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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 22027482   315 ILACESRVSDHMDLGPSELVGR--SCYQFVHGQDATRIRQSHVDLLDKGQVMTGYYRWLQRAGGFVWLQSVATV 386
Cdd:pfam08447   1 IIYWSPRFEEILGYTPEELLGKgeSWLDLVHPDDRERVREALWEALKGGEPYSGEYRIRRKDGEYRWVEARARP 74

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 22027482   315 ILACESRVSDHMDLGPSELVGR--SCYQFVHGQDATRIRQSHVDLLDKGQVMTGYYRWLQRAGGFVWLQSVATV 386
Cdd:pfam08447   1 IIYWSPRFEEILGYTPEELLGKgeSWLDLVHPDDRERVREALWEALKGGEPYSGEYRIRRKDGEYRWVEARARP 74

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 22027482 303 HMIVFRLSLGLTILACESRVSDHMDLGPSELVGRSCYQFVHGQDATRIRQSHVDLLDKGQVMTGYYRWLQRAGGFVWLQS 382
Cdd:cd00130   2 PDGVIVLDLDGRILYANPAAEQLLGYSPEELIGKSLLDLIHPEDREELRERLENLLSGGEPVTLEVRLRRKDGSVIWVLV 81

                ....
gi 22027482 383 VATV 386
Cdd:cd00130  82 SLTP 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. 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
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 22027482   141 HILQSLDGFVFALNQEGKFLYISETVSIYLGLSQVEMTGSSVFDYIHPGDHSEVLEQL 198
Cdd:pfam00989   5 AILESLPDGIFVVDEDGRILYVNAAAEELLGLSREEVIGKSLLDLIPEEDDAEVAELL 62

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

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 22027482    295 LAELPLHGHMIVFRLSLGLTILACESRVSDHMDLGPSELVGRSCYQFVHGQDATRIRQSHVDLLD 359
Cdd:smart00091   3 LRAILESLPDGIFVLDLDGRILYANPAAEELLGYSPEELIGKSLLELIHPEDRERVQEALQRLLS 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 22027482   142 ILQSLDGFVFALNQEGKFLYISETVSIYLGLSQVEMTGSSVFDYIHPGDHSEVLEQLGLR 201
Cdd:TIGR00229   8 IFESSPDAIIVIDLEGNILYVNPAFEEIFGYSAEELIGRNVLELIPEEDREEVRERIERR 67

basic helix-loop-helix-Per-ARNT-Sim (bHLH-PAS) domain found in neuronal PAS domain-containing protein 3 (NPAS3) and similar proteins; NPAS3, also termed neuronal PAS3, or Basic-helix-loop-helix-PAS protein MOP6, or Class E basic helix-loop-helix protein 12 (bHLHe12), or member of PAS protein 6, or PAS domain-containing protein 6 (PASD6), is a bHLH-PAS brain-enriched transcription factor that is involved in central nervous system development and neurogenesis. It is a replicated genetic risk factor for psychiatric disorders. Human chromosomal rearrangements that affect NPAS3 normal expression are associated with schizophrenia and mental retardation.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 22027482  42 LQAQRKEKSRNAARSRRGKENLEFFELAKLLPLPGAISSQLDKASIVRLSVTYLRLRRFAALGAPPWGLRAAGPP 116
Cdd:cd19732   2 LQALRKEKSRDAARSRRGKENFEFYELAKLLPLPAAITSQLDKASIIRLTISYLKMRDFANQGDPPWNLRMEGPP 76

basic helix-loop-helix-Per-ARNT-Sim (bHLH-PAS) domain found in neuronal PAS domain-containing proteins, NPAS1, NPAS3 and similar proteins; The family includes neuronal PAS domain proteins NPAS1 and NPAS3, both of which are master regulators of neuropsychiatric function. NPAS1, also termed neuronal PAS1, or Basic-helix-loop-helix-PAS protein MOP5, or Class E basic helix-loop-helix protein 11 (bHLHe11), or member of PAS protein 5, or PAS domain-containing protein 5 (PASD5), is a bHLH-PAS transcriptional repressor expressed in the central nervous system and involved in neuronal differentiation. It is active during late embryogenesis and postnatal development. NPAS3, also termed neuronal PAS3, or Basic-helix-loop-helix-PAS protein MOP6, or Class E basic helix-loop-helix protein 12 (bHLHe12), or member of PAS protein 6, or PAS domain-containing protein 6 (PASD6), is a bHLH-PAS brain-enriched transcription factor that is involved in central nervous system development and neurogenesis. It is a replicated genetic risk factor for psychiatric disorders. Human chromosomal rearrangements that affect NPAS3 normal expression are associated with schizophrenia and mental retardation.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*
gi 22027482  47 KEKSRNAARSRRGKENLEFFELAKLLPLPGAISSQLDKASIVRLSVTYLRLRRFA 101
Cdd:cd11432   1 KEKSRNAARSRRGKENYEFYELAKLLPLPAAISSQLDKASIVRLTISYLKLRDFM 55

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 22027482  47 KEKSRNAARSRRGKENLEFFELAKLLPLPGAISSQLDKASIVRLSVTYLRLR 98
Cdd:cd11434   2 KEKSKNAARTRREKENAEFYELAKLLPLPSAITSQLDKASIIRLTTSYLKMR 53

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 22027482  47 KEKSRNAARSRRGKENLEFFELAKLLPLPGAISSQLDKASIVRLSVTYLRLRRFA 101
Cdd:cd11391   1 REKSREAAKKRRDKENAEISELASLLPLPPAVGSKLDKLSVLRLAVAYLRLKKFL 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        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 22027482  47 KEKSRNAARSRRGKENLEFFELAKLLPLPGAISSQLDKASIVRLSVTYLRLRrfaalGAPPWGL-RAAGPPAGLAP 121
Cdd:cd19739   2 KEKSKNAAKTRREKENGEFYELAKLLPLPSAITSQLDKASIIRLTTSYLKMR-----AVFPEGLgDAWGQPSRIGP 72

basic helix-loop-helix-Per-ARNT-Sim (bHLH-PAS) domain found in hypoxia-inducible factor 3-alpha (HIF3a) and similar proteins; HIF3a, also termed HIF-3-alpha, or HIF3-alpha, or endothelial PAS domain-containing protein 1 (EPAS-1), or Basic-helix-loop-helix-PAS protein MOP7, or Class E basic helix-loop-helix protein 17 (bHLHe17), or Member of PAS protein 7, or PAS domain-containing protein 7 (PASD7), or HIF3-alpha-1, or inhibitory PAS domain protein (IPAS), is a bHLH-PAS transcriptional regulator in adaptive response to low oxygen tension. It plays a role in the regulation of hypoxia-inducible gene expression.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 22027482  45 QRKEKSRNAARSRRGKENLEFFELAKLLPLPGAISSQLDKASIVRLSVTYLRLRRFAALG 104
Cdd:cd19729   3 QRKEKSRDAARCRRSQETEVFYELAHTLPFPRGVSSHLDKASIMRLTISYLRMHRLIASG 62

PAS fold; The PAS fold corresponds to the structural domain that has previously been defined as PAS and PAC motifs. The PAS fold appears in archaea, eubacteria and eukarya.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 22027482   315 ILACESRVSDHMDLGPSELVGR--SCYQFVHGQDATRIRQSHVDLLDKGQVMTGYYRWLQRAGGFVWLQSVATV 386
Cdd:pfam08447   1 IIYWSPRFEEILGYTPEELLGKgeSWLDLVHPDDRERVREALWEALKGGEPYSGEYRIRRKDGEYRWVEARARP 74

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 22027482 303 HMIVFRLSLGLTILACESRVSDHMDLGPSELVGRSCYQFVHGQDATRIRQSHVDLLDKGQVMTGYYRWLQRAGGFVWLQS 382
Cdd:cd00130   2 PDGVIVLDLDGRILYANPAAEQLLGYSPEELIGKSLLDLIHPEDREELRERLENLLSGGEPVTLEVRLRRKDGSVIWVLV 81

                ....
gi 22027482 383 VATV 386
Cdd:cd00130  82 SLTP 85

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 22027482  48 EKSrNAARSRRGKENLEFFELAKLLPLPGAISSQLDKASIVRLSVTYLRLRRF 100
Cdd:cd11435   3 EKS-NPSKRHRDRLNAELDHLASLLPFPPDIISKLDKLSVLRLSVSYLRVKSF 54

basic helix-loop-helix-Per-ARNT-Sim (bHLH-PAS) domain found in aryl hydrocarbon receptor (AhR) and similar proteins; 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 dimerize with a bHLH-PAS factor ARNT (Aryl hydrocarbon Nuclear Receptor Translocator).

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*....
gi 22027482  52 NAARSRRGKENLEFFELAKLLPLPGAISSQLDKASIVRLSVTYLRLRRF 100
Cdd:cd11436   7 NPSKRHRDRLNTELDRLASLLPFPQDVISKLDKLSVLRLSVSYLRAKSF 55

helix loop helix domain;

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....
gi 22027482     53 AARSRRGKENLEFFELAKLLPlPGAISSQLDKASIVRLSVTYLR 96
Cdd:smart00353   3 RERRRRRKINEAFDELRSLLP-TLPKNKKLSKAEILRLAIEYIK 45

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 22027482  52 NAARSRRGKENLEFFELAKLLPLPGAISSQLDKASIVRLSVTYLRLRRF 100
Cdd:cd19730   9 NPSKRHRERLNAELDHLASLLPFEQSVISKLDKLSILRLSVSYLRTKSY 57

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 22027482  55 RSRRGKENLEFFELAKLLPLPgAISSQLDKASIVRLSVTYLR 96
Cdd:cd00083   2 RRRRDKINDAFEELKRLLPEL-PDSKKLSKASILQKAVEYIR 42

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
                ....*....|....*....|....*....|....*....|....*
gi 22027482  55 RSRRGKENLEFFELAKLLPLPGAISSQLDKASIVRLSVTYLRLRR 99
Cdd:cd11437  10 KRRRDKMNAYIQELSALVPACNAMSRKLDKLTVLRMAVQHLKSLR 54

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 22027482   142 ILQSLDGFVFALNQEGKFLYISETVSIYLGLSQVEMTGSSVFDYIHPGDHSEVLEQLGLR 201
Cdd:TIGR00229   8 IFESSPDAIIVIDLEGNILYVNPAFEEIFGYSAEELIGRNVLELIPEEDREEVRERIERR 67

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
                ....*....|....*....|....*....|....*....|...
gi 22027482  57 RRGKENLEFFELAKLLPLPGAISSQLDKASIVRLSVTYLRLRR 99
Cdd:cd19726  12 RRDKMNTYITELSSMIPMCNAMSRKLDKLTVLRMAVQHMKTLR 54

RocR-type transcriptional regulator, contains PAS, AAA-type ATPase, and DNA-binding Fis domains [Transcription, Signal transduction mechanisms];

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 22027482 141 HILQSLDGFVFALNQEGKFLYISETVSIYLGLSQVEMTGSSVFDYIHPGDHSEVLEQ 197
Cdd:COG3829  15 AILDSLDDGIIVVDADGRITYVNRAAERILGLPREEVIGKNVTELIPNSPLLEVLKT 71