PAS domain; This family includes the PAS-B domain of NCOA1 (Nuclear receptor coactivator 1), which binds to an LXXLL motif in the C-terminal region of STAT6 (Signal transducer and activator of transcription 6).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370487922 274 EEFTSRHSLEWKFLFLDHRAPPIIGYLPFEVLGTSGYDYYHVDDLENLAKCHEHLMQY-GKGKSCYYRFLTKGQQWIWLQ 352
Cdd:pfam14598   2 EQFTTRHDIDGKIISCDTRAPFSLGYEKDELVGRSIYDLVHPQDLRTAKSHLREIIQTrGRATSPSYRLRLRDGDFLSVH 81

                          90       100
                  ....*....|....*....|....*
gi 1370487922 353 THYYITYHQWNSRPEFIVCTHTVVS 377
Cdd:pfam14598  82 TKSKLFLNQNSNQQPFIMCTHTILR 106

N-terminal domain of transcription factor Specificity Proteins (SP) 1-4; Specificity Proteins (SPs) are transcription factors that are involved in many cellular processes, including cell differentiation, cell growth, apoptosis, immune responses, response to DNA damage, and chromatin remodeling. There are many SPs in vertebrates (9 SPs in humans and mice, 7 SPs in chicken, and 11 SPs in teleost fish), but arthropods only have 3 SPs. SPs belong to a family of proteins, called the SP/Kruppel or Krueppel-like Factor (KLF) family, characterized by a C-terminal DNA-binding domain of 81 amino acids consisting of three Kruppel-like C2H2 zinc fingers. These factors bind to a loose consensus motif, namely NNRCRCCYY (where N is any nucleotide; R is A/G, and Y is C/T), such as the recurring motifs in GC and GT boxes (5'-GGGGCGGGG-3' and 5-GGTGTGGGG-3') that are present in promoters and more distal regulatory elements of mammalian genes. SP factors preferentially bind GC boxes, while KLFs bind CACCC boxes. Another characteristic hallmark of SP factors is the presence of the Buttonhead (BTD) box CXCPXC, just N-terminal to the zinc fingers. The function of the BTD box is unknown, but it is thought to play an important physiological role. Another feature of most SP factors is the presence of a conserved amino acid stretch, the so-called SP box, located close to the N-terminus. SP factors may be separated into three groups based on their domain architecture and the similarity of their N-terminal transactivation domains: SP1-4, SP5, and SP6-9. The transactivation domains between the three groups are not homologous to one another. SP1-4 have similar N-terminal transactivation domains characterized by glutamine-rich regions, which, in most cases, have adjacent serine/threonine-rich regions. This model represents the N-terminal domain of SP1-4.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370487922 550 KIQEQLQMVHGQGLQMFLQQSNPGLNFGSVQLSSGNSSNIQQLAPINMQGQVVPTNQIQSGMntghiGTTQHMIQQQTLQ 629
Cdd:cd22540    87 QLQGSQLSSSAPGGQQVFAIQNPTMIIKGSQTRSSTNQQYQISPQIQAAGQINNSGQIQIIP-----GTNQAIITPVQVL 161

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1370487922 630 STSTQSQQNVlsghsQQTSLPSQTQSTLTAPLYNTMVISQPAAGSMVqiPSSMPQNSTQSAAVTT 694
Cdd:cd22540   162 QQPQQAHKPV-----PIKPAPLQTSNTNSASLQVPGNVIKLQSGGNV--ALTLPVNNLVGTQDGA 219

PAS domain; This family includes the PAS-B domain of NCOA1 (Nuclear receptor coactivator 1), which binds to an LXXLL motif in the C-terminal region of STAT6 (Signal transducer and activator of transcription 6).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370487922 274 EEFTSRHSLEWKFLFLDHRAPPIIGYLPFEVLGTSGYDYYHVDDLENLAKCHEHLMQY-GKGKSCYYRFLTKGQQWIWLQ 352
Cdd:pfam14598   2 EQFTTRHDIDGKIISCDTRAPFSLGYEKDELVGRSIYDLVHPQDLRTAKSHLREIIQTrGRATSPSYRLRLRDGDFLSVH 81

                          90       100
                  ....*....|....*....|....*
gi 1370487922 353 THYYITYHQWNSRPEFIVCTHTVVS 377
Cdd:pfam14598  82 TKSKLFLNQNSNQQPFIMCTHTILR 106

helix loop helix domain;

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1370487922   40 NKSEKKRRDQFNVLIKELGSMLPGNA--RKMDKSTVLQKSIDFLRKHKE 86
Cdd:smart00353   1 NARERRRRRKINEAFDELRSLLPTLPknKKLSKAEILRLAIEYIKSLQE 49

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1370487922 109 EFTQLMLEALDGFFLAIMTDGSIIYVSESVTSLLEHLPSDLVDQSIFNFIPEGEHSEVYKILSTHLL 175
Cdd:pfam00989   1 EDLRAILESLPDGIFVVDEDGRILYVNAAAEELLGLSREEVIGKSLLDLIPEEDDAEVAELLRQALL 67

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 1370487922  275 EFTSRHSLEWKFLFLDHRAPPIIGYLPFEVLGTSGYDYYHVDDLENLAKCHEHLMQ 330
Cdd:smart00091  12 DGIFVLDLDGRILYANPAAEELLGYSPEELIGKSLLELIHPEDRERVQEALQRLLS 67

N-terminal domain of transcription factor Specificity Protein (SP) 2; Specificity Proteins (SPs) are transcription factors that are involved in many cellular processes, including cell differentiation, cell growth, apoptosis, immune responses, response to DNA damage, and chromatin remodeling. SP2 contains the least conserved DNA-binding domain within the SP subfamily of proteins, and its DNA sequence specificity differs from the other SP proteins. It localizes primarily within subnuclear foci associated with the nuclear matrix, and can activate, or in some cases, repress expression from different promoters. The transcription factor SP2 serves as a paradigm for indirect genomic binding. It does not require its DNA-binding domain for genomic DNA binding and occupies target promoters independently of whether they contain a cognate DNA-binding motif. SP2 belongs to a family of proteins, called the SP/Kruppel or Krueppel-like Factor (KLF) family, characterized by a C-terminal DNA-binding domain of 81 amino acids consisting of three Kruppel-like C2H2 zinc fingers. These factors bind to a loose consensus motif, namely NNRCRCCYY (where N is any nucleotide; R is A/G, and Y is C/T), such as the recurring motifs in GC and GT boxes (5'-GGGGCGGGG-3' and 5-GGTGTGGGG-3') that are present in promoters and more distal regulatory elements of mammalian genes. SP factors preferentially bind GC boxes, while KLFs bind CACCC boxes. Another characteristic hallmark of SP factors is the presence of the Buttonhead (BTD) box CXCPXC, just N-terminal to the zinc fingers. The function of the BTD box is unknown, but it is thought to play an important physiological role. Another feature of most SP factors is the presence of a conserved amino acid stretch, the so-called SP box, located close to the N-terminus. SP factors may be separated into three groups based on their domain architecture and the similarity of their N-terminal transactivation domains: SP1-4, SP5, and SP6-9. The transactivation domains between the three groups are not homologous to one another. SP1-4 have similar N-terminal transactivation domains characterized by glutamine-rich regions, which, in most cases, have adjacent serine/threonine-rich regions. This model represents the N-terminal domain of SP2.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370487922 550 KIQEQLQMVHGQGLQMFLQQSNPGLNFGSVQLSSGNSSNIQQLAPINMQGQVVPTNQIQSGMntghiGTTQHMIQQQTLQ 629
Cdd:cd22540    87 QLQGSQLSSSAPGGQQVFAIQNPTMIIKGSQTRSSTNQQYQISPQIQAAGQINNSGQIQIIP-----GTNQAIITPVQVL 161

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1370487922 630 STSTQSQQNVlsghsQQTSLPSQTQSTLTAPLYNTMVISQPAAGSMVqiPSSMPQNSTQSAAVTT 694
Cdd:cd22540   162 QQPQQAHKPV-----PIKPAPLQTSNTNSASLQVPGNVIKLQSGGNV--ALTLPVNNLVGTQDGA 219

basic helix-loop-helix-Per-ARNT-Sim (bHLH-PAS) domain found in Drosophila melanogaster Circadian locomotor output cycles protein kaput (dCLOCK) and similar proteins; dCLOCK, also termed dPAS1, is a bHLH-PAS Circadian regulator that acts as a transcription factor and generates a rhythmic output with a period of about 24 hours.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1370487922  27 EEDDKDKAKRVSRNKSEKKRRDQFNVLIKELGSMLPGNARKMDKSTVLQKSIDFLRKHKEITAQSDASEIRQDWKPTFL 105
Cdd:cd19735     2 EEDEKDTIKRKSRNLSEKKRRDQFNVLINELCSMVSTSNRKMDKSTVLKSTIAFLKNHNEVTMQSHQQEIQEDWKPSFL 80

basic helix-loop-helix-Per-ARNT-Sim (bHLH-PAS) domain found in Circadian locomotor output cycles protein kaput (CLOCK) and similar proteins; The family includes CLOCK, neuronal PAS domain-containing protein 2 (NPAS2) and non-mammalian circadian clock protein PASD1. CLOCK, also termed Class E basic helix-loop-helix protein 8 (bHLHe8), is a transcriptional activator which forms a core component of the circadian clock. NPAS2, also termed neuronal PAS2, or basic-helix-loop-helix-PAS protein MOP4, or Class E basic helix-loop-helix protein 9 (bHLHe9), or member of PAS protein 4, or PAS domain-containing protein 4, is a transcriptional activator which forms a core component of the circadian clock. PASD1 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.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1370487922  36 RVSRNKSEKKRRDQFNVLIKELGSMLPGNARKMDKSTVLQKSIDFLRKHKEITA 89
Cdd:cd11441     1 RKSRNLSEKKRRDQFNVLINELASMLPGRGRKMDKSTVLKKTIAFLRKHKELTA 54

PAS domain; This family includes the PAS-B domain of NCOA1 (Nuclear receptor coactivator 1), which binds to an LXXLL motif in the C-terminal region of STAT6 (Signal transducer and activator of transcription 6).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370487922 274 EEFTSRHSLEWKFLFLDHRAPPIIGYLPFEVLGTSGYDYYHVDDLENLAKCHEHLMQY-GKGKSCYYRFLTKGQQWIWLQ 352
Cdd:pfam14598   2 EQFTTRHDIDGKIISCDTRAPFSLGYEKDELVGRSIYDLVHPQDLRTAKSHLREIIQTrGRATSPSYRLRLRDGDFLSVH 81

                          90       100
                  ....*....|....*....|....*
gi 1370487922 353 THYYITYHQWNSRPEFIVCTHTVVS 377
Cdd:pfam14598  82 TKSKLFLNQNSNQQPFIMCTHTILR 106

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 1370487922  36 RVSRNKSEKKRRDQFNVLIKELGSMLPGNA---RKMDKSTVLQKSIDFLRKHKEI 87
Cdd:cd11391     1 REKSREAAKKRRDKENAEISELASLLPLPPavgSKLDKLSVLRLAVAYLRLKKFL 55

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in Saccharomyces cerevisiae centromere-binding protein 1 (CBP-1) and similar proteins; CBP-1, also termed centromere promoter factor 1 (CPF1), or centromere-binding factor 1 (CBF1), is a bHLHzip protein that is required for chromosome stability and methionine prototrophy. It binds as a homodimer to the centromere DNA elements I (CDEI, GTCACATG) region of the centromere that is required for optimal centromere function.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1370487922  29 DDKDKAKRVSRNKSEKKRRDQFNVLIKELGSMLPGNARKMDKSTVLQKSIDFLRKHKEITAQSD 92
Cdd:cd11398     1 EEWHRQRRDNHKEVERRRRENINEGINELAALVPGNAREKNKGAILARAVEYIQELQETEAKNI 64

Helix-loop-helix DNA-binding domain;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1370487922  35 KRVSRNKSEKKRRDQFNVLIKELGSMLP--GNARKMDKSTVLQKSIDFLRK 83
Cdd:pfam00010   1 RREAHNERERRRRDRINDAFDELRELLPtlPPDKKLSKAEILRLAIEYIKH 51

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1370487922 109 EFTQLMLEALDGFFLAIMTDGSIIYVSESVTSLLEHLPSDLVDQSIFNFIPEGEHSEVYKILSTHLL 175
Cdd:pfam00989   1 EDLRAILESLPDGIFVVDEDGRILYVNAAAEELLGLSREEVIGKSLLDLIPEEDDAEVAELLRQALL 67

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        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1370487922  31 KDKAKRVSRNKSEKKRRDQFNVLIKELGSMLPGNA---RKMDKSTVLQKSIDFLRKHKEITAQSDASEIRQ 98
Cdd:cd18928     7 KERQKKDNHNLIERRRRFNINDRIKELGTLIPKSTdpeMRWNKGTILKASVDYIRKLQKEQQRSKEIEMRQ 77

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 1370487922 118 LDGFFLAIMTDGSIIYVSESVTSLLEHLPSDLVDQSIFNFIPEGEHSEVYKILSTHLLESDSLTPEY-LKSKNQLEFCCH 196
Cdd:cd00130     1 LPDGVIVLDLDGRILYANPAAEQLLGYSPEELIGKSLLDLIHPEDREELRERLENLLSGGEPVTLEVrLRRKDGSVIWVL 80

                          90       100
                  ....*....|....*....|
gi 1370487922 197 MLRGTIDPKEPSTYEYVKFI 216
Cdd:cd00130    81 VSLTPIRDEGGEVIGLLGVV 100

basic helix-loop-helix-Per-ARNT-Sim (bHLH-PAS) domain found in aryl hydrocarbon receptor nuclear translocator-like protein 2 (ARNTL2) and similar proteins; 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. ARNT-2 heterodimerize with other bHLH-PAS proteins such as aryl hydrocarbon receptor (AhR), hypoxia-inducible factor (HIF), and single-minded (SIM).

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1370487922  36 RVSRNKSEKKRRDQFNVLIKELGSMLPG---NARKMDKSTVLQKSIDFLRKHKEIT 88
Cdd:cd11469     2 REAHSQTEKRRRDKMNNLIEELSAMIPQcnpMARKLDKLTVLRMAVQHLKSLKGST 57

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
                  ....*....|....*....|....*....|....*....|....*...
gi 1370487922  35 KRVSRNKSEKKRRDQFNVLIKELGSMLPGNARKMDKSTVLQKSIDFLR 82
Cdd:cd18921     6 KRTAHNAIEKRYRSSINDKIIELKDLVVGTEAKLNKSAVLRKAIDYIR 53

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 1370487922  275 EFTSRHSLEWKFLFLDHRAPPIIGYLPFEVLGTSGYDYYHVDDLENLAKCHEHLMQ 330
Cdd:smart00091  12 DGIFVLDLDGRILYANPAAEELLGYSPEELIGKSLLELIHPEDRERVQEALQRLLS 67

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 1370487922  109 EFTQLMLEALDGFFLAIMTDGSIIYVSESVTSLLEHLPSDLVDQSIFNFIPEGEHSEVYKILSTHL 174
Cdd:smart00091   1 ERLRAILESLPDGIFVLDLDGRILYANPAAEELLGYSPEELIGKSLLELIHPEDRERVQEALQRLL 66

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in Max-like protein X (Mlx) family; Mlx, also termed Class D basic helix-loop-helix protein 13 (bHLHd13), or Max-like bHLHZip protein, or protein BigMax, or transcription factor-like protein 4, is a Max-like bHLHZip transcription regulator that interacts with the Max network of transcription factors. It forms a sequence-specific DNA-binding protein complex with some member of Mad family (Mad1 and Mad4) and Mondo family but not the Myc family and bind the E-box DNA to control transcription. The family also includes Saccharomyces cerevisiae INO4, which is a bHLH transcriptional activator of phospholipid synthetic genes (such as INO1, CHO1/PSS, CHO2/PEM1, OPI3/PEM2, etc.). It is required for de-repression of phospholipid biosynthetic gene expression in response to inositol deprivation in yeast.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1370487922  35 KRVSRNKSEKKRRDQFNVLIKELGSMLPG-NARKMDKSTVLQKSIDFLRKHKE 86
Cdd:cd11404     2 RRLNHVRSEKKRRELIKKGYDELCALVPGlDPQKRTKADILQKAADWIQELKE 54

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in MLX-interacting protein (MLXIP), MLX-interacting protein-like (MLXIPL) and similar proteins; The family includes MLXIP and MLXIPL. MLXIP, also termed Class E basic helix-loop-helix protein 36 (bHLHe36), or transcriptional activator MondoA, is a bHLHZip transcriptional activator that binds DNA as a heterodimer with Mlx. It binds to the canonical E box sequence 5'-CACGTG-3' and plays a role in transcriptional activation of glycolytic target genes. MLXIP is most highly expressed in skeletal muscle and functions as an indirect glucose sensor, by sensing glucose 6-phosphate and shuttling between the nucleus and the cytoplasm. MLXIPL, also termed carbohydrate-responsive element-binding protein (ChREBP), or Class D basic helix-loop-helix protein 14 (bHLHd14), or MLX interactor, or WS basic-helix-loop-helix leucine zipper protein (WS-bHLH), or Williams-Beuren syndrome chromosomal region 14 protein (WBSCR14), is a bHLHZip transcriptional factor integral to the regulation of glycolysis and lipogenesis in the liver. It forms heterodimers with the bHLHZip protein Mlx to bind the DNA sequence 5'-CACGTG-3'.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370487922  35 KRVSRNKSEKKRRDQFNVLIKELGSMLPGNAR----KMDKSTVLQKSIDFLRK-HKEITAQSD-ASEIRQ 98
Cdd:cd11405     3 RRLSHISAEQKRRFNIKSGFDTLQSLIPSLGQnpnqKVSKAAMLQKAAEYIKSlKRERQQMQEeAEQLRQ 72

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1370487922  31 KDKAKRVSRNKSEKKRRDQFNVLIKELGSMLPGNA---RKMDKSTVLQKSIDFLRKHKEITAQSDASEIRQ 98
Cdd:cd18926     9 KERQKKDNHNLIERRRRFNINDRIKELGTLIPKSNdpdMRWNKGTILKASVDYIRKLQREQQRAKELENRQ 79

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 1370487922  38 SRNKSEKKRRDQFNVLIKELGSMLP-----GNARKMDKSTVLQKSIDFLRKHKEI 87
Cdd:cd11387     1 SHNAVERRRRDNINEKIQELGSLVPpsrleTKDLKPNKGSILSKAVEYIRELQNQ 55

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in MAX gene-associated protein (MGA) family; The MGA family includes MGA, Schizosaccharomyces pombe ESC1 (spESC1) and similar proteins. MGA, also termed MAX dimerization protein 5 (MAD5), is a dual specificity T-box/ bHLHzip transcription factor that regulates the expression of both Max-network and T-box family target genes. It contains a Myc-like bHLHZip motif and requires heterodimerization with Max for binding to the preferred Myc-Max-binding site CACGTG. In addition to the bHLHZip domain, MGA harbors a second DNA-binding domain, the T-box or T-domain. It thus binds the preferred Brachyury-binding sequence and represses transcription of reporter genes containing promoter-proximal Brachyury-binding sites. spESC1 is a bHLHzip protein with homology to human MyoD and Myf-5 myogenic differentiation inducers. It is involved in the sexual differentiation process.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 1370487922  36 RVSRNKSEKKRRDQFNVLIKELGSMLPGNAR-KMDKSTVLQKSID 79
Cdd:cd19682     1 RLRHKKRERERRSELRELFDKLKQLLGLDSDeKASKLAVLTEAIE 45

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 1370487922  32 DKAKRVSRNKS--EKKRRDQFNVLIKELGSMLPgNARKMDKSTVLQKSIDFLRKHKEITAQS 91
Cdd:cd11455     2 DKALAASKSHSeaERRRRERINSHLATLRTLLP-NLSKTDKASLLAEVVQHVKELKRQAAEI 62

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.

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                  ....*....|....*....|....*....|....*....|....*....
gi 1370487922  40 NKSEKKRRDQFNVLIKELGSMLPGNARKMD-----KSTVLQKSIDFLRK 83
Cdd:cd11396     3 NEVERRRRDKINNWIVKLAKIVPDCEKDNSkqgqsKGGILSKACDYIQE 51

basic helix-loop-helix (bHLH) domain found in Arabidopsis thaliana phytochrome interacting factors (PIFs) and similar proteins; The family includes several bHLH transcription factors from Arabidopsis thaliana, such as PIFs, ALC, PIL1, SPATULA, and UNE10. PIFs (PIF1, PIF3, PIF4, PIF5, PIF6 and PIF7) have been shown to control light-regulated gene expression. They directly bind to the photoactivated phytochromes and are degraded in response to light signals. ALC, also termed AtbHLH73, or protein ALCATRAZ, or EN 98, is required for the dehiscence of fruit, especially for the separation of the valve cells from the replum. It promotes the differentiation of a strip of labile non-lignified cells sandwiched between layers of lignified cells. PIL1, also termed AtbHLH124, or protein phytochrome interacting factor 3-like 1, or EN 110, is involved in responses to transient and long-term shade. It is required for the light-mediated inhibition of hypocotyl elongation and necessary for rapid light-induced expression of the photomorphogenesis- and circadian-related gene APRR9. PIL1 seems to play a role in multiple PHYB responses, such as flowering transition and petiole elongation. SPATULA, also termed AtbHLH24, or EN 99, plays a role in floral organogenesis. It promotes the growth of carpel margins and of pollen tract tissues derived from them. UNE10, also termed AtbHLH16, or protein UNFERTILIZED EMBRYO SAC 10, or EN 99, is required during the fertilization of ovules by pollen.

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                  ....*....|....*....|....*....|....*....|....
gi 1370487922  40 NKSEKKRRDQFNVLIKELGSMLPgNARKMDKSTVLQKSIDFLRK 83
Cdd:cd11445     7 NLSERRRRDRINEKMKALQELIP-NCNKTDKASMLDEAIEYLKS 49

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.

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                  ....*....|....*....|....*....|....*....|....*
gi 1370487922  43 EKKRRDQFNVLIKELGSMLPG-----NARKMDKSTVLQKSIDFLR 82
Cdd:cd11408     6 EKRRRDRINRCLNELGKTVPMalakqTSGKLEKAEILEMTVQYLR 50

basic helix-loop-helix-orange (bHLH-O) domain found in hairy and enhancer of split (HES)-related repressor protein (HERP) family; HERP (also called Hey/Hesr/HRT/CHF/gridlock) proteins corresponds to a family of bHLH-O transcriptional repressors that are related to the Drosophila hairy and Enhancer-of-split proteins and act as downstream effectors of Notch signaling. 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 are involved in cardiovascular development and have roles in somitogenesis, myogenesis and gliogenesis.

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                  ....*....|....*....|....*....|....*....|....*....|...
gi 1370487922  35 KRVSRNKSEKKRRDQFNVLIKELGSMLPG-----NARKMDKSTVLQKSIDFLR 82
Cdd:cd11407     1 RKKRRGIIEKRRRDRINNSLAELRRLVPTafekqGSAKLEKAEILQMTVDHLK 53

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in transcription factor EC (TFEC) and similar proteins; TFEC, also termed Class E basic helix-loop-helix protein 34 (bHLHe34), or transcription factor EC-like (TFEC-L), is a bHLHzip transcriptional regulator that acts as a repressor or an activator and regulates gene expression in macrophages. It plays an important role in the niche to expand hematopoietic progenitors through the modulation of several cytokines.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1370487922  31 KDKAKRVSRNKSEKKRRDQFNVLIKELGSMLPGNA---RKMDKSTVLQKSIDFLRKHKEITAQSDASEIRQ 98
Cdd:cd18925     1 KERQKKDNHNLIERRRRYNINYRIKELGTLIPKSNdpdMRWNKGTILKASVEYIKWLQKEQQRARELEHRQ 71

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.

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                  ....*....|....*....|....*....|....*....|....*.
gi 1370487922  42 SEKKRRDQFNVLIKELGSMLPGNA-----RKMDKSTVLQKSIDFLR 82
Cdd:cd19685     1 SEKRRRQRINDKLNQLKELLPPNLskqsrSKLSKAEILEMAITELR 46

PAS domain [Signal transduction mechanisms];

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1370487922 106 SNEEFTQLMLEALDGFFLaIMTDGSIIYVSESVTSLLEHLPSDLVDQSIFNFIPEGEHSEVYKILSTHL 174
Cdd:COG2202   135 SEERLRLLVENAPDGIFV-LDLDGRILYVNPAAEELLGYSPEELLGKSLLDLLHPEDRERLLELLRRLL 202