Ligand binding domain of hormone receptors;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17543294    160 MFREYDMVTDWAMNsFPQLADFPNDQRKILLKHFYLQFFILESGFMACRNgRNDVWFLPNGDYIDCRDLASFYRDptrpe 239
Cdd:smart00430   1 AERQLLLTVEWAKS-FPGFRELSLEDQIVLLKSFWFELLLLELAYRSVKL-KKELLLAPDGTYIRPDAVLELRKL----- 73

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17543294    240 sssqsISPEHAALMmkgtctgcrRMVTNTMLKDNIDQCEFLALSALILFQTGLEGQSESCMETCKKIRSTVQRELLQYYA 319
Cdd:smart00430  74 -----FSPFLDRIL---------SELVKPLRELKLDDEEYALLKAIVLFNPAVPGLSEEGKEIVEKLQEKYANALHDYYL 139

                          170
                   ....*....|...
gi 17543294    320 GKRTQEYSIRMGN 332
Cdd:smart00430 140 KNYPMNYPGRFAK 152

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 17543294   8 CKICNSPGNGLHFGIDACRGCTSFFRRTIVQEKEYYCNSDDSCEIGKSEaalKSPCRKCRFAKCLEVGMKSEAVQKNRD 86
Cdd:cd06960   1 CAVCGDRATGKHYGVLSCNGCKGFFRRSVRKNRTYTCRFGGNCVVDKDK---RNACRYCRFKKCLEVGMDPEAVQNERD 76

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 17543294   141 SMFSKRIPKPHTFRDTDKLMFREYDMVTDWAMnSFPQLADFPNDQRKILLKHFYLQFFILESGFMACRNGRNDVWFLPNG 220
Cdd:pfam00104   1 KSPPLKKLRKATKEELCELWERDLLLVAEWAK-HFPEFQELPLEDQMALLKSFWLEWLRLEKAARSAKLRRKKILGEDVL 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17543294   221 DYIDCRDLASFYRDptrpeSSSQSISPEHAALMMKGTCTGCRRMVTNTMLKDNIDQCEFLALSALILFQTGLEGQSESCM 300
Cdd:pfam00104  80 MISDDDAMKFVEDD-----SSWCTNYDLEQLLFFLPFFNSYFFELVKPLRELNPDDEELAYLLAQLLFDYAGDGLSGEIL 154

                         170       180       190
                  ....*....|....*....|....*....|..
gi 17543294   301 ETCKKIRSTVQRELLQYYagkrTQEYSIRMGN 332
Cdd:pfam00104 155 EIVEKLQEKLANELHDYY----VNKYSGRLAK 182

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 17543294 166 MVTDWAMnSFPQLADFPNDQRKILLKHFYLQFFILESGFMACRNGRNDVWFLPNGDYIDCRDlasfyrdptrpESSSQSI 245
Cdd:cd06157  13 LIVEWAK-SIPGFRELPLEDQIVLLKSFWLELLVLDLAYRSYKNGLSLLLAPNGGHTDDDKE-----------DEMKLLL 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17543294 246 SPEHAALMMkgtctgcrrMVTNTMLKDNIDQCEFLALSALILFQTGLeGQSESCMETCKKIRSTVQRELLQYYAGKRTQE 325
Cdd:cd06157  81 KGELIRLLF---------EFVNPLRALKLDDEEYALLKAIVLFSPDR-KESLEDRKIVEELQERLLEALQDYLRKNYPEE 150

                ....*..
gi 17543294 326 YSIRMGN 332
Cdd:cd06157 151 APSRFAK 157

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 17543294   8 CKICNSPGNGLHFGIDACRGCTSFFRRTIVQEKEYYCNSDDSCEIGKSEaalKSPCRKCRFAKCLEVGMKSEAVQKNRD 86
Cdd:cd06960   1 CAVCGDRATGKHYGVLSCNGCKGFFRRSVRKNRTYTCRFGGNCVVDKDK---RNACRYCRFKKCLEVGMDPEAVQNERD 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 17543294   8 CKICNSPGNGLHFGIDACRGCTSFFRRTIVQEKEYYCNSDDSCEIGKseaALKSPCRKCRFAKCLEVGMKSEAVQ 82
Cdd:cd06916   1 CAVCGDKASGYHYGVLTCEGCKGFFRRSVRRNLEYTCPAGGNCVIDK---RNRNRCQACRLKKCLAVGMRKEAVR 72

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 17543294   141 SMFSKRIPKPHTFRDTDKLMFREYDMVTDWAMnSFPQLADFPNDQRKILLKHFYLQFFILESGFMACRNGRNDVWFLPNG 220
Cdd:pfam00104   1 KSPPLKKLRKATKEELCELWERDLLLVAEWAK-HFPEFQELPLEDQMALLKSFWLEWLRLEKAARSAKLRRKKILGEDVL 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17543294   221 DYIDCRDLASFYRDptrpeSSSQSISPEHAALMMKGTCTGCRRMVTNTMLKDNIDQCEFLALSALILFQTGLEGQSESCM 300
Cdd:pfam00104  80 MISDDDAMKFVEDD-----SSWCTNYDLEQLLFFLPFFNSYFFELVKPLRELNPDDEELAYLLAQLLFDYAGDGLSGEIL 154

                         170       180       190
                  ....*....|....*....|....*....|..
gi 17543294   301 ETCKKIRSTVQRELLQYYagkrTQEYSIRMGN 332
Cdd:pfam00104 155 EIVEKLQEKLANELHDYY----VNKYSGRLAK 182

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 17543294   8 CKICNSPGNGLHFGIDACRGCTSFFRRTIVQEKEYYCNSDDSCEIGKSEaalKSPCRKCRFAKCLEVGMKSEAVQKNR 85
Cdd:cd07168   9 CSICEDKATGLHYGIITCEGCKGFFKRTVQNKRVYTCVGDGRCEITKAQ---RNRCQYCRFRKCIRKGMMLAAVREDR 83

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 17543294   8 CKICNSPGNGLHFGIDACRGCTSFFRRTIVQEKEYYCNSDDSCEIGKseaALKSPCRKCRFAKCLEVGMKSEAV 81
Cdd:cd07179   1 CRVCGGKSSGFHFGALTCEGCKGFFRRTELSSNSYVCPGGQNCAITP---ATRNACKSCRFRRCLAVGMSKTGS 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        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 17543294     7 PCKICNSPGNGLHFGIDACRGCTSFFRRTIVQEKEYYCNSDDSCEIGKSEaalKSPCRKCRFAKCLEVGMK 77
Cdd:pfam00105   1 LCKVCGDKASGYHYGVLTCEGCKGFFRRSIQKNIVYTCKFNKDCVIDKRN---RNRCQYCRLKKCLEVGMS 68

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 17543294   8 CKICNSPGNGLHFGIDACRGCTSFFRRTIVQEKEYYCNSDDSCEIGKSEaalKSPCRKCRFAKCLEVGMKSEAVQKNRDS 87
Cdd:cd07169   9 CLICGDRATGLHYGIISCEGCKGFFKRSICNKRVYRCSRDKNCVMSRKQ---RNRCQYCRLLKCLQMGMNRKAIREDGMP 85

                ....*
gi 17543294  88 YGKRR 92
Cdd:cd07169  86 GGRNK 90

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 17543294   8 CKICNSPGNGLHFGIDACRGCTSFFRRTIVQEKEYYCNSDDSCEIGKSEaalKSPCRKCRFAKCLEVGMKSEAV 81
Cdd:cd07156   1 CGVCGDRATGYHFNAMTCEGCKGFFRRSMKRKARFTCPFNGDCEITKDN---RRHCQACRLKKCLDIGMKKEMI 71

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 17543294   8 CKICNSPGNGLHFGIDACRGCTSFFRRTIVQEKEYYCNSDDSCEIGKSEaalKSPCRKCRFAKCLEVGMKSEAVQKNR 85
Cdd:cd06956   3 CAICGDRASGKHYGVYSCEGCKGFFKRTVRKDLTYTCRDNKDCLIDKRQ---RNRCQYCRYQKCLAMGMKREAVQEER 77

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 17543294   8 CKICNSPGNGLHFGIDACRGCTSFFRRTIVQEKEYYCNSDDSCEIGKSEaalKSPCRKCRFAKCLEVGMKSEAVQKNR 85
Cdd:cd07171   6 CAVCSDYASGYHYGVWSCEGCKAFFKRSIQGHNDYICPATNQCTIDKNR---RKSCQACRLRKCYEVGMMKGGIRRER 80

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        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17543294   8 CKICNSPGNGLHFGIDACRGCTSFFRRTIVQEKEYYCNSDDSCEIGKSEaalKSPCRKCRFAKCLEVGMKSEAVQKNRDS 87
Cdd:cd07170   7 CLVCGDIASGYHYGVASCEACKAFFKRTIQGNIEYSCPATNECEITKRR---RKSCQACRFMKCLKVGMLKEGVRLDRVR 83

                ....*
gi 17543294  88 YGKRR 92
Cdd:cd07170  84 GGRQK 88

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 17543294   8 CKICNSPGNGLHFGIDACRGCTSFFRRTIVQEKEYYCNSDDSCEIgksEAALKSPCRKCRFAKCLEVGMKSEAVQKNRD 86
Cdd:cd07164   1 CRVCGDRASGKHYGVPSCDGCRGFFKRSIRRNLAYVCKENGSCVV---DVARRNQCQACRFKKCLQVNMNRDAVQHERA 76

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 17543294   7 PCKICNSPGNGLHFGIDACRGCTSFFRRTIVQEKEYYCNSDDSCEIGKSEaalKSPCRKCRFAKCLEVGMKSEAVQKNRD 86
Cdd:cd06968   7 PCKICGDKSSGIHYGVITCEGCKGFFRRSQQNNVSYSCPRQKNCLIDRTN---RNRCQHCRLQKCLALGMSRDAVKFGRM 83

                ....*...
gi 17543294  87 SyGKRREL 94
Cdd:cd06968  84 S-KKQRDS 90

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 17543294   8 CKICNSPGNGLHFGIDACRGCTSFFRRTIVQEKEYYCNSDDS-CEIGKseaALKSPCRKCRFAKCLEVGMKSEAVQKNR 85
Cdd:cd06970   9 CRVCGDTSSGKHYGIYACNGCSGFFKRSVRRKLIYRCQAGTGmCPVDK---AHRNQCQACRLKKCLQAGMNKDAVQNER 84

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 17543294   8 CKICNSPGNGLHFGIDACRGCTSFFRRTIVQEKEYYCNSDDSCEIgksEAALKSPCRKCRFAKCLEVGMKSEAVQKNRDS 87
Cdd:cd06966   3 CGVCGDKALGYNFNAITCESCKAFFRRNALKNKEFKCPFNESCEI---NVVTRRFCQKCRLDKCFAIGMKKEWIMSEEDK 79

                ....*
gi 17543294  88 YGKRR 92
Cdd:cd06966  80 SEKRQ 84

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 17543294   8 CKICNSPGNGLHFGIDACRGCTSFFRRTIVQEKEYY-CNSDDSCEIGKSEaalKSPCRKCRFAKCLEVGMKSEAVQ 82
Cdd:cd07158   1 CKVCGDKASGFHYGVHSCEGCKGFFRRTIQHNLTYRrCLNGGKCVIQRKN---RNRCQYCRFKKCLSVGMSRNAVR 73

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 17543294   8 CKICNSPGNGLHFGIDACRGCTSFFRRTIVQEKEYYCNS-DDSCEIGKseaALKSPCRKCRFAKCLEVGMKSEAVQKNR 85
Cdd:cd06957   1 CKVCGDKSYGKHYGVYCCDGCSCFFKRSVRKGIIYTCIAgNGNCVVDK---ARRNWCPFCRLQKCFAVGMNRAAVQEER 76

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).

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gi 17543294   8 CKICNSPGNGLHFGIDACRGCTSFFRRTIVQEKEYYCNSDDSCEIgksEAALKSPCRKCRFAKCLEVGMKSEAV 81
Cdd:cd06959   2 CVVCGDKASGFHYGVLSCEGCKGFFRRSVTKGAVYACKFGNKCEM---DMYMRRKCQECRLRKCKAAGMRPDCL 72

DNA-binding domain of vitamin D receptors (VDR) is composed of two C4-type zinc fingers; DNA-binding domain of vitamin D receptors (VDR) is composed of two C4-type zinc fingers. Each zinc finger contains a group of four Cys residues which coordinates a single zinc atom. VDR interacts with a VDR response element, a direct repeat of GGTTCA DNA site with 3 bp spacer upstream of the target gene, and modulates the rate of transcriptional initiation. VDR is a member of the nuclear receptor (NR) superfamily that functions as classical endocrine receptors. VDR controls a wide range of biological activities including calcium metabolism, cell proliferation and differentiation, and immunomodulation. VDR is a high-affinity receptor for the biologically most active Vitamin D metabolite, 1alpha,25-dihydroxyvitamin D3 (1alpha,25(OH)2D3). The binding of the ligand to the receptor induces a conformational change of the ligand binding domain (LBD) with consequent dissociation of corepressors. Upon ligand binding, VDR forms a heterodimer with the retinoid X receptor (RXR) that binds to vitamin D response elements (VDREs), recruits coactivators. This leads to the expression of a large number of genes. Approximately 200 human genes are considered to be primary targets of VDR and even more genes are regulated indirectly. Like other members of the nuclear receptor (NR) superfamily of ligand-activated transcription factors, VDR has a central well conserved DNA binding domain (DBD), a variable N-terminal domain, a flexible hinge and a C-terminal ligand binding domain (LBD).

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gi 17543294   8 CKICNSPGNGLHFGIDACRGCTSFFRRTIVQEKEYYCNSDDSCEIGKSEaalKSPCRKCRFAKCLEVGM------KSEAV 81
Cdd:cd06955   9 CGVCGDRATGFHFNAMTCEGCKGFFRRSMKRKALFTCPFNGDCRITKDN---RRHCQACRLKRCVDIGMmkefilTDEEV 85

                        90
                ....*....|..
gi 17543294  82 QKNRDSYGKRRE 93
Cdd:cd06955  86 QRKREMILKRKE 97

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).

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gi 17543294   8 CKICNSPGNGLHFGIDACRGCTSFFRRTIVQEKEYYCNSDDSCEIGKSEaalKSPCRKCRFAKCLEVGMKSEA 80
Cdd:cd06963   1 CLICGDEASGCHYGVLTCGSCKVFFKRAAEGQHNYLCAGRNDCIIDKIR---RKNCPACRLRKCYQAGMTLGA 70

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 17543294   6 EPCKICNSPGNGLHFGIDACRGCTSFFRRTIVQEKEYYCNSDDSCEIGKSEaalKSPCRKCRFAKCLEVGMKSEA 80
Cdd:cd07172   3 KICLVCSDEASGCHYGVLTCGSCKVFFKRAVEGQHNYLCAGRNDCIIDKIR---RKNCPACRLRKCLQAGMNLGA 74

Tumor necrosis factor receptor superfamily member 6 (TNFRSF6) in teleosts; also known as fas cell surface death receptor (FasR); This subfamily of TNFRSF6 (also known as fas cell surface death receptor (FasR) or Fas; APT1; CD95; FAS1; APO-1; FASTM; ALPS1A) is found in teleosts. It contains a death domain and plays a central role in the physiological regulation of programmed cell death. In humans, it has been implicated in the pathogenesis of various malignancies and diseases of the immune system. The receptor interactions with the Fas ligand (FasL), allowing the formation of a death-inducing signaling complex that includes Fas-associated death domain protein (FADD), caspase 8, and caspase 10; autoproteolytic processing of the caspases in the complex triggers a downstream caspase cascade, leading to apoptosis. This receptor has also been shown to activate NF-kappaB, MAPK3/ERK1, and MAPK8/JNK, and is involved in transducing the proliferating signals in normal diploid fibroblast and T cells. In channel catfish and the Japanese rice fish, medaka, homologs of Fas receptor (FasR), as well as FADD and caspase 8, have been identified and characterized, and likely constitute the teleost equivalent of the death-inducing signaling complex (DISC). FasL/FasR are involved in the initiation of apoptosis and suggest that mechanisms of cell-mediated cytotoxicity in teleosts are similar to those used by mammals; presumably, the mechanism of apoptosis induction via death receptors was evolutionarily established during the appearance of vertebrates.

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                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 17543294   6 EPCKICNSPGNglhfgIDACRGCTSFFRRTIVQEKEYYCNSDDSCEIGKseaalksPCRKC 66
Cdd:cd13423  55 EPCTSCDPNAN-----LEVEERCTPSSDTVCRCKEGHYCDKGEECKVCY-------PCDTC 103