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        60
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 31745180 108 FREAHSQTEKRRRDKMNNLIEELSAMIPQCNPMARKLDKLTVLRMAVQHLRSLKGLTNSY 167
Cdd:cd11469   1 FREAHSQTEKRRRDKMNNLIEELSAMIPQCNPMARKLDKLTVLRMAVQHLKSLKGSTSSF 60

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 31745180 192 GFLFVVgCERGKILFVSKSVSKILNYDQASLTGQSLFDFLHPKDVAKVKEQL----SSFDISPREKLIDAKTGLQVHSNL 267
Cdd:cd00130   3 DGVIVL-DLDGRILYANPAAEQLLGYSPEELIGKSLLDLIHPEDREELRERLenllSGGEPVTLEVRLRRKDGSVIWVLV 81

                        90       100
                ....*....|....*....|
gi 31745180 268 HAGRTRVYSGSRRSFFCRIK 287
Cdd:cd00130  82 SLTPIRDEGGEVIGLLGVVR 101

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        60
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 31745180 108 FREAHSQTEKRRRDKMNNLIEELSAMIPQCNPMARKLDKLTVLRMAVQHLRSLKGLTNSY 167
Cdd:cd11469   1 FREAHSQTEKRRRDKMNNLIEELSAMIPQCNPMARKLDKLTVLRMAVQHLKSLKGSTSSF 60

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 31745180 370 EFITRFAVNGKFVYVDQRATAILGYLPQELLGTSCYEYFHQDDHNNLTDKHKAVLQsKEKILTDSYKFRAKDGSFVTLKS 449
Cdd:cd00130   3 DGVIVLDLDGRILYANPAAEQLLGYSPEELIGKSLLDLIHPEDREELRERLENLLS-GGEPVTLEVRLRRKDGSVIWVLV 81

                        90
                ....*....|....*....
gi 31745180 450 QWFSFTNPWTKELEYIVSV 468
Cdd:cd00130  82 SLTPIRDEGGEVIGLLGVV 100

helix loop helix domain;

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*.
gi 31745180    116 EKRRRDKMNNLIEELSAMIPQCnPMARKLDKLTVLRMAVQHLRSLK 161
Cdd:smart00353   4 ERRRRRKINEAFDELRSLLPTL-PKNKKLSKAEILRLAIEYIKSLQ 48

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 31745180 192 GFLFVVgCERGKILFVSKSVSKILNYDQASLTGQSLFDFLHPKDVAKVKEQL----SSFDISPREKLIDAKTGLQVHSNL 267
Cdd:cd00130   3 DGVIVL-DLDGRILYANPAAEQLLGYSPEELIGKSLLDLIHPEDREELRERLenllSGGEPVTLEVRLRRKDGSVIWVLV 81

                        90       100
                ....*....|....*....|
gi 31745180 268 HAGRTRVYSGSRRSFFCRIK 287
Cdd:cd00130  82 SLTPIRDEGGEVIGLLGVVR 101

Sporulation sensor histidine kinase E [Cell cycle control, cell division, chromosome partitioning, Signal transduction mechanisms];

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31745180 201 RGKILFVSKSVSKILNYDQASLTGQSLFDFLHPKDVAKVKEQlssfdispreKLIDAKTGLQVHSNLHagrTRVYSGSRR 280
Cdd:COG5809  34 EGKILKVNPAAERIFGYTEDELLGTNILDFLHPDDEKELREI----------LKLLKEGESRDELEFE---LRHKNGKRL 100

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31745180 281 SFFCRIKSCKISVKEEHGCLPNSKKKEHRKFytihctgylrswppnivgMEEE-RNSKKDNSNFTCLVaigrlqpyivpq 359
Cdd:COG5809 101 EFSSKLSPIFDQNGDIEGMLAISRDITERKR------------------MEEAlRESEEKFRLIFNHS------------ 150

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31745180 360 nsgeinvkpTEFITRFAVNGKFVYVDQRATAILGYLPQELLGTSCYEYFHQDDHNNLTDKHKAVLQSKEkILTDSYKFRA 439
Cdd:COG5809 151 ---------PDGIIVTDLDGRIIYANPAACKLLGISIEELIGKSILELIHSDDQENVAAFISQLLKDGG-IAQGEVRFWT 220

                ....*...
gi 31745180 440 KDGSFVTL 447
Cdd:COG5809 221 KDGRWRLL 228

PAS domain [Signal transduction mechanisms];

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 31745180 369 TEFITRFAVNGKFVYVDQRATAILGYLPQELLGTSCYEYFHQDDHNNLTDKHKAVLQSKEKILTDSYKFRAKDGSFVTL 447
Cdd:COG2202 147 PDGIFVLDLDGRILYVNPAAEELLGYSPEELLGKSLLDLLHPEDRERLLELLRRLLEGGRESYELELRLKDGDGRWVWV 225

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 31745180   181 ELRHLILKTAEGFLFVVGcERGKILFVSKSVSKILNYDQASLTGQSLFDFLHPKDVAKVKEQLS 244
Cdd:TIGR00229   3 ERYRAIFESSPDAIIVID-LEGNILYVNPAFEEIFGYSAEELIGRNVLELIPEEDREEVRERIE 65

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        60
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 31745180 108 FREAHSQTEKRRRDKMNNLIEELSAMIPQCNPMARKLDKLTVLRMAVQHLRSLKGLTNSY 167
Cdd:cd11469   1 FREAHSQTEKRRRDKMNNLIEELSAMIPQCNPMARKLDKLTVLRMAVQHLKSLKGSTSSF 60

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

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 31745180 109 REAHSQTEKRRRDKMNNLIEELSAMIPQCNPMARKLDKLTVLRMAVQHLRSLKGLTNSY 167
Cdd:cd19726   2 RQNHSEIEKRRRDKMNTYITELSSMIPMCNAMSRKLDKLTVLRMAVQHMKTLRGSLTSY 60

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 31745180   370 EFITRFAVNGKFVYVDQRATAILGYLPQELLGTSCYEYFHQDDHNNLTDKHKAVLQSKEKILTDSYKFRAKDGSFVTLKS 449
Cdd:pfam14598   3 QFTTRHDIDGKIISCDTRAPFSLGYEKDELVGRSIYDLVHPQDLRTAKSHLREIIQTRGRATSPSYRLRLRDGDFLSVHT 82

                          90       100
                  ....*....|....*....|...
gi 31745180   450 QWFSFTNPWTKELEYIVSVNTLV 472
Cdd:pfam14598  83 KSKLFLNQNSNQQPFIMCTHTIL 105

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 31745180 370 EFITRFAVNGKFVYVDQRATAILGYLPQELLGTSCYEYFHQDDHNNLTDKHKAVLQsKEKILTDSYKFRAKDGSFVTLKS 449
Cdd:cd00130   3 DGVIVLDLDGRILYANPAAEQLLGYSPEELIGKSLLDLIHPEDREELRERLENLLS-GGEPVTLEVRLRRKDGSVIWVLV 81

                        90
                ....*....|....*....
gi 31745180 450 QWFSFTNPWTKELEYIVSV 468
Cdd:cd00130  82 SLTPIRDEGGEVIGLLGVV 100

Helix-loop-helix DNA-binding domain;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 31745180   109 REAHSQTEKRRRDKMNNLIEELSAMIPqCNPMARKLDKLTVLRMAVQHLRSLK 161
Cdd:pfam00010   2 REAHNERERRRRDRINDAFDELRELLP-TLPPDKKLSKAEILRLAIEYIKHLQ 53

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        50
                ....*....|....*....|....*....|....*....|....*....|....*
gi 31745180 112 HSQTEKRRRDKMNNLIEELSAMIPQC--NPMARKLDKLTVLRMAVQHLRSLKGLT 164
Cdd:cd11389   1 HKVIEKRRRDRINESLAELRRLVPEArkSKGSGKLEKAEILEMTLQHLKALQSST 55

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 31745180 109 REAHSQTEKRRRDKMNNLIEELSAMIPqcnPMARKLDKLTVLRMAVQHLRSLKGLT 164
Cdd:cd11441   1 RKSRNLSEKKRRDQFNVLINELASMLP---GRGRKMDKSTVLKKTIAFLRKHKELT 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 31745180    370 EFITRFAVNGKFVYVDQRATAILGYLPQELLGTSCYEYFHQDDHNNLTDKHKAVLQ 425
Cdd:smart00091  12 DGIFVLDLDGRILYANPAAEELLGYSPEELIGKSLLELIHPEDRERVQEALQRLLS 67

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 31745180 109 REAHSQTEKRRRDKMNNLIEELSAMIPQCNpmaRKLDKLTVLRMAVQHLRSLKGLT-NSYVGS---NYRPSFL 177
Cdd:cd19735  11 RKSRNLSEKKRRDQFNVLINELCSMVSTSN---RKMDKSTVLKSTIAFLKNHNEVTmQSHQQEiqeDWKPSFL 80

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 31745180    181 ELRHLILKTAEGFLFVVGcERGKILFVSKSVSKILNYDQASLTGQSLFDFLHPKDVAKVKEQL 243
Cdd:smart00091   1 ERLRAILESLPDGIFVLD-LDGRILYANPAAEELLGYSPEELIGKSLLELIHPEDRERVQEAL 62

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 31745180 102 QVKMKAFREAHSQTEKRRRDKMNNLIEELSAMIPQCNpmaRKLDKLTVLRMAVQHLRSLK 161
Cdd:cd11398   1 EEWHRQRRDNHKEVERRRRENINEGINELAALVPGNA---REKNKGAILARAVEYIQELQ 57

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.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|..
gi 31745180 112 HSQTEKRRRDKMNNLIEELSAMIPQCN--PMARKLDKLTVLRMAVQHLRSLK 161
Cdd:cd11396   2 HNEVERRRRDKINNWIVKLAKIVPDCEkdNSKQGQSKGGILSKACDYIQELR 53

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.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|..
gi 31745180 111 AHSQTEKRRRDKMNNLIEELSAMIPQC--NPMARKLDKLTVLRMAVQHLRSL 160
Cdd:cd11408   1 SHKVIEKRRRDRINRCLNELGKTVPMAlaKQTSGKLEKAEILEMTVQYLRAL 52

basic helix-loop-helix-orange (bHLH-O) domain found in hairy and enhancer of split (HES) family; The HES family includes bHLH-O transcriptional regulators that are related to the Drosophila hairy and Enhancer-of-split (HES) proteins. They 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. HES family proteins form heterodimers or homodimers via their HLH domain and bind DNA to repress gene transcription that play an essential role in development of both compartment and boundary cells of the central nervous system.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|.
gi 31745180 115 TEKRRRDKMNNLIEELSAMIPQC----NPMARKLDKLTVLRMAVQHLRSLK 161
Cdd:cd11410   1 MEKKRRARINKSLEQLKTLVLEAlnkdNTRYSKLEKADILEMTVKYLKQLQ 51

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 31745180 112 HSQTEKRRRDKMNNLIEELSAMIPQCN--PMARKLDKLTVLRMAVQHLRSLK 161
Cdd:cd11387   2 HNAVERRRRDNINEKIQELGSLVPPSRleTKDLKPNKGSILSKAVEYIRELQ 53

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.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|..
gi 31745180 110 EAHSQTEKRRRDKMNNLIEELSAMIPQCNpmarKLDKLTVLRMAVQHLRSLK 161
Cdd:cd11445   4 EVHNLSERRRRDRINEKMKALQELIPNCN----KTDKASMLDEAIEYLKSLQ 51

basic helix-loop-helix (bHLH) domain found in the spermatogenesis- and oogenesis-specific basic helix-loop-helix-containing protein (SOHLH) family and similar proteins; The SOHLH family includes two bHLH transcription factors, SOHLH1 and SOHLH2. They are specifically in spermatogonia and oocytes and essential for early spermatogonial and oocyte differentiation. The family also includes transcription factor-like 5 protein (TCFL5) and similar proteins. TCFL5, also termed Cha transcription factor, or HPV-16 E2-binding protein 1 (E2BP-1), is a bHLH transcription factor that plays a crucial role in spermatogenesis. It regulates cell proliferation or differentiation of cells through binding to a specific DNA sequence like other bHLH molecules.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....
gi 31745180 109 REAHSQTEKRRRDKMNNLIEELSAMIPQCNPmarKLDKLTVLRMAVQHLRSLKG 162
Cdd:cd19683   3 RERHNAKERQRRERIKIACDQLRKLVPGCSR---KTDKATVFEFTVAYIKFLRE 53

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 31745180 109 REAHSQTEKRRRDKMNNLIEELSAMIPQCNPmaRKLDKLTVLRMAVQHLRSLK 161
Cdd:cd11404   3 RLNHVRSEKKRRELIKKGYDELCALVPGLDP--QKRTKADILQKAADWIQELK 53

basic helix-loop-helix-Per-ARNT-Sim (bHLH-PAS) domain found in neuronal PAS domain-containing protein 2 (NPAS2) and similar proteins; 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 (PASD4), is a bHLH-PAS transcriptional activator which forms a core component of the circadian clock.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*
gi 31745180 104 KMKAFREAHSQTEKRRRDKMNNLIEELSAMIPQcnpMARKLDKLTVLRMAVQHLR 158
Cdd:cd19737   6 KDRAKRASRNKSEKKRRDQFNVLIKELSSMLPG---NTRKMDKTTVLEKVIGFLQ 57

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

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*...
gi 31745180 115 TEKRRRDKMNNLIEELSAMIPQC--NPMARKLDKLTVLRMAVQHLRSL 160
Cdd:cd19685   1 SEKRRRQRINDKLNQLKELLPPNlsKQSRSKLSKAEILEMAITELRRL 48

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in the microphthalmia-associated transcription factor family (MITF) family; The MITF (also known as microphthalmia-TFE, or MiT) family is a small family that contain a basic helix loop helix domain associated with a leucine zipper (bHLHZip). The MITF family 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 family can form homodimers or heterodimers with each other but not with other bHLH or bHLHzip proteins.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|
gi 31745180 112 HSQTEKRRRDKMNNLIEELSAMIPQCNPMARKLDKLTVLRMAVQHLRSLK 161
Cdd:cd11397   9 HNMIERRRRFNINDRIKELGTLLPKSNDPDMRWNKGTILKASVDYIRKLQ 58

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in sterol regulatory element-binding protein (SREBP) family and similar proteins; The SREBP family includes SREBP1 and SREBP2, which are bHLHzip transcriptional activator of genes encoding proteins essential for cholesterol biosynthesis/uptake and fatty acid biosynthesis. SREBP1 and SREBP2 are principally found in the liver and in adipocytes and made up of an N-terminal transcription factor portion (composed of an activation domain, a bHLHzip domain, and a nuclear localization signal), a hydrophobic region containing two membrane spanning regions, and a C-terminal regulatory segment. They recognize a symmetric sterol regulatory element (TCACNCCAC) instead of E-box. The family also includes Saccharomyces cerevisiae transcription factor HMS1 (also termed high-copy MEP suppressor protein 1) and serine-rich protein TYE7. HMS1 is a putative bHLHzip transcription factor involved in exit from mitosis and pseudohyphal differentiation. TYE7, also termed basic-helix-loop-helix protein SGC1, is a putative bHLHzip transcription activator required for Ty1-mediated glycolytic gene expression. TYE7 N-terminal is extremely rich in serine residues. It binds DNA on E-box motifs, 5'-CANNTG-3'. TYE7 is not essential for growth.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 31745180 109 REAHSQTEKRRRDKMNNLIEELSAMIPQCN--------------PMARKLDKLTVLRMAVQHLRSLK 161
Cdd:cd11395   4 RLPHNAIEKRYRSNLNTKIERLRDAIPSLRspegksddgglgglAPTTKLSKATILTKAIEYIRHLE 70

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in Max-like protein X (Mlx) and similar proteins; 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.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 31745180 109 REAHSQTEKRRRDKMNNLIEELSAMIPQCNPMA----RKLDKLTVLRMAVQHLRSL 160
Cdd:cd19687   3 REAHTQAEQKRRDAIKKGYDDLQDIVPTCQQQDdigsQKLSKATILQRSIDYIQFL 58

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

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 31745180 104 KMKAFREAHSQTEKRRRDKMNNLIEELSAMIpQCNPMARKLDKLTVLRMAVQHLRSLKGLT 164
Cdd:cd19736   6 KDRAKRASRNKSEKKRRDQFNVLIKELCTML-QGHGHPLKMDKSTILQRTIDFLQKQKEIT 65

basic helix-loop-helix (bHLH) domain found in Arabidopsis thaliana BES1-interacting Myc-like proteins (BIMs) and similar proteins; The family includes Arabidopsis thaliana BIM1 and its homologs (BIM2 and BIM3), which are bHLH transcription factors that interact with BES1 to regulate transcription of Brassinosteroid (BR)-induced gene. BR regulates many growth and developmental processes such as cell elongation, vascular development, senescence stress responses, and photomorphogenesis. BIM1 heterodimerize with BES1 and bind to E-box sequences present in many BR-induced promoters to regulated BR-induced genes.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 31745180 107 AFREAHSQTEKRRRDKMNNLIEELSAMIPQCNpmaRKLDKLTVLRMAVQHLRSLKGLTNSYVGS 170
Cdd:cd11453   2 TPRSKHSATEQRRRSKINERLQALRDLIPHSD---QKRDKASFLLEVIEYIQALQEKVAKLEEQ 62

PAS domain [Signal transduction mechanisms];

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31745180 369 TEFITRFAVNGKFVYVDQRATAILGYLPQELLGTSCYEYFHQDDHNNLTDKHKAVLQSkEKILTDSYKFRAKDGSFVTLK 448
Cdd:COG2202  21 PDAIIITDLDGRILYVNPAFERLTGYSAEELLGKTLRDLLPPEDDDEFLELLRAALAG-GGVWRGELRNRRKDGSLFWVE 99

                        90       100
                ....*....|....*....|
gi 31745180 449 SQWFSFTNPwTKELEYIVSV 468
Cdd:COG2202 100 LSISPVRDE-DGEITGFVGI 118

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        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31745180 104 KMKAFREAHSQTEKRRRDKMNNLIEELSAMIPQCNPMARKLDKLTVLRMAVQHLRSLKGLTNSYVGSNYRPSFLQDNElR 183
Cdd:cd18926   9 KERQKKDNHNLIERRRRFNINDRIKELGTLIPKSNDPDMRWNKGTILKASVDYIRKLQREQQRAKELENRQKKLEHAN-R 87

                ....*...
gi 31745180 184 HLILKTAE 191
Cdd:cd18926  88 HLLLRIQE 95

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

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*..
gi 31745180 116 EKRRRDKMNNLIEELSAMIPQC--NPMARKLDKLTVLRMAVQHLRSL 160
Cdd:cd19748  17 EKRRRDRINNSLSELRRLVPSAfeKQGSAKLEKAEILQMTVDHLKML 63

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in basic helix-loop-helix domain-containing protein USF3 and similar proteins; USF3, also termed upstream transcription factor 3, is a bHLHzip protein that is involved in the negative regulation of epithelial-mesenchymal transition, the process by which epithelial cells lose their polarity and adhesion properties to become mesenchymal cells with enhanced migration and invasive properties.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|...
gi 31745180 109 REAHSQTEKRRRDKMNNLIEELSAMIPQCNPmaRKLDKLTVLRMAVQHLRSLK 161
Cdd:cd18910   6 RESHNEVERRRKDKINAGINKIGELLPDRDA--KKQSKNMILEQAYKYIVELK 56

basic helix-loop-helix (bHLH) domain found in Arabidopsis thaliana protein IAA-leucine resistant 3 (ILR3) and similar proteins; ILR3, also termed AtbHLH105, or EN 133, is a bHLH transcription factor that plays a role in resistance to amide-linked indole-3-acetic acid (IAA) conjugates such as IAA-Leu and IAA-Phe. It may regulate gene expression in response to metal homeostasis changes.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 31745180 116 EKRRRDKMNNLIEELSAMI-PQCNPmarKLDKLTVLRMAVQHLRSLKGLTNSYVGSNyrpSFLQDnELRHLILKTAE 191
Cdd:cd11446   5 EKLRRDKLNERFMELSNVLePGRPP---KTDKATILGDAIRMLKQLRGEVQKLKEEN---SSLQE-ESKELKAEKNE 74

basic helix-loop-helix-orange (bHLH-O) domain found in hairy and enhancer of split 7 (HES-7) and similar proteins; HES-7, also termed Class B basic helix-loop-helix protein 37 (bHLHb37), or bHLH factor Hes7, is a bHLH-O transcriptional repressor that is expressed in an oscillatory manner and acts as a key regulator of the pace of the segmentation clock. It is regulated by the Notch and Fgf/Mapk pathways. HES-7 is one mammalian counterpart of the Hairy and Enhancer of split proteins that play a critical role in many physiological processes including cellular differentiation, cell cycle arrest, apoptosis and self-renewal ability.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....
gi 31745180 113 SQTEKRRRDKMNNLIEELSAMIPQC-------NPmarKLDKLTVLRMAVQHLRS 159
Cdd:cd11462   6 PLVEKRRRDRINRSLEELRVLLLQNtqdeklkNP---KVEKAEILELTVQFLRN 56

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in Saccharomyces cerevisiae transcription factor HMS1 and similar proteins; HMS1, also termed high-copy MEP suppressor protein 1, is a putative bHLHzip transcription factor involved in exit from mitosis and pseudohyphal differentiation.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 31745180 109 REAHSQTEKRRRDKMNNLIEELSAMIPQC-------------------NPMARKLDKLTVLRMAVQHLRSLKG 162
Cdd:cd11399   4 KTAHNMIEKRYRSNINDRIAELRDSVPALreayksargededeedlggLTPATKLNKATILSKATEYIRHLEK 76