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Hepatocyte Nuclear Factor 4
HNF4 (Hepatocyte Nuclear Factor 4) is a nuclear receptor protein mostly expressed in the liver, gut, kidney, and pancreatic beta cells that is critical for liver development. In humans, there are two isoforms of HNF4, HNF4α and HNF4γ, encoded by two separate genes and respectively. Ligands HNF4 was originally classified as an orphan receptor that exhibits constitutive transactivation activity apparently by being continuously bound to a variety of fatty acids. The existence of a ligand for HNF4 has been somewhat controversial, but linoleic acid (LA) has been identified as the endogenous ligand of native HNF4 expressed in mouse liver; the binding of LA to HNF4 is reversible. The ligand binding domain of HNF4, as with other nuclear receptors, adopts a canonical alpha helical sandwich fold and interacts with co-activator proteins. HNF4 binds to the consensus sequence AGGTCAaAGGTCA in order to activate transcription. Pathology Mutations in the ''HNF4A'' gene have been lin ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Hepatocyte Nuclear Factor 4 Alpha
Hepatocyte nuclear factor 4 alpha (HNF4A) also known as NR2A1 (nuclear receptor subfamily 2, group A, member 1) is a nuclear receptor that in humans is encoded by the ''HNF4A'' gene. Function HNF-4α is a nuclear transcription factor that binds DNA as a homodimer. The encoded protein controls the expression of several genes, including hepatocyte nuclear factor 1 alpha, a transcription factor which regulates the expression of several hepatic genes. This gene plays a role in development of the liver, kidney, and intestines. Alternative splicing of this gene results in multiple transcript variants. HNF4A is required for the PXR and CAR-mediated transcriptional activation of CYP3A4. Genetic mutations in the ''HNF4A'' gene can influence the activity of HNF4α's downstream proteins such as CYP2D6, ''in vitro'' and ''in vivo''. The alkaloid berberine upregulates the expression of HNF4A. This gene also plays a pivotal role in the expression and synthesis of SHBG, an important glyc ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Linoleic Acid
Linoleic acid (LA) is an organic compound with the formula COOH(CH2)7CH=CHCH2CH=CH(CH2)4CH3. Both alkene groups are ''cis''. It is a fatty acid sometimes denoted 18:2 (n-6) or 18:2 ''cis''-9,12. A linoleate is a salt or ester of this acid. Linoleic acid is a polyunsaturated omega-6 fatty acid. It is a colorless liquid that is virtually insoluble in water but soluble in many organic solvents. It typically occurs in nature as a triglyceride (ester of glycerin) rather than as a free fatty acid. It is one of two essential fatty acids for humans, who must obtain it through their diet, and the most essential, because the body uses it as a base to make the others. The word "linoleic" derives from the Latin ''linum'' "flax" + ''oleum'' "oil", reflecting the fact that it was first isolated from linseed oil. History In 1844, F. Sacc, working at the laboratory of Justus von Liebig, isolated linoleic acid from linseed oil. In 1886, K. Peters determined the existence of two double ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Hepatocyte Nuclear Factors
Hepatocyte nuclear factors (HNFs) are a group of phylogenetically unrelated transcription factors that regulate the transcription of a diverse group of genes into proteins. These proteins include blood clotting factors and in addition, enzymes and transporters involved with glucose, cholesterol, and fatty acid transport and metabolism. Function As the name suggests, hepatocyte nuclear factors are expressed predominantly in the liver. However HNFs are also expressed and play important roles in a number of other tissues so that the name ''hepatocyte nuclear factor'' is somewhat misleading. Nevertheless, the liver is the only tissue in which a significant number of different HNFs are expressed at the same time. In addition, there are a number of genes which contain multiple promoter and enhancer regions each regulated by a different HNF. Furthermore, efficient expression of these genes require synergistic activation by multiple HNFs. Hence hepatocyte nuclear factors funct ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Insulin Resistance
Insulin resistance (IR) is a pathological condition in which cells fail to respond normally to the hormone insulin. Insulin is a hormone that facilitates the transport of glucose from blood into cells, thereby reducing blood glucose (blood sugar). Insulin is released by the pancreas in response to carbohydrates consumed in the diet. In states of insulin resistance, the same amount of insulin does not have the same effect on glucose transport and blood sugar levels. There are many causes of insulin resistance and the underlying process is still not completely understood, but sulfate depletion may be the important factor. Risk factors for insulin resistance include obesity, sedentary lifestyle, family history of diabetes, various health conditions, and certain medications. Insulin resistance is considered a component of the metabolic syndrome. There are multiple ways to measure insulin resistance such as fasting insulin levels or glucose tolerance tests, but these are not often use ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
SHBG
Sex hormone-binding globulin (SHBG) or sex steroid-binding globulin (SSBG) is a glycoprotein that binds to androgens and estrogens. When produced by the Sertoli cells in the seminiferous tubules of the testis, it has also been called androgen-binding protein (ABP). Other steroid hormones such as progesterone, cortisol, and other corticosteroids are bound by transcortin. SHBG is found in all vertebrates apart from birds. Function Testosterone and estradiol circulate in the bloodstream, loosely bound mostly to serum albumin (~54%), and to a lesser extent bound tightly to SHBG (~44%). Only a very small fraction of about 1 to 2% is unbound, or "free," and thus biologically active and able to enter a cell and activate its receptor. SHBG inhibits the function of these hormones. Thus, the local bioavailability of sex hormones is influenced by the level of SHBG. Because SHBGbinds to testosterone (T) and dihydrotestosterone (DHT), these hormones are made less lipophilic and become ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
MODY 1
MODY 1 is a form of maturity onset diabetes of the young. MODY 1 is due to a loss-of-function mutation in the ''HNF4A'' (''MODY1'') gene on chromosome 12. This gene codes for hepatocyte nuclear factor 4-alpha (HNF4-α) protein also known as transcription factor 14 (TCF14). HNF4α controls function of HNF1α (see MODY 3; ) and perhaps HNF1β (MODY 5) as well. This transcription network plays a role in the early development of the pancreas, liver, and intestines. In the pancreas these genes influence expression of, among others, the genes for insulin, the principal glucose transporter (GLUT2), and several proteins involved in glucose and mitochondrial metabolism. Although pancreatic beta cells produce adequate insulin in infancy, the capacity for insulin production declines thereafter. Diabetes (persistent hyperglycemia) typically develops by early adult years, but may not appear until later decades. The degree of insulin deficiency is slowly progressive. Many patients with MODY ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Coactivation (Transcription)
A coactivator is a type of transcriptional coregulator that binds to an activator (a transcription factor) to increase the rate of transcription of a gene or set of genes. The activator contains a DNA binding domain that binds either to a DNA promoter site or a specific DNA regulatory sequence called an enhancer. Binding of the activator-coactivator complex increases the speed of transcription by recruiting general transcription machinery to the promoter, therefore increasing gene expression. The use of activators and coactivators allows for highly specific expression of certain genes depending on cell type and developmental stage. Some coactivators also have histone acetyltransferase (HAT) activity. HATs form large multiprotein complexes that weaken the association of histones to DNA by acetylating the N-terminal histone tail. This provides more space for the transcription machinery to bind to the promoter, therefore increasing gene expression. Activators are found in all ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Protein Domains
In molecular biology, a protein domain is a region of a protein's polypeptide chain that is self-stabilizing and that folds independently from the rest. Each domain forms a compact folded three-dimensional structure. Many proteins consist of several domains, and a domain may appear in a variety of different proteins. Molecular evolution uses domains as building blocks and these may be recombined in different arrangements to create proteins with different functions. In general, domains vary in length from between about 50 amino acids up to 250 amino acids in length. The shortest domains, such as zinc fingers, are stabilized by metal ions or disulfide bridges. Domains often form functional units, such as the calcium-binding EF hand domain of calmodulin. Because they are independently stable, domains can be "swapped" by genetic engineering between one protein and another to make chimeric proteins. Background The concept of the domain was first proposed in 1973 by Wetlaufer aft ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Orphan Receptor
In biochemistry, an orphan receptor is a protein that has a similar structure to other identified receptors but whose endogenous ligand has not yet been identified. If a ligand for an orphan receptor is later discovered, the receptor is referred to as an "adopted orphan". Conversely, the term orphan ligand refers to a biological ligand whose cognate receptor has not yet been identified. Examples Examples of orphan receptors are found in the G protein-coupled receptor (GPCR) and nuclear receptor families. If an endogenous ligand is found, the orphan receptor is "adopted" or "de-orphanized". An example is the nuclear receptor Farnesoid X receptor (FXR) and the GPCR TGR5/GPCR19/G protein-coupled bile acid receptor, both of which are activated by bile acids. Adopted orphan receptors in the nuclear receptor group include FXR, liver X receptor (LXR), and peroxisome proliferator-activated receptor (PPAR). Another example of an orphan receptor site is the PCP binding site in the NMDA ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Hepatocyte Nuclear Factor 4 Gamma
__NOTOC__ Hepatocyte nuclear factor 4 gamma (HNF4G) also known as NR2A2 (nuclear receptor subfamily 2, group A, member 2) is a nuclear receptor that in humans is encoded by the ''HNF4G'' ''gene''. See also *Hepatocyte nuclear factor 4 *Hepatocyte nuclear factors Hepatocyte nuclear factors (HNFs) are a group of phylogenetically unrelated transcription factors that regulate the transcription of a diverse group of genes into proteins. These proteins include blood clotting factors and in addition, enzymes a ... References Further reading * * External links * Intracellular receptors Transcription factors {{gene-8-stub ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
HNF4G (gene)
__NOTOC__ Hepatocyte nuclear factor 4 gamma (HNF4G) also known as NR2A2 (nuclear receptor subfamily 2, group A, member 2) is a nuclear receptor that in humans is encoded by the ''HNF4G'' ''gene''. See also *Hepatocyte nuclear factor 4 *Hepatocyte nuclear factors Hepatocyte nuclear factors (HNFs) are a group of phylogenetically unrelated transcription factors that regulate the transcription of a diverse group of genes into proteins. These proteins include blood clotting factors and in addition, enzymes a ... References Further reading * * External links * Intracellular receptors Transcription factors {{gene-8-stub ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
HNF4A
Hepatocyte nuclear factor 4 alpha (HNF4A) also known as NR2A1 (nuclear receptor subfamily 2, group A, member 1) is a nuclear receptor that in humans is encoded by the ''HNF4A'' gene. Function HNF-4α is a nuclear transcription factor that binds DNA as a homodimer. The encoded protein controls the expression of several genes, including hepatocyte nuclear factor 1 alpha, a transcription factor which regulates the expression of several hepatic genes. This gene plays a role in development of the liver, kidney, and intestines. Alternative splicing of this gene results in multiple transcript variants. HNF4A is required for the PXR and CAR-mediated transcriptional activation of CYP3A4. Genetic mutations in the ''HNF4A'' gene can influence the activity of HNF4α's downstream proteins such as CYP2D6, ''in vitro'' and ''in vivo''. The alkaloid berberine upregulates the expression of HNF4A. This gene also plays a pivotal role in the expression and synthesis of SHBG, an important gly ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
