Ligand binding domain of hormone receptors;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32563590    192 TSVQNKLAAELCKTCPGVDLLDNEDILILRKYFQFSNVWIESTWNYLRENNSV----------PIDDSELDLKLLKFINQ 261
Cdd:smart00430   1 AERQLLLTVEWAKSFPGFRELSLEDQIVLLKSFWFELLLLELAYRSVKLKKELllapdgtyirPDAVLELRKLFSPFLDR 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32563590    262 VKSTLLVSFSQLKFNTIEFAAFKSICIWKLVYHETSRAMKIIAQEHYESVMKALNDYYQTYTSMDsmqIATRIGEITLLI 341
Cdd:smart00430  81 ILSELVKPLRELKLDDEEYALLKAIVLFNPAVPGLSEEGKEIVEKLQEKYANALHDYYLKNYPMN---YPGRFAKLLLIL 157

                   ....*.
gi 32563590    342 ISVFQM 347
Cdd:smart00430 158 PELRKI 163

Ligand binding domain of hormone receptors;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32563590    192 TSVQNKLAAELCKTCPGVDLLDNEDILILRKYFQFSNVWIESTWNYLRENNSV----------PIDDSELDLKLLKFINQ 261
Cdd:smart00430   1 AERQLLLTVEWAKSFPGFRELSLEDQIVLLKSFWFELLLLELAYRSVKLKKELllapdgtyirPDAVLELRKLFSPFLDR 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32563590    262 VKSTLLVSFSQLKFNTIEFAAFKSICIWKLVYHETSRAMKIIAQEHYESVMKALNDYYQTYTSMDsmqIATRIGEITLLI 341
Cdd:smart00430  81 ILSELVKPLRELKLDDEEYALLKAIVLFNPAVPGLSEEGKEIVEKLQEKYANALHDYYLKNYPMN---YPGRFAKLLLIL 157

                   ....*.
gi 32563590    342 ISVFQM 347
Cdd:smart00430 158 PELRKI 163

DNA-binding domain of nuclear receptors is composed of two C4-type zinc fingers; DNA-binding domain of nuclear receptors is composed of two C4-type zinc fingers. Each zinc finger contains a group of four Cys residues which co-ordinates a single zinc atom. It interacts with a specific DNA site upstream of the target gene and modulates the rate of transcriptional initiation. Nuclear receptors form a superfamily of ligand-activated transcription regulators, which regulate various physiological functions, from development, reproduction, to homeostasis and metabolism in animals (metazoans). The family contains not only receptors for known ligands but also orphan receptors for which ligands do not exist or have not been identified. NRs share a common structural organization with a central well conserved DNA binding domain (DBD), a variable N-terminal domain, a flexible hinge and a C-terminal ligand binding domain (LBD). Most nuclear receptors bind as homodimers or heterodimers to their target sites, which consist of two hexameric half-sites. Specificity is determined by the half-site sequence, the relative orientation of the half-sites and the number of spacer nucleotides between the half-sites. However, a growing number of nuclear receptors have been reported to bind to DNA as monomers.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 32563590  11 CPVCEFPSNvELHFGGLVCGACAAFFRRTVSLNIRYLCEKNNQC---KGMRKNCRACRFDYCVKiAGMKRNLVK 81
Cdd:cd06916   1 CAVCGDKAS-GYHYGVLTCEGCKGFFRRSVRRNLEYTCPAGGNCvidKRNRNRCQACRLKKCLA-VGMRKEAVR 72

The ligand binding domain of nuclear receptors, a family of ligand-activated transcription regulators; Ligand-binding domain (LBD) of nuclear receptor (NR): Nuclear receptors form a superfamily of ligand-activated transcription regulators, which regulate various physiological functions in metazoans, from development, reproduction, to homeostasis and metabolism. The superfamily contains not only receptors for known ligands but also orphan receptors for which ligands do not exist or have not been identified. The members of the family include receptors of steroids, thyroid hormone, retinoids, cholesterol by-products, lipids and heme. With few exceptions, NRs share a common structural organization with a central well conserved DNA binding domain (DBD), a variable N-terminal domain, a non-conserved hinge and a C-terminal ligand binding domain (LBD).

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32563590 186 EEFLEITSVQNKLAAELCKTCPGVDLLDNEDILILRKYFQFSNVWIESTWNYLRENNSV----------PIDDSELDLKL 255
Cdd:cd06157   1 ELLCELATRDLLLIVEWAKSIPGFRELPLEDQIVLLKSFWLELLVLDLAYRSYKNGLSLllapngghtdDDKEDEMKLLL 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32563590 256 LKFINQVKSTLLVSFSQLKFNTIEFAAFKSICIWKLVYHETSRAMKIIAQEHyESVMKALNDYYQtYTSMDsmQIATRIG 335
Cdd:cd06157  81 KGELIRLLFEFVNPLRALKLDDEEYALLKAIVLFSPDRKESLEDRKIVEELQ-ERLLEALQDYLR-KNYPE--EAPSRFA 156

                       170
                ....*....|..
gi 32563590 336 EITLLIISVFQM 347
Cdd:cd06157 157 KLLLLLPSLRKL 168

Ligand binding domain of hormone receptors;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32563590    192 TSVQNKLAAELCKTCPGVDLLDNEDILILRKYFQFSNVWIESTWNYLRENNSV----------PIDDSELDLKLLKFINQ 261
Cdd:smart00430   1 AERQLLLTVEWAKSFPGFRELSLEDQIVLLKSFWFELLLLELAYRSVKLKKELllapdgtyirPDAVLELRKLFSPFLDR 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32563590    262 VKSTLLVSFSQLKFNTIEFAAFKSICIWKLVYHETSRAMKIIAQEHYESVMKALNDYYQTYTSMDsmqIATRIGEITLLI 341
Cdd:smart00430  81 ILSELVKPLRELKLDDEEYALLKAIVLFNPAVPGLSEEGKEIVEKLQEKYANALHDYYLKNYPMN---YPGRFAKLLLIL 157

                   ....*.
gi 32563590    342 ISVFQM 347
Cdd:smart00430 158 PELRKI 163

DNA-binding domain of nuclear receptors is composed of two C4-type zinc fingers; DNA-binding domain of nuclear receptors is composed of two C4-type zinc fingers. Each zinc finger contains a group of four Cys residues which co-ordinates a single zinc atom. It interacts with a specific DNA site upstream of the target gene and modulates the rate of transcriptional initiation. Nuclear receptors form a superfamily of ligand-activated transcription regulators, which regulate various physiological functions, from development, reproduction, to homeostasis and metabolism in animals (metazoans). The family contains not only receptors for known ligands but also orphan receptors for which ligands do not exist or have not been identified. NRs share a common structural organization with a central well conserved DNA binding domain (DBD), a variable N-terminal domain, a flexible hinge and a C-terminal ligand binding domain (LBD). Most nuclear receptors bind as homodimers or heterodimers to their target sites, which consist of two hexameric half-sites. Specificity is determined by the half-site sequence, the relative orientation of the half-sites and the number of spacer nucleotides between the half-sites. However, a growing number of nuclear receptors have been reported to bind to DNA as monomers.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 32563590  11 CPVCEFPSNvELHFGGLVCGACAAFFRRTVSLNIRYLCEKNNQC---KGMRKNCRACRFDYCVKiAGMKRNLVK 81
Cdd:cd06916   1 CAVCGDKAS-GYHYGVLTCEGCKGFFRRSVRRNLEYTCPAGGNCvidKRNRNRCQACRLKKCLA-VGMRKEAVR 72

Zinc finger, C4 type (two domains); In nearly all cases, this is the DNA binding domain of a nuclear hormone receptor. The alignment contains two Zinc finger domains that are too dissimilar to be aligned with each other.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32563590    10 ICPVCEFPSnVELHFGGLVCGACAAFFRRTVSLNIRYLCEKNNQC---KGMRKNCRACRFDYCVKiAGMK 76
Cdd:pfam00105   1 LCKVCGDKA-SGYHYGVLTCEGCKGFFRRSIQKNIVYTCKFNKDCvidKRNRNRCQYCRLKKCLE-VGMS 68

The DNA-binding domain of Lrh-1 like nuclear receptor family like is composed of two C4-type zinc fingers; The DNA-binding domain of Lrh-1 like nuclear receptor family like is composed of two C4-type zinc fingers. Each zinc finger contains a group of four Cys residues which co-ordinates a single zinc atom. This domain interacts with specific DNA sites upstream of the target gene and modulates the rate of transcriptional initiation. This nuclear receptor family includes at least three subgroups of receptors that function in embryo development and differentiation, and other processes. FTZ-F1 interacts with the cis-acting DNA motif of ftz gene, which is required at several stages of development. Particularly, FTZ-F1 regulated genes are strongly linked to steroid biosynthesis and sex-determination; LRH-1 is a regulator of bile-acid homeostasis, steroidogenesis, reverse cholesterol transport and the initial stages of embryonic development; SF-1 is an essential regulator of endocrine development and function and is considered a master regulator of reproduction; SF-1 functions cooperatively with other transcription factors to modulate gene expression. Phospholipids have been identified as potential ligand for LRH-1 and steroidogenic factor-1 (SF-1). However, the ligand for FTZ-F1 has not yet been identified. Most nuclear receptors function as homodimer or heterodimers. However, LRH-1 and SF-1 bind to DNA as monomers. Like other members of the nuclear receptor (NR) superfamily of ligand-activated transcription factors, receptors in this family have a central well conserved DNA-binding domain (DBD), a variable N-terminal domain, a flexible hinge and a C-terminal ligand binding domain (LBD).

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32563590  11 CPVCEfpSNVE-LHFGGLVCGACAAFFRRTVSLNIRYLCEKNNQC---KGMRKNCRACRFDYCVKIaGMKRNLVKQRR-- 84
Cdd:cd07167   1 CPVCG--DKVSgYHYGLLTCESCKGFFKRTVQNKKRYTCIENQNCqidKTQRKRCPYCRFQKCLSV-GMKLEAVRADRmr 77

                        90
                ....*....|....
gi 32563590  85 --NSTNTPMYILNR 96
Cdd:cd07167  78 ggRNKFGPMYKRDR 91

The DNA-binding domain of vitamin D receptors (VDR) like nuclear receptor family is composed of two C4-type zinc fingers; The DNA-binding domain of vitamin D receptors (VDR) like nuclear receptor family is composed of two C4-type zinc fingers. Each zinc finger contains a group of four Cys residues which co-ordinates a single zinc atom. This domain interacts with specific DNA site upstream of the target gene and modulates the rate of transcriptional initiation. This family includes three types of nuclear receptors: vitamin D receptors (VDR), constitutive androstane receptor (CAR) and pregnane X receptor (PXR). VDR regulates calcium metabolism, cellular proliferation and differentiation. PXR and CAR function as sensors of toxic byproducts of cell metabolism and of exogenous chemicals, to facilitate their elimination. The DNA binding activity is regulated by their corresponding ligands. VDR is activated by Vitamin D; CAR and PXR respond to a diverse array of chemically distinct ligands, including many endogenous compounds and clinical drugs. Like other nuclear receptors, xenobiotic receptors have a central well conserved DNA binding domain (DBD), a variable N-terminal domain, a flexible hinge and a C-terminal ligand binding domain (LBD).

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 32563590  23 HFGGLVCGACAAFFRRTVSLNIRYLCEKNNQC---KGMRKNCRACRFDYCVKIaGMKRNLV 80
Cdd:cd07156  12 HFNAMTCEGCKGFFRRSMKRKARFTCPFNGDCeitKDNRRHCQACRLKKCLDI-GMKKEMI 71

The ligand binding domain of nuclear receptors, a family of ligand-activated transcription regulators; Ligand-binding domain (LBD) of nuclear receptor (NR): Nuclear receptors form a superfamily of ligand-activated transcription regulators, which regulate various physiological functions in metazoans, from development, reproduction, to homeostasis and metabolism. The superfamily contains not only receptors for known ligands but also orphan receptors for which ligands do not exist or have not been identified. The members of the family include receptors of steroids, thyroid hormone, retinoids, cholesterol by-products, lipids and heme. With few exceptions, NRs share a common structural organization with a central well conserved DNA binding domain (DBD), a variable N-terminal domain, a non-conserved hinge and a C-terminal ligand binding domain (LBD).

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32563590 186 EEFLEITSVQNKLAAELCKTCPGVDLLDNEDILILRKYFQFSNVWIESTWNYLRENNSV----------PIDDSELDLKL 255
Cdd:cd06157   1 ELLCELATRDLLLIVEWAKSIPGFRELPLEDQIVLLKSFWLELLVLDLAYRSYKNGLSLllapngghtdDDKEDEMKLLL 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32563590 256 LKFINQVKSTLLVSFSQLKFNTIEFAAFKSICIWKLVYHETSRAMKIIAQEHyESVMKALNDYYQtYTSMDsmQIATRIG 335
Cdd:cd06157  81 KGELIRLLFEFVNPLRALKLDDEEYALLKAIVLFSPDRKESLEDRKIVEELQ-ERLLEALQDYLR-KNYPE--EAPSRFA 156

                       170
                ....*....|..
gi 32563590 336 EITLLIISVFQM 347
Cdd:cd06157 157 KLLLLLPSLRKL 168

DNA-binding domain of retinoic acid receptor (RAR) is composed of two C4-type zinc fingers; DNA-binding domain of retinoic acid receptor (RAR) is composed of two C4-type zinc fingers. Each zinc finger contains a group of four Cys residues which co-ordinates a single zinc atom. RAR interacts with specific DNA sites upstream of the target gene and modulates the rate of transcriptional initiation. RARs mediate the biological effect of retinoids, including both natural dietary vitamin A (retinol) metabolites and active synthetic analogs. Retinoids play key roles in a wide variety of essential biological processes, such as vertebrate embryonic morphogenesis and organogenesis, differentiation and apoptosis, and homeostasis. RAR function as a heterodimer with retinoic X receptor by binding to specific RAR response elements (RAREs), which are composed of two direct repeats of the consensus sequence 5'-AGGTCA-3' separated by one to five base pair and found in the promoter regions of retinoid target genes. Like other members of the nuclear receptor (NR) superfamily of ligand-activated transcription factors, retinoic acid receptors have a central well conserved DNA binding domain (DBD), a variable N-terminal domain, a non-conserved hinge and a C-terminal ligand binding domain (LBD).

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 32563590  11 CPVCEFPSNvELHFGGLVCGACAAFFRRTVSLNIRYLCEKNNQC---KGMRKNCRACRFDYCVKiAGMKRNLVKQRRN 85
Cdd:cd06964   7 CFVCQDKSS-GYHYGVSACEGCKGFFRRSIQKNMVYTCHRDKNCiinKVTRNRCQYCRLQKCFE-VGMSKESVRNDRN 82

DNA-binding domain of the photoreceptor cell-specific nuclear receptor (PNR) like proteins is composed of two C4-type zinc fingers; DNA-binding domain of the photoreceptor cell-specific nuclear receptor (PNR) like proteins is composed of two C4-type zinc fingers. Each zinc finger contains a group of four Cys residues which co-ordinates a single zinc atom. PNR interacts with specific DNA sites upstream of the target gene and modulates the rate of transcriptional initiation. PNR is a member of nuclear receptor superfamily of the ligand-activated transcription factors. PNR is expressed only in the outer layer of retinal photoreceptor cells. It may be involved in the signaling pathway regulating photoreceptor differentiation and/or maintenance. It most likely binds to DNA as a homodimer. Like other members of the nuclear receptor (NR) superfamily of ligand-activated transcription factors, PNR has a central well conserved DNA binding domain (DBD), a variable N-terminal domain, a flexible hinge and a C-terminal ligand binding domain (LBD).

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 32563590  23 HFGGLVCGACAAFFRRTVSLNIRYLCEKNNQCK---GMRKNCRACRFDYCVKiAGMKRNLVKQRR 84
Cdd:cd07164  12 HYGVPSCDGCRGFFKRSIRRNLAYVCKENGSCVvdvARRNQCQACRFKKCLQ-VNMNRDAVQHER 75

DNA-binding domain of retinoid X receptor (RXR) is composed of two C4-type zinc fingers; DNA-binding domain of retinoid X receptor (RXR) is composed of two C4-type zinc fingers. Each zinc finger contains a group of four Cys residues which co-ordinates a single zinc atom. RXR functions as a DNA binding partner by forming heterodimers with other nuclear receptors including CAR, FXR, LXR, PPAR, PXR, RAR, TR, and VDR. All RXR heterodimers preferentially bind response elements composed of direct repeats of two AGGTCA sites with a 1-5 bp spacer. RXRs can play different roles in these heterodimers. RXR acts either as a structural component of the heterodimer complex, required for DNA binding but not acting as a receptor, or as both a structural and a functional component of the heterodimer, allowing 9-cis RA to signal through the corresponding heterodimer. In addition, RXR can also form homodimers, functioning as a receptor for 9-cis RA, independently of other nuclear receptors. Like other members of the nuclear receptor (NR) superfamily of ligand-activated transcription factors, RXR has a central well conserved DNA binding domain (DBD), a variable N-terminal domain, a flexible hinge and a C-terminal ligand binding domain (LBD).

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 32563590   9 PICPVCEFPSNVElHFGGLVCGACAAFFRRTVSLNIRYLCEKNNQC---KGMRKNCRACRFDYCVKiAGMKRNLVKQRR 84
Cdd:cd06956   1 HICAICGDRASGK-HYGVYSCEGCKGFFKRTVRKDLTYTCRDNKDClidKRQRNRCQYCRYQKCLA-MGMKREAVQEER 77

DNA-binding domain of ecdysone-induced DHR4 orphan nuclear receptor is composed of two C4-type zinc fingers; DNA-binding domain of ecdysone-induced DHR4 orphan nuclear receptor is composed of two C4-type zinc fingers. Each zinc finger contains a group of four Cys residues which coordinates a single zinc atom. This domain interacts with specific DNA sites upstream of the target gene and modulates the rate of transcriptional initiation. Ecdysone-induced orphan receptor DHR4 is a member of the nuclear receptor family. DHR4 is expressed during the early Drosophila larval development and is induced by ecdysone. DHR4 coordinates growth and maturation in Drosophila by mediating endocrine response to the attainment of proper body size during larval development. Mutations in DHR4 result in shorter larval development which translates into smaller and lighter flies. Like other members of the nuclear receptor (NR) superfamily of ligand-activated transcription factors, DHR4 has a central well conserved DNA binding domain (DBD), a variable N-terminal domain, a flexible hinge and a C-terminal ligand binding domain (LBD).

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 32563590  10 ICPVCEFPSNvELHFGGLVCGACAAFFRRTVSLNIRYLCEKNNQC---KGMRKNCRACRFDYCVKiAGMKRNLVKQRR 84
Cdd:cd07168   8 LCSICEDKAT-GLHYGIITCEGCKGFFKRTVQNKRVYTCVGDGRCeitKAQRNRCQYCRFRKCIR-KGMMLAAVREDR 83

DNA-binding domain of glucocorticoid receptor (GR) is composed of two C4-type zinc fingers; DNA-binding domains of glucocorticoid receptor (GR) and progesterone receptor (PR) are composed of two C4-type zinc fingers. Each zinc finger contains a group of four Cys residues which co-ordinate a single zinc atom. The DBD from both receptors interact with the same hormone response element (HRE), which is an imperfect palindrome GGTACAnnnTGTTCT, upstream of target genes and modulates the rate of transcriptional initiation. GR is a transcriptional regulator that mediates the biological effects of glucocorticoids and PR regulates genes controlled by progesterone. GR is expressed in almost every cell in the body and regulates genes controlling a wide variety of processes including the development, metabolism, and immune response of the organism. PR functions in a variety of biological processes including development of the mammary gland, regulating cell cycle progression, protein processing, and metabolism. Like other members of the nuclear receptor (NR) superfamily of ligand-activated transcription factors, GR and PR have a central well conserved DNA binding domain (DBD), a variable N-terminal domain, a non-conserved hinge and a C-terminal ligand binding domain (LBD).

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 32563590  23 HFGGLVCGACAAFFRRTVSLNIRYLCEKNNQC---KGMRKNCRACRFDYCVKiAGMK 76
Cdd:cd07172  16 HYGVLTCGSCKVFFKRAVEGQHNYLCAGRNDCiidKIRRKNCPACRLRKCLQ-AGMN 71

The DNA binding domain of GR_like nuclear receptors is composed of two C4-type zinc fingers; The DNA binding domain of GR_like nuclear receptors is composed of two C4-type zinc fingers. Each zinc finger contains a group of four Cys residues which co-ordinates a single zinc atom. It interacts with specific DNA sites upstream of the target gene and modulates the rate of transcriptional initiation. This family of NRs includes four types of nuclear hormone receptors: glucocorticoid receptor (GR), mineralocorticoid receptor (MR), progesterone receptor (PR), and androgen receptor (AR). The receptors bind to common DNA elements containing a partial palindrome of the core sequence 5'-TGTTCT-3' with a 3bp spacer. These four receptors regulate some of the most fundamental physiological functions such as the stress response, metabolism, electrolyte homeostasis, immune function, growth, development, and reproduction. The NRs in this family have high sequence homology and share similar functional mechanisms. The dominant mechanism of function is by direct DNA binding and transcriptional regulation of target genes . The GR, MR, PR, and AR exhibit same modular structure. They have a central highly conserved DNA binding domain (DBD), a non-conserved N-terminal domain, a flexible hinge and a C-terminal ligand binding domain (LBD).

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 32563590  23 HFGGLVCGACAAFFRRTVSLNIRYLCEKNNQC---KGMRKNCRACRFDYCVKiAGM 75
Cdd:cd06963  12 HYGVLTCGSCKVFFKRAAEGQHNYLCAGRNDCiidKIRRKNCPACRLRKCYQ-AGM 66

DNA-binding domain of REV-ERB receptor-like is composed of two C4-type zinc fingers; DNA-binding domain of REV-ERB receptor- like is composed of two C4-type zinc fingers. Each zinc finger contains a group of four Cys residues which coordinates a single zinc atom. This domain interacts with specific DNA sites upstream of the target gene and modulates the rate of transcriptional initiation. REV-ERB receptors are transcriptional regulators belonging to the nuclear receptor superfamily. They regulate a number of physiological functions including the circadian rhythm, lipid metabolism, and cellular differentiation. REV-ERB receptors bind as a monomer to a (A/G)GGTCA half-site with a 5' AT-rich extension or as a homodimer to a direct repeat 2 element (AGGTCA sequence with a 2-bp spacer), indicating functional diversity. When bound to the DNA, they recruit corepressors (NcoR/histone deacetylase 3) to the promoter, resulting in repression of the target genes. The porphyrin heme has been demonstrated to function as a ligand for REV-ERB receptor. Like other members of the nuclear receptor (NR) superfamily of ligand-activated transcription factors, REV-ERB receptors have a central well conserved DNA binding domain (DBD), a variable N-terminal domain, a non-conserved hinge and a C-terminal ligand binding domain (LBD).

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 32563590  10 ICPVCEFPSNvELHFGGLVCGACAAFFRRTVSLNIRY-LCEKNNQCKGMRKN---CRACRFDYCVKIaGMKRNLVKQRR 84
Cdd:cd07166   5 LCKVCGDKAS-GFHYGVHACEGCKGFFRRSIQQKIQYrKCTKNETCSIMRINrnrCQYCRFKKCLAV-GMSRDAVRFGR 81

The DNA-binding domain of peroxisome proliferator-activated receptors (PPAR) like nuclear receptor family; The DNA-binding domain of peroxisome proliferator-activated receptors (PPAR) like nuclear receptor family is composed of two C4-type zinc fingers. Each zinc finger contains a group of four Cys residues which co-ordinates a single zinc atom. These domains interact with specific DNA sites upstream of the target gene and modulate the rate of transcriptional initiation. This family includes three known types of nuclear receptors: peroxisome proliferator-activated receptors (PPAR), REV-ERB receptors and Drosophila ecdysone-induced protein 78 (E78). Like other members of the nuclear receptor (NR) superfamily of ligand-activated transcription factors, PPAR-like receptors have a central well conserved DNA binding domain (DBD), a variable N-terminal domain, a non-conserved hinge and a C-terminal ligand binding domain (LBD).

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 32563590  23 HFGGLVCGACAAFFRRTVSLNIRYL-CEKNNQCKGMRKN---CRACRFDYCVkIAGMKRNLVK 81
Cdd:cd07158  12 HYGVHSCEGCKGFFRRTIQHNLTYRrCLNGGKCVIQRKNrnrCQYCRFKKCL-SVGMSRNAVR 73

DNA-binding domain of Drosophila ecdysone-induced protein 78 (E78) like is composed of two C4-type zinc fingers; DNA-binding domain of proteins similar to Drosophila ecdysone-induced protein 78 (E78) is composed of two C4-type zinc fingers. Each zinc finger contains a group of four Cys residues which coordinates a single zinc atom. E78 interacts with specific DNA sites upstream of the target gene and modulates the rate of transcriptional initiation. Drosophila ecdysone-induced protein 78 (E78) is a transcription factor belonging to the nuclear receptor superfamily. E78 is a product of the ecdysone-inducible gene found in an early late puff locus at position 78C during the onset of Drosophila metamorphosis. An E78 orthologue from the Platyhelminth Schistosoma mansoni (SmE78) has also been identified. It is the first E78 orthologue known outside of the molting animals--the Ecdysozoa. The SmE78 may be involved in transduction of an ecdysone signal in S. mansoni, consistent with its function in Drosophila. Like other members of the nuclear receptor (NR) superfamily of ligand-activated transcription factors, E78-like receptors have a central well conserved DNA-binding domain (DBD), a variable N-terminal domain, a non-conserved hinge and a C-terminal ligand binding domain (LBD).

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 32563590  11 CPVCEFPSNvELHFGGLVCGACAAFFRRTVSLNIRYLCEKNNQCKGMRKN---CRACRFDYCVKiAGMKRNLVKQRR 84
Cdd:cd07165   1 CKVCGDKAS-GYHYGVTSCEGCKGFFRRSIQKQIEYRCLRDGKCEIIRLNrnrCQYCRFKKCLA-AGMSKDSVRYGR 75

The DNA-binding domain of the photoreceptor cell-specific nuclear receptor (PNR) nuclear receptor-like family; The DNA-binding domain of the photoreceptor cell-specific nuclear receptor (PNR) nuclear receptor-like family is composed of two C4-type zinc fingers. Each zinc finger contains a group of four Cys residues which coordinates a single zinc atom. PNR interacts with specific DNA sites upstream of the target gene and modulates the rate of transcriptional initiation. This family includes nuclear receptor Tailless (TLX), photoreceptor cell-specific nuclear receptor (PNR) and related receptors. TLX is an orphan receptor that plays a key role in neural development by regulating cell cycle progression and exit of neural stem cells in the developing brain. PNR is expressed only in the outer layer of retinal photoreceptor cells. It may be involved in the signaling pathway regulating photoreceptor differentiation and/or maintenance. Like other members of the nuclear receptor (NR) superfamily of ligand-activated transcription factors, PNR-like receptors have a central well-conserved DNA-binding domain (DBD), a variable N-terminal domain, a flexible hinge and a C-terminal ligand binding domain (LBD).

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 32563590  11 CPVCEFPSNVElHFGGLVCGACAAFFRRTVSLNIRYLCEKNN-QC---KGMRKNCRACRFDYCVKiAGMKRNLVK 81
Cdd:cd07154   1 CKVCGDRSSGK-HYGVYACDGCSGFFKRSIRRNLLYTCKAGNgSCvvdKARRNQCQACRLKKCLE-VSMNKDAVQ 73

DNA-binding domain of chicken ovalbumin upstream promoter transcription factors (COUP-TFs) is composed of two C4-type zinc fingers; DNA-binding domain of chicken ovalbumin upstream promoter transcription factors (COUP-TFs) is composed of two C4-type zinc fingers. Each zinc finger contains a group of four Cys residues which co-ordinates a single zinc atom. COUP-TFs are orphan members of the steroid/thyroid hormone receptor superfamily. They are expressed in many tissues and are involved in the regulation of several important biological processes, such as neurogenesis, organogenesis, cell fate determination, and metabolic homeostasis. COUP-TFs homodimerize or heterodimerize with retinoid X receptor (RXR) and a few other nuclear receptors and bind to a variety of response elements that are composed of imperfect AGGTCA direct or inverted repeats with various spacings. COUP-TFs are generally considered to be repressors of transcription for other nuclear hormone receptors such as retinoic acid receptor (RAR), thyroid hormone receptor (TR), vitamin D receptor (VDR), peroxisome proliferator activated receptor (PPAR), and hepatocyte nuclear factor 4 (HNF4). Like other members of the nuclear receptor (NR) superfamily of ligand-activated transcription factors, COUP-TFs have a central well conserved DNA binding domain (DBD), a variable N-terminal domain, a flexible hinge and a C-terminal ligand binding domain (LBD).

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 32563590  11 CPVCEFPSNVElHFGGLVCGACAAFFRRTVSLNIRYLCEKNNQC---KGMRKNCRACRFDYCVKIaGMKRNLVK 81
Cdd:cd06958   1 CVVCGDKSSGK-HYGQFTCEGCKSFFKRSVRRNLTYTCRGNRNCpidQHHRNQCQYCRLKKCLKV-GMRREAVQ 72

DNA-binding domain of the photoreceptor cell-specific nuclear receptor (PNR) like is composed of two C4-type zinc fingers; The DNA-binding domain of the photoreceptor cell-specific nuclear receptor (PNR) nuclear receptor-like family is composed of two C4-type zinc fingers. Each zinc finger contains a group of four Cys residues which coordinates a single zinc atom. PNR interacts with specific DNA sites upstream of the target gene and modulates the rate of transcriptional initiation. This family includes nuclear receptor Tailless (TLX), photoreceptor cell-specific nuclear receptor (PNR) and related receptors. TLX is an orphan receptor that plays a key role in neural development by regulating cell cycle progression and exit of neural stem cells in the developing brain. PNR is expressed only in the outer layer of retinal photoreceptor cells. It may be involved in the signaling pathway regulating photoreceptor differentiation and/or maintenance. Like other members of the nuclear receptor (NR) superfamily of ligand-activated transcription factors, PNR-like receptors have a central well-conserved DNA-binding domain (DBD), a variable N-terminal domain, a flexible hinge and a C-terminal ligand binding domain (LBD).

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32563590  11 CPVCEFPSNVElHFGGLVCGACAAFFRRTVSLNIRYLC-EKNNQC---KGMRKNCRACRFDYCVKIaGMKRNLVKQRRNS 86
Cdd:cd06957   1 CKVCGDKSYGK-HYGVYCCDGCSCFFKRSVRKGIIYTCiAGNGNCvvdKARRNWCPFCRLQKCFAV-GMNRAAVQEERGP 78

                ...
gi 32563590  87 TNT 89
Cdd:cd06957  79 RKL 81

DNA-binding domain of peroxisome proliferator-activated receptors (PPAR) is composed of two C4-type zinc fingers; DNA-binding domain of peroxisome proliferator-activated receptors (PPAR) is composed of two C4-type zinc fingers. Each zinc finger contains a group of four Cys residues which co-ordinates a single zinc atom. PPAR interacts with specific DNA sites upstream of the target gene and modulates the rate of transcriptional initiation. Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear receptor superfamily of ligand-activated transcription factors. PPARs play important roles in regulating cellular differentiation, development and lipid metabolism. Activated PPAR forms a heterodimer with the retinoid X receptor (RXR) that binds to the hormone response elements, which are composed of two direct repeats of the consensus sequence 5'-AGGTCA-3' separated by one to five base pair located upstream of the peroxisome proliferator responsive genes, and interacts with co-activators. Several essential fatty acids, oxidized lipids and prostaglandin J derivatives can bind and activate PPAR. Like other members of the nuclear receptor (NR) superfamily of ligand-activated transcription factors, PPAR has a central well conserved DNA binding domain (DBD), a variable N-terminal regulatory domain, a flexible hinge and a C-terminal ligand binding domain (LBD).

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 32563590  22 LHFGGLVCGACAAFFRRTVSLNIRY-LCEKNnqCK---GMRKNCRACRFDYCVkIAGMKRNLVKQRR 84
Cdd:cd06965  12 FHYGVHACEGCKGFFRRTIRLKLVYkPCDLS--CKihkKSRNKCQYCRFQKCL-NVGMSHNAIRFGR 75