIAQLKDLLPEHLKLTTLGH--LEKAVVLELTLKHVKAL 107
Cdd:cd19741    5 YQYRKVTKPLLERKRRARINKCLDELKDLMVEALATEAENVskLEKADILELTVRHLKKL 64

Helix-loop-helix DNA-binding domain;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 332815975   53 YKLPHRLIEKKRRDRINECIAQLKDLLPEHLKLTtlgHLEKAVVLELTLKHVKALT 108
Cdd:pfam00010   1 RREAHNERERRRRDRINDAFDELRELLPTLPPDK---KLSKAEILRLAIEYIKHLQ 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
                 ....*....|....*....|....*....|....*....|....*....
gi 332815975  59 LIEKKRRDRINECIAQLKDLLPEHLKLTTLGHLEKAVVLELTLKHVKAL 107
Cdd:cd11407    7 IIEKRRRDRINNSLAELRRLVPTAFEKQGSAKLEKAEILQMTVDHLKML 55

basic helix-loop-helix-orange (bHLH-O) domain found in transcription factor HES-3 and similar proteins; HES-3, also termed Class B basic helix-loop-helix protein 43 (bHLHb43), or hairy and enhancer of split 3, is a bHLH-O transcription factor expressed in neural stem and progenitor cells that is involved in tissue regeneration. It regulates gene expression, cell growth, and insulin release. HES-3 is one mammalian counterpart of the Hairy and Enhancer of split proteins that play a critical role in many physiological processes including cellular differentiation, cell cycle arrest, apoptosis and self-renewal ability.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 332815975  60 IEKKRRDRINECIAQLKDLLPEHLKLTTLGH-LEKAVVLELTLKHVKALTN 109
Cdd:cd18933    1 MEKKRRARINVSLEQLKSLLEKHYSNNIRKRkLEKADILELTVKYLRSLQN 51

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 332815975  57 HRLIEKKRRDRINECIAQLKDLLPEHLKLTTLGHLEKAVVLELTLKHVKALTNLID 112
Cdd:cd11387    2 HNAVERRRRDNINEKIQELGSLVPPSRLETKDLKPNKGSILSKAVEYIRELQNQNQ 57

basic helix-loop-helix-orange (bHLH-O) domain found in hairy/enhancer-of-split related with YRPW motif-like protein (HEYL) and similar proteins; HEYL, also termed Class B basic helix-loop-helix protein 33 (bHLHb33), or hairy-related transcription factor 3 (HRT-3), is a bHLH-O transcriptional repressor that is strongly expressed in the presomitic mesoderm, the somites, the peripheral nervous system and smooth muscle of all arteries and is a downstream effector of the Notch and transforming growth factor-beta pathways. It promotes neuronal differentiation by activating proneural genes and inhibiting other hairy and enhancer of split (HES) and hairy/enhancer-of-split related with YRPW motif protein (HEY) proteins. HEYL also functions as a tumor suppressor involved in the progression of human cancers.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 332815975  35 QVYKSRRGIkrsedsketyklphrlIEKKRRDRINECIAQLKDLLPEHLKLTTLGHLEKAVVLELTLKHVKAL 107
Cdd:cd11447    7 QARKKRRGI----------------IEKRRRDRINSSLSELRRLVPTAFEKQGSSKLEKAEILQMTVDHLKML 63

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 332815975  61 EKKRRDRINECIAQLKDLLPEHLKLTTlghLEKAVVLELTLKHVKAL 107
Cdd:cd00083    1 ERRRRDKINDAFEELKRLLPELPDSKK---LSKASILQKAVEYIREL 44

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 332815975  54 KLPHRLIEKKRRDRINECIAQLKDLL-PEHLKLTTLGHLEKAVVLELTLKHVK 105
Cdd:cd11461    1 KLRKPVVEKTRRDRINSSIEQLKTLLeKEFQRHQPNSKLEKADILEMTVSFLK 53

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 332815975  54 KLPHRLIEKKRRDRINECIAQLKDLLPEHLKLTTlgHLEKAVVLELTLKHVKALTNL 110
Cdd:cd11391    1 REKSREAAKKRRDKENAEISELASLLPLPPAVGS--KLDKLSVLRLAVAYLRLKKFL 55

basic helix-loop-helix-orange (bHLH-O) domain found in hairy/enhancer-of-split related with YRPW motif protein 2 (HEY2) and similar proteins; HEY2, also termed cardiovascular helix-loop-helix factor 1 (CHF-1), or Class B basic helix-loop-helix protein 32 (bHLHb32), or HES-related repressor protein 2, or hairy and enhancer of split-related protein 2 (HESR-2), or hairy-related transcription factor 2 (HRT-2), or protein gridlock homolog, is a bHLH-O transcriptional repressor expressed preferentially in the developing and adult cardiovascular system. As a downstream effector of Notch signaling, HEY2 may be required for cardiovascular development. It also plays an important role in neurologic development, as well as in the progression of human cancers.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 332815975  59 LIEKKRRDRINECIAQLKDLLPEHLKLTTLGHLEKAVVLELTLKHVKAL 107
Cdd:cd18920   16 IIEKRRRDRINNSLSELRRLVPTAFEKQGSAKLEKAEILQMTVDHLKML 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 332815975  54 KLPHRLIEKKRRDRINECIAQLKDLLPEHL------------KLTTLGHLEKAVVLELTLKHVKALTN 109
Cdd:cd11395    4 RLPHNAIEKRYRSNLNTKIERLRDAIPSLRspegksddgglgGLAPTTKLSKATILTKAIEYIRHLEQ 71

basic helix-loop-helix (bHLH) domain found in Arabidopsis thaliana genes coding transcription factors and similar proteins; bHLH proteins are the second largest class of plant transcription factors that regulate transcription of genes that are involve in many essential physiological and developmental process. bHLH proteins are transcriptional regulators that are found in organisms from yeast to humans. The Arabidopsis bHLH proteins that have been characterized so far have roles in regulation of fruit dehiscence, cell development (carpel, anther and epidermal), phytochrome signaling, flavonoid biosynthesis, hormone signaling and stress responses.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 332815975  57 HRLIEKKRRDRINECIAQLKDLLPehlkltTLGHLEKAVVLELTLKHVKALtnlidqqQQKIIALQ 122
Cdd:cd11393    1 HSIAERKRREKINERIRALRSLVP------NGGKTDKASILDEAIEYIKFL-------QEQVKVLS 53

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 332815975  41 RGIKRSedsketyklPHRLIEKKRRDRINECIAQLKDLL-PEHLKlttlghLEKAVVLELTLKHVKALTNLIDQQQQKII 119
Cdd:cd11394    3 KVEKRS---------AHNAIEKRYRSSINDRIIELKDLVvGPDAK------MNKSAVLRKAIDYIRYLQKVNQKLKQENM 67

                 ....*.
gi 332815975 120 ALQSGL 125
Cdd:cd11394   68 ALKKAL 73

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
                 ....*....|....*....|....*....|....*....|....*....
gi 332815975  59 LIEKKRRDRINECIAQLKDLLPEHlklTTLGHLEKAVVLELTLKHVKAL 107
Cdd:cd11460    9 LVEKKRRARINESLQELRLILADA---ELQSKMENAEVLELTVKRVQGI 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
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 332815975  52 TYKLPHRLIEKKRRDRINECIAQLKDLLPEhlkltTLGHLEKAVVLELTLKHVKAL 107
Cdd:cd11453    2 TPRSKHSATEQRRRSKINERLQALRDLIPH-----SDQKRDKASFLLEVIEYIQAL 52

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 332815975  57 HRLIEKKRRDRINECIAQLKDLLP---EHLKLTTLGHLEKA-VVLELTLKHVKALTNLIDQQQQKIIALQ 122
Cdd:cd11401    4 HNELEKNRRAHLRLCLERLKELVPlgpDATRHTTLSLLTKAkAYIKNLEDKEKRQRQQKEQLRREQRELK 73

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 332815975  56 PHRLIEKKRRDRINECIAQLKDLLPEHLKLTTlgHLEKAVVLELTLKHVKAL 107
Cdd:cd11469    4 AHSQTEKRRRDKMNNLIEELSAMIPQCNPMAR--KLDKLTVLRMAVQHLKSL 53

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 332815975  54 KLPHRLIEKKRRDRINECIAQLKDLLPEHLKLTTlgHLEKAVVLELTLKHVKALTN 109
Cdd:cd11437    2 RSNHSEIEKRRRDKMNAYIQELSALVPACNAMSR--KLDKLTVLRMAVQHLKSLRG 55

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 332815975  54 KLPHRLIEKKRRDRINECIAQLKDLLPEhlkLTTLGHlEKAVVLELTLKHVKALTNLIDQQQQKIIAL 121
Cdd:cd11404    3 RLNHVRSEKKRRELIKKGYDELCALVPG---LDPQKR-TKADILQKAADWIQELKEENEKLEEQLDEL 66

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 332815975  53 YKLPHRLIEKKRRDRINECIAQLKDLLP---EHLKLTTLGHLEKAVVleltlkHVKALTNLIDQQQQKIIALQ 122
Cdd:cd18930    1 NRSTHNELEKNRRAHLRLCLERLKVLIPlgpDCTRHTTLGLLNKAKA------HIKKLEEADRKSQHQLENLE 67

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
                 ....*....|....*....|....
gi 332815975  57 HRLIEKKRRDRINECIAQLKDLLP 80
Cdd:cd11397    9 HNMIERRRRFNINDRIKELGTLLP 32

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in sterol regulatory element-binding protein 1 (SREBP1) and similar proteins; SREBP1, also termed Class D basic helix-loop-helix protein 1 (bHLHd1), or sterol regulatory element-binding transcription factor 1 (SREBF1), is a member of a family of bHLHzip transcription factors that recognize sterol regulatory element 1 (SRE-1). It acts as a transcriptional activator required for lipid homeostasis. It may control transcription of the low-density lipoprotein receptor gene as well as the fatty acid. SREBP1 has dual sequence specificity binding to both an E-box motif (5'-ATCACGTGA-3') and to SRE-1 (5'-ATCACCCCAC-3').

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 332815975  57 HRLIEKKRRDRINECIAQLKDLLpehlkLTTLGHLEKAVVLELTLKHVKALTNLIDQQQQKIIALQSGLQ 126
Cdd:cd18921   10 HNAIEKRYRSSINDKIIELKDLV-----VGTEAKLNKSAVLRKAIDYIRFLQQSNQKLKQENMALKMAVQ 74

basic helix-loop-helix (bHLH) domain found in Arabidopsis thaliana BIG PETAL (BPE) and similar proteins; The family includes several bHLH transcription factors from Arabidopsis thaliana, such as BPE, HBI1 and BEE proteins (BEE1-3). BPE, also termed AtbHLH31, or EN 88, is involved in the control of Arabidopsis petal size, by interfering with postmitotic cell expansion to limit final petal cell size. HBI1, also termed AtbHLH64, or homolog of bee2 interacting with IBH1, or EN 79, is an atypical bHLH transcription factor that acts as positive regulator of cell elongation downstream of multiple external and endogenous signals by direct binding to the promoters and activation of the two expansin genes EXPA1 and EXPA8, encoding cell wall loosening enzymes. BEEs, also termed protein Brassinosteroid enhanced expression, are positive regulators of brassinosteroid signaling.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 332815975  38 KSRRGikRSEDSketyklpHRLIEKKRRDRINECIAQLKDLLPEHLKLTTlghleKAVVLELTLKHVKALTNLIDQQQQK 117
Cdd:cd18919    6 RARRG--QATDS-------HSLAERVRREKISERMKLLQDLVPGCNKVTG-----KALMLDEIINYVQSLQRQVEFLSMK 71

                 ....*...
gi 332815975 118 IIALQSGL 125
Cdd:cd18919   72 LAAVNPRL 79

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 332815975  54 KLPHRLIEKKRRDRINECIAQLKDLLPehlklttLGHLEKA---VVLELTLKHVKALTNLIDQQQQKIIALQ 122
Cdd:cd19682    1 RLRHKKRERERRSELRELFDKLKQLLG-------LDSDEKAsklAVLTEAIEEIQQLKREEDELQKEKARLT 65

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
                 ....*....|....*....|....*..
gi 332815975  54 KLPHRLIEKKRRDRINECIAQLKDLLP 80
Cdd:cd11399    4 KTAHNMIEKRYRSNINDRIAELRDSVP 30