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

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 966986313  24 QGRIKNAREAHSQIEKRRRDKMNSFIDELASLVPTCNAMSRKLDKLTVLRMAVQHMKTLRGATN 87
Cdd:cd11438    1 QGRIKNAREAHSQIEKRRRDKMNSFIDELASLVPTCNAMSRKLDKLTVLRMAVQHMKTLRGATN 64

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 966986313   106 HLILRAADGFLFVVGCDrGKILFVSESVFKILNYSQNDLIGQSLFDYLHPKDIAKVKEQL 165
Cdd:smart00091   4 RAILESLPDGIFVLDLD-GRILYANPAAEELLGYSPEELIGKSLLELIHPEDRERVQEAL 62

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

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 966986313  24 QGRIKNAREAHSQIEKRRRDKMNSFIDELASLVPTCNAMSRKLDKLTVLRMAVQHMKTLRGATN 87
Cdd:cd11438    1 QGRIKNAREAHSQIEKRRRDKMNSFIDELASLVPTCNAMSRKLDKLTVLRMAVQHMKTLRGATN 64

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 966986313 298 VSRHAIDGKFVFVDQRATAILAYLPQELLGTSCYEYFHQDDIGHLAECHRQVLQTREKITTnCYKFKIKDGSFITLRSRW 377
Cdd:cd00130    5 VIVLDLDGRILYANPAAEQLLGYSPEELIGKSLLDLIHPEDREELRERLENLLSGGEPVTL-EVRLRRKDGSVIWVLVSL 83

                         90
                 ....*....|....*.
gi 966986313 378 FSFMNPWTKEVEYIVS 393
Cdd:cd00130   84 TPIRDEGGEVIGLLGV 99

helix loop helix domain;

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 966986313    37 IEKRRRDKMNSFIDELASLVPTCNaMSRKLDKLTVLRMAVQHMKTLR 83
Cdd:smart00353   3 RERRRRRKINEAFDELRSLLPTLP-KNKKLSKAEILRLAIEYIKSLQ 48

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 966986313  103 ELKHLILRAADGFLFVVGcDRGKILFVSESVFKILNYSQNDLIGQSLFDYLHPKDIAKVKEQLSS--SDTAPR---ERLI 177
Cdd:pfam00989   1 EDLRAILESLPDGIFVVD-EDGRILYVNAAAEELLGLSREEVIGKSLLDLIPEEDDAEVAELLRQalLQGEESrgfEVSF 79

                          90       100       110
                  ....*....|....*....|....*....|...
gi 966986313  178 DAKTGLPVKTDITPGPSRLCSGARRSFFCRMKC 210
Cdd:pfam00989  80 RVPDGRPRHVEVRASPVRDAGGEILGFLGVLRD 112

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

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 966986313   298 VSRHAIDGKFVFVDQRATAILAYLPQELLGTSCYEYFHQDDIGHLAECHRQVLQ 351
Cdd:smart00091  14 IFVLDLDGRILYANPAAEELLGYSPEELIGKSLLELIHPEDRERVQEALQRLLS 67

PAS domain [Signal transduction mechanisms];

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 966986313 304 DGKFVFVDQRATAILAYLPQELLGTSCYEYFHQDDIGHLAECHRQVLQTREKITTNCYKFKIKDGSFITLRSR 376
Cdd:COG2202  156 DGRILYVNPAAEELLGYSPEELLGKSLLDLLHPEDRERLLELLRRLLEGGRESYELELRLKDGDGRWVWVEAS 228

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 966986313  107 LILRAADGFLFVVGcDRGKILFVSESVFKILNYSQNDLIGQSLFDYLHPKDIAKVKEQLS 166
Cdd:TIGR00229   7 AIFESSPDAIIVID-LEGNILYVNPAFEEIFGYSAEELIGRNVLELIPEEDREEVRERIE 65

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

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 966986313  24 QGRIKNAREAHSQIEKRRRDKMNSFIDELASLVPTCNAMSRKLDKLTVLRMAVQHMKTLRGATN 87
Cdd:cd11438    1 QGRIKNAREAHSQIEKRRRDKMNSFIDELASLVPTCNAMSRKLDKLTVLRMAVQHMKTLRGATN 64

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 966986313  30 AREAHSQIEKRRRDKMNSFIDELASLVPTCNAMSRKLDKLTVLRMAVQHMKTLRGATN 87
Cdd:cd11437    1 SRSNHSEIEKRRRDKMNAYIQELSALVPACNAMSRKLDKLTVLRMAVQHLKSLRGTGS 58

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        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 966986313  28 KNAREAHSQIEKRRRDKMNSFIDELASLVPTCNAMSRKLDKLTVLRMAVQHMKTLRGATNP 88
Cdd:cd18947    3 RFARENHSEIERRRRNKMTAYITELSDMVPTCSALARKPDKLTILRMAVSHMKSLRGTGNT 63

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 966986313  31 REAHSQIEKRRRDKMNSFIDELASLVPTCNAMSRKLDKLTVLRMAVQHMKTLRGA 85
Cdd:cd11391    1 REKSREAAKKRRDKENAEISELASLLPLPPAVGSKLDKLSVLRLAVAYLRLKKFL 55

Helix-loop-helix DNA-binding domain;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 966986313   31 REAHSQIEKRRRDKMNSFIDELASLVPTCNAmSRKLDKLTVLRMAVQHMKTLR 83
Cdd:pfam00010   2 REAHNERERRRRDRINDAFDELRELLPTLPP-DKKLSKAEILRLAIEYIKHLQ 53

helix loop helix domain;

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 966986313    37 IEKRRRDKMNSFIDELASLVPTCNaMSRKLDKLTVLRMAVQHMKTLR 83
Cdd:smart00353   3 RERRRRRKINEAFDELRSLLPTLP-KNKKLSKAEILRLAIEYIKSLQ 48

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 966986313   106 HLILRAADGFLFVVGCDrGKILFVSESVFKILNYSQNDLIGQSLFDYLHPKDIAKVKEQL 165
Cdd:smart00091   4 RAILESLPDGIFVLDLD-GRILYANPAAEELLGYSPEELIGKSLLELIHPEDRERVQEAL 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. 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 966986313 112 ADGFLFVVgCDRGKILFVSESVFKILNYSQNDLIGQSLFDYLHPKDIAKVKEQLSSSDTA----PRERLIDAKTG--LPV 185
Cdd:cd00130    1 LPDGVIVL-DLDGRILYANPAAEQLLGYSPEELIGKSLLDLIHPEDREELRERLENLLSGgepvTLEVRLRRKDGsvIWV 79

                 ....*.
gi 966986313 186 KTDITP 191
Cdd:cd00130   80 LVSLTP 85

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 966986313  307 FVFVDQRATAILAYLPQELLGT--SCYEYFHQDDIGHLAECHRQVLQTREKITTNcYKFKIKDGSFITLRSRWFSFMNPW 384
Cdd:pfam08447   1 IIYWSPRFEEILGYTPEELLGKgeSWLDLVHPDDRERVREALWEALKGGEPYSGE-YRIRRKDGEYRWVEARARPIRDEN 79

                  ....*..
gi 966986313  385 TKEVEYI 391
Cdd:pfam08447  80 GKPVRVI 86

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 966986313  39 KRRRDKMNSFIDELASLVPTCNAMSRKLDKLTVLRMAVQHMKT 81
Cdd:cd19696    9 KRHRDRLNSELDELASLLPFPEDVISKLDKLSVLRLSVSYLRT 51

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

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 966986313  26 RIKNAREAHSQIEKRRRDKMNSFIDELASLVPTCNAMSRKL--DKLTVLRMAVQHMKTLRgATNPYTEANYK 95
Cdd:cd18923    4 RDERRRAQHNEVERRRRDKINNWIVQLSKIIPDCNTDNSKTgaSKGGILSKACDYIRELR-QTNQRMQETYK 74

basic helix-loop-helix-orange (bHLH-O) domain found in hairy/enhancer-of-split related with YRPW motif-like protein (HEYL) and similar proteins; HEYL, also termed Class B basic helix-loop-helix protein 33 (bHLHb33), or hairy-related transcription factor 3 (HRT-3), is a bHLH-O transcriptional repressor that is strongly expressed in the presomitic mesoderm, the somites, the peripheral nervous system and smooth muscle of all arteries and is a downstream effector of the Notch and transforming growth factor-beta pathways. It promotes neuronal differentiation by activating proneural genes and inhibiting other hairy and enhancer of split (HES) and hairy/enhancer-of-split related with YRPW motif protein (HEY) proteins. HEYL also functions as a tumor suppressor involved in the progression of human cancers.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 966986313  30 AREAHSQI-EKRRRDKMNSFIDELASLVPTC--NAMSRKLDKLTVLRMAVQHMKTL 82
Cdd:cd11447    8 ARKKRRGIiEKRRRDRINSSLSELRRLVPTAfeKQGSSKLEKAEILQMTVDHLKML 63

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 966986313  34 HSQIEKRRRDKMNSFIDELASLVPTCNamsrKLDKLTVLRMAVQHMKTLR 83
Cdd:cd11393    1 HSIAERKRREKINERIRALRSLVPNGG----KTDKASILDEAIEYIKFLQ 46

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 966986313  33 AHSQIEKRRRDKMNSFIDELASLVPTCNA--MSRKLDKLTVLRMAVQHMKTLRGA 85
Cdd:cd11408    1 SHKVIEKRRRDRINRCLNELGKTVPMALAkqTSGKLEKAEILEMTVQYLRALHSA 55

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        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 966986313  37 IEKRRRDKMNSFIDELASLVPTCNAM--SRKLDKLTVLRMAVQHMKTLRGA 85
Cdd:cd19685    1 SEKRRRQRINDKLNQLKELLPPNLSKqsRSKLSKAEILEMAITELRRLQQE 51

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 966986313  34 HSQIEKRRRDKMNSFIDELASLVPTCN--AMSRKLDKLTVLRMAVQHMKTLR 83
Cdd:cd11396    2 HNEVERRRRDKINNWIVKLAKIVPDCEkdNSKQGQSKGGILSKACDYIQELR 53

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 966986313  35 SQIEKRRRDKMNSFIDELASLVPTCNAMSRKLDKLTVLRMAVQHMK 80
Cdd:cd11435    5 SNPSKRHRDRLNAELDHLASLLPFPPDIISKLDKLSVLRLSVSYLR 50

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 966986313  31 REAHSQIEKRRRDKMNSFIDELASLVPTCnamSRKLDKLTVLRMAVQHMKTLRGA 85
Cdd:cd19683    3 RERHNAKERQRRERIKIACDQLRKLVPGC---SRKTDKATVFEFTVAYIKFLREK 54

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

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 966986313  28 KNAREAHSQIEKRRRDKMNSFIDELASLVPTCN--------------AMSRKLDKLTVLRMAVQHMKTL 82
Cdd:cd11395    1 PRKRLPHNAIEKRYRSNLNTKIERLRDAIPSLRspegksddgglgglAPTTKLSKATILTKAIEYIRHL 69

basic helix-loop-helix (bHLH) domain found in Arabidopsis thaliana protein AIG1 and similar proteins; AIG1, also termed AtbHLH32, or EN 54, or protein target of MOOPTEROS 5, is a transcription factor required for MONOPTEROS-dependent root initiation in embryo.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 966986313  34 HSQIEKRRRDKMNSFIDELASLVPTcnamSRKLDKLTVLRMAVQHMKTLRG----ATNPYTEANYKPTF 98
Cdd:cd11455   11 HSEAERRRRERINSHLATLRTLLPN----LSKTDKASLLAEVVQHVKELKRqaaeITTPPDVPTEDEED 75

basic helix-loop-helix-orange (bHLH-O) domain found in hairy/enhancer-of-split related with YRPW motif protein 2 (HEY2) and similar proteins; HEY2, also termed cardiovascular helix-loop-helix factor 1 (CHF-1), or Class B basic helix-loop-helix protein 32 (bHLHb32), or HES-related repressor protein 2, or hairy and enhancer of split-related protein 2 (HESR-2), or hairy-related transcription factor 2 (HRT-2), or protein gridlock homolog, is a bHLH-O transcriptional repressor expressed preferentially in the developing and adult cardiovascular system. As a downstream effector of Notch signaling, HEY2 may be required for cardiovascular development. It also plays an important role in neurologic development, as well as in the progression of human cancers.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 966986313  37 IEKRRRDKMNSFIDELASLVPTC--NAMSRKLDKLTVLRMAVQHMKTLRG 84
Cdd:cd18920   17 IEKRRRDRINNSLSELRRLVPTAfeKQGSAKLEKAEILQMTVDHLKMLQA 66

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in USF/MITF family; The USF (upstream stimulatory factor)/MITF (microphthalmia-associated transcription factor) family includes two bHLHzip transcription factor subfamilies. USFs are ubiquitously expressed and key regulators of a wide number of gene regulation networks, including the stress and immune responses, cell cycle and proliferation, lipid and glucid metabolism. USFs recruit chromatin remodeling enzymes and interact with co-activators and the members of the transcription pre-initiation complex. USFs interact with high affinity to E-box regulatory elements. The MITF (also known as microphthalmia-TFE, or MiT) subfamily comprises four genes in mammals (MITF, TFE3, TFEB, and TFEC); each gene has different functions. MITF is involved in neural crest melanocytes development as well as the pigmented retinal epithelium. TFEB is required for vascularization of the mouse placenta. TFE3 is involved in B cell function. TFEC regulates gene expression in macrophages. The MITF subfamily proteins can form homodimers or heterodimers with each other but not with other bHLH or bHLHzip proteins.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 966986313  34 HSQIEKRRRDKMNSFIDELASLVPTCN--AMSRKLDKLTVLRMAVQHMKTLR 83
Cdd:cd11387    2 HNAVERRRRDNINEKIQELGSLVPPSRleTKDLKPNKGSILSKAVEYIRELQ 53

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in upstream stimulatory factor 1 (USF1) and similar proteins; USF1, also termed Class B basic helix-loop-helix protein 11 (bHLHb11), or major late transcription factor 1, is a bHLHzip transcription factor that binds to a symmetrical DNA sequence (E-boxes) (5'-CACGTG-3') that is found in a variety of viral and cellular promoters. It is ubiquitously expressed and involved in the transcription activation of various functional genes implicated in lipid and glucose metabolism, stress response, immune response, cell cycle control and tumour suppression. USF-1 recruits chromatin remodeling enzymes and interact with co-activators and the members of the transcription pre-initiation complex. Genetic polymorphisms of USF1 are associated with some metabolic and cardiovascular diseases, like diabetes, atherosclerosis, coronary artery calcifications and familial combined hyperlipidaemia (FCHL).

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 966986313  26 RIKNAREAHSQIEKRRRDKMNSFIDELASLVPTCNAMSRKL--DKLTVLRMAVQHMKTLR 83
Cdd:cd18924    1 RDEKRRAQHNEVERRRRDKINNWIVQLSKIIPDCSMESTKSgqSKGGILSKACDYIQELR 60

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
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 966986313  28 KNAREAHSQIEKRRRDKMNSFIDELASLVPTCNAMSRKLDKLTVLRMAVQHMKTLR 83
Cdd:cd18927    9 RQKKDNHNLIERRRRFNINDRIKELGTLIPKTNDLDVRWNKGTILKASVDYIKRMQ 64

basic helix-loop-helix (bHLH) domain found in 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 966986313  31 REAHSQIEKRRRDKMNSFIDELASLVPTCNAMSrklDKLTVLRMAVQHMKTLRG 84
Cdd:cd18909    3 RERHNRMERDRRRRIRICCDELNLLVPFCNAET---DKATTLQWTTAFLKYIQE 53

PAS domain [Signal transduction mechanisms];

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 966986313 304 DGKFVFVDQRATAILAYLPQELLGTSCYEYFHQDDIGHLAECHRQVLQTREKITTNCYKFKIKDGSFITLRSR 376
Cdd:COG2202  156 DGRILYVNPAAEELLGYSPEELLGKSLLDLLHPEDRERLLELLRRLLEGGRESYELELRLKDGDGRWVWVEAS 228

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 966986313  34 HSQIEKRRRDKMNSFIDELASLVPtcNAMSRKLDKLTVLRMAVQHMKTLR 83
Cdd:cd18908    6 HSLKERLRRERIKSSCDQLRDLLP--YIKGRKLDMASVLEMTVKYIRYIQ 53

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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966986313  28 KNAREAHSQIEKRRRDKMNSFIDELASLVPTCNAMSRKLDKLTVLRMAVQHMKTLRGATNPYTEANYKPTFLSDDElKHL 107
Cdd:cd18926   11 RQKKDNHNLIERRRRFNINDRIKELGTLIPKSNDPDMRWNKGTILKASVDYIRKLQREQQRAKELENRQKKLEHAN-RHL 89

                 ...
gi 966986313 108 ILR 110
Cdd:cd18926   90 LLR 92

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in sterol regulatory element-binding protein 1 (SREBP1) and similar proteins; SREBP1, also termed Class D basic helix-loop-helix protein 1 (bHLHd1), or sterol regulatory element-binding transcription factor 1 (SREBF1), is a member of a family of bHLHzip transcription factors that recognize sterol regulatory element 1 (SRE-1). It acts as a transcriptional activator required for lipid homeostasis. It may control transcription of the low-density lipoprotein receptor gene as well as the fatty acid. SREBP1 has dual sequence specificity binding to both an E-box motif (5'-ATCACGTGA-3') and to SRE-1 (5'-ATCACCCCAC-3').

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 966986313  31 REAHSQIEKRRRDKMNSFIDELASLVPTCNAmsrKLDKLTVLRMAVQHMKTLRGATNPYTEAN 93
Cdd:cd18921    7 RTAHNAIEKRYRSSINDKIIELKDLVVGTEA---KLNKSAVLRKAIDYIRFLQQSNQKLKQEN 66

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in transcription factor E3 (TFE3) and similar proteins; TFE3, also termed Class E basic helix-loop-helix protein 33 (bHLHe33), is a bHLHzip transcription factor that is involved in B cell function. It specifically recognizes and binds E-box sequences (5'-CANNTG-3'). Its efficient DNA-binding requires dimerization with itself or with another MiT/TFE family member such as TFEB or MITF.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 966986313  28 KNAREAHSQIEKRRRDKMNSFIDELASLVPTCNAMSRKLDKLTVLRMAVQHMKTLR 83
Cdd:cd18928    9 RQKKDNHNLIERRRRFNINDRIKELGTLIPKSTDPEMRWNKGTILKASVDYIRKLQ 64

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 966986313  31 REAHSQIEKRRRDKMNSFIDELASLVPTCNAMS-------------------RKLDKLTVLRMAVQHMKTLRGATNPYTE 91
Cdd:cd11399    4 KTAHNMIEKRYRSNINDRIAELRDSVPALREAYksargededeedlggltpaTKLNKATILSKATEYIRHLEKKNKRLSR 83

                 ..
gi 966986313  92 AN 93
Cdd:cd11399   84 EN 85

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 966986313  107 LILRAADGFLFVVGcDRGKILFVSESVFKILNYSQNDLIGQSLFDYLHPKDIAKVKEQLS 166
Cdd:TIGR00229   7 AIFESSPDAIIVID-LEGNILYVNPAFEEIFGYSAEELIGRNVLELIPEEDREEVRERIE 65

PAS domain [Signal transduction mechanisms];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966986313 294 SMEYVSRHAIDGKFVFVDQRATAILAYLPQELLGTSCYEYFHQDDIGHLAECHRQVLQtREKITTNCYKFKIKDGSFITL 373
Cdd:COG2202   20 SPDAIIITDLDGRILYVNPAFERLTGYSAEELLGKTLRDLLPPEDDDEFLELLRAALA-GGGVWRGELRNRRKDGSLFWV 98

                         90       100
                 ....*....|....*....|.
gi 966986313 374 RSRWFSFMNPwTKEVEYIVST 394
Cdd:COG2202   99 ELSISPVRDE-DGEITGFVGI 118

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 966986313  34 HSQIEKRRRDKMNSFIDELASLVPTCNAMSR--KLDKLTVLRMAVQHMKTLRGAT 86
Cdd:cd19750   19 HRLIEKKRRDRINECIAQLKDLLPEHLKLTTlgHLEKAVVLELTLKHLKALTALT 73