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).

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gi 1475060986   1 GWRSYRQASGNLLCFAPDLIINEQRMTLPCMYDQCKHMLFISTELQRLQVSYEEYLCMKTLLLLSS 66
Cdd:cd07076    79 GWRSYRQSNGNLLCFAPDLIINEQRMTLPCMYDQCKHMLYVSSELHRLQVSYEEYLCMKTLLLLST 144

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.

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gi 1475060986   1 GWRSYRQASGNLLCFAPDLIINEQRMTLPCMYDQCKHMLFISTELQRLQVSYEEYLCMKTLLLLSS 66
Cdd:cd07076    79 GWRSYRQSNGNLLCFAPDLIINEQRMTLPCMYDQCKHMLYVSSELHRLQVSYEEYLCMKTLLLLST 144

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.

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gi 1475060986   1 GWRSYRQASGNLLCFAPDLIINEQRMTLPCMYDQCKHMLFISTELQRLQVSYEEYLCMKTLLLLSS 66
Cdd:cd07076    79 GWRSYRQSNGNLLCFAPDLIINEQRMTLPCMYDQCKHMLYVSSELHRLQVSYEEYLCMKTLLLLST 144

Ligand binding domain of the mineralocorticoid receptor, a member of the nuclear receptor superfamily; The ligand binding domain of the mineralocorticoid receptor (MR): MR, also called aldosterone receptor, is a member of nuclear receptor superfamily involved in the regulation of electrolyte and fluid balance. The receptor is activated by mineralocorticoids such as aldosterone and deoxycorticosterone as well as glucocorticoids, like cortisol and cortisone. Binding of its ligand results in its translocation to the cell nucleus, homodimerization and binding to hormone response elements (HREs) present in the promoter of MR controlled genes. This results in the recruitment of the coactivators and the transcription of the activated genes. MR is expressed in many tissues and its activation results in the expression of proteins regulating electrolyte and fluid balance. Like other members of the nuclear receptor (NR) superfamily of ligand-activated transcription factors, MR 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, in addition to binding ligand, contains a ligand-dependent activation function-2 (AF-2).

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gi 1475060986   2 WRSYRQASGNLLCFAPDLIINEQRMTLPCMYDQCKHMLFISTELQRLQVSYEEYLCMKTLLLLSSG 67
Cdd:cd07075    80 WRSYKHTNSQFLYFAPDLVFNEERMHQSAMYELCQGMHQISLQFVRLQLTFEEYTIMKVLLLLSTI 145

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.

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gi 1475060986   1 GWRSYRQASGNLLCFAPDLIINEQRMTLPCMYDQCKHMLFISTELQRLQVSYEEYLCMKTLLLLS 65
Cdd:cd07073    79 GWRSFTNVNSRMLYFAPDLVFNEYRMHKSRMYSQCVRMRHLSQEFGWLQITPQEFLCMKALLLFS 143

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).

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gi 1475060986   2 WRSYRQASGnlLCFAPDLIINEQRMTLPCMYDQCKHMLFISTELQRLQVSYEEYLCMKTLLLLSSG 67
Cdd:cd07068    79 WRSLPHPGK--LVFAPDLLLDREQARVEGLLEIFDMLLQLVRRFRELGLQREEYVCLKAIILANSD 142

Ligand binding domain of Estrogen receptor, which are activated by the hormone 17beta-estradiol (estrogen); The ligand binding domain (LBD) of Estrogen receptor (ER): Estrogen receptor, a member of nuclear receptor superfamily, is 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. 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 flexible hinge and a C-terminal ligand binding domain (LBD). The C-terminal LBD also contains AF-2 activation motif, the dimerization motif, and part of the nuclear localization region. Estrogen receptor has been linked to aging, cancer, obesity and other diseases.

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gi 1475060986   2 WRSYRQaSGNLLcFAPDLIINeqRMTLPC---MYDQCKHMLFISTELQRLQVSYEEYLCMKTLLLLSSG 67
Cdd:cd06949    84 WRSMEH-PGKLL-FAPDLLLD--RNQGSCvegMVEIFDMLLATASRFRELQLQREEYVCLKAIILLNSS 148

Ligand binding domain of hormone receptors;

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gi 1475060986    1 GWRSYRQasGNLLCFAPDLIINEQRMTLPC----MYDQCKHMLFISTELQRLQVSYEEYLCMKTLLLLSSG 67
Cdd:smart00430  43 AYRSVKL--KKELLLAPDGTYIRPDAVLELrklfSPFLDRILSELVKPLRELKLDDEEYALLKAIVLFNPA 111