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 1417861804  49 IREAHSQTEKRRRDKMNHLIWKLSSMIPPHIPTAHKLDKLSVLRRAVQYLRSQRGMTEFY 108
Cdd:cd11469     1 FREAHSQTEKRRRDKMNNLIEELSAMIPQCNPMARKLDKLTVLRMAVQHLKSLKGSTSSF 60

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 1417861804  49 IREAHSQTEKRRRDKMNHLIWKLSSMIPPHIPTAHKLDKLSVLRRAVQYLRSQRGMTEFY 108
Cdd:cd11469     1 FREAHSQTEKRRRDKMNNLIEELSAMIPQCNPMARKLDKLTVLRMAVQHLKSLKGSTSSF 60

helix loop helix domain;

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1417861804   57 EKRRRDKMNHLIWKLSSMIPPHiPTAHKLDKLSVLRRAVQYLRSQRGMTE 106
Cdd:smart00353   4 ERRRRRKINEAFDELRSLLPTL-PKNKKLSKAEILRLAIEYIKSLQEELQ 52

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 1417861804  280 EFITRFAMNGKFVYVDQRATAILGYLPQELLGTSCYEYFHQDDHSNLSDKHKAVLQ 335
Cdd:smart00091  12 DGIFVLDLDGRILYANPAAEELLGYSPEELIGKSLLELIHPEDRERVQEALQRLLS 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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1417861804 288 NGKFVYVDQRATAILGYLPQELLGTSCYEYFHQDDHSNLSDKHKAVLQSKEKILTDSYKFRVKDGS 353
Cdd:TIGR00229  22 EGNILYVNPAFEEIFGYSAEELIGRNVLELIPEEDREEVRERIERRLEGEPEPVSEERRVRRKDGS 87

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 1417861804  49 IREAHSQTEKRRRDKMNHLIWKLSSMIPPHIPTAHKLDKLSVLRRAVQYLRSQRGMTEFY 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 1417861804  50 REAHSQTEKRRRDKMNHLIWKLSSMIPPHIPTAHKLDKLSVLRRAVQYLRSQRGMT 105
Cdd:cd11437     2 RSNHSEIEKRRRDKMNAYIQELSALVPACNAMSRKLDKLTVLRMAVQHLKSLRGTG 57

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 1417861804 279 AEFITRFAMNGKFVYVDQRATAILGYLPQELLGTSCYEYFHQDDHSNLSDKHKAVLQsKEKILTDSYKFRVKDGSFVTLK 358
Cdd:cd00130     2 PDGVIVLDLDGRILYANPAAEQLLGYSPEELIGKSLLDLIHPEDREELRERLENLLS-GGEPVTLEVRLRRKDGSVIWVL 80

                          90       100
                  ....*....|....*....|
gi 1417861804 359 SKWFSFTNPWTKKLEYIVSV 378
Cdd:cd00130    81 VSLTPIRDEGGEVIGLLGVV 100

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 1417861804  50 REAHSQTEKRRRDKMNHLIWKLSSMIPPHIPTAHKLDKLSVLRRAVQYLRSQRG 103
Cdd:cd18947     6 RENHSEIERRRRNKMTAYITELSDMVPTCSALARKPDKLTILRMAVSHMKSLRG 59

Helix-loop-helix DNA-binding domain;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1417861804  50 REAHSQTEKRRRDKMNHLIWKLSSMIPPHIPTAhKLDKLSVLRRAVQYLRS 100
Cdd:pfam00010   2 REAHNERERRRRDRINDAFDELRELLPTLPPDK-KLSKAEILRLAIEYIKH 51

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 1417861804  57 EKRRRDKMNHLIWKLSSMIPPHiPTAHKLDKLSVLRRAVQYLRSQR 102
Cdd:cd00083     1 ERRRRDKINDAFEELKRLLPEL-PDSKKLSKASILQKAVEYIRELQ 45

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 1417861804 291 FVYVDQRATAILGYLPQELLGT--SCYEYFHQDDHSNLSDKHKAVLQSKEKILTDsYKFRVKDGSFVTLKSKWFSFTNpW 368
Cdd:pfam08447   1 IIYWSPRFEEILGYTPEELLGKgeSWLDLVHPDDRERVREALWEALKGGEPYSGE-YRIRRKDGEYRWVEARARPIRD-E 78

                          90
                  ....*....|.
gi 1417861804 369 TKKLEYIVSVN 379
Cdd:pfam08447  79 NGKPVRVIGVA 89

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1417861804  50 REAHSQTEKRRRDKMNHLIWKLSSMIPphiPTAHKLDKLSVLRRAVQYLRSQRGMT----EFYLGENAKPSFI 118
Cdd:cd19735    11 RKSRNLSEKKRRDQFNVLINELCSMVS---TSNRKMDKSTVLKSTIAFLKNHNEVTmqshQQEIQEDWKPSFL 80

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 1417861804  53 HSQTEKRRRDKMNHLIWKLSSMIPPHI--PTAHKLDKLSVLRRAVQYLRSQRGMT 105
Cdd:cd11389     1 HKVIEKRRRDRINESLAELRRLVPEARksKGSGKLEKAEILEMTLQHLKALQSST 55

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 1417861804  51 EAHSQTEKRRRDKMNHLIWKLSSMipphIPTAHKLDKLSVLRRAVQYLRS 100
Cdd:cd11445     4 EVHNLSERRRRDRINEKMKALQEL----IPNCNKTDKASMLDEAIEYLKS 49

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
                  ....*....|....*....|....*....|....*....|....*...
gi 1417861804  53 HSQTEKRRRDKMNHLIWKLSSMIPPhiptAHKLDKLSVLRRAVQYLRS 100
Cdd:cd11393     1 HSIAERKRREKINERIRALRSLVPN----GGKTDKASILDEAIEYIKF 44

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 1417861804  53 HSQTEKRRRDKMNHLIWKLSSMIPP--HIPTAHKLDKLSVLRRAVQYLRSQRGMTE 106
Cdd:cd11396     2 HNEVERRRRDKINNWIVKLAKIVPDceKDNSKQGQSKGGILSKACDYIQELRSQNE 57

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 1417861804  58 KRRRDKMNHLIWKLSSMIPPHIPTAHKLDKLSVLRRAVQYLRSQ 101
Cdd:cd19696     9 KRHRDRLNSELDELASLLPFPEDVISKLDKLSVLRLSVSYLRTK 52

PAS domain [Signal transduction mechanisms];

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1417861804 280 EFITRFAMNGKFVYVDQRATAILGYLPQELLGTSCYEYFHQDDHSNLSDKHKAVLQSKEKILTDSYKFRVKDGSFVTL 357
Cdd:COG2202   148 DGIFVLDLDGRILYVNPAAEELLGYSPEELLGKSLLDLLHPEDRERLLELLRRLLEGGRESYELELRLKDGDGRWVWV 225

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
                  ....*....|....*....|....*....|....*....|....*....
gi 1417861804  50 REAHSQTEKRRRDKMNHLIWKLSSMIPPHIPTahKLDKLSVLRRAVQYL 98
Cdd:cd18910     6 RESHNEVERRRKDKINAGINKIGELLPDRDAK--KQSKNMILEQAYKYI 52

PAS domain [Signal transduction mechanisms];

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1417861804 279 AEFITRFAMNGKFVYVDQRATAILGYLPQELLGTSCYEYFHQDDHSNLSDKHKAVLQSkEKILTDSYKFRVKDGSFV 355
Cdd:COG2202    21 PDAIIITDLDGRILYVNPAFERLTGYSAEELLGKTLRDLLPPEDDDEFLELLRAALAG-GGVWRGELRNRRKDGSLF 96

basic helix-loop-helix-Per-ARNT-Sim (bHLH-PAS) domain found in neuronal PAS domain-containing protein 2 (NPAS2) and similar proteins; 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 (PASD4), is a bHLH-PAS transcriptional activator which forms a core component of the circadian clock.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1417861804  50 REAHSQTEKRRRDKMNHLIWKLSSMIPPHiptAHKLDKLSVLRRAVQYLRSQ 101
Cdd:cd19737    11 RASRNKSEKKRRDQFNVLIKELSSMLPGN---TRKMDKTTVLEKVIGFLQKH 59

basic helix-loop-helix-Per-ARNT-Sim (bHLH-PAS) domain found in Drosophila melanogaster protein spineless and similar proteins; 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 1417861804  54 SQTEKRRRDKMNHLIWKLSSMIPPHIPTAHKLDKLSVLRRAVQYLRSQ 101
Cdd:cd19730     8 SNPSKRHRERLNAELDHLASLLPFEQSVISKLDKLSILRLSVSYLRTK 55

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
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1417861804  50 REAHSQTEKRRRDKMNHLIWKLSSMIPPHIPTAHKL--DKLSVLRRAVQYLRSQR 102
Cdd:cd18924     6 RAQHNEVERRRRDKINNWIVQLSKIIPDCSMESTKSgqSKGGILSKACDYIQELR 60

basic helix-loop-helix-orange (bHLH-O) domain found in differentially expressed in chondrocytes protein (DEC) family; The DEC family includes two bHLH-O transcriptional repressors, DEC1 and DEC2, which 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. They mediate the circadian rhythm by negatively regulating the activity of the clock genes and clock-controlled genes. They are induced by CLOCK:BMAL1 heterodimer via the CACGTG E-box in the promoter.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1417861804  53 HSQTEKRRRDKMNHLIWKLSSMIPPHIP--TAHKLDKLSVLRRAVQYLRSQRGMTE 106
Cdd:cd11409     8 HRLIEKKRRDRINECIAQLKDLLPEHLKltTLGHLEKAVVLELTLKHLKALTALTE 63

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 1417861804 288 NGKFVYVDQRATAILGYLPQELLGTSCYEYFHQDDHSNLSDKHKAVLQSKEKILTDSYKFRVKDGS 353
Cdd:TIGR00229  22 EGNILYVNPAFEEIFGYSAEELIGRNVLELIPEEDREEVRERIERRLEGEPEPVSEERRVRRKDGS 87

basic helix-loop-helix-orange (bHLH-O) domain found in differentially expressed in chondrocytes protein 2 (DEC2) and similar proteins; DEC2, also termed Class E basic helix-loop-helix protein 41 (bHLHe41), or Class B basic helix-loop-helix protein 3 (bHLHb3), or enhancer-of-split and hairy-related protein 1 (SHARP-1), is a bHLH-O transcriptional repressor involved in the regulation of the circadian rhythm by negatively regulating the activity of the clock genes and clock-controlled genes.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1417861804  53 HSQTEKRRRDKMNHLIWKLSSMIPPHIP--TAHKLDKLSVLRRAVQYLRSQRGMTE 106
Cdd:cd19750    19 HRLIEKKRRDRINECIAQLKDLLPEHLKltTLGHLEKAVVLELTLKHLKALTALTE 74

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 1417861804  56 TEKRRRDKMNHLIWKLSSMIPP--HIPTAHKLDKLSVLRRAVQYLR 99
Cdd:cd19685     1 SEKRRRQRINDKLNQLKELLPPnlSKQSRSKLSKAEILEMAITELR 46

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 1417861804  47 NGIREA--HSQTEKRRRDKMNHLIWKLSSMipphIPTAHKLDKLSVLRRAVQYLRS 100
Cdd:cd11449     1 NGREEPlnHVEAERQRREKLNQRFYALRAV----VPNVSKMDKASLLGDAISYINE 52

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

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1417861804  55 QTEKRRRDKMNHLIWKLSSMIPPHIPTAH---KLDKLSVLRRAVQYLRSQRGMT 105
Cdd:cd11461     6 VVEKTRRDRINSSIEQLKTLLEKEFQRHQpnsKLEKADILEMTVSFLKQSAKLS 59

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
                  ....*....|....*....|....*....|....*....|....*..
gi 1417861804  53 HSQTEKRRRDKMNHLIWKLSSMIPPHIPTAHKLDKLSVLRRAVQYLR 99
Cdd:cd11397     9 HNMIERRRRFNINDRIKELGTLLPKSNDPDMRWNKGTILKASVDYIR 55

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

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 1417861804  52 AHSQTEKRRRDKMNHLIWKLSSMIPPHI--PTAHKLDKLSVLRRAVQYLR 99
Cdd:cd11440     5 SHRIIEKRRRDRMNNCLADLSRLIPPTYlkKGRGRIEKTEIIEMAIKHIK 54

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 1417861804  53 HSQTEKRRRDKMNHLIWKLSSMIPPHIP--TAHKLDKLSVLRRAVQYLRSQRGMTE 106
Cdd:cd19749    18 HRLIEKKRRDRINECIAQLKDLLPEHLKltTLGHLEKAVVLELTLKHVKALTSLIE 73

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 1417861804  50 REAHSQTEKRRRDKMNHLIWKLSSMIpphIPTAHKLDKLSVLRRAVQYLR 99
Cdd:cd11394     7 RSAHNAIEKRYRSSINDRIIELKDLV---VGPDAKMNKSAVLRKAIDYIR 53

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

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 1417861804  57 EKRRRDKMNHLIWKLSSMIPPHIPT--AHKLDKLSVLRRAVQYLR 99
Cdd:cd11407     9 EKRRRDRINNSLAELRRLVPTAFEKqgSAKLEKAEILQMTVDHLK 53

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 1417861804  54 SQTEKRRRDKMNHLIWKLSSMIPPHipTAH------KLDKLSVLRRAVQYLRSQRGM 104
Cdd:cd11462     6 PLVEKRRRDRINRSLEELRVLLLQN--TQDeklknpKVEKAEILELTVQFLRNSSLS 60

basic helix-loop-helix (bHLH) domain found in Arabidopsis thaliana Fe-deficiency induced transcription factor 1 (FIT) and similar proteins; The family includes bHLH transcription factors from Arabidopsis thaliana, such as FIT and DYT1. FIT, also termed FER-like iron deficiency-induced transcription factor, or FER-like regulator of iron uptake, or AtbHLH29, or EN 43, is a bHLH transcription factor that is required for the iron deficiency response in plant. It regulates FRO2 at the level of mRNA accumulation and IRT1 at the level of protein accumulation. DYT1, also termed AtbHLH22, or protein dysfunctional tapetum 1, or EN 49, is a bHLH transcription factor involved in the control of tapetum development. It is required for male fertility and pollen differentiation, especially during callose deposition.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|...
gi 1417861804  56 TEKRRRDKMNHLIWKLSSmippHIPTAHKLDKLSVLRRAVQYL 98
Cdd:cd11450    10 SERNRRQKLNQRLFALRS----VVPNITKMDKASIIKDAISYI 48