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 564356288  255 YCDERITELMGYEPEELLGR--SIYEYYHALDSDHLTKTHHDMFTKGQVTTGQYRMLAKRGGYVWVETQATVIYNtKNSQ 332
Cdd:pfam08447   3 YWSPRFEEILGYTPEELLGKgeSWLDLVHPDDRERVREALWEALKGGEPYSGEYRIRRKDGEYRWVEARARPIRD-ENGK 81

                  ....*...
gi 564356288  333 PQCIVCVN 340
Cdd:pfam08447  82 PVRVIGVA 89

Hypoxia-inducible factor-1; HIF-1 is a transcriptional complex and controls cellular systemic homeostatic responses to oxygen availability. In the presence of oxygen HIF-1 alpha is targeted for proteasomal degradation by pHVL, a ubiquitination complex.

                          10        20        30
                  ....*....|....*....|....*....|.
gi 564356288  551 SAQDT-DLDLEMLAPYIPMDDDFQLRSFDQL 580
Cdd:pfam11413   1 TTQDMeDLDLEMLAPYIPMDDDFQLNPIIPE 31

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 564356288  255 YCDERITELMGYEPEELLGR--SIYEYYHALDSDHLTKTHHDMFTKGQVTTGQYRMLAKRGGYVWVETQATVIYNtKNSQ 332
Cdd:pfam08447   3 YWSPRFEEILGYTPEELLGKgeSWLDLVHPDDRERVREALWEALKGGEPYSGEYRIRRKDGEYRWVEARARPIRD-ENGK 81

                  ....*...
gi 564356288  333 PQCIVCVN 340
Cdd:pfam08447  82 PVRVIGVA 89

HIF-1 alpha C terminal transactivation domain; Hypoxia inducible factor-1 alpha (HIF-1 alpha) is the regulatory subunit of the heterodimeric transcription factor HIF-1. It plays a key role in cellular response to low oxygen tension. This region corresponds to the C terminal transactivation domain.

                          10        20        30
                  ....*....|....*....|....*....|....*..
gi 564356288  791 ESGLPQLTSYDCEVNAPIQGSRNLLQGEELLRALDQV 827
Cdd:pfam08778   1 LSVLPQLTRYDCEVNAPLQGRSHLLQGEELLRALDQV 37

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 564356288    94 LKALDGFVMVLTDDGDMIYISDNVNKYMGLTQFELTGHSVFDFTHPCDHEEMREML 149
Cdd:smart00091   7 LESLPDGIFVLDLDGRILYANPAAEELLGYSPEELIGKSLLELIHPEDRERVQEAL 62

PAS domain [Signal transduction mechanisms];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564356288 249 LDMKFSYCDERITELMGYEPEELLGRSIYEYYHALDSDHLTKTHHDMFTKGQVTTGQYRMLAKRGGYVWVETQATVIYNT 328
Cdd:COG2202   29 LDGRILYVNPAFERLTGYSAEELLGKTLRDLLPPEDDDEFLELLRAALAGGGVWRGELRNRRKDGSLFWVELSISPVRDE 108

                         90
                 ....*....|.
gi 564356288 329 KNsQPQCIVCV 339
Cdd:COG2202  109 DG-EITGFVGI 118

helix loop helix domain;

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*.
gi 564356288    24 RDAARSRRSKESEVFYELAHQLPlPHNVSSHLDKASVMRLTISYLR 69
Cdd:smart00353   1 NARERRRRRKINEAFDELRSLLP-TLPKNKKLSKAEILRLAIEYIK 45

basic helix-loop-helix-Per-ARNT-Sim (bHLH-PAS) domain found in hypoxia-inducible factor 2-alpha (HIF2a) and similar proteins; HIF2a, also termed HIF-2-alpha, or HIF2-alpha, or endothelial PAS domain-containing protein 1 (EPAS-1), or Basic-helix-loop-helix-PAS protein MOP2, or Class E basic helix-loop-helix protein 73 (bHLHe73), or Member of PAS protein 2, or PAS domain-containing protein 2 (PASD2), or HIF-1-alpha-like factor (HLF), is a bHLH-PAS transcription factor involved in the induction of oxygen regulated genes.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 564356288  13 RMSSERRKEKSRDAARSRRSKESEVFYELAHQLPLPHNVSSHLDKASVMRLTISYLRVRKLLDAG 77
Cdd:cd19728    1 RSSSERRKEKSRDAARCRRSKETEVFYELAHQLPLPHSVSSHLDKASIMRLAISFLRTHKLLSSV 65

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 564356288  16 SERRKEKSRDAARSRRSKESEVFYELAHQLPLPHNVSSHLDKASVMRLTISYLRVRKLLDAGD 78
Cdd:cd19729    1 TEQRKEKSRDAARCRRSQETEVFYELAHTLPFPRGVSSHLDKASIMRLTISYLRMHRLIASGE 63

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 564356288  17 ERRKEKSRDAARSRRSKESEVFYELAHQLPLPHNVSSHLDKASVMRLTISYLRVRKLLDAGD 78
Cdd:cd19732    4 ALRKEKSRDAARSRRGKENFEFYELAKLLPLPAAITSQLDKASIIRLTISYLKMRDFANQGD 65

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 564356288  20 KEKSRDAARSRRSKESEVFYELAHQLPLPHNVSSHLDKASVMRLTISYLRVRKLL 74
Cdd:cd11391    1 REKSREAAKKRRDKENAEISELASLLPLPPAVGSKLDKLSVLRLAVAYLRLKKFL 55

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 564356288  20 KEKSRDAARSRRSKESEVFYELAHQLPLPHNVSSHLDKASVMRLTISYLRVRK 72
Cdd:cd11432    1 KEKSRNAARSRRGKENYEFYELAKLLPLPAAISSQLDKASIVRLTISYLKLRD 53

basic helix-loop-helix-Per-ARNT-Sim (bHLH-PAS) domain found in Drosophila melanogaster protein single-minded (SIM) and similar proteins; 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.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 564356288  20 KEKSRDAARSRRSKESEVFYELAHQLPLPHNVSSHLDKASVMRLTISYLRVRKLLDAG 77
Cdd:cd19740    2 KEKSKNAARSRREKENAEFLELAKLLPLPAAITSQLDKASIIRLTTSYLKMRQVFPDG 59

basic helix-loop-helix-Per-ARNT-Sim (bHLH-PAS) domain found in single-minded homolog 1 (SIM1) and similar proteins; 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.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 564356288  20 KEKSRDAARSRRSKESEVFYELAHQLPLPHNVSSHLDKASVMRLTISYLRVRKLLDAG 77
Cdd:cd19738    2 KEKSKNAARTRREKENSEFYELAKLLPLPSAITSQLDKASIIRLTTSYLKMRVVFPEG 59

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 564356288  20 KEKSRDAARSRRSKESEVFYELAHQLPLPHNVSSHLDKASVMRLTISYLRVRKLLDAG 77
Cdd:cd19739    2 KEKSKNAAKTRREKENGEFYELAKLLPLPSAITSQLDKASIIRLTTSYLKMRAVFPEG 59

Hypoxia-inducible factor-1; HIF-1 is a transcriptional complex and controls cellular systemic homeostatic responses to oxygen availability. In the presence of oxygen HIF-1 alpha is targeted for proteasomal degradation by pHVL, a ubiquitination complex.

                          10        20        30
                  ....*....|....*....|....*....|.
gi 564356288  551 SAQDT-DLDLEMLAPYIPMDDDFQLRSFDQL 580
Cdd:pfam11413   1 TTQDMeDLDLEMLAPYIPMDDDFQLNPIIPE 31

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 564356288  97 LDGFVMVLTDDGDMIYISDNVNKYMGLTQFELTGHSVFDFTHPCDHEEMREMLTH 151
Cdd:cd00130    1 LPDGVIVLDLDGRILYANPAAEQLLGYSPEELIGKSLLDLIHPEDREELRERLEN 55

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 564356288   240 SKTFLSRHSLDMKFSYCDERITELMGYEPEELLGRSIYEYYHALDSDHLTKTHHDMF 296
Cdd:smart00091  10 LPDGIFVLDLDGRILYANPAAEELLGYSPEELIGKSLLELIHPEDRERVQEALQRLL 66

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        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 564356288  29 SRRSKE--SEVFYELAHQLPLPHNVSSHLDKASVMRLTISYLRVRKLLDAG 77
Cdd:cd19696    8 SKRHRDrlNSELDELASLLPFPEDVISKLDKLSVLRLSVSYLRTKNYFQAV 58

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 564356288  21 EKSRDAARSRRSKESEVfYELAHQLPLPHNVSSHLDKASVMRLTISYLRVRKLLDA 76
Cdd:cd11435    3 EKSNPSKRHRDRLNAEL-DHLASLLPFPPDIISKLDKLSVLRLSVSYLRVKSFFQA 57

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        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 564356288  22 KSRDAARSRRSKESEVfYELAHQLPLPHNVSSHLDKASVMRLTISYLRVRKLLDA 76
Cdd:cd11436    5 KSNPSKRHRDRLNTEL-DRLASLLPFPQDVISKLDKLSVLRLSVSYLRAKSFFDV 58

PAS domain; This domain is found in many signalling proteins in which it functions as a sensor domain. It recognizes FMN, Zn(II), FAD and riboflavin (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 564356288  255 YCDERITELMGYEPEELLGRSIYEYYHalDSDHLTKTHHDMFTKGQVTTGQYRMLAKRGGYVWVETQATVIYNTKNsqpq 334
Cdd:pfam13426   6 YVNDAALRLLGYTREELLGKSITDLFA--EPEDSERLREALREGKAVREFEVVLYRKDGEPFPVLVSLAPIRDDGG---- 79

                          90
                  ....*....|....*..
gi 564356288  335 civcvNYVVSGIIQHDL 351
Cdd:pfam13426  80 -----ELVGIIAILRDI 91