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 442616408 279 REARNRAEKNRRDKLNGSIQELSTMVPHVAESPRRVDKTAVLRFAAHALRLKHAF 333
Cdd:cd11391    1 REKSREAAKKRRDKENAEISELASLLPLPPAVGSKLDKLSVLRLAVAYLRLKKFL 55

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 442616408 279 REARNRAEKNRRDKLNGSIQELSTMVPHVAESPRRVDKTAVLRFAAHALRLKHAF 333
Cdd:cd11391    1 REKSREAAKKRRDKENAEISELASLLPLPPAVGSKLDKLSVLRLAVAYLRLKKFL 55

Helix-loop-helix DNA-binding domain;

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 442616408  279 REARNRAEKNRRDKLNGSIQELSTMVPHVAESpRRVDKTAVLRFA 323
Cdd:pfam00010   2 REAHNERERRRRDRINDAFDELRELLPTLPPD-KKLSKAEILRLA 45

helix loop helix domain;

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|..
gi 442616408   283 NRAEKNRRDKLNGSIQELSTMVPHVAESpRRVDKTAVLRFAA 324
Cdd:smart00353   1 NARERRRRRKINEAFDELRSLLPTLPKN-KKLSKAEILRLAI 41

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 442616408 279 REARNRAEKNRRDKLNGSIQELSTMVPHVAESPRRVDKTAVLRFAAHALRLKHAF 333
Cdd:cd11391    1 REKSREAAKKRRDKENAEISELASLLPLPPAVGSKLDKLSVLRLAVAYLRLKKFL 55

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 442616408 278 GREARNRAEKNRRDKLNGSIQELSTMVPHVAESPRRVDKTAVLRFAAHALR 328
Cdd:cd11437    1 SRSNHSEIEKRRRDKMNAYIQELSALVPACNAMSRKLDKLTVLRMAVQHLK 51

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

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 442616408 273 QLSNSgREARNRAEKNRRDKLNGSIQELSTMVPHVAESPRRVDKTAVLRFAAHALR 328
Cdd:cd11438    3 RIKNA-REAHSQIEKRRRDKMNSFIDELASLVPTCNAMSRKLDKLTVLRMAVQHMK 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
                 ....*....|....*....|....*....|....*....|....*....|....
gi 442616408 352 LDSFFLTLTCHGHILLISASIEQHLGHCQSDLYGQSIMQITHPEDQNMLKQQLI 405
Cdd:cd00130    1 LPDGVIVLDLDGRILYANPAAEQLLGYSPEELIGKSLLDLIHPEDREELRERLE 54

basic helix-loop-helix-Per-ARNT-Sim (bHLH-PAS) domain found in Drosophila melanogaster protein cycle and similar proteins; Protein cycle, also termed brain and muscle ARNT-like 1 (BMAL1), or MOP3, is a putative bHLH-PAS transcription factor involved in the generation of biological rhythms in Drosophila. It activates cycling transcription of Period (PER) and Timeless (TIM) by binding to the E-box (5'-CACGTG-3') present in their promoters.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 442616408 278 GREARNRAEKNRRDKLNGSIQELSTMVPHVAESPRRVDKTAVLRFAAHALR 328
Cdd:cd19726    1 RRQNHSEIEKRRRDKMNTYITELSSMIPMCNAMSRKLDKLTVLRMAVQHMK 51

helix loop helix domain;

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|..
gi 442616408   283 NRAEKNRRDKLNGSIQELSTMVPHVAESpRRVDKTAVLRFAA 324
Cdd:smart00353   1 NARERRRRRKINEAFDELRSLLPTLPKN-KKLSKAEILRLAI 41

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
                 ....*....|....*....|....*....|....*....|....*
gi 442616408 279 REARNRAEKNRRDKLNGSIQELSTMVPHVAESPRRVDKTAVLRFA 323
Cdd:cd18947    6 RENHSEIERRRRNKMTAYITELSDMVPTCSALARKPDKLTILRMA 50

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
                 ....*....|....*....|....*....|....*.
gi 442616408 286 EKNRRDKLNGSIQELSTMVPHVAESpRRVDKTAVLR 321
Cdd:cd00083    1 ERRRRDKINDAFEELKRLLPELPDS-KKLSKASILQ 35

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

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|...
gi 442616408 279 REARNRAEKNRRDKLNGSIQELSTMVPHVAEsPRRVDKTAVLR 321
Cdd:cd19736   11 RASRNKSEKKRRDQFNVLIKELCTMLQGHGH-PLKMDKSTILQ 52

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        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 442616408 282 RNRAEKNRRDKLNGSIQELSTMVPHVAESPRRVDKTAVLRFAAHALRLKHAF 333
Cdd:cd11435    4 KSNPSKRHRDRLNAELDHLASLLPFPPDIISKLDKLSVLRLSVSYLRVKSFF 55

basic helix-loop-helix-Per-ARNT-Sim (bHLH-PAS) domain found in single-minded homolog 2 (SIM2) and similar proteins; SIM2, also termed Class E basic helix-loop-helix protein 15 (bHLHe15), is a bHLH-PAS transcription factor that may be a master gene of central nervous system (CNS) development in cooperation with ARNT. It may have pleiotropic effects in the tissues expressed during development.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 442616408 279 REARNRAEKNRRDKLNGSIQELSTMVPHVAESPRRVDKTAVLRFAAHALRLKHAFGNSL 337
Cdd:cd19739    2 KEKSKNAAKTRREKENGEFYELAKLLPLPSAITSQLDKASIIRLTTSYLKMRAVFPEGL 60

basic helix-loop-helix-Per-ARNT-Sim (bHLH-PAS) domain found in single-minded (SIM) family; The SIM family includes Drosophila melanogaster protein SIM and its homologs from vertebrates, single-minded homolog 1 (SIM1) and single-minded homolog 2 (SIM2). SIM is a nuclear bHLH-PAS transcription factor that functions as a master developmental regulator controlling midline development of the ventral nerve cord in Drosophila. SIM1, also termed Class E basic helix-loop-helix protein 14 (bHLHe14), is a bHLH-PAS transcription factor that may have pleiotropic effects during embryogenesis and in the adult. SIM2, also termed Class E basic helix-loop-helix protein 15 (bHLHe15), is a bHLH-PAS transcription factor that may be a master gene of central nervous system (CNS) development in cooperation with ARNT. It may have pleiotropic effects in the tissues expressed during development.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 442616408 279 REARNRAEKNRRDKLNGSIQELSTMVPHVAESPRRVDKTAVLRFAAHALRLKHAFGNSL 337
Cdd:cd11434    2 KEKSKNAARTRREKENAEFYELAKLLPLPSAITSQLDKASIIRLTTSYLKMRAVFPEGL 60

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 442616408 286 EKNRRDKLNGSIQELSTMVP--HVAESPRRVDKTAVLRFAAHALRLKHA 332
Cdd:cd19685    2 EKRRRQRINDKLNQLKELLPpnLSKQSRSKLSKAEILEMAITELRRLQQ 50

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
                 ....*....|....*....|...
gi 442616408 283 NRAEKNRRDKLNGSIQELSTMVP 305
Cdd:cd11387    3 NAVERRRRDNINEKIQELGSLVP 25

basic helix-loop-helix-orange (bHLH-O) domain found in hairy/enhancer-of-split related with YRPW motif protein 1 (HEY1) and similar proteins; HEY1, also termed cardiovascular helix-loop-helix factor 2 (CHF-2), or Class B basic helix-loop-helix protein 31 (bHLHb31), or HES-related repressor protein 1, or hairy and enhancer of split-related protein 1 (HESR-1), or hairy-related transcription factor 1 (HRT-1), is a bHLH-O transcriptional repressor that acts as an essential downstream effector of the Notch signaling pathway and may play a fundamental role in vascular development. HEY1 also participates several cancer-related pathways. It acts as a positive regulator of the tumor suppressor p53.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 442616408 282 RNRAEKNRRDKLNGSIQELSTMVPHVAES--PRRVDKTAVLRFAAHALRLKHAFG 334
Cdd:cd19748   13 RGIIEKRRRDRINNSLSELRRLVPSAFEKqgSAKLEKAEILQMTVDHLKMLHAAG 67