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 3874061    146 QLSCFKIEDCMMIWRivEDLFPSLTW--------NLRKLDKEALLRNFLPKWSVLTAAIDMEVKVQRYSKVNNTEEFKRM 217
Cdd:pfam00104   7 KLRKATKEELCELWE--RDLLLVAEWakhfpefqELPLEDQMALLKSFWLEWLRLEKAARSAKLRRKKILGEDVLMISDD 84

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 3874061    218 IVDFFTYSMPEKFKMPPEDILKVFGPMIVYYVTKIILPIHEKGLDQPEFMALALIILFDGAYSNISVECSEMCRTIRNLI 297
Cdd:pfam00104  85 DAMKFVEDDSSWCTNYDLEQLLFFLPFFNSYFFELVKPLRELNPDDEELAYLLAQLLFDYAGDGLSGEILEIVEKLQEKL 164

                         170       180       190
                  ....*....|....*....|....*....|
gi 3874061    298 FRELKNYQTDKNFDeiQFADTVDTLNIVEK 327
Cdd:pfam00104 165 ANELHDYYVNKYSG--RLAKLLKILPSLRK 192

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 3874061    146 QLSCFKIEDCMMIWRivEDLFPSLTW--------NLRKLDKEALLRNFLPKWSVLTAAIDMEVKVQRYSKVNNTEEFKRM 217
Cdd:pfam00104   7 KLRKATKEELCELWE--RDLLLVAEWakhfpefqELPLEDQMALLKSFWLEWLRLEKAARSAKLRRKKILGEDVLMISDD 84

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 3874061    218 IVDFFTYSMPEKFKMPPEDILKVFGPMIVYYVTKIILPIHEKGLDQPEFMALALIILFDGAYSNISVECSEMCRTIRNLI 297
Cdd:pfam00104  85 DAMKFVEDDSSWCTNYDLEQLLFFLPFFNSYFFELVKPLRELNPDDEELAYLLAQLLFDYAGDGLSGEILEIVEKLQEKL 164

                         170       180       190
                  ....*....|....*....|....*....|
gi 3874061    298 FRELKNYQTDKNFDeiQFADTVDTLNIVEK 327
Cdd:pfam00104 165 ANELHDYYVNKYSG--RLAKLLKILPSLRK 192

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 3874061    3 CQVCGCSDVEPHFGALSCRACAAFFRRYFHSKKVVgQC----NCAV--RFRNShpCRECRIKKCLSIGMNPEKVQEKRE 75
Cdd:cd06960   1 CAVCGDRATGKHYGVLSCNGCKGFFRRSVRKNRTY-TCrfggNCVVdkDKRNA--CRYCRFKKCLEVGMDPEAVQNERD 76

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 3874061  172 NLRKLDKEALLRNFLPKWSVLTAAidmevkvQRYSKVNNTEEFkrmivDFFTYSMPEkfkMPPEDILKVFGPMIVYYVTK 251
Cdd:cd06157  26 ELPLEDQIVLLKSFWLELLVLDLA-------YRSYKNGLSLLL-----APNGGHTDD---DKEDEMKLLLKGELIRLLFE 90

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 3874061  252 IILPIHEKGLDQPEFMALALIILFDGAYSNiSVECSEMCRTIRNLIFRELKNYQTDKNFDEIQ--FADTVDTLNIVEK 327
Cdd:cd06157  91 FVNPLRALKLDDEEYALLKAIVLFSPDRKE-SLEDRKIVEELQERLLEALQDYLRKNYPEEAPsrFAKLLLLLPSLRK 167

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 3874061    146 QLSCFKIEDCMMIWRivEDLFPSLTW--------NLRKLDKEALLRNFLPKWSVLTAAIDMEVKVQRYSKVNNTEEFKRM 217
Cdd:pfam00104   7 KLRKATKEELCELWE--RDLLLVAEWakhfpefqELPLEDQMALLKSFWLEWLRLEKAARSAKLRRKKILGEDVLMISDD 84

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 3874061    218 IVDFFTYSMPEKFKMPPEDILKVFGPMIVYYVTKIILPIHEKGLDQPEFMALALIILFDGAYSNISVECSEMCRTIRNLI 297
Cdd:pfam00104  85 DAMKFVEDDSSWCTNYDLEQLLFFLPFFNSYFFELVKPLRELNPDDEELAYLLAQLLFDYAGDGLSGEILEIVEKLQEKL 164

                         170       180       190
                  ....*....|....*....|....*....|
gi 3874061    298 FRELKNYQTDKNFDeiQFADTVDTLNIVEK 327
Cdd:pfam00104 165 ANELHDYYVNKYSG--RLAKLLKILPSLRK 192

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 3874061    3 CQVCGCSDVEPHFGALSCRACAAFFRRYFHSKKVVgQC----NCAV--RFRNShpCRECRIKKCLSIGMNPEKVQEKRE 75
Cdd:cd06960   1 CAVCGDRATGKHYGVLSCNGCKGFFRRSVRKNRTY-TCrfggNCVVdkDKRNA--CRYCRFKKCLEVGMDPEAVQNERD 76

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

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 3874061    1 MACQVCGCSDVEPHFGALSCRACAAFFRRYFHSKKV----VGQCNCAVRFRNSHPCRECRIKKCLSIGMNPEKVQEKRE 75
Cdd:cd06970   7 LLCRVCGDTSSGKHYGIYACNGCSGFFKRSVRRKLIyrcqAGTGMCPVDKAHRNQCQACRLKKCLQAGMNKDAVQNERQ 85

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

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 3874061    1 MACQVCGCSDVEPHFGALSCRACAAFFRRYFHSKKV---VGQCNCAVRFRNSHPCRECRIKKCLSIGMNPEKVQEKR 74
Cdd:cd07168   7 KLCSICEDKATGLHYGIITCEGCKGFFKRTVQNKRVytcVGDGRCEITKAQRNRCQYCRFRKCIRKGMMLAAVREDR 83

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 3874061    1 MACQVCGCSDVEPHFGALSCRACAAFFRRYFHSKKVVGQC----NCAVRFRNSHPCRECRIKKCLSIGMNPEKVQEKRer 76
Cdd:cd07166   4 VLCKVCGDKASGFHYGVHACEGCKGFFRRSIQQKIQYRKCtkneTCSIMRINRNRCQYCRFKKCLAVGMSRDAVRFGR-- 81

                ....*...
gi 3874061   77 hPPKKNKP 84
Cdd:cd07166  82 -IPKREKA 88

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 3874061    3 CQVCGCSDVEPHFGALSCRACAAFFRRYFHSKKV---VGQCNCAVRFRNSHPCRECRIKKCLSIGMNPEKVQEKRER 76
Cdd:cd07167   1 CPVCGDKVSGYHYGLLTCESCKGFFKRTVQNKKRytcIENQNCQIDKTQRKRCPYCRFQKCLSVGMKLEAVRADRMR 77

DNA-binding domain of thyroid hormone receptors (TRs) is composed of two C4-type zinc fingers; DNA-binding domain of thyroid hormone receptors (TRs) is composed of two C4-type zinc fingers. Each zinc finger contains a group of four Cys residues which co-ordinates a single zinc atom. TR interacts with the thyroid response element, which is a DNA site with direct repeats of the consensus sequence 5'-AGGTCA-3' separated by one to five base pairs, upstream of target genes and modulates the rate of transcriptional initiation. Thyroid hormone receptor (TR) mediates the actions of thyroid hormones, which play critical roles in growth, development, and homeostasis in mammals. They regulate overall metabolic rate, cholesterol and triglyceride levels, and heart rate, and affect mood. TRs are expressed from two separate genes (alpha and beta) in human and each gene generates two isoforms of the receptor through differential promoter usage or splicing. TRalpha functions in the heart to regulate heart rate and rhythm and TRbeta is active in the liver and other tissues. The unliganded TRs function as transcription repressors, by binding to thyroid hormone response elements (TRE) predominantly as homodimers, or as heterodimers with retinoid X-receptors (RXR), and being associated with a complex of proteins containing corepressor proteins. Ligand binding promotes corepressor dissociation and binding of a coactivator to activate transcription. Like other members of the nuclear receptor (NR) superfamily of ligand-activated transcription factors, TR has a central well conserved DNA binding domain (DBD), a variable N-terminal domain, a flexible hinge and a C-terminal ligand binding domain (LBD).

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 3874061    3 CQVCGCSDVEPHFGALSCRACAAFFRRYFHsKKVVGQC----NCAVRFRNSHPCRECRIKKCLSIGMNPEKVQEKRER 76
Cdd:cd06961   2 CVVCGDKATGYHYRCITCEGCKGFFRRTVQ-KKLSYSCkgegKCEIDKVTRNQCQECRFKKCIAVGMAKDLVLDDRKR 78

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 3874061      3 CQVCGCSDVEPHFGALSCRACAAFFRRYFhSKKVVGQC----NCAVRFRNSHPCRECRIKKCLSIGMN 66
Cdd:pfam00105   2 CKVCGDKASGYHYGVLTCEGCKGFFRRSI-QKNIVYTCkfnkDCVIDKRNRNRCQYCRLKKCLEVGMS 68

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 3874061    3 CQVCGCSDVEPHFGALSCRACAAFFRRYFHSK-----KVVGQCNCAVRFRNShpCRECRIKKCLSIGMNPEKVQEKR 74
Cdd:cd07164   1 CRVCGDRASGKHYGVPSCDGCRGFFKRSIRRNlayvcKENGSCVVDVARRNQ--CQACRFKKCLQVNMNRDAVQHER 75

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 3874061    3 CQVCGCSDVEPHFGALSCRACAAFFRRYFhSKKVVGQCN----CAVRFRNSHPCRECRIKKCLSIGMNPE 68
Cdd:cd07156   1 CGVCGDRATGYHFNAMTCEGCKGFFRRSM-KRKARFTCPfngdCEITKDNRRHCQACRLKKCLDIGMKKE 69

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 3874061    3 CQVCGCSDVEPHFGALSCRACAAFFRRYfHSKKVVGQC----NCAVRFRNSHPCRECRIKKCLSIGMNpeKVQEKRERHP 78
Cdd:cd06968   8 CKICGDKSSGIHYGVITCEGCKGFFRRS-QQNNVSYSCprqkNCLIDRTNRNRCQHCRLQKCLALGMS--RDAVKFGRMS 84

                ...
gi 3874061   79 PKK 81
Cdd:cd06968  85 KKQ 87

DNA-binding domain of Germ cell nuclear factor (GCNF) F1 is composed of two C4-type zinc fingers; DNA-binding domain of Germ cell nuclear factor (GCNF) F1 is composed of two C4-type zinc fingers. Each zinc finger contains a group of four Cys residues which coordinates a single zinc atom. This domain interacts with specific DNA sites upstream of the target gene and modulates the rate of transcriptional initiation. GCNF is a transcription factor expressed in post-meiotic stages of developing male germ cells. In vitro, GCNF has the ability to bind to direct repeat elements of 5'-AGGTCA.AGGTCA-3', as well as to an extended half-site sequence 5'-TCA.AGGTCA-3'. Like other members of the nuclear receptor (NR) superfamily of ligand-activated transcription factors, GCNF has a central well conserved DNA-binding domain (DBD), a variable N-terminal domain, a flexible hinge and a C-terminal ligand binding domain (LBD).

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 3874061    3 CQVCGCSDVEPHFGALSCRACAAFFRRYFHSKKVVgQC----NCAVRFRNSHPCRECRIKKCLSIGMNPEKVQEkrERHP 78
Cdd:cd07169   9 CLICGDRATGLHYGIISCEGCKGFFKRSICNKRVY-RCsrdkNCVMSRKQRNRCQYCRLLKCLQMGMNRKAIRE--DGMP 85

                ....*
gi 3874061   79 PKKNK 83
Cdd:cd07169  86 GGRNK 90

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 3874061    3 CQVCGCSDVEPHFGALSCRACAAFFRRYFHSKKVVGQC--NCAVRFRNSHPCRECRIKKCLSIGMNPEKVQEKR 74
Cdd:cd06965   2 CRVCGDKASGFHYGVHACEGCKGFFRRTIRLKLVYKPCdlSCKIHKKSRNKCQYCRFQKCLNVGMSHNAIRFGR 75

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 3874061    3 CQVCGCSDVEPHFGALSCRACAAFFRRYFHSKK---VVGQCNCAVRFRNSHPCRECRIKKCLSIGMNPEKVQ 71
Cdd:cd06969   3 CAVCGDNAACQHYGVRTCEGCKGFFKRTVQKNAkyvCLANKNCPVDKRRRNRCQYCRFQKCLQVGMVKEVVR 74

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 3874061    2 ACQVCGCSDVEPHFGALSCRACAAFFRRYFHsKKVVGQC----NCAVRFRNSHPCRECRIKKCLSIGMNPE 68
Cdd:cd06959   1 NCVVCGDKASGFHYGVLSCEGCKGFFRRSVT-KGAVYACkfgnKCEMDMYMRRKCQECRLRKCKAAGMRPD 70

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 3874061    3 CQVCGCSDVEPHFGALSCRACAAFFRRYFHSK---KVVGQCNCAVRFRNSHPCRECRIKKCLSIGMNPEKVQEKR 74
Cdd:cd07155   1 CLVCGDIASGYHYGVASCEACKAFFKRTIQGNlgySCPSTSECEVDKKRRKSCQACRLQKCLKVGMLKEGVRLDR 75

DNA-binding domain of Farnesoid X receptor (FXR) family is composed of two C4-type zinc fingers; DNA-binding domain of Farnesoid X receptor (FXR) 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. FXR interacts with specific DNA sites upstream of the target gene and modulates the rate of transcriptional initiation. FXR is a member of the nuclear receptor family of ligand activated transcription factors. Bile acids are endogenous ligands for FXRs. Upon binding of a ligand, FXR binds to FXR response element (FXRE), which is an inverted repeat of TGACCT spaced by one nucleotide, either as a monomer or as a heterodimer with retinoid X receptor (RXR), to regulate the expression of various genes involved in bile acid, lipid, and glucose metabolism. Like other members of the nuclear receptor (NR) superfamily of ligand-activated transcription factors, FXR 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 3874061    3 CQVCGCSDVEPHFGALSCRACAAFFRRYFhSKKVVGQC----NCAVRFRNSHPCRECRIKKCLSIGMNPE 68
Cdd:cd06962   4 CVVCGDKASGYHYNALTCEGCKGFFRRSI-TKNAVYKCknggNCEMDMYMRRKCQECRLRKCKEMGMLAE 72

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

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 3874061    3 CQVCGCSDVEPHFGALSCRACAAFFRRYF--HSKKVVGQCN-CAVRFRNSHPCRECRIKKCLSIGMNpeKVQEKRER 76
Cdd:cd07171   6 CAVCSDYASGYHYGVWSCEGCKAFFKRSIqgHNDYICPATNqCTIDKNRRKSCQACRLRKCYEVGMM--KGGIRRER 80

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

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 3874061    2 ACQVCGCSDVEPHFGALSCRACAAFF-RRYFHSKKVVGQC----NCAVRFRNSHPCRECRIKKCLSIGM 65
Cdd:cd07157   2 TCQVCGEPAAGFHHGAYVCEACKKFFmRSSNAISFTISECpnggKCIIDKKNRTKCQACRYRKCLNVGM 70

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

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 3874061    3 CQVCGCSDVEPHFGALSCRACAAFFRRYF---HSKKVVGQCNCAVRFRNSHPCRECRIKKCLSIGMN 66
Cdd:cd06963   1 CLICGDEASGCHYGVLTCGSCKVFFKRAAegqHNYLCAGRNDCIIDKIRRKNCPACRLRKCYQAGMT 67

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

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 3874061    2 ACQVCGCSDVEPHFGALSCRACAAFFRRYF---HSKKVVGQCNCAVRFRNSHPCRECRIKKCLSIGMN 66
Cdd:cd07172   4 ICLVCSDEASGCHYGVLTCGSCKVFFKRAVegqHNYLCAGRNDCIIDKIRRKNCPACRLRKCLQAGMN 71