The ligand binding domain (LBD) of the Ecdysone receptor, a member of the nuclear receptors super family; The ligand binding domain (LBD) of the ecdysone receptor: The ecdysone receptor (EcR) belongs to the superfamily of nuclear receptors (NRs) of ligand-dependent transcription factors. Ecdysone receptor 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 ecdysone receptor are ecdysteroids#the endogenous steroidal hormones found in invertebrates. In addition, insecticide bisacylhydrazine used against pests has shown to act on EcR. EcR must be dimerised with a USP for high-affinity ligand binding to occur. The ligand binding triggers a conformational change in the C-terminal part of the EcR ligand-binding domain that leads to transcriptional activation of genes controlled by EcR. Like other members of the nuclear receptor (NR) superfamily of ligand-activated transcription factors, ec dysone 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 24585968 211 QLAVIYKLIWYQDGYEQPSEEDLRRIMSQPDENESQTDVSFRHITEITILTVQLIVEFAKGLPAFTKIPQEDQITLLKAC 290
Cdd:cd06938   1 QEELINRLVYYQEEFEQPSEEDLKRITEHPQNDEDQSDMRFRHITEMTILTVQLIVEFAKRLPGFDKLSREDQITLLKAC 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24585968 291 SSEVMMLRMARRYDHSSDSIFFANNRSYTRDSYKMAGMADNIEDLLHFCRQMFSMKVDNVEYALLTAIVIFSDRPGLEKA 370
Cdd:cd06938  81 SSEVMMLRVARRYDAKTDSIVFANNQPYTRDSYRKAGMGDSAEDLFRFCRAMCSMKVDNAEYALLTAIVIFSDRPGLLQP 160

                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 24585968 371 QLVEAIQSYYIDTLRIYILNRHCGDSMslVFYAKLLSILTELRTLGNQNAEMCFSLKLKNRKLPKFLEEIWDV 443
Cdd:cd06938 161 KKVEKIQEIYLEALRAYVDNRRPPSQR--VIFAKLLSILTELRTLGNQNSEMCFSLKLKNRKLPPFLAEIWDV 231

The ligand binding domain (LBD) of the Ecdysone receptor, a member of the nuclear receptors super family; The ligand binding domain (LBD) of the ecdysone receptor: The ecdysone receptor (EcR) belongs to the superfamily of nuclear receptors (NRs) of ligand-dependent transcription factors. Ecdysone receptor 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 ecdysone receptor are ecdysteroids#the endogenous steroidal hormones found in invertebrates. In addition, insecticide bisacylhydrazine used against pests has shown to act on EcR. EcR must be dimerised with a USP for high-affinity ligand binding to occur. The ligand binding triggers a conformational change in the C-terminal part of the EcR ligand-binding domain that leads to transcriptional activation of genes controlled by EcR. Like other members of the nuclear receptor (NR) superfamily of ligand-activated transcription factors, ec dysone 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 24585968 211 QLAVIYKLIWYQDGYEQPSEEDLRRIMSQPDENESQTDVSFRHITEITILTVQLIVEFAKGLPAFTKIPQEDQITLLKAC 290
Cdd:cd06938   1 QEELINRLVYYQEEFEQPSEEDLKRITEHPQNDEDQSDMRFRHITEMTILTVQLIVEFAKRLPGFDKLSREDQITLLKAC 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24585968 291 SSEVMMLRMARRYDHSSDSIFFANNRSYTRDSYKMAGMADNIEDLLHFCRQMFSMKVDNVEYALLTAIVIFSDRPGLEKA 370
Cdd:cd06938  81 SSEVMMLRVARRYDAKTDSIVFANNQPYTRDSYRKAGMGDSAEDLFRFCRAMCSMKVDNAEYALLTAIVIFSDRPGLLQP 160

                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 24585968 371 QLVEAIQSYYIDTLRIYILNRHCGDSMslVFYAKLLSILTELRTLGNQNAEMCFSLKLKNRKLPKFLEEIWDV 443
Cdd:cd06938 161 KKVEKIQEIYLEALRAYVDNRRPPSQR--VIFAKLLSILTELRTLGNQNSEMCFSLKLKNRKLPPFLAEIWDV 231

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 24585968    54 LCLVCGDRASGYHYNALTCEGCKGFFRRSVTKSAVYCCKFGRACEMDMYMRRKCQECRLKKCLAVGMR 121
Cdd:pfam00105   1 LCKVCGDKASGYHYGVLTCEGCKGFFRRSIQKNIVYTCKFNKDCVIDKRNRNRCQYCRLKKCLEVGMS 68

c4 zinc finger in nuclear hormone receptors;

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24585968     54 LCLVCGDRASGYHYNALTCEGCKGFFRRSVTKSAVYCCKFGRACEMDMYMRRKCQECRLKKCLAVGMRPE 123
Cdd:smart00399   1 LCCVCGDHASGFHFGVCSCRACKAFFRRTVNLRYKYRCDRKNNCSINKRYRCRCRACRLKKCLGVGMDPE 70

The ligand binding domain (LBD) of the Ecdysone receptor, a member of the nuclear receptors super family; The ligand binding domain (LBD) of the ecdysone receptor: The ecdysone receptor (EcR) belongs to the superfamily of nuclear receptors (NRs) of ligand-dependent transcription factors. Ecdysone receptor 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 ecdysone receptor are ecdysteroids#the endogenous steroidal hormones found in invertebrates. In addition, insecticide bisacylhydrazine used against pests has shown to act on EcR. EcR must be dimerised with a USP for high-affinity ligand binding to occur. The ligand binding triggers a conformational change in the C-terminal part of the EcR ligand-binding domain that leads to transcriptional activation of genes controlled by EcR. Like other members of the nuclear receptor (NR) superfamily of ligand-activated transcription factors, ec dysone 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 24585968 211 QLAVIYKLIWYQDGYEQPSEEDLRRIMSQPDENESQTDVSFRHITEITILTVQLIVEFAKGLPAFTKIPQEDQITLLKAC 290
Cdd:cd06938   1 QEELINRLVYYQEEFEQPSEEDLKRITEHPQNDEDQSDMRFRHITEMTILTVQLIVEFAKRLPGFDKLSREDQITLLKAC 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24585968 291 SSEVMMLRMARRYDHSSDSIFFANNRSYTRDSYKMAGMADNIEDLLHFCRQMFSMKVDNVEYALLTAIVIFSDRPGLEKA 370
Cdd:cd06938  81 SSEVMMLRVARRYDAKTDSIVFANNQPYTRDSYRKAGMGDSAEDLFRFCRAMCSMKVDNAEYALLTAIVIFSDRPGLLQP 160

                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 24585968 371 QLVEAIQSYYIDTLRIYILNRHCGDSMslVFYAKLLSILTELRTLGNQNAEMCFSLKLKNRKLPKFLEEIWDV 443
Cdd:cd06938 161 KKVEKIQEIYLEALRAYVDNRRPPSQR--VIFAKLLSILTELRTLGNQNSEMCFSLKLKNRKLPPFLAEIWDV 231

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        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24585968  52 EELCLVCGDRASGYHYNALTCEGCKGFFRRSVTKSAVYCCKFGRACEMDMYMRRKCQECRLKKCLAVGMRPECVVPENQC 131
Cdd:cd07161   1 EELCLVCGDRASGYHYNALTCEGCKGFFRRSVTKSAVYHCKYGRACEMDMYMRRKCQECRLKKCLSVGMRPECVVPESQC 80

                        90
                ....*....|.
gi 24585968 132 AMKRREKKAQK 142
Cdd:cd07161  81 AIKRREKKQQK 91

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 24585968  54 LCLVCGDRASGYHYNALTCEGCKGFFRRSVTKSAVYCCKFGRACEMDMYMRRKCQECRLKKCLAVGMRPECVV 126
Cdd:cd06959   1 NCVVCGDKASGFHYGVLSCEGCKGFFRRSVTKGAVYACKFGNKCEMDMYMRRKCQECRLRKCKAAGMRPDCLL 73

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 24585968  55 CLVCGDRASGYHYNALTCEGCKGFFRRSVTKSAVYCCKFGRACEMDMYMRRKCQECRLKKCLAVGMRPECV 125
Cdd:cd06916   1 CAVCGDKASGYHYGVLTCEGCKGFFRRSVRRNLEYTCPAGGNCVIDKRNRNRCQACRLKKCLAVGMRKEAV 71

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 24585968    54 LCLVCGDRASGYHYNALTCEGCKGFFRRSVTKSAVYCCKFGRACEMDMYMRRKCQECRLKKCLAVGMR 121
Cdd:pfam00105   1 LCKVCGDKASGYHYGVLTCEGCKGFFRRSIQKNIVYTCKFNKDCVIDKRNRNRCQYCRLKKCLEVGMS 68

Ligand binding domain of hormone receptors;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24585968    260 LTVQLIVEFAKGLPAFTKIPQEDQITLLKACSSEVMMLRMARRYDHSSDSIFFANNRSYTRDSY----KMAGMADNIEDL 335
Cdd:smart00430   3 RQLLLTVEWAKSFPGFRELSLEDQIVLLKSFWFELLLLELAYRSVKLKKELLLAPDGTYIRPDAvlelRKLFSPFLDRIL 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24585968    336 LHFCRQMFSMKVDNVEYALLTAIVIFS-DRPGLEKA--QLVEAIQSYYIDTLRIYILNRHCGDSMSlvFYAKLLSILTEL 412
Cdd:smart00430  83 SELVKPLRELKLDDEEYALLKAIVLFNpAVPGLSEEgkEIVEKLQEKYANALHDYYLKNYPMNYPG--RFAKLLLILPEL 160

                   ...
gi 24585968    413 RTL 415
Cdd:smart00430 161 RKI 163

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        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24585968  54 LCLVCGDRASGYHYNALTCEGCKGFFRRSVTKSAVYCCKFGRACEMDMYMRRKCQECRLKKCLAVGMRPECVVPENQCAM 133
Cdd:cd06961   1 PCVVCGDKATGYHYRCITCEGCKGFFRRTVQKKLSYSCKGEGKCEIDKVTRNQCQECRFKKCIAVGMAKDLVLDDRKRGA 80

                ...
gi 24585968 134 KRR 136
Cdd:cd06961  81 KRK 83

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 24585968  55 CLVCGDRASGYHYNALTCEGCKGFFRRSVTKSAVYCCKFGRACEMDMYMRRKCQECRLKKCLAVGMRPECV 125
Cdd:cd07156   1 CGVCGDRATGYHFNAMTCEGCKGFFRRSMKRKARFTCPFNGDCEITKDNRRHCQACRLKKCLDIGMKKEMI 71

c4 zinc finger in nuclear hormone receptors;

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24585968     54 LCLVCGDRASGYHYNALTCEGCKGFFRRSVTKSAVYCCKFGRACEMDMYMRRKCQECRLKKCLAVGMRPE 123
Cdd:smart00399   1 LCCVCGDHASGFHFGVCSCRACKAFFRRTVNLRYKYRCDRKNNCSINKRYRCRCRACRLKKCLGVGMDPE 70

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 24585968 262 VQLIVEFAKGLPAFTKIPQEDQITLLKACSSEVMMLRMARRYDHSSDSIFFANNRSYTRDSYKMAGMADNIEDLLHFCRQ 341
Cdd:cd06940  25 VREVVEFAKRIPGFRDLSQHDQVTLLKAGTFEVLMVRFASLFDAKERSVTFLSGQKYSVDDLHSMGAGDLLNSMFDFSEK 104

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24585968 342 MFSMKVDNVEYALLTAIVIFS-DRPGLEKAQLVEAIQSYYIDTLRIYILNRHCGDSmslVFYAKLLSILTELRTLGNQNA 420
Cdd:cd06940 105 LNSLQLSDEEMGLFTAVVLVSaDRSGLENVNLVEALQETLIRALRTLIAKNHPNEP---SIFTKLLLKLPDLRTLNNLHS 181

                ....*...
gi 24585968 421 EMCFSLKL 428
Cdd:cd06940 182 EKLLAFKV 189

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        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24585968  55 CLVCGDRASGYHYNALTCEGCKGFFRRSVTKSAVYCCKFGRACEMDMYMRRKCQECRLKKCLAVGMRPECVVPENQCAMK 134
Cdd:cd06966   3 CGVCGDKALGYNFNAITCESCKAFFRRNALKNKEFKCPFNESCEINVVTRRFCQKCRLDKCFAIGMKKEWIMSEEDKSEK 82

                        90
                ....*....|...
gi 24585968 135 RReKKAQKEKDKM 147
Cdd:cd06966  83 RQ-KIEENRAKKR 94

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 24585968  48 PRVqeelCLVCGDRASGYHYNALTCEGCKGFFRRSVTKSAVYCCKFGRACEMDMYMRRKCQECRLKKCLAVGMRPECVVP 127
Cdd:cd06955   6 PRI----CGVCGDRATGFHFNAMTCEGCKGFFRRSMKRKALFTCPFNGDCRITKDNRRHCQACRLKRCVDIGMMKEFILT 81

                        90       100
                ....*....|....*....|..
gi 24585968 128 EN------QCAMKRREKKAQKE 143
Cdd:cd06955  82 DEevqrkrEMILKRKEEEALKE 103

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 24585968  55 CLVCGDRASGYHYNALTCEGCKGFFRRSVTKSAVYCCKFGRACEMDMYMRRKCQECRLKKCLAVGMRPECVVPENQ 130
Cdd:cd07164   1 CRVCGDRASGKHYGVPSCDGCRGFFKRSIRRNLAYVCKENGSCVVDVARRNQCQACRFKKCLQVNMNRDAVQHERA 76

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 24585968  55 CLVCGDRASGYHYNALTCEGCKGFFRRSVTKSAVYCCKFGRACEMDMYMRRKCQECRLKKCLAVGMRPECV 125
Cdd:cd07167   1 CPVCGDKVSGYHYGLLTCESCKGFFKRTVQNKKRYTCIENQNCQIDKTQRKRCPYCRFQKCLSVGMKLEAV 71

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 24585968  53 ELCLVCGDRASGYHYNALTCEGCKGFFRRSVTKSAVYCCKFGRACEMDMYMRRKCQECRLKKCLAVGMRPECVVP 127
Cdd:cd06969   1 GLCAVCGDNAACQHYGVRTCEGCKGFFKRTVQKNAKYVCLANKNCPVDKRRRNRCQYCRFQKCLQVGMVKEVVRT 75

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 24585968  49 RVQEELCLVCGDRASGYHYNALTCEGCKGFFRRSVTKSAVYCCKFGRACEMDMYMRRKCQECRLKKCLAVGMRPECV 125
Cdd:cd07169   3 RAEQRTCLICGDRATGLHYGIISCEGCKGFFKRSICNKRVYRCSRDKNCVMSRKQRNRCQYCRLLKCLQMGMNRKAI 79

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 24585968  54 LCLVCGDRASGYHYNALTCEGCKGFFRRSVTKSAVYCCKFGRACEMDMYMRRKCQECRLKKCLAVGMRPECVVPE 128
Cdd:cd06956   2 ICAICGDRASGKHYGVYSCEGCKGFFKRTVRKDLTYTCRDNKDCLIDKRQRNRCQYCRYQKCLAMGMKREAVQEE 76

The ligand binding domain of xenobiotic receptors:pregnane X receptor and constitutive androstane receptor; The ligand binding domain of xenobiotic receptors: This xenobiotic receptor family includes pregnane X receptor (PXR), constitutive androstane receptor (CAR) and other related nuclear receptors. They function as sensors of toxic byproducts of cell metabolism and of exogenous chemicals, to facilitate their elimination. The nuclear receptor 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. The ligand binding domain of PXR shows remarkable flexibility to accommodate both large and small molecules. PXR functions as a heterodimer with retinoic X receptor-alpha (RXRa) and binds to a variety of response elements in the promoter regions of a diverse set of target genes involved in the metabolism, transport, and elimination of these molecules from the cell. Constitutive androstane receptor (CAR) is a closest mammalian relative of PXR, which has also been proposed to function as a xenosensor. CAR 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, 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        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24585968 253 HITEITILTVQLIVEFAKGLPAFTKIPQEDQITLLKACSSEVMMLRMARRYDhSSDSIFFANNRSYTRDSYKMAGMADN- 331
Cdd:cd06934  39 HFADLTTYMIKQIIKFAKDLPYFRSLPIEDQISLLKGATFEICQIRFNTVFN-EETGTWECGPLTYCIEDAARAGFQQLl 117

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24585968 332 IEDLLHFCRQMFSMKVDNVEYALLTAIVIFS-DRPGLEKAQLVEAIQSYYIDTLRIYILNRHCGDSMSLVfYAKLLSILT 410
Cdd:cd06934 118 LEPLLRFHYTLRKLQLQEEEYVLMQAMSLFSpDRPGVTQHDVIDQLQEKMALTLKSYIDSKRPGPEKRFL-YPKILACLT 196

                       170       180       190
                ....*....|....*....|....*....|....*
gi 24585968 411 ELRTLGNQNAemcfslklknrklpKFLEEIWDVHA 445
Cdd:cd06934 197 ELRTINEEYT--------------KQILHIQDIQP 217

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 24585968 253 HITEitilTVQLIVEFAKGLPAFTKIPQEDQITLLKACSSEVMMLRMARRYDHSSDSIFFANnrSYT-RDSYKMAGMADN 331
Cdd:cd06939  56 KITE----AIQYVVEFAKRIPGFMELCQNDQIVLLKAGSLEVVLVRMSRAFNPSNNTVLFDG--KYApIDLFKSLGCDDL 129

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24585968 332 IEDLLHFCRQMFSMKVDNVEYALLTAIVIFS-DRPGLEKAQLVEAIQSYYIDTLRIYILNRHCGDSmslvFYAKLLSILT 410
Cdd:cd06939 130 ISAVFDFAKSLCELKLTEDEIALFSALVLISaDRPGLQEKRKVEKLQQKIELALRHVLQKNHGDDT----ILTKLLAKMP 205

                ....*
gi 24585968 411 ELRTL 415
Cdd:cd06939 206 TLRAL 210

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 24585968  55 CLVCGDRASGYHYNALTCEGCKGFFRRSVTKSAVYCCKFGRACEMDMYMRRKCQECRLKKCLAVGMRPECV 125
Cdd:cd07155   1 CLVCGDIASGYHYGVASCEACKAFFKRTIQGNLGYSCPSTSECEVDKKRRKSCQACRLQKCLKVGMLKEGV 71

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

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 24585968  54 LCLVCGDRASGYHYNALTCEGCKGFFRRSVTKSAVY-CCKFGRACEMDMYMRRKCQECRLKKCLAVGMRPECV 125
Cdd:cd07166   5 LCKVCGDKASGFHYGVHACEGCKGFFRRSIQQKIQYrKCTKNETCSIMRINRNRCQYCRFKKCLAVGMSRDAV 77

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 24585968 253 HITEITILTVQLIVEFAKGLPAFTKIPQEDQITLLKACSSEVMMLRMARRYDHSSDSIFFANNR-SYTRDSYKMAGMA-D 330
Cdd:cd06933  41 HLADLVSYSIQKVIGFAKMIPGFRDLTAEDQIALLKSSAIEVIMLRSNQSFSLDDMSWTCGSPDfKYKVSDVTKAGHSlE 120

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24585968 331 NIEDLLHFCRQMFSMKVDNVEYALLTAIVIFS-DRPGLEKAQLVEAIQSYYIDTLRIYILNRHCGDSmSLVFYAKLLSIL 409
Cdd:cd06933 121 LLEPLVKFQVGLKKLNLHEEEHVLLMAICILSpDRPGVQDHALIEAIQDRLSDTLQTYIRCRHPPPG-SRLLYAKMIQKL 199

                       170       180
                ....*....|....*....|
gi 24585968 410 TELRTLGNQNAEMCFSLKLK 429
Cdd:cd06933 200 ADLRSLNEEHSKQYRSLSFQ 219

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 24585968  44 KGPAPRVqeeLCLVCGDRASGYHYNALTCEGCKGFFRRSVTKSAVYCCKFGRA-CEMDMYMRRKCQECRLKKCLAVGMRP 122
Cdd:cd06970   1 KGLNPGL---LCRVCGDTSSGKHYGIYACNGCSGFFKRSVRRKLIYRCQAGTGmCPVDKAHRNQCQACRLKKCLQAGMNK 77

                ....*...
gi 24585968 123 ECVVPENQ 130
Cdd:cd06970  78 DAVQNERQ 85

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 24585968  55 CLVCGDRASGYHYNALTCEGCKGFFRRSVTKSAVYC-CKFGRACEMDMYMRRKCQECRLKKCLAVGMRPECV 125
Cdd:cd07158   1 CKVCGDKASGFHYGVHSCEGCKGFFRRTIQHNLTYRrCLNGGKCVIQRKNRNRCQYCRFKKCLSVGMSRNAV 72