PAS domain; This family includes the PAS-B domain of NCOA1 (Nuclear receptor coactivator 1), which binds to an LXXLL motif in the C-terminal region of STAT6 (Signal transducer and activator of transcription 6).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720403043 296 EFISRHNIEGIFTFVDHRCVATVGYQPQELLGKNIVEFCHPEDQQLLRDSFQQVVKLKGQVLSVMFRFRSKTREWLWMRT 375
Cdd:pfam14598   3 QFTTRHDIDGKIISCDTRAPFSLGYEKDELVGRSIYDLVHPQDLRTAKSHLREIIQTRGRATSPSYRLRLRDGDFLSVHT 82

                          90       100
                  ....*....|....*....|.
gi 1720403043 376 SSFTFQNPYSDEIEYIICTNT 396
Cdd:pfam14598  83 KSKLFLNQNSNQQPFIMCTHT 103

PAS domain; This family includes the PAS-B domain of NCOA1 (Nuclear receptor coactivator 1), which binds to an LXXLL motif in the C-terminal region of STAT6 (Signal transducer and activator of transcription 6).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720403043 296 EFISRHNIEGIFTFVDHRCVATVGYQPQELLGKNIVEFCHPEDQQLLRDSFQQVVKLKGQVLSVMFRFRSKTREWLWMRT 375
Cdd:pfam14598   3 QFTTRHDIDGKIISCDTRAPFSLGYEKDELVGRSIYDLVHPQDLRTAKSHLREIIQTRGRATSPSYRLRLRDGDFLSVHT 82

                          90       100
                  ....*....|....*....|.
gi 1720403043 376 SSFTFQNPYSDEIEYIICTNT 396
Cdd:pfam14598  83 KSKLFLNQNSNQQPFIMCTHT 103

Helix-loop-helix DNA-binding domain;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1720403043  25 RENHSEIERRRRNKMTAYITELSDMVPTcSALARKPDKLTILRMAVSHMKSLR 77
Cdd:pfam00010   2 REAHNERERRRRDRINDAFDELRELLPT-LPPDKKLSKAEILRLAIEYIKHLQ 53

PAS fold; The PAS fold corresponds to the structural domain that has previously been defined as PAS and PAC motifs. The PAS fold appears in archaea, eubacteria and eukarya. This domain can bind gases (O2, CO and NO), FAD, 4-hydroxycinnamic acid and NAD+ (Matilla et.al., FEMS Microbiology Reviews, fuab043, 45, 2021, 1. https://doi.org/10.1093/femsre/fuab043).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720403043  97 ELKHLILEAADGFLFIVScETGRVVYVSDSVTPVLNQPQSEWFGSTLYDQVHPDD----VDKLREQLSTSENALTGRV-L 171
Cdd:pfam00989   1 EDLRAILESLPDGIFVVD-EDGRILYVNAAAEELLGLSREEVIGKSLLDLIPEEDdaevAELLRQALLQGEESRGFEVsF 79

                          90       100       110
                  ....*....|....*....|....*....|...
gi 1720403043 172 DLKTGTVKKEGQQSSMRMCMGSR-RSFICRMRC 203
Cdd:pfam00989  80 RVPDGRPRHVEVRASPVRDAGGEiLGFLGVLRD 112

PAS domain; PAS motifs appear in archaea, eubacteria and eukarya. Probably the most surprising identification of a PAS domain was that in EAG-like K+-channels.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1720403043  296 EFISRHNIEGIFTFVDHRCVATVGYQPQELLGKNIVEFCHPEDQQLLRDSFQQVVK 351
Cdd:smart00091  12 DGIFVLDLDGRILYANPAAEELLGYSPEELIGKSLLELIHPEDRERVQEALQRLLS 67

PAS domain; PAS motifs appear in archaea, eubacteria and eukarya. Probably the most surprising identification of a PAS domain was that in EAG-like K+-channels. PAS domains have been found to bind ligands, and to act as sensors for light and oxygen in signal transduction.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720403043 106 ADGFLFIVScETGRVVYVSDSVTPVLNQPQSEWFGSTLYDQVHPDDVDKLREQLSTSENALTGRVLDLKtgTVKKEGQQS 185
Cdd:cd00130     1 LPDGVIVLD-LDGRILYANPAAEQLLGYSPEELIGKSLLDLIHPEDREELRERLENLLSGGEPVTLEVR--LRRKDGSVI 77

                          90
                  ....*....|....*...
gi 1720403043 186 SMRMCMGSRRSFICRMRC 203
Cdd:cd00130    78 WVLVSLTPIRDEGGEVIG 95

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 1720403043  24 ARENHSEIERRRRNKMTAYITELSDMVPTCSALARKPDKLTILRMAVSHMKSLRGTGN 81
Cdd:cd11437     1 SRSNHSEIEKRRRDKMNAYIQELSALVPACNAMSRKLDKLTVLRMAVQHLKSLRGTGS 58

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
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1720403043  24 ARENHSEIERRRRNKMTAYITELSDMVPTCSALARKPDKLTILRMAVSHMKSLRGTGN 81
Cdd:cd11438     7 AREAHSQIEKRRRDKMNSFIDELASLVPTCNAMSRKLDKLTVLRMAVQHMKTLRGATN 64

PAS domain; This family includes the PAS-B domain of NCOA1 (Nuclear receptor coactivator 1), which binds to an LXXLL motif in the C-terminal region of STAT6 (Signal transducer and activator of transcription 6).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720403043 296 EFISRHNIEGIFTFVDHRCVATVGYQPQELLGKNIVEFCHPEDQQLLRDSFQQVVKLKGQVLSVMFRFRSKTREWLWMRT 375
Cdd:pfam14598   3 QFTTRHDIDGKIISCDTRAPFSLGYEKDELVGRSIYDLVHPQDLRTAKSHLREIIQTRGRATSPSYRLRLRDGDFLSVHT 82

                          90       100
                  ....*....|....*....|.
gi 1720403043 376 SSFTFQNPYSDEIEYIICTNT 396
Cdd:pfam14598  83 KSKLFLNQNSNQQPFIMCTHT 103

PAS fold; The PAS fold corresponds to the structural domain that has previously been defined as PAS and PAC motifs. The PAS fold appears in archaea, eubacteria and eukarya.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720403043 307 FTFVDHRCVATVGYQPQELLGK--NIVEFCHPEDQQLLRDSFQQVVKlKGQVLSVMFRFRSKTREWLWMRTSSFTFQNPy 384
Cdd:pfam08447   1 IIYWSPRFEEILGYTPEELLGKgeSWLDLVHPDDRERVREALWEALK-GGEPYSGEYRIRRKDGEYRWVEARARPIRDE- 78

                          90
                  ....*....|.
gi 1720403043 385 SDEIEYIICTN 395
Cdd:pfam08447  79 NGKPVRVIGVA 89

Helix-loop-helix DNA-binding domain;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1720403043  25 RENHSEIERRRRNKMTAYITELSDMVPTcSALARKPDKLTILRMAVSHMKSLR 77
Cdd:pfam00010   2 REAHNERERRRRDRINDAFDELRELLPT-LPPDKKLSKAEILRLAIEYIKHLQ 53

PAS fold; The PAS fold corresponds to the structural domain that has previously been defined as PAS and PAC motifs. The PAS fold appears in archaea, eubacteria and eukarya. This domain can bind gases (O2, CO and NO), FAD, 4-hydroxycinnamic acid and NAD+ (Matilla et.al., FEMS Microbiology Reviews, fuab043, 45, 2021, 1. https://doi.org/10.1093/femsre/fuab043).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720403043  97 ELKHLILEAADGFLFIVScETGRVVYVSDSVTPVLNQPQSEWFGSTLYDQVHPDD----VDKLREQLSTSENALTGRV-L 171
Cdd:pfam00989   1 EDLRAILESLPDGIFVVD-EDGRILYVNAAAEELLGLSREEVIGKSLLDLIPEEDdaevAELLRQALLQGEESRGFEVsF 79

                          90       100       110
                  ....*....|....*....|....*....|...
gi 1720403043 172 DLKTGTVKKEGQQSSMRMCMGSR-RSFICRMRC 203
Cdd:pfam00989  80 RVPDGRPRHVEVRASPVRDAGGEiLGFLGVLRD 112

PAS domain; PAS motifs appear in archaea, eubacteria and eukarya. Probably the most surprising identification of a PAS domain was that in EAG-like K+-channels.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1720403043  296 EFISRHNIEGIFTFVDHRCVATVGYQPQELLGKNIVEFCHPEDQQLLRDSFQQVVK 351
Cdd:smart00091  12 DGIFVLDLDGRILYANPAAEELLGYSPEELIGKSLLELIHPEDRERVQEALQRLLS 67

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 1720403043  32 ERRRRNKMTAYITELSDMVPTCSALaRKPDKLTILRMAVSHMKSLR 77
Cdd:cd00083     1 ERRRRDKINDAFEELKRLLPELPDS-KKLSKASILQKAVEYIRELQ 45

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in Saccharomyces cerevisiae centromere-binding protein 1 (CBP-1) and similar proteins; CBP-1, also termed centromere promoter factor 1 (CPF1), or centromere-binding factor 1 (CBF1), is a bHLHzip protein that is required for chromosome stability and methionine prototrophy. It binds as a homodimer to the centromere DNA elements I (CDEI, GTCACATG) region of the centromere that is required for optimal centromere function.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1720403043  18 ADKERLARENHSEIERRRRNKMTAYITELSDMVPtcsALARKPDKLTILRMAVSHMKSL 76
Cdd:cd11398     1 EEWHRQRRDNHKEVERRRRENINEGINELAALVP---GNAREKNKGAILARAVEYIQEL 56

PAS domain [Signal transduction mechanisms];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720403043 293 QPTEFISRHNIEGIFTFVDHRCVATVGYQPQELLGKNIVEFCHPEDQQLLRDSFQQVVKlKGQVLSVMFRFRSKTREWLW 372
Cdd:COG2202    19 SSPDAIIITDLDGRILYVNPAFERLTGYSAEELLGKTLRDLLPPEDDDEFLELLRAALA-GGGVWRGELRNRRKDGSLFW 97

                          90       100
                  ....*....|....*....|....*.
gi 1720403043 373 MRTSSFTFQNPySDEIEYIICTNTNV 398
Cdd:COG2202    98 VELSISPVRDE-DGEITGFVGIARDI 122

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 1720403043  27 NHSEIERRRRNKMTAYITELSDMVPTC--SALARKPDKLTILRMAVSHMKSLR 77
Cdd:cd11387     1 SHNAVERRRRDNINEKIQELGSLVPPSrlETKDLKPNKGSILSKAVEYIRELQ 53

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 1720403043  19 DKERlaRENHSEIERRRRNKMTAYITELSDMVPTCSALARKP--DKLTILRMAVSHMKSLR 77
Cdd:cd18924     2 DEKR--RAQHNEVERRRRDKINNWIVQLSKIIPDCSMESTKSgqSKGGILSKACDYIQELR 60

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in upstream stimulatory factor 2 (USF2) and similar proteins; USF2, also termed Class B basic helix-loop-helix protein 12 (bHLHb12), or major late transcription factor 2, or FOS-interacting protein (FIP), or upstream transcription factor 2, is a bHLHzip transcription factor that binds to a symmetrical DNA sequence (E-boxes) (5'-CACGTG-3') that is found in a variety of viral and cellular promoters.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1720403043  19 DKERlaRENHSEIERRRRNKMTAYITELSDMVPTCSALARK--PDKLTILRMAVSHMKSLRGTgNTSTDGSYK 89
Cdd:cd18923     5 DERR--RAQHNEVERRRRDKINNWIVQLSKIIPDCNTDNSKtgASKGGILSKACDYIRELRQT-NQRMQETYK 74

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 1720403043  24 ARENHSEIERRRRNKMTAYITELSDMVPTCS--------------ALARKPDKLTILRMAVSHMKSL 76
Cdd:cd11395     3 KRLPHNAIEKRYRSNLNTKIERLRDAIPSLRspegksddgglgglAPTTKLSKATILTKAIEYIRHL 69

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
                  ....*....|....*....|....*....|....*....|....*....|
gi 1720403043  28 HSEIERRRRNKMTAYITELSDMVPTCsalaRKPDKLTILRMAVSHMKSLR 77
Cdd:cd11393     1 HSIAERKRREKINERIRALRSLVPNG----GKTDKASILDEAIEYIKFLQ 46

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

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1720403043  31 IERRRRNKMTAYITELSDMVPTcsALAR----KPDKLTILRMAVSHMKSLRGTG 80
Cdd:cd11407     8 IEKRRRDRINNSLAELRRLVPT--AFEKqgsaKLEKAEILQMTVDHLKMLHSKG 59

basic helix-loop-helix-Per-ARNT-Sim (bHLH-PAS) domain found in Drosophila melanogaster Circadian locomotor output cycles protein kaput (dCLOCK) and similar proteins; dCLOCK, also termed dPAS1, is a bHLH-PAS Circadian regulator that acts as a transcription factor and generates a rhythmic output with a period of about 24 hours.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720403043  12 DDEQSSADKERLAReNHSEieRRRRNKMTAYITELSDMVptcSALARKPDKLTILRMAVSHMKslrgTGNTSTDGS---- 87
Cdd:cd19735     1 DEEDEKDTIKRKSR-NLSE--KKRRDQFNVLINELCSMV---STSNRKMDKSTVLKSTIAFLK----NHNEVTMQShqqe 70

                          90
                  ....*....|
gi 1720403043  88 ----YKPSFL 93
Cdd:cd19735    71 iqedWKPSFL 80

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1720403043  14 EQSSADKERLARENHSEIERRRRNKMTAYITELSDMVPTCSALARKPDKLTILRMAVSHMKSLR 77
Cdd:cd18926     3 EARALAKERQKKDNHNLIERRRRFNINDRIKELGTLIPKSNDPDMRWNKGTILKASVDYIRKLQ 66

basic helix-loop-helix (bHLH) domain found in Arabidopsis thaliana phytochrome interacting factors (PIFs) and similar proteins; The family includes several bHLH transcription factors from Arabidopsis thaliana, such as PIFs, ALC, PIL1, SPATULA, and UNE10. PIFs (PIF1, PIF3, PIF4, PIF5, PIF6 and PIF7) have been shown to control light-regulated gene expression. They directly bind to the photoactivated phytochromes and are degraded in response to light signals. ALC, also termed AtbHLH73, or protein ALCATRAZ, or EN 98, is required for the dehiscence of fruit, especially for the separation of the valve cells from the replum. It promotes the differentiation of a strip of labile non-lignified cells sandwiched between layers of lignified cells. PIL1, also termed AtbHLH124, or protein phytochrome interacting factor 3-like 1, or EN 110, is involved in responses to transient and long-term shade. It is required for the light-mediated inhibition of hypocotyl elongation and necessary for rapid light-induced expression of the photomorphogenesis- and circadian-related gene APRR9. PIL1 seems to play a role in multiple PHYB responses, such as flowering transition and petiole elongation. SPATULA, also termed AtbHLH24, or EN 99, plays a role in floral organogenesis. It promotes the growth of carpel margins and of pollen tract tissues derived from them. UNE10, also termed AtbHLH16, or protein UNFERTILIZED EMBRYO SAC 10, or EN 99, is required during the fertilization of ovules by pollen.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1720403043  24 ARENHSEIERRRRNKMTAYITELSDMVPTCSalarKPDKLTILRMAVSHMKSL 76
Cdd:cd11445     2 AAEVHNLSERRRRDRINEKMKALQELIPNCN----KTDKASMLDEAIEYLKSL 50

PAS fold; The PAS fold corresponds to the structural domain that has previously been defined as PAS and PAC motifs. The PAS fold appears in archaea, eubacteria and eukarya. This domain can bind gases (O2, CO and NO), FAD, 4-hydroxycinnamic acid and NAD+ (Matilla et.al., FEMS Microbiology Reviews, fuab043, 45, 2021, 1. https://doi.org/10.1093/femsre/fuab043).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720403043 302 NIEGIFTFVDHRCVATVGYQPQELLGKNIVEFCHPEDQQLLRDSFQQVVKLKGQVLSVMFRFRSKTREWLWMRTSSFTFQ 381
Cdd:pfam00989  18 DEDGRILYVNAAAEELLGLSREEVIGKSLLDLIPEEDDAEVAELLRQALLQGEESRGFEVSFRVPDGRPRHVEVRASPVR 97

                          90
                  ....*....|...
gi 1720403043 382 NPySDEIEYIICT 394
Cdd:pfam00989  98 DA-GGEILGFLGV 109

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.

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                  ....*....|....*....|....*....|....*....|....*....|..
gi 1720403043  25 RENHSEIERRRRNKMTAYITELSDMVPTCSalARKPDKLTILRMAVSHMKSL 76
Cdd:cd11404     3 RLNHVRSEKKRRELIKKGYDELCALVPGLD--PQKRTKADILQKAADWIQEL 52

basic helix-loop-helix-orange (bHLH-O) domain found in HERP/HES-like family; The HERP/HES-like family includes bHLH-O transcriptional regulators that are related to the Drosophila hairy and Enhancer-of-split (HES) proteins. The HERP (HES-related repressor protein) subfamily proteins contain a basic helix-loop-helix (bHLH) domain with an invariant glycine residue in its basic region, an orange domain in the central region and YXXW sequence motif at its C-terminal region. Hairy and enhancer of split (HES)-related repressor protein (HERP) proteins (HEY1, HEY2 and HEYL) act as downstream effectors of Notch signaling. They are involved in cardiovascular development and have roles in somitogenesis, myogenesis and gliogenesis. Hairy and enhancer of split-related protein HELT is a transcriptional repressor expressed in the developing central nervous system. It binds preferentially to the canonical E box sequence 5'-CACGCG-3' and regulates neuronal differentiation and/or identity. Differentially expressed in chondrocytes proteins, DEC1 and DEC2, are widely expressed in both embryonic and adult tissues and have been implicated in apoptosis, cell proliferation, and circadian rhythms, as well as malignancy in various cancers. Drosophila melanogaster protein clockwork orange (Cwo) is also included in this subfamily. It is involved in the regulation of Drosophila circadian rhythms. It functions as both an activator and a repressor of clock gene expression. The HES subfamily proteins contain a basic helix-loop-helix (bHLH) domain with an invariant proline residue in its basic region, an orange domain in the central region and a conserved tetrapeptide motif, WRPW, at its C-terminal region. They form heterodimers or homodimers via their HLH domain and bind DNA to repress gene transcription that play an essential role in development of both compartment and boundary cells of the central nervous system.

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                  ....*....|....*....|....*....|....*....|....*....
gi 1720403043  31 IERRRRNKMTAYITELSDMVPTCSAL--ARKPDKLTILRMAVSHMKSLR 77
Cdd:cd19685     1 SEKRRRQRINDKLNQLKELLPPNLSKqsRSKLSKAEILEMAITELRRLQ 49

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1720403043  19 DKERLARENHSEIERRRRNKMTAYITELSDMVPTCSalarKPDKLTILRMAVSHMKSLRGT 79
Cdd:cd11455     2 DKALAASKSHSEAERRRRERINSHLATLRTLLPNLS----KTDKASLLAEVVQHVKELKRQ 58

basic helix-loop-helix-orange (bHLH-O) domain found in Drosophila melanogaster protein clockwork orange (Cwo) and similar proteins; Cwo is a bHLH-O transcriptional regulator involved in the regulation of Drosophila circadian rhythms. It functions as both an activator and a repressor of clock gene expression.

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                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1720403043  27 NHSEIERRRRNKMTAYITELSDMVPTcsALARKP----DKLTILRMAVSHMKSLR 77
Cdd:cd11440     5 SHRIIEKRRRDRMNNCLADLSRLIPP--TYLKKGrgriEKTEIIEMAIKHIKHLQ 57

basic helix-loop-helix-orange (bHLH-O) domain found in hairy/enhancer-of-split related with YRPW motif protein 1 (HEY1) and similar proteins; HEY1, also termed cardiovascular helix-loop-helix factor 2 (CHF-2), or Class B basic helix-loop-helix protein 31 (bHLHb31), or HES-related repressor protein 1, or hairy and enhancer of split-related protein 1 (HESR-1), or hairy-related transcription factor 1 (HRT-1), is a bHLH-O transcriptional repressor that acts as an essential downstream effector of the Notch signaling pathway and may play a fundamental role in vascular development. HEY1 also participates several cancer-related pathways. It acts as a positive regulator of the tumor suppressor p53.

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                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1720403043  31 IERRRRNKMTAYITELSDMVPTC-----SAlarKPDKLTILRMAVSHMKSLRGTG 80
Cdd:cd19748    16 IEKRRRDRINNSLSELRRLVPSAfekqgSA---KLEKAEILQMTVDHLKMLHAAG 67

basic helix-loop-helix-Per-ARNT-Sim (bHLH-PAS) domain found in Drosophila melanogaster protein single-minded (SIM) and similar proteins; SIM is a nuclear bHLH-PAS transcription factor that functions as a master developmental regulator controlling midline development of the ventral nerve cord in Drosophila.

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                  ....*....|....*....|....*....|....*....|....*....|
gi 1720403043  25 RENHSEIERRRRNKMTAYITELSDMVPTCSALARKPDKLTILRMAVSHMK 74
Cdd:cd19740     2 KEKSKNAARSRREKENAEFLELAKLLPLPAAITSQLDKASIIRLTTSYLK 51

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.

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                  ....*....|....*....|....*....|....*....|....*....|..
gi 1720403043  25 RENHSEIERRRRNKMTAYITELSDMVPTCSALARKpDKLTILRMAVSHMKSL 76
Cdd:cd18929     3 RSSHNELEKHRRAKLRLYLEQLKQLVPLGPDSTRH-TTLSLLKRAKMHIKKL 53

basic helix-loop-helix (bHLH) domain found in Arabidopsis thaliana protein NAI1 and similar proteins; NAI1, also termed AtbHLH20, or EN 27, is a bHLH transcription activator that regulates the expression of at least NAI2, PYK10 and PBP1. It is required for and mediates the formation of endoplasmic reticulum bodies (ER bodies). It plays a role in the symbiotic interactions with the endophytes of the Sebacinaceae fungus family, such as Piriformospora indica and Sebacina.

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                  ....*....|....*....|....*....|....*....|....*....|..
gi 1720403043  26 ENHSEIERRRRNKMTAYITELSDMVPTCsalaRKPDKLTILRMAVSHMKSLR 77
Cdd:cd11452     4 QDHILAERKRREKLSQRFIALSALVPGL----KKMDKASVLGDAIKHIKQLQ 51

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720403043  28 HSEIERRRRNKMTAYITELSDMVPTC-------------------SALARKPDKLTILRMAVSHMKSLRG 78
Cdd:cd11399     7 HNMIEKRYRSNINDRIAELRDSVPALreayksargededeedlggLTPATKLNKATILSKATEYIRHLEK 76

basic helix-loop-helix-Per-ARNT-Sim (bHLH-PAS) domain found in steroid receptor coactivator (SRC) family; The SRC family of coactivators includes SRC-1 (NcoA-1/p160), SRC-2(TIF2/GRIP1/NcoA-2) and SRC-3(NcoA-3/pCIP/RAC3/ACTR/pCIP/AIB1/TRAM1), which are critical mediators of steroid receptor action. They contain bHLH-PAS domain at the N-terminal that is followed by receptor interacting domain and C-terminal transcriptional activation domain. SRC coactivators interact with nuclear receptors in a ligand-dependent manner and enhance transcriptional activation by the receptor via histone acetylation/methylation.

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                  ....*....|....*....|....*....|....*....|....*....|....
gi 1720403043  32 ERRRRNKMTAYITEL--------SDMvptcSALARKPDKLTILRMAVSHMKSLR 77
Cdd:cd11439     6 EKRRREQENKYIEELaelisasiSDM----DSLSVKPDKCAILQETVKQIRQIK 55

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1720403043  19 DKERlaRENHSEIERRRRNKMTAYITELSDMVPTCsALARKPDKLTILRMAVSHMKSLR 77
Cdd:cd11456     2 DSER--RRNHNILERQRRNDLRSSFLTLRDHVPEL-VKNEKAAKVVILKKATEYVHSLQ 57

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.

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                  ....*....|....*....|....*....|....*....|....*....|.
gi 1720403043  27 NHSEIERRRRNKMTAYITELSDMVPTCSalarKPDKLTILRMAVSHMKSLR 77
Cdd:cd11449     8 NHVEAERQRREKLNQRFYALRAVVPNVS----KMDKASLLGDAISYINELK 54

basic helix-loop-helix-Per-ARNT-Sim (bHLH-PAS) domain found in aryl hydrocarbon receptor repressor (AhRR) and similar proteins; AhRR, also termed AhR repressor, or Class E basic helix-loop-helix protein 77 (bHLHe77), is a member of bHLH-PAS transcription factors that acts as a negative regulator of AhR (or Dioxin Receptor), playing key roles in development and environmental sensing. AhR is activated by Dioxin to control the expression of certain genes to influence biological processes such as apoptosis, proliferation, cell growth and differentiation. To form active DNA binding complexes, AhR dimerizes with a bHLH-PAS factor ARNT (Aryl hydrocarbon Nuclear Receptor Translocator). AhRR functions by competing with AhR for its partner ARNT. AhRR-ARNT complexes are transcriptionally inactive.

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                  ....*....|....*....|....*....|....*....|....*.
gi 1720403043  29 SEIERRRRNKMTAYITELSDMVPTCSALARKPDKLTILRMAVSHMK 74
Cdd:cd11435     5 SNPSKRHRDRLNAELDHLASLLPFPPDIISKLDKLSVLRLSVSYLR 50

Motif C-terminal to PAS motifs (likely to contribute to PAS structural domain); PAC motif occurs C-terminal to a subset of all known PAS motifs. It is proposed to contribute to the PAS domain fold.

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                   ....*....|....*....|....*....|....*....|.
gi 1720403043  358 SVMFRFRSKTREWLWMRTSSFTFQNpYSDEIEYIICTNTNV 398
Cdd:smart00086   1 TVEYRLRRKDGSYIWVLVSASPIRD-EDGEVEGILGVVRDI 40

basic helix-loop-helix (bHLH) domain found in the spermatogenesis- and oogenesis-specific basic helix-loop-helix-containing protein (SOHLH) family; The SOHLH family includes two bHLH transcription factors, SOHLH1 and SOHLH2. They are specifically in spermatogonia and oocytes and essential for early spermatogonial and oocyte differentiation.

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                  ....*....|....*....|....*....|....*....|....*....|
gi 1720403043  28 HSEIERRRRNKMTAYITELSDMVPTCSalARKPDKLTILRMAVSHMKSLR 77
Cdd:cd18908     6 HSLKERLRRERIKSSCDQLRDLLPYIK--GRKLDMASVLEMTVKYIRYIQ 53

basic helix-loop-helix-Per-ARNT-Sim (bHLH-PAS) domain found in hypoxia-inducible factor (HIF) family; The HIF family contains bHLH-PAS transcription regulators involved in oxygen homeostasis, including HIF1a, HIF2a, and HIF3a. They have been implicated in development, postnatal physiology as well as disease pathogenesis. HIF1a, also termed HIF-1-alpha, or HIF1-alpha, or ARNT-interacting protein, or Basic-helix-loop-helix-PAS protein MOP1, or Class E basic helix-loop-helix protein 78 (bHLHe78), or Member of PAS protein 1, or PAS domain-containing protein 8 (PASD8), functions as a master transcriptional regulator of the adaptive response to hypoxia. HIF2a, also termed HIF-2-alpha, or HIF2-alpha, or endothelial PAS domain-containing protein 1 (EPAS-1), or Basic-helix-loop-helix-PAS protein MOP2, or Class E basic helix-loop-helix protein 73 (bHLHe73), or Member of PAS protein 2, or PAS domain-containing protein 2 (PASD2), or HIF-1-alpha-like factor (HLF), is a bHLH-PAS transcription factor involved in the induction of oxygen regulated genes. HIF3a, also termed HIF-3-alpha, or HIF3-alpha, or endothelial PAS domain-containing protein 1 (EPAS-1), or Basic-helix-loop-helix-PAS protein MOP7, or Class E basic helix-loop-helix protein 17 (bHLHe17), or Member of PAS protein 7, or PAS domain-containing protein 7 (PASD7), or HIF3-alpha-1, or inhibitory PAS domain protein (IPAS), is a bHLH-PAS transcriptional regulator in adaptive response to low oxygen tension. It plays a role in the regulation of hypoxia-inducible gene expression.

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                  ....*....|....*....|....*....|....*....|..
gi 1720403043  33 RRRRNKMTAYITELSDMVPTCSALARKPDKLTILRMAVSHMK 74
Cdd:cd11433    10 RCRRGKESEIFYELAHQLPLPHSVSSQLDKASIMRLTISYLK 51