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        40
                  ....*....|....*....|....*....|....*....|....
gi 1034648843 289 PTSRGGASVEETDQSHLATAGSTSSHSLQKYYITGEAEGFPATV 332
Cdd:pfam12743   1 PANRGGAPMEEDNQSQLATTGSTSSHSLQTYYITGEAESFPSTV 44

Ligand binding domain of hormone receptors;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034648843   87 ADRELVHMINWAKRVPGFVDLTLHDQVHLLECAWLEILMIGLVWRSMEHPGKLLFAPNLLLDRN---QGKCVEGMVEIFD 163
Cdd:smart00430   1 AERQLLLTVEWAKSFPGFRELSLEDQIVLLKSFWFELLLLELAYRSVKLKKELLLAPDGTYIRPdavLELRKLFSPFLDR 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034648843  164 MLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEkdhihrVLDKITDTLIHLMAKAGltLQQQHQRLAQ 243
Cdd:smart00430  81 ILSELVKPLRELKLDDEEYALLKAIVLFNPAVPGLSEEGKEIVEK------LQEKYANALHDYYLKNY--PMNYPGRFAK 152

                          170
                   ....*....|.
gi 1034648843  244 LLLILSHIRHM 254
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        40
                  ....*....|....*....|....*....|....*....|....
gi 1034648843 289 PTSRGGASVEETDQSHLATAGSTSSHSLQKYYITGEAEGFPATV 332
Cdd:pfam12743   1 PANRGGAPMEEDNQSQLATTGSTSSHSLQTYYITGEAESFPSTV 44

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 1034648843  52 MVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINWAKRVPGFVDLTLHDQVHLLECAWLEILMIGLVWR 131
Cdd:cd07068     1 LLSALLVAEPDKLYAMNDPTGPDTEVSLLATLSDLADRELVHIISWAKHIPGFSDLSLNDQMHLLQSAWLEILMLGLVWR 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034648843 132 SMEHPGKLLFAPNLLLDRNQGKcVEGMVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTflsstlksLEEKDH 211
Cdd:cd07068    81 SLPHPGKLVFAPDLLLDREQAR-VEGLLEIFDMLLQLVRRFRELGLQREEYVCLKAIILANSDVRH--------LEDREA 151

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1034648843 212 IHRVLDKITDTLIHLMAKAGLTlqQQHQRLAQLLLILSHIRHMSNKGMEHLYSMKCKNVVPLYDLLLEMLDA 283
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 1034648843  80 MGLLTNLADRELVHMINWAKRVPGFVDLTLHDQVHLLECAWLEILMIGLVWRSMEHP--GKLLFAPNLLLDRNQGKCvEG 157
Cdd:cd06930     1 PESLCELADRVLFKTVDWAKNLPAFRNLPLDDQLTLLQNSWAELLLLGLAQRSVHFElsELLLPSPLLVILTEREAL-LG 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034648843 158 MVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVytflsstlKSLEEKDHIHRVLDKITDTLIHLMAKAGltlQQQ 237
Cdd:cd06930    80 LAELVQRLQELLSKLRSLQLDPKEYACLKAIVLFNPDL--------PGLKNQQQVEELQEKAQQALQEYIRKRY---PQQ 148

                         170
                  ....*....|....*..
gi 1034648843 238 HQRLAQLLLILSHIRHM 254
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 1034648843  53 VSALLDAEppILYSEYDPTRPFSEASMMGLLTNL---ADRELVHMINWAKRVPGFVDLTLHDQVHLLECAWLEILMIGLV 129
Cdd:cd06943     4 IERILEAE--LAVEPKSEAVAMVPPEYRDPVSNIcqaADKQLFQLVEWAKRIPHFSELPLDDQVILLRAGWNELLIAAFA 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034648843 130 WRSMEHPGKLLFAPNLLLDRNQGKCVeGMVEIFDMLLAT-SSRFRMMNLQGEEFVCLKSIILLNSGVytflsstlKSLEE 208
Cdd:cd06943    82 HRSIAVKDGILLATGLHLHRNSAHQA-GVGAIFDRILTElVVKMRDLKMDRTELGCLRAIILFNPDV--------KGLKS 152

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1034648843 209 KDHIHRVLDKITDTlihLMAKAGLTLQQQHQRLAQLLLILSHIRHMSNKGMEHLYSMK 266
Cdd:cd06943   153 RQEVESLREKVYAS---LEEYCRQKHPEQPGRFAKLLLRLPALRSIGLKCLEHLFFFK 207

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 1034648843  51 QMVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINWAKRVPGFVDLTLHDQVHLLECAWLEILMIGLVW 130
Cdd:cd07074     1 PLINLLMSIEPDVVYAGYDNTKPETPSSLLTSLNQLCERQLLSVVKWSKSLPGFRNLHIDDQITLIQYSWMSLMVFGLGW 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034648843 131 RSMEH--PGKLLFAPNLLLDRNQGKcvegMVEIFDMLLAT---SSRFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKS 205
Cdd:cd07074    81 RSYKHvsGQMLYFAPDLILNEQRMK----ESSFYSLCLTMwqiPQEFVKLQVSQEEFLCMKALLLLNTIPLEGLRSQTQF 156

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|
gi 1034648843 206 LEEKDHIHRVLDKItdtlIHLMAKAGLTLQQQHQRLAQLL 245
Cdd:cd07074   157 DEMRSSYIRELIKA----IGLRQKGVVASSQRFYQLTKLM 192

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 1034648843  52 MVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINWAKRVPGFVDLTLHDQVHLLECAWLEILMIGLVWR 131
Cdd:cd07076     2 LVSLLEVIEPEVLYSGYDSSVPDSTWRIMSTLNMLGGRQVVAAVKWAKAIPGFRNLHLDDQMTLLQYSWMFLMAFALGWR 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034648843 132 SMEHP-GKLL-FAPNLLLDRNQGKcVEGMVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNsgvyTFLSSTLKSleek 209
Cdd:cd07076    82 SYRQSnGNLLcFAPDLIINEQRMT-LPCMYDQCKHMLYVSSELHRLQVSYEEYLCMKTLLLLS----TVPKDGLKS---- 152

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*....
gi 1034648843 210 dhiHRVLDKITDTLIHLMAKAGLTLQ----QQHQRLAQLLLILSHIRHM 254
Cdd:cd07076   153 ---QELFDEIRMTYIKELGKAIVKREgnssQNWQRFYQLTKLLDSMHEV 198

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        40
                  ....*....|....*....|....*....|....*....|....
gi 1034648843 289 PTSRGGASVEETDQSHLATAGSTSSHSLQKYYITGEAEGFPATV 332
Cdd:pfam12743   1 PANRGGAPMEEDNQSQLATTGSTSSHSLQTYYITGEAESFPSTV 44

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 1034648843  51 QMVSALLDAEPPIL---YSEY----DPTRPFSEASMMGLLTNLADRELVHMINWAKRVPGFVDLTLHDQVHLLECAWLEI 123
Cdd:cd06945     7 ALVRAHVDSTPRKTdldYSKIqenvDPVPPKPDSQQVQQFYDLLTGSVDVIRQWAEKIPGFKDLHREDQDLLLESAFLEL 86

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034648843 124 LMIGLVWRSMEHPGKLLFAPNLLLDRNQgkCVEGMVEIFDMLLATSSRFRMMNLQGEEFVCLksIILLnsgvytFLSSTL 203
Cdd:cd06945    87 FVLRLAYRSNPVDGKLVFCNGLVLHRLQ--CVRGFGEWLDSILAFSSSLQSLLLDDISAFCC--LALL------LLITER 156

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1034648843 204 KSLEEKDHIHRVLDKITDTLIHLMAKAGLTLQQQHqRLAQLLLILSHIRHMSNKGMEHLYSMK 266
Cdd:cd06945   157 HGLKEPKKVEELQNKIISCLRDHVTSNYPGQDKPN-RLSKLLLKLPELRTLSKKGLQRIFFLK 218

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 1034648843  78 SMMGLLTNLADRELVHMINWAKRVPGFVDLTLHDQVHLLECAWLEILMIGLVWRSMEH--PGKLLFAPNLLLDRNQGKCV 155
Cdd:cd07069    40 STFGLMCKMADQTLFSIVEWARSSIFFRELKVDDQMKLLQNCWSELLILDHIYRQVVHgkEGSIFLVTGQQVDYSIIASQ 119

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034648843 156 EGMVeiFDMLLATS----SRFRMMNLQGEEFVCLKSIILlnsgvytfLSSTLKSLEEKDHIHRVLDKITDTLIHLMAkag 231
Cdd:cd07069   120 AGAT--LNNLMSHAqelvAKLRSLQFDQREFVCLKFLVL--------FSLDVKNLENFQLVEGVQEQVNAALLDYTM--- 186

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1034648843 232 LTLQQQHQRLAQLLLILSHIRHMSNKGMEHLYSMKCKNVVPLYDLLLEMLDAHR 285
Cdd:cd07069   187 CNYPQQTEKFGQLLLRLPEIRAISMQAEEYLYYKHLNGDVPYNNLLIEMLHAKR 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 1034648843  60 EPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINWAKRVPGFVDLTLHDQVHLLECAWLEILMIGLVWRSMEHPGK- 138
Cdd:cd07073    10 EPGVVCAGHDNNQPDSFAALLSSLNELGERQLVHVVKWAKALPGFRNLHVDDQMAVIQYSWMGLMVFAMGWRSFTNVNSr 89

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034648843 139 -LLFAPNLLLDRNQGKcVEGMVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNsgvyTFLSSTLKSLEEKDHIHRVLD 217
Cdd:cd07073    90 mLYFAPDLVFNEYRMH-KSRMYSQCVRMRHLSQEFGWLQITPQEFLCMKALLLFS----IIPVDGLKNQKFFDELRMNYI 164

                         170       180
                  ....*....|....*....|....*...
gi 1034648843 218 KITDTLIHLMAKAGLTLQQQHQRLAQLL 245
Cdd:cd07073   165 KELDRIIACKRKNPTSCSRRFYQLTKLL 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 1034648843  53 VSALLDAE-------PPILYSEYDpTRPFSEASMMGLLTNLADRELVhMINWAKRVPGFVDLTLHDQVHLLECAWLEILM 125
Cdd:cd06931     2 ISVLLQAEalsrqqsSPIPTCSGD-IRPKKIASINDVCESMKQQLLV-LVEWAKYIPAFCELPLDDQVALLRAHAGEHLL 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034648843 126 IGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEGMV--EIFDMLLATssrFRMMNLQGEEFVCLKSIILLNSGVytflsstl 203
Cdd:cd06931    80 LGVARRSMPYKDILLLGNDLIIPRHCPEPEISRVanRILDELVLP---LRDLNIDDNEYACLKAIVFFDPDA-------- 148

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1034648843 204 KSLEEKDHIHRVLDKItdtLIHLMAKAGLTLQQQHQRLAQLLLILSHIRHMSNKGMEHLYSMKCKNVVPLYDLLLEM 280
Cdd:cd06931   149 KGLSDPQKIKRLRFQV---QVSLEDYINDRQYDSRGRFGELLLLLPTLQSITWQMIEQIQFARLFGVAKIDNLLQEM 222

The ligand binding domain of Tailless-like proteins, orphan nuclear receptors; The ligand binding domain of the photoreceptor cell-specific nuclear receptor (PNR) like family: This family includes photoreceptor cell-specific nuclear receptor (PNR), Tailless (TLX), and related receptors. TLX is an orphan receptor that is expressed by neural stem/progenitor cells in the adult brain of the subventricular zone (SVZ) and the dentate gyrus (DG). It plays a key role in neural development by promoting cell cycle progression and preventing apoptosis in the developing brain. PNR is expressed only in the outer layer of retinal photoreceptor cells. It may be involved in the signaling pathway regulating photoreceptor differentiation and/or maintenance. Like other members of the nuclear receptor (NR) superfamily of ligand-activated transcription factors, TLX and PNR 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 1034648843  95 INWAKRVPGFVDLTLHDQVHLLECAWLEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEGMVEIfDMLLATSSRFRM 174
Cdd:cd06950    43 VKWAKSIPAFSTLPFRDQLILLEESWSELFLLGAAQWSLPLDSCPLLAVPGLSPDNTEAERTFLSEV-RALQETLSRFRQ 121

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034648843 175 MNLQGEEFVCLKSIILLNSGvytflSSTLKSLEE----KDHIHRVLDKitdtliHLMAkaglTLQQQHQRLAQLLLILSH 250
Cdd:cd06950   122 LRVDATEFACLKAIVLFKPE-----TRGLKDPAQvealQDQAQLMLNK------HIRT----RYPTQPARFGKLLLLLPS 186

                         170
                  ....*....|....*.
gi 1034648843 251 IRHMSNKGMEHLYSMK 266
Cdd:cd06950   187 LRFISSSTIEELFFKK 202

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 1034648843  84 TNLADRELVHMINWAKRVPGFVDLTLHDQVHLLECAWLEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKcVEGMVEIFD 163
Cdd:cd06937    44 SELSTKCIIKIVEFAKRLPGFTTLTIADQITLLKAACLDILILRICTRYTPEQDTMTFSDGLTLNRTQMH-NAGFGPLTD 122

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034648843 164 MLLATSSRFRMMNLQGEEFVCLKSIILlnsgvytfLSSTLKSLEEKDHIhrvlDKITDTLIH-LMAKAGLTLQQQHQRLA 242
Cdd:cd06937   123 LVFTFANQLLPLEMDDTEIGLLSAICL--------ICGDRQDLEEPDRV----EKLQEPLLEaLKIYARKRRPDKPHMFP 190

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|
gi 1034648843 243 QLLLILSHIRHMSNKGMEHLYSMKCKNVVPLYDLLLEMLD 282
Cdd:cd06937   191 KMLMKITDLRSISAKGAERVITLKMEIPGPMPPLISEMLE 230

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 1034648843  78 SMMGLLTNLADRELVHMINWAKRVPGFVDLTLHDQVHLLECAWLEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVeG 157
Cdd:cd06929     2 EKFDHFTEIMTVAIRRVVEFAKRIPGFRELSQEDQIALLKGGCFEILLLRSATLYDPEKNSLTFGDGKGNSRDVLLNG-G 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034648843 158 MVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILlnsgvytfLSSTLKSLEEKDHIHRVLDKITDTLIHLmakAGLTLQQQ 237
Cdd:cd06929    81 FGEFIEPLFEFAEKMNKLQLDDNEYALLTAIVL--------FSPDRPGLQDVDTVEKLQERLLEALQRY---LKVNHPDA 149

                         170       180
                  ....*....|....*....|....*
gi 1034648843 238 HQRLAQLLLILSHIRHMSNKGMEHL 262
Cdd:cd06929   150 PQMFAKLLKKLTELRTLNELHAELL 174

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 1034648843  84 TNLADRELVHMINWAKRVPGFVDLTLHDQVHLLECAWLEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEGMVEIFD 163
Cdd:cd06954    49 TELAILSVQEIVDFAKQLPGFLTLTREDQIALLKASTIEVMLLETARRYNPESEAITFLKDFPYSRDDFARAGLQVEFIN 128

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034648843 164 MLLATSSRFRMMNLQGEEFVCLKSIILlnsgvytfLSSTLKSLEEKDHIHRVLDKITDTlihLMAKAGLTLQQQHQRLAQ 243
Cdd:cd06954   129 PIFEFSKSMRELQLDDAEYALLIAINI--------FSADRPNVQDHHRVERLQETYVEA---LHSYIKIKRPSDRLMFPR 197

                         170       180
                  ....*....|....*....|....*.
gi 1034648843 244 LLLILSHIRHMSNKGMEHLYSMKCKN 269
Cdd:cd06954   198 MLMKLVSLRTLSSVHSEQVFALRLQD 223

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034648843  66 SEYDPTRPFSEASMMGLLTnladRELVHmiNWAKRVPGFVDLTLHDQVHLLECAWLEILMIGLVWRSMEHPGKLLFAPNL 145
Cdd:cd06938    33 DEDQSDMRFRHITEMTILT----VQLIV--EFAKRLPGFDKLSREDQITLLKACSSEVMMLRVARRYDAKTDSIVFANNQ 106

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034648843 146 LLDRNQGKcVEGMVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLnsgvytflsSTLKSLEEKDHIHRVLDKITDTLih 225
Cdd:cd06938   107 PYTRDSYR-KAGMGDSAEDLFRFCRAMCSMKVDNAEYALLTAIVIF---------SDRPGLLQPKKVEKIQEIYLEAL-- 174

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1034648843 226 LMAKAGLTLQQQHQRLAQLLLILSHIRHMSNKGMEHLYSMKCKN-VVPlyDLLLEMLD 282
Cdd:cd06938   175 RAYVDNRRPPSQRVIFAKLLSILTELRTLGNQNSEMCFSLKLKNrKLP--PFLAEIWD 230

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
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1034648843  79 MMGLLTNLADRELVHMINWAKRVPGFVDLTLHDQVHLLECAWLEILmigLVWRSME 134
Cdd:cd06941     3 LWQQLSEALTPSVQRVVEFAKRIPGFCDLSQDDQLLLIKAGFFEVW---LVRISRL 55