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        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 576067746  49 IREAHSQMEKRRRDKMNHLIQKLSSMIPPHIPTAHKLDKLSVLRRAVQYLRSLRGMTELY 108
Cdd:cd11469    1 FREAHSQTEKRRRDKMNNLIEELSAMIPQCNPMARKLDKLTVLRMAVQHLKSLKGSTSSF 60

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 576067746   125 HLILKAAEGFLFVVGcERGRIFYVSKSVSKTLRYDQASLIGQNLFDFLHPKDVAKVKEQL 184
Cdd:smart00091   4 RAILESLPDGIFVLD-LDGRILYANPAAEELLGYSPEELIGKSLLELIHPEDRERVQEAL 62

basic helix-loop-helix-Per-ARNT-Sim (bHLH-PAS) domain found in aryl hydrocarbon receptor nuclear translocator-like protein 2 (ARNTL2) and similar proteins; ARNTL2, also termed Basic-helix-loop-helix-PAS protein MOP9, or brain and muscle ARNT-like 2 (BMAL2), or CYCLE-like factor (CLIF), or Class E basic helix-loop-helix protein 6 (bHLHe6), or member of PAS protein 9, or PAS domain-containing protein 9 (PASD9), is a neuronal bHLH-PAS transcriptional factor, regulating cell cycle progression and preventing cell death, whose sustained expression might ensure brain neuron survival. It also plays important roles in tumor angiogenesis. ARNT-2 heterodimerize with other bHLH-PAS proteins such as aryl hydrocarbon receptor (AhR), hypoxia-inducible factor (HIF), and single-minded (SIM).

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 576067746  49 IREAHSQMEKRRRDKMNHLIQKLSSMIPPHIPTAHKLDKLSVLRRAVQYLRSLRGMTELY 108
Cdd:cd11469    1 FREAHSQTEKRRRDKMNNLIEELSAMIPQCNPMARKLDKLTVLRMAVQHLKSLKGSTSSF 60

Helix-loop-helix DNA-binding domain;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 576067746   50 REAHSQMEKRRRDKMNHLIQKLSSMIPPHIPTAhKLDKLSVLRRAVQYLRSLR 102
Cdd:pfam00010   2 REAHNERERRRRDRINDAFDELRELLPTLPPDK-KLSKAEILRLAIEYIKHLQ 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. 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 576067746 308 AEFITRFAMNGKFVYVDQRATAILGYLPQELLGTSCYEYFHQDDHSSLTDKHKA---------DSYKFRVKDGAFVTLKS 378
Cdd:cd00130    2 PDGVIVLDLDGRILYANPAAEQLLGYSPEELIGKSLLDLIHPEDREELRERLENllsggepvtLEVRLRRKDGSVIWVLV 81

                         90
                 ....*....|....*....
gi 576067746 379 EWFSFTNPWTKELEYIVSV 397
Cdd:cd00130   82 SLTPIRDEGGEVIGLLGVV 100

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 576067746   125 HLILKAAEGFLFVVGcERGRIFYVSKSVSKTLRYDQASLIGQNLFDFLHPKDVAKVKEQL 184
Cdd:smart00091   4 RAILESLPDGIFVLD-LDGRILYANPAAEELLGYSPEELIGKSLLELIHPEDRERVQEAL 62

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 576067746  127 ILKAAEGFLFVVGcERGRIFYVSKSVSKTLRYDQASLIGQNLFDFLHPKDVAKVKEQLSCDGSPREKPIDTKTSQVYSHp 206
Cdd:pfam00989   6 ILESLPDGIFVVD-EDGRILYVNAAAEELLGLSREEVIGKSLLDLIPEEDDAEVAELLRQALLQGEESRGFEVSFRVPD- 83

                          90       100       110
                  ....*....|....*....|....*....|
gi 576067746  207 ytGRPRM----------HSGSRRSFFFRMK 226
Cdd:pfam00989  84 --GRPRHvevraspvrdAGGEILGFLGVLR 111

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
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 576067746  141 ERGRIFYVSKSVSKTLRYDQASLIGQNLFDFLHPKDVAKVKEQLSCDGSPREKPI 195
Cdd:TIGR00229  21 LEGNILYVNPAFEEIFGYSAEELIGRNVLELIPEEDREEVRERIERRLEGEPEPV 75

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 576067746  317 NGKFVYVDQRATAILGYLPQELLGTSCYEYFHQDDHSS--------LTDKHKADSYKFRV--KDG 371
Cdd:TIGR00229  22 EGNILYVNPAFEEIFGYSAEELIGRNVLELIPEEDREEvrerierrLEGEPEPVSEERRVrrKDG 86

basic helix-loop-helix-Per-ARNT-Sim (bHLH-PAS) domain found in aryl hydrocarbon receptor nuclear translocator-like protein 2 (ARNTL2) and similar proteins; ARNTL2, also termed Basic-helix-loop-helix-PAS protein MOP9, or brain and muscle ARNT-like 2 (BMAL2), or CYCLE-like factor (CLIF), or Class E basic helix-loop-helix protein 6 (bHLHe6), or member of PAS protein 9, or PAS domain-containing protein 9 (PASD9), is a neuronal bHLH-PAS transcriptional factor, regulating cell cycle progression and preventing cell death, whose sustained expression might ensure brain neuron survival. It also plays important roles in tumor angiogenesis. ARNT-2 heterodimerize with other bHLH-PAS proteins such as aryl hydrocarbon receptor (AhR), hypoxia-inducible factor (HIF), and single-minded (SIM).

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 576067746  49 IREAHSQMEKRRRDKMNHLIQKLSSMIPPHIPTAHKLDKLSVLRRAVQYLRSLRGMTELY 108
Cdd:cd11469    1 FREAHSQTEKRRRDKMNNLIEELSAMIPQCNPMARKLDKLTVLRMAVQHLKSLKGSTSSF 60

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 576067746  50 REAHSQMEKRRRDKMNHLIQKLSSMIPPHIPTAHKLDKLSVLRRAVQYLRSLRGMT 105
Cdd:cd11437    2 RSNHSEIEKRRRDKMNAYIQELSALVPACNAMSRKLDKLTVLRMAVQHLKSLRGTG 57

basic helix-loop-helix-Per-ARNT-Sim (bHLH-PAS) domain found in aryl hydrocarbon receptor nuclear translocator-like protein 1 (ARNTL) and similar proteins; ARNTL, also termed Basic-helix-loop-helix-PAS protein MOP3, or brain and muscle ARNT-like 1 (BMAL1), or Class E basic helix-loop-helix protein 5 (bHLHe5), or member of PAS protein 3, or PAS domain-containing protein 3 (PASD3), or bHLH-PAS protein JAP3, is a member of the bHLH-PAS transcription factor family that forms heterodimers with another bHLH-PAS protein, CLOCK (circadian locomotor output cycle kaput), which regulates circadian rhythm. ARNTL-CLOCK heterodimer complex activates transcription from E-box (CANNTG) elements found in the promoter of circadian responsive genes. ARNTL is highly homologous to ARNT.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 576067746  50 REAHSQMEKRRRDKMNHLIQKLSSMIPPHIPTAHKLDKLSVLRRAVQYLRSLRGMT 105
Cdd:cd11438    8 REAHSQIEKRRRDKMNSFIDELASLVPTCNAMSRKLDKLTVLRMAVQHMKTLRGAT 63

basic helix-loop-helix-Per-ARNT-Sim (bHLH-PAS) domain found in aryl hydrocarbon receptor nuclear translocator (ARNT) and similar proteins; ARNT, also termed Class E basic helix-loop-helix protein 2 (bHLHe2), or Dioxin receptor, nuclear translocator, or hypoxia-inducible factor 1-beta (HIF1b), or HIF-1-beta, or HIF1-beta, is a member of bHLH-PAS transcription regulators that acts 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.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 576067746  50 REAHSQMEKRRRDKMNHLIQKLSSMIPPHIPTAHKLDKLSVLRRAVQYLRSLRG 103
Cdd:cd18947    6 RENHSEIERRRRNKMTAYITELSDMVPTCSALARKPDKLTILRMAVSHMKSLRG 59

helix loop helix domain;

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 576067746    56 MEKRRRDKMNHLIQKLSSMIPPHiPTAHKLDKLSVLRRAVQYLRSLRGMTE 106
Cdd:smart00353   3 RERRRRRKINEAFDELRSLLPTL-PKNKKLSKAEILRLAIEYIKSLQEELQ 52

basic Helix Loop Helix (bHLH) domain superfamily; bHLH proteins are transcriptional regulators that are found in organisms from yeast to humans. Members of the bHLH superfamily have two highly conserved and functionally distinct regions. The basic part is at the amino end of the bHLH that may bind DNA to a consensus hexanucleotide sequence known as the E box (CANNTG). Different families of bHLH proteins recognize different E-box consensus sequences. At the carboxyl-terminal end of the region is the HLH region that interacts with other proteins to form homo- and heterodimers. bHLH proteins function as a diverse set of regulatory factors because they recognize different DNA sequences and dimerize with different proteins. The bHLH proteins can be divided to cell-type specific and widely expressed proteins. The cell-type specific members of bHLH superfamily are involved in cell-fate determination and act in neurogenesis, cardiogenesis, myogenesis, and hematopoiesis.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*.
gi 576067746  57 EKRRRDKMNHLIQKLSSMIPPHiPTAHKLDKLSVLRRAVQYLRSLR 102
Cdd:cd00083    1 ERRRRDKINDAFEELKRLLPEL-PDSKKLSKASILQKAVEYIRELQ 45

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 576067746  50 REAHSQMEKRRRDKMNHLIQKLSSMIPPHiptAHKLDKLSVLRRAVQYLRS 100
Cdd:cd11441    1 RKSRNLSEKKRRDQFNVLINELASMLPGR---GRKMDKSTVLKKTIAFLRK 48

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 576067746  50 REAHSQMEKRRRDKMNHLIQKLSSMIPPHIPtahKLDKLSVLRRAVQYLRSLRGMTE 106
Cdd:cd11398    8 RDNHKEVERRRRENINEGINELAALVPGNAR---EKNKGAILARAVEYIQELQETEA 61

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 576067746  51 EAHSQMEKRRRDKMNHLIQKLSSMipphIPTAHKLDKLSVLRRAVQYLRSL 101
Cdd:cd11445    4 EVHNLSERRRRDRINEKMKALQEL----IPNCNKTDKASMLDEAIEYLKSL 50

basic helix-loop-helix-orange (bHLH-O) domain found in hairy and enhancer of split-related protein HELT and similar proteins; HELT, also termed HES/HEY-like transcription factor, is a bHLH-O transcriptional repressor expressed in the developing central nervous system. It binds preferentially to the canonical E box sequence 5'-CACGCG-3' and regulates neuronal differentiation and/or identity. HELT could homodimerize and heterodimerize with other bHLH-O protein such as HES-5 or HEY-2 and bound to E box to repress gene transcription.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 576067746  52 AHSQMEKRRRDKMNHLIQKLSSMIPPHIP--TAHKLDKLSVLRRAVQYLRSL 101
Cdd:cd11408    1 SHKVIEKRRRDRINRCLNELGKTVPMALAkqTSGKLEKAEILEMTVQYLRAL 52

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 576067746  57 EKRRRDKMNHLIQKLSSMIPphiPTAHKLDKLSVLRRAVQYLRSLRGMTELY----LGENSKPSFI 118
Cdd:cd19735   18 EKKRRDQFNVLINELCSMVS---TSNRKMDKSTVLKSTIAFLKNHNEVTMQShqqeIQEDWKPSFL 80

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

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 576067746  50 REAHSQMEKRRRDKMNHLIQKLSSMIPPHIPTahKLDKLSVLRRAVQYLRSLRGMTE 106
Cdd:cd18910    6 RESHNEVERRRKDKINAGINKIGELLPDRDAK--KQSKNMILEQAYKYIVELKKKND 60

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 576067746   125 HLILKAAEGFLFVVGcERGRIFYVSKSVSKTLRYDQASLIGQNLFDFLHPKDVAKVKEQL 184
Cdd:smart00091   4 RAILESLPDGIFVLD-LDGRILYANPAAEELLGYSPEELIGKSLLELIHPEDRERVQEAL 62

basic helix-loop-helix-Per-ARNT-Sim (bHLH-PAS) domain found in the aryl hydrocarbon receptor (AhR) family; The AhR family includes AhR, AhR repressor (AhRR) and Drosophila melanogaster protein spineless. AhR, also termed Ah receptor, or Dioxin receptor (DR), or Class E basic helix-loop-helix protein 76 (bHLHe76), is the only member of bHLH-PAS transcription regulators that bind and be activated by small chemical ligands. It 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, also termed 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, playing key roles in development and environmental sensing. AhRR functions by competing with AhR for its partner ARNT. AhRR-ARNT complexes are transcriptionally inactive. Spineless is a bHLH-PAS transcription factor that plays an important role in fly morphogenesis. It is both necessary and sufficient for the formation of the ommatidial mosaic.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|..
gi 576067746  58 KRRRDKMNHLIQKLSSMIPPHIPTAHKLDKLSVLRRAVQYLR 99
Cdd:cd19696    9 KRHRDRLNSELDELASLLPFPEDVISKLDKLSVLRLSVSYLR 50

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.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*...
gi 576067746  54 SQMEKRRRDKMNHLIQKLSSMIP--PHIPTahKLDKLSVLRRAVQYLR 99
Cdd:cd11435    5 SNPSKRHRDRLNAELDHLASLLPfpPDIIS--KLDKLSVLRLSVSYLR 50

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 576067746  56 MEKRRRDKMNHLIQKLSSMIPP--HIPTAHKLDKLSVLRRAVQYLRSLR 102
Cdd:cd19685    1 SEKRRRQRINDKLNQLKELLPPnlSKQSRSKLSKAEILEMAITELRRLQ 49

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 576067746  50 REAHSQMEKRRRDKMNHLIQKLSSMIPPHIPTAHKL--DKLSVLRRAVQYLRSLRgMTELYLGENSK 114
Cdd:cd18923    9 RAQHNEVERRRRDKINNWIVQLSKIIPDCNTDNSKTgaSKGGILSKACDYIRELR-QTNQRMQETYK 74

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

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 576067746  53 HSQMEKRRRDKMNHLIQKLSSMipphIPTAHKLDKLSVLRRAVQYLRSL-RGMTELYL 109
Cdd:cd18918    1 LFATERERREKLNEKFSDLRNL----IPNPTKNDRASILSDAIKYINELqRTVEELKS 54

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 576067746  56 MEKRRRDKMNHLIQKLSSMI----PPHIPTAHKLDKLSVLRRAVQYLRSLR 102
Cdd:cd11410    1 MEKKRRARINKSLEQLKTLVlealNKDNTRYSKLEKADILEMTVKYLKQLQ 51

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 576067746  49 IREAHSQMEKRRRDKMNHLIQKLSSMIPphiPTAHKLDKLSVLRRAVQYLRSLRG 103
Cdd:cd19683    2 SRERHNAKERQRRERIKIACDQLRKLVP---GCSRKTDKATVFEFTVAYIKFLRE 53

basic helix-loop-helix (bHLH) domain found in Arabidopsis thaliana protein transparent testa 8 (TT8) and similar proteins; The family includes several bHLH transcription factors from Arabidopsis thaliana, such as TT8, EGL1, and GL3. TT8, also termed AtbHLH42, or EN 32, is involved in the control of flavonoid pigmentation and plays a key role in regulating leucoanthocyanidin reductase (BANYULS) and dihydroflavonol-4-reductase (DFR). EGL1, also termed AtbHLH2, or EN 30, or AtMYC146, or protein enhancer of GLABRA 3, is involved in epidermal cell fate specification and regulates negatively stomata formation but promotes trichome formation. GL3, also termed AtbHLH1, or AtMYC6, or protein shapeshifter, or EN 31, is involved in epidermal cell fate specification. It regulates negatively stomata formation, but, in association with TTG1 and MYB0/GL1, promotes trichome formation, branching and endoreplication.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 576067746  52 AHSQMEKRRRDKMNHLIQKLSSMipphIPTAHKLDKLSVLRRAVQYLRSLR 102
Cdd:cd11451    5 SHAMAERRRREKLNERFITLRSM----VPFVTKMDKVSILGDAIEYLKQLQ 51

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 576067746 122 ELSHLILKAAEGFLFVVGCErGRIFYVSKSVSKTLRYDQASLIGQNLFDFLHPKDVAKVKE---QLSCDGSPR--EKPID 196
Cdd:COG5809  141 EKFRLIFNHSPDGIIVTDLD-GRIIYANPAACKLLGISIEELIGKSILELIHSDDQENVAAfisQLLKDGGIAqgEVRFW 219

                         90       100
                 ....*....|....*....|....*.
gi 576067746 197 TKTSQVYSHPYTGRPRMHSGSRRSFF 222
Cdd:COG5809  220 TKDGRWRLLEASGAPIKKNGEVDGIV 245

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
                 ....*....|....*....|....*....|....*....|....*....|...
gi 576067746  50 REAHSQMEKRRRDKMNHLIQKLSSMIPPhIPTAHKLDKLSVLRRAVQYLRSLR 102
Cdd:cd11400    2 RRLHNVLERQRRNDLKNSFEKLRDLVPE-LADNEKASKVVILKKATEYIKQLQ 53

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 576067746  53 HSQMEKRRRDKMNHLIQKLSSMIPPHIPTAHKLDKLSVLRRAVQYLRSLR 102
Cdd:cd11397    9 HNMIERRRRFNINDRIKELGTLLPKSNDPDMRWNKGTILKASVDYIRKLQ 58

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
                 ....*....|....*....|....*....|....*....|....*....|...
gi 576067746  50 REAHSQMEKRRRDKMNHLIQKLSSMIppHIPTAHKLDKLSVLRRAVQYLRSLR 102
Cdd:cd19682    1 RLRHKKRERERRSELRELFDKLKQLL--GLDSDEKASKLAVLTEAIEEIQQLK 51

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in sterol regulatory element-binding protein (SREBP) family; The SREBP family includes SREBP1 and SREBP2, which are bHLHzip transcriptional activator of genes encoding proteins essential for cholesterol biosynthesis/uptake and fatty acid biosynthesis. SREBP1 and SREBP2 are principally found in the liver and in adipocytes and made up of an N-terminal transcription factor portion (composed of an activation domain, a bHLHzip domain, and a nuclear localization signal), a hydrophobic region containing two membrane spanning regions, and a C-terminal regulatory segment. They recognize a symmetric sterol regulatory element (TCACNCCAC) instead of E-box.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 576067746  50 REAHSQMEKRRRDKMNHLIQKLSSMIpphIPTAHKLDKLSVLRRAVQYLRSLR 102
Cdd:cd11394    7 RSAHNAIEKRYRSSINDRIIELKDLV---VGPDAKMNKSAVLRKAIDYIRYLQ 56

basic helix-loop-helix-orange (bHLH-O) domain found in differentially expressed in chondrocytes protein 1 (DEC1) and similar proteins; DEC1, also termed Class E basic helix-loop-helix protein 40 (bHLHe40), or Class B basic helix-loop-helix protein 2 (bHLHb2), or enhancer-of-split and hairy-related protein 2 (SHARP-2), or stimulated by retinoic acid gene 13 protein (STRA13), is a bHLH-O transcriptional repressor involved in the regulation of the circadian rhythm by negatively regulating the activity of the clock genes and clock-controlled genes.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 576067746  53 HSQMEKRRRDKMNHLIQKLSSMIPPHIP--TAHKLDKLSVLRRAVQYLRSLRGMTE 106
Cdd:cd19749   18 HRLIEKKRRDRINECIAQLKDLLPEHLKltTLGHLEKAVVLELTLKHVKALTSLIE 73

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
                 ....*....|....*....|....*....|....*....|....*..
gi 576067746  57 EKRRRDKMNHLIQKLSSMIPPHIPTahKLDKLSVLRRAVQYLRSLRG 103
Cdd:cd11446    5 EKLRRDKLNERFMELSNVLEPGRPP--KTDKATILGDAIRMLKQLRG 49

basic helix-loop-helix-orange (bHLH-O) domain found in Drosophila melanogaster protein hairy, protein deadpan and similar proteins; Protein hairy is a bHLH transcriptional repressor of genes that require a bHLH-O protein for their transcription. It acts as a pair-rule protein that regulates embryonic segmentation and adult bristle patterning. Protein deadpan is closely related to the product of the segmentation gene hairy. It is a direct target of Notch signaling and regulates neuroblast self-renewal in Drosophila.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 576067746  56 MEKRRRDKMNHLIQKLSSMIPPHI---PTAH-KLDKLSVLRRAVQYLRSLR 102
Cdd:cd18913   10 MEKRRRARINASLNELKSLLLDALkkdGTRHsKLEKADILEMTVKHLRQVQ 60

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in Max-like protein X (Mlx) and similar proteins; 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 576067746  50 REAHSQMEKRRRDKMNHLIQKLSSMIP----PHIPTAHKLDKLSVLRRAVQYLRslrgmtelYLGENSKPsfiQDKELSH 125
Cdd:cd19687    3 REAHTQAEQKRRDAIKKGYDDLQDIVPtcqqQDDIGSQKLSKATILQRSIDYIQ--------FLHQQKKK---QEEELSA 71

                 .
gi 576067746 126 L 126
Cdd:cd19687   72 L 72

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in Saccharomyces cerevisiae transcription factor HMS1 and similar proteins; HMS1, also termed high-copy MEP suppressor protein 1, is a putative bHLHzip transcription factor involved in exit from mitosis and pseudohyphal differentiation.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 576067746  50 REAHSQMEKRRRDKMNHLIQKLSSMIPP-------------------HIPTAHKLDKLSVLRRAVQYLRSLRGMTELYLG 110
Cdd:cd11399    4 KTAHNMIEKRYRSNINDRIAELRDSVPAlreayksargededeedlgGLTPATKLNKATILSKATEYIRHLEKKNKRLSR 83

                 ...
gi 576067746 111 ENS 113
Cdd:cd11399   84 ENA 86

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in Max-associated protein 3 (Mad3) and similar proteins; Mad3, also termed Max dimerization protein 3, or Max dimerizer 3 (MXD3), or Class C basic helix-loop-helix protein 13 (bHLHc13), or Max-interacting transcriptional repressor MAD3, or Myx, is a bHLHZip Max-interacting transcriptional repressor that plays an important role in cellular proliferation. It suppresses c-myc dependent transformation and is expressed during neural and epidermal differentiation.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 576067746  44 SAPSGIREAHSQMEKRRRDKMNHLIQKLSSMIPPHIPTAhKLDKLSVLRRAVQYLRSLR 102
Cdd:cd18932    1 GAPDSGRSVHNELEKHRRAQLRRCLEQLKQQVPLGADCS-RYTTLSLLRRARLHIQKLE 58

basic helix-loop-helix-orange (bHLH-O) domain found in transcription factor HES-5 and similar proteins; HES-5, also termed Class B basic helix-loop-helix protein 38 (bHLHb38), or hairy and enhancer of split 5, is a bHLH-O transcription factor that is involved in cell differentiation and proliferation in a variety of tissues. HES-5 is an essential effector for Notch signaling. It acts as a transducer of Notch signals in brain vascular development. It also acts as a key mediator of Wnt-3a-induced neuronal differentiation and plays a crucial role in normal inner ear hair cell development. HES-5 is one mammalian counterpart of the Hairy and Enhancer of split proteins that play a critical role in many physiological processes including cellular differentiation, cell cycle arrest, apoptosis and self-renewal ability.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*...
gi 576067746  55 QMEKRRRDKMNHLIQKLSSMIPPHIPTAH---KLDKLSVLRRAVQYLR 99
Cdd:cd11461    6 VVEKTRRDRINSSIEQLKTLLEKEFQRHQpnsKLEKADILEMTVSFLK 53

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
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 576067746  141 ERGRIFYVSKSVSKTLRYDQASLIGQNLFDFLHPKDVAKVKEQLSCDGSPREKPI 195
Cdd:TIGR00229  21 LEGNILYVNPAFEEIFGYSAEELIGRNVLELIPEEDREEVRERIERRLEGEPEPV 75

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        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 576067746  53 HSQMEKRRRDKMNHLIQKLSSMIpPHIPTAhKLDKLSVLRRAVQYLRSLR 102
Cdd:cd18908    6 HSLKERLRRERIKSSCDQLRDLL-PYIKGR-KLDMASVLEMTVKYIRYIQ 53