basic helix-loop-helix-Per-ARNT-Sim (bHLH-PAS) domain found in Drosophila melanogaster protein spineless and similar proteins; Spineless is a bHLH-PAS transcription factor that plays an important role in fly morphogenesis. It is both necessary and sufficient for the formation of the ommatidial mosaic.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 386765906   24 PKDGVTKSNPSKRHRERLNAELDLLASLLPFEQNILSKLDRLSILRLSVSYLRTKSYFQVVMHK 87
Cdd:cd19730     1 PKDHPTKSNPSKRHRERLNAELDHLASLLPFEQSVISKLDKLSILRLSVSYLRTKSYFQAVLQK 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.

                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|....*.
gi 386765906    123 LQALNGFLMILTCEGEVFFATHSIESYLGFHQSDIVHQSVYELVHSEDREELQRQL 178
Cdd:smart00091    7 LESLPDGIFVLDLDGRILYANPAAEELLGYSPEELIGKSLLELIHPEDRERVQEAL 62

basic helix-loop-helix-Per-ARNT-Sim (bHLH-PAS) domain found in Drosophila melanogaster protein spineless and similar proteins; Spineless is a bHLH-PAS transcription factor that plays an important role in fly morphogenesis. It is both necessary and sufficient for the formation of the ommatidial mosaic.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 386765906   24 PKDGVTKSNPSKRHRERLNAELDLLASLLPFEQNILSKLDRLSILRLSVSYLRTKSYFQVVMHK 87
Cdd:cd19730     1 PKDHPTKSNPSKRHRERLNAELDHLASLLPFEQSVISKLDKLSILRLSVSYLRTKSYFQAVLQK 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 386765906  291 ILGYADAELVNMGGYDLVHYDDLAYVASAHQELLKTGASGMIAYRYQKKDGEWQWLQTSSRLVYK-NSKPDFVICTHRQL 369
Cdd:cd00130    24 LLGYSPEELIGKSLLDLIHPEDREELRERLENLLSGGEPVTLEVRLRRKDGSVIWVLVSLTPIRDeGGEVIGLLGVVRDI 103

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
                  ....*....|....*....|....*....|....*....|....*....|...
gi 386765906  126 LNGFLMILTCEGEVFFATHSIESYLGFHQSDIVHQSVYELVHSEDREELQRQL 178
Cdd:cd00130     1 LPDGVIVLDLDGRILYANPAAEQLLGYSPEELIGKSLLDLIHPEDREELRERL 53

PAS domain [Signal transduction mechanisms];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386765906  277 LDFSLVSMDQRGKHILGYADAELVNMGGYDLVHYDDLAYVASAHQELLKTGA-SGMIAYRYQKKDGEWQWLQTSSRLVYK 355
Cdd:COG2202   155 LDGRILYVNPAAEELLGYSPEELLGKSLLDLLHPEDRERLLELLRRLLEGGReSYELELRLKDGDGRWVWVEASAVPLRD 234

                          90
                  ....*....|..
gi 386765906  356 NSKPDFVICTHR 367
Cdd:COG2202   235 GGEVIGVLGIVR 246

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 386765906   291 ILGYADAELVNMGGYDLVHYDDLAYVASAHQELLKTGASGM-IAYRYQKKDGEWQWLQTSSRLVYKNSKPDFVICTHR 367
Cdd:TIGR00229   35 IFGYSAEELIGRNVLELIPEEDREEVRERIERRLEGEPEPVsEERRVRRKDGSEIWVEVSVSPIRTNGGELGVVGIVR 112

Helix-loop-helix DNA-binding domain;

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|..
gi 386765906    35 KRHRERLNAELDLLASLLPFeQNILSKLDRLSILRLSVSYLR 76
Cdd:pfam00010   10 RRRRDRINDAFDELRELLPT-LPPDKKLSKAEILRLAIEYIK 50

basic helix-loop-helix-Per-ARNT-Sim (bHLH-PAS) domain found in Drosophila melanogaster protein spineless and similar proteins; Spineless is a bHLH-PAS transcription factor that plays an important role in fly morphogenesis. It is both necessary and sufficient for the formation of the ommatidial mosaic.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 386765906   24 PKDGVTKSNPSKRHRERLNAELDLLASLLPFEQNILSKLDRLSILRLSVSYLRTKSYFQVVMHK 87
Cdd:cd19730     1 PKDHPTKSNPSKRHRERLNAELDHLASLLPFEQSVISKLDKLSILRLSVSYLRTKSYFQAVLQK 64

basic helix-loop-helix-Per-ARNT-Sim (bHLH-PAS) domain found in aryl hydrocarbon receptor repressor (AhRR) and similar proteins; AhRR, also termed AhR repressor, or Class E basic helix-loop-helix protein 77 (bHLHe77), is a member of bHLH-PAS transcription factors that acts as a negative regulator of AhR (or Dioxin Receptor), playing key roles in development and environmental sensing. AhR is activated by Dioxin to control the expression of certain genes to influence biological processes such as apoptosis, proliferation, cell growth and differentiation. To form active DNA binding complexes, AhR dimerizes with a bHLH-PAS factor ARNT (Aryl hydrocarbon Nuclear Receptor Translocator). AhRR functions by competing with AhR for its partner ARNT. AhRR-ARNT complexes are transcriptionally inactive.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 386765906   27 GVTKSNPSKRHRERLNAELDLLASLLPFEQNILSKLDRLSILRLSVSYLRTKSYFQVV 84
Cdd:cd11435     1 GSEKSNPSKRHRDRLNAELDHLASLLPFPPDIISKLDKLSVLRLSVSYLRVKSFFQAI 58

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 386765906   282 VSMDQRGKHILGYADAELVNMG--GYDLVHYDDLAYVASAHQELLKTGASGMIAYRYQKKDGEWQWLQTSSRLVY-KNSK 358
Cdd:pfam08447    2 IYWSPRFEEILGYTPEELLGKGesWLDLVHPDDRERVREALWEALKGGEPYSGEYRIRRKDGEYRWVEARARPIRdENGK 81

                   ....*...
gi 386765906   359 PDFVICTH 366
Cdd:pfam08447   82 PVRVIGVA 89

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 386765906   30 KSNPSKRHRERLNAELDLLASLLPFEQNILSKLDRLSILRLSVSYLRTKSYF 81
Cdd:cd11391     4 SREAAKKRRDKENAEISELASLLPLPPAVGSKLDKLSVLRLAVAYLRLKKFL 55

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 386765906   32 NPSKRHRERLNAELDLLASLLPFEQNILSKLDRLSILRLSVSYLRTKSYF 81
Cdd:cd11434     7 NAARTRREKENAEFYELAKLLPLPSAITSQLDKASIIRLTTSYLKMRAVF 56

basic helix-loop-helix-Per-ARNT-Sim (bHLH-PAS) domain found in Drosophila melanogaster protein single-minded (SIM) and similar proteins; 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.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 386765906   32 NPSKRHRERLNAELDLLASLLPFEQNILSKLDRLSILRLSVSYLRTKSYF 81
Cdd:cd19740     7 NAARSRREKENAEFLELAKLLPLPAAITSQLDKASIIRLTTSYLKMRQVF 56

basic helix-loop-helix-Per-ARNT-Sim (bHLH-PAS) domain found in single-minded homolog 2 (SIM2) and similar proteins; SIM2, also termed Class E basic helix-loop-helix protein 15 (bHLHe15), is a bHLH-PAS transcription factor that may be a master gene of central nervous system (CNS) development in cooperation with ARNT. It may have pleiotropic effects in the tissues expressed during development.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 386765906   32 NPSKRHRERLNAELDLLASLLPFEQNILSKLDRLSILRLSVSYLRTKSYF 81
Cdd:cd19739     7 NAAKTRREKENGEFYELAKLLPLPSAITSQLDKASIIRLTTSYLKMRAVF 56

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
                  ....*....|....*....|....*....|....*....|....*....
gi 386765906   32 NPSKRHRERLNAELDLLASLLPFEQNILSKLDRLSILRLSVSYLRTKSY 80
Cdd:cd11432     6 NAARSRRGKENYEFYELAKLLPLPAAISSQLDKASIVRLTISYLKLRDF 54

basic helix-loop-helix-Per-ARNT-Sim (bHLH-PAS) domain found in aryl hydrocarbon receptor nuclear translocator (ARNT) family; The ARNT family of bHLH-PAS transcription regulators includes ARNT, ARNT-like proteins (ARNTL and ARNTL2), and Drosophila melanogaster protein cycle. They act as the heterodimeric partner for bHLH-PAS proteins such as aryl hydrocarbon receptor (AhR), hypoxia-inducible factor (HIF), and single-minded (SIM). These bHLH-PAS transcription complexes are involved in transcriptional responses to xenobiotic, hypoxia, and developmental pathways. Heterodimerization of bHLH-PAS proteins with ARNT is mediated by contacts between both the bHLH and the tandem PAS domains. ARNT use bHLH and/or PAS domains to interact with several transcriptional coactivators. It is required for activity of the aryl hydrocarbon (dioxin) receptor. ARNTL, also termed Basic-helix-loop-helix-PAS protein MOP3, or brain and muscle ARNT-like 1 (BMAL1), or Class E basic helix-loop-helix protein 5 (bHLHe5), or member of PAS protein 3, or PAS domain-containing protein 3 (PASD3), or bHLH-PAS protein JAP3, is a member of the bHLH-PAS transcription factor family that forms heterodimers with another bHLH-PAS protein, CLOCK (circadian locomotor output cycle kaput), which regulates circadian rhythm. ARNTL-CLOCK heterodimer complex activates transcription from E-box (CANNTG) elements found in the promoter of circadian responsive genes. ARNTL is highly homologous to ARNT. ARNTL2, also termed Basic-helix-loop-helix-PAS protein MOP9, or brain and muscle ARNT-like 2 (BMAL2), or CYCLE-like factor (CLIF), or Class E basic helix-loop-helix protein 6 (bHLHe6), or member of PAS protein 9, or PAS domain-containing protein 9 (PASD9), is a neuronal bHLH-PAS transcriptional factor, regulating cell cycle progression and preventing cell death, whose sustained expression might ensure brain neuron survival. It also plays important roles in tumor angiogenesis. Protein cycle, also termed brain and muscle ARNT-like 1 (BMAL1), or MOP3, is a putative bHLH-PAS transcription factor involved in the generation of biological rhythms in Drosophila. It activates cycling transcription of Period (PER) and Timeless (TIM) by binding to the E-box (5'-CACGTG-3') present in their promoters.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 386765906   30 KSNPS---KRHRERLNAELDLLASLLPFEQNILSKLDRLSILRLSVSYLRT 77
Cdd:cd11437     2 RSNHSeieKRRRDKMNAYIQELSALVPACNAMSRKLDKLTVLRMAVQHLKS 52

PAS domain [Signal transduction mechanisms];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386765906  277 LDFSLVSMDQRGKHILGYADAELVNMGGYDLVHYDDLAYVASAHQELLKTGA-SGMIAYRYQKKDGEWQWLQTSSRLVYK 355
Cdd:COG2202   155 LDGRILYVNPAAEELLGYSPEELLGKSLLDLLHPEDRERLLELLRRLLEGGReSYELELRLKDGDGRWVWVEASAVPLRD 234

                          90
                  ....*....|..
gi 386765906  356 NSKPDFVICTHR 367
Cdd:COG2202   235 GGEVIGVLGIVR 246

basic helix-loop-helix-Per-ARNT-Sim (bHLH-PAS) domain found in hypoxia-inducible factor (HIF) family; The HIF family contains bHLH-PAS transcription regulators involved in oxygen homeostasis, including HIF1a, HIF2a, and HIF3a. They have been implicated in development, postnatal physiology as well as disease pathogenesis. HIF1a, also termed HIF-1-alpha, or HIF1-alpha, or ARNT-interacting protein, or Basic-helix-loop-helix-PAS protein MOP1, or Class E basic helix-loop-helix protein 78 (bHLHe78), or Member of PAS protein 1, or PAS domain-containing protein 8 (PASD8), functions as a master transcriptional regulator of the adaptive response to hypoxia. HIF2a, also termed HIF-2-alpha, or HIF2-alpha, or endothelial PAS domain-containing protein 1 (EPAS-1), or Basic-helix-loop-helix-PAS protein MOP2, or Class E basic helix-loop-helix protein 73 (bHLHe73), or Member of PAS protein 2, or PAS domain-containing protein 2 (PASD2), or HIF-1-alpha-like factor (HLF), is a bHLH-PAS transcription factor involved in the induction of oxygen regulated genes. HIF3a, also termed HIF-3-alpha, or HIF3-alpha, or endothelial PAS domain-containing protein 1 (EPAS-1), or Basic-helix-loop-helix-PAS protein MOP7, or Class E basic helix-loop-helix protein 17 (bHLHe17), or Member of PAS protein 7, or PAS domain-containing protein 7 (PASD7), or HIF3-alpha-1, or inhibitory PAS domain protein (IPAS), is a bHLH-PAS transcriptional regulator in adaptive response to low oxygen tension. It plays a role in the regulation of hypoxia-inducible gene expression.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 386765906   38 RERLNAELDL---LASLLPFEQNILSKLDRLSILRLSVSYLRTKS 79
Cdd:cd11433    10 RCRRGKESEIfyeLAHQLPLPHSVSSQLDKASIMRLTISYLKLRK 54

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 386765906   122 FLQALNGFLMILTCEGEVFFATHSIESYLGFHQSDIVHQSVYELVHSEDREELQRQLLW 180
Cdd:pfam00989    6 ILESLPDGIFVVDEDGRILYVNAAAEELLGLSREEVIGKSLLDLIPEEDDAEVAELLRQ 64

basic helix-loop-helix-Per-ARNT-Sim (bHLH-PAS) domain found in neuronal PAS domain-containing protein 1 (NPAS1) and similar proteins; NPAS1, also termed neuronal PAS1, or Basic-helix-loop-helix-PAS protein MOP5, or Class E basic helix-loop-helix protein 11 (bHLHe11), or member of PAS protein 5, or PAS domain-containing protein 5 (PASD5), is a bHLH-PAS transcriptional repressor expressed in the central nervous system and involved in neuronal differentiation. It is active during late embryogenesis and postnatal development.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 386765906   32 NPSKRHRERLNAELDLLASLLPFEQNILSKLDRLSILRLSVSYLRTKSY 80
Cdd:cd19731    10 NAARSRRGKENFEFYELAKMLPLPGAITSQLDKASIVRLTISYLKMRDF 58

basic helix-loop-helix-Per-ARNT-Sim (bHLH-PAS) domain found in neuronal PAS domain-containing protein 4 (NPAS4) and similar proteins; NPAS4, also termed neuronal Per-Arnt-Sim homology (PAS) factor 4, or neuronal PAS4, or Class E basic helix-loop-helix protein 79 (bHLHe79), or HLH-PAS transcription factor NXF, or PAS domain-containing protein 10 (PASD10), is a bHLH-PAS neuronal activity-dependent transcription factor which heterodimerizes with ARNT2 to regulate genes involved in inhibitory synapse formation.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 386765906   34 SKRHRERLNAELDLLASLLPFEQNILSKLDRLSILRLSVSYLRTKSYFQ 82
Cdd:cd19697     8 SKQRRDLINAEIRELRDLLPLPESTRQRLSQLQIMSLACVYIRKSNFFS 56

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
                  ....*....|....*....|....*....|....*....|....*..
gi 386765906   31 SNPSKRHRERLNAELDLLASLLPFEQNILSKLDRLSILRLSVSYLRT 77
Cdd:cd11469     6 SQTEKRRRDKMNNLIEELSAMIPQCNPMARKLDKLTVLRMAVQHLKS 52

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
                    ....*....|....*....|....*....|....*
gi 386765906    334 YRYQKKDGEWQWLQTSSRLVY-KNSKPDFVICTHR 367
Cdd:smart00086    4 YRLRRKDGSYIWVLVSASPIRdEDGEVEGILGVVR 38

basic helix-loop-helix-Per-ARNT-Sim (bHLH-PAS) domain found in hypoxia-inducible factor 1-alpha (HIF1a) and similar proteins; HIF1a, also termed HIF-1-alpha, or HIF1-alpha, or ARNT-interacting protein, or Basic-helix-loop-helix-PAS protein MOP1, or Class E basic helix-loop-helix protein 78 (bHLHe78), or Member of PAS protein 1, or PAS domain-containing protein 8 (PASD8), functions as a master transcriptional regulator of the adaptive response to hypoxia.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 386765906   30 KSNPSKRHRERLNAELDL-LASLLPFEQNILSKLDRLSILRLSVSYLRTK 78
Cdd:cd19727     9 KSRDAARSRRSKESEVFYeLAHQLPLPHNVSSHLDKASIMRLTISYLRMR 58

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

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 386765906   35 KRHRERLNAELDLLASLLP--FEQNILSKLDRLSILRLSVSYLRT 77
Cdd:cd11389     6 KRRRDRINESLAELRRLVPeaRKSKGSGKLEKAEILEMTLQHLKA 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.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 386765906   35 KRHRERLNAELDLLASLLP--FEQNILSKLDRLSILRLSVSYLRT 77
Cdd:cd11407    10 KRRRDRINNSLAELRRLVPtaFEKQGSAKLEKAEILQMTVDHLKM 54

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 386765906   35 KRHRERLNAELDLLASLLP--FEQNILSKLDRLSILRLSVSYLR 76
Cdd:cd19685     3 KRRRQRINDKLNQLKELLPpnLSKQSRSKLSKAEILEMAITELR 46