The ligand binding domain of thyroid hormone receptor, a members of a superfamily of nuclear receptors; The ligand binding domain (LBD) of thyroid hormone receptors: Thyroid hormone receptors are members of a superfamily of nuclear receptors. Thyroid hormone receptors (TR) mediate 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 24308535 168 EWELIRMVTEAHRHTNAQGPHWKQKRKFLPEDIGQSP-APTSDNDKVDLEAFSEFTKIITPAITRVVDFAKKLPMFSELP 246
Cdd:cd06935   3 EWELIRTVTEAHVATNAQGSHWKQKRKFLPEDIGQAPiVSAPDGDKVDLEAFSHFTKIITPAITRVVDFAKKLPMFTELP 82

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24308535 247 CEDQIILLKGCCMEIMSLRAAVRYDPESETLTLSGEMAVSREQLKNGGLGVVSDAIFDLGKSLSQFNLDDSEVALLQAVL 326
Cdd:cd06935  83 CEDQIILLKGCCMEIMSLRAAVRYDPESETLTLSGEMAVTREQLKNGGLGVVSDAIFDLGVSLSSFNLDDTEVALLQAVL 162

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24308535 327 LMSSDRSGLTCVEKIEKCQEMYLLAFEHYINHRKHNISHFWPKLLMKVTNLRMIGACHASRFLHMKVECPTELFPPLFLE 406
Cdd:cd06935 163 LMSSDRPGLACVERIEKLQDSFLLAFEHYINYRKHHVPHFWPKLLMKVTDLRMIGACHASRFLHMKVECPTELFPPLFLE 242

                .
gi 24308535 407 V 407
Cdd:cd06935 243 V 243

The ligand binding domain of thyroid hormone receptor, a members of a superfamily of nuclear receptors; The ligand binding domain (LBD) of thyroid hormone receptors: Thyroid hormone receptors are members of a superfamily of nuclear receptors. Thyroid hormone receptors (TR) mediate 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 24308535 168 EWELIRMVTEAHRHTNAQGPHWKQKRKFLPEDIGQSP-APTSDNDKVDLEAFSEFTKIITPAITRVVDFAKKLPMFSELP 246
Cdd:cd06935   3 EWELIRTVTEAHVATNAQGSHWKQKRKFLPEDIGQAPiVSAPDGDKVDLEAFSHFTKIITPAITRVVDFAKKLPMFTELP 82

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24308535 247 CEDQIILLKGCCMEIMSLRAAVRYDPESETLTLSGEMAVSREQLKNGGLGVVSDAIFDLGKSLSQFNLDDSEVALLQAVL 326
Cdd:cd06935  83 CEDQIILLKGCCMEIMSLRAAVRYDPESETLTLSGEMAVTREQLKNGGLGVVSDAIFDLGVSLSSFNLDDTEVALLQAVL 162

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24308535 327 LMSSDRSGLTCVEKIEKCQEMYLLAFEHYINHRKHNISHFWPKLLMKVTNLRMIGACHASRFLHMKVECPTELFPPLFLE 406
Cdd:cd06935 163 LMSSDRPGLACVERIEKLQDSFLLAFEHYINYRKHHVPHFWPKLLMKVTDLRMIGACHASRFLHMKVECPTELFPPLFLE 242

                .
gi 24308535 407 V 407
Cdd:cd06935 243 V 243

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 24308535    56 PCVVCGDKATGYHYRCITCEGCKGFFRRTIQKNLHpsYSCKYDSCCIIDKITRNQCQLCRFRKCISVGM 124
Cdd:pfam00105   1 LCKVCGDKASGYHYGVLTCEGCKGFFRRSIQKNIV--YTCKFNKDCVIDKRNRNRCQYCRLKKCLEVGM 67

Ligand binding domain of hormone receptors;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24308535    229 ITRVVDFAKKLPMFSELPCEDQIILLKGCCMEIMSLRAAVRYDPESETLTLSGEMAVSREQ----LKNGGLGVVSDAIFD 304
Cdd:smart00430   5 LLLTVEWAKSFPGFRELSLEDQIVLLKSFWFELLLLELAYRSVKLKKELLLAPDGTYIRPDavleLRKLFSPFLDRILSE 84

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 24308535    305 LGKSLSQFNLDDSEVALLQAVLLMSSDRSGLT--CVEKIEKCQEMYLLA-FEHYINHRKHNISHFWPKLLMKVTNLRMI 380
Cdd:smart00430  85 LVKPLRELKLDDEEYALLKAIVLFNPAVPGLSeeGKEIVEKLQEKYANAlHDYYLKNYPMNYPGRFAKLLLILPELRKI 163

The ligand binding domain of thyroid hormone receptor, a members of a superfamily of nuclear receptors; The ligand binding domain (LBD) of thyroid hormone receptors: Thyroid hormone receptors are members of a superfamily of nuclear receptors. Thyroid hormone receptors (TR) mediate 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 24308535 168 EWELIRMVTEAHRHTNAQGPHWKQKRKFLPEDIGQSP-APTSDNDKVDLEAFSEFTKIITPAITRVVDFAKKLPMFSELP 246
Cdd:cd06935   3 EWELIRTVTEAHVATNAQGSHWKQKRKFLPEDIGQAPiVSAPDGDKVDLEAFSHFTKIITPAITRVVDFAKKLPMFTELP 82

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24308535 247 CEDQIILLKGCCMEIMSLRAAVRYDPESETLTLSGEMAVSREQLKNGGLGVVSDAIFDLGKSLSQFNLDDSEVALLQAVL 326
Cdd:cd06935  83 CEDQIILLKGCCMEIMSLRAAVRYDPESETLTLSGEMAVTREQLKNGGLGVVSDAIFDLGVSLSSFNLDDTEVALLQAVL 162

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24308535 327 LMSSDRSGLTCVEKIEKCQEMYLLAFEHYINHRKHNISHFWPKLLMKVTNLRMIGACHASRFLHMKVECPTELFPPLFLE 406
Cdd:cd06935 163 LMSSDRPGLACVERIEKLQDSFLLAFEHYINYRKHHVPHFWPKLLMKVTDLRMIGACHASRFLHMKVECPTELFPPLFLE 242

                .
gi 24308535 407 V 407
Cdd:cd06935 243 V 243

The ligand binding domain (LBD) of retinoic acid receptor (RAR), a members of the nuclear receptor superfamily; The ligand binding domain (LBD) of retinoic acid receptor (RAR): Retinoic acid receptors are members of the nuclear receptor (NR) superfamily of ligand-regulated transcription factors. RARs mediate the biological effect of retinoids, including both naturally 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. RARs function as heterodimers with retinoic X receptors by binding to specific RAR response elements (RAREs) found in the promoter regions of retinoid target genes. In the absence of ligand, the RAR-RXR heterodimer recruits the corepressor proteins NCoR or AMRT, and associated factors such as histone deacetylases or DNA-methyltransferases, leading to an inactive condensed chromatin structure, preventing transcription. Upon ligand binding, the corepressors are released, and coactivator complexes such as histone acetyltransferase or histone arginine methyltransferases are recruited to activate transcription. There are three RAR subtypes (alpha, beta, gamma), originating from three distinct genes. For each subtype, several isoforms exist that differ in their N-terminal region, allowing retinoids to exert their pleiotropic effects. 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 24308535 170 ELIRMVTEAHRHTNAQGPhwkQKRKFlpedigQSPAPTSDNDKVDLEAFSEFTKIITPAITRVVDFAKKLPMFSELPCED 249
Cdd:cd06937   1 DLITKVRKAHQETFPSLC---QLGKY------TTNSSADQRVRLDLGLWDKFSELSTKCIIKIVEFAKRLPGFTTLTIAD 71

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24308535 250 QIILLKGCCMEIMSLRAAVRYDPESETLTLSGEMAVSREQLKNGGLGVVSDAIFDLGKSLSQFNLDDSEVALLQAVLLMS 329
Cdd:cd06937  72 QITLLKAACLDILILRICTRYTPEQDTMTFSDGLTLNRTQMHNAGFGPLTDLVFTFANQLLPLEMDDTEIGLLSAICLIC 151

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24308535 330 SDRSGLTCVEKIEKCQEMYLLAFEHYINHRKHNISHFWPKLLMKVTNLRMIGACHASRFLHMKVECPTELfPPLFLEVFE 409
Cdd:cd06937 152 GDRQDLEEPDRVEKLQEPLLEALKIYARKRRPDKPHMFPKMLMKITDLRSISAKGAERVITLKMEIPGPM-PPLISEMLE 230

The ligand binding domain of Liver X receptors, a family of nuclear receptors of ligand-activated transcription factors; The ligand binding domain of Liver X receptors: Liver X receptors (LXRs) belong to a family of nuclear receptors of ligand-activated transcription factors. LXRs operate as cholesterol sensors which protect 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. Upon ligand binding a conformational change leads to recruitment of co-factors, which stimulates expression of target genes. Among the LXR target genes are several genes involved in cholesterol efflux from peripheral tissues such as the ATP-binding-cassette transporters ABCA1, ABCG1 and ApoE. There are two LXR isoforms in mammals, LXRalpha and LXRbeta. LXRalpha is expressed mainly in the liver, intestine, kidney, spleen, and adipose tissue, whereas LXRbeta is ubiquitously expressed at lower level. Both LXRalpha and LXRbeta function as heterodimers with the retinoid X receptor (RX R) which may be activated by either LXR ligands 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. 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 24308535 170 ELIRMVTEAHRHTNAQGPHWKQKRKFLPEDigqspaPTSDNDKVDLEAFSEFTKIITPAITRVVDFAKKLPMFSELPCED 249
Cdd:cd06954   3 EMIEQLVAAQQQCNKRSFEDVPKVTPWPEG------QDPQSREARQQRFAHFTELAILSVQEIVDFAKQLPGFLTLTRED 76

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24308535 250 QIILLKGCCMEIMSLRAAVRYDPESETLTLSGEMAVSREQL-KNGGLGVVSDAIFDLGKSLSQFNLDDSEVALLQAVLLM 328
Cdd:cd06954  77 QIALLKASTIEVMLLETARRYNPESEAITFLKDFPYSRDDFaRAGLQVEFINPIFEFSKSMRELQLDDAEYALLIAINIF 156

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24308535 329 SSDRSGLTCVEKIEKCQEMYLLAFEHYINHRKHNISHFWPKLLMKVTNLRMIGACHASRFLHMKVEcpTELFPPLFLEVF 408
Cdd:cd06954 157 SADRPNVQDHHRVERLQETYVEALHSYIKIKRPSDRLMFPRMLMKLVSLRTLSSVHSEQVFALRLQ--DKKLPPLLSEIW 234

                .
gi 24308535 409 E 409
Cdd:cd06954 235 D 235

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 24308535 170 ELIRMVTEAHRHTNA------QGPHWKqkrKFLPEDIG--QSPAPtsdndkvdlEAFSEFTKI-ITPAITRVVDFAKKLP 240
Cdd:cd06939   5 HLAQNICKAHLETCQylreelQQLRWK---TFSQEEILayQNKSR---------EEMWQLCAEkITEAIQYVVEFAKRIP 72

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24308535 241 MFSELPCEDQIILLKGCCMEIMSLRAAVRYDPESETLTLSGEMAvSREQLKNGGLGVVSDAIFDLGKSLSQFNLDDSEVA 320
Cdd:cd06939  73 GFMELCQNDQIVLLKAGSLEVVLVRMSRAFNPSNNTVLFDGKYA-PIDLFKSLGCDDLISAVFDFAKSLCELKLTEDEIA 151

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24308535 321 LLQAVLLMSSDRSGLTCVEKIEKCQEMYLLAFEHYInHRKHNISHFWPKLLMKVTNLRMIGACHASRFLHMKVECPT--- 397
Cdd:cd06939 152 LFSALVLISADRPGLQEKRKVEKLQQKIELALRHVL-QKNHGDDTILTKLLAKMPTLRALCSLHMEKLQKFKQSYPDivh 230

                       250
                ....*....|.
gi 24308535 398 ELFPPLFLEVF 408
Cdd:cd06939 231 LEFPPLYKELF 241

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 24308535 219 SEFTKIITPAITRVVDFAKKLPMFSELPCEDQIILLKGCCMEIMSLRAAVRYDPESETLTL----SGEMAVSREQLKNGG 294
Cdd:cd06157   1 ELLCELATRDLLLIVEWAKSIPGFRELPLEDQIVLLKSFWLELLVLDLAYRSYKNGLSLLLapngGHTDDDKEDEMKLLL 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24308535 295 LGVVSDAIFDLGKSLSQFNLDDSEVALLQAVLLMSSDR-SGLTCVEKIEKCQEMYLLAFEHYIN-HRKHNISHFWPKLLM 372
Cdd:cd06157  81 KGELIRLLFEFVNPLRALKLDDEEYALLKAIVLFSPDRkESLEDRKIVEELQERLLEALQDYLRkNYPEEAPSRFAKLLL 160

                ....*...
gi 24308535 373 KVTNLRMI 380
Cdd:cd06157 161 LLPSLRKL 168

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 24308535 220 EFTKIITPAITRVVDFAKKLPMFSELPCEDQIILLKGCCMEIMSLRAAVRYDPESETLTLSGEMAVSREQLKNGGLGVVS 299
Cdd:cd06941   6 QLSEALTPSVQRVVEFAKRIPGFCDLSQDDQLLLIKAGFFEVWLVRISRLINSKSGSITFDDGISISRQQLDIIYDSDFV 85

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24308535 300 DAIFDLGKSLSQFNLDDSEVALLQAVLLMSSDRSGLTCVEKIEKCQEMYLLAFEHYINHRKHNISHFWPKLLMKVTNLRM 379
Cdd:cd06941  86 KALFEFSDSFNSLGLSDTEVALFCAVVLLSPDRIGLSEPKKVAILQDRVLEALKVQVSRNRPAEAQLFASLLMKIPELRS 165

                       170       180       190
                ....*....|....*....|....*....|
gi 24308535 380 IGACHASRFLHMKVECPTELFPPLFLEVFE 409
Cdd:cd06941 166 IGAKHQMHLDWYRVNWPLLRLPPLFAEIYD 195

c4 zinc finger in nuclear hormone receptors;

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 24308535     56 PCVVCGDKATGYHYRCITCEGCKGFFRRTIQKNLhpSYSCKYDSCCIIDKITRNQCQLCRFRKCISVGM 124
Cdd:smart00399   1 LCCVCGDHASGFHFGVCSCRACKAFFRRTVNLRY--KYRCDRKNNCSINKRYRCRCRACRLKKCLGVGM 67

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 24308535  57 CVVCGDKATGYHYRCITCEGCKGFFRRTIQKNLHPsySCKYDSCCIIDKITRNQCQLCRFRKCISVGMAMDLVL 130
Cdd:cd07156   1 CGVCGDRATGYHFNAMTCEGCKGFFRRSMKRKARF--TCPFNGDCEITKDNRRHCQACRLKKCLDIGMKKEMIL 72

DNA-binding domain of the TR2 and TR4 (human testicular receptor 2 and 4) is composed of two C4-type zinc fingers; DNA-binding domain of the TR2 and TR4 (human testicular receptor 2 and 4) is composed of two C4-type zinc fingers. Each zinc finger contains a group of four Cys residues which coordinates a single zinc atom. TR2 and TR4 interact with specific DNA sites upstream of the target gene and modulate the rate of transcriptional initiation. TR4 and TR2 are orphan nuclear receptors; the physiological ligand is as yet unidentified. TR2 is abundantly expressed in the androgen-sensitive prostate. TR4 transcripts are expressed in many tissues, including central nervous system, adrenal gland, spleen, thyroid gland, and prostate. It has been shown that human TR2 binds to a wide spectrum of natural hormone response elements (HREs) with distinct affinities suggesting that TR2 may cross-talk with other gene expression regulation systems. The genes responding to TR2 or TR4 include genes that are regulated by retinoic acid receptor, vitamin D receptor, and peroxisome proliferator-activated receptor. TR4/2 binds to HREs as dimers. Like other members of the nuclear receptor (NR) superfamily of ligand-activated transcription factors, TR2-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        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24308535  55 EPCVVCGDKATGYHYRCITCEGCKGFFRRTIQKNLhpSYSCKYDSCCIIDKITRNQCQLCRFRKCISVGMAMDLVLDDSK 134
Cdd:cd06967   4 ELCVVCGDKASGRHYGAVSCEGCKGFFKRSIRKNL--GYSCRGSKDCVINKHHRNRCQYCRLQKCLAMGMKSDSVQCERK 81

                ....*.
gi 24308535 135 RVAKRR 140
Cdd:cd06967  82 PIDVSR 87

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 24308535  57 CVVCGDKATGYHYRCITCEGCKGFFRRTIQKnlHPSYSCKYDSCCIIDKITRNQCQLCRFRKCISVGMAMDLVLDDSKRV 136
Cdd:cd06966   3 CGVCGDKALGYNFNAITCESCKAFFRRNALK--NKEFKCPFNESCEINVVTRRFCQKCRLDKCFAIGMKKEWIMSEEDKS 80

                        90
                ....*....|...
gi 24308535 137 AKRRLIEENREKR 149
Cdd:cd06966  81 EKRQKIEENRAKK 93

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 24308535  56 PCVVCGDKATGYHYRCITCEGCKGFFRRTIQKNLhpSYSCKYDSCCIIDKITRNQCQLCRFRKCISVGMAMDLV 129
Cdd:cd06968   7 PCKICGDKSSGIHYGVITCEGCKGFFRRSQQNNV--SYSCPRQKNCLIDRTNRNRCQHCRLQKCLALGMSRDAV 78

DNA-binding domain of the orphan nuclear receptor, nerve growth factor-induced-B; DNA-binding domain (DBD) of the orphan nuclear receptor, nerve growth factor-induced-B (NGFI-B) is composed of two C4-type zinc fingers. Each zinc finger contains a group of four Cys residues which co-ordinates a single zinc atom. NGFI-B interacts with specific DNA sites upstream of the target gene and modulates the rate of transcriptional initiation. NGFI-B is a member of the nuclear-steroid receptor superfamily. NGFI-B is classified as an orphan receptor because no ligand has yet been identified. NGFI-B is an early immediate gene product of embryo development that is rapidly produced in response to a variety of cellular signals including nerve growth factor. It is involved in T-cell-mediated apoptosis, as well as neuronal differentiation and function. NGFI-B regulates transcription by binding to a specific DNA target upstream of its target genes and regulating the rate of transcriptional initiation. NGFI-B binds to the NGFI-B response element (NBRE) 5'-(A/T)AAAGGTCA as a monomer. Like other members of the nuclear receptor (NR) superfamily of ligand-activated transcription factors, NGFI-B has a central well-conserved DNA binding domain (DBD), a variable N-terminal domain, a flexible hinge and a C-terminal ligand binding domain (LBD).

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 24308535  55 EPCVVCGDKATGYHYRCITCEGCKGFFRRTIQKNlhPSYSCKYDSCCIIDKITRNQCQLCRFRKCISVGMAMDLV 129
Cdd:cd06969   1 GLCAVCGDNAACQHYGVRTCEGCKGFFKRTVQKN--AKYVCLANKNCPVDKRRRNRCQYCRFQKCLQVGMVKEVV 73

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 24308535  57 CVVCGDKATGYHYRCITCEGCKGFFRRTIQKNLhpSYSCKYDSCCIIDKITRNQCQLCRFRKCISVGMAMDLV 129
Cdd:cd07165   1 CKVCGDKASGYHYGVTSCEGCKGFFRRSIQKQI--EYRCLRDGKCEIIRLNRNRCQYCRFKKCLAAGMSKDSV 71

DNA-binding domain of pregnane X receptor (PXRs) is composed of two C4-type zinc fingers; DNA-binding domain (DBD)of pregnane X receptor (PXR) is composed of two C4-type zinc fingers. Each zinc finger contains a group of four Cys residues which co-ordinates a single zinc atom. PXR DBD interacts with the PXR response element, a perfect repeat of two AGTTCA motifs with a 4 bp spacer upstream of the target gene, and modulates the rate of transcriptional initiation. The pregnane X receptor (PXR) is a ligand-regulated transcription factor that responds to a diverse array of chemically distinct ligands, including many endogenous compounds and clinical drugs. PXR functions as a heterodimer with retinoic X receptor-alpha (RXRa) and binds to a variety of promoter regions of a diverse set of target genes involved in the metabolism, transport, and ultimately, elimination of these molecules from the body. Like other nuclear receptors, PXR has a central well conserved DNA-binding domain, a variable N-terminal domain, a flexible hinge and a C-terminal ligand binding domain.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24308535  57 CVVCGDKATGYHYRCITCEGCKGFFRRTIQKNLHpsYSCKYDSCCIIDKITRNQCQLCRFRKCISVGMAMDLVLDDSKrV 136
Cdd:cd07162   2 CRVCGDRATGYHFNAMTCEGCKGFFRRAMKRNAR--LCCPFQKGCVITKSNRRQCQACRLRKCLSIGMKKELIMSDEA-V 78

                ....*
gi 24308535 137 AKRRL 141
Cdd:cd07162  79 EKRRA 83

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 24308535  57 CVVCGDKATGYHYRCITCEGCKGFFRRTIQKNLhpSYSCKYDSCCIIDKITRNQCQLCRFRKCISVGMAMDLV 129
Cdd:cd07164   1 CRVCGDRASGKHYGVPSCDGCRGFFKRSIRRNL--AYVCKENGSCVVDVARRNQCQACRFKKCLQVNMNRDAV 71

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

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 24308535  57 CVVCGDKATGYHYRCITCEGCKGFFRRTIQKNlhPSYSCKYDSCCIIDKITRNQCQLCRFRKCISVGMAMDLVL 130
Cdd:cd06959   2 CVVCGDKASGFHYGVLSCEGCKGFFRRSVTKG--AVYACKFGNKCEMDMYMRRKCQECRLRKCKAAGMRPDCLL 73

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 24308535  57 CVVCGDKATGYHYRCITCEGCKGFFRRTIQKNLhpSYSCKYDSCCIIDKITRNQCQLCRFRKCISVGMAMDLV 129
Cdd:cd06956   3 CAICGDRASGKHYGVYSCEGCKGFFKRTVRKDL--TYTCRDNKDCLIDKRQRNRCQYCRYQKCLAMGMKREAV 73

DNA-binding domain of Farnesoid X receptor (FXR) family is composed of two C4-type zinc fingers; DNA-binding domain of Farnesoid X receptor (FXR) family is composed of two C4-type zinc fingers. Each zinc finger contains a group of four Cys residues which co-ordinates a single zinc atom. FXR interacts with specific DNA sites upstream of the target gene and modulates the rate of transcriptional initiation. FXR is a member of the nuclear receptor family of ligand activated transcription factors. Bile acids are endogenous ligands for FXRs. Upon binding of a ligand, FXR binds to FXR response element (FXRE), which is an inverted repeat of TGACCT spaced by one nucleotide, either as a monomer or as a heterodimer with retinoid X receptor (RXR), to regulate the expression of various genes involved in bile acid, lipid, and glucose metabolism. Like other members of the nuclear receptor (NR) superfamily of ligand-activated transcription factors, FXR has a central well conserved DNA binding domain (DBD), a variable N-terminal domain, a flexible hinge and a C-terminal ligand binding domain (LBD).

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24308535  54 DEPCVVCGDKATGYHYRCITCEGCKGFFRRTIQKNlhPSYSCKYDSCCIIDKITRNQCQLCRFRKCISVGMAMDLVLDDS 133
Cdd:cd06962   1 EELCVVCGDKASGYHYNALTCEGCKGFFRRSITKN--AVYKCKNGGNCEMDMYMRRKCQECRLRKCKEMGMLAECLLTEI 78

                ....*.
gi 24308535 134 KRVAKR 139
Cdd:cd06962  79 QCKSKR 84

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 24308535  54 DEPCVVCGDKATGYHYRCITCEGCKGFFRRTIQKNlhPSYSCKYDSCCIIDKITRNQCQLCRFRKCISVGMAMDLVLDDS 133
Cdd:cd07160  18 NEVCSVCGDKASGFHYNVLSCEGCKGFFRRSVIKG--AQYVCKNGGKCQMDMYMRRKCQECRLRKCREAGMREQCVLSEE 95

                ....*.
gi 24308535 134 KRVAKR 139
Cdd:cd07160  96 QIRLKK 101

The ligand binding domain of xenobiotic receptors:pregnane X receptor and constitutive androstane receptor; The ligand binding domain of xenobiotic receptors: This xenobiotic receptor family includes pregnane X receptor (PXR), constitutive androstane receptor (CAR) and other related nuclear receptors. They function as sensors of toxic byproducts of cell metabolism and of exogenous chemicals, to facilitate their elimination. The nuclear receptor 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. The ligand binding domain of PXR shows remarkable flexibility to accommodate both large and small molecules. PXR functions as a heterodimer with retinoic X receptor-alpha (RXRa) and binds to a variety of response elements in the promoter regions of a diverse set of target genes involved in the metabolism, transport, and elimination of these molecules from the cell. Constitutive androstane receptor (CAR) is a closest mammalian relative of PXR, which has also been proposed to function as a xenosensor. CAR 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, 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        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24308535 221 FTKIITPAITRVVDFAKKLPMFSELPCEDQIILLKGCCMEIMSLRAAVRYDPESETLtLSGEMAVSREQLKNGGLGVVS- 299
Cdd:cd06934  40 FADLTTYMIKQIIKFAKDLPYFRSLPIEDQISLLKGATFEICQIRFNTVFNEETGTW-ECGPLTYCIEDAARAGFQQLLl 118

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24308535 300 DAIFDLGKSLSQFNLDDSEVALLQAVLLMSSDRSGLTCVEKIEKCQEMYLLAFEHYINHRKHNISH--FWPKLLMKVTNL 377
Cdd:cd06934 119 EPLLRFHYTLRKLQLQEEEYVLMQAMSLFSPDRPGVTQHDVIDQLQEKMALTLKSYIDSKRPGPEKrfLYPKILACLTEL 198

                       170       180       190
                ....*....|....*....|....*....|
gi 24308535 378 RMIGACHASRFLHMKVECPteLFPPLFLEV 407
Cdd:cd06934 199 RTINEEYTKQILHIQDIQP--MATPLMQEI 226

Ligand-binding domain of nuclear receptor family 2; Ligand-binding domain (LBD) of nuclear receptor (NR) family 2: This is one of the major subfamily of nuclear receptors, including some well known nuclear receptors such as glucocorticoid receptor (GR), mineralocorticoid receptor (MR), estrogen receptor (ER), progesterone receptor (PR), and androgen receptor (AR), 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 non-conserved hinge and a C-terminal ligand binding domain (LBD).

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24308535 231 RVVDFAKKLPMFSELPCEDQIILLKGCCMEIMSLRAAVRY--DPESETLTLSGEMAVSREQLKNGGLGVVSDAIFDLGKS 308
Cdd:cd06930  14 KTVDWAKNLPAFRNLPLDDQLTLLQNSWAELLLLGLAQRSvhFELSELLLPSPLLVILTEREALLGLAELVQRLQELLSK 93

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 24308535 309 LSQFNLDDSEVALLQAVLLMSSDRSGLTCVEKIEKCQEMYLLAFEHYINHRKHNISHFWPKLLMKVTNLRMI 380
Cdd:cd06930  94 LRSLQLDPKEYACLKAIVLFNPDLPGLKNQQQVEELQEKAQQALQEYIRKRYPQQPARFAKLLLRLPELRSI 165

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 24308535  57 CVVCGDKATGYHYRCITCEGCKGFFRRTIQKNLhpSYSCKYDSCCIIDKITRNQCQLCRFRKCISVGMAMDLVLDDSKRV 136
Cdd:cd07170   7 CLVCGDIASGYHYGVASCEACKAFFKRTIQGNI--EYSCPATNECEITKRRRKSCQACRFMKCLKVGMLKEGVRLDRVRG 84

                        90
                ....*....|...
gi 24308535 137 A----KRRLIEEN 145
Cdd:cd07170  85 GrqkyKRRIDAEN 97

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 24308535  57 CVVCGDKATGYHYRCITCEGCKGFFRRTIQKnlHPSYSCKYDSCCIIDKITRNQCQLCRFRKCISVGM 124
Cdd:cd07171   6 CAVCSDYASGYHYGVWSCEGCKAFFKRSIQG--HNDYICPATNQCTIDKNRRKSCQACRLRKCYEVGM 71

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

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 24308535  55 EPCVVCGDKATGYHYRCITCEGCKGFFRRTIQKNLHPSYSCKYDSCCIIDKITRNQCQLCRFRKCISVGMAM 126
Cdd:cd07157   1 QTCQVCGEPAAGFHHGAYVCEACKKFFMRSSNAISFTISECPNGGKCIIDKKNRTKCQACRYRKCLNVGMSL 72