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 71995620  15 CVVCSDFASGIHYSVASCNGCKTFFRRALVNKQTFTCQFSGDCVVGKSVRCVCRSCRLKKCFDMGMDPKAIQHDRD 90
Cdd:cd06960   1 CAVCGDRATGKHYGVLSCNGCKGFFRRSVRKNRTYTCRFGGNCVVDKDKRNACRYCRFKKCLEVGMDPEAVQNERD 76

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 71995620  15 CVVCSDFASGIHYSVASCNGCKTFFRRALVNKQTFTCQFSGDCVVGKSVRCVCRSCRLKKCFDMGMDPKAIQHDRD 90
Cdd:cd06960   1 CAVCGDRATGKHYGVLSCNGCKGFFRRSVRKNRTYTCRFGGNCVVDKDKRNACRYCRFKKCLEVGMDPEAVQNERD 76

Zinc finger, C4 type (two domains); In nearly all cases, this is the DNA binding domain of a nuclear hormone receptor. The alignment contains two Zinc finger domains that are too dissimilar to be aligned with each other.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 71995620    14 LCVVCSDFASGIHYSVASCNGCKTFFRRALVNKQTFTCQFSGDCVVGKSVRCVCRSCRLKKCFDMGMD 81
Cdd:pfam00105   1 LCKVCGDKASGYHYGVLTCEGCKGFFRRSIQKNIVYTCKFNKDCVIDKRNRNRCQYCRLKKCLEVGMS 68

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 71995620 222 EKLREWFVRDLSLMLEWGKCLPIMERLLLNDKLALMKAFA-PIFpLIQLAFYTRNEFECDIVIKLEPDctpkpiperlnY 300
Cdd:cd06157   1 ELLCELATRDLLLIVEWAKSIPGFRELPLEDQIVLLKSFWlELL-VLDLAYRSYKNGLSLLLAPNGGH-----------T 68

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71995620 301 PDGSFIEKGNKPANTWEEMHTMLIDGcykmMRQLKIKESTFVLYKMLLFHNPDADGlSSLGKKTIENERMRLLTQLFSYL 380
Cdd:cd06157  69 DDDKEDEMKLLLKGELIRLLFEFVNP----LRALKLDDEEYALLKAIVLFSPDRKE-SLEDRKIVEELQERLLEALQDYL 143

                       170
                ....*....|....*...
gi 71995620 381 STERGKEAQTIFSNLLMM 398
Cdd:cd06157 144 RKNYPEEAPSRFAKLLLL 161

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 71995620  15 CVVCSDFASGIHYSVASCNGCKTFFRRALVNKQTFTCQFSGDCVVGKSVRCVCRSCRLKKCFDMGMDPKAIQHDRD 90
Cdd:cd06960   1 CAVCGDRATGKHYGVLSCNGCKGFFRRSVRKNRTYTCRFGGNCVVDKDKRNACRYCRFKKCLEVGMDPEAVQNERD 76

DNA-binding domain of nuclear receptors is composed of two C4-type zinc fingers; DNA-binding domain of nuclear receptors is composed of two C4-type zinc fingers. Each zinc finger contains a group of four Cys residues which co-ordinates a single zinc atom. It interacts with a specific DNA site upstream of the target gene and modulates the rate of transcriptional initiation. Nuclear receptors form a superfamily of ligand-activated transcription regulators, which regulate various physiological functions, from development, reproduction, to homeostasis and metabolism in animals (metazoans). The family contains not only receptors for known ligands but also orphan receptors for which ligands do not exist or have not been identified. NRs share a common structural organization with a central well conserved DNA binding domain (DBD), a variable N-terminal domain, a flexible hinge and a C-terminal ligand binding domain (LBD). Most nuclear receptors bind as homodimers or heterodimers to their target sites, which consist of two hexameric half-sites. Specificity is determined by the half-site sequence, the relative orientation of the half-sites and the number of spacer nucleotides between the half-sites. However, a growing number of nuclear receptors have been reported to bind to DNA as monomers.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 71995620  15 CVVCSDFASGIHYSVASCNGCKTFFRRALVNKQTFTCQFSGDCVVGKSVRCVCRSCRLKKCFDMGMDPKAIQ 86
Cdd:cd06916   1 CAVCGDKASGYHYGVLTCEGCKGFFRRSVRRNLEYTCPAGGNCVIDKRNRNRCQACRLKKCLAVGMRKEAVR 72

DNA-binding domain of retinoic acid receptor (RAR) is composed of two C4-type zinc fingers; DNA-binding domain of retinoic acid receptor (RAR) is composed of two C4-type zinc fingers. Each zinc finger contains a group of four Cys residues which co-ordinates a single zinc atom. RAR interacts with specific DNA sites upstream of the target gene and modulates the rate of transcriptional initiation. RARs mediate the biological effect of retinoids, including both natural dietary vitamin A (retinol) metabolites and active synthetic analogs. Retinoids play key roles in a wide variety of essential biological processes, such as vertebrate embryonic morphogenesis and organogenesis, differentiation and apoptosis, and homeostasis. RAR function as a heterodimer with retinoic X receptor by binding to specific RAR response elements (RAREs), which are composed of two direct repeats of the consensus sequence 5'-AGGTCA-3' separated by one to five base pair and found in the promoter regions of retinoid target genes. Like other members of the nuclear receptor (NR) superfamily of ligand-activated transcription factors, retinoic acid receptors have a central well conserved DNA binding domain (DBD), a variable N-terminal domain, a non-conserved hinge and a C-terminal ligand binding domain (LBD).

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 71995620  15 CVVCSDFASGIHYSVASCNGCKTFFRRALVNKQTFTCQFSGDCVVGKSVRCVCRSCRLKKCFDMGMDPKAIQHDRDKIR 93
Cdd:cd06964   7 CFVCQDKSSGYHYGVSACEGCKGFFRRSIQKNMVYTCHRDKNCIINKVTRNRCQYCRLQKCFEVGMSKESVRNDRNKKK 85

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 71995620  15 CVVCSDFASGIHYSVASCNGCKTFFRRALVNKQTFTCQFSGDCVVGKSVRCVCRSCRLKKCFDMGMDPKAIQHDRD 90
Cdd:cd07164   1 CRVCGDRASGKHYGVPSCDGCRGFFKRSIRRNLAYVCKENGSCVVDVARRNQCQACRFKKCLQVNMNRDAVQHERA 76

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 71995620  14 LCVVCSDFASGIHYSVASCNGCKTFFRRALVNKQTFTCQFSGDCVVGKSVRCVCRSCRLKKCFDMGMDPKAIQHDRDKI 92
Cdd:cd06961   1 PCVVCGDKATGYHYRCITCEGCKGFFRRTVQKKLSYSCKGEGKCEIDKVTRNQCQECRFKKCIAVGMAKDLVLDDRKRG 79

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 71995620  14 LCVVCSDFASGIHYSVASCNGCKTFFRRALVNKQTFTCQFSGDCVVGKSVRCVCRSCRLKKCFDMGMDPKAIQHDrDKIR 93
Cdd:cd06955   8 ICGVCGDRATGFHFNAMTCEGCKGFFRRSMKRKALFTCPFNGDCRITKDNRRHCQACRLKRCVDIGMMKEFILTD-EEVQ 86

                        90
                ....*....|....*..
gi 71995620  94 YTKALKKKREEEKRLKE 110
Cdd:cd06955  87 RKREMILKRKEEEALKE 103

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 71995620  14 LCVVCSDFASGIHYSVASCNGCKTFFRRALVNKQTFTCQFSGDCVVGKSVRCVCRSCRLKKCFDMGMDPKAIQHDR 89
Cdd:cd07168   8 LCSICEDKATGLHYGIITCEGCKGFFKRTVQNKRVYTCVGDGRCEITKAQRNRCQYCRFRKCIRKGMMLAAVREDR 83

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 71995620  15 CVVCSDFASGIHYSVASCNGCKTFFRRALVNKQTFTCQFSGDCVVGKSVRCVCRSCRLKKCFDMGMDPKAIQHDR 89
Cdd:cd07155   1 CLVCGDIASGYHYGVASCEACKAFFKRTIQGNLGYSCPSTSECEVDKKRRKSCQACRLQKCLKVGMLKEGVRLDR 75

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 71995620  15 CVVCSDFASGIHYSVASCNGCKTFFRR-ALVNKQtFTCQFSGDCVVGKSVRCVCRSCRLKKCFDMGMDPKAIQHDRDkir 93
Cdd:cd06966   3 CGVCGDKALGYNFNAITCESCKAFFRRnALKNKE-FKCPFNESCEINVVTRRFCQKCRLDKCFAIGMKKEWIMSEED--- 78

                        90
                ....*....|....*...
gi 71995620  94 ytKALKKKREEEKRLKEM 111
Cdd:cd06966  79 --KSEKRQKIEENRAKKR 94

DNA-binding domain of estrogen related receptors (ERR) is composed of two C4-type zinc fingers; DNA-binding domain of estrogen related receptors (ERRs) is composed of two C4-type zinc fingers. Each zinc finger contains a group of four Cys residues which coordinates a single zinc atom. ERR interacts with the palindromic inverted repeat, 5'GGTCAnnnTGACC-3', upstream of the target gene and modulates the rate of transcriptional initiation. The estrogen receptor-related receptors (ERRs) are transcriptional regulators, which are closely related to the estrogen receptor (ER) family. Although ERRs lack the ability to bind to estrogen and are so-called orphan receptors, they share target genes, co-regulators and promoters with the estrogen receptor (ER) family. By targeting the same set of genes, ERRs seem to interfere with the classic ER-mediated estrogen response in various ways. Like other members of the nuclear receptor (NR) superfamily of ligand-activated transcription factors, ERR 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 71995620  14 LCVVCSDFASGIHYSVASCNGCKTFFRRALVNKQTFTCQFSGDCVVGKSVRCVCRSCRLKKCFDMGMDPKAIQHDR 89
Cdd:cd07170   6 LCLVCGDIASGYHYGVASCEACKAFFKRTIQGNIEYSCPATNECEITKRRRKSCQACRFMKCLKVGMLKEGVRLDR 81

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 71995620   7 EKIPegtlCVVCSDFASGIHYSVASCNGCKTFFRRALVNKQTFTCQFSGDCVVGKSVRCVCRSCRLKKCFDMGMdpkaiq 86
Cdd:cd06968   4 EVIP----CKICGDKSSGIHYGVITCEGCKGFFRRSQQNNVSYSCPRQKNCLIDRTNRNRCQHCRLQKCLALGM------ 73

                        90
                ....*....|....*..
gi 71995620  87 hDRDKIRYTKALKKKRE 103
Cdd:cd06968  74 -SRDAVKFGRMSKKQRD 89

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        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71995620  14 LCVVCSDFASGIHYSVASCNGCKTFFRRALVNKQTFTCQFSGDCVVGKSVRCVCRSCRLKKCFDMGMDPKAIQHDrdkir 93
Cdd:cd07162   1 ICRVCGDRATGYHFNAMTCEGCKGFFRRAMKRNARLCCPFQKGCVITKSNRRQCQACRLRKCLSIGMKKELIMSD----- 75

                        90
                ....*....|....
gi 71995620  94 ytKALKKKREEEKR 107
Cdd:cd07162  76 --EAVEKRRALIKR 87

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 71995620  15 CVVCSDFASGIHYSVASCNGCKTFFRRALVNKQTFTCQFSGDCVVGKSVRCVCRSCRLKKCFDMGMdpkaiqhDRDKIRY 94
Cdd:cd07165   1 CKVCGDKASGYHYGVTSCEGCKGFFRRSIQKQIEYRCLRDGKCEIIRLNRNRCQYCRFKKCLAAGM-------SKDSVRY 73

                ....*...
gi 71995620  95 TKALKKKR 102
Cdd:cd07165  74 GRIPNRQR 81

The second DNA-binding domain (DBD) of the 2DBD nuclear receptor is composed of two C4-type zinc fingers; The second DNA-binding domain (DBD) of the 2DBD nuclear receptor (NR) 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. The proteins contain two DBDs in tandem, probably resulting from an ancient recombination event. The 2DBD-NRs are found only in flatworm species, mollusks and arthropods. Their biological function is unknown.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71995620  15 CVVCSDFASGIHYSVASCNGCKTFFRRALVNKQTFTCQFSGDCVVGKSVRCVCRSCRLKKCFDMGMDPKA 84
Cdd:cd07179   1 CRVCGGKSSGFHFGALTCEGCKGFFRRTELSSNSYVCPGGQNCAITPATRNACKSCRFRRCLAVGMSKTG 70

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

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                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71995620   2 PNNKREKIPE-----GTLCVVCSDFASGIHYSVASCNGCKTFFRRALVNKQTFTCQFSGDCVVGKSVRCVCRSCRLKKCF 76
Cdd:cd07160   3 PPRKRKKGPApkmlgNEVCSVCGDKASGFHYNVLSCEGCKGFFRRSVIKGAQYVCKNGGKCQMDMYMRRKCQECRLRKCR 82

                ....
gi 71995620  77 DMGM 80
Cdd:cd07160  83 EAGM 86

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).

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                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 71995620  14 LCVVCSDFASGIHYSVASCNGCKTFFRRALVNKQTFTCQFSGDCVVGKSVRCVCRSCRLKKCFDMGM 80
Cdd:cd06962   3 LCVVCGDKASGYHYNALTCEGCKGFFRRSITKNAVYKCKNGGNCEMDMYMRRKCQECRLRKCKEMGM 69

DNA-binding domain of the photoreceptor cell-specific nuclear receptor (PNR) like is composed of two C4-type zinc fingers; The DNA-binding domain of the photoreceptor cell-specific nuclear receptor (PNR) nuclear receptor-like family is composed of two C4-type zinc fingers. Each zinc finger contains a group of four Cys residues which coordinates a single zinc atom. PNR interacts with specific DNA sites upstream of the target gene and modulates the rate of transcriptional initiation. This family includes nuclear receptor Tailless (TLX), photoreceptor cell-specific nuclear receptor (PNR) and related receptors. TLX is an orphan receptor that plays a key role in neural development by regulating cell cycle progression and exit of neural stem cells in the developing brain. PNR is expressed only in the outer layer of retinal photoreceptor cells. It may be involved in the signaling pathway regulating photoreceptor differentiation and/or maintenance. Like other members of the nuclear receptor (NR) superfamily of ligand-activated transcription factors, PNR-like receptors have a central well-conserved DNA-binding domain (DBD), a variable N-terminal domain, a flexible hinge and a C-terminal ligand binding domain (LBD).

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                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 71995620  15 CVVCSDFASGIHYSVASCNGCKTFFRRALVNKQTFTC-QFSGDCVVGKSVRCVCRSCRLKKCFDMGMDPKAIQHDR 89
Cdd:cd06957   1 CKVCGDKSYGKHYGVYCCDGCSCFFKRSVRKGIIYTCiAGNGNCVVDKARRNWCPFCRLQKCFAVGMNRAAVQEER 76

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).

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                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 71995620  14 LCVVCSDFASGIHYSVASCNGCKTFFRRALVNKQTFTCQFSGDCVVGKSVRCVCRSCRLKKCFDMGM 80
Cdd:cd07172   4 ICLVCSDEASGCHYGVLTCGSCKVFFKRAVEGQHNYLCAGRNDCIIDKIRRKNCPACRLRKCLQAGM 70

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).

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                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71995620  14 LCVVCSDFASGIHYSVASCNGCKTFFRRALVNK-QTFTCQFSGDCVVGKSVRCVCRSCRLKKCFDMGMdpkaiqhDRDKI 92
Cdd:cd07166   5 LCKVCGDKASGFHYGVHACEGCKGFFRRSIQQKiQYRKCTKNETCSIMRINRNRCQYCRFKKCLAVGM-------SRDAV 77

                        90
                ....*....|
gi 71995620  93 RYTKALKKKR 102
Cdd:cd07166  78 RFGRIPKREK 87

Ligand binding domain of hormone receptors;

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                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71995620    230 RDLSLMLEWGKCLPIMERLLLNDKLALMKAFAPIFPLIQLAFYTRNEFECDIvikLEPDCTpkpiperlNYPDGSFIEKG 309
Cdd:smart00430   3 RQLLLTVEWAKSFPGFRELSLEDQIVLLKSFWFELLLLELAYRSVKLKKELL---LAPDGT--------YIRPDAVLELR 71

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71995620    310 NKPANTWEEMHTMLIdgcyKMMRQLKIKESTFVLYKMLLFHNPDADGLSSLGKKTIENERMRLLTQLFSYLSTERGKEAQ 389
Cdd:smart00430  72 KLFSPFLDRILSELV----KPLRELKLDDEEYALLKAIVLFNPAVPGLSEEGKEIVEKLQEKYANALHDYYLKNYPMNYP 147

                          170
                   ....*....|....*.
gi 71995620    390 TIFSNLLMMSATLSKT 405
Cdd:smart00430 148 GRFAKLLLILPELRKI 163

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.

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                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 71995620  15 CVVCSDFASGIHYSVASCNGCKTFFRR--ALVNKQTFTCQFSGDCVVGKSVRCVCRSCRLKKCFDMGM 80
Cdd:cd07157   3 CQVCGEPAAGFHHGAYVCEACKKFFMRssNAISFTISECPNGGKCIIDKKNRTKCQACRYRKCLNVGM 70

The ligand binding domain of heptocyte nuclear factor 4, which is explosively expanded in nematodes; The ligand binding domain of hepatocyte nuclear factor 4 (HNF4) like proteins: 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). The LBD domain is also responsible for recruiting co-activator proteins. More than 280 nuclear receptors are found in C. ele gans, most of which are originated from an explosive burst of duplications of HNF4.

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gi 71995620 220 SVEKLREWFVRDLSLMLEWGKCLPIMERLLLNDKLALMKAFAPIFPLIQLAfyTRNEFECDIVIkLEPDCT-PKPIPErl 298
Cdd:cd06931  33 SINDVCESMKQQLLVLVEWAKYIPAFCELPLDDQVALLRAHAGEHLLLGVA--RRSMPYKDILL-LGNDLIiPRHCPE-- 107

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71995620 299 nypdgsfiekgnkpantwEEMHTM---LIDGCYKMMRQLKIKESTFVLYKMLLFHNPDADGLSSlgKKTIENERMRLLTQ 375
Cdd:cd06931 108 ------------------PEISRVanrILDELVLPLRDLNIDDNEYACLKAIVFFDPDAKGLSD--PQKIKRLRFQVQVS 167

                       170       180
                ....*....|....*....|....*..
gi 71995620 376 LFSYLSTeRGKEAQTIFSNLLMMSATL 402
Cdd:cd06931 168 LEDYIND-RQYDSRGRFGELLLLLPTL 193