basic helix-loop-helix-Per-ARNT-Sim (bHLH-PAS) domain found in aryl hydrocarbon receptor nuclear translocator (ARNT) and similar proteins; ARNT, also termed Class E basic helix-loop-helix protein 2 (bHLHe2), or Dioxin receptor, nuclear translocator, or hypoxia-inducible factor 1-beta (HIF1b), or HIF-1-beta, or HIF1-beta, is a member of bHLH-PAS transcription regulators that acts 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.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1622830355  86 KERLARENHSEIERRRRNKMTAYITELSDMVPTCSALARKPDKLTILRMAVSHMKSLRGTGNTST 150
Cdd:cd18947     1 KERFARENHSEIERRRRNKMTAYITELSDMVPTCSALARKPDKLTILRMAVSHMKSLRGTGNTST 65

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        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622830355 163 ELKHLILEAADGFLFIVScETGRVVYVSDSVTPVLNQPQSEWFGSTLYDQVHPDDVDKLREQLSTSENALTDCSSHppsG 242
Cdd:pfam00989   1 EDLRAILESLPDGIFVVD-EDGRILYVNAAAEELLGLSREEVIGKSLLDLIPEEDDAEVAELLRQALLQGEESRGF---E 76

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 1622830355 243 RILDLKTGTVKKEGQQSSMRMCMGSR-RSFICRMRC 277
Cdd:pfam00989  77 VSFRVPDGRPRHVEVRASPVRDAGGEiLGFLGVLRD 112

basic helix-loop-helix-Per-ARNT-Sim (bHLH-PAS) domain found in aryl hydrocarbon receptor nuclear translocator (ARNT) and similar proteins; ARNT, also termed Class E basic helix-loop-helix protein 2 (bHLHe2), or Dioxin receptor, nuclear translocator, or hypoxia-inducible factor 1-beta (HIF1b), or HIF-1-beta, or HIF1-beta, is a member of bHLH-PAS transcription regulators that acts 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.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1622830355  86 KERLARENHSEIERRRRNKMTAYITELSDMVPTCSALARKPDKLTILRMAVSHMKSLRGTGNTST 150
Cdd:cd18947     1 KERFARENHSEIERRRRNKMTAYITELSDMVPTCSALARKPDKLTILRMAVSHMKSLRGTGNTST 65

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 1622830355 370 EFISRHNIEGIFTFVDHRCVATVGYQPQELLGKNIVEFCHPEDQQLLRDSFQQVVKlKGQVLSVMFRFRSKNQEWLWMRT 449
Cdd:cd00130     3 DGVIVLDLDGRILYANPAAEQLLGYSPEELIGKSLLDLIHPEDREELRERLENLLS-GGEPVTLEVRLRRKDGSVIWVLV 81

                          90
                  ....*....|....*..
gi 1622830355 450 SSFTFQNPYSDEIEYII 466
Cdd:cd00130    82 SLTPIRDEGGEVIGLLG 98

helix loop helix domain;

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1622830355   95 SEIERRRRNKMTAYITELSDMVPTCSAlARKPDKLTILRMAVSHMKSLR 143
Cdd:smart00353   1 NARERRRRRKINEAFDELRSLLPTLPK-NKKLSKAEILRLAIEYIKSLQ 48

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        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622830355 163 ELKHLILEAADGFLFIVScETGRVVYVSDSVTPVLNQPQSEWFGSTLYDQVHPDDVDKLREQLSTSENALTDCSSHppsG 242
Cdd:pfam00989   1 EDLRAILESLPDGIFVVD-EDGRILYVNAAAEELLGLSREEVIGKSLLDLIPEEDDAEVAELLRQALLQGEESRGF---E 76

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 1622830355 243 RILDLKTGTVKKEGQQSSMRMCMGSR-RSFICRMRC 277
Cdd:pfam00989  77 VSFRVPDGRPRHVEVRASPVRDAGGEiLGFLGVLRD 112

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 1622830355  166 HLILEAADGFLFIVScETGRVVYVSDSVTPVLNQPQSEWFGSTLYDQVHPDDVDKLREQLSTSEN 230
Cdd:smart00091   4 RAILESLPDGIFVLD-LDGRILYANPAAEELLGYSPEELIGKSLLELIHPEDRERVQEALQRLLS 67

PAS domain S-box; The PAS domain was previously described. This sensory box, or S-box domain occupies the central portion of the PAS domain but is more widely distributed. It is often tandemly repeated. Known prosthetic groups bound in the S-box domain include heme in the oxygen sensor FixL, FAD in the redox potential sensor NifL, and a 4-hydroxycinnamyl chromophore in photoactive yellow protein. Proteins containing the domain often contain other regulatory domains such as response regulator or sensor histidine kinase domains. Other S-box proteins include phytochromes and the aryl hydrocarbon receptor nuclear translocator. [Regulatory functions, Small molecule interactions]

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1622830355 378 EGIFTFVDHRCVATVGYQPQELLGKNIVEFCHPEDQQLLRDSFQQVVKLKGQVLSVMFRFRSKNQEWLWMRTS 450
Cdd:TIGR00229  22 EGNILYVNPAFEEIFGYSAEELIGRNVLELIPEEDREEVRERIERRLEGEPEPVSEERRVRRKDGSEIWVEVS 94

basic helix-loop-helix-Per-ARNT-Sim (bHLH-PAS) domain found in aryl hydrocarbon receptor nuclear translocator (ARNT) and similar proteins; ARNT, also termed Class E basic helix-loop-helix protein 2 (bHLHe2), or Dioxin receptor, nuclear translocator, or hypoxia-inducible factor 1-beta (HIF1b), or HIF-1-beta, or HIF1-beta, is a member of bHLH-PAS transcription regulators that acts 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.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1622830355  86 KERLARENHSEIERRRRNKMTAYITELSDMVPTCSALARKPDKLTILRMAVSHMKSLRGTGNTST 150
Cdd:cd18947     1 KERFARENHSEIERRRRNKMTAYITELSDMVPTCSALARKPDKLTILRMAVSHMKSLRGTGNTST 65

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        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1622830355  91 RENHSEIERRRRNKMTAYITELSDMVPTCSALARKPDKLTILRMAVSHMKSLRGTGNTSTD 151
Cdd:cd19726     2 RQNHSEIEKRRRDKMNTYITELSSMIPMCNAMSRKLDKLTVLRMAVQHMKTLRGSLTSYTE 62

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 1622830355  91 RENHSEIERRRRNKMTAYITELSDMVPTCSALARKPDKLTILRMAVSHMKSLRGTGNT 148
Cdd:cd11469     2 REAHSQTEKRRRDKMNNLIEELSAMIPQCNPMARKLDKLTVLRMAVQHLKSLKGSTSS 59

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 1622830355 381 FTFVDHRCVATVGYQPQELLGK--NIVEFCHPEDQQLLRDSFQQVVKlKGQVLSVMFRFRSKNQEWLWMRTSSFTFQNPy 458
Cdd:pfam08447   1 IIYWSPRFEEILGYTPEELLGKgeSWLDLVHPDDRERVREALWEALK-GGEPYSGEYRIRRKDGEYRWVEARARPIRDE- 78

                          90
                  ....*....|.
gi 1622830355 459 SDEIEYIICTN 469
Cdd:pfam08447  79 NGKPVRVIGVA 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. 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 1622830355 370 EFISRHNIEGIFTFVDHRCVATVGYQPQELLGKNIVEFCHPEDQQLLRDSFQQVVKlKGQVLSVMFRFRSKNQEWLWMRT 449
Cdd:cd00130     3 DGVIVLDLDGRILYANPAAEQLLGYSPEELIGKSLLDLIHPEDREELRERLENLLS-GGEPVTLEVRLRRKDGSVIWVLV 81

                          90
                  ....*....|....*..
gi 1622830355 450 SSFTFQNPYSDEIEYII 466
Cdd:cd00130    82 SLTPIRDEGGEVIGLLG 98

helix loop helix domain;

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1622830355   95 SEIERRRRNKMTAYITELSDMVPTCSAlARKPDKLTILRMAVSHMKSLR 143
Cdd:smart00353   1 NARERRRRRKINEAFDELRSLLPTLPK-NKKLSKAEILRLAIEYIKSLQ 48

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        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622830355 163 ELKHLILEAADGFLFIVScETGRVVYVSDSVTPVLNQPQSEWFGSTLYDQVHPDDVDKLREQLSTSENALTDCSSHppsG 242
Cdd:pfam00989   1 EDLRAILESLPDGIFVVD-EDGRILYVNAAAEELLGLSREEVIGKSLLDLIPEEDDAEVAELLRQALLQGEESRGF---E 76

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 1622830355 243 RILDLKTGTVKKEGQQSSMRMCMGSR-RSFICRMRC 277
Cdd:pfam00989  77 VSFRVPDGRPRHVEVRASPVRDAGGEiLGFLGVLRD 112

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 1622830355  94 HSEIERRRRNKMTAYITELSDMVPTCSALAR--KPDKLTILRMAVSHMKSLRGTG 146
Cdd:cd11389     1 HKVIEKRRRDRINESLAELRRLVPEARKSKGsgKLEKAEILEMTLQHLKALQSST 55

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

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1622830355  166 HLILEAADGFLFIVScETGRVVYVSDSVTPVLNQPQSEWFGSTLYDQVHPDDVDKLREQLSTSEN 230
Cdd:smart00091   4 RAILESLPDGIFVLD-LDGRILYANPAAEELLGYSPEELIGKSLLELIHPEDRERVQEALQRLLS 67

PAS domain [Signal transduction mechanisms];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622830355 367 QPTEFISRHNIEGIFTFVDHRCVATVGYQPQELLGKNIVEFCHPEDQQLLRDSFQQVVKlKGQVLSVMFRFRSKNQEWLW 446
Cdd:COG2202    19 SSPDAIIITDLDGRILYVNPAFERLTGYSAEELLGKTLRDLLPPEDDDEFLELLRAALA-GGGVWRGELRNRRKDGSLFW 97

                          90       100
                  ....*....|....*....|....*.
gi 1622830355 447 MRTSSFTFQNPySDEIEYIICTNTNV 472
Cdd:COG2202    98 VELSISPVRDE-DGEITGFVGIARDI 122

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 1622830355  93 NHSEIERRRRNKMTAYITELSDMVPTC--SALARKPDKLTILRMAVSHMKSLR 143
Cdd:cd11387     1 SHNAVERRRRDNINEKIQELGSLVPPSrlETKDLKPNKGSILSKAVEYIRELQ 53

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in transcription factor EB (TFEB) and similar proteins; TFEB, also termed Class E basic helix-loop-helix protein 35 (bHLHe35), is a bHLHzip transcription factor that is required for vascularization of the mouse placenta. 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 TFE3 or MITF.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1622830355  80 EQSSADKERLARENHSEIERRRRNKMTAYITELSDMVPTCSALARKPDKLTILRMAVSHMKSLR 143
Cdd:cd18927     1 EARALAKERQKKDNHNLIERRRRFNINDRIKELGTLIPKTNDLDVRWNKGTILKASVDYIKRMQ 64

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 1622830355  94 HSEIERRRRNKMTAYITELSDMVPTCSALARK--PDKLTILRMAVSHMKSLR 143
Cdd:cd11396     2 HNEVERRRRDKINNWIVKLAKIVPDCEKDNSKqgQSKGGILSKACDYIQELR 53

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 1622830355  91 RENHSEIERRRRNKMTAYITELSDMVPTCSalaRKPDKLTILRMAVSHMKSLRG 144
Cdd:cd19683     3 RERHNAKERQRRERIKIACDQLRKLVPGCS---RKTDKATVFEFTVAYIKFLRE 53

basic helix-loop-helix-orange (bHLH-O) domain found in hairy/enhancer-of-split related with YRPW motif-like protein (HEYL) and similar proteins; HEYL, also termed Class B basic helix-loop-helix protein 33 (bHLHb33), or hairy-related transcription factor 3 (HRT-3), is a bHLH-O transcriptional repressor that is strongly expressed in the presomitic mesoderm, the somites, the peripheral nervous system and smooth muscle of all arteries and is a downstream effector of the Notch and transforming growth factor-beta pathways. It promotes neuronal differentiation by activating proneural genes and inhibiting other hairy and enhancer of split (HES) and hairy/enhancer-of-split related with YRPW motif protein (HEY) proteins. HEYL also functions as a tumor suppressor involved in the progression of human cancers.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1622830355  89 LARENHSEI-ERRRRNKMTAYITELSDMVPTC--SALARKPDKLTILRMAVSHMKSLRGTGNT 148
Cdd:cd11447     7 QARKKRRGIiEKRRRDRINSSLSELRRLVPTAfeKQGSSKLEKAEILQMTVDHLKMLHATGGA 69

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1622830355  86 KERLARENHSEIERRRRNKMTAYITELSDMVPTCSALARKPDKLTILRMAVSHMKSLRGTGNTSTD 151
Cdd:cd18928     7 KERQKKDNHNLIERRRRFNINDRIKELGTLIPKSTDPEMRWNKGTILKASVDYIRKLQKEQQRSKE 72

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.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1622830355  97 IERRRRNKMTAYITELSDMVPTcsALAR----KPDKLTILRMAVSHMKSLRGTG 146
Cdd:cd11407     8 IEKRRRDRINNSLAELRRLVPT--AFEKqgsaKLEKAEILQMTVDHLKMLHSKG 59

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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622830355  78 DDEQSSADKERLAReNHSEieRRRRNKMTAYITELSDMVptcSALARKPDKLTILRMAVSHMKslrgTGNTSTDGS---- 153
Cdd:cd19735     1 DEEDEKDTIKRKSR-NLSE--KKRRDQFNVLINELCSMV---STSNRKMDKSTVLKSTIAFLK----NHNEVTMQShqqe 70

                          90
                  ....*....|
gi 1622830355 154 ----YKPSFL 159
Cdd:cd19735    71 iqedWKPSFL 80

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1622830355  80 EQSSADKERLARENHSEIERRRRNKMTAYITELSDMVPTCSALARKPDKLTILRMAVSHMKSLR 143
Cdd:cd18926     3 EARALAKERQKKDNHNLIERRRRFNINDRIKELGTLIPKSNDPDMRWNKGTILKASVDYIRKLQ 66

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.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1622830355  86 KERLARENHSEIERRRRNKMTAYITELSDMVPTCSALARKPDKLTILRMAVSHMKSLR 143
Cdd:cd18925     1 KERQKKDNHNLIERRRRYNINYRIKELGTLIPKSNDPDMRWNKGTILKASVEYIKWLQ 58

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 1622830355  93 NHSEIERRRRNKMTAYITELSDMVPtcSALAR----KPDKLTILRMAVSHMKSLRGTG 146
Cdd:cd11408     1 SHKVIEKRRRDRINRCLNELGKTVP--MALAKqtsgKLEKAEILEMTVQYLRALHSAD 56

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 1622830355  91 RENHSEIERRRRNKMTAYITELSDMVPTCSalARKPDKLTILRMAVSHMKSL 142
Cdd:cd11404     3 RLNHVRSEKKRRELIKKGYDELCALVPGLD--PQKRTKADILQKAADWIQEL 52

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 1622830355  97 IERRRRNKMTAYITELSDMVPTCSAL--ARKPDKLTILRMAVSHMKSLR 143
Cdd:cd19685     1 SEKRRRQRINDKLNQLKELLPPNLSKqsRSKLSKAEILEMAITELRRLQ 49

basic helix-loop-helix-orange (bHLH-O) domain found in Drosophila melanogaster protein clockwork orange (Cwo) and similar proteins; Cwo is a bHLH-O transcriptional regulator 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 1622830355  93 NHSEIERRRRNKMTAYITELSDMVPTcsALARKP----DKLTILRMAVSHMKSLR 143
Cdd:cd11440     5 SHRIIEKRRRDRMNNCLADLSRLIPP--TYLKKGrgriEKTEIIEMAIKHIKHLQ 57

basic helix-loop-helix-Per-ARNT-Sim (bHLH-PAS) domain found in Circadian locomotor output cycles protein kaput (CLOCK) and similar proteins; CLOCK, also termed Class E basic helix-loop-helix protein 8 (bHLHe8), is a bHLH-PAS transcriptional activator which forms a core component of the circadian clock. It forms heterodimers with another bHLH-PAS protein, Brain-Muscle-Arnt-Like (also known as BMAL or ARNT3 or mop3), which regulates circadian rhythm. BMAL1-CLOCK heterodimer complex activates transcription from E-box (CANNTG) elements found in the promoter of circadian responsive genes.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1622830355  85 DKERLARENHSEIERRRRNKMTAYITELSDMVPtcsALARKPDKLTILRMAVSHMK 140
Cdd:cd19734     2 DKDKAKRVSRNKSEKKRRDQFNVLIKELGSMLP---GNARKMDKSTVLQKSIDFLR 54

Motif C-terminal to PAS motifs (likely to contribute to PAS structural domain); PAC motif occurs C-terminal to a subset of all known PAS motifs. It is proposed to contribute to the PAS domain fold.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|.
gi 1622830355  432 SVMFRFRSKNQEWLWMRTSSFTFQNpYSDEIEYIICTNTNV 472
Cdd:smart00086   1 TVEYRLRRKDGSYIWVLVSASPIRD-EDGEVEGILGVVRDI 40

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in Max-associated protein 4 (Mad4) and similar proteins; Mad4, also termed Max dimerization protein 4, or Max dimerizer 4 (MXD4), or Class C basic helix-loop-helix protein 12 (bHLHc12), or Max-interacting transcriptional repressor MAD4, is a bHLHZip Max-interacting transcriptional repressor that suppresses c-myc dependent transformation and is expressed during neural and epidermal differentiation. It is regulated by a transcriptional repressor complex that contains Miz-1 and c-Myc.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1622830355  91 RENHSEIERRRRNKMTAYITELSDMVPTCSALARKpDKLTILRMAVSHMKSL 142
Cdd:cd18929     3 RSSHNELEKHRRAKLRLYLEQLKQLVPLGPDSTRH-TTLSLLKRAKMHIKKL 53

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in the Myc family; The Myc family is a member of the bHLHzip family of transcription factors that play important roles in the control of normal cell proliferation, growth, survival and differentiation. All Myc isoforms contain two independently functioning polypeptide chain regions: N-terminal transactivating residues and a C-terminal bHLHzip segment. The bHLHzip family of bHLH transcription factors are characterized by a highly conserved N-terminal basic region that may bind DNA at a consensus hexanucleotide sequence known as the E-box (CANNTG) followed by HLH and leucine zipper motifs that may interact with other proteins to form homo- and heterodimers. Myc heterodimerizes with Max enabling specific binding to E-box DNA sequences in the promoters of target genes. The Myc proto-oncoprotein family includes at least five different functional members: c-, N-, L-, S- and B-Myc (which is lacking the bHLH domain).

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1622830355  91 RENHSEIERRRRNKMTAYITELSDMVPtcsALARKPD--KLTILRMAVSHMKSLR 143
Cdd:cd11400     2 RRLHNVLERQRRNDLKNSFEKLRDLVP---ELADNEKasKVVILKKATEYIKQLQ 53

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 1622830355  97 IERRRRNKMTAYITELSDMVPTCSAL----ARKPDKLTILRMAVSHMKSLR 143
Cdd:cd11410     1 MEKKRRARINKSLEQLKTLVLEALNKdntrYSKLEKADILEMTVKYLKQLQ 51

basic helix-loop-helix (bHLH) domain found in Saccharomyces cerevisiae protein INO2 and similar proteins; INO2 is a positive regulatory factor required for depression of the co-regulated phospholipid biosynthetic enzymes in Saccharomyces cerevisiae. It is also involved in the expression of ITR1.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1622830355  90 ARENHSEIERRRRNKMTAYITELSDMVPTCSALARKP-DKLTILRMAVSHMKSLR 143
Cdd:cd11388     3 KKWKHVEAEKKRRNQIKKGFEDLINLINYPRNNNEKRiSKSELLNKAVDDIRGLL 57

basic helix-loop-helix-Per-ARNT-Sim (bHLH-PAS) domain found in single-minded (SIM) family; The SIM family includes Drosophila melanogaster protein SIM and its homologs from vertebrates, single-minded homolog 1 (SIM1) and single-minded homolog 2 (SIM2). SIM is a nuclear bHLH-PAS transcription factor that functions as a master developmental regulator controlling midline development of the ventral nerve cord in Drosophila. SIM1, also termed Class E basic helix-loop-helix protein 14 (bHLHe14), is a bHLH-PAS transcription factor that may have pleiotropic effects during embryogenesis and in the adult. SIM2, also termed Class E basic helix-loop-helix protein 15 (bHLHe15), is a bHLH-PAS transcription factor that may be a master gene of central nervous system (CNS) development in cooperation with ARNT. It may have pleiotropic effects in the tissues expressed during development.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 1622830355  91 RENHSEIERRRRNKMTAYITELSDMVPTCSALARKPDKLTILRMAVSHMK 140
Cdd:cd11434     2 KEKSKNAARTRREKENAEFYELAKLLPLPSAITSQLDKASIIRLTTSYLK 51

basic helix-loop-helix (bHLH) domain found in Arabidopsis thaliana protein maternal effect embryo arrest 8 (AtMEE8) and similar proteins; AtMEE8, also termed AtbHLH108, or EN 132, is a bHLH transcription factor required during early embryo development, for the endosperm formation.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 1622830355  94 HSEIERRRRNKMTAYITELSDMVPTCSalaRKPDKLTILRMAVSHMKSLR 143
Cdd:cd19698     1 HNLLEKKRRERIKDKIEILKGLTPNCT---PKSDIASILSCVIDYIKSLL 47

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in L-Myc and similar proteins; L-Myc, also termed Class E basic helix-loop-helix protein 38 (bHLHe38), or protein L-Myc-1, or V-myc myelocytomatosis viral oncogene homolog, is a bHLHZip oncoprotein belonging to the Myc oncogene protein family. It binds DNA as a heterodimer with MAX. L-Myc is co-expressed with another Myc family member and has weaker transformation/transactivation activities. L-Myc knockout mouse did not exhibit any phenotypic abnormalities.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1622830355  85 DKERLA-RENHSEIERRRRNKMTAYITELSDMVPTCSALARKPdKLTILRMAVSHMKSL 142
Cdd:cd11457     1 DTEDVAkRKNHNFLERKRRNDLRSRFLALRDEVPGLASCSKTP-KVVILSKATEYLRGL 58

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 1622830355  91 RENHSEIERRRRNKMTAYITELSDMVPTCSALARKPDKLTILRMAVSHMK 140
Cdd:cd11432     1 KEKSRNAARSRRGKENYEFYELAKLLPLPAAISSQLDKASIVRLTISYLK 50

basic helix-loop-helix-orange (bHLH-O) domain found in Drosophila melanogaster Enhancer of split proteins, E(spl)m5, E(spl)m8 and similar proteins; The family includes two bHLH-O transcriptional repressors, E(spl)m5 and E(spl)m8, which participate in the control of cell fate choice by uncommitted neuroectodermal cells in the embryo. They bind DNA on N-box motifs, 5'-CACNAG-3'.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1622830355  97 IERRRRNKMTAYITELSDMVPTCSAL--ARKPDKLTILRMAVSHMKSLRGTGN 147
Cdd:cd18916     7 LERQRRARINKCLSELKTLVAECSGDdgCLRMDKAEMLETAVAFMRQQQTAKN 59

basic helix-loop-helix (bHLH) domain found in the spermatogenesis- and oogenesis-specific basic helix-loop-helix-containing protein (SOHLH) family; 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.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 1622830355  94 HSEIERRRRNKMTAYITELSDMVPTCSalARKPDKLTILRMAVSHMKSLR 143
Cdd:cd18908     6 HSLKERLRRERIKSSCDQLRDLLPYIK--GRKLDMASVLEMTVKYIRYIQ 53