basic helix-loop-helix-Per-ARNT-Sim (bHLH-PAS) domain found in circadian clock protein PASD1; PASD1, also termed PAS domain-containing protein 1, is evolutionarily related to Circadian locomotor output cycles protein kaput (CLOCK)and functions as a suppressor of the biological clock that drives the daily circadian rhythms of cells throughout the body. Mammalian PASD1 doesn't harbor the bHLH-PAS domain and is not included in this family.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 190338711  34 MDEDEKDRAKRASRNKSEKKRRDQFNVLIKELCTMLQGQGHPRKMDKSTILQRTIDFLQKQKEITAQTES 103
Cdd:cd19736    1 MDEDEKDRAKRASRNKSEKKRRDQFNVLIKELCTMLQGHGHPLKMDKSTILQRTIDFLQKQKEITAQTEA 70

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 190338711  119 EFTQLMLEALDGFLIALTTDGNIIYVSDSVSSLIGHLPSDMVDQNILNFLPEREHADVYKLLSSHMLLTESS-----TVD 193
Cdd:pfam00989   1 EDLRAILESLPDGIFVVDEDGRILYVNAAAEELLGLSREEVIGKSLLDLIPEEDDAEVAELLRQALLQGEESrgfevSFR 80

                          90
                  ....*....|
gi 190338711  194 LLNSNETHVE 203
Cdd:pfam00989  81 VPDGRPRHVE 90

basic helix-loop-helix-Per-ARNT-Sim (bHLH-PAS) domain found in circadian clock protein PASD1; PASD1, also termed PAS domain-containing protein 1, is evolutionarily related to Circadian locomotor output cycles protein kaput (CLOCK)and functions as a suppressor of the biological clock that drives the daily circadian rhythms of cells throughout the body. Mammalian PASD1 doesn't harbor the bHLH-PAS domain and is not included in this family.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 190338711  34 MDEDEKDRAKRASRNKSEKKRRDQFNVLIKELCTMLQGQGHPRKMDKSTILQRTIDFLQKQKEITAQTES 103
Cdd:cd19736    1 MDEDEKDRAKRASRNKSEKKRRDQFNVLIKELCTMLQGHGHPLKMDKSTILQRTIDFLQKQKEITAQTEA 70

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 190338711 285 DEFTSRHSLEWKFLFLDHRASPIIGYLPFEVLGTSGYDYYHVDDLELIAQCHKQLMQCGKGKSCYYRFLTKGQQWIWLQT 364
Cdd:cd00130    2 PDGVIVLDLDGRILYANPAAEQLLGYSPEELIGKSLLDLIHPEDREELRERLENLLSGGEPVTLEVRLRRKDGSVIWVLV 81

                         90       100
                 ....*....|....*....|..
gi 190338711 365 HYYITYHQWNSKPEFIVCTHSV 386
Cdd:cd00130   82 SLTPIRDEGGEVIGLLGVVRDI 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. 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 190338711  119 EFTQLMLEALDGFLIALTTDGNIIYVSDSVSSLIGHLPSDMVDQNILNFLPEREHADVYKLLSSHMLLTESS-----TVD 193
Cdd:pfam00989   1 EDLRAILESLPDGIFVVDEDGRILYVNAAAEELLGLSREEVIGKSLLDLIPEEDDAEVAELLRQALLQGEESrgfevSFR 80

                          90
                  ....*....|
gi 190338711  194 LLNSNETHVE 203
Cdd:pfam00989  81 VPDGRPRHVE 90

helix loop helix domain;

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 190338711    48 NKSEKKRRDQFNVLIKELCTMLQGQGHPRKMDKSTILQRTIDFLQKQKE 96
Cdd:smart00353   1 NARERRRRRKINEAFDELRSLLPTLPKNKKLSKAEILRLAIEYIKSLQE 49

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 190338711   285 DEFTSRHSLEWKFLFLDHRASPIIGYLPFEVLGTSGYDYYHVDDLELIAQCHKQLMQ 341
Cdd:smart00091  11 PDGIFVLDLDGRILYANPAAEELLGYSPEELIGKSLLELIHPEDRERVQEALQRLLS 67

PAS domain S-box; The PAS domain was previously described. This sensory box, or S-box domain occupies the central portion of the PAS domain but is more widely distributed. It is often tandemly repeated. Known prosthetic groups bound in the S-box domain include heme in the oxygen sensor FixL, FAD in the redox potential sensor NifL, and a 4-hydroxycinnamyl chromophore in photoactive yellow protein. Proteins containing the domain often contain other regulatory domains such as response regulator or sensor histidine kinase domains. Other S-box proteins include phytochromes and the aryl hydrocarbon receptor nuclear translocator. [Regulatory functions, Small molecule interactions]

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 190338711  118 EEFTQLMLEALDGFLIALTTDGNIIYVSDSVSSLIGHLPSDMVDQNILNFLPErEHADVYKLLSSHMLLTESSTV 192
Cdd:TIGR00229   2 EERYRAIFESSPDAIIVIDLEGNILYVNPAFEEIFGYSAEELIGRNVLELIPE-EDREEVRERIERRLEGEPEPV 75

basic helix-loop-helix-Per-ARNT-Sim (bHLH-PAS) domain found in circadian clock protein PASD1; PASD1, also termed PAS domain-containing protein 1, is evolutionarily related to Circadian locomotor output cycles protein kaput (CLOCK)and functions as a suppressor of the biological clock that drives the daily circadian rhythms of cells throughout the body. Mammalian PASD1 doesn't harbor the bHLH-PAS domain and is not included in this family.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 190338711  34 MDEDEKDRAKRASRNKSEKKRRDQFNVLIKELCTMLQGQGHPRKMDKSTILQRTIDFLQKQKEITAQTES 103
Cdd:cd19736    1 MDEDEKDRAKRASRNKSEKKRRDQFNVLIKELCTMLQGHGHPLKMDKSTILQRTIDFLQKQKEITAQTEA 70

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 190338711  35 DEDEKDRAKRASRNKSEKKRRDQFNVLIKELCTMLQGQGhpRKMDKSTILQRTIDFLQKQKEITAQTESCEVRQDWKPSF 114
Cdd:cd19735    2 EEDEKDTIKRKSRNLSEKKRRDQFNVLINELCSMVSTSN--RKMDKSTVLKSTIAFLKNHNEVTMQSHQQEIQEDWKPSF 79

                 .
gi 190338711 115 L 115
Cdd:cd19735   80 L 80

basic helix-loop-helix-Per-ARNT-Sim (bHLH-PAS) domain found in Circadian locomotor output cycles protein kaput (CLOCK) and similar proteins; The family includes CLOCK, neuronal PAS domain-containing protein 2 (NPAS2) and non-mammalian circadian clock protein PASD1. CLOCK, also termed Class E basic helix-loop-helix protein 8 (bHLHe8), is a transcriptional activator which forms a core component of the circadian clock. NPAS2, also termed neuronal PAS2, or basic-helix-loop-helix-PAS protein MOP4, or Class E basic helix-loop-helix protein 9 (bHLHe9), or member of PAS protein 4, or PAS domain-containing protein 4, is a transcriptional activator which forms a core component of the circadian clock. PASD1 is evolutionarily related to Circadian locomotor output cycles protein kaput (CLOCK)and functions as a suppressor of the biological clock that drives the daily circadian rhythms of cells throughout the body.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 190338711  44 RASRNKSEKKRRDQFNVLIKELCTMLQGQGhpRKMDKSTILQRTIDFLQKQKEITA 99
Cdd:cd11441    1 RKSRNLSEKKRRDQFNVLINELASMLPGRG--RKMDKSTVLKKTIAFLRKHKELTA 54

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 190338711  297 FLFLDHRASPIIGYLPFEVLGT--SGYDYYHVDDLELIAQCHKQLMQCGKGKSCYYRFLTKGQQWIWLQTHYYItYHQWN 374
Cdd:pfam08447   1 IIYWSPRFEEILGYTPEELLGKgeSWLDLVHPDDRERVREALWEALKGGEPYSGEYRIRRKDGEYRWVEARARP-IRDEN 79

                          90
                  ....*....|
gi 190338711  375 SKPEFIVCTH 384
Cdd:pfam08447  80 GKPVRVIGVA 89

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 190338711  44 RASRNKSEKKRRDQFNVLIKELCTMLQG-QGHPRKMDKSTILQRTIDFLQKQKEI 97
Cdd:cd11391    1 REKSREAAKKRRDKENAEISELASLLPLpPAVGSKLDKLSVLRLAVAYLRLKKFL 55

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        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 190338711  37 DEKDRAKRASRNKSEKKRRDQFNVLIKELCTMLqgQGHPRKMDKSTILQRTIDFLQKQKEITAQ 100
Cdd:cd11398    1 EEWHRQRRDNHKEVERRRRENINEGINELAALV--PGNAREKNKGAILARAVEYIQELQETEAK 62

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 190338711   119 EFTQLMLEALDGFLIALTTDGNIIYVSDSVSSLIGHLPSDMVDQNILNFLPEREHADVYKLLSSHM 184
Cdd:smart00091   1 ERLRAILESLPDGIFVLDLDGRILYANPAAEELLGYSPEELIGKSLLELIHPEDRERVQEALQRLL 66

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 190338711 128 LDGFLIALTTDGNIIYVSDSVSSLIGHLPSDMVDQNILNFLPEREHADVYKLLSSHMLLTESSTVDL 194
Cdd:cd00130    1 LPDGVIVLDLDGRILYANPAAEQLLGYSPEELIGKSLLDLIHPEDREELRERLENLLSGGEPVTLEV 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 190338711  51 EKKRRDQFNVLIKELCTMLQGQGHPRKMDKSTILQRTIDFLQKQKE 96
Cdd:cd00083    1 ERRRRDKINDAFEELKRLLPELPDSKKLSKASILQKAVEYIRELQS 46

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 190338711  43 KRASRNKSEKKRRDQFNVLIKELCTMLQGQgHPRKMDKSTILQRTIDFLQKQKE 96
Cdd:cd11404    2 RRLNHVRSEKKRRELIKKGYDELCALVPGL-DPQKRTKADILQKAADWIQELKE 54

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.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|..
gi 190338711   347 SCYYRFLTKGQQWIWLQTHYYITYHqWNSKPEFIVCTHSVVS 388
Cdd:smart00086   1 TVEYRLRRKDGSYIWVLVSASPIRD-EDGEVEGILGVVRDIT 41

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 190338711  39 KDRAKRASRNKSEKKRRDQFNVLIKELCTMLQGQGHP-RKMDKSTILQRTIDFLQKQKEITAQTESCEVRQ 108
Cdd:cd18926    9 KERQKKDNHNLIERRRRFNINDRIKELGTLIPKSNDPdMRWNKGTILKASVDYIRKLQREQQRAKELENRQ 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
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 190338711  44 RASRNKSEKKRRDQFNVLIKELCTMLQGQGHPrKMDKSTI----------LQRTIDFLQKQK 95
Cdd:cd19682    1 RLRHKKRERERRSELRELFDKLKQLLGLDSDE-KASKLAVlteaieeiqqLKREEDELQKEK 61

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 190338711  43 KRASRNKSEKKRRDQFNVLIKELCTML-QGQGHPRKMDKSTILQRTIDFLQ 92
Cdd:cd11437    1 SRSNHSEIEKRRRDKMNAYIQELSALVpACNAMSRKLDKLTVLRMAVQHLK 51

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 190338711  51 EKKRRDQFNVLIKELCTML------QGQGhprKMDKSTILQRTIDFLQKQ 94
Cdd:cd11389    5 EKRRRDRINESLAELRRLVpearksKGSG---KLEKAEILEMTLQHLKAL 51

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in MLX-interacting protein (MLXIP), MLX-interacting protein-like (MLXIPL) and similar proteins; The family includes MLXIP and MLXIPL. MLXIP, also termed Class E basic helix-loop-helix protein 36 (bHLHe36), or transcriptional activator MondoA, is a bHLHZip transcriptional activator that binds DNA as a heterodimer with Mlx. It binds to the canonical E box sequence 5'-CACGTG-3' and plays a role in transcriptional activation of glycolytic target genes. MLXIP is most highly expressed in skeletal muscle and functions as an indirect glucose sensor, by sensing glucose 6-phosphate and shuttling between the nucleus and the cytoplasm. MLXIPL, also termed carbohydrate-responsive element-binding protein (ChREBP), or Class D basic helix-loop-helix protein 14 (bHLHd14), or MLX interactor, or WS basic-helix-loop-helix leucine zipper protein (WS-bHLH), or Williams-Beuren syndrome chromosomal region 14 protein (WBSCR14), is a bHLHZip transcriptional factor integral to the regulation of glycolysis and lipogenesis in the liver. It forms heterodimers with the bHLHZip protein Mlx to bind the DNA sequence 5'-CACGTG-3'.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 190338711  43 KRASRNKSEKKRRDQFNVLIKELCTMLQ--GQGHPRKMDKSTILQRTIDFLQK-QKEITAQTESCE 105
Cdd:cd11405    3 RRLSHISAEQKRRFNIKSGFDTLQSLIPslGQNPNQKVSKAAMLQKAAEYIKSlKRERQQMQEEAE 68

basic helix-loop-helix-orange (bHLH-O) domain found in hairy and enhancer of split 7 (HES-7) and similar proteins; HES-7, also termed Class B basic helix-loop-helix protein 37 (bHLHb37), or bHLH factor Hes7, is a bHLH-O transcriptional repressor that is expressed in an oscillatory manner and acts as a key regulator of the pace of the segmentation clock. It is regulated by the Notch and Fgf/Mapk pathways. HES-7 is one mammalian counterpart of the Hairy and Enhancer of split proteins that play a critical role in many physiological processes including cellular differentiation, cell cycle arrest, apoptosis and self-renewal ability.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 190338711  51 EKKRRDQFNVLIKELCTML----QGQG-HPRKMDKSTILQRTIDFLQKQK 95
Cdd:cd11462    9 EKRRRDRINRSLEELRVLLlqntQDEKlKNPKVEKAEILELTVQFLRNSS 58

basic helix-loop-helix (bHLH) domain found in Arabidopsis thaliana protein IAA-leucine resistant 3 (ILR3) and similar proteins; ILR3, also termed AtbHLH105, or EN 133, is a bHLH transcription factor that plays a role in resistance to amide-linked indole-3-acetic acid (IAA) conjugates such as IAA-Leu and IAA-Phe. It may regulate gene expression in response to metal homeostasis changes.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 190338711  51 EKKRRDQFNVLIKELCTMLQgQGHPRKMDKSTILQRTIDFLQK--------QKEITA-QTESCEVRQD 109
Cdd:cd11446    5 EKLRRDKLNERFMELSNVLE-PGRPPKTDKATILGDAIRMLKQlrgevqklKEENSSlQEESKELKAE 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
                 ....*....|....*....|....*....|....*....|....*....|.
gi 190338711  50 SEKKRRDQFNVLIKELCTMLQGQGhprKMDKSTILQRTID---FLQKQKEI 97
Cdd:cd11393    4 AERKRREKINERIRALRSLVPNGG---KTDKASILDEAIEyikFLQEQVKV 51

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.

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gi 190338711  37 DEKDRAKRASRNKSEKKRRDQFNVLIKELCTMLQG-QGHPRKMDKSTILQRTIDFLQ 92
Cdd:cd11438    1 QGRIKNAREAHSQIEKRRRDKMNSFIDELASLVPTcNAMSRKLDKLTVLRMAVQHMK 57

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in basic helix-loop-helix domain-containing protein USF3 and similar proteins; USF3, also termed upstream transcription factor 3, is a bHLHzip protein that is involved in the negative regulation of epithelial-mesenchymal transition, the process by which epithelial cells lose their polarity and adhesion properties to become mesenchymal cells with enhanced migration and invasive properties.

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                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 190338711  38 EKDRaKRASRNKSEKKRRDQFNVLIKELCTMLQGQgHPRKMDKSTILQRTIDFLQKQKE 96
Cdd:cd18910    1 RREK-KRESHNEVERRRKDKINAGINKIGELLPDR-DAKKQSKNMILEQAYKYIVELKK 57

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in transcription factor EB (TFEB) and similar proteins; TFEB, also termed Class E basic helix-loop-helix protein 35 (bHLHe35), is a bHLHzip transcription factor that is required for vascularization of the mouse placenta. 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 TFE3 or MITF.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 190338711  39 KDRAKRASRNKSEKKRRDQFNVLIKELCTMLqgqghPRKMD------KSTILQRTIDFLQK-QKEitaQTESCEVRQDWK 111
Cdd:cd18927    7 KERQKKDNHNLIERRRRFNINDRIKELGTLI-----PKTNDldvrwnKGTILKASVDYIKRmQKD---LQRSRELENHSR 78

                 ....*....
gi 190338711 112 PSFLSNEEF 120
Cdd:cd18927   79 RLEMTNKQL 87

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.

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                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 190338711  41 RAKRasRNKSEKKRRDQFNVLIKEL----CTMLQGQGhPRKMDKSTILQRTIDFLQ 92
Cdd:cd11407    1 RKKR--RGIIEKRRRDRINNSLAELrrlvPTAFEKQG-SAKLEKAEILQMTVDHLK 53

basic helix-loop-helix-Per-ARNT-Sim (bHLH-PAS) domain found in Drosophila melanogaster protein cycle and similar proteins; 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.

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                 ....*....|....*....|....*....|....*....|....
gi 190338711  43 KRASRNKSEKKRRDQFNVLIKELCTML-QGQGHPRKMDKSTILQ 85
Cdd:cd19726    1 RRQNHSEIEKRRRDKMNTYITELSSMIpMCNAMSRKLDKLTVLR 44