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 1958786910 347 IIYCENRITDYMDLTPVDIVGK--RCYHFIHAEDVEGIRHSHLDLLNKGQCVTKYYRWMQKNGGYIWIQSSATIaINAKN 424
Cdd:pfam08447   1 IIYWSPRFEEILGYTPEELLGKgeSWLDLVHPDDRERVREALWEALKGGEPYSGEYRIRRKDGEYRWVEARARP-IRDEN 79

                          90
                  ....*....|
gi 1958786910 425 ANEKNIIWVN 434
Cdd:pfam08447  80 GKPVRVIGVA 89

MSCRAMM family adhesin clumping factor ClfA; Clumping factor A is an MSCRAMM (Microbial Surface Components Recognizing Adhesive Matrix Molecules). It is heavily studied in Staphylococcus aureus both for its biological role in adhesion and for its potential for vaccination. Features of the sequence, but also of other MSCRAMM adhesins, include a long run of Ser-Asp dipeptide repeats and a C-terminal cell wall anchoring LPXTG motif.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958786910 440 PEYKDTPMDIAQLPHLPEKASESSETSDSESDSKDTSGITEDNENSKSDEKGNQSENSEDPEPDRKKSGSACD--NDMNC 517
Cdd:NF033609  545 PEQPDEPGEIEPIPEDSDSDPGSDSGSDSSNSDSGSDSGSDSTSDSGSDSASDSDSASDSDSASDSDSASDSDsaSDSDS 624

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958786910 518 NDDGHSSSNPDSRDSDDSFEHSDFEHPKAAEDGFGALGSMQIKVERYVESEADLRLQPCESLTSDSAKDSDSATEAGAQA 597
Cdd:NF033609  625 ASDSDSASDSDSASDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDS 704

                  ..
gi 1958786910 598 SS 599
Cdd:NF033609  705 DS 706

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 1958786910 347 IIYCENRITDYMDLTPVDIVGK--RCYHFIHAEDVEGIRHSHLDLLNKGQCVTKYYRWMQKNGGYIWIQSSATIaINAKN 424
Cdd:pfam08447   1 IIYWSPRFEEILGYTPEELLGKgeSWLDLVHPDDRERVREALWEALKGGEPYSGEYRIRRKDGEYRWVEARARP-IRDEN 79

                          90
                  ....*....|
gi 1958786910 425 ANEKNIIWVN 434
Cdd:pfam08447  80 GKPVRVIGVA 89

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 1958786910  156 SHILQSLDGFVFALNQEGKFLYISETVSIYLGLSQVELTGSSVFDYVHPGDHVEMAEQL 214
Cdd:smart00091   4 RAILESLPDGIFVLDLDGRILYANPAAEELLGYSPEELIGKSLLELIHPEDRERVQEAL 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. 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 1958786910 156 SHILQSLDGFVFALNQEGKFLYISETVSIYLGLSQVELTGSSVFDYVHPGDHVEMAEQL 214
Cdd:pfam00989   4 RAILESLPDGIFVVDEDGRILYVNAAAEELLGLSREEVIGKSLLDLIPEEDDAEVAELL 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
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1958786910  335 HMFVTRVNMDLNIIYCENRITDYMDLTPVDIVGKRCYHFIHAEDVEGIRHSHLDLLN 391
Cdd:smart00091  11 PDGIFVLDLDGRILYANPAAEELLGYSPEELIGKSLLELIHPEDRERVQEALQRLLS 67

MSCRAMM family adhesin clumping factor ClfA; Clumping factor A is an MSCRAMM (Microbial Surface Components Recognizing Adhesive Matrix Molecules). It is heavily studied in Staphylococcus aureus both for its biological role in adhesion and for its potential for vaccination. Features of the sequence, but also of other MSCRAMM adhesins, include a long run of Ser-Asp dipeptide repeats and a C-terminal cell wall anchoring LPXTG motif.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958786910 474 DTSGITEDNENSKSDEKGNQSENSEDPEPDRKKSGSACDNDMNCNDDGHSSSNPDSRDSDDSFEHSDFEHPKAAEDGFGA 553
Cdd:NF033609  669 DSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDS 748

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 1958786910 554 LGSMQIKVERYVESEADLRLQPCESLTSDSAKDSDSATEAGAQASS 599
Cdd:NF033609  749 DSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDS 794

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        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1958786910 151 EAHLGShILQSLDGFVFALNQEGKFLYISETVSIYLGLSQVELTGSSVFDYVHPGD---HVEMAEQLGMKLPPGRG 223
Cdd:TIGR00229   2 EERYRA-IFESSPDAIIVIDLEGNILYVNPAFEEIFGYSAEELIGRNVLELIPEEDreeVRERIERRLEGEPEPVS 76

PAS domain [Signal transduction mechanisms];

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1958786910 146 AIEVFEAHLgSHILQSLDGFVFALNQEGKFLYISETVSIYLGLSQVELTGSSVFDYVHPGDHVEMAEQL 214
Cdd:COG2202   131 ALRESEERL-RLLVENAPDGIFVLDLDGRILYVNPAAEELLGYSPEELLGKSLLDLLHPEDRERLLELL 198

basic helix-loop-helix-Per-ARNT-Sim (bHLH-PAS) domain found in neuronal PAS domain-containing protein 1 (NPAS1) and similar proteins; 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.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1958786910  55 QALRKEKSRDAARSRRGKENFEFYELAKLLPLPAAITSQLDKASIIRLTISYLKMRDFANQGDPPWNLRMEGPP 128
Cdd:cd19731     1 QALRKEKSRNAARSRRGKENFEFYELAKMLPLPGAITSQLDKASIVRLTISYLKMRDFASHGDPPWSLRAEGPP 74

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 1958786910  59 KEKSRDAARSRRGKENFEFYELAKLLPLPAAITSQLDKASIIRLTISYLKMRDFA 113
Cdd:cd11432     1 KEKSRNAARSRRGKENYEFYELAKLLPLPAAISSQLDKASIVRLTISYLKLRDFM 55

basic helix-loop-helix-Per-ARNT-Sim (bHLH-PAS) domain found in hypoxia-inducible factor (HIF) family; The HIF family contains bHLH-PAS transcription regulators involved in oxygen homeostasis, including HIF1a, HIF2a, and HIF3a. They have been implicated in development, postnatal physiology as well as disease pathogenesis. HIF1a, also termed HIF-1-alpha, or HIF1-alpha, or ARNT-interacting protein, or Basic-helix-loop-helix-PAS protein MOP1, or Class E basic helix-loop-helix protein 78 (bHLHe78), or Member of PAS protein 1, or PAS domain-containing protein 8 (PASD8), functions as a master transcriptional regulator of the adaptive response to hypoxia. 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. 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
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1958786910  58 RKEKSRDAARSRRGKENFEFYELAKLLPLPAAITSQLDKASIIRLTISYLKMR 110
Cdd:cd11433     1 RKEKSRDAARCRRGKESEIFYELAHQLPLPHSVSSQLDKASIMRLTISYLKLR 53

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 1958786910  59 KEKSRDAARSRRGKENFEFYELAKLLPLPAAITSQLDKASIIRLTISYLKMR 110
Cdd:cd19738     2 KEKSKNAARTRREKENSEFYELAKLLPLPSAITSQLDKASIIRLTTSYLKMR 53

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 1958786910  59 KEKSRDAARSRRGKENFEFYELAKLLPLPAAITSQLDKASIIRLTISYLKMR 110
Cdd:cd19739     2 KEKSKNAAKTRREKENGEFYELAKLLPLPSAITSQLDKASIIRLTTSYLKMR 53

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
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1958786910  57 LRKEKSRDAARSRRGKENFEFYELAKLLPLPAAITSQLDKASIIRLTISYLKM 109
Cdd:cd19729     3 QRKEKSRDAARCRRSQETEVFYELAHTLPFPRGVSSHLDKASIMRLTISYLRM 55

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 1958786910 347 IIYCENRITDYMDLTPVDIVGK--RCYHFIHAEDVEGIRHSHLDLLNKGQCVTKYYRWMQKNGGYIWIQSSATIaINAKN 424
Cdd:pfam08447   1 IIYWSPRFEEILGYTPEELLGKgeSWLDLVHPDDRERVREALWEALKGGEPYSGEYRIRRKDGEYRWVEARARP-IRDEN 79

                          90
                  ....*....|
gi 1958786910 425 ANEKNIIWVN 434
Cdd:pfam08447  80 GKPVRVIGVA 89

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 1958786910  156 SHILQSLDGFVFALNQEGKFLYISETVSIYLGLSQVELTGSSVFDYVHPGDHVEMAEQL 214
Cdd:smart00091   4 RAILESLPDGIFVLDLDGRILYANPAAEELLGYSPEELIGKSLLELIHPEDRERVQEAL 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. 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 1958786910 156 SHILQSLDGFVFALNQEGKFLYISETVSIYLGLSQVELTGSSVFDYVHPGDHVEMAEQL 214
Cdd:pfam00989   4 RAILESLPDGIFVVDEDGRILYVNAAAEELLGLSREEVIGKSLLDLIPEEDDAEVAELL 62

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 1958786910  61 KSRDAARsRRGKENFEFYELAKLLPLPAAITSQLDKASIIRLTISYLKMRDFAN 114
Cdd:cd11436     5 KSNPSKR-HRDRLNTELDRLASLLPFPQDVISKLDKLSVLRLSVSYLRAKSFFD 57

helix loop helix domain;

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*.
gi 1958786910   63 RDAARSRRGKENFEFYELAKLLPlPAAITSQLDKASIIRLTISYLK 108
Cdd:smart00353   1 NARERRRRRKINEAFDELRSLLP-TLPKNKKLSKAEILRLAIEYIK 45

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 1958786910  335 HMFVTRVNMDLNIIYCENRITDYMDLTPVDIVGKRCYHFIHAEDVEGIRHSHLDLLN 391
Cdd:smart00091  11 PDGIFVLDLDGRILYANPAAEELLGYSPEELIGKSLLELIHPEDRERVQEALQRLLS 67

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 1958786910  67 RSRRGKENFEFYELAKLLPLPAAItSQLDKASIIRLTISYLKM 109
Cdd:cd00083     2 RRRRDKINDAFEELKRLLPELPDS-KKLSKASILQKAVEYIRE 43

MSCRAMM family adhesin clumping factor ClfA; Clumping factor A is an MSCRAMM (Microbial Surface Components Recognizing Adhesive Matrix Molecules). It is heavily studied in Staphylococcus aureus both for its biological role in adhesion and for its potential for vaccination. Features of the sequence, but also of other MSCRAMM adhesins, include a long run of Ser-Asp dipeptide repeats and a C-terminal cell wall anchoring LPXTG motif.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958786910 474 DTSGITEDNENSKSDEKGNQSENSEDPEPDRKKSGSACDNDMNCNDDGHSSSNPDSRDSDDSFEHSDFEHPKAAEDGFGA 553
Cdd:NF033609  669 DSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDS 748

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 1958786910 554 LGSMQIKVERYVESEADLRLQPCESLTSDSAKDSDSATEAGAQASS 599
Cdd:NF033609  749 DSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDS 794

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        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1958786910 151 EAHLGShILQSLDGFVFALNQEGKFLYISETVSIYLGLSQVELTGSSVFDYVHPGD---HVEMAEQLGMKLPPGRG 223
Cdd:TIGR00229   2 EERYRA-IFESSPDAIIVIDLEGNILYVNPAFEEIFGYSAEELIGRNVLELIPEEDreeVRERIERRLEGEPEPVS 76

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 1958786910  67 RSRRGKENFEFYELAKLLPLPAAITSQLDKASIIRLTISYLK 108
Cdd:cd11437    10 KRRRDKMNAYIQELSALVPACNAMSRKLDKLTVLRMAVQHLK 51

basic helix-loop-helix-orange (bHLH-O) domain found in hairy and enhancer of split (HES)-related repressor protein (HERP)-like family; The HERP-like family includes bHLH-O transcriptional regulators that are related to the Drosophila hairy and Enhancer-of-split proteins. They contain a basic helix-loop-helix (bHLH) domain with an invariant glycine residue in its basic region, an orange domain in the central region and YXXW sequence motif at its C-terminal region. HERP proteins (HEY1, HEY2 and HEYL) act as downstream effectors of Notch signaling. They are involved in cardiovascular development and have roles in somitogenesis, myogenesis and gliogenesis. Hairy and enhancer of split-related protein HELT is a transcriptional repressor expressed in the developing central nervous system. It binds preferentially to the canonical E box sequence 5'-CACGCG-3' and regulates neuronal differentiation and/or identity. Differentially expressed in chondrocytes proteins, DEC1 and DEC2, are widely expressed in both embryonic and adult tissues and have been implicated in apoptosis, cell proliferation, and circadian rhythms, as well as malignancy in various cancers. Drosophila melanogaster protein clockwork orange (Cwo) is also included in this family. It is involved in the regulation of Drosophila circadian rhythms. It functions as both an activator and a repressor of clock gene expression.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|...
gi 1958786910  69 RRGKENFEFYELAKLLPLPAAITSQ--LDKASIIRLTISYLKM 109
Cdd:cd11389     8 RRDRINESLAELRRLVPEARKSKGSgkLEKAEILEMTLQHLKA 50