Oestrogen-type nuclear receptor final C-terminal; This is the very C-terminal region of a subfamily of nuclear receptors that includes oestrogen receptors and other subfamily 3 group A members. The actual function of this region is not known, but the domain is absent from all the other types of nuclear receptors. Oestrogen receptors modulate AP-1-dependent transcription through two distinct mechanisms: via protein-protein interactions on DNA; and via non-genomic actions. The mechanism used depends on the cellular localization of the receptor. In addition to the more extensively studied cross-talk on DNA, additional non-genomic actions might be very important in target tissues in which membrane-associated ERs are found. These non-genomic actions probably contribute to the overall physiological responses mediated by ligand-bound ERs and might possibly be mediated via this C-terminal domain.

                          10        20        30
                  ....*....|....*....|....*....|....*...
gi 1190358958 242 PAARSAAPMEEENQSQL-TTASASSHSMQSFYIGKEEE 278
Cdd:pfam12743   1 PANRGGAPMEEDNQSQLaTTGSTSSHSLQTYYITGEAE 38

Ligand binding domain of hormone receptors;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1190358958   40 ADRELVHMINWAKRVPGFVDLTLHDQVHLLECAWLEILMIGLVWRSMEHPGKLLFAPNLLLDRN---QGKCVEGMVEIFD 116
Cdd:smart00430   1 AERQLLLTVEWAKSFPGFRELSLEDQIVLLKSFWFELLLLELAYRSVKLKKELLLAPDGTYIRPdavLELRKLFSPFLDR 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1190358958  117 MLLATAARFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEkdyihrVLDKITDTLIHLMAKSGlsLQQQHRRLAQ 196
Cdd:smart00430  81 ILSELVKPLRELKLDDEEYALLKAIVLFNPAVPGLSEEGKEIVEK------LQEKYANALHDYYLKNY--PMNYPGRFAK 152

                          170
                   ....*....|.
gi 1190358958  197 LLLILSHIRHM 207
Cdd:smart00430 153 LLLILPELRKI 163

Oestrogen-type nuclear receptor final C-terminal; This is the very C-terminal region of a subfamily of nuclear receptors that includes oestrogen receptors and other subfamily 3 group A members. The actual function of this region is not known, but the domain is absent from all the other types of nuclear receptors. Oestrogen receptors modulate AP-1-dependent transcription through two distinct mechanisms: via protein-protein interactions on DNA; and via non-genomic actions. The mechanism used depends on the cellular localization of the receptor. In addition to the more extensively studied cross-talk on DNA, additional non-genomic actions might be very important in target tissues in which membrane-associated ERs are found. These non-genomic actions probably contribute to the overall physiological responses mediated by ligand-bound ERs and might possibly be mediated via this C-terminal domain.

                          10        20        30
                  ....*....|....*....|....*....|....*...
gi 1190358958 242 PAARSAAPMEEENQSQL-TTASASSHSMQSFYIGKEEE 278
Cdd:pfam12743   1 PANRGGAPMEEDNQSQLaTTGSTSSHSLQTYYITGEAE 38

The ligand binding domain of estrogen receptor and estrogen receptor-related receptors; The ligand binding domain of estrogen receptor (ER) and estrogen receptor-related receptors (ERRs): Estrogen receptors are a group of receptors which are activated by the hormone estrogen. Estrogen regulates many physiological processes including reproduction, bone integrity, cardiovascular health, and behavior. The main mechanism of action of the estrogen receptor is as a transcription factor by binding to the estrogen response element of target genes upon activation by estrogen and then recruiting coactivator proteins which are responsible for the transcription of target genes. Additionally some ERs may associate with other membrane proteins and can be rapidly activated by exposure of cells to estrogen. ERRs are closely related to the estrogen receptor (ER) family. But, it lacks the ability to bind estrogen. ERRs can interfere with the classic ER-mediated estrogen signaling pathway, positively or negatively. ERRs share target genes, co-regulators and promoters with the estrogen receptor (ER) family. Like other members of the nuclear receptor (NR) superfamily of ligand-activated transcription factors, ER and ERRs 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 1190358958   5 MVRALLEAEPPIVYSEYDPNRPFNEASMMTLLTSLADRELVHMINWAKRVPGFVDLTLHDQVHLLECAWLEILMIGLVWR 84
Cdd:cd07068     1 LLSALLVAEPDKLYAMNDPTGPDTEVSLLATLSDLADRELVHIISWAKHIPGFSDLSLNDQMHLLQSAWLEILMLGLVWR 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1190358958  85 SMEHPGKLLFAPNLLLDRNQGKcVEGMVEIFDMLLATAARFRMMNLQGEEFVCLKSIILLNSGVYTflsstlksLEEKDY 164
Cdd:cd07068    81 SLPHPGKLVFAPDLLLDREQAR-VEGLLEIFDMLLQLVRRFRELGLQREEYVCLKAIILANSDVRH--------LEDREA 151

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1190358958 165 IHRVLDKITDTLIHLMAKSGLSlqQQHRRLAQLLLILSHIRHMSNKGMEHLYNMKCKNVVPLYDLLLEMLDA 236
Cdd:cd07068   152 VQQLRDAILDALVDVEAKRHGS--QQPRRLAQLLLLLPHLRQASNKGVRHLYSVKCEGKVPMYKLFLEMLEA 221

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 1190358958  33 MTLLTSLADRELVHMINWAKRVPGFVDLTLHDQVHLLECAWLEILMIGLVWRSMEHP--GKLLFAPNLLLDRNQGKCvEG 110
Cdd:cd06930     1 PESLCELADRVLFKTVDWAKNLPAFRNLPLDDQLTLLQNSWAELLLLGLAQRSVHFElsELLLPSPLLVILTEREAL-LG 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1190358958 111 MVEIFDMLLATAARFRMMNLQGEEFVCLKSIILLNSGVytflsstlKSLEEKDYIHRVLDKITDTLIHLMAKSGlslQQQ 190
Cdd:cd06930    80 LAELVQRLQELLSKLRSLQLDPKEYACLKAIVLFNPDL--------PGLKNQQQVEELQEKAQQALQEYIRKRY---PQQ 148

                         170
                  ....*....|....*..
gi 1190358958 191 HRRLAQLLLILSHIRHM 207
Cdd:cd06930   149 PARFAKLLLRLPELRSI 165

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 1190358958   1 TAEQMVRALLEAEPPIVYSEYDPNRPFNEASMmtlLTSLADRELVHMINWAKRVPGFVDLTLHDQVHLLECAWLEILMIG 80
Cdd:cd06943     3 PIERILEAELAVEPKSEAVAMVPPEYRDPVSN---ICQAADKQLFQLVEWAKRIPHFSELPLDDQVILLRAGWNELLIAA 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1190358958  81 LVWRSMEHPGKLLFAPNLLLDRNQGKCVeGMVEIFDMLLAT-AARFRMMNLQGEEFVCLKSIILLNSGVytflsstlKSL 159
Cdd:cd06943    80 FAHRSIAVKDGILLATGLHLHRNSAHQA-GVGAIFDRILTElVVKMRDLKMDRTELGCLRAIILFNPDV--------KGL 150

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1190358958 160 EEKDYIHRVLDKITDTlihLMAKSGLSLQQQHRRLAQLLLILSHIRHMSNKGMEHLY 216
Cdd:cd06943   151 KSRQEVESLREKVYAS---LEEYCRQKHPEQPGRFAKLLLRLPALRSIGLKCLEHLF 204

Ligand binding domain of the progesterone receptor, a member of the nuclear hormone receptor; The ligand binding domain of the progesterone receptor (PR): PR is a member of the nuclear receptor superfamily of ligand dependent transcription factors, mediating the biological actions of progesterone. PR functions in a variety of biological processes including development of the mammary gland, regulating cell cycle progression, protein processing, and metabolism. When no binding hormone is present the carboxyl terminal inhibits transcription. Binding to a hormone induces a structural change that removes the inhibitory action. After progesterone binds to the receptor, PR forms a dimer and the complex enters the nucleus where it interacts with the hormone response element (HRE) in the promoters of progesterone responsive genes and alters their transcription. In addition, rapid actions of PR that occur independent of transcription, have also been observed in several tissues like brain, liver, mammary gland and spermatozoa. There are two natural PR isoforms called PR-A and PR-B. PR-B has an additional stretc h of 164 amino acids at the N terminus. The extra domain in PR-B performs activation functions by recruiting coactivators that could not be recruited by PR-A. Like other members of the nuclear receptor (NR) superfamily of ligand-activated transcription factors, PR has a central well conserved DNA binding domain (DBD), a variable N-terminal domain, a flexible hinge and a C-terminal ligand binding domain (LBD). The LBD is not only involved in binding to progesterone, but also involved in coactivator binding and dimerization.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1190358958   4 QMVRALLEAEPPIVYSEYDPNRPFNEASMMTLLTSLADRELVHMINWAKRVPGFVDLTLHDQVHLLECAWLEILMIGLVW 83
Cdd:cd07074     1 PLINLLMSIEPDVVYAGYDNTKPETPSSLLTSLNQLCERQLLSVVKWSKSLPGFRNLHIDDQITLIQYSWMSLMVFGLGW 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1190358958  84 RSMEH--PGKLLFAPNLLLDRNQGKcvegMVEIFDMLLAT---AARFRMMNLQGEEFVCLKSIILLNS 146
Cdd:cd07074    81 RSYKHvsGQMLYFAPDLILNEQRMK----ESSFYSLCLTMwqiPQEFVKLQVSQEEFLCMKALLLLNT 144

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 1190358958   4 QMVRALLEAEPPIV---YSEYDPNR----PFNEASMMTLLTSLADRELVHMINWAKRVPGFVDLTLHDQVHLLECAWLEI 76
Cdd:cd06945     7 ALVRAHVDSTPRKTdldYSKIQENVdpvpPKPDSQQVQQFYDLLTGSVDVIRQWAEKIPGFKDLHREDQDLLLESAFLEL 86

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1190358958  77 LMIGLVWRSMEHPGKLLFAPNLLLDRNQgkCVEGMVEIFDMLLATAARFRMMNLQGEEFVCLksIILLnsgvytFLSSTL 156
Cdd:cd06945    87 FVLRLAYRSNPVDGKLVFCNGLVLHRLQ--CVRGFGEWLDSILAFSSSLQSLLLDDISAFCC--LALL------LLITER 156

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1190358958 157 KSLEEKDYIHRVLDKITDTLIHLMAKSGLSLQQQHrRLAQLLLILSHIRHMSNKGMEHLYNMK 219
Cdd:cd06945   157 HGLKEPKKVEELQNKIISCLRDHVTSNYPGQDKPN-RLSKLLLKLPELRTLSKKGLQRIFFLK 218

Ligand binding domain of the glucocorticoid receptor, a member of the nuclear receptor superfamily; The ligand binding domain of the glucocorticoid receptor (GR): GR is a ligand-activated transcription factor belonging to the nuclear receptor superfamily. It binds with high affinity to cortisol and other glucocorticoids. GR is expressed in almost every cell in the body and regulates genes controlling a wide variety of processes including the development, metabolism, and immune response of the organism. In the absence of hormone, the glucocorticoid receptor (GR) is complexes with a variety of heat shock proteins in the cytosol. The binding of the glucocorticoids results in release of the heat shock proteins and transforms it to its active state. One mechanism of action of GR is by direct activation of gene transcription. The activated form of GR forms dimers, translocates into the nucleus, and binds to specific hormone responsive elements, activating gene transcription. GR can also function as a repressor of other gene transcription activators, such as NF-kappaB and AF-1 by directly binding to them, and bloc king the expression of their activated genes. Like other members of the nuclear receptor (NR) superfamily of ligand-activated transcription factors, GR has a central well conserved DNA binding domain (DBD), a variable N-terminal domain, a flexible hinge and a C-terminal ligand binding domain (LBD). The LBD also functions for dimerization and chaperone protein association.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1190358958   8 ALLEA-EPPIVYSEYDPNRPFNEASMMTLLTSLADRELVHMINWAKRVPGFVDLTLHDQVHLLECAWLEILMIGLVWRSM 86
Cdd:cd07076     4 SLLEViEPEVLYSGYDSSVPDSTWRIMSTLNMLGGRQVVAAVKWAKAIPGFRNLHLDDQMTLLQYSWMFLMAFALGWRSY 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1190358958  87 EHP-GKLL-FAPNLLLDRNQGKcVEGMVEIFDMLLATAARFRMMNLQGEEFVCLKSIILLNsgvyTFLSSTLKSleekdy 164
Cdd:cd07076    84 RQSnGNLLcFAPDLIINEQRMT-LPCMYDQCKHMLYVSSELHRLQVSYEEYLCMKTLLLLS----TVPKDGLKS------ 152

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*..
gi 1190358958 165 iHRVLDKITDTLIHLMAKSGLSLQ----QQHRRLAQLLLILSHIRHM 207
Cdd:cd07076   153 -QELFDEIRMTYIKELGKAIVKREgnssQNWQRFYQLTKLLDSMHEV 198

The ligand binding domain of the liver receptor homolog-1, a member of nuclear receptor superfamily,; The ligand binding domain (LBD) of the liver receptor homolog-1 (LRH-1): LRH-1 belongs to nuclear hormone receptor superfamily, and is expressed mainly in the liver, intestine, exocrine pancreas, and ovary. Most nuclear receptors function as homodimer or heterodimers. However, LRH-1 binds DNA as a monomer, and is a regulator of bile-acid homeostasis, steroidogenesis, reverse cholesterol transport and the initial stages of embryonic development. Recently, phospholipids have been identified as potential ligand for LRH-1 and steroidogenic factor-1 (SF-1). Like other members of the nuclear receptor (NR) superfamily of ligand-activated transcription factors, LRH-1 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 1190358958  35 LLTSLADRELVHMINWAKRVPGFVDLTLHDQVHLLECAWLEILMIGLVWRSMEH--PGKLLFAPNLLLDRNQGKCVEGMV 112
Cdd:cd07069    44 LMCKMADQTLFSIVEWARSSIFFRELKVDDQMKLLQNCWSELLILDHIYRQVVHgkEGSIFLVTGQQVDYSIIASQAGAT 123

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1190358958 113 eiFDMLLATA----ARFRMMNLQGEEFVCLKSIILlnsgvytfLSSTLKSLEEKDYIHRVLDKITDTLIHLMAksgLSLQ 188
Cdd:cd07069   124 --LNNLMSHAqelvAKLRSLQFDQREFVCLKFLVL--------FSLDVKNLENFQLVEGVQEQVNAALLDYTM---CNYP 190

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|
gi 1190358958 189 QQHRRLAQLLLILSHIRHMSNKGMEHLYNMKCKNVVPLYDLLLEMLDAHR 238
Cdd:cd07069   191 QQTEKFGQLLLRLPEIRAISMQAEEYLYYKHLNGDVPYNNLLIEMLHAKR 240

Ligand binding domain of the nuclear receptor androgen receptor, ligand activated transcription regulator; The ligand binding domain of the androgen receptor (AR): AR is a member of the nuclear receptor family. It is activated by binding either of the androgenic hormones, testosterone or dihydrotestosterone, which are responsible for male primary sexual characteristics and for secondary male characteristics, respectively. The primary mechanism of action of ARs is by direct regulation of gene transcription. The binding of an androgen results in a conformational change in the androgen receptor which causes its transport from the cytosol into the cell nucleus, and dimerization. The receptor dimer binds to a hormone response element of AR-regulated genes and modulates their expression. Another mode of action is independent of their interactions with DNA. The receptors interact directly with signal transduction proteins in the cytoplasm, causing rapid changes in cell function, such as ion transport. Like other members of the nuclear receptor (NR) superfamily of ligand-activated transcription factors, AR has a central well conserved DNA binding domain (DBD), a variable N-terminal domain, a flexible hinge and a C-terminal ligand binding domain (LBD). The LBD is not only involved in binding to androgen, but also involved in binding of coactivator proteins and dimerization. A ligand dependent nuclear export signal is also present at the ligand binding domain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1190358958   9 LLEA-EPPIVYSEYDPNRPFNEASMMTLLTSLADRELVHMINWAKRVPGFVDLTLHDQVHLLECAWLEILMIGLVWRSME 87
Cdd:cd07073     5 VLEAiEPGVVCAGHDNNQPDSFAALLSSLNELGERQLVHVVKWAKALPGFRNLHVDDQMAVIQYSWMGLMVFAMGWRSFT 84

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1190358958  88 HPGK--LLFAPNLLLDRNQGKcVEGMVEIFDMLLATAARFRMMNLQGEEFVCLKSIILLNsgvyTFLSSTLKSLEEKDYI 165
Cdd:cd07073    85 NVNSrmLYFAPDLVFNEYRMH-KSRMYSQCVRMRHLSQEFGWLQITPQEFLCMKALLLFS----IIPVDGLKNQKFFDEL 159

                         170       180       190
                  ....*....|....*....|....*....|...
gi 1190358958 166 HRVLDKITDTLIHLMAKSGLSLQQQHRRLAQLL 198
Cdd:cd07073   160 RMNYIKELDRIIACKRKNPTSCSRRFYQLTKLL 192

The ligand binding domain of heptocyte nuclear factor 4, which is explosively expanded in nematodes; The ligand binding domain of hepatocyte nuclear factor 4 (HNF4) like proteins: HNF4 is a member of the nuclear receptor superfamily. HNF4 plays a key role in establishing and maintenance of hepatocyte differentiation in the liver. It is also expressed in gut, kidney, and pancreatic beta cells. HNF4 was originally classified as an orphan receptor, but later it is found that HNF4 binds with very high affinity to a variety of fatty acids. However, unlike other nuclear receptors, the ligands do not act as a molecular switch for HNF4. They seem to constantly bind to the receptor, which is constitutively active as a transcription activator. Like other members of the nuclear receptor (NR) superfamily of ligand-activated transcription factors, HNF4 has a central well conserved DNA binding domain (DBD), a variable N-terminal domain, a flexible hinge and a C-terminal ligand binding domain (LBD). The LBD domain is also responsible for recruiting co-activator proteins. More than 280 nuclear receptors are found in C. ele gans, most of which are originated from an explosive burst of duplications of HNF4.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1190358958   6 VRALLEAE-------PPIVYSEYDPnRPFNEASMMTLLTSLADRELVhMINWAKRVPGFVDLTLHDQVHLLECAWLEILM 78
Cdd:cd06931     2 ISVLLQAEalsrqqsSPIPTCSGDI-RPKKIASINDVCESMKQQLLV-LVEWAKYIPAFCELPLDDQVALLRAHAGEHLL 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1190358958  79 IGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEGMV--EIFDMLlatAARFRMMNLQGEEFVCLKSIILLNSGVytflsstl 156
Cdd:cd06931    80 LGVARRSMPYKDILLLGNDLIIPRHCPEPEISRVanRILDEL---VLPLRDLNIDDNEYACLKAIVFFDPDA-------- 148

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1190358958 157 KSLEEKDYIHRVLDKItdtLIHLMAKSGLSLQQQHRRLAQLLLILSHIRHMSNKGMEHLYNMKCKNVVPLYDLLLEM 233
Cdd:cd06931   149 KGLSDPQKIKRLRFQV---QVSLEDYINDRQYDSRGRFGELLLLLPTLQSITWQMIEQIQFARLFGVAKIDNLLQEM 222

Oestrogen-type nuclear receptor final C-terminal; This is the very C-terminal region of a subfamily of nuclear receptors that includes oestrogen receptors and other subfamily 3 group A members. The actual function of this region is not known, but the domain is absent from all the other types of nuclear receptors. Oestrogen receptors modulate AP-1-dependent transcription through two distinct mechanisms: via protein-protein interactions on DNA; and via non-genomic actions. The mechanism used depends on the cellular localization of the receptor. In addition to the more extensively studied cross-talk on DNA, additional non-genomic actions might be very important in target tissues in which membrane-associated ERs are found. These non-genomic actions probably contribute to the overall physiological responses mediated by ligand-bound ERs and might possibly be mediated via this C-terminal domain.

                          10        20        30
                  ....*....|....*....|....*....|....*...
gi 1190358958 242 PAARSAAPMEEENQSQL-TTASASSHSMQSFYIGKEEE 278
Cdd:pfam12743   1 PANRGGAPMEEDNQSQLaTTGSTSSHSLQTYYITGEAE 38

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 1190358958  37 TSLADRELVHMINWAKRVPGFVDLTLHDQVHLLECAWLEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKcVEGMVEIFD 116
Cdd:cd06937    44 SELSTKCIIKIVEFAKRLPGFTTLTIADQITLLKAACLDILILRICTRYTPEQDTMTFSDGLTLNRTQMH-NAGFGPLTD 122

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1190358958 117 MLLATAARFRMMNLQGEEFVCLKSIILlnsgvytfLSSTLKSLEEKDYIhrvlDKITDTLIHlmaksGLSLQQQHRR--- 193
Cdd:cd06937   123 LVFTFANQLLPLEMDDTEIGLLSAICL--------ICGDRQDLEEPDRV----EKLQEPLLE-----ALKIYARKRRpdk 185

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*
gi 1190358958 194 ---LAQLLLILSHIRHMSNKGMEHLYNMKCKNVVPLYDLLLEMLD 235
Cdd:cd06937   186 phmFPKMLMKITDLRSISAKGAERVITLKMEIPGPMPPLISEMLE 230

The ligand binding domain of nuclear receptor steroidogenic factor 1, a member of nuclear receptor superfamily; The ligand binding domain of nuclear receptor steroidogenic factor 1 (SF-1): SF-1, a member of the nuclear hormone receptor superfamily, is an essential regulator of endocrine development and function and is considered a master regulator of reproduction. Most nuclear receptors function as homodimer or heterodimers, however SF-1 binds to its target genes as a monomer, recognizing the variations of the DNA sequence motif, T/CCA AGGTCA. SF-1 functions cooperatively with other transcription factors to modulate gene expression. Phospholipids have been determined as potential ligands of SF-1. Like other members of the nuclear receptor (NR) superfamily of ligand-activated transcription factors, SF-1 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 1190358958  23 PNRPfneaSMMTLLTSLADRELVHMINWAKRVPGFVDLTLHDQVHLLECAWLEILMIGLVWRSMEH--PGKLLFAPNLLL 100
Cdd:cd07070    34 PDQP----APFGLLCRMADQTFISIVDWARRCMVFKELEVADQMTLLQNCWSELLVFDHIYRQVQHgkEGSILLVTGQEV 109

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1190358958 101 DRNQGKCVEGMVEIFDMLLATAARFRMMNLQ--GEEFVCLKSIILlnsgvytfLSSTLKSLEEKDYIHRVLDKITDTLIH 178
Cdd:cd07070   110 ELSTVAAQAGSLLHSLVLRAQELVLQLHALQldRQEFVCLKFLIL--------FSLDVKFLNNHSLVKDAQEKANAALLD 181

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1190358958 179 LMAKSGLSLQQQHRrlaQLLLILSHIRHMSNKGMEHLYNMKCKNVVPLYDLLLEMLDA 236
Cdd:cd07070   182 YTLCHYPHCGDKFQ---QLLLRLVEVRALSMQAKEYLYHKHLGNEMPRNNLLIEMLQA 236

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 1190358958  31 SMMTLLTSLADRELVHMINWAKRVPGFVDLTLHDQVHLLECAWLEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVeG 110
Cdd:cd06929     2 EKFDHFTEIMTVAIRRVVEFAKRIPGFRELSQEDQIALLKGGCFEILLLRSATLYDPEKNSLTFGDGKGNSRDVLLNG-G 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1190358958 111 MVEIFDMLLATAARFRMMNLQGEEFVCLKSIILlnsgvytfLSSTLKSLEEKDYIHRVLDKITDTLIHLmakSGLSLQQQ 190
Cdd:cd06929    81 FGEFIEPLFEFAEKMNKLQLDDNEYALLTAIVL--------FSPDRPGLQDVDTVEKLQERLLEALQRY---LKVNHPDA 149

                         170       180
                  ....*....|....*....|....*
gi 1190358958 191 HRRLAQLLLILSHIRHMSNKGMEHL 215
Cdd:cd06929   150 PQMFAKLLKKLTELRTLNELHAELL 174

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 1190358958  47 MINWAKRVPGFVDLTLHDQVHLLECAWLEILMIGLV--WRSMEHPGKLLFAPNLLLDRNQGKcveGMVEIFDMLLATAAR 124
Cdd:cd06940    28 VVEFAKRIPGFRDLSQHDQVTLLKAGTFEVLMVRFAslFDAKERSVTFLSGQKYSVDDLHSM---GAGDLLNSMFDFSEK 104

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1190358958 125 FRMMNLQGEEFVCLKSIILlnsgvytfLSSTLKSLEEKDYIHRVLDKITDTLIHLMAKSGlslQQQHRRLAQLLLILSHI 204
Cdd:cd06940   105 LNSLQLSDEEMGLFTAVVL--------VSADRSGLENVNLVEALQETLIRALRTLIAKNH---PNEPSIFTKLLLKLPDL 173

                         170
                  ....*....|....*
gi 1190358958 205 RHMSNKGMEHLYNMK 219
Cdd:cd06940   174 RTLNNLHSEKLLAFK 188

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 1190358958  34 TLLTSLADRELVhmiNWAKRVPGFVDLTLHDQVHLLECAWLEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEGMVE 113
Cdd:cd06954    49 TELAILSVQEIV---DFAKQLPGFLTLTREDQIALLKASTIEVMLLETARRYNPESEAITFLKDFPYSRDDFARAGLQVE 125

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1190358958 114 IFDMLLATAARFRMMNLQGEEFVCLKSIILlnsgvytfLSSTLKSLEEKDYIHRVLDKITDTlihLMAKSGLSLQQQHRR 193
Cdd:cd06954   126 FINPIFEFSKSMRELQLDDAEYALLIAINI--------FSADRPNVQDHHRVERLQETYVEA---LHSYIKIKRPSDRLM 194

                         170       180
                  ....*....|....*....|....*....
gi 1190358958 194 LAQLLLILSHIRHMSNKGMEHLYNMKCKN 222
Cdd:cd06954   195 FPRMLMKLVSLRTLSSVHSEQVFALRLQD 223

The ligand binding domain of the orphan nuclear receptors TR4 and TR2; The ligand binding domain of the TR4 and TR2 (human testicular receptor 4 and 2): TR4 and TR2 are orphan nuclear receptors. Several isoforms of TR4 and TR2 have been isolated in various tissues. 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. The expression of TR2 is negatively regulated by androgen, retinoids, and radiation. The expression of both mouse TR2 and TR4 is up-regulated by neurocytokine ciliary neurotrophic factor (CNTF) in mouse. It has 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, peroxisome proliferator-activated receptor. TR4/2 binds to HREs as a dimer. Like other members of the nuclea r 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 1190358958  40 ADRELVHMINWAKRVPGFVDLTLHDQVHLLECAWLEILMIGLVW--RSMEHPGKLLFAPN-----LLLDRNQGKCVEGMV 112
Cdd:cd06952    30 ASRLLFLSIHWARSIPAFQALGAETQTSLVRACWPELFTLGLAQcsQQLSLPTILAAIINhlqtsIQQDKLSADKVKQVM 109

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1190358958 113 EIFDMLLATAARFRMMNLQGEEFVCLKSIILLNsgvytflsSTLKSLEEKDYIHRVLDKITDTLIHLMAKSGLSLQQqhr 192
Cdd:cd06952   110 EHINKLQEFVNSMQKLDVDDHEYAYLKAIVLFS--------PDHPGQELRQQIEKLQEKALMELRDYVGKTYPEDEY--- 178

                         170       180
                  ....*....|....*....|....
gi 1190358958 193 RLAQLLLILSHIRHMSNKGMEHLY 216
Cdd:cd06952   179 RLSKLLLRLPPLRSLSPAITEELF 202

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 1190358958  51 AKRVPGFVDLTLHDQVHLLECAWLEILMIGLVWRsMEHPGKLLFAPNLLLDRNQGKCVE-GMVEIFDMLLATAARFRMMN 129
Cdd:cd06932    83 AKSLPGFRNLDLNDQVTLLKYGVHEVIFTMLASL-YNKDGLLFPEGNGYVTREFLESLRkPFCDIMEPKFEFAEKFNALE 161

                          90
                  ....*....|....*
gi 1190358958 130 LQGEEFVCLKSIILL 144
Cdd:cd06932   162 LTDSELALFCAVIIL 176