basic Helix Loop Helix (bHLH) domain superfamily; bHLH proteins are transcriptional regulators that are found in organisms from yeast to humans. Members of the bHLH superfamily have two highly conserved and functionally distinct regions. The basic part is at the amino end of the bHLH that may bind DNA to a consensus hexanucleotide sequence known as the E box (CANNTG). Different families of bHLH proteins recognize different E-box consensus sequences. At the carboxyl-terminal end of the region is the HLH region that interacts with other proteins to form homo- and heterodimers. bHLH proteins function as a diverse set of regulatory factors because they recognize different DNA sequences and dimerize with different proteins. The bHLH proteins can be divided to cell-type specific and widely expressed proteins. The cell-type specific members of bHLH superfamily are involved in cell-fate determination and act in neurogenesis, cardiogenesis, myogenesis, and hematopoiesis.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 26332829  28 PSPKRSTEKRNREQENKYIEELAELIFANFNDIDNFNFKPDKCAILKETVKQIRQIKEQEKAAA 91
Cdd:cd18950   1 PSPKRSTEKRNREQENKYIEELAELIFANFNDIDNFNVKPDKCAILKETVKQIRQIKEQEKAAA 64

basic helix-loop-helix-Per-ARNT-Sim (bHLH-PAS) domain found in nuclear receptor coactivator 2 (NCoA-2) and similar proteins; NCoA-2, also termed Class E basic helix-loop-helix protein 75 (bHLHe75), or transcriptional intermediary factor 2 (TIF2), or steroid receptor coactivator 2 (SRC-2), or glucocorticoid receptor interacting protein-1 (GRIP1), is a bHLH-PAS transcriptional coactivator for steroid receptors and nuclear receptors. It is required with NCoA-1 to control energy balance between white and brown adipose tissues.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 26332829  28 PSPKRSTEKRNREQENKYIEELAELIFANFNDIDNFNFKPDKCAILKETVKQIRQIKEQEKAAA 91
Cdd:cd18950   1 PSPKRSTEKRNREQENKYIEELAELIFANFNDIDNFNVKPDKCAILKETVKQIRQIKEQEKAAA 64

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 26332829 123 LDGFFFVVNLEGSVVFVSENVTQYLRYNQEELMNKSVYSILHVGDHtEFVKNLLPKSMVNGGSWSGEP--PRRSSHTFNC 200
Cdd:cd00130   1 LPDGVIVLDLDGRILYANPAAEQLLGYSPEELIGKSLLDLIHPEDR-EELRERLENLLSGGEPVTLEVrlRRKDGSVIWV 79

                        90
                ....*....|...
gi 26332829 201 RMLVKPLPDSEEE 213
Cdd:cd00130  80 LVSLTPIRDEGGE 92

PAS fold; The PAS fold corresponds to the structural domain that has previously been defined as PAS and PAC motifs. The PAS fold appears in archaea, eubacteria and eukarya. This domain can bind gases (O2, CO and NO), FAD, 4-hydroxycinnamic acid and NAD+ (Matilla et.al., FEMS Microbiology Reviews, fuab043, 45, 2021, 1. https://doi.org/10.1093/femsre/fuab043).

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 26332829   119 MLEALDGFFFVVNLEGSVVFVSENVTQYLRYNQEELMNKSVYSILHVGDHTEFVKNLL 176
Cdd:pfam00989   6 ILESLPDGIFVVDEDGRILYVNAAAEELLGLSREEVIGKSLLDLIPEEDDAEVAELLR 63

basic helix-loop-helix-Per-ARNT-Sim (bHLH-PAS) domain found in nuclear receptor coactivator 2 (NCoA-2) and similar proteins; NCoA-2, also termed Class E basic helix-loop-helix protein 75 (bHLHe75), or transcriptional intermediary factor 2 (TIF2), or steroid receptor coactivator 2 (SRC-2), or glucocorticoid receptor interacting protein-1 (GRIP1), is a bHLH-PAS transcriptional coactivator for steroid receptors and nuclear receptors. It is required with NCoA-1 to control energy balance between white and brown adipose tissues.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 26332829  28 PSPKRSTEKRNREQENKYIEELAELIFANFNDIDNFNFKPDKCAILKETVKQIRQIKEQEKAAA 91
Cdd:cd18950   1 PSPKRSTEKRNREQENKYIEELAELIFANFNDIDNFNVKPDKCAILKETVKQIRQIKEQEKAAA 64

basic helix-loop-helix-Per-ARNT-Sim (bHLH-PAS) domain found in steroid receptor coactivator (SRC) family; The SRC family of coactivators includes SRC-1 (NcoA-1/p160), SRC-2(TIF2/GRIP1/NcoA-2) and SRC-3(NcoA-3/pCIP/RAC3/ACTR/pCIP/AIB1/TRAM1), which are critical mediators of steroid receptor action. They contain bHLH-PAS domain at the N-terminal that is followed by receptor interacting domain and C-terminal transcriptional activation domain. SRC coactivators interact with nuclear receptors in a ligand-dependent manner and enhance transcriptional activation by the receptor via histone acetylation/methylation.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 26332829  30 PKRSTEKRNREQENKYIEELAELIFANFNDIDNFNFKPDKCAILKETVKQIRQIKEQE 87
Cdd:cd11439   1 NKCLNEKRRREQENKYIEELAELISASISDMDSLSVKPDKCAILQETVKQIRQIKEQE 58

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 26332829    118 MMLEALDGFFFVVNLEGSVVFVSENVTQYLRYNQEELMNKSVYSILHVGDHTEFVKNL 175
Cdd:smart00091   5 AILESLPDGIFVLDLDGRILYANPAAEELLGYSPEELIGKSLLELIHPEDRERVQEAL 62

helix loop helix domain;

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 26332829     35 EKRNREQENKYIEELAELIFANFNdidnfNFKPDKCAILKETVKQIRQIKEQEK 88
Cdd:smart00353   4 ERRRRRKINEAFDELRSLLPTLPK-----NKKLSKAEILRLAIEYIKSLQEELQ 52

basic Helix Loop Helix (bHLH) domain superfamily; bHLH proteins are transcriptional regulators that are found in organisms from yeast to humans. Members of the bHLH superfamily have two highly conserved and functionally distinct regions. The basic part is at the amino end of the bHLH that may bind DNA to a consensus hexanucleotide sequence known as the E box (CANNTG). Different families of bHLH proteins recognize different E-box consensus sequences. At the carboxyl-terminal end of the region is the HLH region that interacts with other proteins to form homo- and heterodimers. bHLH proteins function as a diverse set of regulatory factors because they recognize different DNA sequences and dimerize with different proteins. The bHLH proteins can be divided to cell-type specific and widely expressed proteins. The cell-type specific members of bHLH superfamily are involved in cell-fate determination and act in neurogenesis, cardiogenesis, myogenesis, and hematopoiesis.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|.
gi 26332829  35 EKRNREQENKYIEELAELIFANFNdidnfNFKPDKCAILKETVKQIRQIKE 85
Cdd:cd00083   1 ERRRRDKINDAFEELKRLLPELPD-----SKKLSKASILQKAVEYIRELQS 46

PAS domain [Signal transduction mechanisms];

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 26332829 119 MLEALDGFFFVVNLEGSVVFVSENVTQYLRYNQEELMNKSVySILHVGDHTEFVKNLLPKSMVNGGSWSGEPP--RRSSH 196
Cdd:COG2202  16 LVESSPDAIIITDLDGRILYVNPAFERLTGYSAEELLGKTL-RDLLPPEDDDEFLELLRAALAGGGVWRGELRnrRKDGS 94

                        90
                ....*....|....*..
gi 26332829 197 TFNCRMLVKPLPDSEEE 213
Cdd:COG2202  95 LFWVELSISPVRDEDGE 111

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 26332829  31 KRSTEKRNREQENKYIEELAELIFANFNDIDnfnfKPDKCAILKETVKQIR 81
Cdd:cd11391   4 SREAAKKRRDKENAEISELASLLPLPPAVGS----KLDKLSVLRLAVAYLR 50

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 26332829  35 EKRNREQENKYIEELAELI-FANFNDIDnfnFKPDKCAILKETVKQIRQIKEQ 86
Cdd:cd11387   6 ERRRRDNINEKIQELGSLVpPSRLETKD---LKPNKGSILSKAVEYIRELQNQ 55