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 60115375  73 ECRVCGDKASGFHYGVHACEGCKGFFRRTIRMKLEYEKCERSCKIQKKNRNKCQYCRFQKCLALGMSHNAIRFGRMPEAE 152
Cdd:cd06965   1 ECRVCGDKASGFHYGVHACEGCKGFFRRTIRLKLVYKPCDLSCKIHKKSRNKCQYCRFQKCLNVGMSHNAIRFGRMPRVE 80

                ....
gi 60115375 153 KRKL 156
Cdd:cd06965  81 KEKL 84

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 60115375  73 ECRVCGDKASGFHYGVHACEGCKGFFRRTIRMKLEYEKCERSCKIQKKNRNKCQYCRFQKCLALGMSHNAIRFGRMPEAE 152
Cdd:cd06965   1 ECRVCGDKASGFHYGVHACEGCKGFFRRTIRLKLVYKPCDLSCKIHKKSRNKCQYCRFQKCLNVGMSHNAIRFGRMPRVE 80

                ....
gi 60115375 153 KRKL 156
Cdd:cd06965  81 KEKL 84

c4 zinc finger in nuclear hormone receptors;

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 60115375     74 CRVCGDKASGFHYGVHACEGCKGFFRRTIRMKLEYeKCER--SCKIQKKNRNKCQYCRFQKCLALGM 138
Cdd:smart00399   2 CCVCGDHASGFHFGVCSCRACKAFFRRTVNLRYKY-RCDRknNCSINKRYRCRCRACRLKKCLGVGM 67

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 60115375   236 PPYKEISVHVFYRCQCTTVETVRELTEFAKSIPSFSSLFLNDQVTLLKYGVHE-AIFAMLA--------SIVNKDGLLVA 306
Cdd:pfam00104   3 PPLKKLRKATKEELCELWERDLLLVAEWAKHFPEFQELPLEDQMALLKSFWLEwLRLEKAArsaklrrkKILGEDVLMIS 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 60115375   307 NGSGFVTREFLRS--------LRKPFSD-IIEPKFEFAVKFNALELDDSDLALFIAAIILCGDRPGLMN--VPRVEAIQD 375
Cdd:pfam00104  83 DDDAMKFVEDDSSwctnydleQLLFFLPfFNSYFFELVKPLRELNPDDEELAYLLAQLLFDYAGDGLSGeiLEIVEKLQE 162

                         170       180       190
                  ....*....|....*....|....*....|....*
gi 60115375   376 TILRALEFHLQANHPDaqyLFPKLLQKMADLRQLV 410
Cdd:pfam00104 163 KLANELHDYYVNKYSG---RLAKLLKILPSLRKIS 194

Ligand-binding domain of nuclear receptor family 1; Ligand-binding domain (LBD) of nuclear receptor (NR) family 1: This is one of the major subfamily of nuclear receptors, including thyroid receptor, retinoid acid receptor, ecdysone receptor, farnesoid X receptor, vitamin D receptor, and other related receptors. 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).

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 60115375 244 HVFYRCQCTTVETVRELTEFAKSIPSFSSLFLNDQVTLLKYGVHEAIFAMLASIVNKDGLLVANGSGFVTREFLrSLRKP 323
Cdd:cd06929   2 EKFDHFTEIMTVAIRRVVEFAKRIPGFRELSQEDQIALLKGGCFEILLLRSATLYDPEKNSLTFGDGKGNSRDV-LLNGG 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 60115375 324 FSDIIEPKFEFAVKFNALELDDSDLALFIAAIILCGDRPGLMNVPRVEAIQDTILRALEFHLQANHPDAQYLFPKLLQKM 403
Cdd:cd06929  81 FGEFIEPLFEFAEKMNKLQLDDNEYALLTAIVLFSPDRPGLQDVDTVEKLQERLLEALQRYLKVNHPDAPQMFAKLLKKL 160

                       170
                ....*....|....
gi 60115375 404 ADLRQLVTEHAQMM 417
Cdd:cd06929 161 TELRTLNELHAELL 174

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 60115375  74 CRVCGDKASGFHYGVHACEGCKGFFRRTIRMKLEYeKCERS--CKIQKKNRNKCQYCRFQKCLALGMSHNAIR 144
Cdd:cd06916   1 CAVCGDKASGYHYGVLTCEGCKGFFRRSVRRNLEY-TCPAGgnCVIDKRNRNRCQACRLKKCLAVGMRKEAVR 72

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        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 60115375  74 CRVCGDKASGFHYGVHACEGCKGFFRRTIRMKLEYEKCER--SCKIQKKNRNKCQYCRFQKCLALGMSHNAIR 144
Cdd:cd07158   1 CKVCGDKASGFHYGVHSCEGCKGFFRRTIQHNLTYRRCLNggKCVIQRKNRNRCQYCRFKKCLSVGMSRNAVR 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        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 60115375  74 CRVCGDKASGFHYGVHACEGCKGFFRRTIRMKLEYeKCERS--CKIQKKNRNKCQYCRFQKCLALGMSHNAIRFGRMPEA 151
Cdd:cd07165   1 CKVCGDKASGYHYGVTSCEGCKGFFRRSIQKQIEY-RCLRDgkCEIIRLNRNRCQYCRFKKCLAAGMSKDSVRYGRIPNR 79

                ..
gi 60115375 152 EK 153
Cdd:cd07165  80 QR 81

The ligand binding domain of REV-ERB receptors, members of the nuclear receptor superfamily; The ligand binding domain (LBD) of REV-ERB receptors: REV-ERBs 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. The LBD domain of REV-ERB is unusual in the nuclear receptor family by lacking the AF-2 region that is responsible for coactivator interaction. REV-ERBs act as constitutive repressors because of their inability to bind coactivators. REV-ERB receptors can bind to two classes of DNA response elements as either a monomer or heterodimer, indicating functional diversity. When bound to the DNA, they recruit corepressors (NcoR/histone deacetylase 3) to the promoter, resulting in repression of the target gene. The porphyrin heme has been demonstrated to function as a ligand for REV-ERB. 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 60115375 257 VRELTEFAKSIPSFSSLFLNDQVTLLKYGVHEAIFAMLASI--VNKDGLLVANGSGFvTREFLRSLRKpfSDIIEPKFEF 334
Cdd:cd06940  25 VREVVEFAKRIPGFRDLSQHDQVTLLKAGTFEVLMVRFASLfdAKERSVTFLSGQKY-SVDDLHSMGA--GDLLNSMFDF 101

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 60115375 335 AVKFNALELDDSDLALFIAAIILCGDRPGLMNVPRVEAIQDTILRALEFHLQANHPDAQYLFPKLLQKMADLRQLVTEHA 414
Cdd:cd06940 102 SEKLNSLQLSDEEMGLFTAVVLVSADRSGLENVNLVEALQETLIRALRTLIAKNHPNEPSIFTKLLLKLPDLRTLNNLHS 181

                .
gi 60115375 415 Q 415
Cdd:cd06940 182 E 182

DNA-binding domain of Retinoid-related orphan receptors (RORs) is composed of two C4-type zinc fingers; DNA-binding domain of Retinoid-related orphan receptors (RORs) is composed of two C4-type zinc fingers. Each zinc finger contains a group of four Cys residues which coordinates a single zinc atom. ROR interacts with specific DNA sites upstream of the target gene and modulates the rate of transcriptional initiation. RORS are key regulators of many physiological processes during embryonic development. RORs bind as monomers to specific ROR response elements (ROREs) consisting of the consensus core motif AGGTCA preceded by a 5-bp A/T-rich sequence. There are three subtypes of retinoid-related orphan receptors (RORs), alpha, beta, and gamma, which differ only in N-terminal sequence and are distributed in distinct tissues. RORalpha plays a key role in the development of the cerebellum particularly in the regulation of the maturation and survival of Purkinje cells. RORbeta expression is largely restricted to several regions of the brain, the retina, and pineal gland. RORgamma is essential for lymph node organogenesis. Recently, it has been suggested that cholesterol or a cholesterol derivative are the natural ligands of RORalpha. Like other members of the nuclear receptor (NR) superfamily of ligand-activated transcription factors, retinoid-related orphan 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 60115375  74 CRVCGDKASGFHYGVHACEGCKGFFRRTIRMKLEYEkCER--SCKIQKKNRNKCQYCRFQKCLALGMSHNAIRFGRMPEA 151
Cdd:cd06968   8 CKICGDKSSGIHYGVITCEGCKGFFRRSQQNNVSYS-CPRqkNCLIDRTNRNRCQHCRLQKCLALGMSRDAVKFGRMSKK 86

                ....*..
gi 60115375 152 EKRKLVA 158
Cdd:cd06968  87 QRDSLYA 93

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 60115375  74 CRVCGDKASGFHYGVHACEGCKGFFRRTIRMKLEYeKC--ERSCKIQKKNRNKCQYCRFQKCLALGMSHNAIRFGR 147
Cdd:cd06960   1 CAVCGDRATGKHYGVLSCNGCKGFFRRSVRKNRTY-TCrfGGNCVVDKDKRNACRYCRFKKCLEVGMDPEAVQNER 75

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        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 60115375  72 MECRVCGDKASGFHYGVHACEGCKGFFRRTIRMKLEYEkC--ERSCKIQKKNRNKCQYCRFQKCLALGMSHNAIRFGRMP 149
Cdd:cd07168   7 KLCSICEDKATGLHYGIITCEGCKGFFKRTVQNKRVYT-CvgDGRCEITKAQRNRCQYCRFRKCIRKGMMLAAVREDRMP 85

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 60115375  74 CRVCGDKASGFHYGVHACEGCKGFFRRTIRMKLEYE-KCERSCKIQKKNRNKCQYCRFQKCLALGMSHNAIRFGRMP 149
Cdd:cd06967   6 CVVCGDKASGRHYGAVSCEGCKGFFKRSIRKNLGYScRGSKDCVINKHHRNRCQYCRLQKCLAMGMKSDSVQCERKP 82

The ligand binding domain of Retinoid-related orphan receptors, of the nuclear receptor superfamily; The ligand binding domain (LBD) of Retinoid-related orphan receptors (RORs): Retinoid-related orphan receptors (RORs) are transcription factors belonging to the nuclear receptor superfamily. RORs are key regulators of many physiological processes during embryonic development. RORs bind as monomers to specific ROR response elements (ROREs) consisting of the consensus core motif AGGTCA preceded by a 5-bp A/T-rich sequence. Transcription regulation by RORs is mediated through certain corepressors, as well as coactivators. There are three subtypes of retinoid-related orphan receptors (RORs), alpha, beta, and gamma that differ only in N-terminal sequence and are distributed in distinct tissues. RORalpha plays a key role in the development of the cerebellum, particularly in the regulation of the maturation and survival of Purkinje cells. RORbeta expression is largely restricted to several regions of the brain, the retina, and pineal gland. RORgamma is essential for lymph node organogenesis. Recently, it has been su ggested that cholesterol or a cholesterol derivative is the natural ligand of RORalpha. Like other members of the nuclear receptor (NR) superfamily of ligand-activated transcription factors, retinoid-related orphan 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 60115375 228 WK-QLVNGLPPYKEISVHVFY-RCQCTTVETVRELTEFAKSIPSFSSLFLNDQVTLLKYGVHEAIFAMLASIVNKDGLLV 305
Cdd:cd06939  30 WKtFSQEEILAYQNKSREEMWqLCAEKITEAIQYVVEFAKRIPGFMELCQNDQIVLLKAGSLEVVLVRMSRAFNPSNNTV 109

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 60115375 306 ANGSGFVTREFLRSLrkPFSDIIEPKFEFAVKFNALELDDSDLALFIAAIILCGDRPGLMNVPRVEAIQDTILRALEFHL 385
Cdd:cd06939 110 LFDGKYAPIDLFKSL--GCDDLISAVFDFAKSLCELKLTEDEIALFSALVLISADRPGLQEKRKVEKLQQKIELALRHVL 187

                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 60115375 386 QANHPDAQYLfPKLLQKMADLRQLVTEHAQMMQRIKKTETETSlHPLLQEIYKDMY 441
Cdd:cd06939 188 QKNHGDDTIL-TKLLAKMPTLRALCSLHMEKLQKFKQSYPDIV-HLEFPPLYKELF 241

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 60115375  74 CRVCGDKASGFHYGVHACEGCKGFFRRTIRMKLEYE-KCERSCKIQKKNRNKCQYCRFQKCLALGMSHNAIR 144
Cdd:cd06956   3 CAICGDRASGKHYGVYSCEGCKGFFKRTVRKDLTYTcRDNKDCLIDKRQRNRCQYCRYQKCLAMGMKREAVQ 74

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 60115375  74 CRVCGDKASGFHYGVHACEGCKGFFRRTIRMKLEYE-KCERSCKIQKKNRNKCQYCRFQKCLALGMSHNAIRFGRMP 149
Cdd:cd07164   1 CRVCGDRASGKHYGVPSCDGCRGFFKRSIRRNLAYVcKENGSCVVDVARRNQCQACRFKKCLQVNMNRDAVQHERAP 77

The ligand binding domain of thyroid hormone receptor, a members of a superfamily of nuclear receptors; The ligand binding domain (LBD) of thyroid hormone receptors: Thyroid hormone receptors are members of a superfamily of nuclear receptors. Thyroid hormone receptors (TR) mediate 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        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 60115375 262 EFAKSIPSFSSLFLNDQVTLLKYGVHEAIFAMLASIVNKDG-LLVANGSGFVTREFLRSlrKPFSDIIEPKFEFAVKFNA 340
Cdd:cd06935  70 DFAKKLPMFTELPCEDQIILLKGCCMEIMSLRAAVRYDPESeTLTLSGEMAVTREQLKN--GGLGVVSDAIFDLGVSLSS 147

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 60115375 341 LELDDSDLALFIAAIILCGDRPGLMNVPRVEAIQDTILRALEFHLQANHPDAQYLFPKLLQKMADLRQLVTEHAQMMQRI 420
Cdd:cd06935 148 FNLDDTEVALLQAVLLMSSDRPGLACVERIEKLQDSFLLAFEHYINYRKHHVPHFWPKLLMKVTDLRMIGACHASRFLHM 227

                       170
                ....*....|...
gi 60115375 421 kKTETETSLHPLL 433
Cdd:cd06935 228 -KVECPTELFPPL 239

The ligand binding domain (LBD) of retinoic acid receptor (RAR), a members of the nuclear receptor superfamily; The ligand binding domain (LBD) of retinoic acid receptor (RAR): Retinoic acid receptors are members of the nuclear receptor (NR) superfamily of ligand-regulated transcription factors. RARs mediate the biological effect of retinoids, including both naturally 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. RARs function as heterodimers with retinoic X receptors by binding to specific RAR response elements (RAREs) found in the promoter regions of retinoid target genes. In the absence of ligand, the RAR-RXR heterodimer recruits the corepressor proteins NCoR or AMRT, and associated factors such as histone deacetylases or DNA-methyltransferases, leading to an inactive condensed chromatin structure, preventing transcription. Upon ligand binding, the corepressors are released, and coactivator complexes such as histone acetyltransferase or histone arginine methyltransferases are recruited to activate transcription. There are three RAR subtypes (alpha, beta, gamma), originating from three distinct genes. For each subtype, several isoforms exist that differ in their N-terminal region, allowing retinoids to exert their pleiotropic effects. 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 60115375 255 ETVRELTEFAKSIPSFSSLFLNDQVTLLKYGVHEAIFAMLASIVNKDGLLVANGSGF-VTREFLRSlrKPFSDIIEPKFE 333
Cdd:cd06937  49 KCIIKIVEFAKRLPGFTTLTIADQITLLKAACLDILILRICTRYTPEQDTMTFSDGLtLNRTQMHN--AGFGPLTDLVFT 126

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 60115375 334 FAVKFNALELDDSDLALFIAAIILCGDRPGLMNVPRVEAIQDTILRALEFHLQANHPDAQYLFPKLLQKMADLRQLVTEH 413
Cdd:cd06937 127 FANQLLPLEMDDTEIGLLSAICLICGDRQDLEEPDRVEKLQEPLLEALKIYARKRRPDKPHMFPKMLMKITDLRSISAKG 206

                       170       180
                ....*....|....*....|...
gi 60115375 414 AQMMQRIkKTETETSLHPLLQEI 436
Cdd:cd06937 207 AERVITL-KMEIPGPMPPLISEM 228

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        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 60115375  69 SLNMECRVCGDKASGFHYGVHACEGCKGFFRRTIRMKLEYeKCERS---CKIQKKNRNKCQYCRFQKCLALGMSHNAIRF 145
Cdd:cd06970   4 NPGLLCRVCGDTSSGKHYGIYACNGCSGFFKRSVRRKLIY-RCQAGtgmCPVDKAHRNQCQACRLKKCLQAGMNKDAVQN 82

                ....
gi 60115375 146 GRMP 149
Cdd:cd06970  83 ERQP 86

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).

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 60115375  70 LNMECRVCGDKASGFHYGVHACEGCKGFFRRTIRMKLEY---EKCERSCKIQKKNRNKCQYCRFQKCLALGMSHNAIRFG 146
Cdd:cd07163   5 LDIPCKVCGDRSSGKHYGIYACDGCSGFFKRSIRRNRQYvckSKGQGGCPVDKTHRNQCRACRLKKCFEVGMNKDAVQHE 84

                ...
gi 60115375 147 RMP 149
Cdd:cd07163  85 RGP 87

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 60115375  74 CRVCGDKASGFHYGVHACEGCKGFFRRTIRMKLEYEkCERS--CKIQKKNRNKCQYCRFQKCLALGMSHNAIRFGR 147
Cdd:cd07155   1 CLVCGDIASGYHYGVASCEACKAFFKRTIQGNLGYS-CPSTseCEVDKKRRKSCQACRLQKCLKVGMLKEGVRLDR 75

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 60115375  74 CRVCGDKASGFHYGVHACEGCKGFFRRTIRMKLEYeKC--ERSCKIQKKNRNKCQYCRFQKCLALGMSHNAIRFGR 147
Cdd:cd07171   6 CAVCSDYASGYHYGVWSCEGCKAFFKRSIQGHNDY-ICpaTNQCTIDKNRRKSCQACRLRKCYEVGMMKGGIRRER 80

The ligand binding domain of vitamin D receptors, a member of the nuclear receptor superfamily; The ligand binding domain of vitamin D receptors (VDR): 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 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 60115375 256 TVRELTEFAKSIPSFSSLFLNDQVTLLKYGVHEAIfaML---ASIVNKDGLLVANGSGFVTREFLRSLRKPFSDIIEPKF 332
Cdd:cd06933  49 SIQKVIGFAKMIPGFRDLTAEDQIALLKSSAIEVI--MLrsnQSFSLDDMSWTCGSPDFKYKVSDVTKAGHSLELLEPLV 126

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 60115375 333 EFAVKFNALELDDSDLALFIAAIILCGDRPGLMNVPRVEAIQDTILRALEFHLQANH--PDAQYLFPKLLQKMADLRQLV 410
Cdd:cd06933 127 KFQVGLKKLNLHEEEHVLLMAICILSPDRPGVQDHALIEAIQDRLSDTLQTYIRCRHppPGSRLLYAKMIQKLADLRSLN 206

                       170       180       190
                ....*....|....*....|....*....|
gi 60115375 411 TEHAQMMQRIK-KTETETSLHPLLQEIYKD 439
Cdd:cd06933 207 EEHSKQYRSLSfQPEHSMKLTPLVLEVFGN 236

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 60115375  74 CRVCGDKASGFHYGVHACEGCKGFFRRTIRMKLEYeKC---ERSCKIQKKNRNKCQYCRFQKCLALGMSHNAIRFGRMP 149
Cdd:cd06957   1 CKVCGDKSYGKHYGVYCCDGCSCFFKRSVRKGIIY-TCiagNGNCVVDKARRNWCPFCRLQKCFAVGMNRAAVQEERGP 78

DNA-binding domain of pregnane X receptor (PXRs) is composed of two C4-type zinc fingers; DNA-binding domain (DBD)of pregnane X receptor (PXR) 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. PXR DBD interacts with the PXR 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 pregnane X receptor (PXR) is a ligand-regulated transcription factor that responds to a diverse array of chemically distinct ligands, including many endogenous compounds and clinical drugs. PXR functions as a heterodimer with retinoic X receptor-alpha (RXRa) and binds to a variety of promoter regions of a diverse set of target genes involved in the metabolism, transport, and ultimately, elimination of these molecules from the body. Like other nuclear receptors, PXR 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 60115375  74 CRVCGDKASGFHYGVHACEGCKGFFRRTIRMKLEYeKCER--SCKIQKKNRNKCQYCRFQKCLALGMSHNAI 143
Cdd:cd07162   2 CRVCGDRATGYHFNAMTCEGCKGFFRRAMKRNARL-CCPFqkGCVITKSNRRQCQACRLRKCLSIGMKKELI 72

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 60115375  74 CRVCGDKASGFHYGVHACEGCKGFFRRTIRMKLEYeKC--ERSCKIQKKNRNKCQYCRFQKCLALGM 138
Cdd:cd06955   9 CGVCGDRATGFHFNAMTCEGCKGFFRRSMKRKALF-TCpfNGDCRITKDNRRHCQACRLKRCVDIGM 74

The ligand binding domain of the retinoid X receptor and Ultraspiracle, members of nuclear receptor superfamily; The ligand binding domain of the retinoid X receptor (RXR) and Ultraspiracle (USP): This family includes two evolutionary related nuclear receptors: retinoid X receptor (RXR) and Ultraspiracle (USP). RXR is a nuclear receptor in mammalian and USP is its counterpart in invertebrates. The native ligand of retinoid X receptor is 9-cis retinoic acid (RA). RXR functions as a DNA binding partner by forming heterodimers with other nuclear receptors including CAR, FXR, LXR, PPAR, PXR, RAR, TR, and VDR. RXRs can play different roles in these heterodimers. It 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. Ultraspiracle (USP) plays similar roles as DNA binding partner of other nuclear rec eptors in invertebrates. USP has no known high-affinity ligand and is thought to be a silent component in the heterodimeric complex with partner receptors. Like other members of the nuclear receptor (NR) superfamily of ligand-activated transcription factors, RXR and USP 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 60115375 249 CQCTTvETVRELTEFAKSIPSFSSLFLNDQVTLLKYGVHEAIFAMLA--SIVNKDGLLVANGSgFVTREFLRS--LRKPF 324
Cdd:cd06943  36 CQAAD-KQLFQLVEWAKRIPHFSELPLDDQVILLRAGWNELLIAAFAhrSIAVKDGILLATGL-HLHRNSAHQagVGAIF 113

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 60115375 325 SDIIEpkfEFAVKFNALELDDSDLALFIAAIILCGDRPGLMNVPRVEAIQDTILRALEFHLQANHPDAQYLFPKLLQKMA 404
Cdd:cd06943 114 DRILT---ELVVKMRDLKMDRTELGCLRAIILFNPDVKGLKSRQEVESLREKVYASLEEYCRQKHPEQPGRFAKLLLRLP 190

                ...
gi 60115375 405 DLR 407
Cdd:cd06943 191 ALR 193