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 564329227  325 EFLSRHNSDGIITFVDPRCISVIGYQPQDLLGKDILEFCHPEDQSHLRESFQQVVKLKGQVLSVMYRFRTKNREWLLIRT 404
Cdd:pfam14598   3 QFTTRHDIDGKIISCDTRAPFSLGYEKDELVGRSIYDLVHPQDLRTAKSHLREIIQTRGRATSPSYRLRLRDGDFLSVHT 82

                          90       100
                  ....*....|....*....|.
gi 564329227  405 SSFTFQNPYSDEIEYVICTNT 425
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 564329227  325 EFLSRHNSDGIITFVDPRCISVIGYQPQDLLGKDILEFCHPEDQSHLRESFQQVVKLKGQVLSVMYRFRTKNREWLLIRT 404
Cdd:pfam14598   3 QFTTRHDIDGKIISCDTRAPFSLGYEKDELVGRSIYDLVHPQDLRTAKSHLREIIQTRGRATSPSYRLRLRDGDFLSVHT 82

                          90       100
                  ....*....|....*....|.
gi 564329227  405 SSFTFQNPYSDEIEYVICTNT 425
Cdd:pfam14598  83 KSKLFLNQNSNQQPFIMCTHT 103

Helix-loop-helix DNA-binding domain;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 564329227   54 RENHSEIERRRRNKMTQYITELSDMVPTcSALARKPDKLTILRMAVSHMKSMR 106
Cdd:pfam00010   2 REAHNERERRRRDRINDAFDELRELLPT-LPPDKKLSKAEILRLAIEYIKHLQ 53

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 564329227   325 EFLSRHNSDGIITFVDPRCISVIGYQPQDLLGKDILEFCHPEDQSHLRESFQQVVK 380
Cdd:smart00091  12 DGIFVLDLDGRILYANPAAEELLGYSPEELIGKSLLELIHPEDRERVQEALQRLLS 67

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 564329227  126 ELKHLILEAADGFLFVVAaETGRVIYVSDSVTPVLNQPQSEWFGSTLYEQVHPDD----VEKLREQLCTSENSMTGRI-L 200
Cdd:pfam00989   1 EDLRAILESLPDGIFVVD-EDGRILYVNAAAEELLGLSREEVIGKSLLDLIPEEDdaevAELLRQALLQGEESRGFEVsF 79

                          90       100       110
                  ....*....|....*....|....*....|...
gi 564329227  201 DLKTGTVKKEGQQSSMRMCMGSR-RSFICRMRC 232
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. 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
                 ....*....|....*....|....*....|....*....|....*....|....
gi 564329227 135 ADGFLFVVAAEtGRVIYVSDSVTPVLNQPQSEWFGSTLYEQVHPDDVEKLREQL 188
Cdd:cd00130    1 LPDGVIVLDLD-GRILYANPAAEQLLGYSPEELIGKSLLDLIHPEDREELRERL 53

Sporulation sensor histidine kinase E [Cell cycle control, cell division, chromosome partitioning, Signal transduction mechanisms];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564329227  55 ENHSEIERRRRNKMTQYITELSDMVPTCSALARKPDKLTILRmAVSHMKSMrgtgnkstdgaykPSFLTEQELKH-LILE 133
Cdd:COG5809   83 ESRDELEFELRHKNGKRLEFSSKLSPIFDQNGDIEGMLAISR-DITERKRM-------------EEALRESEEKFrLIFN 148

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564329227 134 AADGFLFVVAAEtGRVIYVSDSVTPVLNQPQSEWFGSTLYEQVHPDDVEKLRE----------------QLCTSENSMtg 197
Cdd:COG5809  149 HSPDGIIVTDLD-GRIIYANPAACKLLGISIEELIGKSILELIHSDDQENVAAfisqllkdggiaqgevRFWTKDGRW-- 225

                        170
                 ....*....|....*.
gi 564329227 198 RILDLKTGTVKKEGQQ 213
Cdd:COG5809  226 RLLEASGAPIKKNGEV 241

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 564329227  53 SRENHSEIERRRRNKMTQYITELSDMVPTCSALARKPDKLTILRMAVSHMKSMRGTGN 110
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        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 564329227  47 EGPSKFSRENHSEIERRRRNKMTQYITELSDMVPTCSALARKPDKLTILRMAVSHMKSMRGTGN 110
Cdd:cd11438    1 QGRIKNAREAHSQIEKRRRDKMNSFIDELASLVPTCNAMSRKLDKLTVLRMAVQHMKTLRGATN 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 564329227  325 EFLSRHNSDGIITFVDPRCISVIGYQPQDLLGKDILEFCHPEDQSHLRESFQQVVKLKGQVLSVMYRFRTKNREWLLIRT 404
Cdd:pfam14598   3 QFTTRHDIDGKIISCDTRAPFSLGYEKDELVGRSIYDLVHPQDLRTAKSHLREIIQTRGRATSPSYRLRLRDGDFLSVHT 82

                          90       100
                  ....*....|....*....|.
gi 564329227  405 SSFTFQNPYSDEIEYVICTNT 425
Cdd:pfam14598  83 KSKLFLNQNSNQQPFIMCTHT 103

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 564329227  54 RENHSEIERRRRNKMTQYITELSDMVPTCSALARKPDKLTILRMAVSHMK 103
Cdd:cd11391    1 REKSREAAKKRRDKENAEISELASLLPLPPAVGSKLDKLSVLRLAVAYLR 50

Helix-loop-helix DNA-binding domain;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 564329227   54 RENHSEIERRRRNKMTQYITELSDMVPTcSALARKPDKLTILRMAVSHMKSMR 106
Cdd:pfam00010   2 REAHNERERRRRDRINDAFDELRELLPT-LPPDKKLSKAEILRLAIEYIKHLQ 53

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 564329227   325 EFLSRHNSDGIITFVDPRCISVIGYQPQDLLGKDILEFCHPEDQSHLRESFQQVVK 380
Cdd:smart00091  12 DGIFVLDLDGRILYANPAAEELLGYSPEELIGKSLLELIHPEDRERVQEALQRLLS 67

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 564329227  126 ELKHLILEAADGFLFVVAaETGRVIYVSDSVTPVLNQPQSEWFGSTLYEQVHPDD----VEKLREQLCTSENSMTGRI-L 200
Cdd:pfam00989   1 EDLRAILESLPDGIFVVD-EDGRILYVNAAAEELLGLSREEVIGKSLLDLIPEEDdaevAELLRQALLQGEESRGFEVsF 79

                          90       100       110
                  ....*....|....*....|....*....|...
gi 564329227  201 DLKTGTVKKEGQQSSMRMCMGSR-RSFICRMRC 232
Cdd:pfam00989  80 RVPDGRPRHVEVRASPVRDAGGEiLGFLGVLRD 112

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 564329227  61 ERRRRNKMTQYITELSDMVPTCSALaRKPDKLTILRMAVSHMKSMR 106
Cdd:cd00083    1 ERRRRDKINDAFEELKRLLPELPDS-KKLSKASILQKAVEYIRELQ 45

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        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 564329227   129 HLILEAADGFLFVVAAEtGRVIYVSDSVTPVLNQPQSEWFGSTLYEQVHPDDVEKLREQL 188
Cdd:smart00091   4 RAILESLPDGIFVLDLD-GRILYANPAAEELLGYSPEELIGKSLLELIHPEDRERVQEAL 62

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 564329227  54 RENHSEIERRRRNKMTQYITELSDMVPTCSALARKP--DKLTILRMAVSHMKSMRGTGNK 111
Cdd:cd18924    6 RAQHNEVERRRRDKINNWIVQLSKIIPDCSMESTKSgqSKGGILSKACDYIQELRQSNHR 65

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 564329227  54 RENHSEIERRRRNKMTQYITELSDMVPTCSALARK--PDKLTILRMAVSHMKSMRGTgNKSTDGAYK 118
Cdd:cd18923    9 RAQHNEVERRRRDKINNWIVQLSKIIPDCNTDNSKtgASKGGILSKACDYIRELRQT-NQRMQETYK 74

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 564329227  53 SRENHSEIERRRRNKMTQYITELSDMVPTCSalaRKPDKLTILRMAVSHMKSMRG 107
Cdd:cd19683    2 SRERHNAKERQRRERIKIACDQLRKLVPGCS---RKTDKATVFEFTVAYIKFLRE 53

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in sterol regulatory element-binding protein (SREBP) family and similar proteins; The SREBP family includes SREBP1 and SREBP2, which are bHLHzip transcriptional activator of genes encoding proteins essential for cholesterol biosynthesis/uptake and fatty acid biosynthesis. SREBP1 and SREBP2 are principally found in the liver and in adipocytes and made up of an N-terminal transcription factor portion (composed of an activation domain, a bHLHzip domain, and a nuclear localization signal), a hydrophobic region containing two membrane spanning regions, and a C-terminal regulatory segment. They recognize a symmetric sterol regulatory element (TCACNCCAC) instead of E-box. The family also includes Saccharomyces cerevisiae transcription factor HMS1 (also termed high-copy MEP suppressor protein 1) and serine-rich protein TYE7. HMS1 is a putative bHLHzip transcription factor involved in exit from mitosis and pseudohyphal differentiation. TYE7, also termed basic-helix-loop-helix protein SGC1, is a putative bHLHzip transcription activator required for Ty1-mediated glycolytic gene expression. TYE7 N-terminal is extremely rich in serine residues. It binds DNA on E-box motifs, 5'-CANNTG-3'. TYE7 is not essential for growth.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 564329227  51 KFSRENHSEIERRRRNKMTQYITELSDMVPTCS--------------ALARKPDKLTILRMAVSHMKSM 105
Cdd:cd11395    1 PRKRLPHNAIEKRYRSNLNTKIERLRDAIPSLRspegksddgglgglAPTTKLSKATILTKAIEYIRHL 69

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 564329227  57 HSEIERRRRNKMTQYITELSDMVPTCSALARK--PDKLTILRMAVSHMKSMR 106
Cdd:cd11396    2 HNEVERRRRDKINNWIVKLAKIVPDCEKDNSKqgQSKGGILSKACDYIQELR 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        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 564329227  60 IERRRRNKMTQYITELSDMVPTcsALAR----KPDKLTILRMAVSHMKSMRGTG 109
Cdd:cd11407    8 IEKRRRDRINNSLAELRRLVPT--AFEKqgsaKLEKAEILQMTVDHLKMLHSKG 59

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
                 ....*....|....*....|....*....|....*....|....*....|....
gi 564329227  60 IERRRRNKMTQYITELSDMVPTC--SALARKPDKLTILRMAVSHMKSMRGTGNK 111
Cdd:cd11447   16 IEKRRRDRINSSLSELRRLVPTAfeKQGSSKLEKAEILQMTVDHLKMLHATGGA 69

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

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 564329227  54 RENHSEIERRRRNKMTQYITELSDMVPTCSALARKPDKLTILRMAVSHMKSMR 106
Cdd:cd11397    6 KDNHNMIERRRRFNINDRIKELGTLLPKSNDPDMRWNKGTILKASVDYIRKLQ 58

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 564329227  54 RENHSEIERRRRNKMTQYITELSDMVPTCSALARKPDKLTILRMAVSHMKSMRGTGNKSTDGAYKPSFLtEQELKHLIL 132
Cdd:cd18928   12 KDNHNLIERRRRFNINDRIKELGTLIPKSTDPEMRWNKGTILKASVDYIRKLQKEQQRSKEIEMRQRKL-EQANRSLQL 89

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        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 564329227  60 IERRRRNKMTQYITELSDMVPTC--SALARKPDKLTILRMAVSHMKSMRGTGNK 111
Cdd:cd18920   17 IEKRRRDRINNSLSELRRLVPTAfeKQGSAKLEKAEILQMTVDHLKMLQATGGK 70

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
                 ....*....|....*....|....*....|....*....|....*....
gi 564329227  60 IERRRRNKMTQYITELSDMVPTCSAL--ARKPDKLTILRMAVSHMKSMR 106
Cdd:cd19685    1 SEKRRRQRINDKLNQLKELLPPNLSKqsRSKLSKAEILEMAITELRRLQ 49

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
                 ....*....|....*....|....*....|....*....|....*....|..
gi 564329227  54 RENHSEIERRRRNKMTQYITELSDMVPTCSalARKPDKLTILRMAVSHMKSM 105
Cdd:cd11404    3 RLNHVRSEKKRRELIKKGYDELCALVPGLD--PQKRTKADILQKAADWIQEL 52

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
                 ....*....|....*....|....*....|....*....|....*....|.
gi 564329227  56 NHSEIERRRRNKMTQYITELSDMVPTCSalarKPDKLTILRMAVSHMKSMR 106
Cdd:cd11449    8 NHVEAERQRREKLNQRFYALRAVVPNVS----KMDKASLLGDAISYINELK 54

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 564329227  54 RENHSEIERRRRNKMTQYITELSDMVPTCSALARKPDKLTILRMAVSHMKSMRGTGNKSTDGAYKPSFLtEQELKHLIL 132
Cdd:cd18926   14 KDNHNLIERRRRFNINDRIKELGTLIPKSNDPDMRWNKGTILKASVDYIRKLQREQQRAKELENRQKKL-EHANRHLLL 91

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.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 564329227  60 IERRRRNKMTQYITELSDMVPTC-----SAlarKPDKLTILRMAVSHMKSMRGTGNKST 113
Cdd:cd19748   16 IEKRRRDRINNSLSELRRLVPSAfekqgSA---KLEKAEILQMTVDHLKMLHAAGGKGY 71

basic helix-loop-helix-Per-ARNT-Sim (bHLH-PAS) domain found in nuclear receptor coactivator 3 (NCoA-3) and similar proteins; NCoA-3, also termed ACTR, or amplified in breast cancer 1 protein (AIB-1), or CBP-interacting protein (pCIP), or Class E basic helix-loop-helix protein 42 (bHLHe42), or receptor-associated coactivator 3 (RAC-3), or steroid receptor coactivator protein 3 (SRC-3), or thyroid hormone receptor activator molecule 1 (TRAM-1), is a bHLH-PAS steroid/nuclear receptor-associated coactivator that directly binds nuclear receptors and stimulates the transcriptional activities in a hormone-dependent fashion. It also plays a central role in creating a multisubunit coactivator complex, which probably acts via remodeling of chromatin.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 564329227  60 IERRRRNKMTQYITELSDMVPT----CSALARKPDKLTILRMAVSHMKSMRGTGNKSTD 114
Cdd:cd18949    5 GEKRRREQESKYIEELAELISAnlsdIDNFNVKPDKCAILKETVRQIRQIKEQGKSSSN 63

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
                 ....*....|....*....|....*....|....*....|....*....|....
gi 564329227  52 FSRENHSEIERRRRNKMTQYITELSDMVPTCSALARKpDKLTILRMAVSHMKSM 105
Cdd:cd18929    1 NNRSSHNELEKHRRAKLRLYLEQLKQLVPLGPDSTRH-TTLSLLKRAKMHIKKL 53

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

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 564329227  60 IERRRRNKMTQYITELSDMVPTCSAL----ARKPDKLTILRMAVSHMKSMR 106
Cdd:cd11410    1 MEKKRRARINKSLEQLKTLVLEALNKdntrYSKLEKADILEMTVKYLKQLQ 51

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

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 564329227  57 HSEIERRRRNKMTQYITELSDMVPTCSalaRKPDKLTILRMAVSHMKSMR 106
Cdd:cd19698    1 HNLLEKKRRERIKDKIEILKGLTPNCT---PKSDIASILSCVIDYIKSLL 47

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in transcription factor EC (TFEC) and similar proteins; TFEC, also termed Class E basic helix-loop-helix protein 34 (bHLHe34), or transcription factor EC-like (TFEC-L), is a bHLHzip transcriptional regulator that acts as a repressor or an activator and regulates gene expression in macrophages. It plays an important role in the niche to expand hematopoietic progenitors through the modulation of several cytokines.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 564329227  54 RENHSEIERRRRNKMTQYITELSDMVPTCSALARKPDKLTILRMAVSHMKSMRGTGNKSTDGAYKPSFLtEQELKHLIL 132
Cdd:cd18925    6 KDNHNLIERRRRYNINYRIKELGTLIPKSNDPDMRWNKGTILKASVEYIKWLQKEQQRARELEHRQKKL-EQANRRLLL 83

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in the Myc family; The Myc family is a member of the bHLHzip family of transcription factors that play important roles in the control of normal cell proliferation, growth, survival and differentiation. All Myc isoforms contain two independently functioning polypeptide chain regions: N-terminal transactivating residues and a C-terminal bHLHzip segment. The bHLHzip family of bHLH transcription factors are characterized by a highly conserved N-terminal basic region that may bind DNA at a consensus hexanucleotide sequence known as the E-box (CANNTG) followed by HLH and leucine zipper motifs that may interact with other proteins to form homo- and heterodimers. Myc heterodimerizes with Max enabling specific binding to E-box DNA sequences in the promoters of target genes. The Myc proto-oncoprotein family includes at least five different functional members: c-, N-, L-, S- and B-Myc (which is lacking the bHLH domain).

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 564329227  54 RENHSEIERRRRNKMTQYITELSDMVPtcsALARKPD--KLTILRMAVSHMKSMRGTGNK 111
Cdd:cd11400    2 RRLHNVLERQRRNDLKNSFEKLRDLVP---ELADNEKasKVVILKKATEYIKQLQQEEKK 58

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.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*..
gi 564329227  57 HSEIERRRRNKMTQYITELSDMVPTCSalARKPDKLTILRMAVSHMK 103
Cdd:cd18908    6 HSLKERLRRERIKSSCDQLRDLLPYIK--GRKLDMASVLEMTVKYIR 50

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        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 564329227  56 NHSEIERRRRNKMTQYITELSDMVPTCSalarKPDKLTILRMAVSHMKSMRGTGNKSTDG 115
Cdd:cd11455   10 SHSEAERRRRERINSHLATLRTLLPNLS----KTDKASLLAEVVQHVKELKRQAAEITTP 65

Sporulation sensor histidine kinase E [Cell cycle control, cell division, chromosome partitioning, Signal transduction mechanisms];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564329227  55 ENHSEIERRRRNKMTQYITELSDMVPTCSALARKPDKLTILRmAVSHMKSMrgtgnkstdgaykPSFLTEQELKH-LILE 133
Cdd:COG5809   83 ESRDELEFELRHKNGKRLEFSSKLSPIFDQNGDIEGMLAISR-DITERKRM-------------EEALRESEEKFrLIFN 148

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564329227 134 AADGFLFVVAAEtGRVIYVSDSVTPVLNQPQSEWFGSTLYEQVHPDDVEKLRE----------------QLCTSENSMtg 197
Cdd:COG5809  149 HSPDGIIVTDLD-GRIIYANPAACKLLGISIEELIGKSILELIHSDDQENVAAfisqllkdggiaqgevRFWTKDGRW-- 225

                        170
                 ....*....|....*.
gi 564329227 198 RILDLKTGTVKKEGQQ 213
Cdd:COG5809  226 RLLEASGAPIKKNGEV 241

RocR-type transcriptional regulator, contains PAS, AAA-type ATPase, and DNA-binding Fis domains [Transcription, Signal transduction mechanisms];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564329227 331 NSDGIITFVDPRCISVIGYQPQDLLGKDILEFCHpedQSHLResfqQVVKLKGQVLSVMYRFRTKNREWLLIRTSSFTfq 410
Cdd:COG3829   28 DADGRITYVNRAAERILGLPREEVIGKNVTELIP---NSPLL----EVLKTGKPVTGVIQKTGGKGKTVIVTAIPIFE-- 98