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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 929229739  83 RIYKPCFVCQDKSSGYHYGVSSCEGCKGFFRRSIQKNMVYTCHRDKNCQINKVTRNRCQYCRLQKCFEVGMSKEGerLRN 162
Cdd:cd06964    2 RIYKPCFVCQDKSSGYHYGVSACEGCKGFFRRSIQKNMVYTCHRDKNCIINKVTRNRCQYCRLQKCFEVGMSKES--VRN 79

                 ....*.
gi 929229739 163 DRNKKK 168
Cdd:cd06964   80 DRNKKK 85

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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 929229739  83 RIYKPCFVCQDKSSGYHYGVSSCEGCKGFFRRSIQKNMVYTCHRDKNCQINKVTRNRCQYCRLQKCFEVGMSKEGerLRN 162
Cdd:cd06964    2 RIYKPCFVCQDKSSGYHYGVSACEGCKGFFRRSIQKNMVYTCHRDKNCIINKVTRNRCQYCRLQKCFEVGMSKES--VRN 79

                 ....*.
gi 929229739 163 DRNKKK 168
Cdd:cd06964   80 DRNKKK 85

c4 zinc finger in nuclear hormone receptors;

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 929229739    87 PCFVCQDKSSGYHYGVSSCEGCKGFFRRSIQKNMVYTCHRDKNCQINKVTRNRCQYCRLQKCFEVGMSKE 156
Cdd:smart00399   1 LCCVCGDHASGFHFGVCSCRACKAFFRRTVNLRYKYRCDRKNNCSINKRYRCRCRACRLKKCLGVGMDPE 70

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 929229739  231 FSELSTKCIIKIVEFAKRLPGFTTLTIADQITLLKSACLDILMLRICTRYTPEQDTMTFSDGLTL--------------- 295
Cdd:pfam00104  16 LCELWERDLLLVAEWAKHFPEFQELPLEDQMALLKSFWLEWLRLEKAARSAKLRRKKILGEDVLMisdddamkfveddss 95

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 929229739  296 ---NRTQMHNAGFGPLTD-LVFAFAGQLLPLEMDDTETGLLSAISL--ISGDRMDLEEPQKVDKLQEPLLEALKIYARRR 369
Cdd:pfam00104  96 wctNYDLEQLLFFLPFFNsYFFELVKPLRELNPDDEELAYLLAQLLfdYAGDGLSGEILEIVEKLQEKLANELHDYYVNK 175

                         170       180
                  ....*....|....*....|..
gi 929229739  370 RpnkPHMFPRMLMKITDLRGIS 391
Cdd:pfam00104 176 Y---SGRLAKLLKILPSLRKIS 194

Ligand-binding domain of nuclear receptor family 1; Ligand-binding domain (LBD) of nuclear receptor (NR) family 1: This is one of the major subfamily of nuclear receptors, including thyroid receptor, retinoid acid receptor, ecdysone receptor, farnesoid X receptor, vitamin D receptor, and other related receptors. 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).

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 929229739 227 LWDKFSELSTKCIIKIVEFAKRLPGFTTLTIADQITLLKSACLDILMLRICTRYTPEQDTMTFSDGLTLNRTQMHNAGFG 306
Cdd:cd06929    3 KFDHFTEIMTVAIRRVVEFAKRIPGFRELSQEDQIALLKGGCFEILLLRSATLYDPEKNSLTFGDGKGNSRDVLLNGGFG 82

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 929229739 307 PLTDLVFAFAGQLLPLEMDDTETGLLSAISLISGDRMDLEEPQKVDKLQEPLLEALKIYARRRRPNKPHMFPRMLMKITD 386
Cdd:cd06929   83 EFIEPLFEFAEKMNKLQLDDNEYALLTAIVLFSPDRPGLQDVDTVEKLQERLLEALQRYLKVNHPDAPQMFAKLLKKLTE 162

                        170
                 ....*....|.
gi 929229739 387 LRGISTKGAER 397
Cdd:cd06929  163 LRTLNELHAEL 173

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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 929229739  83 RIYKPCFVCQDKSSGYHYGVSSCEGCKGFFRRSIQKNMVYTCHRDKNCQINKVTRNRCQYCRLQKCFEVGMSKEGerLRN 162
Cdd:cd06964    2 RIYKPCFVCQDKSSGYHYGVSACEGCKGFFRRSIQKNMVYTCHRDKNCIINKVTRNRCQYCRLQKCFEVGMSKES--VRN 79

                 ....*.
gi 929229739 163 DRNKKK 168
Cdd:cd06964   80 DRNKKK 85

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 929229739  88 CFVCQDKSSGYHYGVSSCEGCKGFFRRSIQKNMVYTCHRDKNCQINKVTRNRCQYCRLQKCFEVGMSKEGER 159
Cdd:cd06916    1 CAVCGDKASGYHYGVLTCEGCKGFFRRSVRRNLEYTCPAGGNCVIDKRNRNRCQACRLKKCLAVGMRKEAVR 72

The ligand binding domain of Drosophila ecdysone-induced protein 78, a member of the nuclear receptor superfamily; The ligand binding domain (LBD) of Drosophila ecdysone-induced protein 78 (E78) like: 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. Two isoforms of E78, E78A and E78B, are expressed from two nested transcription units. 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. 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 929229739 227 LWDKFSELSTKCIIKIVEFAKRLPGFTTLTIADQITLLKSACLDILMLRICTRYTPEQDTMTFSDGLTLNRTQMhNAGFG 306
Cdd:cd06941    3 LWQQLSEALTPSVQRVVEFAKRIPGFCDLSQDDQLLLIKAGFFEVWLVRISRLINSKSGSITFDDGISISRQQL-DIIYD 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 929229739 307 P-LTDLVFAFAGQLLPLEMDDTETGLLSAISLISGDRMDLEEPQKVDKLQEPLLEALKIYARRRRPNKPHMFPRMLMKIT 385
Cdd:cd06941   82 SdFVKALFEFSDSFNSLGLSDTEVALFCAVVLLSPDRIGLSEPKKVAILQDRVLEALKVQVSRNRPAEAQLFASLLMKIP 161

                        170       180       190
                 ....*....|....*....|....*....|....
gi 929229739 386 DLRGISTKGAERAITLKMEIPGP-MPPLIREMLE 418
Cdd:cd06941  162 ELRSIGAKHQMHLDWYRVNWPLLrLPPLFAEIYD 195

The ligand binding domain (LBD) of the Ecdysone receptor, a member of the nuclear receptors super family; The ligand binding domain (LBD) of the ecdysone receptor: The ecdysone receptor (EcR) belongs to the superfamily of nuclear receptors (NRs) of ligand-dependent transcription factors. Ecdysone receptor is present only in invertebrates and regulates the expression of a large number of genes during development and reproduction. ECR functions as a heterodimer by partnering with ultraspiracle protein (USP), the ortholog of the vertebrate retinoid X receptor (RXR). The natural ligands of ecdysone receptor are ecdysteroids#the endogenous steroidal hormones found in invertebrates. In addition, insecticide bisacylhydrazine used against pests has shown to act on EcR. EcR must be dimerised with a USP for high-affinity ligand binding to occur. The ligand binding triggers a conformational change in the C-terminal part of the EcR ligand-binding domain that leads to transcriptional activation of genes controlled by EcR. Like other members of the nuclear receptor (NR) superfamily of ligand-activated transcription factors, ec dysone receptors have a central well conserved DNA binding domain (DBD), a variable N-terminal domain, a non-conserved hinge and a C-terminal ligand binding domain (LBD).

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 929229739 242 IVEFAKRLPGFTTLTIADQITLLKSACLDILMLRICTRYTPEQDTMTFSDGLTLNRTQMHNAGFGPLTDLVFAFAGQLLP 321
Cdd:cd06938   55 IVEFAKRLPGFDKLSREDQITLLKACSSEVMMLRVARRYDAKTDSIVFANNQPYTRDSYRKAGMGDSAEDLFRFCRAMCS 134

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 929229739 322 LEMDDTETGLLSAISLISgDRMDLEEPQKVDKLQEPLLEALKIY-ARRRRPNKPHMFPRMLMKITDLRGISTKGAERAIT 400
Cdd:cd06938  135 MKVDNAEYALLTAIVIFS-DRPGLLQPKKVEKIQEIYLEALRAYvDNRRPPSQRVIFAKLLSILTELRTLGNQNSEMCFS 213

                        170
                 ....*....|....*
gi 929229739 401 LKMEIpGPMPPLIRE 415
Cdd:cd06938  214 LKLKN-RKLPPFLAE 227

The ligand binding domain of Nurr1 and related nuclear receptor proteins, members of nuclear receptor superfamily; The ligand binding domain of nuclear receptor Nurr1_like: This family of nuclear receptors, including Nurr1, Nerve growth factor-induced-B (NGFI-B) and DHR38 are involved in the embryo development. Nurr1 is a transcription factor that is expressed in the embryonic ventral midbrain and is critical for the development of dopamine (DA) neurons. Structural studies have shown that the ligand binding pocket of Nurr1 is filled by bulky hydrophobic residues, making it unable to bind to ligands. Therefore, it belongs to the class of orphan receptors. However, Nurr1 forms heterodimers with RXR and can promote signaling via its partner, RXR. NGFI-B is an early immediate gene product of embryo development that is rapidly produced in response to a variety of cellular signals including nerve growth factor. It is involved in T-cell-mediated apoptosis, as well as neuronal differentiation and function. NGFI-B regulates transcription by binding to a specific DNA target upstream of its target genes and regulating the rate of tr anscriptional initiation. Another group of receptor in this family is DHR38. DHR38 is the Drosophila homolog to the vertebrate NGFI-B-type orphan receptor. It interacts with the USP component of the ecdysone receptor complex, suggesting that DHR38 might modulate ecdysone-triggered signals in the fly, in addition to the ECR/USP pathway. Nurr1_like proteins exhibit a modular structure that is characteristic for nuclear receptors; they 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 929229739 189 ELVNKVSKAHQDTFPSLLQLGKyhtnSSAEQRVQLDLGLWD-----KFSELSTKCIIKIVEFAKRLPGFTTLTIADQITL 263
Cdd:cd06945    3 SLITALVRAHVDSTPRKTDLDY----SKIQENVDPVPPKPDsqqvqQFYDLLTGSVDVIRQWAEKIPGFKDLHREDQDLL 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 929229739 264 LKSACLDILMLRICTRYTPEQDTMTFSDGLTLNRTQMHNaGFGPLTDLVFAFAGQLLPLEMDDTETGLLSAISLISGDRM 343
Cdd:cd06945   79 LESAFLELFVLRLAYRSNPVDGKLVFCNGLVLHRLQCVR-GFGEWLDSILAFSSSLQSLLLDDISAFCCLALLLLITERH 157

                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 929229739 344 DLEEPQKVDKLQEPLLEALKIYARRRRP--NKPHMFPRMLMKITDLRGISTKGAERAITLKMEIPGPMPPLIREMLE 418
Cdd:cd06945  158 GLKEPKKVEELQNKIISCLRDHVTSNYPgqDKPNRLSKLLLKLPELRTLSKKGLQRIFFLKLEDLLPPPPLIDKRFL 234

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 929229739  87 PCFVCQDKSSGYHYGVSSCEGCKGFFRRSIQKNMVYTCHRDKNCQINKVTRNRCQYCRLQKCFEVGMSKEGERlRNDRNK 166
Cdd:cd06968    7 PCKICGDKSSGIHYGVITCEGCKGFFRRSQQNNVSYSCPRQKNCLIDRTNRNRCQHCRLQKCLALGMSRDAVK-FGRMSK 85

                         90
                 ....*....|
gi 929229739 167 KKKDVKEELV 176
Cdd:cd06968   86 KQRDSLYAEV 95

The ligand binding domain of REV-ERB receptors, members of the nuclear receptor superfamily; The ligand binding domain (LBD) of REV-ERB receptors: REV-ERBs are transcriptional regulators belonging to the nuclear receptor superfamily. They regulate a number of physiological functions including the circadian rhythm, lipid metabolism, and cellular differentiation. The LBD domain of REV-ERB is unusual in the nuclear receptor family by lacking the AF-2 region that is responsible for coactivator interaction. REV-ERBs act as constitutive repressors because of their inability to bind coactivators. REV-ERB receptors can bind to two classes of DNA response elements as either a monomer or heterodimer, indicating functional diversity. When bound to the DNA, they recruit corepressors (NcoR/histone deacetylase 3) to the promoter, resulting in repression of the target gene. The porphyrin heme has been demonstrated to function as a ligand for REV-ERB. Like other members of the nuclear receptor (NR) superfamily of ligand-activated transcription factors, REV-ERB receptors have a central well conserved DNA binding domain (DBD), a variable N-terminal domain, a non-conserved hinge and a C-terminal ligand binding domain (LBD).

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 929229739 227 LWDKFSELSTKCIIKIVEFAKRLPGFTTLTIADQITLLKSACLDILMLRICTRYTPEQDTMTFSDGLTLNRTQMHNAGFG 306
Cdd:cd06940   13 IWEEFSMSFTPAVREVVEFAKRIPGFRDLSQHDQVTLLKAGTFEVLMVRFASLFDAKERSVTFLSGQKYSVDDLHSMGAG 92

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 929229739 307 PLTDLVFAFAGQLLPLEMDDTETGLLSAISLISGDRMDLEEPQKVDKLQEPLLEALKIYARRRRPNKPHMFPRMLMKITD 386
Cdd:cd06940   93 DLLNSMFDFSEKLNSLQLSDEEMGLFTAVVLVSADRSGLENVNLVEALQETLIRALRTLIAKNHPNEPSIFTKLLLKLPD 172

                        170
                 ....*....|....*..
gi 929229739 387 LRGISTKGAERAITLKM 403
Cdd:cd06940  173 LRTLNNLHSEKLLAFKV 189

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 929229739  88 CFVCQDKSSGYHYGVSSCEGCKGFFRRSIQKNMVYTCHRDKNCQINKVTRNRCQYCRLQKCFEVGMSKEGERLRNDRNKK 167
Cdd:cd07165    1 CKVCGDKASGYHYGVTSCEGCKGFFRRSIQKQIEYRCLRDGKCEIIRLNRNRCQYCRFKKCLAAGMSKDSVRYGRIPNRQ 80

                 .
gi 929229739 168 K 168
Cdd:cd07165   81 R 81

Ligand binding domain of DHR38_like proteins, members of the nuclear receptor superfamily; The ligand binding domain of nuclear receptor DHR38_like proteins: DHR38 is a member of the steroid receptor superfamily in Drosophila. DHR38 interacts with the USP component of the ecdysone receptor complex, suggesting that DHR38 might modulate ecdysone-triggered signals in the fly, in addition to the ECR/USP pathway. At least four differentially expressed mRNA isoforms have been detected during development. Like other members of the nuclear receptor (NR) superfamily of ligand-activated transcription factors, DHR38 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 929229739 190 LVNKVSKAHQDTFPSL--LQLGKYHTNSSAEQRVQlDLGLWDKFSELSTKCIIKIVEFAKRLPGFTTLTIADQITLLKSA 267
Cdd:cd07072    5 LITALVRAHVDTSPDFanLDYSQYREPSPLEPPMS-EAEKVQQFYSLLTSSIDVIKTFAEKIPGFPDLCKEDQELLFQSA 83

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 929229739 268 CLDILMLRICTRYTPEQDTMTFSDGLTLNRTQMHNAgFGPLTDLVFAFAGQLLPLEMDDTETGLLSAISLISgDRMDLEE 347
Cdd:cd07072   84 SLELFVLRLAYRTAPEDTKLTFCNGVVLHKQQCQRS-FGDWLHAILEFSKSLHAMDIDISAFACLCALTLIT-ERHGLKE 161

                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 929229739 348 PQKVDKLQEPLLEALK--IYARRRRPNKPHMFPRMLMKITDLRGISTKGAERAITLKMEIPGPMPPLIREM 416
Cdd:cd07072  162 PHKVEQLQMKIISSLRdhVTYNAEAQKKPHYFSRLLGKLPELRSLSVQGLQRIFYLKLEDLVPAPPLIENM 232

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 929229739  88 CFVCQDKSSGYHYGVSSCEGCKGFFRRSIQKNMVYTCHRDKNCQINKVTRNRCQYCRLQKCFEVGMSKEGERL 160
Cdd:cd07179    1 CRVCGGKSSGFHFGALTCEGCKGFFRRTELSSNSYVCPGGQNCAITPATRNACKSCRFRRCLAVGMSKTGSRI 73

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 929229739  86 KPCFVCQDKSSGYHYGVSSCEGCKGFFRRSIQKNMVYTCHRDKNCQINKVTRNRCQYCRLQKCFEVGMSKEG---ERLRN 162
Cdd:cd07169    7 RTCLICGDRATGLHYGIISCEGCKGFFKRSICNKRVYRCSRDKNCVMSRKQRNRCQYCRLLKCLQMGMNRKAireDGMPG 86

                 ....
gi 929229739 163 DRNK 166
Cdd:cd07169   87 GRNK 90

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 929229739  88 CFVCQDKSSGYHYGVSSCEGCKGFFRRSIQKNMVYTCHRDKNCQINKVTRNRCQYCRLQKCFEVGMSKEGERL 160
Cdd:cd07155    1 CLVCGDIASGYHYGVASCEACKAFFKRTIQGNLGYSCPSTSECEVDKKRRKSCQACRLQKCLKVGMLKEGVRL 73

The ligand binding domain of Retinoid-related orphan receptors, of the nuclear receptor superfamily; The ligand binding domain (LBD) of Retinoid-related orphan receptors (RORs): Retinoid-related orphan receptors (RORs) are transcription factors belonging to the nuclear receptor superfamily. RORs are key regulators of many physiological processes during embryonic development. RORs bind as monomers to specific ROR response elements (ROREs) consisting of the consensus core motif AGGTCA preceded by a 5-bp A/T-rich sequence. Transcription regulation by RORs is mediated through certain corepressors, as well as coactivators. There are three subtypes of retinoid-related orphan receptors (RORs), alpha, beta, and gamma that differ only in N-terminal sequence and are distributed in distinct tissues. RORalpha plays a key role in the development of the cerebellum, particularly in the regulation of the maturation and survival of Purkinje cells. RORbeta expression is largely restricted to several regions of the brain, the retina, and pineal gland. RORgamma is essential for lymph node organogenesis. Recently, it has been su ggested that cholesterol or a cholesterol derivative is the natural ligand of RORalpha. Like other members of the nuclear receptor (NR) superfamily of ligand-activated transcription factors, retinoid-related orphan receptors have a central well conserved DNA binding domain (DBD), a variable N-terminal domain, a non-conserved hinge and a C-terminal ligand binding domain (LBD).

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 929229739 186 ELEELVNKVSKAHQDT-------------FPSLLQLGKYHTNSSAEQrvqldlgLWDKFSELSTKCIIKIVEFAKRLPGF 252
Cdd:cd06939    2 ELEHLAQNICKAHLETcqylreelqqlrwKTFSQEEILAYQNKSREE-------MWQLCAEKITEAIQYVVEFAKRIPGF 74

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 929229739 253 TTLTIADQITLLKSACLDILMLRICTRYTPEQDTMTFsDGLTLNRTQMHNAGFGPLTDLVFAFAGQLLPLEMDDTETGLL 332
Cdd:cd06939   75 MELCQNDQIVLLKAGSLEVVLVRMSRAFNPSNNTVLF-DGKYAPIDLFKSLGCDDLISAVFDFAKSLCELKLTEDEIALF 153

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 929229739 333 SAISLISGDRMDLEEPQKVDKLQEPLLEALKIYARRRRPNKPHMfPRMLMKITDLRGISTKGAERAITLKMEIPGP---- 408
Cdd:cd06939  154 SALVLISADRPGLQEKRKVEKLQQKIELALRHVLQKNHGDDTIL-TKLLAKMPTLRALCSLHMEKLQKFKQSYPDIvhle 232

                 ....*...
gi 929229739 409 MPPLIREM 416
Cdd:cd06939  233 FPPLYKEL 240

DNA-binding domain of chicken ovalbumin upstream promoter transcription factors (COUP-TFs) is composed of two C4-type zinc fingers; DNA-binding domain of chicken ovalbumin upstream promoter transcription factors (COUP-TFs) 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. COUP-TFs are orphan members of the steroid/thyroid hormone receptor superfamily. They are expressed in many tissues and are involved in the regulation of several important biological processes, such as neurogenesis, organogenesis, cell fate determination, and metabolic homeostasis. COUP-TFs homodimerize or heterodimerize with retinoid X receptor (RXR) and a few other nuclear receptors and bind to a variety of response elements that are composed of imperfect AGGTCA direct or inverted repeats with various spacings. COUP-TFs are generally considered to be repressors of transcription for other nuclear hormone receptors such as retinoic acid receptor (RAR), thyroid hormone receptor (TR), vitamin D receptor (VDR), peroxisome proliferator activated receptor (PPAR), and hepatocyte nuclear factor 4 (HNF4). Like other members of the nuclear receptor (NR) superfamily of ligand-activated transcription factors, COUP-TFs 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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 929229739  88 CFVCQDKSSGYHYGVSSCEGCKGFFRRSIQKNMVYTCHRDKNCQINKVTRNRCQYCRLQKCFEVGMSKE 156
Cdd:cd06958    1 CVVCGDKSSGKHYGQFTCEGCKSFFKRSVRRNLTYTCRGNRNCPIDQHHRNQCQYCRLKKCLKVGMRRE 69

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 929229739  88 CFVCQDKSSGYHYGVSSCEGCKGFFRRSIQKNMVYTCHRDKNCQINKVTRNRCQYCRLQKCFEVGMSKE 156
Cdd:cd06956    3 CAICGDRASGKHYGVYSCEGCKGFFKRTVRKDLTYTCRDNKDCLIDKRQRNRCQYCRYQKCLAMGMKRE 71

The ligand binding domain of peroxisome proliferator-activated receptors; The ligand binding domain (LBD) of peroxisome proliferator-activated receptors (PPAR): Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear receptor superfamily of ligand-activated transcription factors. PPARs play important roles in regulating cellular differentiation, development and lipid metabolism. Activated PPAR forms a heterodimer with the retinoid X receptor (RXR) that binds to the hormone response element located upstream of the peroxisome proliferator responsive genes and interacts with co-activators. There are three subtypes of peroxisome proliferator activated receptors, alpha, beta (or delta), and gamma, each with a distinct tissue distribution. Several essential fatty acids, oxidized lipids and prostaglandin J derivatives can bind and activate PPAR. Like other members of the nuclear receptor (NR) superfamily of ligand-activated transcription factors, PPAR has a central well conserved DNA binding domain (DBD), a variable N-terminal regulatory domain, a flexible hinge a nd a C-terminal ligand binding domain (LBD).

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 929229739 239 IIKIVEFAKRLPGFTTLTIADQITLLKSACLDILMLRICTRYTpeQDTMTFSDG---LTLNRTQMHNAGFGPLTDLVFAF 315
Cdd:cd06932   76 IRELTEFAKSLPGFRNLDLNDQVTLLKYGVHEVIFTMLASLYN--KDGLLFPEGngyVTREFLESLRKPFCDIMEPKFEF 153

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 929229739 316 AGQLLPLEMDDTETGLLSAISLISGDRMDLEEPQKVDKLQEPLLEALKIYARRRRPNKPHMFPRMLMKITDLRGISTKGA 395
Cdd:cd06932  154 AEKFNALELTDSELALFCAVIILSPDRPGLINRKPVERIQEHVLQALELQLKKNHPDSPQLFAKLLQKMVDLRQLVTDHV 233

                        170       180
                 ....*....|....*....|.
gi 929229739 396 ERAITLKM-EIPGPMPPLIRE 415
Cdd:cd06932  234 QMVQQIKKtETDASLPPLLQE 254

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 929229739  88 CFVCQDKSSGYHYGVSSCEGCKGFFRRSIQKNMVYTCHRDKNCQINKVTRNRCQYCRLQKCFEVGMSKEG---ERLRNDR 164
Cdd:cd07170    7 CLVCGDIASGYHYGVASCEACKAFFKRTIQGNIEYSCPATNECEITKRRRKSCQACRFMKCLKVGMLKEGvrlDRVRGGR 86

                         90
                 ....*....|
gi 929229739 165 NKKKKDVKEE 174
Cdd:cd07170   87 QKYKRRIDAE 96

The ligand binding domain of the retinoid X receptor and Ultraspiracle, members of nuclear receptor superfamily; The ligand binding domain of the retinoid X receptor (RXR) and Ultraspiracle (USP): This family includes two evolutionary related nuclear receptors: retinoid X receptor (RXR) and Ultraspiracle (USP). RXR is a nuclear receptor in mammalian and USP is its counterpart in invertebrates. The native ligand of retinoid X receptor is 9-cis retinoic acid (RA). RXR functions as a DNA binding partner by forming heterodimers with other nuclear receptors including CAR, FXR, LXR, PPAR, PXR, RAR, TR, and VDR. RXRs can play different roles in these heterodimers. It 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. Ultraspiracle (USP) plays similar roles as DNA binding partner of other nuclear rec eptors in invertebrates. USP has no known high-affinity ligand and is thought to be a silent component in the heterodimeric complex with partner receptors. Like other members of the nuclear receptor (NR) superfamily of ligand-activated transcription factors, RXR and USP 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 929229739 236 TKCIIKIVEFAKRLPGFTTLTIADQITLLKSACLDILMLRICTRYTPEQDTMTFSDGLTLNRTQMHNAGFGPLTDLVFA- 314
Cdd:cd06943   40 DKQLFQLVEWAKRIPHFSELPLDDQVILLRAGWNELLIAAFAHRSIAVKDGILLATGLHLHRNSAHQAGVGAIFDRILTe 119

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 929229739 315 FAGQLLPLEMDDTETGLLSAISLISGDRMDLEEPQKVDKLQEPLLEALKIYARRRRPNKPHMFPRMLMKITDLRGISTKG 394
Cdd:cd06943  120 LVVKMRDLKMDRTELGCLRAIILFNPDVKGLKSRQEVESLREKVYASLEEYCRQKHPEQPGRFAKLLLRLPALRSIGLKC 199

                 ..
gi 929229739 395 AE 396
Cdd:cd06943  200 LE 201

The DNA-binding domain of Ecdysone receptor (EcR) like nuclear receptor family is composed of two C4-type zinc fingers; The DNA-binding domain of Ecdysone receptor (EcR) like nuclear receptor family is composed of two C4-type zinc fingers. Each zinc finger contains a group of four Cys residues which co-ordinates a single zinc atom. EcR interacts with specific DNA sites upstream of the target gene and modulates the rate of transcriptional initiation. This family includes three types of nuclear receptors: Ecdysone receptor (EcR), Liver X receptor (LXR) and Farnesoid X receptor (FXR). The DNA binding activity is regulated by their corresponding ligands. The ligands for EcR are ecdysteroids; LXR is regulated by oxidized cholesterol derivatives or oxysterols; and bile acids control FXR's activities. Like other members of the nuclear receptor (NR) superfamily of ligand-activated transcription factors, EcR-like receptors have a central well conserved DNA binding domain (DBD), a variable N-terminal domain, a flexible hinge and a C-terminal ligand binding domain (LBD).

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 929229739  88 CFVCQDKSSGYHYGVSSCEGCKGFFRRSIQKNMVYTCHRDKNCQINKVTRNRCQYCRLQKCFEVGMSKE 156
Cdd:cd06959    2 CVVCGDKASGFHYGVLSCEGCKGFFRRSVTKGAVYACKFGNKCEMDMYMRRKCQECRLRKCKAAGMRPD 70

The DNA-binding domain of the photoreceptor cell-specific nuclear receptor (PNR) nuclear receptor-like family; 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).

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 929229739  88 CFVCQDKSSGYHYGVSSCEGCKGFFRRSIQKNMVYTCHR-DKNCQINKVTRNRCQYCRLQKCFEVGMSKEG 157
Cdd:cd07154    1 CKVCGDRSSGKHYGVYACDGCSGFFKRSIRRNLLYTCKAgNGSCVVDKARRNQCQACRLKKCLEVSMNKDA 71

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 929229739  88 CFVCQDKSSGYHYGVSSCEGCKGFFRRSIQKNMVYTCHRDKNCQINKVTRNRCQYCRLQKCFEVGMSKE 156
Cdd:cd07161    4 CLVCGDRASGYHYNALTCEGCKGFFRRSVTKSAVYHCKYGRACEMDMYMRRKCQECRLKKCLSVGMRPE 72