INSIG2
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INSIG2
Insulin induced gene 2, also known as INSIG2, is a protein which in humans is encoded by the ''INSIG2'' gene. Regulation Insulin activates the human INSIG2 promoter in a process mediated by phosphorylated SAP1a. Akt mediates suppression of Insig2a, a liver-specific transcript encoding the SREBP1c inhibitor INSIG2. MCHR2 has been observed to significantly decrease INSIG2. Insig2 is upregulated under hypoxic conditions and is associated with the malignant potential of pancreatic cancer. A novel 1alpha,25-dihydroxyvitamin D3 ,25-(OH)2D3response element in the promoter region of Insig-2 gene was identified which specifically binds to the heterodimer of retinoid X receptor and vitamin D receptor (VDR) and directs VDR-mediated transcriptional activation in a 1,25-(OH)2D3-dependent manner. 1,25-(OH)2D3 transiently but strongly induces Insig-2 expression in 3T3-L1 cells. This novel regulatory circuit may also play important roles in other lipogenic cell types that express VDR. ...
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SAP1a
SAP1A is one of a family of proteins that contains a unique DNA binding domain termed the ETS domain. Transcription The transcriptional activation domain of SAP1a resides within the C-terminal region, the function of which may be impeded by the N-terminus. Several potential ERK consensus sites within the C-terminal region of SAP1a can modulate its transactivation efficacy, implicating that SAP1a is a direct target of ERKs. Interactions SAP1a has been shown to interact with the c-fos serum response element upon recruitment by the serum response factor. SAP1a is a nuclear protein stimulating transcription via the c-fos serum response element, and additionally via an Ets binding site independently of the serum response factor. Insulin activated the human INSIG2 promoter in a process mediated by phosphorylated SAP1a. Sap1a is phosphorylated efficiently by ERKs but not by SAPK/JNKs. Serum response factor-dependent ternary complex formation by Sap1a is stimulated by ERK phosphorylat ...
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Sterol Regulatory Element Binding Protein
Sterol regulatory element-binding proteins (SREBPs) are transcription factors that bind to the sterol regulatory element DNA sequence TCACNCCAC. Mammalian SREBPs are encoded by the genes ''SREBF1'' and '' SREBF2''. SREBPs belong to the basic-helix-loop-helix leucine zipper class of transcription factors. Unactivated SREBPs are attached to the nuclear envelope and endoplasmic reticulum membranes. In cells with low levels of sterols, SREBPs are cleaved to a water-soluble N-terminal domain that is translocated to the nucleus. These activated SREBPs then bind to specific sterol regulatory element DNA sequences, thus upregulating the synthesis of enzymes involved in sterol biosynthesis. Sterols in turn inhibit the cleavage of SREBPs and therefore synthesis of additional sterols is reduced through a negative feed back loop. Isoforms Mammalian genomes have two separate SREBP genes ( and ): * SREBP-1 expression produces two different isoforms, SREBP-1a and -1c. These isoforms differ ...
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MCHR2
Melanin-concentrating hormone receptor 2 (MCH2) also known as G-protein coupled receptor 145 (GPR145) is a protein that in humans is encoded by the ''MCHR2'' gene. MCH2 is also found in dogs, ferrets, and some other primates and carnivores, but is not found in mice or rats. This has delayed research into the receptor as a therapeutic target, due to most early pharmaceutical research usually being conducted in small mammals such as mice, rats or rabbits which lack the MCH2 gene and its receptor product. Clinical significance Treatment of human cells expressing MCHR2 with MCH resulted in upregulation of IDH3A, PCK1 and PFKFB4 and the downregulation of INSIG2 and ACOT8 Acyl-coenzyme A thioesterase 8 is an enzyme that in humans is encoded by the ''ACOT8'' gene. The protein encoded by this gene is a peroxisomal thioesterase that appears to be involved more in the oxidation of fatty acids rather than in their form .... See also * Melanin-concentrating hormone receptor References ...
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SREBP Cleavage Activating Protein
Sterol regulatory element-binding protein cleavage-activating protein, also known as SREBP cleavage-activating protein or SCAP is a protein that in humans is encoded by the ''SCAP'' gene. SCAP contains a sterol-sensing domain (SSD) and seven WD domains. In cholesterol-depleted cells, this protein binds to sterol regulatory element binding proteins (SREBPs) and mediates their transport from the ER to the Golgi apparatus. The SREBPs are then proteolytically cleaved and stimulate sterol biosynthesis. Function SCAP is a regulatory protein that is required for the proteolytic cleavage of the sterol regulatory element-binding protein (SREBP). SCAP is an integral membrane protein located in the endoplasmic reticulum (ER). One of the cytosolic regions of SCAP contains a hexapeptide amino acid sequence, MELADL, that functions to detect cellular cholesterol. When cholesterol is present, SCAP undergoes a conformational change that prevents it from activating SREBP and cholestero ...
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Protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, responding to stimuli, providing structure to cells and organisms, and transporting molecules from one location to another. Proteins differ from one another primarily in their sequence of amino acids, which is dictated by the nucleotide sequence of their genes, and which usually results in protein folding into a specific 3D structure that determines its activity. A linear chain of amino acid residues is called a polypeptide. A protein contains at least one long polypeptide. Short polypeptides, containing less than 20–30 residues, are rarely considered to be proteins and are commonly called peptides. The individual amino acid residues are bonded together by peptide bonds and adjacent amino acid residues. The sequence of amino acid ...
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Gene
In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a basic unit of heredity and the molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protein-coding genes and noncoding genes. During gene expression, the DNA is first copied into RNA. The RNA can be directly functional or be the intermediate template for a protein that performs a function. The transmission of genes to an organism's offspring is the basis of the inheritance of phenotypic traits. These genes make up different DNA sequences called genotypes. Genotypes along with environmental and developmental factors determine what the phenotypes will be. Most biological traits are under the influence of polygenes (many different genes) as well as ...
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Insulin
Insulin (, from Latin ''insula'', 'island') is a peptide hormone produced by beta cells of the pancreatic islets encoded in humans by the ''INS'' gene. It is considered to be the main anabolic hormone of the body. It regulates the metabolism of carbohydrates, fats and protein by promoting the absorption of glucose from the blood into liver, fat and skeletal muscle cells. In these tissues the absorbed glucose is converted into either glycogen via glycogenesis or fats (triglycerides) via lipogenesis, or, in the case of the liver, into both. Glucose production and secretion by the liver is strongly inhibited by high concentrations of insulin in the blood. Circulating insulin also affects the synthesis of proteins in a wide variety of tissues. It is therefore an anabolic hormone, promoting the conversion of small molecules in the blood into large molecules inside the cells. Low insulin levels in the blood have the opposite effect by promoting widespread catabolism, especial ...
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INSIG1
Insulin induced gene 1, also known as INSIG1, is a protein which in humans is encoded by the ''INSIG1'' gene. INSIG1 is short for insulin-induced gene 1; it is located on chromosome 7 (7q36). This human gene encodes for a transmembrane protein of 277 amino acids with probably 6 transmembrane domains. It is localized in the endoplasmic reticulum (ER) and seems to be expressed in all tissues, especially in liver. This gene is called an insulin-induced gene because the molecule insulin can regulate it. Importantly, the protein encoded by this gene plays a critical role in regulating cholesterol concentrations in cells. Function #INSIG1 plays an important role in the SREBP-mediated regulation of cholesterol biosynthesis: by binding to the sterol-sensing domain of SCAP (SREBP cleavage activating protein) it makes the SCAP/SREBP complex stay longer in the ER, thus prohibiting SCAP from carrying activated SREBP to the golgi complex. This ultimately blocks SREBP from acting as a tr ...
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Endoplasmic Reticulum
The endoplasmic reticulum (ER) is, in essence, the transportation system of the eukaryotic cell, and has many other important functions such as protein folding. It is a type of organelle made up of two subunits – rough endoplasmic reticulum (RER), and smooth endoplasmic reticulum (SER). The endoplasmic reticulum is found in most eukaryotic cells and forms an interconnected network of flattened, membrane-enclosed sacs known as cisternae (in the RER), and tubular structures in the SER. The membranes of the ER are continuous with the outer nuclear membrane. The endoplasmic reticulum is not found in red blood cells, or spermatozoa. The two types of ER share many of the same proteins and engage in certain common activities such as the synthesis of certain lipids and cholesterol. Different types of cells contain different ratios of the two types of ER depending on the activities of the cell. RER is found mainly toward the nucleus of cell and SER towards the cell membrane or plasma ...
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Golgi Alpha-mannosidase II
Mannosyl-oligosaccharide 1,3-1,6-alpha-mannosidase (, ''mannosidase II'', ''exo-1,3-1,6-alpha-mannosidase'', ''alpha-D-mannosidase II'', ''alpha-mannosidase II'', ''alpha1-3,6-mannosidase'', ''GlcNAc transferase I-dependent alpha1,3 lpha1,6annosidase'', ''Golgi alpha-mannosidase II'', ''ManII'', ''1,3(1,6)-alpha-D-mannosidase'', ''1,3-(1,6-)mannosyl-oligosaccharide alpha-D-mannohydrolase'') is an enzyme with systematic name ''(1->3)-(1->6)-mannosyl-oligosaccharide alpha-D-mannohydrolase''. This enzyme catalyses the following chemical reaction : Hydrolysis of the terminal (1->3)- and (1->6)-linked alpha-D-mannose residues in the mannosyl-oligosaccharide Man5(GlcNAc)3 This enzyme is involved in the synthesis of glycoproteins. It is a key enzyme of N-linked Glycan processing and is inhibited by small molecule swainsonine Swainsonine is an indolizidine alkaloid. It is a potent inhibitor of Golgi alpha-mannosidase II, an immunomodulator, and a potential chemotherapy drug. As a ...
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Silibinin
Silibinin ( INN), also known as silybin (both from ''Silybum'', the generic name of the plant Plants are predominantly photosynthetic eukaryotes of the kingdom Plantae. Historically, the plant kingdom encompassed all living things that were not animals, and included algae and fungi; however, all current definitions of Plantae excl ... from which it is extracted), is the major active constituent of silymarin, a standardized extract of the milk thistle seeds, containing a mixture of flavonolignans consisting of silibinin, isosilibinin, silychristin, silidianin, and others. Silibinin itself is a mixture of two diastereomers, silybin A and silybin B, in approximately equimolar ratio. The mixture exhibits a number of pharmacological effects, particularly in the fatty liver, non-alcoholic fatty liver, non-alcoholic steatohepatitis, and there is great clinical evidence for the use of silibinin as a supportive element in Alcoholic liver cirrhosis, alcoholic and Child–Pug ...
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