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 17560950   176 SSKKLEIATTIGRNEALLFLEQSFLGAAQWFARLPEFSMLDPQIKIDILKTSWMIWARLDKLAATADFHRQKLLGNDVYM 255
Cdd:pfam00104   1 KSPPLKKLRKATKEELCELWERDLLLVAEWAKHFPEFQELPLEDQMALLKSFWLEWLRLEKAARSAKLRRKKILGEDVLM 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17560950   256 WTDNTCMNpgNVKIDIKWSSNYSVEQLRGFLvPDIEKYWRHALSDLVELDPTNVELNFMLIQLCLNSAGQKYQGHVLEAT 335
Cdd:pfam00104  81 ISDDDAMK--FVEDDSSWCTNYDLEQLLFFL-PFFNSYFFELVKPLRELNPDDEELAYLLAQLLFDYAGDGLSGEILEIV 157

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|..
gi 17560950   336 EKILQIQSDNMHEYYTKKlklvnYSGRLARLMKINRAIEADV 377
Cdd:pfam00104 158 EKLQEKLANELHDYYVNK-----YSGRLAKLLKILPSLRKIS 194

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 17560950   176 SSKKLEIATTIGRNEALLFLEQSFLGAAQWFARLPEFSMLDPQIKIDILKTSWMIWARLDKLAATADFHRQKLLGNDVYM 255
Cdd:pfam00104   1 KSPPLKKLRKATKEELCELWERDLLLVAEWAKHFPEFQELPLEDQMALLKSFWLEWLRLEKAARSAKLRRKKILGEDVLM 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17560950   256 WTDNTCMNpgNVKIDIKWSSNYSVEQLRGFLvPDIEKYWRHALSDLVELDPTNVELNFMLIQLCLNSAGQKYQGHVLEAT 335
Cdd:pfam00104  81 ISDDDAMK--FVEDDSSWCTNYDLEQLLFFL-PFFNSYFFELVKPLRELNPDDEELAYLLAQLLFDYAGDGLSGEILEIV 157

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|..
gi 17560950   336 EKILQIQSDNMHEYYTKKlklvnYSGRLARLMKINRAIEADV 377
Cdd:pfam00104 158 EKLQEKLANELHDYYVNK-----YSGRLAKLLKILPSLRKIS 194

DNA-binding domain of heptocyte nuclear factor 4 (HNF4) is composed of two C4-type zinc fingers; DNA-binding domain of hepatocyte nuclear factor 4 (HNF4) 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. HNF4 interacts with a DNA site, composed of two direct repeats of AGTTCA with 1 bp spacer, which is upstream of target genes and modulates the rate of transcriptional initiation. HNF4 is a member of the nuclear receptor superfamily. HNF4 plays a key role in establishing and maintenance of hepatocyte differentiation in the liver. It is also expressed in gut, kidney, and pancreatic beta cells. HNF4 was originally classified as an orphan receptor, but later it is found that HNF4 binds with very high affinity to a variety of fatty acids. However, unlike other nuclear receptors, the ligands do not act as a molecular switch for HNF4. They seem to constantly bind to the receptor, which is constitutively active as a transcription activator. Like other members of the nuclear receptor (NR) superfamily of ligand-activated transcription factors, HNF4 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 17560950  11 CEICEQPAHGNHFGVLSCRACAAFFRRAALQNAKYQdrvCRK-GNCIGNDLYR--CKICRLKKCCEVGMNSSKFQNDRD 86
Cdd:cd06960   1 CAVCGDRATGKHYGVLSCNGCKGFFRRSVRKNRTYT---CRFgGNCVVDKDKRnaCRYCRFKKCLEVGMDPEAVQNERD 76

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 17560950    10 PCEICEQPAHGNHFGVLSCRACAAFFRRAALQNAKYQdrvCRK-GNCIGNDLYR--CKICRLKKCCEVGMN 77
Cdd:pfam00105   1 LCKVCGDKASGYHYGVLTCEGCKGFFRRSIQKNIVYT---CKFnKDCVIDKRNRnrCQYCRLKKCLEVGMS 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 17560950   176 SSKKLEIATTIGRNEALLFLEQSFLGAAQWFARLPEFSMLDPQIKIDILKTSWMIWARLDKLAATADFHRQKLLGNDVYM 255
Cdd:pfam00104   1 KSPPLKKLRKATKEELCELWERDLLLVAEWAKHFPEFQELPLEDQMALLKSFWLEWLRLEKAARSAKLRRKKILGEDVLM 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17560950   256 WTDNTCMNpgNVKIDIKWSSNYSVEQLRGFLvPDIEKYWRHALSDLVELDPTNVELNFMLIQLCLNSAGQKYQGHVLEAT 335
Cdd:pfam00104  81 ISDDDAMK--FVEDDSSWCTNYDLEQLLFFL-PFFNSYFFELVKPLRELNPDDEELAYLLAQLLFDYAGDGLSGEILEIV 157

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|..
gi 17560950   336 EKILQIQSDNMHEYYTKKlklvnYSGRLARLMKINRAIEADV 377
Cdd:pfam00104 158 EKLQEKLANELHDYYVNK-----YSGRLAKLLKILPSLRKIS 194

DNA-binding domain of heptocyte nuclear factor 4 (HNF4) is composed of two C4-type zinc fingers; DNA-binding domain of hepatocyte nuclear factor 4 (HNF4) 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. HNF4 interacts with a DNA site, composed of two direct repeats of AGTTCA with 1 bp spacer, which is upstream of target genes and modulates the rate of transcriptional initiation. HNF4 is a member of the nuclear receptor superfamily. HNF4 plays a key role in establishing and maintenance of hepatocyte differentiation in the liver. It is also expressed in gut, kidney, and pancreatic beta cells. HNF4 was originally classified as an orphan receptor, but later it is found that HNF4 binds with very high affinity to a variety of fatty acids. However, unlike other nuclear receptors, the ligands do not act as a molecular switch for HNF4. They seem to constantly bind to the receptor, which is constitutively active as a transcription activator. Like other members of the nuclear receptor (NR) superfamily of ligand-activated transcription factors, HNF4 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 17560950  11 CEICEQPAHGNHFGVLSCRACAAFFRRAALQNAKYQdrvCRK-GNCIGNDLYR--CKICRLKKCCEVGMNSSKFQNDRD 86
Cdd:cd06960   1 CAVCGDRATGKHYGVLSCNGCKGFFRRSVRKNRTYT---CRFgGNCVVDKDKRnaCRYCRFKKCLEVGMDPEAVQNERD 76

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 17560950  11 CEICEQPAHGNHFGVLSCRACAAFFRRAALQNAKYqdrVCRK-GNCIGNDLYR--CKICRLKKCCEVGMN 77
Cdd:cd06916   1 CAVCGDKASGYHYGVLTCEGCKGFFRRSVRRNLEY---TCPAgGNCVIDKRNRnrCQACRLKKCLAVGMR 67

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        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17560950  10 PCEICEQPAHGNHFGVLSCRACAAFFRRAALQNAKYqdrVC-RKGNCIGNDLYR--CKICRLKKCCEVGMNSSKFQNDRD 86
Cdd:cd06964   6 PCFVCQDKSSGYHYGVSACEGCKGFFRRSIQKNMVY---TChRDKNCIINKVTRnrCQYCRLQKCFEVGMSKESVRNDRN 82

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 17560950  11 CEICEQPAHGNHFGVLSCRACAAFFRRAALQNAKYqdrVCRKGN--CIGNDLYR--CKICRLKKCCEVGMNSSKFQ 82
Cdd:cd07154   1 CKVCGDRSSGKHYGVYACDGCSGFFKRSIRRNLLY---TCKAGNgsCVVDKARRnqCQACRLKKCLEVSMNKDAVQ 73

DNA-binding domain of the photoreceptor cell-specific nuclear receptor (PNR) is composed of two C4-type zinc fingers; DNA-binding domain of the photoreceptor cell-specific nuclear receptor (PNR) 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 the 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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 17560950  11 CEICEQPAHGNHFGVLSCRACAAFFRRAALQNAKYQdrvCR--KGNCIGNDLYR--CKICRLKKCCEVGMNSSKFQNDR 85
Cdd:cd06970   9 CRVCGDTSSGKHYGIYACNGCSGFFKRSVRRKLIYR---CQagTGMCPVDKAHRnqCQACRLKKCLQAGMNKDAVQNER 84

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 17560950  11 CEICEQPAHGNHFGVLSCRACAAFFRRAALQNAKYqdrVC--RKGNCIGNDLYR--CKICRLKKCCEVGMNSSKFQNDR 85
Cdd:cd06957   1 CKVCGDKSYGKHYGVYCCDGCSCFFKRSVRKGIIY---TCiaGNGNCVVDKARRnwCPFCRLQKCFAVGMNRAAVQEER 76

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 17560950  11 CEICEQPAHGNHFGVLSCRACAAFFRRAALQNAKYqdrVCRKGNCIGNDLY---RCKICRLKKCCEVGM 76
Cdd:cd07160  21 CSVCGDKASGFHYNVLSCEGCKGFFRRSVIKGAQY---VCKNGGKCQMDMYmrrKCQECRLRKCREAGM 86

DNA-binding domain of the TR2 and TR4 (human testicular receptor 2 and 4) is composed of two C4-type zinc fingers; DNA-binding domain of the TR2 and TR4 (human testicular receptor 2 and 4) is composed of two C4-type zinc fingers. Each zinc finger contains a group of four Cys residues which coordinates a single zinc atom. TR2 and TR4 interact with specific DNA sites upstream of the target gene and modulate the rate of transcriptional initiation. TR4 and TR2 are orphan nuclear receptors; the physiological ligand is as yet unidentified. TR2 is abundantly expressed in the androgen-sensitive prostate. TR4 transcripts are expressed in many tissues, including central nervous system, adrenal gland, spleen, thyroid gland, and prostate. It has been shown that human TR2 binds to a wide spectrum of natural hormone response elements (HREs) with distinct affinities suggesting that TR2 may cross-talk with other gene expression regulation systems. The genes responding to TR2 or TR4 include genes that are regulated by retinoic acid receptor, vitamin D receptor, and peroxisome proliferator-activated receptor. TR4/2 binds to HREs as dimers. Like other members of the nuclear receptor (NR) superfamily of ligand-activated transcription factors, TR2-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 17560950  11 CEICEQPAHGNHFGVLSCRACAAFFRRAALQNAKYqdrVCR-KGNCIGNDLY--RCKICRLKKCCEVGMNSSKFQNDR 85
Cdd:cd06967   6 CVVCGDKASGRHYGAVSCEGCKGFFKRSIRKNLGY---SCRgSKDCVINKHHrnRCQYCRLQKCLAMGMKSDSVQCER 80

The first DNA-binding domain (DBD) of the 2DBD nuclear receptors is composed of two C4-type zinc fingers; The first DNA-binding domain (DBD) of the 2DBD nuclear receptors(NRs) 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. NRs interact with specific DNA sites upstream of the target gene and modulate the rate of transcriptional initiation. Theses proteins contain two DBDs in tandem, probably resulted from an ancient recombination event. The 2DBD-NRs are found only in flatworm species, mollusks and arthropods. Their biological function is unknown.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17560950  10 PCEICEQPAHGNHFGVLSCRACAAFFRRAAlQNAKYQDRVCRK-GNCIGNDLYR--CKICRLKKCCEVGM 76
Cdd:cd07157   2 TCQVCGEPAAGFHHGAYVCEACKKFFMRSS-NAISFTISECPNgGKCIIDKKNRtkCQACRYRKCLNVGM 70

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 17560950   9 GPCEICEQPAHGNHFGVLSCRACAAFFRRAALQNAKYqdrVCR-KGNCIGNDLYR--CKICRLKKCCEVGM 76
Cdd:cd06969   1 GLCAVCGDNAACQHYGVRTCEGCKGFFKRTVQKNAKY---VCLaNKNCPVDKRRRnrCQYCRFQKCLQVGM 68

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 17560950  11 CEICEQPAHGNHFGVLSCRACAAFFRRAALQNAKYqdrVCRKGNCIGNDLYR---CKICRLKKCCEVGMNSSKFQNDR 85
Cdd:cd07171   6 CAVCSDYASGYHYGVWSCEGCKAFFKRSIQGHNDY---ICPATNQCTIDKNRrksCQACRLRKCYEVGMMKGGIRRER 80

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 17560950  11 CEICEQPAHGNHFGVLSCRACAAFFRRAALQNAKYqdRVCRKGNCIGN--DLYRCKICRLKKCCEVGMNSSKFQNDR 85
Cdd:cd07169   9 CLICGDRATGLHYGIISCEGCKGFFKRSICNKRVY--RCSRDKNCVMSrkQRNRCQYCRLLKCLQMGMNRKAIREDG 83

DNA-binding domain of thyroid hormone receptors (TRs) is composed of two C4-type zinc fingers; DNA-binding domain of thyroid hormone receptors (TRs) 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. TR interacts with the thyroid response element, which is a DNA site with direct repeats of the consensus sequence 5'-AGGTCA-3' separated by one to five base pairs, upstream of target genes and modulates the rate of transcriptional initiation. Thyroid hormone receptor (TR) mediates the actions of thyroid hormones, which play critical roles in growth, development, and homeostasis in mammals. They regulate overall metabolic rate, cholesterol and triglyceride levels, and heart rate, and affect mood. TRs are expressed from two separate genes (alpha and beta) in human and each gene generates two isoforms of the receptor through differential promoter usage or splicing. TRalpha functions in the heart to regulate heart rate and rhythm and TRbeta is active in the liver and other tissues. The unliganded TRs function as transcription repressors, by binding to thyroid hormone response elements (TRE) predominantly as homodimers, or as heterodimers with retinoid X-receptors (RXR), and being associated with a complex of proteins containing corepressor proteins. Ligand binding promotes corepressor dissociation and binding of a coactivator to activate transcription. Like other members of the nuclear receptor (NR) superfamily of ligand-activated transcription factors, TR 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 17560950  10 PCEICEQPAHGNHFGVLSCRACAAFFRRAALQNAKYQdrvCR-KGNCIGNDLYR--CKICRLKKCCEVGMNSSKFQNDR 85
Cdd:cd06961   1 PCVVCGDKATGYHYRCITCEGCKGFFRRTVQKKLSYS---CKgEGKCEIDKVTRnqCQECRFKKCIAVGMAKDLVLDDR 76

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 17560950  11 CEICEQPAHGNHFGVLSCRACAAFFRRAALQNAKYqdrVCRK-GNCIGNDLY--RCKICRLKKCCEVGMNSSKFQNDR 85
Cdd:cd06956   3 CAICGDRASGKHYGVYSCEGCKGFFKRTVRKDLTY---TCRDnKDCLIDKRQrnRCQYCRYQKCLAMGMKREAVQEER 77

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        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 17560950  10 PCEICEQPAHGNHFGVLSCRACAAFFRRAALQNAKYqdrVCRKGN-CIGNDLYR--CKICRLKKCCEVGMN 77
Cdd:cd07172   4 ICLVCSDEASGCHYGVLTCGSCKVFFKRAVEGQHNY---LCAGRNdCIIDKIRRknCPACRLRKCLQAGMN 71

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 17560950  11 CEICEQPAHGNHFGVLSCRACAaFFRRAALQNAK-YQ---------DRVCRKgncigndlyRCKICRLKKCCEVGMNSSK 80
Cdd:cd07167   1 CPVCGDKVSGYHYGLLTCESCK-GFFKRTVQNKKrYTcienqncqiDKTQRK---------RCPYCRFQKCLSVGMKLEA 70

                ....*
gi 17560950  81 FQNDR 85
Cdd:cd07167  71 VRADR 75