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 28396060 202 HGIGPSLKVDILLLREWVDRIPGFRELSERFQQHLMHRFCLRYTVIEHGLFTAQMPYHKNVWFLSDRTclvsefenlpqe 281
Cdd:cd06157   1 ELLCELATRDLLLIVEWAKSIPGFRELPLEDQIVLLKSFWLELLVLDLAYRSYKNGLSLLLAPNGGHT------------ 68

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 28396060 282 ikkhLTPKVINEQQLLASFTEMLIHEVADPLRRLKPDSVEVATVKTLMLLKPtclreidgDYLSTETDIKSVNDVRNRVI 361
Cdd:cd06157  69 ----DDDKEDEMKLLLKGELIRLLFEFVNPLRALKLDDEEYALLKAIVLFSP--------DRKESLEDRKIVEELQERLL 136

                       170       180       190
                ....*....|....*....|....*....|....
gi 28396060 362 NGLYSHYIKNGmdPEQLPIRVSEILNLTGGVEQC 395
Cdd:cd06157 137 EALQDYLRKNY--PEEAPSRFAKLLLLLPSLRKL 168

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 28396060 202 HGIGPSLKVDILLLREWVDRIPGFRELSERFQQHLMHRFCLRYTVIEHGLFTAQMPYHKNVWFLSDRTclvsefenlpqe 281
Cdd:cd06157   1 ELLCELATRDLLLIVEWAKSIPGFRELPLEDQIVLLKSFWLELLVLDLAYRSYKNGLSLLLAPNGGHT------------ 68

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 28396060 282 ikkhLTPKVINEQQLLASFTEMLIHEVADPLRRLKPDSVEVATVKTLMLLKPtclreidgDYLSTETDIKSVNDVRNRVI 361
Cdd:cd06157  69 ----DDDKEDEMKLLLKGELIRLLFEFVNPLRALKLDDEEYALLKAIVLFSP--------DRKESLEDRKIVEELQERLL 136

                       170       180       190
                ....*....|....*....|....*....|....
gi 28396060 362 NGLYSHYIKNGmdPEQLPIRVSEILNLTGGVEQC 395
Cdd:cd06157 137 EALQDYLRKNY--PEEAPSRFAKLLLLLPSLRKL 168

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 28396060  38 CLVCGRVAnTGHHYGVTACLGCKTFFRRVVLQKNSPKCKYKNHCRLEKSVNAKrlCRSCRYQKCLEVGMTEDALHPCRD 116
Cdd:cd06960   1 CAVCGDRA-TGKHYGVLSCNGCKGFFRRSVRKNRTYTCRFGGNCVVDKDKRNA--CRYCRFKKCLEVGMDPEAVQNERD 76

Ligand binding domain of hormone receptors;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 28396060    208 LKVDILLLREWVDRIPGFRELSERFQQHLMHRFCLRYTVIEHGLFTAQMpyHKNVWFLSDRTCLVSEFENlpqeikkhlt 287
Cdd:smart00430   1 AERQLLLTVEWAKSFPGFRELSLEDQIVLLKSFWFELLLLELAYRSVKL--KKELLLAPDGTYIRPDAVL---------- 68

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 28396060    288 pkviNEQQLLASFTEMLIHEVADPLRRLKPDSVEVATVKTLMLLKPtclreiDGDYLStETDIKSVNDVRNRVINGLYSH 367
Cdd:smart00430  69 ----ELRKLFSPFLDRILSELVKPLRELKLDDEEYALLKAIVLFNP------AVPGLS-EEGKEIVEKLQEKYANALHDY 137

                          170       180
                   ....*....|....*....|.
gi 28396060    368 YIKNGmdPEQLPIRVSEILNL 388
Cdd:smart00430 138 YLKNY--PMNYPGRFAKLLLI 156

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 28396060 202 HGIGPSLKVDILLLREWVDRIPGFRELSERFQQHLMHRFCLRYTVIEHGLFTAQMPYHKNVWFLSDRTclvsefenlpqe 281
Cdd:cd06157   1 ELLCELATRDLLLIVEWAKSIPGFRELPLEDQIVLLKSFWLELLVLDLAYRSYKNGLSLLLAPNGGHT------------ 68

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 28396060 282 ikkhLTPKVINEQQLLASFTEMLIHEVADPLRRLKPDSVEVATVKTLMLLKPtclreidgDYLSTETDIKSVNDVRNRVI 361
Cdd:cd06157  69 ----DDDKEDEMKLLLKGELIRLLFEFVNPLRALKLDDEEYALLKAIVLFSP--------DRKESLEDRKIVEELQERLL 136

                       170       180       190
                ....*....|....*....|....*....|....
gi 28396060 362 NGLYSHYIKNGmdPEQLPIRVSEILNLTGGVEQC 395
Cdd:cd06157 137 EALQDYLRKNY--PEEAPSRFAKLLLLLPSLRKL 168

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 28396060  38 CLVCGRVAnTGHHYGVTACLGCKTFFRRVVLQKNSPKCKYKNHCRLEKSVNAKrlCRSCRYQKCLEVGMTEDALHPCRD 116
Cdd:cd06960   1 CAVCGDRA-TGKHYGVLSCNGCKGFFRRSVRKNRTYTCRFGGNCVVDKDKRNA--CRYCRFKKCLEVGMDPEAVQNERD 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        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 28396060  38 CLVCGRVAnTGHHYGVTACLGCKTFFRRVVLQKNSPKCKYKNHCRLEKSvnAKRLCRSCRYQKCLEVGMTEDALHPCRDV 117
Cdd:cd06961   2 CVVCGDKA-TGYHYRCITCEGCKGFFRRTVQKKLSYSCKGEGKCEIDKV--TRNQCQECRFKKCIAVGMAKDLVLDDRKR 78

                ....
gi 28396060 118 IGRR 121
Cdd:cd06961  79 GAKR 82

Ligand binding domain of hormone receptors;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 28396060    208 LKVDILLLREWVDRIPGFRELSERFQQHLMHRFCLRYTVIEHGLFTAQMpyHKNVWFLSDRTCLVSEFENlpqeikkhlt 287
Cdd:smart00430   1 AERQLLLTVEWAKSFPGFRELSLEDQIVLLKSFWFELLLLELAYRSVKL--KKELLLAPDGTYIRPDAVL---------- 68

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 28396060    288 pkviNEQQLLASFTEMLIHEVADPLRRLKPDSVEVATVKTLMLLKPtclreiDGDYLStETDIKSVNDVRNRVINGLYSH 367
Cdd:smart00430  69 ----ELRKLFSPFLDRILSELVKPLRELKLDDEEYALLKAIVLFNP------AVPGLS-EEGKEIVEKLQEKYANALHDY 137

                          170       180
                   ....*....|....*....|.
gi 28396060    368 YIKNGmdPEQLPIRVSEILNL 388
Cdd:smart00430 138 YLKNY--PMNYPGRFAKLLLI 156

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 28396060  38 CLVCGRVAnTGHHYGVTACLGCKTFFRRVVLQKNSPKCKYKNHCRLEKsvNAKRLCRSCRYQKCLEVGMTED 109
Cdd:cd07171   6 CAVCSDYA-SGYHYGVWSCEGCKAFFKRSIQGHNDYICPATNQCTIDK--NRRKSCQACRLRKCYEVGMMKG 74

DNA-binding domain of Ecdysone receptor (ECR) family is composed of two C4-type zinc fingers; DNA-binding domain of Ecdysone receptor (EcR) family is composed of two C4-type zinc fingers. Each zinc finger contains a group of four Cys residues which co-ordinates a single zinc atom. EcR interacts with highly degenerate pseudo-palindromic response elements, resembling inverted repeats of 5'-AGGTCA-3' separated by 1 bp, upstream of the target gene and modulates the rate of transcriptional initiation. EcR is present only in invertebrates and regulates the expression of a large number of genes during development and reproduction. EcR functions as a heterodimer by partnering with ultraspiracle protein (USP), the ortholog of the vertebrate retinoid X receptor (RXR). The natural ligands of EcR are ecdysteroids, the endogenous steroidal hormones found in invertebrates. Like other members of the nuclear receptor (NR) superfamily of ligand-activated transcription factors, EcRs have a central well conserved DNA binding domain (DBD), a variable N-terminal domain, a non-conserved hinge and a C-terminal ligand binding domain (LBD).

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 28396060  38 CLVCGRVAnTGHHYGVTACLGCKTFFRRVVLQKNSPKCKYKNHCRLEksVNAKRLCRSCRYQKCLEVGMTEDALHP 113
Cdd:cd07161   4 CLVCGDRA-SGYHYNALTCEGCKGFFRRSVTKSAVYHCKYGRACEMD--MYMRRKCQECRLKKCLSVGMRPECVVP 76

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 28396060  38 CLVCGRVAnTGHHYGVTACLGCKTFFRRVVLQKNSPKCKYKNHCRLEKsvNAKRLCRSCRYQKCLEVGMTED 109
Cdd:cd07155   1 CLVCGDIA-SGYHYGVASCEACKAFFKRTIQGNLGYSCPSTSECEVDK--KRRKSCQACRLQKCLKVGMLKE 69

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 28396060  38 CLVCGRVAnTGHHYGVTACLGCKTFFRRVVLQKNSPKCKYKNHCRLEKSVNAKrlCRSCRYQKCLEVGMTEDALHPCRD 116
Cdd:cd06964   7 CFVCQDKS-SGYHYGVSACEGCKGFFRRSIQKNMVYTCHRDKNCIINKVTRNR--CQYCRLQKCFEVGMSKESVRNDRN 82

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 28396060  38 CLVCGRVAnTGHHYGVTACLGCKTFFRRVVLQKNSPKCKYKNHCRLeKSVNAKRlCRSCRYQKCLEVGMTEDAL 111
Cdd:cd07165   1 CKVCGDKA-SGYHYGVTSCEGCKGFFRRSIQKQIEYRCLRDGKCEI-IRLNRNR-CQYCRFKKCLAAGMSKDSV 71

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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 28396060  18 EEEEAGPSTTIKAEEedgpCCLVCGRVAnTGHHYGVTACLGCKTFFRRVVLQKNSPKCKYKNHCRLEKSVnaKRLCRSCR 97
Cdd:cd07160   5 RKRKKGPAPKMLGNE----VCSVCGDKA-SGFHYNVLSCEGCKGFFRRSVIKGAQYVCKNGGKCQMDMYM--RRKCQECR 77

                        90
                ....*....|..
gi 28396060  98 YQKCLEVGMTED 109
Cdd:cd07160  78 LRKCREAGMREQ 89

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 28396060   207 SLKVDILLLREWVDRIPGFRELSERFQQHLMHRFCLRYTVIEHGLFTAqmPYHKNVWFLSDRTCLVSEFENLPQEIKKHL 286
Cdd:pfam00104  19 LWERDLLLVAEWAKHFPEFQELPLEDQMALLKSFWLEWLRLEKAARSA--KLRRKKILGEDVLMISDDDAMKFVEDDSSW 96

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 28396060   287 TPKVINEQQLL-ASFTEMLIHEVADPLRRLKPDSVEVATVKTLMLLkptclrEIDGDYLSTETdIKSVNDVRNRVINGLY 365
Cdd:pfam00104  97 CTNYDLEQLLFfLPFFNSYFFELVKPLRELNPDDEELAYLLAQLLF------DYAGDGLSGEI-LEIVEKLQEKLANELH 169

                  ....*.
gi 28396060   366 SHYIKN 371
Cdd:pfam00104 170 DYYVNK 175

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 28396060  38 CLVCGRVAnTGHHYGVTACLGCKTFFRRVVLQK-NSPKCKYKNHCRLEKsVNAKRlCRSCRYQKCLEVGMTEDAL 111
Cdd:cd07158   1 CKVCGDKA-SGFHYGVHSCEGCKGFFRRTIQHNlTYRRCLNGGKCVIQR-KNRNR-CQYCRFKKCLSVGMSRNAV 72

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        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 28396060  38 CLVCG-RVanTGHHYGVTACLGCKTFFRRVVLQKNSPKCKYKNHCRLEKSvNAKRlCRSCRYQKCLEVGMTEDALHPCRD 116
Cdd:cd07167   1 CPVCGdKV--SGYHYGLLTCESCKGFFKRTVQNKKRYTCIENQNCQIDKT-QRKR-CPYCRFQKCLSVGMKLEAVRADRM 76

                ....
gi 28396060 117 VIGR 120
Cdd:cd07167  77 RGGR 80

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).

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                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 28396060  38 CLVCGRvANTGHHYGVTACLGCKTFFRRVVLQKNSPKCKYKNHCRLEKsVNAKRlCRSCRYQKCLEVGMTEDA 110
Cdd:cd06968   8 CKICGD-KSSGIHYGVITCEGCKGFFRRSQQNNVSYSCPRQKNCLIDR-TNRNR-CQHCRLQKCLALGMSRDA 77

DNA-binding domain of Tailless (TLX) is composed of two C4-type zinc fingers; DNA-binding domain of Tailless (TLX) is composed of two C4-type zinc fingers. Each zinc finger contains a group of four Cys residues which co-ordinates a single zinc atom. TLX interacts with specific DNA sites upstream of the target gene and modulates the rate of transcriptional initiation. TLX is an orphan receptor that is expressed by neural stem/progenitor cells in the adult brain of the subventricular zone (SVZ) and the dentate gyrus (DG). It plays a key role in neural development by promoting cell cycle progression and preventing apoptosis in the developing brain. Like other members of the nuclear receptor (NR) superfamily of ligand-activated transcription factors, TLX has a central well conserved DNA-binding domain (DBD), a variable N-terminal domain, a flexible hinge and a C-terminal ligand binding domain (LBD).

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                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 28396060  38 CLVCGRvANTGHHYGVTACLGCKTFFRRVVLQKNSPKCKYKNH--CRLEKSvnAKRLCRSCRYQKCLEVGMTEDAL 111
Cdd:cd07163   9 CKVCGD-RSSGKHYGIYACDGCSGFFKRSIRRNRQYVCKSKGQggCPVDKT--HRNQCRACRLKKCFEVGMNKDAV 81

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 28396060  38 CLVCGRVAnTGHHYGVTACLGCKTFFRRVVLQKNSPKCKYKNHCRLEKsvNAKRLCRSCRYQKCLEVGM------TEDAL 111
Cdd:cd06955   9 CGVCGDRA-TGFHFNAMTCEGCKGFFRRSMKRKALFTCPFNGDCRITK--DNRRHCQACRLKRCVDIGMmkefilTDEEV 85

                        90
                ....*....|
gi 28396060 112 HPCRDVIGRR 121
Cdd:cd06955  86 QRKREMILKR 95

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.

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                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 28396060  38 CLVCGRVAnTGHHYGVTACLGCKTFFRRVVLQKNSPKCKYKNHCRLEKsvNAKRLCRSCRYQKCLEVGMTEDALHPCRDV 117
Cdd:cd07162   2 CRVCGDRA-TGYHFNAMTCEGCKGFFRRAMKRNARLCCPFQKGCVITK--SNRRQCQACRLRKCLSIGMKKELIMSDEAV 78

                ....
gi 28396060 118 IGRR 121
Cdd:cd07162  79 EKRR 82

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).

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gi 28396060  36 PCCLVCGRVAnTGHHYGVTACLGCKTFFRRVVLQKNSPKCKYKNHCRLEKSVNAKrlCRSCRYQKCLEVGMTEDALHPCR 115
Cdd:cd06956   1 HICAICGDRA-SGKHYGVYSCEGCKGFFKRTVRKDLTYTCRDNKDCLIDKRQRNR--CQYCRYQKCLAMGMKREAVQEER 77

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 28396060  38 CLVCGRVAnTGHHYGVTACLGCKTFFRRVVLQKNSPKCKYKNHCRLEKSvnAKRLCRSCRYQKCLEVGMTEDA 110
Cdd:cd06963   1 CLICGDEA-SGCHYGVLTCGSCKVFFKRAAEGQHNYLCAGRNDCIIDKI--RRKNCPACRLRKCYQAGMTLGA 70

DNA-binding domain of androgen receptor (AR) is composed of two C4-type zinc fingers; DNA-binding domain of androgen receptor (AR) 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. To regulate gene expression, AR interacts with a palindrome of the core sequence 5'-TGTTCT-3' with a 3-bp spacer. It also binds to the direct repeat 5'-TGTTCT-3' hexamer in some androgen controlled genes. AR is activated by the androgenic hormones, testosterone or dihydrotestosterone, which are responsible for primary and for secondary male characteristics, respectively. The primary mechanism of action of ARs is by direct regulation of gene transcription. The binding of androgen results in a conformational change in the androgen receptor which causes its transport from the cytosol into the cell nucleus, and dimerization. The receptor dimer binds to a hormone response element of AR regulated genes and modulates their expression. Another mode of action of androgen receptor is independent of their interactions with DNA. The receptor interacts directly with signal transduction proteins in the cytoplasm, causing rapid changes in cell function, such as ion transport. Like other members of the nuclear receptor (NR) superfamily of ligand-activated transcription factors, AR 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 28396060  38 CLVCGRVAnTGHHYGVTACLGCKTFFRRVVLQKNSPKCKYKNHCRLEKSvnAKRLCRSCRYQKCLEVGMT 107
Cdd:cd07173   6 CLICGDEA-SGCHYGALTCGSCKVFFKRAAEGKQKYLCASRNDCTIDKF--RRKNCPSCRLRKCFEAGMT 72

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 28396060  38 CLVCGRVAnTGHHYGVTACLGCKTFFRRVVLQKNSPKCKYKNHCRLEKSvnAKRLCRSCRYQKCLEVGMT 107
Cdd:cd07172   5 CLVCSDEA-SGCHYGVLTCGSCKVFFKRAVEGQHNYLCAGRNDCIIDKI--RRKNCPACRLRKCLQAGMN 71

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 28396060 207 SLKVDILLLREWVDRIPGFRELSERFQQHLmhrfcLRYTVIEH---GLFTAQMPYhKNVWFLS-DRTCLVSEFEnlpQEI 282
Cdd:cd06931  40 SMKQQLLVLVEWAKYIPAFCELPLDDQVAL-----LRAHAGEHlllGVARRSMPY-KDILLLGnDLIIPRHCPE---PEI 110

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 28396060 283 KkhltpKVINEqqllasftemLIHEVADPLRRLKPDSVEVATVKTLMLLKPtclreiDGDYLSTETDIKSvndVRNRVIN 362
Cdd:cd06931 111 S-----RVANR----------ILDELVLPLRDLNIDDNEYACLKAIVFFDP------DAKGLSDPQKIKR---LRFQVQV 166

                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|...
gi 28396060 363 GLySHYIkNGMDPEQlPIRVSEILNLTGGVEQCAARALEEMHPTRVFNLSSFD 415
Cdd:cd06931 167 SL-EDYI-NDRQYDS-RGRFGELLLLLPTLQSITWQMIEQIQFARLFGVAKID 216