Vitamin D Receptor
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Vitamin D Receptor
The vitamin D receptor (VDR also known as the calcitriol receptor) is a member of the nuclear receptor family of transcription factors. Calcitriol (the active form of vitamin D, 1,25-(OH)2vitamin D3) binds to VDR, which then forms a heterodimer with the retinoid-X receptor. The VDR heterodimer then enters the nucleus and binds to Vitamin D responsive elements (VDRE) in genomic DNA. VDR binding results in expression or transrepression of many specific gene products. VDR is also involved in microRNA-directed post transcriptional mechanisms. In humans, the vitamin D receptor is encoded by the ''VDR'' gene located on chromosome 12q13.11. VDR is expressed in most tissues of the body, and regulates transcription of genes involved in intestinal and renal transport of calcium and other minerals. Glucocorticoids decrease VDR expression. Many types of immune cells also express VDR. Function The VDR gene encodes the nuclear hormone receptor for vitamin D. The most potent natural ag ...
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Nuclear Receptor
In the field of molecular biology, nuclear receptors are a class of proteins responsible for sensing steroids, thyroid hormones, vitamins, and certain other molecules. These receptors work with other proteins to regulate the expression of specific genes thereby controlling the development, homeostasis, and metabolism of the organism. Nuclear receptors bind directly to DNA regulating the expression of adjacent genes; hence these receptors are classified as transcription factors. The regulation of gene expression by nuclear receptors often occurs in the presence of a ligand—a molecule that affects the receptor's behavior. Ligand binding to a nuclear receptor results in a conformational change activating the receptor. The result is up- or down-regulation of gene expression. A unique property of nuclear receptors that differentiates them from other classes of receptors is their direct control of genomic DNA. Nuclear receptors play key roles in both embryonic development a ...
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Bile Acid
Bile acids are steroid acids found predominantly in the bile of mammals and other vertebrates. Diverse bile acids are synthesized in the liver. Bile acids are conjugated with taurine or glycine residues to give anions called bile salts. Primary bile acids are those synthesized by the liver. Secondary bile acids result from bacterial actions in the colon (anatomy), colon. In humans, taurocholic acid and glycocholic acid (derivatives of cholic acid) and taurochenodeoxycholic acid and glycochenodeoxycholic acid (derivatives of chenodeoxycholic acid) are the major bile salts. They are roughly equal in concentration. The salts of their 7-alpha-dehydroxylated derivatives, deoxycholic acid and lithocholic acid, are also found, with derivatives of cholic, chenodeoxycholic and deoxycholic acids accounting for over 90% of human biliary bile acids. Bile acids comprise about 80% of the organic compounds in bile (others are phospholipids and cholesterol). An increased secretion of bile acids ...
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Nuclear Receptor Co-repressor 2
The nuclear receptor co-repressor 2 () is a transcriptional coregulatory protein that contains several nuclear receptor-interacting domains. In addition, NCOR2 appears to recruit histone deacetylases to DNA promoter regions. Hence NCOR2 assists nuclear receptors in the down regulation of target gene expression. NCOR2 is also referred to as a silencing mediator for retinoid or thyroid-hormone receptors (SMRT) or T3 receptor-associating cofactor 1 (TRAC-1). Function NCOR2/SMRT is a transcriptional coregulatory protein that contains several modulatory functional domains including multiple autonomous repression domains as well as two or three C-terminal nuclear receptor-interacting domains. NCOR2/SMRT serves as a repressive coregulatory factor (corepressor) for multiple transcription factor pathways. In this regard, NCOR2/SMRT functions as a platform protein, facilitating the recruitment of histone deacetylases to the DNA promoters bound by its interacting transcription factors. ...
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Nuclear Receptor Co-repressor 1
The nuclear receptor co-repressor 1 also known as thyroid-hormone- and retinoic-acid-receptor-associated co-repressor 1 (TRAC-1) is a protein that in humans is encoded by the ''NCOR1'' gene. NCOR1 is a transcriptional coregulatory protein which contains several nuclear receptor interacting domains. In addition, NCOR1 appears to recruit histone deacetylases to DNA promoter regions. Hence NCOR1 assists nuclear receptors in the down regulation of gene expression. Loss of function of this protein significantly increases the strength and power of mouse muscles. Family It is a member of the family of nuclear receptor corepressors; the other human protein that is a member of that family is Nuclear receptor co-repressor 2.UniProNuclear receptor corepressors familyPage accessed June 26, 2016 Interactions Nuclear receptor co-repressor 1 has been shown to interact with: * Androgen receptor, * CHD1, * Calcitriol receptor * GPS2, * Glucocorticoid receptor, * HDAC3, * HDAC4, * H ...
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MED24
Mediator of RNA polymerase II transcription subunit 24 is an enzyme that in humans is encoded by the ''MED24'' gene. Function This gene encodes a component of the mediator complex (also known as TRAP, SMCC, DRIP, or ARC), a transcriptional coactivator complex thought to be required for the expression of almost all genes. The mediator complex is recruited by transcriptional activators or nuclear receptors to induce gene expression, possibly by interacting with RNA polymerase II and promoting the formation of a transcriptional pre-initiation complex. Multiple transcript variants encoding different isoforms have been found for this gene. Interactions MED24 has been shown to interact with Estrogen receptor alpha, Cyclin-dependent kinase 8, Calcitriol receptor and BRCA1 Breast cancer type 1 susceptibility protein is a protein that in humans is encoded by the ''BRCA1'' () gene. Orthologs are common in other vertebrate species, whereas invertebrate genomes may encode a more dist ...
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MED12
Mediator of RNA polymerase II transcription, subunit 12 homolog (S. cerevisiae), also known as MED12, is a human gene found on the X chromosome The X chromosome is one of the two sex-determining chromosomes (allosomes) in many organisms, including mammals (the other is the Y chromosome), and is found in both males and females. It is a part of the XY sex-determination system and XO sex-d .... Clinical significance Mutations in ''MED12'' are responsible for at least two different forms of X-linked dominant mental retardation, Lujan-Fryns syndrome and FG syndrome, as well as instances of prostate cancer. Mutations in ''MED12'' are associated with uterine leiomyomas and breast fibroepithelial tumors (e.g. fibroadenoma and phyllodes tumors). Interactions MED12 has been shown to Protein-protein interaction, interact with: * Calcitriol receptor, * Cyclin-dependent kinase 8 * Estrogen receptor alpha, * Gli3, G9a, PPARGC1A, * MED26, * SOX9, and * Thyroid hormone receptor alpha. ...
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MED1
Mediator of RNA polymerase II transcription subunit 1 also known as DRIP205 or Trap220 is a subunit of the Mediator complex and is a protein that in humans is encoded by the ''MED1'' gene. MED1 functions as a nuclear receptor coactivator. Function The activation of gene transcription is a multistep process that is triggered by factors that recognize transcriptional enhancer sites in DNA. These factors work with co-activators to direct transcriptional initiation by the RNA polymerase II apparatus. The mediator of RNA polymerase II transcription subunit 1 protein is a subunit of the CRSP (cofactor required for SP1 activation) complex, which, along with TFIID, is required for efficient activation by SP1. This protein is also a component of other multisubunit complexes .g., thyroid hormone receptor-(TR-) associated proteins that interact with TR and facilitate TR function on DNA templates in conjunction with initiation factors and cofactors]. It also regulates p53-dependent ap ...
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Caveolin 3
Caveolin-3 is a protein that in humans is encoded by the ''CAV3'' gene. Alternative splicing has been identified for this locus, with inclusion or exclusion of a differentially spliced intron. In addition, transcripts utilize multiple polyA sites and contain two potential translation initiation sites. Function This gene encodes a caveolin family member, which functions as a component of the caveolae plasma membranes found in most cell types. Caveolin proteins are proposed to be scaffolding proteins for organizing and concentrating certain caveolin-interacting molecules. Clinical significance Mutations identified in this gene lead to interference with protein oligomerization or intra-cellular routing, disrupting caveolae formation and resulting in Limb-Girdle muscular dystrophy type-1C (LGMD-1C), HyperCKemia, distal myopathy or rippling muscle disease (RMD). Other mutations in Caveolin causes Long QT Syndrome or familial hypertrophic cardiomyopathy, although the role of Cav3 ...
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BAZ1B
Tyrosine-protein kinase, or Bromodomain adjacent to zinc finger domain, 1B (BAZ1B) is an enzyme that in humans is encoded by the ''BAZ1B'' gene. Function This gene encodes a member of the bromodomain protein family. The bromodomain is a structural motif characteristic of proteins involved in chromatin-dependent regulation of transcription. This gene is deleted in Williams-Beuren syndrome, a developmental disorder caused by deletion of multiple genes at 7q11.23. BAZ1B has been found to affect the activity of 448 other genes and is very important in the development of the neural crest and the face. Research suggests that changes in BAZ1B may have been involved in " self-domesticating" humans. Animal models Model organisms have been used in the study of ''BAZ1B'' function. A conditional knockout mouse line, called ''Baz1btm2a(KOMP)Wtsi'', was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribu ...
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BAG1
BAG family molecular chaperone regulator 1 is a protein that in humans is encoded by the ''BAG1'' gene. Function The oncogene BCL2 is a membrane protein that blocks a step in a pathway leading to apoptosis or programmed cell death. The protein encoded by this gene binds to BCL2 and is referred to as BCL2-associated athanogene. It enhances the anti-apoptotic effects of BCL2 and represents a link between growth factor receptors and anti-apoptotic mechanisms. At least three protein isoforms are encoded by this mRNA through the use of alternative translation initiation sites, including a non- AUG site. Clinical significance BAG gene has been implicated in age related neurodegenerative diseases as Alzheimer's. It has been demonstrated that BAG1 and BAG 3 regulate the proteasomal and lysosomal protein elimination pathways, respectively. * Interactions BAG1 has been shown to interact with: * Androgen receptor, * C-Raf, * Calcitriol receptor, * Glucocorticoid receptor, ...
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Sonic Hedgehog
Sonic hedgehog protein (SHH) is encoded for by the ''SHH'' gene. The protein is named after the character ''Sonic the Hedgehog''. This signaling molecule is key in regulating embryonic morphogenesis in all animals. SHH controls organogenesis and the organization of the central nervous system, limbs, digits and many other parts of the body. Sonic hedgehog is a morphogen that patterns the developing embryo using a concentration gradient characterized by the French flag model. This model has a non-uniform distribution of SHH molecules which governs different cell fates according to concentration. Mutations in this gene can cause holoprosencephaly, a failure of splitting in the cerebral hemispheres, as demonstrated in an experiment using SHH knock-out mice in which the forebrain midline failed to develop and instead only a single fused telencephalic vesicle resulted. Sonic hedgehog still plays a role in differentiation, proliferation, and maintenance of adult tissues. Abnormal activ ...
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