c4 zinc finger in nuclear hormone receptors;

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1017465576    6 LCSICSRPAQGYHYDVISCKGCKTFFRRMWLSKIKEMCPLNNKCFDFNRRINmslsKCRACRFQRCLNVGMNP 78
Cdd:smart00399   1 LCCVCGDHASGFHFGVCSCRACKAFFRRTVNLRYKYRCDRKNNCSINKRYRC----RCRACRLKKCLGVGMDP 69

c4 zinc finger in nuclear hormone receptors;

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1017465576    6 LCSICSRPAQGYHYDVISCKGCKTFFRRMWLSKIKEMCPLNNKCFDFNRRINmslsKCRACRFQRCLNVGMNP 78
Cdd:smart00399   1 LCCVCGDHASGFHFGVCSCRACKAFFRRTVNLRYKYRCDRKNNCSINKRYRC----RCRACRLKKCLGVGMDP 69

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 1017465576   6 LCSICSRPAQGYHYDVISCKGCKTFFRRMWLSKIKEMCPLNNKC-FDFNRRinmslSKCRACRFQRCLNVGMN 77
Cdd:pfam00105   1 LCKVCGDKASGYHYGVLTCEGCKGFFRRSIQKNIVYTCKFNKDCvIDKRNR-----NRCQYCRLKKCLEVGMS 68

Ligand-binding domain of nuclear hormone receptor; This all helical domain is involved in binding the hormone in these receptors.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1017465576 194 MLTTIEYFKTFKFFHELSSRDKFVLARH--------------------TLLLCQNLHISHYTVSHNFDSCLQPDGSMQPK 253
Cdd:pfam00104  24 LLLVAEWAKHFPEFQELPLEDQMALLKSfwlewlrlekaarsaklrrkKILGEDVLMISDDDAMKFVEDDSSWCTNYDLE 103

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1017465576 254 QDERHYPIAMMS----IEPLVRCKIQHVEYVLLKAICFCNPAVPELSQNAQRILAKERYCFADILINHCLRNYtdgPGHF 329
Cdd:pfam00104 104 QLLFFLPFFNSYffelVKPLRELNPDDEELAYLLAQLLFDYAGDGLSGEILEIVEKLQEKLANELHDYYVNKY---SGRL 180

                         170
                  ....*....|..
gi 1017465576 330 AELIGIFNLLET 341
Cdd:pfam00104 181 AKLLKILPSLRK 192

c4 zinc finger in nuclear hormone receptors;

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1017465576    6 LCSICSRPAQGYHYDVISCKGCKTFFRRMWLSKIKEMCPLNNKCFDFNRRINmslsKCRACRFQRCLNVGMNP 78
Cdd:smart00399   1 LCCVCGDHASGFHFGVCSCRACKAFFRRTVNLRYKYRCDRKNNCSINKRYRC----RCRACRLKKCLGVGMDP 69

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 1017465576   7 CSICSRPAQGYHYDVISCKGCKTFFRRMWLSKIKEMCPLNNKCfdfnrRINMSL-SKCRACRFQRCLNVGMNPAAIQ 82
Cdd:cd06916     1 CAVCGDKASGYHYGVLTCEGCKGFFRRSVRRNLEYTCPAGGNC-----VIDKRNrNRCQACRLKKCLAVGMRKEAVR 72

DNA-binding domain of estrogen receptors (ER) is composed of two C4-type zinc fingers; DNA-binding domain of estrogen receptors (ER) is composed of two C4-type zinc fingers. Each zinc finger contains a group of four Cys residues which coordinates a single zinc atom. ER interacts with specific DNA sites upstream of the target gene and modulates the rate of transcriptional initiation. Estrogen receptor is a transcription regulator that mediates the biological effects of hormone estrogen. The binding of estrogen to the receptor triggers the dimerization and the binding of the receptor dimer to estrogen response element, which is a palindromic inverted repeat: 5'GGTCAnnnTGACC-3', of target genes. Through ER, estrogen regulates development, reproduction and homeostasis. Like other members of the nuclear receptor (NR) superfamily of ligand-activated transcription factors, ER has 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 1017465576   5 HLCSICSRPAQGYHYDVISCKGCKTFFRRMWLSKIKEMCPLNNKC-FDFNRRinmslSKCRACRFQRCLNVGMN 77
Cdd:cd07171     4 HFCAVCSDYASGYHYGVWSCEGCKAFFKRSIQGHNDYICPATNQCtIDKNRR-----KSCQACRLRKCYEVGMM 72

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        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1017465576   7 CSICSRPAQGYHYDVISCKGCKTFFRRMWLSKIKEMCPLNNKCF--DFNRRinmslsKCRACRFQRCLNVGM 76
Cdd:cd07156     1 CGVCGDRATGYHFNAMTCEGCKGFFRRSMKRKARFTCPFNGDCEitKDNRR------HCQACRLKKCLDIGM 66

DNA-binding domain of estrogen receptor (ER) and estrogen related receptors (ERR) is composed of two C4-type zinc fingers; DNA-binding domains of estrogen receptor (ER) and estrogen related receptors (ERR) are composed of two C4-type zinc fingers. Each zinc finger contains a group of four Cys residues which co-ordinates a single zinc atom. ER and ERR interact with the palindromic inverted repeat, 5'GGTCAnnnTGACC-3', upstream of the target gene and modulate the rate of transcriptional initiation. ERR and ER are closely related and share sequence similarity, target genes, co-regulators and promoters. While ER is activated by endogenous estrogen, ERR lacks the ability to bind to estrogen. Estrogen receptor mediates the biological effects of hormone estrogen by the binding of the receptor dimer to estrogen response element of target genes. However, ERRs seem to interfere with the classic ER-mediated estrogen responsive signaling by targeting the same set of genes. ERRs and ERs exhibit the common modular structure with other nuclear receptors. 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        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1017465576   7 CSICSRPAQGYHYDVISCKGCKTFFRRMWLSKIKEMCPLNNKC-FDFNRRinmslSKCRACRFQRCLNVGM 76
Cdd:cd07155     1 CLVCGDIASGYHYGVASCEACKAFFKRTIQGNLGYSCPSTSECeVDKKRR-----KSCQACRLQKCLKVGM 66

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        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1017465576   7 CSICSRPAQGYHYDVISCKGCKTFFRRMWLSKIKEMCPLNNKC-FDFNRRinmslSKCRACRFQRCLNVGMNPAAIQCDG 85
Cdd:cd07164     1 CRVCGDRASGKHYGVPSCDGCRGFFKRSIRRNLAYVCKENGSCvVDVARR-----NQCQACRFKKCLQVNMNRDAVQHER 75

                  ...
gi 1017465576  86 NPK 88
Cdd:cd07164    76 APR 78

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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1017465576   6 LCSICSRPAQGYHYDVISCKGCKTFFRRMWLSKIK-EMCPLNNKCFDFnrRINMslSKCRACRFQRCLNVGMNPAAIQCD 84
Cdd:cd07166     5 LCKVCGDKASGFHYGVHACEGCKGFFRRSIQQKIQyRKCTKNETCSIM--RINR--NRCQYCRFKKCLAVGMSRDAVRFG 80

                  ....*.
gi 1017465576  85 GNPKKD 90
Cdd:cd07166    81 RIPKRE 86

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        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1017465576   6 LCSICSRPAQGYHYDVISCKGCKTFFRR-MWLSKIKEMCPLNNKCFDFNRrinmslSKCRACRFQRCLNVGMNPAAIQCD 84
Cdd:cd06965     1 ECRVCGDKASGFHYGVHACEGCKGFFRRtIRLKLVYKPCDLSCKIHKKSR------NKCQYCRFQKCLNVGMSHNAIRFG 74

                  ....
gi 1017465576  85 GNPK 88
Cdd:cd06965    75 RMPR 78

DNA-binding domain of Germ cell nuclear factor (GCNF) F1 is composed of two C4-type zinc fingers; DNA-binding domain of Germ cell nuclear factor (GCNF) F1 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. GCNF is a transcription factor expressed in post-meiotic stages of developing male germ cells. In vitro, GCNF has the ability to bind to direct repeat elements of 5'-AGGTCA.AGGTCA-3', as well as to an extended half-site sequence 5'-TCA.AGGTCA-3'. Like other members of the nuclear receptor (NR) superfamily of ligand-activated transcription factors, GCNF 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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1017465576   7 CSICSRPAQGYHYDVISCKGCKTFFRRMWLSKIKEMCPLNNKCFDFNRRINmslsKCRACRFQRCLNVGMNPAAIQCDGN 86
Cdd:cd07169     9 CLICGDRATGLHYGIISCEGCKGFFKRSICNKRVYRCSRDKNCVMSRKQRN----RCQYCRLLKCLQMGMNRKAIREDGM 84

                  .
gi 1017465576  87 P 87
Cdd:cd07169    85 P 85

DNA-binding domain of vitamin D receptors (VDR) is composed of two C4-type zinc fingers; DNA-binding domain of vitamin D receptors (VDR) is composed of two C4-type zinc fingers. Each zinc finger contains a group of four Cys residues which coordinates a single zinc atom. VDR interacts with a VDR response element, a direct repeat of GGTTCA DNA site with 3 bp spacer upstream of the target gene, and modulates the rate of transcriptional initiation. VDR is a member of the nuclear receptor (NR) superfamily that functions as classical endocrine receptors. VDR controls a wide range of biological activities including calcium metabolism, cell proliferation and differentiation, and immunomodulation. VDR is a high-affinity receptor for the biologically most active Vitamin D metabolite, 1alpha,25-dihydroxyvitamin D3 (1alpha,25(OH)2D3). The binding of the ligand to the receptor induces a conformational change of the ligand binding domain (LBD) with consequent dissociation of corepressors. Upon ligand binding, VDR forms a heterodimer with the retinoid X receptor (RXR) that binds to vitamin D response elements (VDREs), recruits coactivators. This leads to the expression of a large number of genes. Approximately 200 human genes are considered to be primary targets of VDR and even more genes are regulated indirectly. Like other members of the nuclear receptor (NR) superfamily of ligand-activated transcription factors, VDR 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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1017465576   6 LCSICSRPAQGYHYDVISCKGCKTFFRRMWLSKIKEMCPLNNKC--FDFNRRinmslsKCRACRFQRCLNVGMNPAAIQC 83
Cdd:cd06955     8 ICGVCGDRATGFHFNAMTCEGCKGFFRRSMKRKALFTCPFNGDCriTKDNRR------HCQACRLKRCVDIGMMKEFILT 81

                  .
gi 1017465576  84 D 84
Cdd:cd06955    82 D 82

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 1017465576   7 CSICSRPAQGYHYDVISCKGCKTFFRRMWLSKIKEMCPLNNKCfdfnrRINMSLSK-CRACRFQRCLNVGMNPAAIQCD- 84
Cdd:cd07167     1 CPVCGDKVSGYHYGLLTCESCKGFFKRTVQNKKRYTCIENQNC-----QIDKTQRKrCPYCRFQKCLSVGMKLEAVRADr 75

                          90
                  ....*....|....*
gi 1017465576  85 ---GNPKKDSSHFRD 96
Cdd:cd07167    76 mrgGRNKFGPMYKRD 90

DNA-binding domain of constitutive androstane receptor (CAR) is composed of two C4-type zinc fingers; DNA-binding domain (DBD) of constitutive androstane receptor (CAR) 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. CAR DBD interacts with CAR response element, a perfect repeat of two AGTTCA motifs with a 4 bp spacer upstream of the target gene, and modulates the rate of transcriptional initiation. The constitutive androstane receptor (CAR) is a ligand-regulated transcription factor that responds to a diverse array of chemically distinct ligands, including many endogenous compounds and clinical drugs. It functions as a heterodimer with RXR. The CAR/RXR heterodimer binds many common response elements in the promoter regions of a diverse set of target genes involved in the metabolism, transport, and ultimately, elimination of these molecules from the body. CAR is a closest mammalian relative of PXR and is activated by some of the same ligands as PXR and regulates a subset of common genes. The sequence homology and functional similarity suggests that the CAR gene arose from a duplication of an ancestral PXR gene. Like other nuclear receptors, CAR has a central well conserved DNA binding domain, a variable N-terminal domain, a flexible hinge and a C-terminal ligand binding domain.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1017465576   7 CSICSRPAQGYHYDVISCKGCKTFFRRMWLSKIKEMCPLNNKCfdfnrRINMSLSK-CRACRFQRCLNVGMN 77
Cdd:cd06966     3 CGVCGDKALGYNFNAITCESCKAFFRRNALKNKEFKCPFNESC-----EINVVTRRfCQKCRLDKCFAIGMK 69

DNA-binding domain of the orphan nuclear receptor, nerve growth factor-induced-B; DNA-binding domain (DBD) of the orphan nuclear receptor, nerve growth factor-induced-B (NGFI-B) 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. NGFI-B interacts with specific DNA sites upstream of the target gene and modulates the rate of transcriptional initiation. NGFI-B is a member of the nuclear-steroid receptor superfamily. NGFI-B is classified as an orphan receptor because no ligand has yet been identified. NGFI-B is an early immediate gene product of embryo development that is rapidly produced in response to a variety of cellular signals including nerve growth factor. It is involved in T-cell-mediated apoptosis, as well as neuronal differentiation and function. NGFI-B regulates transcription by binding to a specific DNA target upstream of its target genes and regulating the rate of transcriptional initiation. NGFI-B binds to the NGFI-B response element (NBRE) 5'-(A/T)AAAGGTCA as a monomer. Like other members of the nuclear receptor (NR) superfamily of ligand-activated transcription factors, NGFI-B 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 1017465576   6 LCSICSRPAQGYHYDVISCKGCKTFFRRMWLSKIKEMCPLNNKCFDFNRRINmslsKCRACRFQRCLNVGMNPAAIQ 82
Cdd:cd06969     2 LCAVCGDNAACQHYGVRTCEGCKGFFKRTVQKNAKYVCLANKNCPVDKRRRN----RCQYCRFQKCLQVGMVKEVVR 74

DNA-binding domain of Liver X receptors (LXRs) family is composed of two C4-type zinc fingers; DNA-binding domain of Liver X receptors (LXRs) 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. LXR interacts with specific DNA sites upstream of the target gene and modulates the rate of transcriptional initiation. LXR operates as cholesterol sensor which protects cells from cholesterol overload by stimulating reverse cholesterol transport from peripheral tissues to the liver and its excretion in the bile. Oxidized cholesterol derivatives or oxysterols were identified as specific ligands for LXRs. LXR functions as a heterodimer with the retinoid X receptor (RXR) which may be activated by either LXR agonist or 9-cis retinoic acid, a specific RXR ligand. The LXR/RXR complex binds to a liver X receptor response element (LXRE) in the promoter region of target genes. The ideal LXRE sequence is a direct repeat-4 (DR-4) DNA fragment consisting of two AGGTCA hexameric half-sites separated by a 4-nucleotide spacer. LXR has typical NR modular structure with a central well conserved DNA binding domain (DBD), a variable N-terminal domain, a flexible hinge and the ligand binding domain (LBD) at the C-terminal.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1017465576   6 LCSICSRPAQGYHYDVISCKGCKTFFRRMWLSKIKEMCPLNNKC-FD-FNRRinmslsKCRACRFQRCLNVGM 76
Cdd:cd07160    20 VCSVCGDKASGFHYNVLSCEGCKGFFRRSVIKGAQYVCKNGGKCqMDmYMRR------KCQECRLRKCREAGM 86

DNA-binding domain of Ecdysone receptor (ECR) family is composed of two C4-type zinc fingers; DNA-binding domain of Ecdysone receptor (EcR) 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. EcR interacts with highly degenerate pseudo-palindromic response elements, resembling inverted repeats of 5'-AGGTCA-3' separated by 1 bp, upstream of the target gene and modulates the rate of transcriptional initiation. EcR is present only in invertebrates and regulates the expression of a large number of genes during development and reproduction. EcR functions as a heterodimer by partnering with ultraspiracle protein (USP), the ortholog of the vertebrate retinoid X receptor (RXR). The natural ligands of EcR are ecdysteroids, the endogenous steroidal hormones found in invertebrates. Like other members of the nuclear receptor (NR) superfamily of ligand-activated transcription factors, EcRs 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 1017465576   6 LCSICSRPAQGYHYDVISCKGCKTFFRRMWLSKIKEMCPLNNKCfdfnrRINMSL-SKCRACRFQRCLNVGMNP 78
Cdd:cd07161     3 LCLVCGDRASGYHYNALTCEGCKGFFRRSVTKSAVYHCKYGRAC-----EMDMYMrRKCQECRLKKCLSVGMRP 71

The DNA-binding domain of Ecdysone receptor (EcR) like nuclear receptor family is composed of two C4-type zinc fingers; The DNA-binding domain of Ecdysone receptor (EcR) 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. EcR interacts with specific DNA sites upstream of the target gene and modulates the rate of transcriptional initiation. This family includes three types of nuclear receptors: Ecdysone receptor (EcR), Liver X receptor (LXR) and Farnesoid X receptor (FXR). The DNA binding activity is regulated by their corresponding ligands. The ligands for EcR are ecdysteroids; LXR is regulated by oxidized cholesterol derivatives or oxysterols; and bile acids control FXR's activities. Like other members of the nuclear receptor (NR) superfamily of ligand-activated transcription factors, EcR-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 1017465576   6 LCSICSRPAQGYHYDVISCKGCKTFFRRMWLSKIKEMCPLNNKCfdfnrRINMSLS-KCRACRFQRCLNVGMNP 78
Cdd:cd06959     1 NCVVCGDKASGFHYGVLSCEGCKGFFRRSVTKGAVYACKFGNKC-----EMDMYMRrKCQECRLRKCKAAGMRP 69

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 1017465576   7 CSICSRPAQGYHYDVISCKGCKTFFRRMWLSKIKEMC-PLNNKCF-DFNRRinmslSKCRACRFQRCLNVGMNPAAIQCD 84
Cdd:cd06957     1 CKVCGDKSYGKHYGVYCCDGCSCFFKRSVRKGIIYTCiAGNGNCVvDKARR-----NWCPFCRLQKCFAVGMNRAAVQEE 75

                  ....*
gi 1017465576  85 GNPKK 89
Cdd:cd06957    76 RGPRK 80

DNA-binding domain of Tailless (TLX) is composed of two C4-type zinc fingers; DNA-binding domain of Tailless (TLX) 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. TLX interacts with specific DNA sites upstream of the target gene and modulates the rate of transcriptional initiation. TLX is an orphan receptor that is expressed by neural stem/progenitor cells in the adult brain of the subventricular zone (SVZ) and the dentate gyrus (DG). It plays a key role in neural development by promoting cell cycle progression and preventing apoptosis in the developing brain. Like other members of the nuclear receptor (NR) superfamily of ligand-activated transcription factors, TLX 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).

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1017465576   7 CSICSRPAQGYHYDVISCKGCKTFFRR--------MWLSKIKEMCPLnnkcfDFNRRinmslSKCRACRFQRCLNVGMNP 78
Cdd:cd07163     9 CKVCGDRSSGKHYGIYACDGCSGFFKRsirrnrqyVCKSKGQGGCPV-----DKTHR-----NQCRACRLKKCFEVGMNK 78

                          90
                  ....*....|...
gi 1017465576  79 AAIQCDGNPKKDS 91
Cdd:cd07163    79 DAVQHERGPRNST 91

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        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1017465576   7 CSICSRPAQGYHYDVISCKGCKTFFRRMWLSKIKEMCPLNNKC-FDFNRRINmslskCRACRFQRCLNVGMNPAA 80
Cdd:cd06963     1 CLICGDEASGCHYGVLTCGSCKVFFKRAAEGQHNYLCAGRNDCiIDKIRRKN-----CPACRLRKCYQAGMTLGA 70

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 1017465576   7 CSICSRPAQGYHYDVISCKGCKTFFRRMWLSKIKEMCPLNNKC-FDFNRRinmslSKCRACRFQRCLNVGMNPAAIQ 82
Cdd:cd06958     1 CVVCGDKSSGKHYGQFTCEGCKSFFKRSVRRNLTYTCRGNRNCpIDQHHR-----NQCQYCRLKKCLKVGMRREAVQ 72

The ligand binding domain of orphan nuclear receptor Ecdysone-induced receptor DHR4; The ligand binding domain of Ecdysone-induced receptor DHR4: 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).

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1017465576 198 IEYFKTFKFFHELSSRDkfvlarHTLLLCQNLH-----ISHYTVSHNFDSCLQPDGS-MQPKQDE-RHYPIAMMSIEPLV 270
Cdd:cd06953    44 IQWTKKLPFFTELSIKD------HTHLLTTKWAelillSTITVASLQNLGLLQDCLSkYLPSEDElERFGDEGGEVVERL 117

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1017465576 271 --------RCKIQHVEYVLLKAICFCNPAVPELSQNAQRILAKERYCFAdiLINHCLRNYTDGPGHFAELI 333
Cdd:cd06953   118 tyllakfrQLKVSNEEYVCLKVINFLNQDIDGLTNASQLESLQKRYWYV--LQDFTELNYPNQPNRFSDLL 186